Abstract
Purpose: :
To investigate the cytokine profile of tear fluid from keratoconus participants of the Wilmer Eye Institute Keratoconus Research Center.
Methods: :
Population: Patients diagnosed with keratoconus were identified from electronic patient records over the past 10 years and by new patient appointment records at the Wilmer Eye Institute. Control population consisted of participating family members and non keratoconus individuals. Informed consent was obtained for all participants. A comprehensive patient questionnaire, clinical exam, and corneal modeling were completed for participants. Tear fluid collection: Up to five microliters of tear fluid from each eye was obtained from participants, with the exception of eyes that had undergone penetrating keratoplasty. Samples were obtained using microcapillary pipets and capillary flow by placing pipet on lower conjunctival surface, without nasal stimulation or anesthetic. Tear fluid analysis: Tear samples were stored at -80 and diluted 25x upon assaying. Comparison of patient and control tear fluid inflammatory markers was performed by multiplex cytokine analysis (Biorad, Hercules, CA). Data were stratified for severity and comparison of contact lens use vs non contact lens use was also examined.
Results: :
Tear fluid samples from 18 keratoconus patients and 11 control subjects were analyzed for interleukin (IL)-1β, IL-4, IL-6, IL-12, IL-13, interferon-gamma (IFN-γ), RANTES, and tumor necrosis factor-alpha (TNF-). Compared with controls, significantly decreased levels of IL-4, IL-12, IL-13, IFN-γ, and TNF- were found in keratoconus subjects with Kmax greater than or equal to 52 diopters. Contact lens use in patients was associated with larger decreases in IL-4, TNF-, and IFN-γ compared with control contact lens wearers. No significant difference was found for contact lens use within the control subject group. Repeat analysis with a second independent group of 8 keratoconus patients and 9 controls confirmed a trend toward lower levels of IL-4, IL-12, Il-13, IFN-γ and RANTES.
Conclusions: :
Our analysis indicates that the tear fluid of advanced keratoconus patients contain markedly decreased levels of several cytokines, IL-4 in particular. These alterations may play a role in the pathogenesis of the disease.
Keywords: keratoconus • cornea: tears/tear film/dry eye • cornea: clinical science