Comment on "Perhaps not everyone knows that...", (Ann Oncol 2001; 12: 1186)

A. Sulkes and J. Schlachter

Institute of Oncology, Rabin Medical Center, Petach Tikva, Israel (E-mail: asolkes@ccsg.tau.ac.il)

One of the items in your "Perhaps not everyone knows that..." section in the September 2001 issue of Annals of Oncology [1] deals with the occurrence of retinopathy in patients with malignant melanoma who receive high-dose interferon {alpha}-2b (IFN{alpha}), as reported in the American Journal of Ophthalmology by investigators at the Emory Eye Infirmary [2].

Our group was among the first to describe in the oncology literature, the occurrence of this adverse effect among patients with malignant melanoma on treatment with high-dose IFN{alpha} [3]. Of the 30 patients in our series with high-risk primary malignant melanoma who received adjuvant high-dose IFN{alpha} following resection of the tumor, four (13%) developed retinopathy consisting of cotton wool infiltrates. These changes were diagnosed during routine ophthalmological examination, had no clinical manifestations, usually appeared early in the course of treatment and resolved promptly upon its discontinuation.

Retinopathy has, in fact, been reported previously, mainly as isolated case reports [4, 5] in patients with chronic hepatitis on treatment with interferon. In this context, Kawano et al. conducted serial ophthalmological examinations of 63 patients with chronic hepatitis C receiving IFN{alpha} [6]; 57% developed retinal abnormalities in the form of hemorrhage and/or cotton-wool exudates. In agreement with our observations, these occurred within 8 weeks of the onset of IFN{alpha} administration in the overwhelming majority of the affected patients. The incidence of retinal changes was higher in patients with diabetes and hypertension. A trend has been described correlating the duration and dose of IFN{alpha} with the occurrence of retinopathy [7].

It has been suggested that retinal changes during IFN{alpha} administration may be due to an increase in leukocyte adherence and trapping in the retinal microcirculation leading to microinfarctions and endothelial cell damage [8]. As these changes are mostly, but not always, reversible [2, 4] and do not result in clinical visual impairment, their occurrence and incidence appears to have been largely overlooked. Thus, for instance, in the pivotal work of Kirkwood et al. where 146 patients with resected malignant melanoma were randomized to receive high-dose IFN{alpha} retinopathy is not described among the toxic events [9].

With the widespread use of IFN{alpha} in patients with malignant melanoma and other conditions, oncologists should be aware of the possibility of retinal abnormalities resulting from its administration.

A. Sulkes & J. Schachter

Institute of Oncology, Rabin Medical Center, Petach Tikva, Israel (E-mail: asolkes@ccsg.tau.ac.il)

References

1. Perhaps not everyone knows that... Ann Oncol 2001; 12: 1186.

2. Hejny C, Sternberg P, Lawson DH et al. Retinopathy associated with high-dose interferon alfa-2b therapy. Am J Ophthalmol 2001; 131: 782–787.[ISI][Medline]

3. Schachter J, Brenner B, Fenig E et al. Toxicity of adjuvant high-dose interferon-{alpha}-2b in patients with cutaneous melanoma at high risk of recurrence. Oncol Rep 1999; 6: 1389–1393.[ISI][Medline]

4. Chambers RB, Downie A, Foote B, Davidorf FH. Interferon alfa-associated retinopathy. J Am Osteopath Assoc 1997; 97: 43–45.[Abstract]

5. Louvet B, Sales MJ, Souid M, Barbanel C. Retinopathy caused by interferon. Apropos of a case. J Fr Ophthalmol 1997; 20: 624–627.[ISI][Medline]

6. Kawano T, Shigehira M, Uto H et al. Retinal complications during interferon therapy for chronic hepatitis C. Am J Gastroenterol 1996; 91: 309–313.[ISI][Medline]

7. Hayasaka S, Nagaki Y, Matsumoto M, Sato S. Interferon associated retinopathy. Br J Opthalmol 1998; 82: 323–325.[Free Full Text]

8. Nishiwaki H, Ogura Y, Miyamoto K et al. Interferon alfa induces leukocyte capillary trapping in rat retinal microcirculation. Arch Ophthalmol 1996; 114: 726–730.[Abstract]

9. Kirkwood JM, Strawderman MH, Ernstoff MS et al. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Group trial EST 1684. J Clin Oncol 1996; 14: 7–17.[Abstract]





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