A multifocal electroretinogram model predicting the development of diabetic retinopathy

Abstract

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.

Multifocal Electroretinography in HIV-Positive Patients without Infectious Retinitis

“…Multifocal ERG has been used to localize focal retinal damage occurring in numerous diseases and disorders 20,21,22,23,24,25,26,27 and has been proven to be a reliable diagnostic tool in clinical settings. Mulifocal ERG can measure the function of the outer retina as well as the inner retina.…”

Glial and neuronal dysfunction in streptozotocin-induced diabetic rats

“…A reduction in amplitude of the response to a contrast reversing pattern checkerboard (pattern ERG) has also been observed in eyes that do not have overt clinical signs of retinopathy [6]. More recent studies using the multifocal ERG show that local timing delays can predict those patches of retina that will go on to develop nonproliferative diabetic retinopathy [7,8]. Thus, in general, studies suggest that functional responses arising from postreceptoral pathways, such as oscillatory potentials [9], the photopic negative response [10] and the visual evoked potential [9], decline before outer retinal responses in the course of diabetic eye disease.…”

Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

“…Diabetic retinopathy is classified as a microvascular disease and has been empirically lumped together with diabetic nephropathy and neuropathy for decades. However, modern technologies, such as multifocal electroretinography and microperimetry, which assess neuroglial function in correlation with the structure of the human diabetic retina, have allowed diabetic retinopathy, with its complex pathology and divergent dynamics and disparities, to be distinguished from nephropathy and neuropathy [6][7][8][9]. Discussion of the risk factors relevant to specific damage to target tissues may help to explain these disparities.…”