Pediatric glaucoma is associated with a wide variety of pathology. Several classification systems have been developed to organize and categorize childhood glaucomas. The majority of systems are based on etiology and describe two main groups: primary and secondary glaucoma. Congenital and developmental glaucomas associated with syndromes and systemic abnormalities fall under the umbrella of primary glaucomas. Causative pathologies ranging from uveitis to congenital cataract surgery fall under secondary glaucoma.¹ The incidence of childhood glaucoma is estimated to be 2.29 per 100,000 patients younger than 20 years old based on a defined U.S. Population study in Olmstead County.² Primary congenital glaucoma is the most common form of childhood glaucoma, with a reported prevalence of 2.85 cases per 100,000 births.³ As in adults, pediatric glaucoma is associated with elevated intraocular pressure and progressive optic nerve damage; however, the clinical findings and surgical management are vastly different.

Clinical Findings

Manifestations of elevated IOP in children can vary depending on age of onset and rate of pressure elevation. Gradually increasing pressure can result in little to no corneal clouding. Presentation with buphthalmos and/or symptoms of tearing, blepharospasm and photophobia are more common (See Figure 1). In contrast, those children with acute pressure elevations present with corneal clouding. This finding can also be seen at birth (See Figure 2). Firm tactile pressure in these cases can be apparent and helpful in differentiating other causes of corneal opacification. The presence of a poor red reflex can elucidate subtle corneal clouding, although absence of a red reflex can be related to other pathology as well. Haab’s striae, which represent breaks in Descemet’s membrane, can be present in the absence of elevated pressure (See Figure 3). This finding signifies a history of elevated IOP associated with rapid eye growth.

Figure 1. Buphthalmos of both eyes, right worse than left.

Obtaining IOP measurements in children is challenging. Current methods include rebound tonometry (iCare) and handheld applanation tonometry (Tono-Pen, AccuPen, Kowa and Perkins Tonometer). Rebound tonometry has the advantage of not requiring anesthetic drops; however, the child must be upright. Recent studies have suggested that although IOP by rebound tonometry correlates well with Goldmann Tonometry, there is a tendency to overestimate IOP, particularly in children with glaucoma.^4,5 The iCarePro can be used in all positions; however, the device is currently not available in the United States. Handheld applanation tonometry can also be performed in all positions.

An exam under anesthesia is essential in diagnosing childhood glaucoma. Pre-intubation IOP, refraction, axial length, corneal diameter, gonioscopy, and ultrasound biomicroscopy when visibility is poor, are key components of the exam. Progressive myopia, increasing axial length and changing corneal diameter in the face of borderline IOP and cupping are suggestive of fluctuating high pressures. Tracking these factors also aids in determining treatment response. In children more than 3 years of age, changes associated with buphthalmos become less apparent due to decreased scleral elasticity.⁶ With general anesthesia, a more thorough exam investigating risk factors for glaucoma such as signs of past trauma, uveitis and syndrome manifestations can be assessed.

A large number of syndromes have associated glaucoma. The more common syndromes are: Sturge-Weber; Oculocerebrorenal (Lowe); Axenfeld-Rieger; aniridia; and Neurofibromatosis Type 1.

Sturge-Weber has a sporadic inheritance pattern and is characterized by nevus flammeus (port wine stain) of the face, angioma of the meninges and, rarely, involvement of the airway. Incidence of glaucoma has been reported to be as high as 71 percent.^7,8

Figure 2. Corneal clouding found at birth with elevated intraocular pressure. (Image courtesy Children’s Hospital of Los Angeles-The Vision Center.)

Oculocerebrorenal (Lowe) syndrome is X-linked recessive and presents with congenital cataracts, congenital glaucoma, mental retardation, renal tubular dysfunction (Fanconi’s syndrome), aminoaciduria and hypotonia. Incidence of glaucoma has been reported to be 47 to 71 percent.⁹

Axenfeld-Rieger syndrome (ARS) is autosomal dominant but can occur sporadically.¹⁰ It is associated with anterior segment abnormalities and is often categorized under anterior segment dysgenesis or goniodysgenesis syndromes. Approximately 50 percent of patients diagnosed with ARS will develop glaucoma. Onset typically occurs during late childhood but can present during infancy and into adulthood.¹¹ Physical manifestations include: redundant umbilical skin; telecanthus; broad nasal bridge; dental abnormalities (microdontia, oligodontia or hypodontia); and, in some cases, pituitary abnormalities with growth retardation.

Aniridia is characterized by hypoplastic iris tissue and is associated with foveal hypoplasia, cataracts, keratopathy secondary to limbal stem cell deficiency and, occasionally, optic nerve hypoplasia. The inheritance pattern is autosomal dominant, but can be inherited sporadically. In sporadic cases, patients should be worked up for Wilms’ tumor-aniridia-genital anomalies-retardation (WAGR) syndrome. Prevalance of glaucoma is reported to be from 30 to 50 percent.¹²

Neurofibromatosis Type 1 has an autosomal-dominant inheritance. It carries a spectrum of findings including café-au-lait spots, freckling of the axial/inguinal area, sphenoid dysplasia, S-shaped plexiform neurofibromas of the lids, optic nerve gliomas, Lisch nodules and choroidal hamartomas. Eyes with an associated plexiform neurofibroma have a 50 percent risk of glaucoma.¹³

Treatment

• Medical. Medical therapy in pediatric glaucoma is often supplementary to surgical management. It is often used for preoperative treatment to facilitate clearing of corneal edema. In addition, it can play a role in treating patients who are too unstable to undergo anesthesia. Timolol is often used as a first-line agent and has been shown to effectively lower IOP in the pediatric population. There is an increased risk for bronchospasm, apnea and bradycardia. The use of betaxolol (b1 selective antagonist), timolol 0.25% gel, and timolol 0.1% can help to avoid these side effects. Overall, however, timolol drops are generally well-tolerated.¹⁴ Latanoprost has been shown to have IOP-lowering effects, particularly in older children, but the non-response rate has been shown to be higher than in adults. Side effects are minimal, although darkening of the irides can occur, as in adults.¹⁵ Topical carbonic anhydrase inhibitors are also effective in lowering IOP. They are generally well-tolerated with minimal side effects. Oral acetazolamide has been shown to be more effective in lowering IOP and can be used in children with glaucoma at doses of 5 mg/kg/day to 15 mg/kg/day. Oral treatment carries a risk of systemic side effects, such as metabolic acidosis. Brimonidine has the most well-established side effect profile in children, causing bradycardia, hypotension, hypothermia, hypotonia and apnea in infants and severe lethargy in toddlers.16 Because of these side effects, its use is limited in the pediatric population.

• Surgical. Angle surgery is considered the mainstay of treatment for primary congenital glaucoma, with a reported 70 to 90 percent success rate after one to two procedures in patients treated after 3 months of age and before 1 to 2 years of age. This success rate significantly diminishes in patients presenting outside of this age range and those who fall in the spectrum of developmental glaucoma.¹⁷

Figure 3. Haab’s striae representing breaks in Descemet’s.

Traditional goniotomy is often the first procedure of choice, but it requires a clear cornea to be performed safely. Endoscopic goniotomy has been described to avoid this issue.¹⁸ Trabeculotomy ab externo does not require corneal clarity; however, it requires the technical challenge of finding Schlemm’s canal. Traditional trabeculotomy treats 90 to 180 degrees. Success rates are comparable to goniotomy, but similarly decrease in the setting of developmental glaucoma and significant anatomic angle pathology. 360-degree trabeculotomy is possible using a 6-0 polypropylene suture that is threaded throughout the entire circumference of the angle. The suture is then pulled through the original sclerotomy site and treats the entire angle. It has success rates of up to 92 percent with one procedure.

Complications include misdirection into the suprachoroidal space, hyphema, cyclodialysis cleft and iris tear.^19,20 The use of an illuminated microcatheter (iTRACK 250A; iScience Interventional) has been introduced to avoid misdirection. The illuminated catheter can be easily located. In addition, when 360 degree passage cannot be achieved, a second sclerotomy site can be created over the illuminated tip, allowing for partial treatment of the angle.²¹ Major complications for all angle surgeries include hyphema, hypotony and cataract.

Trabeculectomy has a 60 to 65 percent success rate when performed with antifibrotic agents. Success rates significantly decrease with aphakia. In addition, risk of bleb-related endophthalmitis in the pediatric population has been reported to be 7 to 14 percent.²² This risk appears to increase over time.23 Combination trabeculectomy-trabeculotomy has been described with a reported success rate of 72 percent as a primary procedure; however, it is unclear if there is a difference in success when comparing trabeculotomy alone vs. combined trabeculectomy/trabeculotomy.²⁴

Aqueous shunt implantation has shown significantly greater success when compared to trabeculectomy.²⁵ Low endophthalmitis rates have been reported. It does appear, as in adults, that implants become less effective over time and require reoperation.²⁶ Implants available for use include: Ahmed valve (New World Medical); Baerveldt implant (Pharmacia); and Molteno implant (OP Inc). Ahmed valves and Baerveldt implants are the most commonly used and have both been reported to be effective.^26-28

Cyclodestruction procedures are an option in difficult-to-treat cases. Cyclocryotherapy has been replaced by laser cyclophotocoagulation. A transscleral technique is most commonly used. Endoscopic cyclophotocoagulation has been reported to be effective as well.²⁹

Prognosis

Reports of visual outcomes vary. Cases resulting in visual acuity sufficient to qualify for a motor vehicle driving license range from 29 to 46.6 percent of patients. Vision at the time of diagnosis, type of glaucoma and amblyopia appear to be the largest factors in visual outcomes. Children with primary congenital glaucoma have the best prognosis. In the setting of well-controlled intraocular pressure, amblyopia is a key factor in vision loss. As in pediatric patients with congenital cataracts, unilateral cases often have poorer visual outcomes secondary to amblyopia.^30,31

Counseling patients and their families with regard to potential future vision loss can be challenging. Connecting them to resources for the visually impaired early is of utmost importance. The following are a few organizations with resources for the visually impaired and blind: Lighthouse International ( lighthouse.org); Helen Keller Services for the Blind ( helenkeller.org); American Foundation for the Blind ( afb.org); National Federation for the Blind ( nfb.org); and Family Connect ( familyconnect.org/parentsitehome.aspx).  REVIEW


Dr. Huang is a pediatric ophthalmologist specializing in pediatric glaucoma, amblyopia, eye muscle disorders, pediatric cataracts, congenital blocked tear ducts and other pediatric eye conditions. She is a full-time faculty member of the New York Eye and Ear Infirmary of Mt. Sinai and an assistant professor of ophthalmology. She reports no financial interest in any of the products discussed.



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