A pilot study identifying tear miRNA as biomarkers to stratify Diabetic Macular Edema Patients According to Their Response to Anti-VEGF Treatments

Abstract

Purpose : Diabetic macular edema (DME) remains the major cause of visual loss afflicting diabetic patients globally. With increasing prevalence of diabetes, visual threatening complications such as DME and diabetic retinopathy (DR) are expected to rise resulting in significant socioeconomic burden. While monthly intravitreal anti-vascular endothelial growth factor (VEGF) injections remain the current gold standard treatment, 25% of patients experience only a moderate visual improvement and a further 25% have no response. Given the various treatment options available and significant cost implications, there is a need to stratify patients based on their response to anti-VEGF treatments.
MircoRNAs (miRNAs) are single-stranded, noncoding RNA molecules implicated in many biological processes including the pathogenesis of DR. Found also in tears, they have great potential as biomarkers which can be sampled non-invasively.
To assess the suitability of tear miRNAs in stratifying the response of DME patients to anti-VEGF treatment, the objectives of the study are:
1) To determine the suitability of tears as a medium for miRNA expression analysis
2) To determine the difference between miRNA expression profiles of responders and non-responders of anti-VEGF treatment

Methods : 3 responders and 3 non-responders receiving monthly intravitreal Avastin® injections for DME were recruited for comparison. For each subject, 3 types of specimens (tears, aqueous and serum) were collected at 2 different time points (month 0 and month 4). miRNA extraction, multiplex reverse transcription, cDNA augmentation, qPCR amplification and detection were performed by MiRXES utilising their proprietary technology.

Results : Among the 3 mediums, miRNA expression was the highest in tears. A total of 14 differentially expressed miRNAs were identified between responders and non-responders of treatment in tears collected prior to treatment. Of which, 4 were also differentially expressed in either aqueous or serum samples.

Conclusions : miRNAs may serve as biomarkers for stratifying DME patients according to their anti-VEGF treatment response. Tears are potentially suitable as a medium for analysis. Further prospective studies in larger cohorts are required to validate the identified biomarker candidates.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.