A Blood Test May Help Identify Those at Risk for Diabetic Retinopathy

Retinal imaging is the standard screening method for diabetic retinopathy. But a blood-based biomarker, cystatin C, has the potential to identify those patients in need of further screening of sight-threatening diabetic retinopathy, according to a recent study published in May 2022 JAMA Ophthalmology.

Investigators, led by Sarega Gurudas, M.Sc., and Karen Frudd, Ph.D., both at the Institute of Ophthalmology, University College London, noted that retinal imagining may not always be feasible in low- and middle-income countries. In such low-resource settings, testing for cystatin C could be used to triage patients for retinal imagining.

Cystatin C is a protein mainly used as a biomarker of kidney function. Investigators found that, of the 13 markers they tested for, cystatin C, when added to age, duration of diabetes, race and ethnicity, and HbA1c, was a useful test to determine those at risk for diabetic retinopathy.

This study was conducted in the United Kingdom and India from October 2018 to December 2021 to evaluate previously verified circulating biomarkers for sight-threatening diabetic retinopathy in adults 40 years and older with type 2 diabetes. A total of 538 participants were recruited, including 264 in India and 274 in the United Kingdom.

This cross-sectional study evaluated previously verified circulating biomarkers in clinical practice. Many of the chosen markers did not perform as well as previously reported. But investigators’ research suggests possible use of circulating cystatin C as a triage test.

“A point-of-care cystatin C biosensor is feasible to produce, will not require skilled workers to perform, and may be accessible as a web-based application for self-monitoring by patients,” investigators wrote. “In contrast to many other published studies, which often use mass spectrometry of plasma, we opted for ELISA analyses of serum to remain close to what is routinely available in a healthcare setting. Data for cystatin C, used in our final model, did reflect that seen in the literature.”

Investigators did note a few limitations. They were unable to pool the samples from United Kingdom and India because of the differences in the distribution of some biomarkers. More studies, they said are required to understand intercountry variations in the profiles of these biomarkers.

Additionally, they said their strategy, using samples in stored and freeze-thawed serum, would need to be validated against community screening setting using finger-prick blood test. And while low-cost point-of-care HbA1c kits are already available for community screening, they noted that cystatin C point-of-care kits would be needed before use in a healthcare or community-screening setting.