Overexpression of Tear Inflammatory Cytokines as Additional Finding in Keratoconus Patients and Their First Degree Family Members

Abstract

Keratoconus is a progressive corneal ectasia that may lead to severe visual impairment due to the irregular astigmatism caused by corneal thinning. In addition to its association with atopy, eye rubbing, or genetic component, late reports suggest the involvement of inflammation in the pathogenesis of the disease. Our aim was to determine the concentration of IL-4, IL-6, IL-10, RANTES, IFN gamma, and TNF alpha in the tear film of patients with keratoconus and their first degree family members. We analyzed forty-eight participants in an observational cross-sectional study. The diagnosis of keratoconus had to be confirmed in addition to a minimum of 47 D corneal refractive power by corneal topography readings provided by a Placido-based topography system and analysis of the pattern: irregular astigmatism with an asymmetric “bow-tie.” As for the other groups, the most important diagnosis criteria were a normal topographic pattern with a regular astigmatism. 17 keratoconus patients, 16 relatives, and 15 controls were recruited after clinical assessment as part of the research. The cytokine's mean values were similar in the keratoconus group and the relatives' samples but significantly higher compared to the controls. Important differences were found in IL-4 levels between keratoconus patients and relatives and between relatives and controls (mean difference of 302.42, p < 0.0016 and 219.16, p < 0.033, Tukey's HSD procedure). In the keratoconus group, using the CORR procedure, we found statistically strong correlations of IL-6 lacrimal concentrations with the disease stage (r = 0.56, p < 0.01), keratometry (r = 0.55, p < 0.02), pachymetry (r = −0.64, p < 0.048), and corneal hysteresis (r = −0.53, p < 0.02). Cytokine overexpression may be relevant for the inflammatory etiology of keratoconus. In conclusion, in the case of some first degree family members, the elevated tear biomarkers may represent a supplementary risk factor.

Small Molecule Modulation of the Integrated Stress Response Governs the Keratoconic Phenotype In Vitro

“…Finally, we demonstrate that the effects of ISR modulation are specific to diseased cells, with ISRIB stimulating increased COL1A1 transcription and hydroxyproline production in KC cells only. We also investigated the expression of prospective inflammatory cytokines IL-1β and TNFα, which have been described as being dysregulated in keratoconus 36. We observed that both IL-1β and TNFα were not produced above the detection threshold by DN or KC fibroblasts under untreated conditions and, although there was a trend toward increased expression (by qPCR and ELISA), in both cases the levels of expression were barely above the detection threshold.…”

Association Between Keratoconus and Thyroid Gland Dysfunction: A Cross-Sectional Case–Control Study

“…Higher levels of proinflammatory or inflammatory cytokines were shown. 25,26 Dias et al 12 reported that T4 receptors have been found in the lacrimal gland, confirming that the tear producing gland is a target organ of T4 and the T4 level was elevated in the tears of patients with keratoconus. Likewise, Thanos et al's 17 study, in which tear samples were collected from all patients with keratoconus and thyroid gland dysfunction, from a group of patients with keratoconus but without thyroid gland dysfunction, and from a control group with both keratoconus and thyroid gland dysfunction, compared tear T4 in thyroid gland dysfunction and immunohistochemical staining of its receptors between patients with keratoconus and controls.…”

<p>Refractive Lens Exchange in Hyperopic Presbyopes with the Acrysof IQ Panoptix Intraocular Lens: One-Year Results and Analysis of the Literature</p>

“…15,16 The inflammatory cytokines in the lacrimal tear in patients with keratoconus may alter the postoperative outcomes. 17 A special attention must be given to patients with dry eye disease or meibomian gland dysfunction who can be very unsatisfied after the surgery due to subjective symptoms, regardless of multifocal IOL implantation. In all cases, our clinical judgment was to decide the risk/benefit ratio before implanting a lens of this type.…”