Hyperguides

Ophthalmology / Cornea & anterior segment

Lattice Corneal Dystrophy

Timothy Y. Chou, MD · Henry D. Perry, MD
Article

Timothy Y. Chou, MD · Henry D. Perry, MD

Lattice corneal dystrophy is one of the classical stromal dystrophies marked by deposition of amyloid in the tissue. Lattice corneal dystrophy is autosomal dominant in its inheritance pattern, and typically bilateral. Biber was the first to report the condition in 1890.1

Clinical Presentation


SLIDE 1

SLIDE 2
On biomicroscopy, the amyloid deposits appear as a lattice-like network of refractile branching grayish-white lines within the stroma, which become glassy and clear on posterior transillumination (Slide 1). Subepithelial dots may be present. Yellowish or amber deposits, which represent elastoid degeneration, may be seen.2 Over time, the lines become ropier and opaque. The intervening spaces also become hazy and scarred, which decreases visual acuity (Slide 2).

Recurrent corneal erosions may occur. Lattice and granular dystrophies may coexist. This combined presentation is termed Avellino corneal dystrophy - named after Avellino, Italy, where it was observed in some families. The granular dystrophy appears first in this variant. The amyloid is deposited later and posteriorly.3 In lattice dystrophy type II, patients have underlying systemic amyloidosis.

Affected individuals may have facial nerve palsy, peripheral neuropathy, skin changes, and cardiac complications leading to heart failure. Other ocular manifestations include ptosis, exposure keratopathy, and glaucoma secondary to blockage of the trabecular meshwork.2,4

Pathology


SLIDE 3

SLIDE 4
Amyloid is an insoluble extracellular protein. When the specimens are examined histologically, the amyloid characteristically stains pink-to-red with Congo red (Slide 3). Amyloid displays green birefringence, and red-green dichroism when placed under polarized light (Slide 4). Amyloid stains metachromatically with crystal violet. It also stains with periodic acid-Schiff and Masson trichrome (Slide 5), and thioflavin T. On electron microscopy, 80-nm to 100-nm non-branching fibrils exist, which is consistent with amyloid.5-16

Genetics


SLIDE 5
Several phenotypical presentations exist for lattice dystrophy, which have traditionally defined a subtype. Type I (Biber-Haab-Dimmer) is the most common of the phenotypes. Its onset is in the first to second decade of life and it progresses over the years.

Vision gradually worsens by age 40 and painful recurrent erosions are frequent. The central cornea is affected while the periphery remains clear. Lattice lesions may be found at all depths of the stroma. Type II (Finnish type or Meretoja) is associated with systemic amyloidosis.6 Skin, neurologic, and cardiovascular manifestations may occur. Onset is later than type 1, in the third decade.

Erosions are infrequent and, perhaps as a consequence, visual loss occurs much later in the course, after the fifth decade. Amyloid lines are few, coarse, and thick. They start in the peripheral cornea, radiating inward from the limbus, and will spare the center, until late in the course. Type I and type II are inherited in an autosomal dominant fashion.

Type III (Hida), first described in Japan, is autosomal recessive, and presents even later than the other types.7 Amyloid deposits are coarse and thick, and they run from limbus to limbus. An Italian variant, when inherited in an autosomal dominant fashion, is numbered type IIIA. Corneal erosions are common in this form.8-23

More recently, advances in genetic mapping have helped to elucidate the molecular changes that underlie the clinical picture. Many of the autosomal dominant corneal dystrophies are controlled by the BIGH3 (or TGFBI) gene, which is located on chromosome 5q31.15 The gene regulates the production of the protein, keratoepithelin.

Keratoepithelin is produced in the corneal epithelium (as well as skin and other connective tissues), but resides in the corneal stroma, especially Bowman's layer.16 Keratoepithelin may play a role in cell adhesion or corneal wound healing by blocking epithelial cell proliferation.17 Keratoepithelin accumulates in the tissues of dystrophies linked to 5q31.18 It is comprised of 683 amino acids. Mutations involving a number of these amino acids result in a unique phenotypical expression of different types of corneal dystrophies.12

Type I lattice dystrophy results from a mutation at codon 124, leading to a substitution of cysteine for arginine.13 Gelsolin is an actin filament-binding protein. The gelsolin gene appears to be affected in type II, with the missense mutation Asp187Asn leading to the findings in systemic amyloidosis.8,14 Type IIIA in a French pedigree is an A546T mutation.15 Different mutations have been implicated in several other presentations of lattice dystrophy.16,18-21

At least nine lattice corneal dystrophy types exist.13 Phenotypic and histologic descriptions are no longer sufficient or adequate to distinguish these forms. Endo and colleagues reported a case of type I LCD resulting from an atypical mutation - Leu518Pro, rather than the more common Arg124Cys.22 Afshari and colleagues reported that two patients diagnosed with typical lattice corneal dystrophy were found to have systemic amyloidosis after genetic analysis.8

Unilateral lattice dystrophy is uncommon but has been reported.23-29 Genetic testing can aid in preventing misdiagnosis, as demonstrated in a case of pseudo-unilateral lattice, reported by Aldave and colleagues.30 Dighiero and colleagues also described an asymmetric variant of lattice dystrophy caused by an A to T transition at nucleotide 1924.15 Lattice lesions were found in a patient believed to have unilateral lattice dystrophy 13 years after her first eye was diagnosed. This example should be kept in mind in cases of "unilateral" lattice. The time of onset may be variable, as well.

Treatment

Early in the course of the condition, treatment may be unnecessary. Treatment for recurrent corneal erosions may involve lubricants, bandage contact lenses, and patching. As vision worsens, phototherapeutic keratectomy may be the initial treatment of choice. Superficial lamellar keratectomy is another option.32

Penetrating keratoplasty may be repeated more than once; however, the progressive hyperopic shift may need to be considered. Eventually, penetrating keratoplasty may be necessary. Generally, patients do well, as corneas tend to be relatively uninflamed. However, the dystrophy will begin to recur in the graft over time, ranging from 3 to 26 years.33 Recurrences occur peripherally in the graft and progress centrally. Dots and haze tend to form rather than the lattice lines. As with the original condition, recurrence within the graft may be amenable to treatment with penetrating keratoplasty.3

References

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