Abstract
Purpose:
To assess whether patients with type 2 diabetes (T2D) and foveal eversion (FE) on spectral domain optical coherence tomography have different urine and plasma cytokine profiles to patients with other phenotypic patterns of diabetic macular edema (DME). The FE phenotype of DME is similar to that of macular edema of inflammatory causes such as in uveitis or Irvine Gass syndrome. This led us to hypothesize that this form of DME might have a different cytokine profile and potentially a different pathogenic mechanism. An association between severe diabetic retinopathy (DR) and higher urine monocyte chemoattractant protein-1 (MCP-1) levels than those found in patients with less severe DR has previously been reported.
Methods:
The levels of MCP-1 in the urine of T2D patients with DME causing FE and those with DME not causing FE were compared. A Student t test was used for analysis. Fifteen cytokines (ANG-2, EGF, EPO R, ICAM-1, IL-6, IL-8, IP-10, MCP-1, MMP-9, PDGF-AA, SDF-1, TNF alpha, VCAM-1, VEGF and Kallikrein 14) that have previously been implicated in the development of DME were selected for analysis in plasma. The levels of these cytokines were compared in patients with T2DM, DME and FE vs those without FE. A linear discriminant analysis was used to identify the linear combination of cytokines most likely to be responsible for the difference between the 2 groups.
Results:
Urine samples were obtained from 26 patients with DME and FE and 42 without FE. The difference in urine MCP-1 levels between the groups approached, but did not reach, statistical significance (p = 0.0567). Those with FE had lower urine MCP-1 levels. Eighty-three plasma samples were analysed, revealing a highly statistically significant difference between the means of the cytokine levels in those with and without FE (p value <0.001, 95% CI -1.488 to -0.6). Using a linear discriminant analysis, it was found that the shortest linear combination of loadings of cytokines that could discriminate between the 2 groups, at the 5% significance level, was 2 of the 15 cytokines working in opposite directions. These 2 alone could account for the difference between those with FE and those without (p= 0.0396).
Conclusions:
DME with FE might have a different cytokine profile to that of other forms of DME in T2D. This could be an indication of a different underlying pathogenic mechanism.
Keywords: 490 cytokines/chemokines •
585 macula/fovea •
499 diabetic retinopathy