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PURPOSE: The primary ocular targets of chronic graft-versus-host disease (GVHD) are the lacrimal gland (LG) and the conjunctiva, and their involvement results in keratoconjunctivitis sicca (KCS). The purpose of the present study was to evaluate the frequency of signs and symptoms of KCS present in patients submitted to BMT, to identify the cellular phenotype of the conjunctival and lacrimal gland biopsies of these patients by immunohistochemistry and to correlate the findings with the presence of dry eye due to GVHD. METHODS: Forty-seven patients were clinically classified into two groups: Group I, with ocular GVHD, submitted to allogeneic BMT and Group II, without ocular GVHD, submitted to autologous and allogeneic BMT. Thorough eye examination, including clinical lacrimal function tests and biopsies of the conjunctiva and of the LG were performed in the pre- and posttransplantation period. The biopsies were submitted to immunohistochemical analysis using a panel of monoclonal antibodies. RESULTS: Of the 28 (82.4%) patients with chronic GVHD, 13 (46.4%) presented ocular GVHD. Of the six patients without GVHD, one (16.7%) presented ocular GVHD. None of those submitted to autologous BMT presented ocular GVHD and 14 (41.2%) of 34 patients with allogeneic BMT presented ocular GVHD. All patients with ocular GVHD (Group I) had symptoms and the most frequent were burning, foreign body sensation, blurred vision and dryness. The rose bengal test was one of the most sensitive in this study and slit lamp examination was very useful in the evaluation of corneal and conjunctival alterations, since these alterations were always present in patients with dry eye in our study. Neither symptoms and signs of dry eye nor significant immunologic reaction was observed in the conjunctiva and in the LG of patients without ocular GVHD (Group II). There was an increase in the T lymphocyte population, of T helper lymphocyte (Th/i) and T suppressor-cytotoxic lymphocyte (Ts/c) subpopulation in the conjunctiva and in the LG of patients with ocular GVHD after the transplantation. CONCLUSIONS: Patients submitted to allogeneic BMT may develop ocular GHVD characterized by KCS. The immunohistochemical study of the conjunctiva and lacrimal gland biopsies of these patients suggested that these tissues are the target of the T cell mediated immunological reaction. OBJETIVOS: A glândula lacrimal e a conjuntiva são os tecidos oculares primariamente afetados pela doença enxerto-versus-hospedeiro (DEVH) crônica, e seu envolvimento clínico é caracterizado por ceratoconjuntivite seca (CCS). Os objetivos deste estudo foram os de avaliar a freqüência dos sintomas e sinais de CCS em pacientes submetidos ao transplante de medula óssea (TMO) e identificar a população celular por análise imuno-histoquímica de biópsias da conjuntiva e glândula lacrimal desses pacientes, correlacionando esses achados com o quadro clínico ocular. MÉTODOS: Quarenta e sete pacientes foram classificados em dois grupos: Grupo I, pacientes com DEVH ocular, submetidos ao TMO alogênico e Grupo II, pacientes sem DEVH ocular, submetidos ao TMO alogênico e autólogo. Exame ocular completo, incluindo testes clínicos da função lacrimal, e biópsias de conjuntiva e glândula lacrimal foram realizadas nos períodos pré e pós-transplante. Estudou-se a população celular, por meio de análise imuno-histoquímica das biópsias, utilizando um painel de anticorpos monoclonais. RESULTADOS: Dos 28 (82,4%) pacientes com DEVH crônica, 13 (46,4%) apresentaram DEVH ocular. Dos seis pacientes sem DEVH, um (16,7%) apresentou DEVH ocular. Nenhum paciente submetido a TMO autólogo apresentou DEVH ocular e 14 (41,2%) dos 34 pacientes com TMO alogênico desenvolveram DEVH ocular. Todos os pacientes com DEVH ocular (Grupo I) apresentaram sintomas e os mais freqüentes foram ardor, sensação de corpo estranho, visão borrada e secura ocular. O teste de rosa bengala foi um dos mais sensíveis e o exame biomicroscópico foi considerado muito útil na avaliação das alterações conjuntivais e corneanas, as quais estavam sempre presentes nos pacientes com DEVH ocular deste estudo. Na conjuntiva e na glândula lacrimal dos pacientes sem DEVH ocular não houve reação imunológica significante, concordando com os testes de função lacrimal. Houve aumento da população de linfócitos T, dos linfócitos T auxiliadores (Th/i) e linfócitos T supressores-citotóxicos (Ts/c) após o transplante na conjuntiva e glândula lacrimal de pacientes com DEVH ocular. CONCLUSÕES: Pacientes submetidos ao TMO alogênico podem desenvolver DEVH ocular, caracterizado por ceratoconjuntivite seca. O estudo imuno-histoquímico de biópsias da conjuntiva e glândula lacrimal desses pacientes sugere que esses tecidos são alvo de reação imunológica mediada pelos linfócitos T

Dry eye evaluation and immunohistochemical study of the conjunctiva and lacrimal gland of patients submitted to bone marrow transplantation