Meesmann corneal dystrophy (MECD) is a rare hereditary

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

disease that is characterized as a type of

corneal dystrophy 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. Signs and symptoms Corneal dystrophy may not significantly affect ...

and a

keratin disease A keratin disease is a genetic disorder of one of the keratin genes. An example is monilethrix. The first to be identified was epidermolysis bullosa simplex. Pathology Examples of keratin disease include: See also * List of cutaneous condition ...

. 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. It is named after the German

ophthalmologist Ophthalmology (, ) is the branch of medicine that deals with the diagnosis, treatment, and surgery of eye diseases and disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a ...

Alois Meesmann (1888–1969). It is often considered as the "Meesmann-Wilke syndrome", after the joint contribution of Meesmann and Wilke in 1939.A. Meesmann, F. Wilke. Klinische und anatomische Untersuchungen über eine bisher unbekannte, dominant vererbte Epithel Dystrophie der Horn haut. Klinische Monatsblätter für Augenheilkunde, Stuttgart, 1939, 103: 361-391. Research was later contributed by Stocker and Holt in 1954 through 1955 who found a variant of Meesmann corneal dystrophy called "Stocker-Holt Dystrophy".

Symptoms and signs

* Anterior corneal intraepithelial microcysts * Corneal erosions *

Photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence o ...

Lacrimation Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...

* Intermittent visual acuity loss (rarely seriously impaired) * Nonprogressive

* Fine punctate

corneal opacities 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 diamete ...

* Episodic foreign body sensation * Increased tear production * Eye stinging *

Blepharospasm Blepharospasm is a neurological disorder characterized by intermittent, involuntary spasms and contractions of the orbicularis oculi muscle, orbicularis oculi (eyelid) muscles around both eyes. These result in abnormal twitching or blinking, an ...

Meesmann corneal dystrophy is a non-inflammatory condition that effects the restricted region of the cornea epithelium which is the outermost layer. Onset of symptoms begin during infancy or early childhood but may not become noticeable or problematic for many years.

Genetics

It has been associated with genes KRT3 and KRT12 located on chromosome 12 and 17 respectively found through the use of

Polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...

or PCR. These two genes function for keratin production and code for the production of keratin K3 (type II) and K12 (type I). There are several methods to find errors or mutations in the KRT3 and KRT12 genes including deletion/duplication analysis, sequence analysis of the entire coding region, and targeted variant analysis. These methods includes molecular genetic tests which include Next-Generation (NGS)/

Massively parallel sequencing Massive parallel sequencing or massively parallel sequencing is any of several high-throughput approaches to DNA sequencing using the concept of massively parallel processing; it is also called next-generation sequencing (NGS) or second-generation ...

(MPS) and bi-directional sanger sequence analysis. A heterozygous missense mutation of Leu132Pro in the KRT12 gene exhibits a more severe phenotype while a mutation of Arg135Thr, which is most commonly found, exhibits milder symptoms. The Leu132Pro mutation and the animo acid change of N133K occurs in the helix-initiation motif of the keratin and was found to cause significant structural changes to the KRT12 gene. This mutation also leads to the aggregation of keratine and alters the keratin configuration of the corneal epithelium. The mechanism by which this mutation in K12 causes the formation of microcysts remains poorly understood.

Diagnosis

Patients with Meesmann corneal dystrophy may remain asymptomatic or experience mild symptoms. Symptoms of Meesmann corneal dystrophy often go unnoticed and is usually found and diagnosed during routine eye examinations. This slowly progressive disorder is characterized by microcysts that are filled with debris in the epithelium of the cornea detected and clinically diagnosed with slit-lamp biomicroscopy and retroillumination. Under electron microscopy, there are an abnormal aggregation of keratin filament bundles in the center of the cornea. It was found to not affect the corneal stromal layer or endothelial cell layer. Signs of this disease appear in the early first few years of life and begin as eye irritation. Under magnification, corneal changes consisting of punctate opacities in the epithelium are found. Occasionally, these are found in the Bowman membrane. Patients diagnosed with Meesmann corneal dystrophy are unable to tolerate the use of contact lenses which irritate the corneal epithelium.

Light microscopy Microscopy is the technical field of using microscopes to view subjects too small to be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of microscopy: optical, el ...

and

electron microscopy An electron microscope is a microscope that uses a beam of electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing i ...

found that the basement membrane is thickened with an intracytoplasmic substance. Under slit-lamp photography, the cornea was found to be uneven due to the damage and scarring from the thickening basement membrane and anterior stroma. The buildup of foreign materials may cause vision blurriness or cloudiness.

Treatment

Patients with Meesman corneal dystrophy will develop chronic eye dryness that can be treated with lubricating eye drops but most cases do not require further treatment. In severe cases, surgery may be required due to excessive corneal scarring such as superficial keratectomy (SK),

phototherapeutic keratectomy Phototherapeutic keratectomy (PTK) is a type of eye surgery that uses a laser to treat various ocular disorders by removing tissue from the cornea. PTK allows the removal of superficial corneal opacities and surface irregularities. It is simila ...

(PTK), lamellar keratoplasty, or

penetrating keratoplasty Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue (the graft). When the entire cornea is replaced it is known as penetrating keratoplasty a ...

. Patients may relapse in symptoms but surgery prolongs the reoccurrence and may also lessen severity. Currently there are researchers studying the use of allele-specific siRNA against mutants with single-nucleotide specificity as a potential method of treatment for MECD.

References

External links

{{Human corneal dystrophy Disorders of sclera and cornea