Meridional Anisotropy of Foveal and Peripheral Resolution Acuity in Adults With Emmetropia, Myopia, and Astigmatism

Purpose: To quantify astigmatism-related meridional anisotropy in visual resolution at central, nasal, and inferior visual fields. Methods: Three groups of young adults (range, 18–30 years) with corrected-to-normal visual acuity (logMAR 0) were recruited: (1) myopic astigmats (MA): spherical-equivalent error (SE) < −0.75D, with-the-rule astigmatism ≥ 2.00D, n = 19; (2) simple myopes (SM): SE < −0.75D, astigmatism ≤ 0.50D, n = 20; and (3) emmetropes (EM): SE ± 0.50D, astigmatism ≤ 0.50D, n = 14. Resolution acuity was measured for the horizontal and vertical gratings at central and peripheral visual fields (eccentricity: 15°) using a 3-down 1-up staircase paradigm. On- and off-axis refractive errors were corrected by ophthalmic lenses. Results: The MA group exhibited meridional anisotropy preferring vertical gratings. At the central field, the MA group had better resolution acuity for vertical than horizontal gratings, and their resolution acuity for horizontal gratings was significantly worse than the SM and EM groups. At peripheral visual fields, both the SM and EM groups showed better resolution acuity for the radial (i.e., nasal field: horizontal gratings; inferior field: vertical gratings) than tangential orientation. However, the MA group tended to have better resolution acuity for the tangential orientation (i.e., vertical gratings), and their resolution acuity for horizontal gratings was significantly lower than the SM and EM groups at the nasal field. No significant differences were found in the inferior field among the three groups. Conclusions: This study provided evidence of astigmatism-related meridional anisotropy at the fovea and nasal visual fields, underscoring the significant impact of astigmatism on orientation-dependent visual functions

A Genome-Wide Association Study for Susceptibility to Visual Experience-Induced Myopia

PURPOSE. The rapid rise in prevalence over recent decades and high heritability of myopia suggest a role for gene-environment (G X E) interactions in myopia susceptibility. Few such G X E interactions have been discovered to date. We aimed to test the hypothesis that genetic analysis of susceptibility to visual experience-induced myopia in an animal model would identify novel G X E interaction loci. METHODS. Chicks aged 7 days (n = 987) were monocularly deprived of form vision for 4 days. A genome-wide association study (GWAS) was carried out in the 20% of chicks most susceptible and least susceptible to form deprivation (n = 380). There were 304,963 genetic markers tested for association with the degree of induced axial elongation in treated versus control eyes (A-scan ultrasonography). A GWAS candidate region was examined in the following three human cohorts: CREAM consortium (n = 44,192), UK Biobank (n = 95,505), and Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4989). RESULTS. A locus encompassing the genes PIK3CG and PRKAR2B was genome-wide significantly associated with myopia susceptibility in chicks (lead variant rs317386235, P = 9.54e-08). In CREAM and UK Biobank GWAS datasets, PIK3CG and PRKAR2B were enriched for strongly-associated markers (meta-analysis lead variant rs117909394, P = 1.7e-07). In ALSPAC participants, rs117909394 had an age-dependent association with refractive error (-0.22 diopters [D] change over 8 years, P = 5.2e-04) and nearby variant rs17153745 showed evidence of a G X E interaction with time spent reading (effect size -0.23 D, P = 0.022). CONCLUSIONS. This work identified the PIK3CG-PRKAR2B locus as a mediator of susceptibility to visually induced myopia in chicks and suggests a role for this locus in conferring susceptibility to myopia in human cohorts.</p

High myopia induced by form deprivation is associated with altered corneal biomechanical properties in chicks

The cornea is a soft, transparent, composite organic tissue, which forms the anterior outer coat of the eyeball. Although high myopia is increasing in prevalence worldwide and is known to alter the structure and biomechanical properties of the sclera, remarkably little is known about its impact on the biomechanics of the cornea. We developed and validated a novel optical-coherence-tomography-indentation probe–to measure corneal biomechanical properties in situ, in chicks having experimentally-induced high myopia, while maintaining intraocular pressure at levels covering the physiological range. We found that the cornea of highly myopic chicks was more steeply curved and softer, at all tested intraocular pressures, than that in contralateral, non-myopic eyes, or in age-matched normal, untreated eyes. These results indicate that the biomechanical properties of the cornea are altered in chicks developing experimentally-induced myopia

Differences in Time Course and Visual Requirements of Ocular Responses to Lenses and Diffusers 575

PURPOSE. Myopia can be induced in chickens by having them wear either negative lenses (lens-compensation myopia [LCM]) or diffusers (form-deprivation myopia [FDM]), whereas positive lenses cause lens-compensation hyperopia (LCH). These three conditions were compared with respect to (i) their early time course and (ii) the effect of two manipulations of the lighting. METHODS. Longitudinal changes in ocular dimensions and refractive error were measured in chicks maintained under three different conditions: (i) wearing either Ϫ15 D lenses or diffusers in a normal light/dark cycle; (ii) wearing either ϩ15 D lenses, Ϫ15 D lenses, or diffusers with brief periods of stroboscopic lights at the beginning and end of the dark period; (iii) wearing either ϩ6 D lenses, Ϫ6 D lenses, or diffusers with the nights interrupted by brief periods of white light. In addition, scleral and choroidal proteoglycan synthesis was measured in eyes that wore positive lenses, negative lenses, or diffusers for 3 hours followed by different periods of darkness. RESULTS. (i) The time course of the changes in axial length over the first 72 hours was significantly faster in LCM than in FDM. Indeed, the diffusers did not begin to significantly affect the total length of the globe for 3 days, although the vitreous chamber had deepened after 9 hours, because the choroid thinned extremely rapidly (within 1 hour) with either diffusers or negative lenses. (ii) Scleral proteoglycan synthesis was higher in eyes with negative lenses than in those with diffusers at 11 hours, but the reverse was true at 27 hours. (iii) Brief periods of stroboscopic light attenuated FDM more than LCM. (iv) In contrast, interruption of the nights by brief periods of light attenuated LCM more than FDM. (v) Neither lighting manipulation affected LCH. (vi) Choroidal proteoglycan synthesis decreased similarly with 3 hours of wearing either diffusers or negative lenses. CONCLUSIONS. Although both negative lenses and diffusers cause similar increases in the rate of ocular elongation, the responses differ in time course and in the effect of manipulations of the daily lighting. The responses to positive lenses differ from both of these. (Invest Ophthalmol Vis Sci. 2001;42:575-583) I n the past three decades, research on experimental myopia in several animal species has increased our understanding of refractive development. All the animal species tested developed myopia under conditions of visual form deprivation (e.g. ). However, whether the eye uses the same mechanism to respond to diffusers and lenses is still open to question and is an issue of considerable importance. One possibility is that the responses to diffusers and to negative and positive lenses are all explicable by a simple rule: obscuring the visual image causes growth toward myopia, whereas sharp vision causes growth toward hyperopia. 10 According to this view, diffusers would obscure vision the most and hence would cause the strongest myopia, negative lenses would obscure vision less, and positive lenses would enhance the sharpness of the images (assuming that the chicks mostly looked at nearby objects and that without positive lenses, vision of near objects would be blurred because of accommodative lag). A test of this hypothesis would be to impose novel visual conditions and see if the responses to negative lenses and diffusers are similarly affected. On the basis of evidence from biochemical studies and from the effects of cutting the ciliary nerve or the optic nerve, Schaeffel et al. There have been three explicit comparisons of FDM and LCM that revealed differences between them. First, at the retinal level, the oscillatory potentials of the electroretinogram are reduced only in the FDM eyes, even though the other components of the electroretinogram are the same in FDM and LCM. 12 Second, it is known that optic nerve section does not prevent the myopia and increased vitreous chamber depth of FDM. 13,14 Wildsoet 15 found that optic nerve section reduces the vitreous chamber elongation of eyes with LCM, but has no effect on eyes with FDM. Third, an abstract from Schmid and Wildsoet 16 asserts that continuous stroboscopic illumination attenuates FDM over a wider range of frequencies than that of LCM. In this article, we first compare LCM and FDM with respect to the early time course in ocular elongation, choroidal thinning, and proteoglycan synthesis. (In the case of proteoglycan synthesis, we examined the response to a brief &quot;pulse&quot; of lens or diffuser wear.) Next we ask whether they are similarly affected by two visual manipulations shown by Nickla 17 to affect FDM: (a) brief periods of stroboscopic light at dawn and dusk and (b) brief periods of light interrupting the night. METHODS Subjects Newly hatched White Leghorn chicks (Gallus gallus domesticus) from Truslow Farms (Chestertown, MD) were raised in temperature-controlled brooders from 1 day of age. The chicks were fed Chick Starter Chow (Purina Mills, St. Louis, MO). White fluorescent lights were on from 8 AM to 10 PM every day. Care and use of the animals conformed to the ARVO Resolution on the Use of Animals in Ophthalmic and Vision Research

Inter-ocular differences (mean±SE) in spherical equivalent (M), most myopic meridian (MMM), most hyperopic meridian (MHM), refractive (RA), corneal (CA), and internal astigmatisms (IA) for the control group and a subset of birds from the treatment groups (remark: n = 8 in each group) with both refractive and corneal measurements.

<p>Note that the astigmatic axes in the last three rows are calculated by circular statistics (mean±angular deviation) for the treated eyes only. In experiment A, the comparisons across the controls and treated groups were tested by one-way ANOVA followed by Tukey’s test. In experiment B, the comparisons between high and low magnitudes of imposed astigmatism were tested by two-sample <i>t</i>-tests. The levels of significant difference are indicated by asterisk: * p≤0.05, ** p≤0.01, *** p≤0.001 in experiment A, and ^# p≤0.05, ^## p≤0.01, ^### p≤0.001 in experiment B. Comparisons for the astigmatic axis were performed by Watson-Williams F-tests followed by pairwise comparison tests.</p><p>^a Experiment A</p><p>^b Experiment B</p><p>Inter-ocular differences (mean±SE) in spherical equivalent (M), most myopic meridian (MMM), most hyperopic meridian (MHM), refractive (RA), corneal (CA), and internal astigmatisms (IA) for the control group and a subset of birds from the treatment groups (remark: n = 8 in each group) with both refractive and corneal measurements.</p

Myopia Progression in Children is Associated with Regional Changes in Retinal Function: A Multifocal Electroretinogram Study

Introduction: To determine if retinal function is associated with myopia progression in children over a one-year period. Methods: Twenty-two children (mean = 11±1 years) were recruited in this study. Refraction and global flash multifocal electroretinogram measurements were performed at 49% and 96% contrasts at the initial visit and after 1 year. The amplitudes and implicit times of direct (DC) and induced components (IC) of the mfERG responses were pooled into five concentric rings for analysis. Pearson's correlation (r) was performed to determine if myopia progression was correlated with the changes in these mfERG's parameters. Results: The mean myopia progression was −0.45±0.34D (range = plano∼−1.38). At 49% contrast, the IC implicit times from rings 2 to 5 (r = −0.57∼−0.65, p < 0.01), and the DC implicit time at ring 3 (r = 0.55, p < 0.01), were significantly delayed with myopia progression. At 96% contrast, only the IC implicit time within ring 1 was delayed (r = −0.60, p < 0.01). In contrast, neither DC nor IC amplitudes at both contrasts were affected (r = −0.11∼0.28, all p > 0.05). Conclusions: Myopia progression in children delayed IC implicit time at 49% contrast predominantly at the paracentral retina. These results support our previous findings (Ho et al., 2011) that the effect of myopia development on retinal function is regional dependent

Effects of Optically Imposed Astigmatism on Early Eye Growth in Chicks

<div><p>Purpose</p><p>To determine the effects of optically imposed astigmatism on early eye growth in chicks.</p><p>Methods</p><p>5-day-old (P5) White Leghorn chicks were randomly assigned to either wear, monocularly, a “high magnitude” (H: +4.00DS/-8.00DC) crossed-cylindrical lens oriented at one of four axes (45, 90, 135, and 180; n = 20 in each group), or were left untreated (controls; n = 8). Two additional groups wore a “low magnitude” (L: +2.00DS/−4.00DC) cylindrical lens orientated at either axis 90 or 180 (n = 20 and n = 18, respectively). Refractions were measured at P5 and after 7 days of treatment for all chicks (P12), whereas videokeratography and ex-vivo eyeshape analysis were performed at P12 for a subset of chicks in each group (n = 8).</p><p>Results</p><p>Compared to controls, chicks in the treatment groups developed significant amounts of refractive astigmatism (controls: 0.03±0.22DC; treatment groups: 1.34±0.22DC to 5.51±0.26DC, one-way ANOVAs, p≤0.05) with axes compensatory to those imposed by the cylindrical lenses. H cylindrical lenses induced more refractive astigmatism than L lenses (H90 vs. L90: 5.51±0.26D vs. 4.10±0.16D; H180 vs. L180: 2.84±0.44D vs. 1.34±0.22D, unpaired two-sample <i>t</i>-tests, both p≤0.01); and imposing with-the-rule (H90 and L90) and against-the-rule astigmatisms (H180 and L180) resulted in, respectively, steeper and flatter corneal shape. Both corneal and internal astigmatisms were moderately to strongly correlated with refractive astigmatisms (Pearson’s r: +0.61 to +0.94, all p≤0.001). In addition, the characteristics of astigmatism were significantly correlated with multiple eyeshape parameters at the posterior segments (Pearson’s r: -0.27 to +0.45, all p≤0.05).</p><p>Conclusions</p><p>Chicks showed compensatory ocular changes in response to the astigmatic magnitudes imposed in this study. The correlations of changes in refractive, corneal, and posterior eyeshape indicate the involvement of anterior and posterior ocular segments during the development of astigmatism.</p></div

Refractive astigmatism induced by optically imposed astigmatism of four different orientations.

<p>(A) Distributions of inter-ocular differences in refractive astigmatism (treated/right eye—fellow/left eye) after one week of cylindrical lens treatment (P5-P12) for the four treatment groups (+4.00DS/-8.00DC, n = 20 in each group) with negative cylindrical axis oriented at one of the four directions (45, 90, 135, or 180), as well as the age-matched controls (n = 8). The effects of the axis of cylindrical lens are represented by different coloured symbols as shown in the legend. For example, in chicks treated with H90, the +4.00DC and -4.00DC were oriented vertically and horizontally respectively; to compensate for this astigmatic error, the eyes should develop negative cylindrical axis at 90. As shown in A, the cylindrical lenses of different axes induced compensatory astigmatism in the four treatment groups. (B) The box plots of refractive astigmatism include the values of median (line inside the box), maximum (upper whisker), minimum (lower whisker), upper (upper border of box) and lower quartiles (lower border of box) for the controls and treatment groups at P12. The levels of significant differences in the magnitudes of refractive astigmatism across the treatment groups (lines above the boxes), or between treatment and controls (lines below the boxes), are indicated by asterisk: * p≤0.05, *** p≤0.001 (Tukey’s post hoc tests).</p

Inter-ocular differences in ocular dimensions (mean±SE) related to the eye shape profile for the control and treatment groups (n = 8 in each group).

<p>AL = axial length; ED180 & ED90, horizontal and vertical equatorial diameters, respectively; ADH & ADV, difference in area between the two eyes up to 50° eccentricity along the horizontal and vertical meridians, respectively. In experiment A, the comparisons across the controls and treated groups were tested by one-way ANOVA followed by Tukey’s test. In experiment B, the comparisons between high and low magnitudes of imposed astigmatism were tested by two-sample <i>t</i>-tests. The levels of significant difference are indicated by asterisk: * p≤0.05, ** p≤0.01, *** p≤0.001 in experiment A, and ^# p≤0.05, ^## p≤0.01, ^### p≤0.001 in experiment B.</p><p>^a Experiment A</p><p>^b Experiment B</p><p>Inter-ocular differences in ocular dimensions (mean±SE) related to the eye shape profile for the control and treatment groups (n = 8 in each group).</p