Intraocular Development

Allergan Posurdex Steroid Implant Study

This study tests different doses of the Posurdex steroid implant, which is given by injection in the office (minor procedure, performed at MERSI) in patients with uveitis. The advantages: the pellet dissolves as it releases its medication. This is a large international study, with over 80 participating sites across the world, including the USA, Australia, the UK, South Africa.

MUST Study

This study is the Multi-center Uveitis Steroid Treatment amallicutor study, funded by the National Institute of Health. It is the first clinical trial for uveitis that has been sponsored by the NIH. The goal is to compare standard medical therapy (immunosuppressive pills taken by mouth) for uveitis with a recently approved steroid implant placed inside the eye (surgery), to see which therapy results in better control of uveitis, which therapy patients prefer, and which has fewer side effects. The steroid implant is the Retisert ®, which was approved by the FDA in 2005.  Moorfields Hospital in London is one of the centres involved in the study.  The study is not recruiting any more and will finish in 2011.

Intravitreal anti-inflammatory treatment for uveitis. S Sugita. Japan.2007. One of the problems with IMT is the side effects profile of the systemic drug used. This paper describes research into the delivery of drugs, like cyclosporine, into the eye. While this paper describes the use of intravitreal injected drugs into animal eyes, researchers are developing devices which allow drugs to be implanted into the eye and released slowly and others are developing some of the drugs to be delivered through eye drops. These developments will be of particular benefit to Birdshot patients, many of whom will have no other auto immune disease which requires systemic therapy.

Title of Presentation: The safety of intraocular methotrexate in ocular diseases other than primary CNS lymphoma. Paul W. Hardwig MD; Jose J. Pulido MD; Jay C. Erie MD; Keith H. Baratz  MD; Helmut Buettner MD. US. 2006 Fifteen patients, including 6 with uveitis and 2 with birdshot received intravitreal injections of methotrexate while also receiving a variety of other medical therapies. At follow up, visual acuity had improved in 7 eyes, remained stable in 5 eyes and decreased in 4. The authors are unsure whether it was the pre existing advanced  disease or the methotrexate injection which caused the decreased visual acuity in these 4 patients.

Intraocular Toxicity of Rituximab. Jose S. Pulido, M.D., M.S., M.P.H., M.B.A., Anna S. Kitzmann, MD, Brian G. Mohney, M.D., Keith H. Baratz, M.D., Thomas Grube, M.D., Ronald J. Marler, D.V.M., Ph.D., Mark J. Donaldson, M.D., Brian P. O’Neill, M.D., Patrick B. Johnston, M.D., Kirk M. Johnson, R.Ph., Leslie E. Dixon, B.S., Diva R. Salomao, M.D., J. D. Cameron, M.D. US. 2006.

When these  writers investigated the toxicity of 1mg of intraocular rituximab injected into 4 rabbit eyes and 1 human eye, it showed no toxicity. (Rituximab is currently being used in the UK as an iv infusion to treat rheumatoid arthritis).

PI-88: a potent angiogenesis inhibitor with potential for treatment of back-of-the-eye diseases. Chapman P, Ferro V, Parish C, Freeman C. Ireland and Australia. 2005.Scroll to page  168.
This abstract requires a good degree of knowledge to understand. It is a review of the antiangiogenic drug, PI-88, which has been tested in clinical trials for several cancers. It is well tolerated and shows low systemic toxicity. It displays anti inflammatory activity and it is thought it may be helpful in the treatment of neovascularisation (growth of new  blood vessels in the eye) associated with diabetic retinopathy and macular degeneration. It may also be helpful with the similar processes in uveitis.