Abstract
(1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, aqueous, and blood were collected from patients with treatment-naïve DME for miRNA expression profiling with quantitative polymerase chain reaction. Differentially expressed miRNAs between good and poor responders were identified from tear fluid. Bioinformatics analysis with the miEAA tool, miRTarBase Annotations, Gene Ontology categories, KEGG, and miRWalk pathways identified interactions between enriched miRNAs and biological pathways. (3) Results: Of 24 participants, 28 eyes received bevacizumab (15 eyes) or aflibercept (13 eyes). Tear fluid had the most detectable miRNA species (N = 315), followed by serum (N = 309), then aqueous humor (N = 134). MiRNAs that correlated with change in macular thickness were miR-214-3p, miR-320d, and hsa-miR-874-3p in good responders; and miR-98-5p, miR-196b-5p, and miR-454-3p in poor responders. VEGF-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders. (4) Conclusions: We reported a panel of novel miRNAs that provide insight into biological pathways in DME. Validation in larger independent cohorts is needed to determine the predictive performance of these miRNA candidate biomarkers.
Highlights
Diabetic macular edema (DME) is the most common sight-threatening complication of diabetes afflicting working-age adults [1,2]
vascular endothelial growth factor (VEGF)-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders
Since the advent of anti-VEGF therapy, various landmark studies have demonstrated the efficacy of intravitreal anti-VEGF agents in improving the best corrected visual acuity (BCVA) and retinal central subfield thickness (CST) of patients with DME [5,6]
Summary
Diabetic macular edema (DME) is the most common sight-threatening complication of diabetes afflicting working-age adults [1,2]. Patients who do not respond to anti-VEGF agents may benefit from early commencement of slow-release corticosteroid injection such as Dexamethasone implant (Ozurdex®) This switch should be done as soon as possible to preserve the best visual acuity outcome. MiRNAs were initially thought to exist intracellularly In the cell, they reduce target gene expression via either post-transcriptional regulation of messenger RNA (mRNA) degradation or inhibition of translation [12,13,14]. They reduce target gene expression via either post-transcriptional regulation of messenger RNA (mRNA) degradation or inhibition of translation [12,13,14] They were eventually detected extracellularly in serum, plasma, urine and saliva, tears, aqueous humor, and vitreous humor [15,16,17,18]. We performed a systematic comparison of the miRNA profiles generated from tears, aqueous, and serum and identified potential miRNAs in tears to differentiate between responders and suboptimal responders to anti-VEGF therapy
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