- 1 Disease Entity
- 2 Diagnosis
- 3 Management/Therapeutic Considerations
- 4 Additional Resources
- 5 References
- 249300 – Megalocornea
- 309300 – MGC1
- 300350 – CHRDL1
Megalocornea (MGC1) is a rare developmental defect classified in the spectrum of anterior segment dysgenesis. Megalocornea is characterized by nonprogressive bilateral enlargement of the diameter of the cornea (> 12.5 mm) in the presence of normal intraocular pressure. The condition is also known as “anterior megalophthalmos” since the entirety of the anterior segment is enlarged. In addition to an enlarged cornea, patients present with a very deep anterior chamber and a normal to thin corneal thickness.
Due to the X-linked recessive inheritance of congenital megalocornea, males are more often affected than females. The incidence of megalocornea is unknown.
Inheritance and Molecular Genetics
MGC1 is most often transmitted in a X-linked recessive inheritance but can rarely be seen in both dominant and recessive autosomal inheritance patterns.
MGC1 is caused by a mutation in Chordin-like 1 (CHRDL1). CHRDL1 codes for the protein ventroptin, an antagonist to bone morphogenetic protein 4 (BMP-4). BMP-4 is mainly expressed in the anterior retina, and the interaction between ventroptin and BMP-4 is important for the development of corneal stroma and endothelium. A mutation in the CHRDL1 gene can lead to unregulated growth causing megalocornea.
The definitive mechanism behind the formation of megalocornea is currently unknown, but a common theory is that failure of anterior cup fusion allows more room for the cornea to grow. Posterior placement of the iris-lens diaphragm and normal endothelial density from a primary overgrowth (as opposed to low density from a distended cornea as seen in glaucoma) seem to support this theory.
Megalocornea often occurs as an isolated condition. Clinical outcomes for primary megalocornea are generally good and can present without ocular or systemic symptoms with the only indication of malformation being an enlarged cornea. Endothelial cell density is normal and there is posterior placement of the iris-lens diaphragm.
Megalocornea can also be a presenting symptom of a larger developmental disease. Frank-Ter Haar Syndrome is a rare autosomal recessive disease of skeletal dysplasia that presents with megalocornea and developmental delay. Megalocornea is rarely associated with Marfan Syndrome and can be a helpful diagnostic sign in infants and young children. Neuhauser Syndrome, also known as Megalocornea-Mental Retardation Syndrome, is an unusual autosomally inherited defect that is described by a classic triad of primary megalocornea, mental retardation, and hypotonia. Megalocornea can also be associated with craniosynostosis and rare cases of albinism and Down Syndrome.
Primary megalocornea often does not present with ocular symptoms. In some cases, however, patients can manifest blurred vision, astigmatism, premature cataract formation, retinal detachment, glaucoma, lens subluxation, and primary congenital glaucoma.
Diagnosis of megalocornea is generally made in young patients and requires thorough examination of the eye, often under general anesthesia. Megalocornea is defined as nonprogressive 12.5 mm or greater bilateral enlargement of the diameter of the cornea in the absence of increased intraocular pressure. Deep anterior chambers can also be helpful in making the diagnosis.
- Primary megalocornea
- Frank-Ter Haar Syndrome
- Marfan Syndrome
- Neuhauser Syndrome (Megalocornea-mental retardation syndrome)
- Primary Congenital Glaucoma
- Crouzon Syndrome (craniosynostosis)
- Down Syndrome
Careful routine screening of associated ocular abnormalities is important when considering the management of the condition. Symptomatic primary megalocornea requires the correction of any refractive or visual errors. Many patients with myopia or astigmatism can develop unimpaired vision through regular follow-up and corrective lenses.
Cataract surgery in megalocornea patients is complex due to the large size of the anterior compartment and the weakened zonules. The weakened zonules result in difficulty supporting an artificial intraocular lens (IOL), leading to potential surgical complications including vitreous leakage and loss of lens fragments to the back of the eye. Instead of a standard IOL, patients with megalocornea can instead be treated with a special artisan lens (Verisyse phakic IOL) that clips into the iris to maintain the position of the lens post-operatively (video can be accessed from references).
Glaucoma can be managed by surgically reducing the resistance to aqueous outflow in the anterior chamber angle through goniotomy or trabeculotomy.
Routine examination of these patients is important in order to prevent and treat ocular complications such as cataracts, glaucoma, or retinal detachments.
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