title: Effect of a Matrix Therapy Agent on Corneal Epithelial Healing After Standard Collagen Cross-linking in Patients With Keratoconus: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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 mm2; mean difference, 11.6 mm2; 95% CI, 0.8-23.5 mm2; P = .045) and SLP (11.9 vs 23.5 mm2; mean difference, 11. 6 mm2; 95% CI, 1.3-22.9 mm2; 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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT02119039.
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Ahmed M
authors: AM
authors: Bata
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria2Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: Katarzyna J
authors: KJ
authors: Witkowska
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria3Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland.
authors: Piotr A
authors: PA
authors: Wozniak
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Klemens
authors: K
authors: Fondi
authors: Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.
authors: Gerald
authors: G
authors: Schmidinger
authors: Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.
authors: Niklas
authors: N
authors: Pircher
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Stephan
authors: S
authors: Szegedi
authors: Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: Valentin
authors: V
authors: Aranha Dos Santos
authors: Department of Ophthalmology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.
authors: Anca
authors: A
authors: Pantalon
authors: Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: René M
authors: RM
authors: Werkmeister
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Gerhard
authors: G
authors: Garhofer
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria2Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: Leopold
authors: L
authors: Schmetterer
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria2Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors: Doreen
authors: D
authors: Schmidl
mesh_terms: D000293:Adolescent; D000328:Adult; D003094:Collagen / Q000627:therapeutic use*; D003432:Cross-Linking Reagents / Q000627:therapeutic use*; D019573:Epithelium, Corneal / Q000000981:diagnostic imaging / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006820:Hyaluronic Acid / Q000627:therapeutic use; D007640:Keratoconus / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D012189:Retrospective Studies; D013997:Time Factors; D041623:Tomography, Optical Coherence / Q000379:methods; D016896:Treatment Outcome; D055675:Viscosupplements / Q000627:therapeutic use; D014792:Visual Acuity; D014945:Wound Healing / Q000187:drug effects*; D055815:Young Adult
chemical_list: D003432:Cross-Linking Reagents; D009883:Ophthalmic Solutions; D055675:Viscosupplements; D006820:Hyaluronic Acid; D003094:Collagen