Meesmann corneal dystrophy

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Meesmann Corneal Dystrophy
Other namesMeesmann Epithelial Corneal Dystrophy Meesmann-Wilke Syndrome
Meesmann corneal dystrophy - Multiple opaque spots in the corneal epithelium.JPEG
Multiple opaque spots in the corneal epithelium
Specialty Ophthalmology
Symptoms Anterior corneal intraepithelial microcysts, Corneal erosions, Photophobia, Lacrimation, Intermittent visual, acuity loss (rarely seriously impaired), Nonprogressive corneal dystrophy, Fine punctate corneal opacities, Episodic foreign body sensation, Increased tear production, eye stinging, Blepharospasm
Usual onsetInfancy or Young Childhood
DurationLifelong
TypesMeesmann corneal dystrophy 1, Meesmann corneal dystrophy 2
Diagnostic method Slit Lamp Biomicroscopy
TreatmentEye drops, Corneal Surgery

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. [1] [2] Many with Meesmann corneal dystrophy are asymptomatic or experience mild symptoms. [3]

Contents

Autosomal Dominant Inheritance Pattern Wiki Drawing - Autosomal Dominant (1).svg
Autosomal Dominant Inheritance Pattern

It is named after the German ophthalmologist Alois Meesmann (1888–1969). [4] [5] It is often considered as the "Meesmann-Wilke syndrome", after the joint contribution of Meesmann and Wilke in 1939. [4] [6] Research was later contributed by Stocker and Holt in 1954 through 1955 who found a variant of Meesmann corneal dystrophy called "Stocker-Holt Dystrophy". [3]

Symptoms and signs

Meesmann corneal dystrophy is a non-inflammatory condition that effects the restricted region of the cornea epithelium which is the outermost layer. [2] Onset of symptoms begin during infancy or early childhood but may not become noticeable or problematic for many years. [3] [7] [8]

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 or PCR. [3] [9] These two genes function for keratin production and code for the production of keratin K3 (type II) and K12 (type I). [1] [9] 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 (MPS) and bi-directional sanger sequence analysis. [10]

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. [11] 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. [9] [12] This mutation also leads to the aggregation of keratine and alters the keratin configuration of the corneal epithelium. [2] The mechanism by which this mutation in K12 causes the formation of microcysts remains poorly understood. [2]

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. [13] 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. [1] [9] Under electron microscopy, there are an abnormal aggregation of keratin filament bundles in the center of the cornea. [12] It was found to not affect the corneal stromal layer or endothelial cell layer. [14] 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 and electron microscopy 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. [6]

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. [1] In severe cases, surgery may be required due to excessive corneal scarring such as superficial keratectomy (SK), phototherapeutic keratectomy (PTK), lamellar keratoplasty, or penetrating keratoplasty. [1] Patients may relapse in symptoms but surgery prolongs the reoccurrence and may also lessen severity. [1] 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. [11]

See also

Related Research Articles

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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.

<span class="mw-page-title-main">LASIK</span> Corrective ophthalmological surgery

LASIK or Lasik, commonly referred to as laser eye surgery or laser vision correction, is a type of refractive surgery for the correction of myopia, hyperopia, and an actual cure for astigmatism, since it is in the cornea. LASIK surgery is performed by an ophthalmologist who uses a laser or microkeratome to reshape the eye's cornea in order to improve visual acuity.

<span class="mw-page-title-main">Bowman's layer</span> Layer in the cornea of the eye

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.

<span class="mw-page-title-main">Corneal endothelium</span> Single layer of endothelial cells on the surface of the cornea

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.

<span class="mw-page-title-main">Keratin 12</span> Protein-coding gene in the species Homo sapiens

Keratin 12 is a protein that in humans is encoded by the KRT12 gene.

<span class="mw-page-title-main">Fuchs' dystrophy</span> Medical condition

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.

<span class="mw-page-title-main">Recurrent corneal erosion</span> Medical condition

Recurrent corneal erosion is a disorder of the eyes characterized by the failure of the cornea's outermost layer of epithelial cells to attach to the underlying basement membrane. The condition is excruciatingly painful because the loss of these cells results in the exposure of sensitive corneal nerves. This condition can often leave patients with temporary blindness due to extreme light sensitivity (photophobia).

<span class="mw-page-title-main">Corneal dystrophy</span> Medical condition

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.

<span class="mw-page-title-main">Corneal epithelium</span>

The corneal epithelium is made up of epithelial tissue and covers the front of the cornea. It acts as a barrier to protect the cornea, resisting the free flow of fluids from the tears, and prevents bacteria from entering the epithelium and corneal stroma.

<span class="mw-page-title-main">Band keratopathy</span> Medical condition

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.

<span class="mw-page-title-main">Macular corneal dystrophy</span> Medical condition

Macular corneal dystrophy, also known as Fehr corneal dystrophy, is a rare pathological condition affecting the stroma of cornea first described by Arthur Groenouw in 1890. Signs are usually noticed in the first decade of life and progress afterwards, with opacities developing in the cornea and attacks of pain. This gradual opacification leads to visual impairment often requiring keratoplasty in the later decades of life.

<span class="mw-page-title-main">Corneal keratocyte</span>

Corneal keratocytes are specialized fibroblasts residing in the stroma. This corneal layer, representing about 85-90% of corneal thickness, is built up from highly regular collagenous lamellae and extracellular matrix components. Keratocytes play the major role in keeping it transparent, healing its wounds, and synthesizing its components. In the unperturbed cornea keratocytes stay dormant, coming into action after any kind of injury or inflammation. Some keratocytes underlying the site of injury, even a light one, undergo apoptosis immediately after the injury. Any glitch in the precisely orchestrated process of healing may cloud the cornea, while excessive keratocyte apoptosis may be a part of the pathological process in the degenerative corneal disorders such as keratoconus, and these considerations prompt the ongoing research into the function of these cells.

<span class="mw-page-title-main">Reis–Bucklers corneal dystrophy</span> Medical condition

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.

<span class="mw-page-title-main">Posterior polymorphous corneal dystrophy</span> Medical condition

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.

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<span class="mw-page-title-main">Lattice corneal dystrophy</span> Medical condition

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<span class="mw-page-title-main">Congenital hereditary endothelial dystrophy</span> Medical condition

Congenital hereditary corneal dystrophy (CHED) is a form of corneal endothelial dystrophy that presents at birth.

Peter S. Hersh is an American ophthalmologist and specialist in LASIK eye surgery, keratoconus, and diseases of the cornea. He co-authored the article in the journal Ophthalmology that presented the results of the study that led to the first approval by the U.S. Food and Drug Administration (FDA) of the excimer laser for the correction of nearsightedness in the United States. Hersh was also medical monitor of the study that led to approval of corneal collagen crosslinking for the treatment of keratoconus.

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<span class="mw-page-title-main">Corneal opacity</span> Medical condition

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References

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  3. 1 2 3 4 Online Mendelian Inheritance in Man (OMIM): 122100
  4. 1 2 synd/3139 at Who Named It?
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  6. 1 2 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.
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  11. 1 2 Liao, Haihui; Irvine, Alan D.; MacEwen, Caroline J.; Weed, Kathryn H.; Porter, Louise; Corden, Laura D.; Gibson, A. Bethany; Moore, Jonathan E.; Smith, Frances J. D.; McLean, W. H. Irwin; Moore, C. B. Tara (2011-12-12). "Development of Allele-Specific Therapeutic siRNA in Meesmann Epithelial Corneal Dystrophy". PLOS ONE. 6 (12): e28582. Bibcode:2011PLoSO...628582L. doi: 10.1371/journal.pone.0028582 . ISSN   1932-6203. PMC   3236202 . PMID   22174841.
  12. 1 2 Irvine, A D Coleman, C M Moore, J E Swensson, O Morgan, S J McCarthy, J H Smith, F J D Black, G C M McLean, W H I. A novel mutation in KRT12 associated with Meesmann's epithelial corneal dystrophy. Copyright 2002 British Journal of Ophthalmology. OCLC   680207259.{{cite book}}: CS1 maint: multiple names: authors list (link)
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