Impact of residual retinal fluid on treatment outcomes in neovascular age-related macular degeneration

Abstract

Treatment decisions for neovascular age-related macular degeneration (nAMD) in the setting of individualised treatment regimens are adapted to disease activity. The main marker of disease activity and trigger for re-treatment with anti-vascular endothelial growth factor (anti-VEGF) agents is the presence of retinal fluid on optical coherence tomography (OCT). Recently, attention has focused on the impact of residual retinal fluid on nAMD management. Based on a literature review and the combined clinical experience of an international group of retinal specialists, this manuscript provides expert guidance on the treatment of nAMD according to fluid status and proposes an algorithm for determining when to administer anti-VEGF treatment according to residual fluid status. We explore the role of residual fluid in treatment decisions and outcomes in nAMD, taking into consideration fluid evaluation and, in particular, distinguishing between fluid in different anatomic compartments and at different stages during the treatment course. Current limitations to identifying and interpreting fluid on OCT, and the assumption that any residual retinal fluid reflects ongoing VEGF activity, are discussed.

Keywords: Age-Related Macular Degeneration; Intraretinal Fluid; Neovascularisation; Subretinal Fluid; Vascular Endothelial Growth Factor.

Figure 1. Recommendations on the role of fluid status in guiding treatment of nAMD. ^aThe MNV lesion type, size and location in relation to the fovea should be established and recorded, and the presence and localisation of fluid as seen on OCT should be recorded at baseline. ^bDisease is considered active when the disease stability or disease inactivity states are not achieved, defined as: the presence of IRF and/or SRF attributable to VEGF activity, deterioration in vision attributable to MNV activity, presence of new retinal haemorrhage attributable to MNV activity, increasing amounts of SRF/IRF despite regular injections. ^cDisease inactivity is achieved when there is absence of IRF and SRF attributable to VEGF activity, absence of deterioration in vision attributable to MNV activity or absence of new retinal haemorrhage attributable to MNV activity. ^dDisease stability is achieved when there is no fluid or a small amount of persistent residual SRF without a further decrease, despite adequate regular injections being performed until maximal anatomic effect (with at least an initial three monthly injections during the induction phase), in the absence of any other signs of disease activity. ^eHyporeflective cystoid spaces that are not responsive to anti-VEGF treatment should be re-evaluated for atrophic spaces, loss of tissue and outer retinal tubulations. ^fT&E is the regimen of choice. Treatment options should be discussed with the patient and an individualised treatment regimen offered. Treatment intervals should be extended at the physician’s discretion. ^gSigns of MNV recurrence include any of the following: new retinal haemorrhage, vision deterioration, or new and/or increased IRF, SRF or sub-RPE fluid. BCVA, best-corrected visual acuity; FA, fluorescein angiography; ICGA, indocyanine green angiography; IRF, intraretinal fluid; MNV, macular neovascularisation; OCT, optical coherence tomography; OCT-A, OCT angiography; SRF, subretinal fluid; VEGF, vascular endothelial growth factor.