Effectiveness of hyperopic defocus, minimal defocus, or myopic defocus in competition with a myopiagenic stimulus in tree shrew eyes.

When the young of many animal species first view the world, the axial length of the eye is shorter (closer to the cornea) than the focal plane, so the eye is hyperopic. During subsequent development, the axial length increases until the eye is emmetropic or slightly hyperopic.1-7 In 1988, Schaeffel et al.8 first showed that chronic exposure to plus or minus lenses can alter the emmetropization process. They and others found that imposed hyperopic defocus (focal plane shifted away from the cornea, behind the retina) is uniformly a stimulus for axial elongation. When one, or both, eyes of a tree shrew, macaque monkey, or chick is covered by a concave (minus power) lens held in place by a goggle frame, minus lens compensation occurs: The vitreous chamber elon-gates until, while wearing the lens, the photoreceptors come to be approximately in the same relationship to the focal plane as are the photoreceptors of normal eyes or the untreated fellow control eye.3,9-11 Because the eye's axial length is then longer than normal for that age, the eye is myopic when the lens is removed. Across species, the myopiagenic effect of imposed hyperopic defocus is very consistent. When a convex (plus power) lens, which shifts the focal plane toward the cornea, in front of the retina, is similarly applied, the effect has seemed to be related to both lens power and species. As first reported in chicks, plus-power lenses of +10 D, or even +15 D, cause the lens-treated eye to slow its normal axial growth rate until, while wearing the lens, the eye is approximately emmetropic.8,9 Because the eye is then shorter in axial length than normal, it is hyperopic when the is lens removed. These, and other data (for a review, see Ref. 12) have suggested that myopic defocus is a stimulus for slowed axial elongation. When a similar paradigm was applied in tree shrews and monkeys, a different result was typically reported. In a study of tree shrews exposed binocularly to either +3- or +5-D lenses, normal developmental progression from hyperopia toward emmetropia was generally slowed, and the eyes remained myopic while wearing the lens (Siegwart JT et al., IOVS 2003;44:ARVO E-abstract 1984). Macaque monkeys are usually hyperopic at the start of lens treatment. Therefore, a binocular +3- or +6-D lens corrects the hyperopia. The eyes then typically slow their normal progression toward emmetropia, because they are no longer hyperopic. When the lens is removed, they resume the normal decrease in refractive error toward emmetropia.3 However, in both monkeys and tree shrews, making an eye myopic with a plus lens also causes the eye of some animals to slow its elongation rate and become more hyperopic than it was at the start of lens wear (Venkataraman S et al. IOVS 2005;46:ARVO E-Abstract 1973).3 The interaction of the optics of the eye with viewing distance has made it difficult to determine whether myopic defocus is truly a stimulus for slowed elongation in mammals. If an animal with eyes that are 10 cm above the ground wore a +10-D lens over one eye, the ground would be in good focus for that eye. If that animal bent over to search for food, the eye would experience hyperopic defocus, unless it perfectly accommodated by increasing the power of its crystalline lens. Even with powerful plus lenses, eyes might experience some clear images and even some hyperopic defocus, although the average defocus would be shifted in the direction of myopia. To assess whether myopic defocus is a stimulus for slowed axial elongation, it is necessary to control the viewing distance while the lens is worn. This has typically been done in studies of chicks by keeping the animals in the dark except during a brief period each day when they are exposed to visual stimuli at a controlled viewing distance while wearing plus lenses.13,14 A concern with this procedure is that extensive time in the dark may, in itself, cause changes in the axial length and refractive state of the treated and fellow control eye.15-17 In visually experienced tree shrews, constant dark treatment for a period of 10 days has been found to be myopiagenic.18 A way to allow normal light– dark exposure and provide eyes with visual images throughout the lights-on period while testing the effect of myopic and hyperopic defocus is to use the temporal nonlinearities of the emmetropization mechanism. It has been found, in several species, that if an eye wearing a myopiagenic minus-power lens or a diffuser is given a brief exposure each day to unrestricted vision, the eye never develops significant axial elongation or myopia despite exposure to the minus lens for the rest of the day.19-21 This can be accomplished by removing the minus lens for 1 to 2 hours each day or by substituting a plano (zero power) lens for a similar period. Shaikh et al.20 found that if a tree shrew wore a monocular −5-D lens 23 hours per day in its home cage on a 14/10 lights-on/off schedule, and the lens was removed for 1 hour each day, the eye did not fully compensate, but compensated partially (−2.9 ± 1.6 D, relative to the control eye). In pilot studies in this laboratory, it was found that if the lens was removed for 45 minutes while an animal was restrained so that all objects were >1 m away, the treated eye did not develop significant myopia. The ability of 45 minutes of unaltered visual experience with controlled viewing distance to compete effectively against the myopiagenic effect of a −5-D lens allowed us to test the ability of both hyperopic and myopic defocus to compete against a −5-D lens worn for the rest of the day in the home cage. In the lens-substitution paradigm in tree shrews,22 rather than simply removing the monocular −5-D lens, another lens is substituted for 45 minutes while the viewing distance is controlled so that all objects are >1 m away. To the extent that the lens worn while viewing distance is controlled effectively competes against the −5-D lens, the eye will not develop any axial elongation and myopia, relative to its fellow control eye. To the extent that the substituted lens is ineffective, the eye will elongate and compensate for the −5-D lens A lens-substitution paradigm has also been used, in chicks, by Zhu et al.23 Some of their animals wore minus lenses all the time, except for brief periods of plus lens wear (viewing distance not controlled) and others wore a plus lens briefly, with viewing distance controlled, and had unrestricted vision the rest of the time. In both situations, plus lens wear produced hyperopia.