Considering all the marmosets in this study together, regardless of age, form deprivation by diffusers produced significant myopia in the experimental eyes at the end of the deprivation period (experimental versus control, mean ± SD: -2.8 ± 4.8 D vs. -0.2 ± 2.3 D; paired t-test, P < 0.01). The length of the vitreous chamber of the experimental eyes was, on average, 0.114 ± 0.210 mm longer than in the control eyes (6.31 ± 0.63 mm vs. 6.19 ± 0.67 mm; paired t-test, P < 0.01). The interocular difference (experimental eye minus control eye) in refraction observed at the end of deprivation was well predicted by the interocular difference observed in vitreous chamber depth (r2 = 0.81, P < 0.01; ). There were no significant differences between experimental and control eyes in the radius of corneal curvature (3.43 ± 0.15 mm vs. 3.45 ± 0.23 mm, paired t-test, P = 0.10) or choroid thickness (0.125 ± 0.026 mm vs. 0.127 ± 0.019 mm; paired t-test, P = 0.78).
FIGURE 2 Correlation of interocular refractive difference (experimental minus control eye) with interocular difference in vitreous chamber depth. The change in vitreous chamber depth relative to the control eye was a strong predictor of the change in refractive (more ...)
Dividing the experimental animals into the three groups based on the age of onset of the deprivation revealed significantly different degrees of axial myopia induced by the diffusers. shows the mean interocular difference in refractive error and vitreous chamber depth at the end of deprivation. There was significantly greater axial myopia (ANOVA, P < 0.01) in group 1 (mean ± SD: refractions -8.25 ± 2.83 D; vitreous chamber depth 0.332 ± 0.124 mm) than in either group 2 (-0.4 ± 4.4 D, 0.048 ± 0.238 mm) or group 3 (-1.20 ± 02.2 D; 0.032 ± 0.080 mm). In group 1, corneal curvature was slightly, but significantly, steeper in the experimental eye at the end of deprivation (mean experimental minus control difference in corneal curvature, -0.077 ± 0.06; paired t-test, P < 0.05). This effect, which accounts for approximately 2.4 D of refractive change, was transient and was not observed with subsequent measures during the period after the end of deprivation. There were no significant changes in the average corneal curvature of the experimental eyes in the other age groups. Statistically significant changes in choroidal thickness in the experimental eyes relative to the control eye were not detected in any of the groups at the end of deprivation or in the period thereafter.
FIGURE 3 The average effect of form deprivation by diffuser, grouped by age of onset. The mean differences between experimental and contralateral control eyes (experimental minus control; ○, individual data points for each group) at the end of the deprivation (more ...)
The differences in the magnitude of the responses were due in large part to qualitatively different responses to form deprivation. Specifically, we found that not all marmosets responded to form deprivation with an increase in vitreous chamber depth and myopia. Measures taken after the end of the deprivation period showed several different responses that we categorized as either (1) axial elongation and myopia, (2) no response, (3) delayed-onset axial myopia (axial elongation and myopia were not apparent at the end of deprivation but were observed after the deprivation was discontinued), or (4) reduced axial growth and hyperopia (for examples, see ). In the different responses observed in each of the three groups are tallied. The response to form deprivation was qualitatively more variable in groups 2 and 3 than in group 1. Note that all animals in group 1 (in which form deprivation started before 39 days of age) responded with axial myopia. In groups 2 and 3, only half of the animals in each group responded with axial myopia. We quantified the different effects of form deprivation by sorting the individuals by response without regard to age. The mean and individual refractive errors and vitreous chamber depths are shown for each response category in .
FIGURE 4 Examples of the different responses to form deprivation observed in this study. The interocular differences in refractive state and vitreous chamber depth (experimental minus control eye) are plotted against age. Shaded area: The period of deprivation (more ...)
Categories of Response to Form Deprivation in Marmosets Grouped by Age of Onset
FIGURE 5 Categories of qualitatively different responses to form deprivation diffusers. The plot and symbols are as described in . The four categories of response observed were: (1) Axial myopia: the myopia in the experimental eye was apparent and the (more ...)
Axial myopia relative to the control eye was the most frequently observed response (n = 15, mean interocular difference ± SD: vitreous chamber depth 0.232 ± 0.149 mm, refractive error -5.25 ± 3.24 D). In this group, we also observed slight, but significant, corneal steepening (interocular difference in corneal curvature, -0.044 ± 0.05; paired t-test, P < 0.01) that accounts for approximately 1.4 D of refractive change.
Four animals failed to respond in a clear way (defined as a change in vitreous chamber depth with a corresponding change in refractive error) and are referred to as nonresponders in . In these animals, the mean interocular difference in vitreous chamber depth (0.0 ± 0.03 mm), refractive error (-0.7 ± 1.83), and corneal curvature (-0.012 ± 0.04) were all within resolution limits.
There was one animal that showed a delayed increase in vitreous chamber depth and myopia after a transient increase in vitreous chamber depth and myopia during the period of deprivation (see ) and is referred to as a delayed-onset myope in . At the end of deprivation the vitreous chamber of the experimental eye was 43 μm shallower and the refraction 1.86 D more hyperopic than in the control. This hyperopia appears to be an underestimate, as the cornea of the experimental eye was also found to be 0.09 mm flatter (about 2.7 D more myopic) than the control eye at the end of deprivation. In the period after the end of deprivation, the corneal flattening appears to have largely resolved (mean interocular difference, 0.031). During that same period the vitreous chamber depth increased and refraction shifted toward myopia in the experimental eye. By 106 days after the end of deprivation, the experimental eye had become 0.20 mm longer than the control eye, and the refraction had shifted 3.1 D toward a relative myopia of -1.24 D.
There were four animals that responded to form deprivation with reduced vitreous chamber depth (-0.178 ± 0.160 mm) and corresponding hyperopia (+4.27 ± 2.3 D) relative to the control eyes. There was no detectable change in the corneal curvature of the experimental eyes of these animals relative to their control eyes either at the end of deprivation or in the period after the end of deprivation.
For those animals that responded to form deprivation with myopia (n = 15), we examined the amount of axial elongation and myopia induced and found that they differed as a function of age (see Figs. , ). The mean amount of axial elongation and myopia induced relative to the contralateral control eye at the end of deprivation was significantly greater (ANOVA, P < 0.01) in group 1 (0.332 ± 0.124 mm, -8.25 ± 2.83 D) compared with either group 2 (0.231 ± 0.130 mm, -3.5 ± 1.8 D) or group 3 (0.084 ± 0.082 mm, -3.0 ± 1.1 D). Normalizing the induced changes for treatment period did not reduce the differences between the experimental groups. Analysis of variance by group was still significant for the rate of change in vitreous chamber depth (P < 0.01) and rate of refractive change (P < 0.01). There were no significant changes in the corneal curvature or choroid thickness of the experimental eye relative to the control eye in any of the groups. For all animals that responded with myopia, the age of deprivation onset correlated significantly (P < 0.05) with the relative amount of myopia (r = 0.534) and vitreous chamber elongation (r = 0.619) observed at the end of deprivation. Linear regressions show that the amount of axial myopia induced is inversely proportional to the age of onset ().
FIGURE 6 The effects of diffuser-induced form deprivation grouped by age of onset for those animals that responded with axial myopia. The plot and symbols are as described in . There was a significant reduction in the experimentally induced increase in (more ...)
FIGURE 7 For those eyes with axial myopia, the intraocular difference (experimental eye minus control eye) in refractive error (top) or vitreous chamber depth (bottom) correlated significantly with the age of onset of the deprivation. Linear regressions show that (more ...)
We examined the ability of the eyes to recover from form deprivation-induced axial myopia. In 12 of the animals that responded to diffuser-induced deprivation with axial myopia, we tracked refractions and vitreous chamber depth after the end of deprivation (data from three animals were unavailable for analysis of recovery, because they were killed for biochemistry at the end of deprivation). Of the 12, 6 animals recovered after the end of deprivation (see ). Recovery was observed only in animals from groups 1 and 2 (3/4 animals in group 1 and 3/4 animals in group 2), but there was an insufficient number to determine statistically whether there was an age effect. The development and recovery from form deprivation myopia in the six animals examined are shown in . When all six animals are considered together, the recovery in refractive state is clearly related to a change in vitreous chamber depth after the end of deprivation. In , the change in refraction and vitreous chamber depth relative to control eyes during deprivation is compared with the change after deprivation ended. Refractive error shifted significantly toward myopia during deprivation and toward hyperopia after (-5.2 ± 2.4 vs. +2.8 ± 1.0 D; paired t-test, P < 0.01). Vitreous chamber growth shifts significantly from increasing depth during the period of deprivation to a reduction in depth during the period after (0.234 ± 0.125 mm vs. -0.120 ± 0.067 mm; paired t-test, P < 0.01). Changes in corneal curvature did not contribute to the recovery, nor were significant changes in choroidal thickness observed. Furthermore, in the six myopes that did not recover, the corneal curvature of the experimental eyes were not significantly different from the control eyes, ruling out the possibility that a change in corneal curvature was responsible for the persistence of the myopia in these animals.
FIGURE 8 Six examples of various degrees of recovery from form deprivation myopia. The difference in refractive state and vitreous chamber depth between the experimental eye and the contralateral control eye (experimental minus control eye) are plotted against (more ...)
FIGURE 9 Relative change in refractive error and vitreous chamber depth in eyes undergoing form deprivation myopia followed by recovery after deprivation was discontinued. The relative change during deprivation or the period after the deprivation is shown for (more ...)