Possible role of the vitamin E solubilizer in topical diclofenac on matrix metalloproteinase expression in corneal melting: an analysis of postoperative keratolysis.
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.
Hargrave
Sylvia L
SL
Department of Ophthalmology, University of Texas, Southwestern Medical Center, Dallas, Texas, USA.
Jung
Jae Chang
JC
Fini
M Elizabeth
ME
Gelender
Henry
H
Cather
Christian
C
Guidera
Anne
A
Udell
Ira
I
Fisher
Stephen
S
Jester
James V
JV
Bowman
R Wayne
RW
McCulley
James P
JP
Cavanagh
H Dwight
HD
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014810:Vitamin E; D004008:Diclofenac; D020782:Matrix Metalloproteinases; C014225:tocophersolan