Biomarkers in Diabetic Retinopathy

  • Research type

    Research Study

  • Full title

    Prospective multicentre study on discovery and validation of diagnostic circulating biomarkers to detect sight threatening diabetic retinopathy

  • IRAS ID

    244330

  • Contact name

    Sobha Sivaprasad

  • Contact email

    sobha.sivaprasad@nhs.net

  • Sponsor organisation

    Moorfields Eye Hospital

  • Duration of Study in the UK

    2 years, 0 months, 1 days

  • Research summary

    Research Summary

    Biomarkers in diabetic retinopathy

    Diabetic retinopathy is a complication of diabetes. The disease affects the blood vessels in the retina causing them to swell, leak fluid or close off completely. This disease can progress from a mild to advanced stage, which can lead to blindness. Currently, there are no proven predictors, such as blood tests, that could help us to predict the progression of diabetic retinopathy.

    The purpose of this study is to determine the blood biomarkers (substances which give information about a patient’s condition) for diabetic eye disease. By better understanding why some people with diabetes develop these complications, and others do not, we may be able to predict who is at risk and develop appropriate interventions to prevent or delay these complications. A blood-based test would provide a rapid, cost-effective, time-effective and patient-friendly means of screening for sight threatening diabetic retinopathy.

    We aim to study blood samples taken from at least 300 individuals. The healthy controls may be willing members from the hospital or screening staff, or people who are accompanying the patients for their clinic appointments. Patients who have been diabetic for at least 5 years and do not have diabetic retinopathy will be enrolled from the diabetic retinopathy screening centres. The remaining cohort will be recruited from the hospital outpatient clinics.

    This study involves only one visit and is conducted as part of the routine clinical appointment. After signing the consent form, eligibility will be ascertained by the researcher. A detailed lifestyle and medical history will be obtained. Height, weight, waist and hip circumference and blood pressure will be measured. As part of the routine clinical visits, photos of the back of the eye and scans may also be done.

    Summary of Results

    This multicentre observational study was conducted in 3 sites in the United Kingdom (UK). Thirteen previously verified candidate biomarkers were validated by Enzyme-Linked Immunosorbent Assay (ELISA) on patients with a history of type 2 diabetes for at least 5 years with no diabetic retinopathy compared to those with STDR. First the variables that are associated with sight threatening diabetic retinopathy were identified. Then the discriminatory power of these variables to identify people with this condition was performed using the receiver operating curve (ROC) analysis Findings A total of 274 participants, mean age 58.4 years [SD 8·5]) were recruited. ROC analysis shows that in addition to known risk factors including age, disease duration, ethnicity (in the UK) and HbA1c, Cystatin C had the greatest discriminatory power for detecting sight threatening diabetic retinopathy relative to those with no diabetic retinopathy adjusted OR, 1·12 per 10% increase [95% CI 1·02-1·23], AUC 0.779 [95% CI 0·700-0·857]. A parallel study done in India on the same protocol showed similar discriminatory power for Cystatin C and adjusted OR in India, 1·38 per 10% increase [95% CI 1·16-1·63], AUC 0·696 [95% CI 0·602-0·791]).
    Interpretation
    Circulating Cystatin C levels may be used as a test to identify those who require urgent retinal screening for STDR. However, further validation of the study should be done in routine clinical settings before translating these findings to community screening.

  • REC name

    South Central - Oxford B Research Ethics Committee

  • REC reference

    18/SC/0477

  • Date of REC Opinion

    3 Sep 2018

  • REC opinion

    Favourable Opinion