CLINICAL SCIENCE Inflammatory Response to Contact Lenses in Patients With Keratoconus Compared With Myopic Subjects Isabel Lema, MD, PhD,* Juan A. Dura´n, MD, PhD,† Consuelo Ruiz, MD, PhD,* Elı ´o Dı ´ez-Feijoo, MD, PhD,* Arantxa Acera, DSc,† and Jesu´s Merayo, MD, PhD‡ Purpose: To determine the levels of inflammatory molecules in the tears of patients who wore rigid gas permeable (RGP) contact lenses (CLs) and who had either keratoconus or myopia. Methods: A prospective, case-control study with 4 groups enrolled 20 RGP CL keratoconus wearers and 28 keratoconus non-lens wearers, 20 myopic CL wearers, and 20 subjects with myopia that were non-lens wearers (1 eye per patient). Fifteen microliters of tears were collected by capillary flow. The concentration of cytokines (interleukin-6 [IL-6], IL-10, and tumor necrosis factor [TNF]-a), cell adhesion molecules (intercellular adhesion molecule 1 [ICAM-1] and vascular cell adhesion molecule 1 [VCAM-1]), and matrix metal- loproteinase (MMP-9) was measured by enzyme-linked immunosor- bent assay. Results: The most significant differences associated with the wearing of RGP CLs in patients with keratoconus were seen in in- creased levels of proinflammatory cytokines (IL-6, 23.7 vs. 6.4 pg/mL, P = 0.001; TNF-a, 21.3 vs. 3.8 pg/mL, P = 0.028) and cell adhesion molecules (ICAM-1, 32.8 vs. 7.7 ng/mL, P , 0.0001; VCAM-1, 57.4 vs. 29.3 ng/mL, P , 0.0001). In patients with myopia, increased levels of TNF-a (4.2 vs. 1.8 pg/mL, P , 0.0001) and MMP-9 (12.9 vs. 6.1 ng/mL, P , 0.0001) were associated with the wearing of RGP CLs. Conclusions: Wearing RGP CLs induces overexpression of IL-6, TNF-a, ICAM-1, and VCAM-1 in the tears of patients with keratoconus. These increased levels are higher in cases with severe keratoconus. Key Words: keratoconus, inflammatory molecules, tears, rigid gas- permeable contact lens (Cornea 2008;27:758–763) K eratoconus is a bilateral, asymmetric, progressive primary corneal ectasia associated with stromal thinning and cor- neal protrusion. Its prevalence is ;1:2000 in the general population, although it usually presents with puberty. 1–4 Factors associated with its unclear etiology include atopic disease, 5,6 eye rubbing, 7 genetic inheritance, 8 and con- tact lens (CL) wear. 9–11 The latter factor is relevant because rigid gas-permeable (RGP) CLs are routinely used to neutralize the otherwise uncorrectable irregular astigmatism induced by this condition. Ocular trauma, whether caused by eye rubbing or the mechanical effect of a CL, might speed up the breakdown of corneal tissue in genetically predisposed individuals. 4–7 Extensive studies of the biochemical and pathologic changes that occur at the structural and cellular levels of the cornea have been carried out. 12,13 Tissue degradation in the cornea has been amply docu- mented through the study of the concentration of inflamma- tory mediators collected from the tear film. 14,15 These include proinflammatory cytokines, cell adhesion molecules, and ma- trix metalloproteinases. Clinical management of keratoconus depends on the severity of the disease. Nonsurgical alternatives are the first choice for disease treatment. 3,5,16 In a recent study, 17 we reported the overexpression of certain inflammatory mediators in patients with keratoconus compared with myopic controls. Because RGP CLs remain the sole nonsurgical man- agement option for long-term patients with keratoconus, we thought it worthwhile to compare the concentration of these mediators between patients who wore CLs and those who did not. Both keratoconic and myopic lens wearer groups were selected for this study, with the appropriate non–lens-wearing controls. MATERIALS AND METHODS We measured the concentration of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-a (TNF-a), intercellular adhesion molecule 1 (ICAM-1), vascular adhe- sion molecule 1 (VCAM-1), and matrix metalloproteinase 9 (MMP-9) in tear film samples obtained through capillary tubes. Subjects and Clinical Examination We designed a prospective, case-controlled study, in which 4 groups were enrolled: 20 RGP CL wearers who had Received for publication September 27, 2007; revision received January 7, 2008; accepted January 22, 2008. From the *Instituto Galego de Oftalmoloxı ´a, Universidad de Santiago de Compostela, Santiago de Compostela, Spain; the †Instituto Clı ´nico- Quiru´rgico de Oftalmologı ´a, Universidad del Paı ´s Vasco, Bilbao, Spain; and the ‡IOBA, Universidad de Valladolid, Valladolid, Spain. The authors state that they have no proprietary interest in the products named in this article. Reprints: Isabel Lema, Instituto Galego de Oftalmoloxı ´a (Hospital provincial de Conxo), 15706 Santiago de Compostela, A Corun˜a, Spain (e-mail: isbellg@usc.es). Copyright Ó 2008 by Lippincott Williams & Wilkins 758 Cornea  Volume 27, Number 7, August 2008 Copyright © 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.