| Corneal dystrophy | |
|---|---|
 | |
| Corneal dystrophy, Gelatinous drop-like | |
| Specialty | Ophthalmology |
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]
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.[ citation needed ]
There are over 20 corneal dystrophies that affect all parts of the cornea. These diseases share many traits:[ citation needed ]
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]
Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Mutations in TGFBI which encodes transforming growth factor beta induced 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.[ citation needed ]
Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or rarely X-linked recessive Mendelian mode of inheritance:
| Type | Name | Inheritance | Gene locus | Gene |
|---|---|---|---|---|
| Superficial corneal dystrophies | Meesmann corneal dystrophy | AD (autosomal dominant) | 12q13, 17q12 | KRT3, KRT12 |
| Reis-Bücklers corneal dystrophy | AD | 5q31 | TGFBI | |
| Gelatinous drop-like corneal dystrophy | AR | 1p32 | TACSTD2 | |
| Stromal corneal dystrophies | Macular dystrophy | AR | 16q22 | CHST6 |
| Granular dystrophy | AD | 5q31 | TGFBI | |
| Lattice dystrophy | AD | 5q31, 9q34 | TGFBI, GSN (gene) | |
| Schnyder corneal dystrophy | AD | 1p34.1–p36 | UBIAD1 | |
| Congenital stromal corneal dystrophy | AD | 12q13.2 | DCN | |
| Fleck corneal dystrophy | AD | 2q35 | PIP5K3 | |
| Posterior dystrophies | Fuchs' dystrophy | AD | 1p34.3,13pTel-13q12.13, 18q21.2–q21.32, 20p13-p12, 10p11.2 | COL8A, SLC4A11, TCF8, TCF4 |
| Posterior polymorphous corneal dystrophy | AD | 20p11.2, 1p34.3-p32.3, 10p11.2 | COL8A2, TCF8,OVOL2, GRHL2 | |
| Congenital hereditary endothelial dystrophy | AR (autosomal recessive) | 20p13-p12 | SLC4A11 | |
A corneal dystrophy can be caused by an accumulation of extraneous material in the cornea, including lipids and cholesterol crystals.[ citation needed ]
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.[ citation needed ]
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 4–5 years of age in Reis-Bücklers 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 Thiel–Behnke 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.[ citation needed ]
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 periphery. 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.[ citation needed ]
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 all the 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 (2–3 times thicker than normal) corneas from birth or infancy.[ citation needed ]
Main differential diagnosis include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase 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.[ citation needed ]
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 whirlpool-like 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 α-galactosidase, known as Fabry disease. [3]
Corneal dystrophies were commonly subdivided depending on its specific location within the cornea into anterior, stromal, or posterior according to the layer of the cornea affected by the dystrophy.[ citation needed ]
In 2015 the ICD3 classification was published. [5] and has classified disease into four groups as follows:
The following (now historic) classification was by Klintworth: [3]
Superficial dystrophies:
Stromal dystrophies:
Posterior dystrophies:
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.[ citation needed ]
Suboptimal vision caused by corneal dystrophy may be helped with scleral contact lenses but eventually 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.[ citation needed ]
With penetrating keratoplasty (corneal transplant), the long-term results are good to 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.[ citation needed ]
Phototherapeutic keratectomy (PTK) can be used to excise or ablate the abnormal corneal tissue. Patients with superficial corneal opacities are suitable candidates for this procedure. [3]
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is approximately 43 dioptres. The cornea can be reshaped by surgical procedures such as LASIK.
The Bowman's layer is a smooth, acellular, nonregenerating layer, located between the superficial epithelium and the stroma in the cornea of the eye. It is composed of strong, randomly oriented collagen fibrils in which the smooth anterior surface faces the epithelial basement membrane and the posterior surface merges with the collagen lamellae of the corneal stroma proper.
The corneal endothelium is a single layer of endothelial cells on the inner surface of the cornea. It faces the chamber formed between the cornea and the iris.
Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue. When the entire cornea is replaced it is known as penetrating keratoplasty and when only part of the cornea is replaced it is known as lamellar keratoplasty. Keratoplasty simply means surgery to the cornea. The graft is taken from a recently deceased individual with no known diseases or other factors that may affect the chance of survival of the donated tissue or the health of the recipient.
Fuchs dystrophy, also referred to as Fuchs endothelial corneal dystrophy (FECD) and Fuchs endothelial dystrophy (FED), is a slowly progressing corneal dystrophy that usually affects both eyes and is slightly more common in women than in men. Although early signs of Fuchs dystrophy are sometimes seen in people in their 30s and 40s, the disease rarely affects vision until people reach their 50s and 60s.
Descemet's membrane is the basement membrane that lies between the corneal proper substance, also called stroma, and the endothelial layer of the cornea. It is composed of different kinds of collagen than the stroma. The endothelial layer is located at the posterior of the cornea. Descemet's membrane, as the basement membrane for the endothelial layer, is secreted by the single layer of squamous epithelial cells that compose the endothelial layer of the cornea.
Corneal ulcer, also called keratitis, is an inflammatory or, more seriously, infective condition of the cornea involving disruption of its epithelial layer with involvement of the corneal stroma. It is a common condition in humans particularly in the tropics and in farming. In developing countries, children afflicted by vitamin A deficiency are at high risk for corneal ulcer and may become blind in both eyes persisting throughout life. In ophthalmology, a corneal ulcer usually refers to having an infection, while the term corneal abrasion refers more to a scratch injury.
Band keratopathy is a corneal disease derived from the appearance of calcium on the central cornea. This is an example of metastatic calcification, which by definition, occurs in the presence of hypercalcemia.
Bullous keratopathy, also known as pseudophakic bullous keratopathy (PBK), is a pathological condition in which small vesicles, or bullae, are formed in the cornea due to endothelial dysfunction.
Meesmann corneal dystrophy (MECD) is a rare hereditary autosomal dominant disease that is characterized as a type of corneal dystrophy and a keratin disease. MECD is characterized by the formation of microcysts in the outermost layer of the cornea, known as the anterior corneal epithelium. The anterior corneal epithelium also becomes fragile. This usually affects both eyes rather than a single eye and worsens over time. There are two phenotypes, Meesmann corneal dystrophy 1 (MECD1) and Meesmann corneal dystrophy 2 (MECD2), which affect the genes KRT3 and KRT12, respectively. A heterozygous mutation in either of these genes will lead to a single phenotype. Many with Meesmann corneal dystrophy are asymptomatic or experience mild symptoms.
Reis-Bücklers corneal dystrophy is a disease of the eye, a rare corneal dystrophy of unknown cause, in which the Bowman's layer of the cornea undergoes disintegration. The disorder is inherited in an autosomal dominant fashion, and is associated with mutations in the gene TGFB1.
Posterior polymorphous corneal dystrophy is a type of corneal dystrophy, characterised by changes in Descemet's membrane and endothelial layer. Symptoms mainly consist of decreased vision due to corneal edema. In some cases they are present from birth, other patients are asymptomatic. Histopathological analysis shows that the cells of endothelium have some characteristics of epithelial cells and have become multilayered. The disease was first described in 1916 by Koeppe as keratitis bullosa interna.
Congenital stromal corneal dystrophy (CSCD) is an extremely rare, autosomal dominant form of corneal dystrophy. Only 4 families have been reported to have the disease by 2009. The main features of the disease are numerous opaque flaky or feathery areas of clouding in the stroma that multiply with age and eventually preclude visibility of the endothelium. Strabismus or primary open angle glaucoma was noted in some of the patients. Thickness of the cornea stays the same, Descemet's membrane and endothelium are relatively unaffected, but the fibrils of collagen that constitute stromal lamellae are reduced in diameter and lamellae themselves are packed significantly more tightly.
Lattice corneal dystrophy type is a rare form of corneal dystrophy. It has no systemic manifestations, unlike the other type of the dystrophy, Lattice corneal dystrophy type II. Lattice corneal dystrophy was first described by Swiss ophthalmologist Hugo Biber in 1890.
Congenital hereditary corneal dystrophy (CHED) is a form of corneal endothelial dystrophy that presents at birth.
Dua's layer, according to a 2013 paper by Harminder Singh Dua's group at the University of Nottingham, is a layer of the cornea that had not been detected previously. It is hypothetically 15 micrometres thick, the fourth caudal layer, and located between the corneal stroma and Descemet's membrane. Despite its thinness, the layer is very strong and impervious to air. It is strong enough to withstand up to 2 bars of pressure. While some scientists welcomed the announcement, other scientists cautioned that time was needed for other researchers to confirm the discovery and its significance. Others have met the claim "with incredulity".
Corneal hydrops is an uncommon complication seen in people with advanced keratoconus or other corneal ectatic disorders, and is characterized by stromal edema due to leakage of aqueous humor through a tear in Descemet's membrane. Although a hydrops usually causes increased scarring of the cornea, occasionally it will benefit a patient by creating a flatter cone, aiding the fitting of contact lenses. Corneal transplantation is not usually indicated during corneal hydrops.
Pre Descemet's endothelial keratoplasty (PDEK) is a kind of endothelial keratoplasty, where the pre descemet's layer (PDL) along with descemet's membrane (DM) and endothelium is transplanted. Conventionally in a corneal transplantation, doctors use a whole cornea or parts of the five layers of the cornea to perform correction surgeries. In May 2013, Dr Harminder Dua discovered a sixth layer between the stroma and the descemet membrane which was named after him as the Dua's layer. In the PDEK technique, doctors take the innermost two layers of the cornea, along with the Dua's layer and graft it in the patient's eye.
Descemet membrane endothelial keratoplasty (DMEK) is a method of corneal transplantation. The DMEK technique involves the removal of a very thin sheet of tissue from the posterior (innermost) side of a person's cornea, replacing it with the two posterior (innermost) layers of corneal tissue from a donor's eyeball. The two corneal layers which are exchanged are the Descemet's membrane and the corneal endothelium. The person's corneal tissue is gently excised, peeled off, and replaced with the donor tissue via small 'clear corneal incisions' (small corneal incisions just anterior to the corneal limbus. The donor tissue is tamponaded against the person's exposed posterior corneal stroma by injecting a small air bubble into the anterior chamber. To ensure the air tamponade is effective, it is necessary for people to strictly maintain such a posture that they are looking up at the ceiling during the recovery period until the air bubble has fully resorbed.
Corneal opacification is a term used when the human cornea loses its transparency. The term corneal opacity is used particularly for the loss of transparency of cornea due to scarring. Transparency of the cornea is dependent on the uniform diameter and the regular spacing and arrangement of the collagen fibrils within the stroma. Alterations in the spacing of collagen fibrils in a variety of conditions including corneal edema, scars, and macular corneal dystrophy is clinically manifested as corneal opacity. The term corneal blindness is commonly used to describe blindness due to corneal opacity.
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