Tamoxifen retinopathy: a rare but serious complication.

Bentley, Christopher; Davies, Glanville; Aclimandos, Wagih

doi:10.1136/bmj.304.6825.495

Cited by 40 publications

(21 citation statements)

References 6 publications

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“…These drugs could disturb the function of lysosomal enzymes and thus rod outer segment turnover in retinal pigment epithelium. Tamoxifen-induced retinopathy with corneal opacities and changes in the neural retina and retinal pigment epithelium has been widely reported (Griffiths 1987;Bentley et al 1992;Pavlidis et al 1992;Chern & Danis 1993). Toremifene is a new anticancer drug closely related to tamoxifen, but unlike tamoxifen, no oculotoxic or hepatocarcinogenic properties have been seen (Karlsson et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Effects of Tamoxifen, Toremifene and Chloroquine on the Lysosomal Enzymes in Cultured Retinal Pigment Epithelial Cells

Toimela

Salminen

Tähti

1998

Pharmacology & Toxicology

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Abstract:Retinal pigment epithelial cells carry out phagocytosis and digestion of material shed from the photoreceptor outer segments. In this process, the integrity of lysosomal enzymes is of major importance. In the present study the effects of tamoxifen, toremifene and chloroquine on the activity of two lysosomal enzymes (cathepsin D and N-acetyl-P-Dglucosaminidase) in the retinal pigment epithelial cells were studied. Retinal pigment epithelial cells from pig eyes were cultured for two weeks in Dulbecco's Modified Eagle Medium, after which the cells were exposed to 1-40 pM concentrations of tamoxifen citrate, toremifene citrate and chloroquine diphosphate. To eliminate possible medium-borne oestrogenic mechanisms, the test was repeated using phenol red-free medium with charcoal-stripped fetal calf serum. The exposure time was one week, after which the lysosomal enzymes cathepsin D and N-acetyl-P-glucosaminidase were determined. Cellular injuries were assessed by quantifying the leakage of lactate dehydrogenase into the culture medium. Cathepsin D and N-acetyl-P-D-glucosaminidase showed different sensitivities to tamoxifen, toremifene and chloroquine. The main lysosomal protease cathepsin D was more sensitive than N-acetyl-P-D-glucosaminidase to the effects of tamoxifen and toremifene, possibly due to their antioestrogenic properties. The phenol red-free medium with charcoal-stripped serum seemed to make the drugs more effective than the reference medium. Chloroquine had only a minor effect on the lysosomal protease cathepsin D, but a clearer effect could be seen on N-acetyl-P-glucosaminidase.

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Section: Discussionmentioning

confidence: 99%

Effects of Tamoxifen, Toremifene and Chloroquine on the Lysosomal Enzymes in Cultured Retinal Pigment Epithelial Cells

Toimela

Salminen

Tähti

1998

Pharmacology & Toxicology

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“…Subsequent reports have implicated tamoxifen in a variety of forms of ocular toxicity (Pugesgaard & von Eyben 1986;Griffiths 1987;Gerner 1989;Bentley et al 1992).…”

Section: Tamoxifenmentioning

confidence: 99%

Ocular presentations of breast cancer

Wickremasinghe

Dansingani

Tranos

et al. 2006

Acta Ophthalmologica Scandinavica

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IntroductionBreast cancer is the most common malignancy in women (Office of National Statistics 2002). As ophthalmic manifestations are common, the astute ophthalmologist can instigate the search for primary disease when the first presentation is ophthalmic in nature, or, alternatively, play an important role in detecting the metastatic spread of a known primary. Breast cancer accounts for 29% of new malignancies in women in the UK and is a major cause of mortality and morbidity worldwide.The purpose of this article is to provide a review of the ophthalmic manifestations of breast cancer. The subjects covered include the presenting features of metastatic disease involving the visual systems, treatment modalities and strategies currently available, and the ocular effects and complications of treatment. EpidemiologyIncidence rates of breast cancer have increased over the last decade, rising from 90 to 130 per 100 000 population (1988 versus 1998) (Office of National Statistics 2002). In contrast, mortality rates have remained relatively stable since the 1950s. This increase in the incidence of breast cancer is attributed to more effective screening programmes, although a change in the demographics of developed countries and an increasing elderly population may contribute to the growing incidence. Geographical variations exist in breast cancer incidence rates, with higher rates in Europe, North America and Oceania and lower rates in Asia and Africa (Sasco 2001). Doctors practising in the western world should be familiar with the disease.Male breast cancer is rare. The incidence is 0.8-1.5 cases per 100 000 male population, accounting for 1% of all breast cancer diagnoses (Office of National Statistics 2002; Hodgson et al. 2004). The highest incidence occurs in men aged over 70 years (Kidmas et al. 2005). In families with hereditary breast cancer, younger males may be affected. The BRCA2 gene is often implicated in these cases (Lorenzo Bermejo & Hemminki 2005).Ocular manifestations of male breast cancer can occur and this differential diagnosis should not be overlooked (O'Brien et al. 2000;Silvestris et al. 2003;Dieing et al. 2004). Ophthalmic metastases in breast cancerMetastatic disease to the eye from the breast was first described by Johann ABSTRACT.Context: Breast cancer is the most common malignancy in women, with increasing incidence in Europe and North America. The frequency of involvement of the eye and visual pathways is reported to be as high as 30% in patients with known metastatic disease. In some cases, ophthalmic involvement can be the first sign of metastatic spread. Metastasis occurs via the haematogenous route and predominantly involves the choroid. Metastases to other ocular structures, the orbit and the visual pathways have also been described. Paraneoplastic effects are rare but significant. Treatments: Different modalities are employed in the treatment of breast cancer and its metastases. These include chemotherapy and radiotherapy. The ocular adverse effects of these have been well described,...

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“…Uma pequena redução nas amplitudes fotópicas e escotópicas do ERG de campo total foi descrita em uma paciente que recebeu alta dosagem de tamoxifeno para tratamento de câncer de mama metastático (5) . Dois outros casos relatados mostraram ERGs normais em pacientes com alta dosagem de tamoxifeno (14)(15) . Estudos prévios mostraram que anormalidades retinianas podem ocorrer após no mínimo um ano de tratamento com tamoxifeno.…”

Section: Discussionunclassified

Eletrorretinograma multifocal em pacientes tratadas com tamoxifeno em baixa dosagem

Berezovsky¹,

Salomão²,

Pereira³

et al. 2004

Arq. Bras. Oftalmol.

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Eletrorretinograma multifocal em pacientes tratadas com tamoxifeno em baixa dosagemObjetivo: O tamoxifeno é um antiestrógeno utilizado como agente terapêu-tico eficaz no câncer de mama. A droga pode causar efeitos tóxicos oculares em dosagens altas. O objetivo deste estudo foi determinar possíveis efeitos retino-tóxicos centrais usando o eletrorretinograma multifocal (mfERG) em grupo de pacientes tratadas com baixa dosagem de tamoxifeno (20 mg/dia) após cirurgia do câncer de mama. Métodos: O eletrorretinograma multifocal (mfERG) de 30 graus centrais da retina foi obtido em 3 diferentes grupos: Grupo experimental -15 mulheres (41-59 anos, média 48,6 ± 4,5) com fundo de olho normal, tratadas com tamoxifeno em baixa dosagem por 1 a 55 meses. Grupo controle -6 mulheres (30 -76 anos, média 49,9±18,8) com diagnóstico prévio de câncer de mama que não receberam tratamento com tamoxifeno até o teste do eletrorretinograma multifocal. Grupo controle normal -15 voluntárias normais (30-71 anos, média 47,7 ± 12,9). A amplitude e a latência de eletrorretinograma multifocal para N1-P1 foram analisados estatisticamente (análise de variância de uma via). Resultados: As amplitudes médias N1-P1 (nV/grau 2 ) foram comparáveis para respostas de diferentes excentricidades (0 a 25 graus) nos três grupos. Não houve diferença estatisticamente significativa para a latência de N1 e P1 (ms) do eletrorretinograma multifocal entre os 3 grupos. Conclusões: O tratamento com baixa dosagem de tamoxifeno não mostrou efeitos retino-tóxicos em pequeno grupo de mulheres após cirurgia do câncer de mama. Investigação seriada proporcionará melhor compreensão desses efeitos. INTRODUÇÃOO tamoxifeno é uma droga antiestrógena amplamente utilizada como agente terapêutico eficaz em pacientes submetidos à cirurgia do câncer de mama, com o propósito de reduzir a recidiva e a ocorrência de tumor na mama contralateral (1)(2) . A estrutura química do tamoxifeno é similar à de outras drogas bem conhecidas como causadoras de toxicidade ocular, como a cloroquina e a imipramina. O primeiro estudo sobre toxicidade retiniana provocada pelo uso de tamoxifeno mostrou redução significante da acuidade visual em 3 de 4 pacientes tratados com essa droga (3) . A diminuição da acuidade visual foi relacionada à retinopatia, primariamente afetando a mácula e acompanhada por edema macular.Manifestações oculares tais como opacidades corneanas superficiais, diminuição da acuidade visual e evidência de uma retinopatia com pequenos pontos brancos, lesões no epitélio pigmentado da retina e disfunção foveal,

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Tamoxifen retinopathy: a rare but serious complication.

Cited by 40 publications

References 6 publications

Effects of Tamoxifen, Toremifene and Chloroquine on the Lysosomal Enzymes in Cultured Retinal Pigment Epithelial Cells

Effects of Tamoxifen, Toremifene and Chloroquine on the Lysosomal Enzymes in Cultured Retinal Pigment Epithelial Cells

Ocular presentations of breast cancer

Eletrorretinograma multifocal em pacientes tratadas com tamoxifeno em baixa dosagem

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