Megalocornea: Symptoms, Types, Causes and Treatment

Megalocornea is a rare eye condition characterized by an abnormally large corneal diameter, often present from birth. While the enlarged cornea is the hallmark feature, this condition can also involve other ocular or systemic abnormalities. Understanding megalocornea is crucial for early diagnosis, appropriate management, and genetic counseling. This article provides a comprehensive, evidence-based overview of the symptoms, types, causes, and treatment of megalocornea—synthesizing current research to guide patients, families, and practitioners.

Symptoms of Megalocornea

Megalocornea is more than just "big eyes." The symptoms may be subtle at first, especially in infants, but they can impact vision and eye health throughout life. Recognizing the key symptoms is vital for timely intervention and to distinguish megalocornea from other serious conditions like congenital glaucoma.

Symptom	Description	Frequency/Context	Source(s)
Large cornea	Corneal diameter >12.5–13 mm	Always present	3 4 8
Deep anterior chamber	Increased depth of front eye chamber	Common	3 4 5 8
Clear cornea	No clouding or edema	Typical in isolated cases	3 4 8
Iridodonesis	Tremulous/unstable iris	Frequent	3 4
Lens issues	Lens subluxation, dislocation, cataract	Develops over time	3 4 9 11
Arcus juvenilis	Early-onset corneal arcus	Sometimes present	3 5
Photophobia	Light sensitivity, may persist after surgery	Related to iris translucency	2
Reduced corneal thickness	Thinner than normal cornea	Frequent in X-linked type	12
Myopia/astigmatism	Refractive errors	Mild myopia or astigmatism common	4 14

Table 1: Key Symptoms

Understanding the Clinical Features

Large Cornea and Deep Anterior Chamber

The primary diagnostic feature is a large, clear cornea—usually over 13 mm in diameter, sometimes reaching up to 17 or even 18 mm. Unlike in congenital glaucoma, the cornea remains clear and free of scarring or edema. The anterior chamber (the fluid-filled space between the cornea and iris) is also unusually deep, contributing to the eye's enlarged appearance 3 4 5 8.

Iris and Lens Abnormalities

• Iridodonesis (tremulous iris) is often observed due to the stretched support structures (zonules) of the lens, which itself is often normal in size but can become subluxated or dislocated over time 3 4 9 11.
• Cataracts are more likely to develop earlier in life in these patients. Lens displacement can also result in secondary complications, such as glaucoma 4 9 11.

Additional Ocular Findings

• Arcus juvenilis (a grayish ring at the corneal edge) and mosaic corneal degeneration (shagreen) can occur, especially in X-linked forms 3 5 10.
• Photophobia and iris translucency are noted in some genetic syndromes with megalocornea, such as congenital miosis, and may persist even after surgical intervention 2.

Refractive Errors

Patients may have mild myopia (nearsightedness) or notable astigmatism due to the altered curvature of the cornea 4 14.

How Symptoms Progress

Most symptoms are congenital and non-progressive, but lens complications and secondary glaucoma may develop later, making regular ophthalmologic follow-up essential 9 11.

Types of Megalocornea

Megalocornea is not a single disease entity. It occurs as an isolated eye abnormality or as part of broader syndromes, with several genetic and clinical subtypes.

Type	Key Features	Inheritance	Source(s)
Isolated (Non-syndromic)	Only ocular enlargement, no other anomalies	X-linked, rarely AR	5 8 12
Syndromic	Eye and systemic/neurological features	AR or complex	1 6 7
X-linked Megalocornea (MGC1/XMC)	Large cornea, deep chamber, mosaic degeneration	X-linked	5 10 12
Autosomal Recessive (LTBP2)	Megalocornea, lens dislocation, secondary glaucoma	AR	9 11
Megalocornea-mental retardation (MMR) syndromes	Ocular and cognitive impairment	AR or complex	6 7 12

Table 2: Types of Megalocornea

Breaking Down the Main Types

Isolated (Non-syndromic) Megalocornea

This is the classic form: only the eyes are affected, with no other systemic or neurological problems. Most cases are inherited in an X-linked recessive pattern, predominantly affecting males 5 8 12.

Syndromic Megalocornea

Here, megalocornea is just one feature among others—often involving skeletal, neurological, or metabolic abnormalities. Examples include:

• Frank–ter Haar syndrome: Megalocornea plus skeletal anomalies, facial features, and developmental delay 1.
• Neuhäuser (MMR) syndrome: Megalocornea with mental and motor retardation, sometimes macrocephaly or obesity 6 7.

X-linked Megalocornea (MGC1/XMC)

This form is caused by mutations in the CHRDL1 gene. Hallmarks include a large cornea, deep chamber, and the development of mosaic corneal degeneration and early cataracts. Central corneal thickness is reduced, but the condition does not typically cause blindness 5 10 12.

Autosomal Recessive (LTBP2-Related)

Mutations in the LTBP2 gene lead to megalocornea with lens abnormalities (microspherophakia, ectopia lentis) and a high risk for secondary glaucoma in childhood. This type can mimic primary congenital glaucoma but requires different management 9 11.

Megalocornea-Mental Retardation (MMR) Syndromes

These rare, complex syndromes combine megalocornea with intellectual disability and other anomalies. Classification is evolving and may include multiple subtypes based on specific features 6 7 12.

Causes of Megalocornea

Megalocornea can have diverse genetic and developmental origins. Understanding the underlying causes helps with accurate diagnosis and informs treatment and genetic counseling.

Cause	Mechanism/Mutation	Associated Type(s)	Source(s)
CHRDL1 gene mutations	Defect in bone morphogenetic protein antagonism	X-linked megalocornea	5 10 12
LTBP2 gene mutations	Defective extracellular matrix protein	Autosomal recessive, syndromic	9 11
Other genetic syndromes	Multiple gene defects/metabolic pathways	Syndromic forms	1 6 7
Developmental anomaly	Abnormal anterior segment development	All forms	2 3 4 8

Table 3: Causes of Megalocornea

Diving into the Genetics and Pathophysiology

X-linked Megalocornea and CHRDL1

The CHRDL1 gene, located on the X chromosome, encodes ventroptin, a protein involved in the development of the eye's anterior segment. Mutations disrupt bone morphogenetic protein (BMP) signaling, leading to excessive corneal growth and thinning. The phenotype is typically restricted to the eyes, but recent research suggests possible subtle brain changes 5 10 12.

Autosomal Recessive (LTBP2)

LTBP2 encodes a protein important for the structural integrity of the eye's connective tissue. Mutations cause megalocornea, lens instability, and a high risk for childhood-onset secondary glaucoma. Some patients may also show systemic features resembling Marfan syndrome as they age 9 11.

Syndromic and Complex Genetic Forms

Some forms of megalocornea are part of broader syndromes, like Frank–ter Haar or Neuhäuser (MMR), involving multiple genes or unknown metabolic pathways. These cases often display additional features—skeletal, facial, or neurological—that help distinguish them from isolated megalocornea 1 6 7.

Developmental Mechanisms

Across all types, megalocornea arises from abnormal development of the anterior segment during fetal growth. This can involve not only the cornea but also the iris, lens, and zonular suspensory system, leading to the constellation of symptoms seen in patients 2 3 4 8.

Treatment of Megalocornea

While megalocornea itself does not always require intervention, patients are at increased risk for certain complications. Managing these risks and addressing associated symptoms are the mainstays of treatment.

Issue/Indication	Treatment Approach	Notes/Challenges	Source(s)
Refractive error	Glasses/contact lenses	Astigmatism/myopia common	4 14
Cataract	Modified cataract surgery, IOL selection	Large eye size complicates surgery	13 14 15 16
Aphakia (no lens)	Iris-claw/Artisan lens, custom IOLs	Standard lenses may not fit	15 16
Lens subluxation/dislocation	Surgical removal/repair	Early intervention needed	11 16
Secondary glaucoma	Monitor IOP, lens removal if indicated	Differentiate from primary glaucoma	9 11
Photophobia	Optical iridectomy, tinted lenses	May persist despite surgery	2
Genetic counseling	Family planning, syndrome evaluation	Important for inherited cases	5 6 12

Table 4: Treatment Approaches

Navigating Management and Surgical Challenges

Optical Correction

Most patients benefit from glasses or contact lenses to correct refractive errors, especially myopia and astigmatism. However, fitting contact lenses can be challenging due to the unusually large and curved cornea 4 14.

Cataract and Lens Management

• Cataract surgery in megalocornea requires special planning. The enlarged anterior chamber and weak zonules can complicate both phacoemulsification and lens implantation. Standard intraocular lenses (IOLs) may be unstable or too small, leading to dislocation 13 14 15.
• Artisan/iris-claw lenses or IOLs sutured to a capsular tension ring can provide adequate fixation in these large eyes 15 16.
• Lens subluxation/dislocation may necessitate early surgical intervention, especially in LTBP2-related cases to prevent secondary glaucoma 11 16.

Glaucoma Management

Secondary glaucoma is a risk, particularly in syndromic or LTBP2-related megalocornea. Regular intraocular pressure (IOP) monitoring is essential. In these cases, lens removal (not angle surgery) is often the preferred intervention—highlighting the importance of correct diagnosis 9 11.

Addressing Photophobia and Iris Abnormalities

Patients with iris translucency and photophobia may benefit from optical iridectomy or tinted lenses, though symptoms may persist 2.

Genetic Counseling

Given the hereditary nature of most forms, genetic counseling is important for affected families. Identifying the genetic subtype can inform prognosis, recurrence risk, and guide family planning 5 6 12.

Conclusion

Megalocornea is a rare but important eye condition, often congenital and genetic in origin. Its recognition and proper management can prevent complications and improve quality of life.

Main Points:

• Key symptoms include a large, clear cornea, deep anterior chamber, lens instability, and a risk for early cataract and glaucoma 3 4 5 9 11.
• Types range from isolated, non-syndromic forms (mainly X-linked) to complex syndromic variants with systemic features 1 5 6 7 9 10 11 12.
• Causes are most often genetic, involving mutations in CHRDL1 (X-linked) or LTBP2 (autosomal recessive), among others 5 9 10 11 12.
• Treatment focuses on correcting vision, managing lens and glaucoma complications, and adapting surgical techniques for the unique anatomy of these eyes 4 9 11 13 14 15 16.
• Genetic counseling and careful follow-up are crucial for optimal outcomes in affected individuals and families 5 6 12.

By understanding the full spectrum of megalocornea—its symptoms, types, causes, and treatments—patients and clinicians can work together to safeguard vision and overall health.