Primary Congenital Glaucoma

Pathophysiology

Primary congenital glaucoma originates from incomplete or defective development of the anterior chamber angle—specifically the trabecular meshwork—leading to increased resistance to aqueous outflow. There are several theories regarding the pathogenesis/pathological process. Currently, it’s believed due to developmental arrest of the trabecular meshwork. In utero, the trabecular meshwork is derived from neural crest origin. The tissue migrates from behind the cornea posteriorly and continues until the first year of life. When this maturation process is disrupted, the trabecular meshwork remains immature, thickened, and compressed, thereby impeding fluid drainage and raising intraocular pressure (IOP)³. Persistently elevated IOP then damages retinal ganglion cells, causing visual field loss and a progressive decline in visual acuity³.

Classification

Primary congenital glaucoma (PCG) is often categorised based on age of onset¹:

• Neonatal onset: presents within the first month of life
• Infantile onset: presents between 1 month and 2 years of age
• Late onset: presents after 2 years of age¹

Risk factors

Consanguinity is a known risk factor for primary congenital glaucoma. Although most cases occur sporadically, around 10% follow a genetic inheritance pattern, most commonly autosomal recessive. The most frequently implicated genes are CYP1B1 and LTBP2. Moreover, having an affected sibling (i.e., a positive family history) further increases the risk of developing primary congenital glaucoma⁴.

Clinical features

History

• Classically, elevated intraocular pressure (IOP) in primary congenital glaucoma manifests as a triad of photophobia (light sensitivity), epiphora (excessive tearing), and blepharospasm (involuntary spasm and closure of the eyelid).
• These symptoms arise from a cloudy, hazy cornea, which scatters incoming light and produces significant glare. Parents might note they can’t see their baby’s pupil or their child’s eye is very large⁵.

Examination

• Most cases of primary congenital glaucoma (around 70%) involve both eyes, although it can initially present in only one eye.
• Examination typically reveals elevated IOP, with many of the clinical signs stemming from corneal enlargement, clouding, or oedema. The raised IOP impairs the endothelial pump function in the cornea, which results in the classical sign of corneal oedema.
• On examination, this manifests as a dull or absent corneal reflex. Because the collagen in a child’s cornea and sclera is still immature, high IOP leads to buphthalmos (enlarged eyes) through axial lengthening. Haab striae (tears in Descemet’s membrane) may be visible on examination.
• A normal corneal diameter in infants ranges from 10.5 to 12 mm; any measurement above 12 mm should raise suspicion for PCG. While the anterior chamber is often shallow in infants, it may appear deep in those with elevated IOP.
• In terms of the optic nerve, the normal cup-to-disc ratio in infants less than 1 year old is about 0.1; any ratios above 0.2 suggest optic disc cupping, which in infants can be potentially reversible—unlike in adults—if the IOP is brought under control early⁶.

Ophthalmic Atlas Images by EyeRounds.org, The University of Iowa are licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

Haab Striae- Notice the multiple horizontal breaks on the cornea

Differential diagnosis

When assessing a child who presents with photophobia, epiphora, and blepharospasm, it is important to consider:

• Nasolacrimal duct obstruction: The most common cause of epiphora in infancy, arising from a failure of the nasolacrimal duct to open.
• Conjunctivitis: Often accompanied by discharge, redness, and possible eyelid swelling.
• Uveitis: Inflammation within the eye that can cause photophobia, tearing, and ocular pain.

For corneal enlargement, megalocornea should be considered. It typically presents with an enlarged corneal diameter but without the elevated IOP seen in glaucoma.

When corneal clouding or oedema is present, the mnemonic STUMPED can used for the most common causes⁵:

• S: Sclerocornea
• T: Trauma (e.g., forceps or birth-related injury)
• U: Ulcers
• M: Mucopolysaccharidoses (e.g., Hurler syndrome)
• P: Peters anomaly
• E: Endothelial dystrophy
• D: Dermoids

Investigations

Assessing for primary congenital glaucoma begins with an evaluation of visual behaviour, noting fixation, following responses, and any nystagmus. A thorough anterior chamber and in particular examining the cornea is essential to identify oedema, Haab striae, or other abnormalities. The optic nerve should also be inspected for cupping.

Tonometers are instruments used to measure intra-ocular pressure. Re-bound tonometers (iCare) are easy to use, and particularly useful in setting of corneal scarring. Determining IOP in infants can be challenging when they are awake—crying, eyelid squeezing, and the Valsalva manoeuvre may artificially elevate readings—so examination under anesthesia is often necessary. As a reference, normal IOP for an infant generally ranges between 10–12 mmHg.  Under anaesthesia gonioscopy can be performed to assess the drainage angle and direct opthalmoscope used to assess the optic nerve.

Management

The overarching goal of managing primary congenital glaucoma is to lower intraocular pressure (IOP) and thereby prevent irreversible optic nerve damage. While some children may respond to medical therapy, surgical intervention remains the definitive long-term treatment.

Medical Management

• Medications is rarely effective. Medications are typically used temporarily- used to stabilize IOP before surgery, between surgical procedures, or if surgery has not yielded adequate pressure control.
• Carbonic anhydrase inhibitors (e.g., dorzolamide) are commonly used due to their demonstrated efficacy and safety profile in children.
• Brimonidine (an α-adrenergic agonist) is contraindicated in children under 6 years because of the risk of respiratory depression, apnea, and potential lethality⁴.
• β-blockers (e.g., timolol, betaxolol) must be used cautiously in infants to avoid systemic absorptionand associated cardiopulmonary side effects⁵.

Surgical Management

• Primary congenital glaucoma is often referred to as a surgical disease because angle surgery is invariably necessary to relieve the increased resistance to aqueous outflow.
• Goniotomy and trabeculotomy are the initial procedures of choice; they aim to open the dysgenic angle and facilitate aqueous drainage.
• In cases where angle surgery is unsuccessful or not feasible or further IOP control is required, procedures such as trabeculectomy, glaucoma drainage device implantation (ex tube surgery), or cyclodestructive treatments (ex cyclodiode laser) may be required³.

Complications

• Prompt diagnosis and early surgical management can yield excellent long-term control of IOP, sometimes with a single surgery. Prognosis is poorer for children diagnosed at birth or after 2 years of age. Additionally, the enlarged and thinner ocular structures (buphthalmos) are prone to complications such as high myopia, globe rupture, retinal detachment, and corneal exposure.
• Extensive scarring and corneal decompensation may necessitate corneal transplant. A significant concern is the development of amblyopia, which necessitates close monitoring and appropriate vision rehabilitation measures.

References