Cystatin C levels associated with risk of sight-threatening diabetic retinopathy

The biomarker may be useful for predicting this condition, especially in areas that don't have access to retinal imaging, according to an analysis of ophthalmology patients in the United Kingdom and India.

Circulating cystatin C levels may offer incremental benefit as a triage test in prioritizing people with type 2 diabetes from the community for retinal screening for diabetic retinopathy (DR) in resource-restricted settings, a study found.

A cross-sectional study collected data in parallel in three outpatient ophthalmology clinics in the United Kingdom and two in India from October 2018 to December 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data.

Adults ages 40 years and older were categorized into four groups: no history of diabetes, type 2 diabetes of at least five years with no evidence of DR, nonproliferative DR with diabetic macular edema (DME), or proliferative DR. The latter two conditions were defined as sight-threatening DR. DR and DME were diagnosed using fundus photographs and optical coherence tomography. Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay (ELISA). Researchers used ELISA instead of mass spectrometry, the gold standard, to more closely approximate testing that is routinely available in a health care setting. Results of the study were published May 5 by JAMA Ophthalmology.

Researchers recruited 538 participants; approximately 20% did not have diabetes, 20% had diabetes without DR, and 20% had nonproliferative DR with DME. More than a third had proliferative DR. Comparison by whether patients had DR or not showed that in addition to age, disease duration, ethnicity (in the U.K.), and HbA1c level, inclusion of cystatin C had near-acceptable discrimination power (areas under the receiver-operating characteristic curve, 0.779 [95% CI, 0.700 to 0.857] in 215 patients in the U.K. with complete data and 0.696 [95% CI, 0.602 to 0.791] in 208 patients in India with complete data). The study authors did not pool the samples from the U.K. and India because of differences in the distribution of some biomarkers.

They concluded that serum cystatin C had good discrimination power and could be considered as a test to prioritize retinal screening for sight-threatening DR. “Although retinal imaging is the criterion standard for DR screening and should be advocated for all patients with diabetes on an annual or biennial basis, this is not always feasible in low- and middle-income countries,” the authors wrote. “In such low-resource settings, prescreening models with cystatin-C may potentially be used to identify those who need prioritization for retinal screening.”