Purpose: To determine the natural history of asymptomatic, subretinal fluid (SRF) in intermediate age-related macular degeneration (iAMD) and highlight the entity of nonexudative detachment of the neurosensory retina (NEDNR). Design: Prospective, observational case series. Participants: Cases of iAMD with bilateral drusen >125 μm who were participating in a longitudinal study, in whom spectral-domain (SD)-OCT imaging detected asymptomatic SRF. Methods: Participants underwent clinical examinations every 6 months with multimodal imaging that included infrared reflectance, fundus autofluorescence, and SD-OCT. The grading center identified eyes with SRF. Eyes with SRF ≤30 μm were monitored more regularly, whereas eyes with SRF >30 μm underwent fluorescein angiography (FA) and indocyanine green angiography (ICGA). Subretinal fluid without evidence of neovascularization or polyp was termed “NEDNR”. All cases of SRF underwent swept-source OCT angiography (SS-OCTA) to determine if choroidal neovascularization (CNV) was present and were then followed prospectively. Main Outcome Measures: Natural history of iAMD eyes with SRF that had no evidence of neovascularization during the monitoring period of 30 to 54 months. Results: Sixteen eyes of 12 patients with iAMD developed asymptomatic SRF over a follow-up period of 30 to 54 months. Four eyes developed occult CNV on FA and were no longer followed in this study. Four eyes developed SRF ≤30 μm, and 8 eyes developed SRF >30 μm, with 11 of the 12 eyes developing subretinal hyperreflective material (SHRM). None of these 12 eyes showed any evidence of neovascularization at the initial detection of SRF and were termed “NEDNR”. During the follow-up period of 12 to 36 months after the onset of SRF, only 1 eye developed exudative CNV. The remaining 11 eyes failed to demonstrate any abnormal choroidal vasculature on SS-OCTA, including 4 eyes with cuticular drusen in which SHRM developed into a large subfoveal vitelliform-like deposit. Conclusions: Multimodal imaging is helpful for the interpretation and management of asymptomatic SRF in iAMD. In some eyes, all imaging, including SS-OCTA, failed to demonstrate subclinical neovascularization, and we use the acronym NEDNR to describe these cases. This phenotype within iAMD needs to be recognized and monitored to determine if and when treatment might be needed.
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