Clinical Guidance

Walton and colleagues have shown that the phenotype can vary significantly in the same individual (one eye being more severely affected than the other) . CYP1B1. No consistent genotype-phenotype correlation has been observed for CYP1B1 pathogenic variants. Intra- and interfamilial variability is reported among individuals with identical CYP1B1 pathogenic variants . No information is available on correlation between the CYP1B1 pathogenic variants and the success of surgical therapy. LTBP2. No genotype-phenotype correlation has been observed for LTBP2 pathogenic variants. TEK. No genotype-phenotype correlation has been observed for TEK pathogenic variants.

Source: GeneReviews — "Primary Congenital Glaucoma"

Diagnostic Criteria

Suggestive Findings

Primary congenital glaucoma (PCG) should be suspected in infants or children with the following clinical features:

• Photophobia, blepharospasm, and excessive tearing

• Edema and opacification of the cornea with rupture of Descemet's membrane, known as Haab's striae

• Thinning of the anterior sclera and atrophy of the iris

• Structurally normal posterior segment except for progressive optic atrophy

• Absence of structural changes in the anterior chamber that are consistent with a diagnosis of anterior segment dysgenesis or associated systemic disease.

Establishing the Diagnosis

The diagnosis of PCG is established in a proband by the following clinical criteria:

Source: GeneReviews — "Primary Congenital Glaucoma"

Differential Diagnosis

A number of congenital ocular conditions can mimic PCG and must be considered by the clinician . For example, the nonspecific findings of tearing and redness of the eyes may mimic more common conditions such as conjunctivitis or congenital nasolacrimal duct obstruction; ocular irritation with photophobia and redness may mimic the more frequent problem of corneal abrasion. Congenital glaucoma can be subcategorized by age of onset into the following three types:

Source: GeneReviews — "Primary Congenital Glaucoma"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with primary congenital glaucoma (PCG), examination under anesthesia or sedation is warranted to make a complete assessment of both eyes. The examination includes the following:

• Measurement of intraocular pressure (IOP) within the first few minutes of anesthesia

• Measurement of corneal diameter

• Examination of the anterior segment

• Direct gonioscopy to rule out secondary glaucoma

• Dilated fundus examination to evaluate for optic nerve damage

• If the cornea is opaque, ultrasound biomicroscopy or optical coherence tomography to aid in evaluating the anterior segment structures

• Measurement of axial length

If the child is examined under anesthesia, consent may be obtained to perform the appropriate surgical procedure after evaluation under anesthesia. Consultation with a clinical geneticist and/or genetic counselor is recommended.

Treatment of Manifestations

The primary goal of treatment is to decrease IOP to prevent vision-threatening complications including corneal opacification and glaucomatous optic atrophy. Early treatment to control IOP will reverse some of these complications in children. A Cochcrane review analyzed the literature that addressed the surgical management of congenital glaucoma but could not draw any conclusions from the analysis . Surgical treatment. The following approach is based on the work of , , , , and . PCG is almost always managed surgically.

Source: GeneReviews — "Primary Congenital Glaucoma"

Clinical Guidance

Alpha-2 agonists should be avoided in children in the treatment of elevated IOP because of the risk for apnea and bradycardia.

Source: GeneReviews — "Primary Congenital Glaucoma"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Primary Congenital Glaucoma"

Surveillance Guidelines

Lifelong monitoring is necessary to ensure control of IOP to preserve remaining vision and to prevent further loss of vision; the intervals at which monitoring needs to be performed vary depending on the severity of disease and control of IOP. Once IOP is controlled and the child is visually rehabilitated, follow up is typically every three months to keep IOP at the "target" level, which depends on the severity of the glaucomatous optic nerve damage and the age of the individual. Standard clinical follow-up tests include optic nerve photography and visual field testing. The complete ophthalmic evaluation often requires examination under anesthesia or sedation in infants and in young and uncooperative children. This process may be challenging to the individual, the family, and the treating physician .

Source: GeneReviews — "Primary Congenital Glaucoma"