The link between HLA- A29 and Birdshot Chorioretinopathy is one that interests many people and the paper published by:  Brézin AP, Monnet D, Cohen JH, Levinson RD, on this subject asks the question:

Why do people of European descent tend to get Birdshot, whilst other ethnic groups who also carry the HLA A29 antigen do not?

The paper explains that there are two different subtypes of HLA29A:- HLA29:02 is most frequent in caucasians, whilst HLA29:01 is most frequent in Asians.

It used to be thought that the disease only appeared in people with the HLA-A29:02 version of the antigen.  The paper tells us that is no longer a valid argument.   It suggests that another factor, probably not HLA linked, is either protective in Asians and in Africans or, alternatively, triggers an autoimmune reactivity that is possibly present in Caucasians of european descent and absent in Asians and in Africans.

We might start to make progress if scientists can find the answer to what this might be.

We are trying to get hold of the full research paper so that we can review it in detail.

We came across a piece of French research (published in September 2011) that is very timely in reminding professionals that ICG – Indocyanine Green Angiography (green dye is injected into blood stream and quickly reaches the blood vessels at the back of the eye, which can then be photographed) is still a very useful tool for people with Birdshot as it can identify leakages that are hard to see by other methods such as Optical Coherence Technology (OCT).

This is yet another example of an ‘old’ method that, although superseded by a range of new methods, still has a part to play in our disease and should remain as one of the several monitoring and diagnostic tools used for Birdshot.

Here is an abstract from that research:

Desmettre T, Cohen SY, Devoisselle JM, Gaudric A

“A full interpretation of indocyanine green angiography images involves not only optical issues but also pharmacokinetic and biochemical aspects. These issues may involve biochemical changes in the fluorescence yield and the affinity of the molecule for lipoproteins and phospholipids. For age-related macular degeneration (AMD), the advent of photodynamic therapy and especially anti-VEGF drugs has increased the use of OCT in assessing treatment response and guiding retreatment. The ease and advantages of OCT have become increasingly associated with a decreasing interest in ICG angiography, which is becoming less well suited for the current management of AMD. An aging population, the efficacy of anti-VEGF drugs and the relative rarity of polypoidal choroidal vasculopathy (PCV) in Europe are factors contributing to our proportional increase in AMD patients. However, aside from AMD, the indications for ICG angiography remain little changed over the last decade: it remains important in diagnosing PCV and choroidal hemangiomas, since their prognosis and treatment are specific. Similarly, for certain inflammatory conditions such as Multiple Evanescent White Dot Syndrome (MEWDS) or Birdshot chorioretinitis, the value of ICG angiography remains significant. In addition, for the treatment of chronic Central Serous Chorioretinopathy, ICG angiography helps to find sites of leakage which otherwise might have been missed. The ICG angiographic appearance in this setting may also have prognostic value. Although the indications for ICG angiography are currently decreasing for AMD, these other conditions represent a large enough number of patients to justify the continued use of this original test, which remains complementary to other chorioretinal imaging techniques.”

The full article can be found at: http://www.ncbi.nlm.nih.gov/pubmed/21907446?dopt=Citation

Some of us with Birdshot are currently using adalimumab (Humira®). Rea from BUS is one of those people. We recently came across a study looking at the safety and effectiveness of long-term use of adalimumab for people with intermediate-, pan- and posterior-uveitis. This study is currently recruiting by invitation only as you do need to have been involved in the previous related studies in order to qualify.

It is being conducted across 63 locations in the US, Europe and the UK.  In the UK there are three sites: London, Bristol and Aberdeen.

This study is a Phase 3, open-label multicentre study designed to evaluate long-term safety and efficacy of adalimumab in a group of  adult subjects with non-infectious intermediate, posterior, or pan-uveitis.

If any of our members are enrolled in this study, we would be grateful for feed-back on this.

URL: Long term safety and efficacy of adalimumab in subjects with intermediate, posterior and panuveitis

Some weeks ago we wrote about a novel treatment trial Involving a relatively old immunosuppressant – sirolimus – being used in a new way as an invitreal injection. https://birdshot.org.uk/sirolimus-eye-injections-given-orphan-drug-status/.

Recently we discovered a similar trial, but this time using a different immunosuppressant – methotrexate – as an invitreal injection.

The trial is looking at people who have chronic macular edema (the American spelling – in the UK we spell it oedema) as a secondary or complication to their Birdshot or other form of intermediate or posterior uveitis. The macular edema must affect at least one eye that has not responded to conventional immunosuppressive therapies over the previous 3 months or has recurred while on conventional immunosuppressive therapies. Methotrexate is injected on a monthly basis for 3 months and then as needed. This trial is openly recruiting in Bethesda USA.

This information might be useful for our American members. If you are interested in more information about it you can contact Patient Recruitment and Public Liaison Office prpl@mail.cc.nih.gov (800) 411-1222 TTY 1-866-411-1010

If any of our American members are already on the trial or are thinking of registering for it, we would be really grateful to hear about your experiences. If this therapy proves to be successful, we hope that this will add to the growing range of medications that help us preserve our visual acuity.

Here is a brief summary of the research:-

Uveitis comprises a group of diseases associated with inflammation of the eye that can lead to vision loss. Some people with uveitis also have macular edema (swelling of the retina at the back of the eye). Uveitis and macular edema are treated with medications and sometimes surgery, but treatment does not always prevent vision loss. Previous research has shown that injections of methotrexate into the eye of people with eye disease other than uveitis can help relieve the inflammation, or swelling, that causes macular edema and can slow visual loss. However, it has not yet been approved as a treatment for macular edema associated with uveitis. The objective of the study is to evaluate the safety and effectiveness of methotrexate injections as a treatment for macular edema associated with uveitis. This study requires at least nine visits to the National Eye Institute study clinic over a period of 6 months (24 weeks). Participants will be screened with a full physical and ophthalmic examination, a medical history, blood and urine tests, and additional eye and other tests as needed. An oral dose of folic acid is taken the day after the injection. Participants who tolerate the initial injection may continue to receive injections in their study eye every month for 6 months. After 6 months, participants who show improvement from the injections may be evaluated to receive additional injections every 4 to 8 weeks until researchers end the study.

URL:  Trial using Methotrexate drug as an invitreal injection

Various diseases can be diagnosed by testing for biomarkers, a particular substance in the blood or tissue (e.g. troponin to determine whether someone has had a recent heart attack). So far there are no specific biomarkers for determining whether a patient has non-infectious uveitis. Using a mouse model of autoimmune uveitis, Mattapallil et al. found T-cells activated against a particular protein in the retina (retinal arrestin). This provides support for the theory that autoimmune uveitis is caused by the body attacking the retina and may lead the way to developing a blood test for diagnosing this disease.

Uveitis-Associated Epitopes of Retinal Antigens Are Pathogenic in the Humanized Mouse Model of Uveitis and Identify Autoaggressive T Cells.  (Journal of immunology (Baltimore, Md. : 1950). 2011 Jul 15;PMID: 21765017)

URL – http://www.ncbi.nlm.nih.gov/pubmed/21765017?dopt=Citation