Christine F. Wildsoet

Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks

It is known that when hyperopic or myopic defocus is imposed on chick eyes by spectacle lenses, they rapidly compensate, becoming myopic or hyperopic respectively, by altering the depth of their vitreous chamber. Changes in two components--ocular length and choroidal thickness--underlie this rapid compensation. With monocular lens treatment, hyperopic defocus imposed by negative lenses resulted in substantially increased ocular elongation and a slight thinning of the choroid, both changes resulting in myopia; myopic defocus imposed by positive lenses resulted a dramatic increase in choroidal thickness, which pushed the retina forward toward the image plane, and a slight decrease in ocular elongation, both changes resulting in hyperopia. The refractive error after 5 days of lens wear correlated well with vitreous chamber depth, which reflected the changes in both choroidal thickness and ocular length. The degree of compensation for lenses was not affected by whether the fellow eye was covered or open. Both form-deprivation myopia and lens-induced myopia declined with age in parallel, but wearing a -15 D lens produced more myopia than did form deprivation. The spectacle lenses affected the refractive error not only of the lens-wearing eye, but also, to a much lesser degree, of the untreated fellow eye. At lens removal refractive errors were opposite in sign to the lense worn, and the subsequent changes in choroidal thickness and ocular length were also opposite to those that occurred when the lenses were in place. In this situation as well, effects of the spectacle lenses on the fellow eyes were observed. Eyes with no functional afferent connection to the brain because of either prior optic nerve section or intraocular tetrodotoxin injections showed compensatory changes to imposed defocus, but these were limited to compensation for imposed myopic defocus, at least for the eyes with optic nerve section. In addition, optic nerve section, but not tetrodotoxin treatment, moved the set-point of the visual compensatory mechanism toward hyperopia. Optic nerve section prevents myopia in response to negative lenses but not to diffusers, suggesting that compensation for hyperopia requires the central nervous system.

Moving the Retina: Choroidal Modulation of Refractive State

The chick eye is able to change its refractive state by as much as 7 D by pushing the retina forward or pulling it back; this is effected by changes in the thickness of the choroid, the vascular tissue behind the retina and pigment epithelium. Chick eyes first made myopic by wearing diffusers and then permitted unrestricted vision developed choroids several times thicker than normal within days, thereby speeding recovery from deprivation myopia. Choroidal expansion does not occur when visual cues are reduced by dim illumination during the period of unrestricted vision. Furthermore, in chick eyes presented with myopic or hyperopic defocus by means of spectacle lenses, the choroid expands or thins, respectively, in compensation for the specific defocus imposed. Consequently, when the lenses are removed, the eye finds its refractive error suddenly of opposite sign, and the choroidal thickness again compensates by changing in the opposite direction. If a local region of the eye is made myopic by a partial diffuser and then given unrestricted vision, the choroid expands only in the myopic region. Although the mechanism of choroidal expansion is unknown, it might involve either a increased routing of aqueous humor into the uveoscleral outflow or osmotically generated water movement into the choroid. The latter is compatible with the increased choroidal proteoglycan synthesis either when eyes wear positive lenses or after diffuser removal.

Active emmetropization : evidence for its existence and ramifications for clinical practice

There is increasing evidence from animal studies in support of the concept of an active emmetropization mechanism which has potentially important clinical ramifications for the management of refractive errors. Recent research into refractive development and emmetropization is reviewed, with emphasis given to work involving the chick, tree shrew and monkey, which represent the three most widely used animal models in this field. The findings of this research are reviewed in a clinical context. Compensatory eye growth responses to focusing errors imposed by lenses represent the most compelling evidence for active emmetropization. These observations are complemented by other evidence showing recovery from induced refractive errors such as form-deprivation myopia. Of the animals listed above, chicks show the most impressive emmetropization, being able to compensate fully (using choroidal and scleral mechanisms) to lens powers ranging from +15 D to -10 D. The range of lens powers eliciting appropriate compensatory responses is narrower in the tree shrew and monkey, and the response patterns generally are also more complex to interpret. These data relate to young animals and together indicate refractive plasticity during development. Extrapolation of these findings to humans predicts that natural emmetropization will be inhibited in neonates by early intervention with prescription lenses, and that refractive correction of myopia will lead to accelerated progression. This convincing evidence for active emmetropization warrants due consideration in developing clinical management strategies for refractive errors.

Measurement of monochromatic ocular aberrations of human eyes as a function of accommodation by the howland aberroscope technique

Further development of the objective version of the Howland and Howland [(1976) Science, 193, 580-582; (1977) Journal of the Optical Society of America, 67, 1508-1518] aberroscope technique for measuring ocular aberrations is described. Compensation for refractive corrections and calibration is discussed. The technique was used to investigate the effect of accommodation upon the monochromatic aberrations of the right eyes of 15 subjects. Coma and coma-like aberrations were the dominant aberrations for most people at different accommodation levels, thus confirming previous findings. Variations in aberrations were considerable between subjects. About half the subjects showed the classical trend towards negative spherical aberration with accommodation. Changes in spherical aberration with accommodation in this study were less than found in previous studies where all monochromatic aberration was considered to be spherical aberration.

Effects on the compensatory responses to positive and negative lenses of intermittent lens wear and ciliary nerve section in chicks.

This study examined the ocular compensation to lens-induced defocus in chick and the effect of interrupting lens wear on a daily basis. Eyes fitted with +10 D lenses at hatching compensated rapidly, with almost complete compensation after 4 days of lens wear; they had decreased vitreous chamber depth compared to normal eyes and were thus hyperopic when the lenses were removed. In contrast, adaptation to the -10 D lenses was much slower, was still incomplete after 9 days of lens wear, and in this case, eyes had increased vitreous chamber depth and were myopic without the lenses. Adaptation improved when lens wear was delayed until 7 days after hatching. The effect of interrupting lens wear by periods of normal vision varied with the sign of the lenses worn. Hyperopia was always seen in response to +10 D lenses, although the magnitude of the response decreased as the duration of lens wear was decreased. In contrast, even brief periods of normal vision, i.e., 3 hr, prevented the development of myopia in response to the -10 D lenses; this apparent sensitivity to normal vision is similar to that reported for form-deprivation myopia. Ciliary nerve section used here to eliminate accommodation did not alter these response patterns.

Monochromatic aberrations and myopia.

The monochromatic aberrations present in the eyes of a group of 21 young myopic subjects and 16 young emmetropic subjects were measured along the visual axis at three levels of accommodation. The aberrations were measured using a modified aberroscope technique which makes use of a retinal camera to photograph the shadow image of the aberroscope grid on the retina, while accommodation levels of 0, 1.5 and 3.0 D were induced consensually. Fourth-order aberrations were significantly different between the emmetropic and myopic groups, with the myopes showing lower fourth-order terms. A high proportion of the aberroscope grids photographed in the myopic eyes were too highly aberrated to permit analysis.

Chromatic aberration and accommodation: their role in emmetropization in the chick

The roles of chromatic aberration and accommodation as cues to emmetropization in the chick were investigated. Myopia was induced monocularly by lid suture for a period of 1-2 weeks from hatching, after which eyes were reopened and the recovery process followed. Monochromatic light (ML) rearing conditions and ciliary nerve section surgery were used to eliminate chromatic aberration and accommodative activity respectively. Control animals were reared in white light (WL). When accommodation was left intact, chickens reared under monochromatic light were able to recover normally. However, ciliary nerve section produced hyperopia, deepening of the anterior chamber and a tendency towards axial lens thinning, irrespective of the light conditions used. Hyperopic refractive errors peaked at 4 weeks (mean refractive errors: +5.7 D, +4.21 D for ML, WL groups respectively, 4 weeks), with the ML group still exhibiting significant hyperopia at 7 weeks. Ciliary nerve section did not prevent the myopic response to lid suture (mean refractive errors: -22.65 D; -25 D for ML, WL groups respectively, 1 week) nor the elimination of myopia when eyes were reopened. These data indicate that neither accommodation nor chromatic aberration are fundamental to the gross operation of the emmetropization process although they may be essential for the fine tuning of refraction.

The role of the retinal pigment epithelium in eye growth regulation and myopia: A review

Myopia is increasing in prevalence world-wide, nearing epidemic proportions in some populations. This has led to expanded research efforts to understand how ocular growth and refractive errors are regulated. Eye growth is sensitive to visual experience, and is altered by both form deprivation and optical defocus. In these cases, the primary targets of growth regulation are the choroidal and scleral layers of the eye that demarcate the boundary of the posterior vitreous chamber. Of significance to this review are observations of local growth modulation that imply that the neural retina itself must be the source of growth-regulating signals. Thus the retinal pigment epithelium (RPE), interposed between the retina and the choroid, is likely to play a critical role in relaying retinal growth signals to the choroid and sclera. This review describes the ion transporters and signal receptors found in the chick RPE and their possible roles in visually driven changes in eye growth. We focus on the effects of four signaling molecules, otherwise implicated in eye growth changes (dopamine, acetylcholine, vasoactive intestinal peptide (VIP), and glucagon), on RPE physiology, including fluid transport. A model for RPE-mediated growth regulation is proposed.

Neural pathways subserving negative lens-induced emmetropization in chicks--insights from selective lesions of the optic nerve and ciliary nerve.

Purpose. Active emmetropization describes the process by which young eyes regulate their growth to eliminate refractive errors. The purpose of this study was to re-investigate the role of the brain in compensation to imposed hyperopic defocus (negative lenses), specifically, to assess whether a retina-brain link and/or an intact ciliary nerve are required for this emmetropizing response. Data from previous related studies are equivocal. Methods. Unilateral lesion surgery involving either or both optic nerve section (ONS) and ciliary nerve section (CNS), was performed on 2–3 day old White-Leghorn chicks to interrupt communication between the eye (retina in the case of ONS) and brain. After a recovery period of 4 days, lesioned eyes were fitted with either –5 or –15 D lenses or diffusers (6–9 per group). An additional lesion group underwent unilateral CNS and was fitted with –5D lenses bilaterally. Finally 3 groups that underwent the same unilateral optical treatments but no surgery were included as controls for analyzing lesion-induced changes. Complete sets of measurements, involving retinoscopy for refractive errors, and high frequency A-scan ultrasonography for axial ocular dimensions, were made at the beginning (baseline), and end of a 4 day treatment period. Additional ultrasonography data were collected after 1 and 2 days of treatment. Optical treatment effects were expressed as changes in interocular differences from baseline values. Results. All three lesions produced hyperopic shifts in refraction (evident in baseline values), although this effect was minimal for the ONS+CNS group. Choroidal thickening as well as increased anterior chamber depth and lens thinning were observed in all cases but vitreous chamber depth was reduced in only the ONS group. In response to the –5D lens, the control (nonlesioned) group showed nearly complete compensation, while full compensation was not achieved to the –15 D lens over this short treatment period. The diffuser group showed the largest change, which was also in the direction of myopia. Both the ONS and CNS groups showed near normal compensation, as indexed by the changes in refractive errors relative to their respective baseline values. In contrast, the ONS+CNS lens groups overcompensated, by 130% and 54% for the –5D and the –15 D lens groups respectively. Form deprivation responses were slightly exaggerated in both ONS and ONS+CNS groups, the latter group again showing the largest response. Enhanced vitreous chamber growth was evident under all conditions and correlated well with the refractive changes across the groups. Discussion. The data imply that an intact retina-brain link is not required for compensation to hyperopic defocus and thus emmetropization. However, the data also imply interactions between higher centers and the eye. The emmetropization set-point appears to be recalibrated after ONS surgery. The data also indicate a role of the ciliary nerve as an important conduit for signals that exercise a restraining influence on eye growth.

The Effect of Two-Zone Concentric Bifocal Spectacle Lenses on Refractive Error Development and Eye Growth in Young Chicks

PURPOSE To characterize the effects on refractive error development and eye growth in young chicks of two-zone concentric lens designs, which differentially affect the defocus experiences of central and peripheral retinal regions. METHODS Monocular defocusing lenses were worn for 5 days from 17 days of age. Four two-zone concentric lens designs (overall optical zone diameter, 10 mm) combining plano with either -5- or +5-D power were used. Lens designs were as follows: (1) +5 D center (+5C), (2) +5 D periphery (+5P), (3) -5 D center (-5C), and (4) -5 D peripheral (-5P), with plano in periphery for all C-designs and in the center for P-designs. Five central zone diameters (CZDs) were tested, ranging from 2.5 to 6.5 mm in 1-mm increments. Plano, +5- and -5-D single-vision (SV) lenses were used as the control. A minimum of six birds were included in each lens group. RESULTS For the two-zone lenses, the P designs (i.e., peripheral defocus) had greater effects than the C designs (i.e., central defocus) on both on-axis eye growth and refractions. All but the 6.5-mm CZD +5P lens induced larger changes than the +5SV lens. The +5C lenses with CZD less than 5.5 mm had little effect. The two-zone -5-D lenses had less effect than the -5SV lens, and only the 6.5-mm CZD lens of the -5C series had a significant effect. CONCLUSIONS The results demonstrate that peripheral defocus can influence both peripheral and central refractive development. The inhibitory effect on axial eye growth of the +5P lenses opens the possibility that appropriately designed concentric lenses may control the progression of human myopia.