Erlend C S Landsend1,2, Øygunn A Utheim1,3, Hilde R Pedersen4, Hans Christian D Aass3, Neil Lagali5, Darlene A Dartt6, Rigmor C Baraas4, Tor P Utheim1,3,7,8,9,10. 1. Department of Ophthalmology, Oslo University Hospital, Oslo, Norway. 2. Faculty of Medicine, University of Oslo, Oslo, Norway. 3. Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. 4. National Centre for Optics, Vision and Eye Care, Faculty of Health and Social Sciences, University College of Southeast Norway, Kongsberg, Norway. 5. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 6. Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States. 7. Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway. 8. Department of Maxillofacial Surgery, Oslo University Hospital, Oslo, Norway. 9. Department of Ophthalmology, Stavanger University Hospital, Stavanger, Norway. 10. Department of Clinical Medicine, Faculty of Medicine, University of Bergen, Bergen, Norway.
Abstract
Purpose: To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings. Methods: We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography). Differences in cytokine levels between the two groups were analyzed, and correlations between cytokine concentrations and ophthalmologic findings in the aniridia group investigated. Results: The concentrations of six tear cytokines were significantly higher in aniridia patients than controls in both eyes, and included interleukin 1β (IL-1β), IL-9, IL-17A; eotaxin; basic fibroblast growth factor (bFGF/FGF2); and macrophage inflammatory protein 1α (MIP-1α/CCL3). The ratio between the anti-inflammatory IL-1RA and the proinflammatory IL-1β was significantly lower in patients than controls in both eyes (P = 0.005 right eye and P = 0.001 left eye). Increasing concentration of IL-1β, IL-9, IL-17A, FGF2, and MIP-1α correlated with parameters for meibomian gland dysfunction (MGD) in the aniridia group, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film. Conclusions: A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridia patients, and correlate with parameters for MGD in aniridia. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients, and explain the high prevalence of MGD and dry eye disease in these patients.
Purpose: To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings. Methods: We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography). Differences in cytokine levels between the two groups were analyzed, and correlations between cytokine concentrations and ophthalmologic findings in the aniridia group investigated. Results: The concentrations of six tear cytokines were significantly higher in aniridiapatients than controls in both eyes, and included interleukin 1β (IL-1β), IL-9, IL-17A; eotaxin; basic fibroblast growth factor (bFGF/FGF2); and macrophage inflammatory protein 1α (MIP-1α/CCL3). The ratio between the anti-inflammatory IL-1RA and the proinflammatory IL-1β was significantly lower in patients than controls in both eyes (P = 0.005 right eye and P = 0.001 left eye). Increasing concentration of IL-1β, IL-9, IL-17A, FGF2, and MIP-1α correlated with parameters for meibomian gland dysfunction (MGD) in the aniridia group, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film. Conclusions: A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridiapatients, and correlate with parameters for MGD in aniridia. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridiapatients, and explain the high prevalence of MGD and dry eye disease in these patients.