Association of Aqueous Cytokine Profile and Extracted OCT Features in Diabetic Macular Edema: Assessment of the Anatomic-Biologic Bridge

Abstract

Purpose : The importance of OCT in the management of diabetic macular edema (DME) is well known. However, there is limited research on potential OCT features that may play a role as biomarkers for the underlying dominant pathogenic mechanism and for predicting treatment response. The purpose of this study is to evaluate the association of specific quantifiable OCT characteristics and the expression of intraocular cytokines.

Methods : The DAVE study is a prospective clinical trial for the management of DME with ranibizumab or ranibizumab combined with targeted panretinal photocoagulation. The IMAGINE study is post-hoc assessment of cytokine expression within the aqueous samples and in-depth assessment of the imaging studies obtained throughout the DAVE study. For this analysis, two multiplex arrays measured levels in quadruplicate for 54 cytokines for each eye. The baseline macular OCT cube was evaluated using an automated multi-layer, feature extraction segmentation platform with expert review and segmentation correction, as needed. Retinal anatomic layers, including ellipsoid zone (EZ) integrity, and volumetric fluid were evaluated. Pearson correlation coefficients assessed the correlation between the measured cytokines and OCT features.

Results : The mean age of 24 included subjects was 54 ± 10, and 19 were from men (79%). Of the 54 cytokines measured, 27 were detected at analyzable levels. Increased panmacular intraretinal fluid volume was directly correlated with LIF (r=0.41, p=0.046) and increased panmacular fluid was correlated with MMP-1 (r=0.44, p=0.030). VEGF did not significantly correlate with fluid volumes or retinal thickness parameters. Multiple cytokines correlated with decreased EZ integrity, as measured by reduced mean central subfield EZ-RPE thickness including uPAR (r= -0.44, p=0.37), HGF (r = -0.57, p=0.0048), LIF (r= -0.47, p=0.022), and MCP-1 (r= -0.46, p=0.025).

Conclusions : Elevated LIF is associated with increased intraretinal fluid volume in treatment-naïve DME, aligning with prior reports of increased LIF levels in diabetic retinopathy. Several cytokines, including MCP-1 and LIF, correlated with decreased ellipsoid zone integrity. Further research is needed to evaluate the potential for OCT-derived biomarkers that may provide insights into the underlying expressed cytokine profile.

This is a 2020 ARVO Annual Meeting abstract.