The data indicate that corneal epithelium contributes to elevated MMP9 and inflammatory cytokine expression in tears of KC patients. Cyclosporine A treatment reduced MMP9 and inflammatory cytokine levels in an in vitro inflammation model system. In KC patients, CyA treatment reduced MMP9 levels measured in tears with concomitant arrest of disease progression. Therefore, CyA might be a novel treatment strategy in KC patients but requires additional evaluation in larger cohorts. (ClinicalTrials.gov number, NCT01746823.).
This study provides the first evidence that altered corneal epithelial and stromal expression of specific genes at the corneal cone apex drives focal structural weakness in KC.
Riboflavin+UVA CXL triggers more anterior keratocyte apoptosis than corneal scrape with UVA alone or riboflavin alone. Inflammation monitored by the monocyte marker CD11b was present, but not statistically different among the three groups. Very little myofibroblast generation could be detected after UVA+riboflavin CXL, indicating that the mild stromal haze associated with this procedure is normally related to transient corneal fibroblast generation rather than more persistent haze due to generation of myofibroblasts.
PURPOSE-To compare changes in corneal hysteresis (CH) and the corneal resistance factor (CRF) in myopic and hyperopic laser in situ keratomileusis (LASIK) and evaluate their relationship with the number of photoablative pulses delivered, a surrogate for ablation volume. SETTING-ClevelandClinic Cole Eye Institute, Cleveland, Ohio, USA. METHODS-Preoperative and 1-week postoperative OcularResponse Analyzer measurements in eyes that had femtosecond-assisted LASIK were studied retrospectively. Changes in CH and CRF were compared and tested for correlation with the number of excimer laser pulses.RESULTS-Thirteen myopic eyes and 11 hyperopic eyes were evaluated. Preoperative corneal thickness, CH, CRF, programmed correction magnitude, flap thickness, and total number of fixed spot-size photoablative pulses were similar in the 2 groups (P>.1). Decreases in CH and CRF were greater after myopic LASIK than after hyperopic LASIK (P<.005), and changes in CRF were correlated with the number of excimer laser pulses in the myopic group only (r = −0.63, P = .02). Regardless of ablation profile, changes in CH were more strongly correlated with preoperative CH values than with attempted ablation volume.CONCLUSIONS-With comparable flap thickness and attempted ablation volumes, myopic photoablation profiles were associated with greater decreases in CRF and CH than hyperopic profiles. Results indicate that preoperative corneal biomechanical status, ablation volume, and the spatial distribution of ablation are important factors that affect corneal resistance and viscous dissipative properties differently. Preferential tissue removal in the natively thicker paracentral cornea in hyperopia may partially account for the rarity of ectasia after hyperopic LASIK.During laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), phototherapeutic keratectomy, and other photoablative corneal procedures, immediate Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. circumferential severing of anterior corneal lamellae occurs in the ablation zone. The resulting structural alteration of the cornea has been proposed to decrease resistance to stromal swelling pressure peripheral to the ablation, shift tension to the intact lamellae deep to the interrupted lamellae, and generate centripetal stresses that favor central corneal flattening and a shift toward farsightedness.1 , 2 Because intraocular pressure (IOP) also manifests as a force against the posterior corneal surface, deeper ablations concentrated in the cornea's thinnest regions can lead to offsetting corneal steepening effects.3 , 4 T...
PURPOSE. Corneal collagen cross-linking (CXL) is a method for modifying the natural history of keratoconus and other corneal ectatic diseases. The authors evaluated the use of collagenase for generating an experimental model of ectasia to evaluate the topographic effects of CXL interventions.METHODS. Nine human corneoscleral specimens unsuitable for transplantation were used. After epithelial debridement, mounting, and pressurization on an artificial anterior chamber, a solution of 10 mg/mL collagenase type II with 15% dextran was applied to five corneas for three hours. Three of these corneas subsequently underwent riboflavin/UV-A CXL. Scheimpflug-based tomography was performed before collagenase exposure, after collagenase exposure, and after CXL to evaluate changes in maximum axial curvature of the anterior surface (K max ) at three IOP levels. Results were compared to four control eyes exposed to dextran alone. RESULTS.A statistically significant increase in K max was seen across all IOP levels in the collagenase group compared to the control group (þ6.6 6 1.1 diopters [D] and þ0.3 6 0.8 D, respectively, at physiological IOP). After CXL, K max decreased (À7.6 6 2.0 D at physiological IOP). Anterior corneal aberrations increased after collagenase exposure and decreased after CXL. Light microscopy showed loss of normal stromal collagen architecture and localized edema after collagenase exposure. 2 Ectasia progression can be modified by riboflavin/UV-A-mediated collagen cross-linking (CXL), 3,4 a more conservative method that appears to be safe 4,5 and effective in stopping keratoconus progression. 3,4,6 In 2008, a large retrospective study of CXL showed corneal topographic flattening in more than half of the eyes and statistically significant improvements in astigmatism, best-corrected visual acuity, and maximum simulated keratometry (K max ) values after a year. Vinciguerra et al. 7 have shown significantly less keratoconus progression compared to the untreated contralateral eye. CXL is currently being investigated in clinical trials for US Food and Drug Administration approval in the United States for treatment of keratoconus and postrefractive surgery ectasia. CONCLUSIONS.However, a challenge faced by researchers is that there is currently no tissue model for study of either of these conditions. Proteinases, defective enzymatic activity, and oxidative damage have been implicated in keratoconus, 8,9 and it has been shown that levels of degradative enzymes such as acid esterase, acid phosphatase, and cathepsins B and G are elevated, and degradative enzymes such as inhibitors of a1-proteinase inhibitor and a2-macroglobulin, are reduced in keratoconus corneas. [10][11][12][13] It was thus hypothesized that keratoconus can be simulated through topical collagenase application. After promising results in a pilot study (Hong CW. IOVS 2011;52:ARVO E-Abstract 4386), the authors set out to evaluate the suitability of collagenase treatment for generating a model of corneal ectasia in unaffected donor corneas and to ev...
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