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= Optic nerve disorder = Optic nerve disorder is defined as optic nerve damage leading to partial or wholly impairment in vision. A common sign of optic nerve disorders is pain and discomfort in the eye. The symptoms vary as each has different causes and damaged regions.

There are several types of optic nerve disorders, such as glaucoma, optic neuritis, optic nerve atrophy, coloboma of optic nerve, idiopathic intracranial hypertension, and neuromyelitis optica. Out of these several types, glaucoma is the most common optic nerve disorder that affects more than 3 million people annually in the US.

Eye examination and MRI are standard methods of diagnosis, and surgical methods accompanied by medical treatments can be adapted to treat the disorder.

Signs and symptoms
The main symptom is pain exacerbated during eye movements. Other symptoms may include blurred vision, problems interpreting colors, eye redness, headache, vomiting, nausea, and halos around light. The symptoms displayed in optic nerve disorders generally overlap, but the duration and the symptom types could differ among disorders.

Early stages of glaucoma show no distinctive symptoms giving it the name "the silent thief of sight". Later stages of glaucoma show gradual vision loss, difficulty in night vision, and blurred vision. The peripheral vision is affected first; as it advances, it moves to the central vision. Eye pain, headaches, and other distinctive symptoms may also accompany it. Other symptoms often vary in severity based on the optic nerve's inflammation level. It generally involves, but is not limited to, loss of vision and limitations in the visual hemisphere depending on the location of the atrophy.

Cause
The optic nerve, a bundle of millions of nerve fibers, carries impulses from the retina (the inner surface at the back of the eye) to the brain to interpret the visual information transmitted. Damage along this optic nerve pathway to the brain results in vision loss.

There are three consistent patterns among optic nerve disorders. First, damage in the optic nerve of one eye before the optic chiasm causes the loss of all visual information coming into that eye. The other eye usually continues to function normally. Secondly, damage in the optic chiasm leads to the loss of vision in the outer part of both visual fields. Lastly, damage between one side of the brain's optic chiasm and visual cortex causes vision loss in its opposite field. If the optic nerve of the left brain is damaged, the right field vision is lost.

The etiologies of optic nerve diseases include inflammation, compression, trauma, infiltration, glaucoma, ischemia, papilledema from increased intracranial pressure, hereditary, and congenital. Most optic nerve damages involve primary axonal injury and lead to permanent visual loss, axon degeneration, and ganglion cell death to a varying extent.

Risk factors
Optic nerve disorder is usually associated with pre-existing conditions or characteristics. However, risk factors vary between different types of optic nerve diseases. Some common risk factors are listed as follows:


 * Age: The risk of glaucoma increases with age; the risk of optic neuritis is high in the age of 20 to 40 years
 * Sex: Men are more likely to have glaucoma; optic neuritis most often affects women
 * Genetics and family history
 * Race: High prevalence of glaucoma in the black population; high prevalence of optic neuritis and optic neuropathy in the Caucasian population
 * Hypertension and diabetes

Pathophysiology
Optic nerve disorder is caused by damage to an optic nerve, and its pathogenesis differs between different types of optic nerve diseases. There are various conditions, including glaucoma, optic neuritis, optic nerve atrophy, optic nerve hypoplasia, and more.

Glaucoma
Glaucoma is an umbrella term that covers conditions leading to vision loss induced by damage to the optic nerve. Most glaucoma cases are caused by fluid accumulation inside the front area of the eye. More than 70 million people suffer from the disorder, and it is the second reason for blindness globally.

The most prevalent form of glaucoma is primary open-angle glaucoma (POAG). The majority of its cases come from European or African descent. Although patients rarely progress into complete blindness, many will live with visual limitations. Its pathology is not fully understood. However, the primary site of injury is identified as the optic nerve head (ONH), and there is a characteristic loss of the retinal nerve fiber layer. The damage in the ONH causes adverse effects on the retinal ganglion cells (RGCs) and damages the axons. The accumulation of death in RGCs and axons progressively leads to vision loss.

Primary angle-closure glaucoma (PACG) is a type of glaucoma that primarily occurs from a pupillary block. The closure of the angle of the eye increases intraocular pressure (IOP) and induces optic nerve damage. Iris bombe, a condition when the apposition of the iris prevents aqueous humour from flowing out, causes the pressure difference of the posterior and anterior chamber to be greater than the baseline, 0.23 mmHg. The anterior bows to a convex shape and disrupts the trabecular meshwork, further obstructing the drainage pathway.

PACG also occurs with non-pupillary block mechanisms. Sudden dilation of the eye in dark conditions thickens the peripheral iris, crowding the angle and blocking the drainage of fluid. Suggested treatments for PACG include iridectomy and laser iridotomy (a surgical method using a laser to make an alternative pathway for aqueous flow).

Optic neuritis
Optic neuritis (ON) refers to an inflammatory demyelinating condition of the optic nerve, and common symptoms include pain with eye movement and temporary vision loss in one eye. It develops typically when an autoimmune reaction damages the myelin sheath that surrounds neurons within the optic nerve. Myelin sheath is a layer that helps electrical impulses travel quickly from the eye to the brain. Vision is affected as ON disrupts the conversion of signals into visual information.

The pathogenesis of optic neuritis has limited understanding. It is likely due to increased pro-inflammatory cytokines from T cell, B cell, and glial cell activation. Once cytokines activate microglia and monocyte-derive macrophages, they further recruit CD4- and CD8+ T cells. Then, activated peripheral T-cells cross the blood-brain barrier and cause demyelination, neural cell death, and axonal death. The involvement of axons in addition to the myelin sheath in this process was identified by the latest technologies such as optical coherence tomography.

There are two types of optic neuritis: typical and atypical. Most ON cases are typical, meaning that it is associated with multiple sclerosis, and atypical ON is associated with neuroretinitis, neuromyelitis optica spectrum disorder, chronic recurrent immune optic neuropathy, and autoimmune conditions such as sarcoidosis, systematic lupus erythematosus, and Wegener’s granulomatosis. Neuroretinitis is the most common type of atypical ON and it is characterized by optic disc edema with a macular star figure. Most neuroretinitis is often caused by an immune response triggered by bacterial infections.

Optic nerve atrophy
Optic nerve atrophy refers to any physical damage to the optic nerve. It results from the necrosis of the retinal ganglion cells, which constitutes the optic nerve. Vision loss is associated with optic atrophy since the visual input from the eyes cannot be conveyed to the brain for information processing. Due to the reactively high severity of the condition, optic nerve atrophy is often considered to be an end stage of other optic-related disease conditions.

Optic nerves can be damaged via various causes, such as physical trauma, radiation, or intake of toxic substances. One of the most common causes of the optic nerve is limited blood flow to the eyes, which is referred to as ischemic optic neuropathy. Other optic nerve disorders and eye disease such as glaucoma also can develop into optic nerve atrophy. Disease conditions in the brain and central nervous systems, including brain tumor, sclerosis, stroke, or cranial arteritis, can lead to optic nerve atrophy as the optic nerve is connected to the brain in close proximity via cranial nerves. Due to this, physical injuries on the face or head sometimes lead to optic nerve atrophy. Though optic nerve atrophy is most common in older adults, rare hereditary optic nerve atrophy can influence children and young adults.

Other types of optic nerve disorder
Other causes of optic nerve disorder include congenital conditions such as optic nerve hypoplasia. Optic nerve hypoplasia is a congenital anomaly where optic nerves and ganglion cells are underdeveloped in a child. Certain maternal conditions are reported to be associated with optic nerve hypoplasia, such as fetal alcohol syndrome, premature births, and maternal diabetes. Autoimmune disease can be a cause of optic nerve disorder; Neuromyelitis, known as Devic’s disease, is a condition where the immune system attacks optic nerves and the spinal cord. It is a rare condition and can happen at any age. However, women experience it more often than men.

Diagnosis
Optic nerve disorders can be diagnosed by eye exams, ophthalmoscopy, which is an examination of the back of the eye, and imaging tests such as magnetic resonance imaging (MRI). For eye exams, a dilated eye exam is customarily used and the exam includes a visual acuity test, a visual field test, an eye muscle function test, a pupil response test, a tonometry test, and dilation of pupils. Optic nerve imaging tests use different optic nerve computer imaging techniques for examination. The Heidelberg Retina Tomograph (HRT) is used to produce a three-dimensional high-resolution image of the optic nerve, and the Nerve Fiber Analyzer (GDx) is used to measure the thickness of the nerve fiber layer. Optical Coherence Tomography (OCT) is used to directly measure the thickness of the nerve fiber layer as well as create a three-dimensional representation of the optic nerve.

Treatment
The current stage of medical practice cannot restore the lost axons of the ganglion cells. However, improvement is possible if the damage process is resolved before the cell necrosis occurs. Therefore, treatment of optic nerve diseases depends on different conditions, whether the injuries are reversible or not. For instance, the visual loss from optic neuritis, papilledema, and compressive optic neuropathy can be reversed by treating the axonal damage prior to the retinal ganglion cell death. On the other hand, the visual loss from glaucoma and ischemic optic neuropathy is permanent due to irreversible severe axonal injury. However, treatments such as medical therapy and surgical therapy can slow down the progression of diseases.

Medical therapy
Medical therapies, including eye drops, oral and intravenous medicines, or a combination of approaches can manage many optic nerve diseases. For example, an intravenous steroid can reduce inflammation in the optic nerve in optic neuritis and to lower intraocular pressure (IOP) within the eye to prevent the deterioration of optic nerves in glaucoma. Other treatments that lower IOP in glaucoma include prostaglandin analogs (PGAs) and β-adrenoceptor antagonists or beta-blockers, which are used as the first-line therapy of glaucoma. Moreover, patients with high suspicion of optic ischemia are immediately treated with high-dose corticosteroids to prevent vision loss in another eye. However, long-term steroid use can have an adverse influence on patients by elevating eye pressure.

Surgical therapy
Together with medical therapies, many optic nerve diseases have applied surgical interventions. For example, for the treatment of glaucoma, laser techniques, including argon laser trabeculoplasty and selective laser trabeculoplasty, can increase the outflow of aqueous humour via the canal of Schlemm and reduce elevated intraocular pressure. Also, surgical procedures of glaucoma treatment include deep sclerotome (a non-filtering procedure), trabeculectomy (a filtering procedure), and cyclocryocoagulation, which is used to reduce aqueous humour production. For the treatment of optic neuropathy and optic ischemia, optic nerve sheath decompression or optic nerve sheath fenestration (ONSF) surgery is performed. During ONSF in the setting of elevated intracranial pressure, the optic nerves are decompressed by the release of cerebrospinal fluid from the incision made in the optic nerve sheath. Moreover, there are two types of ONSF: the transcranial approach, which involves invasive and cosmetic problems, and the endonasal approach, which involves relatively narrow decompression.

Prevention
The visual function that is once lost cannot be recovered, and current primary prevention focuses on removing the underlying cause of the optic damage and preventing further loss of axons. Prevention of optic nerve disorders often varies depending on the nature of the disorder. Major causes of optic nerve disorders could be infections and high blood pressure; other hormonal changes may also induce harmful influences on optic nerve disorders.

For most optic nerve disorders, sufficient blood flow and decreasing optic pressure are crucial in maintaining optic health. Avoiding strong stimuli such as bright light or sunlight using eyewear is also recommended. Intense exercise, which increases heart rate and blood pressure can raise intraocular pressure. It is essential to ensure that the patient can perform proper breathing techniques during intense exercise. It is also advised to avoid physical movements and positions that may increase optic pressure in daily life. Postures such as head-down or sleeping positions that apply compulsion to the eyes should be avoided.

Furthermore, modification and control of lifestyle are imperative to prevent severe and secondary optic nerve diseases. For instance, adequate control of risk factors, including smoking, hypertension, diabetes mellitus, hyperlipidemia, and obstructive sleep apnea, has been found to prevent secondary optic neuropathy.