PEDIATRIC AND CONGENITAL GLAUCOMA

Signs and Symptoms

Pediatric glaucoma is a term that includes any form of glaucoma that presents between birth and age 18 years.1,2 Pediatric glaucomas can be either primary or secondary and the angle may be open or closed. However, there is confusing and overlapping terminology. Primary congenital and primary infantile glaucoma occur secondary to trabeculodysgenesis, a developmental angle anomaly. This can be diagnosed any time between birth and early childhood. Pediatric developmental glaucomas are also classified by the time that they appear in a patient; primary congenital glaucoma occurs between birth and two months of age, primary infantile glaucoma between two months and two years of age, and late-onset primary infantile glaucoma (also known as juvenile glaucoma) after two years of age.1

Primary infantile glaucoma overlaps with juvenile-onset open-angle glaucoma (JOAG), a non-developmental glaucoma similar to primary open-angle glaucoma in adults, which develops late in childhood in the absence of angle anomalies.1,2 It is most commonly accepted that the term primary congenital glaucoma refers to patients in all three age groups in the presence of developmental anterior chamber angle abnormalities.1,3

Patients with primary congenital and infantile glaucoma typically manifest a classic triad of photophobia, lacrimation and blepharospasm.1,3,4 These occur due to corneal changes such as edema secondary to elevated intraocular pressure (IOP). Buphthalmos develops from the distensibility of immature collagen within the infant corneal stroma. Horizontal breaks in Descemet’s membrane known as Haab’s striae commonly occur. These findings strongly suggest the presence of primary congenital glaucoma; they are not present if glaucoma develops after the age of three. In older children, glaucoma is diagnosed in the same way it is in adults; that is, by observing optic disc damage, elevated intraocular pressure and structural and functional changes consistent with glaucoma, in the absence of trabeculodysgenesis.

In patients with primary congenital glaucoma, abnormalities in the anterior chamber angle are diagnostic. The iris and ciliary body are anteriorly located, with iris tissue inserting into and overlapping the trabecular meshwork, impeding the outflow of aqueous.

Primary congenital glaucoma is the most common form of pediatric glaucoma.1-4 The second most common form occurs in aphakic or pseudophakic children following congenital cataract surgery.1,5-12 The mechanism in aphakic glaucoma is unclear, but gonioscopy may reveal a blockage of the trabecular meshwork secondary to an acquired repositioning of the iris against the posterior trabecular meshwork. There is often associated abnormal pigmentation and synechiae formation within the meshwork.5 Beyond these conditions, glaucoma can occur in a pediatric patient from a number of other causes, including but not limited to trauma, inflammation, episcleral venous pressure elevation (as seen in Sturge-Weber syndrome), tumor, pupil block from subluxation, retinopathy of prematurity and infectious disease.1,13-18

Pathophysiology

The totality of pediatric glaucoma results in a diverse pathophysiology due to the wide range of possible associated conditions. Primary congenital and infantile glaucoma, however, clearly results from a developmental arrest of the iris and ciliary body in the seventh month of gestation.19 These structures insert in an anterior location with iris tissue overlapping the trabecular meshwork, impeding aqueous outflow resulting in subsequent IOP elevation.1,19 There is also developmental immaturity of the trabecular meshwork, with thickened trabecular tissue and an abnormal ground matrix.1

Primary congenital glaucoma appears to be autosomal recessive.3 Two genetic loci—GLC3A and GLC3B—have been identified in a majority of hereditary cases.20,21 An autosomal dominant JOAG has been linked to the GLC1A gene. Mutations in the trabecular meshwork inducible glucocorticoid response protein (TIGR) gene have also been identified in families with JOAG.3,22

Management

Proper management of any pediatric glaucoma begins with accurate diagnosis and categorization of the glaucoma. In older children with JOAG, IOP measurement, disc analysis, visual field testing and diagnostic retinal nerve fiber layer imaging can all be beneficial. In infants and younger children, these tests may not be possible or practical. In such cases, IOP measurement, along with observation of corneal clouding, corneal diameter measurement and inspection for Haab’s striae become more important. Examination under sedation or general anesthesia may be necessary. Gonioscopy is critically important, as recognizing abnormal angle anatomy (trabeculodysgenesis) plays a significant role in the development of the management plan.

Primary congenital glaucoma is best managed surgically, with medications only used adjunctively. The most performed and successful surgeries for primary congenital glaucoma are the angle surgeries—goniotomy and trabeculotomy. The former involves inserting a goniotomy knife into the anterior chamber and incising the anterior aspect of the middle third of the trabecular meshwork over 120°.1 In trabeculotomy, an external dissection of Schlemm’s canal is performed over 180° of the anterior chamber angle.1

Goniotomy and trabeculotomy are typically very successful for primary congenital glaucoma. Goniotomy is performed when a clear cornea allows angle visualization, while trabeculotomy is preferred in cases involving a cloudy cornea. However, these procedures are less successful for cases of pediatric glaucoma other than primary congenital and infantile forms. In these cases, trabeculectomy with adjunctive antimetabolite application is a common procedure. In refractory cases, combined trabeculectomy with glaucoma drainage implant devices offer the most successful and predictable option.23-30

More recently, deep sclerectomy and circumferential trabeculotomy have met with success in managing congenital and childhood glaucoma.31,32 Even more recently, transscleral cyclophotocoagulation and endoscopic cyclophotocoagulation have been seen to be safe, effective and comparable treatments that may be considered first-line therapy to achieve control of IOP in all forms of pediatric glaucoma. These procedures, when effective, can allow the patient to avoid a penetrating procedure.33

While surgery is the preferred treatment for pediatric developmental glaucoma, there are times where medications may be necessary, either prior to or adjunctively with surgery. For the majority of glaucoma meds, pediatric use is considered off label and safety and efficacy have not been studied; clinical guidance has been obtained through case series and retrospective analyses. Topical beta-blockers have been deemed safe and effective when used in children.34-36 Prostaglandin analogs are safe and well tolerated, but unfortunately not very effective in the pediatric glaucoma population. Older children with JOAG demonstrate the best efficacy response.37-39

When used in children, topical carbonic anhydrase inhibitors (CAIs) are safe and effective in lowering IOP.40,41 Brimonidine, though effective in lowering IOP in children, crosses the blood/brain barrier and can potentially affect the central nervous system. This medication has demonstrated an unacceptable level of adverse events in children and should be avoided if possible.42-44

Upon lowering IOP in infants, reversal of cupping as well as corneal clearing has been observed. However, once buphthalmos has occurred, the globe will not return to normal size.4,45

Clinical Pearls

Aphakic and pseudophakic children must be followed life-long for the development of glaucoma. However, the presence of an intraocular lens seems to reduce the incidence of glaucoma development, though the reasons are unclear.

IOP does not have to be dramat-i-cally high in a child for glaucoma to develop. IOP above 20mm Hg is concerning.

Congenital, infantile and developmental glaucoma implies trabeculodysgenesis. A child with glaucoma but without angle abnormalities has JOAG or another secondary glaucoma.

In rare instances where topical glaucoma medications in children are indicated, preferences include CAIs and beta-blockers. Prostaglandins are reserved only for cases involving older children with JOAG. Brimonidine should always be avoided.

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