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.
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.
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Lattice corneal dystrophy. Image courtesy of James J. Reidy, MD, FACS, Associate Professor of Ophthalmology, State University of New York, School of M....
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.
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]
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]
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.
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.
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.
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.
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]
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.
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.
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]
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]
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.
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.
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.
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.
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.
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.
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.
Clinical Context:
For osmotic pressure control and water distribution. Dehydrates epithelium, allowing epithelium to adhere better to underlying stroma.
Danielle Trief, MD, Assistant Professor of Ophthalmology, Columbia University College of Physicians and Surgeons
Disclosure: Nothing to disclose.
Coauthor(s)
Jonathan D Fay, MD, Cornea Fellow, Department of Ophthalmology, Columbia University College of Physicians and Surgeons
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Avedro; Bio-Tissue; Shire<br/>Received income in an amount equal to or greater than $250 from: AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab.
Chief Editor
Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES
Disclosure: Nothing to disclose.
Joanne W Ho, University of California, San Diego, School of Medicine
Disclosure: Nothing to disclose.
Natalie A Afshari, MD, MA, FACS, Stuart I Brown, MD, Chair in Ophthalmology In Memory of Donald P Shiley, Professor of Ophthalmology, Chief of Cornea and Refractive Surgery, Director of Education, Fellowship Program Director in Cornea and Refractive Surgery, Shiley Eye Center, University of California, San Diego, School of Medicine
Disclosure: Nothing to disclose.
William B Trattler, MD, Ophthalmologist, The Center for Excellence in Eye Care; Volunteer Assistant Professor of Ophthalmology, Bascom Palmer Eye Institute
Disclosure: Received consulting fee from Allergan for consulting; Received consulting fee from Alcon for consulting; Received consulting fee from Bausch & Lomb for consulting; Received consulting fee from Abbott Medical Optics for consulting; Received consulting fee from CXLUSA for none; Received consulting fee from LensAR for none.
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.
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.
Slit lamp image of 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.
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