Progression to complete retinal pigment epithelium and outer retinal atrophy (cRORA): post hoc analysis of the GATHER1 trial.

Autor: Corradetti G; Department of Ophthalmology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA., Karamat A; Doheny Image Reading and Research Lab, Doheny Eye Institute, 150 N. Orange Grove Blvd, Pasadena, CA, 91103, USA., Srinivas S; Doheny Image Reading and Research Lab, Doheny Eye Institute, 150 N. Orange Grove Blvd, Pasadena, CA, 91103, USA., Lindenberg S; Doheny Image Reading and Research Lab, Doheny Eye Institute, 150 N. Orange Grove Blvd, Pasadena, CA, 91103, USA., Velaga SB; Doheny Image Reading and Research Lab, Doheny Eye Institute, 150 N. Orange Grove Blvd, Pasadena, CA, 91103, USA., Corvi F; Doheny Image Reading and Research Lab, Doheny Eye Institute, 150 N. Orange Grove Blvd, Pasadena, CA, 91103, USA., Attiku Y; Doheny Image Reading and Research Lab, Doheny Eye Institute, 150 N. Orange Grove Blvd, Pasadena, CA, 91103, USA., Nittala MG; Doheny Image Reading and Research Lab, Doheny Eye Institute, 150 N. Orange Grove Blvd, Pasadena, CA, 91103, USA., Desai D; Formerly Astellas Pharma Global Development, Inc., Northbrook, IL, USA., Zhu L; Formerly Astellas Pharma Global Development, Inc., Northbrook, IL, USA., Abulon D; Astellas Pharma US, Northbrook, IL, USA., Sadda SR; Doheny Image Reading and Research Lab, Doheny Eye Institute, 150 N. Orange Grove Blvd, Pasadena, CA, 91103, USA. ssadda@doheny.org.; Department of Ophthalmology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA. ssadda@doheny.org.
Jazyk: angličtina
Zdroj: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie [Graefes Arch Clin Exp Ophthalmol] 2024 Nov 14. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.1007/s00417-024-06676-7
Abstrakt: Purpose: Determine rates of progression of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) to complete retinal pigment epithelium and outer retinal atrophy (cRORA) and rates of progression of drusen to iRORA/cRORA in eyes with geographic atrophy (GA) treated with avacincaptad pegol (ACP).
Methods: Post hoc analysis of the GATHER1 prospective, randomized, double-masked Phase II/III study that evaluated ACP 2 mg vs. sham. Optical coherence tomography (OCT) data from GATHER1 were transferred to the Doheny Image Reading and Research Lab for masked analysis by readers experienced with Classification of Atrophy Meeting (CAM) grading features. Regions of OCT volume scans more than 500 µm from the border of GA lesions were evaluated at baseline and at months 6, 12, and 18. Participants with iRORA and/or drusen (≥ 40 µm height on OCT) at baseline were included in the analysis.
Results: The proportion of eyes progressing from iRORA to cRORA in the ACP 2 mg group was 5.0%, 15.0%, and 20.0% at months 6, 12, and 18 respectively, as compared with 11.8%, 30.2%, and 41.8% of eyes in the sham group. The proportion of ACP 2 mg-treated eyes progressing from drusen to iRORA or cRORA was 3.8%, 7.6%, and 7.6% at months 6, 12, and 18 compared with 15.9%, 18.1%, and 27.2% of sham-treated eyes.
Conclusions: Rates of progression from iRORA to cRORA and drusen to iRORA/cRORA were reduced in eyes treated with ACP 2 mg vs. sham, with increasing separation between groups over time, suggesting early intervention may slow disease progression.
Trial Registration: ClinicalTrials.gov identifier: NCT02686658. Date of registration: February 16, 2016.
Key Messages: What is known Geographic atrophy is an advanced form of age-related macular degeneration (AMD) that leads to irreversible vision loss, presenting a significant public health unmet need. The Classification of Atrophy Meeting (CAM) group recommended a new nomenclature for advanced AMD lesions, based on the affected anatomical layers on optical coherence tomography. Accordingly, the terms incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA) were introduced (Guymer et al., Ophthalmology 127:394-409, 2020; Sadda et al., Ophthalmology 125:537-548, 2018). What is new GATHER1 post hoc analysis shows that treatment with avacincaptad pegol (ACP) 2 mg decreases the proportion of eyes that progress from iRORA to cRORA, and from drusen to iRORA or cRORA, compared with sham, over 6, 12, and 18 months. These findings suggest a potential role for ACP in delaying the progression of existing pre-atrophic AMD lesions.
Competing Interests: Declarations Ethics approval The GATHER1 trial was performed in accordance with the tenets of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines [13]. The appropriate ethics committee or institutional review board at each study center involved in the study (80 centers) approved the protocol [13]. Consent to participate Written informed consent was obtained from all participants [13]. Disclosure statement SriniVas R Sadda- although the author is the editor of the journal, there was no involvement with the peer review process for this article. Competing interests GC has received lecture fees from Nidek. AK, SS, SL, SBV, FC, YA, and MGN have no financial disclosures. SR Sadda has consulted/advised for: Apellis Pharmaceuticals, Inc.; Amgen Inc.; AbbVie/Allergan, Inc.; Samsung Bioepis; Biogen; Boehringer Ingelheim; Iveric Bio; Novartis; Roche/Genentech; Bayer Healthcare Pharmaceuticals; Regeneron Pharmaceuticals, Inc.; Pfizer Inc.; Astellas; Nanoscope Therapeutics; Janssen Pharmaceuticals, Inc.; CenterVue, Inc.; Optos, Inc.; and Heidelberg Engineering; has received lecture fees/speakers bureau fees from: Heidelberg Engineering; Roche/Genentech; Novartis; and Optos, Inc.; and has received research equipment from: CenterVue, Inc.; Optos, Inc.; Carl Zeiss Meditec; Topcon Medical Systems, Inc.; Heidelberg Engineering; and Nidek Inc. SR Sadda, the corresponding author, is an editor of the journal; however, there was no involvement with the peer review process for this article. DD and LZ are former employees of Astellas, and DA is an employee of Astellas.
(© 2024. The Author(s).)
Databáze: MEDLINE
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