Abstract
Purpose
To report the clinical presentation of mitomycin-C (MMC)-resistant ocular surface squamous neoplasia (OSSN) and its treatment outcome with topical interferon alpha-2b (IFNα-2b).
Methods
A prospective, non-randomised, pilot study enrolling clinically diagnosed OSSN patients. The inclusion criterion was resistance of OSSN to standard topical MMC (0.02%) chemotherapy. The resistance was defined as ‘no clinical response’ in the terms of reduction in tumour size, extension and vascularity after minimum 6 weeks ‘on-cycles’ of MMC. Any previous surgical intervention or recurrent OSSN lesions were excluded. Topical MMC was stopped in all, and topical IFNα-2b (1million IU/ml) eyedrops were prescribed to each patient. At first presentation, the clinical features and side-effect profile of MMC was noted and therapeutic effect of IFNα-2b was clinically monitored at each follow-up. Topical immunotherapy was continued for 24 weeks and a minimum follow-up of 12 weeks was observed after stopping IFNα-2b.
Results
Six patients with a mean age of 62 years met the inclusion criteria. At presentation, all had unilateral, circumscribed, sessile and unifocal lesions with mean dimensions of 7.67 × 5.17 mm. Four patients had temporal lesions while surface keratin, pigmentation and corneal involvement were noted in three lesions, separately. All lesions had dilated and tortuous feeder vessels. All six tumours resolved completely over a mean tumour resolution time of 16 weeks while the total duration of IFNα-2b treatment was 24 weeks. After stopping immunotherapy, a mean of 14.5 weeks follow-up was observed. None showed any recurrence. The approximate cost of total therapy session was 8400 Indian rupees.
Conclusion
The OSSN lesions showing ‘less or no response’ to topical MMC may be shifted to topical recombinant IFNα-2b before proceeding for a surgical excision.
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References
Nanji AA, Moon CS, Galor A, Sein J, Oellers P, Karp CL (2014) Surgical versus medical treatment of ocular surface squamous neoplasia: a comparison of recurrences and complications. Ophthalmology 121:994–1000
Sturges A, Butt AL, Lai JE, Chodosh J (2008) Topical interferon or surgical excision for the management of primary ocular surface squamous neoplasia. Ophthalmology 115:1297–1302
Poothullil AM, Colby KA (2006) Topical medical therapies for ocular surface tumors. Semin Ophthalmol 21:161–169
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 124:303–311
Yeatts RP, Ford JG, Stanton CA, Reed JW (1995) Topical 5-fluorouracil in treating epithelial neoplasia of the conjunctiva and cornea. Ophthalmology 102:1338–1344
Shah SU, Kaliki S, Kim HJ, Lally SE, Shields JA, Shields CL (2012) Topical interferon alfa-2b for management of ocular surface squamous neoplasia in 23 cases: outcomes based on American Joint Committee on Cancer classification. Arch Ophthalmol 130:159–164
Luqmani YA (2005) Mechanisms of drug resistance in cancer chemotherapy. Med Princ Pract 14:35–48
Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, Sarkar S (2014) Drug resistance in cancer: an overview. Cancers 6:1769–1792
Gorlick R, Goker E, Trippett T, Waltham M, Banerjee D, Bertino JR (1996) Intrinsic and acquired resistance to methotrexate in acute leukemia. N Engl J Med 335:1041–1048
Ashkenazy N, Karp CL, Wang G, Acosta CM, Galor A (2017) Immunosuppression as a possible risk factor for interferon nonresponse in ocular surface squamous neoplasia. Cornea 36:506–510
Tabin G, Levin S, Snibson G, Loughnan M, Taylor H (1997) Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia. Ophthalmology 104:485–492
Stone DU, Butt AL, Chodosh J (2005) Ocular surface squamous neoplasia: a standard of care survey. Cornea 24:297–300
Shields CL, Kaliki S, Kim HJ, Al-Dahmash S, Shah SU, Lally SE, Shields JA (2013) Interferon for ocular surface squamous neoplasia in 81 cases: outcomes based on the American Joint Committee on Cancer classification. Cornea 32:248–256
Shields CL, Demirci H, Karatza E, Shields JA (2004) Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors. Ophthalmology 111:1747–1754
Kao AA, Galor A, Karp CL, Abdelaziz A, Feuer WJ, Dubovy SR (2012) Clinicopathologic correlation of ocular surface squamous neoplasms at Bascom Palmer Eye Institute: 2001–2010. Ophthalmology 119:1773–1776
Kieval JZ, Karp CL, AbouShousha M, Galor A, Hoffman RA, Dubovy SR, Wang J (2012) Ultra-high resolution optical coherence tomography for differentiation of ocular surface squamous neoplasia and pterygia. Ophthalmology 119:481–486
Xu Y, Zhou Z, Xu Y, Wang M, Liu F, Qu H, Hong J (2012) The clinical value of in vivo confocal microscopy for diagnosis of ocular surface squamous neoplasia. Eye 26:781–787
Maskin SL (1994) Regression of limbal epithelial dysplasia with topical interferon (letter). Arch Ophthalmol 112:1145–1146
Boehm MD, Huang AJ (2004) Treatment of recurrent corneal and conjunctival intraepithelial neoplasia with topical interferon alfa 2b. Ophthalmology 111:1755–1761
Singh M, Gautam N, Gupta A, Kaur M (2016) Interferon alfa-2b in the management of recurrent conjunctival papillomatosis. Indian J Ophthalmol 64:778–780
Peksayar G, Altan-Yaycioglu R, Onal S (2003) Excision and cryosurgery in the treatment of conjunctival malignant epithelial tumours. Eye (Lond) 17:228–232
Siganos CS, Kozobolis VP, Christodoulakis EV (2002) The intraoperative use of mitomycin-C in excision of ocular surface neoplasia with or without limbal autograft transplantation. Cornea 21:12–16
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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The written informed consent was obtained from all the participants before starting topical interferon therapy.
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Singh, M., Gautam, N. & Kaur, M. Role of topical interferon alpha-2b in ‘mitomycin-C-resistant’ ocular surface squamous neoplasia: our preliminary findings. Int Ophthalmol 39, 295–301 (2019). https://doi.org/10.1007/s10792-017-0811-0
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DOI: https://doi.org/10.1007/s10792-017-0811-0