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

James J.L Tee,Yesa Yang,Angelos Kalitzeos,Andrew Webster,James Bainbridge,Michel Michaelides

doi:10.1016/j.ajo.2018.10.003

James J.L Tee, Yesa Yang + Show 4 more

Open Access

https://doi.org/10.1016/j.ajo.2018.10.003

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Abstract

PurposeThis 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).DesignProspective, observational cohort study.MethodsThirty-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.ResultsBaseline EZW and EZA measurements were 1963.6 μm and 3.70 mm2, respectively. The mean EZW progression rate was 233.6 μm per year, and the mean EZA rate was 0.67 mm2 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.ConclusionsEZ 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.

Highlights

R ETINITIS PIGMENTOSA (RP) CAUSED BY SEQUENCE variants in the retinitis pigmentosa GTPase regulator gene (RPGR) constitute around threequarters of all X-linked (XL) RP,[1,2,3,4] with RP2 variants predominantly accounting for the remaining cases.[1,3,5,6,7] There is particular interest in RPGR-associated RP, and recently commenced gene therapy trials are underway (NCT03116113, NCT03252847, and NCT03316560)
VTotal and V30 are volumetric metrics that characterize the total amount of sensitivity in the hill-of-vision as defined by the entire test grid (VTotal) or that contained within a central circle of 308 radius (V30)
Associations between EZ width (EZW) and best corrected visual acuity (BCVA)/contrast sensitivity (CS) were studied on 76 eyes of 38 subjects

Summary

Introduction

R ETINITIS PIGMENTOSA (RP) CAUSED BY SEQUENCE variants in the retinitis pigmentosa GTPase regulator gene (RPGR) constitute around threequarters of all X-linked (XL) RP,[1,2,3,4] with RP2 variants predominantly accounting for the remaining cases.[1,3,5,6,7] There is particular interest in RPGR-associated RP, and recently commenced gene therapy trials are underway (NCT03116113, NCT03252847, and NCT03316560). Spectral-domain optical coherence tomography (OCT) is in widespread use as an imaging modality to study retinal structure in a myriad of diseases.

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