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

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.

Figure 1:. Scatterplot for observed BCVA change at 2-years vs. Predicted BCVA change at 2-year based on multivariable model presented in Table 4

The scatterplot with LOESS line shows the agreement between observed BCVA change and predicted BCVA change from baseline at 2 years. These data points are scattered around the LOESS line with R²=0.36 (R² ranges from 0 to 1, with 1 indicating perfect prediction).

Figure 2.. ROC curve for the multivariable regression analysis predicting BCVA gain ≥3-line from baseline at year 2.

The ROC curve shows the prediction for BCVA gain ≥3-line from baseline at year 2 using baseline BCVA and BCVA gain of ≥3-line from baseline at 3 months after treatment. The area under ROC curve is 0.83 (95% CI: 0.81–0.86) indicating moderate prediction. The area under ROC curve ranges from 0 to 1 with 1 indicating perfect prediction.