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. 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. We examined dark adapted thresholds and dark-adaptation kinetics in AMD participants who were categorized into five AMD severity groups based on fundus features. Elevation in DA thresholds across the central retina worsened with increasing AMD severity. RIT increased with AMD group and eccentricity (P<0.001 for both). RITslope, defined as the change in RIT with retinal eccentricity, increased with AMD severity (P<0.0001). Three dark-adaptation phenotypes emerged: normal dark-adapted function (DA1), normal thresholds but slowed DA (DA2), and elevated DA thresholds with slowed DA kinetics (DA3). Aberrant dark adaptation occurred at 32% of loci with no local structural changes and 100% of loci with SDD or ellipsoid band disruption.