The prevalence of diabetes has been accelerating at an alarming rate in the last decade; some describe it as an epidemic. Diabetic eye complications are the leading cause of blindness in adults aged 25-74 in the United States. Early diagnosis and development of effective preventatives and treatments of diabetic retinopathy are essential to save sight. We describe efforts to establish functional indicators of retinal health and predictors of diabetic retinopathy. These indicators and predictors will be needed as markers of the efficacy of new therapies. Clinical trials aimed at either prevention or early treatments will rely heavily on the discovery of sensitive methods to identify patients and retinal locations at risk, as well as to evaluate treatment effects.We report on recent success in revealing local functional changes of the retina with the multifocal electroretinogram (mfERG). This objective measure allows the simultaneous recording of responses from over 100 small retinal patches across the central 45 degree field. We describe the sensitivity of mfERG implicit time measurement for revealing functional alterations of the retina in diabetes, the local correspondence between functional (mfERG) and structural (vascular) abnormalities in eyes with early nonproliferative retinopathy, and longitudinal studies to formulate models to predict the retinal sites of future retinopathic signs. A multivariate model including mfERG implicit time delays and 'person' risk factors achieved 86% sensitivity and 84% specificity for prediction of new retinopathy development over one year at specific locations in eyes with some retinopathy at baseline. A preliminary test of the model yielded very positive results. This model appears to be the first to predict, quantitatively, the retinal locations of new nonproliferative diabetic retinopathy development over a one-year period. In a separate study, the predictive power of a model was assessed over oneand two-year follow-ups. This permitted successful prediction of new retinopathy development in eyes with and without retinopathy at baseline. Finally, we briefly describe our current research efforts to (a) locally predict future sight-threatening diabetic macular edema, (b) investigate local retinal function change in adolescent patients with diabetes, and (c) better understand the physiological bases of the mfERG delays.The ability to predict the retinal locations of future retinopathy based on mfERG implicit time provides clinicians a powerful tool to screen, follow up, and even consider early prophylactic treatment of the retinal tissue in diabetic patients. It also aids identification of 'at risk' populations for clinical trials of candidate therapies, which may greatly reduce their cost by decreasing the size of the needed sample and the duration of the trial.

Purpose This cross-sectional study examines the existence and frequency of functional and structural abnormalities in the adolescent type 1 diabetic retina. We also compare the results to those of adolescents with type 2 diabetes. Methods Thirty-two adolescents with type 1 diabetes (5.7 ± 3.6 yrs; mean duration ± SD), 15 with type 2 diabetes (2.1 ± 1.3 yrs) and 26 age-matched control subjects were examined. Multifocal electroretinogram (mfERG) responses from 103 retinal regions were recorded. Optical coherence tomography was used to measure retinal thickness. Vascular diameter around the optic nerve was also assessed. Results Nine of the 32 (28%) adolescents with type 1 diabetes and 6 of the 15 (40%) with type 2 diabetes had significant mfERG implicit time delays compared to 2 of the 26 controls (8%). Retinal thicknesses in both patient groups were significantly (p ≤ 0.01) thinner than controls. The type 2 group also showed significant (p ≤ 0.03) retinal venular dilation (235.8 ± 5.9μm) compared to controls (219.6 ± 4.0μm). Conclusions The present study illustrates that subtle but significant functional and structural changes occur very early in type 1 diabetes. Adolescents with type 2 diabetes appear to be more affected than those with type 1 diabetes. Further longitudinal examination of the etiology and progression of these abnormalities is warranted.

In the present work, we explore the perceptual bases of infants' spontaneous looking preferences among isoluminant chromatic stimuli (Bornstein, 1975). Three experiments were conducted. In Experiment 1, adult subjects made brightness matches between a white standard and each of six isoluminant chromatic stimuli. The classic variations of brightness with chromaticity were found. In Experiment 2, 12-week-old infants' spontaneous looking preferences were measured for white lights of different luminances. Preference increased with increasing luminance, suggesting that brightness differences are sufficient to create looking preferences among isochromatic stimuli. In Experiment 3, infants' preferences were tested for each of the six chromatic stimuli paired against white, at both isoluminance and (adult) isobrightness. All chromatic stimuli were preferred to white, and the pattern of preferences was similar for both isoluminance and isobrightness conditions. It is concluded that hue and/or saturation, rather than brightness, control infants' spontaneous looking preferences among chromatic stimuli.

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 yrs, were tested. Twenty-six agematched control subjects were also tested.Results-mfERGs of the type 2 diabetic group were significantly (p = 0.03) delayed by 0.49 ms. The diabetic group also showed significant (both; p ≤ 0.03) retinal thinning (10.3 μm) and significant venular dilation (16.2 μm).Conclusions-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.

Neuroretinal function is more abnormal in males than in females for adults with type 2 diabetes and no retinopathy. These results suggest that, relative to males, females may have some protection from, or resistance to, neurodegenerative changes that precede the development of background retinopathy in type 2 diabetes.

Purpose In order to assist identification of macular thickness abnormalities by optical coherence tomography (OCT), we use techniques that improve spatial localization across the retina to establish any age-related retinal thickness changes in healthy eyes. Methods Retinal thickness was measured in 30 eyes of 30 healthy subjects aged 13–69 years. Using Stratus OCT™ 3, twelve radial scans centered at the foveola were acquired and points between scans were interpolated to create a topographic map of the central 20°. The thickness map was divided into 37 hexagonal regions. A mean retinal thickness for each hexagon was computed. Retinal thickness versus age was evaluated for the entire scanned area, 5 anatomical regions, and within individual hexagons. The retinal nerve fiber layer (RNFL) contribution to total retinal thinning was analyzed in the papillomacular region. Results There was a small but significant thinning of the overall macular area with increasing age (2.7 μm/decade; P = 0.027). Comparing the 10 youngest subjects (age 13–27) to the 10 oldest (age 51–68), retinal thicknesses in the temporal, superior, inferior and foveal regions were not significantly different. However, the two age groups differed significantly in retinal thickness in the nasal region (P < 0.008). Across all subjects retinal thickness in this region was linearly correlated with age, decreasing by 4.1μm/decade (P < 0.002). Approximately 43% of the retinal thinning in the nasal region was attributed to RNFL loss. Conclusions The method of OCT acquisition and analysis used in this study allows for greater spatial localization of change in retinal thickness due to age or pathological processes. Based on the results of this study, the macula thins with increasing age, but does so non-uniformly. The greatest amount of thinning occurs nasal to the fovea. RNFL loss accounts for much, but not all of, the thinning in this area.

In the present study, discrete trial familiarization/novelty techniques were used to study lightness constancy in 4-month-old infants. The test stimuli were real objects (paper smiley faces) of two different reflectances, dark gray (17% reflectance) and light gray (54% reflectance). In Experiment 1, the test stimuli were viewed against a white (90% reflectance) surround, and in Experiment 2, against a black (4.6% reflectance) surround. In Experiments 1 and 2, the illumination was changed between familiarization and test phases of each trial. In Experiment 3, the reflectance of the surround was changed from white to mid gray (28.5% reflectance) between familiarization and test phases of each trial. With the white surround, the infants preferred the face with the novel reflectance, consistent with the presence of lightness constancy. With the black surround, the infants showed no preference between faces with novel reflectance vs. novel luminance. With the changing surround, the infants showed a small preference for the stimulus with the novel ratio, as opposed to the stimulus with the novel reflectance and the novel luminance. The results are discussed in the context of adult cues for lightness constancy, including white anchor points and local luminance ratios.

Purpose To determine whether neuroretinal function differs in healthy adult males and females under and over the age of 50 years. Methods This study included one eye from each of 50 normal subjects (29 females and 21 males). Neuroretinal function was assessed using first-order P1 implicit times (IT) and N1-P1 amplitudes (AMP) obtained from photopic multifocal electroretinograms (mfERG). To assess local differences, retinal maps of local IT and (separately) AMP averages were constructed for each subject group. To examine global differences, each subject's 103 ITs and (separately) AMPs were also averaged to create whole eye averages. Subsequently, retinal maps and whole eye averages of one subject group were compared to those of another. Results In subjects <50 years old, neuroretinal function differed significantly between the males and females: local ITs were significantly shorter at 83 of the 103 tested retinal locations, and whole eye IT averages were shorter (P=0.015) in the females compared to the males. In contrast, no analysis indicated that the males and females >50 years old were significantly different. A sub-analysis showed that the females who reported a hysterectomy (n=5) had the longest whole eye ITs of all subject groups (P≤0.0013). In the females who did not report a hysterectomy, neuroretinal function was worse in the females >50 years old compared to the females <50 years old: local ITs were significantly longer at 62 of the 103 retinal locations tested, and whole eye IT averages tended to be greater (P=0.04). Conversely, ITs were not statistically different between the younger and older males. AMP did not differ between the sexes. Conclusions mfERG IT differs between males and females, depending on age group and hysterectomy status.