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v
vi Preface
many valuable comments. John Lisman did the same for the section on
Mechanisms. Janette Atkinson, Marty Banks, Oliver Braddick, Jan Naegele,
Pasko Rakic, and Josh Wallman read individual chapters in their area of
expertise and made many corrections and improvements. Several of my col-
leagues in the Department of Ophthalmology—Ethan Cohen, Jonathan
Kirsch, Thomas Hughes, Colin Barnstable, Silvia Reid and Helen Flavin—
gave comments on various portions of the text, and Marc Weitzman read
two whole sections. I would like to thank them all. However, I did not adopt
all of their suggestions, and the errors and omissions are mine. I would also
like to thank Janet Hescock and Bob Brown for help in the preparation of
the text and figures, together with support from the Core Grant to Yale
University from the National Eye Institute.
It is almost 20 years since the first edition of this book was written, and con-
siderable research has been done in that time. The development of vernier
acuity and contour discrimination have been more carefully defined. Genes
that play a role in myopia have been localized. New techniques using Gabor
patches in various configurations have enabled scientists to define amblyopia
in more careful terms, particularly the concept of spatial uncertainty, and
whether it is due to undersampling or distorted sampling. Amblyopia was
never simply a matter of a deficit in acuity, but it has taken careful experi-
ments to show exactly what it is beyond that.
Ten years ago, the molecules that govern the crossing of the optic nerve
fibers in the chiasm, and which project to the contralateral side, and which to
the ipsilateral side were completely unknown. So were the molecules that
govern the topography of the projections within the visual system. Today, we
know some molecules involved in both these developmental events, as well as
some that mark the boundaries of the visual cortex.
The technique of optical imaging of the visual cortex has enabled scien-
tists to visualize the ocular dominance and orientation columns. Scientists
can now use this technique to study the development of these columns, and
the effect of various forms of visual deprivation on them, in a way that was
not possible with single unit recordings.
It has also become increasingly apparent that there are many critical peri-
ods in the development of the visual system. The critical period for the effect
of a particular form of visual deprivation in many cases lasts longer than the
period of development of the property affected, and the period during which
recovery can be obtained lasts longer still. Moreover, there are different criti-
cal periods for different properties. Properties handled at a higher level of the
system have a later critical period. In addition, the critical period can be
affected by the previous visual history of the animal, and by the technique
used to evaluate it. For all these reasons, the chapter on critical periods has
become much more involved.
Twenty years ago, quite a lot was known about mechanisms of long-term
potentiation and long-term depression, and not much about plasticity in the
visual cortex resulting from monocular deprivation. Today, a considerable
amount is known about mechanisms of ocular dominance plasticity, and what
is known about LTP and LTD does not add a great deal, so the chapter on the
latter has been eliminated.
vii
viii Preface to the Third Edition
The subject of the effect of out-of-focus images on the size of the eyeball has
also been a very active area of research. We still do not know how the signal
gets from the neural retina to the choroid and sclera, but there are a few mole-
cules known that increase in response to plus lenses and decrease in response to
minus lenses, or vice versa, that may be candidates for the signal.
Moreover, the best treatment for amblyopia has become much better
known, as therapists concentrate on properties other than acuity. Basic scien-
tists have quantified the improvements that can be made by not patching the
amblyopic eye all of the time, and working with both eyes to improve binocu-
lar vision at the same time as the acuity in the amblyopic eye. Use of percep-
tual learning and video games has helped by increasing activity and attention
as the therapy is done. Many of the principles have been employed by pediat-
ric vision therapists for some time, but the publicity generated by “Stereo
Sue” and others has helped to broadcast them.
For all these reasons, it is high time that this book should be revised. The
aim of the book is the same as it was in the first edition—to provide a short
summary of findings in the field that can be used by ophthalmology residents,
optometry students, graduate students in neurobiology and psychology,
senior undergraduates, and, since the field is so diverse, for experts to read
chapters outside their area of expertise.
For this third edition, there is a Web site, www.visual-development.net,
with links to various videos that illustrate points and procedures discussed in
the book. See also the list of useful videos after the table of contents.
I am most grateful to Paul Harris for reading the whole book and providing
a number of suggestions for clarification, as well as for professional guidance
on the new chapter on “Treatment of Amblyopia.” I am also very grateful to
Terri Lewis, Len White, Mike Crair, Eileen Birch, Dennis Levi, Donald
Mitchell, John Lisman, Takao Hensch, and David Troilo, who provided com-
ments on individual chapters and hopefully caught most of my errors, but I am
sure that some remain. I also thank Simina Calin, my editor at Springer, for
all her help and guidance.
Contents
1 Introduction .................................................................................. 1
References ...................................................................................... 5
2 Functional Organization of the Visual System .......................... 7
General Anatomical Organization ................................................. 8
Function in the Retina .................................................................... 11
Function in the Lateral Geniculate Nucleus................................... 14
Function in the Visual Cortex ........................................................ 16
The Columnar Organization of Cortex ...................................... 17
Parallel Processing Within the Visual System ............................... 19
Hierarchical Processing Within the Visual System........................ 19
Higher Visual Areas ................................................................... 22
Summary ........................................................................................ 22
References ...................................................................................... 23
ix
x Contents
For Chap. 1
A discussion of Molyneux’s question is given by Dick Held at http://youtu.
be/EDRa-ESxmJY.
For Chap. 2
Recordings at various levels of the visual system by Clay Reid http://youtu.
be/mtPgW1ebxmE.
For Chap. 3
A demonstration of Biological Motion by Sverker Runesson at http://www.psyk.
uu.se/organisation/historia/?languageId=1 including motion demonstrations
in both 2 and 3 dimensions from the work of Professor Gunnar Johansson.
Development of acuity and face perception by David Martin http://youtu.be/
GK3ebhSmC4A.
Development of acuity, depth and color by Sepura Dosetareh http://youtu.be/
wsPIIC2b2wA.
A description of what babies see by Terri Lewis http://youtu.be/
UGqQnR5weTg.
For Chap. 4
A basic description of the development of the brain, focusing on hearing
rather than vision, is given by Joan Stiles at http://youtu.be/FugrcVhi2tg.
Differentiation of neural stem cells and development of cerebral cortex by
Pasko Rakic http://youtu.be/jeSh9t4aMa4.
For Chap. 8
A rapid test for amblyopia by Denis Pelli at http://psych.nyu.edu/pelli/
dualacuity/.
For Chap. 10
A demonstration of the Brock Posture Board by Paul Harris at http://youtu.
be/CEKqNTV8Q3k.
A demonstration of the Brock String by lDoc 2008 at http://youtu.be/
EGlCVTdNqfw.
A demonstration of the Wayne Saccadic Fixator by visionforlifeworks at
http://youtu.be/K3UfrB_VNSw.
Various vision therapy exercises by tglass0000 at http://youtu.be/
MWKWNPdxpyk.
Video games, and how the two eyes are made to work together by Jessica
Bayliss http://youtu.be/71RML96XxCI.
The problems of getting sight back, but not necessarily perception, are
described by Michael May at http://youtu.be/bnefTJx2sCo.
For Chap. 12
The role of immune system molecules in visual plasticity by Carla Shatz
http://youtu.be/WFA9xbhI3yc.
Introduction
1
Abstract
This book discusses the development of the visual system – the psycho-
physics, the anatomy, and the physiology – then goes on to what happens
when this development is disrupted by abnormalities in the visual input
during infancy and childhood. These abnormalities can have permanent
and irreversible effects on the connections in the nervous system, leading
to a form of poor vision known as amblyopia, if not treated in time. The
subject is therefore an important medical problem, which has also been
studied as a model for development and disruption of that development in
all parts of the nervous system. It has engaged the attention of neurobiolo-
gists in a wide variety if disciplines, as well as philosophers studying the
“nature vs. nurture” question.
This book discusses visual development leading This can occur if one eye is in focus, but the other
up to visual deprivation, where the development is is not; if vertical lines are in focus, but horizontal
disturbed by faults in the optics or motor control lines are not; if the two eyes look in different
of the eye. Visual deprivation is an important and directions (strabismus); if the lens or cornea of
fascinating subject from several points of view: one or both eyes is cloudy (cataract or corneal
clinical, philosophical, historical, and scientific. scarring); or if the eyeball grows so much that
Many general questions in these areas have been objects can no longer be focused on the retina.
framed over the years in terms of the visual sys- Frequently these conditions lead to poor vision in
tem. This is not surprising because we are visual one or both eyes, as a result of changes that have
animals. If dogs ruled the world, the title of this occurred in the central visual system, even after
book would be “Olfactory Development.” As it is, the images on the retinas are made clear and
vision is our most important sense, and the first coordinated. After the Greeks, this poor vision is
that we think of in discussing scientific and philo- named amblyopia, meaning blunt vision, or dull
sophical questions. vision. The colloquial term for amblyopia is
A large number of people have personally “lazy eye.” Between 2 and 4 % of the population
experienced some form of visual deprivation. may become amblyopic from visual deprivation.
Anything that affects the images on the retinas of Philosophers became interested in the subject of
young children can have lasting effects on the visual deprivation when William Molyneux posed
part of the brain that processes visual signals. his famous question in the late seventeenth century.
(see http://youtu.be/EDRa-ESxmJY) After his wife disappointing to the patients in terms of their
became blind, Molyneux wrote to John Locke say- visual perception. Daviel stated in 1762 after 22
ing “Suppose a man born blind, and now adult, and cases “I can assert, indeed, with absolute assur-
taught by his touch to distinguish between a cube ance, that not a single one of these patients has
and a sphere of the same metal…Suppose then the recognized the objects shown to him after the
cube and sphere placed on a table and the blind man operation, without the use of touch, unless they
made to see; query, Whether by his sight, before he have been many times shown to him and named…
touched them, he could now distinguish and tell If it has been said that some such patients can
which is the globe, and which the cube? To which distinguish objects exactly and completely imme-
the acute and judicious proposer answers: not. For diately after the operation, then this shows that
though he has obtained the experience of how a they were not really blind from birth, for the lat-
globe, how a cube, affects his touch, yet he has not ter have no real idea at all of even the meanest
yet attained the experience that what affects his objects” (Von Senden 1960, p. 106).
touch so or so, must affect his sight so or so.” Numerous cases were reported following
Locke’s comment in 1690 was “I agree with Daviel’s report, and the results were generally the
this thinking gentleman, whom I am proud to call same. Von Senden collected them in a summary in
my friend, in his answer to this his problem, and 1932 (von Senden, tr. 1960). Where vision was
am of opinion that the blind man, at first sight, tested soon after the operation, patients could dis-
would not be able with certainty to say which was tinguish color and motion, but they had little idea
the globe, which the cube whilst he only saw of form or shape, no idea of distance, no idea of
them; though he could unerringly name them by depth and very little idea of solidity. Their problem
his touch, and certainly distinguish them by the was not just a matter of transferring the recogni-
difference of their figures felt” (see Locke 1846). tion of objects by touch to the recognition of
Some material to test Molyneux’s question was objects by sight. Their visual perception was itself
available during his time. Congenital cataract defective, with little activation of centers for the
was quite common, and an operation for it called recognition of objects and faces in the occipital
couching was described by Sushruta in India in lobe (Fine et al. 2003). Frequently patients became
the fifth century bc (Hirschberg 1982; Kansupada depressed because the gift of sight was confusing
and Sassani 1997). A sharp needle was used to for them (von Senden 1960; Gregory 1974). They
make a hole in the sclera, then a blunt needle was could not, in fact, see like normal people, and their
inserted, and the lens gently pushed downward previous tactual and auditory world was not easily
out of the line of sight. Occasionally the lens was correlated with their new visual world.
removed altogether with a hollow needle, but not Locke was the apostle of empiricism. He
many surgeons were expert enough to do this believed that everything is learned. The opposing
well. Thus the operation was often not success- point of view is that everything is innate. The
ful. Moreover, the image on the retina was not debate between the two points of view raged for
fully restored because of lack of adequate correc- many years under various headings, such as
tion for the absent lens. Consequently, the topic “nature versus nurture”—for the belief that prop-
of Molyneux’s question remained an armchair erties are with us at birth, versus the idea that
discussion for another half century. properties are learned from experience after birth.
Only when doctors finally realized that the One might think, from the cases discussed by von
cataract is in the lens was the vision of substantial Senden, that Locke’s point of view is correct.
numbers of patients restored. At this time, Daviel As we will discuss, neither is strictly correct.
promulgated a cleaner operation for cataract by While some properties are learned, others are
removing the lens through a flap in the cornea. there at birth. Moreover (an answer to Molyneux’s
Generally speaking, the results of this operation question that Locke did not consider), properties
were successful in producing a clear image on the can be present at a few years of age and then
retina, when spectacles were worn, but were degenerate (Fine et al. 2003).
1 Introduction 3
The history of strabismus (i.e., being cross-eyed for cosmetic as for visual effect. From ancient
or squinting) is as venerable as that of cataract. times strabismus was associated with an “evil
It is described in the Edwin Smith papyrus, dat- eye,” and people who had it were frequently
ing from ca. 1500 bc. Hippocrates (460–375 bc) treated with suspicion and contempt, much like the
believed that there was a genetic component, village idiot. They were more concerned about the
saying “If, therefore, bald persons have for the ridicule and shame from their crooked eye than
most part bald children, grey-eyed parents grey- any visual problems caused by it.
eyed children, squinting parents squinting chil- Indeed, surgery for strabismus, like surgery for
dren, and so on…” (see Hippocrates, tr. 1923). cataract, can be a disappointment to the patient.
Paulus of Aegina (625–690) recommended If the crooked eye has established a compensating
wearing a mask with “an opening for each eye so point of fixation away from the fovea that is coor-
placed as to induce the eyes to assume direct dinated with the normal point of fixation at the
positions in order to see through these open- fovea in the good eye, then the operation can lead
ings.” Georg Bartisch (1535–1606) illustrates to double vision. The double vision can be much
such a mask for convergent strabismus, together more disturbing than the amblyopia in the “lazy
with a mask containing prisms for divergent stra- eye” that was there before the operation.
bismus (Fig. 1.1). A non-surgical treatment for amblyopia in
Surgery for strabismus was initially tried by strabismus (patching of the good eye) was men-
Chevalier John Taylor in the eighteenth century tioned by Thabit ibn Qurrah around 900 ad in
(Albert 1992). It is not clear exactly what he did, Mesopotamia, and recommended by Buffon in
but he probably chose patients who looked 1743. This treatment was replaced by surgery, and
straight when their deviating eye was covered, it was not until almost 100 years later that it came
put in a suture on the deviating eye, bandaged the back into vogue, when physicians realized that the
straight eye, claimed success, and left town rap- deviating eye was still amblyopic after surgery
idly. This did not lead to success: he treated both If treatment is to be successful for cataract or
eyes of Johann Sebastian Bach and Bach went strabismus acquired early in life, and disappoint-
blind afterward. However, Taylor was a colorful ment is to be avoided, the treatment must be
personality who gave great publicity to the started early. This point was not fully appreci-
possibility of surgery for the problem. The first ated until the middle of the twentieth century.
successful surgery is attributed to Johann Freidrich More recently, it has become apparent that young
Dieffenbach (1792–1847), 67 years after Taylor’s children can be treated with good outcomes,
death, although others attempted it, some success- but not older children (Von Noorden 1990).
fully, around the same date as Dieffenbach. In the Slowly ophthalmologists have turned from the
early days, the operation was performed as much idea that strabismus is a congenital defect to the