Effects of Optical Defocus on Refractive Development in Monkeys: Evidence for Local, Regionally Selective Mechanisms

In a wide range of species, from fish to primates, the growth and refractive status of the eye are regulated by visual feedback.1 Moreover, evidence from birds and mammals indicate that the effects of vision on ocular growth and refractive development are mediated, in large part, by local retinal mechanisms (i.e., mechanisms that integrate visual signals in a spatially restricted manner and exert their influence selectively on the underlying sclera).1,2 Understanding the operating characteristics of these local, vision-dependent mechanisms is important because peripheral vision, operating through these local mechanisms, could influence the eye's shape and, in particular, its axial length and central refractive development in a manner independent of visual signals from the central retina. The local nature of ocular growth-regulating mechanisms was first demonstrated in chicks by showing that myopia could be produced in one portion of the eye while emmetropization proceeded normally in other parts. For example, in chicks, diffusers3,4 or negative lenses5 that cover only part of the visual field produce axial elongation and myopia that are restricted to the affected portion of the retina. It has subsequently been shown that hemiretinal form deprivation also alters ocular growth and refractive development in a regionally selective manner in tree shrews,2 guinea pigs (McFadden SA. IOVS 2002;43:E-Abstract 189), and monkeys.6 It is, however, not known whether optical defocus, a condition commonly experienced in everyday viewing, can produce localized changes in primate eyes. It is important to determine whether the effects of optical defocus are also mediated by local retinal mechanisms in primates because the effects of form deprivation and optical defocus on ocular growth appear to be mediated by different mechanisms.7–9 In addition to providing insight into how peripheral vision may influence central refractive error, determining whether localized optical defocus can produce predictable changes in eye shape will provide a critical test in primates for the hypothesis that local retinal mechanisms regulate the shape of the eye to ensure the optimum focus across the retina.4,10,11 Therefore, one goal of this study was to investigate the effects of hemiretinal optical defocus on ocular growth and the patterns of peripheral refraction in infant monkeys. Because peripheral vision may influence central refractive development, it is important to know how optical defocus across the entire visual field influences ocular shape and the development of peripheral refractive error. In humans12–17 and monkeys,18 spherical-equivalent refractive errors can vary substantially with eccentricity. The patterns of peripheral refraction are correlated with central refractive error12,14,19,20 and appears primarily to reflect the shape of the posterior globe.18,21–23 For example, in humans, eyes with central axial myopia typically are less oblate/more prolate in shape and usually manifest relative hyperopia in the periphery.24 The patterns of peripheral refraction have potentially significant clinical implications because the relative peripheral hyperopia found in myopic eyes has been implicated as a risk factor for myopia progression.25–27 In particular, Hoogerheide et al.25 reported that military recruits who exhibited relative peripheral hyperopia were more likely to develop myopia or exhibit myopia progression during pilot training than those who showed relative peripheral myopia. In support of the idea that peripheral refractive error are a risk factor for central refractive errors, evidence from laboratory animals indicates that peripheral vision can dominate central refractive development in primates28,29 and, in particular, that optically imposed peripheral hyperopia can promote central axial myopia.30 Full-field form deprivation can alter ocular shape in monkeys. Specifically, in infant rhesus monkeys, full-field form deprivation produces central axial myopia and relative peripheral hyperopia. Relative peripheral hyperopia develops because as the central axial length increases, the eye becomes more prolate.18 However, the effects of optical defocus may not be similar to those produced by form deprivation because, as mentioned, optical defocus and form deprivation are not mediated by identical mechanisms. In addition, the growth-altering effects of form deprivation and optical defocus may differ, at least quantitatively, as a function of eccentricity. Specifically, form deprivation, particularly the severe degrees of form deprivation typically used in studies of refractive development, would be expected to provide a strong signal for eye growth at all eccentricities. On the other hand, small to moderate degrees of optical defocus would likely produce proportionally smaller signals for ocular growth in the periphery than in the central retina because the spatial resolving capacity of the retina decreases with eccentricity. Thus, a second goal was to determine how optical defocus, specifically full-field hyperopic defocus, influences ocular shape and the patterns of peripheral refractive error.