Katrina L. Schmid

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.

Novel, Potent, and Selective GABAC Antagonists Inhibit Myopia Development and Facilitate Learning and Memory

This study reports pharmacological and physiological effects of cis- and trans-(3-aminocyclopentanyl)butylphosphinic acid (cis- and trans-3-ACPBPA). These compounds are conformationally restricted analogs of the orally active GABAB/C receptor antagonist (3-aminopropyl)-n-butylphosphinic acid (CGP36742 or SGS742). cis-[IC50(ρ1) = 5.06 μM and IC50(ρ2) = 11.08 μM; n = 4] and trans-3-ACPMPA [IC50(ρ1) = 72.58 μM and IC50(ρ2) = 189.7 μM; n = 4] seem competitive at GABAC receptors expressed in Xenopus laevis oocytes, having no effect as agonists (1 mM) but exerting weak antagonist (1 mM) effects on human GABAA and GABAB receptors. cis-3-ACPBPA was more potent and selective than the trans-compound, being more than 100 times more potent at GABAC than GABAA or GABAB receptors. cis-3-ACPBPA was further evaluated on dissociated rat retinal bipolar cells and dose-dependently inhibited the native GABAC receptor (IC50 = 47 ± 4.5 μM; n = 6). When applied to the eye as intravitreal injections, cis- and trans-3-ACPBPA prevented experimental myopia development and inhibited the associated vitreous chamber elongation, in a dose-dependent manner in the chick model. Doses only 10 times greater than required to inhibit recombinant GABAC receptors caused the antimyopia effects. Using intraperitoneal administration, cis- (30 mg/kg) and trans-3-ACPBPA (100 mg/kg) enhanced learning and memory in male Wistar rats; compared with vehicle there was a significant reduction in time for rats to find the platform in the Morris water maze task (p < 0.05; n = 10). As the physiological effects of cis- and trans-3-ACPBPA are similar to those reported for CGP36742, the memory and refractive effects of CGP36742 may be due in part to its GABAC activity.

Hyperopia is predominantly axial in nature.

PURPOSE Myopia has been found to be predominantly axial in nature, i.e. myopic eyes have longer than normal axial lengths, with corneal radius variations having only a small influence on the magnitude of the refractive error. In this study we assess whether a similar relationship exists for hyperopia. METHODS Biometric data were collected on 57 subjects with either emmetropic or hyperopic refractive errors ranging in magnitude from -0.37 D to +17.25 D. Our main analysis concentrated on subjects with less than +10 D of hyperopia (group 1, n = 53), as subjects with +10 D of hyperopia or more (group 2, n = 4) exhibited marked differences in their biometric characteristics. RESULTS Analysis of group 1 data revealed a significant relationship (r2 = 0.611, p = 0.0001) between the degree of hyperopia and the measured axial lengths. A weak but statistically significant relationship (r2 = 0.128, p = 0.009) was also found between mean corneal radius measures and mean spherical refractive errors, with the mean corneal radius flattening with increasing hyperopia. In group 2, three of the four subjects exhibited much steeper corneal characteristics than predicted from the group 1 data. CONCLUSIONS Our results suggest that hyperopia, like myopia, is predominantly axial in nature, although the corneal radius also plays a role in determining refractive error magnitude. These results have implications for refractive surgery and visual performance in hyperopic eyes.

Neural and optical limits to visual performance in myopia.

We investigated the relative importance of neural and optical limitations to visual performance in myopia. A number of visual performance measures were made on all or subsets of 121 eyes of emmetropic and myopic volunteers aged 17-35 years. These tests included visual measures that are mainly neurally limited (spatial summation out to +/-30 degrees in the horizontal visual field and resolution acuity out to +/-10 degrees in the horizontal visual field) and central ocular aberrations. We found that myopia affected the neurally limited tests, but had little effect on central higher order aberration. The critical area for spatial summation increased in the temporal visual field at 0.03 log units/dioptre of myopia. Resolution acuity decreased at approximately 0.012 log units/dioptre of myopia. Losses of visual function were slightly greater in the temporal than in the nasal visual field. The observed visual deficit in myopia can be explained by either global retinal expansion with some post-receptor loss (e.g. ganglion cell death) or a posterior polar expansion in which the point about which expansion occurs is near the centre of the previously emmetropic globe.

Optical correction of form deprivation myopia inhibits refractive recovery in chick eyes with intact or sectioned optic nerves.

The finding that the eyes of young chicks recover quickly from form deprivation myopia (FDM) has been interpreted as indirect evidence for active emmetropization. More direct evidence would be the demonstration that correction of FDM with spectacle lenses, thereby removing the defocus signal, prevents recovery. We investigated this issue in eyes with intact and sectioned (ONS) optic nerves. Previous studies suggest that an intact optic nerve is necessary for accurate emmetropization. Seventy day-old male chicks were monocularly deprived using velcro-mounted diffusers, which were removed after 5-6 days and in some (n=51), but not all cases, replaced by spectacle lenses (-5, -10 or -15 D). Approximately half (n=34) of the chicks also underwent ONS on day 1. Refractive errors and axial ocular dimensions were measured when the diffusers were first removed and thereafter at 2-4 day intervals over the following 1-2 weeks. In one case, measurements were continued at less regular intervals to 33 days. Lens powers were selected to either approximately correct or under-correct the refractive errors present when the diffusers were removed. Form deprivation in normal chicks produced large myopic shifts in refraction (means for groups range from -9.20 to -16.07 D). When the deprivation treatment was terminated, the myopia quickly decreased to negligible levels unless optically corrected. Correcting lenses stabilized the myopia to a level consistent with the lens power used. Interocular differences in axial length were consistent with an axial origin to the refractive changes. Results for the ONS groups exhibited similar trends although there was increased variability in the data. The findings support the interpretation that recovery from FDM is a product of active emmetropization. That ONS increased the variability of such responses implies that an intact optic nerve is required for accurate emmetropization.

Randomized Trial of Effect of Bifocal and Prismatic Bifocal Spectacles on Myopic Progression: Two-Year Results

OBJECTIVE To determine whether bifocal and prismatic bifocal spectacles could control myopia in children with high rates of myopic progression. METHODS This was a randomized controlled clinical trial. One hundred thirty-five (73 girls and 62 boys) myopic Chinese Canadian children (myopia of > or =1.00 diopters [D]) with myopic progression of at least 0.50 D in the preceding year were randomly assigned to 1 of 3 treatments: (1) single-vision lenses (n = 41), (2) +1.50-D executive bifocals (n = 48), or (3) +1.50-D executive bifocals with a 3-prism diopters base-in prism in the near segment of each lens (n = 46). MAIN OUTCOME MEASURES Myopic progression measured by an automated refractor under cycloplegia and increase in axial length (secondary) measured by ultrasonography at 6-month intervals for 24 months. Only the data of the right eye were used. RESULTS Of the 135 children (mean age, 10.29 years [SE, 0.15 years]; mean visual acuity, -3.08 D [SE, 0.10 D]), 131 (97%) completed the trial after 24 months. Myopic progression averaged -1.55 D (SE, 0.12 D) for those who wore single-vision lenses, -0.96 D (SE, 0.09 D) for those who wore bifocals, and -0.70 D (SE, 0.10 D) for those who wore prismatic bifocals. Axial length increased an average of 0.62 mm (SE, 0.04 mm), 0.41 mm (SE, 0.04 mm), and 0.41 mm (SE, 0.05 mm), respectively. The treatment effect of bifocals (0.59 D) and prismatic bifocals (0.85 D) was significant (P < .001) and both bifocal groups had less axial elongation (0.21 mm) than the single-vision lens group (P < .001). CONCLUSIONS Bifocal lenses can moderately slow myopic progression in children with high rates of progression after 24 months. APPLICATIONS TO CLINICAL PRACTICE: Bifocal spectacles may be considered for slowing myopic progression in children with an annual progression rate of at least 0.50 D.

Myopia prevalence in Chinese-Canadian children in an optometric practice

Purpose. The high prevalence of myopia in Chinese children living in urban East Asian countries such as Hong Kong, Taiwan, and China has been well documented. However, it is not clear whether the prevalence of myopia would be similarly high for this group of children if they were living in a Western country. This study aims to determine the prevalence and progression of myopia in ethnic Chinese children living in Canada. Methods. Right eye refraction data of Chinese-Canadian children aged 6 to 12 years were collated from the 2003 clinical records of an optometric practice in Mississauga, Ontario, Canada. Myopia was defined as a spherical equivalent refraction (SER) equal or less than −0.50 D. The prevalence of myopia and refractive error distribution in children of different ages and the magnitude of refractive error shifts over the preceding 8 years were determined. Data were adjusted for potential biases in the clinic sample. A questionnaire was administered to 300 Chinese and 300 Caucasian children randomly selected from the clinic records to study lifestyle issues that may impact on myopia development. Results. Optometric records of 1468 children were analyzed (729 boys and 739 girls). The clinic bias adjusted prevalence of myopia increased from 22.4% at age 6 to 64.1% at age 12 and concurrently the portion of the children that were emmetropic (refraction between −0.25 and +0.75 D) decreased (68.6% at 6 years to 27.2% at 12 years). The highest incidence of myopia for both girls (∼35%) and boys (∼25%) occurred at 9 and 10 years of age. The average annual refractive shift for all children was −0.52 ± 0.42 D and −0.90 ± 0.40 D for just myopic children. The questionnaire revealed that these Chinese-Canadian children spent a greater amount of time performing near work and less time outdoors than did Caucasian-Canadian children. Conclusions. Ethnic Chinese children living in Canada develop myopia comparable in prevalence and magnitude to those living in urban East Asian countries. Recent migration of the children and their families to Canada does not appear to lower their myopia risk.

The effect of positive‐lens addition and base‐in prism on accommodation accuracy and near horizontal phoria in Chinese myopic children

The effect of positive‐lens addition (0, +0.75, +1.50, +2.25, +3.00 D each eye) and base‐in prism power (0, 1.5, 3 Δ each eye) on both near focusing errors and latent horizontal deviations was evaluated in 29 Chinese myopic children (age: 10.3 ± 1.9 years, refractive error: −2.73 ± 1.31 D). Accommodation response and phoria were measured by the Shin‐Nippon auto‐refractor (right eye) and Howell–Dwyer near phoria card at 33 cm with each of the 15 lens/prism combinations in random order. The initial accommodative error was −0.96 ± 0.67 D (lag) and near phoria was −0.8 ± 5.0 Δ (exophoria). The positive‐lens addition decreased the accommodative lag but increased the exophoria as the power increased (e.g. up to −9.1 ± 4.1 Δ with +3 D). A 6‐Δ base‐in prism totally controlled the exophoria induced by a +1.50 D addition (−0.3 ± 4.3 Δ), but the accommodative lag was still considerable (−0.69 ± 0.54 D). In the graphical analysis of the data, a lens addition of +2.25 D combined with a 6‐Δ base‐in prism minimized both the lag and lens‐induced exophoria to −0.33 D and −2.4 Δ respectively (regression analysis). This lens and prism combination decreased the lens‐induced exophoria by 4.5 Δ compared with that measured with +2.25 D alone (−2.4 Δ vs −6.9 Δ). The results suggest that incorporating near base‐in prism when prescribing bifocal lenses for young progressing myopes with exophoria could reduce the positive lens‐induced oculomotor imbalance.

Effect of Bifocal and Prismatic Bifocal Spectacles on Myopia Progression in Children: Three-Year Results of a Randomized Clinical Trial

IMPORTANCE Myopia is a significant public health problem, making it important to determine whether a bifocal spectacle treatment involving near prism slows myopia progression in children. OBJECTIVE To determine whether bifocal and prismatic bifocal spectacles control myopia in children with high rates of myopia progression and to assess whether the treatment effect is dependent on the lag of accommodation and/or near phoria status. DESIGN, SETTING, AND PARTICIPANTS This 3-year randomized clinical trial was conducted in a private practice. A total of 135 (73 female and 62 male) Chinese-Canadian children (aged 8-13 years; mean [SE] age, 10.29 [0.15] years; mean [SE] myopia, -3.08 [0.10] D) with myopia progression of at least 0.50 D in the preceding year were randomly assigned to 1 of 3 treatments. A total of 128 (94.8%) completed the trial. INTERVENTIONS Single-vision lenses (control, n = 41), +1.50-D executive bifocals (n = 48), and +1.50-D executive bifocals with 3-Δ base-in prism in the near segment of each lens (n = 46). MAIN OUTCOMES AND MEASURES Myopia progression (primary) measured using an automated refractor following cycloplegia and increase in axial length (secondary) measured using ultrasonography at intervals of 6 months for 36 months. RESULTS Myopia progression over 3 years was an average (SE) of -2.06 (0.13) D for the single-vision lens group, -1.25 (0.10) D for the bifocal group, and -1.01 (0.13) D for the prismatic bifocal group. Axial length increased an average (SE) of 0.82 (0.05) mm, 0.57 (0.07) mm, and 0.54 (0.06) mm, respectively. The treatment effect of bifocals (0.81 D) and prismatic bifocals (1.05 D) was significant (P < .001). Both bifocal groups had less axial elongation (0.25 mm and 0.28 mm, respectively) than the single-vision lens group (P < .001). For children with high lags of accommodation (≥ 1.01 D), the treatment effect of both bifocals and prismatic bifocals was similar (1.1 D) (P < .001). For children with low lags (<1.01 D), the treatment effect of prismatic bifocals (0.99 D) was greater than of bifocals (0.50 D) (P = .03). The treatment effect of both bifocals and prismatic bifocals was independent of the near phoria status. CONCLUSIONS AND RELEVANCE Bifocal spectacles can slow myopia progression in children with an annual progression rate of at least 0.50 D after 3 years. These results suggest that prismatic bifocals are more effective for myopic children with low lags of accommodation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00787579.

Delayed mfERG responses in myopia.

It has been suggested that changes in the multifocal electroretinogram (mfERG) responses in myopes are primarily due to the increased axial length that accompanies myopia development. We investigated the characteristics of mfERG responses between emmetropes and myopes and determined the contribution of axial length to the mfERG data in 30 subjects (10 emmetropes and 20 myopes) using VERIS I. The amplitude and implicit time of the first positive peak (P1) of the first-order kernel were analyzed. We found that P1 implicit time in myopes was significantly longer by 1.3-3.1 ms than that of the emmetropes and this was not explained by the myopes having greater axial lengths than the emmetropes. Axial length contributed to 15% of the implicit time total variance while refractive error accounted for 27%. Delayed mfERG responses observed in myopes were not attributable to the anatomical change that accompanies myopia and may suggest underlying differences in retinal function that result from being myopic.