Genetic Testing for Inherited Retinal Diseases
Understanding Inherited Retinal Diseases
Inherited retinal diseases, often called IRDs, are a large group of conditions that cause the retina to break down over time. The retina contains photoreceptors, which are the cells that detect light and send visual signals to the brain. In IRDs, these photoreceptors or the retinal pigment epithelium (a support layer behind the retina) do not develop properly, stop working correctly, or gradually degenerate.
Nearly 300 different genes have been linked to inherited retinal diseases. Researchers have identified an average of nine new causative genes each year since 1990. Despite this large number of genes, approximately 70% of IRD cases can be traced to just 20 genes (PNAS, 2020).
There are many forms of inherited retinal disease. Each type affects the retina in a different way, and symptoms can vary widely. Some of the most common forms include the following:
- Retinitis pigmentosa: the most common IRD, with a prevalence of approximately 1 in 4,500 individuals (Ophthalmology Science, 2023)
- Stargardt disease: a condition that primarily affects central vision, with a prevalence of approximately 1 in 17,000 (Ophthalmology Science, 2023)
- Usher syndrome: a condition that causes both hearing loss and vision loss, with a prevalence of approximately 1 in 25,000 (Ophthalmology Science, 2023)
- Leber congenital amaurosis: a severe form of retinal disease that begins in infancy, with a prevalence of approximately 1 in 42,000 (Ophthalmology Science, 2023)
IRDs follow different patterns of inheritance depending on the gene involved. The main patterns include autosomal recessive, autosomal dominant, and X-linked. In autosomal recessive inheritance, both parents carry the gene change. In autosomal dominant inheritance, one copy of the changed gene is enough to cause disease. X-linked means the gene change is on the X chromosome.
Mutations within the same gene can cause different symptoms in different people. Even members of the same family who share the same gene change may experience the condition differently. This overlap between genetic causes and clinical symptoms is one reason genetic testing is so valuable.
Who Is Affected and Risk Factors
IRDs affect approximately 1 in 1,380 individuals. An estimated 5.5 million people are affected worldwide (European Journal of Human Genetics, 2022). Collectively, these conditions represent a leading cause of vision loss in the working-age population. Because many IRDs begin in childhood or early adulthood, the impact on daily life and independence can be significant.
Many people carry a gene change linked to an IRD without knowing it. As many as 1 in 2.26 individuals of European descent may be unaffected carriers of at least one IRD-related mutation (PNAS, 2020). This means approximately 36% of healthy people could carry a relevant gene change. Most carriers have normal vision because they have only one copy of the changed gene.
Males are affected by IRDs at a higher rate than females, with a prevalence odds ratio of 1.65 (Ophthalmology Science, 2023). This is partly because X-linked forms of IRD affect males more severely. In children, X-linked inheritance accounts for a higher proportion of cases compared to adults.
Research has also revealed important disparities by race. White patients are more likely to be diagnosed compared to Black patients, with a prevalence odds ratio of 2.37 (Ophthalmology Science, 2023). This gap likely reflects differences in access to genetic testing and specialist care. These findings highlight the need for broader access to genetic evaluation across all communities.
Most IRDs are caused by gene changes inherited from one or both parents. However, some mutations can occur randomly and are not passed down from a parent. A detailed family history is an important part of the evaluation process. Even if no other family members have vision problems, genetic testing can still reveal a causative mutation.
Signs and Symptoms
In young children, inherited retinal diseases may be difficult to recognize at first. Parents may notice that their child does not fix his or her gaze on objects or follow moving objects. Some children rub their eyes frequently because this stimulates the photoreceptor cells. Involuntary eye movements called nystagmus may also be present.
Children with certain forms of IRD, such as Leber congenital amaurosis caused by RPE65 gene mutations, often have profound night blindness from birth. Early recognition of these signs is important so that a retina specialist can begin evaluation promptly.
Many inherited retinal diseases progress gradually. Symptoms often begin with difficulty seeing in dim light, known as night blindness. Over time, peripheral vision (side vision) may narrow, creating a sensation sometimes described as tunnel vision. Color vision can also be affected.
In conditions like Stargardt disease, central vision loss may be the first symptom. This makes it hard to read, recognize faces, or see fine details. The rate and pattern of vision loss vary depending on the specific gene involved.
Some gene changes that cause retinal disease also affect other parts of the body. For example, Usher syndrome causes both vision loss and hearing loss. Other IRDs may be associated with developmental delay, kidney problems, or other systemic conditions. Children with an IRD diagnosis should be evaluated by a pediatrician experienced in treating inherited diseases.
Diagnosis and Testing
A retina specialist will perform a thorough eye examination as the first step in diagnosing an inherited retinal disease. This includes checking visual acuity, examining the retina with specialized instruments, and assessing peripheral vision. These findings help narrow down the possible type of IRD, but a clinical examination alone cannot identify the specific gene involved.
Several tests help evaluate the structure and function of the retina in more detail. These may include the following:
- Optical coherence tomography (OCT), which provides detailed cross-sectional images of the retinal layers
- Fundus autofluorescence, which reveals patterns of retinal cell health and damage
- Electroretinography (ERG), which measures the electrical response of the photoreceptors to light
- Visual field testing, which maps areas of remaining peripheral and central vision
Genetic testing is a critical step in obtaining a definitive diagnosis for anyone with a suspected IRD. A small blood or saliva sample is collected and sent to a specialized laboratory. The laboratory analyzes hundreds of genes known to be associated with IRDs to identify the specific mutation causing the condition.
Current genetic testing can find the underlying cause in roughly 65% of individuals with an inherited retinal disease (European Journal of Human Genetics, 2022). Several comprehensive testing panels are available through major genetic testing laboratories. These panels collectively cover hundreds of genes linked to retinal dystrophies.
Several nonprofit organizations and industry partners provide genetic testing programs for patients with an IRD diagnosis. The Foundation Fighting Blindness offers the My Retina Tracker program. The ID Your IRD program was developed in collaboration with Invitae. A retina specialist or genetic counselor can help connect you with these resources.
Treatment Options
Luxturna (voretigene neparvovec) is the first FDA-approved gene therapy for an inherited retinal disease. Approved in December 2017, it was also the first gene therapy approved in the United States for any inherited disease. Luxturna uses an AAV2 viral vector (a modified, harmless virus) to deliver a working copy of the RPE65 gene directly into the retinal cells.
This treatment is for individuals with inherited retinal dystrophy caused by biallelic RPE65 mutations. This means both copies of the RPE65 gene are affected. Patients as young as 12 months old may be eligible. Luxturna can help improve functional vision and delay disease progression, but it does not fully restore normal sight. Genetic testing is required to confirm RPE65 mutations and determine eligibility.
Research in gene therapy for IRDs is advancing rapidly. More than 30 gene therapy clinical trials are currently underway for a variety of inherited retinal conditions. These include trials for X-linked retinitis pigmentosa, achromatopsia, and Leber congenital amaurosis caused by genes other than RPE65.
Knowing your specific genetic mutation is essential for determining whether you qualify for a clinical trial. A retina specialist can review your genetic results and help identify trials that may be appropriate.
While gene-specific treatments are available for only a small number of IRDs at this time, supportive care remains important. Low vision rehabilitation can help maximize remaining vision through specialized optical devices, adaptive technology, and training in daily living skills. Regular monitoring by a retina specialist helps track disease progression and ensures timely access to new treatments as they become available.
What to Expect
Genetic testing for inherited retinal diseases is straightforward. After a clinical evaluation, a retina specialist or genetic counselor will order the test. A blood draw or saliva sample is all that is needed. The sample is sent to a certified laboratory, and results typically take several weeks. In some cases, whole exome sequencing may be recommended if the initial panel does not identify a mutation.
Genetic test results can be complex. A genetic counselor is a healthcare professional trained to explain what your results mean for you and your family. Results may show a confirmed pathogenic (disease-causing) mutation, a variant of uncertain significance, or no identifiable mutation. Even a negative result provides useful information and does not rule out an inherited condition.
Receiving a genetic diagnosis for yourself or your child can bring a range of emotions. These may include relief at having an answer, grief about the prognosis, or anxiety about the future. These feelings are normal and valid. Genetic counselors are trained to help you process this information. Support organizations such as the Foundation Fighting Blindness also offer resources and community connections that many families find helpful.
Living With an Inherited Retinal Disease
A genetic diagnosis provides important information for family planning. If you know the specific gene change and inheritance pattern, a genetic counselor can explain the chances that future children may be affected or may be carriers. This information can guide personal decisions and help family members understand their own risk.
The field of gene therapy for retinal diseases is evolving quickly. Registering with programs like My Retina Tracker through the Foundation Fighting Blindness allows you to stay informed about new clinical trials. Keeping your genetic test results on file with your retina specialist ensures you can be notified when new treatments targeting your specific mutation become available.
Many people with inherited retinal diseases continue to live full and active lives with appropriate support. Orientation and mobility training can help with navigating safely as vision changes. Assistive technology, including screen readers, magnification apps, and specialized lighting, can support independence at work and at home. Connecting with others through patient advocacy groups can also provide practical advice and emotional encouragement.
When to See a Retina Specialist
While inherited retinal diseases typically progress gradually, any sudden change in vision requires immediate attention. If you experience a sudden increase in floaters, flashes of light, a curtain or shadow across your vision, or sudden vision loss in one eye, see a retina specialist or go to the emergency room immediately. These symptoms may indicate a separate, treatable problem such as a retinal detachment.
Consider seeing a retina specialist for genetic evaluation if you have unexplained vision loss that began in childhood or young adulthood. Other reasons include a family history of retinal disease, night blindness, or progressive peripheral vision loss. If you have been diagnosed with an IRD but have not yet had genetic testing, a genetic evaluation is recommended. Early testing opens the door to emerging treatments and clinical trials.
Questions and Answers
Genetic testing requires only a blood draw or a saliva sample. There is no eye procedure involved in the testing itself. Results typically take several weeks. Many patients find the process simple and are relieved to have clear information about their condition.
In approximately 35% of cases, current genetic testing panels do not identify the causative mutation (European Journal of Human Genetics, 2022). This does not mean you do not have an inherited retinal disease. It may mean the responsible gene has not yet been discovered. The mutation could also be in a region of the genome not covered by standard panels. Your retina specialist may recommend additional testing in the future as technology improves.
Yes. Because unaffected carriers are common, genetic testing can provide valuable information for family planning. Estimates suggest 1 in 2.26 individuals of European descent may carry an IRD-related mutation (PNAS, 2020). Siblings and other relatives of an affected person can learn whether they carry the same gene change and what that means for their own children.
Luxturna (voretigene neparvovec) remains the only FDA-approved gene therapy for an inherited retinal disease as of this writing. However, more than 30 clinical trials are actively investigating gene therapies for other forms of IRD. The pace of research is encouraging. Having your genetic mutation identified positions you to access these treatments as they become available. A retina specialist can help you explore current trial options.
Yes. Genetic testing in children can confirm a diagnosis, guide monitoring plans, and identify eligibility for treatments like Luxturna. This therapy is approved for patients as young as 12 months old. Early diagnosis also helps families connect with educational and developmental resources. Because some IRD-related gene changes affect other organs, a confirmed genetic diagnosis can prompt important evaluations by other specialists.