Total rod ERG suppression with high dose compassionate Fenretinide usage
Abstract
Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inhibiting RPE65 or RBP4 causes reversible night blindness as a side effect.
“As a side effect, reversible night blindness occurs [101,102,103,104].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [101]
Inhibiting RPE65 or RBP4 slows the visual cycle, deprives photoreceptors of 11-cis-retinal, and consequently reduces accumulation of toxic A2E.
“An example is slowing the visual cycle by inhibiting RPE65 or RBP4, which deprives photoreceptors of 11-cis-retinal and consequently reduces the accumulation of toxic A2E.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [101]
Cites
A Membrane Receptor for Retinol Binding Protein Mediates Cellular Uptake of Vitamin A
Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., Ping, P., Wiita, P., Bok, D., & Sun, H. (2007) · Science · doi:10.1126/science.1136244 · Cited by 836 · see citing works
Standard for clinical electroretinography
Marmor, M. F., Arden, G. B., NILSSON, S. E. G., & Zrenner, E. (1989) · Documenta Ophthalmologica · doi:10.1007/bf00154486 · Cited by 807 · see citing works
Self-citationStandard for clinical electroretinography (2004 update)
Marmor, M. F., Holder, G. E., Seeliger, M. W., & Yamamoto, S. (2004) · Documenta Ophthalmologica · doi:10.1023/b:doop.0000036793.44912.45 · Cited by 505 · see citing works
Self-citationIsomerization and Oxidation of Vitamin A in Cone-Dominant Retinas
Mata, N. L., Radu, R. A., Clemmons, R. S., & Travis, G. H. (2002) · Neuron · doi:10.1016/s0896-6273(02)00912-1 · Cited by 382 · see citing works
Retinoid therapy of high-risk neuroblastoma
Reynolds, C. P., Matthay, K. K., Villablanca, J. G., & Maurer, B. J. (2003) · Cancer Letters · doi:10.1016/s0304-3835(03)00108-3 · Cited by 329 · see citing works
Radu, R. A., Han, Y., Bui, T. V., Nusinowitz, S., Bok, D., Lichter, J. B., Widder, K., Travis, G. H., & Mata, N. L. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-0820 · Cited by 225 · see citing works
Phase I trial and pharmacokinetics of fenretinide in children with neuroblastoma.
Garaventa, A., Luksch, R., Piccolo, M. S. L., Cavadini, E., Montaldo, P. G., Pizzitola, M. R., Boni, L., Ponzoni, M., DeCensi, A., Bernardi, B. D., et al. (2003) · PubMed · Cited by 188 · see citing works
(1999) · PubMed · Cited by 154 · see citing works
Formelli, F., Carsana, R., da Costa, A. L. T., Buranelli, F., Campa, T., Dossena, G., Magni, A., & Pizzichetta, M. A. (1989) · PubMed · Cited by 138 · see citing works
Berni, R., & Formelli, F. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)81046-o · Cited by 105 · see citing works
Abnormal Retinal Function Associated With Fenretinide, a Synthetic Retinoid
Kaiser‐Kupfer, M. I., Peck, G. L., Caruso, R. C., Jaffe, M. J., DiGiovanna, J. J., & Gross, E. G. (1986) · Archives of Ophthalmology · doi:10.1001/archopht.1986.01050130079024 · Cited by 91 · see citing works
Megalin-Mediated Reuptake of Retinol in the Kidneys of Mice Is Essential for Vitamin A Homeostasis
Raila, J., Willnow, T. E., & Schweigert�, F. J. (2005) · Journal of Nutrition · doi:10.1093/jn/135.11.2512 · Cited by 75 · see citing works
Effect of the Synthetic Retinoid Fenretinide on Dark Adaptation and the Ocular Surface
DeCensi, A., Torrisi, R., Polizzi, A., Gesi, R., Brezzo, V., Rolando, M., Rondanina, G., AntoniettaOrengo, M., Formelli, F., & Costa, A. (1994) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/86.2.105 · Cited by 67 · see citing works
Functional observations in vitamin A deficiency: diagnosis and time course of recovery
McBain, V. A., Egan, C. A., Pieris, S. J., Supramaniam, G., Webster, A. R., Bird, A. C., & Holder, G. E. (2007) · Eye · doi:10.1038/sj.eye.6702212 · Cited by 64 · see citing works
A novel cone visual cycle in the cone-dominated retina
Muniz, A., Villazana-Espinoza, E. T., Hatch, A. L., Trevino, S. G., Allen, D. M., & Tsin, A. T. C. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2007.05.003 · Cited by 60 · see citing works
Arshavsky, V. Y. (2002) · Neuron · doi:10.1016/s0896-6273(02)00937-6 · Cited by 58 · see citing works
Effects of Fenretinide (4-HPR) on Dark Adaptation
Caruso, R. C. (1998) · Archives of Ophthalmology · doi:10.1001/archopht.116.6.759 · Cited by 30 · see citing works
Long-term effects of fenretinide on retinal function
DeCensi, A., Fontana, V., Fioretto, M., Rondanina, G., Torrisi, R., Orengo, M. A., & Costa, A. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(96)00351-6 · Cited by 30 · see citing works
Ocular effects of fenretinide, a vitamin A analog, in a chemoprevention trial of bladder cancer.
Baglietto, L., Torrisi, R., Arena, G., Tosetti, F., Gonzaga, A. G., Pasquetti, W., Robertson, C., & DeCensi, A. (2000) · PubMed · Cited by 20 · see citing works
Ocular Toxic Effects of Fenretinide
Modiano, M., Dalton, W. S., Lippman, S. M., Joffe, L., Booth, A. R., & Meyskens, F. L. (1990) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/82.12.1063 · Cited by 20 · see citing works
Electroretinographic findings in subjects after administration of fenretinide
Krzeminski, R., Zwas, F., Esper, P. S., & Pienta, K. J. (1995) · Documenta Ophthalmologica · doi:10.1007/bf01214648 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The dynamic nature of Bruch's membrane
Booij, J. C., Baas, D. C., Beisekeeva, J., Gorgels, T. G. M. F., & Bergen, A. A. B. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.08.003 · Cited by 581 · see citing works
Charbel Issa, P., Barnard, A. R., Herrmann, P., Washington, I., & MacLaren, R. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1506960112 · Cited by 124 · see citing works
The Role of Vitamin A in Retinal Diseases
Sajovic, J., Meglič, A., Glavač, D., Markelj, Š., Hawlina, M., & Fakin, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031014 · Cited by 109 · see citing works
SAFETY AND EFFECT ON ROD FUNCTION OF ACU-4429, A NOVEL SMALL-MOLECULE VISUAL CYCLE MODULATOR
Kubota, R., Boman, N. L., David, R., Mallikaarjun, S., Patil, S., & Birch, D. G. (2011) · Retina · doi:10.1097/iae.0b013e318217369e · Cited by 98 · see citing works
RETINAL TOXICITIES OF CANCER THERAPY DRUGS
Liu, C. Y., Francis, J. H., Brodie, S. E., Marr, B. P., Pulido, J. S., Marmor, M. F., & Abramson, D. H. (2014) · Retina · doi:10.1097/iae.0000000000000242 · Cited by 70 · see citing works
Self-citationPeinemann, F., van Dalen, E. C., Enk, H., & Berthold, F. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010685.pub3 · Cited by 58 · see citing works
Dellett, M., Sasai, N., Nishide, K., Becker, S., Papadaki, V., Limb, G. A., Moore, A. T., Kondo, T., & Ohnuma, S. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15479 · Cited by 41 · see citing works
Retinal toxicities of Systemic Anticancer Drugs.
Arora, S., Surakiatchanukul, T., Arora, T., Errera, M., Agrawal, H., Lupidi, M., & Chhablani, J. (2021) · Survey of ophthalmology · doi:10.1016/j.survophthal.2021.05.007 · Cited by 31 · see citing works
Antiviral activity of N-(4-hydroxyphenyl) retinamide (4-HPR) against Zika virus
Pitts, J. D., Li, P., de Wispelaere, M., & Yang, P. L. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.10.014 · Cited by 38 · see citing works
Peinemann, F., van Dalen, E. C., Kahangire, D. A., & Berthold, F. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010685.pub2 · Cited by 29 · see citing works
Retinoid isomerase inhibitors impair but do not block mammalian cone photoreceptor function
Kiser, P. D., Zhang, J., Sharma, A., Angueyra, J. M., Kolesnikov, A. V., Badiee, M., Tochtrop, G. P., Kinoshita, J., Peachey, N. S., Li, W., et al. (2018) · The Journal of General Physiology · doi:10.1085/jgp.201711815 · Cited by 28 · see citing works
Chemoprevention of Head and Neck Cancers: Does It Have Only One Face?
Siemianowicz, K., Likus, W., Dorecka, M., Wilk, R., Dziubdziela, W., & Markowski, J. (2018) · BioMed Research International · doi:10.1155/2018/9051854 · Cited by 19 · see citing works
Pharmacotherapy of Age-Related Macular Degeneration
Blumenkranz, M., Leung, L., Martin, D. F., Rosenfeld, P., & Zarbin, M. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4557-0737-9.00067-9 · Cited by 8 · see citing works
Electroretinography as a Biomarker to Monitor the Progression of Stargardt Disease
Sajovic, J., Meglič, A., Hawlina, M., & Fakin, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416161 · Cited by 5 · see citing works
Moore, A. T. (2009) · Current Opinion in Ophthalmology · doi:10.1097/icu.0b013e32832f8002 · Cited by 5 · see citing works
Review of Emerging Treatments for Age-Related Macular Degeneration
Zarbin, M. A., & Rosenfeld, P. J. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-606-7_1 · Cited by 3 · see citing works
Gender Specific Issues in Hereditary Ocular Disorders
Iragavarapu, S., & Gorin, M. B. (2014) · Current Eye Research · doi:10.3109/02713683.2014.932813 · Cited by 2 · see citing works
Fenretinide-Associated Multilayered Retinal Hemorrhage in a Patient with Hairy Cell Leukemia
Salehi-Had, H., & Puliafito, C. A. (2010) · Ophthalmic surgery, lasers & imaging retina · doi:10.3928/15428877-20101031-17 · Cited by 2 · see citing works
- Authors
- Marmor, M. F., Jain, A., & Moshfeghi, D.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Marmor, Michael F.
- Venue
- Documenta Ophthalmologica
- Published
- 2008-06-04
- Volume
- 117
- Issue
- 3
- Pages
- 257-261
- ISSN
- 0012-4486 (ISSN-L)
- 1573-2622
- OpenAlex
- W2108217633
- Cited by
- 18
- References
- 21
- Citations by year
- 2022: 2 · 2021: 1 · 2018: 2 · 2017: 2 · 2015: 2 · 2014: 3 · 2012: 2
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Documenta Ophthalmologica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- fenretinide, rod photoreceptor function, dark adaptation, vitamin A, retinol-binding protein, neuroblastoma, children, retinal function recovery, cone function, Stargardt disease
- MeSH terms
- Adolescent, Antineoplastic Agents, Child, Dark Adaptation, Electroretinography, Female, Humans, Male, Neuroblastoma, Retinal Diseases, Vitamin A, Fenretinide, Retinal Rod Photoreceptor Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
