Anomalies of the Cornea

Corneal anomalies are conditions in which the function of the cornea is impaired due to various congenital or acquired pathologies. Corneal anomalies are classified based on anomalies of size, clarity, ectatic anomalies, corneal dystrophies, and acquired conditions. Pathological changes can result in opacity or clouding of the cornea and, hence, reduce visual acuity. Corneal anomalies are usually diagnosed based on clinical findings. Management includes correction of refractive errors and treatment of the underlying conditions.

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Overview

Cornea

The cornea is a transparent, avascular, watch glass-like structure that covers the iris, anterior chamber, and pupil.

  • Curvature of the cornea is > the rest of the globe.
  • 5 histological layers:
    • Epithelium
    • Bowman’s membrane 
    • Stroma
    • Descemet’s membrane
    • Endothelium

Classification of corneal abnormalities

  • Cryptophthalmos
  • Anomalies of size:
    • Microcornea
    • Megalocornea
  • Ectatic anomalies:
    • Keratoconus
    • Keratoglobus
  • Anomalies of clarity:
    • Peters anomaly
    • Sclerocornea
  • Corneal dystrophies:
    • Congenital stromal corneal dystrophy
    • Congenital endothelial corneal dystrophy
  • Acquired conditions:
    • Corneal keloids
    • Band-shaped keratopathy

Cryptophthalmos

Cryptophthalmos is an autosomal recessive congenital anomaly associated with systemic anomalies and is characterized by an uninterrupted continuity of the skin extend­ing from the forehead to the malar region.

Epidemiology

  • The incidence of cryptophthalmos is unknown.
    • May occur in isolation
    • Also associated with Fraser syndrome, an autosomal recessive malformation disorder presenting with:
      • Cryptophthalmos
      • Syndactyly
      • Abnormalities of the respiratory and urogenital tracts
  • Bilateral > unilateral

Clinical presentation

Three forms:

  • Complete = total failure of eyelid formation
    • Most common type
    • Eyelids are replaced by a layer of skin extending from the forehead to the malar region.
    • Absence or poor development of the eyebrow
    • Cornea is absent or fused with the skin.
  • Partial = result of the eyelid fold developing abnormally
    • Comprises approximately 20% of the cases
    • Rudimentary lids are present with a small conjunctival sac placed laterally. 
    • The globe is small and almost completely covered by skin.
  • Abortive = The part of the lid fold derived from the frontonasal process fails to develop, whereas the part derived from the maxillary process develops normally.
    • The abnormal upper lid covers and adheres to up to 75% of the upper cornea.
    • No punctum or upper conjunctival fornix
    • Normal lower lid

Management

Treatment is aimed at the surgical reconstruction of the eyelids to allow for visual development. There is no standard approach, and stepwise surgeries differ according to the severity of the abnormalities and orbit development.

Bilateral cryptophthalmos anomalies of the cornea

Bilateral cryptophthalmos

Image: “Bilateral cryptophthalmos with microphthalmos into left ocular globe and abnormal right ocular globe in a female infant with Fraser syndrome” by De Bernardo et al. License: CC BY 4.0

Corneal Ectatic Anomalies

Microcornea

The normal horizontal diameter of the cornea at birth is 10 mm. The adult size of about 11.7 mm is normally attained by 2 years of age.

Overview:

  • Microcornea is characterized by a corneal diameter < 10 mm.
  • Can be unilateral or bilateral
  • Can occur as an independent anomaly
  • May be associated with:
    • Microphthalmos: abnormally small globe
    • Nanophthalmos: abnormally small eye with a normal-sized lens

Clinical presentation:

  • Usually associated with myopia and microcornea
  • May present as isolated microcornea or relative anterior microphthalmos
  • Individuals usually develop glaucoma in the 4th decade of life.
Child with microcornea Anomalies of the cornea

Child with microcornea (diameters < 10 mm)

Image: “At 12 years of age, the child had horizontal corneal diameters of 10 mm but otherwise unremarkable anterior segments by slit-lamp examination” by Hazin R et al. License: CC BY 2.0

Megalocornea

Megalocornea is a bilateral, nonprogressive corneal enlargement characterized by a horizontal diameter of the cornea > 12 mm at birth and 13 mm at 2 years of age. 

Overview:

  • Usually, a clear cornea with normal thickness and vision
  • Inherited as an X-linked recessive trait
  • Systemic associations:
    • Marfan syndrome
    • Ehlers-Danlos syndrome
    • Down syndrome

Pathophysiology:

  • During corneal development, a defect in the formation of the optic cup allows it to overgrow.
  • Considered a primary overgrowth of the cornea 
  • Normal endothelial cell density is present. 

Clinical presentation:

  • Presents after 12 months of age when the cornea has fully developed
  • Symmetric, dome-shaped corneas > 13 mm in diameter
  • Reduced visual acuity is uncommon.
  • Astigmatism is common.
Megalocornea in a child

Megalocornea in a child with a corneal diameter > 14 mm

Image: “Megalocornea in a child with a corneal diameter greater than 14 mm” by Khan AO et al. License: CC BY 3.0, cropped by Lecturio.

Corneal Ectatic Anomalies

Keratoconus

Keratoconus refers to the thinning near the center of the cornea, resulting in corneal steepening and conical shape.

Overview:

  • Noninflammatory 
  • Progressive disorder
  • Caused by a congenital weakness of the cornea
  • Can be secondary to viral keratoconjunctivitis or trauma

Clinical presentation:

  • Presents at puberty or in early adulthood
  • Vision impairment progresses until the 4th decade.
  • Usually bilateral, may often be more severe on 1 side
  • Difficulties in correcting vision for myopia and astigmatism
  • Findings with advanced disease:
    • Munson’s sign: v-shaped indentation of the lower eyelid on downgaze (see image)
    • Vogt striae: deep stromal stress lines that are pathognomonic for keratoconus
    • Fleischer ring: deposition of hemosiderin at the base of the cone 
    • Acute hydrops: Ruptures may develop in the Descemet’s membrane causing the stroma to become suddenly edematous and opaque.
      • Can present with photophobia and a sudden painful drop in visual acuity
      • Treatments include pressure patching and bandage contact lenses.
      • Topical hyperosmotics, cycloplegics, and steroids are used to decrease edema, pain, and inflammation.

Diagnosis:

  • Slit-lamp exam: Cornea may appear normal.
  • Keratometry: may show distortion
  • Corneal topography: may aid in the diagnosis and in assessing disease progression

Management:

  • Corneal collagen crosslinking: A procedure that uses riboflavin drops, UV light, and a photosensitizer to strengthen the bonds in the cornea and measure progression.
  • Glasses: to correct myopic astigmatism as long as the patient can function
  • Contact lenses: 
    • Rigid gas-permeable lenses neutralize the irregularity of the cornea, but may become intolerable.
    • Scleral lenses that sit on the sclera without touching the cornea may be used.
  • Surgical interventions:
    • Keratoplasty: required in 10%–15% of patients 
    • Intrastromal corneal ring segments
Munson’s sign in a patient with keratoconus

Munson’s sign in a patient with keratoconus

Image: “Münson’s sign in a keratoconus patient which appears as bulging of the lower lid during downgaze” by BioMed Research International/Mariam Lotfy Khaled et al. License: CC BY 4.0

Keratoglobus

Keratoglobus is a hemispherical protrusion of the whole cornea with limbus-to-limbus thinning of the cornea.

Overview:

  • If congenital, the condition is bilateral.
  • Acquired forms have also been seen due to:
    • Keratoconjunctivitis
    • Chronic marginal blepharitis
    • Idiopathic orbital inflammation
  • Noninflammatory in origin 
  • Progressive in nature
  • Strong association with Ehlers Danlos syndrome type VI
  • Usually associated with defects in collagen synthesis or degradation

Clinical presentation:

  • Clear corneas, unless patients have episodes of hydrops and scarring
  • High myopia with irregular astigmatism
  • Corneal perforations due to extreme thinning

Management:

  • Refractive correction for high myopia
  • Protective eyewear reduces the incidence of corneal perforations. 
  • Fitting of customized scleral lenses
Diffuse corneal thinning with outward protrusion of the globe

a: diffuse corneal thinning with outward protrusion of the globe
b: indentation of the lower lid
c & d: stretched out limbus with clear anterior chamber

Image: “Clinical picture of the patient showing diffuse thinning of cornea with outward globular protrusion” by Gupta N et al. License: CC BY 4.0

Anomalies of Corneal Clarity

Peters anomaly

Peters anomaly is a congenital form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber results in a central defect in the corneal endothelium and causes leukoma (whitish plaque).

Overview:

  • Multiple gene loci:
    • PAX6
    • PITX2
    • FOXC1
    • CYP1B1
  • Can occur sporadically, but dominant and recessive inheritances are common
  • Systemic associations include:
    • Trisomy 13
    • Trisomy 15
    • Partial deletion of chromosome arm 11q
  • Incidence is unknown: part of the congenital corneal opacities seen in 3–6 individuals per 100,000 
  • Pathogenesis: due to a disruption in neural crest migration or separation that occurs in the 7th week of gestation

Clinical presentation and diagnosis:

  • Central, paracentral, or complete corneal opacity is always present.
  • Iris strands are often seen across the anterior chamber to the posterior surface of the cornea.
  • Peters anomaly type 1 presents with central corneal opacity and iridocorneal adhesions.
  • Peters anomaly type 2:
    • Associated with denser corneal opacification
    • Presents with keratolenticular adhesions
  • Diagnosis: based on clinical findings and confirmed using ultrasonography

Management:

  • Regular monitoring for glaucoma
  • Surgery: full-thickness penetrating keratoplasty plus lensectomy in patients with cataract
Corneal opacity seen in a case of Peters anomaly

Corneal opacity in a patient with Peters anomaly

Image: “Photograph of left eye” by Tuli N et al. License: CC BY 2.0

Sclerocornea

With sclerocornea, the limits of the cornea and sclera are indistinct, resulting in a congenital anomaly of clarity. Irregularly arranged collagen fibrils are noted.

Overview:

  • Additional ocular anomalies, such as cataracts or coloboma, are usually present.
  • Nonprogressive
  • Noninflammatory
  • May affect the entire cornea or be limited to a part of the cornea:
    • Peripheral type of sclerocornea: The affected area is vascularized with superficial scleral vessels.
    • Total sclerocornea: The entire cornea is opaque and vascularized.
  • Etiology:
    • Autosomal dominant or autosomal recessive form (much more severe)
    • Commonly occurs bilaterally
  • Pathophysiology:
    • Corneal development occurs during the 7th and 8th weeks of gestation.
    • Failure of the mesenchymal cells to differentiate into corneal and scleral cells allows the corneal curvature to exceed that of the sclera.

Clinical presentation:

  • Partial sclerocornea: presence of a peripheral, white, vascularized, 1–2-mm corneal rim that blends with the sclera. The central cornea is generally normal.
  • Total sclerocornea: 
    • Entire cornea is involved.
    • Center is clearer than the periphery.

Management:

  • Generally, no treatment is required. 
  • Refractive errors are corrected if present. 
  • Artificial tears may be used. 
  • In generalized sclerocornea, early keratoplasty should be considered to provide vision.
Peripheral scleral changes seen in a patient with sclerocornea

Peripheral scleral changes seen in a patient with sclerocornea

Image: “Sclerocornea” by Mataftsi A et al. License: CC BY 3.0

Corneal Dystrophies

Congenital stromal corneal dystrophy

A noninflammatory, inherited corneal disorder not usually associated with any other ocular or systemic conditions

Overview:

  • Usually involves the central area of the cornea
  • Discrete areas of opacification develop in the superficial layers of the stroma. 
  • Etiology:
    • Caused by mutations in the DCN gene
    • Autosomal dominant

Classification:

  • Lattice dystrophy types I and II 
  • Granular dystrophy types I and II 
  • Macular dystrophy
  • Reis-Bucklers dystrophy

Pathophysiology:

  • Clinical symptoms arise due to atrophy and degeneration of basal epithelial cells.
  • Amyloid and hyaline deposits also contribute to the development of symptoms. 
  • There is an increase in number and density until the Bowman’s membrane becomes eroded and the epithelium desquamates.
  • Corneal dystrophies can present as granular, lattice, or macular forms.
  • The corneal surface is normal or slightly irregular; small opacities are seen throughout the stroma of the entire cornea and give it a cloudy appearance.

Clinical presentation and diagnosis:

  • Reduction of vision due to deposits
  • Strabismus is common.
  • Slit-lamp exam: Anterior cornea displays flaky or feathery opacities.

Management:

  • Glasses or contact lenses for correction of refractive errors
  • Patching or surgical correction of strabismus
  • Keratoplasty

Congenital endothelial corneal dystrophy (CHED)

Congenital hereditary endothelial dystrophy is a corneal dystrophy characterized by bilateral diffuse clouding of corneas.

Etiology and epidemiology

  • Autosomal recessive
  • Mutation on chromosome 20p13
  • Affected gene: SLC4A11
  • Incidence: 3 in 100,000 births
  • Children of consanguineous marriages have a comparatively greater incidence.

Classification:

  • CHED
  • Posterior polymorphous corneal dystrophy (PPCD)

Pathophysiology: 

  • The SLC4A11 gene codes for a transmembrane protein, which acts as a pump between the endothelium and corneal stroma.
  • Dysfunction of this protein leads to deposition of material in the layers of the cornea and corneal clouding.

Clinical presentation and diagnosis:

  • History of congenital or perinatal clouding of the corneas bilaterally
  • Physical exam findings:
    • Reduced vision
    • Amblyopia 
    • Nystagmus

Management:

  • Surgery is the mainstay of treatment.
  • Penetrating keratoplasty or Descemet’s stripping automated endothelial keratoplasty are used.

Acquired Corneal Conditions

Corneal keloids

Corneal keloids are rare, benign, gray-white corneal lesions that result from abnormal fibrous tissue proliferation. Accumulation of collagen and various glycoproteins results in hyperplasia of the epithelium and disruption of the Bowman’s layer.

Overview:

  • Congenital: Bilateral cases of corneal keloids are associated with Lowe syndrome and Rubinstein-Taybi syndrome.
  • Acquired: can develop after ocular trauma or infection
  • Reported in ages ranging from 2 months to 72 years, but rare overall
  • Majority of corneal keloids occur in the 1st 3 decades of life.
  • Pathogenesis: Corneal stromal overgrowth during the healing process results in the transformation of keratocytes into fibroblasts and myofibroblasts, leading to keloid formation.

Clinical presentation:

  • Most patients present with a slow-growing corneal lesion that appears to be raised from the corneal surface.
  • Gray-white appearance
  • Painless, progressive loss of vision
  • Failure to close eyelids in the case of large keloids
  • Diagnosis is made using visual acuity and slit-lamp exams.

Management:

  • No treatment needed when asymptomatic
  • Close monitoring:
    • Size of the keloid
    • Visual acuity
  • Surgery is considered when the keloid causes a decrease in visual acuity:
    • Local excision
    • Superficial lamellar or phototherapeutic keratectomy
    • Keratoplasty
Corneal keloids appear as opacities

Corneal keloids appear as opacities that rise from the epicorneal surface.

Image: “Slit-lamp microscopic photographs of corneal keloids” by BMC Ophthalmology/Hyo Kyung Lee et al. License: CC BY 4.0, cropped by Lecturio.

Band-shaped keratopathy

A degenerative change associated with the deposition of calcium salts in the Bowman’s membrane and anterior stromal lamellae of the corneal epithelium

Overview:

  • Deposition may be due to a multitude of factors:
    • Precipitation of tears
    • pH change
    • Compromise of endothelial function 
    • Corneal edema
  • Remainder of the cornea is clear.
  • Presents as a band-shaped opacity in the interpalpebral zone, with a clear interval between the ends of the band and the limbus
  • Caused by chronic ocular inflammation due to:
    • Uveitis
    • Chronic herpetic keratouveitis
    • Phthisis bulbi
    • Keratoconjunctivitis sicca
    • Juvenile idiopathic arthritis
    • Herpes zoster keratitis
  • May be associated with systemic disorders:
    • Hyperparathyroidism
    • Vitamin D toxicity
    • CKD
    • Hypophosphatasia
    • Sarcoidosis

Clinical presentation:

  • Decreased visual acuity is directly proportional to the amount of calcium deposition in the cornea.
  • Foreign-body sensation
  • Ocular irritation with conjunctival redness
  • Photophobia
  • Calcium deposition begins in the periphery and progresses inwards.

Management:

  • Superficial debridement and lamellar keratectomy 
  • Treat the underlying cause, if known, to decrease further calcium deposition in the cornea.

References

  1. Ventocilla, M. (2021). Megalocornea clinical presentation: History, physical, causes. Medscape. Retrieved July 5, 2021, from https://emedicine.medscape.com/article/1196299
  2. Sihota, R., Tando, R. (2019). Parson’s Diseases of the Eye (22nd ed. Chapter 15). 
  3. Wallang, B.S., Das, S. (2013). Keratoglobus. Eye (London, England), 27(9), 1004–1012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772364/
  4. Ocubillo, M.V. (2018). Congenital clouding of the cornea. Medscape. Retrieved July 3, 2021, from https://emedicine.medscape.com/article/1197148
  5. Trief, D., Ciccone, L. (2021). Congenital hereditary endothelial dystrophy. American Academy of Ophthalmology. https://eyewiki.aao.org/Congenital_Hereditary_Endothelial_Dystrophy
  6. Vu, C.V., Hwang, F.S. (2021). Corneal keloids. American Academy of Ophthalmology. https://eyewiki.aao.org/Corneal_Keloids
  7. Taravella, M. (2018). Band keratopathy. Medscape. Retrieved July 5, 2021, from https://emedicine.medscape.com/article/1194813-overview
  8. Singh, P., Tripathy, K. (2021). Keratopathy. https://www.ncbi.nlm.nih.gov/books/NBK562153/
  9. Katzman, L.R., Reiser, B.J. (2016). Pediatric corneal opacities. Retrieved July 5, 2021, from https://www.aao.org/disease-review/pediatric-corneal-opacities
  10. Reynolds, J.D., Reynolds, A.L. (2019). Overview of glaucoma in infants and children. UpToDate. Retrieved July 3, 2021, from https://www.uptodate.com/contents/overview-of-glaucoma-in-infants-and-children
  11. Corneal diseases in children: Congenital anomalies. https://entokey.com/corneal-diseases-in-children-congenital-anomalies/

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