Subconjunctival methotrexate in the treatment of non infectious ocular inflammatory diseases

Hayashi, Seiji; Belfort Jr, Rubens

doi:10.5935/0004-2749.19970065

SUMMARY

We studied the effect of subconjunctival injections of methotrexate (MTX) in 18 patients with non-infectious ocular inflammatory processes (unilateral anterior uveitis 11 patients, corneal graft rejection 3 patients, nodular sclerouveitis with no systemic disease 2 patients, Vogt-Koyanagi-Harada's disease 1 patient, and Behcet's disease 1 patient). Weekly subconjunctival injections of 7.5mg of MTX were given. Daily slit lamp examination was performed to evaluate the degree of inflammatory activity in the anterior chamber or sclera and conjunctiva during the treatment. Patients were clinically followed for an average of 7.8 months (3 to 12 months) and no patient had evidence of local or systemic side effects. The conjunctiva remained yellowish and edematous for approximately 24hs after the injections and returned to the previous aspect after that. Our results showed that subconjunctival weekly injections oflow dose MTX have a favorable response in the treatment in nine of 11 cases of anterior uveitis, three cases of corneal graft rejection, and one patient of Vogt-Koyanagi-Harada disease. One patient with Behcet disease, and two with scleritis did not respond to the treatment.

Key-Words:
Methotrexate; Eye; Uveitis; Inflammation; Immunosuppression; Drug

RESUMO

Estudou-se o efeito do metotrexate aplicado na forma de injeções subconjuntivais em 18 pacientes com processo inflamatório ocular não infeccioso (11 pacientes com uveíte anterior, 3 pacientes com rejeição de transplante de córnea, 2 pacientes com esclerouveíte nodular anterior não associado a doença sistêmica, 1 paciente com síndrome de Vogt-Koyanagi-Harada e 1 paciente com síndrome de Behcet). As injeções de metotrexate foram aplicadas na dose de 7,5mg e os pacientes foram examinados diariamente por biomicroscopia para avaliar o grau de inflamação na câmara anterior, esclera e conjuntiva durante o tratamento e seguidos por uma média de 7,8 meses (3 a 12 meses). Nenhum paciente apresentou qualquer evidência de efeito colateral local ou sistêmico. A conjuntiva apresentou-se amarelada e edematosa por 24 horas após a injeção, voltando ao aspecto prévio após esse período. Os resultados mostram que injeções subconjutivais de metotrexate apresentam resposta favorável no tratamento de nove dos 11 casos de uveíte anterior, três casos de rejeição de transplante de córnea e um caso de síndrome de Vogt-Koyanagi-Harada. Um paciente com síndrome de Behcet e dois pacientes com esclerite não responderam a medicação.

Palavras-chave:
Metotrexate; Olho; Uveíte; Inflamação; Imunossupressão; Drogas

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REFERENCES

¹
HRYNIUK, W. M.; BROX, L. M.; HENDERSON, J. F.; TAMAOKI, T. - Consequence of methotrexate inhibition of purine biosynthesis in L5178 cells. Cancer Res., 35: 1247, 1975.
²
DECKER, J. L. - Toxicity of immunosupressive drugs in man. Arthritis Rheum., 16: 89-91, 1973.
³
ROENIGK, H. H.; BERGFELD, W. F.; ST. JAQUES, R. - Hepatotoxicity of methotrexate. Arch Dermatol. 103: 250-261, 1971.
⁴
STEINBERG, P. S.; and WINOKUR, S. H. - Immunosupressive and cytotoxic chemotherapy: long term complications. Ann Inter Med., 82: 84-95, 1975.
⁵
WONG, V. G. and HERSH, E. M. - Methotrexate in the therapy of cyclitis. Trans Am Acad Ophthalmol Otolaryngol., 69: 279-293, 1965.
⁶
WONG, W. V. - Methotrexate treatment of uveal disease. Am J Med Sci., 251: 239-244, 1966.
⁷
LOTTENBERG, C. L.; BELFORT JR, R.; ABREU, M. T.; DOMINGUES NETO, S.; HIRATA, P.S.; PETRILLI, A. M. N.; SILVA, M. H.; MULLER, M. E. W.; FARAH, M. E.; PLUT, R. C. A.; KIM, M.; REHDER, J. R. C. L.; BURNIER, M. N. - Seis pacientes com oftalmia simpática: experiência de 13 anos. Arq bras Oftalmol., 49: 82-5, 1986.
⁸
HALL, G. H.; JONES, B. J. M.; HEAD, A. C.; JONES, V. E. - Intra-articular methotrexate - Clinical and laboratory study in rheumatoid and psoriatic arthritis. Ann Rheum Dis., 37: 351-356, 1978.
⁹
SHAH, S. S.; LOWDER, C. Y.; SCHMITT, M. A.; WILKE, W. S.; KOSMORSKY, G. S.; MEISLER, D. M. - Low-dose methotrexate therapy for ocular inflammatory disease. Ophthalmol., 99:1419-1423, 1992.
¹⁰
HOLZ, F. G.; KRASTEL, H.; BREITBART, A.; SCHWARZ-EYWILL, M.; PEZZUTTO, A.; VÖLCKER, H. E. - Low-dose methotrexate treatment in noninfectious uveitis resistant to corticosteroids. German J Ophthalmol. 1: 142-144, 1992.
¹¹
NUSSENBLATT, R. B. and PALESTINE, A. G. - Examination of ocular structures. In Nussenblatt, R. B. and Palestine, A. G. (ed.): Fundamentais and clinical practice, Chicago, Year Book Medical Publishers, Inc., 1989, pp. 59-79.
¹²
CRONSTEIN, B. N. - Molecular mechanism of methotrexate action in inflammation. Inflammation. 16: 411-423, 1992.
¹³
DOROSHOW, J. H.; LOCKER, G. Y.; GAASTERLAND, D. E.; HUBBARD, S. P.; YOUNG, R. C.; MYERS, C. E. - Ocular irritation from high-dose methotrexate therapy: pharmacokinetics of drug in the tear film. Cancer. 48: 2158-2162, 1981.
¹⁴
CRONSTEIN, B. N.; NAIME, D.; OSTAD, E. - The antiiflammatory mechanism ofmethotrexate - Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest. 92: 2675-2682, 1993.
¹⁵
SUAREZ, C. R.; PICKETT, W. C.; BELL, D. H.; McCLINTOCK, D. K.; ORONSKY, A. L.; KERWAR, S. S. - Effect of low dose methotrexate on neutrophil chemotaxis induced by leukotriene 84 and complement C5a. J Rheumatol., 14: 9-11, 1987.

Publication Dates

Publication in this collection
Jun 1997

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[1] ¹
HRYNIUK, W. M.; BROX, L. M.; HENDERSON, J. F.; TAMAOKI, T. - Consequence of methotrexate inhibition of purine biosynthesis in L5178 cells. Cancer Res., 35: 1247, 1975.

[2] ²
DECKER, J. L. - Toxicity of immunosupressive drugs in man. Arthritis Rheum., 16: 89-91, 1973.

[3] ³
ROENIGK, H. H.; BERGFELD, W. F.; ST. JAQUES, R. - Hepatotoxicity of methotrexate. Arch Dermatol. 103: 250-261, 1971.

[4] ⁴
STEINBERG, P. S.; and WINOKUR, S. H. - Immunosupressive and cytotoxic chemotherapy: long term complications. Ann Inter Med., 82: 84-95, 1975.

[5] ⁵
WONG, V. G. and HERSH, E. M. - Methotrexate in the therapy of cyclitis. Trans Am Acad Ophthalmol Otolaryngol., 69: 279-293, 1965.

[6] ⁶
WONG, W. V. - Methotrexate treatment of uveal disease. Am J Med Sci., 251: 239-244, 1966.

[7] ⁷
LOTTENBERG, C. L.; BELFORT JR, R.; ABREU, M. T.; DOMINGUES NETO, S.; HIRATA, P.S.; PETRILLI, A. M. N.; SILVA, M. H.; MULLER, M. E. W.; FARAH, M. E.; PLUT, R. C. A.; KIM, M.; REHDER, J. R. C. L.; BURNIER, M. N. - Seis pacientes com oftalmia simpática: experiência de 13 anos. Arq bras Oftalmol., 49: 82-5, 1986.

[8] ⁸
HALL, G. H.; JONES, B. J. M.; HEAD, A. C.; JONES, V. E. - Intra-articular methotrexate - Clinical and laboratory study in rheumatoid and psoriatic arthritis. Ann Rheum Dis., 37: 351-356, 1978.

[9] ⁹
SHAH, S. S.; LOWDER, C. Y.; SCHMITT, M. A.; WILKE, W. S.; KOSMORSKY, G. S.; MEISLER, D. M. - Low-dose methotrexate therapy for ocular inflammatory disease. Ophthalmol., 99:1419-1423, 1992.

[10] ¹⁰
HOLZ, F. G.; KRASTEL, H.; BREITBART, A.; SCHWARZ-EYWILL, M.; PEZZUTTO, A.; VÖLCKER, H. E. - Low-dose methotrexate treatment in noninfectious uveitis resistant to corticosteroids. German J Ophthalmol. 1: 142-144, 1992.

[11] ¹¹
NUSSENBLATT, R. B. and PALESTINE, A. G. - Examination of ocular structures. In Nussenblatt, R. B. and Palestine, A. G. (ed.): Fundamentais and clinical practice, Chicago, Year Book Medical Publishers, Inc., 1989, pp. 59-79.

[12] ¹²
CRONSTEIN, B. N. - Molecular mechanism of methotrexate action in inflammation. Inflammation. 16: 411-423, 1992.

[13] ¹³
DOROSHOW, J. H.; LOCKER, G. Y.; GAASTERLAND, D. E.; HUBBARD, S. P.; YOUNG, R. C.; MYERS, C. E. - Ocular irritation from high-dose methotrexate therapy: pharmacokinetics of drug in the tear film. Cancer. 48: 2158-2162, 1981.

[14] ¹⁴
CRONSTEIN, B. N.; NAIME, D.; OSTAD, E. - The antiiflammatory mechanism ofmethotrexate - Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest. 92: 2675-2682, 1993.

[15] ¹⁵
SUAREZ, C. R.; PICKETT, W. C.; BELL, D. H.; McCLINTOCK, D. K.; ORONSKY, A. L.; KERWAR, S. S. - Effect of low dose methotrexate on neutrophil chemotaxis induced by leukotriene 84 and complement C5a. J Rheumatol., 14: 9-11, 1987.

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