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 Table of Contents    
CASE REPORT
Year : 2022  |  Volume : 15  |  Issue : 1  |  Page : 81-84  

Pegylated interferon-alpha-2a for the treatment of ocular surface squamous neoplasia


1 Chevron Eye Hospital and Research Centre, Chittagong, Bangladesh
2 Orbit, Oculoplasty and Oncology Clinic, Chittagong Eye Infirmary and Training Complex, Chittagong, Bangladesh

Date of Submission10-May-2021
Date of Decision04-Jul-2021
Date of Acceptance17-Jul-2021
Date of Web Publication02-Mar-2022

Correspondence Address:
Dr. Murtuza Nuruddin
Chevron Eye Hospital and Research Centre, Chittagong
Bangladesh
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ojo.ojo_146_21

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   Abstract 


Ocular surface squamous neoplasia (OSSN) is the most common nonpigmented ocular surface neoplasm. Interferon-alpha (IFNα)-2b has been proved to be an effective immunotherapeutic agent to treat OSSN. We have used intralesional and topical (36 μg/ml) pegylated (peg) IFNα-2a to treat a recurrent surgically failed case of OSSN instead of IFNα-2b. In this case report, we have shared our initial experience with the novel use of peg-IFNα-2a to treat OSSN. According to our brief clinical experience, peg-IFNα-2a is nontoxic to ocular surface and has a promising role to treat OSSN.

Keywords: interferon-alpha-2a, interferon-alpha-2b, ocular surface neoplasm


How to cite this article:
Nuruddin M, Roy SR, Hoque F. Pegylated interferon-alpha-2a for the treatment of ocular surface squamous neoplasia. Oman J Ophthalmol 2022;15:81-4

How to cite this URL:
Nuruddin M, Roy SR, Hoque F. Pegylated interferon-alpha-2a for the treatment of ocular surface squamous neoplasia. Oman J Ophthalmol [serial online] 2022 [cited 2022 May 26];15:81-4. Available from: https://www.ojoonline.org/text.asp?2022/15/1/81/338873




   Introduction Top


Ocular surface squamous neoplasia (OSSN) is the most common ocular surface neoplasm. It usually arises from limbus due to mutations in the limbal stem cells and ranges from squamous dysplasia to invasive squamous carcinoma.[1] The widely practiced treatment strategy for OSSN is surgical excision with no-touch technique along with adjuvant double freeze and thaw cryotherapy.[2] However, this technique does not guarantee the excision of tumor cells at subclinical level. To overcome this disadvantage, medical management by using various chemotherapeutic or immunotherapeutic agents is gaining momentum.[3],[4],[5] In this case report, we share our experience with the innovative use of pegylated (peg) interferon-alpha (IFNα)-2a as an immunotherapeutic agent for management of OSSN. This case report adheres to the Declaration of Helsinki.


   Case Report Top


A 60-year-old patient presented with the complaints of recurrent lesion in the left eye for the last 2 months. He gave the history of surgical excision of the lesion at the same site thrice within the last 8 months. Histopathologically, the lesion was confirmed as squamous cell carcinoma on the last occasion where the margins and base were free of tumor cells. The patient also gave the history of receiving topical mitomycin C (MMC) 0.04% for consecutive 3 weeks following the last surgical intervention.

On examination, his visual acuity was 20/40 in the right eye and 20/80 in the left eye. In the superior limbal region, there was a papillomatous lesion (8 mm in length and 5 mm in width) with some leukoplakia, encroaching the upper part of the cornea [Figure 1]. His other ocular findings were normal except bilateral immature cataract in both eyes. He was diagnosed as left recurrent OSSN of papillary variant. Clinically, the patient was immunocompetent. We also did enzyme-linked immunosorbent assay for human immunodeficiency virus which was reported negative. The lesion was excised again with 4 mm of healthy conjunctiva along with alcohol epitheliectomy of involved cornea and adjunctive double freeze inverse cryotherapy and amniotic membrane graft. Peroperatively, there was suspicion of superficial scleral infiltration. Therefore, he was prescribed topical MMC 0.04% postoperatively, but the patient returned to the clinic after 7 days with severe burning and foreign body sensation, for which we had to discontinue MMC and the patient was advised to remain under close observation. The patient could not attend the follow-up due to COVID-19 lockdown, and after 3 months, he again presented with huge recurrence of the lesion [Figure 2]. At this occasion, the size of the lesion was 18 mm in length with variable breadth having maximum 10 mm at the center, involving most of upper nasal to upper temporal limbus. At this stage, the treatment options were either extended enucleation or the use of chemotherapeutic or immunotherapeutic agent like IFNα-2b. Unfortunately, IFNα-2b was not readily available in the local market, instead peg-IFNα-2a was available at an affordable cost at the concentration of 180 μg (mcg) in 0.5 ml (ml) solution. After taking informed written consent from the patient and approval from the institutional review board, we prescribed intralesional and topical peg-IFNα-2a to treat this recurrent case of OSSN. Topical solution was prepared by adding 4.5 ml of artificial tear (povidone 5%) in 0.5 ml therapeutic solution, so that topical solution was prepared at a concentration of 36 mcg/ml. Intralesional peg-IFNα-2a was injected first [Figure 3]a which was followed by topical therapy (36 mcg/ml) at one drop four times daily. Cold chain was maintained while preparing and transporting the topical solution, and the patient was also advised to keep the topical solution in refrigerator (2°C–8°C). Along with topical peg-IFNα-2a, the patient was also prescribed topical steroid (dexamethasone 0.1%) and artificial tear (carboxymethylcellulose 1%). The patient was reviewed after 1-week, 4-week, and then every 4-week interval. In each follow-up, baseline findings including size and color of the lesion, visual acuity, anterior and posterior segment findings, and intraocular pressure were recorded. On the first follow-up, there was mild improvement with the decrease of vascularity and congestion of the lesion, though no adverse effect was noted. On the second follow-up, the size and redness of the lesion was reduced at a considerable state [Figure 3]b. The intralesional injection (0.25 ml) was repeated on the second follow-up, and topical therapy was continued. The lesion was completely resolved after 12 weeks of initiation of treatment, and the patient was advised to continue topical therapy for further 8 weeks [Figure 3]c. The patient was followed up for 6 months after complete resolution of the lesion, and there had been no recurrence during this period [Figure 3]d.
Figure 1: Ocular surface squamous neoplasia of papillary variant

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Figure 2: Huge recurrence of lesion following surgical management

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Figure 3: Treatment outcome of intralesional and topical pegylated interferon-alpha-2a for recurrent ocular surface squamous neoplasia. (a) Pegylated interferon-alpha-2a is being injected intralesionally (0.25 ml). (b) The size of lesion and vascularity were markedly reduced after 4 weeks of initiation of treatment with peginterferon-alpha-2a. (c) Complete resolution of lesion was observed after 12 weeks of initiation of treatment. (d) Six months after complete resolution of lesion without any sign of recurrence

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   Discussion Top


Interferons are glycoproteins that are produced in large quantities by recombinant DNA technology.[6],[7] They are used as drugs to treat various diseases due to their antineoplastic and antiviral properties.[6],[7] The antineoplastic property is thought to be secondary to antiproliferative, cytotoxic, and antiangiogenic effects.[8] IFNα-2b has been proved to be effective as an immunotherapeutic agent by various authors for management of OSSN.[3],[9],[10],[11],[12],[13] This is considered a safe agent as there is very low toxicity when used on ocular surface. It does not cause limbal ischemia and subsequent dry eye as happened with the topical use of MMC and 5-fluorouracil (FU).[4],[5]

To manage this current case, we have tried peg-IFNα-2a instead of IFNα-2b because of the ease of availability and cost. The cost of each vial of peg-IFNα-2a in the local market is approximately 100 United States Dollar (5 ml of 36 mcg/ml topical solution), whereas IFNα-2b costs around 200 United States Dollar (5 ml of 1 MIU/ml topical solution) and also not readily available in the local market. The only structural difference between IFNα-2a and IFNα-2b is in the amino acid sequences at position 23 (lysine in IFNα-2a and arginine in IFNα-2b).[14] The addition of “peg” (polyethylene glycol) increases the half-life. In peginterferon-alpha-2b, the “peg” chain is covalently attached primarily to histidine-34 of IFNα-2b via an unstable urethane bond that is subject to hydrolysis once injected, releasing native IFNα-2b. On the other hand, “peg” chain of peg-IFNα-2a is covalently attached via stable amide bonds to lysine residues of IFNα-2a and circulates as an intact molecule. As a result, peginterferon-alpha-2a has a very restricted volume of distribution and longer half-life. Another pharmacological difference between these two agents is that IFNα-2a is used at fixed dose whereas the dosage of IFNα-2b depends on body weight. However, this difference in dosage is not practically applicable when the drug is used for management of ocular surface neoplasia.

We have found only one article through MEDLINE search where IFNα-2a has been used for management of OSSN whereas we have used peg-IFNα-2a.[15] Kim and Salvi have used IFNα-2a for management of one case of OSSN and two cases of conjunctival melanoma.[15] They have used this agent for immunoreduction (reducing the size of lesion) followed by surgical excision. We have used peg-IFNα-2a as immunotherapy (complete resolution of lesion) as repeated surgical attempts were failed.

To the best of our knowledge, this is the first reported case where peg-IFNα-2a has been used as an immunotherapeutic agent for management of OSSN. With the use of intralesional and topical IFNα-2a, no ocular surface toxicity or deviation in the intraocular pressure was noted. The patient did not complain of any irritation or watering with the use of peg-IFNα-2a which is very likely with the use of topical MMC or 5-FU. The ocular discomfort that was complained initially was gradually reduced with the resolution of the lesion.

We have used peg-IFNα-2a in only one case of OSSN with an excellent outcome. To prove its efficacy for treatment of OSSN, we need to perform study on a larger case series. From our brief experience, it can be concluded that peg-IFNα-2a is effective for treatment of OSSN and it is nontoxic to ocular surface.

Statement of ethics

The patient gave his informed consent for publication of this case report (text and photographs). The study protocol was approved by the institute's committee on human research. The study involved no animal experimentation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Lee GA, Hirst LW. Ocular surface squamous neoplasia. Surv Ophthalmol 1995;39:429-50.  Back to cited text no. 1
    
2.
Shields JA, Shields CL, De Potter P. Surgical management of conjunctival tumors. The 1994 Lynn B. McMahan Lecture. Arch Ophthalmol 1997;115:808-15.  Back to cited text no. 2
    
3.
Kaliki S, Singh S, Iram S, Tripuraneni D. Recombinant interferon alpha 2b for ocular surface squamous neoplasia: An efficient and cost-effective treatment modality in Asian Indian patients. Indian J Ophthalmol 2016;64:702-9.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Shields CL, Naseripour M, Shields JA. Topical mitomycin C for extensive, recurrent conjunctival-corneal squamous cell carcinoma. Am J Ophthalmol 2002;133:601-6.  Back to cited text no. 4
    
5.
Midena E, Angeli CD, Valenti M, de Belvis V, Boccato P. Treatment of conjunctival squamous cell carcinoma with topical 5-fluorouracil. Br J Ophthalmol 2000;84:268-72.  Back to cited text no. 5
    
6.
Sepulveda R, Pe'er J, Midena E, Seregard S, Dua HS, Singh AD. Topical chemotherapy for ocular surface squamous neoplasia: Current status. Br J Ophthalmol 2010;94:532-5.  Back to cited text no. 6
    
7.
Poothullil AM, Colby KA. Topical medical therapies for ocular surface tumors. Semin Ophthalmol 2006;21:161-9.  Back to cited text no. 7
    
8.
Bracarda S, Eggermont AM, Samuelsson J. Redefining the role of interferon in the treatment of malignant diseases. Eur J Cancer 2010;46:284-97.  Back to cited text no. 8
    
9.
Karp CL, Galor A, Chhabra S, Barnes SD, Alfonso EC. Subconjunctival/perilesional recombinant interferon α2b for ocular surface squamous neoplasia: A 10-year review. Ophthalmology 2010;117:2241-6.  Back to cited text no. 9
    
10.
Shields CL, Kaliki S, Kim HJ, Al-Dahmash S, Shah SU, Lally SE, et al. Interferon for ocular surface squamous neoplasia in 81 cases: Outcomes based on the American Joint Committee on Cancer classification. Cornea 2013;32:248-56.  Back to cited text no. 10
    
11.
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 Ophthalmol 2012;130:159-64.  Back to cited text no. 11
    
12.
Nanji AA, Moon CS, Galor A, Sein J, Oellers P, Karp CL. Surgical versus medical treatment of ocular surface squamous neoplasia: A comparison of recurrences and complications. Ophthalmology 2014;121:994-1000.  Back to cited text no. 12
    
13.
Kim HJ, Shields CL, Shah SU, Kaliki S, Lally SE. Giant ocular surface squamous neoplasia managed with interferon alpha-2b as immunotherapy or immunoreduction. Ophthalmology 2012;119:938-44.  Back to cited text no. 13
    
14.
Charles W, Peter B, editors. “Recombinant interferon-The 20th anniversary”. Recombinant Protein Drugs. Birkhäuser: Milestones in Drug Therapy; 2001. p. 3-41.  Back to cited text no. 14
    
15.
Kim SE, Salvi SM. Immunoreduction of ocular surface tumours with intralesional interferon alpha-2a. Eye (Lond) 2018;32:460-2.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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