What is retinitis pigmentosa?
Retinitis pigmentosa is a disorder that falls into a group of retinal diseases that we call inherited retinal diseases (IRDs). There's typically a genetic basis to the condition, although some patients may not have a family history. RP leads to the gradual degeneration of photoreceptors – “rods” that control our night and peripheral vision typically degenerate first, followed by “cones” that control our central, color, and daytime vision.
RP encompasses a broad spectrum of clinical disease presentations. There are over 100 different genes that have been associated with retinitis pigmentosa, and they can cause different variations of the disease in terms of presentation, severity, age of onset, rates of progression.
Is it a common disease?
It affects about one in 2,500 to one in 4,000 people in the U.S., so it is a common disorder.
What are the first symptoms a person with RP might notice?
In general, patients typically present with night vision loss and difficulty with light-to-dark adaptation. Peripheral vision is affected early in the disease process as well. As time goes on, those symptoms tend to slowly worsen over many years, sometimes even decades. Most people will develop central vision problems and central vision loss to varying degrees with RP.
The age of onset and the rate of progression can significantly vary from patient to patient, even amongst families with the disease.
Because RP can be a slow-moving disease, does it make it a challenge to diagnose?
It can be. Sometimes patients discount their symptoms early-on, and they may not seek an immediate evaluation because those symptoms are slow, but eventually they become problematic enough to see an ophthalmologist.
Clinical examination is usually the first thing that that will tip us off to retinitis pigmentosa. Many patients who present with RP will have typical findings on a dilated retinal exam. We can usually see some changes within the retina, including changes in the in the pigmentation in the in the back wall of the eye – that’s what gave rise to the name when the disease was first described a century ago. Now we know that RP is not an inflammatory disorder; it’s genetic. When the cells degenerate, the immune system can cause low levels of inflammation within the eye as they're trying to repair and clear the damaged cells.
A genetic test can help support the diagnosis of RP and reveal exactly which genes are involved in an individual case. However, the current sensitivity of genetic testing is around 60 to 70%, so sometimes we cannot identify the gene involved.
Are there other symptoms throughout the body that can be tied to RP?
It depends on which genes are involved. Certain genes tend to affect only the eyes, and there are other genes that affect other parts of the body as well. We classify these differences as either syndromic or non-syndromic, which is isolated RP.
The most common syndromic form of RP is called Usher syndrome. It affects both the eyes and hearing, so patients present with sensorineural hearing loss, typically at a young age or from birth. Symptoms present at varying degrees, but as they get older, they typically start to develop problems with night vision and peripheral vision loss.
Is there a cure for RP?
We don’t currently have a cure or many great treatment options for most forms of RP. However, it is an exciting time regarding clinical research and the potential for therapies that we hope will show benefits in this disease over time, either slowing down the disease or reversing some of the vision loss that occurs.
In December of 2017, the U.S. FDA approved the first gene therapy called Luxturna to treat a form of RP due to a gene called RPE65. While this form of RP is relatively rare, it has provided significant momentum in the race to find cures for RP.
This particular gene therapy treatment, called gene augmentation, aims to restore the genetic misspelling that we call a mutation that causes damage to the retinal cells. It doesn't completely reverse the blindness, but many patients who have received treatment with it have experienced significant improvements in many of their symptoms. It's appeared to slow the progression of the disease as well.
Because there is no current cure, low vision optometry resources and support groups are important for the RP community and can optimize their quality of life.
What’s the future of research for RP treatments?
There are a lot of clinical research trials looking at different avenues for therapy. We break them down into what we call gene specific or gene agnostic approaches. Luxturna is an example of a gene specific approach. There are numerous gene specific clinical trials underway, including fully enrolled or soon-to-be enrolling Phase 3 trials for a form of the disease called X-linked RP due to a mutation in the RPGR gene.
For gene agnostic approaches, we can try to slow down or restore vision loss even if we don’t know the specific genetic mutation. There are many clinical trials underway looking at these approaches. For the 30 to 40% of patients in which we cannot identify the mutation, there is still hope for treatment. Developing therapies that rely on knowing the particular genetic misspelling can be challenging because it’s difficult to come up with a treatment that encompasses 100 or more genes. These approaches may be immediately applicable to a large population of patients.
Both avenues have a future in treating this disease and are important to helping patients live their best life with RP.
