- Systematic Review - Macular Neovascularization in Neovascular AMD: A Systematic Review of OCTA-Based Assessments and Challenges in Standardization

TOPIC: This systematic review evaluates the methodologies employed for assessing the macular neovascularization (MNV) in neovascular age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). It focuses on identifying methodological heterogeneity in imaging and analysis protocols and its implications for clinical and research applications. CLINICAL RELEVANCE: Accurate assessment of MNV is critical for understanding disease activity, monitoring treatment response, and guiding clinical management in AMD. OCTA offers non-invasive, high-resolution visualization of neovascular networks, but variability in device types, scan protocols, segmentation strategies, and post-processing methods hampers reproducibility and comparability across studies. METHODS: A systematic literature search was conducted in PubMed (Medline) and the Cochrane Library from inception through April 3, 2025. The review protocol was prospectively registered in PROSPERO (CRD420251046977). Studies included patients with neovascular AMD who underwent OCTA for MNV evaluation, irrespective of device type or scan parameters. Data extraction focused on OCTA technology, scan sizes, segmentation strategies, image processing techniques, quantitative metrics, and approaches to artifact reduction. A descriptive synthesis was performed. RESULTS: A total of 155 studies, comprising 9,025 patients (9,669 eyes), were included. MNV subtypes included type 1 (5,059 eyes), type 2 (973 eyes), type 3 (321 eyes), and mixed lesions (138 eyes); 12 studies did not specify subtype. OCTA devices included spectral-domain (86 studies) and swept-source systems (64 studies), with PLEX Elite 9000 and RTVue XR Avanti most frequently used. Scan sizes varied, predominantly 3×3 mm and 6×6 mm. Segmentation strategies and slab boundaries exhibited marked heterogeneity, with frequent manual corrections required for accurate visualization. Quantitative analyses employed diverse thresholding and binarization techniques, and only a minority of studies addressed projection artifact correction, highlighting substantial variability in methodological approaches across studies. CONCLUSION: OCTA provides detailed, non-invasive assessment of MNV in AMD, but methodological heterogeneity-including variability in devices, scan protocols, segmentation, binarization, and artifact management-limits comparability across studies. Standardized imaging and analytical protocols are urgently needed to improve reproducibility, enable reliable biomarker development, and enhance clinical utility in AMD management.