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Published on: May 26, 2023
Fluid Volumes Longitudinal Modeling to Predict Atrophy and Fibrosis in Neovascular Age-Related Macular Degeneration
Stefano Mercuri1,2, Stefan Sacu1, Sophie Frank-Publig1
1Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.
Purpose:
To evaluate the impact of retinal fluid volumes on the development of atrophy and fibrosis in neovascular age-related macular degeneration (nAMD) during routine care.
Design:
Retrospective longitudinal study.
Participants:
Treatment-naïve eyes with nAMD from the Vienna Imaging Biomarker Eye Study (2007-2018), initiating anti-VEGF therapy.
Methods:
Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were automatically quantified on OCT using an approved artificial intelligence algorithm within the 1-, 3-, and 6-mm ETDRS regions. Macular neovascularization (MNV) type and baseline presence of subretinal hyperreflective material (SHRM) were assessed. Fluid volumes were modeled as time-dependent biomarkers using repeated-measure Cox models to evaluate cumulative effects over time on the development of atrophy and fibrosis, with hazard ratios calculated for quartiles (Qs) at each visit. Associations with change in visual acuity (VA) were performed in a subset of eyes with ≥12 months of follow-up.
Main Outcome Measures:
Retinal fluid volumes, development of atrophy and fibrosis, and change in VA.
Results:
A total of 1060 eyes of 998 patients were included. Higher IRF volumes increased the risk of both atrophy and fibrosis (all P < 0.001). Subretinal fluid reduced the risk of atrophy (Q4, P ≤ 0.001) and fibrosis (1-mm, P = 0.028) in the 1- and 3-mm regions, but increased the risk of fibrosis in the 6-mm region (P ≤ 0.031). Higher PED volumes increased the risk of atrophy in the 6-mm region (P < 0.001), and fibrosis at all locations (P ≤ 0.002). Age and baseline presence of SHRM were associated with atrophy (P < 0.001), whereas type 2 and mixed/undefined MNVs were associated with both atrophy (P < 0.001) and fibrosis (P ≤0.004). In 552 eyes, time-related presence of fibrosis was associated with VA decline at all locations (P < 0.001). In all areas, Q4 of IRF was associated with linear VA decline (P <0.001). Larger SRF volumes (Q4) in the 1-mm region were associated with better vision (P <0.05). Higher PED volumes (Q3, Q4) were linked to VA decline at all locations (P < 0.001).
Conclusions:
Assessment of the cumulative effects of retinal fluid volumes during anti-VEGF therapy using time-dependent biomarker modeling revealed notable associations with risk of atrophy, fibrosis, and VA decline.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
