Lattice Corneal Dystrophy 

Updated: Jun 04, 2019
Author: Danielle Trief, MD; Chief Editor: Hampton Roy, Sr, MD 

Overview

Practice Essentials

Lattice corneal dystrophy is a rare inherited condition characterized by amyloid deposition in the corneal stroma. It is a bilateral, slowly progressive disease that results in recurrent corneal erosions and decreased vision due to opacification of the cornea. There are two genetically distinct types of lattice corneal dystrophy: lattice corneal dystrophy type I (classic type), which is a primary amyloidosis localized to the corneas only, and lattice corneal dystrophy type II (gelsolin type, or Meretoja syndrome), which has systemic amyloidosis manifestations.

The onset of corneal changes generally occurs in the first decade of life in lattice corneal dystrophy type I and in the fourth or fifth decade of life in lattice corneal dystrophy type II. Affected individuals may first develop recurrent corneal erosion syndrome, which is a recurring painful breakdown of the corneal epithelium. Vision compromise generally occurs much later as the density of amyloid deposits in the corneal stroma increases.

Under slit-lamp examination, early manifestations of lattice dystrophy include subtle anterior stromal opacities or small refractile linear lesions. Later manifestations include thicker, radially oriented branching lines that form a latticelike pattern. Later in the course of disease, lattice lines extend to the corneal periphery and progress to deep stroma.[13, 15]

Lattice corneal dystrophy is inherited in an autosomal-dominant fashion. The genetic defect of lattice corneal dystrophy type I has been mapped to the TGFBI (BIGH3) gene on chromosome 5q.[3, 4] Lattice corneal dystrophy type II results from a mutation in the GSN gene.

Treatment of lattice corneal dystrophy includes management of recurrent corneal erosion syndrome and rehabilitation of lost visual acuity. Recurrent erosion syndrome may be treated with hypertonic saline drops, lubricating drops, bandage contact lenses, or laser surface ablation. When compromised visual acuity occurs, treatment options include laser surface ablation and partial or full-thickness corneal transplantation. These treatment modalities have a high success rate, and most patients are able to retain good visual acuity throughout life with proper care.

Background

Lattice corneal dystrophy (LCD), an IC3D category 1 dystrophy, is an autosomal-dominant condition and one of the most common stromal dystrophies. It is a slowly progressive disease that results in significant discomfort and visual impairment.

There are two genetically distinct types: lattice corneal dystrophy type I (classic type), which is isolated to the eye, and the less common lattice corneal dystrophy type II (gelsolin type), which has systemic amyloidosis manifestations.[1] Although lattice corneal dystrophy type II is regarded as a type of familial amyloidosis and not a true corneal dystrophy, it can be easily misdiagnosed as lattice corneal dystrophy type I.[2]

Like granular and Avellino dystrophies, the genetic defect of lattice corneal dystrophy type I has been mapped to the TGFBI (BIGH3) gene on chromosome 5q.[3, 4] Lattice corneal dystrophy type II results from a mutation in the GSN gene. Onset of corneal changes in lattice corneal dystrophy type I usually occurs in the first decade of life, although patients may remain asymptomatic for years. Examination of the cornea in the second to third decade of life reveals branching, refractile lattice lines with intervening haze, which are observed best in retroillumination.

An example of lattice corneal dystrophy is shown in the image below.

Lattice corneal dystrophy. Image courtesy of James Lattice corneal dystrophy. Image courtesy of James J. Reidy, MD, FACS, Associate Professor of Ophthalmology, State University of New York, School of Medicine & Biomedical Sciences, Buffalo, New York.

Pathophysiology

The cornea is the clear outer coat of the front of the eye. A dystrophy of the cornea is defined as a bilateral noninflammatory clouding of the cornea. Corneal dystrophies can be placed into 3 categories based on their location within the cornea: (1) Anterior corneal dystrophies affect the corneal epithelium and may involve the Bowman layer, (2) stromal corneal dystrophies affect the central layer of the cornea (the stroma), and (3) posterior corneal dystrophies involve the Descemet membrane and the endothelium.

Lattice corneal dystrophy is primarily a stromal corneal dystrophy that starts as fine, branching linear central opacities in the Bowman layer and that spread to the periphery. Although the process may involve the deep stroma, it does not reach the Descemet membrane.

The age of onset for most corneal dystrophies is less than 20 years (exceptions include map-dot-fingerprint dystrophy and Fuchs corneal dystrophy). Most corneal dystrophies are inherited in a dominant pattern. Exceptions include macular corneal dystrophy, type 3 lattice corneal dystrophy, and the autosomal-recessive form of congenital hereditary endothelial dystrophy.

Epidemiology

Frequency

United States

Although lattice corneal dystrophy type I is one of the most common stromal dystrophies in the Western world, it is still relatively rare.[5, 1]

International

Cases of lattice corneal dystrophy type I have been recognized throughout the world. Lattice corneal dystrophy type II is most common in Finland.[6]

Mortality/Morbidity

Excessive corneal erosions can lead to decreased visual acuity, which may require a corneal transplant or phototherapeutic keratectomy (PTK).

Sex

No sexual predilection is noted.

Age

In lattice corneal dystrophy type I, onset of the corneal changes such as recurrent epithelial erosions usually occurs in the first decade of life, although patients may remain asymptomatic for years. Examination of the cornea in the second to third decade of life reveals branching, refractile lattice lines, which are observed best in retroillumination. Over time, the lattice lines and other opacities coalesce, forming anterior stromal haze that decreases visual acuity. Onset of corneal changes in lattice corneal dystrophy type II occurs at age 30-40 years, but most patients do not experience symptoms until their seventh decade of life.[2]

Prognosis

Lattice corneal dystrophy demonstrates variable penetrance and expression. Typically, lattice corneal dystrophy type I becomes clinically apparent by age 10 years; however, decreased visual acuity is common after age 40 years. Morbidity associated with painful recurrent erosions is also common. Patients with lattice corneal dystrophy type II commonly present between age 30 and 40 years, retain good visual acuity until age 60 years or later, and infrequently develop recurrent corneal erosions.[2]

The predominantly bilateral nature of lattice corneal dystrophy type I and type II contributes to the morbidity of this condition. The painful recurrent erosion syndrome associated with lattice corneal dystrophy may result in frequent visits to the ophthalmologist and loss of productivity. Loss of visual acuity may progress from mild blurring of vision to debilitating blindness. Fortunately, recurrent erosions and vision loss due to corneal opacity are treatable.

Patients with lattice corneal dystrophy type II may develop pseudoexfoliation and glaucoma in addition to corneal deposits. Systemic manifestations include cranial and peripheral neuropathies, which can result in facial paresis, loss of peripheral vibration sense and touch, orthostatic hypotension, and/or cardiac conduction abnormalities. Therefore, these patients require comanagement with appropriate medical specialists.[17]

Patient Education

Patients should be educated regarding the autosomal-dominant inheritance of lattice corneal dystrophy and understand its implication in childbearing.

Family members should be counseled to establish care with an ophthalmologist, even during childhood or adolescence.

Patients should be educated on the natural history of lattice corneal dystrophy, including issues surrounding recurrent corneal erosion syndrome and loss of corneal clarity. They should be informed that treatment options are available and that, despite the recurrent nature of the condition, proper management often enables good visual acuity throughout the patient’s lifetime.

Patients with lattice corneal dystrophy type II should be educated on the systemic manifestations of amyloidosis and be referred to the appropriate medical specialist.

 

Presentation

History

Patients with lattice corneal dystrophy may have decreased vision, photosensitivity, ocular discomfort, diminished corneal sensation, and/or eye pain (from recurrent corneal erosions). Recurrent corneal erosions may precede corneal opacities and recognizable stromal disease.[1] As the pattern of inheritance for this dystrophy is autosomal dominant, one of the parents of the patient likely also has lattice corneal dystrophy.

Physical

Lattice corneal dystrophy is characterized by branching, refractile lattice lines, which are observed best in retroillumination. Both corneas are usually symmetrically involved. In the most common form, lattice corneal dystrophy type I, the refractile lines are more prominent centrally than peripherally. Later in life, stromal haze can develop. Eventually, significant stromal scarring and subepithelial fibrosis may occur.

Causes

The genetic defect of lattice corneal dystrophy type I has been mapped to the TGFBI (BIGH3) gene of chromosome 5q. Several other corneal dystrophies also have genetic defects of the TGFBI (BIGH3) gene, including granular dystrophy, Avellino dystrophy, and Reis-Bückler dystrophy. Lattice corneal dystrophy type II results from a mutation in the GSN gene.

Physical Examination

Lattice corneal dystrophy is diagnosed based on family history and slit-lamp examination.

Under slit-lamp examination, early manifestations of lattice dystrophy include subtle anterior stromal opacities or small refractile linear lesions. Later manifestations include thicker, radially oriented branching lines that form a latticelike pattern. Patients may also develop a central anterior stromal haze.

Later in the course of disease, lattice lines extend to the corneal periphery and progress to deep stroma. Retroillumination techniques may facilitate visualization of lattice changes.[13]

 

DDx

Diagnostic Considerations

Lattice corneal dystrophy is differentiated among the three major stromal corneal dystrophies (granular, macular, and lattice) based on history and examination.

Family history may distinguish macular dystrophy (autosomal-recessive inheritance) from granular and lattice (autosomal-dominant inheritance). Clinically, all three may present in the first decade of life; however, lattice and granular corneal dystrophy typically do not result in reduced visual acuity until later in life.

On examination, each has a distinct appearance. In granular dystrophy, the corneal opacities are discrete globular opacities with clear intervening stroma sparing the limbus. In macular dystrophy, opacities have indistinct margins, the intervening stroma is hazy, and lesions may extend to the limbus. In lattice dystrophy, lesions are linear and refractile, and, while there may be diffuse central haze, the limbal zone is clear except in extreme cases. The table below, adapted from Cornea (1996), presents characteristics of the three major corneal dystrophies.[13]

Table 1. Characteristics of the Three Major Stromal Corneal Dystrophies (Open Table in a new window)

Feature

Granular Dystrophy

Macular Dystrophy

Lattice Dystrophy

Age of onset

First decade of life

First decade of life

First decade of life

Heredity

Autosomal dominant

Autosomal recessive

Autosomal dominant

Reduced vision

Fourth or fifth decade of life

First or second decade of life

Second or third decade of life

Erosions

Uncommon

Common

Frequent

Opacities

Discrete, intervening stroma

Clear, not to limbus

Indistinct margins, intervening

Stroma hazy, extends to limbus

Refractile lines and dots

Usually not to limbus

Material

Hyaline

Glycosaminoglycans

Amyloid

Recurrent erosions in lattice dystrophy may follow the branching pattern of the underlying lattice network and can therefore appear similar to the dendritic lesions characteristic of epithelial herpetic keratitis. Epithelial lesions associated with lattice dystrophy, however, lack terminal bulbs and elevated borders. Owing to the implications in treatment planning, distinguishing recurrent erosions in lattice corneal dystrophy from herpetic keratitis is essential to the diagnostic process.[15]

Differential Diagnoses

 

Workup

Approach Considerations

Family history and clinical examination are typically sufficient to make the correct diagnosis of lattice corneal dystrophy.

While the genetic basis of lattice corneal dystrophy is known, genetic studies are not commonly used clinically.

Imaging of the cornea with anterior segment optical coherence tomography (OCT) can demonstrate the extent and depth of amyloid deposits and may assist with diagnosis or treatment planning.

Corneal biopsy is not routinely required in the diagnosis of lattice dystrophy; however in the case of corneal biopsy, diagnosis can be made based on histochemical staining and polarization microscopy. Patients with lattice dystrophy type II (systemic amyloidosis) need further workup with the appropriate specialist owing to involvement of the skin, nerves, arteries, and other organs.

Laboratory Studies

A genetic analysis can determine the specific mutation on the TGFBI (BIGH3) gene of chromosome 5, which can allow for the precise diagnosis of the subtype of lattice corneal dystrophy and can be useful for differentiating lattice corneal dystrophy from Avellino dystrophy, granular dystrophy, and Reis-Bückler dystrophy (all which have mutations of the TGFBI,or BIGH3, gene). This, however, is not routinely used clinically at this time.

Procedures

Corneal biopsy, which is not clinically indicated, reveals amyloid in the corneal stroma.

Histologic Findings

Lattice corneal dystrophy is an amyloidosis of the corneal stroma. In lattice dystrophy type I, the source of the amyloid is believed to be localized intracellular production. Histologically, a layer of amyloid and collagen separates the epithelial basement membrane from the Bowman layer. In addition, linear deposits of amyloid fibrils are seen within the corneal stroma, disrupting the regular arrangement of corneal lamellae. Amyloid deposits stain orange with Congo red. They also demonstrate green birefringence under a polarizing filter. Amyloid is a noncollagenous fibrous protein of variable makeup in different forms of amyloidosis.[13]

Imaging Studies

Anterior segment optical coherence tomography (OCT) may be used to measure the depth of the corneal opacities. This can be useful in guiding treatment, particular when considering phototherapeutic keratectomy for the removal of superficial opacities.[16]

Other Tests

Corneal esthesiometry is used to measure tactile sensation at the surface of the cornea. Because lattice dystrophy is associated with decreased corneal sensation, esthesiometry may be of clinical interest. Whether decreased corneal sensitivity is associated with increased morbidity in lattice corneal dystrophy is unknown.

Staging

A staging system for lattice corneal dystrophy is not commonly used at this time.

 

Treatment

Approach Considerations

Recurrent erosions are managed conservatively with medical treatment. If recurrences are frequent or debilitating, laser phototherapeutic keratectomy can be considered.

Decreased visual acuity is treated surgically when indicated based on the patient’s visual acuity complaints. Surgical options include laser phototherapeutic keratectomy to remove superficial opacities and lamellar or full-thickness cornea transplantation. In either case, lattice deposits may recur, requiring repeat treatment.

Medical Care

When recurrent erosions occur with lattice corneal dystrophy, they are treated similarly to any other form of recurrent erosions. Under the care of an ophthalmologist, a bandage contact lens along with antibiotics can be prescribed. Alternatively, patching with an antibiotic ointment can be used. Once the acute episode of recurrent erosions has resolved, preventative treatments may include Muro 128 drops, lubrication drops, and lubricating ointment at bedtime. If recurrent corneal erosions occur despite medical therapy, excimer laser phototherapeutic keratectomy (PTK) may be considered.[7, 8]

Future approaches to management of autosomal-dominant corneal dystrophies may include gene therapy.

Surgical Care

Excessive corneal erosions or mild visual decreases can be treated with laser phototherapeutic keratectomy (PTK). The excimer laser removes anterior opacities, smooths the corneal surface, and allows the epithelium to re-adhere more tightly. In PTK, enough tissue must be removed from the anterior cornea to eliminate the opacities. This can be highly effective for the treatment of superficial opacities. Treatment of deep corneal opacities risks excessive flattening of the cornea and stromal haze. If corneal opacities recur after treatment with PTK, repeat treatment is possible unless the cornea becomes too thin to allow further ablation.

If visual acuity worsens and opacities are deep, a lamellar or full-thickness corneal transplant can be performed. Corneal transplants are usually not necessary until after age 40 years.[1] Although the success rate for a corneal transplant is very high, amyloid deposits can recur in the grafted tissue 2-14 years later.

A recent study examined the histopathological and ultrastructural correlate of delayed epithelial healing in eyes with lattice corneal dystrophy;[9] the study concluded that histopathological findings may correspond to reduced cell matrix interactions and may help explain the delayed healing.

Complications

Recurrent erosion syndrome is a risk factor for infectious keratitis. Patients who present with an acute erosion and an epithelial defect are treated with prophylactic topical antibiotics.

The most frequent complication of phototherapeutic keratectomy is recurrence of amyloid deposits. In this case, further treatment can be considered. However, repeat treatments or the treatment of deep stromal opacities risks excessive flattening of the cornea and unacceptable refractive outcomes. Treatment of the deep corneal stroma also risks haze formation or progressive corneal ectasia. In these cases, corneal transplantation may be indicated.

Corneal transplantation is a highly successful procedure; however, amyloid deposits can also recur in the grafted tissue. PTK can be applied to treat opacities in the transplanted tissue. Repeat corneal transplantation may ultimately be required. Corneal transplantation is associated with refractive error that may require glasses or a contact lens for correction. Less-common risks include graft rejection, graft failure, infection, glaucoma, and vision loss.

Consultations

Patients with lattice corneal dystrophy type II (systemic amyloidosis) require specialty care for the systemic management of this rare condition.

Diet

Diet is not known to affect the onset or progression of lattice corneal dystrophy.

Activity

Activity modification is not known to affect the onset or progression of lattice corneal dystrophy.

Prevention

Lattice corneal dystrophy is an inherited condition without known preventive measures.

Long-Term Monitoring

Patients with lattice corneal dystrophy should undergo regular long-term monitoring with their ophthalmologist. Follow-up care focuses on monitoring for progression and assessing the need for treatment of recurrent erosions or decreased visual acuity.

 

Medication

Medication Summary

Medical therapy for recurrent corneal erosions includes hypertonic saline, which is believed to increase adherence of the epithelium to underlying stroma. Lubrication may also help prevent further corneal erosions.

Hypertonic saline

Class Summary

This agent dehydrates epithelium, allowing epithelium to adhere better to underlying stroma.

Sodium chloride hypertonic, ophthalmic (Muro 128)

For osmotic pressure control and water distribution. Dehydrates epithelium, allowing epithelium to adhere better to underlying stroma.

Lubricating drops

Class Summary

These agents can moisten ocular surface and decrease the number of recurrent erosion episodes.

Artificial tears (GenTeal, Refresh, Bion tears)

Can moisten ocular surface and decrease number of recurrent erosion episodes.