FP208 : “Interferon Alpha 2b for Giant OSSN as a Mono- Immunotherapy”

Dr. Mihir Mishra, M08636, Dr. Deepshikha Agrawal, Dr.Samrat Chatterjee

“Interferon Alpha 2b for Giant OSSN as a Mono- Immunotherapy”

Chief Author: Dr Mihir Mishra, Co-author(s):  DrDeepshikhaAgrawal, DrSamrat Chatterjee

Introduction:

Ocular surface squamous neoplasia (OSSN) includes a spectrum of malignancy ranging from clinically subtle intraepithelial neoplasias to more visible nodular, fleshy tumors and more ominous invasive tumors with a threat to the globe, orbit, and life.It is a disease of the elderly,having predilection for the interpalpebral area mostly the corneo-sclero-limbus in 87.8% of cases. This condition is most often found in elderly or those with extensive sun exposure.

The management of OSSN involves surgical excision for diagnostic and therapeutic reasons, combined with additional topical chemotherapy, antiviral, or immunotherapy agents for extensive tumors, positive margins on histopathology, or prevention of recurrence.Topical treatments including immune modulators such as interferon alpha‐2b (IFNα2b) or chemotherapeutic agents such as mitomycin‐C (MMC) and 5‐uorouracil (5‐FU. However, it has been shown that topical MMC and 5‐FU are toxic to the ocular surface and might cause limbal stem cell deficiency.IFNa2b, have been  applied as  a immunotherapy for single-agent monotherapy, immunoreduction for diminution of tumor size to facilitate anticipated surgical excision, and immunoprevention for tumors after surgical removal, particularly those with positive surgical margins, in an effort to prevent recurrence.Various studies have focused mostly on the use of IFNa2b as immunotherapy.

In this case report, we describe the use of this medication as mono-immunotherapyfor resolution of the disease.

Case Report:

A 66-year-old male labourer presented with history of redness, watering, discharge and foreign body sensation and mass lesion in the right eye gradually increasing in size over a period  of 2 years. On examination the best corrected visual acuity was 20/400 in the right eye and and 20/32 in the left eye. Slitlampbiomicroscopy of right eyerevealed a large papillomatouslobulated  mass of 20x20mm sizefrom 6 O’ clock to 2 O’clock positonwith intrinsic vessels and feeder vessels invading three-fourth of cornea on the temporal side and extending upto 5mm of conjunctiva to the temporal in the right eye.The mass lesion was elevated to about 4mm.Keratinised patches with feeder vessels were present at 4 O’ clock and at 2 O’ clock position over cornea near the limbus.Anterior chamber was deep and quiet.Intraocular pressure would not be assessed as the central cornea was covered with the mass lesion. There was cataract in both the eyes of nuclear sclerosis grade 3. The left eye was within normal limits except cataract.There was no associated lymphadenopathy or any systemic abnormalities. Aprovisional clinical diagnosis of OSSN was made, and was confirmed by incisional biopsy.ELISA test for HIV was done and found to be negative.

As the mass was very large,  incisional biopsy with debulkingwas done along with perilesional and sublesional interferon 2b alpha injection 3MIU of 1ml  in the same sitting. Patient was started with topical interferon Alpha 2b (reconstituted from injectable form) eye drops 3 million IU/ml  4 times daily  on a weeklybasis for 14 cycles.Total of 6 cycles of 1ml sublesional and perilesional injection of Interferon2b alpha  at a concentration of 3 million IU was given at weekly interval and the greatest horizontal and greatest vertical dimensions were noted with caliper along with the  number of quadrants injected in each cycle. 14 cycles at weekly interval of topical Interferon alpha 2b eye drop was instilled 4 times a day (3MIU/ml). Resolution was noted by measuring the vertical and the horizontal diameter of the lesion. Patient did not show any signs or symptoms of drug intolerance during the therapy except for mild irritation which subsided with topical lubricant.The best corrected visual acuity improved from 20/400 to 20/80in the 14^th week. The size of the lesion reduced in horizontal diameter from 17mm to14mm and vertical dimensions from 15mm to 11mm during the first 6 cycles of treatment with both sublesional and topical iimmunotherapy.in the 11^th cycle of immunotherapy the greatest horizontal diameter reduced further to 6.8mm and the greatest vertical diameter to 5.8mm.At the end of the 14^th cycle there was complete resolution of the mass lesion and cornea was lusterless in periphery with multiple superficial vascularization with best corrected visual acuity of 20/80 . There wasno signs of any recurrences at 4 months follow-up period.

Discussion:

In the management of OSSN, excision biopsy, though considered the gold standard, may not eradicate the subclinical lesion if no frozen section has been adopted. More recently, topical medical therapy (Fuchtet al l997;Chen et al 2004;Holocomb et al 2006) is preferred over surgical treatment, as it treats potentially abnormal cells on the entire ocular surface while conserving the limbal stem cell population. The present case is typical as the area of involvement was large and elevated and moreover patient was a laborer with mostly indoor activities without any UV rays exposure. Incisional biopsy was was done for confirmation of diagnosis and to debulk the mass lesion rather than as therapeutic. There have been previous reports on the use of IFNa2b for management of OSSN in small cohorts of 2 to 35 patients. Several studies have shown that topical IFNα2b as a single therapeutic agent is an effective treatment for both primary and recurrent OSSN.Recently, a study used IFNα2b for large OSSNs (tumor diameter ≥15 mm or ≥180° limbal involvement) and achieved 72% success.We employed a higher dose of topical IFN alpha 2b: 3 million IU/ml instead of 1 million IU/ml. In a recent study, Galor et alcompared the effectiveness of these two concentrations of IFNα2b for treatment of OSSN. Our case had 35 % reduction in the greatest horizontal diameter of the lesion and 33% in the greatest vertical diameter after 6 cycle of immunotherapy, and 60% reduction at the 10th cycle followed by complete resolution clinically at 14^th week at a concentration of 3 MIU/ml both topical and injection. No recurrence was seen based on the slit lamp biomicroscopy at final follow up. Patient did not develop any persistent epithelial defect, symblepharon, or any signs indicative of limbal stem deficiency. The patient did not experience any systemic adverse effects related to IFNα2b therapy including malaise, flu like symptoms, bone pain and fatigue.

Conclusion:

IFNa2b as monoimmunotherapy or in combination with surgical excision can be a powerful therapeutic approach to OSSN with high control rate

References:

1. Shields CL, Shields JA. Tumors of the conjunctiva and cornea. SurvOphthalmol. 2004;49:3–24.

 

2. Shields CL, Demirci H, Karatza E, et al. Clinical survey of 1643 mela- nocytic and nonmelanocytic conjunctival tumors. Ophthalmology. 2004; 111:1747–1754.
3. Lee GA, Hirst LW. Ocular surface squamous neoplasia. SurvOphthalmol. 1995;39:429–450.

 

4. Shields JA, Shields CL. Eyelid, Conjunctival, and Orbital Tumors. An Atlas and Textbook. 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2008:286–306

 

5. Sepulveda R, Pe’er J, Midena E, et al. Topical chemotherapy for ocular surface squamous neoplasia: current status. Br J Ophthalmol. 2010;94: 532–535.

 

6. Karp CL, Moore JK, Rosa RH Jr. Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon alpha‐ Ophthalmology 2001;108:1093‐1098.
7. Vann RR, Karp CL. Perilesional and topical interferon alfa‐2b for conjunctival and corneal neoplasia. Ophthalmology 1999;106:91‐97
8. Galor A, Karp CL, Chhabra S, Barnes S, Alfonso EC. Topical interferon alpha 2b eye‐drops for treatment of ocular surface squamous neoplasia: A dose comparison study. Br J Ophthalmol2010;94:551‐554

 

9. Schechter BA, Koreishi AF, Karp CL, Feuer W. Long‐term follow‐up of conjunctival and corneal intraepithelial neoplasia treated with topical interferon alfa‐ Ophthalmology 2008;115:1291‐1296

 

10. Shah SU, Kaliki S, Kim HJ, Lally SE, Shields JA, Shields CL. Topical interferon alfa‐2b for management of ocular surface squamous neoplasia in 23 cases: Outcomes based on American Joint Committee on Cancer classification. Arch Ophthalmol2012;130:159‐

1 – 4 wksOSSN Post Treatment
14thwks OSSN Post Treatment