Inflammatory Response to Contact Lenses in Patients With Keratoconus Compared With Myopic Subjects

Abstract

Wearing RGP CLs induces overexpression of IL-6, TNF-alpha, ICAM-1, and VCAM-1 in the tears of patients with keratoconus. These increased levels are higher in cases with severe keratoconus.

Keratoconus: an inflammatory disorder?

“…102 They could not detect by multiplex immuno-bead assay the levels IL-17 in tears of keratoconus patients, but they found an increase by conventional ELISA on a limited number of pooled tear samples. In addition, they found lower levels of TNF-α, an observation that disagrees with reports from Lema et al 20,21,22 and Balasubramanian et al 18 The possible reasons for this disparity could be either artefactual differences in the antibody-based assays or real differences between patient populations. 103 Whether the altered protein composition of tears in eyes suffering from keratoconus is an effect of events in the corneal epithelium or has a direct influence in the development of the disease remains to be elucidated.…”

“…18,21,23,75,93,125 There is also a decrease in the levels of several antioxidant or anti-inflammatory molecules: SOD, glutathione, lactoferrin, IgA, and IL-10. 19,20,106,[108][109][110]144 An important decrease in the level of protease inhibitors such as cystatins (inhibitors of cysteine proteases) and TIMP-1 (inhibitor of MMPs) have also been reported. 95,96,101,[129][130][131] The increased activity of several proteolytic enzymes results in higher concentrations of ROS, RNS, cytotoxic aldehydes (CAs) and peroxynitrates (Ps) (which decreases the activity of TIMP-1 and increase MMP-2), 63,143,144,146,149 and given the lower production of SOD 143 possibly related to IL-1α, 158 an environment with high oxidative stress and low pH is formed, causing an increase in the activation of the caspases (caspase-9 and -12), mitochondrial dysfunction (MD), and DNA damage, 156 which eventually lead to increased apoptosis.…”

“…The tear film in keratoconus have shown increased levels of pro-inflammatory molecules: IL-1α, -4, -5, -6, -8, and -17, TNF-α, TGF-B1 (TGFβ-1), ICAM-1, and VCAM-1. 18,20,21,86,103 β-Actin gene has been found to be downregulated and the protein absent in corneal buttons from keratoconus patients. 160 The elevated levels of IL-1-α and TNF-α, and low levels of β-actin have been related to triggering apoptosis of keratocytes.…”

“…ICAM-1 has been shown to participate in corneal inflammation. 74 Lema et al 20 concluded that a higher level of inflammatory response to contact lens wearing was present in keratoconus in comparison with normal corneas.…”

“…More recent studies have proved significant action of inflammatory mediators and a possible effect of oxidative stress, thus questioning the noninflammatory status of the disease. 3,[18][19][20][21][22][23][24][25] In 2002, Tachibana et al 26,27 reported that they established an inbred line of spontaneous mutant mice with keratoconus-affected corneas (SKC mice) resembling corneas of human eyes with keratoconus, but which were often associated with a red punctum at the apex.. They found that the red puncta seen in the center of the corneas were due to vascular infiltration and extravasations of blood cells, and the corneas showed lymphocyte infiltration.…”