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

A study, undertaken by scientists in Russia and published in June 2011 has looked at targeting B Cells as a potential way of controlling autoimmune diseases.

Some of us are already on a medication called Rituximab which targets B cells.  Rituximab is a monoclonal antibody which works on a protein found on the B Cells and which may be implicated in our auto-immune disease, Birdshot.  We know that Rituximab seems to work for some people but not for everybody, and we also know there are some side effects of Rituximab.

The Russian study looked at a way of more effectively targeting the B Cells with less toxic side effects, and the study seems to suggest that they have found a possible way forward.  Wonderful – yet another possibility for us.

The full study can be found at:

http://www.ncbi.nlm.nih.gov/pubmed/21677771?dopt=Citation

This study looks at eyes receiving fluocinolone acetonide implants  (Retisert) over a 7 year period and concludes that there is a high risk of developing cataracts and increasing intraocular pressure  (glaucoma).   The study authors include people who were involved in the Bausch and Lomb trials.

This type of  implant is not currently licensed for use in the UK, so you would have to be an extremely special circumstance to qualify for this type of treatment at the moment.

However for those with Birdshot, with bad inflammation, who can not tolerate sytemic steroids they do provide a potential, if not ideal option for treating inflammation in the eye.

http://www.ophsource.org/periodicals/ophtha/article/S0161-6420(11)00229-6/abstract

You can also see  our earlier post about this type of device: –https://birdshot.org.uk/dexamethasone-for-ocular-inflammation/

An important piece of research about treatment with anti-VEGF (anti vascular endothelial growth factor) for complications of Birdshot (and other inflammatory chorioretinal diseases) has been published.  The complications tend to be macular oedema (ME) and choroidal neovascularisation (NVC).  Some of you have been prescribed these anti-VEGFs – the most common of them being Lucentis (called ranibizumab) and Avastin (called bevacizumab).

The research findings seem to show that there have been positive results in retaining visual acuity for many people with complications when using these medications.  However, the researchers also point out that it has not been possible to undertake randomised clinical trials for people with uveitis who have macular oedema or neovascularisation and are on anti-VEGF, so they are suggesting that further trials and longer follow up is needed.   For us, it is another piece of preliminary good news, and another weapon in our armoury against Birdshot and its complications.  We recognise that further testing is required, but at least it gives us another option.

This research was conducted in Italy and we attach below a summary of the findings.

Dev Ophthalmol. 2010; vol. 46 pp. 84-95

Antivascular endothelial growth factors for inflammatory chorioretinal disorders.

Battaglia Parodi M, Iacono P, Verbraak FD, Bandello F

Macular edema (ME) and choroidal neovascularization (CNV) can complicate the course of several inflammatory chorioretinal diseases, leading to a severe visual function impairment. The most frequently involved clinical entities include for example multifocal choroiditis, presumed ocular histoplasmosis syndrome, Beçhet’s disease, multiple evanescent white dot syndrome, birdshot chorioretinopathy, acute multifocal posterior placoid pigment epitheliopathy, serpiginous choroiditis, and persistent placoid maculopathy. Results that have reported on antivascular endothelial growth factor (anti-VEGF) treatment in uveitic patients with CNV or ME have demonstrated positive results in many cases. However, bearing in mind that it has been proven impossible to perform randomized clinical trials with anti-VEGF in uveitic patients with CNV or ME, further studies with longer follow-ups are necessary to assess the value of this therapeutic approach.

PMID: 20703034
URL – http://www.ncbi.nlm.nih.gov/pubmed/20703034?dopt=Citation