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.

• Authors: Justis P Ehlers, Robert Zahid, Peter K Kaiser, Jeffrey S Heier, David M Brown, Xiangyi Meng, Jamie Reese, Thuy K Le, Leina Lunasco, Ming Hu, Sunil K Srivastava
• Journal: Ophthalmology. Retina (Ophthalmol Retina) Vol. 5 Issue 12 Pg. 1204-1213 (12 2021) ISSN: 2468-6530 [Electronic] United States
• PMID: 33640493 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Recombinant Fusion Proteins
• aflibercept
• Receptors, Vascular Endothelial Growth Factor
• brolucizumab

Topics

• Aged
• Angiogenesis Inhibitors (administration & dosage)
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Female
• Fluorescein Angiography (methods)
• Follow-Up Studies
• Fundus Oculi
• Humans
• Male
• Receptors, Vascular Endothelial Growth Factor (administration & dosage, antagonists & inhibitors)
• Recombinant Fusion Proteins (administration & dosage)
• Retinal Pigment Epithelium (diagnostic imaging, drug effects)
• Tomography, Optical Coherence (methods)
• Visual Acuity
• Wet Macular Degeneration (diagnosis, drug therapy)