Retinitis Pigmentosa

What is Retinitis Pigmentosa?

Retinitis pigmentosa (RP), which was first described in 1853 and named in 1857, is a term that is still used today, even if it’s a bit of a misnomer. While the term implies inflammation, in reality, inflammation only plays a minor part in the way the disease progresses. RP is a group of conditions that slowly leads to vision loss. You might also hear it referred to as hereditary retinal dystrophy. This condition affects approximately 1 out of 4000 people in the United States and about 1 in 5000 people across the globe, making RP the most common inherited disease involving the retina, which is the part of the eye that sends visual signals to the brain.

RP typically affects both eyes; however, there have been instances where only one eye is affected. The earliest signs of RP are often loss of night vision and a gradual narrowing of the field of vision. As the disease worses, people with RP may experience tunnel vision or even total vision loss. Other symptoms can include problems distinguishing colors accurately and a decline in sharpness of vision. Most people with RP retain at least some light perception, as a part of the eye called the macula continues working. One distressing late-stage symptom is photopsia, or perceived flashes of light that are likely due to sensory deprivation. This symptom can get so severe that people experience visual hallucinations.

About 70% to 80% of RP cases involve only vision loss, and this is known as “nonsyndromic” RP. On the other hand, “syndromic” RP comes with systemic disease, which means the disease affects the entire body. The most common type of syndromic RP is Usher syndrome, which is characterized by loss of hearing and vision concurrently.

What Causes Retinitis Pigmentosa?

Retinitis Pigmentosa (RP) is a condition that’s caused by genetic mutations affecting certain cells in the retina called rod photoreceptors. These cells affect how well you can see in low light. The genetic faults linked with RP can cause these cells to behave incorrectly, leading to various issues such as programmed cell death, light damage, problems with cell transport, and stress within the cells. This results in the rod photoreceptors dying off, leading to difficulties with night vision and hazy peripheral vision.

Eventually, the large-scale death of these cells affects not only your ability to see in the dark but also the health of the retinal pigment epithelium, a layer of cells at the back of the eye, and other cells called cone photoreceptors. These conditions can lead to changes in colour perception.

There are many different genes that, when faulty, can cause RP, which results in a wide range of symptoms and the severity of the condition. So far, researchers have found more than 3100 different mutations that can lead to RP. This variety of genetic faults also means that RP can be inherited, i.e., passed from parents to their children, in many different ways.

Most patients with RP have autosomal recessive or autosomal dominant patterns of inheritance, where both or just one parent, respectively, carries a copy of the mutated gene. In some cases, RP is passed down through the mother via X-chromosome. In others, it appears in families without a clear pattern of inheritance.

Some of the more commonly mutated genes in RP include ones known as USH2A, ABCA4, CERKL, CRB1, EYS, PDE6A, PDE6B, RPE65, and RP1 among others. These faulty genes are a significant cause of the condition but do not account for all cases of RP. There remains a lot for us to understand about this complex genetic condition.

Risk Factors and Frequency for Retinitis Pigmentosa

Nonsyndromic Retinitis Pigmentosa (RP) affects about 1 out of every 5000 people worldwide. This condition accounts for half of all inherited eye diseases and impacts more than 1.5 million people globally. The number of people affected varies by location, ranging from 1 in 3026 in Denmark, to 1 in 4869 in Birmingham, UK, and even up to 1 in 372 in rural India. These differences may be due to varying research methods and case definitions or a higher prevalence in populations where marriages between relatives are more common, like certain regions of the Middle East and South Asia.

Nonsyndromic RP affects men slightly more often than women due to a version of the condition linked to the X chromosome. Syndromic RP, which co-occurs with other conditions like Usher syndrome, is much less common – hitting only 4 to 17 out of every 100,000 people.

The age when symptoms start to appear depends on the specific genetic variant causing the RP. People with the autosomal recessive form typically start to experience symptoms in their early teens. On the other hand, those with the autosomal dominant form may not have symptoms until their mid-twenties. By age 30, more than three-quarters of people affected by RP will have developed symptoms and sought medical attention for the disease. In a study conducted in Japan, the average age of diagnosis was found to be around 35 years old.

Signs and Symptoms of Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a condition that affects the eyes and generally begins around age 20. Symptoms often include difficulty adjusting to low light situations and problems switching rapidly from light to dark environments. Some people may struggle with driving at night due to bright lights making it hard to adjust to the darkness. Over time, the individual’s field of vision may start to narrow, although this isn’t often noticeable right away.

A patient’s family history is crucial to determine the type of RP, as it can help identify the inheritance pattern and aid in making a prognosis. A thorough medical history is also essential to detect any associated conditions or check for possible exposure to infectious diseases or toxins which could mimic RP’s symptoms.

There are certain characteristic physical signs associated with RP, commonly called the “classic triad”. These are bony spicule pigmentation, vascular narrowing, and an abnormal waxy color of the optic disc. However, these signs might not be noticeable early in the disease, and the severity of these abnormalities can vary. Other possible physical signs may include cataracts and macular edema, fluid buildup in the macula of the eye.

While an external eye examination might seem routine, individuals with RP have a higher risk of developing an eye condition called keratoconus. However, even this is relatively rare. Refractive errors, such as high myopia or astigmatism, are also more common among people with RP. Other features of RP may include a white dot-like appearance or exudative vasculopathy, a condition similar to Coats disease. Another form of RP, sector RP, is characterized by symmetrical changes in the pigment, concentrated in a specific area of the eye. In some cases, RP may also coincide with mild hearing loss.

There are more severe forms of RP, such as juvenile RP and Leber congenital amaurosis. Juvenile RP is a varied and severe form of autosomal recessive RP (arRP). Leber congenital amaurosis is the most aggressive variant and often leads to blindness early in childhood.

Testing for Retinitis Pigmentosa

If you are suspected of having Retinitis Pigmentosa (RP), a thorough eye exam would be necessary. This includes a detailed examination of the back of your eye (fundoscopic exam) and a check on how your retina, the layer at the back of your eye, is functioning.

Part of the check-up will include tests to measure your vision sharpness and your ability to see contrast and color. These tests will not only determine the quality of your vision but will also play a role in gauging the extent of this disease’s damage to your eyes. These tests are important as they help the doctor understand the speed at which the disease is progressing and estimate its future impact on your vision.

You may also have imaging tests such as color wide-field fundus images, which can help monitor the disease’s progression by creating pictures of the back of your eye.

An innovative and non-invasive imaging tool called fundus autofluorescence (FAF) may be used. It’s a special technique that gives your doctor an insight into the health of your retina by detecting a waste product called lipofuscin, which is a sign of cell death in the retina. In patients with RP, FAF is useful in revealing specific patterns related to disease severity and progression. As RP progresses, the FAF outlines show changes which suggest that vision is getting worse.

Visual field assessment with kinetic perimetry is a useful way to check the loss of your peripheral or side vision. Through Humphrey visual field test and electroretinogram (ERG), doctors would be able to know how much vision is left and detect changes in your retina’s electrical activity even before symptoms like night blindness and visible changes at the back of the eye appear. The ERG test results help in understanding how the retina is functioning, and it has been helpful in diagnosing and monitoring disease progression.

Another useful test is fluorescein angiography which shows if there are any abnormalities in blood flow in your retina and even subtle changes in those who carry the RP gene. Typically, RP is associated with a painless swelling of the central part of the retina, called non-leaking macular edema.

Optical coherence tomography (OCT), another imaging technique, has been useful in spotting changes in the retina in people with RP. Through OCT, we can see several changes that happen in the eye with the progression of RP, and these changes can help in assessing how the disease is progressing and what treatment response is.

A recent non-invasive imaging technique, optical coherence tomography angiography (OCTA), provides detailed images of the small blood vessels of the retina. It helps observe vascular changes in RP that correlate with disease severity and progression. With emerging technologies like adaptive optics scanning laser ophthalmoscopy (AOSLO), we can view the retina with high resolution to detect early changes in the disease. Side by side, a complete assessment of the body is done to rule out the chance of syndromic RP, which is RP accompanied by other physical symptoms or conditions.

Treatment Options for Retinitis Pigmentosa

Retinitis pigmentosa (RP) refers to a group of genetic disorders causing progressive vision loss as the cells in the retina at the back of your eye deteriorate. Unfortunately, there is no cure for this condition and it can be challenging to treat due to the many genetic variations causing it. Various treatments are currently being researched, including vitamin A supplements, gene therapy, stem cell therapy, neuroprotective treatments that aim to protect vision cells from damage, and retinal implants.

If you have RP, adjustments such as wearing prescription glasses, using low vision aids like special lenses or software that enlarges text, and undergoing some vision rehabilitation training can improve your day-to-day life. Drugs to slow down fluid buildup in the retina can also help. Steroids can be used if the fluid leak is severe. If you develop significant cataracts, another possible vision complication, surgery to remove the cloudy lens might be needed.

The use of vitamin A for RP treatment has been mixed. Some studies suggest that large doses of vitamin A or even regular use can slow down vision loss. Others, however, state there’s not enough evidence for that. Therefore, while some doctors may recommend vitamin A supplements, this is not a definitive treatment for everyone with RP.

Gene therapy, a technique that introduces, removes or changes genetic material, has been used in trials showing promises of vision restoration. This approach is based on packaging a normal gene into a tiny, harmless virus and delivering it to the retina cells. However, with over 80 different genes linked to RP, it is complex and requires precise genetic diagnosis of each RP patient to target the correct gene. We still need more data before gene therapy can become a standard treatment.

Stem cell therapy is another promising avenue due to the potential of these cells to turn into different types of cells and replace damaged ones. Some studies found that when stem cells are transplanted into animal eyes, they can integrate with the retina and improve vision function. While these results are encouraging, cell transplantation is currently not a routine procedure due to concerns about cell rejection and limited cell integration.

Neuroprotective approaches involve the use of substances like antioxidants or anti-apoptotic agents to slow the death of vision cells.

In addition, retinal implants (artificial retina) are also being studied. These devices, once implanted in the eye, can cause some degree of vision improvement. But the current studies on retinal implants all carry risks of bias due to their design, making it challenging to draw firm conclusions. FDA approved Argus II retinal prosthesis is available on the market and another approach that converts sounds into vision information is also being studied.

Meanwhile, the study of genetic causes of RP progresses. Promising new treatments are being developed based on this new understanding, such as fine-tuning specific gene expressions. In addition, cell replacement therapy that introduces healthy eye cells into the eye to restore retinal function is also being studied.

Lastly, if your RP is caused by disorders like Bassen-Kornzweig disease, Refsum disease, or ataxia with vitamin E deficiency, these are treatable by supplementing certain essential vitamins or reducing dietary intake of certain compounds. If you’ve recently had sudden onset of night blindness, your doctor will also want to rule out vitamin A deficiency, which can be easily treated.

What else can Retinitis Pigmentosa be?

Progressive vision loss can be tricky to diagnose. One condition that can cause it is Retinitis Pigmentosa (RP). Doctors usually identify RP by checking for poor night and peripheral vision in both eyes. One typical way doctors check for this is with a special eye exam (fundoscopic examination) that shows changes in blood flow and color within the eye.

However, RP has several versions, each with a unique set of symptoms. For example, Retinitis punctata albescens (RPA) often starts as night blindness in children. When doctors conduct the special eye exam for RPA, they may not observe some of the typical symptoms found in RP. Instead, they may find small white spots covering most of the back of the eye. It’s crucial for doctors to be aware of these differences to ensure accurate diagnosis.

Several other diseases can appear similar to RP, needing careful examination to arrive at the correct diagnosis. For instance, cone-rod dystrophy is a similar condition, but color blindness starts before night blindness in this case because different parts of the eyes are affected. Another condition to consider is congenital stationary night blindness (CSNB), which appears differently depending on the type. Some cases of CSNB show deviations in the eye during an exam, while others do not. Other diseases that could be mistaken for RP involve infections like syphilis, cytomegalovirus, or Lyme disease. Taking a detailed patient history and performing lab tests can help identify these possibilities.

Other possible causes of vision loss include diseases like sarcoidosis and systemic lupus erythematosus, trauma, Vitamin A deficiency, and possible hidden cancer. In cases where only one eye is affected (Unilateral retinitis pigmentosa or URP), it’s crucial to rule out all possible infectious causes. URP diagnosis comes after several tests that show abnormal eye function in one eye, while the other eye remains normal.

Some conditions can mimic URP, these include:

• Inflammation/excessive reaction of the body due to various causes
• Eye or birth traumas
• Certain infections (syphilis, cytomegalovirus, measles, rubella, toxoplasmosis, tuberculosis)
• Autoimmune disorders that affect the retina
• Certain cancers
• Drug toxicity
• Other retinal disorders
• Vascular diseases

In some cases, RP can be part of larger syndromic disorders, which include a lot of other health problems. These include:

• Usher syndrome: Common syndrome linked to RP. Involves hearing loss and balance issues.
• Bardet-Biedl syndrome: Rare genetic disorder with obesity, extra fingers or toes, kidney dysfunction, among other features.
• Joubert Syndrome: A rare condition with a range of neurological and systemic features.
• Senior-Løken Syndrome: Combines features of an early-onset kidney disease and RP.
• Refsum Disease: A metabolic disorder leading to RP and other symptoms.
• Kearns-Sayre syndrome: A rare disorder involving paralysis of eye muscles, cardiac issues, and other symptoms.
• Abetalipoproteinemia (Bassen-Kornzweig disease): A disorder characterized by low plasma cholesterol, with other features including RP.
• Neurodegeneration with brain iron accumulation (NBIA): A rare genetic disorder with abnormal iron build-up in the brain, which may have retinal abnormalities resembling RP.

Some other diseases linked to RP include familial isolated vitamin E deficiency and Alström syndrome. Doctors usually rely on genetic testing and the expertise of various specialists for an accurate diagnosis and management of these conditions.

What to expect with Retinitis Pigmentosa

The future health outcomes for patients with a condition called retinitis pigmentosa can vary greatly. This largely depends on the age they first start showing symptoms and how the disease was inherited. If you have an inherited form of the disease known as “autosomal recessive RP”, it’s likely you’ll start experiencing symptoms early on in life, which may include significant vision loss and difficulty seeing at night.

Another inherited form, “autosomal dominant RP”, is generally less severe. Symptoms for this type usually begin later in adulthood and progress more slowly. The most severe vision loss, however, is associated with a form of the disease called “X-linked recessive RP”.

Another symptom that often develops later in all forms of retinitis pigmentosa is “tunnel vision”, where your peripheral vision gradually disappears. Almost all patients with retinitis pigmentosa will, at some point, have vision that’s bad enough to be legally classified as blind. However, it’s important to note that total vision loss is quite rare. This is because a part of the eye called the macula often retains its function, so most patients will still be able to perceive light, even when their vision is very poor. Plus, many people with RP keep good central vision until they’re in their 40s or 50s.

Thankfully, genetic testing is now available to identify the specific gene mutation that’s causing a patient’s retinitis pigmentosa. While this doesn’t cure the disease, it can provide valuable information about the severity of the disease and how it may progress in the future.

Possible Complications When Diagnosed with Retinitis Pigmentosa

Retinitis pigmentosa, or RP, can cause a variety of challenges such as difficulty seeing at night, a gradual loss of vision, and a decrease in side and central vision. When the disease progresses, a person might become legally blind or only have very minimal vision. The poor night vision caused by this condition can make it hard to navigate in low light.

A common symptom of RP is a narrowed field of vision, often referred to as “tunnel vision”, which affects normal daily tasks like walking around and driving. Central vision, critical for activities like reading and recognizing faces, can also be impacted. Some people with RP may even struggle to distinguish between colors or experience a decrease in color perception. Increased light sensitivity is another complication. Bright lights could create discomfort and glare, and hinder the ability to function in well-lit areas.

Vision issues from RP can also impact depth perception, making it harder to judge distances accurately. Decreased vision, especially in low light situations, can lead to a higher risk of accidents and injuries. People with RP may also struggle with mental health issues, such as depression and anxiety, and their overall quality of life may be affected.

There are various eye complications associated with RP, including:

• Cataracts, particularly posterior subcapsular cataracts
• Weakening of zonules, leading to issues with the lens post-cataract surgery
• Retrolental or vitreous cells
• Macular complications, such as epiretinal membrane, vitreomacular traction, and choroidal neovascular membrane
• Myopia and astigmatism
• Open-angle and closed-angle glaucoma
• Retinal detachments
• Retinal vascular abnormalities

This disease can drastically impact one’s independence as daily tasks could become increasingly difficult. For children and adults, this condition might create difficulties in educational and occupational settings due to vision-related limitations.

Preventing Retinitis Pigmentosa

After getting diagnosed with RP (an eye disease that slowly leads to vision loss), a key goal is for the patient and their family to fully understand the disease. Interestingly, most RP patients don’t know the specific subtype they have. Understanding this could help them get a clearer picture of how their disease might progress over time and how it can affect their future.

Currently, there are no treatments that can completely stop the loss of vision in RP patients. However, patients should be informed about interventions that might help. For example, nutritional supplements like vitamin A might be beneficial, although this isn’t completely confirmed. Patients are also advised to avoid overly bright light exposure because this can harm the retina, the eye’s light-sensitive layer. Wearing good-quality sunglasses is essential, and patients should also steer clear of smoking.

The patient’s education should also cover what they can expect as RP progresses. After diagnosis, changes can be made at home to help the patient maintain independence for as long as possible. This can be simple things like not moving the furniture around or adding more lights in working areas. Should their vision affect their ability to drive or move around independently, they could be referred to community agencies for support. As the disease impacts their freedom and may lead to isolation, the condition could trigger severe depression. People with RP are five to six times more likely to develop anxiety or depression. Therefore, both patients and their families should be taught about depression warning signs, and doctors should regularly check their mental health.

Patients should also be made aware of ongoing research and potential new treatments. Having this knowledge equips them to make informed decisions about treatment options when these become available. Organizations such as the National Eye Institute of the National Institutes of Health, the Retinitis Pigmentosa Foundation Fighting Blindness, and the American Foundation for the Blind are fantastic resources. They can introduce patients and their families to support groups, provide additional assistance, and inform them about the disease.