Definition

Megalocornea, also known as megalophthalmos or macrocornea, is a congenital abnormality affecting both eyes, characterized by an enlarged corneal diameter of more than 12.5–13 mm at birth, accompanied by a deep anterior chamber and normal intraocular pressure. This rare disorder is inherited in an X-linked manner, predominantly affecting males (90%). The exact incidence of megalocornea is unknown, though studies suggest it is rare. Adults with megalocornea may experience premature cataracts between ages 30–50, glaucoma, lens subluxation, and mosaic corneal dystrophy.

There are two forms of megalocornea:

1. Primary megalocornea: Without other systemic disorders.
2. Secondary megalocornea: With associated systemic disorders (syndromes).

Causes

Megalocornea is primarily caused by a mutation in the Chordin-like 1 (CHRDL1) gene on chromosome Xq23, inherited in an X-linked recessive manner. It can also be inherited in autosomal dominant and recessive patterns. Mutations in CHRDL1 disrupt the formation of the corneal layer and its endothelium. Another implicated mutation is found at Xq21.3-q22. 

The precise mechanism causing megalocornea is unknown, but the leading hypothesis suggests disruption in the fusion of corneal layers, resulting in an enlarged cornea. This is supported by the posterior positioning of the iris and lens compared to the general population. Abnormal collagen formation and congenital glaucoma are also potential contributing factors.

Risk Factor

The only known risk factor for megalocornea is a family history of the condition.

Symptoms

Symptoms and findings that can be observed by parents include:

• The eyes appear relatively large compared to the child's age.
• Clear eyes.
• The child develops normally.
• Absence of symptoms like red or watery eyes.
• A mother with a larger cornea.
• If complications such as cataracts or retinal detachment occur, symptoms may include blurred vision, floating spots, and flashes of light.

Typically, megalocornea is not associated with other ocular or systemic disorders, though it can occur in syndromes like Frank-Ter Haar Syndrome, Marfan Syndrome, Neuhauser Syndrome, and Down Syndrome, where developmental issues may be present. There is a specific questionnaire or examination that can be help in screening the condition of the child.

Diagnosis

Megalocornea is diagnosed through a clinical examination. Typically, patients with megalocornea do not report any visual impairments. The doctor will inquire about the child's eye symptoms, family history of megalocornea, and other symptoms to rule out associated syndromes. The physical examination includes measuring the corneal diameter (which ranges from 14–16 mm in megalocornea), checking intraocular pressure, and examining the iris and anterior chamber using a slit lamp. Ocular tests are performed to help in excluding any other potential diagnosis such as buphthalmos (big eyes), ocular hypertension, change of optic disc, and to see any Haab’s striae on the cornea. Additional tests may include:

• Gonioscopy, to examine the eye's structure, particularly the angle.
• A-scan ultrasound biometry, to detect buphthalmos indicative of glaucoma.
• Specular microscopy, to assess the corneal layers.  

The differential diagnosis for megalocornea includes congenital glaucoma, keratoglobus (a round cornea), and buphthalmos (enlarged eyeball). Children with megalocornea have eye shapes similar to those with glaucoma but maintain normal eye pressure.

Syndromes associated with megalocornea:

• Neuhaüser syndrome, also known as megalocornea-mental retardation (MMR) syndrome, is a condition where children experience megalocornea along with intellectual disability, seizures, and muscle weakness in the arms and legs. Those with this syndrome often have distinct facial features.

• Frank-Ter Haar syndrome is a genetically inherited condition that leads to abnormalities in the eyes, heart, and bones.

• Marfan syndrome is a connective tissue disorder caused by mutations in the fibrillin gene, which is essential for maintaining connective tissue and regulating growth. This syndrome is characterized by distinctive physical features and may also involve megalocornea.

• Albinism, commonly referred to as albino, is a condition where there is a lack of pigment (melanin) in the skin.

• Ritscher-Schinzel syndrome involves abnormalities in the eyes, heart, and facial structure (craniofacial). Megalocornea is the most common eye issue in children with this condition.

• Wolfram-like syndrome is an autosomal dominant disorder that includes eye atrophy, diabetes mellitus, and hearing loss. Osteogenesis imperfecta, caused by a defect in collagen, results in brittle bones and blue sclera (the whites of the eyes). Megalocornea is a key symptom of this disease as well.

Management

Megalocornea has no specific treatment due to its anatomical basis. The treatments will focus on correcting visual impairments, such as myopia (nearsightedness) or astigmatism, which can be addressed with glasses. Regular detection and evaluation of other ocular conditions like cataracts, glaucoma, and retinal detachment are crucial. Cataract surgery is more challenging in megalocornea patients due to the wider cornea and requires special lenses. Collaborative management with a pediatrician is essential to rule out other syndromes.

Education

Children with megalocornea should undergo genetic testing to identify other potential genetic disorders that can be inherited from their parents. Genetic testing is valuable for diagnosis since causes of megalocornea are rare. Megalocornea can affect vision over time, but complications can be managed with glasses, medications, and surgery, positively impacting disease progression.

Complications

Megalocornea is generally asymptomatic in children, allowing the visual acuity to stay normal. Disease prognosis is better in primary megalocornea compared to secondary forms. However, refractive errors such as astigmatism can develop with age. Other complications include presenile cataracts, which are challenging to manage due to anatomical abnormalities, glaucoma, lens subluxation, and mosaic corneal dystrophy.

Prevention

Currently, there is no specific prevention for megalocornea. However, prenatal eye condition checks are advisable. Parents should closely monitor the eye health of children with megalocornea to detect and manage potential glaucoma and cataracts early.

When to See a Doctor?

If you observe that the black part of your child's eye is larger than that of other children of the same age and occurs in both eyes, seek medical evaluation at the nearest health facility.

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