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Total rod ERG suppression with high dose compassionate Fenretinide usage
Michael F Marmor1, Atul Jain, Darius Moshfeghi
1Department of Ophthalmology, Room A-157, Stanford University Medical Center, 300 Pasteur Dr., Stanford, CA, 94305-5308, USA. marmor@stanford.edu
Documenta Ophthalmologica. Advances in Ophthalmology
|June 5, 2008
Summary
High-dose Fenretinide (a synthetic retinoid) significantly suppressed rod function in young patients with neuroblastoma. However, vision and vitamin A levels returned to normal rapidly after discontinuing the drug.
Area of Science:
- Ophthalmology
- Retinal Diseases
- Pharmacology
Background:
- Fenretinide is a synthetic retinoid investigated for Stargardt disease and cancer therapy.
- Standard doses can cause mild visual side effects, including reduced rod function.
- Its mechanism involves interfering with retinol binding protein and potentially inhibiting A2E/lipofuscin accumulation.
Observation:
- Two adolescents received high-dose Fenretinide (800 mg daily for 1 week every 3 weeks) for neuroblastoma over approximately two years.
- Initial examinations revealed significantly elevated dark adaptation thresholds and undetectable rod electroretinogram (ERG) responses.
- No patient-reported night blindness or fundus abnormalities were noted; cone ERG and multifocal ERG (mfERG) remained normal.
Findings:
- High-dose Fenretinide caused profound, but reversible, suppression of rod photoreceptor function.
- Rod function and serum vitamin A levels normalized within three months of drug cessation.
- Cone photoreceptor function appeared unaffected by the high-dose Fenretinide treatment.
Implications:
- High-dose Fenretinide can reversibly impair rod vision, necessitating careful monitoring during treatment.
- The rapid recovery of rod function suggests potential therapeutic windows for retinoid-based therapies.
- Cone photoreceptor function and vitamin A availability seem distinct from Fenretinide's effects on retinol metabolism.
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