4.3 Article

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

Journal

CURRENT EYE RESEARCH
Volume 44, Issue 6, Pages 599-606

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/02713683.2019.1568500

Keywords

Boston keratoprosthesis; primary angle closure glaucoma; tumor necrosis factor alpha; KPro; inflammation

Categories

Funding

  1. Boston Keratoprosthesis Research Fund
  2. Massachusetts Lions Eye Research Fund
  3. Harvard Medical School
  4. Harvard Glaucoma Center of Excellence

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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-) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of soluble TNF-, 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-, 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 5.33.7years. Compared to NA patients (0.720.3pg/ml), KPro G and KPro NoG patients had higher blood plasma levels of TNF- (1.18 +/- 0.58pg/ml, p =0.006; 1.16 +/- 0.50pg/ml, p =0.04, respectively). Similarly, KPro G patients had higher blood plasma levels of TNFR2 (2768 +/- 1368pg/ml) than NA patients (2020 +/- 435pg/ml, p =0.048). In multivariate analysis, KPro status remained positively associated with TNF- levels (=0.36; 95% confidence intervals [CI]: 0.14-0.58; p =0.002) and TNFR2 levels (=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- and TNFR2 in KPro patients. Longitudinal studies are needed to establish TNF- 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-: tumor necrosis factor alpha; TNFR1: tumor necrosis factor receptor 1; TNFR2: tumor necrosis factor receptor 2

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