Retinal volume change is a reliable OCT biomarker for disease activity in neovascular AMD

Current algorithms for automated computer interpretation of optical coherence tomography (OCT) imaging of patients suffering from neovascular age-related macular degeneration (AMD) mostly rely on fluid detection. However, fluid detection itself and correct interpretation of the fluid currently limits diagnostic accuracy. We therefore performed a detailed analysis of the requirements that would have to be met for fluid detection approaches. We further investigated if monitoring retinal volume would be a viable alternative to detect disease activity. Retrospective analysis and manual grading of 764 OCT volume scans of 44 patients with exudative AMD treated with intravitreal anti-VEGF injections at a pro-re-nata (PRN) treatment regimen for at least 24 months. Detection of subretinal fluid (SRF) or intraretinal fluid (IRF) alone is not sufficient for disease detection. A combination of SRF and IRF can detect disease activity with a sensitivity of 98.6% and a specificity of 82%. With further characterization of IRF into exudative and degenerative cysts, specificity can be increased to 100%. However, correct characterization is currently not achieved by published fluid detection approaches. Change of macular retinal volume (MRV) can depict disease activity with sensitivity of 88.4% and specificity of 89.6%. Combination with the detection of SRF can further improve diagnostic accuracy to a specificity of 93.3% and sensitivity of 93.9% without relying on IRF or IRF characterization. Fluid detection without further characterization is not sufficient for AMD monitoring. Either further distinction between exudative and degenerative cysts is necessary, or other activity markers have to be taken into account. MRV offers good potential to fill this diagnostic gap and might become an important monitoring marker.