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.