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Although reduced ambient lighting ("dim" light) can cause myopia in emmetropizing chicks, it does not necessarily lead to myopic changes in emmetropizing rhesus monkeys. Because myopia is rarely spontaneous, a question remained whether dim light would hasten the progression of visually induced myopia. To determine the effects of dim light on the development of and recovery from form-deprivation myopia (FDM), seven 3-week-old infant rhesus monkeys were reared under dim light (mean ± SD = 55 ± 9 lx) with monocular diffuser spectacles until ~154 days of age, then maintained in dim light with unrestricted vision until ~337 days of age to allow for recovery. Refractive errors, corneal powers, ocular axial dimensions and sub-foveal choroidal thicknesses were measured longitudinally and compared to those obtained from form-deprived monkeys reared under typical laboratory lighting (504 ± 168 lx). Five of the seven subjects developed FDMs that were similar to those observed among their normal-light-reared counterparts. The average degree of form-deprivation-induced myopic anisometropia did not differ significantly between dim-light subjects (-3.88 ± 3.26D) and normal-light subjects (-4.45 ± 3.75D). However, three of the five dim-light subjects that developed obvious FDM failed to exhibit any signs of recovery and the two monkeys that were isometropic at the end of the treatment period manifest abnormal refractive errors during the recovery period. All refractive changes were associated with alterations in vitreous chamber elongation rates. It appears that dim light is not a strong myopiagenic stimulus by itself, but it can impair the optical regulation of refractive development in primates., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In a variety of species, the refractive state of the eye differs in different parts of the visual field (VF) with greater myopia in the region that views the ground ("lower field myopia"). We studied the refraction and eye shape of the normal guinea pig eye to determine what feature(s) underlie this visual adaptation. Guinea pigs (n=67) were either newborn or raised under incandescent light until 14, 37 or 45 days of age (20, 44, 20 and 11 eyes respectively). Refractive error was measured on-axis and 30° off-axis in the superior (SVF), inferior (IVF), temporal (TVF) and nasal (NVF) visual fields. Eye shape was analyzed from images of frozen hemisections in both the horizontal and vertical mid plane in 14 day animals, and in the vertical plane at 0, 14 and 45 days of age. Axial distances in vitro were correlated with in vivo high frequency ultrasound (r(2)=0.90). In the horizontal plane, asymmetry was caused by a ± 6° conical zone surrounding the optic nerve (12° off-axis in NVF), suggesting significant myopia in this zone. At 30°, there was no asymmetry in eye length, but the NVF was +1.7D more myopic due to asymmetry in corneal power. In the vertical plane at 30°, the IVF was more myopic than the SVF by -3.8D at 0 days, -5.9D at 14 days and -6.0D at 37 days. It resulted from vertical asymmetry in the distance of the retina from the lens center, which was longest in the mid IVF. This non-linear ramp retina was present at birth. In older animals, the peak of the ramp shifted more centrally, and the eye developed longer lengths in the extreme upper periphery (SVF) which may have been caused by the low position of the room ceiling. The vertical asymmetry in eye shape was mirrored by changes in choroid thickness, suggesting a mechanism by which eye shape was refined by vision during development. In early life, ocular growth in the vertical plane was 1.7 times higher in the center relative to the periphery, a pattern that reversed in the following month. Since emmetropization was achieved over this period, local visual cues related to clear vision may provide a switch to change ocular growth from a central to a peripheral emphasis., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

We determined effects of hemiretinal form deprivation (i.e., form-depriving half of the retina) on central refractive development and posterior eye shape in chicks. Seventy-seven White Leghorn chicks were randomly assigned to receive superior (SRD, "Superior Retinal Deprivation" or inferior visual field deprivation, same principle applies for the following abbreviations, n=17), inferior (IRD, n=14), temporal (TRD, n=23) or nasal hemiretinal (NRD, n=23) form deprivation monocularly from day 5 to day 26. Central refractive errors, expressed as interocular difference in spherical equivalent (M), J0 and J45 astigmatic components, were measured using Hartinger refractometer at the beginning and weekly after treatment for 3weeks. At the end of the treatment period, eyes of a subset of birds were enucleated and eye shape profile was photographed along four different meridians. These digital images were later processed to extract axial length (AL), equatorial diameter (ED), and AL/ED. For comparison purposes, the eye shape profile was also acquired from a separate group of birds reared with monocular full-retinal form deprivation (FRD, n=10). The four hemiretinal form deprivations altered central ametropia and posterior eye shape to different degrees. The biggest contrast in M was found between SRD and IRD groups (mean±SE after 3weeks: SRD=-4.14±0.71 D vs. IRD=+1.24±0.36 D; p<0.05), whereas subtle differences in J0 and J45 components were found across the four treatment groups (both p⩽0.03). SRD group also showed significantly higher AL/ED ratio compared to IRD and NRD groups (0.76±0.05 vs. 0.74±0.07 and 0.75±0.04; both p⩽0.03). Furthermore, M was significantly correlated with AL/ED ratio in the treated eyes of hemiretinal treated chicks (r=-0.55, p<0.001). Our results suggest that mechanism regulating central ametropia can be influenced by selectively interrupting the visual experience at different parts of visual field., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: Defocus imposed to the periphery of the visual field can affect the development of foveal/central refractive errors. To make use of this observation, lenses can be designed to reduce myopia progression, but it is important to know which power profiles of the lenses are most effective. We have studied this question in chickens., Methods: Sixty male white leghorn chickens were used. From day 7 after hatching, they were treated for 5 days either with full field -7D or +7D lenses, with -7D lenses with a 4mm central hole, with hemi-field lenses of the same power, or with two different types of radial refractive gradient (RRG) lenses with increasing positive power from the center to the periphery, which were designed by Rodenstock GmbH, Munich, Germany. A macro file was written for "ImageJ" to trace and average the outlines of several excised eyes after treatment. Shapes of fellow control eyes and lens-treated eyes were compared in the horizontal and vertical meridians. Refractions were determined at -45°, 0°, and 45° over the horizontal visual field, at the beginning and at the end of experiments, using automated infrared photoretinoscopy., Results: (1) Eye length, as determined by the new automated eye shape tracing technique, was well correlated with A-scan ultrasound data. (2) The effects of previously tested lens designs were reproduced with the new tracing technique. Full field lenses were by far the most effective (-7D: external axial length +0.24mm with an increase in eye volume of about 6%, +7D: -0.08 mm, with a decrease in eye volume of about 2%). Hemi-field lenses and negative lenses with a 4mm central hole induced conspicuous local changes in eye shape. (3) The first type of RRG lenses with a plano zone of about 4mm (equivalent to about ± 12.52° in the visual field for a vertex distance of 5mm) had no apparent effect on central refractions but induced small hyperopic shifts in the periphery, more significant in the temporal retina (+1.70 ± 1.70 D, p<0.001, paired t-test to untreated fellow eyes). The second type of RRG lenses with a small plano zone of 2mm (equivalent to ± 6.34°) induced peripheral hyperopia but also changed the central refraction (temporal retina +1.50 ± 1.17D, p<0.001, central retina +0.77 ± 1.15 D, p<0.01, nasal retina +1.47±1.35D, p<0.001, paired t-test to untreated control eyes)., Conclusions: In the afoveate chick, RRG lenses have an effect on central refraction and eye growth only if the central plano zone is small (<4mm). For the second type of RRG lens with a central plano zone of about 2mm, inhibitory effects on eye growth were detected in both the center and periphery even though the optical power of the lenses in the periphery was low., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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 +/-40microm, 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.

Purpose: This study sought further insight into the stimulus dependence of form deprivation myopia, a common response to retinal image degradation in young animals., Methods: Each of 4 Bangerter diffusing filters (0.6, 0.1, <0.1, and LP (light perception only)) combined with clear plano lenses, as well as plano lenses alone, were fitted monocularly to 4-day-old chicks. Axial ocular dimensions and refractive errors were monitored over a 14-day treatment period, using high frequency A-scan ultrasonography and an autorefractor, respectively., Results: Only the <0.1 and LP filters induced significant form deprivation myopia; these filters induced similarly large myopic shifts in refractive error (mean interocular differences+/-SEM: -9.92+/-1.99, -7.26+/-1.60 D, respectively), coupled to significant increases in both vitreous chamber depths and optical axial lengths (p<0.001). The other 3 groups showed comparable, small changes in their ocular dimensions (p>0.05), and only small myopic shifts in refraction (<3.00 D). The myopia-inducing filters eliminated mid-and-high spatial frequency information., Conclusions: Our results are consistent with emmetropization being tuned to mid-spatial frequencies. They also imply that form deprivation is not a graded phenomenon.

Purpose: The purpose of this study was to test the response of the mouse eye to two methods for the induction of experimental myopia., Methods: Growth patterns of eyes were determined by axial length measurements from birth to adult in eyes of both sexes of normal mice examined on post-natal day 1 to 6 months and at 1 year. For the induction of experimental myopia, Balb/cJ mice were prepared with either unilateral lid suture or by a -10D spectacle lens placed over one eye at post-natal day 10. Other mice received a plano lens as a control for lens wear. Refraction was carried out at post-natal days of 28, 42 and 56 in lid suture and spectacle lens wear group by streak retinoscopy. Axial length was measured by a combination of video image photography, digital caliper, or Optical Low Coherence Interferometry (OLCI). Corroborative optical modeling of the mouse eye was carried out using ZEMAX ray tracing software., Results: Axial length (AL) increased linearly between post-natal day 1 to day 56, plateauing at about 140 days. After 18 days of unilateral lid suture initiated 10 days after birth, the AL of experimental eyes was 3.032+/-0.003 mm, while AL in contra-lateral control eyes was 2.981+/-0.005 mm (mean+/-sem, p<0.05, n=40), after 32 days, the AL of experimental eyes was 3.290+/-0.004 mm, and the AL of control eyes was 3.104+/-0.002 mm (p<0.001, n=60). After 46 days of lid closure AL of experimental eyes was 3.592+/-0.003 mm, while AL of control eyes was 3.363+/-0.003 mm (p<0.001, n=80). Spectacle lens wear of 46 days duration increased AL in experimental eyes to 3.721+/-0.002 mm, while AL in control eyes was 3.354+/-0.003 mm (p<0.001, n=100). Refraction and ray tracing analysis substantiated the dimensional changes to be consistent with increased AL., Conclusions: Two procedures to induce experimental myopia, initiated at eye opening, produced significant myopic shifts corresponding to increases in axial lengths after 32 and 46 days of lid suture and after 46 days wearing a -10D spectacle lens.

We studied the potential of myopic corneal refractive laser surgery to induce myopia (axial elongation) and potential interactions between aberrations (generally resulting from the procedure) and myopia development in chicks (Gallus domesticus). Ten white Leghorn chicks were monolaterally treated one day post-hatching with photorefractive keratectomy (PRK), with a nominal dioptric change of -9.9 D (imposed hyperopia). Axial length was measured using an adapted ultrasonic biometer; corneal radius of curvature was measured using a custom-built videokeratometer and spherical error and high order aberrations were measured using custom-built Hartmann-Shack aberrometer post-operatively on days 9, 12, 14 and 16 after hatching. Two-weeks after surgery, there were no significant differences in corneal radius of curvature between treated and control eyes. Astigmatism increased on average by a factor of 2.6 and 3rd and higher order aberrations by a factor of 4.3 after PRK. Both treated and control eyes were close to emmetropia, and no axial elongation was found in the treated eyes. The inability of the refractive procedure to achieve significant reductions in the corneal power could be attributed to the biomechanical properties of the chick eye. High order aberrations induced significant contrast decrease (by a factor of 1.7 at 4.5c/deg). However, reduced image quality neither produced myopic refractive error nor axial elongation in the treated eyes. Both normal and treated eyes emmetropized, indicating that increased amounts of aberrations do not appear to be a risk factor for myopia.

Accommodation may indirectly influence visually guided eye growth by affecting the retinal defocus signal used to guide growth. Specifically, increased lags of accommodation associated with low stimulus-response (S-R) function slopes will impose increased hyperopic blur on the retina and may induce axial elongation and myopia. The purpose of this study was (1) to measure accommodation in awake, free viewing marmosets and (2) compare accommodation behavior in marmosets before and after inducing different amounts of myopia with binocular spectacle lenses. In untreated marmosets, the average accommodation S-R slope approached one, but showed considerable inter-individual variability (mean+/-SD: 0.964+/-0.249 for monocular viewing; 0.895+/-0.235 for binocular viewing; monocular and binocular measures not significantly different). The monocular S-R slopes were significantly reduced following a period of lens rearing that produced axial myopia (change in slope=-0.30+/-0.30, p<.01) and the reduction in slope was proportional to the amount of myopia induced (p<.01). The S-R slopes measured either under monocular or binocular conditions before induction of myopia were not well correlated with the degree of myopia induced (monocular: r=-.240, p=.453; binocular: r=-.060, p=.824). These results support the hypothesis that the reduction in S-R slope in myopes is a consequence of the myopia induced. The alternative hypothesis-that low S-R slope increases susceptibility to the development of myopia--is not supported by the weak correlation between the pre-manipulation S-R slopes and the magnitude of the myopic shift.

Purpose: Guinea pigs have been increasingly used as an animal model for experimental myopia. Infant guinea pigs are susceptible to recovery from myopia within 2 weeks of form deprivation. This study investigated whether adolescent guinea pigs are susceptible to recovery from myopia after a longer period of form deprivation., Method: Twenty-two guinea pigs (age of 3 weeks) were randomly assigned to two groups: MDF (monocularly deprived facemask, n=11) and normal control (free of form deprivation, n=11). All animals underwent biometric measurement (refraction, corneal curvature and axial length) prior to the experiment. Animals in the MDF group wore a facemask that covered the right eye for 4 weeks. The MDF was then removed and biometric measurement was performed immediately and at 2, 6, 10 and 14 days. The same measurement was performed in the normal control group at time-points matching those of the MDF group., Results: The MDF eyes were approximately 4D more myopic with a greater increase in vitreous length by 0.12 mm compared to either the fellow or the normal control eyes after form deprivation (p<0.01). This relative myopia shifted rapidly towards hyperopia within 2 days after removal of the MDF, followed by a more gradual recovery. A complete recovery occurred by 6 days after removal of the MDF compared to the fellow and normal control eyes (p>0.05). Vitreous length in the MDF eyes slightly reduced within 2 days after removal of the MDF and then remained steady. The MDF eyes were similar to both the fellow and normal control eyes in vitreous length (p>0.05) 6 days after removal of the MDF. There was no significant difference between the MDF, fellow and normal control eyes in the other axial components during the form deprivation and recovery period., Conclusion: Adolescent guinea pigs are susceptible to recovery from MDF-induced myopia. The refractive recovery is mainly correlated to the inhibited axial elongation of the vitreous chamber of the previously deprived eyes.

Purpose: Recent experiments in monkeys suggest that deprivation, imposed only in the periphery of the visual field, can induce foveal myopia. This raises the hypothesis that peripheral refractive errors imposed by the spectacle lens correction could influence foveal refractive development also in humans. We have tested this hypothesis in chicks., Methods: Chicks wore either full field spectacle lenses (+6.9 D/-7 D), or lenses with central holes of 4, 6, or 8mm diameter, for 4 days (n=6 for each group). Refractions were measured in the central visual field, and at -45 degrees (temporal) and +45 degrees (nasal), and axial lengths were measured by A-scan ultrasonography., Results: As previously described, full field lenses were largely compensated within 4 days (refraction changes with positive lenses: +4.69+/-1.73 D, negative lenses: -5.98+/-1.78 D, both p<0.001, Dunnett's test, to untreated controls). With holes in the center of the lenses, the central refraction remained emmetropic and there was not even a trend of a shift in refraction (all groups: p>0.5, Dunnetts test). At +/-45 degrees , the lenses were partially compensated despite the 4/6/8mm central holes; positive lenses: +2.63 / +1.44 / +0.43 D, negative lenses: -2.57 / -1.06 / +0.06 D., Conclusions: There is extensive local compensation of imposed refractive errors in chickens. For the tested hole sizes, peripherally imposed defocus did not influence central refractive development. To alter central refractive development, the unobstructed part in the central visual field may have to be quite small (hole sizes smaller than 4mm, with the lenses at a vertex distance of 2-3mm).

While instrument myopia is known to occur when microscopes are used, little is known about the accommodation response during microscopy, or about the factors which may alter the magnitude of instrument myopia. In addition, there has been no real-time objective measurement of instrument myopia during the microscopy task. Twenty inexperienced subjects and 10 experienced microscopists (average work experience of 4.8 years (SD 3.2 yr)) with mean age of 24.1 years (SD 2.9 yr) and 31.2 years (SD 2.9 yr) respectively were recruited to the study. Instrument myopia was measured using an infrared photorefractor (PowerRefractor) under different viewing conditions and microscope settings (with different forms of refractive error correction, changes in target quality, changes in eyepiece power settings, changes in magnification and changes in illumination of the target). Instrument myopia was greater in inexperienced (1.98 D (SD 0.91 D)) than in experienced (1.38 D (SD 0.75 D)) microscope users. There was no statistically significant change in the level of instrument myopia under the different viewing conditions or different microscope settings, and there were large individual variations. Other factors may play more of a role in determining the degree of instrument myopia during microscopy than the task variables altered here.

To test the hypothesis that the same mechanisms mediate form deprivation and lens-induced myopia, the ocular growth responses of chicks alternately exposed to lenses and diffusers at regular intervals (3h) were compared to those of chicks exposed to either negative lenses or diffusers alone. In total, there were four experiments: (1) -15 D lenses and/or diffusers on normal birds, (2) -15 D lenses and/or diffusers on optic nerve-sectioned (ONS) birds, (3) -5/-10/-15 D lenses (sequentially applied) and/or diffusers on normal birds and (4) -5/-10/-15 D lenses and/or diffusers on ONS birds. All treatments were monocular. In all experiments, optical axial lengths (cornea-to-retina distances) in treated eyes were greater than in fellow eyes, irrespective of the optical device (diffuser, lens or switch), lens power (fixed or incremented) and optic nerve condition (intact or severed). In normal chicks, optical axial length responses in the switch group were significantly reduced relative to those of the diffuser but not to those of the -15 D lens group. For both groups of ONS birds, diffusers exaggerated the optical axial length changes. For all groups, the responses to the switch and lens groups were most similar. These results together suggest that the mechanisms mediating form deprivation- and lens-induced myopia are different.

Purpose: To find out how spatial vision in mice is affected by wearing of spectacle lenses or diffusers, and by atropine eye drops. This information is necessary to determine which treatments could effectively induce refractive errors in young mice., Methods: Whole-body optomotor responses were recorded by automated video analysis in freely ranging mice in a large rotating drum that was covered inside with vertical square-wave gratings with spatial frequencies of 0.03, 0.10 and 0.30 cyc/deg, both at "dim light" (0.10 cd/m(2)), and under photopic conditions (30 cd/m(2)). Contrast thresholds were determined by varying the contrasts of the gratings. Mice wore either no lenses, or binocular plano lenses, or lenses with powers ranging from +25 D to -25 D, or diffusers. In another experiment, contrast thresholds were determined 30 min after binocular installation of one drop of 1% atropine solution which is known to suppress myopia development in other animal models., Results: The range of spatial frequencies, at which the mice still responded to stripes with less than the maximal grating contrast, was rather small. At 0.03 cyc/deg, the mice responded to stripes with low contrast down to 24%. At 0.10 cyc/deg, the minimal contrast was 45%, but at 0.30 cyc/deg, only the maximum contrast elicited a significant response. In dim light, spatial vision was severely impaired and only the lowest spatial frequencies, presented at the highest contrast (91%), were detected. The whole-body optomotor response was largest with spectacle lens powers of plano diopters and +7D lenses. The magnitude of the response decreased symmetrically with increasing lens powers for both signs, providing information on the behavioral depth of field (a second-order fit through the data placed the extreme limits of a response at around +25 D and -25 D lens powers). Finally, atropine improved contrast sensitivity, at least at the lowest spatial frequency tested, a result that was previously obtained also in the chicken and could help to explain the inhibitory effect of atropine on myopia., Conclusions: The study shows that mice have sufficient spatial vision to respond to treatment with powerful spectacle lenses or diffusers. Accordingly, these devices should be effective in inducing refractive errors in this animal model, although primarily under photopic conditions.

We performed measurements of refraction (with retinoscopy), axial length (with ultrasound biometry) and ocular aberrations (with a custom-built Hartmann-Shack aberrometer) on seven awake White-Leghorn chicks occluded monolaterally with diffusers for two weeks. Treatment started on the first day after hatching (day 0) and measurements were conducted on several days between day 0 and 13. Non-occluded eyes experienced normal emmetropization (decreasing hyperopia at 0.2 +/- 0.09 D/day and increasing axial length at 0.05 +/- 0.03 mm/day), while occluded eyes developed axial myopia (1.50 +/- 0.2 D/day and 0.12 +/- 0.02 mm/day). Interocular differences in refraction and axial length by day 13 were on average 17.43 D and 0.86 mm, respectively. Monochromatic high order aberrations decreased with age in both eyes. Average RMS (for 1.5 mm pupil diameter) decreased from 0.11 +/- 0.03 at day 0 to 0.06 +/- 0.03 microm (day 13) in occluded eyes, and from 0.12 +/- 0.05 to 0.03 +/- 0.01 microm in non-occluded eyes. MTF-based optical quality metrics also show an improvement with age. However, while this improvement occurs in both eyes, after day 8 myopic eyes tend to show significantly higher amounts of aberrations (and consequently worse best-corrected optical quality) than normal eyes. The degradation imposed by aberrations is small compared to that imposed by defocus and the diffuser. These results suggest a decrease of aberrations during development which does not seem to be visually guided. Myopic eyes showed slightly worse optical quality than normal eyes, suggesting that the geometrical changes resulting from excessive ocular axial growth also affect the optical quality of the ocular components.

Form deprivation (FD) was induced in 61 guinea pigs with a diffuser worn on one eye. The form-deprived eye elongated and developed myopia within 6 days in animals raised under a 12:12 h light/dark cycle, but not when reared in darkness. After 11 days of FD, the average eye was -6.6 D more myopic and 146 microm longer than its fellow eye. Initially the myopia was mostly from vitreous chamber elongation, but with longer periods of FD, corneal power increases predominated. These effects were confirmed in schematic eyes. After a delay, FD also elongated the vitreous chamber of the non-deprived eye. The myopia rapidly abated once the diffusers were removed (65% within 24 h) due to inhibition of elongation and choroidal thickening. The guinea pig provides a fast mammalian model of FD myopia and corneal curvature regulation.

We undertook a detailed analysis of the wavefront aberrations of the eyes of 20 young progressing myopes (mean age=22 years; mean spherical equivalent=-3.84 D, range -1.00 to -7.5 D) and twenty young age matched emmetropes (mean age=23 years; mean spherical equivalent=-0.00 D, range +0.25 to -0.25 D). A wavefront sensor was used to measure the ocular wavefront and a videokeratoscope was used to measure corneal topography. The corneal wavefront was subsequently calculated and the difference between the corneal and ocular wavefront was derived to give the internal wavefront component of the eye. Ocular and corneal wavefronts were measured before and after a 2-h reading task. At the baseline measurements, the myopes showed greater levels of some high order ocular wavefronts than the emmetropes. These differences between the groups became larger following 2 h of reading. Ocular higher order wavefront RMS was (baseline RMS: myopes=0.21 microm, emmetropes=0.16 microm, difference p=0.05 and after 2 h reading was RMS: myopes=0.27 microm, emmetropes=0.17 microm, difference p=0.02). The differences between the groups are primarily due to changes in the corneal wavefront associated with a narrower lid aperture during reading for the myopes. These differences are enhanced by longer periods spent reading, larger pupils and consequently low light levels. We suggest lid induced corneal changes caused by reading in downgaze provides a theoretical framework that could explain the known features of myopia development. The inherited characteristics of facial and lid anatomy would provide a mechanism for a genetic component in the genesis of myopia.

Accommodative lags, induced by a target at 33 cm (distance-induced condition) and by a -3.0 D lens (lens-induced condition), and wavefront aberrations were measured in 27 young myopic eyes. The accommodative lags and Strehl ratios derived from the wavefront aberrations in myopes were compared with those from 57 emmetropes. Accommodation was measured using a Canon R-1 autorefractor, while aberrations were measured using a psychophysical ray-tracing technique. In accord with previous results, larger accommodative lags were found for the myopes than the emmetropes in both the lens-induced and distance-induced conditions. The mean Strehl ratio was smaller in the myopes (0.079) than the emmetropes (0.091); this difference approached significance (p = 0.055). In addition, for myopes the accommodative lag was significantly correlated with the Strehl ratio in the lens-induced condition (r = -0.45, p < 0.02) and approached significance in the distance-induced condition (r = -0.35, p = 0.07). No significant correlations were found for emmetropes. Possible reasons to account for these results are discussed.

Purpose: A major drawback of the mouse model of myopia is that the ocular dimensions cannot be measured in vivo, and that histological techniques post-mortem suffer from limited resolution. We have tested the potential of a newly developed technique, optical low coherence interferometry (OLCI), adapted for short measurement distances by Meditec, Carl Zeiss, Jena, Germany (the "ACMaster"). Using this technique, ocular biometry was performed in mice with normal vision and after deprivation of form vision., Methods: Axial eye length, corneal thickness and anterior chamber depth were measured in 23 mice, aged 25-53 days, and standard deviations from repeated measurements in the same eyes, as well as intra-individual and inter-individual variability were determined in different age groups. The data were compared to those from a preceding study in which biometrical data were obtained from frozen sections [Vision Res. 44 (2004) 1857]. Refractions were measured by automated infrared photorefraction. Mice had either normal visual exposure or were monocularly deprived of form vision for 14 days., Results: Using OLCI, axial length could be determined with an average standard deviation of 8.0 +/- 2.9 microm, corneal thickness with 3.5 +/- 2.1 microm, and anterior chamber depth with 10.6 +/- 12.3 microm. Neither axial length, nor corneal thickness, nor anterior chamber depth were significantly different in left and right eyes of individual mice that had normal visual experience (mean absolute difference between axial lengths: 17 +/- 18 microm, between corneal thickness 5.1 +/- 4.8 microm, and between anterior chamber depths 16.7 +/- 14.8 microm). Compared to the variability that was previously found in frozen sections, the variability of axial length measurements with OLCI was 2.7 times less. After two weeks of form deprivation, OLCI revealed a significant axial elongation in the occluded eyes, compared to the contralateral fellow eyes (+38 +/- 36 microm or 1.16%, p = 0.045, n = 7, paired t-test). In this sample, no accompanying myopic shift was observed in the occluded eyes but this observation is not unexpected given the inherently variable responses of mouse eye growth to visual deprivation., Conclusion: OLCI had sufficient resolution in living mice to detect axial length changes in vivo that were equivalent to a dioptric change of 2 D. Using this technique, it was confirmed that mouse eyes respond to form deprivation by axial elongation, similar to the eyes of other animal models. The lack of a myopic shift in this sample, despite the axial elongation, demonstrates that biometric data are particularly important when the mouse eye is used as a model to study myopia.

If the effective focal length of a growing eye is modified by spectacle lenses, the eye compensates by altering its growth, thereby keeping images in focus, a process we presume is similar to normal emmetropization. Using chicks, we have investigated how much visual exposure the eye needs to exhibit the two principal components of ocular compensation: altered rate of elongation (a scleral mechanism) and altered choroidal thickness. We have found that surprisingly small amounts of vision through spectacle lenses can elicit robust scleral and choroidal compensation if other visual feedback is limited by keeping the animals in the dark when not wearing lenses. Furthermore, we have found that the amount of vision necessary to induce these responses can be summarized as three rules: First, several brief daily episodes are more effective than a single or a few longer daily episodes, even if the total amount of vision is the same. Second, extremely brief episodes, even if very frequent, are relatively ineffective. Third, when plus and minus lenses are worn successively on the same eye, the plus lens has the dominant effect, even if the minus lens is worn five times longer than the plus lens. In addition, we have shown that the elongation rate and choroidal thickness responses are dissociable, such that brief, infrequent lens-viewing produces only an elongation response in the case of plus lens-wear and only a choroid response in the case of minus lens-wear. We thus show that the emmetropization system does not integrate defocus in a simple, linear fashion. These non-linearities, if present in children, might explain why, although education and reading show an epidemiological correlation with myopia, the total time spent reading and doing other nearwork by individual children generally does not predict the degree of myopia. It may therefore be necessary to quantify more complex temporal patterns of nearwork over the day in order to measure the impact of nearwork on eye growth.

The effect of myopic defocus on myopia progression was assessed in a two-year prospective study on 94 myopes aged 9-14 years, randomly allocated to an undercorrected group or a fully corrected control group. The 47 experimental subjects were blurred by approximately +0.75 D (blurring VA to 6/12), while the controls were fully corrected. Undercorrection produced more rapid myopia progression and axial elongation (ANOVA, F(1,374)=14.32, p<0.01). Contrary to animal studies, myopic defocus speeds up myopia development in already myopic humans. Myopia could be caused by a failure to detect the direction of defocus rather than by a mechanism exhibiting a zero-point error.

Higher order optical aberrations were measured in 273 cyclopleged Singaporean school children using a Bausch and Lomb Zywave aberrometer, with 268 of these subjects also undergoing corneal topography measurements (Tomey TMS 2 system). Subjects with low myopia (> -3.00 to -0.50 D) showed slightly, but significantly, less positive levels of spherical aberration than other refractive error groups. Chinese subjects also showed significantly higher amounts of aberrations than Malay subjects, particularly for vertical coma, but also for horizontal coma and spherical aberration. Anterior corneal spherical aberration (calculated from topography) was significantly correlated with whole eye spherical aberration, but did not vary significantly with refractive error or racial background. Residual spherical aberration (i.e. of posterior cornea and crystalline lens) did vary significantly with refractive error and race. Our results do not provide any evidence for aberration-driven form-deprivation as a major mechanism of myopia development.

This study aimed to investigate the effect of reading and near work on myopic development in emmetropic boys in school age. It involved totally 114 children in two groups. Right eyes of 67 randomly selected students (mean age=12.93) with mean 6 h of reading and near work (Group 1) were compared with the right eyes of 47 apprentices (mean age=12.96) working as skilled laborers (Group 2). Cycloplegic refraction, keratometric readings and biometric measurements including anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD) and axial length (AL) were performed for 3 years at 18 month intervals. Two analyses were conducted: (1) for subjects in both groups with baseline refractive error from +0.50 to -0.50 D; (2) for all subjects in both groups with baseline refractive error from +1.00 to -1.00 D. For subjects with baseline refractive error of +/-0.50 D, myopic shift was present in 20 of 41 (48.8%) in group 1 and in seven of 37 (18.9%) in group 2 at the end of the study. The magnitude of the myopic shift was 0.56 and 0.07 D in group 1 and 2, respectively. For subjects with a baseline refractive error of +/-1.00 D, myopic progression was present in 40 of 67 (59.7%) in group 1 and in 10 of 47 (21.3%) in group 2 at the last readings. In this larger refractive range, the magnitude of the myopic shift was 0.61 and 0.12 D in group 1 and 2, respectively. The mean ACD, VCD and AL were significantly higher in the last readings after 36 months than in the first readings (for each, P=0.0001) in group 1. There was no statistically significant difference between two measurements of these parameters in group 2. The final keratometric dioptric readings were lower than the first values (for each, P=0.0001) in both groups at the end of the study. This prospective and controlled study suggested that reading and near work, important environmental factors, might cause refractive myopic shifts in emmetropic students. The myopic shift was primarily related to significant increases in ACD, VCD and AL in this young age group.

Several studies have shown that growth of the primate eye responds in a compensatory direction to both positive and negative spectacle lenses--eyes grow more slowly and become hyperopic in response to positive lenses, and eyes grow more rapidly and become myopic in response to negative lenses. On the other hand, extended wear soft contact lenses, whether positively or negatively powered, induce hyperopia (Hung & Smith, 1996. Extended-wear, soft, contact lenses produce hyperopia in young monkeys. Optometry & Vision Science 73, 579-584.). We investigated whether responses in a compensatory direction occurred to soft contact lenses worn on a daily wear basis (8 h per day on an 8:16 h light:dark cycle). Ten infant marmosets (8-13 weeks of age) wore a soft contact lens, in one eye only, for 5-9 weeks. Lens powers used were zero (n = 2), +2 D (n = 1), +2 D followed after 5 weeks of lens wear by +4 D (n = 1) for 4 weeks, +4 D (n = 2), -2 D followed after 5 weeks of lens wear by -4 D (n = 2) for 4 weeks, -4 D (n = 2). At the end of the lens-wear period the positive lens-wearing eyes were more hyperopic relative to the fellow untreated eyes [mean +2.39 +/- 0.24 D (SE)] and the negative lens-wearing eyes were more myopic than the fellow untreated eyes [mean -2.48 +/- 0.91 D (SE)]. Fellow eyes were unaffected by lens wear [mean final refraction +0.45 +/- 0.09 D (SE)]. Plano lenses did not affect eye growth in either marmoset fitted with plano contact lenses.

To shed light on the potential role of the phenomenon of form-deprivation myopia in normal refractive development, we investigated the degree of image degradation required to produce axial myopia in rhesus monkeys. Starting at about 3 weeks of age, diffuser spectacle lenses were employed to degrade the retinal image in one eye of 13 infant monkeys. The diffusers were worn continuously for periods ranging between 11 and 19 weeks. The effects of three different strengths of optical diffusers, which produced reductions in image contrast that ranged from about 0.5 to nearly 3 log units, were assessed by retinoscopy and A-scan ultrasonography. Control data were obtained from ten normal infants and three infants reared with clear, zero-powered lenses over both eyes. Eleven of the 13 treated infants developed form-deprivation myopia. Qualitatively similar results were obtained for the three diffuser groups, however, the degree of axial myopia varied directly with the degree of image degradation. Thus, form-deprivation myopia in monkeys is a graded phenomenon and can be triggered by a modest degree of chronic image degradation.

While it is now established that astigmatism is more prevalent in infants and young children than in the adult population, little is known about the functional significance of this astigmatism, especially its role, if any, in emmetropization and the development of myopia. Manifest refractions (mean of 16 per subject) were obtained from 245 subjects starting in the first year, with 6-23 years of regular follow-up. Results showed that infantile astigmatism is associated with increased astigmatism and myopia during the school years. Two possible mechanisms underlying this association are discussed: (1) infantile astigmatism disrupts focusing mechanisms; and (2) ocular growth induces astigmatism and myopia.

Experiments in animal models have shown that the retinal analyzes the image to identify the position of the plane of focus and fine-tunes the growth of the underlying sclera. It is fundamental to the understanding of the development of refractive errors to know which image features are processed. Since the position of the image plane fluctuates continuously with accommodative status and viewing distance, a meaningful control of refractive development can only occur by an averaging procedure with a long time constant. As a candidate for a retinal signal for enhanced eye growth and myopia we propose the level of contrast adaptation which varies with the average amount of defocus. Using a behavioural paradigm, we have found in chickens (1) that contrast adaptation (CA, here referred to as an increase in contrast sensitivity) occurs at low spatial frequencies (0.2 cyc/deg) already after 1.5 h of wearing frosted goggles which cause deprivation myopia, (2) that CA also occurs with negative lenses (-7.4D) and positive lenses (+6.9D) after 1.5 h, at least if accommodation is paralyzed and, (3) that CA occurs at a retinal level or has, at least, a retinal component. Furthermore, we have studied the effects of atropine and reserpine, which both suppress myopia development, on CA. Quisqualate, which causes retinal degeneration but leaves emmetropization functional, was also tested. We found that both atropine and reserpine increase contrast sensitivity to a level where no further CA could be induced by frosted goggles. Quisqualate increased only the variability of refractive development and of contrast sensitivity. Taken together, CA occurring during extended periods of defocus is a possible candidate for a retinal error signal for myopia development. However, the situation is complicated by the fact that there must be a second image processing mode generating a powerful inhibitory growth signal if the image is in front of the retina, even with poor images (Diether, S., & Schaeffel, F. (1999).

It is unknown which retinal image features are analyzed to control axial eye growth and refractive development. On the other hand, identification of these features is fundamental for the understanding of visually acquired refractive errors. Cyclopleged chicks were individually kept in the center of a drum with only one viewing distance possible. Defocusing spectacle lenses were used to stimulate the retina with defined defocus of similar magnitude but different sign. If spatial frequency content and contrast were the only cues analyzed by the retina, all chicks should have become myopic. However, compensatory eye growth was still always in the right direction. The most likely cues for emmetropization, spatial frequency content and image contrast, do therefore not correlate with the elongation of the eye. Rather, the sign of defocus was extracted even from very poor images.

To examine the susceptible period for deprivation-induced myopia, six groups of tree shrew pups (Tupaia glis belangeri) were monocularly deprived for 12 days with an opaque occluder starting 7, 15, 21, 33, 48, or 63 days after natural eyelid opening. Compared to the untreated fellow control eye, significant myopia and vitreous chamber elongation were produced by the deprivation in all six groups. The effect was greater in the middle three groups in comparison with the youngest and the two oldest groups and the amount of induced myopia and axial elongation was not proportional to the normal rate of axial growth. The peak period of susceptibility was between approximately 15 and 45 days after eye opening during the juvenile, slow-elongation phase of ocular development when the eye is within 7% of its adult axial length. Significant myopia and axial elongation were also induced in adult animals by 70 days of monocular deprivation. To examine recovery from deprivation-induced myopia, the occluder was removed at the end of the 12 day deprivation period. After an additional 48 days of binocular visual experience, no significant myopia was present in the previously deprived eyes in any experimental group. During the recovery period, the elongation rate of the previously deprived eyes was reduced in comparison with the control eyes while normal corneal flattening and lens development continued, thus reducing the myopia. No difference in corneal curvature, relative to the untreated control eyes, was found after deprivation or after the recovery period. Data are presented which suggests that changes in the thickness of the choroid may occur in this mammal during deprivation and recovery that are in the same direction, but of smaller magnitude, than those reported in the chicken. The results of this study provide evidence that visually guided emmetropization occurs in this mammalian species during a period of ocular development analogous to the juvenile period in humans.

The purpose of this work was to investigate quantitatively the interactions between accommodation, vergence and a mechanism of emmetropization driven by optical blur within the retinal image with a view to developing a model that provides an explanation of both normal emmetropization and near-work associated myopia. The simulations of the change in the refractive state of the eye over time that derive from this model indicate that optical regulation of eye growth can result in emmetropization, i.e. a progressive reduction in refractive errors over time leading towards emmetropia. This occurs when viewing conditions involve a preponderance of distance work. With increasing near work, the model predicts that the refraction of the eyes will converge towards myopia. In keeping with the previously reported associations of myopia with esophoria, poor accommodation function and high AC/A ratios, these conditions increase the amount of myopia produced under intensive near viewing conditions but do not lead to myopia during mainly distance viewing. This model provides quantitative validation of the hypothesis that the epidemiological association between myopia and increased nearwork may be caused by a disturbance of normal emmetropization by steady state errors of accommodation. The same model can explain normal emmetropization, increasing myopia with increasing nearwork demands and the currently recognised oculomotor associations that have been reported to precede the development of myopia.

Depriving the eyes of neonatal animals of form vision induces axial eye elongation and ipsilateral myopia. We studied one-year-old chickens, an age at which full body growth has been attained, to learn if form deprivation myopia can develop at a later stage. We found that ocular reactivity to visual form deprivation continues in one-year-old chickens; but both the growth stimulation and the myopic shift in refraction are attenuated compared with newly hatched birds. Neurochemical changes in visually deprived eyes of one-year-old chickens parallel those in newly hatched chicks: ipsilateral decreases in retinal dopamine and in the activity of ciliary ganglion and uveal choline acetyltransferase. These findings strengthen the relevance of the form deprivation model to more common human myopia and suggest a common eye growth control mechanism at both ages.

This study examined the contrast and spatial-frequency requirements for emmetropization in chicks. Chicks were form deprived from hatching either constantly or had this treatment interrupted with 20 min of "visual stimulation" each day. Visual stimulation comprised exposure to either a normal cage environment (i.e., normal vision) or environments that were restricted in either their spatial contrast or spatial-frequency composition. Constant form deprivation resulted in high myopia (e.g. -11.8 D after 5 days), with refractive changes being much smaller in chicks allowed 20 min of normal vision each day (e.g. -3.4D). The restricted contrast environments (contrast range: 9-78%) were generally only slightly less effective than the normal cage environment in preventing form-deprivation myopia. However, in the case of restricted spatial-frequency environments, both the intermediate (0.86 cycles deg-1) and mixed spatial-frequency environments significantly reduced the form deprivation response, while both the high (4.3 cycles deg-1) and low spatial-frequency (0.086 cycles deg-1) stimuli, as well as the composites of these, were less effective in preventing form-deprivation myopia. This spatial-frequency dependence did not vary when, instead of white light, monochromatic illumination was used to eliminate chromatic aberration, although all groups showed more myopia under this condition. It is assumed that the observed inhibitory effects on form-deprivation myopia reflect the adequacy of the visual information presented during the period of visual stimulation for emmetropization in chicks. In this context, the data imply a mid-spatial-frequency tuning in the current study and a low contrast threshold which was not reached for this emmetropization process. Finally, the data hint that chromatic aberration may have some role as a cue to defocus in emmetropization.

The aim of this study was to determine whether an integrator of neural activity influences the amount of myopia and axial elongation resulting from deprivation of form vision. The effects on ocular parameters of a continuous period of 30 min per day of normal vision was compared to two exposures of 15 min duration each, or three exposures of 10 min each. For the remaining time, chicks had monocular translucent occlusion in a 12 hr light/12 hr dark diurnal cycle, for either 2 or 3 weeks. Fellow eyes and the eyes of bilaterally unoccluded chicks were used as controls. We found that several short periods of normal visual stimulation per day were more effective in preventing the development of form deprivation myopia and axial elongation than was one single period of the same total duration, after both 2 and 3 weeks of treatment. This study suggests that the level of neural activity in the retina may have a cumulative effect in influencing ocular growth.

We have tested whether defocus imposed on local retinal areas can produce local changes in eye growth, even if accommodation is available to clear part of the imposed defocus. Hemi-field lenses were attached to little leather hoods that were worn by young chickens from day 11-15 post-hatching. The lens segments defocused either the nasal or the temporal visual field, or covered the full field. We found that negative lenses (-7.5 D) were incompletely compensated in all three cases but caused significant myopia in the defocused parts of the visual field (differences to fellow eyes with normal vision: nasal visual field -3.13 +/- 1.56 D, P < 0.001; temporal visual field -4.02 +/- 1.38 D, P < 0.001; full field -3.82 +/- 2.48 D, P = 0.01). Myopia was not enhanced if the lenses covered the entire visual field. Positive lenses (+6.9 D) caused larger changes in refraction than negative lenses and, again, there was no significant difference in the amount of induced hyperopia in the nasal or temporal retina, or in the amount of hyperopia with full-field lenses (difference to fellow eyes with normal vision: nasal visual field +6.2 +/- 2.69 D, P < 0.001; temporal visual field +5.95 +/- 2.22 D, full field +7.22 +/- 2.44 D, P < 0.001). To compare the shapes of the excised eyes after lens treatment, we wrote a fully automated image processing program that traced their outlines in digitized video images. We found that the shapes of the eyes treated with positive lenses did scarcely differ from their fellow eyes with normal vision, indicating that hyperopia over this 4 day period was caused mostly by choroidal thickening. Full field negative lenses produced significant axial eye elongation; the effects of locally imposed defocus on eye shape were less conspicuous and were significant only in some areas. That local compensation of defocus was possible for both negative and positive lenses, suggests that the retina can recognize the sign of defocus without accommodation cues. Even more striking is that the presence of accommodation is apparently ignored since the drift in the plane of focus during accommodation does not disturb the compensation process. We re-analyze previous experimental results that argue for different mechanisms for deprivation myopia and lens-induced refractive errors. We propose that lens-induced refractive errors are compensated by similar retinal mechanisms as the ones proposed by Bartmann and Schaeffel [(1994). Vision Research, 34, pp. 873-876] to explain deprivation myopia. The proposed mechanisms can integrate with long time constants over the spatial frequency content in the retinal image while the viewing distances change, and control both choroidal thickening and scleral growth. However, it turns out that the compensation of imposed myopia cannot be explained if only one constant viewing is available. Apparently, there is more than a retinal blur detector to guide refractive development.

Twenty hatchling chickens were injected intravitreally every 4 days from day 2 to day 16 with dimethyl sulphoxide (DS) in one eye and DS or formoguanamine dissolved in DS (FG.DS) with or without occlusion in the other (FG.DS.MD, DS.MD, FG.DS). At day 16, the FG.DS.MD eyes failed to show the high refractive myopia and showed less axial elongation than that developed by the DS.MD eyes. Electroretinograms indicated that at the dosage used, FG.DS does not eliminate phototransduction. Light microscopy showed choroidal and retinal thinning in DS.MD and FG.DS.MD eyes but less than in FG.DS eyes, suggesting that change in choroidal thickness is unlikely to be the primary cause of form deprivation myopia.

Several laboratories studying visual deprivation myopia in the domestic chick report varying degrees of axial elongation and myopia induced by similar visual deprivation techniques. In this study we tested the hypothesis that in different strains of chick the eyes respond differently to visual deprivation. We compared under identical conditions two strains of White Leghorn chick commonly used in ocular development research--the Cornell-K strain (K) and Washington H & N Strain (H/N). The normal development of the eye was found to vary significantly between these strains of White Leghorn chicks. The K strain normally develops flatter corneas, thicker lenses, and larger eyes than the H/N strain. The response to visual deprivation also varies significantly between strains. For example, we find that 2 weeks of visual deprivation in the K strain results in less elongation of the vitreous chamber and flattening of the cornea yielding lower levels of induced myopia compared to the H/N strain. Our results show that while visual experience clearly affects normal ocular development in both strains of chick, the nature of the effect depends upon not only the type and duration of the experience but the genetics of the subject population as well.

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.

(1) We studied the influence of photoperiod and unilateral lid suture on post-natal ocular growth in two types of White Leghorn chicks previously reported to respond differently to visual deprivation, Truslow and Cornell K chicks. We analyzed the chicks after 2 weeks of rearing, a time period commonly used in neuropharmacological studies of eye growth but much shorter than in most prior studies of photoperiod effects on the chick eye. (2) Altering the photoperiod length significantly influenced the refraction and growth of both open and sutured eyes even at this early time, with differences between the two types of chicks. (3) The most prominent effect on the open eyes was the development of hyperopia with rearing under constant light, a response especially prominent in the Cornell K chicks. In the open eyes under this condition, the anterior chamber shallowed and the vitreous chamber elongated in the axial dimension only, reciprocal changes that resulted in no net alteration of axial length at 2 weeks. A high variability in refraction of open eyes reared with constant illumination suggests the need for a dark period in the regulation of eye growth. (4) Compared to contralateral open eyes, the lid-sutured eyes of both types of chicks developed longer total axial lengths and enlarged vitreous chambers in both axial and equatorial dimensions under each photoperiod. The effects on anterior chamber depth and refraction were complex and differed between the two types of chicks. (5) The responses in open eyes support the notion that growth of the vitrious chamber of the chick eye is differentially regulated in the axial and equatorial dimensions, previously indicated by pharmacological studies. The responses in both open and sutured eyes indicate different control mechanisms for anterior chamber and vitreous cavity growth.

Investigations into the plasticity of eye growth and refractive error development have significantly expanded our knowledge of animal models of myopia in the last 15 yr. The applicability of this information is as yet undetermined, but hopefully this information will be useful in learning more about human myopia. This paper presents a critical review of the animal myopia literature as those data relate to the human condition. Differences between the chicken, tree shrew, and primate animal models of myopia are outlined, and the various experimental paradigms used to investigate refractive error development and ocular growth in the chicken are compared. Specific arguments against the application of animal models of myopia to the etiology of human juvenile onset myopia include the following: (1) there is no deprivation of form vision in the environment of the school-aged child as severe as that required to induce myopia in animals; (2) the sensitive period for deprivation myopia in animals appears to be too early to account for human juvenile onset myopia; and (3) studies in the chicken using spectacle lenses to create dioptric blur involve a choroidal thickness modulation that has no human analog. Ultimately, the results of investigations into the cellular and biochemical modulation of eye growth in animals may be the most relevant to human myopia.

The aim of this study was to determine the minimum daily period of exposure to normal visual stimulation required to prevent occlusion induced myopia in chicks. Chicks were treated with monocular translucent occlusion in a 12 hr light/12 hr dark cycle. Occluders were removed for 0 (constant occlusion), 15, 20, 30, 40, 60, 75, 90, 120, 150, 240 or 720 (no occlusion) minutes each day for either 2 or 3 weeks. Fellow eyes and the eyes of normal chicks (bilaterally unoccluded) were used as controls. Occlusion-induced myopia and axial elongation were found to decrease significantly (P < 0.01) with increasing daily exposure to normal visual stimulation. Application of a time series equation to the data estimates that 30 and 130 min of normal visual exposure per day reduces myopia by 50 and 95% respectively. This study demonstrated that the regulation of ocular growth is affected strongly by short periods of normal visual stimulation in the presence of long periods of abnormal stimulation.

To investigate the influence of brain mediated functions on control of ocular growth, young chicks were treated monocularly with intravitreally injected tetrodotoxin (TTX) to block retinal ganglion cell action potentials. TTX injections (0.7 micrograms in 7 microliters) were given on day 6 after hatching in both binocularly open and monocularly deprived chicks. Injections were repeated every 48 hr for a period of 8 days (TTX-open; TTX-MD). Control groups of animals received intravitreally injected phosphate buffered saline (PBS-open; PBS-MD) to one eye on the same schedule. There was a minimum of eight animals in each group. Recovery from form-deprivation myopia during blockade of retinal cell action potentials was also investigated. Results demonstrate that blockade of retinal cell action potentials by TTX produces reduced growth of the anterior segment of the eye and crystalline lens in both binocularly open and MD chicks. Blockade of retinal cell action potentials does not prevent form-deprivation induced vitreous chamber elongation and myopia. Form deprived myopic eyes were found to emmetropize despite blockade of retinal ganglion cell action potentials giving further evidence for local ocular control of emmetropization. Blockade of retinal ganglion cell action potentials did not prevent changes in choroidal thickness in eyes developing axial myopia or eyes recovering from induced myopia.

An ultrastructural examination of the outer retina and choroid of hatchling chicks reared for periods of 1, 2 or 4 weeks with opaque occluders (MD) covering one eye, was instigated to elucidate the mechanism of deprivation myopia. Refractive myopia (approximately 20 D), retinal and choroidal thinning were induced in all deprived eyes. Electron microscopy showed significant changes in the MD eyes compared to normals. Cone inner segments were markedly thicker and outer segment lamellae more damaged. The rod outer segments were elongated and thicker than normal, such that their distal tips either directly apposed the basal lamina of the retinal pigment epithelium, or indented the cell nuclei. We hypothesize that this "rod-push" mechanism leads to thinning of the choroid in deprived eyes, and may directly contribute to axial myopia.

We have carried out a number of different studies in chicks to examine the relationship between choroidal blood flow and myopic eye growth, and between accommodation and myopic eye growth. Our studies on choroidal blood flow show that myopic eye growth produced by form vision degradation leads to dramatic reductions in choroidal blood flow. These reductions appear directly attributable to the eye enlargement and the reduction in choroidal blood flow does not appear to be permissive for eye growth, since experimentally reduced choroidal blood flow hinders eye growth. Choroidal blood flow that is slightly above normal, however, may slightly enhance eye growth. Our studies on accommodation do not reveal any major necessary role of accommodation in regulating normal growth or in form vision degradation induced myopic eye growth. We found preliminary evidence, however, that chronically stimulating accommodation over a 2 week period, thereby producing excessive time in accommodation, may be sufficient for yielding a small but significant degree of myopic refractive error. Our studies suggest that neither fluctuations in choroidal blood flow nor an intact accommodative apparatus are essential for normal eye growth or myopic eye growth produced by form deprivation. Further studies are needed to confirm that excessive time in accommodation might be sufficient for producing myopia. Finally, our finding that choroidal blood flow is substantially reduced in myopic eyes may have implications for the etiology of the retinal problems suffered by humans with moderate to severe myopia.

We examined the spatial organization of the putative dopaminergic amacrine cells in the chicken retina and how this organization was affected by myopic eye enlargement. Myopia was produced by monocular lid suture for 4-7 months from hatching. Dopaminergic amacrine cells (TH-IR) were labelled by tyrosine hydroxylase immunohistochemistry. The somata of the TH-IR cells were usually located at the inner border of the inner nuclear layer; they gave rise to a dense plexus in stratum 1 (S1) of the inner plexiform layer, to a sparse plexus in stratum 3 (S3), and to short spiny dendrites at the border of strata 4 and 5 (S4/S5). The long thin processes in S1 and S3 could seldom be traced to their cell of origin, whereas the S4/S5 dendrites formed discrete fields that tiled the retina with little overlap. Lid suture resulted in retinal expansion of between 25-70%, but the total number of TH-IR amacrine cells was unaltered. Per retina, there were about 4700 TH-IR amacrine cells which showed a 3:1 density gradient from central to peripheral retina. The size of the S4/S5 dendritic fields increased proportionately in the expanded retinae, thus maintaining their coverage across the retina. The increase was achieved through scaled growth of the S4/S5 dendrites, involving both terminal and non-terminal dendrites. These findings suggest that the expansion of retinal neurons during myopia occurred through normal, albeit excessive, growth mechanisms.

Expansion of the retinal pigment epithelium was studied in neonatal chicks after one or two weeks of unilateral form vision deprivation to investigate altered ocular growth mechanisms in this experimental model of myopia. The area of individual retinal pigment epithelial (RPE) cells, measured in tangential sections, was greater in myopic eyes than in contralateral control eyes at both times. The mean RPE cell area in myopic eyes increased to the same extent as the area of the retinal pigment epithelium as a whole. In control eyes between one and two weeks, RPE cell expansion occurred predominantly in the periphery; in myopic eyes, it occurred more generally across the epithelium but was less pronounced in the temporal region. Given the absence of detectable mitotic figures in control and myopic eyes, expansion of the epithelial layer is attributable to passive stretch or growth of existing cells. Whether scleral growth or stretch occurs selectively beneath the areas of more pronounced RPE cell expansion is unknown.

The normal postnatal ocular development of the common marmoset (Callithrix jacchus) and the effects of visual deprivation on eye growth and refractive state are described. The marmoset normally undergoes a developmental process of emmetropization from high hyperopia at birth. This emmetropization is easily disrupted by visual deprivation produced by lid-suture. Myopia and axial elongation of the vitreous chamber are induced by visual deprivations of 12, 5, and 3 weeks duration. The development of axial myopia after 3 weeks of visual deprivation differs from longer duration deprivations in that the experimental eyes are initially shorter than normal and hyperopic at the end of the visual deprivation period, but subsequently become longer than normal and myopic. Visual deprivation myopia in the marmoset persists even after the deprivation is discontinued and a visual signal is restored. In all experimental groups, the development of the eye in response to the cessation of visual deprivation shows no slowing of vitreous chamber enlargement; the axial enlargement relative to the control eye is either maintained or increases and produces significantly greater myopia. These results suggest that the visual control of postnatal eye growth in the marmoset may be unidirectional in its response to visual experience and able only to increase the growth rate of the vitreous chamber, possibly after an initial delay.

Tree shrews were monocularly deprived (MD) from the day of eye opening for periods of 15, 30, 45, 60 and 75 days. The initial structural change after 15 days of MD was a flattening of the corneal curvature in the deprived eye causing a hyperopic increase in refraction, relative to the fellow control eye. A relative myopia was first observed after 30 days of deprivation and increased as the length of MD increased. Animals monocularly deprived for 75 days consistently showed high degrees of myopia (greater -10 D). An increase in vitreous chamber depth was found after 30 days of deprivation and continued to increase, relative to the control eye, throughout the developmental period under investigation. There was a strong correlation (r = 0.84) between increase in vitreous chamber depth and the amount of experimentally-induced myopia. Anterior chamber depth was shallower in the deprived eyes of all animals. The crystalline lens was also consistently thinner in the deprived eye. Based on optical modeling, the observed myopia was consistent with the changes in ocular component dimensions. The susceptible period for experimental myopia begins about 15 days after eye opening.