Association of Intermediate-Stage Age-Related Macular Degeneration with Plasma Inflammatory Biomarkers in Persons with AIDS

Douglas A Jabs; Michael F Schneider; Jeong Won Pak; Gabriele Beck-Engeser; Fay Chan; Gabrielle C Ambayec; Peter W Hunt

doi:10.1016/j.xops.2023.100437

Association of Intermediate-Stage Age-Related Macular Degeneration with Plasma Inflammatory Biomarkers in Persons with AIDS

Ophthalmol Sci. 2023 Nov 23;4(3):100437. doi: 10.1016/j.xops.2023.100437. eCollection 2024 May-Jun.

Authors

Douglas A Jabs^{1

2}, Michael F Schneider¹, Jeong Won Pak³, Gabriele Beck-Engeser⁴, Fay Chan⁴, Gabrielle C Ambayec⁴, Peter W Hunt⁴

Affiliations

¹ Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
² Wilmer Eye Institute, the Department of Ophthalmology, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
³ Department of Ophthalmology and Visual Sciences, the University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
⁴ Department of Medicine, the University of California, San Francisco, School of Medicine, San Francisco, California.

Abstract

Purpose: To evaluate associations of plasma levels of inflammatory biomarkers with age-related macular degeneration (AMD) and cataract in persons with AIDS.

Design: Nested case-control study (analysis 1) and nested cohort study (analysis 2).

Participants: Analysis 1: persons with AIDS and incident intermediate-stage AMD (n = 26) and controls without AMD matched for age, race/ethnicity, and gender (n = 49) from The Longitudinal Study of Ocular Complications of AIDS. Analysis 2: 475 persons from LSOCA with baseline plasma biomarker levels followed prospectively for cataract.

Methods: In both analyses, cryopreserved plasma specimens obtained at baseline were assayed for monocyte chemoattractant protein (MCP)-1 (CC motif chemokine ligand [CCL] 2), macrophage inflammatory protein (MIP)-1β (CCL4), soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, and fractalkine (CX3 motif chemokine ligand 1 [CX3CL1]).

Main outcome measures: Analysis 1: mean difference (cases - controls) in plasma biomarker levels. Analysis 2: incident cataract.

Results: After adjusting for plasma human immunodeficiency virus RNA level, CD4+ T-cell count, and smoking, elevated baseline plasma levels of sTNFR2 and IL-18 (mean differences [cases - controls] 0.11 log₁₀[pg/mL]; 95% confidence interval [CI], 0.01-0.20; P = 0.024 and 0.13 log₁₀[pg/mL]; 95% CI, 0.01-0.24; P = 0.037, respectively) each were associated with incident AMD. In a competing risk (with mortality) analysis, elevated baseline standardized log₁₀ plasma levels of MCP-1, sTNFR2, IL-18, and fractalkine each were associated with a decreased cataract risk.

Conclusions: When combined with previous data suggesting that AMD is associated with elevated plasma levels of C-reactive protein, soluble CD14, and possibly IL-6, the association of elevated plasma levels of sTNFR2 and IL-18 with incident AMD, but not with incident cataract, suggests that innate immune system activation, and possibly NLRP3 inflammasome activation, may play a role in the pathogenesis of AMD in this population.

Financial disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Keywords: Acquired immunodeficiency syndrome; Age-related macular degeneration; Biomarkers; Cataract; Inflammation.

Grants and funding

R01 EY025093/EY/NEI NIH HHS/United States