Primary Congenital Glaucoma
Primary congenital, or infantile, glaucoma is elevated intraocular pressure with onset in the first year of life. It occurs in about 1 out of 10,000 births and results in blindness in approximately 10% of cases and reduced vision (worse than 20/50) in about half of all cases.
Primary congenital glaucoma typically presents in the neonatal or infantile period with the classic triad of epiphora, photophobia, and blepharospasm. Corneal clouding from microcystic edema can occur, accompanied by gradual enlargement of the corneal diameter. As the edema extends through the corneal stroma, breaks called Haab striae can occur in Descemet’s membrane. These breaks are permanent and can be visualized after the edema has subsided. Untreated, the natural history is grim, with most cases progressing to irreversible corneal opacification, buphthalmos (abnormally large “ox eye”), and eventual blindness.
The etiology of primary congenital glaucoma is not known. There are several theories – membrane covering the anterior chamber angle (Barkan membrane), trabecular meshwork obstruction, or developmental arrest of anterior chamber tissue in utero. The disease is more common in males, typically is bilateral, and does not have a racial or geographic preference. Most cases are sporadic, but there is an autosomal recessive inheritance pattern for some cases. The prevalence is higher in cultures with consanguinity, particularly those with a high carrier rate of CYP1B1 gene (GLC3A locus on chromosome 2p21). There appears to be no association with adult primary open-angle glaucoma.
The only known risk factors are genetic - consanguinity and affected siblings. The risk of congenital glaucoma in the second child is approximately 5%, and the risk increases to 25% with two affected siblings.
Primary congenital glaucoma may represent an arrest of the normal development of the anterior chamber. The iris and ciliary body have an anterior insertion with an open angle. The trabecular meshwork is present and appears patent, but the trabecular beams are thickened and the deeper tissues appear compressed. The juxtacanalicular space is also thickened and compressed and is filled with an amorphous extracellular substance that contains collagen. Under the electron microscope, these structures appear similar to the normal fetal anterior chamber development at the 7th or 8th month of gestation.
Primary congenital glaucoma occurs from an increase in the intraocular pressure in the first year of life. The increased intraocular pressure is thought to occur from reduced aqueous outflow at the level of the trabecular meshwork.
There is no known way to prevent primary congenital glaucoma. Early detection and treatment are essential to maximize visual potential.
The diagnosis of primary congenital glaucoma can often be made clinically, even without an accurate measurement of intraocular pressure. The hallmark of the disease, however, is an elevated intraocular pressure in the absence of other conditions that can cause glaucoma, such as Axenfeld-Reiger syndrome or aphakia.
The classic clinical triad is epiphora, photophobia, and blepharospasm in the absence of the discharge that typically accompanies a nasolacrimal duct obstruction or conjunctivitis. A positive family history is helpful but often is not present since most cases are sporadic.
The physical exam follows the standard ophthalmology exam for infants and young children. The vision assessment should specifically look for asymmetry in unilateral cases and the presence of nystagmus and/or reduced fixation response in bilateral cases. The anterior segment exam should specifically look at the corneal diameter. A newborn’s cornea is typically 9.5-10.5 mm in diameter and increases to 10.0-11.5 mm by age 1. Any diameter above 12.5 mm suggests an abnormality, especially if there is asymmetry between the two eyes. The cornea should also be examined for clarity and the presence of Haab striae (breaks in Descemet’s membrane), usually best seen after dilation using retroillumination. A measurement of intraocular pressure may be possible using topical anesthesia in a cooperative child, although an examination under anesthesia may be required in a struggling child to prevent an artificially elevated pressure measurement. The anterior segment exam should also look for structural abnormalities of the cornea, iris, and lens. After dilation, a refraction should be performed to look for myopia, astigmatism, and any corneal irregularity. The fundus exam should include a careful exam of the optic nerve to look for asymmetric or large cupping and for any structural abnormalities.
The clinical signs of primary congenital glaucoma include epiphora, conjunctival erythema, corneal enlargement, corneal clouding, Haab striae, abnormally deep anterior chamber, myopia and/or astigmatism, and enlarged optic nerve cupping.
The primary symptoms of primary congenital glaucoma are epiphora, photophobia, and blepharospasm. Reduced vision can also occur from corneal edema or progressive myopia and/or astigmatism.
The clinical diagnosis of primary congenital glaucoma can be made by measuring an elevated intraocular pressure in the presence of the clinical signs created by the elevated pressure – corneal edema and enlargement, Haab striae, myopia, astigmatism, and optic nerve cupping.
The main diagnostic test for primary congenital glaucoma is the measurement of the intraocular pressure. In a cooperative infant, this measurement can be obtained in the clinic setting with a Perkins applanation tonometer or a Tonopen. In older patients, standard Goldmann applanation tonometry can be performed. For the uncooperative patient, an examination under anesthesia should be performed. Because most anesthetic agents can lower the intraocular pressure, measurements should be obtained as soon as possible after induction of anesthesia. The normal intraocular pressure is lower in infants and young children than adults. A newborn has an average intraocular pressure of 10-12 mm Hg, increasing to 14 mm Hg by age 7 or 8 years of age. An asymmetric measurement or an elevated measurement in the presence of other clinical signs helps make the diagnosis of glaucoma.
There is limited utility of laboratory tests for primary congenital glaucoma. A-scan ultrasound can serially measure axial length, providing an objective parameter to evaluate possible progression of disease.
The differential diagnosis depends on the major presenting symptom. For the classic triad of epiphora, photophobia, and blepharospasm, the differential diagnosis includes nasolacrimal duct obstruction, conjunctivitis, corneal abrasion, and uveitis. For corneal clouding and edema, the differential diagnosis includes congenital corneal dystrophies, birth trauma with tears in Descemet’s membrane, keratitis, congenital ocular anomalies like sclerocornea or Peters anomaly, or storage disesases like mucopolysaccharidoses or cystinosis. For corneal enlargement, the differential diagnosis includes high axial myopia and megalocornea. For optic nerve cupping, the differential diagnosis includes physiologic cupping, optic nerve coloboma, optic nerve atrophy, optic nerve hypoplasia, and an optic nerve malformation.
The management of primary congenital glaucoma is directed toward lowering and controlling the intraocular pressure and treating the secondary complications such as refractive change and amblyopia that develop during the course of the disease.
The mainstay of treatment is angle surgery, either goniotomy or trabeculotomy, to lower intraocular pressure by improving aqueous outflow. If angle surgery is not successful, trabeculectomy enhanced with mitomycin C or glaucoma implant surgery with a Molteno, Barveldt, or Ahmed implant can be performed. In resistant cases, cycloablation can be performed using an Nd:YAG laser, diode laser, or cryotherapy. Medical therapy, either topically or orally, is typically used as a temporizing measure prior to surgery and to supplement intraocular pressure control after surgery.
Medical therapy for primary congenital glaucoma is typically used as an adjunct to surgery. Oral carbonic anhydrase inhibitors include acetazolamide (Diamox 10-20 mg/kg/day divided into 3 or 4 doses) and methazolamide (Neptazane 5-10 mg/kg QID). Side affects include weight loss, lethargy, and metabolic acidosis. Topical carbonic anhydrase inhibitors include dorzolamide 2% (Trusopt) and brinzolamde 1% (Azopt) drops TID. These medications may produce less reduction in intraocular pressure than oral carbonic anhydrase inhibitors, but also appear to have fewer systemic side affects. Beta-blockers (timolol or equivalent) can also be given topically, usually using a lower starting concentration of 0.25% drops BID. Side affects include respiratory distress, caused by apnea or bronchospasm, and bradycardia. A combined beta-blocker/carbonic anhydrase inhibitor (Cosopt) drop BID has been shown to be effective in reducing intraocular pressure in children requiring more than one topical medication. Prostaglandin analogs latanoprost 0.005% (Xalatan), travoprost 0.004% (Travatan), and bimatoprost 0.03% (Lumigan) have been effective in reducing intraocular pressure, although use is discouraged in the presence of inflammatory conditions. Miotic agents (pilocarpine, echothiophate) and adrenergic agents (epinephrine, dipivefrin) are not usually effective. The alpha2-adrenergic agonist brimonidine (Alphagan) is contraindicated in children under age 2 because of potentially serious lethargy, hypotonia, hypothermia, and CNS depression.
Medical follow up
Primary congenital glaucoma requires lifelong serial measurements of intraocular pressure, corneal diameter, refractive error, and optic nerve cupping. Any change in medical regimen should be followed in 1-2 weeks to assess the efficacy of the new treatment regimen. If an adequate assessment of the clinical response is not possible in the outpatient clinic, an examination under anesthesia can be performed.
There are four major surgical options for primary congenital glaucoma. Angle surgery to establish aqueous outflow is the initial procedure of choice. Goniotomy is preferred when the cornea is clear enough to permit visualization of anterior segment structures. An incision is made across the trabecular meshwork under direct gonioscopic visualization. When the cornea is not clear enough to permit visualization of the angle, a trabeculotomy, where Schlemm’s canal is isolated using an external approach and connected to the anterior chamber through an incision through the trabecular meshwork, is the procedure of choice. A modification of the trabeculotomy using a 6’0 Prolene suture or lighted "canaloplasty" device threaded through Schlemm’s canal can open all 360 degrees of trabecular meshwork at the first surgery. If the initial angle surgery is not successful, one additional angle surgery is typically performed before proceeding to another type of surgery. If the second angle surgery is not successful and intraocular pressure cannot be controlled medically, the next procedure can either be a glaucoma implant, Molteno, Barveldt, or Ahmed, or a traditional trabeculectomy, with or without mitomycin C. The final procedure that can be used is cycloablation of the ciliary body using the Nd:YAG laser, diode laser, or cryotherapy. A recent variation of the technique using a micro-endoscopic and direct application of the diode laser to the ciliary processes from an intraocular approach appears to have greater efficacy and fewer complications than the traditional transscleral approach, although the retreatment rate is high for all methods of cycloablation.
Surgical follow up
In the short term, these patients require frequent follow up to monitor for infection or excessive inflammation. Long term, just like patients on medical therapy, these patients require serial measurements of intraocular pressure, corneal diameter, refractive error, and optic nerve cupping. If an adequate assessment of the clinical response is not possible in the outpatient clinic, an examination under anesthesia can be performed.
The most common complication after surgery is poor control of intraocular pressure. The success rate for angle surgery is approximately 80% after 1 or 2 procedures, while the other procedures report a success rate of 33-80%. Other complications after angle surgery include hyphema, damage to the crystalline lens resulting in cataract, and infection, including endophthalmitis. Complications of trabeculectomy include hypotony, late bleb leakage, and endophthalmitis. Complications of glaucoma implant surgery include leakage, erosion of the shunt, migration of the shunt, and endophthalmitis. Complications of cycloablation included significant inflammation and possible phthisis with resulting blindness.
The prognosis for primary congenital glaucoma depends on the age of onset. Glaucoma that presents at birth is more difficult to treat, with at least half of the affected eyes becoming legally blind. Likewise, glaucoma that has progressed to create a corneal diameter of 14 mm or more has a similarly poor prognosis. On the other hand, glaucoma that presents from 3-12 months of age has a favorable prognosis, with 80-90% of cases achieving good control of intraocular pressure with angle surgery. The vision loss in children is multifactorial and does not depend exclusively on the health of the optic nerve. Affected children can develop significant myopia from axial elongation of the globe, astigmatism from unequal enlargement of the cornea, corneal scarring, and even dislocation of the lens from excessive anterior segment enlargement. Correction of the refractive error and aggressive treatment of associated amblyopia and/or strabismus is required to maximize visual outcome.
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