Early pterygium recurrence—Esquenazi 185

Pterygium is one of the most common conditionsencountered in daily practice in areas close to the

equator. It is characterized by an elastotic degenerationof the conjunctiva. It has been considered, in theory, tobe due to a local deficiency of limbal stem cells thatallows the abnormal conjunctival tissue to invade theadjacent cornea.1,2 The main risk factor is excessiveexposure to ultraviolet (UV) radiation. Several surgicaland medical methods of treatment have been de-scribed: surgical excision with bare sclera, primaryclosure, use of free autologous conjunctival and limbalgrafts,3 β-irradiation,4 administration of mitomycin C5

and amniotic membrane placement.6

The recurrence rate has varied from 25–80% afterprimary closure to 6% with free conjunctival and limbalgrafts.3 Histopathological analysis has shown that arecurrent pterygium has predominantly fibroblastic pro-liferation and neovascularization, which is much moreprominent than the elastotic conjunctival degenerationof a primary pterygium. The complications of treatmentof a recurrent pterygium can include superficial punc-tate keratitis, poor epithelial healing, scleral ulceration,microbial infection, corneal edema, glaucoma and en-dophthalmitis. Extensive surgical excision for recurrentor large lesions can lead to further limbal stem cell defi-ciency and cicatricial changes in the ocular surface.

For these reasons, many adjunctive therapies havebeen investigated for the treatment of recurrent pte-rygium, including β-irradiation and the use of mito-mycin C or 5-fluorouracil. Interferons are glycoproteinsthat have been shown to have antiproliferative andantiviral effects.7 Although the exact mechanism of

action of interferons is unknown, the recombinantform of interferon alpha-2b (IFN-α-2b) has been usedwith good results in conjunctival intraepithelial neopla-sia and conjunctival papilloma. Because of its antipro-liferative effect, I decided to try using IFN-α-2b topi-cally, for the first time, in a case of early recurrentpterygium. Treatment was successful.

CASE REPORT

A 32-year-old athletic woman was seen for evaluationof a recurrent lesion in her right eye. She reported sig-nificant UV exposure without protective eyewearthroughout her life. Three months earlier, a nasal pterygi-um (Fig. 1) had been excised and a free autologous con-junctival graft placed. Twenty days before her visit, shehad started to note increasing eye redness, foreign bodysensation and photophobia. At this examination her bestcorrected visual acuity was 20/20 in both eyes. The lefteye had a normal appearance. The right eye showed,adjacent to the surgical scar, a vascularized, highlyfibrotic lesion measuring 3.0 × 2.0 mm that had invadedthe corneal limbal area 1.5 mm (Fig. 2). There was adja-cent conjunctival irregularity and rose bengal staining.

After considering all treatment options, the patientelected to try topical administration of IFN-α-2b (IntronA, Schering Plough, Kenilworth, NJ), 1 million units/mL4 times a day as eye drops. Within 3 weeks the new

From the LSU Eye and Neuroscience Center, Louisiana StateUniversity Health Sciences Center, New Orleans, LA

Originally received Mar. 8, 2004Accepted for publication Sept. 29, 2004

Correspondence to: Dr. Salomon Esquenazi, LSU Eye andNeuroscience Center, 2020 Gravier St., Ste. B, 3rd floor, NewOrleans LA 70112, USA; fax (504) 894-1017; sesque@lsuhsc.edu

This article has been peer-reviewed.

Can J Ophthalmol 2005;40:185–7

Treatment of early pterygium recurrence with topical administration of interferon alpha-2b

Salomon Esquenazi, MD

Fig. 1—Preoperative appearance of initial pterygium.

vessels had regressed significantly and the lesion wasvisibly smaller. An asymptomatic follicular reaction ofthe conjunctiva was noted at the 4-week follow-upvisit. By 6 weeks the corneal invasion had completelyresolved, and by 31⁄2 months there was no clinical evi-dence of recurrence (Fig. 3). The interferon dosagewas tapered to once daily for 1 more month. The fol-licular reaction resolved with cessation of treatment. Atthe time of writing, the woman had remained recur-rence-free for 7 months.

COMMENTS

Treatment of recurrent pterygium includes surgicalexcision, with or without adjunctive therapy, which fre-quently leads to further limbal stem cell deficiency andother ocular surface complications. The use of β-irradi-

ation has been associated with late scleral melting in13% of cases,8 cataract formation and conjunctivaltelangiectasia. The use of mitomycin C has been asso-ciated with depletion of limbal stem cells, scleralmelting and a recurrence rate of 5.4% to 36.6%,depending on exposure time.9 The use of amnioticmembrane is associated with a recurrence rate of 30%to 40%,3 as well as the increased cost, stress and traumaof an additional surgical procedure.

Interferons are naturally occurring glycoproteins thatbind to cell surface receptors. They have antiviral, anti-tumour and antiangiogenic properties.7 IFN-α-2b hasbeen successfully used to treat condylomata acuminata,Kaposi sarcoma, hairy cell leukemia and cervicalintraepithelial neoplasia. I decided to investigate the effi-cacy of topical administration of IFN-α-2b as a lonetherapy for early pterygium recurrence on the basis of itsantitumour and antiangiogenic properties. Furthermore,there had been no discernible histopathological or ultra-structural evidence of conjunctival or corneal adverseeffects in rabbit studies of IFN-α-2b used topically,10–12

in contrast to mitomycin C and 5-fluorouracil, which cancause epitheliopathy, ocular surface inflammation, painand dry eye symptoms when used topically.

Excellent results were achieved with topical IFN-α-2b therapy in this patient without any adjunctive ther-apy and without any systemic side effects. The onlyside effect was follicular conjunctivitis, which resolvedafter discontinuation of the drops. Interferon therapymay also play a role as an adjunct to surgical excision.Further studies are needed to delineate the ideal dosingand tapering schedule for topical IFN-α-2b administra-tion in the treatment of early recurrent pterygium andto prospectively compare this treatment with the otheravailable forms of treatment for pterygium recurrence.

REFERENCES

1. Tseng SC. Concept and application of limbal stemcells. Eye 1989;3(pt 2):141–57.

2. Pfister RR. Corneal stem cell disease: concepts, cate-gorization, and treatment by auto- and homotrans-plantation of limbal stem cells. CLAO J 1994;20:64–72.

3. Prabhasawat P, Barton K, Burkett G, Tseng SCG.Comparison of conjunctival autografts, amnioticmembrane grafts, and primary closure for pterygiumexcision. Ophthalmology 1997;104:974–85.

4. Aswad MI, Baum J. Optimal time for postoperative irra-diation of pterygia. Ophthalmology 1987;94:1450–1.

5. Frucht-Pery J, Siganos CS, Ilsar M. Intraoperativeapplication of topical mytomycin C for pterygiumsurgery. Ophthalmology 1996;103:674–7.

6. Sridhar MS, Bansal AK, Rao GN. Surgically inducednecrotizing scleritis after pterygium excision and con-junctival autograft. Cornea 2002;21:305–7.

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Fig. 2—Appearance of recurrent pterygium 3 months afterresection of initial pterygium and placement of free autol-ogous conjunctival graft.

Fig. 3—No evidence of recurrence after 3.5 months of treat-ment with interferon alpha-2b.

7. Baron S, Tyring SK, Fleischmann WR Jr, CoppenhaverDH, Niesel DW, Klimpel GR, et al. The interferons:mechanisms of action and clinical applications. JAMA1991;266:1375–83.

8. MacKenzie FD, Hirst LW, Kynaston B, Bain C.Recurrence rate and complications after beta irradia-tion for pterygia. Ophthalmology 1991;98:1776–80.

9. Donnenfeld ED, Perry HD, Fromer S, Doshi S,Solomon R, Biser S. Subconjunctival mitomycin C asadjunctive therapy before pterygium excision.Ophthalmology 2003;110:1012–6.

10. Zhang X, Peng D, Zheng H, Liang M. Lack of cornealtoxicity of interferon alpha 2b administered subcon-

junctivally after sclerectomy. Yan Ke Xue Bao 1997;13:35–7.

11. Morlet N, Gillies MC, Crouch R, Maloof A. Effect oftopical interferon alpha 2b on corneal haze afterexcimer laser photorefractive keratectomy in rabbits.Refract Corneal Surg 1993;9:443–51.

12. Prata L, Folgado A, Mara-Seco J, Carvalho A,Mendonca E, Mancio-Santos A. Human alpha 2b inrabbit eyes. Ophtalmologie 1990;4:383–4.

Key words: conjunctival disorders, interferon alpha-2b,limbal stem cells, pterygium, recurrence

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