Flat Cornea

Key points at a glance

Cornea plana is an extremely rare congenital disorder in which the peripheral cornea becomes scleralized and the cornea flattens. It is classified into an autosomal dominant mild type (CNA1) and an autosomal recessive severe type (CNA2). CNA2 is caused by mutations in the KERA gene, leading to impaired keratocan function, and presents with high hyperopia, corneal opacity, and shallow anterior chamber. Treatment primarily involves refractive correction, with attention to the risk of angle-closure glaucoma.

1. What is cornea plana?

Cornea plana is a congenital disorder in which the peripheral cornea becomes scleralized, resulting in flattening of the cornea. The border between the cornea and sclera becomes indistinct, and the clear corneal diameter is reduced. It is often bilateral and affects both males and females.

It is thought to arise from abnormalities in the limbal primordium during development. It is classified into two types: autosomal dominant CNA1 and autosomal recessive CNA2.

Epidemiology

It is an extremely rare disease. CNA2 shows clustering due to founder effects in northern Finland and Saudi Arabia. Finnish cases account for approximately 80% of all CNA2 cases worldwide. Families with CNA1 have been reported in Denmark, Germany, the United States, the Netherlands, and Cuba.

CNA1 (autosomal dominant type)

Severity: Mild

Causative gene: Unidentified (candidate gene in the 12q region)

Corneal refractive power: approximately 38 D (3–7 D lower than normal)

Central cornea: clear

Hyperopia: mild to moderate (mean +6.33 D)

CNA2 (autosomal recessive type)

Severity: severe

Causative gene: homozygous mutation in KERA gene (12q)

Corneal refractive power: approximately 30 D or less¹⁾

Central cornea: often with opacity

Hyperopia: high (greater than +10 D)

Q What is the difference between CNA1 and CNA2 in flat cornea?

A

CNA1 is an autosomal dominant mild type. The central cornea is clear, corneal refractive power is about 38 D (close to normal), and hyperopia is mild. In contrast, CNA2 is an autosomal recessive severe type caused by KERA gene mutation. It involves central corneal opacity, corneal refractive power reduced to about 30 D, and high hyperopia exceeding +10 D. CNA2 often has other ocular complications such as angle abnormalities and iris abnormalities, and the prognosis is worse than CNA1.

2. Main symptoms and clinical findings

Subjective symptoms

Patients often present in childhood due to poor vision from high hyperopia. CNA2 may be accompanied by amblyopia. Some patients complain of decreased vision due to corneal opacity.

Clinical findings

The cornea becomes flattened, and the border between the cornea and sclera is indistinct. The peripheral cornea shows opacification, and in CNA2, central opacification may also be observed. Arcus lipoides appears at a relatively young age. A shallow anterior chamber is noted, with reported anterior chamber depths ranging from 0.8 to 2.1 mm.

Finding	CNA1	CNA2
Corneal refractive power	Approximately 38 D	Approximately 30 D or less
Central cornea	Clear	Opacification present
Hyperopia degree	Around +6.33 D	Over +10 D

In CNA2, a round opaque thickening of 4–6 mm in diameter may be observed in the central cornea. This thickening adheres to Descemet’s membrane, and the cornea is thinnest around it. Iris abnormalities (iris atrophy, iris nodules, pupillary abnormalities) may also be present.

In some cases, K values were extremely flat at 21.8/27.0 D and 19.4/28.7 D, anterior chamber depths were 1.15 mm and 0.97 mm, and central corneal thicknesses were thin at 410 μm and 315 μm¹⁾.

3. Causes and Risk Factors

KERA Gene Mutation (CNA2)

CNA2 is caused by a homozygous mutation in the KERA gene on chromosome 12. The KERA gene encodes keratocan, a cornea-specific proteoglycan involved in regulating collagen fibril spacing and diameter.

Both missense and nonsense mutations have been reported. In particular, seven different KERA mutations have been identified in the Saudi Arabian population. To date, 15 KERA mutations have been reported, of which seven are missense mutations¹⁾.

Causes of CNA1

The causative gene for CNA1 has not been identified. Analysis of two candidate genes on chromosome 12 is ongoing, but known genes such as DCN, DSPG3, LUM, PITX2, and FOXC1 have been excluded as causes.

Genetic Counseling

Since cornea plana is a hereditary condition, both parents are carriers in CNA2. Genetic counseling for families is recommended. Early refractive correction and amblyopia prevention are important, and continuous monitoring for the risk of angle-closure glaucoma is necessary.

4. Diagnosis and Examination Methods

Cornea Plana image

Mohammad-Reza Sedaghat, Hamed Momeni-Moghaddam, Michael W Belin, Maryam Savardashtaki, et al. Acute Hydrops with Total Corneal Edema in a Very Young Child with Keratoconus: The Youngest Age Reported Case 2022 Aug 12 Case Rep Ophthalmol Med. 2022 Aug 12; 2022:2381703 Figure 3. PMCID: PMC9391173. License: CC BY.

Anterior segment OCT of the right and left eyes shows a shallow corneal curvature and a generally flat anterior surface. In both eyes, the anterior and posterior corneal surfaces form gentle arcs, and the anterior chamber appears relatively shallow.

Slit Lamp Examination

Confirm scleralization of the peripheral cornea and corneal flattening. When the observation system of the slit lamp is swung widely to the side, the corneal flattening becomes obvious. In CNA2, central corneal opacity is also assessed.

Keratometry

Measurement of corneal refractive power is useful for differentiating CNA1 and CNA2. In CNA2, the cornea flattens to about 30 D, and in CNA1 to about 38 D. Older keratometers cannot measure below 30 D, so a technique of attaching a weak plus lens to extend the measurement range is used.

Anterior Segment OCT

It is useful for visualizing the relationship between the cornea, angle, and iris. It is also used to evaluate the depth and extent of central corneal opacity.

Differential Diagnosis

Disease	Key Points for Differentiation
Sclerocornea	Corneal opacity and flattening only
EDS Type VI	Associated with systemic symptoms
Rieger Anomaly	Anterior segment dysgenesis

In addition, differentiation from posterior polymorphous corneal dystrophy (PPCD), mucopolysaccharidosis, and microcornea is necessary. Isolated corneal flattening without systemic malformations is likely to be cornea plana.

Q How is cornea plana diagnosed?

A

The diagnosis of cornea plana is based on slit-lamp examination showing corneal flattening and peripheral sclerocornea, and keratometry showing reduced corneal refractive power. In CNA2, corneal refractive power decreases to about 30 D. Anterior segment OCT is useful for detailed evaluation of the cornea and angle. Genetic testing of the KERA gene is used for definitive diagnosis. Differential diagnoses include sclerocornea, Ehlers-Danlos syndrome type VI, and Rieger anomaly, which must be excluded.

5. Standard Treatment

Refractive Correction

When opacities are limited to the periphery, the basic approach is hyperopic refractive correction. For spectacle prescription, it is recommended to prescribe lenses that are 3 to 4 diopters weaker than the objective measurement, based on subjective refraction testing.

Corneal Transplantation

If opacities extend to the central cornea, corneal transplantation should be considered. However, outcomes of full-thickness corneal transplantation are poor, and attention must be paid to glaucoma associated with angle abnormalities.

Cataract Surgery

In flat cornea, cataract surgery is challenging due to shallow anterior chamber and abnormal K values. For intraocular lens power calculation, standard optical biometers may not be usable, and the SRK regression formula is sometimes employed¹⁾. In one case, a 34 D toric intraocular lens was used, achieving a postoperative corrected visual acuity of 6/12¹⁾. During surgery, adequate use of viscoelastic substances and maintenance of the anterior chamber with high irrigation pressure are important¹⁾.

Glaucoma Management

Due to shallow anterior chamber, there is a high risk of angle-closure glaucoma. Cases of open-angle glaucoma have also been reported. Regular intraocular pressure measurement and gonioscopy monitoring are essential.

Amblyopia Prevention

In flat cornea, there is a risk of anisometropic amblyopia due to high hyperopia or astigmatism. Early detection in childhood and appropriate refractive correction greatly influence prognosis. Strabismus is also common, making pediatric ophthalmology management important.

Q Is cataract surgery possible in flat cornea?

A

It is possible but technically difficult. Due to shallow anterior chamber and abnormally flat cornea, intraocular lens power calculation may not be feasible with standard biometers. Alternative calculation methods such as the SRK regression formula are used. During surgery, it is important to maintain the anterior chamber with sufficient viscoelastic substances and protect the corneal endothelium. Toric intraocular lenses can also correct high astigmatism. Recent reports have shown good refractive outcomes.

6. Pathophysiology and Detailed Mechanism

Function of Keratocan

Keratocan, encoded by the KERA gene, belongs to the Small Leucine-Rich Proteoglycan (SLRP) family. Keratocan has 10 leucine-rich repeat (LRR) motifs and controls the spacing (42–44 nm) and diameter of collagen fibrils in the corneal stroma¹⁾. This uniform fibril arrangement is essential for maintaining corneal transparency, refractive power, and strength.

Effects of KERA Mutations

KERA mutations destabilize the structure of keratocan and impair its binding to collagen fibrils. A novel mutation (c.659T>C, p.Leu220Ser) was shown by protein modeling to disrupt the hydrophobic core within the LRR motif and compromise the stability of the asparagine ladder¹⁾.

Related Disease: Posterior Amorphous Corneal Dystrophy (PACD)

PACD is an autosomal dominant disorder caused by heterozygous deletions of four SLRP genes (KERA, LUM, DCN, EPYC) located at 12q21.33²⁾. Similar to cornea plana, it presents with decreased K values (less than 41 D) and corneal thinning²⁾. Both conditions share corneal structural changes due to KERA gene abnormalities, but PACD involves deletions of multiple genes, whereas cornea plana CNA2 results from point mutations in the KERA gene alone.

7. Recent Research and Future Perspectives

Advances in genetic testing have led to the identification of novel KERA mutations. To date, 15 KERA mutations have been reported, contributing to improved accuracy of genetic counseling¹⁾. Pathogenicity prediction of variants of uncertain significance (VUS) using protein modeling is gaining attention as a new approach in genetic diagnosis¹⁾.

In cataract surgery, the use of toric intraocular lenses and refined biometry has enabled favorable refractive outcomes¹⁾. In the future, participation in clinical trials of cell therapy and gene therapy may become possible¹⁾.

Disclaimer

This article is intended for educational purposes for healthcare professionals and medical students and does not serve as a guide for diagnosis or treatment of individual patients. In clinical practice, please follow the latest guidelines and the judgment of specialists.

8. References

1. Abdalla Elsayed MEA, MacLaren RE. Cataract surgery with autosomal recessive cornea plana caused by a novel KERA mutation. Am J Ophthalmol Case Rep. 2026;41:102514.
2. Borselli M, Rossi C, Carnevali A, Scorcia V, Giannaccare G. Petal-shaped corneal pattern in a patient with posterior amorphous corneal dystrophy. Am J Ophthalmol Case Rep. 2024;35:102081.
3. VELICKY J, VRABEC F. [Cornea plana congenita]. Ann Ocul (Paris). 1951;184(8):707-13. PMID: 14878258.