Although many perinatal and prenatal risk factors for ONH have been suggested, the predominant, enduring, most frequent risk factors are young maternal age and primiparity (the affected child being the first child born to the mother). Increased frequency of delivery by caesarean section and fetal/neonatal complications, preterm labor, gestational vaginal bleeding, low maternal weight gain, and weight loss during pregnancy are also associated with ONH.

Optic nerve hypoplasia (ONH) is a congenital condition in which the optic nerve is underdeveloped (small).

Many times, de Morsier’s Syndrome or septo-optic dysplasia (SOD) is associated with ONH, however, it is possible to have ONH without any additional issues like SOD. SOD is a condition that can involve multiple problems in the midline structures of the brain, stemming from miswiring of the brain and central nervous system. Besides having small optic nerves, persons with ONH can have agenesis of the corpus callosum, absence of the septum pellucidum, maldevelopment of the anterior and posterior pituitary gland, and anomalies of the hypothalamus. Because of this, all children with ONH are at risk for developmental delays and hormonal deficiencies, regardless of severity of ONH, or whether abnormalities are visible by MRI.

ONH is the single leading cause of permanent legal blindness in children in the western world. The incidence of ONH is increasing, although it is difficult to estimate the true prevalence. Between 1980 and 1999, the occurrences of ONH in Sweden increased four-fold to 7.2 per 100,000, while all other causes of childhood blindness had declined. In 1997, ONH overtook retinopathy of prematurity as the single leading cause of infant blindness in Sweden, with 6.3 in every 100,000 births diagnosed with ONH. The most recent prevalence report out of England in 2006 is 10.9 per 100,000.

Coloboma of optic nerve, is a rare defect of the optic nerve that causes moderate to severe visual field defects.

Coloboma of the optic nerve is a congenital anomaly of the optic disc in which there is a defect of the inferior aspect of the optic nerve. The issue stems from incomplete closure of the embryonic fissure while in utero. A varying amount of glial tissue typically fills the defect, manifests as a white mass.

Persistent hyperplastic primary vitreous (PHPV), also known as Persistent Fetal Vasculature (PFV), is a rare congenital developmental anomaly of the eye that results

following failure of the embryological, primary vitreous and hyaloid vasculature to regress. It can be present in three forms: purely anterior (persistent tunica vasculosa lentis and persistent posterior fetal fibrovascular sheath of the lens), purely posterior (falciform retinal septum and ablatio falcicormis congenita) and a combination of both. Most examples of PHPV are unilateral and non-hereditary. When bilateral, PHPV may follow an autosomal recessive or autosomal dominant inheritance pattern.

Vision in the affected eye is impaired, the degree of which depends on the size of the defect, and typically affects the visual field more than visual acuity. Additionally, there is an increased risk of serous retinal detachment, manifesting in 1/3 of patients. If retinal detachment does occur, it is usually not correctable and all sight is lost in the affected area of the eye, which may or may not involve the macula.

The most common causes in young children are birth trauma and a type of cancer called neuroblastoma. The cause of about a third of cases in children is unknown.

Sclerocornea is a congenital anomaly of the eye in which the cornea blends with sclera, having no clear-cut boundary. The extent of the resulting opacity varies from peripheral to total ("sclerocornea totalis"). The severe form is thought to be inherited in an autosomal recessive manner, but there may be another, milder form that is expressed in a dominant fashion. In some cases the patients also have abnormalities beyond the eye (systemic), such as limb deformities and craniofacial and genitourinary defects.

According to one tissue analysis performed after corneal transplantation, the sulfation pattern of keratan sulfate proteoglycans in the affected area is typical for corneal rather than scleral tissue.

Sclerocornea may be concurrent with cornea plana.

The primary vitreous used in formation of the eye during fetal development remains in the eye upon birth and is hazy and scarred. The symptoms are leukocoria, strabismus, nystagmus and blurred vision, blindness.

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.

Aphakia is the absence of the lens of the eye, due to surgical removal, a perforating wound or ulcer, or congenital anomaly. It causes a loss of accommodation, far sightedness (hyperopia), and a deep anterior chamber. Complications include detachment of the vitreous or retina, and glaucoma.

Babies are rarely born with aphakia. Occurrence most often results from surgery to remove congenital cataract (clouding of the eye's lens, which can block light from entering the eye and focusing clearly). Congenital cataracts usually develop as a result of infection of the fetus or genetic reasons. It is often difficult to identify the exact cause of these cataracts, especially if only one eye is affected.

People with aphakia have relatively small pupils and their pupils dilate to a lesser degree.

Causes of photophobia relating directly to the eye itself include:

- Achromatopsia

- Aniridia

- Anticholinergic drugs may cause photophobia by paralyzing the iris sphincter muscle.

- Aphakia (absence of the lens of the eye)

- Blepharitis

- Buphthalmos (abnormally narrow angle between the cornea and iris)

- Cataracts

- Coloboma

- Cone dystrophy

- Congenital abnormalities of the eye

- Viral conjunctivitis ("pink eye")

- Corneal abrasion

- Corneal dystrophy

- Corneal ulcer

- Disruption of the corneal epithelium, such as that caused by a corneal foreign body or keratitis

- Ectopia lentis

- Endophthalmitis

- Eye trauma caused by disease, injury, or infection such as chalazion, episcleritis, glaucoma, keratoconus, or optic nerve hypoplasia

- Hydrophthalmos, or congenital glaucoma

- Iritis

- The drug isotretinoin (Accutane/Roaccutane) has been associated with photophobia

- Optic neuritis

- Pigment dispersion syndrome

- Pupillary dilation (naturally or chemically induced)

- Retinal detachment

- Scarring of the cornea or sclera

- Uveitis

Horner's syndrome is acquired as a result of disease, but may also be congenital (inborn, associated with heterochromatic iris) or iatrogenic (caused by medical treatment). Although most causes are relatively benign, Horner syndrome may reflect serious disease in the neck or chest (such as a Pancoast tumor (tumor in the apex of the lung) or thyrocervical venous dilatation).

Causes can be divided according to the presence and location of anhidrosis:

- Central (anhidrosis of face, arm and trunk)

- Syringomyelia

- Multiple sclerosis

- Encephalitis

- Brain tumors

- Lateral medullary syndrome

- Preganglionic (anhidrosis of face)

- Cervical rib traction on stellate ganglion

- Thyroid carcinoma

- Thyroidectomy

- Goiter

- Bronchogenic carcinoma of the superior fissure (Pancoast tumor) on apex of lung

- Klumpke paralysis

- Trauma - base of neck, usually blunt trauma, sometimes surgery.

- As a complication of tube thoracostomy

- Thoracic aortic aneurysm

- Postganglionic (no anhidrosis)

- Cluster headache - combination termed Horton's headache

- An episode of Horner's syndrome may occur during a migraine attack and be relieved afterwards

- Carotid artery dissection/carotid artery aneurysm

- Cavernous sinus thrombosis

- Middle ear infection

- Sympathectomy

- Nerve blocks, such as cervical plexus block, stellate ganglion or interscalene block

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.

Neurological causes for photophobia include:

- Autism spectrum disorders

- Chiari malformation

- Occipital Neuralgia

- Dyslexia

- Encephalitis including Myalgic encephalomyelitis aka Chronic fatigue syndrome

- Meningitis

- Trigeminal disturbance causes central sensitization (hence, multiple other associated hypersensitivities. Causes can be bad bite, infected tooth, etc.

- Subarachnoid haemorrhage

- Tumor of the posterior cranial fossa

It may be acquired from:

- Diseases. Some of the diseases that present nystagmus as a pathological sign:

- Aniridia

- Toxic or metabolic reasons could be the result of the following:

- Central nervous system (CNS) disorders, such as with a cerebellar problem, the nystagmus can be in any direction "including" horizontal. Purely vertical nystagmus is usually central in origin, but it is also a frequent adverse effect of high phenytoin toxicity. Causes include:

Nystagmus is a relatively common clinical condition, affecting one in several thousand people. A survey conducted in Oxfordshire, United Kingdom found that by the age of two, one in every 670 children had manifested nystagmus. Authors of another study in the United Kingdom estimated an incidence of 24 in 10,000 (~0.240 %), noting an apparently higher rate amongst white Europeans than in individuals of Asian origin.

Axenfeld syndrome (also known as Axenfeld-Rieger syndrome or Hagedoom syndrome) is a rare autosomal dominant disorder, which affects the development of the teeth, eyes, and abdominal region.

Among fifth and sixth grade children convergence insufficiency is 13%. In studies that used standardized definitions of Convergence insufficiency, investigators have reported a prevalence of 4.2% to 6% in school and clinic settings. The standard definition of Convergence insufficiency is exophoria greater at near than at distance, a receded near point of convergence, and reduced convergence amplitudes at near.

Papillorenal syndrome, also called renal-coloboma syndrome or isolated renal hypoplasia, is an autosomal dominant genetic disorder marked by underdevelopment (hypoplasia) of the kidney and colobomas of the optic nerve.

Without the focusing power of the lens, the eye becomes very farsighted. This can be corrected by wearing glasses, contact lenses, or by implant of an artificial lens. Artificial lenses are described as "pseudophakic." Also, since the lens is responsible for adjusting the focus of vision to different lengths, patients with aphakia have a total loss of accommodation.

Some individuals have said that they perceive ultraviolet light, invisible to those with a lens, as whitish blue or whitish-violet.

Approximately half of patients with papillorenal syndrome do not have defects in the "Pax2". This suggests that other genes play a role in the development of the syndrome, though few downstream effectors of "Pax2" have been identified.

Lagophthalmos is the inability to close the eyelids completely.

Blinking covers the eye with a thin layer of tear fluid, thereby promoting a moist environment necessary for the cells of the exterior part of the eye. The tears also flush out foreign bodies and wash them away. This is crucial to maintain lubrication and proper eye health. If this process is impaired, as in lagophthalmos, the eye can suffer abrasions and infections. Lagopthalmos leads to corneal drying and ulceration.

Nocturnal lagophthalmos is the inability to close the eyelids during sleep. It may reduce the quality of sleep, cause exposure-related symptoms or, if severe, cause corneal damage (exposure keratopathy). The degree of lagophthalmos can be minor (obscure lagophthalmos), or quite obvious.

It is often caused by an anomaly of the eyelid that prevents full closure. Treatment may involve surgery to correct the malposition of the eyelid(s). Punctal plugs may be used to increase the amount of lubrication on the surface of the eyeball by blocking some of the tear drainage ducts. Eye drops may also be used to provide additional lubrication or encourage the eyes to increase tear production.

The condition is not widely understood; in at least one instance a passenger was removed from a US Airways flight because of it.

Treatment and prognosis depend on the underlying condition. For example, in thiamine deficiency, treatment would be the immediate administration of vitamin B1.

In contrast to generalized MG, purely ocular MG occurs equally among females and males, has a higher incidence in persons of Korean descent, and is likely associated with thyroid disease, thymomas (20% incidence), and other autoimmune diseases such as scleroderma, systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's thyroiditis, multiple sclerosis, and thyroid ophthalmopathy.