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M. F. Marmor, A. Jain, D. M. Moshfeghi; Total Rod Suppression With High Dose Fenretinide Usage. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2162.
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Fenretinide is a synthetic retinoid used for cancer therapy. It interferes with serum retinol binding and in typical doses will cause a partial and reversible reduction in rod function. For this latter reason, which reduces the production of lipofuscin, it has recently been proposed as therapy for Stargardt disease and dry ARMD. Very high does of Fenretinide are sometimes used in compassionate protocols for aggressive cancers. We report two children given high dose Fenretinide therapy who showed total rod suppression.
A girl and boy, aged 12 and 13, were studied while using 800 mg Fenretinide daily (on intermittent weeks), as treatment for neuroblastoma. Their disease had been stable for 2 years, and neither complained of night blindness. Goldmann-Weekers dark adaptometry and ISCEV Standard full-field ERG (LKC UTAS 2000) and mfERG (VERIS) were performed.
Both youngsters had 20/20 visual acuity and normal retinal exams. Dark adaptometry showed final rod thresholds at cone level (elevated roughly 3 log units). Full-field ERGs showed no detectable rod responses, but cone signals and mfERGs were normal. The boy was tested one year later, off medication, at which time rod responses were at the low end of normal. Serum vitamin A levels were normal in both subjects, but were probably drawn during intervals off medication.
Fenretinide can suppress rods very severely at high doses, but this seems largely reversible. Although the drug interferes with vitamin A transport, it does not appear to damage rods as severely as clinical vitamin A deficiency, and cones seem able to access vitamin A through other routes. As more applications of Fenretinide are developed, the potential risk of long-term retinal damage needs to be evaluated.
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