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ABSTRACT The purpose of this study is to report the clinical features and outcomes of ocular surface toxicity following depatuxizumab mafoditin (ABT-414) therapy for unresectable glioblastoma. Ocular signs and symptoms of three patients treated with ABT-414 during a phase III trial for glioblastoma multiforme were evaluated. Both eyes of all patients were damaged during the week after the first infusion of the ABT-414 molecule. In all patients, mild-to-moderate keratitis could be ascertained, along with decreased visual acuity and blurred vision, as well as foreign-body sensation and redness. Symptoms and visual acuity improved 4 weeks. In conclusion, ABT-414 therapy may cause transient ocular surface toxicity. The initiation of artificial tears and lubricant ointment was enough to control the ocular surface signs and symptoms. A multidisciplinary approach, complete ophthalmologic monitorization, and elaboration of protocols are required to adequately manage these patients.
RESUMO Nosso objetivo é relatar as características clínicas e os resultados da toxicidade na superfície ocular após a terapia com depatuxizumabe mafodotina (ABT-414) para glioblastoma irressecável. Os sinais e sintomas oculares de três pacientes que foram tratados com ABT-414 durante um estudo de fase III para glioblastoma multiforme foram avaliados. Ambos os olhos de todos os pacientes foram danificados durante a semana após a primeira infusão da molécula ABT-414. Em todos os pacientes, uma ceratite de leve a moderada pode ser verificada, juntamente com uma diminuição da acuidade visual e visão turva, bem como sensação de corpo estranho e vermelhidão. Os sintomas e a acuidade visual melhoraram em um período de 4 semanas. Em conclusão, a terapia com ABT-414 pode causar toxicidade transitória na superfície ocular. A iniciação com lágrimas artificiais e pomada lubrificante foi suficiente para controlar os sinais e sintomas na superfície ocular. Uma abordagem multidisciplinar, com acompanhamento oftalmológico completo e a elaboração de protocolos são necessários para o manejo adequado desses pacientes.
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Objective To observe the effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at different doses.Methods According to the randomization table,25 healthy rabbits were randomly divided into control group,and voriconazole 50,100,200,and 400 μg groups.Therefore,there were 5 rabbits in each group.The eyes of control group received intravitreal injection of 0.1 ml balanced saline solution,and those treatment groups received 0.1 ml voriconazole injection of corresponding dose.Before the injection and 1,7,and 14 days after the injection,endothelial cell counts and corneal thicknesses were measured;full-field electroretinogram were performed and b-wave amplitudes in maximal combined reaction (Max-R) were recorded.On 14 days after the injection,histologic structures were observed by light microscope and transmission electron microscope.Results There was no significant difference in endothelial cell counts (F=0.320,0.291,0.467,0.649) and corneal thicknesses (F=0.214,0.284,0.360,0.225) with those of control group at any time points (P＞0.05).Before and 1 day after the injection,b-wave amplitudes of each voriconazole group had no significant difference compared with those of control group (F=0.220,0.106;P＞0.05).On 7 days after the injection,b-wave amplitudes decreased significantly at doses of 200 μg and 400 μg (P＜0.05).On 14 days after the injection,there was no significant difference between the the amplitude of 200 μg group and that of control group (P＞ 0.05).However,the amplitude of the 400 μg group decreased continuously and there was still significant difference (P＜0.05).Light microscopy did not reveal any corneal abnormality in both control group and voriconazole groups.The retinas were normal except that of the 400 μg group,which had a thinner and degenerated inner nuclear layer and disordered photoreceptor layer.Under transmission electron microscope,there were no ultrastructure damages of corneas in both control group and voriconazole groups,either.The rabbit retinas of the 50 μg and 200 μg group have normal inner nuclear layer and photoreceptor layer,but degrees of changes in both layers were observed in the eyes of 200 μg and 400 μg group.Conclusions There is no obvious effects on rabbit corneas and retinas after single intravitreal injection of voriconazole at he dose less than or equal 100 μg.There are no obvious effects on rabbit corneas at the dose of 200 μg and 400 μg,while there are damages to the retinas in both functions and histological structures.
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Objective: To evaluate the effect of riboflavin-ultraviolet-A-induced cross-linking (CXL) following corneal alkali burns in rabbits. Methods: The right corneas and limbi of ten rabbits were burned using a 1N solution of NaOH and the animals were then divided into two groups: a control group submitted to clinical treatment alone and an experimental group that was treated 1 h after injury with CXL, followed by the same clinical treatment as administered to the controls. Clinical parameters were evaluated post-injury at 1, 7, 15, and 30 days by two independent observers. Following this evaluation, the corneas were excised and examined histologically. Results: There were no statistically significant differences in clinical parameters, such as hyperemia, corneal edema, ciliary injection, limbal ischemia, secretion, corneal neovascularization, symblepharon, or blepharospasm, at any of the time-points evaluated. However, the size of the epithelial defect was significantly smaller in the CXL group (p<0.05) (day 15: p=0.008 and day 30: p=0.008) and the extent of the corneal injury (opacity lesion) was also smaller (day 30: p=0.021). Histopathology showed the presence of collagen bridges linking the collagen fibers in only the CXL group. Conclusions: These results suggest that the use of CXL may improve the prognosis of acute corneal alkali burns. .
Objetivo: Avaliar o efeito de ligações covalentes de colágeno (cross-linking [CXL]) induzidas pelo tratamento com riboflavina e radiação ultravioleta A após queimaduras por álcali em córneas de coelhos. Métodos: Dez coelhos foram submetidos a queimadura ocular direita abrangendo estruturas da córnea e limbo usando uma solução de NaOH a 1N. A seguir, os animais foram divididos em dois grupos: um grupo controle submetido a tratamento clínico pós dano corneano e um grupo experimental que foi tratado com CXL uma hora após o dano, seguido pelo mesmo tratamento clínico administrado aos controles. Os parâmetros clínicos foram avaliados 1, 7, 15 e 30 dias após a lesão, por dois observadores independentes. Na etapa seguinte, foi realizada a excisão e o exame histológico das córneas. Resultados: Não houve diferenças estatisticamente significantes nos parâmetros clínicos de hiperemia, edema da córnea, injeção ciliar, isquemia límbica, secreção, neovascularização da córnea, simbléfaro ou blefaroespasmo, em qualquer dos momentos da avaliação. Entretanto, o grupo CXL apresentou um defeito epitelial menor (p<0,05) (dia 15: p=0,008 e dia 30: p=0,008) e menor extensão da lesão na córnea (lesão opaca) (dia 30: p=0,021). O exame histopatológico revelou a presença de pontes de colágeno conectando as fibras de colágeno somente no grupo CXL. Conclusões: Estes resultados sugerem que o uso de CXL pode melhorar o prognóstico de queimaduras agudas da córnea causadas por alcáli. .