International Ophthalmology

, Volume 37, Issue 1, pp 71–78 | Cite as

Long-term outcome of amniotic membrane transplantation combined with mitomycin C for conjunctival reconstruction after ocular surface squamous neoplasia excision

  • Kazuomi HanadaEmail author
  • Noriko Nishikawa
  • Naoyuki Miyokawa
  • Akitoshi Yoshida
Original Paper


The aim of the study is to evaluate the long-term clinical results of amniotic membrane transplantation (AMT) combined with mitomycin C (MMC) for reconstruction of conjunctival defects created during the excision of ocular surface squamous neoplasia (OSSN). Eight consecutive eyes of seven patients (five males and two females; mean age, 64 ± 19 years) treated by one surgeon (KH) were included in this study. AMT was performed after excision of a mass region, along with 0.04 % MMC treatment for the exposed sclera. The tumor size, histopathological retrieval, AM graft size after tumor excision, recurrence, and postoperative complications were recorded. During a mean postoperative follow-up period of 60.9 ± 14.6 months (range 36–78 months), the ocular surfaces completely re-epithelialized in all cases. The median size of the tumor was 44.4 ± 21.2 mm2 (range 13–67 mm2). The histopathological diagnoses were five cases of squamous cell carcinoma in situ (SCC in situ) and three cases of dysplasia. The median size of the AM graft after tumor excision was 100.8 ± 32.7 mm2 (range 49–151 mm2). A case of recurrent SCC in situ with a preoperative history of using MMC eye drops developed further corneal limbal deficiency and was treated with therapeutic soft contact lenses. A case of dysplasia with a history of large pterygial excision developed symblepharon postoperatively was treated with AMT 6 months after tumor excision. The tumors recurred in two eyes with SCC in situ and were successfully treated with continuous AMT and MMC. No severe complications, such as infections, corneal or scleral thinning, or ulceration developed in all cases. The combination of AMT and MMC is effective for safe reconstruction over the long-term after the excision of OSSN with postoperative careful observation and treatment. In recurrent tumor excision cases, AMT is a suitable technique for repeated ocular surface reconstruction.


Amniotic membrane transplantation (AMT) Mitomycin C (MMC) Ocular surface squamous neoplasia (OSSN) Ocular surface reconstruction 


  1. 1.
    Shields JA, Shields CL, DePotter P (1997) Surgical management of conjunctival tumors: the 1994 Lynn B McMahan Lecture. Arch Ophthalmol 115:808–815CrossRefPubMedGoogle Scholar
  2. 2.
    Kim JC, Tseng SCG (1995) Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea 14:472–484CrossRefGoogle Scholar
  3. 3.
    Tsubota K, Satake Y, Ohyama M, Toda I, Takano Y, Ono M, Shinozaki N, Shimazaki J (1996) Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol 122:38–52CrossRefPubMedGoogle Scholar
  4. 4.
    Shimazaki J, Yang H-Y, Tsubota K (1997) Amniotic membrane transplantation for ocular surface reconstruction in patients with chemical and thermal burns. Ophthalmology 104:2068–2076CrossRefPubMedGoogle Scholar
  5. 5.
    Lee SH, Tseng SCG (1997) Amniotic membrane transplantation for persistent epithelial defects with ulceration. Am J Ophthalmol 123:303–312CrossRefPubMedGoogle Scholar
  6. 6.
    Shimazaki J, Shinozaki N, Tsubota K (1998) Transplantation of amniotic membrane and limbal autograft for patients with recurrent pterygium associated with symblepharon. Br J Ophthalmol 82:235–240CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Kruse FE, Rohrschneider K, Völcker HE (1999) Multilayer amniotic membrane transplantation for reconstruction of deep corneal ulcers. Ophthalmology 106:1504–1511CrossRefPubMedGoogle Scholar
  8. 8.
    Hanada K, Shimazaki J, Shimmura S, Tsubota K (2001) Multilayered amniotic membrane transplantation for severe ulceration of the cornea and sclera. Am J Ophthalmol 131:324–331CrossRefPubMedGoogle Scholar
  9. 9.
    Shields CL, Shields JA, Armstrong T (2001) Management of conjunctival and corneal melanoma with surgical excision, amniotic membrane allograft, and topical chemotherapy. Am J Ophthalmol 132:576–578CrossRefPubMedGoogle Scholar
  10. 10.
    Espana EM, Prabhasawat P, Gruetrich M, Solomon A, Tseng SCG (2002) Amniotic membrane transplantation for reconstruction after excision of large ocular surface neoplasias. Br J Ophthalmol 86:640–645CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gündüz K, Uçakhan ÖÖ, Kanpolat A, Günalp I (2006) Nonpreserved human amniotic membrane transplantation for conjunctival reconstruction after excision of extensive ocular surface neoplasia. Eye 20:351–357CrossRefPubMedGoogle Scholar
  12. 12.
    Asoklis RS, Damijonaityte A, Butkiene L, Makselis A, Petroska D, Pajaujis M, Juodkaite G (2011) Ocular surface reconstruction using amniotic membrane following excision of conjunctival and limbal tumors. Eur J Ophthalmol 21:552–558CrossRefPubMedGoogle Scholar
  13. 13.
    Tseng SCG, Prabhasawat P, Barton K, Gray T, Meller D (1998) Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol 116:431–441CrossRefPubMedGoogle Scholar
  14. 14.
    Tsubota K, Satake Y, Kaido M, Shinozaki N, Shimmura S, Bissen-Miyajima H, Shimazaki J (1999) Treatment of severe ocular surface disorders with corneal epithelial stem-cell transplantation. N Engl J Med 340:1697–1703CrossRefPubMedGoogle Scholar
  15. 15.
    Frucht-Pery J, Rozenman Y (1994) Mitomycin C therapy for corneal intraepithelial neoplasia. Am J Ophthalmol 117:164–168CrossRefPubMedGoogle Scholar
  16. 16.
    Wilson MW, Hungerford JL, George SM, Madreperla SA (1997) Topical mitomycin C for the treatment of conjunctival and corneal epithelial dysplasia and neoplasia. Am J Ophthalmol 124:303–311CrossRefPubMedGoogle Scholar
  17. 17.
    Heigle TJ, Stulting RD, Palay DA (1997) Treatment of recurrent conjunctival epithelial neoplasia with topical mitomycin C. Am J Ophthalmol 124:397–399CrossRefPubMedGoogle Scholar
  18. 18.
    Frucht-Pery J, Sugar J, Baum J, Sutphin JE, Pe’er J, Savir H, Holland EJ, Meisler DM, Foster JA, Folberg R, Rozenman Y (1997) Mitomycin C treatment for conjunctival- corneal intraepithelial neoplasia—a multicenter experience. Ophthalmology 104:2085–2093CrossRefPubMedGoogle Scholar
  19. 19.
    Rozenman Y, Frucht-Pery J (2000) Treatment of conjunctival corneal intraepithelial neoplasia with topical drops of mitomycin C. Cornea 19:1–6CrossRefPubMedGoogle Scholar
  20. 20.
    Shields CL, Naseripour M, Shields JA (2002) Topical mitomycin C for extensive recurrent conjunctival-corneal squamous cell carcinoma. Am J Ophthalmol 133:601–606CrossRefPubMedGoogle Scholar
  21. 21.
    Tseng SCG, Li DQ, Max X (1999) Suppression of transforming growth factor isoforms, TGF-β receptor II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J Cell Physiol 179:325–335CrossRefPubMedGoogle Scholar
  22. 22.
    Lee SB, Li DQ, Tan DT, Meller DC, Tseng SC (2000) Suppression of TGF-β signaling in both normal conjunctival fibroblasts and pterygial body fibroblasts by amniotic membrane. Curr Eye Rec 20:325–334CrossRefGoogle Scholar
  23. 23.
    Hayasaka S, Noda S, Yamamoto Y, Setogawa T (1988) Postoperative instillation of low-dose mitomycin C in the treatment of primary pterygium. Am J Ophthalmol 106:715–718CrossRefPubMedGoogle Scholar
  24. 24.
    Hayasaka S, Noda S, Yamamoto Y, Setogawa T (1989) Postoperative instillation of mitomycin C in the treatment of recurrent pterygium. Ophthal Surg 20:580–583Google Scholar
  25. 25.
    Chen CW, Huang HT, Bair JS (1990) Trabeculectomy with simultaneous topical application of mitomycin C in refractory glaucoma. J Ocul Pharmacol 6:175–182CrossRefPubMedGoogle Scholar
  26. 26.
    Palmer SS (1991) Mitomycin C as adjunct chemotherapy with trabeculectomy. Ophthalmology 98:317–321CrossRefPubMedGoogle Scholar
  27. 27.
    Tseng SC, Di Pascuale MA, Liu DT, Gao YY, Baradaran-Rafii A (2005) Intraoperative mitomycin C and amniotic membrane transplantation for fornix reconstruction in severe cicatricial ocular surface diseases. Ophthalmology 112:896–903CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Kazuomi Hanada
    • 1
    Email author
  • Noriko Nishikawa
    • 1
  • Naoyuki Miyokawa
    • 1
  • Akitoshi Yoshida
    • 1
  1. 1.Asahikawa Medical UniversityAsahikawaJapan

Personalised recommendations