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Year : 2016  |  Volume : 64  |  Issue : 10  |  Page : 778-780

Interferon alfa-2b in the management of recurrent conjunctival papillomatosis

1 Department of Ophthalmic Plastic Surgery, Sohana Charitable Eye Institute, Sohana, Punjab, India
2 Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Ophthalmic Plastic Surgery, Medipoint Hospital, Pune, Maharashtra, India
4 Department of Ophthalmology, Sankara Eye Hospital, Ludhiana, Punjab, India

Date of Submission02-Jun-2016
Date of Acceptance04-Sep-2016
Date of Web Publication1-Dec-2016

Correspondence Address:
Manpreet Singh
Department of Ophthalmic Plastic Surgery, Sohana Charitable Eye Institute, Sohana, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0301-4738.195013

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A 2-year-old boy presented with a recurrent strawberry-like reddish mass arising from the left caruncular region for 8 months. An incisional biopsy was performed elsewhere 2 months earlier, followed by an increase in size of mass, significant epiphora, and intermittent bleeding. On examination, exuberant exophytic gelatinous mass with multifocal origin was observed arising from inferior forniceal conjunctiva and caruncle. Clinical differential of multifocal conjunctival papilloma was kept, and topical interferon alfa-2b (INFα-2b) was started. No clinical reduction in mass or symptomatology was observed over 6 weeks. Excision biopsy with cryotherapy and subconjunctival injection of INFα-2b was performed over all foci. Conjunctival papilloma was confirmed on histopathology, and topical INFα-2b was continued in postoperative period for 3 months. At 14 months of follow-up, no recurrence, epiphora, or bleeding was noticed. We advocate a possible role of local INF therapy in managing and preventing recurrences of conjunctival papillomatosis.

Keywords: Conjunctival papillomatosis, cryotherapy, interferon alfa-2b, management, surgical excision

How to cite this article:
Singh M, Gautam N, Gupta A, Kaur M. Interferon alfa-2b in the management of recurrent conjunctival papillomatosis. Indian J Ophthalmol 2016;64:778-80

How to cite this URL:
Singh M, Gautam N, Gupta A, Kaur M. Interferon alfa-2b in the management of recurrent conjunctival papillomatosis. Indian J Ophthalmol [serial online] 2016 [cited 2023 Jun 2];64:778-80. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2016/64/10/778/195013

Conjunctival papillomatosis (CP) is a diffuse and multicentric variant of benign conjunctival papillomas. It is commonly (5%–45%) associated with alfa (α) genus of human papillomavirus (HPV) type 6 and 11 (in children) and type 16, 18, and 33 (in adults), the formers having a low risk for malignant transformation. The infants acquire HPV during delivery while in adults, it spreads through “self-inoculation.”[1] Histologically, these are benign squamous epithelial tumors showing acanthosis of keratinizing or nonkeratinizing epithelium mixed with few goblet and mixed inflammatory cells.[1],[2]

Few clinical features (extralimbal location) and histological markers (presence of goblet cells, no elastosis, and nonkeratinizing epithelium) may point toward its viral etiology.[1] They are larger, multiple and have greater tendency to recur in children as compared to their adult counterparts.[3] The pediatric variant of conjunctival papillomas generally requires surgical intervention secondary to their multifocal, exuberant, and fulminant nature. Recently, literature reports the adjunctive use of interferon alfa-2b (INFα-2b) in topical or local injection form, to prevent recurrences of CP.[4],[5],[6] We report a case of unilateral, diffuse, recurrent CP successfully managed using multimodal therapy (surgical excision, cryotherapy, and local INF therapy) in a child with lamellar ichthyosis.

  Case Report Top

A 2-year-old boy presented to us with a reddish fleshy mass protruding from the inner side of the left eye for 8 months. He underwent an incisional biopsy at a local dispensary 2 months ago, following which there was an increase in the size of mass, spontaneous bleeding episodes, and epiphora. He was a diagnosed patient of classical lamellar ichthyosis and was using skin emollients.

On local examination, a 15 mm × 12 mm, strawberry-like polypoidal mass was observed in the left caruncular region [Figure 1]a. The left inferior orbital sulcus was full medially, with hemorrhagic matting of eyelashes. The inferior fornix revealed multiple, gelatinous, frond-like lesions originating from both forniceal and tarsal conjunctiva, along its entire length [Figure 1]b and [Figure 1]c. The caruncular mass mechanically obstructed both normal appearing lacrimal puncta. The mucocutaneous junction of eyelid was normal. The child was not cooperative for superior bulbar, palpebral, and forniceal conjunctival examination. Rest of ocular examination was within normal limits.
Figure 1: (a) Left eye shows reddish, strawberry-like mass in the caruncular region. The inferior orbital sulcus appears full with blood stained matting of temporal eyelashes indicating spontaneous bleeding episodes. Forehead skin showing features of lamellar ichthyosis. (b) On inferior conjunctival examination, florid growth of similar lesions is observed along whole length of tarsal conjunctiva with an old blood clot present medially. (c) Inferior sulcus pressure reveals massive involvement of forniceal conjunctiva with similar lesions. Multiple pinhead-sized hemorrhages are seen on the surface

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A clinical diagnosis of diffuse, multifocal CP was made, and topical fortified eye drops of INFα-2b (Injection Zavinex, Zydus Cadila, India) was started QID (1 million IU/1 ml). The child was kept under regular weekly follow-up for 6 weeks, but there was no mass reduction. However, the mass vascularity and spontaneous bleeding episodes reduced markedly after the topical treatment.

In view of no reduction in mass size, a near-total surgical excision of the papillomas with cryo application at each site (2 “freeze-thaw-freeze” cycles) was performed under general anesthesia. Intraoperatively, similar lesions were noted at the superior tarsal and forniceal conjunctiva [Figure 2]a and [Figure 2]b. The gelatinous exophytic masses were excised with Westcott scissors, keeping its blades flush with the conjunctival surface. After cryo application, total 1 ml (3 million IU) of INFα-2b was injected subconjunctivally at multiple sites [Figure 2]c and [Figure 2]d. No abnormal pigmentation or feeder vessel was identified. The inferior conjunctiva and caruncle appeared to be the tumor epicenter.
Figure 2: (a) Intraoperative double eversion of upper eyelid revealed multiple foci of similar gelatinous lesions over medial tarsal and forniceal conjunctiva. (b) Entire spectrum and extent of conjunctival involvement. (c) After near-total excision with Westcott scissors, application of cryo (2 freeze-thaw-freeze cycles) is being demonstrated. (d) Subconjunctival injection of interferona-2b being administered at multiple foci after the cryotherapy

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The histopathology of excised mass revealed multiple pedunculated papillomatous figures with central core of fibrovascular tissue covered by nonkeratinizing epithelium. There was no cellular atypia, and nuclear-cytoplasmic ratio was normal, ruling out any evidence of malignancy. None of the papillomas showed inverted type of configuration. Hence, the final diagnosis was benign CP. Postoperatively, topical 0.5% moxifloxacin (QID) and 1% carboxymethyl cellulose (2 hourly) were prescribed along with topical fortified INFα-2b (1 IU/ml QID) eye drops. In the 1st postoperative week, the child had mild eyelid edema and nasal subconjunctival hemorrhage [Figure 3]a and [Figure 3]b. Topical steroid ointment (HS) was prescribed for 1 week to reduce cryotherapy-induced inflammation. Topical INFα-2b and carboxymethyl cellulose were continued for 12 weeks and then stopped. No oral treatment was given to the child. At 14-month follow-up, the child is symptom-free (no epiphora and spontaneous bleeding episodes), and there are no signs of local recurrence [Figure 3]c and [Figure 3]d.
Figure 3: (a) Early postoperative period shows diffuse medial subconjunctival blood staining with no evidence of residual papillomas over inferior conjunctiva and caruncle. (b) Superior tarsal conjunctiva is free from the papillomas with few subconjunctival hematoma spots. (c) At 3-month follow-up, no evidence of papilloma recurrence. One small pinpoint hemorrhage presents temporal to plica semilunaris. (resolved in 1 week). (d) At 14-month follow-up, no recurrence of mass and the tumor epicenter appears normal. The child is symptom-free

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  Discussion Top

The INFs are naturally produced glycoprotein molecules in our body secondary to viral infections and tumors. Of late, these molecules have been employed with significant success in various human diseases, including CP, an uncommon ophthalmological condition. In children, due to the diffuse, multicentric nature, and inferior fornix predilection, the topical fortified INFα-2b eye drops has a potential role. This drug has shown satisfactory results in primary and recurrent CP cases.[3],[6],[7]

In the past, many drugs such as oral cimetidine, 5-fluorouracil, mitomycin-C, local INFα-2b (topical or injection), and long-acting pegIFNα-2b have been used in the management of primary and recurrent CP. All these therapeutic agents mainly played the role of an adjunct to the surgical intervention than isolated therapeutic agents.[3],[7],[8] No-touch technique, excisional biopsy ± cryotherapy, is the surgery of choice. Surgical debulking not only provides instant relief but also reduces the viral load which is rather a difficult job for a short-acting, fortified drug such as INFα-2b. Hence, it is a good option in management armamentarium of surgeon handling recurrent cases. Even after these treatment modalities, the recurrence rate exists between 6% and 27%, more in pediatric CP.[3]

Kaliki et al. have described specific clinical tumor details which might be helpful in monitoring the treatment response, for example, tumor epicenter location (clockwise and quadrant wise), basal dimensions and thickness (in millimeters), configuration, pigmentation, and vascularity (intrinsic and feeder vessels).[3] On PubMed search with keywords - ichthyosis and CP, only single case report in literature is available from year 1988 though no association has been established.[9]

In our patient with classical lamellar ichthyosis and unilateral recurrent CP, the topical INFα-2b eye drops mildly reduced the tumor vascularity which probably eliminated spontaneous bleeding but did not show any regression in tumor size. CP showed remission after near-total surgical excision and cryotherapy along with local subconjunctival injection of INFα-2b. This was supplemented with topical INFα-2b eye drops in postoperative period. We postulate that the postoperative topical INFα-2b eye drops prevent the dislodged viruses to establish and form a nidus at other conjunctival sites, which might lead to multifocal recurrences specifically in pediatric CP.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Mlakar J, Kocjan BJ, Hošnjak L, Pižem J, Beltram M, Gale N, et al. Morphological characteristics of conjunctival squamous papillomas in relation to human papillomavirus infection. Br J Ophthalmol 2015;99:431-6.  Back to cited text no. 1
Sjö NC, von Buchwald C, Cassonnet P, Norrild B, Prause JU, Vinding T, et al. Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: Types and frequencies in a large series. Br J Ophthalmol 2007;91:1014-5.  Back to cited text no. 2
Kaliki S, Arepalli S, Shields CL, Klein K, Sun H, Hysenj E, et al. Conjunctival papilloma: Features and outcomes based on age at initial examination. JAMA Ophthalmol 2013;131:585-93.  Back to cited text no. 3
Schechter BA, Rand WJ, Velazquez GE, Williams WD, Starasoler L. Treatment of conjunctival papillomata with topical interferon Alfa-2b. Am J Ophthalmol 2002;134:268-70.  Back to cited text no. 4
de Keizer RJ, de Wolff-Rouendaal D. Topical alpha-interferon in recurrent conjunctival papilloma. Acta Ophthalmol Scand 2003;81:193-6.  Back to cited text no. 5
Kothari M, Mody K, Chatterjee D. Resolution of recurrent conjunctival papilloma after topical and intralesional interferon alpha-2b with partial excision in a child. J AAPOS 2009;13:523-5.  Back to cited text no. 6
Muralidhar R, Sudan R, Bajaj MS, Sharma V. Topical interferon alpha-2b as an adjunctive therapy in recurrent conjunctival papilloma. Int Ophthalmol 2009;29:61-2.  Back to cited text no. 7
Hawkins AS, Yu J, Hamming NA, Rubenstein JB. Treatment of recurrent conjunctival papillomatosis with mitomycin C. Am J Ophthalmol 1999;128:638-40.  Back to cited text no. 8
Slade CS, Katz NN, Whitmore PV, Bardenstein DS. Conjunctival and canalicular papillomas and ichthyosis vulgaris. Ann Ophthalmol 1988;20:251-5.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3]

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