Treatment is dependent upon diagnosis and the stage at which the diagnosis is secured. For toxic and nutritional optic neuropathies, the most important course is to remove the offending agent if possible and to replace the missing nutritional elements, orally, intramuscularly, or intravenously. If treatment is delayed, the injury may be irreversible. The course of treatment varies with the congenital forms of these neuropathies. There are some drug treatments that have shown modest success, such as Idebenone used to treat LOHN. Often treatment is relegated to lifestyle alterations and accommodations and supportive measures.

In most MS-associated optic neuritis, visual function spontaneously improves over 2–3 months, and there is evidence that corticosteroid treatment does not affect the long term outcome. However, for optic neuritis that is not MS-associated (or atypical optic neuritis) the evidence is less clear and therefore the threshold for treatment with intravenous corticosteroids is lower. Intravenous corticosteroids also reduce the risk of developing MS in the following two years in patients with MRI lesions; but this effect disappears by the third year of follow up.

Paradoxically, oral administration of corticosteroids in this situation may lead to more recurrent attacks than in non-treated patients (though oral steroids are generally prescribed after the intravenous course, to wean the patient off the medication). This effect of corticosteroids seems to be limited to optic neuritis and has not been observed in other diseases treated with corticosteroids.

A Cochrane Systematic Review studied the effect of corticosteroids for treating people with acute optic neuritis. Specific corticosteroids studied included intravenous and oral methylprednisone, and oral prednisone. The authors conclude that current evidence does not show a benefit of either intravenous or oral corticosteroids for rate of recovery of vision (in terms of visual acuity, contrast sensitivity, or visual fields)..

Currently there is no effective therapy for dominant optic atrophy, and consequently, these patients are simply monitored for changes in vision by their eye-care professional. Children of patients should be screened regularly for visual changes related to dominant optic atrophy. Research is underway to further characterize the disease so that therapies may be developed.

Treatment of toxic and nutritional optic neuropathy is dictated by the cause of the disorder.

- Toxic optic neuropathy is treated by identification and removal of the offending agent. Depending upon the individual affected, the nature of the agent, total exposure prior to removal, and degree of vision loss at the time of diagnosis, the prognosis is variable.

- Nutritional optic neuropathy is treated with improved nutrition. A well-balanced diet with plenty of protein and green leafy vegetables, vitamin supplementation (thiamine, vitamin B, folic acid, multivitamins), and reduction of smoking and/or drinking are the mainstay of treatment. Again, prognosis is variable and dependent upon the affected individual, treatment compliance, and degree of vision loss at diagnosis.

In both toxic and nutritional neuropathy, vision generally recovers to normal over several days to weeks, though it may take months for full restoration and there is always the risk of permanent vision loss. Visual acuity usually recovers before color vision.

Once NAION happens, it was thought that there was no accepted treatment to reverse the damage. However, a recent uncontrolled retrospective large study has shown that if patients are treated with large doses of corticosteroid therapy during the early stages of NAION, in eyes with initial visual acuity of 20/70 or worse, seen within 2 weeks of onset, there was visual acuity improvement in 70% in the treated group compared to 41% in the untreated group (odds ratio of improvement: 3.39; 95% CI:1.62, 7.11; p ¼ 0.001). That study and a natural history study on NAION (Ophthalmology 2008;115: 298–305.) showed that visual acuity can improve up to 6 months and not after that. To minimize the risk of further visual loss in the fellow eye or the same eye, it is essential to reduce the risk factors. Common sense dictates trying to control the cardiovascular risk factors for many reasons, including protection from this happening to the second eye. Sudden vision loss should lead to an ophthalmological consultation. If NAION is suspected, then ideally a neuro-ophthalmologist's consultation should be obtained.

A recent Cochrane Review sought to determine the extent of safety and efficacy of optic nerve decompression surgery for NAION, compared to other treatments, or no treatment. The one study included in the review found no improvements in visual acuity among patients who underwent surgery for NAION, and adverse events (pain, double vision) experienced by participants who underwent surgery.

There is much research currently underway looking at ways to protect the nerve (neuroprotection) or even regenerate new fibers within the optic nerve. So far there is no evidence in human studies that the so-called neuroprotectors have any beneficial effect in NAION.

However, there is a new current clinical trial for the treatment of NAION in the United States with plans to include sites in India, Israel, Germany and Australia (see NORDICclinicaltrials.com and https://clinicaltrials.gov/). This trial will test the use of a synthetic siRNA that blocks caspase 2, an important enzyme in the apoptosis cycle.

In addition to such research, patents have been applied for by Pfizer, The University of Southern California, Otsuka Pharmaceutical and other individual inventors for innovations related to the treatment of anterior ischemic optic neuropathy.

Idebenone is a short-chain benzoquinone that interacts with the mitochondrial electron transport chain to enhance cellular respiration. When used in individuals with LHON, it is believed to allow electrons to bypass the dysfunctional complex I. Successful treatment using idebenone was initially reported in a small number of patients.

Two large-scale studies have demonstrated the benefits of idebenone. The Rescue of Hereditary Optic Disease Outpatient Study (RHODOS) evaluated the effects of idebenone in 85 patients with LHON 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 this difference was not statistically significant. Importantly, however, patients taking idebenone were protected from further vision loss, whereas the placebo group had a steady decline in visual acuity. Further, individuals taking idebenone demonstrated preservation of color vision and persistence of the effects of idebenone 30 months after discontinuing therapy. A retrospective analysis of 103 LHON 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, further, that these improvements with idebenone persisted for years.

Idebenone, combined with avoidance of smoke and limitation of alcohol intake, is the preferred standard treatment protocol for patients affected by LHON. Idebenone doses are prescribed to be taken spaced out throughout the day, rather than all at one time. 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.

If a diagnosis of GCA is suspected, treatment with steroids should begin immediately. A sample (biopsy) of the temporal artery should be obtained to confirm the diagnosis and guide future management, but should not delay initiation of treatment. Treatment does not recover lost vision, but prevents further progression and second eye involvement. High dose corticosteroids may be tapered down to low doses over approximately one year.

A range of medications that act on the central nervous system has been found to be useful in managing neuropathic pain. Commonly used treatments include tricyclic antidepressants (such as nortriptyline or amitriptyline), the serotonin-norepinephrine reuptake inhibitor (SNRI) medication duloxetine, and antiepileptic therapies such as gabapentin, pregabalin, or sodium valproate. Few studies have examined whether nonsteroidal anti-inflammatory drugs are effective in treating peripheral neuropathy.

Symptomatic relief for the pain of peripheral neuropathy may be obtained by application of topical capsaicin. Capsaicin is the factor that causes heat in chili peppers. The evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option. Local anesthesia often is used to counteract the initial discomfort of the capsaicin. Some current research in animal models has shown that depleting neurotrophin-3 may oppose the demyelination present in some peripheral neuropathies by increasing myelin formation.

High-quality evidence supports the use of cannabis for neuropathic pain.

Transcutaneous electrical nerve stimulation therapy may be effective and safe in the treatment of diabetic peripheral neuropathy. A recent review of three trials involving 78 patients found some improvement in pain scores after 4 and 6, but not 12 weeks of treatment and an overall improvement in neuropathic symptoms at 12 weeks. Another review of four trials found significant improvement in pain and overall symptoms, with 38% of patients in one trial becoming asymptomatic. The treatment remains effective even after prolonged use, but symptoms return to baseline within a month of cessation of treatment.

Rapid blood transfusions, to correct anemia and raise blood pressure, may improve PION outcomes. In one report of a related disease, hypotension-induced AION, 3 out of 3 patients who received rapid transfusions reported partial recovery of vision. While rapid transfusions offer some hope, the prognosis for perioperative PION remains poor. Prevention remains the best way to reduce PION.

One retrospective report proposes that incidence of PION could be reduced in high-risk cases by altering surgical management. For example, for patients undergoing spine surgery, measures could be taken to minimize intraoperative hypotension, to accelerate the process of blood replacement, and to aggressively treat facial swelling.

AON is a rare disease and the natural history of the disease process is not well defined. Unlike typical optic neuritis, there is no association with multiple sclerosis, but the visual prognosis for AON is worse than typical optic neuritis. Thus AON patients have different treatment, and often receive chronic immunosuppression. No formal recommendation can be made regarding the best therapeutic approach. However, the available evidence to date supports treatment with corticosteroids and other immunosuppressive agents.

Early diagnosis and prompt treatment with systemic corticosteroids may restore some visual function but the patient may remain steroid dependent; vision often worsens when corticosteroids are tapered. As such, long-term steroid-sparing immunosuppressive agents may be required to limit the side-effects of steroids and minimize the risk of worsening vision.

Patients with optic disc drusen should be monitored periodically for ophthalmoscopy, Snellen acuity, contrast sensitivity, color vision, intraocular pressure and threshold visual fields. For those with visual field defects optical coherence tomography has been recommended for follow up of nerve fiber layer thickness. Associated conditions such as angioid streaks and retinitis pigmentosa should be screened for. Both the severity of optic disc drusen and the degree of intraocular pressure elevation have been associated with visual field loss. There is no widely accepted treatment for ODD, although some clinicians will prescribe eye drops designed to decrease the intra-ocular pressure and theoretically relieve mechanical stress on fibers of the optic disc. Rarely choroidal neovascular membranes may develop adjacent to the optic disc threatening bleeding and retinal scarring. Laser treatment or photodynamic therapy or other evolving therapies may prevent this complication.

In the treatment of polyneuropathies one must ascertain and manage the cause, among management activities are: weight decrease, use of a walking aid, and occupational therapist assistance. Additionally BP control in those with diabetes is helpful, while intravenous immunoglobulin is used for multifocal motor neuropathy.

According to Lopate, et al., methylprednisolone is a viable treatment for chronic inflammatory demyelinative polyneuropathy (which can also be treated with intravenous immunoglobulin) The author(s) also indicate that prednisone has greater adverse effects in such treatment, as opposed to intermittent (high-doses) of the aforementioned medication.

According to Wu, et al., in critical illness polyneuropathy supportive and preventive therapy are important for the affected individual, as well as, avoiding (or limiting) corticosteroids.

AAION requires urgent and critical intervention with a very long course of corticosteroids to prevent further damage. While this treatment is in itself problematic, non-treatment leads to bilateral blindness and strokes.

There is much research currently underway looking at ways to protect the nerve (neuroprotection) or even regenerate new fibers within the optic nerve.

While radiation or chemotherapy may be helpful, treatment is often not necessary. Optical gliomas often cannot be surgically resected. If no visual symptoms wait 6 months and then in 6 months only treat if there are symptoms (visual loss, eye pain), otherwise do not treat.

Those diseases understood as congenital in origin could either be specific to the ocular organ system (LHON, DOA) or syndromic (MELAS, Multiple Sclerosis). It is estimated that these inherited optic neuropathies in the aggregate affect 1 in 10,000

Of the acquired category, disease falls into further etiological distinction as arising from toxic (drugs or chemicals) or nutritional/metabolic (vitamin deficiency/diabetes) insult. It is worth mentioning that under-nutrition and toxic insult can occur simultaneously, so a third category may be understood as having a combined or mixed etiology. We will refer to this as Toxic/Nutritional Optic Neuropathy, whereby nutritional deficiencies and toxic/metabolic insults are the simultaneous culprits of visual loss associated with damage and disruption of the RGC and optic nerve mitochondria.

The most recognized cause of a toxic optic neuropathy is methanol intoxication. This can be a life-threatening event that normally accidentally occurs when the victim mistook, or substituted, methanol for ethyl alcohol. Blindness can occur with drinking as little as an ounce of methanol, but this can be counteracted by concurrent drinking of ethyl alcohol. The patient initially has nausea and vomiting, followed by respiratory distress, headache, and visual loss 18–48 hours after consumption. Without treatment, patients can go blind, and their pupils will dilate and stop reacting to light.

- Ethylene glycol, a component of automobile antifreeze, is a poison that is toxic to the whole body including the optic nerve. Consumption can be fatal, or recovery can occur with permanent neurologic and ophthalmologic deficits. While visual loss is not very common, increased intracranial pressure can cause bilateral optic disc swelling from cerebral edema. A clue to the cause of intoxication is the presence of oxalate crystals in the urine. Like methanol intoxication, treatment is ethanol consumption.

- Ethambutol, a drug commonly used to treat tuberculosis, is notorious for causing toxic optic neuropathy. Patients with vision loss from ethambutol toxicity lose vision in both eyes equally. This initially presents with problems with colors (dyschromatopsia) and can leave central visual deficits. If vision loss occurs while using ethambutol, it would be best to discontinue this medication under a doctor’s supervision. Vision can improve slowly after discontinuing ethambutol but rarely returns to baseline.

- Amiodarone is an antiarrhythmic medication commonly used for abnormal heart rhythms (atrial or ventricular tachyarrythmias). Most patients on this medication get corneal epithelial deposits, but this medication has also been controversially associated with NAION. Patients on amiodarone with new visual symptoms should be evaluated by an ophthalmologist.

- Tobacco exposure, most commonly through pipe and cigar smoking, can cause an optic neuropathy. Middle-aged or elderly men are often affected and present with painless, slowly progressive, color distortion and visual loss in both eyes. The mechanism is unclear, but this has been reported to be more common in individuals who are already suffering from malnutrition.

Without a known family history of LHON the diagnosis usually requires a neuro-ophthalmological evaluation and blood testing for mitochondrial DNA assessment. It is important to exclude other possible causes of vision loss and important associated syndromes such as heart electrical conduction system abnormalities. The prognosis for those affected left untreated is almost always that of continued significant visual loss in both eyes. Regular corrected visual acuity and perimetry checks are advised for follow up of affected individuals. There is beneficial treatment available for some cases of this disease especially for early onset disease. Also, experimental treatment protocols are in progress. Genetic counselling should be offered. Health and lifestyle choices should be reassessed particularly in light of toxic and nutritional theories of gene expression. Vision aides assistance and work rehabilitation should be used to assist in maintaining employment.

For those who are carriers of a LHON 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) may also be used.

Avoiding optic nerve toxins is generally advised, especially tobacco and alcohol. Certain prescription drugs are known to be a potential risk, 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 LHON. In fact, toxic and nutritional optic neuropathies may have overlaps with LHON in symptoms, mitochondrial mechanisms of disease and management. Of note, when a patient carrying or suffering from LHON 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 in particular.

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.

There are various treatment approaches which have had early trials or are proposed, none yet 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.

Optic pits themselves do not need to be treated. However, patients should follow up with their eye care professional annually or even sooner if the patient notices any visual loss whatsoever. Treatment of PVD or serous retinal detachment will be necessary if either develops in a patient with an optic pit.

One form of LCA, patients with LCA2 bearing a mutation in the RPE65 gene, has been successfully treated in clinical trials using gene therapy. The results of three early clinical trials were published in 2008 demonstrating the safety and efficacy of using adeno-associated virus to deliver gene therapy to restore vision in LCA patients. In all three clinical trials, patients recovered functional vision without apparent side-effects. These studies, which used adeno-associated virus, have spawned a number of new studies investigating gene therapy for human retinal disease.

The results of a phase 1 trial conducted by the University of Pennsylvania and Children’s Hospital of Philadelphia and published in 2009 showed sustained improvement in 12 subjects (ages 8 to 44) with RPE65-associated LCA after treatment with AAV2-hRPE65v2, a gene replacement therapy. Early intervention was associated with better results. In that study, patients were excluded based on the presence of particular antibodies to the vector AAV2 and treatment was only administered to one eye as a precaution. A 2010 study testing the effect of administration of AAV2-hRPE65v2 in both eyes in animals with antibodies present suggested that immune responses may not complicate use of the treatment in both eyes.

Eye Surgeon Dr. Al Maguire and gene therapy expert Dr. Jean Bennett developed the technique used by the Children's Hospital.

Dr. Sue Semple-Rowland at the University of Florida has recently restored sight in an avian model using gene therapy.

Gene-based therapies for patients with HSAN I are not available to date, hence supportive care is the only treatment available for the patients. Ulcero-mutilating complications are the most serious, prominent, and leading diagnostic features in HSAN I. Since the complications mimic foot ulcers caused by diabetic neuropathy, the treatment for foot ulcers and infections can follow the guidelines given for diabetic foot care which starts with early and accurate counseling of patients about risk factors for developing foot ulcerations. Orthopedic care and the use of well fitting shoes without pressure points should also be included. Recently, the treatment of the foot complications has reached an efficient level allowing treatment on an outpatient basis. Early treatment of the foot complications often avoids hospitalization and, in particular, amputations. In sum, the principles of the treatment are removal of pressure to the ulcers, eradication of infection, and specific protective footwear afterwards.

Without treatment, NTG leads to progressive visual field loss and in the last consequence to blindness. The mainstay of conventional glaucoma therapy, reducing IOP by pressure-lowering eye drops or by surgery, is applied in cases of NTG as well. The rationale: the lower the IOP, the less the risk of ganglion cell loss and thus in the long run of visual function. The appearance of disc hemorrhages is always a warning sign that therapeutic approaches are not successful - the small bleedings, usually described as flame-shaped, almost always indicate a progression of the disease.

Besides this classical glaucoma therapy, the vascular component that exists in the majority of NTG patients has to be managed as well. Dips in blood pressure or a generally low blood pressure have to be prevented - which is a rather uncommon approach in modern medicine where high blood pressure is always seen as an immense clinical challenge, affecting large segments of the population. In patients with systemic hypertension under therapy, the blood pressure should not be lowered too rigorously. NTG might be the only severe (= sight-threatening) disease caused in numerous cases by a too low blood pressure. Both magnesium and low dose calcium channel blockers have been employed in the treatment of some NTG patients. There are therapeutic approaches to underlying conditions like Flammer syndrome. A change in nutrition like the intake of sodium-rich foods has been tried as has the oral administration of low-dosed steroids. Lifestyle interventions are recommended in patients with Flammer syndrome like avoidance of fasting and certain stimuli like a cold environment and stress.

Treatment typically involves improving the patient's quality of life. This is accomplished through the management of symptoms or slowing the rate of demyelination. Treatment can include medication, lifestyle changes (i.e. quit smoking, adjusting daily schedules to include rest periods and dietary changes), counselling, relaxation, physical exercise, patient education and, in some cases, deep brain thalamic stimulation (in the case of tremors). The progressive phase of MS appears driven by the innate immune system, which will directly contribute to the neurodegenerative changes that occur in progressive MS. Until now, there are no therapies that specifically target innate immune cells in MS. As the role of innate immunity in MS becomes better defined, it may be possible to better treat MS by targeting the innate immune system.

Treatments are patient-specific and depend on the symptoms that present with the disorder, as well as the progression of the condition.

Mitochondria play a central role in maintaining the life cycle of retinal ganglion cells because of their high energy dependence. Mitochondria are made within the central somata of the retinal ganglion cell, transported down axons, and distributed where they are needed. Genetic mutations in mitochondrial DNA, vitamin depletion, alcohol and tobacco abuse, and use of certain drugs can cause derangements in efficient transport of mitochondria, which can cause a primary or secondary optic neuropathy.

If patients with HSAN I receive appropriate treatment and counseling, the prognosis is good. Early treatment of foot infections may avoid serious complications. Nevertheless, the complications are manageable, thus allowing an acceptable quality of life. The disease progresses slowly and does not influence the life expectancy if signs and symptoms are properly treated.