Inherited Retinal Diseases & Ophthalmology

Inherited Retinal Diseases & Ophthalmology

January 25, 2021

Inherited retinal diseases (IRDs) are a group of rare blinding conditions caused by one of more than 250 different genes. Some people living with IRDs experience a gradual loss of vision, eventually leading to complete blindness.

Others may be born with or experience vision loss in infancy or early childhood. Obtaining a confirmed genetic diagnosis through genetic testing is the only way to verify the exact gene mutation that is the underlying cause of an IRD.

The maturation of gene therapy has changed the paradigm of inherited retinal diseases (IRDs) from a diagnostic field to one in which promising therapies may be able to prevent blindness in patients with IRDs in the future.

It is important for every retina specialist to educate himself or herself about these diseases and about what new treatments or diagnostics might be available for these patients.


Patients with IRDs require a different approach and workflow compared with patients with more typical diseases such as age-related macular degeneration and diabetic retinopathy. Careful history-taking is important, and counseling the patient about the diagnosis is a key part of the visit.

This requires significant chair time as these patients have likely been told previously by other providers that they will go blind and that there are no treatments available.

Addressing patients’ psychological concerns about the diagnosis is as important as any medical treatment.

Gene-based classification of IRDs is becoming the norm, replacing the previous nomenclature based on fundus findings. Lower costs have made DNA sequencing more accessible to the general public, and genetic testing is becoming the standard of care for patients with IRDs.

This can include single-gene testing if there is strong suspicion for a particular disease (eg, a mutation of RPE65 leading to Leber congenital amaurosis), but it is common to order a panel of approximately 270 genes that have been implicated in retinal degenerations in which a genetic cause of the disease is found in about 50% of patients.

This type of testing can give patients a definitive diagnosis, which can be a great relief, and can also help physicians identify patients for potential enrollment in clinical trials.

There are a number of ways to arrange for genetic testing. One is through the Foundation Fighting Blindness My Retina Tracker portal.

Through this portal, patients are entered into a registry that alerts them to clinical trials for which they may qualify and can receive free commercial genetic testing with counseling.

Alternatively, commercial CLIA-certified laboratories such as Blueprint Genetics and GeneDx now offer relatively affordable genetic testing for retinal diseases. In general, insurance only partially covers the costs of these tests; out-of-pocket expense may range from $500 to $2,000.


Although technology now allows us to perform sequencing rapidly, the interpretation of these tests to identify a causative mutation is not always straightforward. Many times, there are mutations in multiple genes that are predicted to cause changes in a protein, but these mutations have not been determined to cause a deleterious effect responsible for the disease.

These mutations are termed variants of unknown significance. Additionally, the phenotype may be caused by a compound heterozygous mutation, meaning heterozygous mutations in two separate genes.

Because of this complexity, it can be extremely helpful for genetic counselors to discuss findings with patients. Genetic counselors who have specialized training in interpreting these tests can explain the findings to patients, freeing up the retina specialist for other aspects of patient care.

Retina specialists who do not have easy access to a genetic counselor can consider using third-party genetic counseling groups such as InformedDNA.


The US FDA approval of the first gene therapy has ushered in a new era in the treatment of IRDs.

In addition to voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics), there are more than 30 middle- and late-stage clinical trials ongoing using gene therapy or other molecular therapies for IRDs, some with encouraging results.

Resources such as can be useful when searching for clinical trials for specific IRDs, but clinical trials for IRDs are dynamic and constantly changing.

The best way to find an appropriate trial is to directly contact retina specialists at centers that are participating in many of these clinical trials to learn the latest updates.


There is no consensus on nutritional supplementation for IRDs, although a healthy balanced diet is recommended.

Vitamin A should be avoided by patients with Best disease or the cone-rod dystrophy Stargardt disease, as vitamin A may exacerbate these diseases due to increased toxicity through the visual cycle.

A number of studies have investigated whether nutritional supplements such as high-dose vitamin A, docosahexaenoic acid, lutein, and beta carotene can prevent progression of vision loss in patients with IRDs.

A combination of high-dose vitamin A (15,000 IU) and carotenoids has shown a modest effect with decreased vision loss in patients with retinitis pigmentosa, but the combination is currently not recommended given equivocal efficacy, hepatotoxicity, and other side effects.

How should a clinician who is not an IRD expert work up a patient with an IRD? Currently, the standard workup to diagnose and follow patients includes a standard ophthalmic examination with fundus photos, fundus autofluorescence, and OCT imaging.

Genetic testing can be considered. Additional workup that is not common in the retina clinic may include periodic kinetic perimetry (eg, Goldman or automated kinetic perimetry) and electroretinography, which may be done at a more specialized IRD clinic.


IRD centers can serve as one-stop shops for the needs of patients with IRDs. IRD specialists can provide specialized workups, an infrastructure for genetic testing and counseling, and access to the latest clinical trials and research.


Patient communities and online groups are invaluable for patients with IRDs. As noted previously, many of these patients have been told that they will go blind and that there is no treatment available, which can have significant psychological and functional effects on patients.

Patient advocacy groups and foundations provide excellent venues for patients to support each other, and such support can have a dramatic effect on patients’ quality of life. The largest of these is the Foundation Fighting Blindness.

The foundation has many local chapters across the United States. Additionally, online communities such as Facebook groups can be helpful. I recommend referring patients to these groups because, many times, this support can have as great of a significance on quality of life as any medical treatment.


A multidisciplinary approach is important when treating patients with IRDs.

Given the complicated nature of care for these patients, such a multidisciplinary team should include a retina specialist, preferably with some training in IRDs; a genetic counselor; a low-vision specialist; and social workers.

All of these individuals play essential roles in making sure these patients are taken care of at all levels.

It is an exciting time in the care of patients with IRDs. Today, clinicians can provide treatments that can potentially prevent blindness for some patients with IRDs.

As these patients present to retina clinics, I hope that the information presented here will be helpful and can serve as a framework to care for these patients.