Effect of Topical Phenytoin in Treatment of Corneal Epithelial Defect in Rabbits

Document Type: Research(Original) Article



Re-epithelialization of corneal epithelium is a major problem in delayed corneal wound healing. Phenytoin has been used topically for different type of cutaneous wounds and ulcers. The aim of this this study was to assess the efficacy of topical phenytoin eye drop and ointment 1% and on induced sterile corneal epithelial ulcer in rabbit eyes.Fifty eyes from 30 rabbits were evaluated for induction of corneal epithelial ulcer in this study. The right corneas of all rabbits underwent total epithelial debridement. Randomization was made. Odd labeled eyes as control group received artificial tear and even labeled eyes as case group received phenytoin 1% eye drop. Slit lamp examination was performed on day 1, 3, 5 &7. After healing of the right eyes, same procedure was performed on 20 corneas of left eyes. In the left eyes, phenytoin ointment 1% was used instead of phenytoin  eye drop 1%.There was no statistically significant difference between corneas that received phenytoin 1% eye drop (n=15) and control group that received placebo (n=15) in right eyes (p > 0.05). Also,  difference between corneas received phenytoin ointment 1% (n=10) or placebo (n=10) in the left eyes (p > 0.05) was not significant.The results of this study did not show positive effect of phenytoin on acceleration of healing process in rabbit’s corneal ulcer. Further study in non-healing corneal ulcers is required to show phenytoin efficacy. Phenytoin ointment in comparison to phenytoin drop was a better applicant for ophthalmic usage. Application of topical phenytoin 1% in corneal ulcer in rabbits was safe and no sever side effect was observed.


  1. Ramamurthi S, Rahman MQ, Dutton GN, Ramaesh K. Pathogenesis, clinical features and management of recurrent corneal erosions. Eye (Lond) 2006;20:635-44.
  2. - Kimball OP, Horan TN. The use of Dilantin in the treatment of epilepsy. Ann Int Med 1939;13:787e93.
  3. - Shapiro m. Acceleration of gingival wound healing in non-epileptic patients receiving diphenylhydantoin sodium (dilantin, epanutin). Exp Med Surg 1958;16:41-53.
  4. - Inchingolo F1, Vermesan D, Inchingolo AD, Malcangi G, Santacroce L, Scacco S, Benagiano V, et. al. Bedsores successfully treated with topical phenytoin. Acta Biomed 2017;88:45-8.
  5. - Patil V, Patil R, Kariholu PL, Patil LS, Shahapur P. Topical Phenytoin Application in Grade I and II Diabetic Foot Ulcers: A Prospective Study. J Clin Diagn Res 2013;7:2238-40.
  6. - Sayar H, Gergerlioglu N, Seringec N, Ozturk P, Bulbuloglu E, Karabay G. Comparison of efficacy of topical phenytoin with hypericin in second-degree burn wound healing: an experimental study in rats. Med Sci Monit Basic Res 2014;20:36-46.
  7. - Modaghegh S, Salehian B, Tavassoli M, Djamshidi A, Rezai AS. Use of phenytoin in healing of war and non-war wounds. A pilot study of 25 cases. Int J Dermatol1989;28:347-50.
  8. - Bhatia A, Nanda S, Gupta U, Gupta S, Reddy BS. Topical phenytoin suspensionand normal saline in the treatment of leprosy trophic ulcers: a randomized, double-blind, comparative study. J Dermatolog Treat 2004 ;15:321-7.
  9. - Mohammad Naeim Aminifard, Hamid Reza Barkhordari Yazdi, Shabnam Pahlavanzadeh, Evaluation of Topical Phenytoin Eye Drop 1% Therapeutic Effects on Corneal Alkali Burns in Rabbit Model. Iranian Journal of Ophthalmology 2012;24:33-8.
  10. - Swamy SM, Tan P, Zhu YZ, Lu J, Achuth HN, Moochhala S. Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun 2004;314:661-6.
  11. - Bhatia A, Prakash S. Topical phenytoin for wound healing. Dermatol Online J2004;10:5. Review.
  12. - Jaber S, Rihy Z, Joseph R, Al-Khayat M. Does phenytoin improve the healing of gastrointestinal fistulas? Case Rep Gastroenterol 2011;5:52-5.
  13. - Shaw J, Hughes CM, Lagan KM, Bell PM. The clinical effect of topical phenytoin on wound healing: a systematic review. Br J Dermatol 2007;157:997-1004.
  14. - Anstead GM, Hart LM, Sunahara JF, Liter ME. Phenytoin in wound healing. Ann Pharmacother 1996;30:768-75.
  15. - Hao XY, Li HL, Su H, Cai H, Guo TK, Liu R, Jiang L, Shen YF. Topical phenytoinfor treating pressure ulcers. Cochrane Database Syst Rev 2017;2:CD008251
  16. - Abdou AG, Abdelwahed Gaber M, Elnaidany NF, Elnagar A. Evaluation of the effect and mechanism of action of local phenytoin in treatment of vitiligo. J Immunoassay Immunochem 2017.
  17. - Lodha SC, Lohiya ML, Vyas MC, Bhandari S, Goyal RR, Harsh MK. Role of phenytoin in healing of large abscess cavities. Br J Surg 1991;78:105-8.
  18. - Lemp MA. Cornea and sclera. Arch Ophthalmol 1974;92:158-70.