Deep Learning-Based Generation of Retinal Nerve Fibre Layer Thickness Maps from Fundus Photographs: A Comparative Analysis of U-Net Architectures for Accessible Glaucoma Assessment

Introduction: Optical coherence tomography (OCT) is the gold standard for retinal nerve fibre layer (RNFL) assessment; its high cost and limited accessibility hinder widespread use. This study aims to develop deep learning models that generate RNFL thickness maps from fundus images, providing a cost-effective alternative to OCT. Methods: A dataset of 5000 fundus-OCT image pairs from 5000 unique glaucoma patients was used to train and compare the following four U-Net-based deep learning models: ResU-Net, R2U-Net, Nested U-Net, and Dense U-Net. All models were trained for up to 1000 epochs with early stopping (patience = 50 epochs). Performance was evaluated using Mean Squared Error (MSE), Mean Absolute Error (MAE), Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index Measure (SSIM), and Fréchet Inception Distance (FID). Results: ResU-Net demonstrated the best performance, achieving MSE = 0.00061, MAE = 0.01877, SSIM = 0.9163, PSNR = 32.19 dB, and FID = 30.08. These results represent a 108% improvement in SSIM and a 67% improvement in PSNR compared to previously published benchmark for this task. Conclusions: This study demonstrates that deep learning models, particularly ResU-Net, can generate high-fidelity RNFL thickness maps from fundus photographs, substantially outperforming prior published benchmarks. This approach represents a potential contribution toward accessible glaucoma assessment, contingent upon prospective clinical validation and regulatory evaluation.