Gradeability and Reproducibility of Geographic Atrophy Measurement in GATHER 1, a Phase 2/3 Randomized Interventional Trial

ObjectiveTo validate GATHER-1 inclusion criteria and the study’s primary anatomic endpoint by assessing the reproducibility of geographic atrophy (GA) measurements and factors that affect reproducibility.DesignPost-hoc analysis of Phase 2/3 clinical trialSubjects, Participants, and/or ControlsAll 286 participants included in the GATHER-1 studyMethods, Intervention, or TestingFor each subject, blue light fundus autofluorescence (FAF), color fundus photographs, fluorescein angiograms, and OCT scans were obtained on the study eye and fellow eye. GA area and other lesion characteristics were independently graded by two experienced primary readers. If the two 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 MeasuresThe 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.ResultsA total of 2004 images (1002 visits, 286 participants) were analyzed. Gradeability (90.5%) and inter-reader gradeability concordance (90.2%) were high across all visits. Study eye images were more gradable compared to fellow eye images. A greater proportion of smaller lesions required arbitration, but inter-reader 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 to 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 non-diffuse patterns but had no difference in lesion area or lesion area concordance.ConclusionsThere 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 endpoint.