Systemic Levels of C-Reactive Protein in Patients with Age-Related Macular Degeneration: A Meta-Analysis of 53 Studies with >60.000 Participants

Author: Yousif Subhi (Denmark)

Co-authors: Chen Feng, Marie Krogh Nielsen, Torben Lykke Sørensen

Purpose

C-reactive protein (CRP) is an important and easily measurable marker of chronic low-grade inflammation. It has been measured in a large number of studies of age-related macular degeneration (AMD) because chronic low-grade inflammation plays an important role in ageing and age-related diseases.

Setting/Venue

Systematic review with meta-analyses.

Methods

We searched the literature databases PubMed/MEDLINE, EMBASE, Web of Science and the Cochrane Central using relevant phrases and Boolean combinations. Identified references were examined and full-text studies were screened for eligibility and data extraction by two authors in an independent fashion with a third author to decide on disagreements. For the meta-analyses, random effects model was employed, and summary measures were reported in standardized mean difference (SMD). Primary outcome was SMD in CRP between any AMD and healthy controls. Separate subgroup analyses were made for early AMD vs. healthy controls, late AMD vs. healthy controls, and more specifically, geographic atrophy vs. healthy controls, and neovascular AMD vs. healthy controls.

Results

We identified 53 studies with 60,598 participants (10,392 patients and 38,901 controls). Our meta-analyses revealed that early AMD was not associated to systemic CRP (Cohen’s d = 0.03 [-0.04 to 0.10]; OR = 1.06 [0.93 to 1.20]; P = 0.39) whereas late AMD (Cohen’s d = 0.38 [0.24 to 0.51]; OR = 1.99 [1.55 to 2.52]; P < 0.0001), and neovascular AMD (Cohen’s d = 0.40 [0.24 to 0.56]; OR = 2.07 [1.55 to 2.76]; P < 0.0001) was associated with a small-to-moderate increase in systemic CRP. Geographic atrophy secondary to AMD was not associated with any difference in systemic CRP (Cohen’s d = -0.26 [-0.99 to 0.47]; OR = 0.62 [0.17 to 2.35]; P = 0.48).

Conlusions

There is now an extensive evidence base documenting an increased systemic CRP in AMD. This increase seems to be isolated to neovascular AMD. Future studies need to investigate whether modulating systemic CRP may be an approach to stop progression to neovascular AMD or if modulation of systemic CRP possesses any role in the treatment of macular neovascularization.

Financial Disclosure

None.