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Emma Stackpole, Yvette Conley, Mark Perlin, Michael B Gorin, Steven Nusinowitz; Rod- and Cone- Mediated Dark-Adaptation Kinetics in Pre-Clinical Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2018;59(9):1259.
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© ARVO (1962-2015); The Authors (2016-present)
To test the hypothesis that the kinetics of cone and rod dark-adaptation at multiple locations within the macular region can provide a sensitive means of detecting early retinal dysfunction in an at-risk population of individuals without clinical evidence of early AMD as compared to clinically normal, low- genetic risk individuals.
Preliminary data from eighteen subjects (mean age = 60.0 ± 4.3 years, range 51.5 to 68.9 years) participated in this prospective study. Subjects were recruited based on the presence of a family history of AMD in one or both parents. The “at-risk” participants were screened for variants in genes commonly associated with AMD. Seventeen risk SNPs were included in the computation of the genetic risk. Following a significant photobleach, dark-adapted thresholds were measured repeatedly over 40 minutes using the Medmont DAC Perimeter. Threshold measurements were made simultaneously at four retinal locations centered on the fovea at eccentricities of 6o (0o, 90o, 180o, and 270o). For each subject, the recovery curves were analyzed using a Markov chain model fitting algorithm to extract the time at which the cone-rod (C-R) break occurs.
The average (+ 1 sd) time of the cone-rod break for “at risk” group of subjects was 14.4 (+2.1) minutes (range = 11.3 to 18.2 minutes) as compared to 12.01 (+0.62) minutes (range = 11.3 to 13.1) for normal age-matched controls without a family history of AMD (t=2.24, df= 20, p =0.04). There were no significant differences in the time of the cone-rod break between eyes (14.5 vs 14.8 minutes, t=-0.63, df=14, p=0.54) nor were there significant differences across the four retinal locations in the at-risk cohort. Of the 18 subjects in the “at-risk” cohort, two were clearly identified as outliers with C-R breaks of 19.1 and 18.4 minutes and two were borderline with C-R breaks of 16.6 and 16.4 minutes. A consistent effect of delayed timing with disease classification was observed. Higher genetic risk is generally associated with delayed timing of the cone-rod break.
A subset of individuals with elevated genetic risks for the development of AMD, but who do not yet manifest clinical and retinal structural changes, will demonstrate delayed dark-adaptation following a significant photopigment bleach. Whether delayed dark-adaptation combined with genetic risk is predictive of the development of AMD, is under study.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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