Corneal dystrophy is a group of rare hereditary disorders characterised by bilateral abnormal

deposition of substances in the transparent front part of the eye called the cornea.[1][2][3]
Contents

1 Pathophysiology

2 Signs and symptoms

3 Diagnosis

4 Differential diagnosis

5 Classification

6 Treatment

7 Genetics

8 See also

9 References

Pathophysiology
A corneal dystrophy can be caused by an accumulation of extraneous material in the cornea, including
lipids and cholesterol crystals.
Signs and symptoms
Corneal dystrophy may not significantly affect vision in the early stages. However, it does require
proper evaluation and treatment for restoration of optimal vision. Corneal dystrophies usually
manifest themselves during the first or second decade but sometimes later. It appears as grayish white
lines, circles, or clouding of the cornea. Corneal dystrophy can also have a crystalline appearance.
There are over 20 corneal dystrophies that affect all parts of the cornea. These diseases share many
traits:

They are usually inherited.

They affect the right and left eyes equally.

They are not caused by outside factors, such as injury or diet.

Most progress gradually.

Most usually begin in one of the five corneal layers and may later spread to nearby layers.

Most do not affect other parts of the body, nor are they related to diseases affecting other parts
of the eye or body.

Most can occur in otherwise totally healthy people, male or female.

Corneal dystrophies affect vision in widely differing ways. Some cause severe visual impairment,
while a few cause no vision problems and are diagnosed during a specialized eye examination by an
ophthalmologist. Other dystrophies may cause repeated episodes of pain without leading to permanent
loss of vision.[4]
Diagnosis
Diagnosis can be established on clinical grounds and this may be enhanced with studies on surgically
excised corneal tissue and in some cases with molecular genetic analyses. As clinical manifestations
widely vary with the different entities, corneal dystrophies should be suspected when corneal
transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and
especially in the presence of a positive family history or in the offspring of consanguineous parents.
Superficial corneal dystrophies - Meesmann dystrophy is characterized by distinct tiny bubble-like,
punctate opacities that form in the central corneal epithelium and to a lesser extent in the peripheral
cornea of both eyes during infancy that persists throughout life. Symmetrical reticular opacities form
in the superficial central cornea of both eyes at about 45 years of age in Reis-Bcklers corneal
dystrophy. Patient remains asymptomatic until epithelial erosions precipitate acute episodes of ocular
hyperemia, pain, and photophobia. Visual acuity eventually becomes reduced during the second and
third decades of life following a progressive superficial haze and an irregular corneal surface.In ThielBehnke dystrophy, sub-epithelial corneal opacities form a honeycomb-shaped pattern in the superficial
cornea. Multiple prominent gelatinous mulberry-shaped nodules form beneath the corneal epithelium
during the first decade of life in Gelatinous drop-like corneal dystrophy which cause photophobia,
tearing, corneal foreign body sensation and severe progressive loss of vision. Lisch epithelial corneal
dystrophy is characterized by feather shaped opacities and microcysts in the corneal epithelium that
are arranged in a band-shaped and sometimes whorled pattern. Painless blurred vision sometimes
begins after sixty years of life.
Corneal stromal dystrophies - Macular corneal dystrophy is manifested by a progressive dense
cloudiness of the entire corneal stroma that usually first appears during adolescence and eventually
causing severe visual impairment. In Granular corneal dystrophy multiple small white discrete
irregular spots that resemble bread crumbs or snowflakes become apparent beneath Bowman zone in
the superficial central corneal stroma. They initially appear within the first decade of life. Visual
acuity is more or less normal. Lattice dystrophy starts as fine branching linear opacities in Bowman's
layer in the central area and spreads to the preiphery. Recurrent corneal erosions may occur. The
hallmark of Schnyder corneal dystrophy is the accumulation of crystals within the corneal stroma
which cause corneal clouding typically in a ring-shaped fashion.
Posterior corneal dystrophies - Fuchs corneal dystrophy presents during the fifth or sixth decade of
life. The characteristic clinical findings are excrescences on a thickened Descemet membrane (cornea
guttae), generalized corneal edema and decreased visual acuity. In advanced cases, abnormalities are
found in the all layers of the cornea. In posterior polymorphous corneal dystrophy small vesicles
appear at the level of Descemet membrane. Most patients remain asymptomatic and corneal edema is
usually absent. Congenital hereditary endothelial corneal dystrophy is characterized by a diffuse
ground-glass appearance of both corneas and markedly thickened (23 times thicker than normal)
corneas from birth or infancy.
Differential diagnosis
Main differential diagnosis include various causes of monoclonal gammopathy, lecithin-cholesterolacyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic

lysosomal storage diseases, and several skin diseases (X-linked ichthyosis, keratosis follicularis
spinolosa decalvans).
Historically, an accumulation of small gray variable shaped punctate opacities of variable shape in the
central deep corneal stroma immediately anterior to Descemet membrane were designated deep
filiform dystrophy and cornea farinata because of their resemblance to commas, circles, lines, threads
(filiform), flour (farina) or dots. These abnormalities are now known to accompany X-linked
ichthyosis ,steroid sulfatase deficiency, caused by steroid sulfatase gene mutations and are currently
usually not included under the rubric of the corneal dystrophies.
In the past, the designation vortex corneal dystrophy (corneal verticillata) was applied to a corneal
disorder characterized by the presence of innumerable tiny brown spots arranged in curved whirlpoollike lines in the superficial cornea. An autosomal dominant mode of transmission was initially
suspected, but later it was realized that these individuals were affected hemizygous males and
asymptomatic female carriers of an X-linked systemic metabolic disease caused by a deficiency of galactosidase, known as Fabry disease.[3]
Classification
Corneal dystrophies are commonly subdivided depending on its specific location within the cornea. It
can be basically divided into anterior, stromal, or posterior according to the layer of the cornea
affected by the dystrophy.
The following classification is by Klintworth: [3]
Superficial dystrophies:

Epithelial basement membrane dystrophy

Meesmann juvenile epithelial corneal dystrophy

Gelatinous drop-like corneal dystrophy

Lisch epithelial corneal dystrophy

Subepithelial mucinous corneal dystrophy

Reis-Bucklers corneal dystrophy

Thiel-Behnke dystrophy

Stromal dystrophies:

Lattice corneal dystrophy

Granular corneal dystrophy

Macular corneal dystrophy

Schnyder crystalline corneal dystrophy

Congenital stromal corneal dystrophy

Fleck corneal dystrophy

Posterior dystrophies:

Fuchs' dystrophy

Posterior polymorphous corneal dystrophy

Congenital hereditary endothelial dystrophy

Treatment
Early stages may be asymptomatic and may not require any intervention. Initial treatment may
include hypertonic eyedrops and ointment to reduce the corneal edema and may offer symptomatic
improvement prior to surgical intervention.
Suboptimal vision caused by corneal dystrophy usually requires surgical intervention in the form of
corneal transplantation. Penetrating keratoplasty, a common type of corneal transplantation, is
commonly performed for extensive corneal dystrophy.
With penetrating keratoplasty (corneal transplant), the long term results are good-excellent. Recent
surgical improvements have been made which have increased the success rate for this procedure.
However, recurrence of the disease in the donor graft may happen. Superficial corneal dystrophies do
not need a penetrating keratoplasty as the deeper corneal tissue is unaffected, therefore a lamellar
keratoplasty may be used instead.
Phototherapeutic keratectomy (PTK) can be used to excise or ablate the abnormal corneal tissue.
Patients with superficial corneal opacities are suitable candidates for a this procedure. [3]
Genetics
Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3,
SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Mutations in TGFB1 which encodes
transforming growth factor beta cause several forms of corneal dystrophies including granular corneal
dystrophy, lattice corneal dystrophy, epithelial basement membrane dystrophy, Reis-Bucklers corneal
dystrophy, and Thiel-Behnke dystrophy.
Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or rarely X-linked
recessive Mendelian mode of inheritance:
Name
Inheritance
Gene locus
Superficial corneal dystrophies
Meesmann dystrophy
AD
12q13, 17q12
Reis-Bcklers corneal
AD
5q31
dystrophy
Gelatinous drop-like corneal
AR
1p32
dystrophy
Stromal corneal dystrophies
Macular dystrophy
AR
16q22
Granular dystrophy
AD
5q31
Lattice dystrophy

AD

5q31, 9q34

Gene
KRT3, KRT12
TGFB1
TACSTD2
CHST6
TGFB1
TGFB1, GSN
(gene)

Schnyder corneal dystrophy AD

Congenital stromal corneal
AD
dystrophy
Fleck corneal dystrophy
AD
Posterior dystrophies
Fuchs dystrophy
posterior polymorphous
corneal dystrophy
Congenital hereditary
endothelial dystrophy

1p34.1p36

UBIAD1

12q13.2

DCN

2q35

PIP5K3

AD

1p34.3,13pTel-13q12.13, 18q21.2
q21.32, 20p13-p12, 10p11.2

COL8A,
SLC4A11, TCF8

AD

20p11.2, 1p34.3-p32.3, 10p11.2

COL8A2, TCF8

AR

20p13-p12

SLC4A11