Assessment of Interocular Disease Progression in Retinitis Pigmentosa GTPase Regulator (RPGR)-associated Retinopathy with Quantitative Fundus Autofluorescence (FAF) Image Analysis

Abstract

Purpose : Parafoveal hyperautofluorescent rings are present in eyes with retinitis pigmentosa (RP). Ring size is related to visual function. RPGR retinopathy is a particularly severe form of RP and is an important target for gene therapy trials. We aim to quantitatively analyze ring constriction with FAF imaging and characterize the natural history of this condition.

Methods : This prospective observational study supplemented with retrospective FAF images was conducted in Moorfields Eye Hospital, UK. All subjects have molecular confirmation of mutations in RPGR resulting in RP. Spectralis HRA (Heidelberg, Germany) was used for image acquisition. Ring area measurements were performed with Spectralis RegionFinder software. The latest FAF image from each eye was measured on two occasions to construct a Bland Altman plot for assessment of intra-observer repeatability. Ring area measurements were graphed with Excel trendline to obtain individual rates of constriction.

Results : Forty-six subjects. Data presented as mean±SD unless stated. Repeatability differences were 0.10±0.46 mm² and 0.11±0.56 mm² for right and left eyes. 95% limits of agreement were -0.80 to 1.00 mm² and -0.99 to 1.21 mm² for right and left eyes. Age at baseline was 16.3±7.9 years. Follow-up period was 43±34 months. Baseline ring area was 11.83±13.40 mm² for right eyes and 11.44±13.17 mm² for left eyes. Interocular symmetry at baseline was investigated, Spearman’s r= 0.946, p<0.0001 indicated strong interocular correlation. Wilcoxon sign-rank test p-value= 0.233 indicated insignificant interocular baseline difference. Rate of ring constriction was obtained for 40 subjects with longitudinal data. This was 1.50±1.99 mm²/year for right eyes and 1.33±1.90 mm²/year for left eyes. Interocular symmetry of constriction rates were probed. Spearman’s r= 0.832, p<0.0001 indicated strong interocular rate correlation, Wilcoxon sign-rank test p-value= 0.337 indicated that the interocular rate difference was insignificant. Annual constriction rate was 12.68% and 11.28% for right and left eyes.

Conclusions : There is interocular symmetry in general. FAF ring area metrics are sensitive in quantifying progression and can be used together with other modalities in future trials where one eye could serve as control for the other undergoing treatment.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.