Leber congenital amaurosis

What is Leber congenital amaurosis?

Leber congenital amaurosis (LCA) is a group of genetic eye conditions that cause blindness or severe vision loss. LCA mainly affects the retina, the specialised light-sensitive layer that lines the back of the eye, and is usually congenital (a condition you are born with). 

Even though it is rare, LCA is one of the most common causes of severe sight loss in children. 

There are several different types of LCA, which are differentiated by their genetic cause, patterns of sight loss, and related eye abnormalities.

What causes Leber congenital amaurosis?

LCA affects the light-sensing cells called photoreceptors, which play a vital role in making eyesight possible by converting light into electrical signals that are transmitted to the brain. When these cells stop working properly or are lost, this causes sight loss.

LCA is a congenital condition because it is present from birth. It is also a genetic condition caused by faulty genes passed down to an affected child from their parents.

Each of the genes associated with LCA provides the instructions for making various proteins that play important roles in the healthy development and functioning of the retina. For instance, some are essential for the correct development of photoreceptor cells, while others are involved in converting light into electrical signals. Faults in these genes disrupt the smooth working of the retina, resulting in sight loss.

Scientists have so far identified faults in at least 27 different genes that can cause Leber congenital amaurosis. Faults in these genes account for about 80 to 90 percent of cases of LCA – and so it is likely that more are yet to be identified. The most commonly affected genes are CEP290, CRB1, GUCY2D, RDH12, and RPE65.

LCA is almost always inherited in an autosomal recessive inheritance pattern. That means both parents will have one faulty copy of an LCA gene and one healthy copy. They will usually be unaware they carry the faulty gene, as you need two faulty copies to develop sight loss. Each of their children will have a one in four chance of inheriting two faulty copies of the gene (one from each of their parents). 

In rare cases, LCA can have an autosomal dominant pattern of inheritance – meaning that only one copy of the faulty gene is enough to cause the condition. In these cases, the child will usually inherit the faulty gene from one affected parent.

What are the signs and symptoms of Leber congenital amaurosis?

Children with LCA usually have severe visual impairment from birth. Within the first few months, parents often notice their baby isn’t responding to normal visual cues, such as following moving objects. They might poke, press, and rub their eyes, which may contribute to their eyes looking sunken or deep-set. 

Other symptoms of LCA include:

• Keratoconus – an abnormal shape to the cornea at the front of the eye
• Light sensitivity – photophobia or dislike of bright light. Very rarely a child may be very attracted to light
• Cataracts – clouding of the lens of the eyes
• Involuntary eye movements - this is known as nystagmus
• Crossed eyes – also known as strabismus  or squint
• Deep-set eyeballs – that seem to be further back in the eye sockets. This is called enophthalmos 
• Farsightedness – The eyes are smaller than normal, meaning it is harder to bring an image into focus
• Slow or missing pupil reactions – the pupils don’t adjust normally to changes in light conditions

In rare cases, a child may have symptoms affecting other parts of the body, including kidney disease, hearing loss, learning difficulties, and/or developmental delay. This may be caused by a related syndrome rather than LCA itself.

Is Leber congenital amaurosis serious?

LCA is one of the most common causes of severe sight loss in children, and it significantly impacts quality of life from a very young age. Usually, symptoms will be present from birth or the first months of life, andif the child has some eyesight, it may get worse over time.

The severity of the symptoms and speed of sight loss can vary widely.

How is Leber congenital amaurosis diagnosed?

A test known as electroretinography (ERG) can help doctors to assess how well a child’s retina is working. This show electrical activity in the retina - a child with LCA will have abnormally low or no electrical activity due to problems with their photoreceptors.

As the retina breaks down and starts to get thinner over time, this can lead to abnormal changes to the pigment at the back of the eye, which the eye doctor can see from clinical examination or specialised photographs.

Genetic testing can help confirm an LCA diagnosis and identify the responsible faulty gene. This can also provide information about the inheritance pattern of the condition and risks to other family members, helping to inform accurate genetic counselling.

What are the treatments for Leber congenital amaurosis?

There is currently no cure for Leber congenital amaurosis. But the development of cutting-edge gene therapies is offering hope for some people. These new treatments are gene-specific, meaning they are only suitable for a small group of patients. They work by introducing a healthy copy of the faulty gene into the eye.

Since 2018, the first gene therapy for Leber congenital amaurosis has been available in the UK. The treatment, called voretigene neparvovec (brand name Luxturna), is currently approved to treat patients with LCA caused by faults in the RPE65 gene. It aims to deliver healthy copies of the RPE65 gene into the eye, restoring the levels of an enzyme needed for the healthy functioning of photoreceptors.

Luxturna is the first and only gene therapy available in Europe to treat inherited retinal disease. In the UK, affected patients can receive this treatment under the NHS at four specialist centres – in London, Manchester, and Oxford.

Luxturna is administered by an injection underneath the retina, under general anaesthetic. While the treatment does not completely restore vision, it can help prevent further sight loss and restore some functional vision in LCA patients. However, there is a risk of surgical complications, which may lead to further sight loss.

What can help Leber congenital amaurosis?

Some people with LCA may benefit from low-vision aids to help maximise their remaining sight, such as electronic, computer-based, and optical aids.

If someone in your family has LCA, you can access genetic testing along with support from a genetic counsellor. As well as helping you to make informed medical and personal decisions, a genetic diagnosis will also provide up-to-date information about potentially suitable new treatments that are currently in development.

Have your eyes tested every two years even if you think your vision is fine. An eye test can spot some eye conditions and, if caught early, treatment may prevent further deterioration.

What research is there into Leber congenital amaurosis?

Researchers are working to find the remaining genes that cause LCA and to develop new treatments that can help slow down, stop, or reverse sight loss in patients.

Scientists are investigating several gene therapies that could benefit people with faults in genes that cause LCA.

Fight for Sight helped to fund the initial research that led to the world’s first clinical trial of a potential new genetic technique for patients with LCA caused by faults in the CEP290 gene.

Other approaches include developing new small-molecule drugs and stem cell-based therapies, which involve transplanting new retinal cells into the eye to replace those that are damaged.

See our research projects