Standardization of Imaging Criteria for Detecting Macular Fibrosis in Neovascular Age-Related Macular Degeneration

Purpose: To evaluate conventional imaging modalities for detecting fibrosis in neovascular age-related macular degeneration (nAMD) and to develop a standardized diagnostic workflow. Design: Systematic discussion and grading exercise assessing multiple imaging modalities. Participants: Retina specialists from the International Fibrosis Consensus workgroup and members of the International Retinal Imaging Society. Methods: An international panel assessed the advantages and limitations of 5 imaging modalities-color fundus photography (CFP), fluorescein angiography (FA), spectral domain OCT (SD-OCT), near-infrared reflectance, and fundus autofluorescence-for detecting fibrosis in nAMD. A structured debate was followed by 2 online, masked image grading surveys. Sensitivity, specificity, and predictive accuracy of each modality, alone and in combination, were determined. Intergrader agreement was calculated. Imaging features were also correlated with histology in a nonhuman primate laser model. Based on consensus discussions at 2 in-person meetings and survey results, a 2-step diagnostic approach using SD-OCT as the primary modality was proposed. Main Outcome Measures: Recommendation for a standardized approach for diagnosing fibrosis in eyes with nAMD. Results: Among the 5 modalities, SD-OCT was considered essential by all workgroup members. Hyperreflective material on OCT was unanimously identified as a key indicator of fibrosis. However, its limited specificity was acknowledged. In 2 masked grading exercises, SD-OCT showed the highest sensitivity (0.88 and 0.84) but only moderate specificity (0.56 and 0.57). The area under the curve (AUC) for SD-OCT was 0.72 and 0.70. A 2-step strategy combining SD-OCT with CFP or FA improved diagnostic accuracy. Hyperreflective material was defined as material with reflectivity equal to or greater than normal retinal pigment epithelium (RPE), well-defined margins, RPE disruption, and a laminated appearance. Corresponding CFP findings included well-defined yellow/white/gray subretinal lesions, and FA findings included early blocked fluorescence and late staining. This 2-step approach increased AUC to 0.85, with sensitivity of 0.83 and specificity of 0.87. Conclusions: The study establishes a 2-step approach using OCT as the primary modality in clinical studies for the detection of fibrosis. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.