Rod and Cone Mediated Function in Retinal Disease

National Eye Institute

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Abstract

The first two Aims of this protocol require establishing the normal ranges for dark-adapted retinal sensitivity and the kinetics of dark adaptation using a new instrument, the Medmont dark-adapted chromatic (DAC) perimeter. Specific Aim 1: To establish the normal ranges of dark-adapted retinal sensitivities for the Medmont red and blue stimuli in healthy volunteers. With 2-color dark-adapted perimetry, calculation of the difference in dark-adapted retinal sensitivity to blue and red stimuli is fundamental to determining whether a sensitivity at a given retinal location is mediated by rods and/or cones. We have established preliminary normal values for mean ( SD) dark-adapted retinal sensitivities for the blue (57.9 1.9 dB) and red (35.5 1.6 dB) stimuli, and for the difference in sensitivity between these two colors (22.5 1.7 dB). The mean difference obtained with the Medmont DAC is close to previously reported difference values of 18 dB and 19 dB for LCD and tungsten sources respectively. The direct implication of our result is that a difference value of less than 19.1 dB (mean 2SD) would indicate abnormal rod function in a patient. Dark-adapted retinal sensitivity was not significantly correlated with age although there was a trend for lower blue sensitivity with age. This question will be more thoroughly evaluated in the coming year by recording from a greater number of healthy volunteers and from older subjects (oldest healthy volunteer to date was 63 years). Specific Aim 2: To establish the normal ranges for the kinetics of dark adaptation for the Medmont DAC blue and red stimuli in healthy volunteers. The time course of dark adaptation has historically been measured clinically following exposure to an achromatic background light that bleaches approximately 50-100% of rhodopsin. Given that dark adaptation can be very delayed (several hours) in patients with AMD and some genetic disorders (e.g. Fundus Albipunctatus) and many patients with retinal degenerations have marked photo aversion, we are seeking to examine the kinetics of dark adaptation to smaller bleaches. We examined the kinetics of dark adaptation to a range of bleaches (30-60%) obtained by varying background light exposures (duration, intensity, color). To date, a 30% rhodopsin bleach obtained by a 5-minute exposure to 505 nm light has been tolerated by all participants and this will be our default for AMD subjects (see below). Specific Aim 3: To quantify local changes in rod and cone photoreceptor function across the retina in participants with retinal disease. Dark adaptation kinetics are known to be delayed in AMD patients. In preparation for a larger study, we examined DA kinetics in 5 participants with varying levels of AMD severity. We examined two spatial patterns and used vary levels of rhodopsin bleaching (30%-60%). We found that the DA kinetics vary with spatial eccentricity and that a 30% bleach will likely be sufficient to characterize AMD patients. In two of the five patients tested, we saw no evidence of rod recovery over the 30 min following a bleach. We also measured dark-adapted retinal sensitivity in six patients with ABCA4 retinopathy and relatively good acuity (20/40 or better). We are seeking to determine whether peripheral rod function is altered in this disease but will need to test a greater number of subjects before we are able to examine this question.