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Year : 2000  |  Volume : 48  |  Issue : 3  |  Page : 251

Safety of oral methotrexate pulsed therapy.

Correspondence Address:
S Saxena

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Source of Support: None, Conflict of Interest: None

PMID: 11217262

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Keywords: Administration, Oral, Adult, B-Lymphocytes, drug effects, immunology, pathology, Cell Division, drug effects, Comparative Study, Humans, Immunosuppressive Agents,

How to cite this article:
Saxena S, Kumar D. Safety of oral methotrexate pulsed therapy. Indian J Ophthalmol 2000;48:251

How to cite this URL:
Saxena S, Kumar D. Safety of oral methotrexate pulsed therapy. Indian J Ophthalmol [serial online] 2000 [cited 2023 Sep 25];48:251. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2000/48/3/251/14863

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Eales' disease is an idiopathic obliterative vasculopathy that primarily affects the peripheral retina of adults.[1] Retinal changes include vasculitis, peripheral nonperfusion and neovascularization. An extraneous agent could result in exposure of normally sequestered uveitopathogenic retinal antigens of the immune system leading to an immune response in the eye that may initiate the disease process.[2]

Vasculitis is a good target for immunotherapy. The vascular endothelium is more accessible to biological reagents. The unique immunologic environment in the eye may facilitate the re-establishment of regulatory immune circuits following therapy. Methotrexate is a folic acid antagonist. The drug reduces the synthesis of DNA by acting on the enzyme dihydofolate reductase. It has a marked effect on rapidly proliferating cells and causes B-cell and T-cell suppression. Our recent study has highlighted the efficacy of oral methotrexate pulsed therapy in the treatment of retinal vasculitis in Eales' disease.[3] A pulse-dose therapy differs from chronic moderate-dose therapy in its ability to "reset" an aberrant immune response. Inhibition of the proliferating lymphocyte clines, the temporary removal of recirculating T-lymphocytes from the blood and eye and the profound suppression of peripheral inflammation all occur simultaneously. Antigens exposed by viral, bacterial or autoimmune injury are perpetuated by the inflammatory response. In such a system, a pulse may abolish the source of the antigen at the same time as it suppresses the immune response. When memory T-lymphocytes recirculate, the disease falters in the absence of the antigens.

Forty-nine consecutive cases of Eales' disease presenting with retinal vasculitis, between February 1997 and October 1999, were administered methotrexate pulsed therapy after approval from the ethical committee of our tertiary-care institution. Oral methotrexate (12.5mg) was started on a weekly basis for 3 months (cumulative dose 150mg), upon informed consent. All the cases were kept under the strict supervision of a physician and twice-weekly blood cell counts and monthly liver function tests, were monitored. After completion of therapy, patients were followed up for 6 months. Nausea/vomitting was observed in 2.04% (n=l) and 4.08% (n=2) cases respectively, while undergoing therapy. These side effects were reversible upon reduction or discontinuation of therapy.

Most immunosuppressive agents when properly administered and monitored for side effects have similar risk profiles with relatively few serious therapeutic mishaps and largely reversible side effects.[4] Methotrexate still remains a reserve or salvage medicine in the repertoire of many physicians. It has been found to be not only effective but less toxic too. The much feared hepatotoxicity has been softened by data accumulated on liver biopsies in patients with rheumatoid arthritis who were treated with methotrexate. This treatment failed to show accumulation of collagen or evidence of significant fibrosis.[5] Oral methotrexate pulsed therapy in Eales' disease appears to be a safe modality of treatment.

  References Top

Gieser SC, Murphy RP. Eales' disease. In: Ryan SJ, editor. Retina Vol II. Medical Retina. St. Louis: CV Mosby 1994. ppl503-7.  Back to cited text no. 1
Saxena S, Rajasingh J, Biswas S, Kumar D, Shinohara T, Singh VK. Cellular immune response to retina! S antigen and interphotoreceptor retinoid binding protein fragments in Eales' disease. Pathobiology 1999;67:37-44.  Back to cited text no. 2
Saxena S, Kumar D, Kapoor S. Efficacy of oral methotrexate pulsed therapy in Eales' disease. Ann Ophthalmol 2000;32:60-62.  Back to cited text no. 3
Tamesis RR, Rodriguez A, Christen WG, Akova YA, Messmer E, Foster CS. Systemic drug toxicity trends in immunosuppressive therapy of immune and inflammatory ocular disease. Ophthalmology 1996;103:768-75.  Back to cited text no. 4
Kremer JM, Lee RG, Tolman KG. Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. Arthritis Rheum 1989;32:121-27.  Back to cited text no. 5


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