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.