Ethnicity is not biology: retinal pigment score to evaluate biological variability from ophthalmic imaging using machine learning.

Background: Few metrics exist to describe phenotypic diversity within ophthalmic imaging datasets, with researchers often using ethnicity as an inappropriate marker for biological variability.

Methods: We derived a continuous, measured metric, the retinal pigment score (RPS), that quantifies the degree of pigmentation from a colour fundus photograph of the eye. RPS was validated using two large epidemiological studies with demographic and genetic data (UK Biobank and EPIC-Norfolk Study).

Findings: A genome-wide association study (GWAS) of RPS from UK Biobank identified 20 loci with known associations with skin, iris and hair pigmentation, of which 8 were replicated in the EPIC-Norfolk cohort. There was a strong association between RPS and ethnicity, however, there was substantial overlap between each ethnicity and the respective distributions of RPS scores.

Interpretation: RPS serves to decouple traditional demographic variables, such as ethnicity, from clinical imaging characteristics. RPS may serve as a useful metric to quantify the diversity of the training, validation, and testing datasets used in the development of AI algorithms to ensure adequate inclusion and explainability of the model performance, critical in evaluating all currently deployed AI models. The code to derive RPS is publicly available at: https://github.com/uw-biomedical-ml/retinal-pigmentation-score.

Funding: The authors did not receive support from any organisation for the submitted work.