newsletter_no 12 march 06

IContents

· Introduction

· News

Moorfields Oct 06
Bristol Nov 06

Welcome to the latest news from the Uveitis Information Group. This particular edition is the first to be circulated to all UK Consultant Ophthalmologists as well as patient members. I hope you find it useful and interesting and we would very much welcome any comments and suggestions for future coverage, especially from Ophthalmologists. We would also be very keen to make contact with Ophthalmologists or their staff who would be interested in making information available to patients. We can provide information and posters for clinics, for example.

You will also notice the enclosed copy of a new journal, ‘Uveitis’. This journal is the first to be produced by a new association of patient interest groups across Europe. The content of this journal is aimed at all those interested in uveitis, but particularly at patients, Ophthalmologists who don’t necessarily specialise in uveitis and ancillary staff including nursing staff. More about the European association, EUPIA, below.

The UIG and EUPIA are both being funded by donations and subscriptions from patients. If you have found these journals useful and would like to support patient interest issues and the production of patient information, please consider donating to the UIG develop its work.

Cheques can be made payable to ‘Uveitis Information Group’ and sent to the address on the back of this newsletter.

The European Uveitis Patient Interest Group was formed at a Uveitis scientific meeting of the International Ocular Inflammation Society (IOIS) meeting at Granada in Spain in May 05, following an initial meeting the previous September in Italy.

EUPIA aims to promote the interest of patients across Europe, encourage and aid the establishment of patient groups in countries where they do not exist and to increase the profile of uveitis, often described as the ‘Cinderalla’ of the eye conditions. By ‘joining forces’ in this way patient interest groups should have a greater voice and influence with organisations such as drug companies.

Enclosed is a complementary copy of the first journal to be produced by EUPIA, ‘Uveitis’. The aim is to produce 2 journals a year and to take an important aspect or topic in uveitis as a main theme for each journal. The journals, so far, have been printed in English, German and French.

Bausch and Lomb and Alcon have funded the production of the first journal. More fundraising and participation will be required to fulfil the aims of the association and patients and Ophthalmologists are both invited to help with the work of EUPIA.

Mr Teifi James, a uveitis specialist in Yorkshire, has been involved in developing the ‘eyebag’, a device which can be used to relieve the symptoms of anterior uveitis. The bag is heated in a microwave and placed and then massaged over the closed eyes. It works by dilating the pupil, which is an important part of the treatment of anterior uveitis, relieving symptoms and preventing complications. It does not replace treatment with eye drops but is a useful addition to the standard treatment, especially if applied immediately after dilating drops are instilled.

The idea of using warm compresses in this way is not new, but this device provides a very practical way of using this method.

Details of obtaining an ‘eyebag’ are given below. We would be very interested to hear how anyone using the eyebag gets on with it.

Please note, subscribed members of the UIG are being offered a discount on the eyebag. Please contact us for details.

The eyebag can be obtained online (secure site ordering) by phone using credit or debit card, by mail order with invoice and cheque by post. Payment accepted in Sterling or Euros. sell at £17 + VAT of £3 + 1.85 post/packing. Total of £21.85.

The annual meetings at Moorfields and Bristol are reported on below. It is hoped that public meetings can be set up to cover all of the UK.

To cover Scotland, we are hoping to arrange a meeting based in Edinburgh. It is necessary to build up numbers of people interested in attending a meeting before setting a date and so please get in touch if you would be interested in attending. The aim of these meetings is to cover current themes in treatment and research of uveitis and to help doctor and patient communication. We will try to make both patients and Ophthalmologists aware of meeting dates as it has been found so far that these meetings have been useful to both.

Phil Hibbert welcomed everyone who came along to meet and learn more about uveitis. He was glad to be able to introduce Professor Susan Lightman and two of her staff at Moorfields, Paolo Ferrante an Ophthalmologist in the Uveitis Clinic and pharmacist, Zeeshan Siddiqui.

Phil began by summarizing the main aims and work of the UIG, before introducing Paolo Ferrante who gave a talk on “Procedures and Investigations that go on at the Uveitis Clinic”.

With the help of some slides featuring some very well known “doctors” from very old ‘Carry on’ films, Paolo took us along the path that a patient may take through the uveitis clinic, from reporting the first symptoms to being investigated in the uveitis clinic. He described how the “route” taken by each uveitis patient depended on the type and severity of uveitis. This will vary a great deal between each hospital especially when there is not a dedicated uveitis clinic.

This system recognises that cases of uveitis vary a great deal and by dealing with straightforward cases of acute recurrent anterior uveitis in the primary care clinic, this frees as much time as possible for more complicated cases to be dealt with in the Uveitis clinics.

Paolo continued to explain the reasoning behind all the various investigations that take place in the clinics, from the very important visual acuity and close vision tests, to monitoring blood tests, blood pressure, sugar levels and weight of those patients on systemic steroid or immunosuppressant treatment.

For the majority of patients with uveitis, no cause is ever found, although it is known now that these cases can be described as an ‘autoimmune’ condition. However some medical conditions have well known associations with uveitis and so investigations may be carried out to rule this out, if they are suspected. Examples are rheumatoid arthritis and sarcoidosis. There are also ‘genetic markers’ which turn up more commonly in uveitis patients than in the general population. The main one of these is HLA B-27. Typing the uveitis in this way helps to characterise the type of uveitis a patient has and may predict how best to manage it.

Paolo went on to cover some of the newer tests which are used to look at the back of the eye and which offer additional or different information to the established flouroscein angiography. This will be covered in more detail in future newsletters and on the website.

One fascinating aspect of Paolo’ s talk was the demonstration on slides of what the doctors are seeing when they look into patient’s eyes. Using slides of ‘cells’ of active inflammation or cataracts etc, the view through the slit lamp satisfied the curiosity of many patients who had always wondered what the view was like.

The next speaker was Zeeshan Siddiqui, who is a pharmacist at Moorfields and he explained about the main drugs used in the treatment of uveitis. He concentrated mostly on eye drops and a fuller report will be made of this in the form of a fact sheet and will feature in the next newsletter.

Next Professor Susan Lightman talked about ‘Tablets in Uveitis’, - systemic treatment.

Prof. Lightman started by explaining how eye drops don’t go past the lens and so won’t penetrate to the back of the eye. Therefore for any inflammation or complications that affect the back of the eye, tablets are needed.

Corticosteroids (‘steroids’) are the mainstay of treatment and have been used in medicine since about 1940 and so are very well known about. Although they seem to have a questionable reputation these days, Prof Lightman explained how steroids are actually a very effective treatment for uveitis. They have the advantage of being reliable in working for nearly all patients and they have a fast action.

When the inflammation is present, that is the uveitis is active (either an acute ‘flare up’ or a longer chronic episode), then steroids dampen down the activity of the immune system and hence dampen down the inflammation. The steroids don’t actually make the uveitis ‘go away’. An attack of uveitis will remain until our own body deals with it. It is very important to dampen down the inflammation while we have an attack of uveitis to stop the eye from being damaged by the active inflammation.

For most people, steroid treatment will be all that is needed to control their uveitis. However, for some patients, steroids are not effective or the inflammation is too severe so that only very high doses of steroid are effective. For other patients their tolerance to steroids may be very poor and they suffer bad side effects. In this type of case then there are a range of second line drugs, usually referred as the immunosuppressant drugs.

Professor Lightman then went on to explain the ever widening choice of these powerful and often very new second line drug treatments.

Predicting how patients do on these drugs is very difficult and there seems to be a very personal variation in tolerance to these drugs. The types of problem encountered are not just purely medical either.

Cyclosporin, for example is an effective immunosuppressive drug, but often has the side effect of increasing the growth of body hair. This may be an extremely relevant and difficult problem for some female patients.

There are a lot more factors which come into play when young patients are treated when growth and development have to be considered.

The other major factor which can not be ignored is the cost of some of the treatments. Infliximab, one of the newer drugs has a cost of approx. £2000 every 8 weeks.

There are many varied side effects which may be experienced with steroids and other immunosuppressant drugs, most of which may be uncommon. Prof. Lightman described the most common side effects seen in the uveitis clinics. These were:

It is important to monitor these side effects and do as much as possible to prevent them, (diet, exercise, for example for high BP, weight), and discussing with the doctors taking medication to prevent osteoporosis. Indigestion is usually manageable with various levels of treatment.

Some people who get diabetes when they start these drug treatments will continue to suffer from diabetes when they stop the drugs. It seems that this group of patients may have been susceptible to diabetes in the first place and this has been triggered by the drug treatment.

Prof. Lightman went on to look at some of the promising areas of research and treatment for the future. Some of these are listed below where they are not covered in the other meeting report from Bristol

Steroid implants There are now early trials of a small ‘staple’ like implant which is attached to the inside of the eye and which releases a steroid, over a reasonably long period of time. First trials of these will be undertaken this year in the UK. Whilst early results of trials in the US show that this can be very effective at controlling inflammation, they also have very high rates of the 2 main side effects of steroid eye drops; that is high pressure, leading to glaucoma and cataract. If these implants are used for patients with very severe disease where drops and tablets are not successful, then cataract and glaucoma may be the ‘lesser of the evils’ and be acceptable side effects. At the moment, then the steroid implant treatment would not be advisable or suitable for the majority of patients.

Early work on a long acting injection looks promising and further development of the range of immunosuppressant drugs including the use of interferon A was covered.

There is never a shortage of questions and whilst it is difficult sometimes to tackle questions in as general way as possible, Prof Lightman handled the many questions splendidly and in the process covered some very common questions and also some more obscure ones. Some of the common questions which arise are covered in the Bristol report and also in our ‘Commonly Asked questions’ section of our website. (http://www.uveitis.net/pt.infocommonly_asked_questions.htm )

Again in general they should have no significant systemic side effects. Some eye drops such as beta blockers used for high pressure can have systemic side effects

In some cases it seems to be but in others there may an existing predisposition to diabetes and it can be permanent.

It would be inadvisable and unlikely anyway for them to be used during an acute attack of anterior uveitis.

In general the wearing of contacts will vary and the doctor should always be asked. Hard lenses are usually Ok, but there are more problems with soft lenses as they absorb the preservatives in most eye drops used in uveitis.

It may be possible to use preservative free uveitis drops. If drops are only used once or twice a day, then it can be possible to use a soft lens if it is put in an hour after the eye drop was placed. The important thing is to ask the doctor at the clinic.

There is no absolute indication against this for uveitis patients but there is a general point. If you already have an eye condition which may or not give problems in the future, is it worth accepting a further risk, however small, of undergoing sight correction surgery? Ultimately this has to be a personal choice.

Probably sarcoidosis, although this would vary as to where the patient lived or came from originally.

The meeting finished off with some time set by for people attending the meeting to meet and chat. There was a feeling that it would be a good idea to have a patient get together in the London area. Hopefully this can be added to the yearly Moorfields meetings. If interested in this then please contact Phil via the UIG contacts at the back of the newsletter.

Phil Hibbert welcomed patients and relatives the meeting and was glad to welcome also one of the local Ophthalmologists. He introduced Professor Andrew Dick from Bristol Eye Hospital, and Annie Hinchcliffe, Uveitis nurse at Prof. Dick’s clinic.

Phil spoke initially about the Uveitis Information Group and its aims. He explained how the main function of the UIG was to provide good quality info in plain English and to forge good links with Specialists in Uveitis and to help raise the profile of uveitis. Fundraising was at a level which could support the business of producing information but major fundraising for uveitis research and treatment was not part of the UIG. It would be very welcome if these types of public meetings would trigger some sort of activity in that direction. Formation of local contacts and groups would also be a very good idea.

Phil handed over to Professor Dick who spoke firstly on the different types of uveitis and tried to simplify the confusion that can arise out of all the different names. There are many types of uveitis and many are given specific names.

From a patient’s point of view, it is probably best to divide the types of uveitis into:

Knowing the name of a distinct type, eg Birdshot retinochoroidopathy, or PIC etc is useful as long as the patient can place it into one of the 3 main groups above to help understand what type of disease they have.

The term iritis has been used historically. Iritis literally means inflammation of the iris. Although many people just have inflammation in the iris, some people with anterior uveitis have inflammation in other parts of the front of the eye. Anterior uveitis is now a better term to use.

Only about 2% of people with anterior uveitis will develop significant irreversible vision problems.

However, anterior uveitis is potentially damaging to vision so patients must be monitored well, especially their eye pressures and they should always get in touch with their eye clinic straight away if any recurrence or new signs or symptoms develop.

Posterior uveitis accounts for about the same level of sight loss in the working population as Diabetic retinopathy, yet Diabetic retinopathy is about 200 times more common than posterior uveitis. However there are now more and more ways to treat posterior uveitis with newer immunosuppressant drugs now available.

Whilst there are many forms of posterior uveitis, the most relevant point to think of here is that any inflammation at the back of the eye is going to be potentially more sight threatening. Prof Dick explained that the management or treatment of posterior uveitis concentrates on anything which threatens vision. Once again, from the patient’s point of view this should be more important than what caused the uveitis in the first place, which frequently will remain a mystery.

Prof. Dick went on to explain how steroids are still very reliable and fast acting for the treatment of posterior uveitis, but an increasing number of newer ‘immunosuppressant’ drugs have enabled additional possibilities especially where steroids are not effective or poorly tolerated.

There has also been a trend to use combinations of drugs, for example steroid and an immunosuppressant such as cyclosporine, tacrolimus and others. This allows an effective treatment but with reduced side effects because the doses of each drug in the combination therapy can be reduced.

Prof Dick pointed out that before 1945 the most common cause of uveitis were infections, notably Tuberculosis and Syphilis. Now infections are much better controlled, most people’s uveitis is of an unknown cause and is of the ‘autoimmune’ type.

Prof Dick went on to explain how the immune system works very clearly and simply, and how it involves a constant ‘surveying’ process reading surface markings, like bar codes, on all cells encountered in the body to determine whether they are ‘self’ or ‘foreign’. If foreign, for example a virus, then these immune cells will set off a chain of events resulting in inflammation and the destruction of the foreign cells.

It appears that in autoimmune diseases such as uveitis, then possibly if there is an actual infection (eg with a virus), present while this surveying process is going along then the immune system gets ‘confused’ and is directed to ‘attack’ our own self as though it is a virus. Once this has been triggered, then there is really nothing that can be done to undo this.

Some questions for Prof Dick followed and this led nicely into clinic procedures, or “What goes on in a Uveitis clinic”, a subject that Prof Dick and Annie Hinchcliffe, are always interested to hear of from the patient’s point of view.

Prof Dick explained how, at Bristol, they had adopted a different method in the uveitis clinic in response to voiced patients concerns. This was to address the difficulty of which patients need to be seen by Prof Dick at any given clinic. From the patients point of view, this often is seen as the “not being able to seen by the same doctor” problem.

Now instead of the Prof having his own list of patients, he is free to ‘float’ around the clinic being asked by the other medical staff on the clinic to see certain patients if there were any specific problems or concerns. This allows the Prof to see more patients and is able to cover all the more immediate or complex problems that arise on any given day.

It is important that if the patient has any particular worries or questions, then this allows them access to the consultant.

At Bristol, patients are fortunate to have a member of the nursing staff with a special interest and remit for uveitis. Annie Hinchcliffe has this role and can be contacted by patients with any concerns. This will enable a patient to get good advice and information and make best use of clinic time.

After a break, Prof Dick spoke about the promising areas of new treatment and research and answered questions on this area.

The whole process, of how new treatments are discovered and then researched, through to becoming available to patients, was explained.

Ideally all new treatments would be licensed for use in uveitis. To achieve a license a new drug has to go through various stages:

(This is a clinical trial in which patients are given at random the new drug or a control eg another more established drug).

This whole process can take upward of 10 years and for a single drug may cost in the region of £5-10 million and for full licence would involve drug companies and costs over £50 million.

Uveitis as a rare condition tends not to attract a lot of interest from the big drug companies who fund this development. One necessary approach in uveitis is that a lot of the newer drugs do not go through this process fully. Instead Uveitis Specialists would use the experience gained with other autoimmune conditions such as arthritis. A lot of the newer immunosuppressant drugs, even ones used for some years now have no license to be used for uveitis (so called ‘off license’ drugs). One of the disadvantages of this is that eye clinics can have problems finding the funding to carry out some of these ‘off license’ treatments.

There is some early promising work on possible use of a non-steroid preparation to dampen down the immune system.

The importance of simple solutions should never be overlooked. Some of the recent improvements in results in treating uveitis patients have been in the improvements made in surgical techniques and methods. Now complications of uveitis, which were always the things that caused most vision loss, can be dealt with more effectively. The main examples are surgery for cataract (better control of inflammation with steroids used inside the eye, for example) and glaucoma surgery.

Steroid implants These have featured in newspaper reports recently. The ‘Retisert’ implant has recently been given a license in the US to be used for uveitis. It is a tiny ‘package’ of steroid which is in effect ‘stapled’ to the infer surface of the eye, to release steroid over a long period to time. Initial studies have shown these to be successful but there is a drawback. The steroid implant causes most patients to get a cataract and it causes a significant number of patients to get high pressure inside the eye (some of these will need surgery to relieve the pressure problem). This means that the implant is still not a suitable treatment for most patients who can be controlled with eye drops but in carefully selected cases, will be useful for patients who do not respond to other treatments or might have unacceptable side effects from systemic drugs.

Continued development of immunosuppressant drugs The majority of patients with sight threatening posterior uveitis will respond to steroid tablets (systemic steroid treatment). Steroids can work very quickly and most people respond to them. Despite the side effects this makes steroid still very important in uveitis.

Some people will not respond to, or tolerate, steroids well and so there have now been a number of ‘second line’ immunosuppressant drugs available.

Prof Dick explained how experience is improving with these drugs and that new ones are continuing to be introduced.

There is an increasing tendency to use combination therapies of drugs, usually steroids along with one of the immunosuppressants. An example was given of one of the antibody treatments, anti -TNF. Usually as stated before this type of drug is used along with steroids but next year trials are to start giving anti-TNF alone with no steroid.

Other examples of newer immunosuppressants have been used for some time now and the exact type may tend to vary from clinic to clinic.

Work has been underway for some time on a novel approach to autoimmune conditions such as uveitis. Prof Dick referred back to how the immune system attacks its own ‘self’ in autoimmune disease. The idea in immune tolerance is to ‘feed’ the patient with the ‘self’’ substance, a protein in the eye, which is triggering the autoimmune reaction. The best way to do this is via a nose spray. The immune system gets bombarded with the substance and eventually learns to tolerate it more or ‘get used to it’. The autoimmune response which causes the inflammation in the eye is then reduced.

Actual treatments are now being trialled in 2 major conditions which are largely autoimmune in nature, MS and early onset diabetes.

Stem cell research is an area which shows great promise in major medical fields. Stem cells are basically ‘blank building blocks’ for the cells or our bodies. These cells will develop into all the different types of cells that make up the body, nerve cells, muscle cells, liver cells etc. If these cells can be triggered to make chosen types of cells, eg nerve cells, liver cells muscle cells etc, then there is a potential to ‘repair’ tissues damaged by disease.

Recently stem cells have been found in the retina. It is not known whether they can be used in the future to repair damaged retinas, but this is a very interesting area of research. This is one area where probably much more time will need to pass before therapies are available.

Prof Dick explained how one of the main problems with uveitis was how varied each case could be, from mild and easily controlled to severe and difficult to control. Things would be much better if it were possible to predict which patients would get severe inflammation or to predict which drugs would tend to work best for each patient.

Work in the UK has been looking at the genetic make up of different uveitis patients. It is hoped that it may be possible to ‘profile’ patients and be able to predict the likely course of their uveitis. Treatment would then be able to be tailored to suit this, eg early aggressive treatment for high risk patients.

The meeting concluded with a commitment from those attending to meet up again, and to discuss possible ways of forming local contacts and of arranging for information about uveitis to be better distributed in the South West.

Anyone who would like to hear about meetings in the South West or to meet up with others with uveitis should contact the UIG,