Anthony J. Adams

Visual evoked potentials in three-dimensional color space: Correlates of spatio-chromatic processing

Visual evoked potentials (VEPs) were measured for sinusoidal gratings with spatio-chromatic modulation defined in a three-dimensional color space. The spatio-chromatic modulation of the gratings can be decomposed into contributions from an achromatic luminance varying component, an isoluminant component which modulates only the activities of L cones and M cones, and an isoluminant component corresponding to modulation of only S-cone activity. The emphasis of this report is the nature of VEPs resulting from isoluminant spatio-chromatic modulation. The VEP response was characterized along a number of spatial, temporal, and chromatic stimulus dimensions: contrast, spatial frequency, chromaticity in the isoluminant plane, chrominance/luminance ratio, orientation, and temporal frequency. Isoluminant VEPs resulting from stimuli modulating L and M cones are compared with those from S-cone modulation. When appropriate spatiotemporal conditions are employed, both types produce robust VEPs; however, the S-pathway VEPs show considerably longer latencies than do those from LM-pathway activation. The VEP results are compared to psychophysical and single unit electrophysiological observations. VEP latencies exhibit the lowpass character of psychophysical chromatic contrast sensitivity functions but VEP amplitudes show bandpass tuning along both the S and LM axes. An oblique effect, i.e. shorter latencies for horizontal and vertical gratings than for diagonal, is observed in the isoluminant VEP. S-pathway VEPs are used to demonstrate an electophysiological correlate of transient tritanopia. Normative amplitude and latency data for VEPs from selectivity stimulated chromatic mechanisms provide a baseline for clinical electrodiagnostic applications.

Initial cross-sectional results from the Orinda Longitudinal Study of Myopia.

Background. Although investigations of human refractive error development and normal ocular growth have been conducted for the last 50 years, no previous study of refractive error and the ocular components has measured all the ocular components. Methods. The Orinda Longitudinal Study of Myopia was initiated to characterize the development of refractive error and normal eye growth in a sample of predominantly Caucasian children ages 6 to 14 years. Results. Crosssectional results from 530 children ages 5 to 12 years in the 1st, 3rd, and 6th grades are presented. Conclusions. This samples refractive error decreased toward emmetropia with age from an average of +0.73 D at age 6 years to an average of +0.50 D by age 12 years. Between the ages of 6 and 12 years, the vitreous chamber elongated (by 0.52 mm) and the crystalline lens power decreased (by 1.35 D); surprisingly, the crystalline lens thinned by 0.14 mm during this same time period

Optical density of human macular pigment

Foveal and parafoveal spectral sensitivities of the G cone mechanism were used to derive the difference spectrum for the macular pigment for 12 observers. Measurements of the peak density of the macular pigment were obtained with a shortened version of the same procedure for an additional 15 observers. The mean density for all 27 observers at 460 nm was 0.77 +/- 0.06 with a range of 0.21-1.22. The mean density is higher than that previously reported and, compared to the standard absorbance curve (Wyszecki and Stiles, 1967), the results indicate higher density values for wavelengths on the long wavelength side of the absorption maximum.

Optimum parameters for short-wavelength automated perimetry.

PurposeTo determine the optimum parameters for short-wavelength automated perimetry (SWAP) and to recommend these for standardization of the procedure. MethodsWe used a variety of stimulus and background configurations to determine the optimum background spectral distribution and luminance, and the optimum target spectral distribution, maximum luminance, and duration. We measured threshold versus intensity curves to determine which combination provided (a) the greatest isolation of the short-wavelength sensitive mechanisms and (b) the largest dynamic range for perimetry. We also evaluated the effect of lens absorption and cataract on these two factors. ResultsA broad-band yellow background at 100 candela/m2 with a narrow-band 440-nm (27-nm half-bandwidth), 1.8° diameter (Goldmann size V) stimulus presented for 200 ms was optimum at all retinal eccentricities. Specific recommendations for how to modify existing perimeters are given. ConclusionAgreement regarding the optimum parameters for SWAP should lead to standardization of the test that will facilitate comparison of results from different centers. Normative data can be collected at several sites and incorporated into statistical analysis packages currently available with various perimeters. This will greatly improve the clinical utility of this test.

Local Diabetic Retinopathy Prediction by Multifocal ERG Delays over 3 Years

PURPOSE To derive and validate a model for use in predicting local retinal areas in which nonproliferative diabetic retinopathy (NPDR) lesions will develop over a 3-year period, by using primarily the implicit time (IT) of the multifocal electroretinogram (mfERG). METHODS Eighteen diabetic patients were examined at baseline and at three annual follow-ups. Ophthalmic examinations, including fundus photographs and mfERG testing, were performed at each visit. Thirty-five retinal zones were constructed from the 103-element stimulus array, and each zone was assigned the maximum IT z-score within it based on 30 age-similar control subjects. Logistic regression was used to investigate the development of retinopathy in relation to baseline mfERG IT delays and additional diabetic health variables. Receiver operating characteristic (ROC) curves were used to evaluate the models. RESULTS Retinopathy developed in 77 of the 1208 retinal zones, of which 25 had recurring retinopathy. Multivariate analyses yielded baseline mfERG IT, duration of diabetes, and blood glucose concentration as the most important predictors of recurring retinopathy. mfERG ITs were not predictive of transient retinopathy. ROC curves based on the multivariate model for the prediction of recurring retinopathy resulted in an area under the curve of 0.95, sensitivity of 88%, and specificity of 98%. Ten-fold cross-validation confirmed the high sensitivity and specificity of the model. CONCLUSIONS The development of recurring retinopathy over a 3-year period can be well predicted by using a multivariate model based on mfERG implicit time. Multifocal ERG delays are promising candidate measures for trials of novel therapeutics directed at preventing or slowing the progression of NPDR.

Disruption of the Retinal Parafoveal Capillary Network in Type 2 Diabetes before the Onset of Diabetic Retinopathy

PURPOSE To establish, using adaptive optics scanning laser ophthalmoscopy (AOSLO), that the retinal parafoveal capillary network is altered before the onset of diabetic retinopathy in adult patients with type 2 diabetes. METHODS AOSLO videos were acquired in the parafoveal region of one eye from control subjects and from patients with type 2 diabetes and no retinopathy. Detailed images of the parafoveal capillary network were generated with custom motion contrast enhancement algorithms. The combination of AOSLO images and videos enabled the simultaneous assessment of several features of the parafoveal capillary network. Arteriovenous (AV) channels were identified by finding the least tortuous capillary channels connecting terminal arterioles to postcapillary venules. Measures of capillary dropout and capillary hemodynamics were also quantified. RESULTS The average tortuosity of AV channels was 26% higher in patients with type 2 diabetes when compared with controls, even though there were no signs of diabetic retinopathy in any of the eyes that were assessed (P < 0.05). In addition, the metrics of capillary dropout showed small changes (between 3% and 7%), leukocyte speed 14% lower, and pulsatility 25% higher, but none of these differences was statistically significant. CONCLUSIONS It is often difficult to find consistent changes in the retinal microvasculature due to large intersubject variability. However, with a novel application of AOSLO imaging, it is possible to visualize parafoveal capillaries and identify AV channels noninvasively. AV channels are disrupted in type 2 diabetes, even before the onset of diabetic retinopathy.

Comparison of cyclopentolate versus tropicamide cycloplegia in children.

This double masked study compares the cycloplegic effects of tropicamide 1% and cyclopentolate 1% in 20 nonstrabismic, nonamblyopic, hyperopic 6- to 12-year old children with a mean refractive error=+1.48 ± 1.10 diopters (D). Unlike previous studies which used only amplitude of accommodation to measure the depth of cycloplegia, this study compares refractive error as determined by retinoscopy, distance subjective refraction, and distance autorefraction (Canon R-1). In addition, we compare the amplitude of accommodation as measured by subjective push-up and objective autorefraction methods. There is no statistically significant difference between cyclopentolate and tropicamide for either cycloplegic retinoscopy or distance subjective refraction. Autorefraction measurement of refractive error shows a statistically significant but clinically unimportant bias (0.14 ± 0.30 D) toward more hyperopia with cyclopentolate. Both drops reveal latent hyperopia, and the mean latencies are not statistically different between the two cycloplegic agents. Latent hyperopia is not systematically related to the degree of hyperopia after tropicamide, but this relation is significant after cyclopentolate. No differences were found between refractive results with either agent at 30 min compared to 60 min after drop instillation. When measured objectively with the autorefractor, accommodation is inhibited more effectively by cyclopentolate than by tropicamide. Our results suggest that although tropicamide is not as effective as cyclopentolate in inhibiting accommodation it is, nevertheless, a useful cycloplegic agent for measuring distance refractive error of low to moderate hyperopia in school-aged children.

Dark adaptation in age-related maculopathy

Dark adaptation was measured for patients with age‐related maculopathy (ARM) and for age‐matched controls; green and red test stimuli were flashed 15d̀ from the fovea to examine differential effects of ARM on rod and cone functions, respectively. The ARM patients showed decreases in sensitivity for both rods and cones (0.5‐ 1.5 log units) and an increased time constant of recovery for rod function. After 20 min in the dark, sensitivity to both red and green stimuli was depressed at the fovea and at 5, 10, 15 and 25d̀ eccentric to the fovea. The greatest sensitivity loss was found in the macular area (fovea and 5d̀ eccentric). Our data suggest that the ARM patients have an abnormality in both rod‐ and cone‐adaptation systems over a relatively large retinal area which extends beyond the zone of visual field abnormality.

Adolescents with Type 2 Diabetes: Early Indications of Focal Retinal Neuropathy, Retinal Thinning and Venular Dilation

Purpose: The eye provides a unique window into the neural and vascular health of a patient with diabetes. The present study is the first of its kind to examine the neural retinal function, structure, and retinal vascular health in adolescents with Type 2 diabetes. Methods: Focal neural responses from 103 discrete retinal regions of the eye were tested using multifocal electroretinography. Optical coherence tomography was utilized to measure retinal thickness. Digital fundus photographs were examined for the presence of retinopathy and to measure vascular caliber using retinal vessel analysis. Fifteen adolescents diagnosed with Type 2 diabetes, aged 13 to 21 years with a mean diabetes duration of 2.1 ± 1.3 years, were tested. Twenty-six age-matched control subjects were also tested. Results: Multifocal electroretinograms of the Type 2 diabetic group were significantly (P = 0.03) delayed by 0.49 milliseconds. The diabetic group also showed significant (both; P ≤ 0.03) retinal thinning (10.3 &mgr;m) and significant venular dilation (16.2 &mgr;m). Conclusion: The present study shows early indications of focal retinal neuropathy, retinal thinning, and venular dilation in adolescents with Type 2 diabetes. Early detection of functional and structural changes will hopefully aid in the prevention of permanent damage or further functional loss.

Chromatic and Luminosity Processing in Retinal Disease

Color vision loss can be an early sign of eye disease; in many retinal disorders the loss precedes any change in visual acuity. Noninvasive psychophysical methods allow factoring out of preretinal, receptoral, and postreceptoral (neural) components of the color vision change. A loss of chromatic but not achromatic sensitivity occurs for diabetics; the loss is selective for pathways subserving blue-sensitive photoreceptors. Both chromatic and achromatic pathways are altered in glaucoma and senile macular degeneration; the most marked change in central serous choroidopathy is loss of sensitivity somewhere in the blue-sensitive cone pathway. There is evidence that the pathways subserved by blue-sensitive cones have anatomically and physiologically different properties from those served by other receptor types, and they appear particularly vulnerable to disturbances of retinal integrity.