Terry Kim

BASICS

DESCRIPTION

• An autosomal dominant dystrophy of Bowman’s layer (CDB) of the cornea; Reis-Bucklers (RBCD) or CDB-1 is linked to the BIGH3 gene on chromosome 5q31 (1)[B]. It is associated with specific mutations of the TGFBI protein: Arg124leu² and, less typically, Gly23asp.

• Alternate names: Corneal dystrophy of Bowman’s layer type 1 (CDB-1) and granular dystrophy type III.

Pediatric Considerations

Onset of symptoms is typically at 4–5 years of age and may include photophobia, eye rubbing, tearing, or other signs of ocular surface discomfort.

EPIDEMIOLOGY

Incidence

The incidence of Reis-Bucklers corneal dystrophy (RBCD) is rare, with most cases occurring in families with a known mutation in chromosome 5q31. The exact incidence and prevalence are unknown.

RISK FACTORS

Patients with specific mutations of TGFI are at risk of RBCD. This is an inheritable condition.

Genetics

As in “Description” above; autosomal dominant

GENERAL PREVENTION

No method of prevention exists; therapy is supportive and targeted at reducing ocular surface disease.

PATHOPHYSIOLOGY

Superficial ring-shaped deposits in the central cornea are composed of fibrocellular material which is further composed of mutated transforming growth factor-beta induced protein. These localize to Bowman’s layer. Recurrent erosions lead to stromal scarring by young adulthood.

ETIOLOGY

See “Description” and “Pathophysiology.”

COMMONLY ASSOCIATED CONDITIONS

RBCD has no known systemic associations. Other conditions resulting in mutations of the BIGH3 gene include Thiel-Behnke dystrophy (CDB-2), lattice dystrophy, and Avellino dystrophy.

DIAGNOSIS

HISTORY

• Family history of early onset ocular surface disease or known mutation in the BIGH3 gene.

• Recurrent epithelial erosions which last from days to weeks during childhood; patients experience symptomatic improvement in pain by young adulthood with decreased vision due to superficial stromal scarring.

• During acute attacks, symptoms include pain, hyperemia, and photophobia.

PHYSICAL EXAM

• Slit lamp biomicroscopy reveals multiple bilateral, central, reticular, honeycomb-shaped opacities within Bowman’s layer early in life. As patients reach adulthood, gray-white opacities become interspersed and the anterior corneal surface becomes irregular (2).

• The cornea’s appearance by broad-beam illumination is said to resemble “curdled milk.”

• The corneal appearance by optical cross section shows fibrillar projections from Bowman’s layer into the epithelium.

• Retroillumination of the cornea reveals a frosted glass appearance.

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Genetic testing for known BIGH3 mutations including Arg124leu and Gly23asp, in combination with pedigree analysis, supports the diagnosis of Reis-Bucklers dystrophy. Electron microscopy is also diagnostic (see below).

Imaging

The appearance of RBCD using in vivo confocal imaging has been characterized (3)[B]; however, this is not a commonly utilized modality for diagnosis.

Pathological Findings

• Masson’s trichrome stain of histopathologic specimens shows red deposits in the anterior cornea with disruption of Bowman’s layer (1).

• Transmission electron microscopy (TEM) of specimens in RBCD shows lamellated deposits parallel to collagen fibers in the anterior cornea. TEM is required to distinguish RBCD, or CDB-1, from Thiel-Behnke corneal dystrophy, or CDB-2. In contrast to RBCD, corneas with Thiel-Behnke dystrophy show arcuate, rounded fibers termed “curly fibers” (4)[B]. The slit lamp biomicroscopic appearances of CDB-1 and CDB-2 can be indistinguishable.

DIFFERENTIAL DIAGNOSIS

• Thiel-Behnke corneal dystrophy (CDB-2)

• Granular corneal dystrophy

• Epithelial basement membrane dystrophy

• Lattice dystrophy

• Meesmann’s corneal dystrophy

• Subepithelial mucinous corneal dystrophy

• Herpetic keratitis

TREATMENT

MEDICATION

Lubrication (artificial tears, lubricating ointments applied 3–6 times per day) .

ADDITIONAL TREATMENT

General Measures

• Bandage contact lenses may be utilized for symptomatic relief of epithelial erosions .

• Topical antibiotic prophylaxis (during episodes of epithelial erosions)

• Topical corticosteroid medication (to avoid or minimize corneal scarring)

Issues for Referral

Stromal scarring with poor visual acuity or persistent surface disease can be addressed by a corneal specialist using the surgical options below.

SURGERY/OTHER PROCEDURES

• Phototherapeutic keratectomy (PTK) treats superficial scarring and anterior surface irregularity [B]. Recurrence of deposits has been reported at 58% (5)[B]. Intraoperative administration of mitomycin-C has been proposed as a way to slow the recurrence of TGFBI deposition, with encouraging results 1 year after surgery (6).

• Epithelial debridement or superficial keratectomy can be utilized when excimer laser PTK is unavailable .

• Deep lamellar keratoplasty or penetrating keratoplasty are infrequently indicated. The rate of recurrence is estimated at 17.5% at 5 years in corneal dystrophies of Bowman’s layer, which includes RBCD .

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

• Patients should be monitored closely during episodes of recurrent erosion to avoid microbial ulcers and control pain.

• Patients should also be monitored for decreased vision due to the corneal opacities, irregular surface, and stromal scarring.

PROGNOSIS

The natural history of RBCD involves recurrent corneal erosions starting at the 4th year of life with scarring and decreased vision that continues to progress in the 2nd, 3rd, and 4th decades. RBCD recurs quickly in penetrating keratoplasty (averaging 2 years in one study) as well as in PTK. Best-corrected visual acuity is limited by corneal scarring.

COMPLICATIONS

• Microbial infection: Monitor patients closely during episodes of corneal erosion and consider antimicrobial prophylaxis.

• Corneal scarring: Monitor patients for scarring and consider topical corticosteroids as treatment.

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