Leber Congenital Amaurosis
Leber congenital amaurosis (LCA) is a genetic disorder that causes severe visual impairment at birth or in early childhood. It was first outlined in a paper published in 1869 by the German ophthalmologist Theodor Karl Gustav von Leber, which is where the disease gets its name. Leber originally suggested that the disease is a rare form of retinitis pigmentosa (RP), and that continues to be accepted today. LCA is unique in several ways, however: the symptoms are often noticed in the first weeks or months after a child’s birth, and vision loss is more rapid and severe, as opposed to the slow progression associated with other forms of RP. The disease is less prevalent than RP as well, affecting approximately 1 in 33,330 to 1 in 50,000 individuals.
LCA is the result of a mutation in one of at least 17 different genes, which is why it is called a “genetic” or “inherited” disorder. Depending on which gene or genes are mutated, different characteristics of the retina will be affected, but in all cases the retina’s ability to develop and function properly is inhibited. In some cases, for example, the photoreceptors, the light-sensitive retinal cells that convert light into messages for the brain, are no longer sending electrical signals correctly, resulting in severe visual impairment.
As stated above, the symptoms of LCA are typically noticed very early in a child’s life—in the first weeks or months after birth. Parents may observe that the child does not focus on things in the surrounding environment, or they may notice “wibbly” back-and-forth movements of the call called “nystagmus.” Some children may even press or push on their eyes with their fingers or fist. During an eye exam, the child’s retina may not look different than a normal one, but further testing will reveal that the eye and brain are not communicating they way they should.
Children with LCA usually have severe vision loss of 20/400 or worse, meaning that they can see at 20 feet what a person with “normal” vision can see at 400 feet. Some children may have only light/dark perception, and in fewer cases no vision at all. Children with some vision may have other symptoms such as night blindness, light sensitivity, and far-sightedness.
There are rare genetic syndromes that mimic LCA vision loss in young children, including Alström syndrome, Batten disease, Joubert syndrome, and peroxisomal diseases (Zellweger syndrome or Refsum disease). Children with these conditions have vision loss similar to LCA, as well as other physical or mental disabilities. A child diagnosed with true LCA (not one of the syndromes listed above) may, in rare cases, be more vulnerable to kidney disease than other children. Compared to the general population, however, they do not have a greater risk of either intellectual disabilities or autism.
An ophthalmologist may suspect LCA on the basis of a child’s symptoms and the findings of a simple eye examination. Two tests can be used to clarify the diagnosis:
- ERG (electroretinography): this is a test that measures the electrical responses of the retina to light, evaluating responses of both rod and cone photoreceptors. The ERG test involves staying in a darkened room for 30 minutes, with drops put into the eye or eyes being tested. A special contact lens or gold-foil electrode is then placed on the eye or lower eyelid, and the eye is exposed to flashes of light.
- OCT (optical coherence tomography): this is an imaging technique that involves taking digital images of the various layers of the retina. The process uses light rather than sound or radio waves, which is why the images are in high resolution.
- Genetic counselling: while not a test in the traditional diagnostic sense, genetic counselling is an important part of the diagnostic process. It can help determine the gene or genes that have been mutated, as well as the hereditary factors that are involved.
Existing treatments and Standards of Care
Currently, there are two innovative treatments available for some forms of LCA—a gene therapy, Luxturna, and the Argus II retinal prosthesis. A gene therapy called Luxturna, which can halt vision loss and even restore some sight in individuals with a biallelic mutation of their RPE65 gene (manifesting as either retinitis pigmentosa or LCA), was approved by the FDA in 2017 and is currently available to patients in the United States. Though patients with this mutation comprise only a portion of the overall LCA patient group, the medical effectiveness of Luxturna and its materialization as a pharmaceutical product demonstrate that there is significant potential for gene therapy to treat other forms of LCA in the future.
Retinal prosthetics, such as the Argus II or “Bionic Eye,” use computer technology to generate vision—one of the first Canadians to receive the Argus II implant has a diagnosis of LCA. Fighting Blindness Canada helped to support the first Canadian trial of the Argus II and continues to work closely with health policy experts across Canada to ensure that patients who could benefit from the Argus II device have access to this innovative treatment. The Argus II device is on track to be publicly funded and available to patients in Ontario in 2018. At FBC, we are meeting with key stakeholders across Canada to ensure that this life-changing treatment is available to those who might benefit from it.
Clinical trials are essential to the scientific process of developing new treatments. They test the viability and safety of experimental drugs and techniques, called “interventions,” on human beings. While there is no guarantee that enrolling in a clinical trial will provide any medical benefit, some patients do experience positive results after receiving an experimental therapy.
The website clinicaltrials.gov is a centralized database of clinical trials that are offered globally. But as the disclaimer on the site’s home page states, there is no guarantee that a listed trial has been evaluated or approved—the National Institutes of Health runs the site but does not vet its content. This means that there could be bogus or dangerous trials listed that are preying on patients. It is essential that you discuss a clinical trial with your ophthalmologist before enrolling, and that you pay close attention to enrollment criteria.
If you are interested in exploring what is available on the site you can click on the button below, which will take you to clinicaltrials.gov and initiate a search for trials relevant for patients living with LCA.
For individuals living with an inherited retinal disease (a disease caused by a genetic mutation), such as LCA, participation in a clinical trial could be a logical next-step (for a description of clinical trials, see above). But in Canada there is no centralized, guided mechanism for enrolling in a trial. With this in mind, Fighting Blindness Canada has developed a secure medical database of Canadian patients living with inherited retinal diseases. We call it the Patient Registry.
By enrolling in the Patient Registry, your information will become a part of this essential Canadian database that can be used to help connect you to a relevant clinical trial. The availability of relevant trials depends on a number of factors, so this tool provides no guarantees, but signing onto it will put you in a position to be connected to something appropriate. It is also a way of standing up and being counted: the more individuals enrolled in the Patient Registry, the better our chances of showing policymakers that there is a significant need for new treatments for inherited retinal diseases. The Patient Registry also helps to drive more sight-saving research!
You can begin the process of enrolling in the Patient Registry by clicking the button below.
Research Developments and Health Policy
Fighting Blindness Canada is committed to advancing the most promising sight-saving research, and has invested over $40 million into cutting-edge science and education since the organization was founded. Recognizing that science is tied to policy frameworks, FBC is also actively involved in health policy activities across Canada.
Many research groups are working to develop treatments and cures for RP. Experimental treatments can be divided into three broad categories:
- Protective Therapies
- Corrective Therapies
- Sight-Restoring Therapies
Protective therapies aim to stop (or at least slow) the damage caused by genetic mutations. Often protective therapies are not specific to one mutation, but may benefit people with different genetic forms of LCA. These include treatments to stop the process of photoreceptor death (apoptosis), as well as cell-derived therapies that aim to help photoreceptors survive.
Some protective therapies aim specifically to prevent the death of cone cells in LCA – and thus, the loss of central vision.
Corrective therapies aim to reverse the underlying genetic defect that causes vision loss. If these therapies are successful they might prevent a person who is treated when first diagnosed, from ever developing vision loss. Corrective therapies might also help slow the disease in people whose vision has already been affected, especially in the earlier stages. The corrective therapies being developed now are specific to certain genetic forms of LCA. Gene therapies, which replace a non-functioning gene, are one type of corrective therapy; for example, this is how the FDA-approved gene therapy, Luxturna, works to treat people living with LCA caused by biallelic mutations in the RPE65 gene. Clinical trials of gene therapies for several types of LCA are underway, and the results so far are encouraging.
Sight-restoring therapies are also a growing area of research success. These therapies are intended for people who have already lost all, or much, of their vision. Stem cell therapies aim to replace the retina’s lost photoreceptors. There are promising early results with stem cell trials involving other retinal degenerative diseases. Drug and gene therapies are also being developed that may give non-photoreceptor nerve cells in the retina the capacity to sense light.
Thanks to our generous donors, we are funding ground-breaking research in these areas.
Click on the button below to review the full list of FBC-funded projects:
Fighting Blindness Canada has developed additional resources that can be helpful in plotting an optimal path through vision care. Below is a link to our must-read resources, where you will find information on genetic testing, clinical trials, stem cell research, and more as well as a link to View Point (FBC’s virtual educational events).
Health Information Line
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Updated on August 29, 2019.
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