Tuesday, January 27, 2009
Carol L. Karp, MD describes the treatment of ocular surface tumors in an interview with David Goldman, MD. Ocular surface tumors can be put into three categories: pigmented, non-pigmented and lymphomas. Ocular squamous neoplasias (which used to be called CIN -- corneal and conjunctival intraepithelial neoplasia) is part of the spectrum of squamous cell carcinomas and are invasive whereas CIN is full thickness or partial thickness of the epithelium only. These tumors are almost always non-pigmented. Appearance varies: papillary, gelatinous, leukoplakic, opalescent if on cornea. Rose Bengal staining is very helpful in differential diagnosis. When there’s a breakdown of the mucin layer of the eye, the keratin of the tumor stains. It can also demonstrate the margins of the lesion.
The decision to perform surgery is based on size and surgical risk (damage to limbus), and complexity of reconstruction. Another factor is that some patients prefer surgery. Other options are medical treatments. Mitomycin-C (MMC), 5-fluorouracil (5-FU), or Interferon (IFN).
Dr. Karp’s personal preference is for IFNs because of their biology. IFNs are used systemically for leukemia and melanomas. Use in eye is off-label. Can be used as drops and is well tolerated. Compounded at 1M IU/mL. Dosed q.i.d. for 3 months of treatment is generally efficacious. Sub-conjunctival injection is another option – no compliance issues. Each injection is 3M IU. Side effects of the subconjunctival IFN injection can cause a flu-like malaise for the next 4 to 6 hrs. Injections are given once or twice a week.
Mitomycin-C is used in trabeculectomies and pterygium surgeries. In this setting, it is administered q.i.d. at either 0.02% or 0.04%. Punctal plugs used to protect lachrymal ducts. Used 7 to 14 days depending on how long the patient can stand the discomfort – epithelial toxicity. Once compounded, the solution is stable for only about two weeks with refrigeration. Several rounds of this may be necessary. It is effective but is really rough when compared to IFN.
5-FU, also used in glaucoma surgery, is another alkylating agent. More stabile than MMC, 5-FU is used similarly (q.i.d. for 7 to 14 days). Patrick Yeatts, MD suggests using 4 days of treatment, taking the rest of the month off, then cycling again. 5-FU seems to be somewhat less effective but causes less toxicity than MMC.
If a patient is on IFN and reaches a plateau, you could then try a course of MMC. Conversely, a patient on MMC can be switched to IFN if MMC is poorly tolerated.
Dr. Karp often does a biopsy at the slit lamp to confirm the diagnosis. This is because not everything that looks like a CIN is a CIN: could be an amelonotic melanoma, or a sebaceous cell carcinoma. So if you’re treating a patient clinically and there is little response to treatment, it could be one of these other diseases.
Dr. Karp then goes on to describe three cases in which successful resolution was demonstrated using MMC drops, IFN injections and topical IFN.
IFN is used to treat cervical intraepithelial neoplasia. This disease and conjunctival intraepithelial neoplasia have a lot of parallels: both are at transition zones between non keratinized epithelium, Langerhans cells immune vigilance, and HPV 16 and 18 have a role in disease.
Dr. Karp performs post-treatment biopsies on occasion to verify the absence of residual neoplastic cells.