Refractive plasticity of the developing chick eye

We have developed a lightweight plastic goggle with rigid contact lens inserts that can be applied to the eyes of newly hatched chicks to explore the range and accuracy of the developmental mechanism that responds to retinal defocus. Convex and concave lenses of 5, 10, 15, 20 and +30 D were applied to one eye on the day of hatching. The chick eye responds accurately to defocus between -10 and +15 D, although hyperopia develops more rapidly than myopia. Beyond this range there is first a levelling off of the response and then a decrease. The resulting refractive errors are caused mainly by increases and decreases in axial length, although high levels of hyperopia are associated with corneal flattening. If +/- 10 D defocusing lenses are applied nine days after hatching the resulting myopia and hyperopia are equal to about 80% of the inducing power. After one week of inducing myopia and hyperopia with +/- 10 D lenses, the inducing lenses were reversed. In this case, the refractive error did not reach the power of the second lens after another week of wear. Instead, astigmatism in varying amounts (0-12 D) was produced, being greater when reversal was from plus to minus. Finally, astigmatism can also be produced by applying 9 D toric inducing lenses on the day of hatching. The astigmatism produced varies from 2 to 6 D, and the most myopic meridian coincides with the power meridian of the inducing lens. This astigmatism appears to be primarily due to corneal toricity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Animal models in myopia research

Our current understanding of the development of refractive errors, in particular myopia, would be substantially limited had Wiesel and Raviola not discovered by accident that monkeys develop axial myopia as a result of deprivation of form vision. Similarly, if Josh Wallman and colleagues had not found that simple plastic goggles attached to the chicken eye generate large amounts of myopia, the chicken model would perhaps not have become such an important animal model. Contrary to previous assumptions about the mechanisms of myopia, these animal models suggested that eye growth is visually controlled locally by the retina, that an afferent connection to the brain is not essential and that emmetropisation uses more sophisticated cues than just the magnitude of retinal blur. While animal models have shown that the retina can determine the sign of defocus, the underlying mechanism is still not entirely clear. Animal models have also provided knowledge about the biochemical nature of the signal cascade converting the output of retinal image processing to changes in choroidal thickness and scleral growth; however, a critical question was, and still is, can the results from animal models be applied to myopia in children? While the basic findings from chickens appear applicable to monkeys, some fundamental questions remain. If eye growth is guided by visual feedback, why is myopic development not self‐limiting? Why does undercorrection not arrest myopic progression even though positive lenses induce myopic defocus, which leads to the development of hyperopia in emmetropic animals? Why do some spectacle or contact lens designs reduce myopic progression and others not? It appears that some major differences exist between animals reared with imposed defocus and children treated with various optical corrections, although without the basic knowledge obtained from animal models, we would be lost in an abundance of untestable hypotheses concerning human myopia.     

Higher order aberrations,refractive error development and myopia control: a review

Evidence from animal and human studies suggests that ocular growth is influenced by visual experience. Reduced retinal image quality and imposed optical defocus result in predictable changes in axial eye growth. Higher order aberrations are optical imperfections of the eye that alter retinal image quality despite optimal correction of spherical defocus and astigmatism. Since higher order aberrations reduce retinal image quality and produce variations in optical vergence across the entrance pupil of the eye, they may provide optical signals that contribute to the regulation and modulation of eye growth and refractive error development. The magnitude and type of higher order aberrations vary with age, refractive error, and during near work and accommodation. Furthermore, distinctive changes in higher order aberrations occur with various myopia control treatments, including atropine, near addition spectacle lenses, orthokeratology and soft multifocal and dual-focus contact lenses. Several plausible mechanisms have been proposed by which higher order aberrations may influence axial eye growth, the development of refractive error, and the treatment effect of myopia control interventions. Future studies of higher order aberrations, particularly during childhood, accommodation, and treatment with myopia control interventions are required to further our understanding of their potential role in refractive error development and eye growth.     

Effects of continuous light on experimental refractive errors in chicks

It is possible to induce ametropias in young chicks either by depriving the developing eye of clear form vision with a translucent goggle or by defocusing the retinal image with convex or concave lenses. The refractive properties of the developing chick eye are also altered by raising young birds in a continuous light environment. The effects of superimposing form deprivation or defocus treatments on chicks raised in continuous light are unclear. Newly hatched (n = 31) chicks were raised for 2 weeks under continuous light while wearing either translucent goggles or + 10 or ? 10 diopter (D) lenses over one eye. Refractive states, corneal curvature and intraocular dimensions were measured periodically by retinoscopy, keratometry and A-scan ultrasound. The birds were sacrificed after 2 weeks and the eyes removed and measured with calipers. Under continuous light, all eyes treated with translucent goggle and ? 10D lens developed moderate myopia (? 2.6 ± 0.5 D and ? 1.4 ± 0.3 D, respectively) by day 4. The eyes treated with a + 10 D lens developed moderate hyperopia (+ 4.8 ± 0.5 D) at day 4. Corneal curvatures of all treated eyes were slightly, but significantly, larger than contralateral control eyes by day 4. After 2 weeks of goggle or lens application, all the treated eyes were hyperopic due to corneal flattening. But the eyes treated with a goggle or a ? 10 D lens still showed relative myopia compared to the fellow eyes (treated minus untreated = ? 3.8 ± 0.4 D and ? 2.8 ± 0.4 D, respectively), and the eyes treated with a + 10 D lens showed more hyperopia than fellow eyes (treated minus untreated = + 5.1 ± 0.6 D). Compared with the control eyes, the axial length (mainly vitreous chamber depth) was slightly, but significantly, increased in the eyes treated with a goggle or a ? 10 D lens, and the axial length decreased slightly in the eyes treated with + 10 D lens. The results suggest that form deprivation and retinal defocus (induced by ± 10 D lenses) could still induce experimental refractive errors (myopia and hyperopia) in chicks kept under continuous light, but the effects of form deprivation and retinal defocus were partially suppressed by continuous light.     

Evidence for a potential role of glucagon during eye growth regulation in chicks

Eye growth and refraction are regulated by visual processing in the retina. Until now, the messengers released by the retina to induce these changes are largely unknown. Previously, it was found that glucagon amacrine cells respond to defocus in the retinal image and even to its sign. The expression of the immediate-early gene product ZENK increased in this cell population in eyes wearing plus lenses and decreased in minus lens-treated chicks. Moreover, it was shown that the amount of retinal glucagon mRNA increased during treatment with positive lenses. Therefore, it seems likely that these cells contribute to the visual regulation of ocular growth and that glucagon may act as a stop signal for eye growth. The purpose of the present study was to accumulate further evidence for a role of glucagon in the visual control of eye growth. Chicks were treated with plus and minus lenses after injection of different amounts of the glucagon antagonist des-His1-Glu1-glucagon-amide or the agonist Lys17,18,Glu21-glucagon, respectively. Refractive development and eye growth were recorded by automated infrared photorefraction and A-scan ultrasound, respectively. The glucagon antagonist inhibited hyperopia development, albeit only in a narrow concentration range, and at most by 50%, but not myopia development. In contrast, the agonist inhibited myopia development in a dose-dependent fashion. At high concentrations, it also prevented hyperopia development. The amount of glucagon peptide in the retinae and choroids of lens-treated chicks and its diurnal variation was measured by using a radio-immunoassay. Retinal glucagon content decreased after minus lens treatment and choroidal glucagon content increased after plus lens treatment. No diurnal variation in the retinal amount of glucagon was detected. In addition, using an optokinetic nystagmus paradigm, the effect of glucagon and the antagonist des-His1-Glu9-glucagon-amide on suprathreshold contrast sensitivity was studied. Glucagon reduced contrast sensitivity (which might be linked to a signal for growth inhibition) whereas the antagonist des-His1-Glu9-glucagon-amide increased contrast sensitivity. The results of the study are in line with the hypothesis that glucagon plays a role in the visual control of eye growth in the chick.     

Visually induced changes in components of the retinoic acid system in fundal layers of the chick

Eye growth is visually regulated via messengers that are released from the retina. The retina involves a yet unknown algorithm to analyse the projected image so that the appropriate growth rates for the back of the eye are ensured. One biochemical candidate that could act as a growth controller, is retinoic acid (RA). Previous work (Seko, Shimokawa and Tokoro, 1996; Mertz et al., 1999) has shown that retinal and choroidal RA levels are indeed predictably changed by visual conditions that cause myopia or hyperopia, respectively. We have studied in which fundal tissues aldehyde dehydrogenase-2 (AHD2) and retinaldehyde dehydrogenase-2 (RALDH2), enzymes involved in RA synthesis, are expressed and at which levels the effects of vision on RA levels may be controlled. Using Northern blot analysis, we have found that the retinal mRNA level of the AHD2 is up-regulated after 3 days of treatment with negative lenses (negative lenses place the image behind the retina). The abundance of the retinal mRNA of a RA receptor, RAR-beta, was up-regulated already after 6 hr of treatment with positive lenses (positive lenses place the image in front of the retina). The up-regulation persisted for at least 1 week. Finally, we have studied the effects of an inhibitor of RA synthesis, disulfiram, on the visual control of eye growth. We found inhibition of myopia as induced by frosted goggles ('deprivation myopia') but no significant inhibitory effects on refractive errors induced by +7D or -7D lenses. Our results are in line with the hypothesis that RA may play a role in the visual control of eye growth. The RA system differs from a number of other candidates (dopamine, cholinergic agents, opiates) in that it distinguishes between positive and negative defocus, similar to the immediate early gene ZENK (Stell et al., 1999). The exact time kinetics of the changes have still to be worked out since it is possible that the changes in RA relate to already occurring changes in growth rather than to initial steps of the signaling cascade.     

The effect of positive lens defocus on ocular growth and emmetropization in the tree shrew

Optical defocus influences postnatal ocular development in animal models. Induced negative lens defocus results in accelerated ocular elongation and myopia. Positive lens-induced defocus findings across animal models have been inconsistent. Specifically, in the tree shrew, positive lens-induced defocus has produced equivocal results. This study evaluated the response of the tree shrew to induced positive lens defocus. One treatment group wore positive lenses binocularly, which were increased in power sequentially from +2 to +4, +6, +8, and +9.5 D over 8 weeks. Other groups wore +4, +6, and +9.5 D lenses, respectively, for 8 weeks. Animals wearing zero-powered (plano) lenses served as controls. Refractive error and ocular dimensions were measured at the start of treatment and every week thereafter. Sequentially increasing positive lens power caused a relative hyperopia of +5.6 D (p < 0.01) compared to the plano lens group (+10.9 +/- 1.8 D vs +5.3 +/- 0.5 D). Constant +4 D lens wear produced +6.9 D relative hyperopia, while +6 and +9.5 D lens wear did not induce hyperopia. Lens-induced defocus changes in refractive state were significantly correlated with vitreous chamber depth changes. The threshold for consistent responses to positive lens defocus in tree shrew was between +4 and +6 D. The results will enable targeted investigation of the efficacy of positive lens defocus in inhibiting myopic ocular growth.     

角膜塑形镜离焦技术在近视防控中的研究进展

近视发病率在全球范围内呈逐渐上升趋势,严重影响青少年儿童的眼部健康,引起了巨大的经济和社会效益损失。因此,近视防控工作至关重要且刻不容缓。近年来,角膜塑形镜逐渐在近视防控领域体现出其优越性。目前,角膜塑形镜控制近视发展的原理主要以视网膜远视性光学离焦学说为主,促使近视患者的远视性离焦向近视性离焦漂移从而延缓眼轴增长。其控制近视发展的效果与多种因素相关,包括离焦总量、瞳孔直径、光学区设计及镜片偏心等。角膜塑形镜的广泛使用将有效降低青少年儿童的近视发病率,本文就角膜塑形镜利用离焦技术控制近视发展的原理、离焦量和离焦环位置与近视防控效果的关系等方面进行综述,旨在阐明角膜塑形镜离焦技术在近视防控中的研究进展。     

Ocular compensation for alternating myopic and hyperopic defocus

During development, the eye grows under visual feedback control, as shown by its compensating for defocus imposed by spectacle lenses. Under normal conditions the sign and magnitude of defocus vary with viewing distance, accommodative status and other factors. To explore how periods of myopic and hyperopic defocus are integrated over time we presented rapidly alternating episodes of myopic and hyperopic defocus by sequentially illuminating a nearby scrim and the wall beyond it to chick eyes wearing lenses that put the far point between the two surfaces. We found that equal periods of myopic and hyperopic defocus generally led to compensatory hyperopia, showing that myopic defocus had a disproportionate effect. Furthermore, the degree of hyperopia depended on the frequency of alternation: low frequencies (1 cycle/30 min) resulted in more hyperopia, whereas at high frequencies (1 cycle/s) the myopic and hyperopic defocus nearly cancelled each other. If similar temporal integration effects apply to humans, they may help explain why brief accommodation events may not influence lens-compensation and why a child's total reading time may be a poor predictor of myopic progression.     

Imposed retinal image size changes--do they provide a cue to the sign of lens-induced defocus in chick?

BACKGROUND: Young chicks can adjust their eye growth to compensate for both imposed hyperopia and myopia (using negative and positive spectacle lenses); the rate of eye elongation increases in the former and slows in the latter case. This emmetropizing behavior implies that the eye can distinguish the sign and magnitude of defocus, although the identity of the cue(s) involved is unknown. As the spectacle lenses used in these studies generally introduce significant retinal image size differences that are in opposite directions for negative and positive lenses (minification vs. magnification), we asked whether retinal image size might provide the required sign information. METHODS: This question was addressed by manipulating retinal image size while keeping lens power constant. We also investigated the effect of eliminating other potential cues, accommodation and chromatic aberration, under these conditions. Three negative "size" lenses of approximately -11 D optical power were used, with 2 of the lenses producing magnification rather than minification as typical of negative lenses (i.e. +1.9% and +6.9% compared to -2.9%). The lenses were fitted monocularly to 7-day-old chicks, which were subsequently measured at 9 and 11 days of age (refractive error and axial dimensions). The same lens-wearing schedule was applied to two other groups of chicks that had monocular ciliary nerve section surgery to prevent accommodation 2 days posthatching; one of these groups was reared under monochromatic yellow light instead of white light. RESULTS: Near-perfect refractive compensation was seen by the end of the treatment period with all three lenses, for all three treatment groups, and there was also little difference in the rate of compensation among the various groups. In all cases, the typical responses of axial (mainly vitreous chamber) elongation and myopia were observed. CONCLUSIONS: That manipulations to retinal image size, which either decrease or reverse the usual effects of negative lenses, did not disrupt compensation to the imposed hyperopic defocus, even in the absence of accommodation and chromatic aberration cues, argues against imposed retinal image size changes being the directional cue to defocus in experimental emmetropization.     

光学离焦技术控制近视的研究进展

近视是一种常见的眼病,近年来,近视的发生率在全球范围内呈逐年上升趋势,高度近视会增加视力丧失的风险,近视的并发症可引起巨大的经济和社会效益损失。因此,实施控制近视的有效措施至关重要且迫在眉睫。人们对近视的发病机制研究表明,周围远视离焦引起眼球轴向伸长不受控制可能是近视发展的机制之一,由此引申的各种光学策略尤其是光学离焦技术控制近视日益成为近视管理主流临床实践的一部分。本文从光学离焦控制近视的原理、离焦性近视动物实验研究、不同光学离焦技术控制近视的最新临床应用等方面进行综述,总结了使用渐进多焦眼镜、周边离焦框架眼镜、多点近视离焦框架眼镜、角膜塑形镜及多焦点软性角膜接触镜控制近视的临床研究结果,拟为延缓近视进展的治疗方案设计提供新的选择。     

IMI Prevention of Myopia and Its Progression

The prevalence of myopia has markedly increased in East and Southeast Asia, and pathologic consequences of myopia, including myopic maculopathy and high myopia-associated optic neuropathy, are now some of the most common causes of irreversible blindness. Hence, strategies are warranted to reduce the prevalence of myopia and the progression to high myopia because this is the main modifiable risk factor for pathologic myopia. On the basis of published population-based and interventional studies, an important strategy to reduce the development of myopia is encouraging schoolchildren to spend more time outdoors. As compared with other measures, spending more time outdoors is the safest strategy and aligns with other existing health initiatives, such as obesity prevention, by promoting a healthier lifestyle for children and adolescents. Useful clinical measures to reduce or slow the progression of myopia include the daily application of low-dose atropine eye drops, in concentrations ranging between 0.01% and 0.05%, despite the side effects of a slightly reduced amplitude of accommodation, slight mydriasis, and risk of an allergic reaction; multifocal spectacle design; contact lenses that have power profiles that produce peripheral myopic defocus; and orthokeratology using corneal gas-permeable contact lenses that are designed to flatten the central cornea, leading to midperipheral steeping and peripheral myopic defocus, during overnight wear to eliminate daytime myopia. The risk-to-benefit ratio needs to be weighed up for the individual on the basis of their age, health, and lifestyle. The measures listed above are not mutually exclusive and are beginning to be examined in combination.     

Optical and pharmacological strategies of myopia control

Recent increases in global myopia prevalence rates have raised significant concerns as myopia increases the lifelong risk of various sight‐threatening ocular conditions. This growing public health burden has generated significant research interests into understanding both its aetiology and developing effective methods to slow down or stop its development, methods collectively termed ‘myopia control’. The growing body of research has demonstrated benefits of various optical and pharmacological treatments resulting in myopia control management increasingly becoming a part of main stream clinical practice. This review will discuss the peer‐reviewed literature on the efficacy of various myopia control interventions including multifocal spectacles and contact lenses, orthokeratology and pharmaceutical eye drops, as well as potential future research directions.     

光学离焦性近视眼视网膜pax-6基因表达的研究

目的 研究幼猴光学离焦性近视眼发生、发展过程中视网膜pax-6 基因的表达情况，探讨pax-6基因是否参与近视眼的发生、发展和正视化过程。 方法 选用猴龄为1~3个月的恒河猴9只，采用配戴眼镜或施行角膜屈光手术的方法，造成幼猴视网膜光学离焦。用反转录聚合酶链反应及定量分析方法检测不同时间视网膜pax-6基因的表达，并与非光学离焦眼进行比较。 结果 远视性光学离焦导致幼猴玻璃体腔增长速度加快，形成近视眼，其视网膜pax-6 基因表达量明显比正常对照眼高（t=3.480，P=0.004）。 结论 远视性光学离焦幼猴的视网膜pax-6 基因表达明显增加，表明pax-6基因可能参与视觉依赖的眼球生长和正视化过程。 （中华眼底病杂志，2003，19：201-268）     

Developing eyes that lack accommodation grow to compensate for imposed defocus

The eyes of growing chicks adjust to correct for myopia (eye relatively long for the focal length of its optics) or hyperopia (eye relatively short for the focal length of its optics). Eyes made functionally hyperopic with negative spectacle lenses become myopic and long, whereas eyes made functionally myopic with positive spectacle lenses become hyperopic and short. We report here that these compensatory growth adjustments occur not only in normal eyes but also in eyes unable to accommodate (focus) because of lesions to the Edinger-Westphal nuclei. Thus, at least in chicks, accommodation is not necessary for growth that reduces refractive errors during development, and may not be necessary for the normal control of eye growth.     

The effect of refractive error on perimetric thresholds using the Humphrey Field Analyser

Five normal young (20 ± 5 years) subjects had the central and peripheral fields of their right eyes measured using the Humphrey Field Analyser under emmetropic conditions and fitted with 38 per cent water content Hema spherical contact lenses to simulate distance refractive errors of 4 D, 6 D, 8 D, and 10 D of both myopia and hyperopia. The results for each induced refractive state were merged and averaged so that comparisons could be made with the averaged normal results. There was a mean decrease in sensitivity of 0.89 decibels (dB) per dioptre of uncorrected distance myopic refractive error or an estimated 1.27 dB per dioptre of myopic defocus (induced refractive error less 3 D due to the testing distance) for each of the 144 points for which thresholds were measured. For induced hyperopia, the mean decrease in sensitivity was 0.63 dB per dioptre of uncorrected distance refractive error or 1.01 dB per dioptre of estimated defocus (induced refractive error plus 3 D for the testing distance, less two-thirds of the accommodation). These reductions in sensitivity were significant centrally for 6 D or more of induced myopia (3 D or more of defocus) or 4 D or more of induced hyperopia (0.2 D or more of estimated defocus). Peripherally, the losses were significant in the temporal (and particularly inferior temporal) field for 6 D or more of induced myopia (3 D of defocus) and 4 D or more of induced hyperopia (0.2 D of estimated defocus). These results give ophthalmic practitioners a reference for use when assessing the peripheral fields of patients with high refractive errors.     

Spectacle lens compensation in the pigmented guinea pig

When a young growing eye wears a negative or positive spectacle lens, the eye compensates for the imposed defocus by accelerating or slowing its elongation rate so that the eye becomes emmetropic with the lens in place. Such spectacle lens compensation has been shown in chicks, tree-shrews, marmosets and rhesus monkeys. We have developed a model of emmetropisation using the guinea pig in order to establish a rapid and easy mammalian model. Guinea pigs were raised with a +4D, +2D, 0D (plano), −2D or −4D lens worn in front of one eye for 10 days or a +4D on one eye and a 0D on the fellow eye for 5 days or no lens on either eye (littermate controls). Refractive error and ocular distances were measured at the end of these periods. The difference in refractive error between the eyes was linearly related to the lens-power worn. A significant compensatory response to a +4D lens occurred after only 5 days and near full compensation occurred after 10 days when the effective imposed refractive error was between 0D and 8D of hyperopia. Eyes wearing plano lenses were slightly more myopic than their fellow eyes (−1.7D) but showed no difference in ocular length. Relative to the plano group, plus and minus lenses induced relative hyperopic or myopic differences between the two eyes, inhibited or accelerated their ocular growth, and expanded or decreased the relative thickness of the choroid, respectively. In individual animals, the difference between the eyes in vitreous chamber depth and choroid thickness reached ±100 and ±40 μm, respectively, and was significantly correlated with the induced refractive differences. Although eyes responded differentially to plus and minus lenses, the plus lenses generally corrected the hyperopia present in these young animals. The effective refractive error induced by the lenses ranged between −2D of myopic defocus to +10D of hyperopic defocus with the lens in place, and compensation was highly linear between 0D and 8D of effective hyperopic defocus, beyond which the compensation was reduced. We conclude that in the guinea pig, ocular growth and refractive error are visually regulated in a bidirectional manner to plus and minus lenses, but that the eye responds in a graded manner to imposed effective hyperopic defocus.     

加强我国儿童青少年近视的科学预防与控制

我国儿童青少年近视率居高不下,近视低龄化、重度化日益严重,已成为重要的公共卫生问题,儿童青少年近视防控也已上升为国家战略。目前,近视的病因尚未明确。因此,仍需深入探讨遗传和环境因素对近视的影响,进一步明确户外活动、角膜塑形镜、多焦点隐形眼镜、框架眼镜、阿托品滴眼液、重复低强度红光照射治疗等措施的优势及可能存在的局限性,综合考虑和应用现有的近视防控措施,制定科学有效的干预策略,加强我国儿童青少年近视的科学预防与控制。     

视网膜周边离焦与近视防控的研究进展

近视患病率在全球范围逐年增高,随之导致诸多眼健康问题和社会学影响。近年来,视网膜周边离焦被证实与近视的发生发展密切相关,改变视网膜的周边离焦状态能够显著影响近视发展和正视化进程,但其具体作用机制仍不明确。目前临床中尚无能够完全控制近视的方法,现有的主要方法包括硬性角膜塑形镜、周边离焦镜、多焦软镜等均被证实与视网膜周边离焦紧密相关,本文将总结归纳周边离焦相关的控制手段的发展、控制效果。并对国内外视网膜周边离焦与近视防控的相关机制研究进行回顾,提出周边离焦防控近视的潜在机制,以期为进一步提高各种防控手段的效果或研发新的防控措施以及降低近视的发病率和发展速度提供思路。     

Aberrations and myopia

It has been suggested that high levels of axial aberration or specific patterns of peripheral refraction could play a role in myopia development. Possible mechanisms involving high levels of retinal image blur caused by axial aberrations include form deprivation through poor retinal image quality in distance vision, enhanced accommodative lags favouring compensatory eye growth, and an absence of adequate directional cues to guide emmetropization. In addition, in initially emmetropic eyes, hyperopia in the retinal periphery may result in local compensatory eye growth, which induces axial myopia. Evidence in support of these ideas is reviewed and it is concluded that, for any fixed pupil diameter, evidence for higher levels of axial aberration in myopes in comparison with other refractive groups is weak, making involvement of axial aberrations in myopization through image degradation at the fovea unlikely. If, however, some potential myopes had unusually large pupil diameters, their effective aberration levels and associated retinal blur would be larger than those of the rest of the population. There is stronger evidence in favour of differences in patterns of peripheral refraction in both potential and existing myopes, with myopes tending to show relative hyperopia in the periphery. These differences appear to be related to a more prolate eyeball shape. Longitudinal studies are required to confirm whether the retinal defocus associated with the peripheral hyperopia can cause patterns of eyeball growth which lead to axial myopia.