TY - JOUR
T1 - Longitudinal Assessment of Ellipsoid Zone Integrity, Subretinal Hyperreflective Material, and Subretinal Pigment Epithelium Disease in Neovascular Age-Related Macular Degeneration
AU - Ehlers, Justis P.
AU - Zahid, Robert
AU - Kaiser, Peter K.
AU - Heier, Jeffrey S.
AU - Brown, David M.
AU - Meng, Xiangyi
AU - Reese, Jamie
AU - Le, Thuy K.
AU - Lunasco, Leina
AU - Hu, Ming
AU - Srivastava, Sunil K.
N1 - Funding Information:
The authors thank all the OSPREY investigators. Editorial support was provided by IMPRINT Science, New York, NY, USA, and was funded by Novartis Pharmaceuticals. This work was funded by a research grant provided by Novartis Pharmaceuticals, East Hanover, NJ, USA, and also supported through the NIH/NEI K23-EY022947-01A1.
Funding Information:
Supported by Novartis Pharmaceuticals, East Hanover, New Jersey, which participated in the design of the study, conducting of the study, data collection, data management, and data analysis; interpreted the data; and prepared, reviewed, and approved the manuscript. Also supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: K23-EY022947-01A1; R34-EY029308 [J.P.E.]); The Tom and Maryanne Wagner Advanced Imaging Research Fund (J.P.E.); The Betty Powers Optical Coherence Tomography Research Fund (J.P.E.); The Norman C. and Donna L. Harbert Endowed Chair Fund (J.P.E.); and The Tony and Leona Campane Image-Guided Surgery and Advanced Image Analysis Research Fund (J.P.E.). Editorial support was provided by IMPRINT Science, New York, New York, and was funded by Novartis Pharmaceuticals.
Funding Information:
The authors thank all the OSPREY investigators. Editorial support was provided by IMPRINT Science, New York, NY, USA, and was funded by Novartis Pharmaceuticals. This work was funded by a research grant provided by Novartis Pharmaceuticals, East Hanover, NJ, USA, and also supported through the NIH/NEI K23-EY022947-01A1. The author(s) have made the following disclosure(s): J.P.E.: Consultant ? Novartis, Leica/Bioptigen, Alcon, Allergan, Alimera, Thrombogenics, Aerpio, Genentech, Roche, Regeneron, Allegro; Financial support ? Oxurion, Ohio Department of Development TECH-13-059; Thrombogenics, Genentech, Regeneron, Alcon, Aerpio, Novartis, Zeiss; Patent ? Bioptigen/Leica. R.Z.: Employee ? Novartis. X.M.: Employee ? Novartis. P.K.K.: Consultant ? Novartis, Allergan, Regeneron, Bayer, Kanghong, Kodiak, RegenexBio. J.S.H.: Consultant ? 4DMT, Adverum, Aerie, Aerpio, Aldeyra, Allegro, Alzheon, Annexon, Apellis, Asclepix, Beaver-Visitec, Galimedix, Genentech, Gyroscope, iRenix, jCyte, Kala, Kanghong, NGM, Notal Vision, Novartis, Ocugenix, Oculis, Ocunexus, Ocular Therapeutix, Palatin, Pfizer, Regeneron, Regenxbio, Santen, Scifluor, Shire, Stealth, Tyrogenex, Voyant; Financial support ? Aerie, Aerpio, Apellis, Genentech, Graybug, Gyroscope, Hemera, Janssen R&D, KalVista, Kanghong, Novartis, Ophthotech, Optovue, Regeneron, Regenxbio, Stealth. D.M.B.: Consultant and Financial support ? Novartis, Heidelberg Engineering, Carl Zeiss Meditec. S.K.S.: Consultant ? Novartis, Bausch and Lomb, Allergan, Abbvie, Clearside, Eyepoint, Zeiss, Regeneron; Financial support ? Allergan. Supported by Novartis Pharmaceuticals, East Hanover, New Jersey, which participated in the design of the study, conducting of the study, data collection, data management, and data analysis; interpreted the data; and prepared, reviewed, and approved the manuscript. Also supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: K23-EY022947-01A1; R34-EY029308 [J.P.E.]); The Tom and Maryanne Wagner Advanced Imaging Research Fund (J.P.E.); The Betty Powers Optical Coherence Tomography Research Fund (J.P.E.); The Norman C. and Donna L. Harbert Endowed Chair Fund (J.P.E.); and The Tony and Leona Campane Image-Guided Surgery and Advanced Image Analysis Research Fund (J.P.E.). Editorial support was provided by IMPRINT Science, New York, New York, and was funded by Novartis Pharmaceuticals. Obtained funding: Ehlers
Publisher Copyright:
© 2021 American Academy of Ophthalmology
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Ellipsoid zone
KW - OCT
KW - neovascular age-related macular degeneration
KW - subretinal hyperreflective material
KW - sub–retinal pigment epithelium
UR - http://www.scopus.com/inward/record.url?scp=85106248861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85106248861&partnerID=8YFLogxK
U2 - 10.1016/j.oret.2021.02.012
DO - 10.1016/j.oret.2021.02.012
M3 - Article
C2 - 33640493
AN - SCOPUS:85106248861
VL - 5
SP - 1204
EP - 1213
JO - Ophthalmology Retina
JF - Ophthalmology Retina
SN - 2468-6530
IS - 12
ER -