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

To evaluate conventional imaging modalities for detecting fibrosis in neovascular age-related macular degeneration (nAMD) and to develop a standardized diagnostic workflow.

Systematic discussion and grading exercise assessing multiple imaging modalities.

Retina specialists from the International Fibrosis Consensus workgroup and members of the International Retinal Imaging Society.

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.

Recommendation for a standardized approach for diagnosing fibrosis in eyes with nAMD.

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.

The study establishes a 2-step approach using OCT as the primary modality in clinical studies for the detection of fibrosis.

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