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Objective: To validate GATHER-1 inclusion criteria and the study’s primary anatomic end point by assessing the reproducibility of geographic atrophy (GA) measurements and factors that affect reproducibility. Design: Post hoc analysis of phase II/III clinical trial. Subjects: All 286 participants included in the GATHER-1 study. Methods: For each subject, blue-light fundus autofluorescence (FAF), color fundus photographs, fluorescein angiograms, and OCT scans were obtained on the study eye and fellow eye. Geographic atrophy area and other lesion characteristics were independently graded by 2 experienced primary readers. If the 2 readers differed on gradeability, GA area (> 10%) or other lesion characteristics, the image was graded by an arbitrator whose measurement or characterization was the final grade. Main Outcome Measures: The main outcome measures were gradeability and reproducibility of FAF imaging data. Imaging data included lesion area, confluence of GA with peripapillary atrophy (PPA), whether GA involved the foveal centerpoint, and type of hyperautofluorescence pattern. Results: A total of 2004 images (1002 visits, 286 participants) were analyzed. Gradeability (90.5%) and interreader gradeability concordance (90.2%) were high across all visits. Study eye images were more gradable compared with fellow-eye images. A greater proportion of smaller lesions required arbitration, but interreader reproducibility was consistently high for all images. There was no difference in gradeability, gradeability concordance, or lesion-area concordance for images with PPA-confluent GA compared with those with nonconfluent PPA. Foveal centerpoint-involving lesions had lower gradeability and lesion-area concordance. Images with diffuse patterns of hyperautofluorescence had better gradeability and gradeability concordance than those with nondiffuse patterns but had no difference in lesion-area or lesion-area concordance. Conclusions: There is high gradeability and excellent reproducibility measures across all images. These data support the validity of conclusions from GATHER-1 and the chosen inclusion criteria and end point. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: The aim of this analysis was to characterize the spectrum of inflammatory changes arising from brolucizumab use in routine clinical practice. Design: Retrospective analysis of fluorescein angiography (FA), fundus photography (FP) and OCT images taken at the time of adverse event. Subjects: Brolucizumab-treated patients with neovascular age-related macular degeneration with retinal vasculitis (RV) and/or retinal vascular occlusion (RO) reported to Novartis Patient Safety between February 2020 and January 2021. Methods: Ocular images were reviewed by an external reading center using predefined grading lists for FA, FP, and OCT. Main Outcome Measures: Classification of images, the most common imaging features of RV and/or RO by each imaging modality, and the anatomical location of the adverse event in relation to the macula. Results: Gradable images (N = 475; 222 eyes; 198 patients) were classified as RV only (n = 72); RO only (n = 9), RV + RO (n = 63); posterior segment intraocular inflammation (n = 31); or none by imaging (n = 47). Of the 144 eyes with RV and/or RO, the most common imaging features were vascular leakage on FA, perivascular sheathing on FP, and hyperreflective dots in the vitreous humor on OCT. Retinal vascular occlusion was mainly branched and arterial, affecting multiple vessels. Conclusions: Although no distinct inflammatory phenotype pathognomonic to brolucizumab-related inflammation was identified, this study increases our understanding of the spectrum of posterior segment inflammatory changes that may occur in brolucizumab-treated neovascular age-related macular degeneration patients, highlighting the potential value of widefield retinal imaging and angiography to detect these inflammatory adverse events. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.