Correlation of Intraocular Cytokine Expression with Higher Order OCT Features in Retinal Venous Occlusive Disease

Abstract

Purpose : The clinical presentation of retinal vein occlusion and response to anti-VEGF therapy is variable. The variable expression of select cytokines may significantly impact prognosis and optimal therapeutic response. The purpose of this study is to correlate underlying cytokine expression with extracted higher order OCT imaging features, including as intraretinal fluid volume and outer retinal integrity measures in eyes with retinal vein occlusion (RVO).

Methods : The WAVE study is a prospective clinical trial for management of RVO comparing ranibizumab monotherapy to ranibizumab combined with targeted panretinal photocoagulation. The IMAGINE study includes a post-hoc assessment of the WAVE clinical trial evaluating the underlying cytokine expression with associated imaging features. Eyes were included from the WAVE study with retinal vein occlusions had aqueous humor samples and macular cube OCT obtained at baseline. Using multiplex cytokine arrays, 54 cytokines were measured in quadruplicate. Higher order OCT features were extracted using an automated multi-layer and fluid segmentation platform to quantify volumetric panmacular anatomy including ellipsoid zone integrity and intraretinal fluid. Pearson’s correlation coefficients compared the association between baseline cytokine levels and OCT characteristics.

Results : Twenty-six eyes from the WAVE study were included. Thirteen of the eyes were from women (50%), and 13 were from men (50%). From the 54 cytokines in the 2 arrays, 27 were detected at measureable levels. Both VEGF (r=0.48, p=0.012) and MMP-9 (r=0.40, p=0.040) levels correlated with increased panmacular intraretinal fluid volume. Increased expression of several cytokines correlated with EZ disruption (i.e., decreased mean EZ-RPE central subfield thickness) including AgRP (r= -0.41, p=0.035), ANG-1 (r = -0.45, p=0.02), MMP-9 (r= -0.52, p=0.0071), and uPAR (r= -0.46, p=0.017).

Conclusions : Intraocular cytokine concentrations correlate with OCT-based higher order features. Higher presenting VEGF and MMP-9 are associated with increased macular edema, while increased ANG-1, AgRP, MMP-9, and uPAR correlate with decreased ellipsoid zone integrity. Future research will clarify the longitudinal cytokine dynamics in retinal vein occlusion and whether these imaging biomarkers can predict treatment response.

This is a 2020 ARVO Annual Meeting abstract.