Elsevier

Ophthalmology

Volume 112, Issue 4, April 2005, Pages 654-659
Ophthalmology

Original article
Inflammatory Molecules in the Tears of Patients with Keratoconus

Presented in part at: Association for Research in Vision and Ophthalmology meeting, May, 2003; Fort Lauderdale, Florida.
https://doi.org/10.1016/j.ophtha.2004.11.050Get rights and content

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 Oftalmoloxía, 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 α [TNF-α]), 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-α (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-α, and MMP-9 are overexpressed in the tears of patients with keratoconus, indicating that the pathogenesis of keratoconus may involve chronic inflammatory events.

Section snippets

Subjects and Examinations

We have designed a prospective, case-controlled study in which 28 patients with keratoconus and 20 normal subjects were enrolled. Patients with keratoconus had never worn contact lenses or had not worn lenses for a period of more than 1 year (52.3% males; mean age, 22.4±6.5 years). Normal subjects had never worn contact lenses (47.8% males; mean age, 22.6±6.6 years). We studied 1 eye from each patient, generally the right eye. Exclusion criteria included the existence of active inflammatory or

Clinical Features

No age-related or gender-related statistical differences were detected between patients with keratoconus and control subjects. The duration of patient-reported keratoconus varied from 1 to 16 years (mean, 7.0–6.2 years). Only 1 patient (5%) from the control group was diagnosed as having allergic disease, whereas 16 patients (57.1%) from the keratoconus group had experienced at least 1 allergic episode. Eighteen patients with keratoconus (64.3%) admitted frequent and vigorous eye rubbing; no

Discussion

Despite extensive basic and clinical studies of keratoconus in recent years, the precise mechanisms underlying this pathology still remain largely unknown. Most of these studies used corneas that had been obtained from transplants, and erroneous conclusions have been drawn from a number of these studies.20 Moreover, it has been shown that the reported increased levels of TNF-α and IL-1 are not specific to keratoconus but are present in other pathologies of the cornea as well.8 Nevertheless,

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