Corneal dystrophy

Corneal dystrophies are a group of rare inherited eye conditions. Corneal dystrophies affect the cornea (the clear surface at the front of the eye) and cause changes to the cornea without any inflammation or other infections.

How does corneal dystrophy impact sight?

The cornea is the clear window at the front of the eye, which acts as a protective barrier and helps to focus light coming into the eye. In people with corneal dystrophy, abnormal materials build up within the cornea causing it to lose its transparency and become cloudy.

They usually affect both eyes and can cause sight loss.

• See About the Eye for more about the anatomy of the eye

How common are corneal dystrophies?

Corneal dystrophies are characterised as rare due to the relatively small number of people who have the disease. The prevalence of the different superficial corneal dystrophies is unknown, but all are rare and found mainly in populations containing the responsible mutated gene.

What are the symptoms of corneal dystrophies?

Some corneal dystrophies are asymptomatic (no symptoms). Others may cause a variety of symptoms. Some signs of corneal dystrophy include the following:

• Pain or grittiness in the eye,
• Blurred vision,
• A progressive loss of vision.

When you develop corneal dystrophy, the type and severity of the symptoms will vary depending on the type of corneal dystrophy. Corneal dystrophies often worsen over time, but this usually happens slowly over years or decades.

Are corneal dystrophies inherited?

Corneal dystrophies tend to run in families but not always. If there is a family history of corneal dystrophy, a parent who has corneal dystrophy, in general, tends to pass it on, and half their children will inherit it.

Unfortunately, there is currently no cure for the underlying causes of these diseases. If symptoms become very severe, they may require a corneal transplant.

What are the different types of Corneal Dystrophy?

There are five different layers in the cornea, and each plays a role in keeping the cornea healthy and clear. There are over 20 different types of corneal dystrophy. Each type can affect one or more of these layers. From the outer part of the eye inwards, these layers are:

• The epithelium: the thin outermost layer of the cornea. It provides a barrier that helps to protect the eye from foreign bodies, such as dust or grit, and infections.
• Bowman’s layer: A thin, transparent layer of the cornea directly below the epithelium.
• The stroma is the middle and thickest layer of the cornea, mainly made up of water and a protein called collagen. It is very strong, flexible, and transparent.
• Descemet’s membrane: A thin, strong inner layer of the cornea.
• The endothelium: The innermost, extremely thin layer of the cornea. It comprises a single layer of cells that act as a pump, controlling the movement of fluids in and out of the cornea.

What are the groups of corneal dystrophies called?

Corneal dystrophies are often classified into three main categories according to the layers that they mainly affect. These groups are:

1.     Anterior or superficial corneal dystrophies

Anterior or superficial corneal dystrophies affect the outermost layers of the cornea (the epithelium and Bowman’s membrane). This group includes:

• Epithelial basement membrane dystrophy (also called map-dot-fingerprint or Cogan’s dystrophy)
• Lisch corneal dystrophy
• Meesmann’s corneal dystrophy
• Reis-Bücklers corneal dystrophy
• Thiel-Behnke corneal dystrophy

2.     Stromal corneal dystrophies

These types of dystrophies affect the stoma, and this group includes the following:

• Gelatinous drop-like corneal dystrophy
• Granular corneal dystrophy
• Lattice corneal dystrophy
• Macular corneal dystrophy
• Schnyder crystalline corneal dystrophy

3.     Posterior corneal dystrophies

Posterior corneal dystrophies affect the innermost parts of the cornea, including the endothelium and the Descemet’s membrane. This group includes:

• Congenital hereditary endothelial dystrophy
• Fuchs’ endothelial corneal dystrophy
• Posterior polymorphous corneal dystrophy

What causes corneal dystrophy?

Most corneal dystrophies are inherited. So, they usually pass down through families. However, this is not always the case, and it isn’t always possible to identify why someone has a corneal dystrophy.

Because most corneal dystrophies are genetic, having a family history of the disease is a risk factor. Genetic testing may help to identify the specific gene responsible for the disease and help to inform genetic counselling for families.

Genetic risk for corneal dystrophy

Corneal dystrophies are inherited in two different ways, depending on the condition and the responsible gene:

1. Autosomal dominant inheritance

Most corneal dystrophies are inherited in an autosomal dominant pattern. So, someone only needs to inherit one copy of the faulty gene from either of their parents to develop the disease. So, if one parent has the condition, their children have a 50% (one in two) chance of having it too. In most cases, the mistake in the DNA is just one single letter of the coding sequence for the gene that causes the disease.

2. Autosomal recessive inheritance

In this inheritance pattern, two faulty copies of the responsible gene are required to develop the condition. Both parents are often unaffected carriers, carrying one faulty copy of the responsible gene and one healthy copy. Each of their children will have a 25% (one in four) chance of having the condition by inheriting two faulty copies of the gene – one from each of their parents - and a 50% (one in two) chance of being an unaffected carrier by inheriting a faulty copy from either parent.

What are the symptoms of corneal dystrophy?

The symptoms of corneal dystrophy will depend on the type of the disease. They may include:

• A ‘gritty’ sensation where a person feels like there’s something in their eye
• Eye pain
• Sensitivity to light
• Glare or halos in a person’s vision
• Blurred vision
• Progressive sight loss

The type of symptoms that a patient may experience often relate to the affected layers of the cornea, as follows:

Anterior or superficial corneal dystrophies

The corneal epithelium is full of sensitive, tiny nerve endings. Corneal dystrophies affecting this layer tend to cause grittiness, discomfort, and pain. The breakdown of the corneal surface is known as ‘corneal erosion’.

It happens when the epithelium loosens from the Bowman’s membrane. As the epithelium can heal quickly, these symptoms may be short-lived but recurrent. Corneal dystrophies affecting deeper layers, such as the stroma and endothelium, do not usually cause these symptoms.

Stromal corneal dystrophies

Deposits build up in this layer, making the stroma less clear, affecting a person’s vision.

Posterior corneal dystrophies

Problems with endothelium can cause the cornea to take on water and swell. As well as cloudy corneas, these changes can cause life-long vision problems such as blurred vision, glare and halos and sensitivity to light.

How are corneal dystrophies diagnosed?

Corneal dystrophies are usually diagnosed through an eye examination. An ophthalmologist will use a slit light microscope to shine a thin, bright light into the eye, enabling them to examine the front part of the eye thoroughly.

The ophthalmologist may also ask about a person’s family history of eye disease, which can help identify other affected family members.

A family history may also help to diagnose a particular type of corneal dystrophy. In some cases, genetic testing can help identify the gene responsible for their condition.

• Access genetic counselling services

Treatments for corneal dystrophy

The treatment for corneal dystrophy depends on the type of condition and the severity of symptoms. Asymptomatic patients may not require treatment, but they will be closely monitored to see if the disease progresses.

People in the early stages of corneal dystrophy experiencing mild symptoms are usually offered treatments to help manage their disease. Treatments may include the following:

• Using glasses or contact lenses to improve vision,
• Lubricating eye drops, ointments or specialised eye patches or contact lenses that help stop the eyelids from rubbing against the cornea,
• Antibiotics during acute flare-ups of corneal erosions can prevent infections,
• Regular monitoring to see if the disease is progressing.

Will I need surgery for Corneal Dystrophy?

A patient with severe symptoms may require surgery. For example, if they have significant and permanent vision impairment or eye pain. The type of surgery depends on the corneal layer affected. Procedures for corneal dystrophy include the following:

Alcohol epitheliectomy with mechanical debridement: A technique that involves scraping off the deposits in the corneal epithelium.

Excimer laser superficial phototherapeutic keratectomy (PTK): A type of laser treatment that removes deeper deposits up to the stromal layer.

Corneal transplant (or keratoplasty): This major eye surgery involves removing and replacing the affected corneal tissue with clear donor corneal tissue.

Unfortunately, most therapeutic modalities currently available for corneal dystrophies do not give long-term solutions, and recurrence is common after treatment.

The time to recurrence varies from 1-5 years.

The latest research on corneal dystrophy

An important goal for corneal dystrophy research is to find the exact genetic cause behind each person’s condition. This means that affected patients and their relatives can receive clearer genetic counselling about the expected progression of their condition and how it might affect their family.

With the help of funding from Fight for Sight, researchers discovered a new genetic cause of a type of corneal dystrophy called posterior polymorphous corneal dystrophy (PPCD). Two years earlier, the team identified changes in another gene that can also cause PPCD, or another condition called congenital hereditary corneal dystrophy (CHCD).

A proof-of-concept study with funding from Fight for Sight highlighted the potential of a cutting-edge antisense oligonucleotide (ASO) therapy to treat Fuchs endothelial corneal dystrophy patients with a fault in a gene called TCF4. And the results from another study will help pave the way for early diagnosis of this condition using an innovative method to sequence the gene fault responsible for more than three-quarters of cases. The technique could also help the development of new treatments targeted to this mutation.

Research initially funded by Fight for Sight to develop novel gene therapy approaches to treat Meesmann’s Epithelial corneal dystrophy and Avellino GCD2is still ongoing with a commercial partner USA company Avellino labs. siRNA gene silencing for both these cornea dystrophies is moving forward.

It aims to deliver eye drops to the front of the eye and prevent the disease from progressing by specifically cutting and destroying the faulty gene message that causes symptoms.

Last updated June 2023
Dr Tara Moore, Ulster University