Temporal Properties of Compensation for Positive and Negative Spectacle Lenses in Chicks

During early post-natal life, ocular growth is modulated by the visual input from the retina, resulting in the correction of refractive errors (reviewed by refs. 1–4). Eyes use two compensatory mechanisms to reduce defocus: When the eye wears a positive lens, which would put the images of distant objects in front of the photoreceptors (myopic defocus), it slows its rate of elongation and thickens the choroid, pushing the retina forward toward the image plane. When the eye wears a negative lens, which would put the images of distant objects behind the photoreceptors (hyperopic defocus), it accelerates its rate of elongation and thins the choroid, pulling the retina back toward the image plane. Compensation by changing the eye size has been found in fish5, chicks6,7, guinea pigs8, tree shrews9,10, cats11, marmosets12, and rhesus monkeys13. Compensation by changing choroidal thickness has been shown in chicks14, tree shrews9, guinea pigs15, marmosets16, and macaque monkeys17. In normal life, of course, the retina does not exclusively experience continuous myopic or hyperopic defocus. Rather, most parts of the retina experience frequent episodes of myopic and hyperopic defocus depending on the spatial layout of the environment, the distance of the objects viewed, and the eye’s refraction and its accommodative state. How does the retina sum together these episodes of defocus over time to determine the direction of the eye’s growth toward emmetropia? The simplest model of integration would be that the defocus is summed linearly, i.e., the resulting compensation is proportional to the average amount of defocus that the retina experiences summed over a period of time (Fig. 1A). If the eye were experiencing myopic defocus, for example, the emmetropization signal favoring hyperopic growth would keep rising as long as the defocus is present. When there is no defocus (e.g., in darkness), the signal would remain stable. When the sign of defocus reverses, the signal would switch direction. FIGURE 1 Schematics showing the linear model (A) and the nonlinear model (B) of the hypothesized internal emmetropization signal. (A) The linear model has the magnitude of the signal being proportional to the sign and duration of defocus experienced over time, ... Despite of its appealing simplicity, there is evidence against this linear model. When chicks had the same total amount of lens-wear (28 min) each day given in various numbers of episodes with darkness in between18: (1) Many episodes of lens-wear (14 episodes, 2 min each) were more effective than one single episode (of 28 min) in causing compensation for either positive or negative lenses, in agreement with findings that several episodes of normal vision each day were more effective than a single episode of the same total duration in reducing form-deprivation myopia in chicks19. These results imply either that the hypothesized internal emmetropization signal reaches saturation within an episode or that it declines between episodes. (2) Very brief episodes were ineffective at causing compensation, even if repeated very often (2-sec episodes given every 2 min for a total duration of 28 min), suggesting that the signal must accumulate to threshold within each episode before downstream effects are initiated. In light of the above evidence, we hypothesize that episodes of myopic and hyperopic defocus are integrated in a nonlinear fashion, as proposed by Flitcroft20: Lens-wear causes one or several internal emmetropization signals to rise and eventually become saturated during episodes of lens-wear and decline slowly between episodes (Fig. 1B). As a start to exploring this hypothesis, we studied the time-constants of the signals regulating compensation for positive and negative lenses. Because we do not know the nature of these signals, we cannot measure them directly, but can measure their effects on the rate of ocular elongation and choroidal thickness. Because a single brief episode of lens-wear would not generally have a measurable effect, we estimated the rise- and fall-times of these inferred signals by measuring the eye before and after 3 days of many episodes of viewing through positive or negative lenses: (a) We estimated how quickly the hypothesized signals rise during each episode by giving frequent episodes of lens-wear of a range of durations, reasoning that the ocular responses will increase with increasing duration up to an asymptote. (b) We estimated how quickly the signals decay between episodes by giving long (saturating) episodes of lens-wear with a range of intervals between the episodes, reasoning that the ocular responses will decline with increasing intervals. We find that the signals for the effects of both positive and negative lenses on both the rate of ocular elongation and choroidal thickness rise at a similar rate (within minutes), but they decline at slower, very different rates, with the signal regulating the rate of ocular elongation declining the slowest in the case of positive lens-wear, and the fastest in the case of negative lens-wear. Some of these results have been presented in an abstract (Zhu X, et al. IOVS 2004;42:ARVO E-Abstract 4285).