Inherited Retinal Diseases (IRD)

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Inherited Retinal Disease (IRD)

Inherited retinal diseases (IRD) are both uncommon, as well as diverse, in how they affect a patient’s vision. Advances in genetics have greatly expanded our understanding of what causes these conditions. Specialized training and experience with these rare diseases is of value to patients and their families.

Colorado Retina is a tertiary referral center for patients with these rare and complex diseases, evaluating and diagnosing patients from Colorado and surrounding states. Recent advances in genetic testing increasingly provide new information regarding which of more than 270 genes could be responsible for vision loss. The scientific advances in genomics led to the very first FDA-approved gene therapy for an inherited retinal disease (Leber’s congenital amaurosis, RPE65 gene) in December 2017. Subsequently, dozens of other gene therapy trials were designed and are currently underway. Cell-based therapies (stem cells) and implantable, electronic retinal prosthesis comprise other areas of intensive research. Advances in inherited retinal diseases now inform exciting new therapies for more common eye diseases, such as both the dry and wet forms of age-related macular degeneration.

Types of Inherited Retinal Diseases (IRDS)

There are many different conditions that comprise the category of Inherited retinal diseases.

Retinitis pigmentosa is a group of diseases that share a number of features. These include poor night vision and constricted visual fields, but are highly variable in age of onset and progression. Most forms of poor night vision are progressive, while some rare forms are stationary and do not worsen with time.

These night-blinding disorders include early-onset forms such as Leber’s congenital amaurosis, all the various forms of inheritance (recessive, dominant, X-linked, sporadic) causing retinitis pigmentosa, choroideremia, congenital stationary night-blindness, and syndromic forms of retinitis pigmentosa such as Usher syndrome, Bardet-Biedl syndrome and other ciliopathies.

Another group of diseases affecting primarily the central vision, with the macula showing abnormal yellowish deposits, followed later by thinning and atrophy leading to a loss of detail vision. These “macular dystrophies” include Stargardt’s disease, Best’s disease, cone-dystrophies, cone-rod dystrophies, achromatopsia, x-linked juvenile retinoschisis, and pattern dystrophies.

There are forms of IRDs that affect more than the eye alone. These include conditions such as Usher syndrome that affects hearing and speech, as well as Bardet-Biedl syndrome with a range of other symptoms.

Risk Factors, Causes & Symptoms

The risk factors for the inherited retinal diseases are better understood today compared with recent decades ago and include a family history of vision problems and the presence of specific genetic mutations. Advances in genetics at the molecular level (DNA, RNA, proteins) over the years drive rapid progress on a global scale. The cost to analyze a single person’s genetic signature has dropped significantly, leading to genetic testing moving out of academic research labs into the higher-throughput commercial labs. With ever increasing amounts of genetic information available for analysis, the accuracy of genetic testing has significantly improved. New information has likewise increased our understanding of the complexities of how the human genome works. New knowledge in genomics rapidly replaces what we knew even five years ago.

Symptoms of persons with inherited eye diseases may vary widely from person to person, even with the same disease. However, some features are shared and may include:

• Decreased night vision with an inability to see the stars at night
• Slower adaptation from light to dark environments
• Feelings of "clumsiness", but actually due to abnormal peripheral vision
• "Jiggly eyes" (nystagmus), due to many causes, but sometimes from poor vision early in life
• Loss of central vision (loss of detail vision and/or color sense)
• Sometimes, but not always, a family history of similar eye problems, as above
• Sometimes, combined speech and hearing problems that accompany poor night vision and/or constricted peripheral vision
• Rarely, a history of a sixth finger or toe removed shortly after birth

Treatment

While there are a growing number of clinical trials showing encouraging, early-stage results, there are only two FDA-approved therapies for IRDs:

Luxterna for bi-allelic, RPE65 gene mutations in Leber’s congenital amaurosis and Argus II retinal prosthesis for severely affected patients with visual loss.

Some forms of retinitis pigmentosa produce abnormally leaking retinal vessels that lead to swelling in the central retina (cystoid macular edema). Various step-wise treatments can reduce the leakage, though side-effects may limit their usage. Some patients with retinitis pigmentosa eventually may require cataract surgery with intraocular lens replacement. Referral to our network of highly qualified cataract surgeons skilled in operating upon patients presenting with these cataracts is another aspect of Colorado Retina’s approach to serving IRD patients.

Unique to the inherited retinal disease space, Colorado Retina has gathered together a diverse portfolio of community-based resources. These services include references to a range of low-vision service providers, technology-assistance devices for computing and smartphones, vocational rehabilitation, and social support groups.

Finally, Colorado Retina was honored with recognition by the (FFB) Foundation Fighting Blindness as the top fundraiser last year for research into inherited retinal diseases. We have been the leading practice in the state for FFB’s signature fundraising event, VisionWalk, held every fall in Denver’s City Park. Colorado Retina also participates in the annual Scramble for Sight golf tournament to raise funds, and lectures to update the inherited retinal disease community throughout the year, after attending international eye research meetings.

Testing & Diagnosis

The state of the art currently begins with taking a good history of visual symptoms and family ocular history, followed by a detailed dilated eye examination.

Next, a photographer will image the back of the eye using a combination of devices (color photos, fluorescein angiography, fundus autofluorescence, and optical coherence tomography). These images provide exceptional detail regarding the structure of the retina beyond what can be resolved in a standard eye examination.

Critical information regarding the eye’s functional health are obtained using highly-specialized equipment available through Colorado Retina’s Eye Lab. These tests include digital electrophysiologic testing (ERG, EOG) and digital, static and kinetic perimetry (Humphrey central visual fields, Octopus kinetic perimetry).

The current emphasis in diagnosis of inherited retinal diseases is upon genetic testing. Colorado Retina is designated as a genetic testing service center by the Foundation Fighting Blindness (FFB). A certified genetics counselor will discuss the results of genetic testing with the patient, as part of the testing service. The value of this genetic testing is further increased by sharing the results on a secure data registry maintained by the FFB, accessible by an approved group of international researchers in inherited retinal diseases. The rarity of these diseases has been a barrier to research that would lead to treatments, but now recruitment for clinical trials is facilitated by these collective efforts.