Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review / Tratamento adjuvante ou monoterapia tópica primária para a neoplasia de células escamosas de superfície ocular: uma revisão sistemática

ABSTRACT In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

RESUMO Revisão sistemática envolvendo estudos sobre o tratamento adjuvante e tratamento tópico primário para a neoplasia escamosa da superfície ocular. Os resultados foram: (i) 5-fluorouracil adjuvante reduziu o risco de recidiva após a excisão cirúrgica com efeitos colaterais leves (nível Ib, Grau de recomendação (GR) A). (ii) Mitomicina tópica primária produziu uma alta taxa de resposta completa, baixa taxa de recorrência e efeitos colaterais leves (nível Ib, GR A). (iii) Quimioterapia primária versus adjuvante produz taxas semelhantes de recorrência (nível IIb, GR B). (iv) 5- 5-FU versus mitomicina adjuvante não mostrou diferenças significativas nas taxas de recorrencia, com efeitos coalterais leves em ambos os grupos e melhor perfil de toxicidade para mitomicina (nível III, GR C). (v) 5- 5-FU tópico primário versus mitomicina ou interferon (INF) apresentam taxa similar de recorrência, com efeito colateral leve, mas com maior incidencia no braço 5- 5-FU, seguido pela Mitomicina e IFN (nível III, GR C).

Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type of the ocular adnexa: Retrospective single institution review of 95 patients.

Context: There are few reports on the management of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT), which are based on the experience of a single institution, as opposed to large multicenter randomized trials. Aim: The aim of this study was to report on the clinical experience of a single institution. Materials and Methods: A retrospective review was undertaken of records of 95 patients with MALT lymphoma of the ocular adnexa. Histologic diagnosis of MALT lymphoma was made according to established criteria, and clinical staging was carried out to determine treatment modalities. All patients were treated by external beam irradiation (30.6–45.0 Gy) after biopsy. Additional chemotherapy was performed in accordance with the clinical stage of the disease. All the patients were treated by the same hemato-oncologist and radio-oncologist. Results: Almost all patients showed complete response, except for four patients who showed partial response. In two of 95 patients, contralateral eye showed recurrence, and they were salvaged by additional radiotherapy. The 3-year overall survival and event-free survival rates were 100 and 97%, respectively, by Kaplan–Meier survival analysis. Moreover, there were no serious radiation-associated complications. Conclusions: Radiotherapy alone can be an important treatment modality for the local control and survival in patients with localized MALT lymphoma of ocular adnexa. Systemic chemotherapy should be considered in patients with advanced stage disease.

A Case of Primary Intraocular Lymphoma Treated by Intravitreal Methotrexate

A 40-year-old female visited our clinic for visual disturbance of the right eye, in which a few creamy-yellow retinal lesions and visual field constrictions were noted. She had been treated for primary CNS lymphoma and was in complete remission. After failure to follow-up for three months, she lost vision in the right eye, at which time active panuveitis was seen. Decreased vision and field constriction was observed in the left eye. Her left eye showed a granular pattern and dye leakage from the vessels and disc on fluorescein angiography and small RPE humps were seen in optical coherence tomography (OCT). Diffuse large malignant B-cells with strong immunoreactivities with CD20 immunostaining were seen in the epiretinal membrane biopsy specimen. Intravitreal injections of methotrexate (MTX) (800 microgram/0.1 ml in the right eye, 400 microgram/0.05 ml in the left eye) were performed twice weekly for one month, once weekly for the following month, once every two weeks for the next month, followed by nine monthly injections. Both eyes were free from malignant cells on vitreous biopsy six months later. There was no leakage seen by angiography, but the granular pattern persisted. Visual field constriction was slightly improved, and the small RPE humpsdetachments seen in OCT disappeared. EOG Arden ratio was decreased in both eyes, and b wave amplitude of scotopic ERG was decreased in the left eye. She was free from recurrence until six months later. No ocular complications except minimal opacity of the crystalline lenses were noted in both eyes.

Experiencia de 10 años en linfomas oculares y de anexos oculares / Ten year experience with ocular lymphomas and ocular adnexae lymphomas

Antecedentes. Los linfomas oculares (LO) y de los anexos oculares (LAO) tienen una incidencia de 7- 8% de todos los tumores extraganglionares. Objetivo. Describir las características clínicas, morfológicas e inmunofenotípicas de los LO y LAO atendidos en el Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Material y métodos. Se revisaron los expedientes de los pacientes con diagnóstico de LO y LAO de julio de 1994 a julio del 2005. Se analizaron los siguientes datos: presentación clínica, tratamiento, respuesta al tratamiento, supervivencia global, y supervivencia libre de enfermedad (SVLE). Resultados. Se analizaron 10 pacientes, 8 mujeres y 2 hombres. La media de edad fue de 50 años. La remisión completa (RC) se presentó en 8 de 10 pacientes y en los 6 pacientes con linfoma de tejido linfoide asociado a mucosas (MALT). Se encontraron dos con enfermedad refractaria, los cuales estaban en estadio IV. Conclusiones. En este estudio los LO y LAO correspondieron a 0.02% de todos los linfomas no Hodgkin (LNH) estudiados (498 casos). Los linfomas tipo MALT se presentan a edad más avanzada, se encontraron en estadios más tempranos y en todos hubo RC, con una SVLE promedio de 868 días y una media de supervivencia de 442 días.

BACKGROUND: Ocular lymphomas and ocular adnexae lymphomas (OL and OAL) constitute 7-8% of all extranodal lymphomas. OBJECTIVE: Describe the clinical, morphologic and immunophenotypic characteristics of OAL seen in our hospital. MATERIAL AND METHODS: Retrospective analysis of patient records with OL and OAL between July 1994 and July 2005. The following data was analyzed: Clinical presentation, therapy, treatment response, overall survival and disease free survival. RESULTS: Ten patients with OL and OAL were identified. Of these, 8 were women and 2 men. Median age was 50. Eight of 10 patients achieved complete remission, 6 of the 6 presenting MALT Lymphoma. Two patients with stage IV had refractory disease. CONCLUSIONS: In our series 0.02% of lymphomas were OL and OAL of a total 498 LNH. MALT lymphomas appear at a more advanced age, sixty percent of the cases were MALT lymphomas and were diagnosed during their early stages. Patients were followed during 21 months, global survival was 100%, free illness survival had a mean of 868 days and a survival median of 442 days.

Uso de mitomicina C em neoplasia intra-epitelial córneo-conjuntival: modalidades de abordagem - relato de casos / Use of mitomycin C for corneal-conjunctival intraepithelial neoplasia: management options - case reports

São relatados três casos de neoplasia intra-epitelial córneo-conjuntival nos quais a mitomicina C foi utilizada em abordagens distintas de acordo com a situação clínica encontrada. Os pacientes selecionados foram atendidos no Departamento de Oftalmologia da Casa de Saúde Santo Inácio, com diagnóstico clínico e/ou histopatológico de neoplasia intra-epitelial córneo-conjuntival. Com base na apresentação clínica das lesões, utilizou-se a mitomicina C a 0,04 por cento em três abordagens terapêuticas distintas: 1) quimioablação pós-operatória; 2) quimiorredução pré-operatória; e 3) quimioablação isolada. Obteve-se regressão da lesão tumoral nos três casos, sem recorrência em tempo de seguimento variando de 18-29 meses. Hiperemia conjuntival em um dos casos foi a única complicação observada. A mitomicina C mostrou-se eficaz e segura para tratamento de neoplasia intra-epitelial córneo-conjuntival, possibilitando várias abordagens terapêuticas de acordo com as características das lesões.

The Clinical Characteristics and Treatment Results of Ocular Adnexal Lymphoma

PURPOSE: To assess the clinical pattern, the histopathological findings, the response to treatments, the recurrence pattern and the prognosis of malignant lymphoma in the ocular adnexa. METHODS: This study was performed on 22 total eyes from 17 patients who were diagnosed with ocular adnexal malignant lymphoma. We retrospectively analyzed the medical records for patient information including the histological classification based on age, the gender of each patient, the symptoms and signs at the initial diagnosis, the presence of binocular invasion, the findings of the surgical biopsy, the clinical stage of each patient's tumor, and the treatment methods used and their effectiveness. The mean follow-up period was 24.8 months. RESULTS: The mean age of patients studied was 46.8 years old. Six females and 11 males were included in the study. Fifteen cases consisting of 20 total eyes represented extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Five of seven patients (71.4%) whose lymphoma occurred within the conjunctiva relapsed after irradiation or chemotherapy, and four of the relapsed patients were salvaged with further therapy. CONCLUSIONS: Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) constituted 88.2% of all lymphomas involving the ocular adnexa. Lymphoma in the ocular adnexa responded well to conventional treatment, but the recurrence rate of lymphoma in the conjunctiva was significantly high.

Primary lymphoma of the eye

Lymphomas in the eye tend to be localized and to have a better prognosis. We reviewed the clinical presentation, treatment outcome and complications of primary lymphomas of the eye at a single institute focusing on the clinical significance of adequate staging and the prognostic value of pathological subtypes. Twenty-four patients with lymphoproliferative lesion of the eye were treated and followed up. The orbit was the most commonly involved site. Twenty-one patients had unilateral diseases and three patients had bilateral. Histological findings revealed 22 malignant lymphomas, one inflammatory pseudotumor and one atypical lymphoid hyperplasia. Using the NCI Working Formulation, most of the malignant lymphomas were primarily low grade: diffuse small lymphocytic, 15; diffuse small cleaved three; diffuse large cell, three; and diffuse mixed, one. The stages of lymphoma were IAE in 21 patients, IBE in one patient, and IIAE in two patients. Twenty-five of the 27 treated eyes remained disease-free during the median follow-up period of 16 months. Nineteen patients received radiotherapy, five patients received chemo-radiotherapy and one patient received only surgical excision. Two patients relapsed outside the treated field. None of the patients complained of severe dry eye syndrome or cataract formation. In conclusion, after complete staging work-up, locally-confined low grade orbital lymphomas can be up to 90% controlled with radiotherapy alone. By contrast, combined treatment is advised in patients with intermediate and high grade lesions.

Chemotherapy in patients with retinoblastoma.

Chemotherapy composed of vincristine, cyclophosphamide, procarbazine and intrathecal thiotepa/methotrexate (in the indicated ones) were given for 1.5 years in the doubtful and very unfavorable (Reese-Ellsworth classification) cases of retinoblastoma. There were 58 new cases treated at the Department of Ophthalmology and the Department of Pediatrics, Ramathibodi Hospital from October 1, 1985 to December 31, 1991. Eight cases had refused the surgery prior to admission. Nine cases were not given chemotherapy due to the very advanced cases and refusal. Forty-nine cases received chemotherapy. Eighteen cases were not followed. Among 31 evaluable cases, three cases had progression of the disease. Twenty-eight cases (90%) were clinically well 2 months-6 years after discontinuation of chemotherapy. The good result could be attributable to spontaneous regression (minimal percentage), surgery, radiation therapy or chemotherapy. However, obvious chemotherapeutic effects were seen in some cases. Even though 28 cases seemed to have good result including three of the 8 cases who had refused surgery before admission, we should stress that retinoblastoma is a curable disease provided that early diagnosis and treatment are rendered. Ophthalmologic examination in first degree relatives should be done in the bilaterally involved cases.

Chemosensitization to adriamycin by cyclosporin A and verapamil in human retinoblastoma cell lines

The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were investigated using MTT assay against two human retinoblastoma cell lines, Y79 and WERI-Rb-1. Y79 and WERI-Rb-1 were totally resistant to doses up to 5.0 micrograms/ml of verapamil. Cyclosporin A inhibited the survival of Y79 and WERI-Rb-1 dose-dependently, however, the maximum inhibition at the highest concentration tested (5.0 micrograms/ml) was less than 50% (% survival at 5.0 micrograms/ml of cyclosporin A: 65.6% and 66.9% in Y79 and WERI-Rb-1, respectively). Combination of cyclosporin A and verapamil did not further inhibit the survival of Y79 and WERI-Rb-1 compared with cyclosporin A alone. Adramycin inhibited the survival of Y79 and WERI-Rb-1 dose-dependently. The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were evaluated in terms of sensitizing index (SI: the ratio of IC50 to adriamycin alone to IC50 to adriamycin in the presence of cyclosporin A and/or verapamil). Cyclosporin A significantly enhanced SI and the addition of verapamil enhanced SI further: SI values at 5.0 micrograms/ml of cyclosporin A, 5.0 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of verapamil, 5.0 micrograms/ml of cyclosporin A plus 3.0 micrograms/ml of verapamil were 2.0, 2.6 and 2.8 in Y79 and 2.6, 5.8 and 9.7 in WERI-Rb-1, respectively. These results suggest that cyclosporin A and verapamil are promising chemosensitizers to adriamycin in the treatment of retinoblastoma.

Tumores intra-oculares / Intraocular tumours

O autor apresenta a sua casuística de tumores oculares demonstrando a possibilidade do tratamento conservador nos casos específicos. Em 13 pacientes foram usadas placas radioativas contendo cobalto e suturadas à esclera. O autor discute os resultados

Duplo padräo de regressäo no retinoblastoma / Double regression pattern in retinoblastoma

O retinoblastoma é suscetível de apresentar regressäo espontânea ou pós-terapia espontânea ocorre em 1-2% dos casos, sendo unilateral e unifocal geralmente. A regressäo após o uso de radioterapia classifica-se em quatro tipos diferentes conforme o aspecto morfológico. Apresentamos um paciente acompanhado no Serviço de Oftalmologia do Hospital de Clínicas de Porto Alegre, com 3 anos de idade, no qual foi diagnosticado retinoblastoma no olho esquerdo, aos quatro meses de idade, sendo enucleado neste momento. Juntamente, observou-se no olho contralateral duas massas tumorais, caracterizando o estagio Ia, de acordo com a classificaçäo de Howarth. Após dois ciclos de radioterapia e dois protocolos de quimioterapia realizados intercaladamente, no período de três anos, esses focos tumorais apresentaram sinais claros de regressäo diferentes entre si: massa tumoral periférica com padräo tipo I e outra, paramacular, com padräo tipo II de regressäo. Salientamos a coexistência de dois tipos distintos de regressäo tumoral pós-terapia no mesmo olho, fato raramente descrito na literatura pesquisada

Challenge of the two neural tumors: neuroblastoma and retinoblastoma.

Fifty cases of neuroblastoma and 29 retinoblastoma patients who had additional chemotherapy were analyzed retrospectively. Male:Female ratio were 1:1 and 0.8:1, the ages ranged from birth to 14 years (4 +/- 3.42 year) for neuroblastoma, and one month to 5.5 years (2.4 +/- 1.4 year) for retinoblastoma. More than 70%-90% of them came in advanced stages. The treatment consisted of surgical resection, enucleation or exenteration if feasible. Radiation therapy and chemotherapy were given as specific and palliative measures. All of the neuroblastoma who were younger than 8 months old survived long-term. Various chemotherapeutic agents did not seem to effect the outcome of the advanced cases of these two diseases. The retinoblasts did not seem to be sensitive to MTX and Ara-C. Thio-tepa intrathecally seems to be worth trying. Since these two tumors are not sensitive to treatment and are still a great challenge to the developed countries, awareness of the diseases, early diagnosis and early treatment are appropriate approaches for the developing countries.