Longitudinal Assessment of Ellipsoid Zone Integrity, Subretinal Hyperreflective Material, and Subretinal Pigment Epithelium Disease in Neovascular Age-Related Macular Degeneration

Abstract

Purpose: To assess longitudinally the effect of anti-vascular endothelial growth factor (VEGF) treatment on ellipsoid zone (EZ) integrity, subretinal hyperreflective material (SHRM), and the sub-retinal pigment epithelium (sub-RPE) compartment in eyes with neovascular age-related macular degeneration (nAMD).

Design: Post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase 2 study comparing brolucizumab 6 mg with aflibercept 2 mg over 56 weeks.

Participants: Participants with treatment-naïve nAMD at the initiation of the trial were included in the analysis.

Methods: Eyes were evaluated with spectral-domain OCT at 4-week intervals in the OSPREY trial (n = 81). Spectral-domain OCT scans collected from each visit were segmented automatically using a proprietary, machine learning-enabled higher-order feature-extraction platform for retinal layer, SHRM, and sub-RPE boundary lines, which were evaluated and corrected as needed by masked trained graders. The current analysis focused only on patients evaluated with the Cirrus (Zeiss) platform (n = 28).

Main outcome measures: Outcome measures included change from baseline in EZ-RPE (i.e., photoreceptor outer segment) volume, EZ-RPE central subfield thickness (CST), total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume. The correlation between each of these measures and best-corrected visual acuity (BCVA) at each visit was evaluated.

Results: EZ-RPE volume and EZ-RPE CST showed significant increases, and total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume showed significant decreases from baseline at each visit from weeks 4 through 56 (P < 0.05 at each visit). Ellipsoid zone integrity measures and SHRM volume correlated significantly with BCVA at most visits (P < 0.05). No significant correlation was found between total sub-RPE volume and BCVA.

Conclusions: EZ integrity, SHRM, and sub-RPE disease features in eyes with nAMD showed improvement as early as week 4 of anti-VEGF treatment. EZ integrity measures and SHRM volume were predictors of visual acuity over the first year of treatment.

Keywords: Ellipsoid zone; OCT; neovascular age-related macular degeneration; subretinal hyperreflective material; sub–retinal pigment epithelium.

Figure 1.. Change in EZ Integrity.

(A) Mean change from baseline in EZ-RPE volume. (B) Mean change from baseline in EZ-RPE CST. (C) Representative B-scans (top) and en face EZ-RPE thickness maps (bottom) from the OSPREY study, showing improvement in EZ integrity with treatment. CST = central subfield thickness; EZ = ellipsoid zone; RPE = retinal pigment epithelium.

Figure 2.. Correlations with BCVA.

Pearson correlation coefficients between OCT outcome measures and BCVA (ETDRS letters) at each study visit. Red indicates a positive correlation, and blue indicates a negative correlation. Lighter tints correspond to weaker correlations. *P≤.05; **P≤.01; ***P≤.001. BCVA = best corrected visual acuity; CST = central subfield thickness; ETDRS = Early Treatment Diabetic Retinopathy Study; EZ = ellipsoid zone; OCT = optical coherence tomography; RPE = retinal pigment epithelium; SHRM = subretinal hyperreflective material.

Figure 3.. Change in SHRM.

(A) Mean change from baseline in SHRM volume. (B) Mean change from baseline in SHRM CST. (C) Representative B-scans for 2 subjects (first subject in rows 1 and 2; and second subject in rows 3 and 4 from the OPSREY study, showing reduction in SHRM with treatment. Rows 2 and 4 are the same as rows 1 and 3, respectively, but with SHRM highlighted in yellow. CST = central subfield thickness; SHRM = subretinal hyperreflective material.

Figure 4.. Change in total sub-RPE volume.

(A) Mean change from baseline in total sub-RPE volume. (B) Representative B-scans (top) and en face sub-RPE thickness maps (bottom) for 1 subject from the OSPREY study, showing reduction in sub-RPE volume with treatment. RPE = retinal pigment epithelium.