Prognostic value of SHRM as an imaging biomarker in the treatment of neovascular Age-Related Macular Degeneration: A Systematic Review

Subretinal hyperreflective material (SHRM) has been lately recognized as a biomarker in neovascular age-related macular degeneration (nAMD), with potential prognostic value for visual and structural outcomes. The aim of this systematic review is to synthesize and critically evaluate the evidence on the prognostic significance of SHRM characteristics in patients with nAMD. A systematic search of PubMed, Scopus and Web of Science was conducted for studies published between March 2015 and March 2025. Eligible studies included human participants with nAMD, under anti-VEGF treatment, in which SHRM was assessed using optical coherence tomography (OCT) and outcomes included best-corrected visual acuity (BCVA), fibrosis or macular atrophy. Thirty-three studies met the inclusion criteria. The majority of the studies (22/28) demonstrated a significant association between the presence of SHRM and worse BCVA over time, particularly correlated to SHRM thickness, width or persistence after anti-VEGF therapy. Well-defined and hyperreflective SHRM was repeatedly linked to poorer functional outcomes. Twelve studies reported SHRM as a strong predictor of subretinal fibrosis, with larger size, defined borders and persistence conferring the greatest risk. The relationship with macular atrophy was less clear, while some studies suggested that thicker or persistent SHRM increased the likelihood of atrophy, others found no association. Overall, the evidence suggests that SHRM is one of the strongest imaging biomarkers of poor prognosis in nAMD. While this review highlights consistent patterns and values, differences in how SHRM is defined and measured across studies remain a limitation. For this reason, it will be important for future research to focus on standardizing SHRM assessment in order to establish its use in personalized treatment decisions.