Genetic Testing for Inherited Retinal Diseases

Some inherited retinal diseases, particularly Leber congenital amaurosis, appear very early in life. Parents may notice that their infant does not fix their gaze on objects or follow moving items with their eyes. A child with LCA may also rub their eyes frequently. This eye rubbing, known as the oculodigital sign, occurs because pressing on the eye stimulates the remaining photoreceptor cells.

Another condition, X-linked retinoschisis, is typically diagnosed in males between 3 months and school age. Symptoms can include crossed eyes (strabismus), abnormal eye movements (nystagmus), and reduced vision. When vision loss is mild, it may not be detected until a child fails a routine vision screening at school.

Many inherited retinal diseases, such as retinitis pigmentosa, develop gradually over years or decades. Early symptoms often include difficulty seeing in dim light or at night. This is sometimes called night blindness. Over time, the visual field narrows, creating a tunnel vision effect.

Stargardt disease tends to appear in childhood or early adulthood and primarily affects central vision. A person may notice blurry or distorted vision when reading, difficulty recognizing faces, or a gradual decline in color perception.

Any unexplained or progressive change in vision should be evaluated by a retina specialist. Symptoms that warrant prompt attention include increasing difficulty seeing at night, loss of side vision, blurry or distorted central vision, and unusual sensitivity to light. If a child shows signs of poor visual tracking, eye rubbing, or abnormal eye movements, a thorough eye examination is important.

Early evaluation can lead to earlier diagnosis. An earlier diagnosis, in turn, can open the door to genetic testing and potential treatments while vision is still preserved.

In 2017, the U.S. Food and Drug Administration approved Luxturna (voretigene neparvovec), the first gene therapy for an inherited retinal disease (FDA, 2017). Luxturna is a one-time treatment that delivers a healthy copy of the RPE65 gene directly to retinal cells. It is designed for patients with vision loss caused by mutations in both copies of the RPE65 gene.

Genetic testing is required to determine whether a patient carries RPE65 mutations and is eligible for Luxturna. Without genetic confirmation, this treatment cannot be offered. The approval of Luxturna has increased the number of patients being tested for RPE65 mutations.

Dozens of clinical trials are currently underway to develop gene therapies for other forms of inherited retinal disease. Researchers are studying treatments for Stargardt disease, choroideremia, X-linked retinitis pigmentosa, and achromatopsia. Some trials test gene replacement approaches similar to Luxturna, while others explore gene editing techniques.

Genetic testing plays a critical role in clinical trial eligibility. Many trials require participants to have a confirmed mutation in a specific gene. Patients who have undergone genetic testing are better positioned to participate in these studies.

For the many forms of IRD that do not yet have an approved gene therapy, supportive care remains important. This may include regular monitoring by a retina specialist, use of low vision aids such as magnifiers, orientation and mobility training, and assistive technology for reading and daily tasks.

Maintaining overall eye health through regular examinations and protecting the eyes from excessive light exposure can help preserve remaining vision. Some retina specialists may also discuss nutritional supplements studied in certain retinal conditions, though no supplement has been proven to stop IRD progression.

Yes. A negative or inconclusive result reflects the current state of scientific knowledge and testing technology. As researchers identify new IRD genes and laboratory methods improve, it becomes possible to detect mutations that earlier tests could not find. Retesting after several years may yield a positive result. It is worth maintaining contact with a retina specialist or genetic counselor to stay informed about when retesting may be beneficial.

Genetic testing requires only a blood draw or saliva sample. A blood draw involves a brief needle stick, which may cause minor discomfort. A saliva sample is collected by spitting into a tube. No eye procedures are involved in the sample collection itself. The clinical eye examination that precedes genetic testing may include pupil dilation, which causes temporary light sensitivity and blurred near vision for a few hours.

Not necessarily. Whether a child is affected depends on the inheritance pattern of the specific gene mutation. In autosomal recessive conditions, a child must inherit a changed copy of the gene from each parent to develop the disease. If only one parent carries the mutation, the child may be a carrier but would not be affected. In autosomal dominant conditions, each child has a 50 percent chance of inheriting the gene change. A genetic counselor can provide a personalized risk assessment based on the specific mutation and family history.

As of now, Luxturna (voretigene neparvovec) remains the only FDA-approved gene therapy for an inherited retinal disease. However, numerous clinical trials are investigating gene therapies for other IRDs. These include choroideremia, X-linked retinitis pigmentosa, Stargardt disease, and achromatopsia. The pace of research is encouraging, but new therapies must go through rigorous testing before approval. A retina specialist can help determine whether any current clinical trials are relevant to a specific genetic diagnosis.