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

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

Douglas A Jabs  1   2 , Michael F Schneider  1 , Jeong Won Pak  3 , Gabriele Beck-Engeser  4 , Fay Chan  4 , Gabrielle C Ambayec  4 , Peter W Hunt  4
Affiliations

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

Douglas A Jabs et al. Ophthalmol Sci. .

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.

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References

    1. Palella F.J., Jr., Delaney K.M., Moorman A.C., et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. N Engl J Med. 1998;338:853–860. - PubMed
    1. Cooney E.L. Clinical indicators of immune restoration following highly active antiretroviral therapy. Clin Infect Dis. 2002;34:224–233. - PubMed
    1. Murphy E.L., Collier A.C., Kalish L.A., et al. Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Ann Intern Med. 2001;135:17–26. - PubMed
    1. Jabs D.A. Cytomegalovirus retinitis and the acquired immunodeficiency syndrome–bench to bedside: LXVII Edward Jackson Memorial Lecture. Am J Ophthalmol. 2011;151:198–216. - PMC - PubMed
    1. Schneider M.F., Gange S.J., Williams C.M., et al. Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984-2004. AIDS. 2005;19:2009–2018. - PubMed