Imaging Biomarkers and Their Impact on Therapeutic Decision-Making in the Management of Neovascular Age-Related Macular Degeneration

Abstract

These recommendations, produced by a group of Canadian retina experts, have been developed to assist both retina specialists and general ophthalmologists in the management of vision-threatening neovascular age-related macular degeneration (nAMD). The recommendations are based on published evidence as well as collective experience and expertise in routine clinical practice. We provide an update on practice principles for optimal patient care, focusing on identified imaging biomarkers, in particular retinal fluid, as well as current and emerging therapeutic approaches. Algorithms for delivering high-quality care and improving long-term patient outcomes are provided, with an emphasis on timely and appropriate treatment to preserve and maintain vision. In the context of nAMD, increasing macular fluid or leakage on fluorescein angiography (FA) may indicate disease activity regardless of its location. Early elimination of intraretinal fluid (IRF) is of particular relevance as it is a prognostic indicator of worse visual outcomes. Robust referral pathways for second opinion and peer-to-peer consultations must be in place for cases not responding to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.

Pathways of Fluid Leakage in Age Related Macular Degeneration

“…Currently recognized OCT biomarkers for neovascular activity include intraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid, and subretinal hyperreflective material (SHRM), which are critical factors guiding therapy. 2–4 Fluid is a major hallmark of exudation and angiogenic activity in eyes with neovascular AMD, indicating the need for treatment with anti–vascular endothelial growth factor (VEGF) injection. 2,3,5…”

“…2–4 Fluid is a major hallmark of exudation and angiogenic activity in eyes with neovascular AMD, indicating the need for treatment with anti–vascular endothelial growth factor (VEGF) injection. 2,3,5…”

“…[2][3][4] Fluid is a major hallmark of exudation and angiogenic activity in eyes with neovascular AMD, indicating the need for treatment with anti-vascular endothelial growth factor (VEGF) injection. 2,3,5 A long list of pivotal clinical trials essential for the ratification and approval of various anti-VEGF therapies, including aflibercept, 6 brolucizumab, 7 and faricimab, 8 relied on the OCT response of anatomical biomarkers of neovascular activity to corroborate the observed functional efficacy of the investigated agent. In all cases, the study drug was no less effective or was better in resolving fluid markers such as IRF and SRF, and these OCT outcomes were critical factors that were evaluated to determine the treatment effect of the anti-VEGF agent.…”

“…Currently recognized OCT biomarkers for neovascular activity include intraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid, and subretinal hyperreflective material (SHRM), which are critical factors guiding therapy. [2][3][4] Fluid is a major hallmark of exudation and angiogenic activity in eyes with neovascular AMD, indicating the need for treatment with anti-vascular endothelial growth factor (VEGF) injection. 2,3,5 A long list of pivotal clinical trials essential for the ratification and approval of various anti-VEGF therapies, including aflibercept, 6 brolucizumab, 7 and faricimab, 8 relied on the OCT response of anatomical biomarkers of neovascular activity to corroborate the observed functional efficacy of the investigated agent.…”

Evaluation of an Artificial Intelligence-Based Detector of Sub- and Intraretinal Fluid on a Large Set of Optical Coherence Tomography Volumes in Age-Related Macular Degeneration and Diabetic Macular Edema

“…The advent of high-resolution optical coherence tomography (OCT) has led to the identification of biomarkers in diabetic retinopathy with diabetic macular edema (DME) and neovascular age-related macular degeneration (AMD), delivering a vast amount of morphological information, which could be used to individualize treatment decisions [1][2][3]. In neovascular AMD, subretinal fluid (SRF) is associated with a better visual outcome and a lower rate of transformation into geographic atrophy, while intraretinal fluid (IRF) has a poorer visual outcome with increasing rates of macular atrophy [4,5].…”