Increased Systemic C-Reactive Protein Is Associated With Choroidal Thinning in Intermediate Age-Related Macular Degeneration

Abstract

Purpose C-reactive protein (CRP) and decreased choroidal thickness (CT) are risk factors for progression to advanced age-related macular degeneration (AMD). We examined the association between systemic levels of CRP and CT in patients with intermediate AMD (iAMD). Methods Patients with iAMD in the Colorado AMD Registry were included. Baseline serum samples and multimodal imaging including spectral domain–optical coherence tomography (SD-OCT), fundus photography, and autofluorescence were obtained. Medical and social histories were surveyed. CT was obtained by manual segmentation of OCT images. High-sensitivity CRP levels were quantified in serum samples. Univariate and multivariable linear regression models accounting for the intrasubject correlation of two eyes were fit using log-transformed CT as the outcome. Results The study included 213 eyes from 107 patients with a mean age of 76.8 years (SD, 6.8). Median CT was 200.5 µm (range, 86.5–447.0). Median CRP was 1.43 mg/L (range, 0.13–17.10). Higher CRP was associated with decreased CT in the univariate model ( P = 0.01). Older age and presence of reticular pseudodrusen (RPD) were associated with decreased CT ( P < 0.01), whereas gender, body mass index, and smoking were not associated with CT. Higher CRP remained significantly associated with decreased CT after adjustment for age and RPD ( P = 0.01). Conclusions Increased CRP may damage the choroid, leading to choroidal thinning and increased risk of progression to advanced AMD. Alternatively, CRP may be a marker for inflammatory events that mediate ocular disease. The results of this study further strengthen the association between inflammation and AMD. Translational Relevance Increased CRP is associated with choroidal thinning, a clinical risk factor for AMD.

C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration

“…While choroidal thickness was found here to be increased in early/intermediate patients with higher CRP levels, previous research studies have related increased CRP levels with thinner choroid ( 25 ), thus supporting a role for CRP as an inflammation biomarker of AMD progression. However, such studies did not differentiate among AMD stages and could be explained by the presence of atrophy or previous treatment in advanced AMD.…”

Plasma C-C Chemokine Concentrations in Intermediate Age-Related Macular Degeneration

“…Although much of the understanding of this process has been focused on complement and specifically on CFH mutations, we believe that complement does not function in isolation in immune-mediated responses and that other soluble mediators as well as cellular components of inflammation may be important. For example, C reactive protein (CRP) has also been shown to be related to AMD development and we have shown that increased serum CRP is correlated with decreased choroidal thickness in iAMD (14). The final pathology in AMD is local damage to the RPE and outer retina, however the systemic inflammatory milieu may alter the local inflammatory responses.…”

Biomarkers for the Progression of Intermediate Age-Related Macular Degeneration

“…In one study, reduction in the choriocapillaris complex thickness was significantly associated with AMD progression over 5 years of follow-up ( p < 0.001): a thickness of < 10.5 µm was associated with a high probability of progression, whereas a thickness of > 10.5 but < 20.5 µm was associated with moderate probability [ 87 ]. However, the relationship between choroidal thickness and AMD status is affected by several other factors, such as axial length, age, and possibly the presence of RPD, which complicates the reported associations [ 86 , 88 ].…”

“…Interestingly, a combination of elevated CRP and the CC (Y402H) genotype in the CFH gene resulted in a superadditivity of risks, with an OR of 19.3 (95% CI 2.8–134) for late AMD and 6.8 (95% CI 1.2–38.8) for AMD progression [ 146 ]. In another study, CRP was significantly associated with choroidal thinning in patients with iAMD ( p = 0.01) [ 88 ].…”