Retinoblastoma treatment in a Brazilian population. Presentation and long-term results.

INTRODUCTION: Retinoblastoma is a malignant tumor with a high cure potential when proper therapy is used. The purpose of this paper is to report the clinical features and outcomes of patients with retinoblastoma who were treated with a combination of local and systemic chemotherapy-based protocols. METHOD: We retrospectively studied patients treated with systemic chemotherapy plus local treatment between 2003 and 2015 with a follow-up ≥2 years. We correlated clinical and pathological characteristics with decimal visual acuity (VA) and death. RESULTS: Among 119 patients, 60% had unilateral disease (UNI), and 52% were male. The median presentation age was 19.5 months, 10% had a positive family history, and the most frequent sign was leukocoria (68.8%). Advanced disease was more frequent in eyes with UNI (98.4%) than in eyes with bilateral retinoblastoma (BIL: 55.3%). Enucleation was performed in 97% of UNI eyes and in 55.8% of BIL eyes. The overall globe salvage was 26.6%, 44.25% of BIL eyes. Bilateral enucleation was required in 5%. High-risk pathologic features occurred in 50% and 37% of eyes enucleated without and with neoadjuvant chemotherapy, respectively. High-risk features were related to the presence of goniosynechiae in the pathologic specimen and were more frequent in children younger than 10 months or older than 40 months. Extraocular disease was present in 5% of patients, and the death rate related to metastasis of the tumor was 8%. The final VA was ≥ 0.7 in 72.8% and ≥0.1 in 91% of BIL patients. CONCLUSIONS: Treatment of retinoblastoma with conservative systemic-based chemotherapy was associated with an excellent survival rate (92%). Albeit the low overall globe salvage rate, in BIL patients, approximately half the eyes were conserved, and a satisfactory functional visual result was achieved The evaluated protocol is an important treatment option, especially in developing countries.

Sickle cell retinopathy: diagnosis and treatment.

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

Sickle cell retinopathy: diagnosis and treatment / Retinopatia falciforme: diagnóstico e tratamento

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

As hemoglobinopatias são um grupo de doenças hereditárias caracterizadas por mal-formações quantitativas ou qualitativas da hemoglobina (Hb). Algumas destas doenças podem apresentar fenômenos vaso-oclusivos, responsáveis por alta morbidade do ponto de vista clínico e/ou oftalmológico. O diagnóstico das hemoglobinopatias é feito exclusivamente através da eletroforese de hemoglobinas. Do ponto de vista oftalmológico, a representante mais importante deste grupo de doenças é a retinopatia falciforme, que pode apresentar um amplo espectro de manifestações fundoscópicas, podendo, inclusive, levar à perda visual irreversível se não for corretamente diagnosticada e tratada. O objetivo desta revisão é apresentar a classificação desta doença, a conduta no tratamento atual, bem como suas perspectivas futuras de tratamento, considerando-se as particularidades no manejo clínico destes pacientes.

Orbital retinoblastoma: case report.

We describe the case of a 9-month old boy with unilateral retinoblastoma and bulftalmo. Primary enucleation was the treatment of choice due to the lack of visual prognosis. The histology of the enucleated eye showed massive choroidal invasion by the tumor and the optic nerve free of neoplastic tissue. Therefore, no adjuvant chemotherapy or radiotherapy was indicated. Three months after the enucleation, the patient returned with massive orbital retinoblastoma with exposure of the conjunctiva. Treated with chemotherapy, the patient has been in remission for 12 months. The risk factors for orbital recurrence are discussed.

Orbital retinoblastoma: case report / Retinoblastoma orbitário: relato de caso

We describe the case of a 9-month old boy with unilateral retinoblastoma and bulftalmo. Primary enucleation was the treatment of choice due to the lack of visual prognosis. The histology of the enucleated eye showed massive choroidal invasion by the tumor and the optic nerve free of neoplastic tissue. Therefore, no adjuvant chemotherapy or radiotherapy was indicated. Three months after the enucleation, the patient returned with massive orbital retinoblastoma with exposure of the conjunctiva. Treated with chemotherapy, the patient has been in remission for 12 months. The risk factors for orbital recurrence are discussed.

Relatamos paciente de 9 meses de idade com buftalmo e retinoblastoma unilateral. O paciente foi tratado com enucleação primária devido à falta de prognóstico visual. O exame do olho enucleado mostrou invasão maciça de coroide e ausência de comprometimento do nervo óptico não sendo, portanto, submetido a tratamento adjuvante de quimioterapia ou de radioterapia. Três meses após a enucleação, o paciente apresentou-se com retinoblastoma orbitário volumoso com exposição da conjuntiva. Tratado com quimioterapia permanece em remissão após 12 meses. São discutidos os fatores de risco para a ocorrência da recidiva orbitária.

Retinoblastoma: a three-year-study at a Brazilian medical school hospital.

OBJECTIVE: To present the characteristics and treatment outcomes of patients with retinoblastoma. METHODS: A retrospective case series was conducted to review the records of all new patients diagnosed with retinoblastoma between 2003 and 2005. Eyes with early disease, or advanced disease with potential vision were treated with chemotherapy (carboplatin and etoposide) in conjunction with early local therapy (laser or cryo). Radiotherapy was used in cases where the disease did not respond to the above protocols or in recurrent cases. Eyes in the late stage of disease with no potential vision in the initial examination or eyes and where conservative treatment had failed were enucleated. RESULTS: In total, we reviewed 28 new cases of retinoblastoma, 15 of which were unilateral and 13 of which were bilateral (46%). These data correspond to a mean of 9.3 new cases per year (0.77 case/ month). The mean age at diagnosis was 33.8 months for unilateral cases, and 19.15 months for bilateral cases (p=0.015). Leucocoria was the major presenting symptom (75%). All but one patient with unilateral disease had the affected eye enucleated due to advanced disease (mean follow-up: 39.91 months). Among the 13 bilateral cases, 13 eyes (50%) were enucleated, 11 eyes (42.4%) were saved with chemotherapy in conjunction with local therapy and 2 eyes (7.6%) were saved using external beam radiotherapy (mean follow-up: 41.91 months). In unilateral and bilateral disease, pathology data revealed choroid involvement in 50% and 30%, respectively, and optic nerve invasion in 92% and 50%, respectively. CONCLUSION: In this population, retinoblastoma was diagnosed too late and most eyes were consequently enucleated. In cases with bilateral disease, half of the eyes were preserved.

Retinoblastoma: a three-year-study at a Brazilian medical school hospital

OBJECTIVE: To present the characteristics and treatment outcomes of patients with retinoblastoma. METHODS: A retrospective case series was conducted to review the records of all new patients diagnosed with retinoblastoma between 2003 and 2005. Eyes with early disease, or advanced disease with potential vision were treated with chemotherapy (carboplatin and etoposide) in conjunction with early local therapy (laser or cryo). Radiotherapy was used in cases where the disease did not respond to the above protocols or in recurrent cases. Eyes in the late stage of disease with no potential vision in the initial examination or eyes and where conservative treatment had failed were enucleated. RESULTS: In total, we reviewed 28 new cases of retinoblastoma, 15 of which were unilateral and 13 of which were bilateral (46 percent). These data correspond to a mean of 9.3 new cases per year (0.77 case/ month). The mean age at diagnosis was 33.8 months for unilateral cases, and 19.15 months for bilateral cases (p=0.015). Leucocoria was the major presenting symptom (75 percent). All but one patient with unilateral disease had the affected eye enucleated due to advanced disease (mean follow-up: 39.91 months). Among the 13 bilateral cases, 13 eyes (50 percent) were enucleated, 11 eyes (42.4 percent) were saved with chemotherapy in conjunction with local therapy and 2 eyes (7.6 percent) were saved using external beam radiotherapy (mean follow-up: 41.91 months). In unilateral and bilateral disease, pathology data revealed choroid involvement in 50 percent and 30 percent, respectively, and optic nerve invasion in 92 percent and 50 percent, respectively. CONCLUSION: In this population, retinoblastoma was diagnosed too late and most eyes were consequently enucleated. In cases with bilateral disease, half of the eyes were preserved.

[Peripheral retinal arterial obstruction associated with hyperhomocysteinemia: case report]. / Obstrução arterial retiniana periférica associada com hiper-homocisteinemia: relato de caso.

Hyperhomocysteinemia is a risk factor for thromboembolic events of the retina associated with vascular venous or arterial occlusion. We describe a patient with occlusion of the peripheral arteriolar network without active vasculitis, associated with neovascular proliferation, peripheral vitreous-retinal traction and relapsing vitreous hemorrhage. The high serum homocysteine level resulting from vitamin B12 and folic acid deficiency, without further changes in the coagulation cascade including the test for Leiden's Factor V, indicates hyperhomocysteinemia as a direct causal factor in this clinical condition. Despite a high PPD, Eales Disease, a major differential diagnosis, was not fully considered, since it is established by exclusion. The patient was treated with photocoagulation and vitamin supplements and the condition was successfully controlled. Patients with retinal vascular obstruction should have their total plasma homocysteine levels measured, since this modifiable risk factor can be easily treated with dietary approaches including vitamin supplementation.

Obstrução arterial retiniana periférica associada com hiper-homocisteinemia: relato de caso / Peripheral retinal arterial obstruction associated with hyperhomocysteinemia: case report

A hiperhomocisteinemia é fator de risco para fenômenos trombo-embólicos retinianos associados a quadro de oclusão vascular venosa e arterial. Descrevemos um paciente com obstrução arterial retiniana periférica, sem sinais de vasculite ativa, associada a proliferação de neovasos com tração vítreo-retiniana e hemorragia vítrea recidivante. O alto nível sérico de homocisteína decorrente de deficiência de vitamina B12 e ácido fólico, sem outras alterações na cascata da coagulação, inclusive com a pesquisa do fator V de Leiden, sugere que a hiper-homocisteinemia esteja diretamente ligada como fator causal deste quadro clínico. Embora apresentasse PPD elevado, o diagnóstico diferencial mais importante de doença de Eales foi menos considerado por ser diagnóstico de exclusão. O controle do quadro clínico foi feito com suplemento de vitaminas (B12 e ácido fólico) e fotocoagulação retiniana periférica. A homocisteína plasmática total deve ser dosada em pacientes com obstrução vascular retiniana, já que a hiper-homocisteinemia é fator de risco modificável e de fácil tratamento por meio de dieta ou suplementação vitamínica.

Hyperhomocysteinemia is a risk factor for thromboembolic events of the retina associated with vascular venous or arterial occlusion. We describe a patient with occlusion of the peripheral arteriolar network without active vasculitis, associated with neovascular proliferation, peripheral vitreous-retinal traction and relapsing vitreous hemorrhage. The high serum homocysteine level resulting from vitamin B12 and folic acid deficiency, without further changes in the coagulation cascade including the test for Leiden's Factor V, indicates hyperhomocysteinemia as a direct causal factor in this clinical condition. Despite a high PPD, Eales Disease, a major differential diagnosis, was not fully considered, since it is established by exclusion. The patient was treated with photocoagulation and vitamin supplements and the condition was successfully controlled. Patients with retinal vascular obstruction should have their total plasma homocysteine levels measured, since this modifiable risk factor can be easily treated with dietary approaches including vitamin supplementation.

Descolamento regmatogênico de retina: avaliação pós-operatória da mácula / Rhegmatogenous retinal detachment: a postoperative study of the macula

OBJETIVO: Avaliar função e estrutura macular de pacientes submetidos a cirurgia de descolamento regmatogênico da retina. MÉTODOS: Estudo prospectivo de pacientes submetidos a retinopexia pneumática ou introflexão escleral com seguimento feito por meio de exame oftalmológico completo e tomografia de coerência óptica. RESULTADOS: A amostra foi composta por 14 olhos (14 pacientes), sendo 10 (71,4 por cento) submetidos a introflexão escleral e 4 (28,6 por cento), a retinopexia pneumática. A idade variou entre 24 e 59 anos, média de 39,3 anos. Houve correlações negativas entre a acuidade visual final e a idade (r= -0,64 e p= 0,0127) e entre a acuidade visual final e o tempo de descolamento (r= -0,54 e p= 0,0447). Houve correlação positiva entre as acuidades visual do seguimento inicial e final (r= 0,69 e p= 0,0059). Na tomografia de coerência óptica, quatro olhos (28,6 por cento) apresentaram descolamento residual na fóvea, com resolução espontânea e melhora na acuidade visual (p= 0,031); não houve relação entre tempo de resolução e acuidade final (p= 0,5546). CONCLUSÃO: Os resultados mostram que quanto mais jovem o paciente e mais precoce a intervenção cirúrgica, melhor acuidade visual final. Adicionalmente, quanto maior acuidade no início do pós-operatório, melhor acuidade final. Todos os casos de descolamento foveal evidenciados por meio da tomografia de coerência óptica, no pós-operatório, cursaram com reabsorção do líquido subfoveal e melhora da visão.

PURPOSE: To evaluate the structure and function of the macula following rhegmatogenous retinal detachment surgery. METHODS: Prospective study of patients submitted to scleral buckle surgery or pneumatic retinopexy. The follow-up comprised a complete ophthalmologic exam and optical coherence tomography. RESULTS: The sample was composed of 14 eyes (14 patients), 71.4 percent operated with the scleral buckle technique, and 28.6 percent with the pneumatic retinopexy. The age range was from 24 to 59 years (mean of 39.3 years). There was a negative correlation between the final visual acuity and age of patient (r=-0.64, p=0.0127) and between final vision and duration of detachment (r=-0.54, p=0.0447). There was a positive correlation between visual acuity at initial follow-up and that at the final follow-up (r=0.69, p=0.0059). The optical coherence tomography of the initial follow-up showed subclinical foveal detachment in four eyes (28.6 percent of cases); at the final follow-up the retina was applied by itself with improved vision in all eyes (p=0.031), regardless the time span until reapplication (p=0.5546). CONCLUSION: The results show that the younger the patient and the earlier the surgical procedure, the better the final visual acuity. Furthermore, there is a positive correlation between initial and final postoperative vision and, all cases that presented foveal detachment on the optical coherence tomography at the initial follow-up had the retina flattened and the vision improved at the final examination.

Intravitreal bevacizumab for foveal detachment in idiopathic perifoveal telangiectasia.

PURPOSE: To report the use of intravitreal bevacizumab injection for the treatment of foveal detachment in idiopathic perifoveal telangiectasia (IPT). DESIGN: Prospective, interventional case series. METHODS: Three eyes from two patients with IPT and foveal detachments were treated with a 1.25 mg/0.05 ml intravitreal injection of bevacizumab. The following variables were evaluated: visual acuity and optical coherence tomography (OCT) images. RESULTS: The OCT images showed marked reversal of the foveal detachment after the injection, with restoration of foveal depression in all eyes. The vision of all treated eyes improved and remained unchanged up until the last follow-up visit (mean, 24 weeks). CONCLUSIONS: A single intravitreal bevacizumab injection provides short-term improvement in visual acuity and foveal detachment associated with IPT. These findings should be followed by further studies to evaluate the long-term effects on retinal structure and function.

Ki-67 cell proliferation in familial and in esporadic unilateral retinoblastoma: case report.

PURPOSE: Ki-67 is a nuclear protein that is expressed at all phases of the cell cycle except the resting phase. This study is a clinicopathologic observational case report that aims to report on the cell proliferation rates, as measured by the Ki-67 antigen, in two enucleated retinoblastoma eyes. METHODS: One unilateral familial (mother with unilateral disease - patient 1) and one unilateral sporadic retinoblastoma (patient 2) patients were submitted to enucleation without previous treatment. The tumor cell proliferation rate was assessed by the Ki-67 antigen labeling index (stained cells / 100 cells) in five different fields of the tumor. RESULTS: Patient 1 was 23 months old and the tumor was exophytic with associated neovascularization of the iris; patient 2 was 6 years old and the tumor was endophytic with coarse vitreous seeds. Both enucleated eyes presented optic nerve with free surgical margins. Positive Ki-67 cell index in patient 1 varied from 75 to 90 (MD +/- SD: 79.5 +/- 6.61) and in patient 2 from 38 to 60 (MD +/- SD: 46.6 +/- 8.2). CONCLUSIONS: The familial retinoblastoma, besides the earlier age presentation, showed 45.8% more Ki-67 positive cells than the same stage sporadic one. This proliferation rate may explain the earlier presentation age of the tumor in the inherited disease.

Ki-67 cell proliferation in familial and in esporadic unilateral retinoblastoma: case report

PURPOSE: Ki-67 is a nuclear protein that is expressed at all phases of the cell cycle except the resting phase. This study is a clinicopathologic observational case report that aims to report on the cell proliferation rates, as measured by the Ki-67 antigen, in two enucleated retinoblastoma eyes. METHODS: One unilateral familial (mother with unilateral disease - patient 1) and one unilateral sporadic retinoblastoma (patient 2) patients were submitted to enucleation without previous treatment. The tumor cell proliferation rate was assessed by the Ki-67 antigen labeling index (stained cells / 100 cells) in five different fields of the tumor. RESULTS: Patient 1 was 23 months old and the tumor was exophytic with associated neovascularization of the iris; patient 2 was 6 years old and the tumor was endophytic with coarse vitreous seeds. Both enucleated eyes presented optic nerve with free surgical margins. Positive Ki-67 cell index in patient 1 varied from 75 to 90 (MD ± SD: 79.5 ± 6.61) and in patient 2 from 38 to 60 (MD ± SD: 46.6 ± 8.2). CONCLUSIONS: The familial retinoblastoma, besides the earlier age presentation, showed 45.8 percent more Ki-67 positive cells than the same stage sporadic one. This proliferation rate may explain the earlier presentation age of the tumor in the inherited disease.

OBJETIVO: O Ki-67 é antígeno nuclear que se expressa em todas as fases do ciclo celular, exceto no período de repouso. Este é um estudo de casos com correlação clínico-patológica que visa avaliar a taxa de proliferação celular, medida pelo antígeno Ki-67, em 2 olhos enucleados com retinoblastoma. MÉTODOS: Um paciente com retinoblastoma unilateral familiar (mãe com doença unilateral - paciente 1) e outro com retinoblastoma unilateral esporádico (paciente 2) foram submetidos à enucleação ocular sem outro tratamento prévio. A taxa de proliferação celular foi avaliada segundo índice obtido pela contagem de células marcadas com Ki-67, em 5 campos sob microscópia óptica (células marcadas/100 células). RESULTADOS: O paciente 1, com 23 meses de idade, apresentou tumor exofítico com neovascularização de íris associada; o paciente 2, de 6 anos, apresentou tumor de crescimento endofítico, com sementes vítreas importantes. Ambos os olhos enucleados apresentaram margens cirúrgicas do nervo óptico livres de neoplasia. O índice de células positivas no paciente 1 variou de 75 a 90 (Média ± DP: 79,5 ± 6,61), e no paciente 2, de 38 a 60 (Média ± DP: 46,6 ± 8,2). O retinoblastoma familiar, além de sua manifestação em idade mais precoce, apresentou 45,8 por cento mais células positivas que o retinoblastoma esporádico com o mesmo estadiamento. CONCLUSÃO: O retinoblastoma familiar, além de surgimento mais precoce, apresentou 45,8 por cento mais células em proliferação que o retinoblastoma esporádico em mesmo estádio. Essa taxa de proliferação pode explicar a menor idade de aparecimento do tumor nos casos de doença herdada.

[Vitelliform macular detachment associated with basal laminar drusen: case report]. / Descolamento viteliforme macular associado a drusas da lâmina basal: relato de caso.

The vitelliform macular lesion is usually observed in Best's disease and the adult type of foveomacular dystrophy. We describe a rare case of macular vitelliform lesion in association with basal laminar drusen. The patient has been followed at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo for the last four years. The differential diagnosis, clinical evolution, pathogenesis and treatment of this rare condition are discussed.

Descolamento viteliforme macular associado a drusas da lâmina basal: relato de caso / Vitelliform macular detachment associated with basal laminar drusen: case report

Lesão viteliforme da mácula é mais observada nas distrofias de Best e foveomacular do adulto. No presente estudo, os autores relatam caso raro de descolamento viteliforme macular associado a drusas da lâmina basal, acompanhado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo há aproximadamente quatro anos, avaliado periodicamente com exames complementares. Os autores descrevem aspectos relevantes desta doença como etiopatogenia, evolução, diagnósticos diferenciais e tratamento.