Abstract:AIM: To develop a classifier for differentiating between healthy and early stage glaucoma eyes based on peripapillary retinal nerve fiber layer (RNFL) thicknesses measured with optical coherence tomography (OCT), using machine learning algorithms with a high interpretability. METHODS: Ninety patients with early glaucoma and 85 healthy eyes were included. Early glaucoma eyes showed a visual field (VF) defect with mean deviation >-6.00 dB and characteristic glaucomatous morphology. RNFL thickness in every quadrant, clock-hour and average thickness were used to feed machine learning algorithms. Cluster analysis was conducted to detect and exclude outliers. Tree gradient boosting algorithms were used to calculate the importance of parameters on the classifier and to check the relation between their values and its impact on the classifier. Parameters with the lowest importance were excluded and a weighted decision tree analysis was applied to obtain an interpretable classifier. Area under the ROC curve (AUC), accuracy and generalization ability of the model were estimated using cross validation techniques. RESULTS: Average and 7 clock-hour RNFL thicknesses were the parameters with the highest importance. Correlation between parameter values and impact on classification displayed a stepped pattern for average thickness. Decision tree model revealed that average thickness lower than 82 µm was a high predictor for early glaucoma. Model scores had AUC of 0.953 (95%CI: 0.903- 0998), with an accuracy of 89%. CONCLUSION: Gradient boosting methods provide accurate and highly interpretable classifiers to discriminate between early glaucoma and healthy eyes. Average and 7-hour RNFL thicknesses have the best discriminant power.