FP361 :Comparison of topical Interferon alpha 2b and topical Mitomycin C for the treatment of primary Ocular Surface Squamous Neoplasia.

Dr. Rakhi Kusumesh, K11392, Dr. Ambastha Anita, Dr. Gyan Bhaskar

Introduction:

Ocular surface squamous neoplasia (OSSN) encompasses the entire spectrum of dysplastic and carcinomatous lesions of the ocular surface. ^1,2 Medical treatment alone or as an adjuvant has been used increasingly for OSSN. Possible advantages of medical therapy include the ability to treat the entire ocular surface and the potential to avoid the stem cell deficiency associated with extensive surgical excisions.^{4, 5} Various topical agents have been advocated, including topical treatment such as mitomycin C (MMC), 5-fluorouracil (5- FU)], and interferon alfa 2b (IFN a2b). The purpose of this study is toevaluate and compare the efficacy and safety of topical MMC and IFNa2b in OSSN.

Material and Methods

Medical records of 51 patients who received topical therapy (either IFN a2b 1MIU/ml QID or Mitomycin C 0.04% 1 week off and on cyclefor primary OSSN were reviewed at the Regional Institute of Ophthalmology during June 2013 to January 2016. The diagnosis of OSSN was primarily clinical, based on thorough examination with slit-lamp biomicroscopy. OSSN was diagnosed on the basis of its characteristic macroscopic appearance and classified into papillomatous, gelatinous, and leukoplakic. Topical therapy was stopped as the lesion resolved.  Pretreatment findings included the diagnosis along with all tumor characteristics, pre-treatment and post treatment tumor size as measured by the greatest linear diameter and limbal clock hours involvement. Treatment information comprised the dose, frequency, duration and adverse effects of treatment. Post treatment clinical course was also noted. The primary outcome measure was frequency of clinical resolution of tumors along with failure and recurrence rates after treatment. Statistical analysis was performed using Epi Info 7 (CDC, Atlanta, GA).

Results:

A total of 51 eyes of 50 patients with primary OSSN received topical medication. 26 eyes were treated with 1 million IU/ ml of topical IFNa2b; 25 eyes were treated with 0.04% of topical MMC. There was no statistical difference in macroscopic appearance, greatest linear dimension, limbal involvement, location of tumors and risk factors between two study medication groups. Complete response was achieved in 88.46% and 92% cases with topical IFNa2b and MMC respectively (P= 0.41). The median time to lesion resolution was significantly different between the groups (median 3.5 months in IFNa2b group and 1.5 months in MMC group) with average difference of 1.71 months (95% CI (1.35 to 2.079). Five (9.8%) of 51 patients failed or partially responded to topical therapy; subsequently, they underwent surgical excision. In MMC group, 88% eyes had conjunctival hyperemia while minimal side effects were noted in the IFN a2b treated group..

Discussion:

Keeping in view the high recurrence rate following surgical excision in OSSN, there has been a paradigm shift in the treatment approach of OSSN over the past few years. MitomycinC is an alkylating agent. It acts preferentially on rapid dividing cells by inhibiting DNA synthesis and produces cell death by apoptosis and necrosis. Interferons are a family of glycoproteins. They act by binding to cell surface receptors to promote antiviral and antitumor properties by activating immune cells, as well as increase the recognition of tumor cells by upregulating antigen presentation to T-lymphocytes. Though both the groups of patients had similar tumor characteristics and mean greatest linear dimension, we found significantly prolonged time to lesion resolution with average difference of 1.71 month (95% CI (1.35 to 2.079), p<.005) in eyes treated with IFNa2b. For topical INFa2b treatment, the reported average time to complete tumor response was 11 weeks (range 2-59). In conjunction with previous knowledge of MMC action, we can suggest that MMC has faster action on tumor cells in comparison to INFa2b,probably, because of direct action of MMC on rapidly proliferating tumor cells. In the present study, out of 51 patients, three patients (11.5%) failed to respond to topical IFNa2b whereas two patients (8.0%) did not respond to topical MMC. All case underwent surgery and were histopathology proved as SCC.

Time to tumor resolution depends on the type, size, and mode of therapy. In this study, topical MMC treated lesions took 1.48±.54 months (median 1.5) to resolve completely which is less than the documented case series of Shields CL et al ³ who reported 100% success in three median cycles (1-4 cycles), which could be because all of his cases had extensive, recurrent conjunctival-corneal squamous cell carcinoma. On the other hand, lesions treated with IFNa2b in our study took 3.19±.73 months (Median 3.5) to resolve completely.  Besley J et al ⁴ noted that lesion size and location, gender, age, treatment duration and treatment type did not significantly influence recurrence of OSSN. Our study demonstrated significantly higher ocular adverse reaction in MMC cases 88% in comparison to IFNa2b 11.5% (P < .001). Most common adverse effect was conjunctival hyperemia followed by burning sensation associated with hyperemia in theses eye drops. Few adverse effects of topical IFNa2b have been reported such as photophobia, follicular conjunctivitis, and conjunctival hyperemia.

In conclusion, Interferonalpha2b and Mitomycin C appear to be equally effective topical therapy for primary OSSN. Conjunctival hyperemia may be limiting factor for the use of topical MMC.

References

1. Lee GA, Hirst LW. Incidence of ocular surface epithelial dysplasia in metropolitan Brisbane. A 10-year survey. Arch Ophthalmol. 1992 ; 110(4):525-7
2. Hirst LW. Randomized controlled trial of topical mitomycin C for ocular surface squamous neoplasia: early resolution. Ophthalmology. 2007; 114:976Y982.
3. Shields CL, Naseripour M, Shields JA. Topical mitomycin C for extensive, recurrent conjunctival-corneal squamous cell carcinoma. Am J Ophthalmol.2002; 133(5):601-6.
4. Besley J, Pappalardo J, Lee GA, et al. Risk factors for ocular surface squamous neoplasia recurrence after treatment with topical mitomycin C and interferon alpha-2b. Am J Ophthalmol. 2014; 157:287Y293.