Anophthalmia/Microphthalmia Symptoms, Causes and Treatment

Anophthalmia and microphthalmia are disorders that affect eye development before birth. Microphthalmia is a birth defect in which one or both eyes do not develop fully and are abnormally small. Anophthalmia is a more severe birth defect in which one or both eyes do not form at all. While people who have anophthalmia have no vision in the affected eye, people who have microphthalmia may or may not have significant vision loss. Because both conditions are characterized by impaired eye development, anophthalmia and microphthalmia are often considered to be related disorders (anophthalmia/microphthalmia).

Anophthalmia and microphthalmia can occur along with other eye abnormalities. People who have one missing eye (unilateral anophthalmia) can have additional eye abnormalities in the unaffected eye, while people who have microphthalmia can have additional eye abnormalities in one or both eyes (complex microphthalmia). The presence of other eye problems can worsen vision. Additional eye abnormalities can include a missing piece of tissue that may appear as a notch or gap in one of several parts of the eye (coloboma); a clouding of the lens of the eye (cataract); abnormal development of the cells in the retina (retinal dysplasia);  or microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.

Some individuals have anophthalmia or microphthalmia as part of a syndrome that affects multiple parts of the body (syndromic anophthalmia or microphthalmia). As many as 45 percent of people with anophthalmia or microphthalmia have the condition as part of a recognized syndrome, such as CHARGE syndrome, Fraser syndrome type 1 or 2, and oculofaciocardiodental syndrome. When people have anophthalmia or microphthalmia but do not have additional abnormalities of the eye or other body systems, this is known as isolated anophthalmia or microphthalmia.

Microphthalmia occurs in approximately 1 in 7,000 people, while anophthalmia occurs in approximately 1 in 30,000 people. 

Variants (also called mutations) in one of the many genes that are involved in the early development of the eye can cause anophthalmia or microphthalmia. Researchers believe that variants in as many as 90 different genes can cause these conditions. Many of the genes that are associated with anophthalmia and microphthalmia have been identified in only a very small number of affected individuals. 

A genetic variant is more likely to be found in individuals who have anophthalmia or severe microphthalmia that affects both eyes (bilateral). Variants in the SOX2 gene are found in approximately 10 to 15 percent of these cases. Variants in many other genes account for a small percentage of cases. Together, variants in the SOX2 and OTX2 genes are believed to cause more than half of all cases of bilateral anophthalmia or bilateral and severe microphthalmia. 

Some people who have anophthalmia or microphthalmia have a change in the number or structure of chromosomes. Occasionally, environmental factors that affect the development of the eyes before birth, such as a shortage of certain vitamins, infections such as rubella, or exposure to substances that cause birth defects (teratogens), can cause anophthalmia or microphthalmia