Clinically, there is an acute onset of visual loss, first in one eye, and then a few weeks to months later in the other. Onset is usually young adulthood, but age range at onset from 7-75 is reported. The age of onset is slightly higher in females (range 19–55 years: mean 31.3 years) than males (range 15–53 years: mean 24.3). The male to female ratio varies between mutations: 3:1 for 3460 G>A, 6:1 for 11778 G>A and 8:1 for 14484 T>C.

This typically evolves to very severe optic atrophy and a permanent decrease of visual acuity. Both eyes become affected either simultaneously (25% of cases) or sequentially (75% of cases) with a median inter-eye delay of 8 weeks. Rarely only one eye may be affected. In the acute stage, lasting a few weeks, the affected eye demonstrates an edematous appearance of the nerve fiber layer especially in the arcuate bundles and enlarged or telangiectatic and tortuous peripapillary vessels (microangiopathy). The main features are seen on fundus examination, just before or subsequent to the onset of visual loss. A pupillary defect may be visible in the acute stage as well. Examination reveals decreased visual acuity, loss of color vision and a cecocentral scotoma on visual field examination.

"LHON Plus" is a name given to a rare variant of the disorder with eye disease together with other conditions. The symptoms of this higher form of the disease include loss of the brain's ability to control the movement of muscles, tremors, and cardiac arrhythmia. Many cases of LHON plus have been comparable to multiple sclerosis because of the lack of muscular control.

The generalized, common presentation for this broad and inclusive group of diseases is painless, bilateral loss of visual acuity and pallor of the optic disc accompanied with varying degrees of dyschromatopsia and central/cecocentral scatomas. On examination the papillary response may be sluggish to light, one would not expect to find an afferent papillary defect. This is because optic neuropathies are often bilateral and symmetric. The optic disc may be mildly hyperemic with small splinter hemorrhages on or around the disc. Optic atrophy may early on be non-existent and only later become mild. In later stages the optic atrophy is severe and this indicates less opportunity for recovery.

The duration of onset can vary between immediate and insidious, owing to the specific etiology. Two key features may be helpful in distinguishing acquired from inherited optic neuropathies: absence of a family history and simultaneous involvement of both eyes; the former more commonly characterized by these two features.

This disease is a heterogenous group of inherited neuropathies, stemming from a MFN2 mutation, in which both motor and sensory nerves are affected, resulting in distal limb weakness, sensory loss, decreased deep tendon reflexes, and foot deformities. Affected individuals develop progressive optic nerve dysfunction starting later in childhood.

Autosomal dominant optic atrophy can present clinically as an isolated bilateral optic neuropathy (non-syndromic form) or rather as a complicated phenotype with extra-ocular signs (syndromic form).

Dominant optic atrophy usually affects both eyes roughly symmetrically in a slowly progressive pattern of vision loss beginning in childhood and is hence a contributor to childhood blindness. Vision testing will reveal scotomas (areas of impaired visual acuity) in the central visual fields with peripheral vision sparing and impaired color vision (color blindness). Visual acuity loss varies from mild to severe, typically ranging from 6/6 (in meters, equivalent to 20/20, ft) to 6/60 (20/200, ft) with a median value of 6/36 (roughly equivalent to 20/125 ft), corrected vision. In rare cases, vision loss is more severe.

Characteristic changes of the fundus evident on examination is temporal pallor (indicating atrophy) of the optic disc and in its end stage, excavation of the optic disc, as is also seen in Leber hereditary optic neuropathy and normal tension glaucoma.

Because the onset of Dominant optic atrophy is insidious, symptoms are often not noticed by the patients in its early stages and are picked up by chance in routine school eye screenings. First signs of Kjer's typically present between 4–6 years of age, though presentation at as early as 1 year of age has been reported. In some cases, Dominant optic atrophy may remain subclinical until early adulthood.

Progression of dominant optic atrophy varies even within the same family. Some have mild cases with visual acuity stabilizing in adolescence, others have slowly but constantly progressing cases, and others still have sudden step-like decreases in visual acuity. Generally, the severity of the condition by adolescence reflects the overall level of visual function to be expected throughout most of the patient’s adult life (Votruba, 1998). Slow decline in acuity is known to occur in late middle age in some families.

In complicated cases of autosomal dominant optic atrophy, in addition to bilateral optic neuropathy, several other neurological signs of neurological involvement can be observed: peripheral neuropathy, deafness, cerebellar ataxia, spastic paraparesis, myopathy.

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

The inherited optic neuropathies typically manifest as symmetric bilateral central visual loss. Optic nerve damage in most inherited optic neuropathies is permanent and progressive.

- Leber’s hereditary optic neuropathy (LHON) is the most frequently occurring mitochondrial disease, and this inherited form of acute or subacute vision loss predominantly affects young males. LHON usually presents with rapid vision loss in one eye followed by involvement of the second eye (usually within months). Visual acuity often remains stable and poor (around or below 20/200) with a residual central visual field defect. Patients with the 14484/ND6 mutation are most likely to have visual recovery.

- Dominant optic atrophy is an autosomal dominant disease caused by a defect in the nuclear gene OPA1. A slowly progressive optic neuropathy, dominant optic atrophy, usually presents in the first decade of life and is bilaterally symmetrical. Examination of these patients shows loss of visual acuity, temporal pallor of the optic discs, centrocecal scotomas with peripheral sparing, and subtle impairments in color vision.

- Behr’s syndrome is a rare autosomal recessive disorder characterized by early-onset optic atrophy, ataxia, and spasticity.

- Berk–Tabatznik syndrome is a condition that shows symptoms of short stature, congenital optic atrophy and brachytelephalangy. This condition is extremely rare.

Vision loss in toxic and nutritional optic neuropathy is bilateral, symmetric, painless, gradual, and progressive. Dyschromatopsia, a change in color vision, is often the first symptom. Some patients notice that certain colors, particularly red, are less bright or vivid; others have a general loss of color perception. Loss of visual acuity may start with a blur or haze at the point of fixation, followed by a progressive decline. The degree of vision loss can extend to total blindness, but a loss beyond 20/400 is rare, except in the case of methanol ingestion. Peripheral vision is usually spared since the pattern of loss typically involves a central or cecocentral scotoma, a visual field defect at or surrounding the point of fixation. This pattern can be revealed via visual field testing.

Upon examination, the pupils usually demonstrate a normal response to light and near stimulation. In those who are practically blind, the pupils will be dilated with a weak or absent response to light. The optic disc may appear normal, swollen, or hyperemic in early stages. With hyperemia, disc hemorrhages may also be present. Continued damage to the optic nerve results in the development of optic atrophy, classically seen as temporal pallor of the optic disc.

A nutritional optic neuropathy may be present in a patient with obvious evidence of under-nutrition (weight loss and wasting). Months of depletion are usually necessary to deplete body stores of most nutrients. Undernourished patients often suffer from many vitamin and nutrient deficiencies and have low serum protein levels. However, the optic neuropathy associated with pernicious anemia and vitamin B deficiency can even be seen in well-nourished individuals. Gastric bypass surgery may also cause a vitamin B deficiency from poor absorption.

Patients who suffer from nutritional optic neuropathy may notice that colors are not as vivid or bright as before and that the color red is washed out. This normally occurs in both eyes at the same time and is not associated with any eye pain. They might initially notice a blur or fog, followed by a drop in vision. While vision loss may be rapid, progression to blindness is unusual. These patients tend to have blind spots in the center of their vision with preserved peripheral vision. In most cases, the pupils continue to respond normally to light.

Nutritional deficiencies affect the whole body, so pain or loss of sensation in the arms and legs (peripheral neuropathy) is often seen in patients with nutritional optic neuropathies. There was an epidemic of nutritional optic neuropathy among afflicted Allied prisoners of war of the Japanese during World War II. After four months of food deprivation, the prisoners of war developed vision loss in both eyes that appeared suddenly. They also had pain in their extremities and hearing loss. There is an endemic tropical neuropathy in Nigeria that may be due to a nutritional deficiency, but this has not been proven.

The term congenital refers to a condition present from birth (not acquired) and amaurosis refers to a loss of vision "not" associated with a lesion. However, beyond these general descriptions, the presentation of LCA can vary, because it is associated with multiple genes.

LCA is typically characterized by nystagmus, sluggish or absent pupillary responses, and severe vision loss or blindness.

Optic nerve damage is progressive and insidious. Eventually 75% of patients will develop some peripheral field defects. These can include nasal step defects, enlarged blind spots, arcuate scotomas, sectoral field loss and altitudinal defects. Clinical symptoms correlate to visibility of the drusen. Central vision loss is a rare complication of bleeding from peripapillar choroidal neovascular membranes. Anterior ischemic optic neuropathy (AION) is a potential complication.

Toxic and nutritional optic neuropathy is a group of medical disorders defined by visual impairment due to optic nerve damage secondary to a toxic substance and/or nutritional deficiency. The causes of these disorders are various, but they are linked by shared signs and symptoms, which this article will describe. In several of these disorders, both toxic and nutritional factors play a role, acting synergistically.

Onset : Early childhood

Progression: Chronic progressive

Clinical: Cerebellar ataxia plus syndrome / Optic Atrophy Plus Syndrome

Ocular: Optic atrophy, nystagmus, scotoma, and bilateral retrobulbar neuritis.

Other: Mental retardation, myoclonic epilepsy, spasticity, and posterior column sensory loss. Tremor in some cases.

Musculoskeletal

Contractures, lower limbs, Achilles tendon contractures, Hamstring contractures, Adductor longus contractures

Systemic

Hypogonadotrophic hypogonadism.

In most patients, optic disc drusen are an incidental finding. It is important to differentiate them from other conditions that present with optic disc elevation, especially papilledema, which could imply raised intracranial pressure or tumors. True papilledema may present with exudates or cotton-wool spots, unlike ODD. The optic disc margins are characteristically irregular in ODD but not blurred as there is no swelling of the retinal nerve fibers. Spontaneous venous pulsations are present in about 80 percent of patients with ODD, but absent in cases of true disc edema. Other causes of disc elevation clinicians must exclude may be: hyaloid traction, epipapillary glial tissue, myelinated nerve fibres, scleral infiltration, vitreopapillary traction and high hyperopia. Disorders associated with disc elevation include: Alagille syndrome, Down syndrome, Kenny-Caffey syndrome, Leber Hereditary Optic Neuropathy and linear nevus sebaceous syndrome.

NAION typically presents suddenly and upon awakening. The patient notes seeing poorly in one eye. Vision in that eye is obscured by a dark shadow, often involving just the upper or lower half of vision, usually the area towards the nose. There is no pain. In approximately 6 months following the infarct visual acuity improves by 3 or more lines of vision on the Snellen Chart (the chart with smaller letters on each lower line) in 42.7% of patients. In addition, vision had worsened by 3 lines or more in 12.4% of patients. Second eye involvement occurs in approximately 15% to 20% of patients with NAION within 5 years. Fortunately, it may not be terribly devastating as the visual acuity may remain only moderately impaired. Furthermore, most cases of NAION involve the loss of a hemifield (either the upper or lower half of the visual field, but not both). A few cases of NAION involve almost total loss of vision.

Since arteritic AION is similar in presentation to non-arteritic AION, patients over the age of 50 diagnosed with NAION must be evaluated to exclude AAION (symptoms: painful jaw muscle spasms, scalp tenderness, unintentional weight loss, fatigue, myalgias and loss of appetite). Furthermore, NAION patients over the age of 75 should often be blood tested regardless.

Leber's congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life.

One form of LCA was successfully treated with gene therapy in 2008.

It affects about 1 in 40,000 newborns. LCA was first described by Theodor Leber in the 19th century. It should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodor Leber.

Major symptoms are sudden loss of vision (partial or complete), sudden blurred or "foggy" vision, and pain on movement of the affected eye. Early symptoms that require investigation include symptoms from multiple sclerosis (twitching, lack of coordination, slurred speech, frequent episodes of partial vision loss or blurred vision), episodes of "disturbed/blackened" rather than blurry indicate moderate stage and require immediate medical attention to prevent further loss of vision. Other early symptoms are reduced night vision, photophobia and red eyes. Many patients with optic neuritis may lose some of their color vision in the affected eye (especially red), with colors appearing subtly washed out compared to the other eye. Patients may also experience difficulties judging movement in depth which can be particular troublesome during driving or sport (Pulfrich effect). Likewise transient worsening of vision with increase of body temperature (Uhthoff's phenomenon) and glare disability are a frequent complaint. However, several case studies in children have demonstrated the absence of pain in more than half of cases (approximately 60%) in their pediatric study population, with the most common symptom reported simply as "blurriness." Other remarkable differences between the presentation of adult optic neuritis as compared to pediatric cases include more often unilateral optic neuritis in adults, while children much predominantly present with bilateral involvement.

On medical examination the head of the optic nerve can easily be visualized by a slit lamp with high plus or by using direct ophthalmoscopy; however, frequently there is no abnormal appearance of the nerve head in optic neuritis (in cases of retrobulbar optic neuritis), though it may be swollen in some patients (anterior papillitis or more extensive optic neuritis). In many cases, only one eye is affected and patients may not be aware of the loss of color vision until they are asked to close or cover the healthy eye.

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

Although it is an autosomal recessive disorder, heterozygotes may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

MELAS is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). In most cases, the signs and symptoms of this disorder appear in childhood following a period of normal development. Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia). The stroke-like episodes can be mis-diagnosed as epilepsy by a doctor not aware of the MELAS condition.

Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, loss of bowel control, and difficulty breathing. Less commonly, people with MELAS may experience involuntary muscle spasms (myoclonus), impaired muscle coordination (ataxia), hearing loss, heart and kidney problems, diabetes, epilepsy, and hormonal imbalances.

The presentation of some cases is similar to that of Kearns-Sayre syndrome.

The most common symptom of ONSM is a gradual loss of vision in one eye. In a minority of patients this may be intermittent, at least to begin with. Less common symptoms include pain in the affected eye, protrusion of the eye, or double vision.

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.

AON was first described in 1982. It presents with visual loss and signs of optic nerve dysfunction, such as loss of color vision, afferent pupil defect, and sometimes abnormalities of the optic disc. The clinical features of AON can be variable and present in several unilateral or bilateral forms:

- Acute anterior or retrobulbar optic neuritis sometimes associated with pain.

- Anterior or retrobulbar ischemic optic neuropathy not associated with pain.

- Chronic progressive vision loss that mimics a compressive lesion.

The main features that differentiate AON from the more common typical demyelinating optic neuritis is the poor recovery of vision and the chronic or recurrent or bilateral course of AON. Furthermore, the workup for multiple sclerosis including MRI, will be negative. Thus, it may be necessary to diagnose AON after a period of observation, noting the problem is not behaving as expected for demyelinative disease.

Optic papillitis is a specific type of optic neuritis. Inflammation of the optic nerve head is called "papillitis" or "intraocular optic neuritis"; inflammation of the orbital portion of the nerve is called "retrobulbar optic neuritis" or "orbital optic neuritis". It is often associated with substantial losses in visual fields, pain on moving the globe, and sensitivity to light pressure on the globe. It is often an early sign of multiple sclerosis.

Papillitis may have the same appearance as papilledema. However, papillitis may be unilateral, whereas papilledema is almost always bilateral. Papillitis can be differentiated from papilledema by an afferent pupillary defect (Marcus Gunn pupil), by its greater effect in decreasing visual acuity and color vision, and by the presence of a central scotoma. Papilledema that is not yet chronic will not have as dramatic an effect on vision. Because increased intracranial pressure can cause both papilledema and a sixth (abducens) nerve palsy, papilledema can be differentiated from papillitis if esotropia and loss of abduction are also present. However, esotropia may also develop secondarily in an eye that has lost vision from papillitis. Retrobulbar neuritis, an inflamed optic nerve, but with a normal-appearing nerve head, is associated with pain and the other findings of papillitis. Pseudopapilledema is a normal variant of the optic disk, in which the disk appears elevated, with indistinct margins and a normal vascular pattern. Pseudopapilledema sometimes occurs in hyperopic individuals.

Workup of the patient with papillitis includes lumbar puncture and cerebrospinal fluid analysis. B henselae infection can be detected by serology. MRI is the preferred imaging study. An abnormal MRI is associated with a worse visual outcome.

Clinical examination will show an abnormal optic disc, either swollen or atrophic. Optociliary shunt vessels may be seen; the combination of these with progressive visual loss and optic disc atrophy is known as the Hoyt-Spencer triad. Visual acuity is usually but not always reduced.

When ONSM is suspected, MRI of the brain or orbits should be performed. This will usually show characteristic findings and confirm the diagnosis.

Optic neuritis is a demyelinating inflammation of the optic nerve. It is also known as optic papillitis (when the head of the optic nerve is involved) and retrobulbar neuritis (when the posterior part of the nerve is involved). It is most often associated with multiple sclerosis, and it may lead to complete or partial loss of vision in one or both eyes.

Partial, transient vision loss (lasting less than one hour) can be an indication of early onset multiple sclerosis. Other possible diagnoses include: diabetes mellitus, low phosphorus levels, or hyperkalaemia.