Daniel T. Weaver
Alex V. Levin
• Trabeculodysgenesis with aqueous outflow obstruction resulting in increased intraocular pressure detected at birth or by age 3–4 years
• Differentiated from secondary forms of childhood glaucoma that may be associated with: Persistent fetal vasculature, Peters anomaly, Axenfeld-Rieger spectrum, aniridia, retinopathy of prematurity, Marfan syndrome, and microspherophakia.
• Differentiated from acquired forms of pediatric glaucoma, such as aphakic or pseudophakic glaucoma, infectious, uveitic, or trauma-related glaucoma.
• Unilateral (25%) or bilateral (75%)
• Variable depending on country
• In some Middle Eastern countries: 1 per 4 to 10,000
• In the US, 0.38 per 100,000 (1)[C]
• In the US, 1.46 per 100,000 (1)[C]
• 3:2 Males:Females
• Family history
• 10% are autosomal recessive with variable penetrance and expressivity; autosomal dominant forms are less common.
• Four loci have been identified (2)[C]:
– GLC3A (2p21), due to mutations in the cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) gene
– GLC3B (1p36), gene not yet identified
– GLC3C (14q24.3), gene not yet identified
– GLC3D, due to mutations in the latent transforming growth factor binding protein 2 (LTBP2) gene
– Digenic with mutations in CYP1B1 and FKHL7/FOXC1/forkhead transcription factor
• Mutations in the myocillin (MYOC) gene have been identified in some cases of infantile glaucoma (autosomal dominant)
• Other loci are thought to exist but have not yet been characterized (2)[C]
• No known modes of prevention, other than genetic counseling. Prenatal testing only available if mutation known.
• There are several theories of pathogenesis:
– Barkan’s membrane covering the trabecular meshwork (may not be true)
– Anterior insertion of the ciliary body (due to arrest in the normal migration of the uvea) may contribute to narrowing or collapse of Schlemm’s canal
– Absent Schlemm’s canal
– Anomalous trabecular meshwork development (neural crestopathy)
• May result from genetic or teratogenic interference with neural crest cell formation, migration, and final differentiation during fetal development.
COMMONLY ASSOCIATED CONDITIONS
• Congenital glaucoma may be associated with many systemic syndromes including Sturge-Weber syndrome, Lowe syndrome, congenital rubella, Kniest skeletal dysplasia, Robinow syndrome, and others as well as with chromosomal abnormalities.
• Classic triad:
• Large or asymmetric eyes
• Iris heterochromia may be present
• Cloudy cornea(s)
• Rapid myopic shift
• Exam under anesthesia or sedation may be needed to detect the following signs:
– Long axial length by A-scan
– Large corneal diameter (>12 mm for full term infants)
– Hand held slit-lamp examination may reveal cloudy corneas or Haab’s striae (breaks in Descemet’s membrane, usually horizontal)
– Cycloplegic streak retinoscopy may be useful in detecting progressive myopia or rapid loss of hyperopia
– Tonometry should be obtained at anesthesia induction with the Tonopen or Perkins tonometer. Normal infant IOP is 10–15 mm Hg; IOP in congenital glaucoma typically 25–35 mm Hg
– Gonioscopy may reveal an anterior iris insertion and indistinct trabecular meshwork.
– Ophthalmoscopy will reveal optic nerve cupping, which is usually concentric with healthy surrounding disc tissue until late stages (sloping, notching, and hemorrhage are uncommon). May be reversible.
• In the office, assess the following:
– Visual acuity
– Pupils (assess for afferent pupillary defect)
Beware of falsely high (hypercarbia, speculum, pressure from anesthetic mask, 2–5 minutes after intubation, ketamine) or falsely low (corneal epithelial edema, halothane, hypocarbia) IOP