*ttl

THE BOWMAN LECTURE

SOME HEREDITARY
DISEASES OF THE EYE

E. NETTLESHIP

[From the ' Transactions of the Ophthalmological Society,'
Vol. XXIX, 1909]

ftott&m

PRINTED BY ADLAED AND SON
BARTHOLOMEW CLOSE

1909

/3

ON SOME HEREDITARY DISEASES OF
THE EYE.

BEING

THE BOWMAN LECTURE,
Delivered on Thursday, June 10th, 1909,

BY

E. NETTLESHIP.

INTRODUCTORY.

I HAVE chosen the heredity of certain diseases of the
eye as my subject, because whilst possessing great
attractions, it furnishes a theme upon which one who
is to some extent out of touch with the newest clinical
ophthalmology may still, perhaps, hope to speak without
presumption. I believe also that all here who had, like
myself, the great privilege of acquaintance with Sir
William Bowman, of experiencing the charm of his voice
and diction, and of seeing him at work, will agree that had
he been alive to-day he would, with the keen but discern-
ing enthusiasm that he always brought to bear upon new
scientific problems, have recognised that the study of
heredity confronts us with subjects of absorbing interest,
the right interpretation of which must have important
consequences for the future of our race. As a matter
of fact Bowman actually communicated to Charles Darwin
some of the earliest generalised observations upon the
heredity of cataract, and, as we shall see further -on, later
work has but confirmed his statements.

Taking a few of the principal ophthalmic diseases, the
hereditary transmission of which is now recognised, I
propose to-day to consider them from that point of view,

M375305

LVIII BOWMAN LECTURE.

and at the same time to indicate some of the directions in
which further reseach into their nature is most needed.
Many, such as the heredity of errors of refraction and
of the musculature of the eye, I cannot touch. We
could all cite plenty of examples showing the family
prevalence of both these classes of defect, but I do
not think much has yet been done in the direction most
suitable for clinical observers — the careful record and
analysis of individual pedigrees. The elaborate statistical
enquiry upon the inheritance of arnetropia lately brought
out by Professor Karl Pearson and Miss Amy Barrington*
will help to elucidate the ever-present problem of environ-
ment versus heredity in the causation of myopia, although
the imperfection of the data (data derived from ophthalmo-
logical examinations, be it confessed) often detracts from
their value to the biometrical statistician.

I shall say but little on the theoretical side of my
subject, being, as I am, quite unable to deal with the
biological and mathematical complexities in which the
modern student of heredity finds himself involved. As
one who must be content with a very modest share of
spade work I am grateful that in the medical domain
there is still virgin ground where the tasks of ex-
cavating, collecting and recording may be safely under-
taken by those who enjoy them. And here I wish
to express my deep indebtedness and cordial gratitude
to the many colleagues and friends who have generously
furnished me with cases and numerical records bearing
upon heredity, and have, often at much tedious trouble
to themselves, aided me in the collection and disen-
tanglement of genealogical details. I could have done
next to nothing without such help.

Before getting to close quarters with individual diseases
I must ask your indulgence whilst, in order to avoid need-
less repetition, I refer to certain generalities.

* " A First Study of the Inheritance of Vision and of the Eelative
Influence of Heredity and Environment on Sight." By Amy Barrington
and Karl Pearson, F.R.S., Eugenics Laboratory Memoirs, v, 1909. London :
Dulau and Co.

BOWMAN LECTURE. LIX

One of the first questions generally raised when heredity
is under discussion is the influence of consanguinity in the
parents or ancestors. The belief that kinship between
parents is a source of disease or degeneracy in the
children is widely spread and has its roots deep in the
past ; and yet we meet every day with marked differences
of opinion and practice in regard to the matter, between
one house or family and another. The real question is
this : Can the marriage of blood relations produce disease
of which neither the parents nor ancestors showed any
trace, or does the consanguinity operate simply by increas-
ing the likelihood that both of a pair of parents will contain
the seeds of the same undesirable, or it may be desirable,
character ? If the former be true no cousin- marriage can
be said to be safe. But if the latter be the correct position
—and the results of all modern research appear to point
that way — the outcome of the consanguineous union will
depend entirely upon whether the particular disease, or
other heritable character, is carried by both parents, by
only one of them, or by neither ; the consanguinity will be
operative only if it increase the chance that both parents
are tainted. If the transmissible condition be one that is
very common there may be as much chance of its presence
in both of an unrelated pair as in both of a pair of
cousins; but any comparatively rare disease is more likely
to be present in two cousins than in two unrelated persons.

Accordingly we find a general belief in the medical
profession that in diseases so relatively infrequent as
retinitis pigmentosa and deaf-mutism consanguinity of
the parents plays an important part. And the same is
true of some other conditions where, as in the diseases
just named, both sexes are liable to suffer from, and both
liable to transmit, the disease.

But in sex-limited conditions, such as Leber's disease
and congenital colour-blindness, where only the males
suffer, though the disease is carried down by (apparently)
normal females, consanguinity of parents is known to be
infrequent. If we start with a colour-blind male we know

LX BOWMAN LECTURE.

that all his children will, as a rule, have normal colour-
perception ; that if his sons, who neither exhibit nor carry
the defect, have issue, that issue too will be normal ; but
that some of the sons of some of his daughters will show
the defect, whilst the other daughters, who we presume do
not carry it, will have all normal children. If one of these
normal children of a normal daughter marries a cousin,

A i • *• -n t 1 1

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the issue of one of the normal sons, the result, as regards
colour-perception, will be the same as if two unrelated
normals marry. In fact, if the sex-limitation were in-
variable in colour-blindness and other sex-limited con-
ditions, only one kind of cousin-marriage out of the
several possible kinds shown in Figs. 1 to 5 (I speak of
first cousinship throughout) would be attended by special
risk, i'Vz., when the mothers of the parents are sisters who,

BOWMAN LECTURE.

LXT

although not manifestly colour-blind, both carry the
defect (Fig. 1, II). If one of these two grandmothers of
the male IV, 1 is free from taint (as in II, Figs. 2 and 3),
it is impossible to understand that she can have any more
influence than if she came from a different stock; and the
same will be true if one or both of the two grand-
parents (parents of the cousins) be male and unaffected
(II, Figs. 4 and 5).

In this connection Fig. 48 (Leber's disease, a sex-
limited affection; Klopfer's case, 1898), is instructive.

f Comsin-Mavriafte in Sen-limited Disease.
Fi<j. I Ffy 2. _ Fifl. 3 ^ Fij. 4 Fi«. S

r

ying

Disease

The disease appeared only in the last two of the eight or
nine known generations, in three childships cousins to
each other, and, according to rule, affected males only."*

Each of these childships was the issue of a con-
sanguineous marriage ; but, as the lines show, these
parental cousinships all came from grandfathers who were
unaffected, and therefore, on the hypothesis, did not
contain the disease. If the normal rule obtained, as
seems to have been the case, the disease must have
followed the thick, black line to an affected male
* Some particulars of this pedigree will be found at p. cvm.

LXII

BOWMAN LECTURE.

ascendant of V, 23, in which case the cousinships do
not count, for V, 23 was from an outside stock.

But limitation of the disease to the males and trans-
mission through normal females is not invariable. For

though I believe that an unaffected male never carries
colour-blindness, exceptions are found to the other part of
the rule. Thus an affected male sometimes transmits to
his son, and colour-blindness is sometimes seen in females.
The influence, whatever it is, that usually prevents the
colour-blind male from passing the defect on to, or
through, his sons and compels him to transmit it only

BOWMAN LECTURE. LXI1I

through daughters who do not themselves show it, is
sometimes lacking.

The effect of consanguinity and the facts as to sex-
limitation can both be considered in relation to the
Mendelian theory. According to this theory of inheri-
tance, a character and its opposite or absence is repre-
sented in the gametes by particles ; this at least applies to
certain characters, pathological as well as physiological.
These particles occur in even numbers or pairs in each
gamete. The members of each pair may be similar (both
representing presence of the character, or both representing
its absence), or may be dissimilar (each pair containing one
of each kind). In the fertilised germ the pairs derived
from the gametes, so to speak, change partners. The
constitution of the particles in the resulting zygote
depends upon that in the original gametes ; the zygote
may contain only pairs representing the character, only
those for its complement or absence, or a hybrid between
the two. For convenience, one of the characters (or its
participate representative) is called " dominant " (D.D.,
Fig. 6 A and B) , because when it unites with the other, or
" recessive " (R.R., Fig. 6 B), the resulting hybrid shows
only the former character, although carrying both (D. R.,
Fig. 6 B). The other character, the " recessive/' although
potentially present, is undeveloped and does not show.
In some cases, however, the " recessive " factor does
show, and then the visible result is an intermediate form.
As I understand the matter, the vital point in Mendel's
interpretation of the facts of heredity is the separate, and
numerically equal, p articulate representation of qualities
in the gametes. Visible dominance is not an essential
part of the theory, because intermediates occur showing
both the constituent qualities. The terms " dominant "
and "recessive" are convenient and useful, but must be
dissociated from any conception of what may be either
" good " or " bad/' " desirable " or " undesirable,"
"strong" or "weak " ; indeed, as we shall see presently,
in some cases the disease or defect behaves as what Mendel

LXIV

BOWMAN LECTURE.

called a dominant over the normal condition, in other cases
as a recessive. Bat since the victims of the same hereditary
disease, be it purely dominant or purely recessive, scarcely
ever intermarry, no trace of pure disease is established.

In most cases, using Mendelian terms, an hereditary
disease is transmitted by the mating of an impure, or
hybrid, dominant (D.R.) with a recessive (R.R., Fig. 6 E),

Inheritance

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and if sufficiently large numbers be taken half of the result-
ing offspring should be normal and half diseased, whether
the disease be the dominant or the recessive partner.

If the disease be dominant it is of course rare for
mating to occur between two persons suffering from it.
When such union does occur all the offspring should be
diseased if the dominance in one parent or both be pure
(Fig. 6 A, B, and c), three quarters if both parents be
hybrid dominants (Fig. 6 D).

BOWMAN LECTURE. LXV

If the disease be recessive the matings shown in c and
D will also be frequent, for then either one parent or
both will appear normal ; mating c will give only normals,
but half of them should carry the disease ; in mating D
one quarter of the offspring should show the disease if
sufficiently large numbers be taken, and one half should
carry it invisible or potential ; in mating E, as just stated,
the disease should appear in half and be carried by the
other half, if sufficient numbers be taken.

Therefore if the simple Mendelian theory be applicable
to any human disease or defect we shall expect that, in
most cases, either one quarter or one half of the offspring
will show the condition (Fig. 6 D and E).

The assumption is that dominance and recessiveness
are constant for the same character in all stocks and
families ; that the same character or disease cannot be
dominant in one pedigree and recessive in another. But
when a given character is linked with sex in such a way
as to be manifest only in one sex (the male), although
carried in an in completed and invisible state by the other
(female), the fact has been explained in Mendelian terms
by Professor Bateson on the assumption that the character,
although dominant in the male, becomes recessive in the
female. This hypothesis appears to explain some other-
wise difficult cases. For example it can be made to
account for the clinical fact — invariable as far as we yet
know — that a colour-blind woman transmits her defect to
all her sons, and that she herself has always had a colour-
blind father. But on the other hand it does not explain
the ordinary experience that a colour-blind father very
seldom has colour-blind sons.

And in many other cases the experimental breeding of
plants and animals has given results which, in order to
bring them within the four corners of the Mendelian
theory, require the assumption of various modifying or
controlling influences. But this is not the time, nor am
I the person, to discuss the hypotheses dealing with such
subjects as (: dihybridism/' " gametic coupling," " rever-

LXVI BOWMAN LEOTCRE.

sion on crossing," " epistatic " and " liypostatic " factors,
and the complex results that flow from them, results in
which the actual and the expected numbers are often so
strikingly near.

Whether the Mendelian theory, or any one of the
current doctrines of heredity, contains the whole truth
is perhaps doubtful ; but we may rest assured that sooner
or later a ground will be discovered upon which the
advocates of the various theories can meet in common.
Meantime, I conceive that our contribution to the problem,
as students of the natural history of living man, should
consist in the collection, classification and analysis of
fresh pedigrees of disease or defect wherever we can find
them.

The Mendelian theory in its simple form is so precise,
and in regard to a number of unit characters in certain
plants and animals its expectation has been found to fit so
nearly with experimental results, that no surprise can be
felt at the attraction it has for workers in human heredity.
But, founded as the theory is upon a strictly quantitative
conception, it would certainly never have been formulated
from data afforded by human disease alone, and this
for several reasons. Thus it is difficult and often impos-
sible to get a record of all the maternal conceptions ; and
even then we do not know how many of the miscarriages
and stillbirths, and but rarely how many of those born
alive but dying in infancy, would have been affected."*
Again, when dealing with a condition that comes on many
years after birth the record is incomplete unless all can
be followed quite up to the susceptible age. Then it is,
to say the least, probable that in some cases the disease
which exists potentially may never appear for lack of some
agent or influence — called for want of a better name an
excitant or stimulant — that is necessary to complete it,
e. g. Fig. 38, retinitis pigmentosa probably brought out

* We can at present only assume that had these immaturities and
early deaths survived they would have suffered in the same proportion
as those who lived. This assumption, however, may be unwarranted.

BOWMAN LECTUKE. LXVII

by haemorrhage. Further, there can be little doubt that
in certain cases we have to deal with equivalent, substi-
tute, or heteromorphic diseases — cases in which the same
cause produces disease of one part, e. g. the retina, in one
person and of another part, e. g. the organ of hearing, in
another member of the same genealogy. In popular no
less than medical belief such heteromorphisrn is sufficiently
notorious in the case of gout, though the evidence is some-
what lacking in precision. Lastly, can we regard it as
certain that single births, occurring at comparatively long
intervals, always follow the same laws of transmission as
frequently recurring multiple broods ?

Amongst normal human characters the colour of the
iris has been investigated, and Hurst has shown that pig-
mentation is in Mendel ian terms dominant to lack of
pigment, i. e. the brown or otherwise pigmented iris is
dominant to the pure bine or grey iris. Captain Hurst* was
good enough to let me see, on May 17th last, at the Village
School at Burba ge, his home in Leicestershire, a consider-
able sample (thirty-eight) of the persons upon the colour of
whose irides his paper was based. I wished particularly to
know whether entire lack of visible pigment meant the
same thing to myself as to Mr. Hurst. Mr. Hurst's
method is to examine the iris with a magnifier out of doors
in good daylight. The ones I saw were all children
attending the school and we examined them in the open
'yard outside at about 2 o'clock. In those tliat ]\lr. Hurst
had recorded as " simplex/' i. e. entirely free from visible
strom a pigment, I could find not the least evidence of
pigment in any, except a doubtful slight trace at one part
of one iris in one child, so slight that I thought the
appearance might perhaps be due to the colour of an
unusually large blood-vessel. In the slightly and par-
tially pigmented ones Mr. Hurst's observations and mine
were also in complete agreement; in many of this class
the pigment, although very evident on careful scrutiny

* Hurst, C. C,"The Inheritance of Eye-Colour in Man," Proc. Roy.
Soc , B., Ixxx, 1908.

LXVIJI BOWMAN LECTURE.

at close quarters, was invisible to casual inspection and
the colour of such irides would undoubtedly have been
passed as " blue " or " grey/' meaning " devoid of stroma
pigment," if examined without a lens, or at a distance of
twelve or more inches, or in a not very well lighted room.
In regard to human diseases and defects I consider that,
in spite of, or allowing for, numerical discrepancies that
must occur from such causes as have been mentioned,
many pedigrees are, in their broad features, consistent
with Mendelian theory. I purposely use no stronger
term ; for although, as I have said, human pedigrees do
not, and cannot, prove the theory, we may well be inter-
ested in finding that some of them are at least compatible
with it so far as they go. Pedigrees abound in which
the rule, " once free always free," required by Mendelism
for a dominant disease is found to hold good; and others
occur in which the frequency of consanguineous marriage
and of discontinuity in transmission are consistent with a
recessive. It is when we come to quantities that the rela-
tive numbers of diseased and normal are often found to be
wide of the mark, sometimes far too many, sometimes not
nearly enough, being affected. In regard to such discre-
pancies we may remember, besides the hindrances to
complete knowledge above mentioned, that at present we
know very little about the indications and measure of
inherited liability or soil as distinguished from actual
disease, e. g. liability to tubercle or to mental disease ;
nor do we know whether in certain cases death in infancy
may not itself take the place of the disease that is to
appear later in life in the survivors."* Then, again, grant-
ing exact numerical segregation of unit characters, it seems
reasonable to expect, for man and the higher animals,

* For a case in which D.E. x D.R. gave, in self-fertilised variegated
antirrhinum (snapdragon) 2 instead of 3 D. to 1 E., because the
remaining fraction died for want of chlorophyll diiring germination, see
Baur, quoted by Bateson in his Mendel's Principles of Heredity, 1909,
p. 253, where, under the heading " Departures from Numerical Expec-
tation," other facts and suggestions bearing on the subject will be
found.

BOWMAN LECTURE. LXIX

complexities due to interaction far more intricate than any
yet dealt with in experimental biology. Finally the par-
ticulate representatives of hereditary disease must often,
if not always, be far less ancient in origin than those
representing normal charcters, and therefore presumably
more easily modified by disturbing influences during
embryonic life.

Even the term " unit " needs to be defined, for just as
hardly any two persons are exactly alike even in a single
normal feature, and as in cases of family disease or defect
minor differences can often, perhaps generally, be observed
between the morbid appearances in one or another of the
affected members, so we can safely take it for granted that
the germinal representatives differ slightly amongst them-
selves in some of their attributes. The alternative would
be to suppose that all slight variations of inherited condi-
tion were due to environmental causes either before or after
birth.

I propose, nevertheless, to give, for what they may be
considered to be worth, the numbers of affected and normal
actually found in the collected pedigrees of a few of the
diseases we are concerned with to-day, for comparison with
Mendelian expectation.

Only those sibships (childships) were used that were
probably complete, and either contained a case or cases of
the disease or were the offspring of an affected parent.
Early deaths, stillbirths and miscarriages have been
omitted, as well as all sibships that were certainly, or
even probably, incomplete. When the disease Avas dis-
continuous the intervening (free) generation was not
counted. All these omissions, though making for
accuracy, entail large deductions from the total. *

I. Acquired or post-natal cataract at all ages. Descent
continuous: total 440 (100), affected 177 (40), normal
263 (60), numbers that are quite wide of Mendelian
requirements. But we may assume without the least
hesitation that had every member been examined
* The data used are given in Appendix I.

LXX BOWMAN LECTURE.

incipient senile cataract would have been found in some,
perhaps a fair number, of those who, judging only from
report, have been entered as normal ; the 40 per cent,
is therefore too low, though we cannot say by how much.

II. Congenital cataract of all kinds. Descent contin-
uous : total 566 (100), affected 260 (46), normal 306 (54),
a bad approximation to the equality required by the
Mendelian scheme, Fig. 6 E, if the pedigrees used are
as complete as they are supposed to be.

III. Retinitis pigmentosa; pedigrees showing contin-
uous descent only: total 387 (100), affected 198 (51),
normal 189 (49). Practical equality as in Fig. 6 E.

IV. Congenital night - blindness with continuous
descent. For quantitative purposes the great Cunier
pedigree is too inexact for this purpose. Other data
give : total 63, affected 33, normal 30. Not far from
equality, as required by Fig. 6 E.

V. Leber's disease. Descent discontinuous, all cases,
female as well as male, being counted: total 547 (100),
affected 245 (45), normal 302 (55). A poor approach to
equality.

It must, however, be mentioned that in this disease the
proportion of diseased to normal is influenced by sex.

(a) In families where the disease affects males exclu-
sively the numbers are — total, both sexes, 402 (100),
affected males only, 165 (41), normal, both sexes, 237 (59).

(h) In families where the disease affects some females
as well as males the numbers are — totals, both sexes, 145
(100), affected, both sexes, 80 (55), normal, both sexes,
65 (45).

VI. Retinitis pigmentosa; pedigrees showing invariably
discontinuous descent.

The numbers in this group can be interpreted in
Mendelian terms on the assumption that the disease is
dominant in some sibships and generations, recessive in*
others.

The totals are small, but may, for the present, be
analysed into three sub-groups as follows :

BOWMAN LECTURE. LXXI

(a) Seventeen completed sibships containing — total
117 (100), affected 55 (48), normal 62 (52).

(6) Ten similar sibships containing — total 58 (100),
affected 15 (26), normal 43 (74).

(c) Three similar sibships, containing — total 13, affected
1J, normal 2.

It will be noticed that in these three small sub-groups,
where in all cases the parents were normal, only the
second (b) fits the Mendelian expectation of Fig. 6 D,
where two impure dominants carry the disease as recessive
and throw one quarter of their offspring diseased. Both
(a) and (c) require dominant to have changed place with
recessive in the second generation in order to bring them
into the theory at all. (Fig. 6 A and c.)

The numbers I have just quoted are the outcome of
careful examination and the exclusion as far as possible
of incomplete examples ; I hope, therefore, that they will
not be without interest at the present time. I may say
that I Avas quite unprepared for such a near approximation
to halves and quarters as are shown by certain of these
groups.

Allusion has been made to the change of dominance
supposed to occur in sex-limited disease. I believe there
is clinical ground for suspecting that dominance, if we
use the term, may sometimes change, or rather may
be different, for the same disease in different families
irrespective of sex ; and if this be true, the factor causing
the alternation of dominance in the sex-limited cases may
be, not sex itself, but something else, usually, but not
invariably, associated with sex. Retinitis pigmentosa, for
instance, appears to be recessive in many families, but in
the largest recorded pedigrees it behaves as a dominant,
and yet it is the same disease in both instances. If
such change can occur at all, we need go only a step
further in order to explain the first appearance of a
dominant disease. A condition that has for want of
meeting with another similar gamete been propagated for
generations as recessive in an impure dominant would at

LXXII BOWMAN LECTURE.

once become apparent, i. e. dominant, if it came under
the action of the supposed transforming influence.

I now leave these crude speculations and come to the
safer ground of observation.

Anticipation in hereditary disease means the manifesta-
tion of the morbid change at an earlier age in each
successor, either in members of each succeeding generation
as a whole, or in successively born children of one
parentage. Bowman was one of the first to notice antici-
pation in successive generations in hereditary acquired
cataract,"* and examples. of the phenomenon will be quoted
later. It is only seen in some of the families, and we
do not yet know in what proportion of them.

Anticipation in generations is also a marked feature
in hereditary glaucoma, but the material hitherto collected
is smaller than for cataract.

Anticipation is also seen fairly well marked in connection
with Leber's disease, both in successive generations and
successively born siblings.

Anticipation is not known to occur in retinitis pigmen-
tosa, and I believe has not been proved in the now well-
known hereditary reticular and nodular keratitis.

This anticipation in heredity is by no means peculiar
to diseases affecting the eye. It appears to occur in
phthisis,t and is certainly sometimes met with in heredi-
tary diabetes (Fig. 7),J and hereditary jaundice with
enlarged spleen (Figs. 8 and 9)§; also in at least one
* Bowman communicated these observations to Darwin, who incorpo-
rated them in his chapters on "Inheritance" in Animals and Plants
under Domestication, i, p. 453, and ii, p. 56 (1868). They do not seem
to have been published in any other form.

t Pollock, J. E., Medical Handbook of Life Assurance, 4th edition, 1895.
Karl Pearson, A First Study of the Statistics of Pulmonary Tuberculosis,
1907. (Drapers' Company Research Memoirs : Studies in National
Deterioration, ii.)

J The ages at death are given in Fig. 7 (unpublished case, E. N.), but
they could not be conveniently inserted in Figs. 8, 9 and 10.

§ Figs. 8 and 9 are constructed from the paper, " Some Cases showing
Hereditary Enlargement of the Spleen," by Claude Wilson, Clin. Soc.
Trans., xxiii, 162 (1890), and xxvi, 163 (1893).

BOWMAN LECTUEE.

LXXIII

extensive pedigree of hereditary ataxy* (Fig. 10), and
possibly in some of the other chronic diseases of cord
and brain. When a disease tends always to occur at a
later age in one sex than the other, the comparison as to
anticipation in hereditary examples must of course be
made between members of the same sex.

It appears to me that the subject of anticipation
deserves much more attention than it has received in
relation to theories of heredity and to the origin and
extinction of heritable conditions.

We may note that the reverse process, appearance of
the disease at a later age in the later born, though
* Sanger Brown, Brain, xv, 1892, p. 250, and xx, 1897, p. 276.

2

LXXrV BOWMAN LECTURE.

sometimes taking place irregularly in successive siblings,
does not seem to occur in successive generations.*

Two different heritable conditions may be met with
in the same pedigree, and care is then necessary to
distinguish coincidence from correlation or equivalence.
Thus in Fig. 1 1 we have congenital lamellar cataract,
congenital ptosis, and progressive goitre; and it is seen
that, whatever may have been the source of the ptosis,
the goitre undoubtedly came in from an entirely distinct
stock. Many analogous cases might be quoted.

Reference has been made to cases in which a heritable
condition, though apparently limited to one anatomical or
physiological system, may invade different parts of that
system in different persons. The best of the well-defined
cases is seen in the trio — retinitis pigmentosa, progressive
nerve deafness, and feeble-mindedness or idiocy, diseases
that seem capable of acting as mutual equivalents or
substitutes; some correlation also seems to exist between
Leber's disease and epilepsy; and of course the neuro-
pathic constitution may show itself in several different
forms of mental disease. Albinism is also compli-
cated with defects of the nervous system in a dispro-
portionate number of cases, and the association must
therefore be looked upon as more than a coincidence.
The possibility that early death may in certain cases
represent a substitute form of a heritable disease has
already been mentioned.

It appears that the individuals affected by hereditary
imperfections and disease are very often members of unusu-
ally large sibships. This has been mentioned by Dr. James
Taylort in relation to hereditary ataxy, whilst Karl
Pearson J concludes that both tuberculous and deaf-mute
stocks are quite as fertile as, and probably more fertile

* Darwin makes a general statement to the same effect (Animals and
Plants under Domestication, ii, p. 56).

t James Taylor, T.O.S., xvii, 1897, p. 63.

I A First Study of the Statistics of Pulmonary Tuberculosis, 1907, p. 20.

BOWMAN LECTURE. LXXV

than, normal stocks of the same social class. In regard
to more general signs of inferiority we are told by Mr.
Heron that, at any rate for the London districts, " there
is a very close relationship between undesirable social
status and a high birth-rate."* We shall see presently
that the same is apparently true for retinitis pigmentosa
and other eye diseases. Some caution, however, is
needful in concluding that large birth-rate and disease
are as closely connected as they appear to be ; for some
pedigrees of disease have been selected for investigation
just because they contain large numbers of accessible
members,, and the prevalence in them of large childships
may be only what is normal to the particular population,
class or stock.

I will refer next to the question of sex liability in some
of the hereditary eye-conditions.

We have first the sex-limited group — ordinary colour-
blindness, Leber's disease of the optic nerves, and one
form of congenital stationary night-blindness. In these
so large a majority of the affected persons are males that
affected females are regarded as rare exceptions ; and
this rule holds in general terms for each separate family
as welt as for the aggregate.

Next come diseases that have 110 special correlation
with sex ; the lump sum of males and females is about
equal, or at most not widely different, although separate
families often display marked departures from the rule,
one having a great excess of males, another of females.
The best examples are all forms of post-natal cataract,
glaucoma (so far as we yet know), and a second form
of congenital stationary night-blindness. Probably other
diseases will be added to this group.

In the third group — containing all forms of congenital

* " On the Relation of Fertility in Man to Social Status and on the
Changes in this Relation that have taken place during the last Fifty
Years," David Heron, 19()o, Drapers' Company Research Memoirs : Studies
in National Deterioration, p. 21.

LXXVI BOWMAN LECTURE.

cataract, retinitis pigmentosa, albinism, and probably
some of the less frequent affections, such as congenital day-
blindness — we still find great discrepancies as to sex
numbers in individual families, but when large numbers
are taken a fairly uniform, though not extreme, pre-
ponderance of males.

As the sex-inequality in this last class cannot be
accounted for by any obvious cause it is probably the
expression of some general law, and the following facts
seem to support this view : (1) Although more boys than
girls are born (about 104 boys to every 100 girls in
England and Wales in 1807)* the inequality is more
than redressed by the higher general death-rate for males
so that the total living population shows a deficit of
males (about 93 males to every 100 females in England
and Wales in 1907). (2) The males die in excess chiefly
(a) between birth and five years of age, (?;) between
fifteen and sixty-five ; between five and fifteen the sexes
die in nearly equal numbers (about fifty-one females to
forty-nine males). The higher mortality of males under
five, which alone concerns us now, is due chiefly to deaths
from causes classed by the Registrar-General collectively
as " immaturity," i. e. premature birth, congenital defects,
teething and congenital hydrocephalus. In 1907 out of
every hundred children dying from these causes under
five years old fifty-six were males, forty-four females.
(8) There appears to be a similar excess of boys over
girls with various " defects of development," principally
of the sense-organs and intelligence, such as Dr. Francis
Warner described in 1894 in children at the elementary
schools. t Dr. Warner's statistics show that if the
number of boys and girls examined by him had been
equal there would have been sixty defective boys to forty
defective girls in every hundred of those selected by him
as showing deficiencies. %

* The data from which these and the succeeding statements are drawn
may be found in the Report of the Registrar-General.

t Warner, Francis, Report of British Association.

£ Since the above was written Mr. Alan Barlow has supplied me with

BOWMAN LECTURE. LXXVJ1

Archibald Grairod* states that the rare heritable con-
ditions, alkaptonuria, cystinnria and pentosuria are all
more frequent in males than females. In 157 subjects of
these three diseases he finds no less than 113 males.

Now it is not a little remarkable, as regards the third
group of eye diseases just mentioned, that in retinitis pig-
mentosa (1381 cases) and lamellar cataract (1793 cases),
62 per cent, of those affected are male and 38 female ;
whilst in other forms of congenital cataract (335 cases)
and in albinism (upwards of 1000 cases) the proportions
are not very different — about 55 per cent, males and 45
per cent, female. In day-blindness there is a consider-
able excess of males.

It is said also that there is a marked excess of males
over females amongst deaf-mutes.

I feel sure that stores of information as to the relative
liability of the sexes to hereditary disease must exist.
But meanwhile the few facts now brought forward favour
the view that, in man, the male is on the Avhole more
liable than the female to many innate defects and diseases,
and perhaps especially to such as affect the organs of
sense and intelligence.

It is extremely important to know whether the inheri-
tance of an imperfection influences the longevity of the
affected who survive ; either by the direct effect of the
disease upon vitality as in diabetes or haemophilia, or by
some figures from the Education Office, which, although probably needing
correction in certain particulars, appear to point in the same direction.
These figures are taken from the Statistics of Public Education, 1906-7-8,
and refer to the number of children between the ages of five and sixteen
attending schools for the defective and epileptic in England. The
average number of children attending about 160 such schools in each of
the three years mentioned was 10,464, of whom 6019 were boys and 4445
girls. The numbers are vitiated to some extent by the facts that (a)
they include a certain number with physical rather than mental defects,
and (6) boys tend to leave the schools at an earlier age than girls ; but
these two sources of error may not improbably tend to cancel each
other, and in any case would not be likely to account for nearly all the
difference between 57 and 43 per cent, shown by the above numbers.
* Archibald Garrod, Inborn Errors of Metabolism, 1909, p. 20.

LXXVIII BOWMAN LECTURE.

its indirect power of lowering the resistance to hurtful
influences. The purely hereditary diseases of the eye do
not seem to have any relation to length of life, at any
rate a good many old persons are found in pedigrees of
cataract, glaucoma, retinitis pigmentosa, Leber's disease,
and albinism. But the subject has not yet been at all ade-
quately looked into ; and attention may suitably be called
to the importance of recording everything we can about
age in every member of a morbid pedigree; age of parents
at marriage ; age at onset of the disease in those affected ;
age at death, especially when the disease has " anticipated/'
Every effort should also always be made to get the
order of all the births, or rather of all the conceptions,
and the intervals between them. Only in that way can
we find out whether a disease tends to affect the earlier
or the later births to excess. Karl Pearson's studies of
the statistics of phthisis, insanity and crime lead him to
believe that the earlier born children are more frequently
predisposed to those conditions than the later ones.*
Laqueur considered that the first and second born were
decidedly less likely to suffer from hereditary diseases of
the eye than the third and later births ; but his remarks
were based on only forty-eight families, containing in all
no more than 244 children.t Berry has pointed out that
in' a particular pedigree of cataract (Fig. 24) the eldest
born girl of each sibship invariably had the disease.

CATARACT. J

(Figs. 11 to 27.)

It is well known that cataract often runs in families,
sometimes appearing in several generations. This has
been ascertained beyond doubt for several of the best-

* A First Study of the Statistics of Pulmonary Tuberculosis, 1907, p. 25,
Boyle Lecture. Also The Problem of Practical Eugenics, 1909, p. 19, etc.

t Laqueur, Zeitschrift f. PraUische Aerzte, 1897, No. 21, p. 8.

+ For the abbreviated titles of periodical publications referred to in
this or subsequent sections see Appendix IX.

BOWMAN LECTURE. LXXTX

marked varieties, and will probably be found true for all
as opportunities for investigation occur. When cataract
occurs at birth, or early in life, in brothers and sisters, both
parents being free and no history obtainable of ancestral
or collateral cases, when it is, in fact, what is cfi\]ed familial
without proof of heredity, there may be grounds for attri-
buting it to some defect of intra-uterine nutrition. But this
explanation, unlikely even when the mother is affected, is
impossible when the father, not the mother, suffers, for in
this case there must be a germinal cause. That the germ-
cell, whether male or female, should be able to transmit
a well-defined and often almost identical imperfection
limited to so small a part of the body as the lens, and
often to only a small portion even of it, shows how incon-
ceivably minute the morbid germinal representation may
be, and this whether we think of the lens itself or the
parts upon which it depends for nourishment at different
stages of its growth. From Priestley Smith's researches*
we may take it that the weight of the normal human lens
at between 20 and 80 years of age is about 175 mgrm.
or roughly three millionths of the ordinary body-weight
at that time of life.t Yet even this is too much. The
opacity in a typical case of discoid (or "Coppock")
cataract occupies only a small fraction of the entire lens,
possibly one twentieth or even less. The malign germinal
influence, whatever it is, presumably acts upon the lens
only at its earliest stage, possibly even before the closure
o£ the lens cup, and even then is so limited in its range
as to damage no other part of the epiblast ; or if another
interpretation be preferred, affects no other part of the
mesoblast than the minute portion concerned in the nutri-
tion of the rudimentary lens.

In hereditary lamellar cataract the dimensions of the
opacity are not so extremely minute, but it also, like the

* Priestley Smith, " On the Growth of the Crystalline Lens/' T.O.S.,
Hi, 1883, p. 79.

t Average body-weight of $ + V at 20 to 25 about 130 lb., or say 59
kilogrammes = 59,000,000 millegrammes -4- 175 = 337,154, or, say, one
third of a million.

LXXX BOWMAN LECTURE .

discoid form, must be due to the influence of the male
parent in many cases (e.g. Fig. II). Some fairly large
pedigrees have now been collected, and one of them seems
to show conclusively that the discoid or " Coppock " form
and ordinary lamellar cataract are essentially the same,
and not, as we at first thought, independent forms ; so
that the two names, discoid and lamellar, should be used
only when convenient for descriptive purposes. (In the
pedigree furnishing Fig. 12 both forms occurred.) The
discoid is probably only the smallest possible form of
lamellar, so small that the two layers are united or indis-
tinguishable. The position of the disc or flattened lamella
at a deeper level than the nucleus of the normal lens, but
in front of the posterior capsule, still awaits satisfactory
explanation, though perhaps related to displacement of the
nucleus backwards from some developmental cause. *

Opinions have differed for many years as to whether
lamellar cataract of ordinary sizes is always congenital,
i. e. actually formed before birth, or sometimes post-
natal. I think the evidence is conclusive that it may be
either one or the other according to the diameter of
the opaque s^ell, but that in most of the hereditary cases
the process occurs towards the end of foetal life. The
diameter of the human lens at the fourth month of foetal
life is about 3'3 mm., at the sixth month 4'5 mm., at the
seventh month 5 mm., and at birth 5'75 mm.f Between
birth and one year old the diameter is about 7'4 mm.J
If shrinkage of the nucleus is the first stage in the
formation of the opaque peri-nuclear layer the dimensions
of the opacity may be a trifle less than the dimensions
of the clear cortex from which the opacity was formed;

* According to Treacher Collins displacement of the nucleus back-
wards may occur in the foatal lens as a consequence of faulty backward
growth of the lateral lens-fibres. "Developmental Deformities of the
Crystalline Lens/' The Ophthalmoscope, 1908.

f Treacher Collins, Researches into Ihe Anatomy and Pathology of Eye,
1896, p. 5.

t Dub, quoted by Parsons in his Pathology of the Eye, ii, 1905,
p. 405.

BOWMAN LECTURE. LXXXI

thus if a lamellar opacity measures 6 mm. across, the lens
must have had at least that diameter, or a little more, say
7 mm., before the opacity formed, and in such a case we
should probably be right in concluding that the cataract
developed shortly after birth.* Now the largest lamellar
opacity that has been measured after extraction of the
lens had a diameter of 6 mm. ; the ordinary size is from 5
to 5*5 mm. In some it is much less, down to, say, 3'5 and
4 mm., and in these cases of small-sized opacity we should
be justified in assuming that the morbid process had
begun and ended before birth, even if there were no
clinical evidence to that effect. There is, however, enough
of such evidence to be convincing. We have first the
observation attributed by Hulkef to Bowman about the
year 1846, of lamellar cataract found in a kitten a few
days old. Of later observations Hosch in 1397 pub-
lished a case in which a mother had seen cataract in her
baby's eyes at its birth, the diagnosis of lamellar being
made by Professor Horner when the child was six weeks
old and the opacity measuring 4 mm. across at the
age of six years. The same woman detected the opacity
in another of her children two days after birth. J Mr.
Fisher has given me the case of a female baby (Fig. 14 ;
IV, 2), in whom he diagnosed dense lamellar cataract at

* Collins, however, concludes that the opacity must always be ante-
natal if the part affected is, as is assumed, the most peripheral layer ; or
that if post-natal the part affected is not the most peripheral.

f Hulke (T.O.S., vii, 1887, p. 27), defending in his Bowman Lecture
(in 1886) the pre-natal formation of lamellar cataract, writes as follows :
. . . " the first distinct recognition of lamellar and zonular cataract
based on dissection was, so far as I know, made by Mr. Bowman, the
subject being a kitten, killed and prepared for lecture in the physio-
logical laboratory in King's College. The date of this was, so far as
my recollection serves me, 1846, but it might have been slightly
later." Mr. Hulke, who, as he tells us in another part of the same
Address, was about this time one of Mr. Bowman's dressers, states that
he (Hulke) wrote down at the time a description of the appearances
although he was unable to find it at the date of the above occasion —1886.
The kitten was only a few days old.

£ Quoted a? Case 69 in my paper upon "Heredity in Cataract," Jf.L.O.H.,
xvi, p. 229.

LXXXIT BOWMAN LECTURE.

three months of age, the history being perfectly clear that
the opacity had been seen by the parents at fourteen days
old, the child not having opened its eyes until then.

In another family of lamellar cataracts, one of the
mothers (Fig. 11; 'Gen. Ill, 3), told me that she had
seen the cataract within an hour or two of birth in more
than one of her children, and as in some of them there was
a conspicious white opacity at the anterior pole of the
front layer, almost filling the pupil, I have no doubt she
was correct in her observation.

After writing the above I had the opportunity of seeing
the newly born male infant of a cataractous brother of
the above woman (Fig. 11 ; Gen. 1Y, 14a), and found
the usual small, perfectly well defined lamellar cataract,
of about 4'5 mm., in both eyes exactly a week after birth
(child born April 19th, eyes examined under mydriatic
on the 26th) ; the cortex was clear so far as a moderately
exhaustive examination in the mother's bedroom allowed
one to see. Here also there was a dense anterior polar
opacity which had been seen by the nurse and mother as
soon as the baby's face was cleaned after birth * In
another case of typical small, dense, lamellar opacity
(Dearsley) the clear testimony was that the opacity had
been seen the day after birth. Lamellar cataract has
doubtless been seen repeatedly at less than one year old.t
Some of the small lamellar opacities have no doubt been
described as congenital nuclear or perinuclear cataract.

The condition of the enamel of the permanent teeth in
a patient with lamellar cataract helps us indirectly to
decide the time at which the opacity was formed. It is

* Later still, on July 3rd, I examined IV, 19 in the same pedigree, a
female born on June 19th, i. e. get. 14 days, and found precisely similar^
small, lamellar cataracts. On the same occasion I was told that IV, 15a,
born in September, 1908 (after my original visit, which was in August),
was certainly affected ; it was a feeble baby and died in May ; my
informants were the mother, III, 10 and III, 11, who live in the same
village, and may both be counted as skilled observers for this purpose. —
E. N., July llth, 1909.

t See R.L.O.H., xvi, p. 228, Case 65, for such an example.

BOWMAN LECTURE. LXXXIII

chiefly with the larger specimens of lamellar cataract that
the well-known and characteristic deficiency of enamel in
the permanent incisors and first molars is found, and Mr.
Norman G. Bennett, after careful consideration of the
evidence in connection with the date of formation of the
enamel, has come to the conclusion that the cause of the
deficiency is active from shortly after birth until about
two years of age;"* and that the correlated lenticular
change is probably not ante-natal. He points out that
the epiblastic elements of both lens and enamel become
isolated within mesoblastic tissue, and that both might
therefore not improbably be affected by a common cause
of malnutrition.

Now I have myself often noticed that in cases of
unusually small lamellar cataract (as well as in its
minimal discoid variety), there is usually no defect of
the enamel of the permanent teeth. This fact comes out
strongly in all the extensive pedigrees of lamellar cataract
hitherto published, for in these the opacity is almost in-
variably small and the teeth good.t

The conclusion, therefore, is that when lamellar
cataract is hereditary the small size of the lenticular
opacity, and the absence of dental deformity, both point
to the cataractous change having occurred during intra-
uterine life. It has been assumed that the visible results
— lack of enamel for the permanent teeth and lamellar
opacity in the lens — mark the commencement of the
morbid process, but this can hardly be true, at least for
the lens ; something is probably wrong both in the lens
and the uncalcified enamel before we can detect any

* Norman G Bennett, " Etiology of Lamellar Cataract," T.O.8., xxi,
1901, p. 42.

t Exceptions are, of course, seen, but I believe they are not very
frequent or very well marked. See R.L.O.H., xvi, p. 231, Case 74
and Case 75,1 (Elizabeth). On the contrary, for confirmation of the
general statement see Cases 72, 74 (mother), and 76, 5 (Louisa). The
point is also illustrated in Fig. 12 (from T.0.8 , xxviii, p. 226), where
the only one (IV, 102) with large lamellar cataract had the character-
istic teeth, whilst the teeth were normal in those with small-sized
cataract.

LXXXTV

BOWMAN LECTURE.

change, and thus the number of cases that should
be classed as intra-nterine is increased rather than
diminished.

The degree and manner in which small lamellar and
discoid cataract may be heritable is shown in Figs. 11,
12, 13, 14, 15, and in sundry other pedigrees not exhibited

BOWMAN LECTURE.

LXXXV

to-day * Several new pedigrees are, I know, being worked
out at the present time by members of this Society.

The descent of lamellar cataract appears to be always

Fiq . 13

..4..1U.I..I-...4.J....4..J..'.

^flJAe fl &&

Fig • I 4
I i V a»

Fifl IS

,6 3-J$ ,9

K

continuous, and there are hardly any consanguineous

marriages. Lamellar cataract, whether hereditary or

sporadic, is, I need hardly say, not confined to either sex ;

* R.L.O.H., xvi, p. 225 et seq. and p. 395 et seq.

LXXXVI BOWMAN LECTURE.

but whereas in senile and presenile cataract as a whole
there are more females than males,"* the reverse occurs
in lamellar cataract. I have been able to collect, through
the kindness of several friends in various parts of the
United Kingdom, with the assistance of Mr. J. F.
Cunningham at Moorfields, and from published sources,
the particulars as to sex in 1887 subjects of lamellar
cataract,t and find 1166 males to 721 females. Although
the excess of males varies greatly in different batches it is
present, little or much, in practically every separate
return ; in a few lots the sex numbers are equal, or
nearly so, and in only one is there an excess, and that
merely nominal, of females. J

Isolated cases of lamellar cataract, usually of larger
size than in the hereditary cases, are of course common
enough, and the same is true of other forms of so-called
congenital cataract. Although we may feel sure that
some of these would have furnished pedigrees if they
could have been followed up, there is at present little
doubt that such single specimens may often arise inde-
pendently of hereditary influence, and be due to some
nutritional defect confined to the individual.

I will refer next to the form of hereditary cataract
that Mr. Gunn§ has named " coralliform," in which the
principal opacities radiate forwards from the central
part of the lens, ending anteriorly in expansions that
appear to be tubular, and remind one of the separate
"mouths" of a madrepore coral. Mr. Treacher Collins
conjectures that these tube-like opacities lie in the planes
of suture between the lens-fibres. || I published a large
pedigree of this form of cataract in 1905^[ ; another

* Nettleship, R.L.O.H., xvi.
f See Appendix II.

\ The numbers in the separate returns are given in Appendix II.
§ Gunn, T.O.8., xv, p. 119.

|| Treacher Collins, "Developmental Deformities of the Crystalline
Lens/' loc. cit.

f Nettleship, R.L.O.H., xiv, p. 218, Case 58 (Betts).

BOWMAN LECTURE.

LXXXVII

(Fig. 16), shown at a recent meeting here,*" I owe to the
kindness of Mr. Gunn and Mr. Leslie Paton; for a third,
shown at the same meeting, I am indebted to Mr.
Treacher Collins (Tomes family), and I know of others.
The mode of descent is the same as in lamellar cataract.
Although coralliform cataract is probably not very rare it
has been apt to escape differential observation, its features
not being prominent, whilst the characteristic trumpet-
like or tube- like opacities are often intermingled with
a number of discrete dots and spots of opacity. It is
generally looked upon as congenital because it has been

seen several times in children, and only progresses with
extreme tardiness ; a middle-aged subject of the disease
calls himself " short-sighted," and cannot remember ever
seeing better ; in old age nuclear haze is apt to increase
the difficulty. We have, however, no record of coralliform
cataract having been seen before the age of eighteen
months. f Moreover, the average number and size of the

* T.O.S., xxix (1909).

f In the Betts' pedigree (R.L.O.H., xvi, p. 218, Case 58) Gen. IV, 23
was operated upon for the cataract at two years of age, his brother, IV,
22, at three years, and another brother, IV, 21 at about five. V, 12 was
also operated upon at the age of five. IV 11, who died at eighteen
months of age, was reported by other members of the family to have
had cataract like the others.

LXXXV1II BOWMAN LECTURE.

characteristic opacities has seemed to me decidedly less
in the young than in middle-aged and old subjects, and I
am therefore inclined to think that in these people the lens
may be clear at birth and for some months afterwards.
But few of those affected have had anything done, and
not much can be said about the outcome of operations ;
but there have certainly been several poor results. In the
68 known cases 36, or rather more than half, were females,
29 males, the pedigrees containing them showing a total of
167 persons — males 73, females 75, sex not recorded 19.
These numbers are much too small for finality as to sex
distribution ; they may easily be upset by fuller data, as
may be evident when I say that in one large pedigree
(Betts) there were 20 affected males to 1 1 affected
females — a great excess of males — whilst in the other five
pedigrees the females were in such large majority that,
in the whole six, the male excess was more than neutra-
lised, leaving, as just stated, a definite majority of females.

We find similar examples of extreme difference between
one pedigree and another in the proportion of affected
males to females in many conditions besides cataract ;
precisely as in normal families where the offspring of
some parents may be nearly all male, of others female.*
No conclusion as to sex incidence of an hereditary disease,
except it be a really sex-limited one, is worth anything
unless based on very considerable numbers.

Of other distinct varieties hitherto included under the
general title of " congenital cataract " accurate pedigrees
will no doubt be forthcoming in. future, and several in-
complete ones might be quoted. In the best that I am
acquainted with, given by Zirm and Bergmeister under
the title "congenital stellate" cataract f (Fig. 17), at

* Gf. R.L.O.H., xvi, p. 188, for further facts as to sex-incidence in
family cataract.

f Given in R.L.O.H., p. 400, Fig. 54. The four younger generations
appear to be completely recorded to date and contain fifteen cases of
cataract in about forty persons ; but the sixth generation, consisting of
young children, may have increased since. Several other interesting
pedigrees of cataract are to be found in the same paper.

BOWMAN LECTURE.

LXXXIX

least sixteen cases of cataract occurred in six generations,
the disease as usual behaving like a " dominant."

It is much to be hoped that someone will collect informa-
tion methodically about the minute vacuoles or dots of
opacity so often seen in the lenses of the young ; are they
congenital, do they run in families, do they lead to cataract,
and do they occasion, or only happen to accompany, the
asthenopic symptoms from which their owners so often
suffer ?

Such minute changes have been noticed in several

JSL .

members of congenital cataract pedigrees who were them-
selves free from the definite family complaint (e. g. in the
families shown in Figs. 12 and 13). For the present it
is uncertain whether such slight alterations are related to
the family cataract or are merely accidental.

Post-natal or acquired cataract (Figs. 18 to 27), is
often hereditary, and quite a number of pedigrees have
been collected by many observers. A considerable number
of these — I do not know what true proportion — show anti-
cipation in generations and sometimes in successive siblings,

3

xc

BOWMAN LECTUIJE.

and the pedigrees I have chosen for illustrating the
heredity of senile cataract to-day (Figs. 18 to 25), all
illustrate this phenomenon in a greater or less degree.

fUl
ttfil* f

*r f 4. 70 •?/ f

T7T

It is impossible to make the family record as full in
hereditary senile cataract as in the congenital forms ;
the older members are scattered and may die with
incipient cataract undetected. But we already know
enough to say that senile, pre-senile and juvenile

BOWMAN LECTURE.

XCI

cataract may be transmitted through several generations,
that, as in the congenital forms, either sex may pass it on
to either sex or to both sexes, and that the descent is,
so far as we know, practically always continuous.*
Although either sex may transmit, the tendency is, how-
ever, in fact, passed on oftener by women than men, and

©

2. i9 |+ if 14 17 18 iy it, LI

not infrequently clings to the female sex through several
generations of a long pedigree.

In one and the same family hereditary cataract often
begins at about the same age in all who have it. But
exceptions to this are very numerous, for, as we have just

* Apparent discontinuity, however, is seen in one or two places in a

few pedigrees, viz., in R.L.O.H., xvi, p. 390 (Fig. 46) ; ibid., p. 208, etc

Cases 40, 80, 92, 100. The generation marked as normal in these,

'pedigrees may, however, have contained some individuals with incipient

cataract.

XC1I

BOWMAN LECTURE.

seen, hereditary cataract often occurs at an earlier age in
the children than in the parents,* whilst in those of the same
generation it frequently begins at about the same age in
each. Fuchsf remarks that when senile cataract is a
family disease it often comes on unusually early.

This earlier incidence in each generation — " anticipa-
tion"— is not known to be accompanied by disease or early
degeneracy of other parts of the body; but more data are
much needed upon this important point.

Of postponement — onset later in the next generation —
there is next to no evidence in cataract, but ocasionally when

cataract begins at the same age in near relatives it may
progress at very different rates in each of them.t

* For good published pedigrees showing anticipation see R.L.O.H.,
xvi, p. 179, et seg., Cases 2, 4, 5, 7, 8, 15, 46 and 390 ; Dr. Green's Case
Fig. 18 in present lecture, the numbers on which are from Dr.
Green's figure and do not represent ages; R.L.O.H., loc. cit., Cases
40, 41 (p. 208) ; a case published in T.O.S., xxviii, p. 220 (present Fig.
25) ; another published in T.O./S'., xxix, p. 209 (present Fig. 24, giving
some of the ages). Also Figs. 21 (Westly, Mr. Fisher's case) and 23
(Helyer, Dr. E. J. Smyth's case) now recorded for the first time, and
giving the ages of onset. Figs. 19 (Sichelfils), 20 (Louis Strieker), and
22 (unpublished case of my own) all show the same feature and some of
the ages are indicated.

f Fuchs, Text-Book of Ophthalmology.

t R.L.O.H., xvi, p. 179, et. seq., Case 13.

BOWMAN LECTURE.

XC1II

Cases are met with that may be called "hereditary
infantile senile cataract," general opacity of the lens

coming on quite early in life (Figs. 26, Tathain Thompson,
and 27, Berry) . In the latter family the author states that

XC1V BOWMAN LECTURE.

the opaque lenses were much harder than normal lenses of
corresponding age.

GLAUCOMA.

(Figs, and descriptions 28 to 34 in Appendix III.}

About glaucoma as a hereditary disease I need not say
very much, since the known cases (some twenty-four families)
have been quite lately collected by Mr. Lawford. So far
the most striking features are the strong tendency to anti-
cipation in the younger generation and the continuous
descent.* Probably many of us have seen one or two
cases of typical primary glaucoma in children, and it will
be of extreme interest in future to investigate the family
history of these very rare cases.

In some of the glaucoma families there seems to be a
possible relationship between this disease and myopia, and
an attempt might well be made to ascertain whether, in
such families, the two conditions can in any degree
replace one another.

The prognosis for operation is another point whose
importance needs only to be mentioned ; in the members
of some pedigrees the prospect is as good as possible, but
I am inclined to suspect there are other families in which
operation is generally unfavourable.

These and other considerations show how urgently we
need the collection of much more material relating to the
heredity of glaucoma.

RETINITIS PIGMUNTOSA.

(Figs. 35 and 36 in text • 37, 38 and 39 in Appendix IV.}

This malady, which, especially since Liebreich/s observa-
tions in 1861, has been a rich source of material to those
interested in the influence of heredity and of consanguinity
in family disease, has lately been dealt with at some length

* Lawford, R.L.O.H., xvii, 1907, p. 57. Anticipation is shown in Cases
1,3,6,7,8, 10, 11, 13, 14, 15, 16, 17 and 24 of the series. Only one,
Case 2, shows discontinuity of descent.

BOWMAN LECTURE.

XCV

elsewhere,* and to-day I need only allude to some of the
principal points and ask attention to some of the unsettled
problems in the natural history of this disease and its
equivalents. I will keep almost clear of numbers, but may
mention that the paper referred to was based upon notes of
nearly 1000 families (strictly 976) containing an average
of close upon two ascertained cases of the disease in each.
There was proof of heredity in one quarter of the families
and of consanguinity of parents or ancestors of those
affected in another quarter (I use round numbers, the

exact figures are given in the original paper). In the
remaining half, where no history of either consanguinity
or heredity was recorded, the notes were often very imper-
fect, and there can be no doubt that such a history would
often have been forthcoming had more pains been taken.
In the largest pedigreest of retinitis pigmentosa the
descent of the disease is continuous from parent to child,
no healthy member ever producing affected offspring
(Fig. 35).

* Nettleship, R.L.O.H., xvii.

f To the fully recorded pedigrees quoted in the paper above referred
to Snell has since added another in T.O.S., xxvii, 1907, p. 217.

XCVI

BOWMAN LECTURE.

But we meet with some in which the direct line of
transmission is without doubt interrupted by a healthy
generation (Figs. 36 and 37).* I say "without doubt "
advisedly, because the statement so often made by a

subject of this disease, that his or her parents had

perfect sight and were not related by blood, though

usually correct, does certainly need revision in some
instances.

* Figs. 37, 38 and 39, not previously published, are fully described in
Appendix IV.

BOWMAN LECTURE.

XCVII

A similar caution is necessary as to the families in
which only a single example of the disease can be

ff

Rctimtii P^mtntuitv
? Ud »i^St
Jiea<n«is fvorn CGT!^ l»<t

discovered (Figs. 38 and 39); in some of these the disease
may have existed latent in several members, but become

XCVJII BOWMAN LECTUEE.

manifest only in the solitary one who was reached by
some efficient determining cause. In others deafness or
mental defect, easily omitted from the record unless
directly sought for, may take the place of the eye
disease (as in Fig. 39), and thus partly or wholly restore
the continuity.

In respect to consanguinity we have to confess that
but few of the records tell us the source and kind of
cousinship, an omission that may very much lower their
value. In future when taking the family histories of
persons whose parents were cousins, it will usually be easy
to record whether they both belonged to the affected side
of the genealogy or not, and whether they were children of
two sisters, or of two brothers, or of a brother and sister,
or of a sister and brother.

Of the persons seen at all ages with retinitis pigmen-
tosa a considerable majority are males (at least sixty males
to rather less than forty females). This fact may, as
suggested before, be an expression of some wider law ;
but two other interpretations suggest themselves for the
time being, viz., either that the females in these families
die in excess before they are old enough to show the
disease, or that the malady occurs most in the families
that contain an excess of male births. It may be of
interest to note that a marked excess of males is also seen
in the chronic renal diseases, and in diabetes, whilst the
reverse is found in the interstitial keratitis of congenital
syphilis.

Next to heredity and consanguinity comes the influence
of ill-health in bringing out a liability to retinitis pig-
mentosa where, but for such an exciting cause, it might
have remained latent. Probably such an influence may
sometimes explain the solitary cases. Of such determin-
ing causes some of the acute exanthemata seem to be the
commonest, but probably tubercle and syphilis and in
rare cases even severe loss of blood may have the same
effect (Fig. 38). We may suppose that anything capable
of damaging the arterioles might determine the onset of

BOWMAN LECTURE. XCIX

retinitis pigmentosa in a choroid and retina predisposed
to the disease. This part of the subject is well worth
more attention.

Retinitis pigmentosa may set in very early in life or
even before birth ; and on the other hand there is reason
to believe that its advent is sometimes delayed until quite
an advanced age. The amount and distribution of the
pigment varies a great deal, but the extreme periphery
of the retina is usually free even in cases of long standing ;
when visible vessels are ensheathed in pigment such
vessels are, in rny experience, always veins, i. e. the pig-
ment travels in the direction of the blood-current.
Retinitis pigmentosa sine pigmento is nearly always merely
retinitis pigmentosa at an early stage before the pigment
has accumulated in the superficial retinal layers and
become ophthalmoscopically visible ; but in rare cases,
although the retinal atrophy progresses, pigment does not
travel inwards in any quantity, and then the term sine
pigmento may be appropriate even at a later stage.*
There does not seem to be any correlation between the
quantity of pigment as judged by the ophthalmoscope and
the colour of the patient's hair, irides and choroid. Reti-
nitis pigmentosa does not hinder fertility ; the subjects
of the disease often have very many brothers and sisters,
whilst if they themselves marry they frequently produce
many children ; whether the average fertility is above

* A case which may throw an important side-light on the seat and
nature of the early changes in retinitis pigmentosa has lately been
published by Bordley (Johns Hopkins Hosp. Bull., September,, 1908). In
a negro pedigree night-blindness occurred during five generations, and
progressed through gradual constriction of fields to total blindness ; in
the older members there were ophthalmoscopic signs of pronounced
arterio-sclerosis, but even in them no other changes and no pigmentation.
In the pedigree of forty-three individuals thirty-four are marked as night-
blind. There are some improbabilities in the record, since it is stated that
there is no record of any normal- sighted member having had children,
and that all eight children of one night-blind parent were affected. The
occurrence of night-blindness in relation to disease of the liver is the
subject of an interesting section in Parsons's Pathology of the Eye, iv, p.
1292.

C BOWMAN LECTUEE.

the normal can perhaps hardly yet be either asserted or
denied. Until more, and more precise, data are collected,
we cannot tell whether the order of the birth of the
children, or the age of the parents at marriage, have any
influence in determining the disease. The relative fre-
quency with which the same fundamental cause produces
retinitis pigmentosa in one, deafness in another, and
mental inferiority in a third member of the same pedi-
gree, has not yet been worked out ; but we find on the
other hand that certain stocks produce only retinitis pig-
mentosa and others only the equivalent deafness. It is
especially noteworthy that the largest pedigrees of the
retinitis are quite free from the other degeneracies, and
the survival of such families is probably due to this cir-
cumstance.

I should like to return for a few moments to the two
kinds of descent, continuous and discontinuous, met with
in this disease. As I said in my introductory remarks,
continuous descent in Mendel ian terminology usually
means " dominance," and interrupted descent, except in
sex-limited conditions, means " recessiveness." Retinitis
pigmentosa, although more frequent in the male, cannot be
put into the sex-limited class with colour-blindness, Leber's
disease and others in which women very seldom suffer.
Therefore since, as Figs. 36 and 37 show, pedigrees exist
in which a healthy generation always comes in the direct
line between two that contain retinitis pigmentosa, or
one of its equivalents, and since the normal c: carrier "
may be of either sex, the disease must then, in Mendel's
terms, be recessive."* And yet in the largest pedigrees the
descent, as I have already said, is always continuous and
the disease therefore dominant.

This is as far as we can go at present. In the discon-
tinuous pedigrees we can make sure that the intervening
generation has neither eye disease, deafness nor mental
defect ; but there may perhaps be other morbid states,
other equivalents of retinitis pigmentosa, that give no con-
* For the data see Appendix I d.

BOWMAN LECTURE. CI

spicuous signs, and at present, therefore, escape detection.
This is mere speculation for future work ; the arteriole
disease leading to retinitis pigmentosa, or to deafness or
mental deficiency, may possibly in some cases affect an
entirely different region, e. g. the arterioles of kidneys or
liver or even of the hands or feet. But at present, if we are
to test our data for retinitis pigmentosa by the Mendelian
scheme, we must assume that change in mode of descent
means change of dominance, however improbable this may
appear. We were formerly content to say that a given
disease or character could become latent for a generation
or more and then re-appear, either capriciously, or perhaps
when re-inforced by a marriage between cousins. But
the Mendelian conception of pairs of complementary
characters, one of which, in virtue of some attribute, domi-
nates or prevents the appearance of the other, does not
in its simple form allow the dominant to lose dominance or
the recessive to gain it. But if the members of a pair
representing a given character, say retinitis pigmentosa
and its absence, could, without losing their affinity, become
linked with, and influenced by, a pair representing some
other character, a change of dominance in the original
pair might conceivably be brought about, the second or
linked character not necessarily attracting attention.*
This is only the crudest possible indication of the ingenious
hypothesis of " coupling," by which some of the complex
and unexpected results obtained in experimental breeding
are explained, and which appears to have been verified
by control experiments in certain cases.

Of the varieties of retinitis pigmentosa, retinitis punc-
tata albescent has, so far as I know, never been seen in
a well-marked form in more than one generation, and if
it is not a new departure, a " mutation," it must, in some
cases, have skipped several generations.

* Of. Lock, R. H., " On the Inheritance of Certain Invisible Characters
in Peas," Proc. Roy. Soc., Ixxix B., JC07, p. 28.

CTI

BOWMAN LECTURE.

HEREDITARY NIGHT-BLINDNESS.

(Figs. 40 to 43 in text ; 44 in Appendix F.)

Two sorts of hereditary night-blindness are met with
which may be conveniently taken next, although they are,
so far as we can tell, absolutely distinct from retinitis
pigmentosa, and probably also from each other. * Both
are, so far as can be ascertained, present from birth,
stationary, and not associated with any other defects or
degeneracies. In one of them the defect (it seems hardly

right to say disease) affects both sexes almost equally,
descends continuously through either parent, and is not
connected with any other peculiarity of the eyes or sight,
nor with any unnatural appearances at the fundus.
Besides the now well-known genealogy originally published
by Cunier, there are only about half a dozen recorded
pedigrees of this abnormality (Figs. 40 and 41 show two of
them). Probably, however, the condition is less rare than
* A list of the cases, and the pedigrees of some of them given in
Appendices I, o and H, and V.

BOWMAN LECTURE.

cm

we suppose, and how that attention has been drawn to it
we may hope soon to hear of more cases. There has
been no opportunity for anatomical examination, and
nothing is known of the intimate nature of the night-
blindness ; we cannot even be sure whether its seat is
retinal or cerebral.

In the other group of hereditary night-blindness shown
in Figs. 42, 43, and 44 (Appendix V), the leading features
are limitation to males with descent through normal-sighted
females and myopic refraction, but visual acuity with cor-

rection often subnormal. Slight changes are sometimes
found at the fundus, but even when present they are not
constant either in character or situation. Considerable
myopia has certainly been present in childhood in some of
them, and perhaps in all; 3'5 D. to 9 D. are the usual
figures, 11 D. the maximum recorded. No case has been
found with steadily progressive myopia or severe myopic
changes at the fundus. Colour-vision was normal in such
as were tested. Nystagmus has been noticed in a few.
Nothing is known of the nature of this condition; but the
association of early myopia, frequently defective central

CIV BOWMAN LECTURE.

vision and occasional nystagmus, and the occurrence in
some cases of various slight ophthalrnoscopic changes,
suggest that in this group the night-blindness, although
congenital, is truly pathological, the result of a limited
intra-uterine elongation of the eyeball interfering with
the development of the choroid and outer layers of the
retina. But why the condition should usually be limited
to males is as great a mystery as in other sex-limited
conditions. It is to be noted that ordinary myopes some-
times complain of seeing worse in twilight, but the
significance of the symptom in such patients is open to
more than one interpretation, and its proper analysis is
full of difficulties, as I believe some of my friends who
are investigating the subject have found. About a dozen
fairly good pedigrees of this sex-limited myopic night-
blindness are known, and may be found in my paper
already mentioned. Consanguinity of the parents was
present in at least three of them.

Since the publication of the paper in which all the
above cases are given I have obtained the new and
quite characteristic, although small, pedigree of this
sex-limited myopic night-blindness, fully described with
its Fig. 44 in Appendix Y. There was no consanguinity.

Another case (44a), seen at the same time as the
above, was less thoroughly examined, and is given in the
same Appendix for what it is worth. In this case two of
the three affected siblings were girls ; the parents were
first cousins.

I owe these two new examples to the kindness of Mr.
W. J. Cant and Mr. Clements, of Lincoln, who courteously
allowed me and Mr. C. H. Usher to examine the affected
members for ourselves last autumn. To the Rev. C. N.
Usher, of Wellingore, I am indebted for the kindness
and trouble he took in arranging for our meetings with
the patients at his house.

Some few small pedigrees of night-blindness are found
in which, though descent is discontinuous, the disease
affects both sexes ; myopia appears to be common in the

BOWMAN LECTURE. CV

affected members, but nothing like universal, and V.
corrected is also apt to be subnormal. The relations of
this group will have to be worked out by future
observers.

LEBER'S DISEASE.

(Figs. 45 to 52 in text, 48 being inserted at p. Ixii.)

The hereditary optic neuritis, or, as it is often called,
optic atrophy, described by Leber, is so well known that
I need dwell only upon certain points that call for further
study.

Although nearly always symmetrical and usually
simultaneous in onset, it is sometimes unequal in
intensity in the two eyes even to the degree of
occasionally leaving one eye untouched, as in a case by
Johnson Taylor,* or but slightly affected, as in Norris's
case (Fig. 49, IV. 13), whilst an interval of weeks between
one eye and the other is not very rare, and even years
occasionally intervene (see Fig. 51). After an acute
or subacute onset the climax is generally reached in a
few weeks or months and no further change takes place,
the leading permanent feature being a central or nearly
central scotoma that varies in size and density in different
cases. Peripheral loss of field is much less common.
Total blindness is said to ensue in rare instances, but I
believe this has generally rested on lay testimony. The
usual age of onset is about 20 years. The subjects
are males in a large majority of cases, but descent nearly
always takes place through the unaffected mother. Con-
sanguinity of parents is but seldom met with. In only a
few cases do we find a history of other neuroses (most
often epilepsy) in the patient or his relations. The
following are good illustrative pedigrees of Leber's dis-
ease :t

* T.O.8., xii, p. 146, Case 3. June 12th, 1909: Mr. Johnson Taylor
has kindly re-examined the members of this genealogy quite recently
and brought the history down to date. See Fig. 110, Appendix VI, a.
f For the other data on Leber's disease see Appendices I, i, and VI.

4

CVI

BOWMAN LECTURE.

1893. (Fig. 45.) Gould (George M.), Pan-American
Congress, Section Ophthalmology, and Annals of Oph-
thalmology and Otology, ii, p. 303.

I, 1, blind rather late in life. IF, 1 age at onset unknown,
IT, 2 at 40. Ill, 1 affected, died at 86 ; III, 2 affected
at 28 ; III, 4 doubtful case, died at 40 ; II F, 3 died at 62 ;
III, 5 died at 74 and was blind in old age, cause unknown.

. 45

IV, 7 died at 40. V, 3 affected at 23, V, 4 at 28, V, 5
at 33, V, 8 at 52, V, 15 at 34, V, 16 at 28, V, 17 at 23, VI,
5 at 27. Author observes that the disease is dying out
for want of child-bearing daughters in the later genera-
tions.

1893. (Fig. 46.) Gould. Ibid. Author's Cases 3 and 4.

Ill, 2 affected at 25; his 4 siblings all living, 27 to 12.
Ill, 5 affected at 24, seen at 36 ; III, 10 failed at 21,
seen soon after. All very severe cases. Ages of III, 5
to 11, from 36 to 18; III, 12 and 13 died of "croup" at
3 and 2 years. II, 3 sight bad after smallpox at 40;

BOWMAN LECTURE.

CVII

lived to 65. All in I and II lived to good age, and I, 3
was alive at 93.

1908. (Fig. 47). Hancock, R.L.O.H., xvii, p. 167.

Twelve cases, all males, in 5 generations ; 6 recovered

17 ft 46

9

BL

S (, 1 S 9

practically full V. in from twelve to eighteen months, viz.,
I, 1 ; IV, 5, 8, 9, 13, 14; and III, 5 improved enough to
resume business. Ill, 1, 7, 8; IV, 7 and V, 2 did not

Ki"

£.

recover. IV, 9 very epileptic since 16; aged 26 at
record. The following were intemperate in alcohol and
tobacco: III, 1, III, 7; IV, 7, IV, 13, IV, 14. The
following were very moderate in alcohol and tobacco,
III, 5; IV, 5, IV, 8, IV, 9 (total abstainer from alcohol,

CVIII BOWMAN LECTURE.

small smoker, epileptic, takes bromide). The age of
onset was as follows: I, 1 about 25 ; 25 in III, 1, 5, 8,
IV, 7 and 9; 26 in IV, 13; 30 in III, 8; 31 in IV, 14 ;
17 in V, 2; 41 in IV, 5. No early deaths. Descent
strictly according to rule. Of the 12, 8 had no children
and apparently did not marry ; the 4 who married had at
least 20 children between them. As to present age, IV,
14 is now (J909) 42 ; IV, 13, 41 ; IV, 9, 29. I, 1 died at
a ripe age, about LOO years ago. No consanguinity.

1898. (Fig. 48, inserted at p. Ixii, supra,) Klopfer,
Inaug. Dissert. Tubingen.

The J in VII (author's Case 5) reported to have had
the same disease. In VIII (counting from the left), No.
1 (author's Case 4) was affected at or about 20. VIII, 4
(author's Case 2) affected in 24th year, seen soon after;
three years later, no recovery; V. fingers. VIII, 5
(author's Case 1) affected at 21, seen six months later;
five years later, no recovery. VIII, 6 (author's Case 3)
affected in 20th year, seen three years later. Much con-
sanguinuity, but disease probably derived through VI, 23.

1884. (Fig 49.) Norris, T.A.O.S., iii, p. 662.

Four generations, 14 cases. I, 1 female, no details, but
family records seemed trustworthy. II, 1 affected at 14,
died 45 ; his first-born (III, 1), 45' at date of record, normal,
had two children (IV, 1 and 2) of whose sight nothing-
known ; second son, III, 2 affected at 18, died at 22. II, 2,
normal, five children; III, 3 affected at 15, died childless
at 50; III, 4 affected at 35, living, aged 50 at date; III,
5, 48 at date, and her husband, examined and found quite
normal ; they were not consanguineous ; III, 7 normal,
childless at 40; III, 8 affected at 19, aged 40 at date;
two sons (IV, 14 and 15), aged 6 and 3 at date and normal.
IV, 3, affected at 18, died at 30; IV, 4, affected at 14,
died at 18 ; IV, 5, normal, 20; IV, 6, 18, no information to
be got. IV, 7 to 13, issue of III, 5 and 6, all affected
and all examined (author's Cases 1 to 7) : — IV, 7 aged
22 at date (author's Case 5), failed at 14, stationary 3
years, then improved so that she could sew, and at date

BOWMAN LKCTURE.

C1X

V. 2\-; IV, 8 (author's Case 6) affected at 19, no re-
covery in a year, V. -QQ ; IV, 9 (author's Case 7) affected
at 18, under care at date; IV, 10 (author's Case 1),
affected at 14, V. ^-, no recovery in nine months ; IV,
13 (author's Case 4), affected at 7, seen at 8, V. of R.
much worse than L., marked neuritic appearances in both,
R. -6%, L. f ; IV, 12 (author's Case 2), affected at 8£,
seen at 10, V. -fg, slight neuritic and atrophic changes ;
IV, 11 (author's Case 3) affected at 8, seen at 12 with V.

A to ~h aild °-Ds- Pale-

1901. (Fig. 51.) Mathieu (Jules), These tie Pari*, No.

117, p. 51.

TZ.

.. ....~.

3 t S 6

II, 4 failed at 50, no recovery, lived to 69 ; her first child
(III, 1) born several years before marriage, affected at 40
(author's Case 1). Ill, 2 born several years after III, 1,
affected at about 40 (author's Case 3) ; III, 3 married
twice ; children by both husbands, but the two paterni-
ties not separated on pedigree ; III, 4 affected at 22
(author's Case 2), living at record, not married; III, 5
died at two days ; III, 6 died at 34, sight was " beginning
to decrease." II, 5 had two illegitimate sons, III, 7 and 8
(who assert that they had different fathers), both affected
at 28 and 32 respectively (author's Cases 4 and 5). IV,
1 to 6, 14 children of III, 1 ; IV, 1 (author's Case 6)
affected between 16 and 19 ; IV, 4 (author's Case 7)
attacked at same period of life, recovered completely ; IV,

CX BOWMAN LECTURE.

3 all died young, and IV, 6 all dead at record; IV, 9
(author's Case 8) affected ab'out same age as IV, 1 and 4,
seen at 25, improved very decidedly 2 to 3 years after
onset. In III, 1 there was interval of 8 years between
the two eyes, E. before L. ; and in III, 8 between 2 and
3 years, R. before L. All the five affected ones in III
had pterygium.

In respect to prognosis, the chance of recovery has,
I think, been put too low — how much too low it is
impossible to say. There do not seem to be any signs by
which we can forecast the future for a given attack ; but

Fig. 51

with our present knowledge I am sure we not only may,
but should, speak hopefully about any case seen within
a couple of years from the onset or even longer. I
find records of at least 25 affected persons (22 males,
3 females), in 16 genealogies who recovered either perfect
or quite useful central vision; and minor degrees
of improvement are probably rather common.*" Most
of these recoveries took place between the ages of 20
and 30, viz., at the period when the disease is most
frequent; but 2 were in children. In the same
genealogy and even in the same sib ship some may
recover and others not : thus in Hancock's recent remark-
able case (Fig. 47), 6 recovered out of 12 attacked; in
* Appendix VI, I.

BOWMAN LECTURE. CXI

one of Leber's earliest cases (1871), 3 siblings were
attacked and all recovered ; and in a case of my
own 2 cousins recovered out of 4 attacked. In the
recovered cases many different lines of treatment had
been tried and we cannot be sure that any of them had
much effect. A very important feature in these cases
is the length of time that may elapse before notice-
able improvement of sight begins, often 12 or 18 months,
and, in one case, if we can believe the history, as
much as 3 years. This possibility of considerable delay
in recovery should lead to a more hopeful prognosis
being given in future cases; one can, indeed, hardly
doubt that the list of favourable results would have been
longer had cases been more frequently followed up.
Probably some of the t( astonishing cures" of long-
standing " blindness " of which we hear from time to time
may have been examples of delayed recovery from this
disease.

We shall probably be right in attributing certain cases
that individually resemble the type but are without family
history of the disease to the same essential cause, what-
ever that may be. Such cases, sometimes diagnosed as
tobacco amblyopia, do not improve on ceasing to smoke
and sometimes show contraction of fields as well as central
defect. Interesting communications on such, possibly
borderland, cases have been made by Lawford, and
Edgar Brown. *

There is a tendency to anticipation in Leber's disease,
both in successive generations and to a less marked
degree in successive births in the same sibship ; but
the phenomenon is not so pronounced as it is in
successive generations affected by glaucoma or by senile
cataract.

Anticipation in successive generations was shown in 14

pedigrees out of 31 that gave the necessary information,

the difference between ages of onset in the elder and

younger generation being from 15 to 25 years. In 11

* T.O.8., x, 1890, p. 166.

CXII BOWMAN LECTURE.

others the age of onset was practically the same in both
generations. In only 3 cases was there evidence that
the disease began later in the second generation than the
first.* In the rare cases where a mother is affected the
onset of the disease at an earlier age in her sons than in
herself can hardly be called " anticipation/' because the
disease usually appears earlier in all males than in all
females.

Anticipation in successively born brothers or sisters is
not so frequent, being found in only 29 out of 82 completed
sibships containing 2 or more cases of the disease. In 14
others the disease began at a later age in each successive
birth, in 16 at practically the same age in each case, and in
23 the ages of the successive siblings when attacked varied
irregularly. The differences of age-onset, are of course
much less between successive siblings than between
successive generations, the age of onset in the junior
sibling being usually about 3 years less than in the
senior, and seldom as much as 5 years. t

It is of interest to inquire whether when a mother
suffers from the disease her children will have it in greater
numbers or with a different sex- distribution than if she
had merely carried it as a potential in the usual manner?

In the corresponding case of congenital colour-blindness,
Professor Bateson finds, as already mentioned, that if a
woman be colour-blind the history always shows that her
father was so, and that if she have sons they will all be
colour-blind ; whereas we know that in the ordinary case,
where the mother is unaffected but carries the defect,
only a proportion of her sons will have it.J Careful
examination of the corresponding data for Leber's disease
shows that it does not conform to this rule§ : — I. A man
with Leber's disease who has children seldom transmits it;

* Norris, Amer. Ophth. Soc., iii, p. 673, Cases 58, 75 and 93 in Appendix
VI, 6.

f For the data relating to anticipation see Appendix VI, &.

£ Bateson, Mendel's Principles af Heredity, 1909.

§ The data for what follows are given in Appendix VI, b.

BOWMAN LECTURE. CXIII

in 11 pedigrees 23 affected males became fathers and
had 100 children who lived long enough to have the
disease, the males and females being in about equal
numbers; only 6 of the JOO became affected, 4 males and
2 females. II. An affected female has generally,, like an
affected male, had both parents normal ; it is rare to
find that she had an affected father or an affected
mother. III. An affected female may transmit the
disease to her children of either sex, but of her sons
some usually escape. It is not clear why there should
be this difference between colour-blindness and Leber's
disease in the transmission to and by an affected female.
We may note, however, that the one condition is an
actually innate physiological defect, the other a disease
of which in the vast majority of cases we cannot say
more than that the liability to it is innate.

But although a woman suffering from Leber's disease
does not, as a rule, give the disease to all her sons, she
does give it to a larger proportion of her total issue than
she would do if she only carried it incomplete or latent
in the ordinary way : — I. In 12 completed sibships, where
the mothers were affected but the fathers normal and the
siblings of the necessary age normal, 64 children survived
and 33 had the disease, viz., 21 males and 12 females.
II. In 38 similar sibships where the mothers were
normal, but carried the disease (the fathers also being
normal), there were 215 eligible children of whom 65 got
the disease, 64 males and 1 female. In the first case one
half, and in the second case rather less than one third of
the children suffer, and the difference is almost entirely
due to the excess of affected daughter a in the first group,
viz., the group where the mother had the disease.

In one extraordinary case (Case 49, supra) all 7
children (4 male, 3 female) of the normal and unrelated
parents (III, 5 and 6) had the disease, and had it unusually
early in life.

The number of children born in the childships con-
taining cases of Leber's disease is seldom less than the

BOWMAN LECTURE.

normal, and is sometimes very large. In 44 completed
childships, each containing one or more affected, with
both parents normal, 28 contained 7 children or more, 10
of these having from 10 to 14 each, and one had 16. In
19 similar affected childships where one parent had the
disease, 8 had 7 or more children, 2 of these having 10
and 2 having 14, 11 contained 6 or less. It is notice-
able that in both these sets of sibships (44 and 19), those
in which females as well as males were diseased averaged
rather larger than those with only males diseased, as
8'25 to 7. The normal branches of affected stocks are
seldom fully recorded, but in such of them as seem
complete we find several containing 9 and 10 children
each. So it is clear, on the whole, that the stocks in
which Leber's disease is found are quite up to the normal
in fertility, that the sibships in which the disease occurs
are larger than normal, and frequently very large; and
further, that the affected ones who marry often beget full
families.

JUit if the births are too many the early mortality is
large, sometimes very large, especially among the male
children. This has been pointed out by several writers,
notably by Gould. We find that in the sibships that
have been reduced by a high early death-rate, the pro-
portion of the survivors who get the disease is larger
than in those sibships where few or none have died ;
almost half of the former became affected, including
several females, but where no early deaths took place the
proportion affected is one third.

One naturally suspects that a disproportionate number
of those who died early would have suffered from the
disease had they lived long enough, and that thus early
deaths may contribute to the extinction of the disease ;
but this, of course, is at present a mere guess.

In several families there has been a high mortality from
phthisis, but the number of such families is too small to
justify any inference.

The characters of the disease are usually the same in

BOWMAN LECTURE. CXV

eacli individual at whatever age the attack occurs. In
pedigrees where it comes on early, i.e., before the
fourteenth year, some females are usually affected ; the
reverse is true of the pedigrees where the onset is deferred
until 30 or later, female cases being found in only a few
of these. There seems, therefore, to be some connection
between early age of onset and the female sex.

We have not much information about the longevity
and causes of death of those who are afflicted, but the
records show that a fair number were alive at 50 and
later, up to 75 ; one died at 69, a pair of brothers at 72
and 73 respectively, and one man at 86. I have lately
(thanks to the kindness of Mr. Doyne) seen a woman,
now 71 (Fig. 52, II, 2), who has had the disease since
birth or infancy ; whilst in another woman, seen at 75
by Mr. Sym, the disease did not set in till she was 51.
The subject is worth following up.

Case and Fig. 52, 1898 to 1909, unpublished, kindly
communicated by Mr. Doyne, is a very important one.

I, 3 had some defect of sight, but not so bad as
daughter (II, 2), and could do needlework and read ; it
may have been only myopia. Had 14 siblings (I, 2) ;
her first child (II, 2) illegitimate, aged about 71 when
seen (1909), sight failed in childhood, and has remained
same ever since ; symptoms and appearances characteristic
in her and the other cases, all of which have been seen ;
has been very deaf for many years. I, 2 afterwards
married I, 4, and had by him 2 sons and 4 daughters
(II, 3 and 4), who all saw well. II, 2 married apparently
after 30. Husband (II, 1) of about same age, after-
wards lost both eyes from a boiler accident. They
have had 4 children, who are all living ; III, 2, aged 84
(1909), who has one living child, IV, 2, aged 8, normal,
and one who died (IV, 1) ; III, 3, aged 32, normal, has 3
children (IV, 3, 4, 5), aged 5 years to 10 months, all
normal ; III, 4 seen by Mr. Doyne at 20 and by E. N. at
30 (1909), "born with the sight as it is now," is married
to III, 1, who was examined and found normal ; III, 5,

CXVI

BOWMAN LECTURE.

aged 29 (1909), single. IV,. 6 to 10, issue of III, I and 4.
IV, 6 believed to have seen well till about 3 years old,
when he began to have to look about for things ; when
about 8 Mr. Doyne found myopia from 7 to 8 D. in each
eye, with 3 D. of As. in R., V. fingers, O.Ds. pale ;
ordered - 7 D. In March, 1909, I (E. N.) found IV, 6
about the same ; could read 3 or 4 J. slowly, held
very close. IV, 7 saw well till about 4 ; at 5 Mr.
Doyne found O.Ds. pale, V. fingers at 3 ft., refraction
H. 2 D., no As. ; in March, 1909, I (E. N.) found her in the
same state. IV, 8 died at nine months with good sight ;

IV, 9, miscarriage. IV, 10 noticed by mother to see
badly when two months old, or even earlier ; at six months
Mr. Doyne found irregular nystagmic movements,, and
noted that child did not follow a light ; in March, 1909,
ret. !•}-§• years, I (E. N.) found the O.D. decidedly pale on
Y.S. side, and the mother said the child saw so badly that
he would run against the table or chair, and " has to look
under the light to see/' IV, 6-10 all suckled, intelligent,
and show no other degeneracies ; same general remarks
apply to IFF, 4 and 5. Circumstances prevented proper
examination of Fs. in any of these subjects, but it was
quite evident from the manner in which they looked at
objects that sight was best towards periphery ; central

BOWMAN LECTURE. CXVII

vision very bad in all, and they all Lave more or less
nystagmus; O.Ds. much alike in all, pale all over in the
adults, but especially so on Y.S. side; in the children
nasal side is fairly coloured, but Y.S. side quite pale.
None of those affected, from the grandmother (II, 2) to
the youngest (IV, 10) are getting either worse or better.
No consanguinity.

Apart from early deaths, we do not meet with any
very prevalent morbid tendencies in these families. The
most frequent seem to be epilepsy and aggravated
hysteria ; such conditions are recorded in several families,
sometimes in the subject of the Leber's disease, some-
times in a sibling or a maternal relative. In one case
Basedow's disease occurred in the sister of a man with
Leber's disease.^ Insanity or mental defect is recorded
in three affected brothers, and in one other affected
male, whose affected brother was epileptic. Diabetes is
mentioned in two or three cases. At least two males, one
affected, the other normal, and perhaps a third affected
male, were congenitally colour-blindt — probably a normal
coincidence ; likewise, the association of retinitis pigmen-
tosa with Leber's disease, observed by Wider, Coppez,
and H. Schmidt, appears to have been purely accidental.

As to sex, I find about 60 females against about 300
males. J It has been said that in females the disease
tends to come on with special frequency at about the
climacteric, but little evidence of this can be found.
Of the 57 affected females the disease came on before the
age of 13 in 13 cases, almost equally spread over the

* Case mentioned (on Liebreich's authority) by A. Terson in his
article " Maladies de 1'CEil " in the Traite de Chirurgic of Dentu-Delbct,
T.V., 1897, p. 198.

t Cases 106, 117, 147.

+ The exact number depends upon the inchision or exclusion of a few
doubtful cases. There are probably more than 300 males to 60 females ;
small pedigrees with only males affected are relatively common and not
always recorded, but cases in females have been more generally published
on account of their rarity. Perhaps some few of the cases in females that
I have included would be rejected as atypical by others.

CXVI1I BOWMAN LECTURE.

25 years between 14 and 39 in 26 cases, in the critical
years between 40 and 50 in only 10 cases.

We commonly notice that the age of onset is almost
the same for all cases in the same genealogy — all very
early in one, all unusually late in another. But marked
exceptions are seen, as in a case (Fig 103) where one of
two brothers lost his sight at 21, the other not until 60.
The latter was diabetic at about the same period, and one
cannot help suspecting that had he not been so he might
have escaped the disease of his optic nerves.

Consanguinity of parents is seldom met with ; I find
at present only 6 or possibly 8 cases. In Arnold Knapp's
case, given fully below, a woman with Leber's disease
(Fig. 50 ; III, 3), whose father was also affected, married
her normal first cousin, the son of a normal brother
of the affected father. In Gunn's case*" a woman with
the optic nerve disease from childhood married her healthy
first cousin and has so far two children, female and male,
both affected at 3 or 4 years of age.

1904. (Fig. 50.) Knapp (Arnold), A. of 0., xxxiii,
p. 383 (1904, and further information, March, 1909).

I, 1 and 2 normal. If, 1 failed at 24, recovered
slowly enough to read, is now 67 (1904) j had 2 brothers
and 3 sisters, 1 of whom died at 17, 1 at 30, 1 at 67
and 2 still living ; none affected. Ill, 1 to 4 all failed
during their early school years. I, 1 has 2 sons, normal
(1909). Ill, 2 lately married (1909). Ill, 4 married, no
issue (1909). Ill, 3 married son of her father's brother;
6 children, of whom IV, 2, 4 and 5 all failed at early
school age. IV, 3 and 6 remain normal, ages 15 and 9 in
1909. IV, 7 died at 4, with good sight.

This scarcity of consanguineous parentage in the history
of Leber's disease is what we expect in a sex-limited affec-
tion. In such a disease, as already shown (Figs. 1 to 5),
when two unaffected cousins marry only one, the wife, can
possibly carry the disease, since the husband will so far as
we know always show it at the proper age if he contains
* Fig. 46, Appendix VI, a.

BOWMAN LECTURE.

CX IX

it*; here,, therefore, the cousinship does not increase the
risk to the children. Next, if the cousinship comes
through the wife's unaffected father she will not, any
more than her unaffected husband, contain the disease,
and might have been unrelated so far as risk of this
particular disease is concerned. The only case in which
a cousin marriage increases the risk is when the man is
affected with the disease and his cousin wife carries it
latent, deriving it either from her affected father or
through her mother from an affected male of an earlier
generation.

The differential diagnosis of Leber's disease, generally

Fiq.So

II

easy, may now and then be difficult when we have to
distinguish it from familial optic atrophy associated with
tower-skull and other cranial deformities. t I have pro-
visionally included the cases by Eampoldi and Suckling,
which, although probably genuine, presented some unusual
features and are not described in sufficient detail ; and one
of Higgeiis's cases is also included, although the author
seems inclined to think that syphilis in the mother may
have taken a share in causing the optic atrophy that

* But compare the suggestion on last page as to the possible influence
of diabetes or other agencies in exciting a latent tendency to the disease.

f Patry, " Contribution a Fetude des Lesions Oculaires dans les Mal-
formations Craniemes/' These de Paris, 1904. Several cases of tower-skull
or oxyeephaly will be found in the T.O S. and elsewhere in British
literature.

CXX BOWMAN LECTURE.

occurred in three of lier children ; (these three are
Figs. 181a, 1816 and 181c, Appendix Via).

Cases of family or hereditary congenital optic atrophy
have been described as if forming a group in some way
distinct from Leber's disease. I believe that most of
these are true Leber's disease setting in very early in
life or perhaps sometimes before birth. Certainly several
of those given in Appendix Via present the classical
symptoms; and I doubt whether we have at present
sufficient evidence to justify us in setting up any of these
family infantile cases as a distinct group.

There does not seem to be any connection between
juvenile Leber's disease and the cases of progressive
failure of sight with slight macular and papillary changes,
and coincident mental degeneracy, in children, described
by F. B. Batten, Mayou, Sydney Stephen son and others.*

As outlying cases the following may be mentioned:

I have once seen double chronic stationary central
amblyopia with partial optic atrophy corning on in an
old man at about the age of 76, and ordinary acute
retrobulbar neuritis, first in one eye, and after a year's
interval in the other, in his daughter aged 23—24 who had
symptoms suspiciously like early disseminated sclerosis
(P. 49, 62 and 52, 146).

I also saw in 1881—1882 retrobulbar neuritis limited to
one eye and following an attack of diplopia due to paresis
of one of the rotators, in a man set. 50 years,t whose
daughter was under Mr. Holmes Spicer's care 20 years
later, set. 33 years, for retrobulbar neuritis of left eye, which
relapsed slightly 4 years later (1906), when she also had
threaten ings of disseminated sclerosis.

Acute retrobulbar neuritis has also been seen in two
sisters in more than one instance.

* T.O.S., xxiii, 1903, p. 386, and xxiv, 1904, p. 142, et se<j.
t Ibid., iv, p. 210, Case 17.

BOWMAN LECTURE. CXXI

HEREDITARY NYSTAGMUS (Sections a and 6).

Without attempting a thorough search, I have found
about twenty-five pedigrees in literature under the title of
" Hereditary or Family Congenital Nystagmus," and
have added a few of my own. Generally speaking, more
attention has been paid to the oscillation than to its
causes, so that we are often unable to classify the cases
in any natural order. One is almost reminded of the
time when every case of obscure blindness was called
" amaurosis."

It may safely be asserted that infantile nystagmus, as
a family affection, is in the vast majority of cases a
symptom of defective sight, and not due to a primary
central cause. Our business is to find out the nature of
the amblyopia, and to arrange the cases accordingly.
The defect of sight is always dated either from birth or
early infancy ; it is often due to some affection that causes
little or no ophthalmoscopic change ; and as the oscil-
lation, especially in a baby or young child, often renders
a refined ophthalmoscopic examination impossible, we
may be unable to make an exact diagnosis until the
patient is old enough to answer questions and have his
visual functions tested. In some cases, however, we can
come to a conclusion before that period.

Perhaps the first thing to note is that nystagmus in
general is more easily produced in some persons than
others ; this is evident enough in cases where it follows
blindness; and I am told that coal-miners and others do
not all acquire it with equal facility under like conditions
of work.* The same surely must be true for nystagmus
produced in early infancy by defective sight ; some
infants will learn steady fixation sooner, more readily and
with less perfect vision than others ; those who have most

* The last letter I received from Mr. Simeon Snell, written a few
weeks before his death, was in reply to a question I had asked him on
this subject ; it was to the effect that some coal-miners are more sus-
ceptible than others.

CXX1I BOWMAN LECTURE.

difficulty are likely, other things being equal, to develop
nystagmus. Therefore, from time to time we meet with
nystagmus dated from birth, or soon after, with only
slight defect of visual acuity, such as may perhaps be due
to nothing more than a moderate degree of astigmatism"* ;
but as a rule the defect of acuity required to produce
the oscillation is considerable.

Nystagmus dating from early life often becomes less
marked in later years ; it may even cease entirely,
although such complete cure seems to be rare. Nys-
tagmus is often less marked in some one position of the
eyes, a position constant for the same person, but not the
same for different persons ; it also varies much in the
rapidity and range, and also the direction, of the move-
ments.

We can seldom be sure of the precise date at which
the nystagmus begins in albinos and others with con-
genitally defective vision. In some albinos, however, the
oscillation has certainly not been noticed until the child was
many weeks or even some months old, and the movements
are slower and perhaps less rhythmical at first than they
become afterwards. Albinotic infants not infrequently
keep their eyelids closed for weeks after birth, and this
has sometimes led to the report that albinos were born
blind ; but when such infants have been seen it has
been found that, with the eyelids held open, they evidently
perceived the difference between light and shade, and
that the pupils responded to light.

There must be several different intra-uterine, or very
early infantile, diseases or defects of retina, choroid, or
optic nerve that, running in families, cause hereditary
nystagmus ; but for the present the two that stand out
as best known are albinism of various degrees and the
affection called, for want of a better name, " total colour-
* I am not yet convinced that astigmatism alone can produce nys-
tagmus, because the frequency of astigmatism in albinos suggests a cor-
relation between deficient pigmentation and the corneal deformity, and
in cases of nystagmus apparently due to astigmatism only we are not
yet in a position to exclude a defect in the retinal epithelial pigment.

BOWMAN LECTURE. CXXIJI

blindness " or " day-blindness." A large unclassed residue
remains, but in all probability had attention been paid in
these cases to the colour-sense and to the pigmentation
of the eye some of them would have been placed in one
or other of the two categories just named.

I have nine or ten pedigrees illustrating nystagmus in
families affected by what I look upon as incomplete
albinism limited to the eyes, ten of nystagmus with day-
blindness or total colour-blindness, and fifteen of unclassed
nystagmus.

(a) ALBINISM.

(Fig*. 54 and 55 in text ; 53, and 56 to 60 in Appendix VII a.)

What little I have time to say about albinism must be
in connection with the incomplete or partial cases that, as
I believe, have often hitherto been entered as hereditary
nystagmus. Pedigrees of ordinary conspicuous albinism
with and without consanguinity, with continuous or dis-
continuous descent, and with, as well as without, other
correlated or coincident disease, are seen in Figs. 56,
57,58, 59, 60 in Appendix VII.* A typical case of
the slight degree of albinism in which the deficiency
of pigment falls mainly upon the eye is seen in Fig.
53 (Appendix VII) (Mr. Jameson Evans's case). Here
a child set. 15 months (Gen. IV, 1), had nystagmus,
slight pink reflex from the pupils, grey irides, and
nearly white hair; whilst its brother, when seen at
six weeks old, had steady eyes, black pupils, grey-blue
irides and yellow hair, " not so light as the elder one at
fifteen months old." The one marked III, 9, aet. 8
years, with slightly pink pupils, grey irides, decided
lack of pigment in choroid, nystagmus, from 2 to 3 D. of
astigmatism and V., corrected, -2— ^, had hair of a light
shade of dull-brown which had formerly been lighter.
The prevalent hair-colour in the others was dull brown
and the irides grey. .In this family with nystagmus, had

* From a forthcoming memoir upon albinism by Professor Karl
Peason, Mr. Usher, and the writer.

CXXIV

BOWMAN LECTURE.

the evidences of albinism afforded by the eyes of the two
children above described (IV, 1 and III, 9) not been
forthcoming, the true bearings of the case could hardly
have been discovered.

In a case of my own (Albinism Memoir, Fig. 402)*, a

Fiq.54-

i.Sb"

JE

^

similar state of affairs existed, except that there was no
nystagmus and V., with the moderate myopia and slight
astigmatism corrected, was •§. I have myself no doubt
that Lloyd Owen's well-known case, Fig. 54 (Albinism
Memoir, Fig. 449), was really albinism limited to the eyes
* This lecture, Fig. 186, Appendix VII.

BOWMAN LECTURE. CXXV

and incomplete even in them. I put the same inter-
pretation on Fig. 55 (Albinism Memoir, Fig. 410, my own
case, Mansfield), and Figs. 187 and 188, Appendix VII.*
The note of all these cases is the blue or grey iris,
hair now brown, but with the history that it was very
fair or even " white " in early childhood, and a more or
less albinotic fundus ; almost all have nystagmus and
marked arnblyopia; when, as in a few of the cases, sight
is good and the eyes steady, we must suppose that the
retinal epithelium, at least at the yellow-spot region, is
sufficiently pigmented, however lacking in pigment the
choroid may be.t

* The suggestion that the cases just mentioned, and others like them
were of albinotic nature was made, so far as I am aware, for the first time
by myself in R.L.O.H., xv, p. 110, 1902. It is evident that the idea of
albinism was present to the minds both of Mr. Lloyd Owen in connection
with Fig. 54 in 1882 and myself in relation to Fig. 55 in 1887, but it was
mentioned by each of us at those dates, only to be dismissed.

t The hypothesis is that the imperfect sight, and with it the nys-
tagmus, is caused by deficiency of pigment in the retinal epithelium ;
that this want may vary in degree, and may even, perhaps, affect only a
part — say the central region — of the fundus ; and lastly, that such
relative or absolute lack of pigment in the epithelium is not recognisable
with any certainty by ophthalmoscopic examination, the different depths
of tint at the fundus depending far more upon differences of pig-
mentation of the choroid than of the hexagonal epithelium. In support
of this speculation we may say (1) that in albinism with quite trans-
lucent iris, i. e. no pigment in the retinal layer, stroma pigment is occa-
sionally present in sufficient quantity to give the iris an ordinary brown
colour; (2) that microscopical examination of the choroid of normal
European eyes shows — in the comparatively small number of specimens
where attention has been carefully directed to the point — that the
quantity of pigment in the retinal epithelium appears to be sensibly the
same in eyes with pigmented iris and choroid as in those with iris
and choroid almost, or quite, devoid of stroma pigment. Whether this
position will be maintained when a larger number have been examined
remains to be seen. Also we must be careful, for the present at least, to
allow for probable differences in the kind of pigment in the eyes of
European and of dark races ; the eye-pigment of a Negro may be darker
than that of a Scandinavian although the qviantity be the same in the
two. These are nice, but important, problems for future determination,
and I have reason to believe that work is already in progress upon them.
Examination of partly albinotic eyes, the so-called " wall eyes " or pie-
bald eyes they might be called, of dogs and horses by Mr. Coats and Mr.

CXXVI BOWMAN LECTURE.

There are all sorts and degrees of albinism between
these cases which I have ventured to include and the
well-marked general albino whom we all know. It may
be hoped that in describing future cases of hereditary
nystagmus attention will be bestowed upon the present
and past colour of hair, eyebrows, eyelashes and iris,
aspect of fundns, colour-vision and refraction.*

In their heredity these partial cases appear to be
almost perfectly sex-limited ; of forty- three affected per-
sons, forty were males, and the descent was through the
mother in every case ; no affected male ever had an
affected child. t In these characters, the group I am
calling incomplete ocular albinism differs from general
albinism. It is true that in general albinism the descent
is usually discontinuous, but the normal parent who
acts as carrier is by no means always the mother ; again,
although there is a decided excess of males with general
albinism over females it is much less than in the small

Usher within the last year have shown that — apart from the tapetum in
those animals — every possible combination of pigment deficiency in the
retinal epithelium and choroid or iris may be present, a result supporting-,
so far as it goes, the above contention. I believe we do not know any-
thing positive about increase of pigment in the hexagonal epithelium
after birth ; but even if such increase were proved to occur in cases of
incomplete albinism, it does not follow that visual acuity would be im-
proved ; the pigment might come too late for the otherwise developed
retina to benefit by it ; we know as a fact that improvement of visual
acuteness in albinos, although by no means unknown, is decidedly rare.
A great puzzle is the frequency and high grade of the ametropia and
especially of astigmatism in nearly all recognised albinos, and the same
problem meets us for these cases of blue-eyed nystagmus, and appears to
furnish another link between the two groups.

* I do not suggest that everyone with blue eyes, nystagmus, and
amblyopia is albinotic in any degree : but some certainly are so, and
many others probably ; whilst if the essential feature of an albinotic eye
is lack of pigment in the hexagonal retinal epithelium, we are not yet in
a position to deny the possibly albinotic nature of any clinical case where
no more reasonable explanation of the nystagmus and defective acuity
can be found.

t These small numbers are given for what they are worth. But even
if a few other pedigrees of nystagiims are included where the evidence
for albinism is even less than in the above, the excess of males affected
over females affected remains very large — 3 or 4 to 1 .

BOWMAN- LECTURE. CXXVII

series mentioned above,- being about fifty-five males to
forty-five females."*

In the small series available (-ten families) consanguinity
has not been recorded in any, but I am not sure that
inquiry was always rnade; and even if it had been we could
not attach importance to tji^.a^sence of consanguinity in
so small a number. In general albinism consanguinity of
parents is common. This '-fact together with the very
great frequency of discontinuous; descent in human albinism
point to its being a MeAdelian "recessive. But apart from
the question of correct numerical proportions, the infinite
varieties both of degree and distribution of albinism in man,
i. e. the frequency of intermediates, appears to militate
against the applicability of the theory. This leads to the
remark that in speaking of albinism we need a definition,
and, without going into controversial matters with which,
in the present case, I am not fitted to deal, I may at once
say that, whatever may be true for such of the lower
animals as have been fully examined, it is quite clear that
for man we cannot limit the term to persons whose skin,
hair and eye tissues are perfectly devoid of pigment. Jn
the first, or last, place you cannot tell without micros-
copical examination whether a given skin or hair or eye
contains a little pigment in certain places or none at all
anywhere ; and therefore if we refuse the term " albinism "
when any trace of pigment is present we must refuse to
diagnose albinism in man at all until someone has examined
a human eye thoroughly and found it absolutely free from
pigment. So far as I know this has not yet been done
— not because such eyes do not exist, but because in them-
selves they are rare and the opportunity of getting them
for anatomical examination enormously more so. Clinically
we all know that every degree of defective pigmentation
occurs in skin or hair or eyes, or in all together, to which
we cannot refuse the term " albinism," qualified when

* In upwards of 1000 albinos of all races and various degrees, the
excess of males is found not only in the aggregate, but in each separate
group used in the summation.

CXXV1II BOWMAN LECTURE.

necessary by such terms as* '" partial" or "incomplete."
The problem for human Tn*e"cfical observers is, not whether
degrees of human albinism, either general or localised,
exist, but how far we may carry our subdivisions — what
are the smallest tracts or lowest decrees of deficient pig-
mentation that may be intl^flej. an the species. It is, I
think, likely, although we cannot' -j^s yet either prove or
disprove the point, that pwpfafflt j&ibinism of any one part
does not occur without peiffe^t albinism of the whole body.
But as we have already «3ee2i f qjv the eye, and as is well
known also for the skin and-jjair/we find short of albinism
perfect dissimilar degrees &£ it in the same individual,
irregularities of distribution*, and differences in the same
tissue or organ at different periods of life.

(b) DAY-BLINDNESS WITH TOTAL COLOUK-BLINDNESS.

(Figs. 61 to 64.}

This interesting but rare hereditary disease is always
accompanied by amblyopia, often of high degree, due to
defect at the centre of the field ; the f undus may appear
normal, or slight changes about the macular region and
at the disc may be present, not, however, such as would
lead one to expect any serious defect of sight. There is
always colour-blindness, and in the severer cases it is, as
the title indicates, total, but in some milder cases the
want of colour sense is less pronounced. No special kind
or degree of ametropia is found. Nystagmus is a usual
but not invariable symptom. The condition is always
said to date <( from birth/' and it gets neither worse nor
better with age. The patients almost always say they see
best in a dull light, and sometimes put it that they are
" blind " in bright daylight ; this, the ordinary condition
in toxic amblyopia, retrobulbar neuritis and central
retinal disease, is often much more strongly marked in
the condition I am describing. The disease often occurs
in several siblings, but has, I believe, not yet been seen in
parent and child; it is, however, known to have occurred

BOWMAN LECTURE. CXX1X

in two sibships of cousins and once or twice in an uncle.
The total number of affected persons I have been able to
find recorded, including the fifty-two collected by Grunert
in 1903* is eighty-four, including single cases without
family history. Whether we consider this grand total, or
only the instances of family prevalence, we find consider-
ably more males than females with the disease with no
corresponding excess of males amongst the healthy.
There is, in the small series collected hitherto, a decided
prevalence of consanguinity of parents. Mental defects
have been relatively frequent either in the subjects of the
disease or in collaterals. In these broad general characters
the disease reminds us of retinitis pigmentosa — indeed, in
one of my cases typical pigmentation of the retina was
actually present,t and another case J one was tempted
to interpret as transitional between the two conditions ;
but the non-progressive character of the present affection
appears to constitute an absolute difference.

No case has been examined post-mortem ; Galezowski,
who published one of the earliest of the modern cases
(1868), conjectured that the seat of the disease lay in the
cones, and Grunert, working on much larger clinical
material and by improved methods, also sums up in favour
of cone-blindness. It is interesting to note in this con-
nection that Stock believes he has microscopical evidence
that the bacillary layer is the first part to undergo visible
change in retinitis pigmentosa. §

My first case (shown in Fig. 61), was so striking that
as the disease seems still to be but little known, I venture to
quote it from the paper in which it appeared almost thirty
years ago.|| This patient, an intelligent, fairly educated
woman, aet. 25 years, came to St. Thomas's Hospital in 1879,
with one of her sisters, who was affected like herself.

* Grunert, A.f.O., 1903.
t Fig. 185, Appendix VII.
J Miss A—, T. 0. S., xxviii, p. 86, Case 9.

§ Stock, Heidelberg Congress, 1906 (published 1907) p. 48, and Klin-
Mon.f. A., xlvi, p. 226, 1908.

|| Ht. Thomas's Hosp. Repts., 1880.

CXXX BOWMAN LECTUKE,

The chief complaint was that she could not see by day and
could not tell colours. She said that in the daytime her
sight was so bad that she was afraid to cross the street
though she could do it with ease in the evening, and that
she could read small print by a light so dull that other
people had to put away their books. She was so colour-
blind that she always dressed in black and white to avoid
making absurd mistakes. Her refraction was very slightly
H., and V. -£$$ and J. 6 held very close in daylight ;
constant slight lateral nystagmus. She saw worse after
eserine had contracted the pupils. She sorted Holmgren's
wools entirely according to their brightness, yellow looking
the brightest. Disc and retinal vessels of healthy appear-

Fia 61

ance/but a slight whitish haze of doubtful meaning about
the Y.S. A sister, aet. 20 years, who came with her had
exactly the same defects of sight, and the spectrum to
her was a band or stripe of one colour, brightest in the
middle and darker at each end. I afterwards saw a brother,
set. 22 years, who was affected in the same way. They
were members of a childship of 1 J, of whom 6 were living.
The parents were said to have perfect sight and no colour-
defect, but an uncle was said to be colour-blind.

I afterwards saw a still more interesting family (Pike-
Channon), (Fig. 62), in which two sets of cousins were
affected, two of the victims being idiotic and quite blind.
The colour-blindness of the brothers 111, 4 and 5 was
carefully examined by Captain, now Sir William Abney,

BOWMAN LECTURE. CXXXI

several years later and recorded in his work on colour-
vision.^

This case is given as two separate cases by Grunert, one
attributed to me, the other to Abney. Fig. 63 shows
another case carefully gone into by Mr. Holmes Spicer
and myself several years ago, in which the father probably

IL,

HL

had the same disease. The last case 1 know of (Fig. 64),
has been given to me recently by Mr. Holmes Spicer, with
very careful and detailed notes taken by Dr. W. C. Souter
in 1908. One girl and two boys, ast. from 8 to 6 years (IV,
4, 5, 6), are affected in a sibship of 8; only one other, a

boy, aet. 3 years, has lived, and he appears normal ; two died
at 3 months, one at birth, and one was a miscarriage; no
reason to suspect syphilis; parents second cousins through
their mothers, who were first cousins. No other cases
known in a fairly extensive pedigree. Family from
Dorsetshire.

* Abney, Colour Vision ("The Tyndall Lectures," 181J4), 1895, p. 126.

CXXXIT BOWMAN LECTURE.

I have fourteen pedigrees of nystagmus not recorded
fully enough .to allow of their being assigned with certainty
to either of the two classes we have just considered, or to
any other recognised disease, although several of them
are very extensive. Eleven of them are published, the
latest being the one by Dr. W. H. Dudley.* Though
these pedigrees are inconclusive as to the nature of the
disease and probably in some cases not quite accurate in
details, they are readily divisible to sub-groups, showing :
(1) Continuous descent, seven pedigrees containing about
50 cases of nystagmus with defective sight, one of the

pedigrees alone containing 25 cases ; in two of these
there was consanguinity, in the remaining five it was not
mentioned. (2) Discontinuous descent; four pedigrees
with more than 20 cases, only 4 being females ; descent
proved to be through unaffected mother in several
instances ; apparently no consanguinity in any. Mr.
Ernest Clarke's case belongs to this little group, but is
so extraordinary that I have counted it separately ; this
pedigree shows 22 males affected out of 23, and every
one of the 20 females escaping; Mr. Clarke has been
unable to see the recorder again in order to verify the
particulars. (3) In three pedigrees the descent was
* Dudley, W. H., A. of O., 1908.

BOWMAN LECTUKE. CXXXIII

continuous in some instances, discontinuous in others in
the same genealogy ; two of these (Audeoud, 1895, and
Burton-Fanning, the same year), have evidently been
drawn up with much care in all respects except as to the
ocular details. A list of these pedigrees is given at the
end of Appendix VII.

CHOROID.

Data as to the family prevalence and heredity of
various diseases of the choroid and of the cornea are
beginning to accumulate.

(1) We know that central senile choroiditis is apt to
occur in several brothers and sisters.*

(2) It is of course sometimes difficult to say whether a
case should be classed clinically as choroidal or retinal.
I have for convenience placed several family cases to
which this doubt applies at the end of my recent paper on
retinitis pigmentosa, viz., one such group called atrophia
gyrata choroidas et retinse by Fuchs, the other (rather
paradoxically) a small series in which the choroid is con-
genitally absent except over a small area at the macular
region. t Putting these two little groups together pro-
visionally, we have 23 affected persons of whom 17 or
perhaps 18 were male and 5 female. Five were, judging
from the records, single cases; the other eighteen occurred
in seven families, most of them in siblings only, but once
in father and son and once in great-uncle and nephew. In
one family the choroidal disease was associated with dulness
of intellect, undergrowth of body, and arrest of sexual de-
velopment. It is unnecessary to dwell longer on this group.
The cases are evidently very rare, and in future examples
the family history should be inquired into much more fully.

* Hutcliinson R.L.O.H., viii, p. 231, in three sisters (1875). I have
recorded several such in The Ophthalmoscope, iv, 1906. Magers published
one in 1889, Ueler hereditdre Sehnervatrophie u. Tiereditdre Choroiditis
Inaiig. Dissert., Jena, 1899.

t The best known cases of these allied conditions are given in abstract
in R.L.O.H., xvi, pp. 369-377, 1908.

CXXXIV BOWMAN LECTURE.

(3) In another group of cases a multitude of small,
round, whitish dots or spots of what appears to be super-
ficial disease of the choroid occupy the central area of
the fundus, and in some examples pigmentary changes are
described more peripherally. Mr. Doyne recorded the first
definitely hereditary case of this variety in 1899,* using
the term " honey-comb choroiditis." His patient was one
of several siblings similarly affected, and the disease had
occurred in the ascendants for three generations ; I believe
that Mr. Doyne has not hitherto published the genealogy
of this remarkable family in full. A case probably of
the same sort in a brother and sister had been published
by Mr. Langt in 1885, and a single case perhaps of the
same type, without record of others in the patient's family,
by Mr. Juler in 1893,J whilst in 1897 Mr. K. D. Batten
and Mr. Holthouse§ recorded another single case, agreeing
with the description of honey-comb choroiditis in a woman,
aged 25 years, the last born of 24 children, 20 of whom had
died young from some obscure cerebral disease. A case,
probably similar, with coloured illustration, was published
by Mr. Reginald E. Bickerton in 1900.|| In 1901 Mr.
Hugh Thompson^! put on record the case of a woman, set. 57
years, with extensive superficial choroidal changes around
the discs which had caused no symptoms; but her father
and three brothers who were his grandsons, i. c. were
nephews of the patient, were night-blind, and one of
them who was seen had the appearances of atypical
retinitis pigmentosa.

The case given by Liebredht** as retinitis punctata
albescens in 1895 does not agree in all respects with that

* Doyne, T.O.8., xix, 1899, p. 71.

t Lang, T.O.S., v, 1885, pp. 140 and 141.

I Juler, T.O.S., xiii, 1893, p. 143.

§ E. H. Holthouse and E. D. Batten, T.O.8., xvii, 1S97, p. 62, and xx,
p. 95, with Plate III, fig. 2.

II Reginald E. Bickerton, T.O.8., xx, p. 93, with Plate III, fig. 1.
f Hugh Thompson, T.O.8., xxi, 1901, p. 66.

** Liebrecht, Klin. Monats. f. Augen., 1895, p. 169. The case is quoted
almost in full in my account of retinitis punctata albescens in R.L.O.H.,
xvii, p. 392.

BOWMAN LECTURE. CXXXV

condition, and may, I think, have been of the same character
as Doyne's " honey-comb " cases.

(4) In 1872, Mr. Co well * published in much detail a
peculiar case of destructive irido-choroiditis in a father
and two of his children, and detachment of retina in a
third child, but as the author thought that the whole
affair was very probably syphilitic the case cannot be
quoted with confidence as an example of heredity.

(5) I find notes of two sisters, set. 20 and 21 years, seen
at St. Thomas's Hospital in 1883, with identical extensive
superficial choroidal atrophy which appeared to have
come on at the age of 8 in one and 12 in the other, and
was apparently not progressing; there was no pig-
mentation of retina and no evidence of hereditary
syphilis. Both were myopic and had V. 1^7777 with
correction. The cases may have been of the same kind
as that of Miss A — , referred to in the Section on Day-
blindness.

(6) I am indebted to Mr. Fisher for the notes of a
case in which two sisters and a brother, aet. from 39 to 33
years in 1908, have changes similar to the last case (5) and
dating, as in that case, from late childhood ; the refrac-
tion hypermetropic. There was not the slightest facial or
dental evidence of syphilis. They were the third, fourth
and fifth born in a sibship of nine. The mother, who
died at 53, had had poor sight for many years but was
not blind.

(7) Two cases of family choroiditis have also been
recorded by Hutchinson,t but in at least one of them there
was a strong suspicion of syphilis in the father

CORNEA.

(Figs. 65 to 69 in Appendix VIII.)
(1) "Nodular" and " Reticular" Opacity of the Cornea.

Of these conditions, classing them together as probably
* Cowell, R.L.O.H., vii, 1872, p. 335.

t Hvitchinson, Archives of Surgery, xi, 1900, p. 122; and R.L.O H., v,
1866, p. 324.

CXXXVI BOWMAN LECTURE.

of essentially similar nature, we have now at least eight
pedigrees showing the disease in from two to four genera-
tions, quite half a dozen others of " familial " preval-
ence, and perhaps a dozen other single cases.

In the pedigree and familial cases the sexes are about
equal, descent continuous with one exception, and from
either sex to the same or to the opposite sex.

We shall no doubt have larger numbers to deal with
before long.

Descriptions of the most extensive pedigrees (Holmes
Spicer, Freund,* Doyne and Stephenson, and Folker) are
given with Figs. 65 to 69 in Appendix VIII.

(2) Several other affections of the cornea are known to
occur as family diseases from time to time.

In February, 1905, Mr. Jessop wrote to me that he
had then lately seen conical cornea in a lady of about 50,
who stated that her mother had gone blind from conical
cornea. In June, 1906, I heard from Mr. Laws that he
had just seen the case of a young woman with conical
cornea, whose mother stated that the daughter's eyes had
been like they now were from birth, and that three more
of her children were affected in the same way ; she had
had eleven children, most of whom died in childhood ;
one was in an asylum; the parents were first cousins.

Buphthalmos has been seen in several brothers and
sisters, and it is not unlikely that the case published by
Crompton in 1840 1 as congenital opacity of the cornea
in two siblings out of ten and the earlier one by Farar J
in 1790, in three siblings, were of that nature.

* Freund's Case 2 (Bienert) has been brought up to date by the
author in courteous reply to inquiry (June, 1909), and is now correctly
shown by Fig. 67.

f S. Crompton, London Medical Gazette, xxvii, 1840, p. 432.

£ Samuel Farar, " An Account of a Very Uncommon Blindness in the
Eyes of Newly -born Children," Medical Communications of Society for
Promoting Medical Knowledge, ii, 1790, p. 463.

BOWMAN LECTURE. CXXXVIJ

APPENDICES.

The following appendices will enable the reader to verify the more
important statements made in the Lecture, especially those as to the
numbers of diseased to normal, the relative liability of the two sexes to
be affected by each of the diseases in question, and the occurrence of
anticipation. In some cases the data themselves are given, in others
specific references are made to papers I have lately published which
contain the necessary information.

The subject of Leber's disease is so important that I have thought it
well to make a short abstract of every case published and unpublished
that I could lay hands upon, and to insert figures of the pedigrees of a
large number; this collection is based primarily upon Hormuth's Dis-
sertation,* published in 1900, towards which the considerable series pub-
lished by Habershon in our Transactions (vol. viii, 1888) furnished an
important contingent. A number of other cases, piiblished and unpub-
lished, have been added to Hormuth's series.

The illustrative cases and figures are numbered serially from 1 to 188.
Of these, 47 are inserted in the text of the Lecture, the remainder appear
in the appendices in connection with their respective diseases. Although
this plan will cause some inconvenience to the reader, it is preferable to
the alternative of having two separate series of numbers, one for the
Lecture, the other for the Appendices.
The following are the Appendices :
I. Illustrating the introductory section of the lecture.
Frequency tables for :

(A) Cataract, post-natal.

(B) „ congenital, lamellar and discoid.
(c) „ „ other forms.

(D) Retinitis pigmentosa, continuoiis descent.

(E) „ „ discontinuous descent.

(F) Diseases allied to retinitis pigmentosa.

(G) Night-blindness, continuous descent.
(H) „ discontinuous descent,
(i) Leber's disease.

(j) Proportion of females carrying disease in certain sex-
limited affections.

II. Relative numbers of males and females affected by lamellar
cataract and other forms of congenital cataract.

III. Glaucoma, Case-figs. 28-34.

IV. Retinitis pigmentosa, Case-figs. 37, 38, 39.
V. Night-blindness without changes.

(a) References.

(6) Mr. W. J. Cants' new case of congenital night-blindness,

Case and Fig. 44; also Case 41a.

* Hormuth (Philipp), " Beitr. z. Lehre v. d. hereditiiren Sehnerven-
leiden," Inaug. Dissert., Heidelberg, 1900; published also in Detitsch-
mann's Beitr. z. Augenheillc., 89, Heft 42.

6

CXXXVIII BOWMAN LECTURE.

VI. Leber's disease.

(a) Abstracts of all the cases with figures., except Case-figs. 45-

52 placed in the text of the lecture.
(I) References to cases or figures in a, illustrating various

features of the disease discussed in the lecture.
VII. Nystagmus.

(a) Albinism section : (1) Case-figs. 53, 56, 57, 58, 59, 60.

(2) Various references to published cases
and the following new cases, Figs.
" 182, 183, 184, and 188.

(6) Day-blindness section : Various references to cases and Case-
fig. 185.

(c) Unclassed nystagmus ; references to places of publication.
VIII. Cornea, Case-figs. 65-69. List of principal publications.
IX. Abbreviations for titles of periodical publications.

APPENDIX I.

FREQUENCY TABLES.

Data upon which the Statements at p. Ixix et seq. of the Lecture as to the
Relative Numbers of Normal and Diseased are based.

Only those sibships (childships) have been used that Avere either
known or judged on good grounds to be complete as to numbers and sex
record ; only those in which (with one single exception) the youngest
member was old enough to be siisceptible to the disease in question ; and
only those in which either one or more of the siblings or one of the
parents of the sibship was affected. Therefore, from the childships
selected all members are excluded who died before the usually vulnerable
age and all still-births and miscarriages. I am well aware that the
omission of these items might lead to inferences that in the present
state of our knowledge are unwarranted : for whether the numbers here
given from human data do or do not agree with Mendelian requirements
we are certainly not at present entitled either to affirm or deny that the
proportions of normal and diseased would have been the same if all the
conceptions had lived to the susceptible age. My object has been only
to ascertain, on a somewhat larger scale than has been attempted before,
how far the available numbers, as they stand, do or do not fit with
Mendelian expectation as based upon experimental breeding.

In such diseases as post-natal cataract, very small lamellar or discoid
cataract, and even retinitis pigmentosa, the proportion of affected to
normal is almost certain to be more or less too low, for in these diseases,
and especially post-natal in cataract, the earliest stages of the malady
may pass iindiscovered unless the eyes of every member be examined — a
condition that can seldom be fulfilled.

When descent is continuous every completed sibship in which the
disease occurs is counted, and every sibship of which either parent is
affected, whether any of the children are so or not. When descent is
discontinuous only the sibships showing the disease can be used.

'A) Cataract : Post-nasal or Acquired Cataract, at all Ages.

1 U

K.

1

o

1 x

"8
"3 rt .

1
"5

o

Reference.

•J-iil

ill?

•

!•

Reference.

|||

Sils

£ & rt ^

!•

jl 3

|ifi

|

§ "

!*l •

1

0

tn

~

£

SB

R.L.O.H., xvi, pp.

Ibid. Case 100

II

6-1 =

3

179-210 and

5 (lob.

389-395.

inf'cy.)

Case 1

III

6

2

» 102

III

2

2

Ibid. „ 5

II

8

2

„ 105

I

6

3

n 17

I

8

6

II

5

3

Ila

8

1

„ p. 408,

II

6

3

6

5

1

Casey Wood's

Ilia

8

4

c

4

1

Case 2 (Hussa)

b

5

2

18

II 10- 2

8

3

c

4

2

06.

Ibid. Casey

II

6

3

infancy

Wood's Case 3

Ilia

7

2

IKa

4

1

(Smith)

b

4

1

b

7

1

T.O.S., xxviii, p.

Ila

2

1

H 19

Ila

4

2

220

6

9-3-6 1

b

3

2

(3 06.

Ilia

6

5

inf'cv.)

IVa

3

2

III

10

7

b

2

0

Ibid., xxix, and

Ila

4

1

c

6

0

Fig 21 in this

b

8

> 2

„ 26

II

6

3

lecture (Westly,

III6

8-2-C

2

„ 27

III

9

5

Fisher)

(2 ob.

IV

8

4

inf'cy.)

V

6

4

Ibid1., and Fig. 24

III

6

1

Via

5

4

in this lecture

IVa

16-7-

4

6

2

0

(E.N.,Oldfield)

9 (7ob

c

1

0

young)

Vila

3

1

Ibid., (E. N.,

IV

8

4

b

1

1

Deasley)

Va

8

2

c

3

1

b

7

1

'„ 28

II 8-1

7

5

Ibid., xxix, p.

III

8

2

too

( Fisher, Hibleii)

young

Crzellitzer,

II

4

3

„ 30

II

4

2

Deutsch. med.

,, 34

II

4

3

Wochenschr.,

u 36

II

5

1

1908, p. 1894

III

3

2

This lecture, Fig.

II

4

1

IVa

3

2

23 (E.N. and

Ilia

10

1

Va

5

4

Smyth, Helyer)

„ 38

7

3

Ibid , Fig. 22

II

7

2

„ 46

II

13

9

(E.N.,St.John)

Ilia

5

3

Unpublished —

II

7

1

b

10

2

Mr. Hinnell's

III

7

1

c

5

3

case (Hall)

d

4

1

e

4

1

„ 48

—

7

3

Summary.

„ 98

Ilia

3

3

Total. Normal. Cataract.

b

12 2

126 . . 52

IV

9 5

135 . . 60

Va

3 3

132 . . 54

b

4 1

47 .11

c

2 1

d

8 1

440 263 177

e

8 0

(100) (60) (40)

CXL

BOWMAN LECTUKE.

B) Lamellar and Discoid Cataract.

Reference.

y
Hi

)ns counted ;
'ected and
normal.
• + 0

ber affected.

•

Reference.

sration and
sibslrip
Midship ; .

ns counted ;
ected and
normal.

•+0

ber affected.

•

§ 3

a «H

a

s xS

O SR

1

&

(£

s
&

i

fc83

PH.

JZ.L.O.H.,xvi,pp.

Ilia

4

2

Ibid., Fig. 12, cent

h

4

1

225-334 and

b

6

1

(Stephens)

Va

12

2

395-400.

c

4

2

Ibid., Fig. 13

IVa

10

5

Case 62

d

4

2

(Coppock)

Va

4

1

Ibid. „ 66

IVa

3

2

b

3

2

b

2

1

c

9

1

„ 69

II

5

1

d

7

3

III

10

3

Via

4

3

, 70

II

4

2

I)

6

2

„ 71

6

2

c

2

0

>, 72

7

2

Ibid., Fig. 14

Ilia

5

1

,, 73

4

2

(Fisher's case,

„ 77

8

6

Pucknitt)

„ 108

Ha

7

3

Unpublished —

III

6

5

Ilia

9

0

Mr. Syrn's case.

b

12-7

5

This lecture,

= 5(7

Fig. 15

ob. in-

Bishop Har-

II

5

3

fancy)

inan (Turner)

Ilia

5

4

,, 109

III

4

2

T.O.S., xxix, p.

b 8

6

3

„ ,, 1JO

V

6

3

101

-2=6

« HI

II

5

3

(2 ob.

p. 215.
Case 56

II

6

2

young)

c

2

0

p. 408,

IV

12

10

IVa

5

2

Casey Wood's

b2

1

1

Case 1 (Charl-

-1 = 1

ton).

(1 ob.

This lecture, Fig.
11 (Everett)

Ila
Ilia

4
10

3

8

young)
c

3

2

IVa

9

6

d

7

4

b

3

3

d

3

1

Ibid., Fig. 12
(Stephens)

Illb

c

6
9

4

7

Summary.

IVa

7

2

Total. Normal. Cataract.

b

13

3

150 . . 77

c

6

2

135 . . 51

d

5

1

34 . . 19

e

4

1

f

4

1

319 172 147

9

9

4

(100) (54) (46)

BOWMAN LECTURE.

CXLI

Congenital Cataract other than Lamellar : Coralliform,
Stellate, and Undescribed Forms.

1

-d

T3

1

i

1

"Q,

rt S .

i

o3 '"^

fH £

0

Reference.

§s3

iii

m

111?
II *•

.ber aff<
•

Reference.

ill

o^i°

o QJ a +

§«&•
6 <u pi

1

r

£ s

£^

a

§ ^)-

^

a •

_

&

&

<3

2

0

fc

R.L.O.ff.,xvi,pp.

Ibid. Case 113

II

7

4

211-216 and

„ H8

Ila

7

0

400-408.

6

5

2

Case 51

6

3

„ 119

IV

6

3

Ibid. „ 54

ill

6

3

„ 120

Ilia

7

3

IVa

7

1

b

5

2

„ „ 57

11

2

IV

4

3

„ 57a

II

7

4

T.O.8., xxix, and

Ila

5

2

„ 58

II

8

6

this lecture,

Ilia

5

2

Ilia

5

3

Fig. 16 (Perrin)

IVa

4

2

b

5

2

b

8

4

IVa

2

1

c

8

5

6

6

4

Ibid., Collins

II

4

1

c

10

7

and E. N.

III

7

3

Va

3

2

(Tomes)

b

3

0

Unpublished :

II

13-3

1

c

5

1

Collins and E.

= 10 (3

d

4

? 2

N. (Revell)

06. in-

or 1

fancy)

e

2

1

„ 58a

II

7

2

Summary.

„ 60

II

6

4

Normal. Total. Cataract.

p. 233.

II

5

3

124 . 223 . 99

Case 78

(56) . (100) . (44)

„ „ 112

III

5

2

Lamellar . 172 . 319 . 147

IVa

7

2

(54) . (100) . (46)

b

1

1

Va

5

4

*Grand total. 296 . 542 . 246

b

5

2

(55) . (100) . (45)

* P. 8. — If we add two pedigrees showed at this Society by Mr. Bishop
Harman at the July meeting (his Cases 1 and 2) the numbers are 306
(54 per cent.) normal, 206 (46 per cent.) cataract, total 566 (100).

(D) and (E) Retinitls Pigmentosa.

In compiling- the following tables of retinitis pigmentosa I have
omitted 9 childships — containing an aggregate of 70 children, the
smallest having 6 — each of which contains only one case of the disease,
viz., R.L.O.H. xvii, Cases 43, 81, 83a, 835, 83c, 83d1, 83e, 83/, 83i.

In the following 5 childships used in the tables either deafness or
idiocy has been taken as equivalent to retinitis pigmentosa, viz., R.L.O.H.,
xvii, Cases 32, 2 r.p. + 1 idiot - 3; 33, 3 r.p. + 1 idiot = 4; 84, 3 r.p.
+ 1 deaf = 4; 119, 1 r.p. + 1 idiot = 2 ; this lecture Case-fig. 39, 1 r.p.
+ 1 deaf - 2.

(D) Retinitis Pigmentosa — Continuous Descent.

Reference.

Generation and
sibship

(childship).

Persons counted :
affected and
normal.
• + 0

Number affected.
•

Reference.

Generation and
sibship
(childship).

Persons counted ;
affected and
normal.
• + 0

Number affected.

•

R.L.O.H., xvii,

Ill

8

4

Jli'd. Case 62

VI

11 - 3

5

pp. 1-56, 151-

IVa

4

3

- 8 (3

166, 333-427.

I

1

0

ob. in-

Case 1

c

6

2

fancy)

Va

3

1

„ 44

III

2

1

b

7

5

„ 53

III

12

4

c

6

3

,, 54

IV

5

3

d

2

2

„ 55

IV

7

5

e,

5

2

., 71

IV

3

2

Via 12

9

4

„ 69

III

13 - 3

5

-3=9

= 10 (3

(3 ob. in-

06.

fancy)

y ciing)

VI6

4

0

„ 67

III

6 -1 =

2

c

1

1

5 (1 06.

d

7

3

inf'cy)

e

3

2

, 73

V

1

1

f

3

1

, 68

V

9

3

g

1

1

, 61

III

4

2

Hid. „ 2

III

6

4

, 65

V

4

2

IVa

11

0

, 80a

10-2

5

b

4

3

- 8 (2

c

1

1

ob.

Va

3

1

young)

b

1

0

., 84

9

4

c

12

8

„ 89

III

6 - 1

2

d

3

3

- 5 (1

e

4

2

ob. in-

3

II

3

2

fancy)

IV

11 - 5

2

., 92

4

4

= 6(5

',, 104

II

5

3

ob. in-

Ilia

1

1

fancy)

b

12

10

V

3

1

IVa

2

1

„ 4

IV

5

3

b

1

1

„ 6a

II

3

2

c

9-4

1

III

7

4

= 5 (4

IVa

5

0

oh. in-

b

6

2

fancy)

„ 11

II

5

2

,,H8

8

3

Ilia

7

4

„ H9

6

2

b

5

0

T.O.S., xxvii, p.

Ilia

3

1

» 12

III

8

5

217 (Snell).

b

7

4

„ 13

II

6

2

IVa

4

0

III

3

2

b

9

4

„ 28a

III

3

2

c

3

0

„ 29

III

4

1

„ 60

IV

7 - 1

2

= 6(1

Summary.

06. in-

Total. Normal. Affected.

fancy)

115 . . 61

„ 44a

III

5

3

120 . . 53

„ 76

III

12-2

4

152 . . 75

= 10

„ 74

I la

6

2

387 . 198 . 189

Ilia

4

2

(100) (51) (49)

BOWMAN LECTURE.

CXLIII

(E) Retiniti* Pigmentosa — Discontinuous Descent, i. e. Parents
Normal; Both Sexes Affected.

rt

aj ^— .

is

1

d

03 ^

]N •

"5

gP-.S*
.rtiS'S

cJNo

f

o'S'is

l5lo

6

Reference.

° a> S +

- ^

Reference. '-g "» r^

o a> S +

9

o3'S)H

S| §•

s

qj'S 2

ill*

1

s -

30 *§

a

£ -S

QQ «H

t-i a3

a

1

1

1

5

I

&

.R.Z/.O..ff.,xvii,p.l7,

Ibid., xvii, p. 366.

Ilia 8

2

et seq. Case 15

IVa

11-4 =

3

Case 118 (Nolte)

b 4

2

7 (4 06

Liebreich, ^4rr7j,.

I Fa 6

3

young)

Gen. de Med.,

6

1

1

1861. Case 2

Ibid. ., loa

III

4

2

Gronin, ^.ti. d' Ocu-

11

7

4

„ 156

III

8

7

list, pp. 125, 101

„ „ 16

III

5

3

(1901), and 128,

„ 18

III

4

2

91, and 128

„ 20

Ilia

8

3

(1902). Case 1.

6

13

6

Family D.)

» 25

III

6

3

Webster, Trans.

II 7

3

„ 26

III

7

4

Am. Oph. Soc.,

„ 27

III

4

2

ii, p. 504. Cases

„ 32

V

5

3

20 to 23.

» 33

Ilia

9

4

Coleman, W. F.,

II 13

5

„ 38

IV

4

1

Amer. Practi-

„ 40

IV

4

1

tioner, 1889, p.

Unpublished

Ilia

8

3

49.

case : Mr. C. H.

b

4

1

Unpublished— V 7

2

Usher (Row-

(Mr. Fisher's

and), lecture,

case), this lec-

Fig. 37

ture, Fig. 39

This lecture, Fig.

Ilia

11

4

36 (and T.O.8.,

IVa

4

1

xxviii, p. 226)

Va

4

1

6

8

2

Summary.

c

4

3

d

7

2

Total. Normal. Affected.

R.L.O.H, ix, p.

IVa

10-2 =

2 or

199 . 113 . 86

172(Allen). Case

8 (2 ob.

3

(100) . (57) . (43)

II

young)

The above 22 cases contain 31 sibships available for the foregoing
tables. Thirty of these sibships may be classed into three groups, show-
ing respectively (c) almost every individual affected, (a) nearly one half,
(&) nearly one quarter. Only one, Fig. 36, Ilia, with 4 affected out of 11,
is widely inconsistent.

CXLIV

BOWMAN LECTORE.

(c) Nearly all affected.
R.L.O.H., xvii, p. 17, et seq.
Case.

15. IV6

156. Ill

36. Vc

Totals

(a) Nearly one half affected.
Ibid,

Case.

15. IVa .
loa

16 ...

18 ....

20 Ilia + b, a =-- 8 and 3 ; b = 13 and 6 .
25

26 ...
27

Ibid.

Case.

32 .

33

This Lecture, 37, Ilia
Liebreich, Arch. Gen. de Med., 1861, Case

2, Ha . . .

Gonin, An. d'Oc., 125 and 128 (1902).

Family D. II .
Webster, T.A.O.S., ii, 504, Cases 20 to

33, II .

Coleman, Amer. Pract., 1889, p. 49, II
R.L.O.H., xvii, p. 366, Case 118, III6.

Totals

(b) Nearly one quarter affected.
R.L.O.H., ibid., Fig. 38 ...

„ 40
This Lecture, Fig. 37, III&

36, IVa, Ya, 6 and d,
all same proportions
This Lecture, Fig. 39, V.

R L.O.H., ibid., p. 366, Case 118, Ilia
„ vol. ix, p. 172, 2, IVa

Totals

Total.
1

8
4

13

Total.

7
4
5
4
21
6
7
4

58

Affected.
1

7
3

11

Affected.
3
2
3
2
9
3
4
2

28

Total.

Affected.

5

3

9

4

8

3

6

3

7

4

7

3

13

5

4

2

59

27

117

55

4

1

4

1

4

1

23

6

7

2

42

11

Total.

Affected.

8

2

8

2?3

16

4 or 5

53

15 or 16

'F) Diseases Allied to Retinitis Pigmentosa.

1

f-g 1

1 ~

s^

|

§•- §

^g'o n

".g3

.SiS^

&"'3O

!«

Reference.

"+3 "o5 ,i§ 5 5 £ + K 9

Reference.

«Sg +

i '"I 2 « « a * ' rS

S.-Sg

Pl*

j>

1 °

p 1

O> ! £

1 &

02 *»H

&

Atrophia gyrata choroidx et Retinte

Retinitis pu

nctata alb

escews.

(Fuchs}.

R.L.O.H., xvii,

R.L.O.H., xvii,

pp. 377-393.

pp. 369-373.

Case 141

5

4

Case 125

—

10 3

Ibid. „ 142

10-4 =

3

Ibid. „ 127

JI

5-2=3 1

6

(2 06.
inf'cy)

(4 died
inf'cy)

„ 129 II

10-1= 4

„ 143

Ha

2 1

9 (1 06.

,, 144

IV

7-1=6 2

inf'cy.)

(1 06.

1

inf'cy)

,, 145

8-6 = 2

2

(6 ob.

Congenital Absence of Choroid.

inf'cy)

„ 146 VI

10-2 =

2

R.L.O.H., xvii,

8 (2 06.

pp. 373-377.

inf'cy)

Case 131

—

y 2

„ 150

5

4

Ibid. „ 133

—

8 3

Liebrecht's case : diagnos is doub tful.

» 134

—

11-3= 1

8 (3 ob.

Summary.

inf'cy)

Total. Normal.

Affected.

81 . 50

31

Congenital Night-blindness without Changes — Continuous
Descent ; Both Sexes Affected. Cunier Group.

1

^ '|

1

|

I

ifti

"S §— ' §

d a^

^ §— '

|

Reference.

1!

tu ao A

SlK r

Reference.

111

f-t '>H 'rH

<D 'X! ,£3

jiSs

8K

* ft
1

§ •— '

2s S

JO

g

O

p 5

OH ^

I

S

R.L.O.H., xxvii,

1

I6id. Case 154

III

5

3

pp. 401-4-05.

„ 156

III

3

1

Case 152 II

10 5

IV

7

3

III

3 2

Va

5

2

IVa

5-2=3 2

6

4

3

(2 06.

inf'cy)

Ibid. „ 153 IVa

4 2

?>

3 2

Summary.

c

3 2

Total. Normal. Affected.

d

7 4

63 30 . 33

Ve,f

6 2

(H) Congenital Night-blindness without Changes — Discontinuous

Descent.

1

id

1

1 ^

i* ;l

o3 ""^

~£ 3 . «

"S Pi ^

S P<-~

0-S"_t

§ ^'Sn as

Reference.

ill
g^-g

§» S +

IP*

r

Reference.

||j

§!g +

I*

1*

s

<B ^

^ cd

3

e

j§

a

£

»

Both Sexes Affected.

Ibid. Case 171

IVb

u

i

c

8,

i

R.L.O.H., xvii,

4^4?

pp. 406-410.

Va

2,

i

Case 158

II

10

5

1 (? 1 ?

Ibid. „ 160

Ha

8

3

c

24

2

„ 161

11

13

3

d

7,

1

„ 162

II

5

2

3J 4?

III

1

1

Via

6,

1

» 164

—

6

2

3^ 3?

„ 173

Ilia

2

Grcfy JlfaZes Affected.

b

4,

2

Hid., pp. 410-

c

' 2(?

2

422.

V

3 c?

1

Case 166 , III 6, 3

„ n 175

II

11-5 =

2

5 c? 1 ?

6 (5 ob.

„ 168 Ilia 9, 3

young)

3<JC?.

2 c? 4 9

„ 169 III 4, 1

Ilia

2<?

1

2c? 29.

b

3 c?

2

IVa 5,

3

» 176

IVa

10-4 =

3

3<? 29

6 (4 ob.

b

4,

0

inf'cy)

2$ 29

o •* o o

o (3 o y

Vc

2,

1

b

6<J

3

1 <? 1 9

c

73

3

d

9,

2

d

3 <?

2

5c? 4?

„ „ 177

IVa

5,

2

e

8,

3

3<J 2?

4<? 49

,, 178

Ilia

2(?

2

/'

1 <?

1

b

5,

2

Via

2,

1

3£ 2?

1<J 1?

c

8,

4

b

7,

3

5<? 3?

4 <? 3 9

I

7,

3

c

3,

2

3 c? 4?

e

7,

2

„ 170

III 7,

2

34 4?

3<J 4?

f

5,

2

IVa 4-1 = 3

1

3£2?

1 $ (1<J

IVa

4,

2

ob.

2«J 2?

inf'cy)

b

8,

2

b 4, 1

2^ 69

2(? 2?

c

2c?

1

c 3, 1

!<? 2?

Summary.

„ 171

III

6,

3

Totnl. Normal. Affected.

3 <? 2 9

260 . 159 . 101

IVa

8,

2

(100) (64) (36)

44 49

BOWMAN LECTURE.

CXLV1I

(i) Letter's Disease (only Males Affected).

1 .

id

|

1

|

•g

jff

l||o

1

gpf

|l|o

1

Reference.

o £ B +

1

Reference.

III

<u =° A

w £ S +

|| §•

|*

1 ~

|*

|

rH Q

<3 ^~-

p

PH

«

£

&

Published cases :

^

Published cases :

o

87. Pufahl

—

6,

3

115. Ogilvie

Ha

16-10

3

3<J 3?

= 6

89. Fuchs

—

8,

4

(10 ob.

4 c? 4 V

young,

90. „

I

6,

2

5<J3?)

2c?4?

living

II

5,

0

3c? 32

4 (? 1 9

46. Snell .

Ha

3,

1

94. Schliiter .

Ila + b

7,

4

1 $ 2 2

4<? 3?

III

9-2 = 7

2

Ilia + b

5,

3

(2ob.

3<J 2?

younir)

96.

II

4,

1

2$ 5?

2 cT 2 2

120. „

II

7-2-5

3

102. E.N. (piibl.

II

11,

5

(2ob.

}>y Habershon,

8<J 39

young)

T.OS., viii).

4<J 1?

103. E. N. Ibid.

Ha

6j

2

136. Leber.

III, a,b,c

9,

4

2(? 3?

6<? 32

105. E. N". Ibid.

—

6,

2

139. Westhoff .

II

4,

2

3<? 3?

3 (? 1 ?

107. Browne

—

5,

3

Ilia

4j

3

3<J2?

3 <? 1 ?

45. Gould

Ill

5,

2

IV

6,

4

2<? 3?

5 <? 1 ?

IVfl

10-4 =

1

143. E. N. .

II

8,

4

6 (4 ob.

6c? 2?

young)

III

3,

1

4<? 2?

1(? 2?

Va

8-4 = 4

3

144. „ .

II

6,

2

(4 06.

2$ 3?

young)

1, ? sex

3 <? 1 9

III

16-12

2

b

8-1=7

1

= 4(12

$

ob. in-

(1 ob.

fancy)

young)

2<J 2?

No 2

47. Hancock .

Ilia

8,

3

c

4-1=3

3

3J 5?

(J

IVa

6,

1

(1 ob.

4<J 2?

yoiing)

b

6,

3

no 2

q j< q Q

o c) «V

Via

8-3 = 5

1

c

2 J

2

(Sob.

no 2

young)

Va

1 c?

1

3«J 2?

no ?

CXLVIII

BOWMAN LECTURE.

Leber's Disease (only Males Affected) — continued.

1 ~

i*

1

o

rt

o3 'o*

ll

1

o

I -fa

IJUo

5

gj-3o

1

Reference.

1^1

" 5 S +

•

Reference.

"i %^

" « 3 +

•

gj> 1*

a

i'sa

II ^*

1

1 s

Is

2

o

V *

1

Published cases :

£

Published cases :

^

147. Lawford .

Ila

7,

3

171. Batten

lib

7,

2

3 $ 49

3<? 49

149. Schilling .

—

6,

5

83a. Batten .

II

10,

4

5 (J 1 9

6(J 49

79. Leber.

—

6,

5

84. Vossius

IVa

6,

2

5 <? 1 9

4£ 29

152. Leitner, Case

II

4,

3

86. Buisson

Ilia

5,

2

1 (second paper).

III

3(J 19

3

23. Ha swell .

Ilia

2*8?

9,

6

no 9

7c?29

154. Posey

II

13-3 =

1

IVa

8,

1

10 (3 ob.

i<?79

young)

24. Taylor

Ilia

12-1 =

4

4 <£ 6 y

11 (lob.

Ilia

5,

1

int'cy)

2 (J 3 9

6J 59

48. Klopfer .

VIII

8,

1

25. Sym .

Ila

o,

3

29 19

3J 29

IXa

6,

1

42. Strminski .

III

7,

5

b

23/

3

49. E. N. .

Ila

5,

2

no 9

4<? 1 9

155. Leitner,

Ilia

6,

3

91. Raymond .

II

10-4 =

3

Case 1 (first

3c? 39

6 (4 ob.

paper).

b

7,

1

young)

4 <? 3 9

3(? 3V

c

9,

1

Ilia

2J

1

2^79

no 9

156. Leitner(Case

Ila

5,

2

b

3,

1

2, second paper).

2<£ 3 9

1 c? 2 9

163. Heinsberger

—

6,

3

85. Usher

III

U,

3

4<J 29

8J 39

166. Raymond .

Ilia

5,

I

IV

3c?

2

3 (J 2 9

no 9

168. Costa.

Ilia

4,

2

b

2,

1

IV

2,

1

Summary.

1 <? 1 9

Total. Normal. Affected.

171. Batten

I

11,

1

402 . 237 . 165

6<? 59

(100) . (59) . (41)

Ila

7,

1

4£ 39

BOWMAN LECTURE.

CXLIX

Leber' a Disease — Males and Females Affected.

Reference.

77. Leber

78. „
49. Norris

98. Story

99. Holz

112. Despagnet

113. Somya .

116. Batten .

117. Snell

140. E.N.
(Wilson, etc.
unpublished

141. E. N.
(Donovan)

unpiiblished

142. E. N.
(Laxford)

xinpublished
50. Knapp

£

1

•a

1

83

£

o*

d

C g.

S x-i

•

at

c d

£ ^-*

•

fll

II

s§

J

"3

o

Reference.

O '£

~ -

|

I

o'S

i ""

£

&

1"

fe

1

!

1

1

6,

2

1

52. Doyne

III

4,

1

1

3* 3?

(Perrin)

3*1?

—

4,

1

1

unpublished

IV

5-2 = 3' 2

1

1* 3?

(2 06.

Ilia

2*

1

0

inf'cy.)

no ?

2* 1?

6

5,

2

1

51. Matthieu

Ila

5-1 = 4

1

1

2* 3?

(1 06.

IVa

4,

1

1

inf'cy.)

2* 2?

1* 3?

6

7,

4

3

Ilia

14-7 =

1

1

4* 3?

7 (7 06.

—

8,

4

1

young)

4*4?

4* 3?

—

5,

1

2

162. Lauber .

IV

14-6 =

4

1

2*3?

8 (6 06.

Ilia

7-2 = 5

3

1

young)

(2 ob.

4* 4?

young)

159. Galle-

Ila

5,

2

1

4* 1?

inaerts

3* 2?

Ila

5,

2

1

128. Leber .

—

o,

2

1

3*2?

2*3?

III

4-1 = 3

1

1

153. Leitner,

II

6,

1

1

1*2?

Case 2 (first

1*5?

—

8,

3

1

paper).

Ilia

5,

1

0

6*2?

4* 1?

Ilia

10- 6 =

1

2

b

2, 1

0

4 (6 o6.|

i* i?|

young)

c

6, 1

0

1*3?

3*3?

Ilia

14-10

1

1

= 4 (10

ofr.y'ng.

1*3?

Ilia

7,

3

1

Summary of this Table.

5*2?

Total. Normal. Affected.

145 65 . 80

III

8-1 = 7

2

2

(100) (45) (55)

(1 06.

young)

Summary of both Tables.

4* 3?

Total. Normal. Affected.

IV

6,

3

0

547 . 302 . 245

5* 1?

(100) (55) (45)

CL BOWMAN LECTURE.

(j) Proportion of Females Carrying Disease in Certain
Sex-limited Affections.

In a disease transmitted only by unaffected females the number of
sisters in any childship who carry it can, Avith our present knowledge,
be known only if they all have children. The following are the only
examples I have been able to find, and even in them the evidence must
be regarded as incomplete for such of the sisters as had very few
children :

(1) Discontinuous retinitis |)igmentosa: Fig. 36, IV6,* contains 5
sisters, 1 of whom dies single ; of the others 2 have 12 children in all,
some of whom have the disease ; the other 2 have 4 children in all (only
3 of these are shown in the Figure), none of whom have the disease.

(2) Discontinuous night-blindness : Fig. 42, IVa, contains 4 sisters ;
2 of them have 9 children in all, some affected ; the other 2 have 4 in all,
all normal.

(3) Discontinuous night-blindness (R.L.O.H., xvii, p. 419: Fig. 175),
II, contains 4 sisters ; 2 of them have in all 5 children, some affected ;
the other 2 have in all 3 children, all normal.

(4) Discontinuous night-blindness (ibid., xvii, p. 422: Fig. 178, III&),
contains 2 sisters ; 1 has 4 children, some affected ; the other 2 children
both normal.

(5) Leber's disease (this Appendix: Fig. 108, Ilia), contains 2 sisters,
both of whom had affected issue. Note that of their 7 brothers 6 had
the disease.

(6) Leber's disease (ibid. : Fig. 94), the two small childships Ila
and b, contain 3 females, 2 of whom married, and both had some affected
children.

(7) Leber's disease (ibid.) : Fig. 143, II, contains 2 sisters, of whom
one certainly bore affected issue.

(8) Leber's disease (ibid.) : Fig. 166, Ilia, contains 2 sisters, of whom
one bore three children, one of them affected; the other had an only
child who was affected.

In these eight instances we have 24 sisters, of whom 21 certainly had
children (1 died childless and 2 others appear to have been unmarried
at date of record). Of these 21, 13 had amongst them rather more than
51 children (exact number in one case not given), containing 18 affected.
The remaining 8 had amongst them only 14 children, all normal.

* IV6. — The letter b signifies the second eligible childship in Gen. IV
counting from the left ; the first is a. These letters are not marked on
the Figure. The same explanation applies to the other relevant Figures.

BOWMAN LECTURE.

OLE

APPENDIX II.

Sex in Lamellar Cataract, whether Hereditary or Sporadic
(including Discoid Cataract).

[The following returns have been kindly supplied to mo by various colleagues
and friends."!

Source.

1

Females.

I

Source.

0)

1

Females.

H

Moorfields Hospital, over

405

195

600

Oxford (Mr. Doyne) .

36

29

65

about ten to fifteen

Birmingham, Queen's

57

38

95

years.

Hospital (Mr. Priestley

St. Thomas's Hospital,

60

30

90

Smith).

since 1878.

Birmingham Eye Hos-

18

9

27

St. Bartholomew's Hos-

113

65

178

pital, four and a half

pital, twenty-four

years.

years.

Cases from forty, pub-

140

130

270

St. George's Hospital,

29

18

47

lished and unpub-

about twenty years.

lished.

London Hospital, the last

18

10

28

Cases seen in private

58

57

115

few years.

practice, seven sepa-

4

2

6

Dublin (Sir H. K,

45

18

63

rate returns.

8

6

14

Swanzy), ten years.

6

5

11

Aberdeen (Mr. C. H.

32

33

65

12

7

19

Usher).

28

5

33

Manchester (Mr. Hill

58

41

99

39

23

62

Griffith) four years.

_

Totals. .

1166

721

1887

Sex in Congenital Cataracts other than Lamellar.

Source.

1

1

Females.

j

Source.

J8

Q

1 I 1

e i *

Moorfields Hospital (par-
tial return only).
St. Bartholomew's Hos-
pital, twenty-four
years.
Dublin (Sir H. K.
Swanzy), ten years.

58
22

18

38
18

8

96

40

26

Birmingham, Queen's
Hospital (Mr Priestley
Smith).
Birmingham Eye Hos-
pital (Mr. Bales), five
years.
Cases from various pub-
lished pedigrees.
Totals. .

25
45

82
250

20 45

55 100

82 164
221 471

cur

BOWMAN LECTURE.

APPENDIX III.

GLAUCOMA.

The paper by Lawford in R.L.O.H., xvii, p. 57 (1907), "Examples of
Hereditary Primary Glaucoma/' contains particulars of twenty-four
families in which the disease prevailed, and a list of nineteen references
to the literature. Six of the cases are new, eighteen had been published
before.

Anticipation was well marked in at least half of the series, viz., Cases
1, 3, 6, 7, 8, 10, 11, 13, 14, 16, 17, 24, taking them serially as they come
in Lawford's paper. The following seven of these were shown in
pedigree form at the lecture.

Fig. 28 (Lawford, Case 7, from Lucien Howe) : 1, 4 affected at about 40,
and became blind; II, 2 affected at 28 ; II, 3 at 25 ; III, 1 at 28 ; III, 3
probably about the same age ; III, 5 at 17 ; III, 6 at 26 ; III, 8 at 19.

Fig. 29 (Lawford, Case 1) : I, 1 blind from " amaurosis " (? glaucoma
simplex) for some years before death at 85 ; II, 6, double, quiet glaucoma
at 66, operated upon, died at 71 ; his wife (II, 14) died at 63 ; 3 of his

siblings died in infancy, 2 others (II, 5 and 9) died as adults, all the
others living and reported to see well ; III, 1 to 7 issue of II, 6 and ] 4,
aged, at record, from 53 to 36, and all except III, 1 examined by author ;
III, 3 and 5 got glaucoma simplex at 48 and 40 respectively, and III, 2
had, at 52, signs of the incipient disease. In IV all are reported to
see well, the eldest of IV, 1 being 27, and of IV, 3, 29.

Fig. 30 (Lawford, Case 8 : Nettleship, The Ophthalmoscope, September
and October, 1906). I, 1 affected at about 71 ; II, 1 at 45 ; III, 1 at 23.

Fig. 31 (Lawford, Case 3) : I, 1 blind at 60, almost certainly from glau-
coma, died at 68 ; II, 1 attacked at 58 ; II, two years younger, attacked
at 47 ; II, 3, 6 other living siblings who see well ; II, 4, 4 who died.

Fig. 32 (Lawford, Case 14) : I, 2 glaucoma at 47 ; of his 2 children by
first wife, II, 2 had glaucoma at 26, and of the two by third wife, II, 4

BOWMAN LECTURE. CLIII

glaucoma at 13 ; second wife (I, 3) childless. This case also shows coin-
cidence of high myopia and glaucoma in II, 4

Fig. 33 (Lawford, Case 15, Mules, O.R., ii, p. 48, 1883) : I, 1 glaucoma

I >

iil. *7 T i»4. »•"»•

simplex at 49 ; II, 1 the same at 18 ; II, 2 at 16 : II, 3 at 15 had increased
tension, but no other signs.

Fig. 34 (Lawford, Case 24; Jacobson,A/.0., 1886, iii, p. 96) : 1, 1 glaucoma
simplex at 70 ; II, 1 at 45, and II, 2 at 40.

APPENDIX IV.

RETINITIS PIGMENTOSA.

The principal pedigrees upon which I base what is said at p. xcv et seq.
of the text as to continuous and discontinuous descent in different families
may be found in R.L.O..H., xvii, pp. 7-17 and 360 for continuous descent,
and at pp. 18-24 and 26-31 for discontinuous descent. I have gone over
these again carefully, and find no errors except that in Fig. 33 Gen. I
should be omitted, there being no information.

Discontinuous descent of retinitis pigmentosa side by side with con-
tinuous descent of lamellar cataract is shown in a pedigree published in
T.O.S., xxviii, p. 226 (1908). In the text of the lecture the two parts of
this genealogy were treated separately, the part containing the cataract
cases being shown in Fig. 12, and that containing retinitis pigmentosa
in Fig. 36.

The details of the cases shown by Figs. 37, 38, and 39 are as follows :

Fig. 37 (p. xcvi), sent by Mr. C. H. Usher (Ro wand family), 1909.
I, 3 was invalided from the Army as a young man for ' moon-blindness,"
and was told it would get worse ; could see well in the day, but not
in the evening ; got steadily worse, was quite blind at 50, and died at 70.

I, 1, 2, and 4 all good sight. II, 1 and 5 both good sight. Ill, 8, oet.
36 years, typical advanced retinitis pigmentosa ; has one child with good
sight (IV, 4). Ill, 7, set. 38 years, conditions much like III, 8; hearing
very quick ; has four sons, all living, and one daughter, who died lately,
all with good vision (IV, 2 and 3). Ill, 9, set. 34 years, conditions as in
the other two ; married fourteen years, no issue. Ill, 12, set. 50 years,
nearly blind of retinitis pigmentosa, a drinker, and has been under care
for delirium tremens ; twice married ; no issue by first wife, but by

7

CLiV BOWMAN LECTURE.

second has five or six children, in one or two of whom sight is bad both
day and night. Ill, 4 died in infancy. Ill, 5 at 14. Ill, 6 is 40 ; has
good sight and three normal children. Ill, 10 and 11, and the child,
IV, 5, all see well.

Fig. 38 (p. xcvii), from Mr. Lawford and Mr. E. Collier Green (Paynter
family). A single case in a large childship ; possible influence of severe
loss of blood.

Ill, 3,, Mr. Lawford's patient at Moorfields Hospital in the spring of
1909 for typical retinitis pigmentosa. He is set. 38 years. From his
account, confirmed by personal investigation of his family history and
examination of his mother and several siblings by Mr. E. C. Green, of
Derby, it may be considered certain that no other cases of bad sight or of
degeneracies are known in his generation or the next. He considers
his sight to have been failing ten or twelve years, but can give no
precise date, and did not himself connect it with the haemorrhages
of which he gives a history. When 26, a railway porter, he bled
violently from the nose one day from 9 a.m. till noon, and was
plugged at St. Bartholomew's Hospital. When 33 (five years ago) was
operated at the Great Northern Hospital for " appendicitis/' and says
that about two weeks after the operation he vomited a quantity of blood.
Again a year ago he was in bed for six weeks, and passed blood both
from the bowel and bladder. The history of the epistaxis is clear enough,
but his statements as to the internal hemorrhages are, of course, of less
value. Has not had typhoid or other infectious illnesses to his know-
ledge, and denies venereal disease of any kind, and shows no signs of
congenital syphilis. Married ten years; two children, of which IV, 2
died at 13 months and would now be 8 ; IV, 2 living, set. 2 r22- years.
Mother (II, 2), set. 60 years, examined by Mr. Green, and found normal ;
by first husband (II, 3), who died at 52 from an accident, sixteen concep-
tions (III, 1 to 16) , of whom III, 1, get. 40 years, and III, 9 and 10 (the
latter the youngest living, eet. 23 years) have been examined by Mr.
Green and found normal. Ill, 2, 6 and 11 to 15 miscarriages (seven in
all), and III, 16 died of measles at 9 months. IV, 1, 8 children (3 boys,
5 girls) of III, 1, set. from 17 to 3 years ; 7 are living, and were examined
by Mr. Green and found normal ; the boys are the first, eighth, and fifth ;
the latter died of " brain fever " after an accident three years ago ;
the girls are Nos. 2, 3, 4, 6, and 7. The other sixteen (IV, 4 and 5)
and their parents are scattered, and could not be seen, but all are
confidently reported to see well. II, 2 had no issue by her second
husband. Her brother (II, 1) married, but had no issue. I, 1 living ;
I, 2 dead ; sight good in both. No consanguinity.

Fig. 39 (p. xcvii), from Mr. Herbert Fisher. The family records have
been accurately kept for many generations. The figure shows only
the parts of the family tree that bear upon the occurrence of retinitis
pigmentosa and deafness.

V, 5 set. 45 years, well-marked typical retinitis pigmentosa, and is
moderately deaf. V, 8 deaf, but good sight ; V, 4 died of phthisis as
a young man ; V, 3, 6, 7 and 9 normal. No other cases known of bad

BOWMAN LECTURE.

CLV

sight like V, 5, but a vague history of defective sight in IV, 12 and
III, 10. Clear history of deafness from early life in II, 6, IV, 7 and 11,
V, 8 and 10 ; the deafness has varied in severity in the different persons,
very bad in II, 6 and IV, 11, moderate in the others. VI, 2 has had
attacks of mania ; her brother, a medical man, says she resembles her
aunt, V, 5, closely in some respects. VI, 6 died in infancy " from some
defect in the larynx/' and VI, 7, the two children of V, 8, also died in
infancy. IV, 7 and his wife, IV, 3 were second cousins, but the con-
sanguinity was from another stock in which there are no known cases
of blindness or deafness.

APPENDIX V.

NIGHT-BLINDNESS WITHOUT CHANGES.

(a) The cases used, being all I have been able to find either in the
literature or amongst my own notes, are given in R.L.O.U., xvii, pp. 401
to 426, and there numbered Cases 151 to 190 (1908).

(f>) Mr. W. J. Cant's case, Case and Fig. 44. — Night-blindness without
visible changes affecting myopic males.

In this small pedigree only three or four cases are known. Two of

them have been seen and examined with care, and I therefore record the
case fully.

I, 1 was a woman who lived to be 90 ; she became blind in her old age,
but there is nothing to show that she had night-blindness.

She had at least one daughter, II, 1, but whether there were other
children is not known. II, 1 had three children, no more.

CLVJ BOWMAN LECTURE.

The first-born, III, 2, is reported by his daughter to have been " very
short-sighted and night-blind, and had always to be led about after
dusk all his life"; as he lived to be 76, and is never known to have
worn reading spectacles, he was probably myopic. He had a sister
and a brother (III, 4 and 6) who had perfect vision until they died; both
left children and grandchildren. Of the latter, two had some affection
of sight, but no one knows whether they were night-blind or not (see
below) ; all their other descendants in IV and V are normal.

He (III, 2) married twice, there being no consanguinity between him
and either wife or between the wives. By the first he had an only child
? (IV, 2), with good sight, who had an only child (V, 1, illegitimate),
now aged thirty-five and night-blind; his only child (VI, 1) is normal.
By his second wife, III, 2 had 5 children (IV, 3 to 7) all with good sight,
three <J , two $ . One of the daughters (IV, 4), who died in 1908, left a
son who is night-blind (V, 4) and a daughter (V, 3) with normal eyes.
Of the numerous other grandchildren of III, 2, none are night-blind,
but it is noteworthy that the other female who might transmit (IV,
5), has had only one child.

Description of the Cases.

Ill, 2 a compositor, who died at 76, is reputed to have been always
unable to see at night but to have had no defect in the day; his
daiighter, IV, 4, remembers (speaking in 1907) having often in former
years had to lead her father home by the arm at night ; he never Avore
any spectacles, and was therefore probably myopic in some degree.

V, 1, set. 35 years, a clerk at Doncaster, was examined by Mr. C. H.
Usher and myself at the house of Mr. Usher's brother in Lincolnshire
in 1908. Has been short-sighted and unable to see at night as long as
he can remember ; as a small boy when first at school he could not see
the blackboard ; the night-blindness has got no worse. Has never had
glasses, and the progress or otherwise of the myopia therefore cannot be
ascertained ; refraction now, estimated about 7 D. and 10 D. in R. and L.
at posterior pole, decidedly less at periphery ; f undus of medium com-
plexion and normal in every particular except for moderate myopic
crescents. Black hair, colour of irides not noted. Married eight years,
one child only. The tests as to light sense defect were necessarily
inexact but were made with much care, and in all cases were compared
with our own sight under the same conditions of light, but his myopia
was not corrected.

As to reading : — with a considerably lowered light, he was unable to
read print with his myopia uncorrected, which I (E.N.) could read per-
fectly with + 4 or + 5 D. ; but in good lamp-light he read J. 1 easily.
When shown a screen and a bed-cover, each with large patterns of different
but somewhat sombre colours, he required much more light than we did
to recognise the pattern, and this at his own normal far point. No defect
of Fs. could be discovered, but we noticed that when seeking to see
an object beyond his far point, viz., a picture, or the pattern on the

BOWMAN LECTURE. CLVII

screen, he always looked considerably above the object, i. e., he used the
retina a little above the Y.S. He was then tested in the garden in
brilliant moonlight, and the following notes made : he could not see a
white handkerchief on the grass only a foot from him, although it was
visible to all of us at many yards off ; he could not see the white cuff of
his own shirt when his coat sleeve was drawn up ; he was qiiite unable to
see a number of flowers that were easily visible to the rest of us ; finally
he was quite unable to find his way about the lawn (a flat one) without
a guide, and on turning to the house said that the lighted window was
the only thing by which he could at all guide himself ; and it was obvious
that if there had been any pit or obstacle on the ground he woiild have
walked into it unless guided. The whole result was very striking,
and certainly not to be explained merely by the uncorrected myopia.
Married eight years, one child, get. 8 years (VI, 1), seen and found to
have H. 2 D, with normal fundus, perfect sight, and no night-blindness.

V, 4 began glasses at four years old, and was first seen by Mr. W. J.
Cant in 1889, viz., when from five to six years of age, and found to be using
- 9 D. spectacles ; Mr. Cant gave him - 6 D. In April, 1904 (set. about
10 years) the E. was found to be divergent and somewhat amblyopic, V.
Avith correction being only -£± against yV with the L., and he had difficulty
in maintaining fixation with R. ; it was probably then that his present
full correction was ordered. There is no further record until the early
part of 1908 (set. 14 years), when Mr. E. C. Clements and Mr. Cant made
a careful examination, with the following results : R. — 10 D. ^ ; L.
— 9 D. sph. with — 1'5 D. cyl. £ partly; is already wearing glasses of
this strength. When the illumination is reduced to half light, V. with
correction equals only ^, and with one quarter illumination only „% and
with the window-blind drawn still further down he was unable to see a
piece of white paper 10 in. (25 cm.) square at 6 ft., even when it was
moved about. Fields for white ; L. normal in full light, much
reduced in the same half and quarter light ; when the blind was
drawn more than three quarters down the fixation object was invisible
to him even when 1 in. square ; R. (amblyopic eye) smaller for full light
than L., and shows similar further contraction in lowered light. Fundus
perfectly healthy in appearance in every detail, except for ordinary
sharply defined crescents from one quarter to one third the width of
O.D. ; especially, retinal vessels of full size and no trace of retinal pig-
mentation.

His mother noticed that his sight was not right before he was a year
old, and that when between two and three he could not see his toys if
the light was at all bad, but had to grope for them.

When Mr. C. H. Usher and I saw him (October 3rd, 1908) we found
him a tall, narrow-chested boy, 5 ft. 6 in. high, of between 14 and 15
years, with, as already noted, perfectly normal fundi ; by estimation the
myopia was much less at the periphery than at posterior pole of globe ;
choroids rather fair. Various comparative qualitative tests applied whilst
wearing his correction, such as a square of white paper several inches in
the side viewed tinder different degrees of illumination, showed repeatedly

CLVIII BOWMAN LECTURE.

that his light-minimum was much higher than ours, and that he required
longer than we did in order to see the object even when the light was
enoiigh (viz., slow adaptation) ; and with light below his minimum a
slight increase at once made the object visible to him (this also shows
slow adaptation). Fields to rough hand tests did not show contraction.
He always takes his sister's arm when out with her in the dusk. At
home he often knocks against a certain door-prop which his sister says
no one else would do.

V, 3, only sister of the last, aet. about 20 years, a school teacher, not
myopic, fundus perfectly normal.

V, 9, said to have been " very short-sighted, held his book very close,"
and his aunt, IV, 4, who knew him, wrote that " she thought he was
afflicted in much the same way as her son," V, 4 ; he did not use spec-
tacles ; died at 25. He had about six siblings, who all saw quite well.

V, 11 said never to have had good sight, and eventually went quite
blind, but no particulars are known. She is dead. She was one of the
seven or eight children. She did not wear glasses.

V, 13 known to have good sight.

IV, 4, who died during 1908, had perfect sight, as has her husband,
IV, 14.

Ill, 4 and 6 had perfect vision.

Xo consanguinity between IV, 4 and 14.

Case 44a (no figure). — By a curious coincidence another family with the
same complaint lives in the next village to V, 4 of the case just narrated.
The two families are not related in any way on either side ; the former
came from a distance in recent years, the latter has been settled as
farmers at or near Navenby for a long time.

This second family could not be fully searched out ; the information
obtained is given for what it is worth.

Ill, 1 and 2 were first cousins and I, 1 was the grandfather of one of
them and he became blind, probably from cataract, in old age, and died
recently (1907 or 1908) at 80. II, 1 is living and sees well; her
husband, who also had good sight, died in middle age. They have 5
children, and I believe there were no more.

Ill, 1, set. 24 years, very poorly educated on account of his bad sight, is
said by his mother to have been very short-sighted and night-blind since
early childhood. When examined (October 3rd, 1908) we estimated his
myopia at about 10 D. by direct ophthalmoscopic measurement, and found
the retinal vessels normal and no fundus changes, except moderate cres-
cents. With his spectacles on his sight was conspicuously defective for
objects 4m. to 5m. off in a dim light (partially darkened passage in his
own house) ; without glasses he only read J. 4 word for word, but as he
was almost illiterate this test Avas inconclusive ; the Fs. to rough hand
test seemed full. His mother said that he always had to be led home
from church after evening service.

Ill, 2, at. 17 years, now has about 3 D. of myopia, and did not show
any shortness of sight till she was about 13. Nothing was said about
night-blindness in her; fundus normal.

BOWMAN LECTURE. CLTX

III, 5, set. 13 years, is just like III, 1 in his sight ; has been very short-
sighted and blind at night since early childhood ; now has about 10 D. of
myopia, with moderate crescents, but no other fundus changes ; read J.
3 and 4 fluently both with and without her glasses. Like her brother,
III, 1, she has always to be led home from evening church. The other
two have no defect. There is a history of " blindness " in a half-cousin,
biit no particulars were to be had.

APPENDIX VI.

LEBER'S DISEASE.

(a) Abstracts of Published Cases in Chronological Order beginning with
r. Graefe's case, 1858, to which are added some hitherto unpublished
Cases communicated by friends or taken from my own note-books.

The references down to 1899 are taken chiefly from Habershon's paper
in T.O.8., viii (1888), and Hormuth's Dissertation published in 1900
(title given on p. cxxxvii). The particulars of each case are also in
many instances taken from Hormuth's tables. When, however, his
abstract of a case seemed unsatisfactory reference was made to the
original ; but such reference has seldom led to any correction of
Hormuth's rendering. All cases consulted in the original are marked
with a star (*).

1858. Case 70. v. Graefe, A. P.O., iv, 2, p. 256.

Male, onset at twenty years of age ; failure progressed three months,
both eyes ; recovered to reading small print in four weeks ; no ophthalmo-
scopic note. His brother, onset set. 20 years, J. 20, no improvement ;
fundus normal three years later. Third brother, also attacked in same
way at nineteen. Parents normal.

1862.* Case 71. Sedgwick, Med. Times and Gaz., i, p. 309.

Usually quoted as Leber's disease, but the coincident family paralysis

f

and absence of ophthalmoscopic examination exclude precise diagnosis.
I, 1 blind from " amaurosis " at about 55. II, 1 amaurotic both eyes at
56 ; 2, living, Bet. 63 years, good eyes ; 3, died paralysed but good vision,

CLX BOWMAN LECTURE.

at 56; 4, living at 60,, paralysed, good sight ; 5, living, set. 56 years, good
sight, no mention of paralysis ; 6, amaurotic, both eyes, at 48, died para-
lysed ; 7, left eye amaurotic at 48 ; 8, amaurotic both eyes at 42, died,
but age and cause not given ; 9, normal, place in childship not noted ;
10, normal, set. 38 years.

1885. Case 72. v. Graefe, K.M./.A., iii, p. 222.

Two brothers, both attacked at 23, in both eyes ; central scotoma,
moderate optic atrophy in one patient, no note in other ; no recovery.
Family history negative.

1867.* Cases 73-76. Mooren, Ophthalmiatrische Beobachtungen, p. 305.

Three brothers and an uncle, loss of central V. with slight neuro-
retinitic appearances. Ibid., three brothers ; ibid., two brothers ; ibid.,
two brothers. All attacked between 18 and 23. Some improvement in
early period of treatment in all.

1871. Case 77. Leber, A./.O., xvii, 2, p. 249, family II. Two brothers
and a sister affected out of six. Parents normal. II, 1 affected at 17,

T

M

seen at 30. II, 3 affected at 28, and II, 6 at 19, both seen at early stage.
All three recovered after some months from finger V. to J. 1

1871. Case 78. Ibid.

Family III. A brother and sister affected out of four. Parents normal.
II, 2 affected at 27 ; II, 3 at 21. No recovery.

1871. Case 79. Ibid.

Family I. Five brothers in a sibship of six, and two maternal

uncles. Parents normal. No recovery. II, 1 affected at 20 ; II, 2 at 13 ;
II, 3 at 28 ; II, 4 at 13 ; II, 5 at 21 ; II, 6, sister, place in childship not

BOWMAN LECTURE. CLXI

stated, escaped. I, 1 and 2, two brothers of mother affected, ages at
onset not given.

1867 and 1871.* Case 80. Hutchinson, R.L.O.H., vii, p. 170, and ix, p.
301, and Med.-Chir. Trans., 1, 1867, Case 24.

Mother, I, 2, affected at 43, her son and her nephew (II, 2 and 1) as
young adults (exact ages not given). No note as to sex of 1, 1 or sib-
lings of II, 1 and 2.

1872 and 1873.* Case 81. Daguenet and Galezowski, Journ. d'Ophthal-
mologie, i, 342, and Prouff, These de doctorat, No. 112, Paris.

I, 3 affected at 21 ; II, 1 affected at 26 ; II, 2 at 24 ; II, 3 at 21 ; II,
4 at 27 ; II, 5 at 21. The three mothers, I, 1, 2, 4, normal.

1873.* Case 82. Leber, Nagel's Jahresbericht, ii, p. 324, foot-note.

Two brothers; elder affected in twentieth year, E. beginning six
months before L., 110 recovery; younger brother (age not stated) affected
in exactly same way.

1874. Cases 83-85. Mooren, loc. cit., p. 87.

Two brothers ; ibid., two other brothers ; ibid., three brothers. Ages of
onset not given. One of them with V. reduced to J. 15 improved to
reading J. 1 in eighteen months.

1874. Case 86. Alexander, KM.f. A., xii, p. 62.

I, 1 age of onset not given; did not recover. II, 1-3, sons of sister of
I, 1. II, 1 affected at 29 ; II, 2 at 23 ; II, 3 at 20 ; all attacked in same
year. No recovery. No other cases in family. (Sex signs omitted in II,
by oversight.)

1876. Case 87. Pufahl, Berliner Tdin. Wochenschrift, No. 10.

I, 1 affected in his youth, and improved enough to read writing. II, 1
affected at 21 ; II, 2 at 27, " temporary improvement " in both ; II, 3
affected, no particulars. The three sisters and parents normal.

1878. Case 88. Pufahl, Beitriige z. prakt. Augenheilk. v. Hirschberg, iii,
p. 75.

I, 1 and 2 affected at 20 ; I, 3 not until 57 ; II, 1 at 19 ; II, 2 at 17.
No improvement. Parents normal.

CLXI1 BOWMAN LECTUKE.

1879. Case 89. Fuchs, K.M.f. A., xvii, p. 332.

In a childship of eight, first-born ( <J ) and four sisters normal. The

± \ f

1 ••$ »9

other three brothers (II, 2, 3, and 4) affected at 32, 25, and 22 respectively.
Parents normal.

1879.* Case 90. Ibid.

I, 1 and 2 affected at 21 ; I, 1, set. 59 years when seen ; I, 3 to 6 normal
sisters, one of whom (6) had five sons and one daughter by normal

husband. The five sons (II, 1, 2, 3, 5, 6) all affected, II, 3 at 33, the other
four about 20-21. No recovery.

1879. Case 91 . Ibid.

Three brothers ; eldest affected at 52, next at 49, last at 48. No
recovery.

1880.* Case 92. Higgens, Med. Times and Gaz., i, p. 450.

Father, I, 2, died at 74, 1878, good sight, his last child then quite young.
Mother, I, 1, living in 1880, good sight, had fourteen conceptions, of
which two miscarried ; five boys and two girls (II, 6 and 7) died young
of measles or whooping-cough ; five living at date of record, viz., II, 1
affected at 16, II, 2 at 15, watched till 19, no recovery, severe case ; II, 3,
age at onset not given, but apparently younger than 1 and 2 ; II, 4 and
5 quite young at date of record.

1882.* Case 93. Norris, T.A.O.S., iii, p. 355.

Five generations ; transmission by affected malos. No consanguinity.
I, II, and II [, 1, all said to have been affected. IV, 1 affected, but after

BOWMAN LECTURE.

CLXT1I

being "blind" recovered enough sight to resume ordinary occupations ;
his son (V, 1) affected, no details. IV, 2 normal, had nine children (V,
2-10), of whom first (V, 2) was affected at 48 and seen at 49, and fourth
(V, 5) seen at 43, age at onset not given. The two daughters (V, 3 and
8) normal at 46 and 33 respectively. The other five died in infancy,

2.3-^5-67

sexes not stated. IV, 3 affected, age of onset not recorded ; her son
(V, 11) affected at 49, seen at 50. "Most became affected between 25
and 40."

1882. Case 94. Schluter, "Uber Neuritis Optica," Inaugural Dissert.,
Bonn.
* Family I. I, 1 and 2 normal sisters. II, 1 affected at 25 ; II, 4, 5, 6

95-

i ,9 ,0

. f& m

9 "9

all affected at 20. Ill, 1 at 20; III, 3 and 4 between 17 and 20
consanguinity.

No

1882.* Case 95. Hid. Family II.

I, 1 affected at 20; his two sisters, I, 2 and 3, normal. II, 1 affected

CLX[\r BOWMAN LECTURE.

at 39, seen at 44; II, 2 affected at 12, seen at 33 ; II, 4 affected at 25,
died at 28 of diabetes ; II, 5 and 6, brothers, affected at 20. No con-
sanguinity. No record of any sisters in II. (Numerals omitted from
Figure, in error.}

1882.* Case 96. Ibid. Family III.

I, 1 affected at 20; I, 2, age at onset not stated; I, 3 normal. Of her
four children the youngest, II, 4, affected at 11 and seen soon after ;
eldest, II, 1, set. 24 years, and the two daughters, normal. I, 4 an
affected female cousin of I, 3. No consanguinity.

1883. Case 97. De Keersmaecker, Recueil d'Ophtal., 1883, p. 193.

Four brothers affected at 20, 40, 32, and 37 ; order of birth not recorded.
Also a male nephew at 19 ; presumably his mother was sister to the four
affected brothers, but this not stated.

1885.* Case 98. Story, Ophthalmic Review, iv, p. 33.

In a sibship of 8, 4 brothers and 4 sisters, the eldest brother affected
before 23, and died of epilepsy at 23 ; second brother affected at 21, died
of phthisis, and was alcoholic ; third brother affected as a young man,
and died in an asylum ; fourth brother affected at 30, was 45 at date
of record, and had had attacks of insanity. Of the sisters, the third,
affected at 40, was seen in the early stage at about same date as the
fourth brother ; her two older sisters (places in sibship not recorded)
very excitable ; youngest sister and eighth born normal.

1885.* Case 99. Holz, "Drei Fiille von genuiner Atrophia nervor.

opticor. simplex progressiva bei (resell wistern/'Jnawgr. Dissert., Greifswald.

Notwithstanding the title the cases read like typical examples of

I 2. 3

Leber's disease. Parents (I, 1 and 2) and grandparents normal; II, 1,
set. 28 years, normal ; II, 2 affected at 22, seen at 23 (avithor's Case 3) ;
II, 3 affected at 18, and seen at same age and until 20 (author's Case 1) ;
II, 4, aet. 18 years, normal ; II, 5, affected at 15, seen nearly a year later
(author's Case 2). No improvement of II, 3 in two years.

1887.* Case 100. Habershon, T.O.S., viii, p. 190. Author's Case 1.

Two brothers ; one failed at 22 rapidly, seen at 31, had not improved;
My. 1'5 D., V. J. 19 ; married at 19, and had two children before eyes
failed, who are living and well. Other brother, five years younger, failed

BOWMAN LECTURE.

CLXV

at 17, seen at 26 (same time as elder brother), and again at 34 (1895) ;
no improvement ; V. J. 16, close to and fingers 2 m., My. 6 D. There are
several other brothers all normal (no mention of sisters) ; parents saw
well ; father died of cancer, mother phthisis.

1887.* Case 101. Ibid., Case 2 (E. N.'s case, P. 4, 215).
Three brothers: one affected at 31, and seen at 32; the other two
failed in exactly same way, but ages not given.

1887.* Case 102. Ibid., Case 3 (E. N.'s case, P. 14, 177).

I, 1 a weakly woman ; I, 2 died of cancer at 67 ; II, 1 not much in-
formation, but no cases known on her side ; II, 2 was one of a very
large sibship, of whom only three lived to grow up, all males ; he died

HE

at 55 ; no consanguineous marriages ; no recoveries ; III, 1 affected at 16,
seen at 45 ; married, no issue ; III, 4 affected at 15, seen at 39, some
children ; III, 7 affected at 17, at 32 had some children ; III, 9 affected
at 12, set. 27 years when III, 1 was 45 ; III, 2, 3 and 10 died of phthisis
between 17 and 22; III, 5 of disease of spine at 24; III, 6, 8 and 11
(set. 24 years) normal.

1887.* Case 103. Ibid., Case 4 (E. N/s case, P. 10, 26).

I, 1 and 2 brothers, normal; II, 6 affected at 21, set. 50 years at date

CLXVI BOWMAN LECTURE.

(1884); II, 7 not affected until 60, and became diabetic later; III, 2
affected at 34, no recovery, living aged 55 (1906) ; III, 3, age of onset not
known ; III, 4 affected at 16; II, 3 all died of phthisis, normal sight ; II,
8, 9 and her two adult sons III, 5 and 6, and II, 10, single, all normal.

1887.* Case 104. Ibid., Case 5 (E. N.'s case, T.O.P., in, p. 147, and
T.LP., 1881, and pp. 5, 11 [Crane]).

Two brothers : the elder attacked at 22, and seen soon after ; the
younger attacked at 19}, seen at intervals for four years, and V. remained
about ¥80. The brothers failed within about four months of each other.
A brother of their mother (Boxall) has had bad sight many years.

1887.* Case 105. Ibid., Case 6 (E. N.'s case, M., i).

Two brothers and, perhaps, a sister. Elder brother affected at 23,
set. 30 years at record, no recovery ; other affected brother failed at 19
when elder brother was 30. A sister bad sight and wears glasses, not
seen, and has fits (P epileptic). One other brother and two other sisters
normal ; the brother died of phthisis. Parents normal sight ; father
died of phthisis.

1887.* Case 106. Ibid., Case 7 (E. N.'s case, M., i).

II, 1 attacked at 23, died unrecovered at 40 ; II, 2 married at 23, and
had eight children and one miscarriage in eighteen years, the eldest
eet. 17 years ; the last child, set. 1 1 months, born when she was 40 ; all
suckled. Her sight failed at 40 when suckling last child.

1888.* Case 107. Edgar Browne, ibid., p. 235.

Three brothers; II, 1, firstborn, attacked at 27, seen at 40; II, 2
attacked at 32, seen very soon after ; III, 3 seen soon after onset, age not
given. The two sisters, places in sibship not given, normal.

1888.* Case 108. Haswell, Brit. Med. Journ., ii, p. 1279.

I, 1 and 2 normal, but an indefinite history of bad sight in relations of
I, 2. II, 1 normal, and II, 2 attacked at 48 ; II, 3 at 9 ; II, 4 at 21 ; II, 5
at 14. Ill, 2 attacked at 27 ; III, 5 at 33 ; III, 7 at about 20; III, 8 'at
29 ; III, 9 at 18, set. 37 years at record ; III, 10 at 20. IV, 4, age at attack

BOWMAN LECTUEE.

CLXVU

not given ; IV, 9 at 17. Four of those affected were seen ; onset rapid in
all, then stationary at V. about fingers, with atrophic discs when seen

Fi'q.108

about 15 to 20 years after onset. In March, 1909, Dr. Has well was
unable to supplement the notes.

1888.* Case 109. Thomsen, Munch, med. Wochenschr., xxxv, p. 222 ;
Berliner Gesellsch.f. Psychiatrie u. Nervenkranlcheit (1888).

Six brothers, and two of their maternal uncles. Age of onset 21 in one
of the six brothers, not given for the others.

1892.* Case 110. Taylor (S. Johnson), T.O.8., xii, p. 146, and later
notes, 1909.

Pedigree of four generations : I, 1 became blind or nearly so at 40, eyes

looking natural. II, 1 and 2 had respectively 10 and 5 normal children.
II, 3 married 4, both normal and not consanguineous ; issue, 11 children,
all grew up, and one miscarriage ; of the 0 sons, 4 affected, III, 3 at 28,
seen at 27, died of lung inflammation at 37, leaving one son (a soldier in

CLXVI1I

BOWMAN LECTURE.

1909, with good sight), and 5 daughters, all good sight ; III, 4 affected at
21, seen at 25, living in 1909 and has 5 normal children ; III, 7, one eye
only aft'ected at 6, and still same in 1909 ; III, 10 affected at 6, seen at
13, and heard of in 1909 as in same state at 30, unmarried. The 3
daughters, III, 5, 6, and 8, aged in 1909 about 40, 39, and 35 years, have
19 children, all normal.

1891.* Case 111. Sym, Edin. Med. Journ., xxxvi, p. 1133.

I, 2 affected at 51, living at 75 ; her ascendants not known. II, 1
affected at 26 ; II, 3 affected soon after severe cupping for yellow fever at
20, now 47 (1891) ; II, 4 at 33 ; II, 5 at 25, now 36, has two sons of 8 and
6 (1891) (III, 3 and 4). Ill, 1 and 2, set. 18 to 12 years, all normal.

1892.* Case 112. Despagnet, Soc. Franc. d'Ophtalmol, p. 392.

I, 1 to 4 all normal. II, 3, first wife of 4, issue normal ; 1, 2, and 4 all
normal ; II, 4 died at 62, alcoholic ; II, 5, second wife of 4, died at 58 ; of her
siblings, II, 7 failed in sight at 50, cause unknown, died at 52. Ill, 3
affected at 26,41 at record; her "eldest son," (IV, 1) affected at 20,
papillitis chiefly L. V. £ in L., normal in R., F. contracted. Ill, 4 at 30 ;
III, 5 at 31, married at 27 ; III, 6 at 32, married a.t 28 ; III, 7 doubtful,
slight case, at 30. No consanguinity. (Cf. Case 110.)

1892.* Case 113. Somya, K.M.f.A., xxx, p. 256.

Vague history of similar blindness in ascendants of I, 1 and 2. II, 2
affected at 34, II, 3 at 28, II, 5 at 18, seen by author ; II, 6 and his
ascendants normal. Ill, 1 " blind," III, 2 very amblyopic but exact data
wanting. Ill, 3 affected at 19, seen by author.

1892.* Case 114. Thompson (J. Tatham), T.O.8., xii, p. 156.

A man, set. 37 years, E.. affected about two months before L., typical,
except for a small hsemorrhage in L. retina near O.D. in early stage
when neuritic appearances were present. A brother of his mother was
" blind " from " disease of optic nerves."

1896. Case 115. Ogilvie (F. Menteith), T.O.S , xvi, p. 3.

Three brothers in childship of 16 ; II, 4 affected at 24 ; II, 9 at 27 ; II,

BOWMAN LECTURE.

CLXIX

13 at 22. Eight others died in infancy and 2 miscarried. Ill, 1 to 10,
set. from 6 years to a few months, the twins (III, 2) and III, 6 died or
still-born. I, 6 and 7 normal ; one of I, 5, and also II, 14, bad hysterical
fits. In II, 9 L. eye improved from ¥30 to /T in between two and three
months.

1896.* Case 116. Batten (E. D.), T.O.8., xvi, p. 125.

I, 1 and 2 and collaterals normal. II, 1 affected at 11, seen at 51, no

i. 115

improvement ; II, 2 affected at 10, died at 33 ; II, 3 at 12, seen at 48 with
V. ¥20, age at marriage not stated ; has had only 4 children, 3 of them
affected; III, 1 died set. 3 years ; III, 2 affected at 11, V. with H. 4'5 D.
corrected •£%, four months later /T, a year after second note £ ; III, 3
failed down to ^ at set. 9 years, with pale O.Ds. ; III, 4 failed at 8,
with H. 3 and slight As. corrected £ , O.Ds. much congested ; two years
later only T\ (1898). No consanguinity.

1897'* Case 117. Snell, T.O.S., xvii, p. 66. Author's Case 1.

I, 1 to 4, and II, 1 to 3 all known to have had good sight. In III, 1
set. 32 years ; 4, 29 ; 5, 27 ; 7, 24 ; and 8, 21, all severe amblyopia from
their earliest recollection with pale O.Ds. and no other changes, no
scotoma (but V. " better at night") and no contraction of Fs. V. from J»n
in III, 1 to ^ in III, 8. Ill, 2 doubtful, is colour-blind like the rest, but
V. R. £, L. T°2-, and no note of condition of O.D. IV, 1 and 2, young
children, 1 set. 3 years examined and normal.

1897.* Case 118. Ibid. Author's Case 2.
Two brothers, both affected in same way at 17 years,
guinity and no other cases known in relations.

No consan-

1897.* Case 119. Ibid. Author's Case 5.

Ill, 1, 3 and 5 all affected at 13, seen at same date at 40, 32, and 26
respectively. Ill, 2 at 36 ; 4 at 29 ; 6 at 23, normal. Ill, 1 and 3
married some years, no issue ; III, 5 has three normal children. All in
I and II lived to good age with good sight. No consanguinity. II, 1,
63, and 2, 64 at record, and were about 22 and 23 at marriage.

8

CLXX

BOWMAN LECTUEE.

1897.* Case 120. Ibid. Author's Case 6.

II, 1 " blind " in middle age and never recovered ; II, 2 lived to 85, good
sight ; II, 3 lived to 67, he and I, 1 good sight ; III, 1 affected at 52, seen

again at 62, has three sons all normal ; III, 2 at 57, seen same time, six
children all normal, subject to fits from age of 24 to 40 ; III, 4 affected
at 36, seen at 44, married, no issue. Ill, 5, set. 43 years ; III, 6 and 7
died in infancy. No consanguinity.

1896. Case 121. Velhagen, Deutsche med. Woch., p. 841.
Three brothers affected, II, 1 at 19, II, 2 at 25, II, 3 at 20, set. 24 years
at record ; several others died young. Parents normal.

1897.* Case 122. Higier, Deiitsche Zeitschriftf. Nervenheilkunde, x, p.
489.

I, 1 affected at 20, and improved in about a year. II, 1 at 27, seen
soon after ; II, 2, six years younger than II, 1, affected at 20 ; II, 3
epileptic and subject to migraine. Parents normal and not consan-
guineous.

1900. Case 123. (First of Leber's 9 new unpublished cases) Hormuth's
text, p. 16, and his Tables, p. 114.

BOWMAN LECTDEE. CLXXI

III, 1 affected between 22 and 23, nine months' interval between the
two eyes, final result not reached at date of record ; III, 2, L. six
months before R. at 22 ; E/. recovered perfectly, L. did not recover
seen finally five years after onset; III, 3 affected at 17, improved some-
what, but not enough to read ; I, 2 was " blind " for six months at 27,
but recovered ; her brother, I, 1, also had some disease of the eyes, and
got better.

1900.* Case 124. Ibid., p. 11. Family 1. Tables, p. 110.
Four males, sons of three sisters, ages not given; first case (II, 1)
seen a year after onset.

1900.* Case 125. Ibid., p. 12. Family 2. Tables, p. 110.
Two brothers; elder affected at 39, younger at 18. Family history
not given.

1900.* Case 126. Ibid., p. 14. Family 3. Tables, p. 112.
Two brothers affected at 20 and 27 ; an uncle, brother of their mother,
had same disease at 24.

1900.* Case 127. Ibid., p. 18. Family 5. Tables, p. 116.

Two male cousins affected at 21 and 30; their mothers were sisters. A
brother of the two mothers, maternal uncle of the other two cases, also
affected at about 18 or 20.

1900.* Case 128. Ibid., p. 20. Family 6. Tables, p. 116.

In a childship of 5, the 2 brothers affected at 25 and 17, and of the 3
sisters, 1, much younger than the brothers, affected at 42 ; the other 2
sisters normal. Parents normal.

1900.* Case 129. Ibid., p. 20. Family 7. Tables, p. 118.
Two brothers, affected at 24 and 32. History incomplete.

1900.* Case 130. Ibid., p. 22. Family 8. Tables, p. 118.
In a sibship of 8, 2 brothers affected at or about 20 ; the elder now 40,
the other quite recent, set. 20 years, at date of record. Parents normal.

1900. Case 131. Ibid., p. 23. Family 9. Tables, p. 118.
Two brothers affected at 18. Nothing else recorded.

1900.* Case 132. Ibid., p. 154. Leber's supplementary cases, not pre-
viously ptiblished, given to Hormuth. Family 1. Not in tables.

Sibship of 3 ; 2 brothers, the elder affected at 27, the other, 9 years
younger, at 18 ; one sister between them normal. Both recovered, the
elder to being able to read, the other to being able to resume his
painting.

1900.* Case 133. Ibid., p. 157. Family 3. Not in tables.

I, 3 affected, but age of onset not noted. II, 1 and 2 each affected at
about 23, 1 being two years older than 2. One normal sister, age not
given.

BOWMAN LECTURE.

1900.* Case 134. Ibid., p. 156. Family 2. Not in tables.

Two brothers ; one affected at 14, seen at 40, V. -f^ or -^^ ; the other
about two years younger, not affected till 40, seen soon after. No other
cases known in family.

1900.* Case ]35. Ibid., p. 158. Family 4. Not in tables.
Nephew and uncle ; nephew attacked at 31 and seen at 37 ; age of
onset in mother's brother not recorded.

it **6l
•J

I 2. 3 ^ S (, 7

1900.* Case 136. IbidL, p. 158. Family 5. Not in tables.

I, 1 and her husband, 2, a physician, normal. II, 1, 2, 3, three normal
daughters ; no record of any other children. Ill, 1 affected at about 55,
seen some months later, and improved definitely in four months ; III, 3
affected at 22 ; III, 8 at 40 ; age at onset in III, 4 not given.

1900.* Case 137. Ibid., p. 160. Family 6. Not in tables.

Two brothers ; one failed at about 48, seen two and a half years later,
set. 51 years ; other brother affected at 27, present age not given.
Parents, good eyes.

1899.* Case 138. Strzminski, Ann. d' Oculistique, cxxi, p. 99.

I, 1 said to have had the disease. II, 1 affected at 25, seen at 58
(1897), typical central defect with also concentric contraction of Fs. Ill,
1 affected at 24, seen at 36 (1897) ; III, 2 at 25, seen at 35. Age of
onset in III, 3, 4, and 5 not given. One of these three epileptic, and
others mentally affected.

1895.* Case 139. Westhoff, C.f.A., p. 168.

Five generations. I, 1 and 2 normal, had one normal daughter, II, 3,
who transmitted the disease to her sons by both her husbands, and 2
sons, II, 4 affected at 25, and II, 5 at 23 ; all their descendants in III
and 4 and 5 to date, normal. Ill, 2 affected at 20 ; III, 4 and 5 both at
19. IV, 1 at 21 ; IV, 3 at 22 ; IV, 4 at 17 ; IV, 5 at 19. Connecting line
between II, 4 and his children III, 6 and 7, also betiveen II, 5 and his
children III, 8 and 9, accidentally omitted in the Figure.

1895. Case 140. E. N., unpublished, St. Thomas's Hospital, 1890-91.
(Pitt, Barrett, and Wilson.)

BOWMAN LECTUKE.

CLXXIII

I, 1 and 2, no information. II, 2 to 6, their issue. II, 2 had bad sight
and married a first cousin with bad sight, but no particulars of the dis-
ease or of kind of cousinship, nor of sight of their 12 children (III, 1).
II, 3 had 10 children, of whom a son and daughter (III, 2 and 3) had
some defect of sight, but no details. II, 4 also some unknown affection

of sight ; II, 5 affected at 14, and went to Moorfields then ; living, aet. 61,
in 1891, sight not improved ; II, 6 living, with good sight. Ill, 5 (Mrs.
Pitt) failed at 30, married at 18, no children ; III, 8 (Mrs. Barrett) failed
at 20, has had children, too young to show the disease (IV, 1 and 2j ;
III, 9 (Lynham) failed at about 22, seen nine months later ; III, 10
(Wilson) failed at 22i after influenza, seen six months later; III, 12
(fifth born), fits.

1895. Case 141. E. N., unpublished, St. Thomas's Hospital, 1885 and
1893. (Donovan.)

I, 1 and 2 had good eyes. II, 1, Hodgkins, of Birmingham, had a son
(III, 1) affected at about 40; 11,3 married Jones and had son (III, 3)
affected so early that he never learned to read, set. 30 years in 1893 ; II, 4
married Donovan II, 5 and had issue. Ill, 4 ( J. Donovan) affected at 30,
seen at 30 and again at 43 ; III, 5 (Mrs. Leonard) married at 22, affected
at 33, and seen soon after ; III, 8, 10 who died quite young. IV, 1
affected in early life, could never see his work properly ; IV, 2, five
children of III, 4, two dying early ; IV, 3, four children of III, 5, two
dying early.

1895. Case 142. E. N., unpublished, Moorfields Hospital, 1896.
(Laxford.)

I, 1 believed to have had bad sight ; had two sons undoubtedly affected
like the rest (II, 1 and 2) ; I, 2 certainly affected ; had one normal
daughter (II, 3) with normal children (III, 1, 2, and 3), one affected
daughter (II, 4) and two affected sons (II, 5 and 0) ; no record of other

CLXXIV

BOWMAN LECTUKE.

children. II, 5 and 6 apparently s.p., but II, 4 had seven children, viz.,
Ill, 4 died in infancy ; III, 5 died unaffected at 60, probably heart
failure ; III, 6, set. 60 years in 1896, no issue, believed to be affected ;

"f 1 ...
'4£pzi

- :Sto3 *

1£

,© &

III, 7 affected, set. 58 years in 1896, had then had four children, IV, 1
died of influenza, and 3 living ; III, 8 probably affected, died suddenly
at 30; III, 9, patient, failed at 26, seen at 56 (1896), has normal children
(IV, 5 and 6). IV, 8 to 11, 9 children of III, 10, 6 of whom died young.

1895. Case 143. E. N. (unpublished), Moorfields Hospital, 1897.
(Philbrick.)

I, 2 was affected ; II, 1 affected at 14, recovered sufficiently to be able
to read ; II, 2 affected at 33 ; II, 3 and 4 each at 25 ; II, 5 and 6 are the
last born of the childship ; III, 1 patient, set. 22 years.

Fi«. /44

HL •00*^ UL

I Z 3 <V S 6 7

1895. Case 144. E. N. (unpublished), Moornelds Hospital, 1890.
(Haile and Drudge.)

I, 2 reported to have had the family blindness ; II, 1 to 6, order of
birth not knoAvn ; II, 1 and 2 affected ; II, 4 had 16 children, of whom
first born, III, 1, was affected at 22 and seen at 29, unmarried; III, 2 and

BOWMAN LECTURE.

-CLXXV

3 unmarried ; III, 4 affected at 17, and seen then ; III, 5, 12 who died
young. No consanguinity.

1895. Case 145. E. N. (unpublished), Moorfields Hospital, 1891.
(Booty.)

I, 1 affected, " nearly blind/' has children, but no details ; I, 2 similarly
affected, and has an affected son (II, 2) ; II, 7 affected at 12, seen at 49,
no recovery, married, no issue ; II, 8 also affected, unmarried ; II, 9 un-
married. No consanguinity.

1907.* Case 146. Gunn (E. Marcus), T.O.S., xxvii, p. 221.

Incomplete, and cannot be completed. I, 1 affected in childhood,
married a first cousin (kind of cousinship not recorded), and had (up to
1907) two children ; II, 1 affected at 5, seen at 8 ; II, 2 affected at 3,
seen at 4.

1887.* Case 147. Lawford, St. Thomas's Hospital Reports, xvii, p. 158.
Author's Case 1.

I, 1 and 2 sisters; I, 1 had at least three children, of whom II, 1
certainty got the affection at 19, and 2 and 3 probably suffered; I, 2 had

seven children, of whom all the sons suffered ; II, 7 at 31, seen at 32 ;
II, 8 (4 years younger than 7) at about 18 ; and II, 9 (3 years younger
than 8) at 19 ; eldest, II, 4, set. 39 years, and youngest, II, 10, 22 at
record ; II, 7 was also congenitally colour-blind.

1887.* Case 148. Ibid. Author's Case 2.

I, 1 good sight, but epileptic fits, husband good sight ; II, 1 affected
at 18 ; II, 3 living and normal; II, 2 died at 2, " consumptive bowels" ;
II, 4 still-born ; II, 5 at 1 year ; II, 6 and 7 at 1 year of diarrhoea.

1875.* Case 149. Schilling, Inaug. Dissert., Berlin.

I, 2 married twice, by first husband (I, 1) three sons ; II, 1 affected at
14, seen at 38 ; II, 2 affected at 10|, seen at 36 ; II, 3 began at 29, seen
at 34 ; by second husband (I, 3) 2 sons ; II, 4 affected in eleventh year,
26 at record ; II, 5 affected in twentieth year, 24 at record ; one daughter
II, 6, who at 20 became extremely amblyopic of both eyes (.fingers 12 in.)
with contracted Fs. but no ophthalmoscopic changes, and recovered
perfectly ; no note about her pupillary reaction ; probably hysterical
amblyopia. No positive information about vision in parents, nor as to
consanguinity.

CLXXVI

BOWMAN LECTORE.

1890. Case 150. Nicolai, Naff el's Jahresbericht, xxi, p. 353. (Original
in Dutch, not seen.)

Three brothers attacked at 32, 29 and 25, and a nephew at 36 ; no
female suffered.

1895.* Case 151. Linde (Max), C.f.A., p. 363.

Mother and daughter. Mother, eet. 26 years, sight bad as now from
earliest recollection ; fingers 8 feet, scotoma, O.Ds. white, retinal vessels
normal ; very undergrown, but well-proportioned, teeth and skull normal ;
has 4 living siblings, one of whom (?) is, like her, very small ; one other
died at 2 ; her parents normal sight. Daughter, set. 3$ years, sight fail-
ing 2 years, sees large objects ; O.Ds. white with some surrounding haze,
no choroiditis ; had many convulsions at about 18 months old ; teething
and walking both delayed ; rather undergrown ; skull normal ; no note
of any siblings.

1897.* Case 152. Leitner, Szemeszet, Nos. 3, 4. Author's Case 1.
I, 1 and 2 normal ; II, 1 affected at 23, II, 3 at 24, II, 4 at 25 ; III, 1
normal. III, 2 affected at 25, III, 3 at 23, III, 4 at 24.

1897.* Case 153. Ibid. Author's Case 2.

I, 1 and 2 both normal : II, 1 affected at 39, II, 4 at 25, III, 5 at 13,
III, 7 at 22, III, 13 at 20.

.liL

1898.* Case 154. Posey, Ann. of Ophthal. and Otol., vii, p. 357.

I, 1 died at 60 and I, 2 at 72, both with good V. II, 1 (author's Case 3)

BOWMAN LECTURE.

CLXXVJI

failed at 30. II, 2 had glaucoma, married, no issue. II, 8, 3 who died
" young " but with good sight. Ill, 2 (author's Case 2) failed at 24, has
one child of 14 (IV, 1). Ill, 7 "bad sight" without further details.
IV, 2 (Author's Case 1) failed at 25 ; IV, 3 two young children, good
sight. Married, but without issue, II, 3 ; III, 1, 4, 5, 9, 10, and 12.

1898.* Case 155. Leitner, second paper. Ibid., No. 3. Author's

Case 1.

I, both normal ; II, 9 sisters and 3 brothers all normal and all having

children. Ill, 1 affected at 18, III, 2 at 24, III, 3 at 20 ; III, 4, three
normal sisters ; III, 15 at 18, set. 24 years at record. Ill, 14 normal at
32 ; III, 24, 11 siblings, eldest 21 ; III, 25, another 11, eldest 24; III, 26
set. 9 years. No consanguinity, no early deaths.

1898.* Case 156. Ibid. Author's Case 2.

I, 1, 2, and 3, normal. II, 1, set. 20 years, and 2, set. 18 years, also 3 and
4, all normal. II, 5 affected at 15, II, 6 at 12, both seen four years later,
no recovery. No consanguinity.

1898.* Case 157. Ibid. Author's Case 3.

Single case in a $ coming on at 16, seen at 17 ; V., fingers 0'5m.,
symptoms typical ; has 2 sisters, normal. No other details. No consan-
guinity.

1899.* Case 158. Magers, Inaug. Dissert., Jena. Author's Case 1.

Male twins ; one affected about a year before other, at about 16 and 17
respectively. E. eye failed before L. in both. Parents, good sight, but a
brother of the mother had the same disease at about 20.

1901.* Case 159. Galleniaerts, Policlinique, Bruxelles, April 1st.
Author's Cases 3 and 4.

I, 3 reported affected like the others, and all his 5 children (II, 6) said to
have bad sight of the same kind ; II, 1 affected at 21, set. 33 years and
unmarried at record (author's Case 4) ; II, 2 affected at 17, seen soon
after (author's Case 3).

1901.* Case 160. Stood (Dr. W., of Barmen), K.M.f.A., 39, i, p. 238.

CLXXVI1I

BOWMAN LECTURE.

Fourteen members of a family affected. Two of them, a young man
whose case at first looked hopeless, and his sister, recovered V. £.

1902.* Case 161. Velhagen, Miinch. med. Woch., p. 941.

1, 1 died insane. Ill, 3 affected at 21, now 50 (1902). IV, 1 affected
at 21, now 27 ; IV, 2 and 3, both at 21, now 44 and 29 with V. from ^ to
-^y. Numerous other descendants of I, 1, but no other cases. No known
consanguinity.

1902.* Case 162. Lauber, Wiener Uin. Woch., p. 1264.

I, 1, father of either II, 1 or II, 2, was " blind " ; no details. II, 1 to 4
all saw well to end of life ; III, 1 died at 53 of liver disease ; III, 2 lived
to 73, good sight. IV, 1, probably firstborn, about 44 (1902), IV, 6,
37 and IV, 7, 36 ; two of these three sisters have several children, the
eldest 12. IV, 2 affected at 22, now 43 (1902) ; IV, 3 at 22, now 42 ; IV,
4 at 27 ; IV, 5 at 22 ; IV, 8, patient, at 30, seen soon after, final result
not known. None of the four affected brothers recovered ; IV, 9 died at
13, IV, 11 at 11, IV, 10 at 1T\- ; the other three at a few months.

1902.* Case 163. Heinsberger, Inaug. Dissert., Griessen. Author's
Case 1.

I and II all said to have been normal ; III, 1 affected at 20, 29 at
record ; III, 3 at 20, 24 at record ; III, 5 at 20, seen soon after ; skull
normal.

1902.* Case 164. Ibid. Author's Case 2.

I, 1 and 2 affected at 20, one of them died of " cardiac dropsy " ; I, 3
also died of " dropsy " at 60 ; I, 4 at 70 of " stroke " ; II, 1 said to have
had " weak sight" ; II, 2 affected at 21, no recovery, 47 at record ; skull
normal ; II, 3, patient, at about 27, no recovery, 41 at record.

1906.* Case 165. Kowalewski, C.f.A., xxx, p. 114.

I, 1 affected when in Army 1871, now about 55 (1905), no recovery.

BOWMAN LECTURE.

CLXXJX

II, 1 affected at 20, died of dropsy at 32 (1889), would be 48 in 1905, no
recovery ; II, 2 affected at 25, seen at 35 (1905), no recovery, married

IE i

at 28, no issue ; II, 4 affected at 21 (1905), seen soon after, skull unsyni-
metrical, slight proptosis on both sides from shallowness of orbits.

1898.* Case 166. Raymond (F.), Lerons sur la Maladies du Systeme
Nerveux. Troisieme serie (Annee, 1896-97), Paris, 1898, p. 399. Author's
Family 1.

I, 1 and 2, first cousins, but kind of cousinship not given. II, 1 died
of diabetes at 43 ; II, 2 living, 86 at record ; II, 3 became rapidly blind
at 30, probably optic atrophy, died at 49. Ill, 1 died at 43, cerebral
tumour; III, 3 at 51, cerebral softening ; they had a son, IV, 4 (author's

F.q.l&G

rc.S *<S sAlo6 600

•"»• T ][: T^s-b 789

Case 2), affected by typical Leber's disease at 26, seen at 38, no recovery ;
syphilis two years before failure of V. Ill, 4 affected at 24, seen at
53, said to have remained the same for 20 years, and then improved to
reading largish letters ; for years could only with difficulty see to go
about (author's Case 3). IV, 3 affected at 22, seen at 26, somewhat
improved, V. i at record (author's Case 1). (Indicating numerals to IV
omitted in error.)

CLXXX BOWMAN LECTURE.

1898.* Case 167. Ibid. Author's Family 2.

I, 1 gouty. Ill, 3 affected at 24, seen soon after (author's Case 4) ;
III, 1' affected at 23, seen at 46, when he was absolutely blind and had
paralysis agitans (author's Case 5). II, 1, 2, and 4, all suffered from
same disease at almost same age as the other two. II, 3, 5, 6, died
young ; II, 7 died at 18.

1907.* Case 168. Coste, These pour le doctorat en Medicine, Toulouse.

Four cases with typical symptoms and mode of descent ; consanguinity
of paternal ancestors of one case, but no cases of the disease on that side.
Narrow base of skull in some of the affected ones, but this still more
marked in III, 2 frem unaffected division. No miscarriages, and apparently
no early deaths. Ages in I V : 1 was 27 in 1907, 3 was 17, 6 was 16. Ill,
6 married at 1 9 ; only two children, IV, 1 born five years, and IV, 2 ten
years after marriage ; both labours natural, no forceps. Ill, 4 affected
at 23, 58 at record (1907), unmarried (author's Case 2) ; III, 7 affected at

35, 48 in 1907 (author's Case 3) ; III, 8 affected at 48, 53 in 1907 (author's
Case 4). IV, 2 affected at 2£, seen six months later. Ill, 9 had gross
central choroiditis in both when seen at 42 in 1907, with V. much reduced
and My. 2 D.

1909.* Case 169. Bach, Munchen med. Wochenschr., p. 210.

I, 1 to 4 normal. II, 2 affected, her sister normal. Ill, 1 normal, her
three brothers affected, two with reduction of V. to fingers at 2 m., the
other to V. T"g in E., f in L. IV, 1 affected at 15, seen three months
after.

1909.* Case 170. Mr. Eayner D. Batten, T.O.S., February llth, 1909.

Single case in boy coming on at 8 in September, 1908, with slight
neuritic appearances. V. went down to E. „% L. T/^, with Fs. much
reduced, then, at end of December, began to improve rapidly, and by end
of January, 1909, V. was £ in each, E. betfcer than L. No other cases
known, but mother very ignorant of the family history.

BOWMAN LECTURE.

CLXXXI

1909.* Case 171. Ibid., T.O.8., February llth, 1909.

I, 1 affected. II, 3 affected. Ill, 1 affected at about 20, patient of
Mr. Doyne at Oxford, now set. 33 years, his six siblings all normal ; III, 9
affected at 16, seen 1907 and again 1909 when set. 24 years, V. /0 ; III, 13
affected at 10 (March, 1904), V. down to /n, in July began to improve,
and by March, 1905, had recovered to -«- each eye, and remained same in
February, 1909 (set. 15 years) ; O.D/s became somewhat pale some months
after onset. HI, 12 died set. 3 years ; III, 14 also died in childhood. No
miscarriages. Ill, 8 set. 27 years. II, 9 died at 21 ; II, 10 married, no
issue ; II, 1 died at 40.

Fio/72.

Case 172 seen by Leber, 1871 ; Magers, 1898 ; Vossius,* 1899-90.

I, 1 affected at 20, no recovery, lived to 72 ; I, 2 at 21, no recovery,
lived to 73 ; I, 3 normal, lived to 86. II, 3 affected in 17th year in
1866, and seen by v. Graefe then and by Ewers in 1869 ; married later
and in 1899 had two sons and two daughters (erroneously marked
as one of each), aged from 24 to 16 years. Ill, 2 affected at 23 (1894),
improved, and in 1897 could read newspaper with a magnifier; had
variola, whooping-cough, scarlet fever, and diphtheria in childhood,
with nephritis and dropsy, and later paralysis of right arm and leg,
and later of left leg, then good health till 16, when he had pneumonia,
now (1897, set. 28 years) healthy. Ill, 3 affected at 22, set. 27 in 1897 ;
III, 1 set. 29 years, and III, 6 set. 22 years (1897) ; III, 7 affected at 19,
when he was seen by Magers two years later (1898) with V. fingers 5 m.

1896-1909. Case 173. Family of French. Messrs. Eayner D. Batten,
Lawford, Worth, and E. N.

I, 1 failed in sight after a slight accident, and did not recover; I, 3
and 4 living, biit no record of their sight, presumably both normal. II,
1 a blind and idiotic daughter of I, 2; she cannot walk. II, 2 to 12, 11
siblings, of whom ]^ died at 5, the other ten living and aged (in 1909)
from 41 to 20 years. II, 3 affected at 27 (1896, Moorfields, under care of
E. N., seen by Mr. Batten, 1909) ; no recovery. II, 4 affected at about
37, attending Mr. Worth (Moorfields). II, 5 affected at about 22-23, now
36, and still attending Mr. Batten (Western Ophthalmic Hospital). II,

CLXXXII

BOWMAN LECTURE.

6 affected at 22 (1897), and still tinder Mr. Batten's care, set. 34 years.
Question of lead poisoning was raised, as at least three of the affected
brothers were plumbers, but there was no decided evidence of plumbism.

1906. Case 174. Mr. C. H. Usher. Cases of Leber's disease in a
pedigree drawn up to illustrate albinism. (Forthcoming- Albinism
Memoir, Fig. 130.)

Ill, 10 and II Leber's disease set in at about 30 ; age of onset in III, 12
not recorded. In IV, 4 Leber's disease present at 30, and in IV, 5 at 25.
In II, 6 sight failed in old age, and also in two of her brothers, but the
nature of the failure not known. I, 1 also said to have failed in sight as
an old man. The albinos were offspring of two mothers by same
father, the father (III, 12) having Leber's disease, the two mothers
almost certainly unrelated to each other. No consanguinity.

1899.* Case 175. Buisson, These, No. 564. Paris, 1899.

I, 2 good sight at 86 ; no information about 1, 3 and 4 ; II, 1 first wife

I Tig. 176

of II, 2 had only one child (III, 1), who in her turn had five normal
children (IV, 1) ; II, 3, second wife of II, 2, had five children (III, 2 to 6),
of whom III, 2 failed at 30 and was seen at 31 (aiithor's Case 2) ; and

BOWMAN LECTURE. CLXXXIII

III, 5 failed at 19, and was seen three months later (author's Case 1) ;

IV, 1, 2 and 3 all normal, and 110 miscarriages or early deaths ; IV, 4,
a seven months child, paralysis of lower limbs.

1899.* Case 176. Ibid. Author's Cases 3 and 4.

I, 1 died of phthisis at 35 ; I, 2 died blind and paralysed at 50, no
details of the blindness ; II, 1 progressive failure of V. at 48 and
optic atrophy found, at 50 sudden hemiplegia ; II, 3 died from heart
disease, blind, at 58, no details of the blindness ; either she or another
sister (II, 2) had a son (III, 6) who went " blind " at 30, no details ; III,
1 affected at 31, seen at 33, no recovery (author's Case 4), has 2 children
set. 8 and 7 years (IV, 1 and 2), and no miscarriages; III, 2 affected
during military service and recovered ; III, 3 affected at 27, seen soon
after (author's Case 3), has one child who died young; III, 4, five who
died young ; III, 5, two stillborn.

1866.* Case 177. Hutchinson, R.L.O.H., v, p. 349.

I, 1 and 2 first cousins, but kind of cousinship not noted ; II, 1 died at
4 months ; II, 2 said to have never seen, at 4 could only see large objects
and O.Ds. very atrophied (author's Case 2) ; III, 3 thought to have
seen well till 6 months old; at 1£ years sees large objects, O.Ds. very
white. Both children intelligent and good tempered. Syphilis not
mentioned. No other history of blindness in family. This case has
sometimes been quoted as perhaps being an instance of Leber's con-
genital retinal atrophy without pigmentation.

1907.* Case 178. Lawson (Arnold), T.O.S., xxvii, p. 169.

I, 1 affected at 14, if not earlier ; L. much worse than E,., typical
scotoma in each ; now 31 (1907). II, 1 now 10 with typical scotoma in
each, affected since early infancy. II, 2 age not stated, sees quite well.
At date of record there had been no more births.

1903.* Case 179. E. N., T.O.8., xxiii, p. 108.

Male affected in 28th year, perfect recovery in a year or year and a

half. His brother, ten years younger, attacked at 25 ; final result not
known. Two males, first cousins, had the disease at set. 28 and 35 years
respectively; the latter is said to have recovered perfectly, the former
did not. These two pairs of brothers were sons of two sisters.

1894. Case 180. Konig (Hormuth, p. 94).

Man, set. 22 years, no recovery in one year. A brother of his mother
(maternal uncle) and a cousin also on mother' side were blind of optic

CLXXXIV BOWMAN LECTURE.

atrophy ; the uncle improved. Also a great uncle on mother's side was
affected. Four cases, all males.

Case 181. E. N. (Littlechild). St. Thomas's Hospital (Out-Patient's
Boole, v, p. 133), February to May, 1890.

Blindness from birth with optic neuritis and large skull in three sib-
lings. Probably not a true case of Leber's disease. Parents, first cousins,
had 8 children and no miscarriages.

No history of blindness in rest of family, except, perhaps, in a male,
"second cousin" of I, 3 said to have been blind all his life. I, 1 and 2
good health. No history of syphilis.

II, 1 and 2 good sight and health ; one of them squints ; 6 and the
next born, which by mistake is not shown and should be 1, also healthy and
see well. II, 4 died at 7 weeks, but could see.

II, 3, quite blind from birth ; taken to Middlesex Hospital when a baby
and told "the nerve was inflamed." February 28th, 1890, set. 7 years;
Ps. motionless before mydriatic, but dilate widely after its use ; L. O. D.
seen with difficulty ; it is ha.zy, and one vein decidedly enlarged, but
no swelling and no visible atrophy; E,. not seen; shadows some H.,
but degree not measured. Cranium rather large, forehead broad and
prominent, the eyebrows overhanging the orbits very much, so that the
eyes are extremely sunken and look small, although really of normal
size ; nose short ; face well formed ; speaks well, and seems intelligent.

II, 5 was blind from birth ; died at 15 months of age ; no particulars.

II, 8 (erroneously marked 7) brought in February, 1890, set. 7 months.
Appeared to have no p.L, and mother said she was certain the child
had never seen. Her seeing children had all noticed the light very
soon after birth ; this one never did so at all. February 28th,
1890 : Pupils small, equal and motionless to light ; irregular slow
nystagmic movements and frequent strong convergence of eyes. O.Ds.
swollen and very hazy, and veins tortuous. Head large and square,
fontanelle open, frontal eminences square ; ribs slightly beaded ; spleen
1 }, in. below costal margin ; for some weeks past head sweating ; suckled,
but for the last two months some bread and oatmeal in addition ; has
had no illness and no fits. Thoiigh quite blind the child screws up
her eyes in sunlight, but takes no notice of lamplight. Last seen in
May, 1890, in statu quo.

Case 181a.* Eampoldi, Ann. di Ott., xii, pp. 269-271.

1, 1 blind of " gutta serena " at 35, dead at date of record ; II, 1 good
sight ; II, 2 became blind at 35 and II, 3 between 35 and 40, also of
" gutta serena " ; III, 3, optic atrophy came on in E., soon followed by L.
early in 1883, set. 67 years, E. going to complete blindness, L. not so
severe ; had an attack of gastro-enteritis with some loss of blood two or
three years before eyes failed. Ill, 4 living, good sight ; III, 5 living
but blind, probably of same disease ; III, 6, set. 73 years at record and
quite blind ; sight failed from the same disease at 65. IV, 1 set. 33
years, good sight ; IV, 3, set. 31 years, nearly blind, age of onset not
stated ; is married.

BOWMAN LECTUEE.

CLXXXV

Case 1816.* Higgens, Lancet, 1881, ii, p. 869.

Optic atrophy without other changes coming on in II, 4 at about 14 }
and reducing V. to finger-counting in a few months ; in II, 5 at 11£, and
in II, 8 at 10. The disease set in in all three during about the first half
of 1881. Mother showed evident signs of syphilis shortly before birth of

6 7 a 9 10

II, 4 ; she also had four or five miscarriages (not marked on the diagram,
Fig. 181b) between II, 4 and 5 ; also II, 3 died at 14 months and II, 7 at
1 day old. II, 1, 2, 9, and 10 reported healthy. [If syphilis were the
cause of the optic atrophy in these three siblings, why did the disease set
in at approximately the same date (1881) in all of them? Was there
some additional cause, such as lead poisoning or influenza ? — E.N.]

Case 181c.* Suckling, Lancet, 1887, ii, p. 1271.

I, 1 became blind at 50. II, 1 went completely blind from double optic
atrophy which came on gradually when he was 50 ; his sister, II, 2, was
blind, and a female cousin (II, 3) on his mother's side is also quite blind
(sex of I, 2 not given). No history of syphilis or disease of nervous
system, and no signs of locomotor ataxy.

Wo information

Fig. 181 D.

Fig. I8ld. Unpublished. Case C3mmuiiicated by Mr. Ja.meson Evans
(Birmingham).

9

CLXXXVI BOWMAN LECTURE.

No information about the ascendants of Gen. I. I, 1 to 7, five
brothers, of whom three were affected, and two sisters, both of whom
married and had children ; one of them (I, 3) carried the disease,
the other (I, 6), had only daughters, and therefore the point could not be
determined. II, 4 to 12, nine children of I, 3, six male, of whom three
are affected, three female of whom one (II, 8) died at 2 ; one of the sur-
vivors (II, 7) carries the disease, and the other (II, 6) has children of
both sexes, none of whom have suffered hitherto (but their ages not

stated). II, 11 and 12, twins, died at three months ; III, 4 still-born;

III, 5 set. 14 years, affected ; III, 6, 7, 8 have not reached the usually
vulnerable age.

(b) References to Cases of Leber's Disease Illustrating Various Statements
in the Lecture.

Eecovery or marked improvement of sight is to be found in affected
members of the following pedigrees : 77 ; one of either 83, 84, or 85 ; 87,
93, 49, 115, 116, 122, 132, 136, 141, 144, 160, 170, 171, 172; and in a few
others.

"Anticipation" in Leber's Disease.

(i) In successive generations, the phenomenon is well shown in the
following cases : 80, 49, 96, 108, 111, 112, 113, 50, 153, 154, 51, 168, 174.

Case 112, Despagnet, shows the anticipation in three generations, and
in the case occurring in the third generation one eye recovered whilst
the other passed into atrophy of the optic nerve.

(ii) Anticipation in successively born siblings, and occasionally in suc-
cessive sibships of first cousins : 81, 88, 89, 91, 93,49, 98, 99, 102, 105, 110,
45, 116, 117, 46, 132, 140, 144, 147, 113, 123, 181a, 150, 48, 156, 159, 171,
172, 175.

Transmission by Affected Males.

In six pedigrees containing only male cases of the disease 13 of the
affected men became fathers, and had from 48 to 56 children, not one
of which suffered from the disease, viz., 45 omitting Gens. I and II, 120,
47, 168, 174, 167.

In five pedigrees containing cases of the disease in both males and
females, 10 affected men became fathers and had 44 children, of whom
4 <$ and 2 ? , six in all, had the disease, viz., 93, 49, 108, 142, 50.

Adding the two series together we have 23 affected males, who had
between them from 92 to 100 children, of whom only 6 became affected,
and these six occurred exclusively in pedigrees containing some affected
females as well as males.

Condition of the Parents of Affected Females.

Both parents normal : 77, 78, 49, 95, 99, 105, 106, 112, 116, 119, 120, 141,
123. Father affected, 50 and 93 IV, 1 ; mother affected, 93 and 49.

BOWMAN LECTURE. CLXXXVII

Condition of the Children of Affected Females.

All the sons of an affected mother were affected in Cases 111, 138, and
146.

Some of the sons of an affected mother escaped in Cases 108, 142, 50,
and 52.

Proportion of affected to normal in the total surviving issue of an
affected mother and normal father, shown in 32 sibships of the following
9 pedigrees : 93, 49, 108, 116, 140, 50, 52, 51, 176.

Proportion of affected to normal in the total surviving issue of normal
father, and mother normal but carrying the disease, shown in 38 sibships
of the following 19 pedigrees : 92, 102, 105, 45, 115, 46, 120, 130, 144, 47,

148, 154, 48, 155, 168, 171, 174, 167.

Effect of Early Deaths upon the Proportion of the Survivors who suffer, in
Childships originally consisting of Seven Children or more.

In the following 10 cases there were 12 sibships of 7 or more, with few, if
any, early deaths, and one third of the individuals suffered from the disease.

Total births, 102, of whom 33 males and 3 females got the disease (36
in all) : 110, 117, 130, 138, 142, 143, 47, 147, 158, 174.

In the following 16 cases, containing 18 sibships of 7 or more, a number
of the children died early, and one half of the survivors suffered from the
disease : 92, 93, 45, 115, 119, 120, 121, 140, 141, 144, 148, 154, 51, 162, 176,
167.

These 18 childships produced 195 children, of whom 96 died in infancy;
of the 99 survivors 39 males and 7 females got the disease (46 in all).

Longevity of those Affected.

The following cases contain affected persons who lived to be 50 or
more. Cases in which the disease set in after 40 in males are excluded.
All cases in females who lived to 50 are counted, at whatever age the
disease set in, as it has been supposed that the disease is especially likely
to occur during the climacteric in women : 90, 103, 49, 111, 45, 116, 120,
140, 142, 50, 52, 154, 51, 161, 166, 168, 172, 176.

Early and Late Age of Onset.

(i) Cases in which the disease occurred early in life, i. e. from earliest
childhood up to 13 years old: 92, 96, 95, 110, 116, 119, 141, 145, 50, 52,

149, 151, 153, 156, 171, 177, 178, 146; also two atypical cases, 181, 181&.
(ii) Cases in which the disease set in late, i. e. from 30 years old up-
wards.

A. Pedigrees showing examples of late onset in males :

(1) In the following only males were affected: 89, 90, 103, 107, 45, 46,
120, 136, 143, 47, 147, 168, 175.

(2) The following contained cases in both males and females : 93, 49,
111, 112, 141.

B. Pedigrees showing late onset in females : 80, 49, 95, 98, 106, 108,
110, 111, 113, 140, 141, 153, 51, 162, 176 ; also atypical cases, 181a, 181c.

CLXXXVIII

BOWMAN LECTUEE.

Other affections., chiefly of the nervous system, in the stocks contain-
ing Leber's disease .—Epilepsy, Case 77, 98, 105, 120, 122, 138, 148 ;
insanity or idiocy, 98, 173 ; mental defect, 45, in the only female (VI, 2)
whose female ascendants went back to male with Leber's disease ; severe
hysteria, 115; diabetes, 95, 103; phthisis prevalent in 102, 98, 103;
congenital colour-blindness, 106?, 117, 147.

The affected females are to be found in the following cases : 77,
78, 80, 93, 49, 95, 98, 99, 105, 106, 108, 110, 111, 112, 113, 116, 117, 119,
138, 140, 141, 142, 145, 50, 52, 123, 151, 153, 159, 51, 162, 165, 169, 176, 177,
178, 53 ; and in the following atypical cases : 181, 181a, 1816, 181c.

APPENDIX VII.

NYSTAGMUS.
(a) ALBINISM.

(1) Under " Hereditary Nystagmus," allusion is made at p. cxxii et seq.
of the Lecture to Albinism. With the exception of certain cases of
nystagmus that I regard as a form of partial albinism and have already
written about as such, the problem of albinism in general was not discussed
in the Lecture since it forms the subject of a long and elaborate memoir
planned and initiated some five years ago by Professor Karl Pearson, who
has taken by far the largest share in its execution, although in certain
sections Mr. C. H. Usher and I have been mainly responsible. This memoir
is now very near completion, and may appear either a little before or a
little after the present writing ; although, therefore, any discussion of
albinism as a whole in my Lecture would have been out of place, there is
no impropriety in using a few of the pedigrees (somewhat condensed to
save space) that will appear in the memoir to illustrate certain clinical
features. Of course no general conclusions are to be drawn from these
samples.

Fig. S3

.- ,u

Fig. 53 illustrates the condition of incomplete albinism affecting chiefly
the eyes, and is described at p. cxxiii of the Lecture. It is to be taken in

BOWMAN LECTURE.

CLXXX1X

conjunction with Figs. 54 and 55, which, having been published, are in-
serted in the Lecture (p. cxxiv). (Fig. 53 is Fig. 295 in the forthcoming
memoir upon albinism in man above mentioned, and is from a case sent
by Mr. Jameson Evans, of Birmingham.)

Fig. 56. General albinism with both discontinuous and continuous
inheritance, the latter occurring where an albinotic woman marrying a
normal first cousin of the same stock has albinotic children. Bisexual
twins occur twice, and in one of them one member is an albino, the other
normal. (Forthcoming memoir upon albinism in man, Fig. 27, Mr.
C. H. Usher.)

Fig. 57. Discontinuous and continuous descent of albinism,
sanguinity. (Ibid., Fig. 28, Mr. C. H. Usher.)

No con-

Fig. 58. Continuous and discontinuous descent. No consanguinity.
A normal man of the albinotic stock marries twice, both wives being

I® Deaf mute
f&ir.

from unrelated stocks ; he has albinotic children by one wife, all normal
children by the other. (Ibid., Fig. 226, Dr. Schoute, Amsterdam).

Fig. 59. Discontinuous descent. Albinism and deaf-mutism in
different members of same sibship. No history of deaf -mutism in any
ascendants on either parental side (father's side not shown but inquiry
made). No consanguinity. (Ibid., Fig. 211, Mr. Wherry.)

Fig. 60. Marriage between two albinotic stocks that are believed to
be unrelated, and between one of them and a third stock containing
insanity and epilepsy, but no albinism. (Ibid., Fig. 30 Mr C H
Usher.)

cxc

BOWMAN LECTURE.

(2) The cases upon which, the remarks on Hereditary Nystagmus in
relation to Albinism at p. cxxv of the text of the lecture are based are as
follows :

(1) Lloyd Owen, O.R., i, p. 239 (1882), Fig. 54 in present Lecture.
(Fig. 449 in forthcoming Memoir on Albinism.}

(2) Lawford, 8t. Thomas's Hospital Reports, xvii, p. 166. Case 1. Fig.
187 in present Lecture. (Fig. 68 in Memoir on Albinism.)

(3) E. Nettleship, R.L.O.H., ii, p. 366 (1887). Fig. 55 in Lecture.
(Fig. 410 in Memoir on Albinism.)

(4) McGiUivray, O.R., xiv, p. 260 (1895). Case B. Gorrie family.
Fig. 188 in present Lecture. (Fig. 448 in Memoir on Albinism.)

(5) E. Nettleship (1897). Fig. 186 in present Lecture. (Fig. 402
Memoir as above.)

(6) Caspar, G.f.A., 1908, p. 199. Fig. 182 below.

Fiq.

In III are four childships, the first containing 4 males all affected and

4 females all free ; second, 2 males both affected, 5 females free ; third,

5 females free ; fourth, 1 male and 5 females all free. Dr. Caspar has
been unable to send any further information (February, 1909).

BOWMAN LECTURE. CXCI

(7) E. N., unpublished, St. Thomas's Hospital out-patient, Octo-
ber 24th, 1881 (Simpson). (Fig. 183.)

Ill, 1, set. 3| years, fair complexion, choroid pale around O.D., but
fundus normal, marked lateral nystagmus ; healthy ; did not have
ophthalmia neonatorum ; is thought by mother to be " short-sighted."
Refraction not recorded. Ill, 2 treated for ophthalmia neonatorum at
St. Thomas's ; saw well, and had steady eyes ; died of convulsions ; no
note of sex or colour of hair and eyes. II, 6 mother, set. 22 years, normal
eyes, some H., colour of hair and eyes not noted. Her 3 brothers and

II, 1, a son of a sibling (I, 1) of her mother (I, 2) had moving eyes like

III, 1 ; her sisters (II, 2), number not given, had steady eyes.

(8) Jameson Evans, Fig. 53 above described.

(9) Dr. R. J. Smyth and E.Nettleship (1907). (Fig. 184.)

I, 1 and 2 lived to 70 and 65, not consanguineous ; II, 1 operated by

E. N. for glaucoma when 35 ; II, 2 died at 35 ; II, 3, 4 and 5 steady eyes ;

II, 6, 7 and 8 set. 35, 32, and 30 years, nystagmus and more or less As.,

with defective vision (^6T to •£% corrected) ; irides of these 3 grey with

pigment at sphincter circle ; fundus not suggestive of albinism in any ;
II, 7 has reddish-brown hair which was lighter formerly. There are
about 20 children in III, all said to have good sight and steady eyes (not
shown in Figure).

The above 9 pedigrees contain 43 cases of nystagmus, 40 males, 3
females ; and in the same childships about 65 to 70 normals, viz.. 20 males
and 45 to 50 females, total 109 to 114.

(&) DAY-BLINDNESS WITH COLOUR-BLINDNESS.

The family cases known to me are the following :

(1) Nettleship, St. Thomas's Hospital Reports, x, 1880. (Family 1,
Foster.) Qiioted in text of Lecture, p. cxxix, with Fig. 61.

CXC1I BOWMAN LECTUEE.

(2) Nettleship, ibid. (Families 3 and 4, Pike, Channon.) Ibid., with
Fig. 62.

(3) Nettleship, ibid. (Family 6, Gould.) (Fig. 185.)

I, 1 and 2 brothers, reported to have seen well. Ill, 1 who was liable
to melancholic attacks, but had good sight, married II, 2, her first cousin
once removed, who also saw well, and had 9 children, of whom 8 were
living at date of record, IV, 5 having died ; IV, 1, set. 34 years, not seen
said to be affected in same way as her two brothers, IV, 6, set. 25 years,

and IV, 7, set. 23 years ; both of these, with clear media, saw better in
dull than in bright light, and were afraid of summer days and preferred to
hold the head down to shade the eyes, in spite of having much contracted
Fs. and retinitis piginentosa ; both colour-blind. They had nystagmus,
and their sight, according to their own and their mother's account, had
been in exactly the same state since early childhood. All the others
said to have very good sight.

(4) Nettleship, R.L.O.H., xi, p. 373 (Case 27), 1887. (Mr. Waren Tay's
case.)

In a childship of 5, the first-born male, the other 4 female, the 2 elder
girls (Nos. 2 and 3 born) totally colour-blind, day-blind, and amblyopic,
V. with H. 3 D. corrected about ^V Parents first cousins, but exactly how
is not stated.

(5) Nettleship, Ibid. Case 28.

In a childship of 7, 1 of the 3 males and 1 of the 4 females affected ;
quite typically. H. 3 to 4 D. V. corrected -^. No consanguinity.

(6) Nettleship, Ibid. Case 30.

In a childship of 4, Nos. 1 and 2, both female, typically affected ; No. 3
female and No. 4 male, normal. Parents first cousins, but kind of cousin-
ship not noted.

(7) Nettleship, unpublished, Joseph Thompson, 22 (T.O.P., v, p. 7,
1885).

Parents normal, and not related by blood. Patient is second born of
8, all living, set. from 24 to 2 years. His case is typical. The first born,
male, 24, said to be similarly affected, and the youngest, female, 2,

BOWMAN LECTURE. CXCIII

thought to have same defect. Nos. 3 and 6 (males) and 4, 5 and 6
(females) all good sight. Interval of 8 years between No. 2 (patient, set.
22 years) and No. 3 (set. 14 years).

(8) 1897. Colburn (J. E.), Amer. Journ. of Ophthalmology, xiv, 1897,
p. 237.

Nystagmus with total colour-blindness and V. about T65 in a brother
and sister of 14 and 12. Not albinotic. Very incompletely reported.

(9) Nettleship and Holmes Spicer, T.O.S., xxviii, p. 83 (1908), with
Fig. 63 in Lecture, p. cxxxi.

(10) Mr. Holmes Spicer and Dr. Souter, unpublished (1908), with
Fig. 64, ibid.

The above 10 pedigrees contain 34 cases of this day-blindness with
colour-blindness : 18 males, 15 females, and 1 sex not recorded. The
same childships contain at least 45 (probably more) normals : 17 male,
22 female, and 6 or more sex unrecorded, total about 80 to 85.

The total of 84 cases mentioned at p. cxxix of the lecture is made up of
my own and Grunert's series, including some single cases of mine not
given above, but useful in relation to sex prevalence, and three others
published since the appearance of Grunert's paper by Wehrli, 1903
(Abstract in NageFs Jahresbericht, xxxiv, p. 92) ; Bjerrum, 1904 (Ab-
stracted, ibid., xxxv, p. 105, and again p. 205) ; Konne, 1906 (abstracted-
ibid., xxxvii, p. 78, and original reproduced in full in K.M.f.A. (Beilage,
heft), xliv, p. 193. In Bjerrum's case, two brothers of the (male)
patient were also affected.

(c) NYSTAGMUS, UNCLASSED.

The references to the fourteen unclassed cases of hereditary or family
nystagmus, spoken of at p. cxxxii of the lecture, are given in chronological
order below.

Published—

1892.* Wood (Casey A.), The North American Practitioner, April, p. 153.

1893.* Boulland, Rec. d'Ophth., p. 569. This is an abstract by Eolland
from the Echo Medicale, which appears to have copied from the original
in the Limousin Medical of unspecified date.

1895.* MacGillivray (Angus), O.R., xiv, p. 260. Case A (Neilson).

1895.* Audeoud, Ann. d'Oculist, cxiii, p. 412.

1895.* Burton-Fanning (F. W.), The Lancet, ii, p. 1497.

1898.* Morton (H. McL), Ophth. Rec., vii, p. 28.

1902.* Fisher (Theodore), Brit. Med. Journ., September 6th.

1903.* Clarke (Ernest), The Ophthalmoscope, i, p. 86.

1903.* Hawthorne (C. O.), Brit. Med.- Journ., February 21st.

1903.* Sinclair (M. Mclntyre), ibid., May 23rd.

1908.* Dudley (W. H.), A. of 0., xxxvii, 565.

Unpublished —

1905. Case communicated by Dr. Angus MacG-illivray (Dundee).

1906. Case communicated by Mr. Lawford (London).

1908. Case communicated by Dr. Vilhelm Magnus (Christiania).

CXCIV

BOWMAN LECTURE.

APPENDIX VIII.

CORNEA.

Reticular and Nodular Keratitis.
Description of Figs. 65-69.

Fig. 65. Holmes Spicer, T.O.S., xxiv, p. 42 (1904), and later informa-
tion.

I, 1 believed to have had good eyes ; I, 2 lived to 101, and is known to
have had perfect sight to the end. II, 3, second wife of II, 2, and her
brothers, II, 4 (number not recorded), said to have suffered in same way
as III, 4 and his daughter. II, 2 and his first wife, II, 1, and her
children, all had perfect eyes. Ill, 2, set. 65 years at record, probably
normal ; III, 3 probably affected, sight " peculiar " in same way as III, 4 ,
and an opera glass was useless to her ; III, 4 seen by author, set. 50 years,
typical changes, eyes have been troublesome all his life ; III, 5 had
symptoms like those in III, 4, and on trying to enter the Navy failed to

pass the sight test, he died at 30 ; III, 6 has never had any trouble with
his eyes. IV, 1, only child, seen by author at 23, characteristic changes,
no severe symptoms, and V. with slight M. As. corrected £ and £ in E.
and L., and appears to have been same for many years.

Fig. 66. Freund, A.f.O., Ivii, p. 377 (1904), and Wien. Jclin. Woch., xix,
No. 5, 1906. Family 2 (Hermann).

All marked " + " were examined by the author. The only ones
believed, or known, not to have the family disease are II, 5, who died
many years before the record ; III, 1, who died at 23, and is said to have
had " scrofulous inflammation of the eyes " ; and IV, 2 and 3, set. 10 and
6 years at record, and definitely stated by the author to have been free
from the disease at that time ; though not starred they were probably

BOWMAN LECTCJRE.

CXCV

examined. The ages of the affected ones when seen were : II, 1
(author's Case 8) 61, II, 2 (Case 9) 56, III, 2 (Case 10) 26, III, 3 (Case
12) 39, III, 4 (Case 14) 38, IV, 1 (Case 13) 13, III, 5 (not seen, Case 15),
26. In II, 3 (Case 11), age not stated, the eye disease had existed more
than twenty years. II, 4 not seen or described, but stated to be affected;
was 46 at date of record. Nothing said about early deaths.

Fig. 67. Freund, ibid., Family 1, Bienert.

In this genealogy the ages, unless otherwise stated, are as given in the
author's earlier publication (A./.O., Ivii), and refer apparently to 1902,
or sometimes perhaps rather earlier. The pedigree now presented in
Fig. 67 is the result of collating the published ones of 1904 and 1906., and
adding important new information that Dr. Freund has with the greatest
courtesy supplied to me in reply to questions.

Dr. Freund's latest reply, dated June 14th, 1909, three days after the
delivery of the lecture, gives the result of his examination of the eight
children IV, 10 to 18 ; whilst in a letter of May 3rd he gave the present

condition of the four siblings, V, 1 to 4, who were all normal seven years
ago, whilst three of them now show the typical condition. I reproduce
the names of all the members as given by Dr. Freund in order to
facilitate reference if still further information should be forthcoming in
future. I, 1 died young, had good eyes. I, 2, Wenzel Bienert, husband
of I, 1, also died young, between 1860 and 1870 ; is reported to have
had the family disease. II, 1, 2, 3, order of birth not recorded, died
before Karl (II, 4) ; all three had bad eyes, the eldest being quite
blind, no other details. II, 4, Karl Bienert (the elder), died in 1889,
age not given ; reported to have had the family disease ; his place in

* Gen. VI, 1909, should be V
1902 and again in 1909.— E. N.

The same childship was examined in

CXCVI BOWMAN LECTUEE.

the childship not given. II, 6, set. 84 years at date of first record, and
still living (May, 1909) ; eyes affected for more than fifty years ; the
cornese are densely opaque and scarred, and it cannot now be proved
that she has the family disease ; her only child, Daniel, set. 56 years
(III, 14) has normal eyes. II, 5, Karoline Wolf, set. 72 years and
still living (May, 1909), has had the family disease all her life. Ill,
1, Karl Bienert (the younger), 63, has had the corneal disease thirty
years. Ill, 2, Ferdinand Bienert (the elder), died at 36 in 1876; had
the family disease and his sight was very bad. Ill, 3, Josef Bienert,
53, cornese clear but iris shows remains of foetal pupillary mem-
brane. Ill, 4, Edward Bienert, died at 30 in 1879, believed to have
had good sight. Ill, 5, Antoine Bartosch, 49, and III, 6, Johann
Bienert, 48, both typically affected. Ill, 7, Wenzel Wolf, 50, affected,
but sight still relatively good. Ill, 8, Ant. Wolf, 48, affected and sight
very bad. Ill, 9, Karoline Beer, died at 43 between 1890 and 1900, was
affected by the family disease, but is said to have still seen well. Ill,
10, Berta Jung, 45, affected and sight very bad. Ill, 11, Leopold Woll-
mann, 41, affected and sight very bad. Ill, 12, Matilda Rosier, 39,
affected, but sight stiU good. Ill, 13, Marie Wolf, 17 (? 37), affected, and
sight very bad. Ill, 14, see II, 6. IV, 1, Emil Bienert, 39, affected.
IV, 2, Frau Engelfeld, about one year younger than IV, 1, reported to be
normal, as also her six children, but could not be seen (May, 1909). IV,
3, Karl Bienert (the third), examined at 13 (? 1900), high myopia but no
corneal disease. IV, 4, Karl Bienert (the fourth), 31, and his sister, IV,
5, Auguste, 29, both affected. IV, 6, Ferdinand Bienert (the younger),
26, moderately high myopia, no corneal changes. IV, 7 and 8 examined
and normal ; IV, 9 died at 24 nearly blind, but believed not to have had
the " Bienert disease." IV, 10, Hedwig Bartosch, 23, affected. IV, 11 to
18, eight children of III, 6, examined, June 1909 ; IV, 17, Max Bienert, 5,
" already shows small, spotted, sub-epithelial opacity of both cornese ; it
extends to the periphery of the cornea, and the corneal surface is at
present smooth ; it is not altogether identical with the family disease."
The other seven, IV, 11, Marie, 20; 12, Hans, 19; 13, Eleonore, 17; 14,
Margarete, 11 ; 15, Walter, 9 ; 16, Curt, 8 ; and 18, Gerda, 1 year, are normal.

IV, 19 to 21, Karoline Jung, 26, Emma. 11, and their siblings, no informa-
tion obtainable. V, 1 to 4, examined in 1902 and again in May, 1909 :

V, 1, Mathilde Bienert, 14, normal, and is still normal in May, 1909, set.
21 years ; V, 2, first seen at 10 with normal cornese ; when re-examined
at 17 (May 1st, 1909) characteristic changes in the cornese ; the same is
true of V, 3, normal when seen at 8, the same corneal changes at 15 ; and
of V, 4, normal at 4 and characteristically diseased at 11. In the figure
Gen. VI, 1909, should have been V.

Fig. 68. Doyne and Stephenson, The Ophthalmoscope, in, 213 (1905).

I, 1, eyes bad from youth, and towards end of life sight so bad that
she had to be led about ; died at 65. II, 2 seen at 48, with very
advanced opacity of E., and less of L. ; age of onset 39, or perhaps
earlier. II, 4, a sister, now dead, said to have had the family disease.

BOWMAN LECTURE.

CXCVII

III, 1, set. 24 years, eyes began to fail at about 16, but with interval of
three years between E. and L. ; now almost universal dense opacity ;
III, 2 began at 9, now 22, and as bad as III, 1 ; III, 4 disease began at 7
and has steadily got worse, and now, at 15, is nearly as bad as III, 2, and
has much severe acne on face* ; III, 5 began at about 11, seen at 12 ;
chief part of opacity showed much resemblance to "transverse cal-
careous film," and, as is common in that condition, showed numerous
small, clear holes. No consanguinity.

Case 68a. A new case has been given to me this year by Mr. Herbert
Fisher, but as there has not yet been an opportunity for examining all
the available members of the family I withhold it ; at least two sisters are
affected, and probably two or three of their siblings.

Fig. 69. Folker, T.O.S., xxix, p. 42 (1909).

I, 1 now 92, history of first failure when about 50 ; about ten years later

operated for cataract in both eyes ; wife living, has had 13 or 14 children,
7 still living, and no miscarriages. II, 3, now 50, sight "always" been
defective; 11 children, 8 living, 3 died under 2 years; II, 5, &t. 46 years,
sight " always " been defective ; has 9 children. Ill, 1, set. 30 years, sight
defective as long as she can remember, and apparently getting steadily
worse after each confinement ; has had 6 children in 8 years, one dying in
infancy, 5 living ; III, 2, set. 28 years, sight defective all his life, now
V. T6¥ ; III, 4, set. 21 years, sight defective as long as she can remember,
now V. T<y, married, 1 child, set. 10 weeks ; III, 5, set. 18 years, no definite
history of commencement, but is getting worse, V. T\ ; III, 9, set. 21
years, has never noticed any defect of sight, and has now £ in R., § in L.,
but central area of each cornea shows 20 to 30 small scattered spots ;
III, 13, set. 12 years, no symptoms, and V. f with each eye, but has a few
small dots of corneal opacity like his brother.

A general review of the disease illustrated by these pedigrees leaves
one in no doubt that it is often, if not always, progressive, that in an
early stage sight may be so little affected that nothing short of careful

* Severe scar-leaving acne was observed by Marcus Gunn in one of his
cases : T.O.S., xix, p. 97.

CXCVIII BOWMAN LECTURE.

examination of the cornese can be taken as conclusive, and that practical
blindness may ensue from gradual extension of the area and increase
in the density of the opacity. Careful inquiry in many of the cases has
shown that there is no reason whatever for thinking that syphilis takes
any part in causing the disease.

The following is a list of the principal papers upon nodular and
reticular opacity of the cornea. * Most important. Some others may be
found at end of the article by Doyne and Stephenson.

*1890. Biber, Inaug. Dissert., Zurich.

*1890. Groenouw, A. of 0., xix, p. 245.
1891. Chevallereau, France Medic ale, May 2nd.

1891. Manz, Wien. med. Woch., Nos. 3 and 4.

1892. Oliver (C. A.), Amer. Journ. of Ophth., p. 234 ; also given in
O.R., ii, p. 349 (same year.

1893. Eversbuch, Deutsche med. Woch., No. 41.
*1898. Groenouw, A.f.O., 46, i, p. 85.

*1899. Haab, Z.f.A., ii.

*1899. Dimmer, ibid., ii.

*1899. Collins (E. T.), T.O.S., xix, p. 30.

1899. Block, Niederland Ophth. Gesellsch., December 10th.

*1902. Fuchs, A.f.O., 53, iii, p. 423.

*1902. Collins (E. T.), T.O.S., xxii, p. 148.

*1902. Gunn, T.O.S., xxii, p. 97.

1903. Hess, A.f.O., p. 378.

*1904. Freund, A.f.O., Ivii, p. 377 ; also (*1906) Wien. klin. Woch.,
xix, No. 5.

1904. Fehr., C.f.A., xxviii, January and June.
*1904. Veasey (C. A.), A. of O., xxxiii, p. 510.
*1904. Spicer (T. Holmes), T.O.S., xxiv, p. 42.

1904. Deutschmann, Beitr. z. Augenheilk., H. 61, p. 14 (1904).
*1905. Doyne and Stephenson, The Ophthalmoscope, iii, p. 213.
*1908. Hudson, T.O.S., xxix, p. 11.
*1908. Folker (H. H.), T.O.S., xxix, p. 42.

APPENDIX IX.

ABBREVIATIONS OF TITLES OF PERIODICAL PUBLICATIONS.

A.f.O. — Von Graefe's Archivfiir Ophthalmologie.
K.M.f.A. — Zehender's Klinische Monatsbldtter filr Augenheilkunde.
R.L.O.H. — Royal London (Moorfields) Ophthalmic Hospital Reports.
T.A.O.S. — Transactions of the American Ophthalmological Society.
T.0.8. — Transactions of the Ophthalmological Society of the United
Kingdom.

C.f.A.— Hirschberg's Centralblatt fur praktische Augenheilkunde.
A. o/O.— Knapp's Archives of Ophthalmology.
O.R. — Ophthalmic Review.

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