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.

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.

Retinitis pigmentosa is the leading cause of inherited blindness, with approximately 1/4,000 individuals experiencing the non-syndromic form of their disease within their lifetime. It is estimated that 1.5 million people worldwide are currently affected. Early onset RP occurs within the first few years of life and is typically associated with syndromic disease forms, while late onset RP emerges from early to mid-adulthood.

Autosomal dominant and recessive forms of retinitis pigmentosa affect both male and female populations equally; however, the less frequent X-linked form of the disease affects male recipients of the X-linked mutation, while females usually remain unaffected carriers of the RP trait. The X-linked forms of the disease are considered severe, and typically lead to complete blindness during later stages. In rare occasions, a dominant form of the X-linked gene mutation will affect both males and females equally.

Due to the genetic inheritance patterns of RP, many isolate populations exhibit higher disease frequencies or increased prevalence of a specific RP mutation. Pre-existing or emerging mutations that contribute to rod photoreceptor degeneration in retinitis pigmentosa are passed down through familial lines; thus, allowing certain RP cases to be concentrated to specific geographical regions with an ancestral history of the disease. Several hereditary studies have been performed to determine the varying prevalence rates in Maine (USA), Birmingham (England), Switzerland (affects 1/7000), Denmark (affects 1/2500), and Norway. Navajo Indians display an elevated rate of RP inheritance as well, which is estimated as affecting 1 in 1878 individuals. Despite the increased frequency of RP within specific familial lines, the disease is considered non-discriminatory and tends to equally affect all world populations.

Many environmental conditions have also been known to cause anophthalmia. The strongest support for environmental causes has been studies where children have had gestational-acquired infections. These infections are typically viral. A few known pathogens that can cause anophthalmia are Toxoplasma, rubella, and certain strains of the influenza virus. Other known environmental conditions that have led to anophthalmia are maternal vitamin A deficiency, exposure to X-rays during gestation, solvent abuse, and exposure to thalidomide.

Genetic tests and related research are currently being performed at Centogene AG in Rostock, Germany; John and Marcia Carver Nonprofit Genetic Testing Laboratory in Iowa City, IA; GENESIS Center for Medical Genetics in Poznan, Poland; Miraca Genetics Laboratories in Houston, TX; Asper Biotech in Tartu, Estonia; CGC Genetics in Porto, Portugal; CEN4GEN Institute for Genomics and Molecular Diagnostics in Edmonton, Canada; and Reference Laboratory Genetics - Barcelona, Spain.

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.

Of these, cataract is responsible for >65%, or more than 22 million cases of blindness, and glaucoma is responsible for 6 million cases.

Cataracts: is the congenital and pediatric pathology that describes the greying or opacity of the crystalline lens, which is most commonly caused by intrauterine infections, metabolic disorders, and genetically transmitted syndromes. Cataracts are the leading cause of child and adult blindness that doubles in prevalence with every ten years after the age of 40. Consequently, today cataracts are more common among adults than in children. That is, people face higher chances of developing cataracts as they age. Nonetheless, cataracts tend to have a greater financial and emotional toll upon children as they must undergo expensive diagnosis, long term rehabilitation, and visual assistance. Also, according to the Saudi Journal for Health Sciences, sometimes patients experience irreversible amblyopia after pediatric cataract surgery because the cataracts prevented the normal maturation of vision prior to operation. Despite the great progress in treatment, cataracts remain a global problem in both economically developed and developing countries. At present, with the variant outcomes as well as the unequal access to cataract surgery, the best way to reduce the risk of developing cataracts is to avoid smoking and extensive exposure to sun light (i.e. UV-B rays).

The most extensive epidemiological survey on this congenital malformation has been carried out by Dharmasena et al and using English National Hospital Episode Statistics, they calculated the annual incidence of anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus from 1999 to 2011. According to this study the annual incidence of congenital microphthalmia in the United Kingdom was 10.8 (8.2 to 13.5) in 1999 and 10.0 (7.6 to 12.4) in 2011.

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.

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.

RP may be:

(1) Non-syndromic, that is, it occurs alone, without any other clinical findings,

(2) Syndromic, with other neurosensory disorders, developmental abnormalities, or complex clinical findings, or

(3) Secondary to other systemic diseases.

- RP combined with deafness (congenital or progressive) is called Usher syndrome.

- Alport's syndrome is associated with RP and an abnormal glomerular-basement membrane leading nephrotic syndrome and inherited as X-linked dominant.

- RP combined with ophthalmoplegia, dysphagia, ataxia, and cardiac conduction defects is seen in the mitochondrial DNA disorder Kearns-Sayre syndrome (also known as Ragged Red Fiber Myopathy)

- RP combined with retardation, peripheral neuropathy, acanthotic (spiked) RBCs, ataxia, steatorrhea, is absence of VLDL is seen in abetalipoproteinemia.

- RP is seen clinically in association with several other rare genetic disorders (including muscular dystrophy and chronic granulomatous disease) as part of McLeod syndrome. This is an X-linked recessive phenotype characterized by a complete absence of XK cell surface proteins, and therefore markedly reduced expression of all Kell red blood cell antigens. For transfusion purposes these patients are considered completely incompatible with all normal and K0/K0 donors.

- RP associated with hypogonadism, and developmental delay with an autosomal recessive inheritance pattern is seen with Bardet-Biedl syndrome

Other conditions include neurosyphilis, toxoplasmosis and Refsum's disease.

An interstitial deletion of chromosome 14 has been known to occasionally be the source of anophthalmia. The deletion of this region of chromosome has also been associated with patients having a small tongue, and high arched palate, developmental and growth retardation, undescended testes with a micropenis, and hypothyroidism. The region that has been deleted is region q22.1-q22.3. This confirms that region 22 on chromosome 14 influences the development of the eye.

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.

Vitamin A supplementation plays an important role, specifically vitamin A deficiency is a top causes of preventable childhood blindness. Though in measles cases, the administration of the vitamin to offset visual impairment has not been proven effective, as of yet.

Blindness can occur in combination with such conditions as intellectual disability, autism spectrum disorders, cerebral palsy, hearing impairments, and epilepsy. Blindness in combination with hearing loss is known as deafblindness.

It has been estimated that over half of completely blind people have non-24-hour sleep–wake disorder, a condition in which a person's circadian rhythm, normally slightly longer than 24 hours, is not entrained (synchronized) to the light/dark cycle.

Oguchi disease, also called congenital stationary night blindness, Oguchi type 1 or Oguchi disease 1, is an autosomal recessive form of congenital stationary night blindness associated with fundus discoloration and abnormally slow dark adaptation.

In utero exposure to cocaine and other street drugs can lead to septo-optic dysplasia.

Achromatopsia (ACHM), also known as total color blindness, is a medical syndrome that exhibits symptoms relating to at least five conditions. The term may refer to acquired conditions such as cerebral achromatopsia, also known as color agnosia, but it typically refers to an autosomal recessive congenital color vision condition, the inability to perceive color and to achieve satisfactory visual acuity at high light levels (typically exterior daylight). The syndrome is also present in an incomplete form which is more properly defined as dyschromatopsia. It is estimated to affect 1 in 40,000 live births worldwide.

There is some discussion as to whether achromats can see color or not. As illustrated in "The Island of the Colorblind" by Oliver Sacks, some achromats cannot see color, only black, white, and shades of grey. With five different genes currently known to cause similar symptoms, it may be that some do see marginal levels of color differentiation due to different gene characteristics. With such small sample sizes and low response rates, it is difficult to accurately diagnose the 'typical achromatic conditions'. If the light level during testing is optimized for them, they may achieve corrected visual acuity of 20/100 to 20/150 at lower light levels, regardless of the absence of color. One common trait is hemeralopia or blindness in full sun. In patients with achromatopsia, the cone system and fibres carrying color information remain intact. This indicates that the mechanism used to construct colors is defective.

Acquired achromatopsia/dyschromatopsia is a condition associated with damage to the diencephalon (primarily the thalamus of the mid brain) or the cerebral cortex (the new brain), specifically the fourth visual association area, V4 which receives information from the parvocellular pathway involved in colour processing.

Thalamic achromatopsia/dyschromatopsia is caused by damage to the thalamus; it is most frequently caused by tumor growth since the thalamus is well protected from external damage.

Cerebral achromatopsia is a form of acquired color blindness that is caused by damage to the cerebral cortex of the brain, rather than abnormalities in the cells of the eye's retina. It is most frequently caused by physical trauma, hemorrhage or tumor tissue growth.

The number of children who suffer from blindness worldwide is approximately 1.4 million. 75% of the world’s blind children live in Africa and Asia. A 2014 review indicated that an estimated of 238,500 children with bilateral blindness (rate 1.2/1,000) in the Eastern Mediterranean region.

Choroideremia (; CHM) is a rare, X-linked recessive form of hereditary retinal degeneration that affects roughly 1 in 50,000 males. The disease causes a gradual loss of vision, starting with childhood night blindness, followed by peripheral vision loss, and progressing to loss of central vision later in life. Progression continues throughout the individual's life, but both the rate of change and the degree of visual loss are variable among those affected, even within the same family.

Choroideremia is caused by a loss-of-function mutation in the "CHM" gene which encodes Rab escort protein 1 (REP1), a protein involved in lipid modification of Rab proteins. While the complete mechanism of disease is not fully understood, the lack of a functional protein in the retina results in cell death and the gradual deterioration of the choroid, retinal pigment epithelium (RPE), and retinal photoreceptor cells.

As of 2017, there is no treatment for choroideremia; however, retinal gene therapy clinical trials have demonstrated a possible treatment.

Microphthalmia in newborns is sometimes associated with fetal alcohol syndrome or infections during pregnancy, particularly herpes simplex virus, rubella and cytomegalovirus (CMV), but the evidence is inconclusive. Genetic causes of microphthalmia include chromosomal abnormalities (Trisomy 13 (Patau syndrome), Triploid Syndrome, 13q deletion syndrome, and Wolf-Hirschhorn Syndrome) or monogenetic Mendelian disorders. The latter may be autosomal dominant, autosomal recessive or X linked.

The following genes have been implicated in microphthamia, many of which are transcription and regulatory factors:

How these genes result in the eye disorder is unknown but it has been postulated that interference with the process of eye growth after birth may be involved in contrast to anophthalmia (absence of eyeball) which originates much earlier during foetal development. SOX2 has been implicated in a substantial number (10-15%) of cases and in many other cases failure to develop the ocular lens often results in microphthamia. Microphthalmia-associated transcription factor (MITF) located on chromosome 14q32 is associated with one form of isolated microphthalmia (MCOP1. In mammals the failure of expression of the transcription factor, MITF (microphthalmia-associated transcription factor), in the pigmented retina prevents this structure from fully differentiating. This in turn causes a malformation of the choroid fissure of the eye, resulting in the drainage of vitreous humor fluid. Without this fluid, the eye fails to enlarge, thus the name microphthalmia.The gene encoding the microphthalmia-associated transcription factor (MITF) is a member of the basic helix-loop-helix-leucine zipper (bHLH-ZIP) family. Waardenburg syndrome type 2 (WS type 2) in humans is also a type of microphthalmia syndrome. Mutations in MITF gene are thought to be responsible for this syndrome. The human MITF gene is homologous to the mouse MITF gene (aka mouse mi or microphthalmia gene); mouse with mutations in this gene are hypopigmented in their fur. The identification of the genetics of WS type 2 owes a lot to observations of phenotypes of MITF mutant mice.

While choroideremia is an ideal candidate for gene therapy there are other potential therapies that could restore vision after it has been lost later in life. Foremost of these is stem cell therapy. A clinical trial published in 2014 found that a subretinal injection of human embryonic stem cells in patients with age-related macular degeneration and Stargardt disease was safe and improved vision in most patients. Out of 18 patients, vision improved in 10, improved or remained the same in 7, and decreased in 1 patient, while no improvement was seen in the untreated eyes. The study found "no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue." A 2015 study used CRISPR/Cas9 to repair mutations in patient-derived induced pluripotent stem cells that cause X-linked retinitis pigmentosa. This study suggests that a patient's own repaired cells could be used for therapy, reducing the risk of immune rejection and ethical issues that come with the use of embryonic stem cells.

This condition is linked to the X chromosome.

- Siberian Husky - Night blindness by two to four years old.

- Samoyed - More severe disease than the Husky.

Hemeralopia is known to occur in several ocular conditions. Cone dystrophy and achromatopsia, affecting the cones in the retina, and the anti-epileptic drug Trimethadione are typical causes. Adie's pupil which fails to constrict in response to light; Aniridia, which is absence of the iris; Albinism where the iris is defectively pigmented may also cause this. Central Cataracts, due to the lens clouding, disperses the light before it can reach the retina, is a common cause of hemeralopia and photoaversion in elderly. C.A.R (Cancer Associated Retinopathy) seen when certain cancers incite the production of deleterious antibodies against retinal components, may cause hemeralopia.

Another known cause is a rare genetic condition called Cohen Syndrome (aka Pepper Syndrome). Cohen syndrome is mostly characterized by obesity, mental retardation, and craniofacial dysmorphism due to genetic mutation at locus 8q22-23. Rarely it may have ocular complications such as hemeralopia, pigmentary chorioretinitis, optic atrophy or retinal/iris coloboma, having a serious effect on the person's vision.

Yet another cause of hemeralopia is uni- or bilateral postchiasmatic brain injury. This may also cause concomitant night blindness.