“Everyone was cordial and professional. Dr. Paul Lagonigro was personable and performed an outstanding eye exam with modern equipment. He explained results clearly and outlined future treatment paths.”
Gene Therapy for Inherited Retinal Diseases
Who Gets Inherited Retinal Diseases?
Inherited retinal diseases, often called IRDs, affect people of all backgrounds and ages, including young children. Understanding who is at risk and how these conditions are passed down through families is an important first step toward early diagnosis and timely care.
Inherited retinal diseases affect approximately 1 in 2,000 people worldwide, impacting more than two million individuals globally. These conditions are among the leading causes of blindness in working-age adults. Retinitis pigmentosa, one of the most prevalent inherited retinal diseases, affects roughly 1 in 3,000 to 7,000 individuals.
Inherited retinal diseases can follow several different patterns of genetic inheritance. The specific pattern affects who in a family may be at risk and how the condition is passed from one generation to the next.
- Autosomal dominant: only one copy of the altered gene is enough to cause the disease
- Autosomal recessive: two copies of the altered gene are required, one from each parent
- X-linked: the altered gene is located on the X chromosome, which most often affects males
Populations where marriages between close relatives are more common tend to see higher rates of autosomal recessive conditions. X-linked retinoschisis, the most common form of juvenile-onset retinal degeneration in males, affects an estimated 1 in 15,000 to 30,000 individuals.
Many different genes can cause inherited retinal diseases. For retinitis pigmentosa alone, 87 individual disease-causing genes have been identified. Three genes, RHO, USH2A, and RPGR, account for a substantial proportion of all retinitis pigmentosa cases.
Mutations in the RPE65 gene are responsible for certain severe forms of Leber congenital amaurosis, a childhood-onset retinal disease, and some types of retinitis pigmentosa. These biallelic, meaning two-copy, RPE65 mutations account for a meaningful percentage of Leber congenital amaurosis cases and are the target of the first FDA-approved retinal gene therapy.
Signs and Symptoms
The symptoms of inherited retinal diseases vary depending on the specific condition, the genes involved, and how early the disease begins. Some conditions appear in infancy, while others progress gradually over many years. Recognizing the warning signs early gives patients the best chance to access evaluation and available treatments.
Some inherited retinal diseases are present from birth or become apparent in early childhood. Leber congenital amaurosis is typically detected when infants show profound visual impairment. Parents may notice that their child does not fix their gaze on objects, does not follow moving objects, or rubs their eyes frequently.
The eye-rubbing behavior is significant because it stimulates the retina and creates brief sensations of light. It is sometimes one of the earliest observable signs in an affected child.
In retinitis pigmentosa, the earliest symptom is usually difficulty seeing in dim light, a condition called night blindness. Patients may also struggle to adjust when moving between bright and dark environments. Over time, the visual field begins to narrow, typically starting in the mid-peripheral zone and gradually closing inward, a pattern often described as tunnel vision.
One form of Leber congenital amaurosis caused by RPE65 mutations also tends to affect night vision first, creating particular challenges for children and young adults navigating low-light settings.
Most inherited retinal diseases are progressive, meaning vision typically worsens over months or years. The rate of decline varies widely from person to person, even among people with the same genetic mutation. Some patients retain useful central vision for many years, while others experience more rapid changes. Because progression can be gradual, patients sometimes do not notice early losses without specialized testing.
Diagnosis and Testing
Diagnosing an inherited retinal disease requires a combination of clinical examination, specialized imaging, and genetic analysis. A thorough workup helps identify the exact condition, assess how much retinal function remains, and determine whether a patient may be a candidate for gene therapy or a clinical trial.
A Retina Specialist can identify signs of inherited retinal diseases during a comprehensive dilated eye exam. Characteristic findings may include bone spicule pigment deposits, which are dark spots shaped like bone fragments, thinning of the retinal layers, or a pale optic nerve. These findings, combined with the patient's symptoms and family history, guide the diagnostic process and inform the next steps.
Several advanced tests help confirm the diagnosis and measure how much retinal function is still present. Our team uses a full range of retinal imaging and functional testing tools to build a detailed picture of each patient's condition.
- Optical coherence tomography (OCT): creates detailed cross-sectional images of the retinal layers
- OCT angiography: maps blood flow within the retina without the need for dye injection
- Electroretinography (ERG): measures the electrical activity of retinal cells in response to light
- Fundus autofluorescence: reveals patterns of retinal cell health and early damage
- Wide-field imaging and fundus photography: documents the overall state of the retina over time
- Visual field testing: maps the areas of remaining peripheral and central vision
Genetic testing is a critical step for anyone with a suspected inherited retinal disease. A blood sample or cheek swab can identify the exact gene mutation responsible for the condition. This information is essential for determining whether a patient may qualify for an existing approved gene therapy or an active clinical trial.
Genetic counseling is strongly recommended alongside testing. A counselor can help patients and their families understand what results mean, how the condition may be inherited, and what options are available going forward.
Current and Emerging Treatment Options
The treatment landscape for inherited retinal diseases is advancing rapidly. While only a small number of therapies have received FDA approval to date, dozens of clinical trials are evaluating new approaches. Understanding the available options helps patients and families plan their care with realistic expectations.
Luxturna (voretigene neparvovec) was the first FDA-approved gene therapy for a genetic disease. It is designed for patients with vision loss caused by biallelic, meaning two-copy, mutations in the RPE65 gene. An estimated 1,000 to 3,000 patients in the United States have this specific form of retinal dystrophy.
Luxturna is delivered through a subretinal injection performed during a vitrectomy procedure. A Retina Specialist injects the therapy beneath the retina, allowing a healthy copy of the RPE65 gene to enter the appropriate cells. Each eye is treated in a separate surgical session. The treatment aims to restore the retinal cells' ability to produce a protein essential for the visual cycle, particularly for vision in low light.
In 2025, the FDA approved Encelto (revakinagene taroretcel), an encapsulated cell-based gene therapy for adults with idiopathic macular telangiectasia type 2. This is a condition in which abnormal blood vessels develop in the central retina, leading to gradual central vision loss. Encelto is administered during a single surgical procedure and works by continuously producing a protective protein called ciliary neurotrophic factor, or CNTF, to support the affected retinal cells.
Optogenetics is a newer strategy being explored for patients who have already lost most of their photoreceptor cells, the light-sensing cells of the retina. This approach uses a one-time intravitreal injection to deliver light-sensing molecules into surviving retinal cells, essentially reprogramming those cells to detect light in place of the ones that have been lost.
Early clinical testing of one optogenetic therapy, MCO-010, showed that up to 50 percent of treated patients with advanced retinitis pigmentosa gained three lines of vision on a standard eye chart. Researchers are exploring whether similar approaches may benefit patients with other forms of retinal degeneration as well.
More than three dozen retinal gene therapy clinical trials are currently in progress, targeting a wide range of genetic mutations and conditions. Research strategies include gene augmentation, which adds a working copy of a defective gene, gene editing, which attempts to correct the mutation directly, and delivery of protective molecules to support surviving retinal cells.
- Multiple research programs are developing gene therapies for X-linked retinitis pigmentosa caused by RPGR mutations
- Some trials are testing delivery approaches that do not require vitrectomy surgery
- Therapies targeting USH2A mutations are in development for patients with retinitis pigmentosa and Usher syndrome
- RGX-314, evaluated in the AAVIATE trial, has shown promising results in reducing the number of injections needed for certain retinal conditions
A Retina Specialist can help determine whether a patient's specific genetic mutation is being studied in an active trial and whether they may meet eligibility requirements.
What to Expect From Gene Therapy
Gene therapy for inherited retinal diseases is not a routine procedure. It involves careful pre-treatment evaluation, a specialized surgical or injection technique, and close follow-up care. Knowing what to expect at each stage helps patients prepare and make well-informed decisions.
Patients being considered for gene therapy undergo a thorough evaluation before any procedure. This includes genetic testing to confirm the specific mutation, detailed retinal imaging, and functional vision testing to assess how much viable retinal tissue remains. A Retina Specialist will determine whether enough living retinal cells are present for the therapy to be effective.
For therapies like Luxturna, both eyes are not treated at the same time. Sessions are scheduled weeks apart so the response in the first eye can be monitored before the second is treated.
For subretinal gene therapies, the procedure involves a vitrectomy. The Retina Specialist removes the vitreous gel and carefully injects the gene therapy solution in a small bleb beneath the retina. The surgery is performed under anesthesia and requires a skilled surgical team experienced in retinal procedures.
For intravitreal gene therapies, the injection is delivered into the vitreous cavity in a manner similar to other eye injections, though often performed in an operating room setting. Suprachoroidal delivery is a newer approach that may be completed in a clinic setting. Early studies suggest it is safe and well tolerated.
Recovery after subretinal gene therapy typically involves several weeks of restricted activity. Patients may need to maintain specific head positions to support retinal healing. Multiple follow-up visits with a Retina Specialist are necessary to monitor the retina and assess visual outcomes.
Vision improvements, when they occur, tend to develop gradually over weeks to months rather than immediately. Not all patients experience the same degree of benefit. Outcomes depend on factors including the type of mutation, the amount of retinal function remaining at the time of treatment, and the patient's age. Gene therapy should not be expected to restore vision to normal levels.
Living with an Inherited Retinal Disease
Most patients with inherited retinal diseases live with progressive vision changes for years, both before any treatment is available and alongside ongoing monitoring afterward. Building a practical support system and staying connected to the latest developments can make a meaningful difference in quality of life.
Many practical adaptations can help patients maintain independence as vision changes over time. These may include using magnifying devices, improving home lighting, learning orientation and mobility skills, and working with low vision rehabilitation specialists. Patient advocacy organizations and support groups offer both resources and a sense of community for people navigating these challenges.
Even if no approved gene therapy exists for a specific mutation today, genetic testing remains an important step. Knowing the exact genetic cause helps patients understand their condition, informs family planning decisions, and may qualify them for clinical trials that are actively enrolling participants. The field is advancing quickly, and new therapies are entering clinical testing regularly.
A Retina Specialist or genetic counselor can help patients stay informed about developments that are relevant to their specific diagnosis.
Receiving a diagnosis of an inherited retinal disease carries significant emotional weight. This is especially true for parents learning that their child has a condition that may cause progressive vision loss. Feelings of grief, anxiety, and uncertainty are a normal part of the process. Connecting with mental health professionals who have experience with chronic illness, as well as with patient communities, can provide meaningful support. Open conversations with a Retina Specialist about realistic expectations for current and future treatments also help patients and families navigate their path forward with greater confidence.
When to See a Retina Specialist
Early evaluation is one of the most important steps a patient with a suspected inherited retinal disease can take. The sooner a diagnosis is made, the more options are available, including access to genetic testing, clinical trials, and approved therapies. Some symptoms also require immediate attention.
Any unexplained difficulty with night vision, gradual narrowing of the visual field, or progressive vision loss should prompt a referral to a Retina Specialist. Parents who notice that their child does not fix their gaze on objects, does not follow movement, or rubs their eyes frequently should seek evaluation without delay. Early diagnosis allows for timely genetic testing and consideration of all available treatment and trial options.
While inherited retinal diseases are typically slow-moving, certain symptoms require immediate attention. A sudden increase in floaters, new flashes of light, a curtain or shadow covering part of the vision, or sudden loss of vision in one eye are warning signs of a possible retinal emergency such as a retinal tear or detachment. These are separate from inherited disease and require urgent evaluation. If any of these symptoms occur, patients should contact a Retina Specialist immediately or go to the nearest emergency room.
Frequently Asked Questions
Below are answers to common questions patients and families have about gene therapy for inherited retinal diseases. These are intended to add practical guidance beyond what is covered in the sections above.
Not yet. Currently, Luxturna is approved specifically for patients with biallelic RPE65 mutations, and Encelto is approved for adults with macular telangiectasia type 2. These represent a small fraction of all inherited retinal diseases. However, dozens of clinical trials are actively evaluating gene therapies for a wide range of other mutations. If your specific mutation does not have an approved therapy today, that may change as trials progress. Staying under the care of a Retina Specialist who tracks this field ensures you are notified when relevant options become available.
The first step is confirming your exact genetic mutation through testing. Once that information is in hand, a Retina Specialist can search clinical trial databases to identify studies that match your genetic profile and evaluate whether you meet eligibility criteria based on your remaining vision, retinal health, and other clinical factors. Some trials have strict requirements about how much retinal function must remain, so earlier evaluation often expands the options available to you.
Gene therapy cannot regenerate retinal cells that have already been destroyed. It works by supporting or restoring the function of cells that are still alive. This is why the amount of surviving retinal tissue at the time of treatment directly affects how much benefit a patient may experience. In patients with sufficient remaining function, improvements in low-light vision and certain aspects of visual performance have been documented. The therapy is not expected to return vision to normal, and results vary meaningfully from person to person.
Gene augmentation delivers a working copy of a defective gene to cells that still exist and can benefit from the correction. This approach depends on having viable photoreceptor cells that are still alive and receptive to treatment. Optogenetics takes a different approach for patients who have already lost most or all of their photoreceptors. It reprograms other surviving retinal cells, ones that do not normally detect light, to take over that function. These two strategies are suited for different stages of disease progression, which is one reason why evaluation timing matters so much.
Genetic testing for family members can be genuinely valuable. It can identify carriers who show no symptoms but could pass the condition to their children, and it can reveal relatives who may be in the early stages of the same disease before significant vision loss occurs. Early identification gives those individuals the best chance to access monitoring, protective measures, and potentially treatment. A genetic counselor can guide families through this process and explain what results mean for each person's specific situation.
A diagnosis is still highly actionable even without an immediately available therapy. Establishing a baseline through detailed retinal imaging and functional testing allows a Retina Specialist to track changes over time with precision. Genetic confirmation opens the door to clinical trial eligibility. Low vision resources and rehabilitation services can help preserve independence throughout childhood and beyond. Staying connected to a specialist who monitors this field means families are prepared to act quickly when new options become available.
Partner with Our Team for Expert Retinal Care
Atlantic Retina Center is dedicated exclusively to the health of the retina, vitreous, and macula, bringing specialized expertise in inherited retinal diseases to patients throughout the Eastern Shore of Maryland and central and southern Delaware. Our team of fellowship-trained, ABO board-certified Retina Specialists provides the genetic evaluation coordination, advanced retinal imaging, and personalized guidance needed to navigate these complex conditions. Whether you are seeking a first evaluation, monitoring a known diagnosis, or exploring eligibility for emerging therapies, we are here to support you at every step of your journey.