Minoxidil-induced alteration of corneal topography after radial keratotomy.
OBJECTIVE
To determine the antiproliferative effect of minoxidil on human corneal epithelium (hCE) proliferation in vitro and to assess whether topical minoxidil can significantly alter corneal topography after radial keratotomy (RK) by inhibiting myofibroblast activity in the keratotomy wound.


METHODS
Corneal Research Laboratory, University of Chicago, Illinois, USA.


METHODS
In the in vitro evaluation, proliferating hCE was exposed to minoxidil (0.1 to 2.0 mM) for 96 hours to determine the minimum inhibitory dose. Human corneal epithelium cell proliferation was assessed by the incorporation of bromodeoxyuridine (BRDU) into DNA. In the in vivo analysis, eight New Zealand albino rabbits had an eight-incision bidirectional RK on one eye and were divided into two groups. The control eyes (n = 3) received tobramycin and dexamethasone (TobraDex), ciprofloxacin hydrochloride (Ciloxan), and balanced salt solution (BSS) drops four times a day for 3 weeks, while the treatment eyes (n = 5) received TobraDex, Ciloxan, and minoxidil 1.0 mM drops four times daily for 3 weeks. The net change in corneal curvature at 3 weeks was analyzed with corneal topography. Myofibroblast activity in the keratotomy wound was assessed using alpha smooth muscle actin staining techniques.


RESULTS
At concentrations of 1.0 mM and above, minoxidil caused a statistically significant, dose-dependent reduction in hCE cellular proliferation ranging from 29 to 44% (P < .05). Minoxidil (1.0 mM) caused a statistically significant central corneal flattening effect of 4.66 diopters (D) after RK in the treatment eyes compared with 1.11 D in the control eyes (P = .05). Histologically, minoxidil-treated keratotomy wounds lacked cells with contractile elements consistent with myofibroblast differentiation. Corneal epithelial wound healing was similar in both groups.


CONCLUSIONS
At the appropriate dose, topical minoxidil may be a useful adjunctive treatment that can reduce the number of undercorrections after mini-RK without apparent toxicity to the corneal epithelium.
Goins
K M
KM
University of Chicago, Department of Ophthalmology and Visual Sciences, Illinois 60637-1454, USA.
Karp
K O
KO
Gabrielian
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D019781:Corneal Topography; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019573:Epithelium, Corneal / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007646:Keratotomy, Radial; D008914:Minoxidil / Q000494:pharmacology*; D009883:Ophthalmic Solutions; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000037:antagonists & inhibitors*; D011817:Rabbits; D014945:Wound Healing / Q000187:drug effects
D004791:Enzyme Inhibitors; D009883:Ophthalmic Solutions; D008914:Minoxidil; D004247:DNA; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase