Natural History Study of Retinal Structure, Progression, and Symmetry Using Ellipzoid Zone Metrics in RPGR-Associated Retinopathy

Purpose This is a quantitative study of retinal structure, progression rates, and interocular symmetry in retinitis pigmentosa GTPase regulator gene ( RPGR )-associated retinopathy using spectral-domain optical coherence tomography (OCT). Design Prospective, observational cohort study. Methods Thirty-eight subjects at Moorfields Eye Hospital in London were assessed with 2 spectral-domain OCT–derived ellipzoid zone (EZ) metrics with repeatability assessments. EZ width (EZW) measurements were made on transfoveal line scans. En face images of the EZ area (EZA) were generated from high-density macular volume scans and were quantified. Baseline size, progression rate, symmetry, associations with age and genotype, and baseline structure–function correlation were investigated. Results Baseline EZW and EZA measurements were 1963.6 μm and 3.70 mm 2 , respectively. The mean EZW progression rate was 233.6 μm per year, and the mean EZA rate was 0.67 mm 2 per year. Relative interocular difference as an index of symmetry was 3% for both metrics, indicating good baseline symmetry in general—although significant variation existed across the cohort. Analysis of variance found a significant effect of age but not genotype on EZ dimension and progression rates. Larger EZ dimension and greater progression were seen in younger subjects. A positive correlation between EZ dimension and progression was evident. Overall exponential decline rates of 8.2% with EZW and 15.5% with EZA were obtained. Good functional correlation was found with EZW demonstrating stronger correlation; however, EZA correlation with function was also significant. Conclusions EZ metrics are sensitive structural biomarkers for measuring residual extent and progression in RPGR -associated retinopathy. Our elucidation of the natural history will provide clinicians and patients with more knowledge about the condition and inform the design and interpretation of interventional trials.