Inflammatory Molecules in the Tears of Patients with Keratoconus

Purpose: To determine levels of a panel of inflammatory molecules and matrix metalloproteinases in the tears of patients with keratoconus.

Design: A prospective, case-control study.

Participants: Twenty-eight patients (1 eye from each) diagnosed with keratoconus at the Instituto Galego de Oftalmoloxia, Santiago de Compostela, Spain, during the period from September 2001 to June 2002, and 20 normal control subjects (1 eye each) were studied.

Methods: Patients with keratoconus were examined in a routine fashion, and keratometric readings were taken to monitor the degree of ectasia. Fifteen microliters of tears was collected by capillary flow from each eye.

Main Outcome Measures: The concentrations of cytokines (interleukin-4 [IL-4], IL-6, IL-10, and tumor necrosis factor alpha [TNF-alpha]), cell adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and matrix metalloproteinase 9 (MMP-9) were measured by enzyme-linked immunoadsorbent assay.

Results: Patients with keratoconus initially had significantly higher levels of IL-6 (6.7 [4.8-10.8] pg/ml vs. 2.2 [1.0-4.1] pg/ml in control subjects [P<0.0001]), TNF-alpha (3.8 [2.9-14.4] pg/ml vs. 1.8 [1.5-2.3] pg/ml in control subjects [P<0.0001]), and MMP-9 (66.5 [49.2-139.3]ng/ml vs. 6.1 [3.9-8.3] ng/ml in control subjects. The extent of the increase was found to be associated with the severity of keratoconus.

Conclusions: Interleukin-6, TNF-alpha, and MMP-9 are overexpressed in the tears of patients with keratoconus, indicating that the pathogenesis of keratoconus may involve chronic inflammatory events.