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Optom Vis Sci. Author manuscript; available in PMC 2007 March 5. Published in final edited form as: | PMCID: PMC1810233 NIHMSID: NIHMS13041 |
Astigmatism in Monkeys with Experimentally Induced Myopia or
Hyperopia CHEA-SU KEE, BS(Optom), MA(Bio), PhD, LI-FANG HUNG, OD, PhD, YING QIAO-GRIDER, MD, RAMKUMAR RAMAMIRTHAM, BS(Optom), and EARL L. SMITH, III, OD, PhD, FAAO College of Optometry, University of Houston, Houston, Texas; and Vision CRC, University of New South Wales, Sydney, Australia Purpose Astigmatism is the most common ametropia found in humans and is often
associated with large spherical ametropias. However, little is known about
the etiology of astigmatism or the reason(s) for the association between
spherical and astigmatic refractive errors. This study examines the
frequency and characteristics of astigmatism in infant monkeys that
developed axial ametropias as a result of altered early visual
experience. Methods Data were obtained from 112 rhesus monkeys that experienced a variety
of lens-rearing regimens that were intended to alter the normal course of
emmetropization. These visual manipulations included form deprivation (n
= 13); optically imposed defocus (n = 48); and
continuous ambient lighting with (n = 6) or without optically
imposed defocus (n = 6). In addition, data from 19 control
monkeys and 39 infants reared with an optically imposed astigmatism were
used for comparison purposes. The lens-rearing period started at
approximately 3 weeks of age and ended by 4 to 5 months of age. Refractive
development for all monkeys was assessed periodically throughout the
treatment and subsequent recovery periods by retinoscopy, keratometry, and
A-scan ultrasonography. Results In contrast to control monkeys, the monkeys that had experimentally
induced axial ametropias frequently developed significant amounts of
astigmatism (mean refractive astigmatism = 0.37 ±
0.33 D [control] vs. 1.24 ± 0.81 D
[treated]; two-sample t-test, p < 0.0001),
especially when their eyes exhibited relative hyperopic shifts in refractive
error. The astigmatism was corneal in origin (Pearson’s r; p
< 0.001 for total astigmatism and the JO and J45 components), and the
axes of the astigmatism were typically oblique and bilaterally mirror
symmetric. Interestingly, the astigmatism was not permanent; the majority of
the monkeys exhibited substantial reductions in the amount of astigmatism at
or near the end of the lens-rearing procedures. Conclusions In infant monkeys, visual conditions that alter axial growth can also
alter corneal shape. Similarities between the astigmatic errors in our
monkeys and some astigmatic errors in humans suggest that vision-dependent
changes in eye growth may contribute to astigmatism in humans. Keywords: astigmatism, ametropia, refractive error, primate, emmetropization Astigmatism is the most common refractive error, occurring frequently in both
healthy (for a review, see reference 1) and
diseased eyes. 2– 4 For instance, in a recent multicentered, school-based study
(ages 5–17 years), significant amounts of astigmatism were more prevalent
(≥1.0 D, 28.4%) than myopia (≥−0.75 D,
9.2%) or hyperopia (≥+1.25 D,
12.8%). 5 However, astigmatic
errors, particularly large astigmatic errors, are frequently associated with significant
spherical ametropias. Although emmetropes or subjects who have low degrees of spherical
ametropia usually also exhibit small amounts of astigmatism, subjects who have high
amounts of myopia or hyperopia frequently exhibit high amounts of astigmatism. 6– 11 In fact, it has been reported that the magnitudes of astigmatism and myopia
are linearly correlated in children 12 and young
adults. 7, 13Why is astigmatism associated with spherical ametropias? Although mechanical
factors such as eyelid tension 2, 3, 14 and ocular
rigidity 15 have been implicated in the
genesis of astigmatism, little is known about the etiology of astigmatism or the
mechanism(s) underlying the association between astigmatism and spherical ametropia.
However, our recent studies in monkeys 16, 17 indicate that visual experience can alter
corneal shape resulting in astigmatism. Specifically, when we reared infant monkeys with
cylinder lenses in front of their eyes, we found that the optically imposed astigmatism
not only altered emmetropization resulting in axial ametropias, 17 but it also promoted the development of significant
amounts of astigmatism. 16 However, the fact that
the axis of the ocular astigmatism was not in the appropriate direction to neutralize
the astigmatic errors imposed by the treatment lenses suggested that the eye does not
have an active vision-dependent “sphericalization” process
analogous to emmetropization. 18 Instead, the
ocular astigmatism found in the cylinder lens-reared monkeys, which was associated with
both axial myopia and hyperopia, 17 seemed to be a
byproduct of the vision-dependent mechanisms that regulate axial elongation and the
emmetropization process. If this is true, then eyes that experienced altered
refractive-error development as a result of other visual manipulations should also show
a high frequency of astigmatism. A variety of rearing strategies have been shown to predictably alter refractive
development. For example, in many different animal species, including humans, form
deprivation consistently produces axial myopia (e.g., humans, 19 rhesus monkeys, 20
marmosets, 21 tree shrews, 22 and chickens 23).
Moreover, optically imposing either myopia or hyperopia in young animals with spherical
lenses results in compensating axial ametropias that are dependent on the sign and power
of the treatment lenses (e.g., rhesus monkeys, 24
marmosets, 25 tree shrews, 26 and chickens 27).
However, in part because experimentally induced refractive errors have traditionally
been expressed in a spherical-equivalent format (i.e., the averaged correction for the
two principal astigmatic meridians), only a few studies in chickens have previously
noted an association between astigmatism and either axial hyperopia or myopia. 28, 29 The
purpose of this study was to determine if vision-dependent alterations in axial growth
also lead to the development of astigmatism in primates. Specifically, we examined the
frequency and characteristics of astigmatism in infant monkeys that developed axial
ametropias in response to a variety of different types of altered visual experience. Subjects Data were obtained from 112 experimental monkeys (Macaca
mulatta) that were each subjected to one of a variety of lens-rearing
regimens early in life. An advantage of including monkeys reared under a variety
of conditions was that, as a group, the experimental monkeys exhibited a wide
range of spherical-equivalent refractive errors (−7.50 D to
+8.50 D) that were primarily axial in nature. All of the monkeys were obtained at 2 to 3 weeks of age and were housed
in our primate nursery that was maintained on a 12-hour light/12-hour dark
lighting cycle. After the initial biometry measurements that were performed at
approximately 3 weeks of age, the monkeys were randomly assigned to either the
control group (normal unrestricted vision, n = 16; bilateral plano
lenses, n = 3) 16, 17, 30– 32 or one of
the experimental groups. The details of the individual rearing regimens and our
methods for assessing refractive development have been described in detail in
previous studies 16, 24, 32– 35 and are
therefore outlined briefly here. All of the rearing and experimental procedures
were reviewed and approved by the University of Houston’s
Institutional Animal Care and Use Committee and were in compliance with the
Association for Research in Vision and Ophthalmology Statement on the Use of
Animals in Ophthalmic and Vision Research. Visual Manipulations To control an animal’s visual experience, we used
lightweight helmets to hold diffuser lenses or spherical- or cylindrical-powered
spectacle lenses in front of one or both eyes of infant monkeys. The
lens-rearing regimens were started at approximately 3 weeks of age (mean
= 23.4 days; range = 16–35 days), and the
monkeys wore the helmets and treatment lenses continuously for an average of 109
± 15 days. After the lens-rearing period, the helmets were removed
and the monkeys resumed unrestricted vision. Form Deprivation by Diffusers (n = 13) A wide range of predominantly axial myopia was produced by rearing
individual monkeys with one of three different diffuser lenses (weakest, n
= 3; intermediate, n = 4; strongest, n =
6) over one eye while the fellow eyes viewed through plano lenses. 33 The different diffusers produced
varying degrees of image degradation. The strongest diffusers reduced the
spatial contrast sensitivity for normal human observers by more than 1 log
unit at 0.125 cycles/degree (c/deg) with a resulting cutoff spatial
frequency below 1 c/deg, whereas the weakest diffusers decreased contrast
sensitivity by only 0.1 log units at 0.125 c/deg and by 0.75 log units at 8
c/deg. Optically Imposed Defocus by Spherical Lenses (n = 48) The effective refractive errors of these infant monkeys were altered
by securing spherical spectacle lenses (+12 to −6 D)
in front of one (n = 4) or both eyes (n = 44).
Although most of the treated monkeys wore constant and equal-powered lenses
in front of both eyes throughout the treatment period (positive, n
= 10; negative, n = 14), two rearing strategies were
used to increase the magnitude of the compensating ametropias. In one case,
the treatment-lens powers were increased systematically in either the
negative or positive directions for both eyes during the treatment period
(sequential positive increments, n = 6; sequential negative
increments, n = 4). The goal was to maintain a relatively
constant degree of imposed hyperopia or myopia throughout the treatment
period. In a second group of monkeys that wore positive lenses in front of
one eye and negative lenses in front of the other eye, the degree of imposed
anisometropia was increased systematically during the treatment period by
increasing the power of the lenses in front of each eye. To ensure that the
animals in this group actively fixated with both eyes, each eye was occluded
for half the daily lighting cycle with the occluder being switched between
the eyes halfway through the lighting cycle (alternating occlusion group, n
= 10). Continuous Ambient Lighting (n = 12) Twelve infants were reared under continuous ambient lighting
beginning at approximately 1 month of age. 34, 35 Half of these monkeys
were reared with unrestricted vision (the “control”
group for continuous light, n = 6), whereas the other half were
reared with either +3.0 D (n = 3) or
−3.0 D lenses (n = 3) in front of one eye and plano
lenses in front of the fellow eye from the onset of continuous light until 4
months of age. All the animals were returned to a normal diurnal lighting
cycle at an average age of 207.1 ± 15.7 days. Optically Imposed Astigmatism (n = 39) This group of monkeys was included for comparison purposes because
we had previously shown that these animals developed both
axial myopia or hyperopia 17 and
significant amounts of astigmatism. 16
During the rearing period, with-the-rule (WTR), against-the-rule (ATR), and
oblique astigmatism were optically imposed by appropriately orienting the
principal meridians of the spherocylindrical treatment lenses
(+1.50–3.00 × 90, 180, 45, or 135). Six
animals wore cylindrical lenses over one eye that optically imposed WTR
astigmatism, whereas six others experienced monocular ATR astigmatism; the
fellow eyes of these animals viewed through plano lenses. Twenty-seven
animals wore cylindrical lenses in front of both eyes. For 19 of these
binocularly treated animals, the direction of imposed astigmatism was the
same in each eye (WTR, n = 7; ATR, n = 6; or oblique
astigmatism, n = 6). Eight animals experienced ATR astigmatism
with their right eyes and WTR astigmatism with their left eyes. 16, 17 Biometry Measurements Beginning at the onset of the treatment period and typically every 2 to
3 weeks thereafter, refractive error, corneal curvature, and the
eye’s axial dimensions were measured by retinoscopy, keratometry,
and A-scan ultrasonography, respectively. To perform these measurements, the
monkeys were anesthetized (intramuscular injection of 15–20 mg/kg
ketamine hydrochloride and 0.15–0.2 mg/kg acepromazine maleate;
topically 1–2 drops of 0.5% tetracaine hydrochloride)
and cyclopleged (multiple drops of 1% tropicamide topically
20–30 minutes before retinoscopy). Spectacle-plane refractive
corrections along the eye’s pupillary axis were determined
independently by two investigators using a streak retinoscope and handheld trial
lenses. The mean spherocylindrical corrections were calculated 36 and specified in minus cylinder notation. The
retinoscopy measurements were reasonably repeatable with 95% limits
of agreement of ±0.60 and ±0.45 D for
spherical-equivalent 17 and astigmatic
errors, respectively. Corneal curvature was measured with a handheld keratometer
(Alcon Auto-keratometer; Alcon Systems Inc., St. Louis, MO) and/or a
videotopographer (EyeSys 2000; EyeSys technologies Inc., Houston, TX). We have
previously shown that both instruments provide repeatable and comparable
measures of corneal curvature in infant monkeys. 32 Ocular axial dimensions were measured by A-scan ultrasonography
implemented with a 7-MHz transducer (Image 2000; Mentor, Norwell, MA).
Intraocular distances were calculated from the average of 10 separate
measurements using a weighted average velocity of 1550 m/sec. Data Analysis Minitab (release 12.21; Minitab Inc., State College, PA) or JMP
Statistics (version 4, SAS Institute, Cary, NC) software were used for
statistical analyses. Comparisons between the two eyes of a given monkey were
made using paired t-tests. Comparisons across groups were performed using
one-way analyses of variance (ANOVAs). If the one-way ANOVA revealed a
significant effect, Tukey’s pairwise comparisons were used to
determine which groups were significantly different. Rayleigh’s
test 37 was used to determine whether
the axis of astigmatism was randomly distributed in our subject populations. To
determine the relationship between two dependent variables (e.g., corneal
astigmatism and refractive astigmatism), a regression line was generated using
orthogonal regression analysis. 38Refractive Characteristics: Onset and End of the Treatment Period At the onset of our experiment, the infant monkeys exhibited very
similar refractive properties in their two eyes. As a group, there were no
significant interocular differences in spherical-equivalent refractive error,
corneal curvature, or the magnitude of refractive (i.e., as measured by
retinoscopy) or corneal astigmatism (paired t-test, p =
0.07–0.64). Moreover, at the end of the lens-rearing period, there
were no significant interocular differences between the left and right eyes of
control and binocularly treated animals (paired t-test, p =
0.13–0.69). Consequently, for the following statistical analyses, we
used the right-eye data from the control and binocularly treated animals, data
for both eyes from the alternating-occlusion group, and the treated-eye data
from animals subjected to the monocular rearing regimens. As shown in and (open symbols), there were no significant differences in
either the spherical-equivalent refractive error or the magnitude of refractive
or corneal astigmatism between the control animals and any experimental group at
the onset of the experiment (open symbols, one-way ANOVA, all p > 0.28).
In general, the infant monkeys’ eyes were moderately hyperopic
(median = +4.13 D) with only small amounts of refractive
(median = 0.13 D) or corneal astigmatism (median = 0.55
D). | TABLE 1Refractive characteristics (mean ± standard deviation) at the
onset and end of the treatment period. |
By approximately 4 months of age (, filled symbols), i.e., at or near the end of the treatment period,
both the control animals reared under diurnal lighting conditions and those that
were reared under continuous ambient lighting conditions had become less
hyperopic (i.e., emmetropization occurred) and showed similar refractive errors
(diurnal light: median = +2.4 D, range =
+0.88 to +5.38 D; constant light: median =
+2.8 D, range = +1.69 to +3.50
D; see also ). All of the
lens-rearing regimens significantly altered the normal course of emmetropization
and led to either relative myopic or hyperopic refractive errors (one-way ANOVA,
all p ≤ 0.001). The direction of the refractive-error changes was
typically consistent within a given experimental group. 16, 24, 32– 35 Compared with control monkeys, relative myopia was
found in monkeys reared with diffusers or negative spectacle lenses, whereas
relative hyperopia was found in the monkeys that were treated with positive
lenses (range = −7.5 to +7.0 D). The
cylinder lens-reared animals also showed a wider range of spherical-equivalent
refractive errors (range = −4.6 to +8.5 D)
than the control animals at the end of the treatment period. The
spherical-equivalent refractive errors observed in the experimental subjects
were significantly correlated with vitreous chamber depth (Pearson’s
r = −0.82, p < 0.001). In addition to the
expected alterations in spherical ametropia, the lens-rearing regimens also
resulted in significantly higher amounts of refractive (; ) and corneal astigmatism (; ) (one-way ANOVAs, p
< 0.01). However, there were no significant differences in the average
corneal curvatures (i.e., average of the steeper and flatter corneal meridians)
between the control and experimental animals (one-way ANOVA, p =
0.34). Frequency of Ocular Astigmatism – illustrate the longitudinal changes in the
magnitude of refractive (filled symbols) and corneal astigmatism (open symbols)
that occurred during the treatment period for representative monkeys reared with
diffusers, negative lenses, and positive lenses, respectively. The experimental
monkeys in each figure were chosen because, as a group, they exhibited the range
of astigmatic errors found in each treatment group. As shown in –, in all treatment groups, the magnitudes of refractive and corneal
astigmatism typically increased systematically over time but tended to level off
after approximately 3 months of age. Although higher magnitudes of astigmatism
were typically found near the end of the lens-rearing period, the highest
amounts of astigmatism for individual monkeys were often achieved before the end
of the treatment period (: KIT, IRA,
BEN; : ZEB, FAI; : KYL, WIN, SAM, CHU). However, in all animals,
both the increases and the decreases in the magnitudes of refractive and corneal
astigmatism were closely synchronized in time. compares the frequency of
refractive (left column) and corneal astigmatism (right column) in the control
animals and the different groups of experimental monkeys at 4 months of age.
Because there were no significant differences in the magnitudes of refractive
(two-sampled t-test, T = 0.18, p = 0.86) or corneal
astigmatism (two-sampled t-test, T = −0.34, p
= 0.74) between the control group reared under normal diurnal
lighting conditions and the control animals that were reared under constant
light, their data were combined for the following analyses. Overall, the
frequency of significant astigmatism (defined as >1.0 D) in the treated
groups was much higher than that in the control groups. Although none of the
control monkeys had more than 1.0 D of refractive astigmatism, the percentage of
treated monkeys that showed >1.0 D of refractive astigmatism varied from
21.4–66.7% for the four experimental groups (chi-squared
test, df = 4, p < 0.001). Similarly, although only
20% of the control monkeys showed >1.0 D of corneal
astigmatism, 53.8–83.3% of the experimental monkeys had
corneal astigmatic errors that were >1.0 D (chi-squared test, df
= 4, p < 0.001). One-way ANOVAs showed that at 4 months of
age, all of the experimental groups had significantly higher magnitudes of
refractive and corneal astigmatism (mean value marked by the arrows in ) than the control monkeys (df
= 4, both p < 0.001; Tukey’s pairwise
comparisons). Properties of the Astigmatism Axis of Astigmatism The axes of the refractive and corneal astigmatism were similar for
all of the experimental regimens and were typically oblique and
mirror-symmetric in the two eyes. To illustrate the characteristics of the
ocular astigmatism, the polar plots in show the distributions of astigmatism for the right (filled
symbols) and left eyes (open symbols) of individual experimental monkeys at
4 months of age. The magnitude and axis of astigmatism for individual
monkeys are represented by the distance from the origin of the polar plots
and the vector angle, respectively. It is obvious from the plots that the
axes for both refractive and corneal astigmatism were clustered along the
oblique meridians. Because there were no apparent differences in the
direction of the astigmatism between the different treatment groups (), the data from all of the
experimental groups were pooled. Rayleigh’s test 37 showed that the axes for both refractive and
corneal astigmatism were not randomly distributed in either eye (all
r 2 > 0.63, p < 0.001). For the right eyes, the axes
for refractive and corneal astigmatism were clustered about means of
145.5° and 145.0°, respectively. The axes for
refractive and corneal astigmatism for the left eyes were clustered about
means of 30.7° and 22.1°, respectively. These mean
values were very similar to the average astigmatic axes observed previously
in cylinder lens-reared monkeys (right: refractive =
135.1°, corneal = 139.9°; left:
refractive = 38.9°, corneal =
31.6°). 16
Furthermore, like in the cylinder lens-reared monkeys, 16 the axis of astigmatism was fairly stable
during development. For instance, the average standard deviation of the
astigmatic axes during the emergence of astigmatism for the 49 treated eyes
that developed at least 1.0 D of refractive astigmatism was
11.2° (median = 9.0°; the standard
deviation for individual monkeys was calculated by analyzing all the data
from the time the magnitude of astigmatism first exceeded 0.50 D until the
time when the highest amount of astigmatism was detected). To quantify the symmetry of the astigmatic axes in the two eyes, we
calculated for individual monkeys the angular difference between the normal
astigmatic axis for the right eye and the
“reflected” astigmatic axis for the fellow left eye
(referred to subsequently as the “reflected
difference”). The reflected axes for the left eyes were
calculated by subtracting the left eyes’ axes from
180°. For example, the reflected axis for an axis of
30° is 150°. shows the distributions of the “reflected
differences” for the experimental monkeys that wore diffusers or
spherical lenses. The reflected differences for refractive and corneal
astigmatism were less than ±30° in 77.6%
and 62.7% of the treated monkeys, respectively. Furthermore,
Rayleigh’s test revealed that the reflected differences between
the two eyes were not randomly distributed, but instead were clustered near
0° for both refractive and corneal astigmatism (refractive: mean
= −4.3°; r2 =
0.64; corneal: mean = −11.5°,
r2 = 0.59; n = 67, p < 0.001),
indicating that the axes of astigmatism in the two eyes were
mirror-symmetric. Refractive vs. Corneal Astigmatism compares the three
astigmatic components for refractive and corneal astigmatism at 4 months of
age for individual animals, i.e., the total amount of astigmatism, the J0
component, which primarily represents with- or against-the-rule astigmatism,
and the J45 component, which primarily represents oblique astigmatism. The
J0 and J45 astigmatic components were decomposed from the spherocylindrical
correction by Fourier analysis. 39
Because there were no differences in the magnitudes of refractive or corneal
astigmatic components between the treatment groups (one-way ANOVA, all p
> 0.56), data from the different treatment groups were pooled for
statistical analysis. Pearson’s correlational analysis indicated
that the corneal and refractive astigmatic errors were significantly
correlated for all three components (r = 0.83, 0.55 and 0.84 for
total astigmatism, the J0, and the J45 components, respectively; all p
< 0.001). Presumably, the correlation was higher for the J45 versus
the J0 component because the astigmatic errors were typically oblique. The
slopes of the best-fitting lines obtained using orthogonal regression
analysis (short-dashed lines in )
were 0.82 for total astigmatism, 0.60 for the J0 components, and 1.14 for
the J45 components, in agreement with the values that we previously observed
in cylinder lens-reared monkeys (0.86 for total astigmatism, 0.38 for J0,
and 0.76 for J45). 16 Reversibility of the Astigmatic Errors The astigmatism that developed during the treatment period was
reversible. illustrates the
longitudinal changes in refractive and corneal astigmatism that occurred
during and after the lens-rearing period for four representative monkeys.
These four monkeys were among those monkeys in each treatment group that
developed high amounts of astigmatism. As shown in , these monkeys showed systematic
increases and decreases in the magnitudes of refractive and corneal
astigmatism during the observation period. The recovery from the highest
magnitudes of astigmatism frequently occurred before the end of the
treatment period (see also –). Almost all of the experimental monkeys that developed significant
amounts of astigmatism showed complete recovery from astigmatism. shows the magnitudes of
refractive and corneal astigmatism for individual monkeys at three time
points, i.e., at the onset of the rearing period, at the time when the
highest magnitude of astigmatism was observed, and at approximately 9 months
of age. One-way ANOVAs and Tukey’s pairwise comparisons showed
that the magnitudes of the peak refractive (1.74 ± 0.93 D) and
corneal astigmatism (2.13 ± 0.84 D) were significantly higher
than those at the onset of the experiment or at 9 months of age (both p
< 0.001). In contrast, there were no significant differences in the
magnitudes of refractive (0.17 ± 0.19 vs. 0.40 ±
0.38 D) or corneal astigmatism (0.66 ± 0.37 vs. 0.58
± 0.40 D) at 1 and 9 month of age, indicating that the monkeys
had recovered fully by 9 months of age. Association of Astigmatism with Spherical Ametropias If the experimental monkeys had spherical ametropias that fell outside
the range for control monkeys, they were more likely to exhibit higher than
normal amounts of ocular astigmatism. shows the magnitude of refractive astigmatism at 4 months of age as a
function of the refractive error for the most hyperopic meridian for control
monkeys (open circles) and monkeys that wore spherical lenses in front of both
eyes (filled diamonds). Although none of the control monkeys exhibited more than
1.0 D of refractive astigmatism, as a group, the experimental monkeys showed a
wide range of astigmatic errors. The experimental monkeys that had spherical
ametropias that were similar to those of control monkeys usually exhibited
smaller amounts of refractive astigmatism. In contrast, the experimental animals
that had larger spherical ametropias typically also had high amounts of
refractive astigmatism.
illustrates the frequency distributions of spherical ametropia for the same
control and experimental monkeys. The data for the lens-reared monkeys were
subdivided into groups according to the degree of astigmatism. As shown in , the range of spherical ametropias
in lens-reared monkeys was much larger than in control monkeys. In particular,
the distributions of spherical ametropia in the experimental monkeys that
exhibited the higher amounts of astigmatism were broader and shifted in the
hyperopic direction relative to the mode of control monkeys. Indeed, all of the
monkeys that exhibited more than 2.0 D of astigmatism had hyperopic refractive
errors that were greater than +3.8 D. The association between high amounts of spherical ametropia and high
amounts of astigmatism was also observed in experimental monkeys from the other
treatment groups. shows data at
4 months of age for monkeys that were treated with monocular or binocular
cylindrical lenses (A), monocular spherical lenses (B), and monocular diffusers
(C). In general, the more the spherical ametropia deviated from the control
values, the more likely it was that the monkey would have high amounts of
refractive astigmatism. To quantify the relationship between the magnitude of
spherical ametropia and the magnitude of refractive astigmatism, we pooled the
data obtained at 4 months of age from control monkeys and all of the
experimental monkeys. Because the slopes of the functions on either side of the
median value for the control animals (i.e., +2.4 D) had opposite
signs (see and ), we specified ametropia as the absolute difference
from the median value for control animals. For example, the
“absolute difference” for a spherical myopia of
−1.0 D was 3.4 D. Pearson’s correlational analysis
showed that the magnitude of refractive astigmatism was significantly correlated
with the absolute difference in spherical ametropia from the median value for
control monkeys (Pearson’s r = 0.26; p =
0.002). Analyzing the data for experimental animals with relative hyperopic and
myopic errors separately revealed that the degree of correlation between
spherical ametropia and the magnitude of astigmatism was stronger for hyperopes
(Pearson’s r = 0.39; p < 0.001) than for myopes
(Pearson’s r = 0.13; p = 0.33). The main findings of this study were that 1) in contrast to control monkeys,
experimental monkeys that developed axial ametropias also showed a high frequency of
significant astigmatism; 2) high amounts of astigmatism were more frequently
associated with large spherical ametropias, especially high hyperopia; 3) the
characteristics of the experimentally induced astigmatic errors were similar for all
of the experimental lens-rearing regimens; and 4) the astigmatic errors observed in
the experimental monkeys were corneal in nature, oblique in axis, bilaterally
mirror-symmetric, and reversible. In addition to the well-known effects of visual experience on spherical
refractive development and axial growth, 17,
20, 24, 33, 35, 40, 41 the results of the present study show that a
wide range of visual experiences can also alter corneal development resulting in
astigmatic errors. In particular, both open-loop viewing conditions that result in
unregulated axial elongation (e.g., form-deprivation) and closed-loop viewing
conditions that either increase (negative lenses) or decrease axial growth (positive
lenses) alter corneal shape and produce qualitatively very similar astigmatic
errors. The close similarity in the properties of these astigmatic errors reinforces
the conclusion reached in our previous study of cylinder lens-reared monkeys, 16 specifically that the observed astigmatism
is a secondary outcome or side effect of vision-dependent alterations in axial
growth associated with the emmetropization process. Although in our experiments,
visual experience provided the stimulus for altered axial growth, it is possible
that any condition that perturbs axial growth would produce similar astigmatic
changes. In this respect, the presence of significant amounts of corneal
astigmatism, and specifically oblique astigmatism in monkeys, can be taken as an
indicator that the normal axial growth of the eye has been or is being altered. On
the other hand, the recovery from the induced astigmatic errors, which could be an
age-dependent phenomenon, may be taken as an indication that the stimulus for
altered axial growth has been reduced or eliminated (for example, after an eye has
compensated for an optically induced ametropia) or that axial growth rates have
returned to normal. A variety of visual manipulations have also been shown to alter corneal
development in chickens. 28, 29, 42– 47 For example,
rearing chickens with cylinder lenses results in greater than normal amounts of
astigmatism, 28, 29 and rearing chickens with form deprivation results in
astigmatic errors that are significantly different from those in their fellow
control eyes. 28 Moreover, as observed in our
experimental monkeys, the astigmatic errors produced in chickens by these viewing
conditions were largely corneal in nature and associated with altered axial
growth. 28, 29 It has previously been argued that the many
similarities between chickens and monkeys in the emmetropization process and in the
effects of visual experience on spherical refractive development (see, for example,
reference 48) indicate that the
vision-dependent mechanisms that regulate ocular growth have generally been
conserved across species. The fact that the effects of visual experience on the
eye’s astigmatic error are also comparable in monkeys and chickens
reinforces this idea and suggests that visual experience may promote astigmatic
errors in other species, including humans. Although oblique astigmatism is not common in humans, the properties of the
astigmatism observed in our experimental monkeys are comparable to those reported in
humans in many respects. First, as numerous human studies have shown, 1, 49– 53 the induced
astigmatism in our experimental monkeys was primarily corneal in nature. Second, as
observed in our monkeys, bilateral mirror symmetry in the axes of astigmatism () has been commonly observed in clinical
practice 54 and has been found in
large-scale clinical studies 55, 56 (however, see also reference 57). Third, the magnitude of astigmatism in monkeys and
humans is correlated with the amount of spherical ametropia. 7, 8, 11– 13 In particular, the correlation coefficient (r = 0.26)
between the magnitude of astigmatism and spherical ametropia found in our
experimental monkeys is very similar to the degree of correlation observed in humans
(e.g., astigmatism and myopia, r = 0.38, 7 0.12, 12 0.20, 13 and 0.15 11;
astigmatism and hyperopia, r = 0.28 11). Moreover, as observed in our experimental monkeys (), high amounts of astigmatism have been more
frequently associated with high hyperopia than high myopia in humans. 8, 58 Fourth,
astigmatism is frequently transient and reversible during early childhood in humans
when axial growth rates are high. 59– 66 The
similarities in the properties of astigmatic errors between humans and our
experimental monkeys suggest that visual experience may contribute to common
astigmatic errors found in humans. What is the etiology of the corneal astigmatism observed in the experimental
monkeys? We have previously shown that the development of astigmatism in cylinder
lens-reared monkeys appears to be caused by altered corneal flattening rates in the
two oblique meridians, i.e., the steeper principal meridian flattens at a
slower-than-normal rate, whereas the flatter principal meridian flattens at a
faster-than-normal rate. The resulting alterations in corneal curvature are
associated with changes in corneal diameter. Specifically, the steeper principal
meridian, which is in the superior–nasal to
inferior–temporal direction, also has a smaller corneal diameter than
the flatter principal meridian. 16 The
consistent and characteristic direction of the induced astigmatic errors suggests
that vision-dependent alterations in astigmatism are a consequence of some normal
and consistent anisotropy in ocular physiology or anatomy. For example, it is
possible that the induced astigmatism reflects regional variations in the
cornea’s biomechanical properties that are impacted by the development
of axial ametropias. In this respect, the collagen fibrils in the center of the
human cornea 67– 69 are not randomly oriented, but are predominantly
oriented in the superior–inferior or nasal–temporal
directions. It is likely that this anisotropy contributes to the predominance of WTR
and ATR astigmatism in humans and presumably the low prevalence of oblique
astigmatic errors. 1, 9, 70, 71 Interestingly, the corneal collagen fibrils
in the marmoset are predominantly oriented in only the superior–inferior
direction. 72 Although the distribution of
collagen fibril orientations in the macaque monkey is not known, measures of corneal
polarization suggest that the predominate fibril orientation in macaques is
different from those in humans, 72 which could
explain why ametropic monkeys typically manifest oblique astigmatism, whereas humans
typically have WTR or ATR astigmatism. WTR corneal astigmatism has been observed in humans during convergence,
which suggests that mechanical forces exerted by extraocular muscles could
potentially alter corneal shape. 73, 74 Because the insertions of the oblique
muscles are somewhat aligned with the flatter principal meridians in our
experimental monkeys, one could imagine that when the eyes were undergoing axial
ametropic changes, the actions of the oblique muscles on the posterior globe could
somehow produce astigmatism. For example, the normal tension exerted by the oblique
muscles on the posterior globe may be influenced by the altered mechanical
properties of the sclera during the development of refractive errors 75 and indirectly alter corneal shape. If this is the
case, we would expect that eyes that developed axial hyperopia would exhibit
different directions of astigmatism than axially myopic eyes. Obviously, our results
are not consistent with this prediction. The observed alterations in corneal diameter and corneal curvature could
reflect asymmetries in the growth and/or the biomechanical properties of the sclera.
It has been reported that in human myopes, the shape of the posterior pole is
different in the vertical and horizontal meridians; specifically, the horizontal
meridian is more prolate in shape. 76 It is
not clear how this would affect corneal diameter and/or curvature, but the direction
of this anisotropy corresponds to the most common directions of astigmatism in
humans. 1, 9, 70, 71 It is possible that vision-induced alterations in
axial growth in monkeys produce similar asymmetries in the shape of the posterior
globe in the oblique meridians. A longitudinal investigation of eyeball shape
(particularly the posterior segment) in animals that are subjected to altered early
visual experience could shed light on the etiology of astigmatism. The authors thank Dr. Ying-Sheng Hu for her assistance with some of the statistical
analyses. This work was supported by an Ezell Fellowship to C.K. from the American
Optometric Foundation, grants from the National Eye Institute (EY 03,611, EY
07,551), Vision CRC (University of New South Wales), and funds from the
Greeman-Petty Professorship, UH Foundation. | TABLE A1 data. The
magnitude and axis of astigmatism for a data point are given in adjacent
columns within a row. The data are divided into subgroups according to
the (more ...) |
| TABLE A2 data. The
frequency distributions for different lens-rearing groups are given in
separate columns. For example, the column with heading
“Sph-RAst-F” (more ...) |
| TABLE A3
data. .
Astigmatic components for a data point are represented in separate
columns within a row. The data are divided into subgroups (more ...) |
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