Key Features

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  Characteristically bilateral.

  
  
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  Progressive.

  
  
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  Isolated to the cornea.

Associated Features

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  Usually autosomal dominant.

  
  
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  Not associated with systemic disease, with rare exceptions.

Introduction

Corneal dystrophy is classically bilateral, progressive, and isolated to the cornea. The disorder is generally inherited, usually in a dominant fashion, and often appears clinically to involve only one layer of the cornea. With the progressive identification of genes involved in these entities, a better pathophysiological understanding and ultimately better treatment will be developed. Epithelial and endothelial dystrophies are discussed in their respective chapters.

The stromal dystrophies are classified as such because they appear to accumulate material predominantly in the stroma. As was noted in Chapter 4.19 this categorization is, however, arbitrary because many of the stromal dystrophies also involve Bowman’s layer and the epithelium. The genetic understanding of these disorders makes this classification even less appropriate. Many of these conditions ultimately will be classified and named by their specific biochemical defects ( Table 4.20.1 ). The classification of corneal dystrophies has recently been reviewed in 2015 and standardized by an international committee and published as “The International Classification of Corneal Dystrophies (IC3D).”

Gelatinous Drop-Like Dystrophy

Gelatinous drop-like dystrophy was previously categorized as stromal but is now considered an epithelial/subepithelial dystrophy, as described in the most recent IC3D classification.

Lattice Dystrophy Type I

Ocular Manifestations

Rod-like glassy opacities appear in the anterior stroma in the first or second decade and become denser over time, resulting in linear, often branching opacities ( Figs. 4.20.1 and 4.20.2 ). These opacities are most dense anteriorly and centrally, with a clear zone in the periphery. The lines are relatively fine, as opposed to the more ropy opacities seen in lattice dystrophy type III. Although this disorder is bilateral, it can be asymmetrical.

Lattice Dystrophy Type I.

This patient has very fine, rod-like opacities in the anterior stroma.

Lattice Dystrophy Type I.

Denser, ropier opacities than those shown in Fig. 4.20.1 .

Pathology

Histopathologically, dense deposits are seen in the stroma. These stain with Congo red, periodic acid–Schiff (PAS), and Masson’s trichrome ( Fig. 4.20.3 ). Dichroism and birefringence are seen with polarized light and fluorescence is seen with thioflavin-T. All of these findings are characteristic for amyloid, a β-pleated protein structure. The amyloid appears to be distinct from that seen in lattice dystrophy type II. Descemet’s membrane and the endothelium are normal. Electron microscopy shows extracellular masses of fine, electron-dense randomly aligned fibrils characteristic of amyloid protein.

Lattice Dystrophy Type I.

Histopathology using Congo red stain shows the amyloid accumulations throughout the stroma (arrows) .

Genetics

This disorder is autosomal dominant, with mutation in the transforming growth factor-β–induced ( TGFBI ) gene, resulting in abnormal keratoepithelin production at locus 5q31. The most common mutation is at codon 124, where arginine is replaced by cysteine.

Ocular Manifestations

Rod-like glassy opacities appear in the anterior stroma in the first or second decade and become denser over time, resulting in linear, often branching opacities ( Figs. 4.20.1 and 4.20.2 ). These opacities are most dense anteriorly and centrally, with a clear zone in the periphery. The lines are relatively fine, as opposed to the more ropy opacities seen in lattice dystrophy type III. Although this disorder is bilateral, it can be asymmetrical.

Lattice Dystrophy Type I.

This patient has very fine, rod-like opacities in the anterior stroma.

Lattice Dystrophy Type I.

Denser, ropier opacities than those shown in Fig. 4.20.1 .

Clinical Presentation

Patients often present in their first and second decades with pain and decreased vision. Recurrent erosions are common and, over time, can lead to anterior stromal haze that can limit vision. Patients often need corneal transplantation by their fourth decade.

Pathology

Histopathologically, dense deposits are seen in the stroma. These stain with Congo red, periodic acid–Schiff (PAS), and Masson’s trichrome ( Fig. 4.20.3 ). Dichroism and birefringence are seen with polarized light and fluorescence is seen with thioflavin-T. All of these findings are characteristic for amyloid, a β-pleated protein structure. The amyloid appears to be distinct from that seen in lattice dystrophy type II. Descemet’s membrane and the endothelium are normal. Electron microscopy shows extracellular masses of fine, electron-dense randomly aligned fibrils characteristic of amyloid protein.

Lattice Dystrophy Type I.

Histopathology using Congo red stain shows the amyloid accumulations throughout the stroma (arrows) .

Treatment

Initial treatment consists of soft contact lenses for corneal epithelial erosions. Phototherapeutic keratectomy may be a good option to treat anterior visually significant deposits, although epithelial healing may be delayed, and recurrences may occur. When visual acuity decreases significantly, deep anterior lamellar keratoplasty (DALK) is the procedure of choice because it has a benefit over penetrating keratoplasty (PKP) in minimizing the risk of rejection. Epithelial cells are thought to be the source of these deposits, and although PKP has not shown statistically significant results, presence of transplanted limbal stem cells may have fewer recurrences. Recently, investigators have been studying the efficacy of fibronectin drops after corneal epithelium debridement in improving visual acuity in this condition.

Systemic Amyloidosis With Corneal Lattice

Genetics

Locus 9q34 mutation in gelsolin protein is involved in actin modulation.

Ocular Manifestations

Often classified as lattice dystrophy type II, this is part of the systemic disorder familial amyloid polyneuropathy type IV (Finnish type), also known as Meretoja’s syndrome. In this disorder, fine lattice lines extend to the limbus and are not related to corneal nerves, although the sub-basal nerve density is reduced. Patients may have increased risk of glaucoma and also can present with facial weakness with lid lag.

Systemic associations include multiple cranial neuropathies and systemic amyloid deposition.

Patient Presentation

Patients often present with this condition during routine examinations. Visual disturbance is less compared with that in lattice dystrophy type I, and recurrent erosions are less frequent. Patients also can present with lid lag and corneal exposure.

Pathology

The pathology is similar to that of lattice dystrophy type I.

Treatment

Treatment, if necessary, is the same as for lattice dystrophy type I, although additional consideration must be given to the risk of corneal exposure from facial neuropathy. Animal studies on gene silencing therapy hold promise.

Other Lattice Dystrophies

Multiple subtypes of lattice dystrophy have been described based on genotypical and phenotypical variations, especially as the genetics of those with atypical features are further explored. Lattice dystrophy types III, I/III, and IV and the polymorphic variant have delayed onset at age greater than 40 years and have thicker, ropy lattice lines. Type IIIA has identical changes but has more recurrent erosions. Many of these variants are geographically restricted.

Granular Corneal Dystrophy Type I

Ocular Manifestation

Previously called Groenouw’s dystrophy type I , granular corneal dystrophy is characterized by the presence of discrete opacities in the corneal stroma that do not extend to the limbus, and the intervening stroma is clear. The opacities have irregular crumb-like or flake-like shapes and are whitish or slightly glassy in appearance ( Fig. 4.20.4 ). The pattern within a given family appears to be consistent. No systemic associations are known.

Granular Dystrophy.

Note the more crumb-like opacities in this patient who has sufficient clear cornea to have normal acuity.

Pathology

Histopathological findings show red staining ( Fig. 4.20.5 ) with Masson’s trichrome stain without Congo red staining. Electron microscopy shows electron-dense, rod-like deposits and microfibrils, which are present in keratocytes as well as epithelial cells. The material is thought to be phospholipid.

Granular Corneal Dystrophy.

Masson’s trichrome staining shows accumulation of hyaline material in the corneal stroma and beneath the epithelium.

Genetics

This disorder is autosomal dominant, with mutation in the TGFBI gene at locus 5q31.

Ocular Manifestation

Previously called Groenouw’s dystrophy type I , granular corneal dystrophy is characterized by the presence of discrete opacities in the corneal stroma that do not extend to the limbus, and the intervening stroma is clear. The opacities have irregular crumb-like or flake-like shapes and are whitish or slightly glassy in appearance ( Fig. 4.20.4 ). The pattern within a given family appears to be consistent. No systemic associations are known.

Granular Dystrophy.

Note the more crumb-like opacities in this patient who has sufficient clear cornea to have normal acuity.

Patient Presentation

Many patients have no symptoms, whereas some patients develop recurrent erosions. In the fifth decade or later, some patients develop visual difficulties as the opacities become prominent in the superficial stroma. Anterior stromal opacities tend to be much more visually significant than posterior stromal opacities.

Pathology

Histopathological findings show red staining ( Fig. 4.20.5 ) with Masson’s trichrome stain without Congo red staining. Electron microscopy shows electron-dense, rod-like deposits and microfibrils, which are present in keratocytes as well as epithelial cells. The material is thought to be phospholipid.

Granular Corneal Dystrophy.

Masson’s trichrome staining shows accumulation of hyaline material in the corneal stroma and beneath the epithelium.

Treatment

Because the superficial deposits are often the most visually significant, vision often improves with excimer ablation and does not impair future keratoplasty. Patients who require keratoplasty do well, and DALK is the procedure of choice. Granules do recur superficially in the graft, at times in a swirling pattern that suggests the epithelium is the source of the deposits. There are a few case reports of concurrent limbal stem cell transplantations with improved long-term outcomes.

Granular Corneal Dystrophy Type 2

A dystrophy that combines features of both granular and lattice dystrophies has been described, with the majority of the original patients coming from the Avellino region of Italy. This is also referred to as Avellino granular dystrophy .