Perioperative PION patients have a higher prevalence of cardiovascular risk factors than in the general population. Documented cardiovascular risks in people affected by perioperative PION include high blood pressure, diabetes mellitus, high levels of cholesterol in the blood, tobacco use, abnormal heart rhythms, stroke, and obesity. Men are also noted to be at higher risk, which is in accordance with the trend, as men are at higher risk of cardiovascular disease. These cardiovascular risks all interfere with adequate blood flow, and also may suggest a contributory role of defective vascular autoregulation.

As illustrated by the risk factors above, perioperative hypoxia is a multifactorial problem. Amidst these risk factors it may be difficult to pinpoint the optic nerve’s threshold for cell death, and the exact contribution of each factor.

Low blood pressure and anemia are cited as perioperative complications in nearly all reports of PION, which suggests a causal relationship. However, while low blood pressure and anemia are relatively common in the perioperative setting, PION is exceedingly rare. Spine and cardiac bypass surgeries have the highest estimated incidences of PION, 0.028% and 0.018% respectively, and this is still extremely low. This evidence suggests that optic nerve injury in PION patients is caused by more than just anemia and low blood pressure.

Evidence suggests that the multifactorial origin of perioperative PION involves the risks discussed above and perhaps other unknown factors. Current review articles of PION propose that vascular autoregulatory dysfunction and anatomic variation are under-investigated subjects that may contribute to patient-specific susceptibility.

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

The mechanism of injury for NAION used to be quite controversial. However, experts in the field have come to a consensus that most cases involve two main risk factors. The first is a predisposition in the form of a type of optic disc shape. The optic disc is where the axons from the retinal ganglion cells collect into the optic nerve. The optic nerve is the bundle of axons that carry the visual signals from the eye to the brain. This optic nerve must penetrate through the wall of the eye, and the hole to accommodate this is usually 20-30% larger than the nerve diameter. In some patients the optic nerve is nearly as large as the opening in the back of the eye, and the optic disc appears "crowded" when seen by ophthalmoscopy. A crowded disc is also referred to as a "disc at risk". While a risk factor, the vast majority of individuals with crowded discs do not experience NAION.

The second major risk factor involves more general cardiovascular risk factors. The most common are diabetes, hypertension and high cholesterol levels. While these factors predispose a patient to develop NAION, the most common precipitating factor is marked fall of blood pressure during sleep (nocturnal arterial hypotension)- that is why at least 75% of the patients first discover visual loss first on waking from sleep. These vascular risk factors lead to ischemia (poor blood supply) to a portion of the optic disc. The disc then swells, and in a crowded optic disc, this leads to compression and more ischemia.

Since both eyes tend to have a similar shape, the optometrist or ophthalmologist will look at the good eye to assess the anatomical predisposition. The unaffected eye has a 14.7% risk of NAION within five years.

A number of uncontrolled single case or small number of patient reports have associated NAION with use of oral erectile dysfunction drugs.

In ischemic optic neuropathies, there is insufficient blood flow (ischemia) to the optic nerve. The anterior optic nerve is supplied by the short posterior ciliary artery and choroidal circulation, while the retrobulbar optic nerve is supplied intraorbitally by a pial plexus, which arises from the ophthalmic artery, internal carotid artery, anterior cerebral artery, and anterior communicating arteries. Ischemic optic neuropathies are classified based on the location of the damage and the cause of reduced blood flow, if known.

- Anterior ischemic optic neuropathy (AION) includes diseases that affect the optic nerve head and cause swelling of the optic disc. These diseases often cause sudden rapid visual loss in one eye. Inflammatory diseases of the blood vessels, like giant cell arteritis, polyarteritis nodosa, Churg-Strauss syndrome, granulomatosis with polyangiitis, and rheumatoid arthritis can cause arteritic AIONs (AAION). The vast majority of AIONs are nonarteritic AIONs (NAION). The most common acute optic neuropathy in patients over 50 years of age, NAION has an annual incidence of 2.3-10.2/100,000. NAION presents as a painless loss of vision, often when awakening, that occurs over hours to days. Most patients lose the lower half of their visual field (an inferior altitudinal loss), though superior altitudinal loss is also common. The pathophysiology of NAION is unknown, but it is related to poor circulation in the optic nerve head. NAION is often associated with diabetes mellitus, elevated intraocular pressure (acute glaucoma, eye surgery), high cholesterol, hypercoagulable states, a drop in blood pressure (bleeding, cardiac arrest, peri-operative esp. cardiac and spine procedures), and sleep apnea. Rarely, amiodarone, interferon-alpha, and erectile dysfunction drugs have been associated with this disease.

- Posterior ischemic optic neuropathy is a syndrome of sudden visual loss with optic neuropathy without initial disc swelling with subsequent development of optic atrophy. This can occur in patients who are predisposed to AAION and NAION as described above as well as those who had cardiac and spine surgery or serious episodes of hypotension.

- Radiation optic neuropathy (RON) is also thought to be due to ischemia of the optic nerve that occurs 3 months to 8 or more years after radiation therapy to the brain and orbit. It occurs most often around 1.5 years after treatment and results in irreversible and severe vision loss, which may also be associated with damage to the retina (radiation retinopathy). This is thought to be due to damage to dividing glial and vascular endothelial cells. RON can present with transient visual loss followed by acute painless visual loss in one or both eyes several weeks later. The risk of RON is significantly increased with radiation doses over 50 Gy.

- There is also some evidence that interferon treatment (pegylated interferon with ribavirin) for hepatitis C virus can cause optic neuropathy.

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.

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.

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.

Prompt diagnosis is critical, since the sudden blindness in the one eye is often followed, within days, by similar sudden blindness in the second eye. Treatment may prevent further damage (see below). Any patient diagnosed with non-arteritic AION over the age of 50 must be asked about the constitutional symptoms mentioned above. Furthermore, AION patients over the age of 75 should often be blood tested regardless.

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.

The two most common causes of retinopathy include diabetic retinopathy and retinopathy of prematurity. Diabetic retinopathy affects about 5 million people and retinopathy of prematurity affect about 50,000 premature infants each year worldwide. Hypertensive retinopathy is the next most common cause affecting anywhere from 3 to 14% of all non-diabetic adults.

Genetic mutations are rare causes of certain retinopathies and are usually X-linked including "NDP" family of genes causing Norrie Disease, FEVR, and Coats disease among others. There is emerging evidence that there may be a genetic predisposition in patients who develop retinopathy of prematurity and diabetic retinopathy. Trauma, especially to the head, and several diseases may cause Purtscher's retinopathy.

Optic disc drusen (ODD) or optic nerve head drusen (ONHD) are globules of mucoproteins and mucopolysaccharides that progressively calcify in the optic disc. They are thought to be the remnants of the axonal transport system of degenerated retinal ganglion cells.

ODD have also been referred to as congenitally elevated or anomalous discs, pseudopapilledema, pseudoneuritis, buried disc drusen, and disc hyaline bodies. They may be associated with vision loss of varying degree occasionally resulting in blindness.

The central retinal vein is the venous equivalent of the central retinal artery and, like that blood vessel, it can suffer from occlusion (central retinal vein occlusion, also CRVO), similar to that seen in ocular ischemic syndrome. Since the central retinal artery and vein are the sole source of blood supply and drainage for the retina, such occlusion can lead to severe damage to the retina and blindness, due to ischemia (restriction in blood supply) and edema (swelling).

It can also cause glaucoma.

Nonischemic CRVO is the milder form of the disease. It may progress to the more severe ischemic type.

Treatment consists of Anti-VEGF drugs like Lucentis or intravitreal steroid implant (Ozurdex) and Pan-Retinal Laser Photocoagulation usually. Underlying conditions also require treatment. Non-Ischemic CRVO has better visual prognosis than Ischemic CRVO.

A systematic review studied the effectiveness of the anti-VEGF drugs ranibizumab and pagatanib sodium for patients suffering from non-ischemic CRVO. Though there was a limited sample size, participants in both treatment groups showed improved visual acuity over 6 month periods, with no safety concerns.

The pathogenesis of this disease is unclear. Arteriosclerosis obliterans has been postulated as the cause, along with errors of the clotting and fibrinolytic pathways such as antiphospholipid syndrome.

A large number of conditions may cause symptoms and signs similar to diabetic myonecrosis and include: deep vein thrombosis, thrombophlebitis, cellulitis, fasciitis, abscess, haematoma, myositis, pseudothrombophlebitis (ruptured synovial cyst), pyomyositis, parasitic myositis, osteomyelitis, calcific myonecrosis, myositis ossificans, diabetic myotrophy, muscle strain or rupture, bursitis, vasculitis, arterial occlusion, haemangioma, lymphoedema, sarcoidosis, tuberculosis, cat-scratch disease, amyloidosis, as well as tumours of lipoma, chondroma, fibroma, leiomyoma and sarcoma.

Because the cause of Behçet's disease is unknown, the cause responsible for neuro-Behçet's disease is unknown as well. Inflammation starts mainly due to immune system failure. However, no one knows what factors trigger the initiation of auto-immune disease like inflammation. Because the cause is unknown, it is impossible to eliminate or prevent the source that causes the disease. Therefore, treatments are focused on how to suppress the symptoms that hinders daily life activities.

In one study of 387 Behçet's disease (BD) patients that has been done for 20 years, 13% of men with BD developed to NBD and 5.6% of women developed to NBD.

Combining all statistical reports, approximately 9.4% (43 of 459) BD patients advanced to NBD. In addition, men were 2.8 times more likely to experience NBD than women. This fact indicates possible gender-based pathology.

In speaking about age of NBD patients, the general range was between 20 and 40. NBD patients with age less than 10 or more than 50 were very uncommon.

Giant-cell arteritis (GCA), also called temporal arteritis, is an inflammatory disease of blood vessels. Symptoms may include headache, pain over the temples, flu-like symptoms, double vision, and difficulty opening the mouth. Complication can include blockage of the artery to the eye with resulting blindness, aortic dissection, and aortic aneurysm. GCA is frequently associated with polymyalgia rheumatica.

The cause is unknown. The underlying mechanism involves inflammation of the small blood vessels that occur within the walls of larger arteries. This mainly affects arteries around the head and neck, though some in the chest may also be affected. Diagnosis is suspected based on symptoms, blood tests, and medical imaging, and confirmed by biopsy of the temporal artery. However, in about 10% of people the temporal artery is normal.

Treatment is typically with high doses of steroids, such as prednisone. Once symptoms have resolved the dose is then decreased by about 15% per month. Once a low dose is reached, the taper is slowed further over the subsequent year. Other medications that may be recommended include bisphosphonates to prevent bone loss and a proton pump inhibitor to prevent stomach problems.

It affects about 1 in 15,000 people over the age of 50 a year. The condition typically only occurs in those over the age of 50 being most common among those in their 70s. Females are more often affected than males. Those of northern European descent are more commonly affected. Life expectancy is typically normal. The first description of the condition occurred in 1890.

The varicella-zoster virus antigen was found in 74% of temporal artery biopsies that were GCA-positive, suggesting that the VZV infection may trigger the inflammatory cascade.

The disorder may coexist (in a half of cases) with polymyalgia rheumatica (PMR), which is characterized by sudden onset of pain and stiffness in muscles (pelvis, shoulder) of the body and is seen in the elderly. GCA and PMR are so closely linked that they are often considered to be different manifestations of the same disease process. Other diseases associated with temporal arteritis are systemic lupus erythematosus, rheumatoid arthritis, and severe infections.

Giant-cell arteritis can involve branches of the aorta as well, leading to an aortic aneurysm or dissection. For this reason, patients should be followed with serial chest X-rays.

X-linked congenital stationary night blindness (CSNB) is a rare X-linked non-progressive retinal disorder. It has two forms, complete, also known as type-1 (CSNB1), and incomplete, also known as type-2 (CSNB2), depending on severity. In the complete form (CSNB1), there is no measurable rod cell response to light, whereas this response is measurable in the incomplete form. Patients with this disorder have difficulty adapting to low light situations due to impaired photoreceptor transmission. These patients also often have reduced visual acuity, myopia, nystagmus, and strabismus. CSNB1 is caused by mutations in the gene NYX, which encodes a protein involved in retinal synapse formation or synaptic transmission. CSNB2 is caused by mutations in the gene CACNA1F, which encodes a voltage-gated calcium channel Ca1.4.

Not all Congenital Stationary Night Blindness (CSNB) are inherited in X-linked pattern. There are also dominant and recessive inheritance patterns for CSNB.

Non-occlusive disease has a poor prognosis with survival rate between 40-50%.

The X-linked varieties of congenital stationary night blindness (CSNB) can be differentiated from the autosomal forms by the presence of myopia, which is typically absent in the autosomal forms. Patients with CSNB often have impaired night vision, myopia, reduced visual acuity, strabismus, and nystagmus. Individuals with the complete form of CSNB (CSNB1) have highly impaired rod sensitivity (reduced ~300x) as well as cone dysfunction. Patients with the incomplete form can present with either myopia or hyperopia.

There are suggestions in the medical literature that treatment with radioactive iodine for Graves' hyperthyroidism may be a trigger for pretibial myxedema which would be consistent with radioiodine ablation causing or aggravating ophthalmopathy, a condition which commonly occurs with pretibial myxedema and is believed to have common underlying features.

Other known triggers for ophthalmopathy include thyroid hormone imbalance, and tobacco smoking, but there has been little research attempting to confirm these are also risk factors for pretibial myxedema.