The prognosis for those left untreated is almost always continued significant visual loss in both eyes. Regular corrected visual acuity and perimetry checks are advised for affected people. There is beneficial treatment for some cases of<unk> , especially for early-onset disease, and experimental treatment protocols are in progress. Genetic counseling should be offered. Health and lifestyle choices should be reassessed, particularly in light of toxic and nutritional theories of gene expression. Vision aids assistance and work rehabilitation should be used to assist in maintaining employment. For those who carry a<unk>  mutation, preclinical markers may be used to monitor progress. For example, fundus photography can monitor nerve fiber layer swelling. Optical coherence tomography can be used for more detailed study of retinal nerve fiber layer thickness. Red green color vision testing may detect losses. Contrast sensitivity may be diminished. There could be an abnormal electroretinogram or visual evoked potentials. Neuron-specific enolase and axonal heavy chain neurofilament blood markers may predict conversion to affected status. Cyanocobalamin (a form of B12) should be avoided as it may lead to blindness in<unk>  patients. Avoiding optic nerve toxins is generally advised, especially tobacco and alcohol. Certain prescription drugs are potential risks, so all drugs should be treated with suspicion and checked before use by those at risk. Ethambutol, in particular, has been implicated as triggering visual loss in carriers of<unk> . In fact, toxic and nutritional optic neuropathies may have overlaps with<unk>  in symptoms, mitochondrial mechanisms of disease and management. And when a patient carrying or suffering from<unk>  or toxic/nutritional optic neuropathy suffers a hypertensive crisis as a possible complication of the disease process, nitroprusside (trade name: Nipride) should not be used, due to increased risk of optic nerve ischemia in response to this anti-hypertensive. Idebenone has been shown in a small placebo-controlled trial to have modest benefit in about half of patients. People most likely to respond best were those treated early in onset. α-Tocotrienol-quinone, a vitamin E metabolite, has had some success in small open-label trials in reversing early onset vision loss. Various treatment approaches have had early trials or been proposed, but so far none with convincing evidence of usefulness or safety for treatment or prevention, including brimonidine, minocycline, curcumin, glutathione, near infrared light treatment, and viral vector techniques. "Three person in vitro fertilization" is a proof-of-concept research technique for preventing mitochondrial disease in developing human fetuses. So far, viable macaque monkeys have been produced. But ethical and knowledge hurdles remain before use of the technique in humans is established. Idebenone Idebenone is a short-chain benzoquinone that interacts with the mitochondrial electron transport chain to enhance cellular respiration. When used in people with<unk> , it is believed to allow electrons to bypass the dysfunctional complex I. Successful treatment with idebenone was initially reported in a small number of patients. Two large-scale studies have demonstrated the benefits of idebenone. The Rescue of<unk>  Optic Disease Outpatient Study (RHODOS) evaluated the effects of idebenone in 85 patients with<unk>  who had lost vision within the prior five years. In this study, the group taking idebenone 900 mg per day for 24 weeks showed a slight improvement in visual acuity compared to the placebo group, though the difference was not statistically significant. But patients taking idebenone were protected from further vision loss, whereas the placebo group had a steady decline in visual acuity. Further, people taking idebenone demonstrated preservation of color vision and persistence of the effects of idebenone 30 months after discontinuing therapy. A retrospective analysis of 103<unk>  patients by Carelli et al. builds upon these results. This study highlighted that 44 subjects who were treated with idebenone within one year of onset of vision loss had better outcomes, and that these improvements persisted for years. Idebenone, combined with avoidance of smoke and limitation of alcohol intake, is the preferred treatment protocol for people with<unk> . Idebenone doses are prescribed to be taken spaced out throughout the day, rather than all at once. For example, to achieve a dose of 900 mg per day, patients take 300 mg three times daily with meals. Idebenone is fat-soluble, and may be taken with a moderate amount of dietary fat in each meal to promote absorption. It is recommended that patients on idebenone also take vitamin C 500 mg daily to keep idebenone in its reduced form, as it is most active in this state. Estrogen Replacement Therapy Estrogens have been shown to have a protective role in the pathogenesis of<unk> . Experiments using<unk>  cybrids have demonstrated that the estrogen receptor localizes to the mitochondria where it directly mediates mitochondrial biogenesis. Estrogens upregulate the antioxidant enzyme superoxide dismutase 2 and mitochondrial DNA synthesis. These experiments helped to explain the mechanism behind the lower penetrance of disease among female carriers. While additional factors have been theorized, the protective role of estrogens appears to be a significant contributor. In addition to the experimental evidence, clinical data also points towards the protective role of estrogens. Penetrance among female carriers is substantially lower (between 3 and 8 to 1 male to female ratios depending on the mutation) while average age at onset is significantly higher. Multiple case series of various<unk>  pedigrees have described female carriers converting after menopause or cessation of hormone replacement therapies. Together, these form a shifting paradigm towards considering reduced estrogen states, such as menopause, as potential triggers of visual loss similar to smoking or excessive alcohol consumption. Hormone replacement therapy (HRT) is emerging as an effective therapeutic target for female mutation carriers. In one recent case study where the affected female converted following cessation of HRT, idebenone, and HRT were given together. Visual acuity improved much faster than is typically expected. The patient's vision returned to 20/40 and 20/60 from 20/60 and 20/200 in the right and left eyes respectively after only one month and was back normal by 8 months compared to the months to years timeframe seen in most cases. While the balance between risks and benefits of HRT remains controversial, the decision to start HRT requires an individualized approach based on the patient's context. While not applicable for all post-menopausal women, prophylactic (and therapeutic) HRT should be considered in all female carriers of a known<unk>  mutation given the substantial risk of vision loss associated with menopause.
Leber's hereditary optic neuropathy
Kjer's optic neuropathy
Alexander disease
Graves' ophthalmopathy
Bosch-Boonstra-Schaaf optic atrophy syndrome
Sorsby's fundus dystrophy
Neuromyelitis optica spectrum disorder
Akureyri disease