Effect of a Matrix Therapy Agent on Corneal Epithelial Healing After Standard Collagen Cross-linking in Patients With Keratoconus

Abstract

IMPORTANCE Corneal abrasions are frequent after standard (epithelium-off [epi-off]) corneal collagen cross-linking (CXL) in patients with progressive keratoconus. A new matrix therapy agent (ReGeneraTing Agent [RGTA]) has been developed to promote corneal wound healing. OBJECTIVE To assess the effect of the new type of matrix therapy agent on corneal wound healing after epi-off CXL in patients with keratoconus. DESIGN, SETTING, AND PARTICIPANTS This double-masked randomized clinical trial enrolled 40 patients with keratoconus undergoing epi-off CXL from July 18, 2014, to October 21, 2015, when the last follow-up was completed. The analysis of the intention-to-treat population was performed at the Department of Clinical Pharmacology in cooperation with the Center for Medical Physics and Biomedical Engineering and the Department of Ophthalmology and Optometry of the Medical University of Vienna. INTERVENTIONS Patients were randomized to receive the matrix therapy agent or hyaluronic acid-containing eyedrops, 0.1%, every other day starting immediately after surgery. The size of the corneal defect was measured using ultrahigh-resolution optical coherence tomography (OCT) and slitlamp photography (SLP) with fluorescein staining. MAIN OUTCOMES AND MEASURES Corneal wound healing rate, defined as the size of the defect over time. RESULTS Among the 40 patients undergoing epi-off CXL (31 men; 9 women; mean [SD] age, 31 [10] years), wound healing was significantly faster in the matrix therapy agent group compared with the hyaluronic acid group (4.4 vs 6.1 days; mean difference, 1.7 days; 95% CI, 0.25-3.15 days; P = .008). The defect size was smaller in the matrix therapy agent group than in the hyaluronic acid group as measured with OCT (12.4 vs 23.9 mm 2 ; mean difference, 11.6 mm 2 ; 95% CI, 0.8-23.5 mm 2 ; P = .045) and SLP (11.9 vs 23.5 mm 2 ; mean difference, 11. 6 mm 2 ; 95% CI, 1.3-22.9 mm 2 ; P = .03). A correlation between the defect size measured with OCT and SLP was found (r = 0.89; P < .001). No ocular or serious adverse events occurred. CONCLUSIONS AND RELEVANCE Use of a new matrix therapy agent appears to improve corneal wound healing after CXL in patients with keratoconus. Monitoring of corneal wound healing using ultrahigh-resolution OCT might be an attractive alternative to SLP because OCT provides an objective and 3-dimensional evaluation of the corneal defect. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02119039

Effect of Topically Administered Chitosan-N-acetylcysteine on Corneal Wound Healing in a Rabbit Model

“…In addition, it appears that high-resolution OCT is a suitable technique for the noninvasive measurement of corneal epithelial damage in the rabbit model of corneal debridement. This is in agreement with a recent study in humans where ultra-high-resolution OCT was used to quantify epithelial defects in keratoconus patients undergoing standard collagen cross-linking [17]. …”

“…The data of the current study supports the concept that this holds also true for C-NAC. The underlying mechanism is not entirely clear but may be at least partially related to the effects of unmodified chitosan on wound healing [17, 18]. It has been shown in previous studies that in a rabbit alkali burn model, chitosan reduces scar formation and increases the collagen density in the conjunctiva [19].…”

“…We have used this system in several human studies to assess precorneal tear film thickness [14, 30–32] as well as to measure corneal wound healing in humans (Bata et al 2016 JAMA Ophthalmology, in press). The latter study shows that in humans, there is a good correlation between corneal wound size measured with OCT and measurements based on corneal fluorescein staining [17]. …”

Case Reports for Topical Treatment of Corneal Ulcers with a New Matrix Therapy Agent or RGTA® in Dogs

“…OTR4120 is a polysaccharide specifically designed (substituted with carboxymethyls and sulfates) to replace degraded heparan sulfates in injured tissues. The unique properties of OTR4120, as described above, permit the reconstruction of the ECM, restoring the homeostasis of the tissue, facilitating the processes of tissue repair and regeneration [1,4,[8][9][10].…”

“…Furthermore, OTR4120 was described in a case report concerning one patient with a neurotrophic ulcer [26]. During the last few years, OTR4120 eye drops have been successfully used for the treatment of resistant corneal neurotrophic ulcers [8], as well as for the treatment of keratoconus in humans [9]. OTR4120 has been available on the European market for veterinary use as Clerapliq ® for more than 5 years [8,9,[25][26][27].…”