Toxic optic neuropathy refers to the ingestion of a toxin or an adverse drug reaction that results in vision loss from optic nerve damage. Patients may report either a sudden loss of vision in both eyes, in the setting of an acute intoxication, or an insidious asymmetric loss of vision from an adverse drug reaction. The most important aspect of treatment is recognition and drug withdrawal.

Among the many causes of TON, the top 10 toxins include:

- Medications

- Ethambutol, rifampin, isoniazid, streptomycin (tuberculosis treatment)

- Linezolid (taken for bacterial infections, including pneumonia)

- Chloramphenicol (taken for serious infections not helped by other antibiotics)

- Isoretinoin (taken for severe acne that fails to respond to other treatments)

- Ciclosporin (widely used immunosuppressant)

- Acute Toxins

- Methanol (component of some moonshine, and some cleaning products)

- Ethylene glycol (present in anti-freeze and hydraulic brake fluid)

Metabolic disorders may also cause this version of disease. Systemic problems such as diabetes mellitus, kidney failure, and thyroid disease can cause optic neuropathy, which is likely through buildup of toxic substances within the body. In most cases, the cause of the toxic neuropathy impairs the tissue’s vascular supply or metabolism. It remains unknown as to why certain agents are toxic to the optic nerve while others are not and why particularly the papillomacular bundle gets affected.

TAA is an old term for a constellation of elements that can lead to a mitochondrial optic neuropathy. The classic patient is a man with a history of heavy alcohol and tobacco consumption. Respectively, this combines nutritional mitochondrial impairment, from vitamin deficiencies (folate and B-12) classically seen in alcoholics, with tobacco-derived products, such as cyanide and ROS. It has been suggested that the additive effect of the cyanide toxicity, ROS, and deficiencies of thiamine, riboflavin, pyridoxine, and b12 result in TAA.

Kearns–Sayre syndrome occurs spontaneously in the majority of cases. In some cases it has been shown to be inherited through mitochondrial, autosomal dominant, or autosomal recessive inheritance. There is no predilection for race or sex, and there are no known risk factors. As of 1992 there were only 226 cases reported in published literature.

Chronic progressive external ophthalmoplegia (CPEO), also known as progressive external ophthalmoplegia (PEO), is a type of eye disorder characterized by slowly progressive inability to move the eyes and eyebrows. It is often the only feature of mitochondrial disease, in which case the term CPEO may be given as the diagnosis. In other people suffering from mitochondrial disease, CPEO occurs as part of a syndrome involving more than one part of the body, such as Kearns-Sayre syndrome. Occasionally CPEO may be caused by conditions other than mitochondrial diseases.

CHED has two types:

- type I or the autosomal dominant form.

- type II or the autosomal recessive form is linked to mutations in SLC4A11 gene

Congenital hereditary corneal dystrophy (CHED) is a form of corneal dystrophy which presents at birth.

Kearns–Sayre syndrome (KSS) is a mitochondrial myopathy with a typical onset before 20 years of age. KSS is a more severe syndromic variant of chronic progressive external ophthalmoplegia (abbreviated CPEO), a syndrome that is characterized by isolated involvement of the muscles controlling movement of the eyelid (levator palpebrae, orbicularis oculi) and eye (extra-ocular muscles). This results in ptosis and ophthalmoplegia respectively. KSS involves a combination of the already described CPEO as well as pigmentary retinopathy in both eyes and cardiac conduction abnormalities. Other symptoms may include cerebellar ataxia, proximal muscle weakness, deafness, diabetes mellitus, growth hormone deficiency, hypoparathyroidism, and other endocrinopathies. In both of these diseases, muscle involvement may begin unilaterally but always develops into a bilateral deficit, and the course is progressive. This discussion is limited specifically to the more severe and systemically involved variant.

Megalocornea (MGCN, MGCN1) is an extremely rare nonprogressive condition in which the cornea has an enlarged diameter, reaching and exceeding 13 mm. It is noted in some patients with Marfan syndrome. It is thought to have two subforms, one with autosomal inheritance and the other X-linked (Xq21.3-q22). The X-linked form is more common and males generally constitute 90% of cases.

CPEO is a rare disease that may affect those of all ages, but typically manifests in the young adult years. CPEO is the most common manifestation of mitochondrial myopathy, occurring in an estimated two-thirds of all cases of mitochondrial myopathy. Patients typically present with ptosis (drooping eyelids). Other diseases like Graves' disease, myasthenia gravis and glioma that may cause an external ophthalmoplegia must be ruled out.

Cornea plana 1 (CNA1) is an extremely rare congenital hereditary deformity of the eye surface, leading to severe decrease in corneal curvature.

This disease is more common in women and an association with the gene FLT4 has been described. FLT4 codes for VEGFR-3, which is implicated in development of the lymphatic system.

Milroy's disease is also known as primary or hereditary lymphedema type 1A or early onset lymphedema.

It is a very rare disease with only about 200 cases reported in the medical literature. Milroy's disease is an autosomal dominant condition caused by a mutation in the FLT4 gene which encodes of the vascular endothelial growth factor receptor 3 (VEGFR-3) gene located on the long arm (q) on chromosome 5 (5q35.3).

In contrast to Milroy's disease (early onset lymphedema type 1A,) which typically has its onset of swelling and edema at birth or during early infancy, hereditary lymphedema type II, known as Meige disease, has its onset around the time of puberty. Meige disease is also an autosomal dominant disease. It has been linked to a mutations in the ‘forkhead’ family transcription factor (FOXC2) gene located on the long arm of chromosome 16 (16q24.3). About 2000 cases have been identified. A third type of hereditary lymphedema, that has an onset after the age of 35 is known as lymph-edema tarda.

Several mutations have been implicated as a cause of Oguchi disease. These include mutations in the arrestin gene or the rhodopsin kinase gene.

The condition is more frequent in individuals of Japanese ethnicity.

Cornea plana 2 (CNA2) is an extremely rare congenital hereditary deformity of the eye surface, leading to severe decrease in corneal curvature. There is evidence that cornea plana 2 is caused by mutations in KERA gene encoding "keratocan".

There have been cases of improvement in extra-ocular movement with botulinum toxin injection.

Although no cure currently exists, there is hope in treatment for this class of hereditary diseases with the use of an embryonic mitochondrial transplant.

The most common finding is oculomotor nerve dysfunction leading to ophthalmoplegia. This is often accompanied by ophthalmic nerve dysfunction, leading to hypoesthesia of the upper face. The optic nerve may eventually be involved, with resulting visual impairment.

Jacod Syndrome is commonly associated with a tumor of the middle cranial fossa (near the apex of the orbit); but it can have several other causes.

In the United States, the incidence of primary congenital glaucoma is about one in 10,000 live births. Worldwide, the incidence ranges from a low of 1:22,000 in Northern Ireland to a high of 1:2,500 in Saudi Arabia and 1:1,250 in Romania. In about two-thirds of cases, it is bilateral. The distribution between males and females varies with geography. In North America and Europe it is more common in boys, whereas in Japan it is more common in girls.

- Congenital glaucoma

- Incidence: one in every 10000-15000 live births.

- Bilateral in up to 80% of cases.

- Most cases are sporadic (90%). However, in the remaining 10% there appears to be a strong familial component.

Aniridia is the absence of the iris, usually involving both eyes. It can be congenital or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular and optic nerve hypoplasia, cataract, and corneal changes. Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract. Aniridia in some individuals occurs as part of a syndrome, such as WAGR syndrome (kidney nephroblastoma (Wilms tumour), genitourinary anomalies and intellectual disability), or Gillespie syndrome (cerebellar ataxia).

Aniridia may be broadly divided into hereditary and sporadic forms. Hereditary aniridia is usually transmitted in an autosomal dominant manner (each offspring has a 50% chance of being affected), although rare autosomal recessive forms (such as Gillespie syndrome) have also been reported. Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). These patients often also have genitourinary abnormalities and intellectual disability (WAGR syndrome).

Several different mutations may affect the PAX6 gene. Some mutations appear to inhibit gene function more than others, with subsequent variability in the severity of the disease. Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have foveal hypoplasia, and retain relatively normal vision. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder phenotype.

- AN

- Aniridia and absent patella

- Aniridia, microcornea, and spontaneously reabsorbed cataract

- Aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome)

VLDLR-associated cerebellar hypoplasia (VLDLRCH; alternative names: dysequilibrium syndrome, DES; nonprogressive cerebellar disorder with mental retardation) is a rare autosomal recessive condition caused by a disruption of the VLDLR gene. First described as a form of cerebral palsy in the 1970s, it is associated with parental consanguinity and is found in secluded communities, with a number of cases described in Hutterite families.

Parinaud's Syndrome results from injury, either direct or compressive, to the dorsal midbrain. Specifically, compression or ischemic damage of the mesencephalic tectum, including the superior colliculus adjacent oculomotor (origin of cranial nerve III) and Edinger-Westphal nuclei, causing dysfunction to the motor function of the eye.

Classically, it has been associated with three major groups:

1. Young patients with brain tumors in the pineal gland or midbrain: pinealoma (intracranial germinomas) are the most common lesion producing this syndrome.

2. Women in their 20s-30s with multiple sclerosis

3. Older patients following stroke of the upper brainstem

However, any other compression, ischemia or damage to this region can produce these phenomena: obstructive hydrocephalus, midbrain hemorrhage, cerebral arteriovenous malformation, trauma and brainstem toxoplasmosis infection. Neoplasms and giant aneurysms of the posterior fossa have also been associated with the midbrain syndrome.

Vertical supranuclear ophthalmoplegia has also been associated with metabolic disorders, such as Niemann-Pick disease, Wilson's disease, kernicterus, and barbiturate overdose.

Congenital fibrosis of the extraocular muscles, or CFEOM, is a class of rare genetic disorders affecting one or more of the muscles that move the eyeballs. Individuals with CFEOM have varying degrees of ophthalmoplegia (an inability to move the eyes in one or more directions) and ptosis. The condition is present from birth and non-progressive, runs in families, and usually affects both eyes similarly. In the most common form, the superior recti are dysfunctional and the inferior recti, lacking proper opposition, pull the eyes down, forcing the head to be tilted upward in order to see straight ahead.

There are three types of CFEOM, numbered 1-3. CFEOM1, the most common type, is now known to be caused by one of several mutations in the KIF21A gene, while CFEOM2 is caused by mutations in the PHOX2A gene. CFEOM3 is caused by mutations in the TUBB3 gene.

CFEOM was first named in 1956, although papers describing conditions now known or assumed to be CFEOM appear in the medical literature as early as 1840. Due to its rarity, it has been independently cited numerous times under many different names.

Causes of the one and a half syndrome include pontine hemorrhage, ischemia, tumors, infective mass lesions such as tuberculomas, and demyelinating conditions like multiple sclerosis.

The eye findings of Parinaud's Syndrome generally improve slowly over months, especially with resolution of the causative factor; continued resolution after the first 3–6 months of onset is uncommon. However, rapid resolution after normalization of intracranial pressure following placement of a ventriculoperitoneal shunt has been reported.

Treatment is primarily directed towards etiology of the dorsal midbrain syndrome. A thorough workup, including neuroimaging is essential to rule out anatomic lesions or other causes of this syndrome. Visually significant upgaze palsy can be relieved with bilateral inferior rectus recessions. Retraction nystagmus and convergence movement are usually improved with this procedure as well.