Earl L. Smith

Rapid reorganization of cortical maps in adult cats following restricted deafferentation in retina

The retinotopic map in the visual cortex of adult mammals can reorganize in response to a small injury in a restricted region of retina. Although the mechanisms underlying this neural plasticity in adults are not well understood, it is possible that rapid, adaptive alterations in the effectiveness of existing connections play a key role in the reorganization of cortical topography following peripheral deafferentation. In order to test this hypothesis, a small retinal lesion was made in one eye of adult cats and the visual cortex was mapped before and immediately after enucleating the non-lesioned eye. We found that substantial reorganization takes place within hours of enucleation.

The role of optical defocus in regulating refractive development in infant monkeys

Early in life, the two eyes of infant primates normally grow in a coordinated manner toward the ideal refractive state. We investigated the extent to which lens-induced changes in the effective focus of the eye affected refractive development in infant rhesus monkeys. The main finding was that spectacle lenses could predictably alter the growth of one or both eyes resulting in appropriate compensating refractive changes in both the hyperopic and myopic directions. Although the effective operating range of the emmetropization process in young monkeys is somewhat limited, the results demonstrate that emmetropization in this higher primate, as in a number of other species, is an active process that is regulated by optical defocus associated with the eyes effective refractive state.

Relative peripheral hyperopic defocus alters central refractive development in infant monkeys

Understanding the role of peripheral defocus on central refractive development is critical because refractive errors can vary significantly with eccentricity and peripheral refractions have been implicated in the genesis of central refractive errors in humans. Two rearing strategies were used to determine whether peripheral hyperopia alters central refractive development in rhesus monkeys. In intact eyes, lens-induced relative peripheral hyperopia produced central axial myopia. Moreover, eliminating the fovea by laser photoablation did not prevent compensating myopic changes in response to optically imposed hyperopia. These results show that peripheral refractive errors can have a substantial impact on central refractive development in primates.

Decrease in Rate of Myopia Progression with a Contact Lens Designed to Reduce Relative Peripheral Hyperopia: One-Year Results

PURPOSE To determine whether a novel optical treatment using contact lenses to reduce relative peripheral hyperopia can slow the rate of progress of myopia. METHODS Chinese children, aged 7 to 14 years, with baseline myopia from sphere -0.75 to -3.50 D and cylinder ≤1.00 D, were fitted with novel contact lenses (n = 45) and followed up for 12 months, and their progress was compared with that of a group (n = 40) matched for age, sex, refractive error, axial length, and parental myopia wearing normal, single-vision, spherocylindrical spectacles. RESULTS On adjusting for parental myopia, sex, age, baseline spherical equivalent (SphE) values, and compliance, the estimated progression in SphE at 12 months was 34% less, at -0.57 D, with the novel contact lenses (95% confidence interval [CI], -0.45 -0.69 D) than at -0.86 D, with spectacle lenses (95% CI, -0.74 to -0.99 D). For an average baseline age of 11.2 years, baseline SphE of -2.10 D, a baseline axial length of 24.6 mm, and 320 days of compliant lens wear, the estimated increase in axial length (AL) was 33% less at 0.27 mm (95% CI, 0.22-0.32 mm) than at 0.40 mm (95% CI, 0.35-0.45 mm) for the contact lens and spectacle lens groups, respectively. CONCLUSIONS The 12-month data support the hypothesis that reducing peripheral hyperopia can alter central refractive development and reduce the rate of progress of myopia. (chictr.org number, chiCTR-TRC-00000029 or chiCTR-TRC-00000032.).

Visual field defects and neural losses from experimental glaucoma

Glaucoma is a relatively common disease in which the death of retinal ganglion cells causes a progressive loss of sight, often leading to blindness. Typically, the degree of a patients visual dysfunction is assessed by clinical perimetry, involving subjective measurements of light-sense thresholds across the visual field, but the relationship between visual and neural losses is inexact. Therefore, to better understand of the effects of glaucoma on the visual system, a series of investigations involving psychophysics, electrophysiology, anatomy, and histochemistry were conducted on experimental glaucoma in monkeys. The principal results of the studies showed that, (1) the depth of visual defects with standard clinical perimetry are predicted by a loss of probability summation among retinal detection mechanisms, (2) glaucomatous optic atrophy causes a non-selective reduction of metabolism of neurons in the afferent visual pathway, and (3) objective electrophysiological methods can be as sensitive as standard clinical perimetry in assessing the neural losses from glaucoma. These experimental findings from glaucoma in monkeys provide fundamental data that should be applicable to improving methods for assessing glaucomatous optic neuropathy in patients.

Spectacle lenses designed to reduce progression of myopia: 12-month results.

Purpose. To report the results of 12-month wear of three novel spectacle lens designs intended to reduce peripheral hyperopic defocus and one standard design control lens and their effect on the progression of myopia in Chinese children aged 6 to 16 years. Methods. Chinese children (n = 210) with myopia (−0.75 D to −3.50 D sphere, cylinder ≤−1.50 D) were randomized to one of four groups wearing either one of three novel spectacle lens designs (types I, II, or III) or conventional, single-vision spectacle lenses. Data were collected at 6 and 12 months. Primary and secondary outcome measures were the changes in central cycloplegic auto-refraction and eye axial length, respectively. Peripheral refraction along the horizontal meridian (nasal and temporal) was taken at baseline with and without spectacle lenses. Multivariate linear regression was used to adjust analyses for important covariates. Results. Progression in eyes wearing control spectacle lenses at 6 and 12 months was −0.55 D ± 0.35 D and −0.78 ± 0.50 D, respectively. For the entire group, no statistically significant differences were observed in the rates of progression with the novel designs in comparison to control spectacle lenses. However, in younger children (6 to 12 years) with parental history of myopia (n = 100), there was significantly less progression (−0.68 D ± 0.47 D vs. −0.97 D ± 0.48 D) with lens type III compared with control spectacles (mean difference, 0.29 D, std error, 0.11, p = 0.038). Conclusions. There were no statistically significant differences in the rate of progression of myopia between the control and novel lens wearing eyes for the age group 6 to 16 years. The finding of reduced progression of myopia with type III lens design in younger children with parental myopia needs to be validated in a more targeted study.

Protective Effects of High Ambient Lighting on the Development of Form-Deprivation Myopia in Rhesus Monkeys

PURPOSE Time spent outdoors reduces the likelihood that children will develop myopia, possibly because light levels are much higher outdoors than indoors. To test this hypothesis, the effects of high ambient lighting on vision-induced myopia in monkeys were determined. METHODS Monocular form deprivation was imposed on eight infant rhesus monkeys. Throughout the rearing period (23 ± 2 to 132 ± 8 days), auxiliary lighting increased the cage-level illuminance from normal lighting levels (15-630 lux) to ∼25,000 lux for 6 hours during the middle of the daily 12-hour light cycle. Refractive development and axial dimensions were assessed by retinoscopy and ultrasonography, respectively. Comparison data were obtained in previous studies from 18 monocularly form-deprived and 32 normal monkeys reared under ordinary laboratory lighting. RESULTS Form deprivation produced axial myopia in 16 of 18 normal-light-reared monkeys. In contrast, only 2 of the 8 high-light-reared monkeys developed myopic anisometropias, and in 6 of these monkeys, the form-deprived eyes were more hyperopic than their fellow eyes. The treated eyes of the high-light-reared monkeys were more hyperopic than the form-deprived eyes of the normal-light-reared monkeys. In addition, both eyes of the high-light-reared monkeys were more hyperopic than those of normal monkeys. CONCLUSIONS High ambient lighting retards the development of form-deprivation myopia in monkeys. These results are in agreement with the hypothesis that the protective effects of outdoor activities against myopia in children are due to exposure to the higher light levels encountered outdoors. It is possible that therapeutic protection against myopia can be achieved by manipulating indoor lighting levels.

Effects of Optical Defocus on Refractive Development in Monkeys: Evidence for Local, Regionally Selective Mechanisms

PURPOSE To characterize the influence of optical defocus on ocular shape and the pattern of peripheral refraction in infant rhesus monkeys. METHODS Starting at 3 weeks of age, eight infant monkeys were reared wearing -3 diopter (D) spectacle lenses over one eye that produced relative hyperopic defocus in the nasal field (NF) but allowed unrestricted vision in the temporal field (NF group). Six infants were reared with monocular -3 D lenses that produced relative hyperopic defocus across the entire field of view. Control data were obtained from 11 normal monkeys. Refractive development was assessed by streak retinoscopy performed along the pupillary axis and at eccentricities of 15 degrees, 30 degrees, and 45 degrees along the vertical and horizontal meridians. Central axial dimensions and eye shape were assessed with magnetic resonance imaging. RESULTS In response to full-field hyperopic defocus, the eye developed relative central axial myopia, became less oblate, and exhibited relative peripheral hyperopia in both the nasal and the temporal hemifields. Conversely, nasal-field hyperopic defocus produced relative myopia that was largely restricted to the nasal hemifield; these alterations in the patterns of peripheral refraction in the NF monkeys were associated with local, region-specific alterations in vitreous chamber depth in the treated hemiretina. CONCLUSIONS Optically imposed defocus can alter the shape and pattern of peripheral refraction in infant primates. Like those of form deprivation, the effects of optical defocus in primates are dominated by mechanisms that integrate visual signals in a spatially restricted manner and exert their influence in a regionally selective manner.

Prentice Award Lecture 2010: A case for peripheral optical treatment strategies for myopia.

It is well established that refractive development is regulated by visual feedback. However, most optical treatment strategies designed to reduce myopia progression have not produced the desired results, primarily because some of our assumptions concerning the operating characteristics of the vision-dependent mechanisms that regulate refractive development have been incorrect. In particular, because of the prominence of central vision in primates, it has generally been assumed that signals from the fovea determine the effects of vision on refractive development. However, experiments in laboratory animals demonstrate that ocular growth and emmetropization are mediated by local retinal mechanisms and that foveal vision is not essential for many vision-dependent aspects of refractive development. However, the peripheral retina, in isolation, can effectively regulate emmetropization and mediate many of the effects of vision on the eyes refractive status. Moreover, when there are conflicting visual signals between the fovea and the periphery, peripheral vision can dominate refractive development. The overall pattern of results suggests that optical treatment strategies for myopia that take into account the effects of peripheral vision are likely to be more successful than strategies that effectively manipulate only central vision.

Effects of optically induced blur on the refractive status of young monkeys

In each of eight rhesus monkeys, one eye was defocused with a -9 D contact lens beginning before 1 month of age for periods of 2-3 months. At the end of the rearing period, interocular comparisons showed that one subject had developed a relative axial myopia (3.0 D), however, five monkeys had developed a relative axial hyperopia (2.0-3.5 D). After discontinuing the contact-lens rearing procedure, the induced refractive errors diminished over time in all subjects. These results indicate that the defocus threshold for form-deprivation myopia is relatively high and that substantial levels of optical defocus which do not exceed this threshold typically produce axial hyperopia. The recovery data suggests that monkeys have an emmetropization mechanism which is sensitive to optical defocus, but the failure of this mechanism to compensate for the refractive errors simulated during the lens-rearing procedures suggests that this mechanism has a limited operating range.