Description

Retinitis Pigmentosa (RP) refers to a group of inherited retinal degenerations that affect the light sensitive photoreceptor cells of the retina which are important for vision. This condition causes progressive vision loss, initially presenting with a loss of peripheral (side) vision and followed by a loss of central vision. RP is highly variable in terms of the age of presentation, rate of progression and inheritance pattern.

People with RP experience a gradual decline in their vision because the two types of light sensitive photoreceptor cells, rod and cone cells die. Rod cells are present throughout the retina, except for at the very centre where they help with night vision. Cone cells are also present throughout the retina but are concentrated in the central region known as the macula. They are useful for central (reading) vision and for colour vision. In RP, the rod cells and eventually the cone cells stop working, causing vision loss; however, many people with RP retain useful central vision well into middle age.

In Ireland, it is estimated that 1 in 4,000 people have RP. Some forms of RP may form parts of syndromes which affect other organs, such as Usher Syndrome and Bardet-Biedl Syndrome.

Symptoms

The age range at which symptoms of Retinitis Pigmentosa (RP) may develop is variable. Some individuals are diagnosed in childhood, while others are not affected until they are adults.

One of the earliest symptoms is a difficulty seeing in dim light, including transitioning from light to dark and vice versa. This is as a result of the death of the rod photoreceptor cells in the retina, which are important for seeing in lower light levels.

The condition is slowly degenerative, with a loss of peripheral vision followed over time by impairment and loss in central vision. This is due to the death of rod photoreceptors then followed by cone photoreceptor cells. Cone photoreceptors are also important for detailed and colour vision, which can become increasingly impaired with a loss of central vision. Both eyes are usually affected in a similar way.

The rate of progression and degree of visual loss can vary from person to person, even among affected members of the same family. It can therefore be very difficult to predict what an individual’s vision will be like at a specific time in the future.

However in general, the autosomal dominant form of RP tends to follow a milder course with maintenance of preserved vision well into late middle age. The X-linked form of RP is the most severe and central vision may be lost by the third decade. This form of RP generally tends to only affect males, although due to a genetic process called non-random X-chromosome inactivation, some females may be affected.

Causes

Retinitis Pigmentosa (RP) is a genetic condition. It is caused by mutations in one of a number of genes associated with vision. RP is one of the most complicated of all inherited retinal degenerations, with over 50 different genes identified so far to be causative for RP. These genes are recognised to play critical roles in the structure and function of the rod and cone photoreceptor cells.

There are various inheritance patterns for RP, including autosomal dominant (30-40%), autosomal recessive (50-60%) and X-linked (5-15%). If the condition is inherited in an autosomal dominant manner, this means that one copy of a gene doesn’t work properly, giving rise to the condition. In this case, a person will have received one copy of a mutated gene from an affected parent. If the condition is inherited in an autosomal recessive manner, this means that both copies of a gene linked with the condition don’t work properly, giving rise to the condition.

In this case, the individual’s mother and father have both passed on a mutation in the gene in question. If the condition is inherited in an X-linked manner, this means that if a male has an X-chromosome with the mutated gene, they will develop the condition as they only have one copy of the X-chromosome, containing the gene. As females almost always have another functioning X-chromosome, they typically don’t develop the condition. Although in rare circumstances, due to the phenomenon of ‘non-random X-chromosome activation’ some females may develop symptoms of the condition.

Approximately 50% of RP patients will have a history of at least one other family member being affected, while the remaining 50% of patients will not have a family history. While their RP is still caused by a gene alteration, it might not be possible to determine the inheritance pattern in these patients.

***Click here for more information about inheritance patterns.

Whilst RP is a genetic disease, there are also cases where there is no family history of RP. If a family member is diagnosed with RP, it is strongly advised that other members of the family also have an eye exam by an eye doctor (ophthalmologist) who is specially trained to detect retinal diseases.

Diagnosis

Retinitis Pigmentosa (RP) is diagnosed through a number of assessments which help with providing the correct diagnosis.

The eye doctor will ask about a person’s medical history, including any family history of eye conditions. Individuals will receive a clinical eye examination where they may be asked to read letters off a chart (Snellen chart). They may also check intraocular pressure and examine visual acuity and the visual field.

An individual may receive a number of imaging tests. Information about the condition may be identified using colour or wide-field fundus photography (which essentially takes photos of the back of the eye). Fundus autofluorescence may be used to identify stress or damage to the retinal pigment epithelium. Optical coherence tomography (OCT) can also be used to assess the various layers at the back of the eye.

An individual may also have an electroretinogram (known as an ERG), which is used to evaluate the functioning of the different types of photoreceptor cells (rods and cones).

A genetic test is also an important component of testing, to ensure the correct condition is diagnosed. For people living in Ireland, genetic testing for RP can be performed through the Target 5000 programme.

For further information, please contact the Research Department on 01 6789004.

Genetic Diagnosis

It’s often impossible to tell which type of retinal disease a person has just by looking into the eye. As such, a genetic test may be necessary to confirm the diagnosis.

The Target 5000 programme provides free genetic and clinical testing to all individuals living in Ireland with a genetic retinal degeneration, including Retinitis Pigmentosa (RP). Through genetic screening of the person awaiting diagnosis and their family members, the Target 5000 programme will provide more detailed information about the nature and inheritance pattern of the condition.

As gene-specific clinical trials and treatments become available, knowing the genetic mutation associated with a genetic retinal degeneration will become even more important. Taking part in this programme ensures participants are included on a national registry from which participants can be identified for clinical trials and treatments and from which further information about each of the genetic retinal degenerations can be defined. For further information on the Target 5000 programme, please contact the Research Department on 01 6789004 or email research@fightingblindness.ie.

Treatment

Recent advances in research have yielded a breakthrough for the treatment of inherited retinal degenerations, with the first ever gene therapy (Luxturna™)** now approved for use in some cases of Retinitis Pigmentosa (RP) where a mutation in both copies of the RPE65 gene exists. Whilst this treatment is not available for all types of RP, this milestone signals the potential of gene therapy and the potential for other treatments to reach the clinics in the near future.

The gene therapy Luxturna™** is available to treat those who have been diagnosed with a type of RP where they have mutations in both copies of the RPE65 gene (and have functioning photoreceptor cells as observed on clinical examination). This gene therapy works by delivering a normal, functioning copy of the RPE65 gene directly into the cells of the retina at the back of the eye to restore vision. This is a one-time treatment delivered by a specially-trained surgeon who administers the treatment by a sub-retinal injection.

Whilst not directly a therapy, retinal implant technology, of which a number of devices are available provides a potential option for those living with advanced RP. It works by delivering a form of artificial vision where total vision has been lost due to RP. When all or most of the photoreceptor cells have died, they can theoretically be replaced by an electronic microchip that brings a visual image to the remaining cells of the retina. These microchips electronically signal the remaining retinal cells which pass the signal down the optic nerve for processing as a visual image by the brain.

At the moment, these devices do not restore natural vision, but with an intensive rehabilitation programme following surgery can help to restore mobility, by allowing an individual to see a difference in light and dark to the point where they can tell how to walk through a doorway. A number of these devices have been awarded CE markings for Europe, bringing them to the market (IRIS®II, Argus®II and Alpha AMS).

There are no other approved treatments or devices for other types of RP as of yet, although recent years have noted advances in clinical research and development. To find out more about advances made in this area, please visit the ‘Latest Research’ section.

Maximising an individual’s remaining vision is a crucial step to take, and there are many low vision aids including telescopic and magnifying lenses which may offer benefit. This technology has also removed many barriers to education and employment.

General eye check-ups are important for people living with RP, as these individuals may still be at risk of developing other kinds of eye problems that can affect the general population, some of which may be treatable.

No matter what level of vision a person may have, it is important to look after the eyes. To find out more about what can be done to take care of the eyes on a daily basis, please visit our Tips for Good Eye Health.

For further information, please contact the Research Department on 01 6789004.

** Fighting Blindness does not endorse any of the products, medications, treatments or information reported here, or on any of our communication platforms. Articles on Fighting Blindness websites and social media are intended for informational purposes only. We strongly advise that you discuss all medications, treatments, and/or products with your doctor.

Research

In recent years, there has been acceleration in the pace of research for Retinitis Pigmentosa (RP). Researchers now have a better understanding of this condition, with the work of researchers at Trinity College Dublin in the last few decades significantly contributing to this. Equipped with this information, researchers have been able to develop targeted interventions for evaluation in clinical trials, but also more recently for use in the clinic as seen with the gene therapy, Luxturna™**.

Researchers are actively gathering as much information (such as the information from clinical tests and genetic testing) as possible in an effort to fully understand this condition. The aim is that this information will bring benefits such as yielding new treatments and ways to improve quality of life.

Gene therapy has become an area of intense investigation for conditions including RP. It may be a suitable therapeutic approach as individuals with RP generally only have damage to one gene, making it amenable for gene therapy. With this technique, researchers use small, safe viruses to deliver the correct version of the gene of interest to the retina. However, it is important to note that there is an added level of complexity to developing gene therapies for RP, as there are over 50 genes associated with this condition and each gene therapy will only target a single gene of interest.

In addition, these therapies are suited to those at and early to mid-stage of disease progression, where there are still some viable rod and cone cells present. There are a number of active gene therapy clinical trials for RP at present, targeting a number of different genes (RPGR, PDE6A, RLBP1 and PDE6B). These follow suit from Luxturna™**, which is designed for the RPE65 gene (mutations in both copies) now approved for use in various sites across the world. Researchers continue to examine this treatment in those who have received it, to evaluate how it performs over time.

For individuals who may have lost a significant portion or all of their vision, there are other technologies that are being investigated, such as stem cell therapies and retinal implant technologies.

Stem cell technology holds great potential to replace retinal cells that have already died due to degeneration. Stem cells are like precursor cells which have the potential to self-renew and generate many other different cell types. There are a number of stem cell clinical trials for RP, demonstrating the promise of this therapy for RP. Early phase clinical trials have investigated the transplantation of bone marrow stem cells, to which positive findings have been noted.

Other clinical trials at a number of sites worldwide continue to evaluate bone marrow stem cells as a treatment option. Another intervention being investigated involves the transplantation of human retinal progenitor cells, to which studies have found them to be safe, although research is ongoing to determine how effective they can be.

Researchers have developed a lot of interest in examining promising drug treatments, many of which are re-purposed drugs or dietary supplements for their effectiveness in RP. Researchers hope that these interventions will provide benefit to the retina in ways including to preserve rod and cone photoreceptor cells and to support the retinal pigment epithelium. It is estimated that as few as 5% of cone cells need to be preserved by such a treatment in order to have a huge impact on quality of life by the maintenance of a small but significant amount of central vision. Re-purposed drugs are an area of interest, with work ongoing to investigate the benefit of a medication used in Parkinson’s disease.

A number of dietary supplements have been examined with lutein and Vitamin A among those examined. Further work is required to elucidate the role these interventions may play and also for who they may be of benefit. In the context of Vitamin A, it is known that Vitamin A supplements should not be taken by those diagnosed with an ABCA4 mutation, so appropriate patient selection will be important to eliminate risks.

Other areas of investigation include in the study of recombinant human nerve growth factor and antioxidants. While the findings from the recombinant human nerve growth factor are awaited, other research continues. Previous work in animal models of RP have demonstrated the beneficial effects of antioxidants (N-Acetylcysteine; NAC) in prolonging cone photoreceptor cell function and survival. An early stage clinical trial is now underway to determine its safety and tolerability in humans.

Retinal implants are a form of biomedical technology currently being developed for retinitis pigmentosa. A number of these implants have shown success in delivering a form of artificial vision to individuals with total vision loss due to RP. When all or most of the photoreceptor cells have died, they can theoretically be replaced by an electronic microchip that brings a visual image to the remaining cells of the retina. These microchips electronically signal the remaining retinal cells which pass the signal down the optic nerve for processing as a visual image by the brain.

At the moment, these devices do not restore natural vision, but can help to restore mobility, by allowing an individual to see a difference in light and dark to the point where they can tell how to walk through a doorway. A number of these devices have been awarded CE markings for Europe, bringing them to the market (IRIS®II, Argus®II and Alpha AMS). A number of clinical trials are now underway to evaluate further evaluate these retinal implants for individuals living with RP. Further information is required to fully determine the safety of these implants and their overall benefits.

Information about clinical trials can be found on their website by clicking the following link: Clinical Trials Website and can be searched by condition and trial location.

Fighting Blindness currently support a number of research initiatives which aim to improve the diagnosis, care and quality of life of individuals living with RP.

Target 5000 research, largely funded by Fighting Blindness aims to determine the genetic cause and understand the nature of the condition over time. Through Target 5000, a national registry will also be developed which will greatly improve access to suitable clinical trials and treatments for people living in Ireland with RP. For further information, please visit ***(insert link to Target 5000).

Dr Sarah Doyle based in Trinity College Dublin is conducting a study to investigate if a protein known as SARM1 plays a role in retinal degeneration, a key component of RP. This work aims to further understand the underlying mechanisms of retinal degeneration and identify potentially new therapeutic targets. To find out more about this study, please visit ***(insert link to Dr Doyle’s research project).

A study conducted by Professor Breandán Kennedy is investigating a group of neuroprotective drugs, known as HDAC inhibitors, for their potential to delay vision loss in retinal degenerations. This work seeks to identify new therapeutics which could provide significant benefit to individuals. To find out more about this study, please visit ***(insert link to Prof Kennedy’s research project).

For further information, please contact the Research Department on 01 6789004.

** Fighting Blindness does not endorse any of the products, medications, treatments or information reported here, or on any of our communication platforms. Articles on Fighting Blindness websites and social media are intended for informational purposes only. We strongly advise that you discuss all medications, treatments, and/or products with your doctor.

Support

Receiving a diagnosis can be overwhelming for anyone, but this is not a journey that you have to make alone. There are many groups and resources available to provide support for people living with Retinitis Pigmentosa.

Fighting Blindness offers a free and confidential counselling service (Insight Counselling). For further information please contact insight@fightingblindness.ie or call 01 6746496.

A mindfulness group is also available on every Wednesday at the Fighting Blindness office at 11am.

For technology support and guidance, the Dublin-based Technology Exchange Club meets every Monday at the Fighting Blindness office at 11am. Another Technology Exchange Club, based in Cork, meet every Saturday in the Cork City Library, Grand Parade, Cork City at 11am. The Cork-based club do not meet on Bank Holiday weekends or on the second Saturday of the month. For further information please contact insight@fightingblindness.ie or call 01 6746496.

 

Resources

Féach provides support for parents of children living with sight loss in Ireland.
Click the following link to view their website: Feach Website

ChildVision is the national education centre for children with sight loss in Ireland.
Click the following link to view their website: ChildVision Website

NCBI (National Council for the Blind in Ireland) provides support and services for people living with sight loss in Ireland.
Click the following link to view their website: NCBI Website

Irish Guide Dogs for the blind helps individuals and their families to achieve improved mobility and independence.
Click the following link to view their website: Irish Guide Dogs Website

Retina UK is an organisation which helps to provide assistance and information for those diagnosed with RP.
Click the following link to view their website: Retina UK Website

 

Last Updated: 4th February 2019