Common Corneal Dystrophies

Corneal dystrophies are a group of inherited, (usually) bilateral, (usually) symmetric disorders of the cornea. The dystrophies involve deposition of irregular materials not caused by inflammation, infection or secondary to trauma; these irregularities may or may not impact visual acuity and/or ocular surface integrity. These conditions are typically slowly progressive and not influenced by environmental or systemic health factors.^1,2

A study completed by Musch et al. found that the incidence of corneal dystrophy in the United States is 897 per million. The most common class of corneal dystrophy encountered was endothelial, such as Fuch’s Dystrophy, at 60%. The second most common was anterior corneal dystrophy, such as Epithelial Basement Membrane Dystrophy, which accounted for approximately 16%. There was a female predilection among all corneal dystrophies.²

Corneal dystrophy symptoms can range from completely asymptomatic to mildly symptomatic with glare or ocular surface disease, to severely symptomatic with photophobia, pain, recurrent corneal erosions, and/or permanent decrease in vision.¹ Based on signs and symptoms, corneal dystrophy treatment can range from none at all to requiring corneal transplant in severe cases. More common treatments include lubrication and ocular surface care along with managing recurrent corneal erosions.

When indicated, bandage contact lenses, anti-inflammatory and antibiotic regimens are also commonly utilized.¹ Of corneal transplants for corneal dystrophy, Fuch’s Corneal Dystrophy was the most common indication at 84%, followed by granular dystrophy at 4%. Lattice dystrophy, posterior polymorphous dystrophy and macular dystrophy were approximately 2% each, and the remainder of the dystrophies were less than 1% each.²

The cornea is composed of 5 layers, the outermost of which is the corneal epithelium, primarily responsible for protection, nutrient collection and oxygen absorption. At the epithelium’s posterior aspect is the fibrous layer of Bowman’s membrane. The most substantial portion of the cornea is the stroma, which consists of collagen and is primarily responsible for corneal transparency. The most posterior layer is the endothelial cell layer, primarily responsible for nutrient exchange with the aqueous humor. The final layer is the endothelial basement membrane, Descemet’s membrane.

All of these layers must be clear and structurally sound in order to achieve ideal optical clarity. Corneal dystrophies can impact the integrity of the corneal layers and lead to a wide spectrum of sequelae. The International Committee for Classification of Corneal Dystrophies divides the conditions into multiple categories.¹ We will discuss corneal dystrophies starting most anteriorly and moving posteriorly through the cornea.

Also known as Anterior Basement Membrane Dystrophy (or ABMD) and Map, Dot, Fingerprint Dystrophy. EBMD presents as sub-epithelial microcysts in patterns of lines, dots or geographic-type map shapes. The irregular epithelial appearance is caused by thickening of the epithelial basement membrane which presses into the epithelium causing striae, dots and geographic patterns. The dot lesions can either be composed of degenerated cellular material (Cogan’s cysts) or fibro-granular material. The presentation is usually bilateral but asymmetric and about 10% are associated with recurrent corneal erosion. The hereditary component is still unknown but current research suggests either an autosomal dominant or x-linked inheritance pattern.³

This is a rare, bilateral corneal dystrophy that presents within the first few years of life. It is characterized by intra-epithelial microcysts which, though visually asymptomatic, can painfully rupture. The cysts appear on slit lamp microscopy as small circular or oval opacities. The inheritance pattern is primarily autosomal dominant though cases of autosomal recessive variants have been reported.³

This corneal dystrophy primarily impacts Bowman’s Layer and can lead to painful recurrent corneal epithelium erosions, especially within the early diagnosis period. As recurrences take place, the irregular Bowman’s tissue becomes denser, which can decrease corneal sensitivity, thereby decreasing the pain associated, but cause visual impairment. During the second decade after diagnosis, ring and map-shaped opacities in Bowman’s membrane can be observed. The most common gene mutation associated with this condition is of the transforming growth factor beta-induced gene (TGFBI); however, there are also several other less-common mutations that have been linked to diagnosis.³

This is the most common of the epithelial-stromal class of corneal dystrophies. This condition presents as a branching pattern of amyloid material in the stroma. The most common subset of Lattice Dystrophy is Type 1 which presents in the first or second decades as linear deposits which progress and can sometimes cause central opacities in the anterior stroma and recurrent corneal erosions. It has an autosomal dominant inheritance and has been attributed to an abnormality of keratoepithelin (a protein coded for by TGFB1); this abnormality impacts the integrity of the extracellular matrix. Subtypes have been associated with systemic amyloidosis, called Meretoja syndrome; this can involve the eyes, skin and cranial nerves. Such cases have been noted to have thicker and more prominent stromal lesions.^1,3

Type 1 of this corneal dystrophy is characterized by granular hyaline opacities in the mid-stroma which extend more posteriorly as the condition progresses. The opacities have clear cornea between them at first but can progress to coalesced lesions that cause decreased vision. The deposition is usually noted in the first decade of life and follows an autosomal dominant inheritance pattern. Type 2 (also called Avellino Dystrophy) is characterized by a mix of granular and lattice-type stromal opacities; the granular opacities occur earlier, and the lattice opacities occur later. The granular opacities are composed of hyaline material and tend to be more anterior in location while the lattice opacities are amyloid based and located more in the posterior stroma. Presentation can vary and depending on the density and location of the opacity and vision may or may not be impacted. Both types result from TGFB1 mutations and have autosomal dominant inheritance patterns.^1,3

This corneal condition involves mucopolysaccharide stromal opacities that start centrally and eventually spread peripherally to involve the entire stroma. In addition to the opacities themselves, cloudy cornea extends between the opacities and concurrent corneal thinning occurs; these findings can lead to visual impairment. The presentation is due to a gene mutation impacting the enzyme, N-acetylglucosamine 6-O-sulfotransferase, responsible for cellular spacing, hydration and transparency in the cornea.³ This condition is the most common of the stromal dystrophies and is the only stromal dystrophy that is autosomal recessive.¹

This is a rare condition in which distinct, white-gray, round opacities are observed throughout the stroma early in life. They are slowly progressive but are most often visually insignificant. It is an autosomal dominant condition without any correlation to systemic disease. The presentation is attributed to a gene mutation that leads to accumulation of intracellular materials.³

Also called Schnyder’s Crystalline Corneal Dystrophy, this condition is characterized by central stromal cholesterol crystals and lipoid deposits. The cause is a metabolic defect in corneal keratocytes. It can sometimes, but not always, be associated with systemic hyperlipidemia and hypercholesterolemia. Signs usually manifest in the second or third decade starting with a central ring shaped opacity and progressing to include stromal haze extending mid-peripherally by the patient's late 30s. By age 50, many patients will have resulting glare, photophobia and/or decreased corneal sensation.¹ An autosomal dominant inheritance pattern has been identified.³

This is a rare condition present at birth (or shortly after) with bilateral central corneal clouding. White stromal, crystalized opacities will progress with age and can be associated with nystagmus and/or strabismus. A mutation in the proteoglycan, decorin, has been identified as the cause. Unfortunately, the majority of patients diagnosed with this condition require corneal transplant at a young age. This condition is autosomal dominant.³

This condition is characterized by polygonal, centrally located, gray opacities. The opacities are primarily located in the posterior stroma more than the anterior and are usually separated by clear zones creating a crocodile-like appearance. An autosomal dominant inheritance pattern is suspected. This condition can be very difficult to distinguish from crocodile shagreen, an age-related corneal degeneration.

This is the most common endothelial corneal dystrophy. It usually manifests bilaterally with the presence of guttata, stromal edema, and sometimes microcystic epithelial changes. It can be associated with recurrent corneal erosions, stromal opacification, and progressive vision loss. The condition is attributed to defects in collagen and membrane proteins which disrupt normal water-pumping mechanism of the endothelium. An autosomal dominant hereditary link has been found, but this condition can also occur without a family history.³

This is a rare condition in which the endothelium is uninhibited and can proliferate into areas of the angle and iris. The endothelial cells are altered in such a way that they are almost acting as epithelial cells histologically. There is an irregular deposition of collagen on Descemet’s membrane and irregular patterns of endothelial cells that present as vacuole shaped, bands and/or patchy gray opacified areas. Because of these changes, a similar presentation to iridocorneal endothelial syndromes may be observed and patients need to be monitored for synechiae and glaucoma accordingly. Patients generally develop symptoms which may include pain, photosensitivity and foreign body sensation.³

This condition usually has its onset at birth or shortly after and presents as central corneal opacification with a ground-glass appearance. Concurrent nystagmus may also be present. In this condition, the corneal endothelium malfunctions causing corneal edema, thickening of Descemet’s membrane and ultimately atrophy of endothelial cells. There are two classifications, one is autosomal dominant and the other is autosomal recessive, the latter is more common and usually more severe.³

In summary, corneal dystrophies are disorders involving deposition of irregular material within the layers of the cornea; they can be classified based on the location of corneal involvement. A spectrum of progression, laterality and inheritance is often observed with this type of condition. Resulting symptoms and signs can vary according to diagnosis, onset and progression. For more information on this topic, the references below provide excellent resources. You can also test your knowledge with the following quiz questions.