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Abstract

We thank Dr Huevra for his interest and thoughtful comments on our paper and largely agree with his views on managing this problematic condition. We did not set out to compare topical with subconjunctival delivery of interferon—this was beyond the scope of the original study. As Dr Huevra points out, topical treatment has a better patient acceptance and side effect profile. On the issue of compliance, our clinical impression is that it is high for topical treatment; we suspect because many patients' fear of cancer. We also agree that a major advantage of topical treatment is the therapeutic agent comes into contact with much of the ocular surface—of particular importance in a disease that can be multifocal in origin in as high as 23% of cases,1Yousef Y.A. Finger P.T. Squamous carcinoma and dysplasia of the conjunctiva and cornea: an analysis of 101 cases.Ophthalmology. 2012; 119: 233-240Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar as well as the fact that the true extent of disease is not clinically visible. Furthermore, there is the potential advantage of protection of the lacrimal drainage system, given reports of an association between primary acquired melanosis (PAM) and subsequent development of melanoma of the lacrimal drainage system and lacrimal gland ductules despite excision of the areas of PAM.2McNab A.A. McKelvie P. Malignant melanoma of the lacrimal sac complicating primary acquired melanosis of the conjunctiva.Ophthalmic Surg Lasers. 1997; 28: 501-504PubMed Google Scholar Although squamous neoplasia of the lacrimal drainage system seems to be uncommon, it is conceivable that such lesions could originate from ocular surface disease that was small in size or of a variety that can spontaneously resolve. Whether these remote lesions occur as a result of multifocal disease, direct spread, or seeding of tumor cells, our modality of treatment would offer protection. Because the sine pigmento form of PAM is in the differential diagnosis of epithelial neoplasia and because PAM responds to topical interferon,3Finger P.T. Sedeek R.W. Chin K.J. Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex.Am J Ophthalmol. 2008; 145: 124-129Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar we believe that all such lesions should be biopsied before the initiation of treatment. Our early experience with retinoic acid alone was similar to that so well-documented by Dr Huevra and before the availability of topical interferon used it routinely as an initial treatment in preference to destructive techniques such as surgery with or without chemotherapeutic agents. Because of this approach and when topical interferon became available, one of our patients used both agents together when each had failed alone. Thus, by serendipity we discovered that the 2 agents worked synergistically against ocular surface neoplasia as had previously been reported for nonocular malignancy. We were impressed by the rapidity of the clinical response as confirmed in the paper under discussion with a median time to resolution of 1.6 months. We did in fact point this out in comparing our data with a similar study in which topical interferon monotherapy was used (Table 2).4Schechter B.A. Koreishi A.F. Karp C.L. Feuer W. Long-term follow-up of conjunctival and corneal intraepithelial neoplasia treated with topical interferon alfa-2b.Ophthalmology. 2008; 115: 1291-1296Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar What is most impressive about this treatment as we noted was that the tissue appearance and in particular the limbal appearance were normal after lesion resolution. Although one could speculate as to the mechanism of action of this combined treatment regime, this clinical result is perhaps suggestive of “clonal deletion” of neoplastic cells (a known chemopreventive effect of retinoids5Okuno M. Kojima S. Matsushima-Nishiwaki R. et al.Retinoids in cancer chemoprevention.Curr Cancer Drug Targets. 2004; 4: 285-298Crossref PubMed Scopus (126) Google Scholar), perhaps allowing repopulation of limbus by normal stem cells. This might also explain the excellent response rate and long-term results. We also agree with Dr Huevra that there is no clear consensus on the best way to manage this disorder and that there is a need for long-term, well-designed multicenter studies. Treatment of CIN with Retinoic Acid and Topical Interferon Alfa-2bOphthalmologyVol. 120Issue 8PreviewI have read with interest the recent report from Krilis et al1 about topical treatment of conjunctiva-cornea intraepithelial neoplasia (CIN) using a combination of 1 million IU/ml topical interferon (INF)-α2b drops 4 times daily and 0.01% retinoic acid once every second day. They concluded that 0.01% topical transretinoic acid once every second day and INF-α2b may act synergistically and that a combined treatment of INF-α2b and retinoic acid may offer a superior alternative to INF-α2b alone when treating CIN. Full-Text PDF