Ophthalmology: Macular Corneal Dystrophy

BASICS

Description

Macular corneal dystrophy, also known as Groenouw corneal dystrophy type II or Fehr spotted dystrophy, is a bilateral, progressive, noninflammatory corneal disorder inherited in an autosomal recessive pattern. It is characterized by numerous stromal opacities accompanied by diffuse haziness of the intervening corneal tissue.

Corneal clouding generally becomes apparent during childhood, most commonly between 3 and 9 years of age.

The corneal lesions appear as poorly demarcated, gray-white opacities that extend toward the peripheral cornea. Deposits may involve the full thickness of the corneal stroma. As the disorder advances, abnormalities may extend to Descemet’s membrane and the corneal endothelium, resulting in guttae-like excrescences and corneal edema. Centrally, the lesions are usually situated more superficially, whereas peripheral deposits tend to occur deeper within the posterior stroma.

When compared with other stromal corneal dystrophies, particularly granular and lattice corneal dystrophies, macular corneal dystrophy is less common and tends to impair vision at an earlier age. Central corneal thickness may also be reduced early in the course of the disease. Unlike granular and lattice dystrophies, clear areas are generally absent between the opacities, and the deposits characteristically extend into the peripheral cornea. Patients often require corneal transplantation earlier in life. Although graft replacement is required less frequently than in some other corneal dystrophies, recurrence of macular dystrophy within the transplanted cornea remains possible.

Common clinical complaints include gradually worsening vision, glare, photophobia, and recurrent corneal epithelial erosions. Visual impairment often becomes severe during the second or third decade of life.

EPIDEMIOLOGY

Incidence and Prevalence

Macular corneal dystrophy is considered an uncommon disorder. Reliable population-based incidence and prevalence figures have not been well established in the medical literature.

RISK FACTORS

Parental consanguinity increases the likelihood of the condition because of its autosomal recessive inheritance pattern.

GENETICS

Macular corneal dystrophy follows an autosomal recessive mode of inheritance.

The associated genetic locus is located on chromosome 16q22. Mutations involve the carbohydrate sulfotransferase 6 gene (CHST6).

PATHOPHYSIOLOGY

The corneal opacities result from the abnormal accumulation of glycosaminoglycans (GAGs), also referred to as mucopolysaccharides. These materials are deposited both intracellularly and extracellularly within the corneal stroma and may also involve Descemet’s membrane and endothelial cells.

In macular corneal dystrophy, glycosaminoglycan material accumulates within the endoplasmic reticulum of affected cells. This differs from systemic mucopolysaccharidoses, in which similar substances accumulate predominantly within lysosomal vacuoles.

Histochemical staining demonstrates the deposits using Alcian blue, Hale colloidal iron, metachromatic stains, and periodic acid-Schiff (PAS).

Electron microscopy demonstrates abnormal GAG-containing material within keratocytes and endothelial cells. Similar fibrillogranular deposits can also be identified within the extracellular stromal matrix.

ETIOLOGY

Macular corneal dystrophy develops as a result of an inherited defect affecting glycosaminoglycan metabolism. The disorder is autosomal recessive and produces progressive, bilateral, noninflammatory accumulation of abnormal material throughout the corneal stroma.

These mucopolysaccharide deposits are responsible for the characteristic corneal clouding that usually becomes evident between 3 and 9 years of age.

DIAGNOSIS

History

A typical history consists of progressive bilateral corneal clouding beginning in childhood. Because the disorder is inherited in an autosomal recessive manner, patients may report a family history of the disease or parental consanguinity.

Symptoms generally include gradually declining visual acuity, glare, photophobia, and episodes of recurrent corneal erosion. Significant visual impairment commonly develops by the second or third decade of life.

Physical Examination

A complete ophthalmic evaluation should be performed. This includes assessment of visual function, measurement of intraocular pressure, slit-lamp examination, and a dilated fundus examination whenever the posterior segment can be adequately visualized.

If dense corneal opacification prevents visualization of the posterior segment, B-scan ultrasonography may be performed to exclude significant vitreoretinal or other posterior segment abnormalities.

Ultrasound pachymetry can be used to assess central corneal thickness, while specular microscopy, when technically possible, can provide information regarding corneal endothelial cell density and morphology.

Slit-Lamp Findings

Typical slit-lamp findings include:

• Multiple gray-white stromal opacities with poorly defined margins
• Extension of the lesions into the peripheral cornea
• Diffuse haze involving the corneal tissue between individual deposits
• Absence of clear intervening stromal spaces
• Deposits occurring at different depths throughout the corneal stroma
• More superficial involvement centrally and deeper involvement toward the corneal periphery
• Extension to Descemet’s membrane and the endothelium in advanced cases
• Guttae-like endothelial changes and corneal edema in severe disease

DIAGNOSTIC TESTS AND INTERPRETATION

Laboratory Testing

An enzyme-linked immunosorbent assay (ELISA) may be used to measure circulating sulfated keratan sulfate when further biochemical characterization is required.

Follow-Up Investigations

Clinical monitoring may include repeated:

• Slit-lamp examinations
• Corneal pachymetry
• Specular microscopy

These investigations help document progression of stromal disease, corneal thickness, and endothelial involvement.

Pathological Findings

Microscopically, macular corneal dystrophy is characterized by intracellular and extracellular deposition of glycosaminoglycans within the corneal stroma. Abnormal material may also be found in Descemet’s membrane and endothelial cells.

Unlike the lysosomal storage seen in systemic mucopolysaccharidoses, intracellular deposits in macular corneal dystrophy are predominantly located within the endoplasmic reticulum.

The abnormal deposits stain positively with Alcian blue, Hale colloidal iron, metachromatic dyes, and PAS.

Electron microscopy reveals abnormal material within keratocytes and endothelial cells as well as fibrillogranular deposits within the extracellular matrix.

Immunohistochemical testing using antibodies directed against sulfated epitopes of antigenic keratan sulfate (AgKS) allows macular corneal dystrophy to be divided into three biochemical subtypes. Despite these laboratory differences, their clinical appearances are generally similar.

Type I

In Type I macular corneal dystrophy, AgKS is not detectable in either the corneal tissue or serum.

Type IA

In Type IA, keratocytes demonstrate AgKS reactivity, whereas the extracellular stromal matrix and serum remain nonreactive.

Type II

In Type II, AgKS can be demonstrated both within the cornea and in the serum.

DIFFERENTIAL DIAGNOSIS

Conditions that may resemble macular corneal dystrophy include:

• Granular corneal dystrophy
• Lattice corneal dystrophy
• Avellino corneal dystrophy
• Schnyder crystalline corneal dystrophy

The diffuse stromal haze, lack of clear spaces between deposits, peripheral extension, and autosomal recessive inheritance are useful features for distinguishing macular corneal dystrophy from several other stromal dystrophies.

TREATMENT

Medication

Medical therapy is primarily directed toward relieving symptoms and managing recurrent epithelial erosions rather than eliminating the underlying stromal deposits.

Artificial tears may be used to lubricate the ocular surface and reduce symptoms associated with recurrent corneal erosions.

Topical hypertonic saline 5% may also be prescribed. Drops can be administered several times during the day, with hypertonic ointment applied at bedtime when appropriate. Hypertonic therapy can help reduce epithelial and stromal edema in symptomatic patients.

ADDITIONAL TREATMENT

General Measures

Tinted contact lenses may help reduce photophobia and glare.

A temporary pressure patch may occasionally be used to promote healing of a corneal epithelial defect, although careful observation is required because patching may increase the risk of infection.

Therapeutic or bandage contact lenses can be useful for recurrent corneal erosions. When used for an epithelial defect, topical antibiotic prophylaxis is commonly provided to reduce the risk of microbial keratitis.

Both pressure patching and therapeutic contact lens wear carry a potential risk of corneal infection. Patients therefore require close follow-up until complete re-epithelialization has occurred.

Indications for Referral

Prompt ophthalmologic reassessment is appropriate when there is:

• Progressive or substantial deterioration in vision
• A persistent or nonhealing corneal epithelial defect

SURGERY AND OTHER PROCEDURES

Phototherapeutic Keratectomy

Phototherapeutic keratectomy (PTK) can be considered in patients with relatively early disease when the deposits are primarily confined to the anterior corneal stroma.

PTK may also be useful in selected patients with troublesome recurrent corneal erosions.

Because the disorder can involve deeper layers over time, PTK is generally less suitable for advanced stromal disease.

Keratoplasty

Corneal transplantation may be necessary when deeper stromal opacification produces substantial visual impairment.

Possible procedures include lamellar keratoplasty, deep anterior lamellar keratoplasty (DALK), and penetrating keratoplasty (PKP).

Deep Anterior Lamellar Keratoplasty

DALK may be considered when the disease involves the corneal stroma but Descemet’s membrane and the endothelium remain unaffected.

Because the patient’s own endothelium is retained, DALK avoids endothelial graft rejection and reduces some of the risks associated with full-thickness transplantation.

Penetrating Keratoplasty

Penetrating keratoplasty provides full-thickness replacement of the diseased cornea and may be required when macular dystrophy extends deeply or involves Descemet’s membrane or the endothelium.

Even after successful keratoplasty, deposits may gradually recur within the donor cornea.

INPATIENT AND DISCHARGE CONSIDERATIONS

Patients being treated for recurrent epithelial erosions should remain under close observation until the epithelial surface has completely healed.

Because pressure patches and therapeutic contact lenses can increase the likelihood of corneal infection, patients should be instructed to seek urgent care if symptoms suggestive of infection develop.

ONGOING CARE

Follow-Up Recommendations

Long-term ophthalmic follow-up is required to monitor the progression of corneal opacities, visual function, and the development of complications.

The frequency of follow-up depends on disease severity and current symptoms.

Patients with stable disease may generally be reassessed every 6 to 12 months.

Patients experiencing recurrent epithelial erosions may require examination approximately every 1 to 7 days until healing is complete.

Patients managed with a pressure patch should usually be reassessed within approximately 24 to 48 hours.

PATIENT EDUCATION

Patients should understand that macular corneal dystrophy is a progressive inherited disorder and that visual function may worsen with time.

They should seek immediate ophthalmic attention if they develop significant ocular pain, sudden reduction in vision, marked redness, purulent discharge, or severe photophobia, as these symptoms may indicate an epithelial complication or corneal infection.

When corneal opacification causes substantial visual impairment, surgical treatment such as PTK or corneal transplantation may eventually be necessary.

Patients should also be informed that recurrence of abnormal corneal deposits is possible even after apparently successful surgery.

PROGNOSIS

Macular corneal dystrophy usually progresses gradually throughout life. Patients commonly experience increasing loss of vision together with glare, photophobia, and recurrent corneal erosions.

Visual impairment may become severe by the second or third decade, although the rate of progression can vary among individuals.

COMPLICATIONS

Important complications include progressive loss of visual acuity, glare, photophobia, recurrent corneal epithelial erosions, corneal edema, and possible endothelial dysfunction in advanced disease.

Although PTK and corneal transplantation can provide substantial symptomatic and visual improvement, recurrence of macular dystrophic deposits can occur following either procedure.