Chemotherapy-induced organ toxicity mitigation
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The rapid and near-complete recovery after metabolic therapy supports a mechanistic link between ifosfamide-induced mitochondrial dysfunction, NAD depletion, and reversible foveal injury.
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PURPOSE: To describe a case of acute, severe bilateral foveolysis following systemic ifosfamide therapy and the subsequent anatomical and functional recovery after discontinuation of the drug and administration of metabolic therapy targeting mitochondrial dysfunction. METHODS: The patient had a comprehensive ophthalmological examination including high resolution optical coherence tomography. After cessation of ifosfamide, she was treated with nicotinamide adenine dinucleotide 850 mg, alpha lipoic acid 600 mg, and coenzyme Q10 100 mg daily. RESULTS: A 34-year-old woman receiving ifosfamide for an inoperable skull-base chordoma developed rapid bilateral 20/60 visual acuity. Optical coherence tomography revealed complete dissolution of the central fovea in each eye with accumulation of necrotic debris centrally. Given the known pathway of ifosfamide neurotoxicity, mitochondrial complex I inhibition with depletion of nicotinamide adenine dinucleotide (NAD), the patient received high-dose oral NAD, coenzyme Q10, and alpha-lipoic acid. Over the next several weeks, both eyes showed symmetrical reconstitution of the fovea with centripetal migration of the outer nuclear layer and eventual restoration of outer retinal architecture. By 12 weeks, foveal structure was normal and visual acuity improved to 20/25 and 20/20. CONCLUSIONS: Systemic ifosfamide was associated with an acute symmetrical dissolution of the central fovea, termed foveolysis. Although spontaneous improvement after drug withdrawal cannot be excluded, the rapid and near-complete recovery after metabolic therapy supports a mechanistic link between ifosfamide-induced mitochondrial dysfunction, NAD depletion, and reversible foveal injury. The foveal architecture was restored through the defined sequence of foveation, demonstrating the capacity of the adult fovea for organized structural reconstitution.
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@article{Spaide2026Reconstitution,
title = {Reconstitution of the Fovea Through Foveation After Ifosfamide-Induced Foveolysis},
author = {Richard F. Spaide},
journal = {Retinal Cases & Brief Reports},
year = {2026},
doi = {10.1097/icb.0000000000001979},
url = {https://doi.org/10.1097/icb.0000000000001979}
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