Şeyda ERDOĞAN, Kemal YAR, Altan A. OZCAN, Yurdun KUYUCU, Sait POLAT

Evaluation of Corneal Histopathologic Changes in Rabbits Due To Topical Mitomycin C Application in Different Doses and Periods

Purpose: To evaluate the histopathologic changes in the cornea due to topical mitomycin C (MMC) application at various doses and administration periods. Materials and Methods: The study group consisted of 35 albino rabbits with a mean age of 6 months. The animals were divided into the 7 groups, each comprising 10 eyes of five rabbits. Five rabbits were used as the control group. Other subjects were divided into the 2 groups according to the application period. The first 3 groups subsequently underwent 0.2, 0.4, and 0.8 mg/mL mitomycin C application 6 times at weekly intervals. Groups 4, 5 and 6 underwent MMC application at the same doses 12 times. The control group underwent topical physiologic serum application. After the last treatment, the rabbits were sacrificed and enucleation was performed . Results: Light and electron microscopic examinations of mitomycin C treated animals revealed different histopathologic changes in the corneal epithelium and endothelium according to various doses and administration periods. Discussion: Topical mitomycin C has toxic effects on the cornea related to dose and period and is known to be more toxic, especially in increased doses.. In this study, we identified the most effective dose without side effects. Long-term treatment with MMC at low doses is more advantageous than short-term treatment at high doses.

PDF

___

Abraham LM, Selva D, Casson R, Leibovitch I. Mitomycin Clinical Applications in Ophthalmic Practice. Drugs. 2006;66(3):321-40. Review.
Nanji AA, Sayyad FE, Karp CL. Topical chemotherapy for ocular surface squamous neoplasia. Curr Opin Ophthalmol. 2013 Jul;24(4):336-42. doi: 10.1097/ICU.0b013e3283622a13. Review.
Song JS, Kim JH, Yang M, Sul D, Kim HM. Concentrations of mitomycin cin rabbit corneal tissue and aqueous humor after topical application. Cornea. 2006 Dec;25(10 Suppl 1):S20-3.
Mohan RR, Hutcheon AE, Choi R, Hong J, Lee J, Mohan RR, Ambrósio R Jr, Zieske JD, Wilson SE. Apoptosis, necrosis, proliferation, and myofibroblast generation in the stroma following LASIK and PRK. Exp Eye Res. 2003 Jan;76(1):71-87.
Gharaee H, Zarei-Ghanavati S, Alizadeh R, Abrishami M. Endothelial cell changes after photorefractive keratectomy with graded usage of mitomycin C. Int Ophthalmol. 2018 Jun;38(3):1211-1217..
Zare M, Jafarinasab MR, Feizi S, Zamani M The effect of mitomycin-C on corneal endothelial cells after photorefractive keratectomy. J Ophthalmic Vis Res. 2011; 6(1):8–12
Shojaei A, Ramezanzadeh M, Soleyman-Jahi S, Almasi Nasrabadi M, Rezazadeh P, Eslani M. Short-time mitomycin-C application during photorefractive keratectomy in patients with low myopia. J Cataract Refract Surg. 2013; 39(2):197–203
Khong JJ, Muecke J.Complications of mitomycin ctherapy in 100 eyes with ocular surface neoplasia. Br J Ophthalmol. 2006 Jul; 90(7):819-22. Epub 2006 May 3.
Avisar R, Apel I, Avisar I, Weinberger D. Endothelial cell loss during piterygium surgery: importance of timing of mitomycin capplication. Cornea. 2009 Sep;28(8):879-81.
Chang SW. Early corneal edema following topical applicationof mitomycin c.J Cataract Refract Surg. 2004;30:1742-1750.
Poothullil AM, Colby KA.Topical Medical Therapies for Ocular Surface Tumors Semin Ophthalmol. 2006 Jul-Sep;21(3):161-9. Review.
Prabhasawat P, Tarinvorakup P, Tesavibul N, Uiprasertkul M, Kosrirukvongs P, Booranapong W, Srivannaboon S. Topical 0.002% mitomycin cfor the treatment of conjunctival-corneal intraepithelial neoplasia and squamous cell carcinoma. Cornea. 2005 May;24(4):443-8.