title: Possible role of the vitamin E solubilizer in topical diclofenac on matrix metalloproteinase expression in corneal melting: an analysis of postoperative keratolysis.
abstract: OBJECTIVE
  To analyze tissue matrix metalloproteinase (MMP) expression in three patients who developed postoperative corneal melts after treatment with topical diclofenac sodium 0.1% (Falcon; Fort Worth, TX) ophthalmic solution.
  
  
  METHODS
  Retrospective noncomparative interventional case series with tissue analysis.
  
  
  METHODS
  Three patients were examined in this study. We report two patients from the same center with acute corneal melts after uncomplicated photorefractive keratectomy (PRK). Prior to these cases, 1500 patients were treated at the Zale Lipshy University Laser Center for Vision with no adverse effects. All 1500 patients were treated with the same postoperative regimen of ciprofloxacin, rimexolone, and suprofen ([Profenal, (CIBA, Duluth, GA]). The next 27 cases were treated postoperatively with ciprofloxacin and rimexolone. However, diclofenac sodium 0.1% was used instead of Profenal. A third case was also discussed. This melt occurred at another center in a postoperative cataract patient who developed cystoid macular edema after cataract extraction with intraocular lens placement. He was initially treated with diclofenac sodium 0.1% (Ciba Vision, Duluth, GA) then with diclofenac sodium 0.1%. He subsequently developed a corneal perforation requiring penetrating keratoplasty. All tissue specimens were examined by light microscopy. Microbiologic cultures and stains were also performed. Immunolocalization and in situ hybridization were performed on all keratoplasty specimens to detect expression and localization of MMPs. All patients had a complete diagnostic evaluation for systemic autoimmune diseases.
  
  
  RESULTS
  Postoperatively, all patients developed corneal perforations requiring surgical intervention while being treated with diclofenac sodium 0.1%. Microbiologic cultures and special stains were negative for microorganisms. Induced expression of specific tissue degrading enzymes of the matrix metalloproteinase family was demonstrated within corneal epithelial cells, stromal keratocytes, and at the level of Descemet's membrane. The uniform distribution pattern of expression was not consistent with the localization expected of a repair response, suggesting the involvement of some outside agent.
  
  
  CONCLUSIONS
  Whereas MMP expression is a normal component of repair, excessive or inappropriate MMP activity is associated with corneal keratolysis. Our study provides preliminary evidence that topical application of diclofenac sodium 0.1% may be associated with aberrant MMP expression in the cornea.
authors.affiliation: Department of Ophthalmology, University of Texas, Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Hargrave
authors.forename: Jae Chang
authors.initials: JC
authors.lastname: Jung
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Fini
authors.forename: Henry
authors.initials: H
authors.lastname: Gelender
authors.forename: Christian
authors.initials: C
authors.lastname: Cather
authors.forename: Anne
authors.initials: A
authors.lastname: Guidera
authors.forename: Ira
authors.initials: I
authors.lastname: Udell
authors.forename: Stephen
authors.initials: S
authors.lastname: Fisher
authors.forename: James V
authors.initials: JV
authors.lastname: Jester
authors.forename: R Wayne
authors.initials: RW
authors.lastname: Bowman
authors.forename: James P
authors.initials: JP
authors.lastname: McCulley
authors.forename: H Dwight
authors.initials: HD
authors.lastname: Cavanagh
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D002387:Cataract Extraction; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology / Q000601:surgery; D003316:Corneal Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000601:surgery; D004008:Diclofenac / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D015948:Keratoplasty, Penetrating; D054018:Lasers, Excimer; D019654:Lens Implantation, Intraocular; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D018903:Photorefractive Keratectomy; D011183:Postoperative Complications / Q000139:chemically induced* / Q000201:enzymology / Q000601:surgery; D054140:Refractive Surgical Procedures; D012189:Retrospective Studies; D014810:Vitamin E / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014810:Vitamin E; D004008:Diclofenac; D020782:Matrix Metalloproteinases; C014225:tocophersolan