Ultrasounds can be used to diagnose anophthalmia during gestation. Due to the resolution of the ultrasound, however, it is hard to diagnose it until the second trimester. The earliest to detect anophthalmia this way is approximately 20 weeks. 3D and 4D ultrasounds have proven to be more accurate at viewing the fetus's eyes during pregnancy and are another alternative to the standard ultrasound.

It is possible to diagnose prenatally with amniocentesis, but it may not show a correct negative result. Amniocentesis can only diagnose anophthalmia when there is a chromosomal abnormality. Chromosomal abnormalities are only a minority of cases of anophthalmia.

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.

The presence of a small eye within the orbit can be a normal incidental finding but in most cases it is abnormal and results in blindness. The incidence is 14 per 100,000 and the condition affects 3-11% of blind children.

Lenz microphthalmia syndrome (or LMS) is a very rare inherited disorder characterized by abnormal smallness of one or both eyes (microphthalmos) sometimes with droopy eyelids (blepharoptosis), resulting in visual impairment or blindness. Eye problems may include coloboma, microcornea, and glaucoma. Some affected infants may have complete absence of the eyes (anophthalmia). Most affected infants have developmental delay and intellectual disability, ranging from mild to severe. Other physical abnormalities associated with this disorder can include an unusually small head (microcephaly), and malformations of the teeth, ears, fingers or toes, skeleton, and genitourinary system. The range and severity of findings vary from case to case. Formal diagnosis criteria do not exist.

Lenz microphthalmia syndrome is inherited as an X-linked recessive genetic trait and is fully expressed in males only. Females who carry one copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder, such as an abnormally small head (microcephaly), short stature, or malformations of the fingers or toes. Molecular genetic testing of BCOR (MCOPS2 locus), the only gene known to be associated with Lenz microphthalmia syndrome, is available on a clinical basis. One additional locus on the X chromosome (MCOPS1) is known to be associated with LMS.

Lenz microphthalmia syndrome is also known as LMS, Lenz syndrome, Lenz dysplasia, Lenz dysmorphogenetic syndrome, or microphthalmia with multiple associated anomalies (MAA: OMIM 309800). It is named after Widukind Lenz, a German geneticist and dysmorphologist.

A somewhat similar X-linked syndrome of microphthalmia, called oculofaciocardiodental syndrome (OFCD) is associated with mutations in BCOR. OFCD syndrome is inherited in an X-linked dominant pattern with male lethality.