Primary Congenital Glaucoma

By definition, primary congenital glaucoma is present at birth; however, its manifestations may not be recognized until infancy or early childhood. It is characterized by improper development of the eye's aqueous outflow system, leading to increased intraocular pressure (IOP), with consequent damage to ocular structures, resulting in loss of vision. Although the disease is relatively rare, the impact on visual development can be extreme. Early recognition and appropriate therapy of the glaucoma can significantly improve the child's visual future.

Primary congenital glaucoma is restricted to a developmental abnormality that affects the trabecular meshwork. This serves to distinguish it from other childhood glaucomas associated with other ocular and systemic congenital abnormalities, as well as childhood glaucomas that may be secondary to other ocular disorders, such as inflammation, trauma, and tumors.

Frequency

United States

Primary congenital glaucoma is estimated to affect less than 0.05% of ophthalmic patients and 0.05% of children. Although patients with the disease account for a significantly higher incidence in institutions for the blind, with various studies suggesting from 2-15%.

International

For genetic reasons, the incidence can be much higher, for example, in Saudi Arabia and among Romanian gypsies.

Mortality/Morbidity

The disease is bilateral in approximately 75% of cases.

Race

Congenital glaucoma affects all races

Sex

Male patients are found to have a higher incidence of the disease, comprising approximately 65% of cases.

Age

Primary congenital glaucoma usually is diagnosed at birth or shortly thereafter, and most cases are diagnosed in the first year of life.

The classic triad of manifestations in an infant or young child, any one of which should arouse suspicion of glaucoma, includes epiphora, photophobia, and blepharospasm.

Complete ophthalmologic examination

Large corneal diameters or increases in corneal diameters within the first few years of life provide strong additional support for the diagnosis of congenital glaucoma.

The average horizontal corneal diameter at birth is less than 10.5 millimeters. Distention of the globe in response to elevated intraocular pressure leads to enlargement of the cornea. If the measurement from corneoscleral junction horizontal to the opposing corneoscleral junction is more than 12 in the first year of life, it is highly suggestive of glaucoma. Grossly, this is more evident in asymmetric cases. Enlargement of the globe is called buphthalmos.

Corneal edema may be a direct result of the elevated intraocular pressure, producing a corneal haze that clears with normalization of the pressure. Haab striae represent tears in the Descemet membrane as a result of elevated intraocular pressure. In advanced cases, a dense opacification of the corneal stroma may occur secondary to the corneal edema, and it may persist, despite reduction of the intraocular pressure.

The early presence of glaucoma may deepen the anterior chamber. Because of the frequent occurrence of iris abnormalities in many types of both primary and secondary childhood glaucomas, the iris and angles always should be studied carefully and with thorough gonioscopy.

By the time that glaucoma is diagnosed in a child, the optic nerve head is usually abnormal. Variable cupping is present, usually annular in form, with nasalization of vessels and initial preservation of the well-vascularized rim. Optic nerve pallor is first seen temporally and represents an advanced stage of the disease.

Tonometry in the office setting often can be accomplished in a child's eye with a handheld instrument, such as a Perkins tonometer or a Tono-Pen. Accuracy of intraocular pressure measurements taken in the office may be artificially elevated from struggling on the part of the restrained infant.

Most cases of primary congenital glaucoma are sporadic in occurrence. However, evidence suggests that some cases of the disease may be transmitted through an autosomal recessive pattern, with variable penetrance, or a polygenic inheritance pattern. Polygenic inheritance is glaucoma resulting from the interaction of 2 or more nonhomologous genes. This has been shown in humans for the CYB1B1 and MYOC gene loci and in the mouse for CYP1B1 and FOXC1.[1]

CYP1B1, (locus GLC3A) the gene encoding cytochrome P4501B1 (P450, family I, sub family B, polypeptide 1) is associated with primary congenital glaucoma. GLC3B located on band 1p36 and GLC3C located on band 14q24.3 are loci that are linked to primary congenital glaucoma.

The incidence of CYP1B1 in familial cases is 93% in Saudi Arabia, 50% in Brazil, and 20-30% in ethnically mixed populations, and its incidence in nonfamilial (simplex) cases is 10-15%. Mice with this defect have structural abnormalities of the aqueous drainage system resembling those seen in humans.

Laboratory methods of diagnosing primary congenital glaucoma include the following:

• Hybridization analysis using hybridization of a mutant nucleic acid probe to the CYP1B1 gene

• Direct mutation analysis by restriction digest

• Sequencing of the CYP1B1 gene

• Hybridization of an allele-specific oligonucleotide with amplified genomic DNA

• Identification of the presence of mutant proteins encoded by the CYP1B1 gene

High-resolution anterior segment optical coherence tomography

Examination under anesthesia can supply important information about the childhood patient.

In addition to tonometry, corneal measurements, gonioscopy, and ophthalmoscopy should be performed in the operating room and carefully documented.

Intraocular pressures recorded under general anesthesia are usually lower than those obtained in the office because of the effects of the anesthetic agents. In unilateral cases, asymmetry of otherwise normal intraocular pressures may be diagnostic, along with other signs, such as corneal diameter.

If available in the operating room, pachymetry to quantify corneal edema and A-scan ultrasound to determine axial distention often are useful.[2]  Photography of the optic nerves is advised. Portable, handheld SD-OCT scanners allow for imaging of retinal nerve fiber layers. Microscope integratede OCT systems may also be used to determine ganglion cell and nerve fiber layer thicknesses and segmental changes. 

Multiple examinations may be needed before a definitive diagnosis can be made.

Primary congenital glaucoma almost always is managed surgically. Medical therapy is used only as a temporizing measure prior to surgery and to maximize pressure control after surgery.

The primary surgical techniques are designed to eliminate the resistance to aqueous outflow created by the structural abnormalities in the anterior chamber angle. This may be accomplished through an internal approach with goniotomy or through an external approach with trabeculotomy.

Goniotomy is a technique in which abnormal tissue is incised under direct visualization with the aid of a goniolens. This presumably relieves the compressive traction on the anterior uvea on the trabecular meshwork, which eliminates any resistance imposed by incompletely developed inner trabecular meshwork.

Viscotrabeculotomy (canalotomy) uses a high-viscosity viscoelastic to open the canal.[3]

In trabeculotomy, the Schlemm canal is identified by external dissection, and the trabecular meshwork is incised by passing a probe into the canal and, then, rotating it into the anterior chamber. One advantage of this procedure is that it can be performed in eyes with cloudy corneas, which is not the case with goniotomy.

Both goniotomy and trabeculotomy have their advocates; however, reported success rates for both procedures are approximately 80%. The worst prognosis occurs in infants with elevated pressures and cloudy corneas present at birth. The most favorable outcome is seen in infants operated between the second and eighth month of life. Surgery has been found to be less effective in preserving vision, with increasing age.

When multiple goniotomies and/or trabeculotomies have failed, the surgeon usually resorts to a filtering procedure, such as trabeculectomy. This may be accomplished either with or without antimetabolites. Should these procedures fail, shunts may be used. In those situations, in which all else has failed, ciliary body destructive procedures may be useful.[4, 5, 6, 7]

The follow-up care of patients with primary congenital glaucoma has several important facets. In the early postoperative period, close observation is required regarding success of the procedure. This may require multiple examinations under anesthesia.

Serious complications of surgical intervention include hyphema, infection, lens damage, and uveitis.

The most serious complications in children often are caused by general anesthesia. Because of anesthetic risks, bilateral procedures are indicated in some children.

Corneal edema may persist for weeks after successful reduction of the intraocular pressure. Changes in the optic nerve head provide the most important indicator of the course of the disease. Cupping can reverse in successfully treated cases.

The intraocular pressure also is a significant factor in postoperative visual capacity, with substantially better vision among those patients whose pressures remain no higher than 19.

Even when the intraocular pressure is well controlled, approximately 50% of children do not achieve vision better than 20/50.

Reduced visual acuity may result from persistent corneal edema, nystagmus, amblyopia, or large refractive errors.

The patient and family must understand that intraocular pressure elevation can recur at any age in individuals with primary congenital glaucoma, and these patients must receive follow-up care throughout their lives.

For excellent patient education resources, visit eMedicineHealth's Eye and Vision Center. Also, see eMedicineHealth's patient education articles Primary Congenital Glaucoma and Glaucoma Overview.