What Is the Most Common Inherited Retinal Disease?

Vision loss is usually first noticed in childhood or early adulthood. The disease worsens over time. Vision loss can become severe after several years.

Symptoms differ depending on the type of retinal cell affected. Both eyes frequently suffer from similar vision loss.

In general, retinitis pigmentosa (RP) may result in the following:

• Night blindness (the most common symptom)
• Reduced peripheral vision/visual field narrowing, also known as “tunnel vision”
• Eyes require more time to adjust to dim lighting or take time to adjust from bright sunlight to indoor lighting
• Symptoms worsen in foggy or rainy weather
• Difficulties seeing colors, particularly blue
• Visual loss, whether partial or total, usually progresses gradually
• Clumsiness is caused by a lack of vision, particularly in small spaces such as doorways
• Cataracts can cause blurred vision, which can exacerbate RP later in the disease

Many types of retinitis pigmentosa (RP) are caused by a genetic mutation. Some cases occur sporadically.

• Men are more likely to have RP, as are those who have a family member who has the condition.
• The disorder can be passed down from parents who pass on mutant (affected) genes to their children in an autosomal dominant fashion, which means even one copy of an altered gene in each cell is sufficient to cause the disorder.
• Although RP is a genetic disease, a child doesn't need to have a family history of the condition. 40 to 50 percent of people with RP are the only ones with the condition in their families.
• The condition often skips generations.
• RP is one of the most complex genetic conditions, affecting 1 in 3,000 to 1 in 4,000 people and being caused by more than 50 genes.

Three treatment options for retinitis pigmentosa (RP) include:

1. Gene therapy:
   • ProQR Therapeutics is in the process to develop a gene therapy that could stop vision loss in people with RP.
     • In this therapy, a protein called QR-421a is injected into the retina that allows cells to produce a healthier version of the USH2A protein that stops the disease.
     • This has shown positive results in people with both advanced and early moderate disease.
     • ProQR Therapeutics expects to test the therapy in phases two to three clinical trials by 2021 to 2022.
   • Another study by ProQR Therapeutics is for people who have RHO gene-related RP.
     • This mutation causes people to produce a faulty version of the rhodopsin protein. The faulty rhodopsin protein eventually becomes toxic to the retina.
     • The new treatment called QR-1123 is still in the developmental phase. It is injected into the eye and prevents the faulty protein from being synthesized.
2. Retinal implants:
   • Retinal implant technology stimulates cells in the retina by surgically implanting an electronic chip into the back of the eye.
   • Although photoreceptor cells may have died, nearby nerve cells may still be functional. These “bionic eyes” send signals to the remaining cells, which the brain interprets as vision.
3. Nutrition:
   • According to some studies, vitamins A and E may slow the progression of RP.
   • However, there is concern that too much could be harmful, so supplements are not advised until directed by the doctor appropriately.

Inherited retinal diseases (IRDs), or hereditary retinal dystrophies or congenital retinal degenerations, are a class of rare genetic disorders that can result in severe vision loss or blindness.

• Mutations in one of more than 250 genes cause IRDs.
• About two million people worldwide are affected by IRDs.
• IRDs are a group of rare eye diseases marked by the progressive loss of function or death of photoreceptor (light-sensitive) cells in the retina, resulting in vision loss or blindness.

The presence of mutations in genes involved in the development and normal function of photoreceptors or other retinal cells is the underlying cause of all inherited retinal diseases (IRDs).

1. Mistakes, or mutations, in a specific gene that are inherited at birth cause IRDs.
2. To cause IRDs, one or both copies of the gene must be mutated, depending on the gene involved.
3. If only one mutated gene causes the disease to manifest, the disease is said to be dominant.
4. If two mutated genes are required, the disease is said to be recessive.
5. The inheritance of X-linked disease differs between men and women.
6. In all cases, the mutation causes a specific protein to malfunction, preventing the retina from functioning properly.
7. IRDs are caused by hundreds of different mutations, and only a genetic test can tell one is malfunctioning.

Symptoms of inherited retinal diseases (IRDs) usually develop through the genetic mutation that causes the condition. Some people with IRDs lose their vision gradually, eventually leading to total blindness, whereas others are born with or experience vision loss in infancy or early childhood.

The 6 common symptoms of IRDs include:

1. Going blind/progressive vision loss:
   • Many IRDs are characterized by progressive vision loss throughout a person’s life, which can eventually lead to blindness.
   • Severe visual impairment can occur as early as the first year of life in some cases of IRDs.
   • Some IRDs primarily affect cone photoreceptors in the central retina, resulting in central vision loss.
   • Other IRDs affect rod photoreceptors, which are mostly found in the peripheral retina, resulting in peripheral vision loss.
2. Tunnel vision:
   • Loss of peripheral vision is referred to as tunnel vision. When tunnel vision occurs, the only usable vision a person may have is central vision, which produces a tunnel effect similar to looking through a narrow tube.
   • There are numerous causes of tunnel vision, and a person’s vision fields may eventually become so narrow that they are blind.
   • Tunnel vision is caused by genetic mutations that cause degeneration of rod photoreceptors in the peripheral retina in various IRDs, including retinitis pigmentosa (RP).
3. Nyctalopia (night blindness):
   • The inability to see well at night or in low light conditions is referred to as night blindness or nyctalopia.
   • Rod photoreceptors in the retina enable vision in low-light conditions. Night blindness can occur when rods are harmed by a condition or disease.
   • In the early stages of the disease, RP frequently causes night blindness.
4. Photophobia (sensitivity to light):
   • Photophobia is a common but debilitating symptom characterized by light sensitivity or intolerance.
   • A photophobic person may experience eye discomfort in bright sunlight or indoor lighting.
5. Nystagmus (eye tremors):
   • Nystagmus, also known as “wiggly eyes” or “dancing eyes,” occurs when the eye makes an involuntary repetitive back-and-forth eye movement.
   • These movements, which usually affect both the eyes, can be up and down, rotational, or side to side.
   • Nystagmus frequently causes blurred vision and depth perception, as well as problems with balance and coordination.
   • This symptom occurs when the part of the brain or inner ear that controls eye movement and positioning does not function properly. It can be genetic or acquired due to an injury or other circumstances.
6. Colorblind:
   • Color blindness is a defect in how a person perceives color.
   • Color blindness does occur when one or more types of color cone photoreceptors in the eye are absent or not functioning properly, causing people to have difficulty distinguishing certain colors.

Although there are no treatments or cures for the majority of IRDs, doctors can help slow the disease's progression and prevent or delay additional vision loss.

Moreover, doctors can discuss the possibility of participating in gene therapy clinical trials. Many clinical trials are showing promising results, and doctors can help you determine whether you are a good fit for one.

Retinitis pigmentosa is the most common inherited retinal disease (IRD).

Four other common IRDs include:

1. Cone rod dystrophy (CRD):
   • The cone photoreceptors are the first to be affected by this childhood disease, followed by the rods.
   • As a result, people with CRD typically lose their central and color vision first.
   • There is a progressive loss of peripheral vision.
   • Currently, there are treatment options available to slow the degenerative process. However, there is currently no cure for CRD.
2. Leber congenital amaurosis (LCA):
   • LCA appears in infancy or early childhood and is caused by mutations in more than 19 genes.
   • Involuntary eye movements decreased light sensitivity, and a proclivity to press, poke, or rub the eyes are all symptoms.
   • LCA can cause severe vision impairment in infancy, which can lead to childhood blindness.
   • Clinical trials are currently being conducted to improve vision in people with LCA.
   • Gene replacement therapy is beneficial, and results are promising.
3. Choroideremia (CHM):
   • CHM is caused by the degeneration of the choroid and retinal cells.
   • CHM, which is linked to the X chromosome, causes night blindness, tunnel vision, and central vision loss.
   • The majority of people with CHM are men.
   • CHM, like LCA, can be treated with gene replacement therapy.
4. Juvenile macular degeneration (JMD):
   • Adult-onset macular degeneration is most common in people older than 60 years.
   • JMD, on the other hand, can appear much sooner.
   • Stargardt disease is the most common type of JMD.
   • Symptoms appear during childhood or adolescence.
   • Although there is no cure for JMD at the moment, some forms of the disorder may respond to laser therapy.

It is estimated that one-third of inherited systemic diseases are accompanied by eye abnormalities. Their presence is frequently the most crucial factor in confirming a diagnosis. When possible, learning about your family's medical history can provide important clues about your proclivity for many eye diseases and vision problems.

• In the early stages of many eye diseases, there are no symptoms.
• It is critical to seek treatment as soon as possible before these conditions worsen. 
• Remember that many eye diseases are passed down through families.
• Learn about your family history and share it with your eye care provider to take a proactive approach.

Even if you have no family history of eye disease or are unaware of your family history, annual eye exams are essential for everyone.

The onset of early signs of eye disease and vision changes can occur at any age. Doctors recommend that everyone get a baseline eye screening when they reach the age of 40 years. Your eye doctor will advise you on how frequently you should have follow-up exams based on the results.