Validating Ellipsoid Zone Area Measurement With Multimodal Imaging in Choroideremia

PURPOSE: To assess en face ellipsoid zone (EZ) maps of remaining retinal structure as outcome measures for the future clinical research in patients with choroideremia. METHODS: Twenty eyes from 12 patients with a confirmed genetic diagnosis of choroideremia were included retrospectively from a single site. From spectral domain-optical coherence tomography volume scans, slabs including the EZ were manually segmented to create the en face EZ maps. The preserved EZ area was measured by two graders. Lengths of the EZ were recorded at 0°, 45°, 90°, and 135°. The intraclass correlation coefficients and Bland–Altman plots were used to show intergrader agreement. The Pearson correlation coefficient evaluated the correlation between length and area. A Bland–Altman plot compared en face EZ and the preserved fundus autofluorescence area. RESULTS: Measurements of EZ area by two graders showed excellent agreement with an intraclass correlation coefficient of 0.992 (95% confidence interval, 0.980–0.997). A Pearson correlation analysis showed that the existing marker for preserved photoreceptor (horizontal EZ length) was correlated with the area (r = 0.722). The average EZ length in four meridians showed a much better correlation with the EZ area (r = 0.929). The fundus autofluorescence area was found to be a mean of 0.45 ± 0.99 mm(2) greater than the EZ area. CONCLUSIONS: EZ area measurement provides excellent intergrader reliability, although the process is time consuming. We propose a less time-consuming alternative to estimate the EZ by using the average EZ band length in meridians. Our data also suggest that the loss of photoreceptor inner segments is an early change in choroideremia and may happen before the loss of the retinal pigment epithelium. TRANSLATIONAL RELEVANCE: En face EZ mapping is a potential tool for future clinical trials to quantify preserved photoreceptor structure in choroideremia.