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Diagnosis

Leber Congenital Amaurosis (LCA) is a rare inherited retinal degeneration. It appears at birth or in the first few months of life with loss of vision, which varies from person to person and can be quite severe (with little to no light perception). In some cases, blindness can occur in infancy.

There are many different types of LCA as defined by differences in genetic cause, patterns in visual loss and presentation of other eye abnormalities. LCA is estimated to affect around 1 in 50,000 individuals in the population.

Symptoms

As there are different types of Leber Congenital Amaurosis (LCA), this condition can present differently among individuals. However, there are some basic symptoms that are often associated with LCA. These include nystagmus (involuntary jerky rhythmic eye movements), photophobia (sensitivity to light) and slow pupillary response to light. Other symptoms include strabismus (eyes not aligned properly), cataracts (clouding of the eye lens) and keratoconus (thin, cone-shaped cornea).

Eye-pressing and rubbing the eyes with a knuckle or finger can be common with babies and children who have very little vision. This is known as Franceshetti’s oculo-digital sign. This can cause damage to the lens and may result in a loss of fatty tissue around the eyes, causing the eyes to look deep-set.

The extent of retinal degeneration depends on the type of LCA the child has. For some types of LCA the degree of vision a child has can remain stable over time or it can progressively deteriorate.

Causes

Forms of Leber Congenital Amaurosis (LCA) are caused by a mutation in a number of genes that are important for retinal function; GUCY2D, CEP290, RPE65, RPGRIP1, RDH12, SPATA7, AIPL1, RD3, CRB1, CRX, IMPDH1, IQCB1, KCNJ13, LCA5, NMNAT1, and TULP1. Given the severity of the condition, it is one of the most extensively researched inherited retinal disorders.

LCA is usually inherited in an autosomal recessive manner, meaning both copies of a gene don’t work correctly. In this case, the individual develops the condition when they receive a mutation in the same gene inherited from their mother and from their father.

However, there are rare incidences where the inheritance pattern may be autosomal dominant. In this case, a person will develop the condition when they receive one copy of a mutated gene from an affected parent.

More information on genetic inheritance can be found at our Genetic Inheritance section.

Diagnosis

Leber Congenital Amaurosis (LCA) is diagnosed through a number of assessments which help with providing the correct diagnosis.

The eye doctor will ask about a person’s medical history, including any family history of eye conditions. Individuals will receive a clinical eye examination where they may be asked to read letters off a chart (Snellen chart). They may also check intraocular pressure and examine visual acuity and the visual field.

An individual may receive a number of imaging tests. Information about the condition may be identified using colour or wide-field fundus photography (which essentially takes photos of the back of the eye). Fundus autofluorescence may be used to identify stress or damage to the retinal pigment epithelium. Optical coherence tomography (OCT) can also be used to assess the various layers at the back of the eye.

An individual may also have an electroretinogram (known as an ERG), which is used to evaluate the functioning of the different types of photoreceptor cells (rods and cones).

A genetic test is also an important component of testing, to ensure the correct condition is diagnosed. For people living in Ireland, genetic testing for LCA can be performed through the Target 5000 programme.

If a family member is diagnosed with LCA, it is strongly advised that other members of the family also have an eye exam by an eye doctor (ophthalmologist) who is specially trained to detect retinal diseases.

Genetic Diagnosis

It’s often impossible to tell which type of retinal disease a person has just by looking into the eye. As such, a genetic test may be necessary to confirm the diagnosis.

The Target 5000 programme provides free genetic and clinical testing to all individuals living in Ireland with a genetic retinal degeneration, including Leber Congenital Amaurosis (LCA). Through genetic screening of the person awaiting diagnosis and their family members, the Target 5000 programme will provide more detailed information about the nature and inheritance pattern of the condition.

As gene-specific clinical trials and treatments become available, knowing the genetic mutation associated with a genetic retinal degeneration will become even more important. Taking part in this programme ensures participants are included on a national registry from which participants can be identified for clinical trials and treatments and from which further information about each of the genetic retinal degenerations can be defined. For further information on the Target 5000 programme, please contact the Research Department on 01 6789004 or email research@fightingblindness.ie.

Treatment

Recent advances in research have yielded a breakthrough for the treatment of inherited retinal degenerations, with the first ever gene therapy (Luxturna™)** now approved for use in some cases of Leber Congenital Amaurosis (LCA), where a mutation in both copies of the RPE65 gene exists. Whilst this treatment is not available for all types of LCA, this milestone signals the potential of gene therapy and the potential for other treatments to reach the clinics in the near future.

The gene therapy Luxturna™ is available to treat those who have been diagnosed with a type of LCA where they have mutations in both copies of the RPE65 gene (and have functioning photoreceptor cells as observed on clinical examination and ERG). This gene therapy works by delivering a normal, functioning copy of the RPE65 gene directly into the cells of the retina at the back of the eye to restore vision. This is a one-time treatment delivered by a specially-trained surgeon who administers the treatment by a sub-retinal injection.

There are no other approved treatments for other genetic types of LCA as of yet, although recent years have noted advances in clinical research and development. To find out more about advances made in this area, please visit the ‘Latest Research’ section.

Maximising an individual’s remaining vision is a crucial step to take, and there are many low vision aids including telescopic and magnifying lenses which may offer benefit. This technology has removed many of the barriers to education and employment.

General eye check-ups are important for people living with LCA, as these individuals may still be at risk of developing other kinds of eye problems that can affect the general population, some of which may be treatable.

No matter what level of vision a person may have, it is important to look after the eyes. To find out more about what can be done to take care of the eyes on a daily basis, please visit our Tips for Good Eye Health.

For further information, please contact the Research Department on 01 6789004.

** Fighting Blindness does not endorse any of the products, medications, treatments or information reported here, or on any of our communication platforms. Articles on Fighting Blindness websites and social media are intended for informational purposes only. We strongly advise that you discuss all medications, treatments, and/or products with your doctor.

Research

Advances in research have yielded a greater understanding of the condition, with much progress made to develop and deliver therapies to the clinic. Marking these advances so far has been the development of a gene therapy (Luxturna™) which is now licensed for treatment at certain sites across the world.

Scientists have been studying the genes associated with Leber Congenital Amaurosis (LCA) and are actively gathering as much information (such as the information from clinical tests and genetic testing) as possible in an effort to fully understand this condition. The aim is that this information will bring benefits such as yielding new treatments and ways to improve quality of life.

Following recent success, gene therapy remains an active area of interest for LCA, most commonly for the RPE65 gene. Of note, much research is still ongoing into examining the effects of Luxturna™ in those who have received this treatment already. It is important to investigate how this gene therapy performs over time. Other early-phase clinical trials investigating gene therapies for the RPE65 gene have revealed some positive results so far, with some work still ongoing. Further follow-up in the coming years will provide greater insight into the effectiveness of these interventions.

Another area of intense focus is in the treatment of LCA using antisense oligonucleotides. These are molecules which can alter RNA, the exact copy of your DNA, which provides the template for protein production. In the eye, proteins can play essential roles, including in eye structure and function. Where a person has a genetic mutation in their DNA, this will also be present in their RNA (as it is an exact copy) – leading to the generation of an incorrect or damaged protein. Antisense oligonucleotides can skip the mutation in the RNA and either reduce, restore or modify the generation of the protein. Clinical trials are now investigating the potential for this type of intervention for certain forms of LCA.

Another area being investigated includes stem cell treatment, which aims to provide a repair for damaged areas at the back of the eye. Stem cells are like precursor cells which have the potential to self-renew and generate many different types of cells. Transplantation of human retinal pigment epithelium is being investigated in a clinical trial for LCA, with this study currently ongoing.

Information about clinical trials can be found on their website and can be searched by condition and trial location.

Fighting Blindness currently support a number of research initiatives which aim to improve the diagnosis, care and quality of life of individuals living with LCA.

Target 5000 research, largely funded by Fighting Blindness aims to determine the genetic cause and understand the nature of the condition over time. Through Target 5000, a national registry will also be developed which will greatly improve access to suitable clinical trials and treatments for people living in Ireland with LCA.

Dr Sarah Doyle based in Trinity College Dublin is conducting a study to investigate if a protein known as SARM1 plays a role in retinal degeneration, a key component of LCA. This work aims to further understand the underlying mechanisms of retinal degeneration and identify potentially new therapeutic targets.

A study conducted by Professor Breandán Kennedy is investigating a group of neuroprotective drugs, known as HDAC inhibitors, for their potential to delay vision loss in retinal degenerations. This work seeks to identify new therapeutics which could provide significant benefit to individuals.

A study by Professor Kennedy and Ms Rebecca Ward is currently examining an animal model (zebrafish) of LCA in an effort to further understand the genetic basis of the condition. This study also aims to examine neuroprotectant drugs which may slow the rate of photoreceptor cell loss and hence identify new therapeutic targets.

For further information, please contact the Research Department on 01 6789004.

Support

Receiving a diagnosis can be overwhelming for anyone, but this is not a journey that you have to make alone. There are many groups and resources available to provide support for people living with Leber Congenital Amaurosis.

Fighting Blindness offers a free and confidential counselling service (Insight Counselling). For further information please contact insight@fightingblindness.ie or call 01 6746496.

A mindfulness group is also available on every Wednesday at the Fighting Blindness office at 11am.

For technology support and guidance, the Dublin-based Technology Exchange Club meets every Monday at the Fighting Blindness office at 11am. Another Technology Exchange Club, based in Cork, meet every Saturday in the Cork City Library, Grand Parade, Cork City at 11am. The Cork-based club do not meet on Bank Holiday weekends or on the second Saturday of the month. For further information please contact insight@fightingblindness.ie or call 01 6746496.

 

Resources

Féach provides support for parents of children living with sight loss in Ireland.

ChildVision is the national education centre for children with sight loss in Ireland.

NCBI (National Council for the Blind in Ireland) provides support and services for people living with sight loss in Ireland.

Irish Guide Dogs for the blind helps individuals and their families to achieve improved mobility and independence.

 

Last Updated: 4th February 2019