Dominique Geoffrion1,2, Marie-Claude Robert1, Adriana Di Polo1,3, Robert K Koenekoop4, Younes Agoumi1, Mona Harissi-Dagher1. 1. Department of Ophthalmology, Université de Montréal, Centre hospitalier de l'Université de Montréal, Montreal, Quebec, Canada. 2. Department of Experimental Surgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. 3. Department of Neurosciences, Université de Montréal, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada. 4. Departments of Experimental Surgery, Paediatric Surgery, Adult Ophthalmology, and Human Genetics, Montreal Children's Hospital, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
Abstract
Purpose: Inflammatory cytokines are involved in glaucoma pathogenesis. The purpose is to compare cytokine levels in the tear film of Boston keratoprosthesis (KPro) patients with and without glaucoma, relative to controls, and correlate levels with clinical parameters. Methods: This cross-sectional study enrolled 58 eyes (58 patients): 41 KPro eyes with glaucoma, 7 KPro eyes without glaucoma, and 10 healthy controls. Twenty-seven cytokines were measured by multiplex bead immunoassay. Intraocular pressure (IOP), cup-to-disk ratio (CDR), retinal nerve fiber layer, visual acuity, topical medications, and angle closure were assessed in all KPro eyes. Cytokine levels between groups were analyzed by nonparametric tests, and correlations with clinical parameters by Spearman's test. Results: Levels of TNF-ɑ, IL-1β, FGF-basic, and IFN-ɣ were significantly higher in KPro with glaucoma compared to KPro without (P = 0.020; 0.008; 0.043; 0.018, respectively). KPro groups had similar characteristics and topical antibiotic/steroid regimen. Levels of IL-1Ra, IL-15, VEGF, and RANTES were significantly higher in KPro with glaucoma compared to controls (P < 0.001; = 0.034; < 0.001; = 0.001, respectively). IL-1β and IFN-ɣ levels were positively correlated with CDR (r = 0.309, P = 0.039 and r = 0.452, P = 0.006, respectively) and IOP (r = 0.292, P = 0.047 and r = 0.368, P = 0.023, respectively). TNF-α and FGF-basic levels were positively correlated with CDR (r = 0.348, P = 0.022 and r = 0.344, P = 0.021, respectively). Conclusions: TNF-α, IL-1β, FGF-basic, IFN-ɣ are elevated in tears of KPro patients with glaucoma and correlate with CDR and IOP. These results show, for the first time in humans, concordance with documented elevations of TNF-α and IL-1β in the murine KPro model. Ocular surface inflammation may reflect inflammatory processes of KPro glaucoma.
Purpose: Inflammatory cytokines are involved in glaucoma pathogenesis. The purpose is to compare cytokine levels in the tear film of Boston keratoprosthesis (KPro) patients with and without glaucoma, relative to controls, and correlate levels with clinical parameters. Methods: This cross-sectional study enrolled 58 eyes (58 patients): 41 KPro eyes with glaucoma, 7 KPro eyes without glaucoma, and 10 healthy controls. Twenty-seven cytokines were measured by multiplex bead immunoassay. Intraocular pressure (IOP), cup-to-disk ratio (CDR), retinal nerve fiber layer, visual acuity, topical medications, and angle closure were assessed in all KPro eyes. Cytokine levels between groups were analyzed by nonparametric tests, and correlations with clinical parameters by Spearman's test. Results: Levels of TNF-ɑ, IL-1β, FGF-basic, and IFN-ɣ were significantly higher in KPro with glaucoma compared to KPro without (P = 0.020; 0.008; 0.043; 0.018, respectively). KPro groups had similar characteristics and topical antibiotic/steroid regimen. Levels of IL-1Ra, IL-15, VEGF, and RANTES were significantly higher in KPro with glaucoma compared to controls (P < 0.001; = 0.034; < 0.001; = 0.001, respectively). IL-1β and IFN-ɣ levels were positively correlated with CDR (r = 0.309, P = 0.039 and r = 0.452, P = 0.006, respectively) and IOP (r = 0.292, P = 0.047 and r = 0.368, P = 0.023, respectively). TNF-α and FGF-basic levels were positively correlated with CDR (r = 0.348, P = 0.022 and r = 0.344, P = 0.021, respectively). Conclusions: TNF-α, IL-1β, FGF-basic, IFN-ɣ are elevated in tears of KPropatients with glaucoma and correlate with CDR and IOP. These results show, for the first time in humans, concordance with documented elevations of TNF-α and IL-1β in the murineKPro model. Ocular surface inflammation may reflect inflammatory processes of KPro glaucoma.