THIRD PRIZE - COS Awards for Excellence in Ophthalmic Research - Papers

Authors:

Dominique Geoffrion¹, Marie-Claude Robert², Robert K. Koenekoop³, Younes Agoumi², Mona Harissi-Dagher².
¹Experimental Surgery, McGill University, ²Ophthalmology, Université de Montréal, ³Ophthalmology, McGill University.

Disclosure Block:

D. Geoffrion: None. M. Robert: None. R.K. Koenekoop: None. Y. Agoumi: None. M. Harissi-Dagher: None.

Abstract Title:

Tear film cytokine profiles of Boston keratoprosthesis type 1 patients with and without glaucoma

Abstract Body:

Purpose: Cytokines are biomarkers for glaucoma and play a role in its pathogenesis. The purpose was to compare cytokine levels in the tear film of Boston keratoprosthesis (KPro) patients with and without glaucoma, relative to healthy controls, and correlate levels with clinical parameters.
Study Design: Prospective cross-sectional study.
Methods: A total of 58 eyes (from 58 patients) were included in this study: 41 KPro eyes with glaucoma, 7 KPro eyes without glaucoma, and 10 healthy controls. The levels of 27 cytokines in the tear fluid were measured using a multiplex bead immunoassay. Intraocular pressure (IOP), cup-to-disk ratio (CDR), visual acuity, topical medications, retinal nerve fiber layer thickness, and angle closure were clinically assessed in all KPro patients. Differences in cytokine levels between groups were analyzed by non-parametric tests, and correlations with clinical parameters by Spearman’s test, with a significance level of P<0.05.
Results: Tear levels of TNF-a, IL-1b, FGF-2, and IFN-g were significantly higher in KPro patients with glaucoma compared to KPro patients without glaucoma (P= 0.020; 0.008; 0.043; 0.018, respectively). Both KPro groups had similar baseline characteristics, pre-KPro diagnoses, and topical antibiotic and steroid regimen (P>0.05). Tear levels of IL-1Ra, IL-15, VEGF, RANTES were significantly higher in KPro patients with glaucoma compared to controls (no KPro and no glaucoma) (P= <0.001; 0.034; <0.001; 0.001, respectively). In KPro patients, tear IL-1b and IFN-g 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). Tear TNF-a and FGF-2 levels were positively correlated with CDR (r=0.348, P=0.022 and r=0.344, P=0.021, respectively).
Conclusions: Cytokines TNF-a, IL-1b, FGF-2, and IFN-g are elevated in tear fluid of KPro patients with glaucoma and correlate with CDR and IOP. These results show, for the first time in humans, concordance with the documented elevation of TNF-a and IL-1b in murine KPro model. Ocular surface inflammation may reflect an inflammatory process of glaucoma in KPro.