Fig. 9 shows examples of accommodative changes under the three different lens-imposed anisometropic conditions (plano/−3 D, plano/+3 D, −3 D/+3 D) used to alter eye growth and refractive state. We see evidence of different strategies for focusing through the imposed anisometropia. In the examples shown, the relatively more myopic eye was better focused to changing accommodative stimuli in the plano/−3 D and −3 D/+3 D conditions and the negative-lens–treated eyes remained relatively hyperopic. In the plano/+3 D lens condition the relatively more hyperopic eye was the better-focused eye and the plus-lens–reared eye was relatively myopic. Taken together, the data in Figs. 7, 8 and 9 indicate that even though marmosets are able to accommodate through the hyperopia imposed by the contact lenses used in this study, they do not consistently clear the lens- imposed defocus. The combinations of lenses worn produce patterns of binocular accommodation that maintain retinal defocus that are consistent with the changes in ocular growth and refractive state observed.
The average state of accommodation through the lenses, shown as the effective refractive states of both eyes from all animals examined at the 3 D and 6 D accommodative stimuli, also indicate different strategies for accommodating under lens-imposed anisometropia (Fig. 10, ANOVA, p < 0.01). In the plano/+3 D lens condition the eye wearing the plano lens was, on average, better focused to the stimulus while the contralateral eye with the +3 D was relatively myopic. In the +3 D/−3 D condition, the effectively more myopic eye wearing +3 D lens was better focused to the stimulus for the 6 D stimulus and the contralateral eye wearing the negative lens was relatively hyperopic. For the 3 D stimulus the eye wearing the −3 D lens was better focused and the eye with the +3 D lens was relatively myopic. In the plano/−3 D lens condition, both eyes under-accommodated, particularly for the 6 D stimulus, and were relatively hyperopic.
The mean interocular difference in the effective refractive state between the two eyes differed significantly between lens conditions during accommodation (Fig. 11, ANOVA, p < 0.01). Although the imposed anisometropic conditions created the expected differences in the accommodative demand between the two eyes (Fig. 11, x-axis), the mean difference in the effective refractive state (Fig. 11, y-axis) was, on average, less than the demand difference when a negative lens was worn: The mean difference in the response in the plano/−3 D condition and the −3 D/+3 D condition was about 50% less than the difference in the demand suggesting that the binocular accommodative response averages the demand under anisometropic conditions. However, the mean interocular difference in effective refractive state for the plano/+3 D condition was about what was expected (3 D) from the lenses.
In this paper, we describe the results of our contact lens rearing paradigm for studying the visual control of eye growth in the marmoset monkey, a new world primate that we have used in earlier studies of form deprivation myopia.22–26 The results presented here confirm and extend results from an early study on the effects of contact lens in marmoset monkeys7 and are consistent with other studies examining the effects of spectacle imposed retinal defocus on eye growth and refractive state in chicks,27–29 primates,9,30 and other mammals.31,32 Imposing anisometropia in marmosets with monocular positive or negative power contact lenses, or with binocular contact lenses of opposite sign, results in compensatory changes of the refractive state by altering the rate of axial eye growth. Wearing soft contact lenses did not affect corneal power in any of the experimental groups used in this study. Moreover, in control experiments, plano contact lenses had no effect on corneal power, eye growth, or refractive state relative to untreated eyes.
There were significant shifts toward hyperopia in the positive-lens–treated eyes with imposed myopic defocus, but the negative-lens-imposed hyperopic defocus produced larger and faster changes in eye growth and shifts toward myopia. This may be due, in part, to small amounts of naturally occurring hyperopia in young marmosets that would reduce the effect of the positive lens by that amount, but earlier attempts at imposing larger amounts of myopic defocus did not produce larger compensatory responses.5 The response to myopic defocus can, however, be extended if the defocus is stepped up gradually30,32 and we increased positive lens power gradually to try to increase the effects we report here. We speculate that this response bias toward hyperopic defocus in the primate eye is because it is easier for the eye to effect a compensatory refractive change by increasing the rate of axial eye growth rather than what is needed to compensate for imposed myopic defocus. The latter can be acheived either by reducing axial growth while equatorial growth increases (and reduces optical power by flattening the cornea and lens) or by reversing eye growth and actually reducing axial length. The choroid also contributes to a compensatory response to myopic defocus, but earlier studies indicate that the contribution in marmosets is small.33 We did not see direct evidence supporting the existence of an axial growth mechanism that is reversible in the marmosets examined in this study, although several of the positive-lens–treated eyes did show periods where axial growth stopped over a period of weeks while the contralateral eye continued to grow (data not shown). In addition, our finding that rearing with binocular lenses of opposite sign produced generally larger interocular differences than seen in the monocular imposed defocus paradigms suggests that both mechanisms are capable of being activated independently in the two eyes.
There is, however, evidence of interocular effects when one eye is experimentally manipulated. We found in our monocular lens paradigms that the control eyes were affected slightly in such a way that control eyes for monocular positive-lens–treated marmosets were longer and relatively more myopic than the control eyes from the monocular negative-lens–treated marmosets. Control eye changes in monocular rearing paradigms (aphakia or form deprivation) have also been reported in macaques, but in the same direction as the effect in the experimental eye.34 Our results suggest that use of the treated eye alter the visual experience of the control eye because of yoked accommodation resulting in a shift in eye growth and refractive state.
Accommodation Under Imposed Anisometropia
Both accommodation and emmetropization use hyperopic defocus as a stimulus, therefore they must interact in some way so that accommodation does not reduce or eliminate the error signal for emmetropization. Several possibilities exist.23 Emmetropization may use the residual hyperopic defocus from accommodative lag. It is also possible that the time constants for the accommodation and emmetropization controllers may differ sufficiently so that emmetropization is largely unaffected by normal accommodation behavior. Neither possibility has been adequately explored. The temporal pattern of accommodative behavior under real world conditions has only recently started to receive attention in order to determine how it actually affects retinal focus over time.35 Moreover, the accommodative response through experimental lens-imposed defocus has never been adequately described. In this study, we describe the binocular accommodative response under the same contact lens-imposed anisometropic conditions that we are using for our studies of experimental emmetropization, but before the eye growth responses are produced. This allows us to estimate the type and approximate amount of defocus being experienced by each eye under the lens-imposed anisometropic conditions.
Our results suggest that in primates reared under conditions of imposed anisometropia, the way the eyes accommodate and are used preferentially during near vision is affected. We observed that the effectively more myopic eye is preferred under near viewing conditions in most situations, but the effectively more hyperopic eye may be used in others. Imposing anisometropia with binocular contact lenses of opposite sign did not produce a consistent accommodative response; at the 6 D accommodative stimulus the effectively more myopic eye was better focused, but at the 3 D stimulus the effectively more hyperopic eye was better focused. The plano/+3 D condition resulted in over accommodation (although the plano eye was well-focused to the 6 D stimulus) and the plano/−3 D condition resulted in under accommodation at both stimulus positions. In general, the negative-lens–treated eyes were always hyperopic (with the exception of the +3 D/−3 D condition at the 3 D stimulus) and positive-lens–treated eyes were always myopic relative to the stimulus. In all situations, the eye contralateral to the better focused eye will have a larger accommodative error of the same sign of defocus that it experiences during distance vision. These observations, together with the observation that accommodation is not typically sustained through lens imposed hyperopia (Fig. 7), helps explain how compensatory shifts in eye growth and refractive state occur despite the ability to use accommodation to clear the hyperopia. Additional studies are needed to determine how longer periods of lens wear, including after the compensatory changes in eye growth and refractive state have taken place, affect the accommodative response.
Hung et al.9 described the preferential near fixation pattern in rhesus monkeys reared with either plano/negative or plano/positive spectacle lens conditions. Although the accommodative response was not quantified, their results suggested that the eye with less accommodative demand was preferred. Flitcroft et al.36 suggested a different mechanism. In that study, they examined the accommodative response to sinusoidal stimuli presented to the eyes in counterphase and found that in some cases the eye with less accommodative demand was used but in others the response was averaged for the demands between the two eyes. Our observations in marmosets support the idea that the different demands are averaged under certain conditions. In the plano/−3 D and the +3 D/−3 D conditions, the mean difference in the effective refractive state is only half of what would be expected from the interocular power of the lenses (Fig. 11). However, the data shown are the average effective refractive states for each eye under a given accommodative stimulus and so we cannot distinguish whether the eyes are alternating fixation and accommodation, or whether aniso-accommodation is taking place, or both. Although we cannot rule out the possibility that aniso-accommodation may be involved, the amount needed to explain the reduced interocular difference in effective refractive estate (up to 3 D) is much more than what has been reported.8
Knowledge of how accommodation behaves under real world conditions during binocular viewing is important for understanding emmetropization and may have therapeutic significance concerning the development of myopia. Harb et al.35 reported that accommodation in myopes was more variable during reading than compared with emmetropes. In that study the subjects were not anisometropes and the effective refractive state was monitored in only one eye. Ip et al.21 described the characteristics of dynamic accommodation responses between the dominant and the non-dominant eye in human subjects and found that the speed and response times of accommodation were faster in the dominant eye, although there was no difference in accommodation amplitude. The use of contact lens-induced anisometropia in humans (monovision), has been suggested as a potential therapy for the treatment of myopia.37 In that study, Phillips hypothesized that making the non-dominant eye relatively myopic compared with the dominant eye (corrected for distance) would reduce the overall accommodation response at near and myopia progression in schoolchildren. However, the results of the study found that children preferred to use the distance-corrected dominant eye for accommodation, thus imposing relative myopia on the non-dominant eye. The rate of myopia progression in that eye was reduced, suggesting that the imposed myopic defocus slowed eye growth.
The results of our studies shed further light on the relationship of accommodation and the visual control of eye growth and refractive state. The data presented in this study show that accommodative behavior under the three anisometropia-producing lens conditions result in retinal defocus conditions that are consistent with the ocular growth and changes in refractive error observed in other marmosets reared for extended periods under the same lens conditions. The induced changes in eye growth and refractive state provide more evidence for the visual regulation of emmetropization in the primate eye, and our observations of accommodation under imposed anisometropia helps to explain how visual control of eye growth using retinal defocus as an error signal interacts with accommodation.
We thank Chea-su Kee, Debora Nickla, Mark O’Conner, and Sanbrita Ghosh for their assistance with various parts of this study.
This work was supported by National Eye Institute, National Institutes of Health, Bethesda, MD, grant 11228 (to DT).
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Keywords:© 2009 American Academy of Optometry
accommodation; animal models; emmetropization; myopia; refractive error development