Efficacy and safety of Methotrexate injections into the eye for inflammatory diseases of the eye.

Uveitis is a term that refers to inflammatory diseases of the eye. Uveitis accounts for about 10% of the legal blindness in developed countries such as Australia and the United States and is roughly comparable to diabetes in terms of years of visual loss. The most severe forms of uveitis have the highest risk of vision loss. One of the common causes of vision loss in uveitis is swelling of the central retina, or “macular oedema”. This is due to the abnormal leakage of fluid from blood vessels within the retina as a result of uncontrolled inflammation. Standard treatments for severe uveitis and associated complications like macular oedema include systemic medication or injections of long acting steroid into, or around the eye. Systemic treatments include steroid tablets or low doses of drugs that are also used in chemotherapy like cyclophosphamide or cyclosporine. These systemic treatments have significant associated side effects and therefore are not ideal, particularly in people who only have uveitis in one eye. Injections of a long acting steroid (triamcinolone) directly into the eye (“intra-vitreally”) is another established treatment modality for some types of uveitis and blinding complications like uveitic macular oedema, particularly in those with uveitis in only one eye. However, there are known side effects of this treatment such as cataract, glaucoma, infection (endophthalmitis) and retinal detatchment. Of these, cataract and glaucoma are by far the most common and, unlike the other complications, are the direct result of the effect of triamcinolone on the eye, rather than being a complication of the injection procedure. Although the visual loss from cataract may be reversed with cataract surgery, visual loss from glaucoma can only be halted with available treatments and not reversed. Therefore patients who have glaucoma, or are known to develop raised intraocular pressures in response to steroid treatment (such as triamcinolone), are not offered this treatment, thereby limiting the available options for the management of their uveitis and/or uveitic macular oedema. Methotrexate is a drug that has been used in chemotherapy but also in low doses to control inflammatory diseases like rheumatoid arthritis in both adults and children. More recently, it has also been used as an injection intravitreally to treat both ocular lymphoma as well as uveitis and uveitic macular oedema. Preliminary studies using methotrexate intravitreally as treatment for severe forms of uveitis and associated sight threatening complications like macular oedema appear promising, without the side effects known to be associated with steroid treatment such as cataract and glaucoma. We therefore have 2 specific aims: Aim 1: To prospectively evaluate the efficacy of intavitreal methotrexate in the treatment of active intermediate, posterior or panuveitis Aim 2: To prospectively evaluate the efficacy of intravitreal methotrexate in the treatment of uveitic macular oedema