Investigative Ophthalmology & Visual Science, Vol. 31, No.

6, June 1990
Copyright Association for Research in Vision and Ophthalmology

Postnatal Axial Eye Elongation in Normal and

Visually Deprived Rhesus Monkeys
Margarefe Tigges, Johannes Tigges, Alcides Fernondes,* Howard M. Eggers, and J. Allen Gammonf
The influence of anomalous visual experience on the postnatal regulation of axial eye elongation was
explored by raising newborn rhesus monkeys under different types of monocular and binocular deprivation and comparing their eye growth pattern with that of age-matched normal monkeys. Monocular
manipulations included eyelid suture to eliminate pattern vision; continuous occlusion with an opaque
lens to prevent visual experience; surgical removal of the natural lens to induce continuous blur; and
correction of surgically induced aphakia with extended-wear contact lenses (EWCLs) to provide a
focused image of near objects. Binocular manipulations involved correction of aphakia with an EWCL
in one eye and continuous or partial occlusion of the phakic fellow eye. After monocular eyelid suture
or occlusion, the deprived eyes were longer than the unmanipulated fellow eyes. Aphakic eyes, however, were shorter than their unmanipulated fellow eyes. The unmanipulated eyes followed the eye
elongation pattern of age-matched normal monkeys. Binocular manipulations also resulted in differences in axial length between the two eyes. Aphakic eyes were shorter, and continuously occluded eyes
were longer, than eyes of age-matched controls. After partial occlusion, however, the axial length of
occluded eyes was similar to that of normal eyes. The finding that lid-sutured and occluded eyes
become longer while aphakic eyes remain shorter than normal eyes suggests that additional factors
besides retinal image quality control postnatal eye growth. Invest Ophthalmol Vis Sci 31:10351046,1990

Our research group has developed a monkey model

to induce amblyopia. We are using this animal model
to examine the effects of treatment methods suitable
for human infants with congenital visual system disorders, such as unilateral cataracts.5'6 In the course of
these studies, we found that eye manipulations which
affect visual image quality to different degrees resulted in different effects on postnatal axial eye elongation.7 These initial observations led to the current
in-depth study of the postnatal eye elongation process
of infant rhesus monkeys. Axial eye elongation was
monitored in monkeys raised under a variety of monocular and binocular deprivation conditions. In addition, the time course of normal postnatal axial eye
elongation was determined as a necessary prerequisite to assess the effects of various modifications of
the visual environment on eye growth. Results from
these experiments support the idea that multiple factors control postnatal eye elongation to achieve emmetropia. Some of our findings have been published
as an abstract.8

During investigations of the effects of visual deprivation on the postnatal development of the visual
system in rhesus monkeys, Wiesel and Hubel discovered that lid-sutured eyes grew longer than the unsutured fellow eyes (see Ref. 1). This observation renewed interest in the search for mechanisms involved
in the control of postnatal eye elongation and for
suitable animal models to gain a better understanding
of the regulation of eye growth. Lid suture deprives
the eye of pattern vision. Therefore, lack of proper
visual stimuli appears to interfere with the normal
growth pattern of the globe, and this implicates the
visual environment as a controlling factor in eye
elongation.2"4 The exact nature of regulating mechanisms, however, is still obscure.
From the Yerkes Regional Primate Research Center, Departments of Anatomy and Cell Biology and of Ophthalmology, Emory
University, Atlanta, Georgia, and the Department of Ophthalmology, Columbia University, New York, New York. ""Currently affiliated with the Instituto Hilton Rocha, Belo Horizonte, Brazil.
fCurrently working in Modesto, California.
Supported by National Institutes of Health grants EY-06001
(MT), EY-05361 (JAG), and EY-05975 (RGB), and by RR-00165
from the Division of Research Resources to the Yerkes Regional
Primate Center.
Submitted for publication: June 14, 1989; accepted October 13,
1989.
Reprint requests: Dr. Margarete Tigges, Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322.

Materials and Methods

Axial length measurements were made in both eyes
of 38 normal newborn rhesus monkeys between 1
and 5 days of age and in 22 normal infant and juvenile monkeys between the ages of 1 month and 4

1035

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e versus axial length of the rhesus monkey eye: number of eyes

Age
1-5 days

2 mo

1 mo

3 mo

5 mo

6 mo

7 mo

8 mo

10 mo

9 mo

11 mo

12 mo

13 mo

2yr

3-4

2
2

5
13
33
20
5
76
13.1

1
I
2

14.2

15.2

3
3
1
1
2

10
15.8

3
3
2

1
5

16.8

16.5

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8
4
2
3
1

18
16.8

1
2
1
2

2
2

1
1
1

9
1
2

2
3

2
2

1
2
2

16.9

17.1

16.8

17.0

12

10

17.4

17.3

6
18.3

1037

POSTNATAL EYE ELONGATION IN RHESUS MONKEYS / Tigges er ol

No. 6

years (Table 1). Axial elongation of both eyes was

monitored in 19 monocularly and 18 binocularly manipulated monkeys from birth up to 40 months of
age. All monkeys were born at the Yerkes Regional
Primate Research Center and reared according to established procedures in an environment with an artificial light cycle of 12 hr light and 12 hr dark beginning at 0600 hr.
The eye manipulations were performed within 1-5
days after birth. Lensectomies and eyelid sutures were
done under general anesthesia provided by the veterinary staff, who also supervised postsurgical care.
(Lensectomy and eyelid suture procedures have been
described previously.5'7'9) All surgical and clinical
procedures were in accordance with the ARVO Reso-

lution on the Use of Animals in Research. The

Yerkes Regional Primate Center is fully accredited by
the American Association for Accreditation of Laboratory Animal Care.
Table 2 provides details of the experimental histories of all monocularly manipulated monkeys. The
lid of one eye was sutured (LS) in two monkeys. This
procedure resulted in a translucent membrane of skin
covering the eye. The skin appeared to stretch even
thinner as the monkeys grew. In nine monkeys, one
eye was fitted with an opaque occluder lens (CO).
Four of these animals, which served as controls in a
pharmacologic experiment, received a topical application of 2 drops 2.2% sterile glycerol into the conjunctival sac of both eyes three times per day. The

Table 2. Types of monocular manipulations, axial lengths at birth and at last A-scan measurements, and
differences in axial length between manipulated and unmanipulated eyes
Axial length at birth
(mm)
Monkey

OD

OS

RAo-1

12.82

12.96

RTr-1
RBo-1
RLq-1
RTt-1
RNs-1
RHr-1
RSi-2
RRi-2
RJg-2

NA

13.44
12.36
13.04
12.97
12.45
13.71
13.81
13.82

NA

13.38
12.61
13.29
13.07
12.65
13.68
13.81

OS

Axial length,
manipulated minus
unmanipulated
(mm)

LS

UM

-0.02

13.76

13.78
+ 1.37

15

+0.80

+0.33

+0.10

+0.51

+ 1.05

12

+ 1.54

+ 1.10

Manipulation and axial

length at last A-scan
OD

LS

UM

18.24

16.87

CO
14.41

13.61

UM

CO

UM

15.58

15.25

CO

UM

16.11

16.01

CO

UM

16.37

15.86

CO

UM

18.56

17.51

CO

UM

18.98

17.44

CO

UM

19.01

17.91

13.63

CO

UM

+0.83

18.18
UM
17.92

-0.53

-1.31

11

-2.64

24

-2.59

27

-2.44

28

-3.06

13

-1.04

16

-3.23

24

-1.80

29

RDh-2

13.27

13.16

19.01
CO
17.39

RHn-1

13.05

13.18

ANC

UM

16.35

17.66

RKn-1
RUo-1
RTm-1
RNn-1
RAP-20*
ROq-1
RJn-1

13.35
12.50
13.05
12.81
NA

13.37
13.57

Age at last
A-scan
(months)

13.30
12.20
13.18
12.23
NA

13.22
13.50

ANC

UM

15.06

17.70

ANC

UM

15.43

18.02

ANC

UM

16.43

18.87

ANP

UM

13.39

16.45

ANP

UM

17.76

18.80

ANP

UM

14.83

18.06

ANP

UM

17.16

18.96

* Monkey used by Wilson et al.7

ANC, aphakia, not corrected; ANP, aphakia, near-point corrected; CO,

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continuous occlusion; LS, eyelid suture; NA, not available; OD, right eye;
OS, left eye; UM, unmanipulated.

1038

Vol. 31

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / June 1990

natural lens of one eye was removed surgically from

eight monkeys. In four of these monkeys, the aphakic
eye remained uncorrected (ANC). In the other four
monkeys, the aphakic eye was corrected initially with
a +40D extended-wear contact lens (EWCL) to
provide a focused image of objects at close distances (ANP).
Table 3 provides details of the experimental history
of all binocularly manipulated monkeys. Lensectomies were performed on one eye, which was corrected
subsequently for the resulting aphakia with an EWCL
while the unoperated fellow eye was fitted with an

opaque occluder. Eleven of these monkeys wore the

occluder continuously (CO), ie, during the entire 12
hr light/12 hr dark cycle. The seven remaining monkeys were occluded only for predetermined lengths of
the 12 hr daily light cycle: two monkeys wore the
occluder from 0900 to 1200 hr (25% occlusion), two
others from 0900 to 1500 hr (50% occlusion), and
three from 0900 to 1800 hr each day (75% occlusion).
The percentages of partial occlusion are relative to
the 12 hr light (= 100%) of continuous occlusion.
The lenses for the steep, small monkey eyes were
custom-made in our own lens manufacturing labora-

Table 3. Types of binocular manipulations, axial lengths at birth and at last A-scan measurements, and
differences in axial length between aphakic and occluded eyes
Axial length at birth
(mm)
Monkey

OD

OS

RAp-15

13.27

13.58

Manipulation and axial

length at last A-scan
OD
ANP

17.60
(18.54)
RAr-1

12.76

12.88

AUC

14.24
RAp-22

NA

NA

AUC

RSk-1*

12.96

13.14

CO

RQk-1*

12.93

13.07

ANP

17.55
17.53
15.24
(17.51)
RTk-1*

13.23

12.81

RAp-24

12.80

12.93

AUC

16.68
14.27
(14.26)
13.90

ANP

17.59
(17.96)
+ANP
14.81
+ANP
15.45

RRs-1

13.14

13.01

RTs-1

12.94

13.03

RQs-1

12.86

13.07

ANP

14.37
RPt-1

12.77

12.93

ANP

RQo-1

13.16

13.07

ANP

RNr-1

13.00

13.15

ANP

RLr-1

13.40

13.50

ANP

RNt-1

13.08

13.05

ANP

ROM

13.36

13.36

ANP

14.76
17.49
13.86
15.67
16.27
16.06
* Monkeys used by Wilson et al (1987).
Parentheses indicate measurements made after contact lens-wear was discontinued.
ANP, aphakia, near-point corrected; +ANP, aphakia, near-point cor-

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9
(23)

16.48

-2.24

15

-2.31

20

-1.53

20

-2.18
(-0.69)

22
(39)

-3.37
(-2.71)

22
(31)

-2.57

27

-2.03
(-2.14)

26
(29)

-1.13
(-1.19)

27
(40)

-3.05

13

-1.88

13

-2.11

18

-1.98

18

-1.11

26

-4.27

13

-2.86

19

-1.12

14

-1.55

14

CO

19.86
ANP

16.00
CO

17.42
(18.20)
18.87
(18.85)
CO
19.25

AUC

-0.52
(-0.77)

CO

CO

NA

13.82

18.12
(19.31)

15.50
(16.14)
NA

Age at last
A-scan
(months)

CO

ANP

RAp-23

RPk-1*

OS

Axial length,
aphakic minus
occluded (mm)

CO

16.30
(16.40)
CO

18.72
(19.15)
CO

17.86
CO

17.33
PO; 25%
16.48
PO; 25%
16.74
PO; 50%
18.60
PO; 50%
18.13
PO; 50%
18.53
PO; 75%
17.39
PO; 75%
17.61

rected after 6 weeks; AUC, aphakia, undercorrected; CO, continuous occlusion; NA, not available; OD, right eye; OS, left eye; PO, partial occlusion;
UM, unmanipulated; 25% 3 hr daily; 50% 6 hr daily; 75% 9 hr daily.

No. 6

POSTNATAL EYE ELONGATION IN RHESUS MONKEYS / Tigges er ol

tory. Piano lenses were dyed black to serve as occluders. Light transmission measurements of occluder lenses with a photographic densitometer
showed more than 99% attenuation of light by these
lenses. The occluders fitted under the upper and
lower eyelids, covering the sclera over the entire front
of the eye. We cannot exclude the possibility that
some stray light entered the eye through the sclera
and choroid past the edge of the occluder lens. Two of
the authors wore occluder lenses as a subjective test of
light perception and were unable to detect either light
or movement. This is quite different from the light
and movement perception that one experiences with
one's eyelids closed. Details of contact lens design,
manufacturing, and fitting have been described elsewhere.5'6 In all monkeys fitted with lenses, lens-wear
compliance was monitored every 2 hr throughout the
day and night, at least during the 1st yr of life. This
close surveillance ensured that a lost lens was replaced immediately. For the majority of monkeys,
lens-wear compliance was excellent.6
Axial length measurements of the eyes were obtained by A-scan ultrasonography with an Ophthalmic A-scan A1000 unit (Sonomed Technology). To
allow accurate measurements of the small monkey
eyes, the instrument was fitted with a short focal
length crystal and used modified software. All contact
lenses were removed from the eyes prior to A-scan
measurements and reinserted at the end of the A-scan
procedure. Most monkeys were examined under ketamine anesthesia administered by the veterinary
staff. For calculation of the axial length from ultrasonic measurements, sound velocities for monkey
eyes were assumed to be similar to those of human
eyes.310 Thus, a sound velocity of 1550 m/sec was
assumed in the unoperated phakic eyes and of 1532
m/sec in the aphakic eyes." The average often consecutive measurements from each eye was used as the
true value for the axial length of the eye. In the two
lid-sutured and in five of the nine occluded monkeys,
axial length was measured only before and at the end
of the deprivation experiment in order to avoid repeated opening and suturing of the eyelid and to prevent exposure of the occluded eye to light. In the
remaining four occluded monkeys, axial eye growth
was monitored biweekly until the age of 8 months.
Axial length was measured under a red safety light to
minimize light exposure.
In addition to axial length measurements, all aphakic and all aphakic and occluded monkeys underwent routine eye examinations including keratometry, tonography, and refraction before and shortly
after surgery and thereafter at about 4-6 week intervals. Based on the outcome of these examinations,
lens powers were adjusted in compliance with the

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1039

monkeys' rearing protocols. Postnatal changes in refraction and the relation between refraction and axial
length of the visually deprived monkeys are currently
being analyzed and will be described in a separate
communication.
Results
Postnatal Axial Eye Elongation in Normal Monkeys

Axial length measurements of eyes of newborn and

of normal infant and juvenile monkeys were collected to determine how fast and for how long their
eyes elongate. Table 1 illustrates that the most rapid
axial eye elongation occurred during the first 5-7
months. During the next 6 months, the eyes grew at a
slower pace. By 1 yr, the eye had elongated by an
average of 4.26 mm. Axial elongation continued past
the 1st yr. Axial length measurements from the oldest
monkeys in our study suggest that the eye grows at
least until 4 yr of age (Fig. 1), the age when rhesus
monkeys approach asymptotal skeletal growth.12
In newborn monkeys, interanimal variations of
axial length were observed (Table 1). Also, the axial
length of the right and left eyes differed slightly. However, the mean interocular difference of the normal
group was not significantly different from zero (F
= 0.718; P = 0.4). The standard deviation of the
interocular differences was 0.23 mm, indicating that
differences larger than 0.44 mm would be expected in
less than 5% of the normal population. There also
was no statistically significant difference in axial
length of the eyes between male and female neonates.
Interanimal variations of axial length persisted
during postnatal development. At 3 months, for example, axial length ranged from 14.78 to 16.59 mm,
and at 7 months it varied between 15.74 and 17.39
mm. By 1 yr, the longest eye was 17.73 mm and the
shortest eye was 16.60 mm in length (Table 1).
20--

is-

le-

0.1

10
Age (years)
Log Scale

Fig. 1. Postnatal axial eye elongation of normal rhesus monkeys

as a function of age, based on the average of axial length measurements from two to nine monkeys per age group.

1040

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / June 1990

Effects of Monocular Manipulations

Four types of monocular manipulations were used.

The first was eyelid suture, which results in a patternless image on the retina without depriving the eye of
light.113"15 The second manipulation was continuous
occlusion with an opaque occluder lens, which prevents visual experience by the attenuation of more
than 99% of the light entering the eye. The third type
of manipulation was surgical removal of the natural
lens, which results in a continuously blurred image.
The fourth experimental condition involved the correction of surgically induced aphakia with EWCLs to
provide a focused image of objects at a close distance.
The rearing conditions of all monocularly manipulated monkeys and some of the results are listed in
Table 2. Additional information is provided in Figures 2 to 4.
1. Eyelid suture (LS): The axial length measurements of two lid-sutured monkeys are included here
for comparison with earlier results from our own7
and from other laboratories.1'316 After 1 month of lid
suture (RAo-1), axial lengths of the lid-sutured and its
unmanipulated fellow eye were similar: both eyes had
elongated to approximately the same length (Table
2), which was in the range of 1-month-old normal
infant monkeys. After 15 months of lid suture
(RTr-1), however, axial lengths of the two eyes differed. Moreover, a comparison with the eye elongation pattern of age-matched normal monkeys revealed that elongation of the unmanipulated fellow
eye was in the normal range, whereas the sutured eye
had elongated excessively. This finding is in agreement with previous reports on eye elongation after lid
suture, and supports the notion that lack of pattern
vision without deprivation of light interferes with the
normal postnatal eye elongation process.131617
2. Continuous occlusion (CO): In eight of the nine
monkeys in this experimental group, the occluded
eyes were longer compared to the unmanipulated fellow eyes (Table 2, Fig. 2). The exception was monkey
RDh-2, in which the unmanipulated fellow eye was
slightly longer than the occluded eye. At the time of
the last A-scan available at 8 months of age, both eyes
had grown since birth: the occluded eye by 4.12 mm
and the unmanipulated companion eye by 4.76 mm.
The unmanipulated eye was longer than the eyes of
normal 8-month-old monkeys. It also had a larger
myopic refracted error than the fellow eye. We have
no explanation for this exception, which is not entirely unusual. From 49 monocularly lid-sutured
monkeys reported in the literature, the deprived eyes
of 4 animals also did not develop a longer axial
length, or became more myopic or less hyperopic
than the undeprived fellow eye.4

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21 j
20-191817161514-

Vol. 01

o o Normal eyes
* A Occluded monkeys, occluded eyes
A
* Occluded monkeys, unmonipuloted eyes

1312
Age (months)

Fig. 2. Postnatal axial eye elongation of three monocularly occluded monkeys (RSi-2, RRi-2, RJg-2) compared to that of agematched normal monkeys. The curves for the occluded monkeys
are based on the combined average axial length measurements of
all three monkeys and also show the minimum and maximum
values as recorded at regular intervals during the first 8 months of
life. The curve of axial eye elongation of age-matched normal
monkeys in this graph and in Figures 3-7 is based on the average of
axial length measurements from two to nine monkeys per age
group and also includes the minimum and maximum values for
each age group.

In five monkeys (RBo-1, RLq-1, RTt-1, RNs-1,

RHr-1) axial length was measured only at birth and at
the end of the occlusion experiment (Table 2). All
unmanipulated eyes elongated similarly to eyes of
age-matched normal monkeys. All occluded eyes
grew longer than their unmanipulated fellow eyes.
The differences between the two eyes were rather
modest after 3 months of occlusion (RLq-1, RTt-1).
Twelve months of occlusion (RHr-1), however, had a
pronounced effect. The unmanipulated eye had elongated since birth by 4.86 mm, which is close to the
average normal eye elongation for 1-yr-old monkeys,
whereas the occluded eye had elongated by 6.14 mm.
In the remaining three monkeys (RSi-2, RRi-2,
RJg-2), axial eye elongation was monitored biweekly.
Figure 2 illustrates their eye growth pattern until 8
months of age. After 1 month of occlusion, axial eye
elongation of both eyes was almost identical. By 2
months, however, differences became apparent, and
after 3 months these differences continued to increase
rather rapidly. At the time of the last A-scan available, the average difference in axial length between
the two eyes was 0.83 mm. The overall shape of the
growth curves for both eyes resembled the growth
curve of eyes of age-matched normal monkeys. However, the unmanipulated fellow eyes were longer than
eyes of age-matched normal monkeys. It is possible
that genetically these monkeys have larger eyes than
the normal monkeys in our sample. Also, an effect on
eye growth due to the application of glycerol cannot
be ruled out.

No. 6

POSTNATAL EYE ELONGATION IN RHESUS MONKEYS / Tigges er ol

Therefore, occlusion results in excessive elongation

of the occluded eye compared to the unmanipulated
fellow eye and compared to eyes of age-matched normal monkeys, suggesting that lack of visual experience from birth also interferes with normal postnatal
axial eye elongation.
3. Aphakia (ANC): We reported previously that 21
months after lensectomy the aphakic eye of one
monkey was 1.4 mm shorter than the unmanipulated
fellow eye.7 We have reared four additional aphakic
monkeys (RHn-1, RKn-1, RUo-1, RTm-1) and have
monitored their eye elongation process for up to 28
months (Table 2). After 2 months, the aphakic eyes
already were shorter than their unmanipulated fellow
eyes (Fig. 3). Subsequently, axial elongation of the
unmanipulated fellow eyes corresponded closely to
axial elongation of eyes of age-matched normal monkeys. The aphakic eyes, however, remained shorter.
The most rapid growth for both eyes occurred between birth and 7 months of age, approximately the
period when normal eyes experience their fastest
growth. By the end of the 1st yr, the differences between aphakic and unmanipulated eyes of the four
monkeys ranged from 1.31 to 2.33 mm. The four
aphakic eyes elongated during the 1st yr between 1.4
and 3.15 mm (average, 2.39 mm), but elongation of
the four unmanipulated fellow eyes was almost twice
as great, between 3.78 and 5.13 mm (with an average
of 4.58 mm, which is close to normal). During the
next 12-16 months, the eyes continued to elongate,
but at a reduced rate. The increase in length ranged
from 0.31 to 0.89 mm for the aphakic eyes, and from
0.56 to 0.97 mm for the unmanipulated fellow eyes.
Therefore, aphakia results in eyes that are shorter
compared to their unmanipulated fellow eyes and to

21
20

o o Normal eyes
Aphakic monkeys, unmanipulated eyes

Aphakic monkeys, aphakic eyes

19
18
17
16
15
14
13
12 I I I I I I I I I I I I I I I I I I I I I I I I I I I
0
12
24
Age (months)

Fig. 3. Postnatal axial eye elongation of four monocularly aphakic monkeys (RHn-1, RKn-1, RUo-1, RTm-1) compared to that of
age-matched normal monkeys. The curves for the aphakic monkeys are based on the combined average axial length measurements
of all four monkeys and also show the minimum and maximum
values as recorded at regular intervals up to 28 months of age.

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1041

o o Normal eyes
o
Aphakic monkeys, unmanipulated eyes

Aphakic monkeys, aphakic corrected eyes

21 j
20--

12
Age (months)

Fig. 4. Postnatal axial eye elongation of three monocularly

aphakic, optically corrected monkeys (RNn-1, ROq-1, RJn-1),
compared to that of age-matched normal monkeys. Data from
RAP-20 are not included because of errors in the calibration of the
A-scan instrument during some early measurements. The curves
for the aphakic monkeys are based on the combined average axial
length measurements of all three monkeys and also show the minimum and maximum values as recorded at regular intervals up to
28 months of age.

eyes of age-matched normal monkeys. These data

imply that removal of the natural lens at birth interferes with normal postnatal axial eye elongation.
4. Aphakia corrected with EWCLs (ANP): The
aphakic eyes of four monkeys (RNn-1, RAp-20,
ROq-1, RJn-1) were corrected with EWCLs which
provided a focused image of objects at a close distance. In all monkeys, the corrected aphakic eyes
were much shorter than the unmanipulated fellow
eyes (Table 2). Axial length of the unmanipulated
fellow eyes was similar to that of eyes of age-matched
normal monkeys (Fig. 4). Thus, providing an aphakic
eye with a focused image of objects at a nearpoint still
causes abnormal axial eye elongation.
Effects of Binocular Manipulations

Both eyes of the monkeys in this experimental

group were manipulated simultaneously, but differently. One eye was made aphakic and optically corrected with an EWCL, and the fellow eye occluded
either continuously or part-time. The rearing conditions of all monkeys and some of the results are listed
in Table 3. Additional data are illustrated in Figures 5
to 7.
1. Corrected aphakia (ANP, A UC) combined with
continuous occlusion (CO) of the unoperated fellow
eye: We reported previously the effects of these manipulations on eye elongations in 8 newborn monkeys. By 1 yr of age, the aphakic eyes were shorter
than the occluded fellow eyes.7 We have monitored
eye growth in an additional monkey (RAp-15) reared
according to the same experimental protocol. Two

1042

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / June 1990

additional monkeys (RRs-1, RTs-1) were made

aphakic shortly after birth, but the fitting of the
aphakic eye with a corrective EWCL and of the unoperated fellow eye with an occluder was delayed for
6 weeks (+ANP). The axial eye elongation of these
monkeys was similar to that of other continuously
occluded animals. We also monitored eye elongation
in four monkeys (RAr-1, RAp-22, RAp-23, RAp-24)
which had their aphakic eyes optically undercorrected (AUC). Since their eye growth patterns resembled those of the nearpoint corrected monkeys, the
results from all aphakic and corrected eyes combined
with continuous occlusion of the fellow eyes will be
described together.
Postnatal axial eye elongation of monkey RTk-1 is
illustrated in Figure 5 as a representative example.
After 2 months, the elongation process of the two
eyes diverged. The aphakic eye remained shorter than
the fellow occluded eye and shorter than the eyes of
age-matched normal monkeys. From 9 months of
age, the occluded eye also was longer than eyes of
age-matched normal monkeys. Wear of the corrective and of the occluder lens was discontinued when
the monkey was 22 months old. From this time until
the last A-scan measurement at 31 months of age, the
axial length of the occluded eye did not change. The
aphakic eye elongated slightly, but remained permanently much shorter than the previously occluded eye
and eyes of age-matched normal monkeys.
Figure 6 depicts the postnatal elongation of both
manipulated eyes of nine monkeys of this group at
five different stages during development. It illustrates
several aspects of postnatal eye elongation observed
under these binocular deprivation conditions. The
most obvious is that the aphakic eyes were always
shorter than their occluded fellow eyes. This is in
agreement with our previous report.7 Moreover, most
aphakic eyes were much shorter than eyes of ageo Normal eyes
A RTk-1. OS
* RTk-1, OD

I I I I I I I I I I I I I I I I I t I I I I I I I I I I I I I

12
Age (months)

Fig. 5. Postnatal axial eye elongation of monkey RTk-1 that was

reared with surgically induced, optically corrected aphakia in one
eye (OD) and continuous occlusion of the fellow eye (OS) compared to age-matched normal monkeys.

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Vol.

31

22
OCCLUDED
RAR1
RAP24
RTK1
RSK1
RQK1
RPK1
RAP23
RAP22
RAP15

3-5

6-9

12-13

18-20

22-24

MONTHS

Fig. 6. Axial length differences between the aphakic corrected eye

(open symbols) and the occluded fellow eye (filled circles) of nine
monkeys at different ages. The dashed line represents the average
axial eye lengths of age-matched normal monkeys.

matched normal monkeys. Furthermore, interanimal

variations were found in eye size and in the axial
elongation process as a function of age. By 3-5
months of age, eye sizes varied between monkeys, but
the differences in axial length between the two manipulated eyes were relatively similar from animal to
animal. After 6-9 months of deprivation, however,
the differences became much more variable; for example, compare monkey RQk-1 with RAp-23. Figure 6 also illustrates that starting at the age of 12-13
months, the rate of axial eye elongation had leveled
off. At this age, the axial length of six of nine occluded
eyes exceeded the axial length of eyes of age-matched
normal monkeys. Thus, deprivation from birth of
both eyes by aphakia combined with continuous occlusion results in pronounced axial length differences
between the two manipulated eyes.
In monkey RAp-15, there was only a small difference in axial length between the two eyes by 9 months
of age. At this time, the monkey had learned to manipulate the occluder. With the back of his hand he
habitually pushed the lens under the upper eyelid and
peeked around the occluder.
Finally, we continued to monitor axial eye elongation in four monkeys (RQk-1, RTk-1, RAp-24,
RPk-1) which were between 22 and 27 months old
when all corrective and occluder lens-wear was discontinued; axial lengths were measured from 3-17
months later (Table 3, numbers in parentheses). In
this group, we found interanimal variations, which
may be due in part to the differences in age when all
lenses were removed and to the length of the time the
monkeys experienced vision without corrective and
occluder lenses. Monkey RAp-24, with the shortest
period of 3 months without lenses, showed no significant changes in axial length of both eyes. In another
monkey (RPk-1), both eyes elongated similarly during 13 months without lenses. On the other hand, in

No. 6

1043

POSTNATAL EYE ELONGATION IN RHESUS MONKEYS / Tigges er ol

one monkey (RQk-1), the aphakic eye elongated by

2.27 mm, but the occluded eye only by 0.78 mm
during 17 months of no lens-wear. This resulted in
considerable narrowing of the axial length differences
between the two eyes. In the last monkey of this
group (RTk-1), the formerly occluded eye did not
elongate any further during 9 months without occluder lens, whereas the aphakic eye grew longer by
0.64 mm without a corrective lens (see also Fig. 5).
All aphakic eyes, however, remained consistently
shorter than the formerly occluded fellow eyes and
eyes of age-matched normal monkeys.
2. Corrected aphakia (ANP) combined with partial
occlusion (PO) of the fellow eye: Of the seven monkeys in this group, two were occluded for 3 hr (25%),
two for 6 hr (50%), and three for 9 hr (75%) during the
normal daily lighting cycle (Table 3). In contrast to
the continuously occluded monkeys, we had difficulties keeping the occluder lenses in the eyes of these
monkeys. Around 4-6 months of age, the monkeys
developed the habit of pushing the occluder under the
upper eyelid and to peek around it, often combined
with the habit of rubbing the occluder out of the eye.
The aphakic eyes of all seven monkeys were shorter
than the occluded fellow eyes and also much shorter
than eyes of age-matched normal monkeys (Fig. 7).

21
20
19

o
*
A

o
*
A

Normal eyes
R N t - 1 , OS
R N t - 1 , OD
R O t - 1 , OS
R O t - 1 , OD

The reaction of the occluded eyes, however, varied.

In the three monkeys experiencing 9 hr of occlusion
(two are shown in Fig. 7A) and in the two monkeys
with 6 hr of occlusion (Fig. 7B), the axial length of the
occluded eyes were at or slightly above the maximal
values of normal eyes. However, in both monkeys
with the shortest occlusion period, 3 hr daily, the
axial length of the occluded eyes fell into or below the
range of age-matched normal monkeys (Fig. 7C).
Therefore, continuous occlusion seems to be a necessary condition for excessive axial eye elongation.
Discussion
Rhesus monkeys are used widely to explore the
postnatal development of the visual system under
normal and deprivation conditions. Numerous similarities have been described in the anatomy and
function of their visual system with that of humans;
therefore, they serve as a valuable animal model to
study normal visual system development as well as
causes underlying visual system disorders in humans.
Our data of the postnatal eye elongation process of
normal infant rhesus monkeys revealed another similarity. The course of postnatal eye elongation in infant and juvenile rhesus monkeys corresponds closely

o o Normal eyes
A
A R N r - 1 , OS
o
* R N r - 1 , OD

21 -r
20-

19--

18

18-'

17

17-

16

1 6

15

15--

14

1 4

13

13--

12

12

R L r - 1 , OS
a R L r - 1 , OD

12
Age (months)

21 j
20Fig. 7. Postnatal axial eye elongation of six monkeys reared with
an aphakic corrected eye (OD) and a partially occluded fellow eye
(OS) compared to age-matched normal monkeys. (A) These two
monkeys were occluded for 9 hr/day (75% occlusion). (B) These two
monkeys were occluded for 6 hr/day (50% occlusion). (C) These two
monkeys were occluded for 3 hr/day (25% occlusion).

19-

o
o
A*
A
A
- -
--

Normal
RQs-1,
RQs-1,
RPt-1,
RPt-1.

eyes
OS
OD
OS
00

18-

17-161514-13-

12

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1044

INVESTIGATIVE OPHTHALMOLOGY b VISUAL SCIENCE / June 1990

to the postnatal axial eye elongation process reported

in humans 1819 : an initially rapid early postnatal
growth phase is followed by a slower infantile and an
even slower juvenile growth phase.
A variety of mechanisms has been proposed to account for the achievement of proper eye size during
postnatal eye growth. The results of numerous studies
with different animal species point to visual image
quality as an important factor because loss of a focused image on the plane of the retina during development perturbs coordinated eye elongation. In
chicks, for example, eyes deprived of normal vision
either by eyelid suture or by translucent occluders
elongated excessively.20"26 In monkeys, poor retinal
image quality early in life due to eyelid suture13'4 or
opacification of the cornea27 caused excessive eye
elongation. In humans, after monocular deprivation
due to congenital lens opacity28 and to neonatal eyelid closure,29 the deprived eyes were longer than the
undeprived fellow eyes and normal eyes. Furthermore, a high incidence of myopia was reported in
human patients suffering from a variety of ocular
anomalies that caused disruption of pattern vision
during early development.30 These findings support
the idea that emmetropization is a vision-dependent
phenomenon in humans also. Another study, however, found a less consistent effect of visual deprivation on axial eye elongation in humans.31 In patients
with unilateral dense congenital cataracts and unilateral complete blepharoptosis, the deprived eyes were
longer than normal fellow eyes in some cases, but
shorter or unchanged in others. These authors concluded that axial eye elongation as a result of visual
deprivation is less predictable in humans than in
monkeys.
There is consensus in the literature that eyelid suture prevents form or pattern vision without depriving the eye of light.113"15 Calculations of the amount
of light reaching the retina of a lid-sutured monkey
eye range from 10%13 to an attenuation of about half
a log unit.1 On the other hand, occlusion by means of
opaque occluder lenses, as in the current experiments, results in more than 99% light attenuation.
Therefore, our data imply that absence of visual stimulation is another cause of excessive axial postnatal
eye elongation. Some recent findings raise the possibility that visual deprivation by means of occluder
lenses has different effects than lack of form vision by
means of eyelid suture. For example, we found that
continuous occlusion with opaque lenses affects the
retinal dopamine (DA) system in monkeys.32'33 The
contents of DA and of its metabolite 3,4-dihydroxyphenylacetic acid are significantly decreased in the
occluded compared to the unmanipulated fellow eye.
In contrast, eyelid suture had a less consistent and
smaller effect on the DA system than does occlusion.33 Furthermore, it is well established that lid su-

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Vol. 31

ture of infant monkeys leads to profound functional

changes in the striate cortex.34 In agreement with
these studies, we found that only a small percentage
of neurons in the striate cortex of a lid-sutured monkey respond to visual stimulation of the sutured eye.
In comparison to a lid-sutured eye, however, a higher
percentage of responses could be elicited by visual
stimulation of an occluded eye in the striate cortex of
monkeys reared with an aphakic eye and a continuously occluded fellow eye (Wilson, Tigges, Tigges,
Boothe, and Gammon, unpublished results). Additional experiments are necessary to separate the effects of visual stimulation absence via occlusion from
those of pattern vision absence via eyelid suture.
Neurochemical changes in the retina have been reported not only after occlusion, but also after eyelid
suture. For example, immunoreactivity for vasoactive intestinal peptide (VIP) increases in amacrine
cells in eyelid-sutured monkeys.17 The effects of occlusion on VIP have not been investigated. In
chicks,26 changes occur in the DA system as a result
of deprivation. Additional support for the involvement of DA in eye growth control comes from the
recent finding that apomorphine, an agent that interacts with DA receptors, prevents excessive axial elongation of eyes of visually deprived chicks.2635 Since
deprivation apparently causes neurochemical alterations in the retina itself, retinal neurotransmitter/
neuromodulator substances may play a role in eye
size regulation.
In chicks36'37 and in monkeys,1 lid-sutured eyes
continue to elongate abnormally after sectioning of
the optic nerve. Also, in tree shrews,38 lid-sutured
eyes become longer after blockage of retinal ganglion
cell action potentials by intravitreal injections of tetrodotoxin. Since excessive axial eye elongation proceeds in the absence of retinal ganglion cell activity
and of centrally arriving action potentials, retinal
cells other than ganglion cells may be a source of
growth regulating and coordinating factors.
A genetically determined regulatory mechanism of
eye growth is implied by our observation that manipulated eyes, regardless of the type of manipulation,
undergo their most prolific growth at about the same
age when normal eyes grow fastest. Furthermore,
elongation of the occluded eyes seems to slow down
at around 1 yr of age, in parallel with slower globe
growth during normal postnatal development. It also
appears that the growth of each eye is regulated independently from the other, because an unmanipulated
eye grows like eyes of age-matched normal monkeys,
whereas the deprived fellow eye does not. Lack of
growth coordination between manipulated and unmanipulated eyes also has been reported for
chicks.22'24
The available resources did not permit us to resolve
whether the lens undergoes changes in the phakic

No. 6

POSTNATAL EYE ELONGATION IN RHESUS MONKEYS / Tigges er ol

elongated globes' of occluded eyes. Furthermore, our

experiments were not designed to test the role of accommodation in excessive eye elongation. Changes
in the steepness of the cornea were not obvious; keratometry measurements of the aphakic and the occluded fellow eye of individual monkeys had similar
values (unpublished observations). Elevated intraocular pressure can also be ruled out because pressure
differences between the two eyes of a pair were insignificant. Thermal or mechanical effects of a sutured
eyelid over the globe as reported in chicks39 are unlikely in monkeys, because monocular eyelid suture
combined with dark-rearing resulted in identical
axial length in both eyes of two monocularly lid-sutured monkeys raised for 10-12 months in darkness.40
How do our occlusion data compare with darkrearing results? The axial length of the eyes of two
dark-reared monkeys40 is within the range of our agematched normal monkeys. Therefore, it could be argued that dark-rearing does not interfere with normal
postnatal axial eye growth. Moreover, since during
dark-rearing both eyes are subjected to the identical
deprivation condition, there is no unmanipulated
fellow eye as an "internal control"2441 against which
the actual eye growth pattern can be assessed. The
problem is further complicated by the high incidence
of interanimal variations in eye size, in the tempo of
postnatal eye growth (current results), and in postnatal refractive changes.42 Therefore, the issue of occlusion versus dark-rearing effects is still unsettled because of insufficient data.
In accordance with previous results,1 we determined the vitreous chamber as a locus of axial eye
elongation. In three monocularly occluded monkeys,
the vitreous in the occluded eyes was significantly
longer than the vitreous in the unoccluded fellow eyes
(Iuvone, Tigges, Stone, Lambert, and Laties, manuscript in preparation).
Our finding that surgical removal of the natural
lens in newborn rhesus monkeys leads to a shorter
globe is at variance with recent findings in human
infants. The aphakic eyes of children with unilateral
cataracts were consistently longer than the normal
fellow eye.43 The most likely reason for this discrepancy is that in these patients surgical removal of the
cataracts occurred at an older age, leaving the children with a blurred image in the cataractous eye during the sensitive postnatal period.
Aphakic eyes in our experimental monkeys were
shorter, regardless of whether the eyes were corrected
optically or not. Absence of the lens and removal of
part of the vitreous cannot be ruled out unequivocally as a cause for shortening of the aphakic eyes. To
determine whether surgical intervention by itself is
sufficient to disrupt postnatal eye growth, a surgical
approach identical to lensectomy, but leaving the nat-

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1045

ural lens intact, was used in one eye of a newborn

monkey. The postnatal elongation rate was similar
for both eyes of this monkey. It is known that chicken
eyes grow more slowly in the absence of the lens
compared to a normal fellow eye.4445 Experiments in
chicks to determine the relation of lens and retina
during eye growth also established that lens differentiation and development are promoted by a factor
originating from the neural retina.46 Recently, retinal
growth factors have been identified.47'48 They may
interact with the lens or with other ocular tissues in
coordinating eye growth. All of these findings indicate that the process of postnatal regulation of eye
size until emmetropia is achieved must be complex.
Besides a genetically determined component, the retina may coordinate eye elongation through a variety
of mechanisms. These include retinal image quality,
regulation of the release and metabolism of neurotransmitter/neuromodulator substances, and retinaderived growth factors. By appropriate interactions
between these mechanisms as well as by some others
as yet unidentified, the fine-tuning of the refractive
state of the eye is accomplished. Interference with
these processes, however, results in refractive errors
leading to myopia, a common cause of impaired vision of still unresolved etiology in humans.49
Key words: monocular and binocular visual deprivation,
aphakia, occlusion, development
Acknowledgments
We thank Sarah Hamm and Sherry Raskin for skillful
technical support, Frank Kiernan for help with the graphs
and with the densitometry measurements of the occluder
lenses, and Jean Torbit for expert secretarial assistance. We
are greatly indebted to the animal care staff for excellent
care of the monkeys and to the veterinary staff for assistance with anesthesia during surgery and eye examination.
We are also grateful to Kevin Vaughan for expertise in
manufacturing lenses and supervising lens-wear compliance schedules. Thanks are also due to Drs. J. Wallman,
R. G. Boothe, and J. R. Wilson for helpful comments on
an early draft of the manuscript, and to Drs. R. A. Stone,
A. M. Laties, and P. M. Iuvone for making available four
occluded monkeys.

References
1. Raviola E and Wiesel TN: An animal model of myopia. N Engl
JMed 312:1609, 1985.
2. Criswell MH and Goss DA: Myopia development in nonhuman primates: A literature review. Am J Optom Physiol Opt
60:250, 1983.
3. Smith EL III, Harwerth RS, Crawford MLJ, and von Noorden
GK: Observations on the effects of form deprivation on the
refractive status of the monkey. Invest Ophthalmol Vis Sci
28:1236, 1987.
4. Smith EL III, Harwerth RS, Crawford MLJ, and von Noorden
GK: The influence of the period of deprivation on experimental refractive errors. In Strabismus and Amblyopia, Lennerstrand G, von Noorden GK, and Campos EC, editors. New
York, Plenum Press, 1988, pp. 197-206.

1046

INVESTIGATIVE OPHTHALMOLOGY b VISUAL SCIENCE / June 1990

5. Gammon JA, Boothe RG, Chandler CV, Tigges M, and Wilson JR: Extended-wear soft contact lenses for vision studies in
monkeys. Invest Ophthalmol Vis Sci 26:1636, 1985.
6. Fernandes A, Tigges M, Tigges J, Gammon JA, and Chandler
C: Management of extended-wear contact lenses in infant
rhesus monkeys. Behav Res Methods Instrum Comp 20:11,
1988.
7. Wilson JR, Fernandes A, Chandler CV, Tigges M, Boothe RG,
and Gammon JA: Abnormal development of the axial length
of aphakic monkey eyes. Invest Ophthalmol Vis Sci 28:2096,
1987.
8. Tigges M, Tigges J, Fernandes A, Eggers HM, and Gammon
JA: Axial eye growth of normal and visually deprived infant
monkeys. ARVO Abstracts. Invest Ophthalmol Vis Sci
30(Suppl):301, 1989.
9. Tigges M, Hendrickson AE, and Tigges J: Anatomical consequences of long-term monocular eyelid closure on lateral geniculate nucleus and striate cortex in squirrel monkey. J Comp
Neurol 227:1, 1984.
10. Thorn F, Doty RW, and Gramiak R: Effect of eyelid suture on
development of ocular dimensions in macaques. Curr Eye Res
1:727, 1982.
11. Jansson F and Kock E: Determination of the velocity of ultrasound in the human lens and vitreous. Acta Ophthalmol
40:420, 1962.
12. Brizzee KR and Dunlap WP: Growth. In Comparative Primate Biology, Vol 3, Reproduction and Development, Dukelow WR and Envin J, editors. New York, Alan R. Liss, 1986,
pp. 363-413.
13. Crawford MLJ and Marc RE: Light transmission of cat and
monkey eyelids. Vision Res 16:323, 1976.
14. Movshon JA and Van Sluyters RC: Visual neural development. Annu Rev Psychol 32:477, 1981.
15. Sherman SM and Spear PD: Organization of visual pathways
in normal and visually deprived cats. Physiol Rev 62:738,
1982.
16. Wiesel TN and Raviola E: Myopia and eye enlargement after
neonatal lid fusion in monkeys. Nature 266:66, 1977.
17. Stone RA, Laties AM, Raviola E, and Wiesel TN: Increase in
retinal vasoactive intestinal polypeptide after eyelid fusion in
primates. Proc Natl Acad Sci USA 85:257, 1988.
18. Larsen JS: The sagittal growth of the eye: IV. Ultrasonic measurement of the axial length of the eye from birth to puberty.
Acta Ophthalmol 49:873, 1971.
19. Gordon RA and Donzis PB: Refractive development of the
human eye. Arch Ophthalmol 103:785, 1985.
20. Hayes BP, Fitzke FW, Hodos W, and Holden AL: A morphological analysis of experimental myopia in young chickens.
Invest Ophthalmol Vis Sci 27:981, 1986.
21. Schaeffel F and Howland HC: Visual optics in normal and
ametropic chickens. Clin Vision Sci 3:83, 1988.
22. Schaeffel F and Howland HC: Mathematical model of emmetropization in the chicken. J Opt Soc Am [A] 5:2080, 1988.
23. Wallman J and Turkel J: Extreme myopia produced by modest
change in early visual experience. Science 201:1249, 1978.
24. Wallman J and Adams JI: Developmental aspects of experimental myopia in chicks: Susceptibility, recovery and relation
to emmetropization. Vision Res 27:1139, 1987.
25. Gottlieb MD, Fugate-Wentzek LA, and Wallman J: Different
visual deprivations produce different ametropias and different
eye shapes. Invest Ophthalmol Vis Sci 28:1225, 1987.
26. Stone RA, Lin T, Laties AM, and Iuvone PM: Retinal dopamine and form-deprivation myopia. Proc Natl Acad Sci USA
86:704, 1989.
27. Wiesel TN and Raviola E: Increase in axial length of the macaque monkey eye after corneal opacification. Invest Ophthalmol Vis Sci 18:1232, 1979.

Downloaded From: http://iovs.arvojournals.org/ on 03/04/2016

Vol. 31

28. Johnson CA, Post RB, Chalupa LM, and Lee TJ: Monocular
deprivation in humans: A study of identical twins. Invest
Ophthalmol Vis Sci 23:135, 1982.
29. Hoyt CS, Stone RD, and Fromer C: Monocular axial myopia
associated with neonatal eyelid closure in human infants. Am J
Ophthalmol 91:197, 1981.
30. Rabin J, Van Sluyters RC, and Malach R: Emmetropization:
A vision-dependent phenomenon. Invest Ophthalmol Vis Sci
20:561, 1981.
31. Von Noorden GK and Lewis RA: Ocular axial length in unilateral congenital cataracts and blepharoptosis. Invest Ophthalmol Vis Sci 28:750, 1987.
32. Tigges M, Iuvone PM, Tigges J, Fernandes A, and Gammon
JA: Effects of monocular occlusion on lateral geniculate nucleus (LGN) anatomy and histochemistry, and on retinal dopamine system in infant rhesus monkeys. Soc Neurosci Abstr
13:1535, 1987.
33. Iuvone PM, Tigges M, Fernandes A, and Tigges J: Dopamine
synthesis and metabolism in rhesus monkey retina: Development, aging, and the effects of monocular visual deprivation.
Vis Neurosci 2:465, 1989.
34. Movshon JA, Eggers HM, Gizzi MS, Hendrickson, AE,
Kiorpes L, and Boothe RG: Effects of early unilateral blur on
the macaque's visual system: III. Physiological observations. J
Neurosci 7:1345, 1987.
35. Stone RA, Lin T, Laties AM, Iuvone PM, Fugate-Wentzek
LA, Gottlieb MD, and Wallman J: Apomorphine blocks axial
elongation of the visually deprived chick eye. ARVO Abstracts.
Invest Ophthalmol Vis Sci 3O(Suppl):31, 1989.
36. Troilo D, Gottlieb MD, and Wallman J: Visual deprivation
caused myopia in chicks with optic nerve section. Curr Eye Res
6:993, 1987.
37. Wildsoet CF and Pettigrew JD: Lid-suture induced myopia in
chickens is not dependent on ganglion cell activity. Invest
Ophthalmol Vis Sci 30:31, 1989.
38. Norton TT, Essinger JA, and McBrien NA: Lid-suture myopia
in tree shrew despite blockade of ganglion cell action potentials. ARVO Abstracts. Invest Ophthalmol Vis Sci
3O(Suppl):31, 1989.
39. Hodos W, Revzin AM, and Kuenzel WJ: Thermal gradients in
the chick eye: A combining factor in experimental myopia.
Invest Ophthalmol Vis Sci 28:1859, 1987.
40. Raviola E and Wiesel TN: Effect of dark-rearing on experimental myopia in monkeys. Invest Ophthalmol Vis Sci 17:485,
1978.
41. Wallman J, Gottlieb MD, Rajaram V, and Fugate-Wentzek
LA: Local retinal regions control local eye growth and myopia.
Science 237:1, 1987.
42. Guyton DL, Greene PR, and Stone RT: Dark-rearing interference with emmetropization in the rhesus monkeys. Invest
Ophthalmol Vis Sci 30:761, 1989.
43. Rasooly R and BenEzra D: Congenital and traumatic cataract.
Arch Ophthalmol 106:1066, 1988.
44. Coulombre AJ and Coulombre JL: Lens development: I. Role
of the lens in eye growth. J Exp Zool 156:39, 1964.
45. Coulombre AJ: The eye. In Organogenesis, DeHaan RL and
Ursprung H, editors. New York, Holt, Rinehart and Winston,
1965, pp. 219-251.
46. Coulombre JL and Coulombre AJ: Lens development: Fiber
elongation and lens orientation. Science 142:1489, 1963.
47. Lobb RR, Harper JW, and Fett JW: Purification of heparinbinding growth factors. Anal Biochem 154:1, 1986.
48. Courty J, Loret C, Moenner M, Chevallier B, Lagente O,
Courtois Y, and Barritault D: Bovine retina contains three
growth factor activities with different affinity to heparin: Eyederived growth factor I, II, III. Biochimie 67:265, 1985.
49. Curtin BJ: The Myopias. Philadelphia, Harper & Row, 1985,
pp. 61-151.