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.

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.

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.

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.

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.

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.

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.

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.

Dominant optic atrophy is also known as autosomal dominant optic atrophy, Kjer type; Kjer optic atrophy; or, Kjer's autosomal dominant optic atrophy.

Optic disc drusen are found clinically in about 1% of the population but this increases to 3.4% in individuals with a family history of ODD. About two thirds to three quarters of clinical cases are bilateral. A necropsy study of 737 cases showed a 2.4% incidence with 2 out of 15 (13%) bilateral, perhaps indicating the insidious nature of many cases. An autosomal dominant inheritance pattern with incomplete penetrance and associated inherited dysplasia of the optic disc and its blood supply is suspected. Males and females are affected at equal rates. Caucasians are the most susceptible ethnic group. Certain conditions have been associated with disc drusen such as retinitis pigmentosa, angioid streaks, Usher syndrome, Noonan syndrome and Alagille syndrome. Optic disc drusen are not related to Bruch membrane drusen of the retina which have been associated with age-related macular degeneration.

It is estimated that the incidence of AION is about 8,000/year in the U.S.

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.

In industrialized nations, toxic and nutritional optic neuropathy is relatively uncommon and is primarily associated with specific medications, occupational exposures, or tobacco and alcohol abuse. However, in developing nations, nutritional optic neuropathy is much more common, especially in regions afflicted by famine. Both genders and all races are equally affected, and all ages are susceptible.

Ischemic optic neuropathy (ION) is the loss of structure and function of a portion of the optic nerve due to obstruction of blood flow to the nerve (i.e. ischemia). Ischemic forms of optic neuropathy are typically classified as either anterior ischemic optic neuropathy or posterior ischemic optic neuropathy according to the part of the optic nerve that is affected. People affected will often complain of a loss of visual acuity and a visual field, the latter of which is usually in the superior or inferior field.

When ION occurs in patients below the age of 50 years old, other causes should be considered. Such as juvenile diabetes mellitus, antiphospholipid antibody-associated clotting disorders, collagen-vascular disease, and migraines. Rarely, complications of intraocular surgery or acute blood loss may cause an ischemic event in the optic nerve.

Anterior ION presents with sudden, painless visual loss developing over hours to days. Examination findings usually include decreased visual acuity, a visual field defect, color vision loss, a relative afferent pupillary defect, and a swollen optic nerve head. Posterior ION occurs arteritic, nonarteritic, and surgical settings. It is characterized by acute vision loss without initial disc edema, but with subsequent optic disc atrophy.

Although there is no recognized treatment that can reverse the visual loss. Upon recent reports, optic nerve health decompression may be beneficial for a select group of patients with a gradual decline in vision due to ION.

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.

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.

Currently, there is no treatment for the disease. However, ophthalmologists recommend wearing sunglasses and hats outdoors and blue-light blocking glasses when exposed to artificial light sources, such as screens and lights. Tobacco smoke and second-hand smoke should be avoided. Animal studies also show that high doses of vitamin A can be detrimental by building up more lipofuscin toxin. Dietary non-supplemental vitamin A intake may not further the disease progression.

Clinical trials are being conducted with promising early results. The trials may one day lead to treatments that might halt, and possibly even reverse, the effects of Stargardt disease using stem cell therapy, gene therapy, or pharmacotherapy.

The Argus retinal prosthesis, an electronic retinal implant, was successfully fitted to a 67-year-old woman in Italy at the Careggi Hospital in 2016. The patient had a very advanced stage of Stargardt’s disease, and a total absence of peripheral and central visual fields.

Progressive retinal atrophy (PRA) is a group of genetic diseases seen in certain breeds of dogs and, more rarely, cats. Similar to retinitis pigmentosa in humans, it is characterized by the bilateral degeneration of the retina, causing progressive vision loss culminating in blindness. The condition in nearly all breeds is inherited as an autosomal recessive trait, with the exception of the Siberian Husky (inherited as an X chromosome linked trait) and the Bullmastiff (inherited as an autosomal dominant trait). There is no treatment.

Though there is no treatment for Cone dystrophy, certain supplements may help in delaying the progression of the disease.

The beta-carotenoids, lutein and zeaxanthin, have been evidenced to reduce the risk of developing age related macular degeneration (AMD), and may therefore provide similar benefits to Cone dystrophy sufferers.

Consuming omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) has been correlated with a reduced progression of early AMD, and in conjunction with low glycemic index foods, with reduced progression of advanced AMD, and may therefore delay the progression of cone dystrophy.

ONSM does not improve without treatment. In many cases, there is gradual progression until vision is lost in the affected eye. However, this takes at least several months to occur, and a minority of patients remain stable for a number of years.

Commonly affected breeds:

- Akita - Symptoms at one to three years old and blindness at three to five years old. Selective breeding has greatly reduced the incidence of this disease in this breed.

- Miniature longhaired Dachshund - Symptoms at six months old.

- Papillon - Slowly progressive with blindness at seven to eight years old.

- Tibetan Spaniel - Symptoms at three to five years old.

- Tibetan Terrier - PRA3/RCD4 disease of middle age dogs. http://www.ttca-online.org/html/Petersen-Jones_PRA_article.pdf

- Samoyed - Symptoms by three to five years old.

Treatment modalities currently under clinical investigation include cell therapy, gene therapy and oral therapies.

Regarding cell therapy, Advanced Cell Technology, now called Ocata Therapeutics, has completed Phase I/II multicenter clinical trial using retinal cells derived from human embryonic stem cells (hESCs) to treat patients with Stargardt. After treating and collecting data on 18 patients, Advanced Cell was given approval to test its stem cell therapy on patients with 20/100 vision. In October 2014, the results of the Phase I/II clinical trial were published in "the Lancet".

Research at the preclinical (animal) stage include a new compound that can remove lipofuscin from retinal pigment epithelial cells.

Optic pits occur equally between men and women. They are seen in roughly 1 in 10,000 eyes, and approximately 85% of optic pits are found to be unilateral (i.e. in only one eye of any affected individual). About 70% are found on the temporal side (or lateral one-half) of the optic disc. Another 20% are found centrally, while the remaining pits are located either superiorly (in the upper one-half), inferiorly (in the lower one-half), or nasally (in the medial one-half towards the nose).

Most ophthalmologists will not advocate any treatment unless visual loss is present and ongoing. Reports of patients with ONSM having no change in their vision for multiple years are not uncommon. If loss of vision occurs, radiation therapy will improve vision in about ⅓ of cases, and preserve vision in about ⅓ of cases. Surgery has traditionally been associated with rapid deteroriation of vision. However, newer surgical techniques may prove better for the treatment of ONSM.

Historically, papilledema was a potential contraindication to lumbar puncture, as it indicates a risk for tentorial herniation and subsequent death via cerebral herniation, however newer imaging techniques have been more useful at determining when and when not to conduct a lumbar puncture. Imaging by CT or MRI is usually performed to elicit whether there is a structural cause i.e., tumor. An MRA and MRV may also be ordered to rule out the possibility of stenosis or thrombosis of the arterial or venous systems.

The treatment depends largely on the underlying cause. However, the root cause of papilledema is the increased intracranial pressure (ICP). This is a dangerous sign, indicative of a brain tumor, CNS inflammation or idiopathic intracranial hypertension (IIH) that may become manifest in the near future.

Thus, a biopsy is routinely performed prior to the treatment in the initial stages of papilledema to detect whether a brain tumor is present. If detected, laser treatment, radiation and surgeries can be used to treat the tumor.

To decrease ICP, medications can be administered by increasing the absorption of Cerebrospinal fluid (CSF), or decreasing its production. Such medicines include diuretics like acetazolamide and furosemide. These diuretics, along with surgical interventions, can also treat IIH. In IIH, weight loss (even a loss of 10-15%) can lead to normalization of ICP.

Meanwhile, steroids can reduce inflammation (if this is a contributing factor to increased ICP), and may help to prevent vision loss. However, steroids have also been known to cause increased ICP, especially with a change in dosage. However, if a severe inflammatory condition exists, such as multiple sclerosis, steroids with anti-inflammatory effects such as Methylprednisolone and prednisone can help.

Other treatments include repeated lumbar punctures to remove excess spinal fluid in the cranium. The removal of potentially causative medicines including tetracyclines and vitamin A analogues may help decrease ICP; however, this is only necessary if the medication is truly felt to contribute to the ICP increase.