Opportunities for Improving Glaucoma Clinical Trials via Deep Learning-Based Identification of Patients with Low Visual Field Variability.

Purpose: Develop and evaluate the performance of a deep learning model (DLM) that forecasts eyes with low future visual field (VF) variability, and study the impact of using this DLM on sample size requirements for neuroprotective trials.

Design: Retrospective cohort and simulation study.

Methods: We included 1 eye per patient with baseline reliable VFs, OCT, clinical measures (demographics, intraocular pressure, and visual acuity), and 5 subsequent reliable VFs to forecast VF variability using DLMs and perform sample size estimates. We estimated sample size for 3 groups of eyes: all eyes (AE), low variability eyes (LVE: the subset of AE with a standard deviation of mean deviation [MD] slope residuals in the bottom 25th percentile), and DLM-predicted low variability eyes (DLPE: the subset of AE predicted to be low variability by the DLM). Deep learning models using only baseline VF/OCT/clinical data as input (DLM1), or also using a second VF (DLM2) were constructed to predict low VF variability (DLPE1 and DLPE2, respectively). Data were split 60/10/30 into train/val/test. Clinical trial simulations were performed only on the test set. We estimated the sample size necessary to detect treatment effects of 20% to 50% in MD slope with 80% power. Power was defined as the percentage of simulated clinical trials where the MD slope was significantly worse from the control. Clinical trials were simulated with visits every 3 months with a total of 10 visits.

Results: A total of 2817 eyes were included in the analysis. Deep learning models 1 and 2 achieved an area under the receiver operating characteristic curve of 0.73 (95% confidence interval [CI]: 0.68, 0.76) and 0.82 (95% CI: 0.78, 0.85) in forecasting low VF variability. When compared with including AE, using DLPE1 and DLPE2 reduced sample size to achieve 80% power by 30% and 38% for 30% treatment effect, and 31% and 38% for 50% treatment effect.

Conclusions: Deep learning models can forecast eyes with low VF variability using data from a single baseline clinical visit. This can reduce sample size requirements, and potentially reduce the burden of future glaucoma clinical trials.

Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.