Granular corneal dystrophy is a rare, inherited condition affecting the cornea, the clear, dome-shaped front surface of the eye. It is characterized by the gradual accumulation of distinct, crumb-like protein deposits within the stroma, the thick middle layer of the cornea. These deposits, primarily hyaline material, are caused by genetic changes, not inflammation, infection, or trauma. Their presence can progressively interfere with corneal transparency, leading to visual impairment.
Causes and Inheritance of Granular Corneal Dystrophy
Granular corneal dystrophy stems from genetic mutations within the transforming growth factor beta-induced (TGFBI) gene on chromosome 5q31. This gene provides instructions for keratoepithelin, a protein maintaining the cornea’s extracellular matrix structure. When TGFBI mutations occur, this protein misfolds and accumulates as insoluble deposits within the corneal stroma. Over 70 different TGFBI mutations have been identified.
The inheritance pattern is autosomal dominant. If one parent has the condition, each child has a 50% chance of inheriting the mutated gene and developing the dystrophy. A single copy of the defective gene is sufficient. Individuals inheriting two copies (homozygous) often experience a more severe form with earlier onset and more extensive corneal opacities.
Granular corneal dystrophy is classified into two main types. Type 1 (GCD1), or classic granular dystrophy, involves hyaline material appearing as discrete, grayish-white, crumb-like opacities primarily in the anterior to mid-stroma. These deposits form during late adolescence or early adulthood and slowly enlarge. Type 2 (GCD2), also called Avellino corneal dystrophy, is caused by a specific mutation (p.Arg124His) in the TGFBI gene. It involves both hyaline and amyloid material deposition. This type presents in early to late childhood with fewer, irregularly shaped granular deposits, which can later develop into lattice-like lines in the deeper stroma.
Symptoms and Progression
Granular deposits in the cornea lead to symptoms impacting vision and comfort. Common complaints include progressively blurry or hazy vision due to increasing corneal cloudiness. Many individuals also experience light sensitivity (photophobia) and a persistent foreign body sensation. These symptoms can significantly interfere with daily activities.
Recurrent corneal erosions are a painful manifestation. This occurs when the outermost corneal layer, the epithelium, does not adhere properly and repeatedly breaks down. Erosions cause sharp pain, especially upon waking or when eyes are dry, and can be accompanied by tearing and redness. The pain arises because the loose epithelium can be sheared off when eyelids open, exposing sensitive nerve endings.
The dystrophy’s progression is slow, with symptoms often appearing in childhood or early adulthood and gradually worsening over decades. Opacities may be noticeable in the first decade, but many Type 1 patients maintain good visual acuity until their fifth decade. The disease gradually decreases vision clarity as deposits increase in size and number, eventually hazing the clear spaces between them. Type 2 may lead to earlier vision loss and progresses more rapidly after corneal injury or surgery.
The Diagnostic Process
Diagnosing granular corneal dystrophy primarily involves a thorough eye examination by an ophthalmologist. A slit-lamp examination is the most common tool. During this procedure, the doctor uses a specialized microscope with a narrow light beam to inspect corneal layers. The distinct, crumb-like deposits in the corneal stroma are visible indicators of the condition.
The appearance, size, and location of these deposits help differentiate granular corneal dystrophy from other disorders. For instance, Type 1 deposits are discrete and well-demarcated, while Type 2 may show both granular and lattice-like patterns. In some cases, genetic testing can confirm the diagnosis and identify the specific TGFBI gene mutation. This genetic confirmation is useful for distinguishing between the two types or when clinical presentation is unclear.
Medical and Surgical Treatments
Management of granular corneal dystrophy focuses on alleviating symptoms and, when vision is significantly affected, removing corneal deposits. For mild symptoms and recurrent corneal erosions, conservative treatments are the first approach. These include regular use of lubricating eye drops or ointments to keep the eye surface moist and reduce irritation. Bandage contact lenses may be prescribed to protect the cornea, promote erosion healing, and reduce pain by acting as a barrier. Antibiotic drops can also prevent infection if an erosion occurs.
When conservative measures are insufficient or vision loss is substantial, surgical interventions are necessary. Phototherapeutic Keratectomy (PTK) is a laser procedure using an excimer laser to precisely remove superficial corneal deposits and smooth the surface. This improves vision and reduces symptoms like glare and recurrent erosions. While PTK provides rapid visual improvement, the dystrophy can recur in the treated area, sometimes within a few years, necessitating repeat treatments.
For deeper or more widespread deposits, or when PTK is no longer effective, corneal transplantation may be considered. Deep Anterior Lamellar Keratoplasty (DALK) replaces only the diseased anterior corneal layers, preserving the patient’s healthy inner layers. Penetrating Keratoplasty (PKP), a full-thickness corneal transplant, replaces all layers of the affected cornea with healthy donor tissue. Both procedures can restore vision, but the dystrophy can recur in the transplanted cornea over time. Recurrence rates vary by surgery type; PKP generally shows a longer recurrence-free period compared to DALK or PTK.