People suffering from Usher Syndrome slowly become both deaf and blind. The loss of hearing is usually congenital, whereas the symptoms of the first eye problems show during childhood. Night-blindness and an ever narrowing field of vision are the first signs of the eye disease Retinitis Pigmentosa (RP). What actually is Retinitis Pigmentosa? Can the deterioration process be slowed down by taking dietary supplements and is it necessary to annually go to the ophthalmologist for a check? We visited the Radboudumc in Nijmegen, the Netherlands, and asked ophthalmologist Prof Dr C.B. Hoyngthese questions, among others.
Actually, Retinitis Pigmentosa (also called TRD = TapetoRetinal Dystrophy) is not one disease but a collective name for a group of diseases characterised by poor eyesight in the dark (night-blindness) and very gradual narrowing down of the field of vision, which will eventually lead to tunnel vision. The seriousness and the development may widely vary. The first symptoms can show already during childhood, but sometimes the disease is diagnosed in middle life.
In case of Retinitis Pigmentosa (RP) the photoreceptors (the rods and the cones) in the retina are affected. The eye disease starts with the dying of the rods, mainly located in the outer edge of the retina. Dropping out of the rods leads to night-blindness (nyctalopia) and narrowing down of the field of vision (tunnel vision). Later the cones may be affected as well, as a result of which the sharpness of vision and the vision of colours and contrast are reduced as well.
About 4000 people in the Netherlands suffer from Retinitis Pigmentosa (RP). 800 to 1000 people of this group suffer from Usher Syndrome (RP with hearing disorders).
How is the diagnosis made?
Patients often come to the ophthalmologist for the first time in a later phase of the eye disease RP. Because of the very slow development, they almost unconsciously adapt themselves to the deterioration of their eyesight. Sometimes they only afterwards realise that the symptoms have been there for ten years or even longer. An ophthalmologist can quite easily confirm the diagnosis by looking at the retina with the eye mirror and by testing the field of vision. The field of vision testchecks whether parts of the field of vision are (not) functioning well. The ophthalmologist will sometimes not only do a field of vision test but also make an ERG (electroretinogram) and an EOG (electrooculogram) in order to be sure of the diagnosis. These record the electric activity sent by de retina after a flash of light.
With Retinitis Pigmentosa the ERG particularly deviates in an early stage (the part recording the functioning of the rods). After having administered narcotic and pupil widening drops, thin threads are attached to the eye or to the lower eyelid and the patient has to sit in the dark for some time. The examination takes 30 to 45 minutes. This can be difficult for children. Also the eyes can be a bit irritated after the examination.
By means of a genetic test (DNA test) changes in the hereditary material (gene mutations) can be found. Based on the clinical symptoms, results of the examinations and a DNA test, Usher Syndrome and the type can be diagnosed. These types can be Usher Syndrome type 1, 2 or 3. Read more about the three different manifestations (phenotypes) of Usher Syndrome. ‘If you become both deaf and blind.’
Usher Syndrome also includes congenital hardness of hearing or deafness. Nowadays, newborn babies and young children are tested for hereditary deafness diseases at a very young age. Then the DNA test may show that Usher Syndrome is involved and the parents of these children are given the diagnosis by an ENT specialist. Parents are at an early stage confronted with the diagnosis of their child while no symptoms of RP are showing yet.
How will things develop?
As the development of RP can be so variable, there are no certainties about the prognosis. In principle, there will be a slow, gradual deterioration. Sometimes there is a period in which the disease seems to be stable (fluctuation) to be followed again by a period of accelerated deterioration. The eyesight can remain reasonably well until a fairly high age. This makes seeing in the distance and reading well possible (as we use the cones in the central part of the retina and not the rods for this). As a result of the dropping out of the rods on the edges of the retina, the field of vision (the surroundings) gradually narrows down. This eventually leads to tunnel vision (this is like looking through a straw). This will make people literally stumble on things or they do not see people when crossing the street. A good field of vision is important when driving a car. Because of the slow narrowing down of the field of vision, driving a car will eventually no longer be possible. Should we mention a minimum field of vision here? About 25% of the patients retains a sharp vision and can read.
The simultaneous ability to see details very well and not seeing large obstacles is sometimes hard to understand for other people. It is good to inform family and colleagues about the disorder. This leads to a better understanding in general daily functioning.
With respect to the loss of hearing, usually recovery is possible with hearing aids or cochlear implants. However, these hearing aids cannot compensate the loss of eyesight. Because of their hardness of hearing, it remains difficult for patients to orientate themselves in a room and to localise and/or recognise sounds.
It is not always easy to live with the uncertainty about the future. It is normal that after having been diagnosed, the patient needs a period to deal with his/her changed picture of the future.
Do you want to know more about heredity, perspective and impact of Usher Syndrome? Read the infographic: ‘Everything you want to know about Ushers.’
Presently, various natural development studies are running, such as the RUSH2a, the CRUSH and the USH1B. With these studies, future trials can be analysed more efficiently and the throughput time can be shortened, also physicians can give a better prognosis about the development, thus enabling people to better organise their lives. With the help of these studies also the individual differences within families can be explained and the question which external factors have influence on the development of RP and the loss of hearing can be answered.
Is there any treatment?
At this moment there is no effective treatment for Usher Syndrome yet. By means of a DNA test changes in the genes (mutations) can be found. A DNA test can be useful for any gene therapy in the near future. With gene therapy a healthy piece of DNA that is to supplement the missing or wrongly produced proteins (substitute) is placed into the eye.
The first clinical trials have already been started for some types and mutations of Usher Syndrome. Various research institutes all over the world are very busy finding solutions for all types of Usher Syndrome.
[The Usher Syndrome Foundation has recently started an overview of all these studies and the current status of these developments on this website. Read here Usher Syndrome and DNA diagnostics]
Is it useful to keep going to the ophthalmologist for a check?
Although the ophthalmologist cannot remove or cure the RP, he or she may sometimes be able to help. RP can be accompanied by other disorders which require regular checking of the eyes. As the eyes are more vulnerable than ‘healthy’ eyes because of the RP, there is an increased chance of:
- Short-sightedness (myopy): this type of refraction deviation regularly occurs. This can be checked by the ophthalmologist or the optician. If the sharpness of vision becomes too low, prescribing loupes or other aids can be useful.
- Cateract: Cateract often occurs with RP. Cateract can be remedied by cateract surgery. This may improve the sharpness of vision, but the field of vision will not be widened. As the retina is functioning less well, the prognosis of cateract surgery can be limited. RP patients do not have a higher risk with respect to surgery than ‘normal’ cateract patients, but the choice of having surgery or not can be difficult. To what extent is the cateract and to what extent is de RP responsible for the deterioration of the eyesight? This makes the result of the surgery hard to foretell. In general, RP patients undergo cateract surgery at an earlier age (on average between 45 and 65 years) than ‘healthy’ patients (70-75 year) do. Although with most patients the sharpness of vision does increase after surgery, this unfortunately does not hold for a part of the RP patients (10-50% of the patients). Despite the fact that the sharpness of vision does not always increase, there often is a functional improvement of the visual problems. The result depends on the initial situation: the prognosis is better for patients with a less severe form of RP (based on the level of drop-out of the central field of vision and deviations in the OCT scan).
The risk of cateract surgery itself is not higher for RP patients than it is for non-RP patients. However, after surgery the chance of posterior cateract is larger (60-80%), but this can be solved with a posterior cateract treatment (laser).
A new artificial lens can be provided with a UV filter. Of course, the own lens also has a UV filter, but this is only minimal. Apart from that, a UV filter only protects the lens and not the retina.
- Malcula oedema: with about 10%of the RP patients the sharpness of vision decreases as a result of accumulation of fluid in the yellow spot. The ophthalmologist can prescribe a kind of diuretic (Diamox). This medicine has quite some side effects and does not always help.
- Glaucoma: a very small percentage of RP patients suffers from ocular hypertension. As this can usually be treated relatively easily (with eye drops), the checking of the ocular tension is important to prevent (unnecessary) damage.
Prof Dr C.B. Hoyng: “RP makes the eyes extra vulnerable. The above-mentioned risk factors, such as malcula oedema and cateract, are not symptoms of RP. Everyone can develop these problems, but people with RP do have a higher risk, as their eyes already are in a worse condition. It is very easy for an ophthalmologist to also check the malcula and to measure the ocular tension during a visit to the clinic for a check. I advise to have the ophthalmologist check the eyes every two years.”
Can taking extra vitamins, such as RetinaComplex, or wearing sunglasses slow down RP?
“RetinaComplex particularly contains extra vitamin A. This vitamin is soluble in fats as a result of which the surplus of vitamins is not removed by urination but is stored in the body. It accumulates. There are types of RP in which this accumulation is absolutely harmful to the eyes. This does not apply to other types of RP. Usher Syndrome is probably a problem in the transport of the proteins and therefore it is expected that any accumulation of vitamin A will not be harmful to the eyes. Advising to take Retina Complex or other dietary supplements is controversial. Patient really want to ‘do something’ to retain their eyesight as long as possible. There is no scientific proof that these supplements are helpful, but expectations are that these will not be harmful with respect to Usher Syndrome.”
“Scientific proof is not always needed. There is also no scientific proof for sunglasses protecting the eyes. Any sunglasses make sure that less light comes into the eyes. Light activates the photoreceptors and these send an electric signal through the optic nerve to the brains. This makes us observe light and enables us to see. With RP the photoreceptors are very vulnerable and are slowly dying. Sunglasses make sure that these photoreceptors are less activated and perhaps they remain intact for a longer time because of this.”
Do you see more severe deterioration of the eyesight with patients in southern Europe or in tropical countries because they are more exposed to bright sunlight? “This could be a very interesting study, but unfortunately not feasible. A proper study into this would require a comparison between a large group in the south and a just as large group of patients in the north. All patients with the same type and mutation of RP or Usher Syndrome. This is impossible for such a rare disease of which too few patients are known.”
Desire to have children, but how do I make sure that my children will not get Usher Syndrome (as well)?
“If you have Usher Syndrome yourself, you always pass on an Usher mutation to your child. The chance that your child will suffer from Usher Syndrome too isvery small (less than 1%). In fact, in order to develop Usher Syndrome you need two Usher mutations, one from your father and one from your mother.
If you are the child of a parent with Usher and you want to have children, then your partner can have a genetic test. If your partners appears to be a carrier of an Usher gene mutation, there is a 25% chance that your child will suffer from Usher Syndrome. Usher Syndrome is such a rare disease, that the chance of the next generation suffering from it as well remains very small. Partners who are family (e.g. cousins) do have an increased chance of having a child with Usher.Besides, the choice of preventing or interfering with this is a very personal one. Therefore a general advice cannot be given. If you want to have children and if you have questions about heredity with respect to RP or Usher, please talk about this with your general practitioner.
If you want a genetic test, you can discuss this with your ophthalmologist or clinical geneticist.”
Are there any medicines that are harmful to RP eyes?
“Anti-malaria medicines are not good for people suffering from RP. Apart from this, long-term use of Chloroquine in high doses is harmful to the eyes. These medicines are prescribed for rheumatism, but they can well be replaced with other medicines. Therefore always tell your treating physician that you suffer from RP/Usher Syndrome.”
What are those strange, white ‘worm-like moving spots’ that sometimes appear in my eye?
“Those are ‘floaters’. This is a natural process in the vitreous humour of the eyes. It is caused by protein condensation, which everybody sometimes suffers from. There is no harm in this.”
RP is a serious eye disease which cannot be cured at this moment. Generally it shows a slow deterioration to which people can often adapt quite well. However, the uncertainty about the development is hard to accept. The uncertain development of RP and the loss of hearing has consequences for daily functioning and work.
In case of questions, please contact your own ophthalmologist (RP) and ENT specialist (hearing). You can also contact the Eye help line of the Eye Association Netherlands (Oogvereniging)
The Usher Syndrome Foundation and the Usher Syndrome contact group can also help and provide support in case of questions about living and dealing with Usher Syndrome. Please contact through mail firstname.lastname@example.org (Usher Syndrome Foundation) or through email@example.com (contact group).
The Usher Syndrome Foundation issues a newsletter every two months on average. Do you want to keep up to date with all developments with respect to scientific research and therapy? Subscribe here for the newsletter (Only in Dutch)
With thanks to C.B. Hoyng, ophthalmologist in Radboudumc in Nijmegen, the Netherlands, and involved in, among other things, the natural development studies RUSH2a and the CRUSH study.
A part of the information in this article was supplied by the Netherlands Ophthalmologists Society and Oogartsen.nl