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Congenital and Pediatric Glaucoma
Ali Aminlari, MD, FACS
Reprinted with permission from Aminlari A. Congenital and pediatric glaucoma. In: Sassani J, ed. Ophthalmic Fundamentals: Glaucoma. Thorofare, NJ: Slack; 2000:163.
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Primary congenital glaucoma is the most common type of glaucoma in children; however, it occurs less frequently than the primary glaucomas that are seen in adults (Slide 1). It has been estimated that every ophthalmologist will have the chance to see only one case every 5 years, and an ophthalmic resident has the opportunity to see only two or three cases of congenital glaucoma during his or her training. Approximately 60% to 70% of congenital glaucoma cases are bilateral.
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Primary congenital glaucoma usually is diagnosed at birth or shortly thereafter. Most cases are diagnosed in the first year of life; however, it may become apparent at anytime throughout childhood or early adult life. Photophobia, blepharospasm, and epiphora are the most common presenting symptoms of congenital glaucoma (Slide 2 and Slide 3).
During the first 3 years of life, the collagen fibers of the eye are softer and more elastic than in older individuals. Thus, elevation of intraocular pressure (IOP) in children younger than 3 years of age (infantile glaucoma) causes rapid enlargement of the globe. The globe enlargement occurs primarily at the corneoscleral junction. As the cornea and limbus enlarge, the endothelium of the cornea and Descemet's membrane are stretched. This stretching can result in a linear rupture of the Descemet's membrane (Haab's striae). The Descemet's membrane rupture may occur acutely, causing an influx of aqueous into the stroma and epithelium, resulting in sudden corneal edema. The corneal edema produces photophobia, blepharospasm, and tearing. The child becomes irritable and may hide his or her face from bright lights.
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Continuous enlargement of the eye leads to progressive myopia and scleral thinning. In advanced cases, these changes result in a bluish appearance of the sclera and severe stretching of the corneoscleral junction to the extent that the limbus cannot be identified (Slide 4). The iris also is stretched and appears thin. The iris root and trabecular meshwork become degenerated and Schlemm's canal collapses. The ciliary body, choroid, and the retina are atrophic. Zonular fibers may break resulting in dislocation of the lens. The optic disc eventually becomes cupped. In such advanced cases, the prognosis is poor, and any intraocular procedure may lead to phthisis bulbi.
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Late onset glaucoma, after age 3 years, is termed juvenile glaucoma (Slide 5 and Slide 6). These patients develop glaucoma from the same anomalies as neonates and infants with primary congenital glaucoma. Their glaucoma presents at a later date either as a primary process or as a recurrence after seemingly successful surgery. They usually present like chronic glaucoma in adults. This group is often overlooked because the possibility of juvenile glaucoma is not considered.
In juvenile glaucoma, the posterior sclera may still have some elasticity permitting it to expand secondary to high IOP. Progressive myopia results from such expansion; however, the cornea does not enlarge. Therefore, progressive myopia, although it is not a pathognomonic sign, should prompt consideration of congenital glaucoma in this age group.
Classification of Glaucoma in Children
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Glaucoma in infants and children is classified into three groups: primary congenital or infantile glaucoma, secondary glaucoma, developmental glaucoma.
Primary congenital or infantile glaucoma
Primary
congenital glaucoma refers to a type of glaucoma that results from an isolated
maldevelopment of the trabecular meshwork region not associated with other
developmental ocular or systemic anomalies or any ocular diseases that can
cause an increase in IOP. It is the most common type of glaucoma in infancy,
occurring in approximately one per 10,000 live births.1
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Secondary glaucoma
Secondary glaucoma results from
ocular pathology (e.g., inflammation or tumors). This form of glaucoma is
usually said to be less common than the primary type; however, Barsoum-Homsy
and Chevrette studied 63 cases (95 eyes) of glaucoma in children and found
secondary glaucoma to be the most common type of glaucoma in children.2
Developmental glaucoma
Developmental glaucoma is a
type of congenital glaucoma associated with developmental anomalies of the eye
and other parts of the body, which present at birth (Slide 7). Hoskins has classified congenital glaucoma on the basis of clinically
identifiable anatomic defects of the eye.3 These congenital
anatomical defects may involve trabecular meshwork, cornea, iris, or a
combinations of these structures. The Shaffer-Weis classification divides the
developmental glaucomas into primary, secondary, and acquired glaucoma.4
Approximately 90% of primary congenital glaucoma cases are sporadic in occurrence. In 10% of patients where a hereditary pattern is evident, it is believed to be autosomal recessive.5
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A basic understanding of embryology of the anterior segment of the eye is helpful in relation to the pathogenesis of childhood glaucoma.
Tissue derived from the neural crest has been demonstrated to contribute extensively to the embryologic development of the head and neck, particularly ocular tissues. In the head and neck, tissue derived from neural crest functions embryologically in a manner similar to mesoderm in other bodily regions. The reader is referred to extensive reviews, which discuss the role of neural crest tissue in cephalic embryology and in the classification of the glaucomas.6-9 Only a brief overview is presented in this tutorial.10-15
The anterior chamber angle is formed by three primordial embryonic tissues:
The anterior surface of the iris meets the corneal endothelium at 5 months' gestation to form the peripheral aspect of the anterior chamber angle.16 Adjacent and posterior to this area, cells form the trabecular meshwork and the ciliary body overlaps the trabecular meshwork.
The trabecular meshwork is gradually exposed to the anterior chamber as the iridocorneal angle deepens and moves posteriorly.
The mechanism of the tissue changes that lead to the formation of the anterior chamber angle is not well known. There are several theories including atrophy of tissue and cell death in the angle.17 Another theory proposes that the angle is formed by a process of cleavage between the cells that form the trabecular meshwork and the cells that form the root of the iris and ciliary body.18 Anderson believes that the trabecular meshwork becomes exposed to the anterior chamber by posterior sliding of the iris and ciliary body.16 Continued posterior sliding of the uveal tissue occurs during the first 6 to 12 months of life. This forms the angle recess, which is not normally present at birth.
The iris and ciliary body in primary congenital glaucoma are similar to one of seven or eight months' gestation rather than one which is at full-term development.16 The iris insertion and anterior ciliary body overlap the posterior portion of the trabecular meshwork. Histopathologic examination of the angle structure in primary congenital glaucoma demonstrates thickening of trabecular beams, thickened cords of uveal meshwork, and compression of trabecular meshwork with a resultant decrease of trabecular spaces.19 These changes may be the cause of obstruction to the outflow of aqueous fluid and, therefore, result in elevation of IOP.
Thickening of juxtacanalicular tissue and production of an amorphous material in the subendothelial area of the inner wall of Schlemm's canal also have been found in histopathologic examination of infants' eyes with congenital glaucoma.19,20
Anterior insertion of longitudinal and circular fibers of ciliary muscle into trabecular meshwork rather than into scleral spur is suggested by Maumenee to be a typical histopathologic finding in primary congenital glaucoma.21
Barkan's membrane, which is a postulated semitransparent membrane that extends over trabecular meshwork, is suggested to be the cause of elevated IOP in childhood glaucoma.22 The existence of such a membrane has not been verified.23
Ocular embryology will be discussed further relative to some
Diagnosis of Congenital Glaucoma
In the majority of cases, the clinical presentation of primary congenital glaucoma leads to the diagnosis of this disease. A complete office examination or an examination under anesthesia is necessary in evaluating children suspected to have glaucoma.
An office examination can be performed on children as young as 3 years of age using chloral hydrate sedation, if needed. A brief office examination can be performed on children younger than 6 months of age. Pacifying the child with a bottle is helpful when checking IOP. Various tonometers (e.g., Schiötz, Perkins applanation, or hand-held electronic tonometers [Tono-Pen, Mentor O&O, Inc, Norwell, Mass]) can be used.
For a complete ophthalmological examination, general anesthesia is usually required in infantile glaucoma. Mask anesthesia is adequate and safe for a brief follow-up examination, but endotracheal intubation is necessary when surgery is required or when the examination is expected to be prolonged.
Except for ketamine, which may increase IOP, general anesthetics usually lower the IOP. It is recommended that the IOP be checked in early stage of anesthesia to reduce errors. Different types of tonometers can be used for IOP check. The Schiötz tonometer occasionally is used; however, it is not as accurate as the Perkins hand-held applanation tonometer. The Tono-Pen is convenient and easy to use. In my experience, Tono-Pen reading may be 2 mm Hg to 3 mm Hg lower than an applanation measurement.
The normal IOP in infants under anesthesia is usually in the low teens. A pressure of 20 mm Hg or more should be considered abnormal.
Elevated IOP alone is not sufficient to confirm a diagnosis of congenital glaucoma. Other signs of this disease (e.g., corneal haze, increased corneal diameter, and increased optic disc cupping) are as important as elevated IOP.
Accurate measurement of corneal size is important in the diagnosis and follow-up examination of children with glaucoma. Using calipers for this purpose, the corneal diameter measurement should be taken from limbus to a similar point 180° away at the opposite limbus. The 95% ranges of normal corneal diameters are: 9.4 mm to 11.0 mm at age 1 month, 10.5 mm to 11.7 mm at age 6 months, and 10.8 mm to 12.0 mm at age 12 months.24 Morin and colleagues found a corneal diameter of 11 mm or less in only 24% of patients 3 months old or younger with primary congenital glaucoma and only in 9% of patients older than 3 months.25 In congenital glaucoma, the diameter of cornea may enlarge to as much as 17 mm. Changes in corneal diameter less than 0.5 mm in the follow-up examination should be interpreted cautiously.
A 14-mm Koeppe lens provides a clear view of the angle of the eye, and a hand-held microscope with a Barkan light or any type of illuminator is necessary for gonioscopy during anesthesia. If the cornea is cloudy, removing the corneal epithelium clears the view. During gonioscopy, the site of iris insertion should be evaluated carefully. In congenital glaucoma, the iris usually is inserted anterior to scleral spur, and the angle recess is poorly formed.
Dilated fundus examination and disc evaluation are essential in diagnosing congenital glaucoma. Cupping of the optic disc occurs much faster than in adults. Optic disc cupping larger than 30% of disc diameter, especially if asymmetric between two eyes, is strong evidence that the disc is under pressure and may be glaucomatous.
The normal infant optic disc is as pink as in the normal adult. In the past, it had been thought that the optic disc in a newborn was paler than in adults; however, Khodadoust,26 and Shaffer and Hetherington27 have demonstrated the ease with which blood could be shunted from the infant's optic disc by a small increase in IOP. Even the pressure of a lid speculum or the pressure generated by separating the lids may cause shunting of blood and a pale appearing disc.
Changes in the optic disc occur readily with changes in IOP in infants.28 Richardson and Shaffer28 in 1966 and Khodadoust26 in 1968 documented the early response of the infant disc to elevated IOP. These findings demonstrate the greater vulnerability of the infant optic disc to increased IOP compared to the adult disc.
How rapidly does this cupping occur in infant eyes? When congenital glaucoma is diagnosed at birth, it is not uncommon to find a significant degree of optic disc cupping. This finding proves that disc damage can start during intrauterine development. If IOP is not controlled, increased cupping can be demonstrated in 4 to 6 weeks. This early rapid change in disc contour may be related to mechanical distortion in the disc supporting elements, and in its initial stages may not represent neuronal loss. Thus, posterior bowing of the lamina cribrosa is a late occurrence in adult glaucoma but it occurs early in infants.
Glaucomatous cupping in infants, unlike in adults, is usually reversible after normalization of IOP. This was first reported in 1965 by Chandler and Grant.29 Marked decreases in cupping commonly are seen at 4 to 6 weeks after normalization of pressure. The younger the child, the faster this reversibility. This phenomenon is so constant that it can be used as the main criterion for control of glaucoma in infants rather than using the height of IOP. I have observed a marked decrease in cup-to-disc ratio in some of our patients in just 2 weeks following a successful goniotomy. Such a rapid change in optic disc cupping is probably related to mechanical changes cited earlier. Improvement in the amount of cupping may be limited by many factors including the extent of nerve fiber loss.
Children younger than age 3 with epiphora and photophobia should be suspected as having congenital glaucoma. Nasolacrimal duct obstruction also must be considered; however, it is rarely accompanied by photophobia.
Conjunctivitis, corneal abrasion, some types of corneal dystrophies (e.g., Meesman's and Reis-Buckler's) also may present with irritation and tearing. A careful history and examination will reveal the correct diagnosis.
High myopia can present with a large eye, but without other signs and symptoms of congenital glaucoma. Similarly, megalocornea, which is a very large corneal diameter, may mimic the corneal enlargement of congenital glaucoma (Slide 8). Eyes with (congenital) megalocornea have deep anterior chambers and the corneal diameter may be as large as 16 mm; however, the IOP is normal and no Descemet's rupture or corneal edema should be present. Photophobia or tearing is not present with this condition.
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Megalocornea is a sex-linked disorder and occurs mainly in males. The IOP of these patients should be monitored closely, as they may develop glaucoma. I have followed a 4-year-old boy with megalocornea who developed glaucoma at the age of 10.
Traumatic rupture of Descemet's membrane is another condition to be differentiated from congenital glaucoma. Forceps delivery is a common cause of unilateral Descemet's rupture, mostly in the left eye, which is due to the high incidence of left anterior occiput presentation at birth. These types of Descemet's ruptures are commonly vertical but they may run in various directions. Corneal edema may be present with photophobia, lacrimation, and blepharospasm, but IOP is normal. Treatment consists of topical steroids to reduce inflammation. Corneal edema resolves when reendothelialization of the Descemet's break is complete. This repair takes 6 to 10 weeks.
Congenital hereditary endothelial dystrophy (CHED) and posterior polymorphous corneal dystrophy (PPED) involve a cloudy cornea at birth or later in life. The differentiation from congenital glaucoma is crucial. Normal IOP and corneal diameter, which do not increase in time, and mainly stromal rather than epithelial edema speak in favor of dystrophy rather than glaucoma. Corneal cloudiness is due to corneal edema and thickening of stroma. These may sometimes be accompanied by photophobia and tearing. Occasionally these patients may have been misdiagnosed and subjected to unnecessary glaucoma surgery. I have observed this misdiagnosis on one occasion.
Other congenital anomalies such as sclerocornea, cystinosis, and mucopolysaccharidosis, which may be accompanied by a cloudy cornea, should be differentiated from congenital glaucoma. Anomalies of the optic nerve head are sometimes difficult to distinguish from glaucomatous cupping. Tilted disc, coloboma of the nerve head, pits, hypoplasia, and highly myopic discs are in this category.
Corneal edema due to keratitis in newborns (e.g., rubella keratitis) should be differentiated from congenital glaucoma.
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Several developmental anomalies of the eye have been described, which have traditionally been believed to represent dysgenesis of mesoderm of the anterior ocular segment but are probably secondary to abnormalities in development of neural crest-derived tissue. These conditions may involve the cornea, iris, lens, or iridocorneal angle. Glaucoma may be present with any of these conditions including Axenfeld's, Rieger's, and Peter's anomalies.
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Posterior embryotoxon or prominent Schwalbe's line is present in approximately 15% of the general population (Slide 9).30 Axenfeld reported a condition in which strands of peripheral iris traversed the angle of the eye and attached to the prominent Schwalbe's line (Slide 10).31 In Rieger's anomaly, there is stromal hypoplasia of the iris in addition to Axenfeld changes.32 There may be some iris hole formation, ectropion uveae, and corectopia. If Rieger's anomaly is part of a systemic manifestation of this disorder, then it is called Rieger's syndrome. These systemic findings include facial and dental anomalies, including broad and flat nasal bridge, telecanthus (wide interorbital distance), hypertelorism (wide intercanthal distance), maxillary hypoplasia, and a protruding lower lip.33
About 50% of patients with Axenfeld's or Rieger's anomaly develop glaucoma. The incidence is slightly higher in Rieger's. Diagnosis is generally made between age 5 and 30 years.34
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In 1897, Von Hippel reported a case of buphthalmos with bilateral central corneal opacities and adhesion of these opacities to the iris.35 Peters described similar cases in 1906, which became generally known as Peters' anomaly.36 Most of these cases are hereditary with autosomal recessive inheritance. They are generally bilateral and present at birth. Corneal endothelium and Descemet's membrane are missing in the center of the cornea with thinning and opacification of overlying stroma. Cataract may be present. Approximately 50% of patients with this anomaly have glaucoma. Goniotomy or trabeculotomy is not as effective as in primary congenital glaucoma, and trabeculectomy may offer the best chance of success. Corneal graft frequently is necessary.
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Table 1 lists other developmental anomalies that may be accompanied by congenitalglaucoma. Sturge-Weber syndrome is characterized by a hemangioma of the skin along the trigeminal distribution and ipsilateral leptomeningeal angioma. The latter may cause a seizure disorder. Involvement is usually unilateral but bilateral lesions may occur. Cortical calcification is a characteristic radiographic sign (railroad tracks). Fifty percent of these patients develop glaucoma, which is more common when the hemangioma involves the upper eyelid (Slide 11 and Slide 12). Glaucoma may occasionally be present on the side opposite the upper lid involvement (Slide 13).
The cause of glaucoma in Sturge-Weber syndrome is believed to be increased episcleral venous pressure. A congenital anomaly of the anterior chamber angle similar to primary congenital glaucoma also has been described.37
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The management of glaucoma in Sturge-Weber syndrome is primarily surgical when it presents early in life; however, medical treatment should be tried when it occurs later in life.
Combined trabeculotomy-trabeculectomy may offer the best hope of surgical success. Aniridia is a bilateral condition, which may be associated with multiple ocular defects including corneal opacity, cataract, and foveal hypoplasia. It is inherited as autosomal dominant. The name aniridia is a misnomer, because the iris is only partially absent. A rudimentary stump always is present. Wilms tumor of kidney or other genitourinary anomalies may be present.
Glaucoma occurs in 50% to 75% of patients with aniridia, but usually does not appear before late childhood or early adolescence. Medical therapy may control the pressure for a short period; however, the majority of patients require surgery to control the pressure. Trabeculotomy or goniotomy may not be helpful, and filtration procedures often fail. Cyclocryotherapy is effective in some cases.
Treatment of Congenital Glaucoma
The management of primary congenital glaucoma is essentially surgical.38 Goniotomy and trabeculotomy have been the most successful procedures for congenital glaucoma.39,40 Goniopuncture was proposed by Scheie and is believed to increase success rate.41 These procedures are more successful in infants younger than 1 year.
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Medical treatment is used primarily in the preoperative management of these patients. Beta-blockers (e.g., timolol or betaxolol) may be administered one drop twice daily for a short period. Nevertheless, one must be aware of the comparatively high drug concentration of one drop of such medications applied to an infant. Thus, these patients must be watched carefully for the development of side effects, which may be life threatening. Pilocarpine, in low concentration, and carbonic anhydrase inhibitors (e.g., acetazolamide, 5 mg to 10 mg per kilogram of body weight), in suspension can be given. Dorzolamide, a topical carbonic anhydrase inhibitor, may not be as effective as the oral suspension. The newer glaucoma drops, brimonidine and latanoprost have not yet been approved to be used in children.
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Surgical procedures such as goniotomy and trabeculotomy are effective when performed skillfully (Slide 14 and Slide 15). One or two goniotomies can cure 94% of children with congenital glaucoma presenting within the first 2 years of life.42 Congenital glaucoma presenting within the first month of life or after age 2 years has a poorer surgical outcome.
I prefer trabeculotomy to goniotomy. Nevertheless, others indicate no preference between the two procedures.40,43,44
Serious complications in trabeculotomy or goniotomy are rare. Difficulty locating Schlemm's canal, transient hyphema, cyclodialysis or iridodialysis, and cataract or lens dislocation rarely occur. Hyphema can be prevented by injecting air into the anterior chamber if bleeding occurs intraoperatively. Residual hyphema is usually cleared in 24 hours; however, hyphema may at times be large and persistent. If two or three goniotomies or trabeculotomies fail, trabeculectomy is the next best treatment. Antimetabolites can be used in low doses. Glaucoma setons can be inserted if trabeculectomy fails. Cyclodestructive procedures have a very low success rate.45
Topical steroids and antibiotics should be used for 4 to 6 weeks. The patient should be examined 2 to 4 weeks after the initial procedure, sooner if indicated. Decreased photophobia and tearing is a good indication that the treatment has been successful, at least partially. If there is no increase in corneal diameter or optic disc cupping or if there is a decrease in corneal cloudiness and in IOP, reexamination is performed 3 to 4 months later, then every 6 months for 1 year and yearly thereafter. During the follow-up period, a cycloplegic refraction should be performed and any evidence of amblyopia, if present, should be managed aggressively. Amblyopia can be due to anisometropia, significant astigmatism, or corneal cloudiness.
The long-term prognosis for patients with primary congenital glaucoma is excellent when successfully treated.
If congenital glaucoma is recognized early and appropriate treatment is instituted, prognosis is excellent. There is a poor prognosis if glaucoma presents within the first month or after 2 years of age. Treatment is primarily surgical; however, medical therapy is indicated immediately following the diagnosis in the preoperative period if surgery is to be delayed. It is also indicated in patients who do not respond well to the surgical treatment. Patients with congenital glaucoma require long-life follow-up. An IOP rise can occur anytime and must be detected early and treated appropriately.
