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

Purpose: 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-α) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of soluble TNF-α, TNF receptors 1 (TNFR1) and 2 (TNFR2), and leptin in patients with Boston type I KPro.

Methods

Venous blood samples were collected from KPro patients with glaucoma (KPro G, n = 19), KPro patients without glaucoma (KPro NoG, n = 12), primary angle closure glaucoma without KPro (PACG, n = 13), and narrow angles without glaucoma or KPro (NA, n = 21). TNF-α, 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.

Results

All groups had similar age, body mass index (BMI), IOP, and ESR (p ≥ 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-α (1.18 ± 0.58 pg/ml, p = 0.006; 1.16 ± 0.50 pg/ml, p = 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, p = 0.048). In multivariate analysis, KPro status remained positively associated with TNF-α levels (β = 0.36; 95% confidence intervals [CI]: 0.14-0.58; p = 0.002) and TNFR2 levels (β = 458.3; 95% CI: 32.8-883.7; p = 0.035) after adjusting for age, gender, BMI, glaucoma status, and ESR. TNFR1 and leptin levels were not significantly different in the study groups.

Conclusions

We detected elevated serum levels of TNF-α and TNFR2 in KPro patients. Longitudinal studies are needed to establish TNF-α and TNFR2 as serum biomarkers related to KPro surgery. Abbreviations: 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.