Retinopathy Associated with Adjuvant High-Dose Interferon-α2b in a Patient with Resected Melanoma: A Case Report and Review of the Literature

Abstract

Interferon is the only accepted adjuvant treatment for patients with melanoma; hence, oncologists should be aware of the possibility of retinal abnormalities resulting from its use. Interferon-associated retinopathy in patients being treated for resected melanoma is a rare phenomenon with a proposed immunological basis. Patients are usually asymptomatic or have mild visual impairments, with cotton wool infarcts and hemorrhages. These symptoms and signs usually resolve with the discontinuation of interferon, but in a few severe presentations the visual impairments and retinal changes can be irreversible. The Oncologist 2012; 17:384 -387 CASEA healthy, 35-year-old woman was receiving high-dose adjuvant interferon-␣2b (HD-IFN) for a resected stage 3a superficial spreading cutaneous malignant melanoma of the right arm. She had received induction treatment of 33 million units (20 million units/m 2 ) of HD-IFN i.v. 5 days per week for 4 weeks, and maintenance therapy of 16 million units (10 million units/ m 2 ) s.c. 3 days per week had been initiated for a planned total of 11 months. Four months into treatment, she presented with painless blurred vision inferotemporal to fixation in her left eye. Other than her new visual symptoms, she did not have any other significant side effects that would warrant discontinuing her treatment. Moreover, she denied any headache, fever, diplopia, or orbital pain. On examination, her vital signs, including blood pressure, were normal. Her cardiovascular, respiratory, and abdominal examinations were unremarkable. Her remaining cranial nerves and neurological examinations were unremarkable. She had mild anemia (hemoglobin, 114 g/L; hematocrit, 0.347 L/L) and no thrombocytopenia. She was referred urgently to an ophthalmologist for evaluation. Her central vision was 6/6 in each eye without correction. Pupil reactions were normal. Examinations of the anterior segments, anterior chambers, optic discs, and retinal vasculature were all normal. Color vision was not tested. There were cotton wool infarcts between the optic disc and fovea in the left eye and along the superotemporal arcades in both eyes (Fig. 1A and 1B, arrows). There was a paracentral scotoma on Amsler grid testing in the left eye. The etiology of the retinopathy was felt to be associated with her HD-IFN and she was instructed to stop the agent immediately. Three weeks later, there was a marked reduction in the cotton wool spots (Fig. 1C and 1D, arrows), and by 10 weeks they had almost completely resolved. The left eye scotoma had also resolved. DISCUSSIONHD-IFN has been the standard adjuvant treatment for melanoma since researchers first demonstrated that it could produce longer relapse-free survival (RFS) and overall survival (OS)

Interferon-associated retinopathy in a patient with metastatic melanoma

“…This is thought to increase leukocyte adhesion, which may trigger microcirculation obstruction (1)(2)(3) . Furthermore, it has been reported that IFN induces thrombogenic antibody proliferation (9) .…”

“…It should be noted that our patient had no history of diabetes mellitus, arterial hypertension, or previous cardiovascular risk factors, all of which are known to be associated with the development and progression of retinopathy in patients undergoing IFN treatment (1,7,8) . Nevertheless, given the patients' background, cerebral and orbital TC was requested, which revealed a retro-orbital mass of 15 × 25 mm compatible with orbital metastases.…”

“…They have wide clinical uses in multiple viral and tumorigenic processes, and have been classically used in the treatment of severe diseases such as hepatitis C and mul tiple sclerosis. IFN is also the only accepted adjuvant treatment for patients with cutaneous melanoma (1) . Although generally well tolerated, incidences of IFN toxicity are commonly reported.…”

“…In a previous report describing patients with re sected high-risk melanoma who received adjuvant IFN, 13% developed retinopathy (5) . Since most of the adverse effects are due to toxicity, these symptoms usually resolve or improve after therapy discontinuation (1) . Fur thermore, there is a direct relationship between the dose and duration of treatment and the likelihood of retinopathy, with its appearance occurring between 8 and 12 weeks after the beginning of treatment (6) .…”

“…However, in some cases complications that result in significant visual impairment can occur. Thus, monitoring and periodic ophthalmologic evaluation of patients undergoing IFN treatment is highly recommended (1,2) . Here we report a case of atypical IFN-associated retinopathy involving macular changes, appearing in a young woman with cutaneous melanoma.…”