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John Carey Fitzpatrick, Archana Nair, Sarah Al-Awamlh, Kurt Scavelli, Paul Mallory, Jinsong Sheng, Sapna Gangaputra, Stephen Jae Kim; Cytokine Profiles of Normal Eyes in the INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy (INSPIRE) Study. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2368 – A0052.
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© ARVO (1962-2015); The Authors (2016-present)
INSPIRE is a prospective, randomized, 3-year study, with aims of characterizing the role of aqueous cytokines with diabetic retinopathy progression. This analysis establishes the cytokine levels in eyes without diabetic retinopathy or other ocular inflammatory conditions. These levels will serve as a normal for comparison with diabetic retinopathy and other inflammatory ocular conditions.
104 eyes of 104 non-diabetic patients were enrolled. All eyes underwent unilateral vitrectomy for non diabetic causes such as epiretinal membrane, macular hole, vitreous opacities, vitreous hemorrhage, and retinal detachment. Approximately 0.2 mL of undiluted aqueous sample was obtained with a 30 gauge needle at the time of vitrectomy. These samples were collected and stored at -80 degrees C and later analyzed for 24 pro and anti inflammatory cytokine levels using the Millipore Multiplex Human Cytokine Kit (Millipore Corporation, Burlington, MA) according to the manufacturer's instructions.
Baseline characteristics of the cohort are shown in Table 1. The mean age was 68.4 years +/- SD 7.91. 48 patients were phakic, 55 patients were pseudopakic, and 1 was aphakic. Four patients were on systemic immunosuppressive mediations including methotrexate, fingolimod, azathioprine, and imatinib for systemic autoimmune conditions. Six patients were on topical prostaglandin analogs and one patient was on fluorometholone drops. Six patients had systemic inflammatory diseases including gout, psoriasis, multiple sclerosis, Crohn's disease, and undifferentiated connective tissue disease.24 cytokines were measured in all 104 eyes. The most clinically relevant cytokines measured included VEGF, TNF-a, IL-8, IP-10, IL-6, IL-1b, IL-17A, IL-10. These cytokine levels are summarized in Table 2. Additional cytokines also detected included FGF-2, Eotaxin, G-CSF, Fit-3L, GRO, MCP-3, MDC, PDGF-AA, PDGF-AB/BB, sCD40L, IL-1RA, IL-2, IL-4, MCP-1, MIP-1b, and RANTES.
To our knowledge, this is the first large scale characterization of normal cytokine levels in eyes without diabetic retinopathy or other ocular inflammatory conditions. This data will be integral to better understand the inflammatory drivers of diabetic retinopathy progression and subsequent therapeutic targets.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
Baseline Patient Characteristics
VEGF and Cytokine Levels
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