An Artificial Intelligence Enabled System for Retinal Nerve Fiber Layer Thickness Damage Severity Staging

To develop an objective glaucoma damage severity classification system based on OCT-derived retinal nerve fiber layer (RNFL) thickness measurements.

Algorithm development for RNFL damage severity classification based on multicenter OCT data.

A total of 6561 circumpapillary RNFL profiles from 2269 eyes of 1171 subjects to develop models, and 2505 RNFL profiles from 1099 eyes of 900 subjects to validate models.

We developed an unsupervised k-means model to identify clusters of eyes with similar RNFL thickness profiles. We annotated the clusters based on their respective global RNFL thickness. We computed the optimal global RNFL thickness thresholds that discriminated different severity levels based on Bayes' minimum error principle. We validated the proposed pipeline based on an independent validation dataset with 2505 RNFL profiles from 1099 eyes of 900 subjects.

Accuracy, area under the receiver operating characteristic curve, and confusion matrix.

The k-means clustering discovered 4 clusters with 1382, 1613, 1727, and 1839 samples with mean (standard deviation) global RNFL thickness of 58.3 (8.9) μm, 78.9 (6.7) μm, 87.7 (8.2) μm, and 101.5 (7.9) μm. The Bayes' minimum error classifier identified optimal global RNFL values of > 95 $\mu m$, 86 to 95 $\mu m$, 70 to 85 $\mu m\text{,}$ and < 70 $\mu m$ for discriminating normal eyes and eyes at the early, moderate, and advanced stages of RNFL thickness loss, respectively. About 4% of normal eyes and 98% of eyes with advanced RNFL loss had either global, or ≥ 1 quadrant, RNFL thickness outside of normal limits provided by the OCT instrument.

Unsupervised machine learning discovered that the optimal RNFL thresholds for separating normal eyes and eyes with early, moderate, and advanced RNFL loss were 95 $\mu m$, 85 μm, and 70 $\mu m$, respectively. This RNFL loss classification system is unbiased as there was no preassumption or human expert intervention in the development process. Additionally, it is objective, easy to use, and consistent, which may augment glaucoma research and day-to-day clinical practice.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.