Treatment of Leber's hereditary optic neuropathy: theory to practice.

Dramatic advances in our understanding of the molecular genetic basis of Leber's hereditary optic neuropathy (LHON) have revolutionized our ability to diagnose and prognosticate this disease. Unfortunately no corresponding advances in the treatment of LHON have emerged. Glaucoma is a prevalent form of optic neuropathy that has been studied extensively. Lessons learned from treatment of LHON and glaucoma may have important implications for both diseases. LHON presents formidable challenges to the design and conduct of clinical trials. The acutely symptomatic LHON patient with monocular vision loss provides a unique clinical situation in which to test an agent during a critical therapeutic window. Advances in neuroprotection, apoptosis, and neurodegenerative diseases may provide important clues for potential therapeutic agents for LHON. Antioxidants and agents that interfere with the critical steps of mitochondrial-dependent, oxidative stress-induced apoptosis are candidates for future LHON therapy. A variety of neuroprotective agents, under active investigation in other diseases, may be useful in LHON therapy. Effective pharmacotherapy will complement the current management approach that has changed little in the 130 years since LHON was originally described.