Lattice Corneal Dystrophy

What is Lattice Corneal Dystrophy?

Lattice corneal dystrophy (LCD) is a genetically inherited eye condition, while you are born with. It is caused by a substance called amyloid building up in the eye, which gradually leads to a loss of vision. These deposits form a pattern that looks like a grid or “lattice” mainly in the center of the cornea (the clear outer layer of the eye). The outer part of the cornea is usually unaffected. These lattice patterns come along with a slow, superficial clouding of the cornea. Recurrent damage to the epithelial layer of the cornea, which can cause eye irritation and lead to additional vision loss, could often accompany the condition. This damage can even occur before visible amyloid deposits are detected. LCD is part of a wider group of conditions known as corneal dystrophies and it has several different subtypes.

Type I LCD (LCD1), also known as classic lattice corneal dystrophy or Biber-Haab-Dimmer dystrophy, is the most common form of LCD. It is passed down through families (autosomal dominant) and occurs because of mutations or changes in a gene called the transforming human growth factor beta-induced (TGFBI) gene. Even though the TGFBI gene and the protein it produces are present throughout the body, it’s not known to affect any other part of the body outside of the eye. This condition usually starts showing symptoms in childhood or early adulthood.

The LCD variants are subtypes of LCD that result from different mutations on the same TGFBI gene. Formerly thought of as separate types, these variations all result from the same disease process that causes type I LCD, just with small differences in their characteristics. Specific patterns of the disease can be traced back to specific mutations in the TGFBI gene. These variants are often specific to certain geographic locations and can sometimes be traced back to a single mutation in a family line.

LCD type II is no longer considered a corneal dystrophy because it primarily affects the body beyond the eye. While it was originally grouped with the LCD conditions because of similar eye symptoms, it is now better described as familial amyloid polyneuropathy (FAP) type IV or Meretoja syndrome. Systemic symptoms include nerve-related issues, facial paralysis, and loose skin and usually start appearing in a person’s twenties.

Another disease often mistakenly grouped with the LCD conditions is granular corneal dystrophy type II (GCD type II), also known as Avellino dystrophy. Previously considered a hybrid of two types of corneal dystrophies, it is characterized by both granular deposits, and branching linear deposits. However, this makes it hard to distinguish it from the LCDs, so it’s differentiated in this article under the name Avellino dystrophy, to avoid confusion with type II LCD.

What Causes Lattice Corneal Dystrophy?

Lattice corneal dystrophy type I (LCD type I) is caused by changes in a specific gene called transforming human growth factor beta-induced (TGFBI), otherwise known as BIGH3. This gene is found on a part of our DNA referred to as chromosome 5, at a specific location known as locus 5q31. Various kinds of changes within this gene can lead to LCD type I and the different changes may result in variations of the condition. These same kinds of changes in the gene can also cause other variants of LCD.

Meanwhile, Lattice corneal dystrophy type II (LCD type II) is caused by changes in a different gene, called GSN. This gene is located on a part of our DNA known as chromosome 9, at a specific location called the 9q34 locus. As with LCD type I, there are several identified changes within this gene that can cause LCD type II.

Risk Factors and Frequency for Lattice Corneal Dystrophy

Lattice corneal dystrophy affects both men and women. The time when the condition starts can vary widely. Type I LCD, one type of lattice corneal dystrophy, is particularly common and is mostly seen in the western world, although it can be found everywhere. However, it is most common in Japan and Italy.

Type II LCD, another type of lattice corneal dystrophy, is seen most frequently in Finland. However, it is not exclusive to Finland and a few cases have been found in America, Denmark, the Netherlands, the Czech Republic, and other countries around the world.

Signs and Symptoms of Lattice Corneal Dystrophy

Type I LCD, or Lattice Corneal Dystrophy, is a condition that usually develops during the early years of one’s life and progressively worsens over time. It often results in visual impairment and discomfort in the eyes. It usually affects both eyes, though not always equally, and tends to run in families.

Like Type I, other variants of LCD frequently show up later in life. They also possess similar symptoms and are usually inherited, with Type III being a potential exception.

In contrast, symptoms of Type II LCD typically start appearing after the age of 20. The average age of diagnosis is around 39 years. Mild Lattice Corneal Dystrophy is often the first symptom to emerge. Vision usually isn’t majorly affected until later in life, possibly as late as the seventh decade. However, the actual onset of symptoms varies depending on the specific mutation. Patients with double copies of the mutation typically experience visual symptoms at a younger age. Like Type I, this condition also exhibits a pattern of being passed down in families.

Testing for Lattice Corneal Dystrophy

Type I diagnosis is made by looking at your eyes very closely, with a special microscope used for examining the eyes, known as a slit-lamp. It starts from small spots or flecks in the central part of your eye and it can progress to a diffuse haziness, giving the eye a ground-glass appearance. The microscope also reveals a pattern of branching or lattice-like lines that spread towards the outer parts of your cornea. These spots can cause your cornea (which is the clear, front surface of your eye) to erode periodically. The condition affects both eyes but may not be symmetric and sometimes can be seen in only one eye. Genetic analysis can also confirm this type of corneal dystrophy with a specific mutation in the TGFBI gene.

Different variants of Type I corneal dystrophy exist. For instance, Type IA is similar to type I, with the added characteristic of having gelatinous deposits in the corneas. It typically shows up in adolescence. Type IIB variants show thicker lattice lines and occur later in life, after the age of 70. Type IIIA has thicker, rope-like lines extending across the cornea and also occurs later in life. The characteristics of all these variants differ slightly in terms of the appearance and density of the lattice lines, and their age of onset.

Some variants have not been fully described. For instance, Type V has deposits that resemble type I, but is also referred to as French type IIIA. Type VI shows thin lattice lines and usually presents in the second or third decade of life. Similarly, Type VII also presents later in life and is marked by asymmetry in how it affects the eyes. This condition is also referred to as Asymmetric corneal dystrophy.

Type II diagnosis is also determined by clinical examination, but this form of the disorder is tied to other conditions such as poor skin elasticity and worsening symptoms of the nervous system. Symptoms of Type II manifest due to the buildup of a harmful protein, called amyloid, across the body. This alters the function of various organs, leading to symptoms such as skin fragility, cognitive impairment, numbness, imbalance, and even heart rhythm abnormalities, amongst others.

It’s important to distinguish these conditions from Avellino dystrophy, which also causes changes to the cornea. It’s characterized by a different pattern of deposits in the cornea with dense, hyperreflective spots in the front part of the cornea and irregular disruptions of the surface layer. While these deposits might resemble a lattice, they don’t often cross, making them less likely to form a true lattice.

It’s also worth noting that the size and appearance of lattice lines in this disease often change with the patient’s age and disease progression.

Treatment Options for Lattice Corneal Dystrophy

When Lattice Corneal Dystrophy (LCD) advances to the stage where medical treatment is necessary, a procedure known as Penetrating Keratoplasty (PK) is typically the preferred approach. PK, or corneal transplant, is generally not required until a person reaches their forties, although it can sometimes be necessary as early as the teenage years. After the transplant, a good outcome is expected; however, the disease could return, resulting in protein build-ups in the transplanted cornea.

Deep Anterior Lamellar Keratoplasty (DALK) is another procedure that offers similar results to PK. Recent improvements in surgical techniques and equipment suggest that DALK could even have better visual outcomes and less likelihood of graft rejection. Thus, DALK is now preferred therapy for LCD alongside PK.

Another method, Phototherapeutic Keratectomy (PTK), may also be used to enhance vision. This approach addresses the three most common vision-limiting problems in LCD: lattice changes, erosions, and opacifications. However, it’s more of a backup option to Keratoplasty because it has difficulties accessing deeper lesions. PTK may be quite beneficial in various circumstances, including delaying the need for corneal grafting, treating the recurrence of LCD post-grafting, and dealing with corneal dystrophy in children.

Femtosecond Laser-Assisted Lamellar Keratectomy (FLK) and Femtosecond Laser-Assisted Lamellar Keratoplasty (FALK) are other treatment approaches for LCD. FLK, similar to PTK, removes a portion of the front cornea but can reach further down. FALK, on the other hand, uses a precise laser to remove diseased tissue and replace it with grafted corneal tissue.

Regardless of the treatment method used, recurrence of LCD is likely due to the buildup of amyloid over 5 to 10 years. Temporary measures can be applied to delay the need for long-term treatments. This includes methods like corneal scraping, using ointments, or wearing contact lenses or topical steroids.

Treatment for Type II LCD, which is systemic, involves more methods. The dystrophy itself is treated with PK or PTK, with great results. Dry eye symptoms can be managed with topical lubricants, tear duct plugs, or contact lenses.

About gene therapies; because researchers are successfully identifying specific mutations related to LCD, gene therapies are becoming more feasible as potential treatments for LCD. Nanobodies and small interfering RNA (siRNA), as well as the gene-editing tool CRISPR and antisense oligonucleotides, have all been suggested as potential treatments for LCD.

What else can Lattice Corneal Dystrophy be?

Lattice corneal dystrophy is a rare eye disease which is typically identified from other similar eye conditions by looking at unique clinical features or through genetic testing.

The second type of this disease (Type II LCD), which is a form of systemic amyloidosis – a disease where an abnormal protein, known as amyloid, builds up in your organs – is sometimes mixed up with other conditions. This could be due to the similarity of symptoms such as skin laxity, which is also found in Ehlers-Danlos syndrome, a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues.

Moreover, individuals with Type II LCD also often experience dry eyes, a symptom common in Sjögren syndrome, an autoimmune disease that typically features inflammation and damage to various body glands. Hence, it is also important to differentiate Type II LCD from this syndrome.

In addition, this condition needs to be distinguished from other forms of systemic amyloidoses, which are a group of diseases where amyloid proteins accumulate in various body organs.

What to expect with Lattice Corneal Dystrophy

Lattice corneal dystrophy (LCD) is a disease that gets worse over time and can ultimately lead to a loss of vision if untreated. When this disease is only affecting the cornea (the clear front surface of the eye), patients often respond very well to surgery. However, symptoms might come back because the amyloid (abnormal proteins) may continue to invade the new tissue, requiring additional or repeated treatment. But with continued treatment, patients can go on leading normal lives with very little impact on their vision.

In a type II form of LCD, patients may experience a wider range of symptoms that can impact their lives. While treatments are often successful for addressing the eye-related symptoms, conditions like nerve disease (neuropathy) and facial paralysis are more challenging to treat and may cause ongoing issues.

Possible Complications When Diagnosed with Lattice Corneal Dystrophy

The complications associated with LCD (Laparoscopic cholecystectomy) mainly stem from not getting treated, the risks involved during and after the operation, and the possibility of the medical condition recurring after treatment.

Complications related to LCD:

• Lack of treatment
• Intraoperative risks
• Postoperative risks
• Recurrence of the medical condition after treatment

Preventing Lattice Corneal Dystrophy

If there is a history of LCD, a type of eye disorder, in your family, an eye doctor must examine you. This is especially important for children to get diagnosed at an early stage, as it can prevent amblyopia, which is also known as “lazy eye”.

Undergoing genetic counselling and testing can be useful in diagnosing the illness and can also assist with family planning, especially if there’s a risk of passing on the illness to any future children.

Anyone who has been diagnosed with LCD needs to continually meet with an eye doctor. It’s very important not to put off any recommended treatments. If you are a parent of a child with LCD, you must share this information with their pediatrician, a child’s primary healthcare provider. This is because, if needed, they can do a proper investigation for systemic amyloidosis – a disease that can affect different organs in the body.