Correlation of Ultra-widefield Fluorescein Angiographic Features with Intraocular Cytokine Expression in Diabetic Macular Edema: Exploring the Angiographic-Biologic Phenotype

Abstract

Purpose : The dominant underlying biologic pathways driving diabetic macular edema (DME) have been implicated as predictors of therapeutic response. Elucidating the relationship between these key cytokine expression profiles and imaging biomarkers could aid in precision medicine and therapeutic selection. This study investigates the association of intraocular cytokine expression and ultra-widefield fluorescein angiography (UWFA) quantitative imaging biomarkers in DME.

Methods : The DAVE study is a prospective clinical trial that included prospective collection of aqueous humor samples and UWFA at select timepoints. The IMAGINE analysis is a post-hoc assessment of image biomarker association with underlying intraocular cytokine expression. Cytokines were evaluated through multi-plex arrays that measured 54 cytokines associated with inflammation and angiogenesis. UWFA parameters were assessed quantitatively using an automated feature analysis platform with manual validation to determine ischemic and leakage indices and microaneurysm count. Cytokine concentrations and quantitative angiogram parameters were correlated using Pearson’s correlation coefficients.

Results : Twenty eyes were included with a mean age of 54 ± 10 years. Increased panretinal leakage index correlated with VEGF (r=0.55, p=0.012), IL-6 (r= 0.48, p=0.034), ANGPTL4 (r=0.64, p=0.0024), uPAR (r=0.49, p=0.028), MMP1 (r=0.48, p=0.03), while increased microaneurysms correlated with increased MCP-1 (r=.47, p=0.037), MCP-4 (r=0.57, p=0.008), and PECAM-1 (r=0.51, p=0.022). No statistically significant relationship was found between panretinal ischemic index and cytokine expression. However, zonal assessment of posterior pole ischemic index demonstrated correlation with IL12p40 (r=0.49, p=0.028) and TIMP-2 (r=0.49,p=0.03).

Conclusions : Quantitative UWFA imaging parameters correlated with multiple aqueous humor cytokine concentrations. In particular, panretinal leakage and microaneurysm count were associated with multiple unique cytokines. Further research is needed to assess the possible implications of utilizing these findings for evaluating treatment response.

This is a 2020 ARVO Annual Meeting abstract.