Hyperreflective Material Boundary Remodeling in Neovascular Age-Related Macular Degeneration: A Post Hoc Analysis of the AVENUE Trial.

OBJECTIVE To describe the spatial and temporal characteristics of hyperreflective material (HRM) on spectral-domain optical coherence tomography (SD-OCT) in neovascular age-related macular degeneration (nAMD) during antiangiogenic treatment and explore associations with best-corrected visual acuity (BCVA) and macular atrophy (MA). DESIGN Retrospective regrading of SD-OCT-images from the multicenter randomized controlled AVENUE trial (NCT02484690, conducted August 2015-September 2017). PARTICIPANTS Treatment-naïve nAMD patients enrolled from 50 sites in the US. METHODS Retrospective regrading and secondary analysis. MAIN OUTCOME MEASURE SD-OCT images from 207 study eyes that fitted criteria for the present analysis were graded for HRM features, its evolution, and associated hypertransmission into choroid (HTC), a proxy for MA. The appearance of a well-defined hyperreflective inner boundary that separated persistent HRM from the neurosensory retina continuous with the adjacent retinal pigment epithelium layer was defined as HRM boundary remodeling (HRM-BR). Patterns of HRM composition/evolution were defined: 1) no subretinal HRM at baseline, 2) fully resolved, 3) persistent with complete HRM-BR, or 4) partial/absent HRM-BR. Associations of HRM patterns with BCVA and HTC were analyzed. Predictive factors for complete HRM-BR were explored. RESULTS Of 207 included eyes, subretinal HRM was present in 159 (76.8%) at baseline and persisted until month 9 in 118 (57.0%) eyes. Of these 118 eyes, 44.9% developed complete HRM-BR and had similar BCVA outcomes by month 9 compared with no/fully resolved subretinal HRM. Partial/absent HRM-BR had a strong negative association with BCVA outcome (-6.1 Early Treatment Diabetic Retinopathy Study letters; P = 0.016) and a higher frequency of intralesional HTC (69.2%) compared with eyes with complete HRM-BR (20.8%) at month 9. Older age (odds ratio [OR] 0.96; P = 0.054) and presence of intralesional HTC (OR 0.06; P = 0.010) at baseline were associated with lower odds of complete HRM-BR at month 9. CONCLUSIONS In nAMD eyes under antiangiogenic treatment, complete HRM-BR occurred frequently and was associated with better BCVA than when HRM-BR was only partial/absent

Fibrosis in neovascular age-related macular degeneration: A review of definitions based on clinical imaging

Despite the success of antiangiogenic therapy in controlling exudation in neovascular age-related macular degeneration (nAMD), the involvement of the outer retina in fibrosis results in gradual vision loss over time. The development of drugs that prevent or ameliorate fibrosis in nAMD requires that it is accurately detected and quantified with reliable endpoints and identification of robust biomarkers. Achievement of such an aim is currently challenging due to the lack of a consensus definition of fibrosis in nAMD. As a first step towards the establishment of a clear definition of fibrosis, we provide an extensive overview of the imaging modalities and criteria used to characterize fibrosis in nAMD. We observed variety in the selection of individual and combinations of imaging modalities, and criteria for detection. We also observed heterogeneity in classification systems and severity scales for fibrosis. The most commonly used imaging modalities were color fundus photography (CFP), fluorescence angiography (FA) and optical coherence tomography (OCT). A multimodal approach was frequently utilized. Our review suggests that OCT offers a more detailed, objective and sensitive characterization than CFP/FA. Thus, we recommend it as a primary modality for fibrosis evaluation. This review provides a basis for future discussions to reach a consensus definition using standardized terms based on a detailed characterization of fibrosis, its presence and evolution, and taking into consideration impact on visual function. Achieving this goal is of paramount importance for the development of antifibrotic therapies