The Effect of Spectacle Lenses Containing Peripheral Defocus on Refractive Error and Horizontal Eye Shape in the Guinea Pig.

Purpose: It has been proposed that the peripheral retina, responding to local optical defocus, contributes to myopia and associated altered eye growth in humans. To test this hypothesis, we measured the changes in central (on-axis) and peripheral ocular dimensions in guinea pigs wearing a concentric bifocal spectacle lens design with power restricted to the periphery. Methods: Five groups of guinea pigs (n = 83) wore either a unifocal (UF) spectacle lens (-4, 0, or +4 Diopters [D]), or a peripheral defocus (PF) spectacle lens that had a plano center (diameter of 5 mm) with either -4 or +4 D in the surround (-4/0 or +4/0 D). The overall optical diameter of all lenses was 12 mm. Lenses were worn over one eye from 8 to 18 days of age for negative and plano lenses, or from 8 to 22 days of age for positive lenses. Refractive error was measured centrally and 30° off-axis in the temporal and nasal retina. The shape of the eye was analyzed from images of sectioned eyes. Results: Lenses of -4 D UF induced myopia, reflecting enhanced ocular elongation, which was centered on the optic nerve head and included the surrounding peripapillary zone (PPZ, 18° in diameter). Some ocular expansion, including within the PPZ, also was recorded with -4/0 and +4/0 D PF lenses while the +4 D UF lens inhibited rather than enhanced elongation, centrally and peripherally. Conclusions: Peripheral defocus-induced ocular expansion encompasses the PPZ, irrespective of the sign of the inducing defocus. Understanding the underlying mechanism potentially has important implications for designing multifocal lenses for controlling myopia in humans and also potentially for understanding the link between myopia and glaucoma.

The relationship between image degradation and myopia in the mammalian eye.

BACKGROUND: In all species studied, myopia develops if the eye is deprived of detailed vision during development (form deprivation myopia). However, different degrees of spatial image deprivation produce different effects and have not been described in the mammalian eye. Therefore, the effect of image degradation on guinea pig emmetropisation was investigated. METHODS: Eighty-one guinea pigs wore a treatment on one eye from 6 to 13 days of age. There were four treatments: a translucent diffuser (no lines or edges were visible through the diffuser); one of five Bangerter foils (BF: 0.8, 0.6, 0.4, 0.2, light perception only), which differed in their cut-off spatial frequencies; a 'ring mount' control with no filter; or one of two neutral density filters that reduced luminance only (ND, optical density grades 0.1 and 0.6). Refractive error and ocular elongation were measured after seven days of treatment. RESULTS: The extent of induced myopia and ocular growth were related to the amount of image degradation (mean difference between the treated and untreated eyes changed in a graded manner -7.0 D to -0.2 D and from 85 µm to seven µm respectively, for spatial frequency cut-offs between zero and 24 cycles per degree). Corresponding reductions in luminance from ND filters did not increase eye growth and caused significantly less myopia than the BFs that caused a similar luminance decrement. The greatest myopia occurred when no or limited spatial information was available to the eye, but moderate myopia still occurred with spatial frequency cut-offs of six and 12 cycles per degree, well beyond the visual acuity range of guinea pigs. CONCLUSION: Excessive ocular growth and myopia are most robust when induced by spatial frequency reductions within the visual acuity range but can also be induced beyond this. Either the mechanism of ocular growth can detect supra-threshold spatial frequencies, possibly due to aliasing, or it is sensitive to small amounts of contrast degradation.

Egr-1 mRNA expression is a marker for the direction of mammalian ocular growth.

PURPOSE: The immediate early gene Egr-1 is thought to form part of the pathway that mediates abnormal ocular growth. This study investigated whether the mRNA expression levels of Egr-1 in a mammalian retina are modulated differentially, depending on the direction of ocular growth. METHODS: To induce accelerated growth and myopia, guinea pigs wore a -5 diopter (D) lens over one eye from 4 to 11 days of age. To induce inhibited growth, the lens was removed after 7 days of -5 D lens wear, and the eye allowed to recover from myopia for 3 days. Ocular parameters and Egr-1 mRNA levels were subsequently assessed, and compared to untreated fellow eyes and eyes from untreated littermates. Possible circadian changes in Egr-1 mRNA levels were also determined in 18 additional animals by taking measures every 4 hours during a 24-hour cycle. RESULTS: Ocular compensation to a -5 D lens occurred after 7 days (Δ -4.8 D, Δ +147 µm growth, N = 20). In 5 highly myopic eyes (Δ -7.4 D), Egr-1 mRNA levels in the retina were significantly downregulated relative to contralateral control (51%) and age-matched untreated (47%) eyes. Three days after the -5 D lens was removed, eyes had recovered from the myopia (Δ -0.5 D, relative change of +2.9 D, N = 4) and Egr-1 mRNA levels were significantly elevated relative to contralateral (212%) and untreated (234%) eyes, respectively. Normal Egr-1 mRNA expression was higher in the middle of the day than in the middle of the night. Immunolabeling showed strong Egr-1 reactivity in cell bodies in the inner nuclear and ganglion cell layers. CONCLUSIONS: Egr-1 mRNA levels in a mammalian retina show a bi-directional persistent response to opposing ocular growth stimuli. This suggests retinal Egr-1 might act as a signal for the direction of ocular growth in different species.

Integration of defocus by dual power Fresnel lenses inhibits myopia in the mammalian eye.

PURPOSE: Eye growth compensates in opposite directions to single vision (SV) negative and positive lenses. We evaluated the response of the guinea pig eye to Fresnel-type lenses incorporating two different powers. METHODS: A total of 114 guinea pigs (10 groups with 9-14 in each) wore a lens over one eye and interocular differences in refractive error and ocular dimensions were measured in each of three experiments. First, the effects of three Fresnel designs with various diopter (D) combinations (-5D/0D; +5D/0D or -5D/+5D dual power) were compared to three SV lenses (-5D, +5D, or 0D). Second, the ratio of -5D and +5D power in a Fresnel lens was varied (50:50 compared with 60:40). Third, myopia was induced by 4 days of exposure to a SV -5D lens, which was then exchanged for a Fresnel lens (-5D/+5D) or one of two SV lenses (+5D or -5D) and ocular parameters tracked for a further 3 weeks. RESULTS: Dual power lenses induced an intermediate response between that to the two constituent powers (lenses +5D, +5D/0D, 0D, -5D/+5D, -5D/0D and -5D induced +2.1 D, +0.7 D, +0.1 D, -0.3 D, -1.6 D and -5.1 D in mean intraocular differences in refractive error, respectively), and changing the ratio of powers induced responses equal to their weighted average. In already myopic animals, continued treatment with SV negative lenses increased their myopia (from -3.3 D to -4.2 D), while switching to SV positive lenses or -5D/+5D Fresnel lenses reduced their myopia (by 2.9 D and 2.3 D, respectively). CONCLUSIONS: The mammalian eye integrates competing defocus to guide its refractive development and eye growth. Fresnel lenses, incorporating positive or plano power with negative power, can slow ocular growth, suggesting that such designs may control myopia progression in humans.

Temporal properties of the myopic response to defocus in the guinea pig.

PURPOSE: Hyperopic defocus induces myopia in all species tested and is believed to underlie the progression of human myopia. We determined the temporal properties of the effects of hyperopic defocus in a mammalian eye. METHODS: In Experiment 1, the rise and decay time of the responses elicited by hyperopic defocus were calculated in 111 guinea pigs by giving repeated episodes of monocular -4 D lens wear (from 5 to 6 days of age for 12 days) interspersed with various dark intervals. In Experiment 2, the decay time constant was calculated in 152 guinea pigs when repeated periods of monocular -5 D lens-wear (from 4 days of age for 7 days) were interrupted with free viewing periods of different lengths. At the end of the lens-wear period, ocular parameters were measured and time constants were calculated relative to the maximum response induced by continuous lens wear. RESULTS: When hyperopic defocus was experienced with dark intervals between episodes, the time required to induce 50% of the maximum achievable myopia and ocular elongation was at most 30 min. Saturated 1 h episodes took at least 22 h for refractive error and 31 h for ocular length, to decay to 50% of the maximum response. However, the decay was an order of magnitude faster when hyperopic defocus episodes were interrupted with a daily free viewing period, with only 36 min required to reduce relative myopia and ocular elongation by 50%. CONCLUSIONS: Hyperopic defocus causes myopia with brief exposures and is very long lasting in the absence of competing signals. However, this myopic response rapidly decays if interrupted by periods of 'normal viewing' at least 30 min in length, wherein ocular growth appears to be guided preferentially by the least amount of hyperopic defocus experienced.