Rod and Cone Mediated Function in Retinal Disease

National Eye Institute

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Abstract

Specific Aim 1: To establish the normal ranges of dark-adapted retinal sensitivities for the Medmont, and for RF hyperacuity function on the Display++ monitor in healthy volunteers. Dark-adapted retinal sensitivity has been measured with the Medmont from 35 healthy volunteers aged between 16 and 59 years. To be examine rod photoreceptor function, we developed a scotopic version of radial frequency (RF) hyperacuity test using the Display++. Such a scotopic shape discrimination task has not previously been described. We found that humans are sensitive to small deformations from circularity in arcs presented a few degrees outside the fovea. We concluded that sensitivity to our stimuli required a healthy rod matrix, as contour information is being integrated across an extended section of retina (See reference 1 in section 24 below). We havemeasured scotopic shape discrimination from 39 healthy volunteers aged between16 and 80 years (some participants also completed retinal sensitivity and dark adaptation testing). 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. Dark adaptation has been measured with the Medmont from 32 healthy volunteers aged between 16 and 53 years (participants were the same recorded for retinal sensitivity). Specific Aim 3: To quantify local changes in rod and cone photoreceptor function across the retina in participants with retinal disease. Delayed dark adaptation (DA) is an early phenotypic marker in late onset retinal degeneration (L-ORD) and may precede symptoms and retinal changes. We measured rod-mediated function within, and around retinal areas with structural changes in L-ORD. Rod function was most severely affected in the temporal retina where structural changes have been first observed. Rod function was best preserved in the nasal and far temporal retina, but functional rods may still be present in the macula as demonstrated with overnight dark adaptation. The spatial gradient in DA abnormality suggests abnormal retinal function precedes degeneration. The combined results suggest rods may be preserved after onset of symptoms, and retinal changes follow perhaps because of abnormal retinal/RPE function. (See reference 2 in section 24 below). In AMD patients, loss of rod sensitivity precedes loss of photopic sensitivity and dark adaptation may also be markedly delayed. Although scotopic sensitivity and dark adaptation have been used to characterize AMD severity, we and others report low sensitivity for detecting functional changes in early AMD. We hypothesized that scotopic shape discrimination may have good sensitivity in detecting any changes in rod function in early AMD. As a first step towards this goal we examined scotopic shape discrimination in AMD patients with and without subretinal drusenoid deposits. There was a large effect of disease severity on test performance, which suggests that rod cell integrity may in disturbed in AMD (See reference 3 in section 24 below). We examined spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity. Scotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with subretinal drusenoid deposits or IS/OS band disruption, and at 32% of loci with no local structural changes. (See reference 4 in section 24 below). 1. Flynn OJ, Jeffrey BG. Scotopic contour and shape discrimination using radial frequency patterns. J Vis 2019 Feb 1; 19(2) doi: 10.1167/19.2.7. 2. Jeffrey BG, Huryn L, Sieving PA, Cukras CA. Spatial Variation of Rod-Mediated Function in Late-Onset Retinal Degeneration (L-ORD) ARVO Abstract. Invest Ophthalmol Vis Sci. 2019; Abstract nr 4495. 3. Flynn OJ, Cukras CA, Huryn L, Jeffrey BG. Scotopic shape discrimination in AMD patients and healthy volunteers ARVO Abstract. Invest Ophthalmol Vis Sci. 2019; Abstract nr 1208. 4. Flynn OJ, Cukras CA, Jeffrey BG. Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits. Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2411-2421. doi: 10.1167/iovs.17-22874.