A deep learning approach to explore the association of age-related macular degeneration polygenic risk score with retinal optical coherence tomography: A preliminary study

Purpose: Age-related macular degeneration (AMD) is a complex eye disorder affecting millions worldwide. This article uses deep learning techniques to investigate the relationship between AMD, genetics and optical coherence tomography (OCT) scans. Methods: The cohort consisted of 332 patients, of which 235 were diagnosed with AMD and 97 were controls with no signs of AMD. The genome-wide association studies summary statistics utilized to establish the polygenic risk score (PRS) in relation to AMD were derived from the GERA European study. A PRS estimation based on OCT volumes for both eyes was performed using a proprietary convolutional neural network (CNN) model supported by machine learning models. The method's performance was assessed using numerical evaluation metrics, and the Grad-CAM technique was used to evaluate the results by visualizing the features learned by the model. Results: The best results were obtained with the CNN and the Extra Tree regressor (MAE = 0.55, MSE = 0.49, RMSE = 0.70, R² = 0.34). Extending the feature vector with additional information on AMD diagnosis, age and smoking history improved the results slightly, with mainly AMD diagnosis used by the model (MAE = 0.54, MSE = 0.44, RMSE = 0.66, R² = 0.42). Grad-CAM heatmap evaluation showed that the model decisions rely on retinal morphology factors relevant to AMD diagnosis. Conclusion: The developed method allows an efficient PRS estimation from OCT images. A new technique for analysing the association of OCT images with PRS of AMD, using a deep learning approach, may provide an opportunity to discover new associations between genotype-based AMD risk and retinal morphology.