Blood Levels of Tumor Necrosis Factor Alpha and Its Type 2 Receptor Are Elevated in Patients with Boston Type I Keratoprosthesis

<b>Purpose</b>: Boston keratoprosthesis (KPro) patients are prone to glaucoma even with well-controlled intraocular pressure (IOP). Recent experimental data have shown that soluble tumor necrosis factor alpha (TNF-<i>α</i>) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of soluble TNF-<i>α</i>, TNF receptors 1 (TNFR1) and 2 (TNFR2), and leptin in patients with Boston type I KPro. <b>Methods</b>: Venous blood samples were collected from KPro patients with glaucoma (KPro G, <i>n</i> = 19), KPro patients without glaucoma (KPro NoG, <i>n</i> = 12), primary angle closure glaucoma without KPro (PACG, <i>n</i> = 13), and narrow angles without glaucoma or KPro (NA, <i>n</i> = 21). TNF-<i>α</i>, TNFR1, TNFR2, and leptin levels were quantified using the enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate (ESR) was assessed using the Westergren test. Patients with underlying autoimmune conditions or diabetes were excluded from the study. <b>Results</b>: All groups had similar age, body mass index (BMI), IOP, and ESR (<i>p</i> ≥ 0.11). The mean time from KPro surgery to blood draw was 5.3 ± 3.7 years. Compared to NA patients (0.72 ± 0.3 pg/ml), KPro G and KPro NoG patients had higher blood plasma levels of TNF-<i>α</i> (1.18 ± 0.58 pg/ml, <i>p</i> = 0.006; 1.16 ± 0.50 pg/ml, <i>p</i> = 0.04, respectively). Similarly, KPro G patients had higher blood plasma levels of TNFR2 (2768 ± 1368 pg/ml) than NA patients (2020 ± 435 pg/ml, <i>p</i> = 0.048). In multivariate analysis, KPro status remained positively associated with TNF-<i>α</i> levels (<i>β</i> = 0.36; 95% confidence intervals [CI]: 0.14–0.58; <i>p</i> = 0.002) and TNFR2 levels (<i>β</i> = 458.3; 95% CI: 32.8–883.7; <i>p</i> = 0.035) after adjusting for age, gender, BMI, glaucoma status, and ESR. TNFR1 and leptin levels were not significantly different in the study groups. <b>Conclusions</b>: We detected elevated serum levels of TNF-<i>α</i> and TNFR2 in KPro patients. Longitudinal studies are needed to establish TNF-<i>α</i> and TNFR2 as serum biomarkers related to KPro surgery. <b>Abbreviations</b>: BCVA: best corrected visual acuity; BMI: body mass index; CDR: cup-to-disc ratio; EDTA: ethylenediaminetetraacetic acid; ELISA: enzyme-linked immunosorbent assay; ESR: erythrocyte sedimentation rate; HVF: Humphrey visual field; IOP: intraocular pressure; KPro G: keratoprosthesis with glaucoma; KPro NoG: keratoprosthesis without glaucoma; KPro: keratoprosthesis; MD: mean deviation; NA: narrow angle; non-KPro: without keratoprosthesis; PACG: primary angle closure glaucoma; RNFL: retinal nerve fiber layer; TNF-α: tumor necrosis factor alpha; TNFR1: tumor necrosis factor receptor 1; TNFR2: tumor necrosis factor receptor 2