Symmetry Between Left and Right Eyes in Bietti Crystalline Dystrophy

Abstract

Purpose : Due to scarcity of eligible participants, treatment trials for rare inherited retinal diseases often employ the contralateral eye as an internal control. However, for people with Bietti Crystalline Dystrophy (BCD), there is uncertainty as to whether disease extent and course in one eye reflects that in the other. Therefore, we performed an observational clinical study with prospective and retrospective data aimed at evaluating the inter-eye symmetry of anatomical features and functional vision in individuals with BCD, with a focus on the number, area, and distribution of the characteristic retinal crystalline deposits.

Methods : Thirteen Australian and New Zealand participants with confirmed biallelic CYP4V2 mutations and a characteristic BCD fundus appearance underwent comprehensive multimodal clinical examination. Crystals visible on color fundus photography were manually counted and superimposed onto aligned fundus autofluorescence imaging. The distribution of fundus crystals and their phenotypic associations with areas of absent autofluorescence (absent-AF) were then analyzed. Spearman’s correlation coefficients (ρ), intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to quantify symmetry of functional and imaging parameters between eyes.

Results : Median participant age was 48 years, interquartile range 40–60 years. Nine (69%) were female, and five (38%) were of East Asian descent. Distance visual acuity ranged from 20/16 to light perception. Crystal density was higher in the foveal region, and decreased in the periphery. The peripapillary region and areas of well-demarcated absent-AF contained few crystals. Inter-eye correlation was high for fundus crystal area (ρ=1.00, 95% CI 1.00–1.00; ICC=0.97, 95% CI 0.88–0.99), fundus crystal count (ρ=0.98, 95% CI 0.92–1.00; ICC=0.97, 95% CI 0.89–0.99), and absent-AF area (ρ=0.88, 95% CI 0.53–0.98; ICC=0.98, 95% CI 0.90–0.99). Average foveal volume was moderately correlated between eyes (ρ=0.73, 95% CI 0.18–0.93; ICC=0.85, 95% CI 0.53–0.96). No significant correlation was found for foveal crystal count and area, average or central foveal thickness, best corrected visual acuity, and average macular or central foveal sensitivity.

Conclusions : This study demonstrated strong inter-eye symmetry measured by fundus crystal area, fundus crystal number, and absent-AF area. This data may influence the choice of outcome measures of future therapeutic trials for BCD.

This is a 2021 ARVO Annual Meeting abstract.