Machine Learning to Predict Faricimab Treatment Outcome in Neovascular Age-Related Macular Degeneration

To develop machine learning (ML) models to predict, at baseline, treatment outcomes at month 9 in patients with neovascular age-related macular degeneration (nAMD) receiving faricimab.

Retrospective proof of concept study.

Patients enrolled in the phase II AVENUE trial (NCT02484690) of faricimab in nAMD.

Baseline characteristics and spectral domain-OCT (SD-OCT) image data from 185 faricimab-treated eyes were split into 80% training and 20% test sets at the patient level. Input variables were baseline age, sex, best-corrected visual acuity (BCVA), central subfield thickness (CST), low luminance deficit, treatment arm, and SD-OCT images. A regression problem (BCVA) and a binary classification problem (reduction of CST by 35%) were considered. Overall, 10 models were developed and tested for each problem. Benchmark classical ML models (linear, random forest, extreme gradient boosting) were trained on baseline characteristics; benchmark deep neural networks (DNNs) were trained on baseline SD-OCT B-scans. Baseline characteristics and SD-OCT data were merged using 2 approaches: model stacking (using DNN prediction as an input feature for classical ML models) and model averaging (which averaged predictions from the DNN using SD-OCT volume and from classical ML models using baseline characteristics).

Treatment outcomes were defined by 2 target variables: functional (BCVA letter score) and anatomical (percent decrease in CST from baseline) outcomes at month 9.

The best-performing BCVA regression model with respect to the test coefficient of determination (R²) was the linear model in the model-stacking approach with R² of 0.31. The best-performing CST classification model with respect to test area under receiver operating characteristics (AUROC) was the benchmark linear model with AUROC of 0.87. A post hoc analysis showed the baseline BCVA and the baseline CST had the most effect in the all-model prediction for BCVA regression and CST classification, respectively.

Promising signals for predicting treatment outcomes from baseline characteristics were detected; however, the predictive benefit of baseline images was unclear in this proof-of-concept study. Further testing and validation with larger, independent datasets is required to fully explore the predictive capacity of ML models using baseline imaging data.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.