Meesmann Corneal Dystrophy

What is Meesmann corneal dystrophy?

Meesmann corneal dystrophy is a rare, inherited eye condition that affects the cornea, which is the clear front surface of the eye. It causes tiny, bubble-like sacs called cysts in the top or outer layer (the epithelium) of the cornea.

It is sometimes known as Meesmann dystrophy, Meesmann epithelial corneal dystrophy, juvenile hereditary epithelial dystrophy, or Meesmann-Wilke syndrome.

Corneal dystrophy is the umbrella term for a group of over 20 different eye diseases. They are usually caused by genetic variations that cause abnormal material to build up in the cornea. The most common corneal dystrophy is Fuchs dystrophy, which affects the innermost layer (the endothelium) of the cornea.

Corneal dystrophies can be classified by which of the five layers of the cornea they affect. Meesmann corneal dystrophy mainly affects the top or outer layer (the epithelium) of the cornea. In medical terms, this is called a ‘superficial’ corneal dystrophy.

How common is Meesmann corneal dystrophy?

Meesmann corneal dystrophy is rare, but we don’t know for sure how many people it affects. One study in the United States found that corneal dystrophies overall affect less than 1 in 10,000 people.

The majority of these are other types of corneal dystrophy, especially Fuchs dystrophy. Meesmann corneal dystrophy is much rarer and is estimated to affect less than 3 in a million.

What causes Meesmann corneal dystrophy?

Meesmann corneal dystrophy is a genetic condition caused by a mutation in one of two specific genes: KRT3 or KRT12. These genes hold the instructions for producing proteins called keratin 3 and keratin 12. These keratins are important in the cornea’s outer layer (the epithelium), where they link together to form a strong structural framework.

A fault in either the KRT3 or KRT12 gene disrupts this framework, making the epithelium fragile. This weakness leads to the formation of the small cysts, which are thought to contain clumps of the abnormal keratin protein and waste materials. The cysts usually appear early in life, sometimes in the first year, although they may not be noticeable. Symptoms only happen at a later stage, when the cysts break open and cause irritation.

Meesmann corneal dystrophy is usually inherited in an autosomal dominant pattern. This means that you only need to inherit one copy of the faulty gene from one parent to develop the condition. If a parent has the condition, each of their children has a 50% (one in two) chance of inheriting it.

Who is most at risk of developing Meesmann corneal dystrophy?

The main risk factor for developing Meesmann corneal dystrophy is having a family history of the condition. It affects men and women in roughly equal numbers.

Although the gene variation is usually inherited, it can occasionally randomly occur for the first time in a family. It’s also possible for a parent to have the condition and pass it on without ever being diagnosed themselves.

What are the signs and symptoms of Meesmann corneal dystrophy?

Many people with Meesmann corneal dystrophy have no symptoms, particularly in childhood. When symptoms do happen, this is usually because the tiny cysts on the cornea break open. It usually affects both eyes.

Common symptoms include:

• Tiny cysts in the cornea: The condition causes numerous, tiny, clear bubble-like cysts in the outer layer of the cornea. Usually these are only visible to an eye specialist using a microscope.

• Eye irritation and discomfort: A common symptom is feeling like there is something in the eye, especially when the cysts burst. This can also cause stinging or general irritation.

• Corneal erosion: The surface of the cornea can become damaged, exposing the sensitive nerve endings. This can feel like there is something in your eye, and can be painful.

• Light sensitivity: The condition can cause sensitivity to bright light, which is known as photophobia.

• Blurred or fluctuating vision: Vision can become temporarily blurred or hazy from time to time.

• Watery eyes and redness: The eyes may produce excess tears in response to irritation.

• Twitching eyelids: This is called blepharospasm and can happen when the eye is irritated after cysts have ruptured.

• Amblyopia and/or astigmatism: In more severe cases, it can cause amblyopia (lazy eye), or astigmatism (a type of refractive error that can cause blurry vision), which is caused by the surface of the cornea not being evenly curved.

Is Meesmann corneal dystrophy serious?

For most people with Meesmann corneal dystrophy, it’s a mild condition that doesn’t cause symptoms or significant vision problems. For some people, it can affect the quality of life, causing light sensitivity and pain or discomfort from corneal erosions.

While the condition lasts for life, it does not usually lead to vision loss. In more severe cases, scarring can develop on the cornea, which can lead to a slight clouding of vision, but this is unusual. It doesn’t typically affect long-term vision in a way that would stop people from driving, reading, or working, though severe episodes of corneal erosion may affect these temporarily. Very rarely, the condition can lead to complications that might affect the eyesight.

How does Meesmann corneal dystrophy affect vision over time?

Meesmann corneal dystrophy is usually a slowly progressive condition, meaning its effects develop gradually over years or even decades. More cysts tend to develop as you get older, spreading outwards from the centre of the cornea.

In childhood and early life, most people have no symptoms and have normal vision. Symptoms like eye irritation, light sensitivity and intermittent blurred vision tend to begin anywhere between adolescence and middle age. In severe cases, scarring on the cornea can cause blurred vision in older people. Usually, vision is not severely affected.

How is Meesmann dystrophy diagnosed?

An eye specialist (ophthalmologist) can diagnose Meesmann corneal dystrophy through specialised tests and a review of your family history.

The diagnosis usually involves:

• Slit-lamp examination: This is the most important tool for diagnosis. A slit-lamp is a powerful microscope that shines a thin beam of light into the eye, allowing the specialist to see the tiny cysts in the cornea.

• Eye examination: This involves assessing your vision and the overall health of your eyes. The doctor will ask about your symptoms and any family history of eye conditions.

• Optical coherence tomography (OCT): An OCT scan can be used to create detailed cross-sectional images of the cornea, which can show the cysts within the epithelial layer.

• Genetic testing: To confirm the diagnosis, a genetic test can be done to identify the specific mutation in the KRT3 or KRT12 gene. This involves taking and analysing a small blood sample.

What are the treatments for Meesmann dystrophy?

Many people with Meesmann corneal dystrophy don’t have symptoms and don’t need any treatment. For people who do experience discomfort and irritation, treatment is focused on managing the symptoms.

Common treatments include:

• Lubricating eye drops and ointments: Artificial tears and gels help to relieve dryness and irritation and protect the corneal surface to prevent the painful rupture of cysts.

• Hypertonic saline eye drops or ointments: These special salt-based solutions work by drawing excess fluid out of the cornea. This can help the outer epithelial layer to stick to the layer beneath it, reducing the risk of recurrent corneal erosions.

• Specialised contact lenses: In some cases, a ‘bandage’ contact lens can be worn. This is a soft lens that covers the cornea, protecting it from any damage from the eyelids and allowing it to heal. A bandage lens is usually kept in for days or weeks.

• Management of corneal erosions: If a corneal erosion happens, treatment may include antibiotic eye drops to prevent infection, pain relief medication, and sometimes a bandage contact lens.

• Phototherapeutic keratectomy (PTK): In rare cases with severe, frequent corneal erosions that don’t respond to other treatments, a laser procedure called PTK might be used. A laser is used to remove the abnormal surface layer of the cornea, allowing a new, healthier layer to regrow.

• Corneal Crosslinking (CXL): For severe cases of Meesmann corneal dystrophy that result in significant pain and epithelial breakdown, combining CXL with surface ablation techniques like PTK offers an effective dual-action treatment approach. The CXL procedure can help stiffen and stabilize the cornea, while PTK removes abnormal surface tissue to create a smoother, healthier ocular surface.

Can Meesmann corneal dystrophy be prevented?

Because Meesmann corneal dystrophy is a genetic condition caused by an inherited gene mutation, it cannot be prevented. If you carry the faulty gene, the cysts in the cornea will develop early in life, although symptoms may not appear until you are older.

If you have a family history of the condition, a genetic counsellor can explain the inheritance patterns and discuss the chances of passing it on to your children.

What complications can Meesmann corneal dystrophy lead to?

Meesmann corneal dystrophy is usually mild, but sometimes leads to complications. These can include:

• Recurrent corneal erosion: This is the most common and painful complication. When the cysts burst, the damaged outer layer of the cornea can stick to the eyelids and get pulled away from the underlying layer. This can cause sharp pain (especially when you wake up in the morning), light sensitivity and blurred vision until it heals. Although the cornea heals quickly, if it is recurrent, it can happen over and over again.

• Corneal scarring: In severe cases, repeated episodes of corneal erosion can eventually lead to scarring on the cornea. This can cause the cornea to become slightly cloudy, which may affect eyesight.

How can Meesmann corneal dystrophy affect daily life?

The impact of Meesmann corneal dystrophy on daily life varies from person to person. For many people there is no impact at all.

For people who do have symptoms, these are some of the areas that may be affected:

• Quality of life: For people who get eye irritation and recurrent corneal erosions, the discomfort and pain of these can be the main impact. This can be disruptive and frustrating. Light sensitivity can make being in bright environments uncomfortable.

• Driving: In most cases, your eyesight won’t be affected. But if you are having an episode of pain (for example from corneal erosion), blurred vision or light sensitivity, driving may be temporarily unsafe or uncomfortable.

• Reading: This is usually not affected, although it may be if you are having an episode of pain or blurred vision. Sometimes, looking at screens for a long time might make dryness and irritation a bit worse. More frequent use of lubricating eye drops can help with this.

• Ability to wear contact lenses: Standard contact lenses may feel irritating to the eye.

What research is there into Meesmann corneal dystrophy?

Fight for Sight funds pioneering research that can lead to new treatments. Understanding exactly which gene variations cause specific corneal dystrophies and exactly how they affect the cornea is the first step towards developing targeted therapies. Testing new treatments is another area of research.

Understanding the genetic causes of inherited corneal diseases

Funded by Fight for Sight, Professor Alice Davidson at UCL Institute of Ophthalmology is looking to identify the specific genetic mutations that cause inherited corneal diseases, where these are not currently known, and to understand exactly how these genetic faults affect the cornea’s normal function.

For people living with corneal dystrophy, having a genetic diagnosis can be important. It provides a clear understanding of their condition, informs them about the risk for other family members, and helps doctors develop the most effective care plan.

What’s more, by pinpointing the root cause, scientists can begin to design new treatments that can directly correct the fault or its effects. This is important for many reasons, including the fact that there is a global shortage of donated corneas for transplants. Corneal transplants are not usually necessary as a treatment for Meesmann corneal dystrophy, but they can be important for more severe cases of corneal disease, including for some people with Fuchs dystrophy.

Developing new ways to test treatments for corneal dystrophies

A project we funded, led by Professor Alison Hardcastle at UCL Institute of Ophthalmology, has had some important successes. Firstly, the research team identified the precise genetic cause of corneal dystrophy for over 120 families. This molecular diagnosis helps with earlier and more accurate clinical care and informs families of the risk of passing the condition to their children. Having a confirmed genetic diagnosis also means they are in a better position to be included in future clinical trials for their specific condition.

Secondly, the project discovered some people with these conditions who did not have a genetic difference in one of the genes known to be linked to corneal dystrophy. They are now being studied in more detail to better understand which genes are involved.

Thirdly, the team developed an innovative ‘cornea in a dish’ model to test new therapies in the lab. They took skin cells from patients with a common form of corneal dystrophy, reprogrammed them into stem cells, and then grew them into corneal cells that carried the genetic fault. Using this model, they successfully tested a new type of gene therapy called antisense oligonucleotides (ASOs), which was able to ‘switch off’ the faulty copy of the gene. These results show that ASOs have potential for stopping certain corneal dystrophies, paving the way for future treatments.