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

Abstract

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 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.

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.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Horizontal transfoveal spectral domain optical coherence tomography scans of both eyes of a subject with retinitis pigmentosa GTPase regulator gene–associated retinopathy. Vertical arrows mark the extent of the ellipzoid zone on the scans. The ellipzoid zone width was 7163 μm in the left eye (top) and 1534 μm in the right eye (bottom). Note that the large interocular difference found in this subject is not in keeping with the cohort.
Figure 2
Figure 2
(Top) En face images of the ellipzoid zone area generated from high-resolution macular volume scans of 2 subjects with retinitis pigmentosa GTPase regulator gene–associated retinopathy. (Bottom) Delineation and quantification of respective ellipzoid zone areas from the top images. Images on the right column were generated from a macular volume scan acquired with an average of 12 images per b-scan.
Figure 3
Figure 3
Bland-Altman plot showing interocular differences in ellipzoid zone width (EZW) at baseline. Interocular difference for each individual is plotted on the y axis against the mean EZW value of both eyes. The long horizontal dashed line refers to the mean of interocular differences; horizontal dotted lines denote 95% limits of agreement.
Figure 4
Figure 4
Linear trend lines indicating progression, plotted from observations of ellipzoid zone width (EZW). Each line represents the right eye of a subject. Data from 28 subjects who underwent ≥3 observations over an interval >1 year are shown.
Figure 5
Figure 5
(Left) Scatterplots of ellipzoid zone width (EZW) and (right) ellipzoid zone area (EZA), both plotted against subjects' age. An exponential decline is evident for both. The reader is directed to Table 5 for further information on exponential decline rates calculated with the mixed-models method.

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