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Lawrence Chan, Jessica Wong, Shane Griffin, Stephanie K Lynch, Travis C Porco, Austin John Roorda, Jacque L Duncan; Variability in high resolution cone spacing measures in eyes with retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2021;62(8):19.
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To evaluate inter-visit, intragrader, inter-grader, and inter-ocular variability in cone spacing measures at baseline in a clinical trial of sustained-release ciliary neurotrophic factor (CNTF) treatment in retinitis pigmentosa using confocal adaptive optics scanning laser ophthalmoscopy (AOSLO) images.
A single-center, double-masked clinical trial (NCT01530659) of patients with retinitis pigmentosa or Usher syndrome type 2 or 3 randomly assigned 1 eye in each patient to receive a high- or low-dose (20 or 5 ng/day) CNTF-secreting implant and the contralateral eye to receive sham surgery. AOSLO was used to image the macula in each eye at 2 baseline visits separated by no more than 1 month to identify regions of interest (ROIs) of 100 arcmin2 with at least 50 contiguous, unambiguous cones. Cones were marked by 2 independent, trained graders at baseline. Cone spacing Z-scores (standard deviations from the mean of 37 normal subjects) were reported to account for the known relationship between cone spacing and eccentricity from the fovea. Cone spacing Z-scores from all ROIs in each eye were averaged and compared to the contralateral eye of each patient. We computed the agreement intraclass correlation coefficient (ICC) between mean Z-scores of sham- and CNTF-treated eyes.
22 participants were enrolled ranging in age from 19-66 (mean 39.8±11.9) years, and 13 were male. Intragrader repeatability of measurements for the same visit showed ICC=0.88 and 0.86 for the 2 graders. Intragrader agreement ICC of cone spacing measurements between 2 baseline visits was excellent (0.82, 95% CI=0.80 to 0.83), as was agreement ICC of cone spacing scores between the graders at the baseline visit (ICC=0.78, 95% CI=0.76 to 0.80). The agreement ICC between the mean Z-scores for each of the 2 eyes at baseline was excellent (ICC=0.94, 95% CI=0.86 to 0.97).
Cone spacing measures were repeatable within a single grader at the same visit and between visits separated by no greater than 1 month, and were repeatable between graders. Cone spacing measures were also similar between contralateral eyes of patients with retinitis pigmentosa. Interocular agreement of cone spacing measures suggests the contralateral eye may serve as a control for uniocular treatments. AOSLO cone spacing measurements may be a reliable and sensitive means of monitoring disease progression in patients with retinitis pigmentosa.
This is a 2021 ARVO Annual Meeting abstract.
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