Prediction for 2-Year Vision Outcomes Using Early Morphologic and Functional Responses in the Comparison of Age-related Macular Degeneration Treatments Trials

Ophthalmol Retina. 2023 Jul;7(7):564-572. doi: 10.1016/j.oret.2023.02.008. Epub 2023 Feb 19.

Abstract

Objective: To predict 2-year visual acuity (VA) responses to anti-VEGF therapy, using early morphologic and functional responses in patients with neovascular age-related macular degeneration (nAMD).

Design: Cohort within a randomized clinical trial.

Participants: A total of 1185 participants with untreated active nAMD and best-corrected visual acuity (BCVA) 20/25 to 20/320 at baseline.

Methods: Secondary analysis of data from participants randomized to either ranibizumab or bevacizumab and to 1 of 3 dosing regimens. Associations of 2-year BCVA responses with baseline morphologic and functional characteristics and their change from baseline at 3 months were assessed, using univariable and multivariable linear regression models for BCVA change and logistic regression models for ≥ 3-line BCVA gain from baseline. The performance of predictions for 2-year BCVA outcomes using these characteristics was assessed using R2 for BCVA change and area under the receiver operating characteristic curve (AUC) for ≥ 3-line BCVA gain.

Main outcome measures: Best-corrected visual acuity change and ≥ 3-line gain from baseline at year 2.

Results: In multivariable analyses that included previously reported significant baseline predictors (baseline BCVA, baseline macular atrophy, baseline retinal pigment epithelium elevation [RPEE], and maximum width and early BCVA change from baseline at 3 months), new RPEE occurrence at 3 months was significantly associated with more BCVA gain at 2 years (10.2 letters vs. 3.5 letters for RPEE resolved, P < 0.001), and none of the other morphologic responses at 3 months were significantly associated with BCVA responses at 2 years. These significant predictors moderately predicted 2-year BCVA gain with an R2 = 0.36. Baseline BCVA and ≥ 3-line BCVA gain at 3 months predicted 2-year ≥ 3-line gain with AUC 0.83 (95% confidence interval, 0.81-0.86).

Conclusions: Most structural responses on OCT at 3 months were not independently predictive of the 2-year BCVA responses, which were associated with baseline factors and the 3-month BCVA response to anti-VEGF therapy. A combination of baseline predictors, early BCVA, and morphologic responses at 3 months only moderately predicted the long-term BCVA responses. Future research is needed to better understand the factors contributing to the variation in long-term vision outcomes with anti-VEGF therapy.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Keywords: Anti-VEGF therapy; Morphological responses; Neovascular AMD; Prediction; Visual acuity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Angiogenesis Inhibitors* / therapeutic use
  • Bevacizumab
  • Humans
  • Macular Degeneration* / diagnosis
  • Macular Degeneration* / drug therapy
  • Ranibizumab
  • Vascular Endothelial Growth Factor A

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Ranibizumab
  • Bevacizumab