Congenital primary glaucoma

Synonym: trabeculodysgenesis

Introduction

There are various forms of congenital glaucoma. Some arise in the context of other abnormalities (eg, Reiger's syndrome, Sturge-Weber syndrome and neurofibromatosis). Childhood glaucoma can develop secondary to ocular problems such as tumours, trauma (accidental or surgical), inflammation or infection.

Congenital glaucoma is a developmental glaucoma occurring before the age of 3 years due to an obstruction that prevents adequate drainage of aqueous humour caused by abnormal development of the trabecular meshwork and anterior chamber angle. The aged of 3 has been estimated since it corresponds to the age at which the eye grows in response to high intraocular pressure.¹

Early recognition of this condition is very important, as prompt treatment can significantly improve the child's vision.

For more information about later-onset glaucoma, see separate articles: Glaucoma and Ocular Hypertension, Primary Open Angle Glaucoma, and Angle-Closure Glaucoma.

You may also find the following separate articles relevant: Eye Problems in Babies, Ophthalmia Neonatorum, Vision Testing and Screening in Young Children, Amblyopia, Coloboma and Hereditary Retinal Dystrophies.

How common is congenital primary glaucoma? (Epidemiology)

The most common type of infantile glaucoma is primary congenital glaucoma. Primary congenital glaucoma is a rare disease with variable incidence across countries and ethnic groups. The incidence in western countries, such as Ireland, Britain, and the USA, lies within 1 per 10–20,000 live births. However, the incidence is higher in the Middle East, including Saudi Arabia, where consanguineous marriages are more prevalent.¹

• In 90% of cases, this is sporadic and in the remaining 10% of cases, there is an autosomal recessive pattern of inheritance.²

• It may also be associated with abnormalities of the CYP1B1 gene (which encodes for cytochrome P4501B1)³ as well as others such as the LTBP2 gene.²

• The problem lies in defective aqueous outflow from the anterior chamber due to malformation of the trabecular meshwork, the main drainage passage for aqueous. This results in a rise in intraocular pressure (IOP):

  • In true congenital glaucoma (40% of cases), this occurs during intrauterine life.

  • In infantile glaucoma (55% of cases), the rise is evident before the child's third birthday.

  • The remainder of cases fall into the juvenile glaucoma group whose problem manifests itself after the third birthday but before the age of 16.

• Most cases (75%) are bilateral although involvement is usually asymmetrical.⁴

• 65% of patients are boys.

• Its impact, if unrecognised, can be significant on the child's vision.

Congenital primary glaucoma symptoms (presentation)¹

Epiphora, photophobia and blepharospasm are the three most common manifestations.

Children with congenital glaucoma typically present with globe enlargement (buphthalmos), oedema and opacification of the cornea, with rupture of Descemet's membrane (Haab’s striae).

Additional clinical features include thinning of the anterior sclera and iris atrophy, anomalously deep anterior chamber and structurally normal posterior segment, except for progressive glaucomatous optic atrophy.

Visual acuity may be reduced and/or visual fields may be restricted. In untreated or treated late cases, severe sight impairment always occurs.

Differential diagnosis⁵

• Cloudy cornea at birth - birth trauma, intrauterine rubella, some metabolic disorders (eg, mucopolysaccharidoses), congenital corneal dystrophies.

• Large cornea - very high myopia, megalocornea.

• Epiphora - delayed canalisation of the nasolacrimal duct (very common).

• Raised IOP - tumours (eg, retinoblastoma), retinopathy of prematurity, intraocular inflammation, trauma.

Other early-onset glaucomas may arise secondary to developmental abnormalities, such as glaucomas that occur with aniridia or as part of Axenfeld-Rieger syndrome.⁶

Investigations

This depends on the age of the child. The ophthalmologist will need to ascertain the visual acuity, and the intraocular pressure and have a good look at the trabecular meshwork as well as the fundus via dilated fundoscopy. Visual acuity can be determined to a certain extent when the child is awake but a full examination of the globe usually warrants a general anaesthetic.

Associated diseases

By definition, primary congenital glaucoma occurs in an otherwise healthy eye with no associated systemic disease.

Congenital primary glaucoma treatment and management⁷

Management includes:

• Surgery (goniotomy, trabeculotomy, trabeculectomy, or deep sclerectomy) as early as possible.

• Drainage implants or cyclodestruction if surgery fails.

• Medication preoperatively and postoperatively to help control intraocular pressure.

• Routine treatment of refractive errors and amblyopia.

• Surveillance: Lifelong monitoring to ensure control of IOP.

• Evaluation of relatives at risk: if the pathogenic variant(s) have been identified in the family, molecular genetic testing of at-risk sibs as soon as possible after birth in order to avoid repeated examinations under anaesthesia in young children who do not have the pathogenic variant(s).

• Genetic counselling: primary congenital glaucoma caused by biallelic pathogenic variants in CYP1B1 or LTBP2 is inherited in an autosomal recessive manner. PCG caused by a heterozygous pathogenic variant in TEK is inherited in an autosomal dominant manner.

• Prenatal testing for a pregnancy at increased risk is possible if the PCG-causing pathogenic variant(s) in the family are known.
  

Complications

Undiagnosed glaucoma can lead to lifelong visual impairment. Diagnosis can be missed due to the rare and insidious nature of the problem. The most serious complications are unusual but tend to relate to having a general anaesthetic or to the surgery itself (hyphaema, infection, lens damage and uveitis).

Prognosis

• The corneal oedema may persist for several weeks but often resolves, as does the optic disc cupping (unlike adults).⁸

• Apparently stable congenital glaucoma may progress with sight-threatening complications after many years of stable intraocular pressure. Monitoring of these patients is therefore usually indicated throughout life.⁹

• An acceptable visual acuity and stereoacuity can be achieved with treatment, particularly in cases of timely intervention and close follow-up.¹⁰