Anophthalmia refers to complete absence of the globe in the presence of ocular adnexa (eyelids, conjunctiva, and lacrimal apparatus). Microphthalmia is defined as a globe with a total axial length (TAL) that is at least two standard deviations below the mean for age. Classification of microphthalmia is according to the anatomic appearance of the globe and severity of axial length reduction. Severe microphthalmia refers to a globe with a corneal diameter less than 4 mm and a TAL less than 10 mm at birth or less than 12 mm after age one year. Simple microphthalmia refers to an eye that is anatomically intact except for its short TAL. Complex microphthalmia refers to an eye with anterior segment dysgenesis and/or posterior segment dysgenesis. Anophthalmia/microphthalmia (A/M) can be unilateral or bilateral. A/M is a heterogenous condition with various etiologies. It can be isolated or can occur with other anomalies or as part of a well-defined syndrome. One-third of individuals with A/M have associated malformations. Heritable causes of A/M include chromosome abnormalities and syndromic or nonsyndromic single gene disorders.
The diagnosis of anophthalmia/microphthalmia (A/M) is based on clinical examination and imaging studies including: A-scan ultrasonography to measure total axial length; B-scan ultrasonography to evaluate the internal structures of the globe; and CT scan or MRI of the brain and orbits to evaluate the size and internal structures of the globe, the optic nerve and extraocular muscles, and brain anatomy. Evaluation for other malformations, assessment of hearing, chromosome analysis, family history, and parental eye examinations may help establish the underlying cause. Mutations in the following genes are associated with A/M: SIX3, HESX1, BCOR, SHH, PAX6, RAX, CHD7 (CHARGE syndrome), IKBKG (incontinentia pigmenti), NDP (Norrie disease), SOX2 (SOX2-related eye disorders), POMT1 (Walker-Warburg syndrome), and SIX6.
If a proband has an inherited or de novo chromosome abnormality or a specific syndrome associated with A/M, genetic counseling, and possibly genetic testing, for that condition is indicated. Rarely, isolated anophthalmia may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Assuming that one-half of cases are sporadic and one-half inherited, the empiric risk for sibs without a clear etiology or family history is 10%-15%. Prenatal diagnosis for pregnancies at increased risk for chromosome abnormalities and some syndromic forms of A/M is possible. Transvaginal ultrasound examination may detect the eyes from 12 weeks' gestation onward; in most reports, eye malformations are detected only after 22 weeks' gestation. The sensitivity of transvaginal ultrasound examination in detecting A/M is not known. Three-dimensional and four-dimensional ultrasound examination may be used in some centers to detect complex malformations of the face, including A/M. MRI may be a useful adjunct to ultrasound examination in detection of anophthalmia.