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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.
ABSTRACT
Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs,including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been proven to be effective in the treatment of wet age-related macular degeneration (wAMD).However,there are still some patients with poor efficacy,such as no response to initial treatment or poor response,and even relapse during the course of treatment.In view of the different targets and molecular characteristics of anti-VEGF drugs,the switch of anti-VEGF drugs and the adjustment of delivery pattern,dosages and intervals have been the strategies to cope with the poor efficacy in clinic.However,there are some differences in the results of current studies.Overall,the recovery of retinal anatomical outcome achieves more benefits,and it is relatively difficult to improve visual acuity.To determine which regimen would get the biggest benefits,a large number of randomized controlled clinical trials and long study period will be needed.
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Background Intravitreal injection of ranibizumab (IVR) is one of the most effective therapies for neovascular age-related macular degeneration (nAMD).Understanding the influence of IVR on retinal pigment epithelium (RPE) and choroidal thickness is helpful for us to choose the operative times and timing based on pharmacologic effects and tissue response.However,limited studies are available about quantitative analysis of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD.Objective This study was to report the changes of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD.Methods A prospective series cases-observational study was designed.Forty-one eyes of 41 consecutive patients with nAMD were enrolled in Renmin Hospital of Wuhan University from January 2015 to June 2015,and written informed consent was obtained from each patient prior to entering the cohort.The affected eyes received intravitreal injection of 0.05 ml ranibizumab (10 mg/ml) and then followed up monthly for 12 months.The RPE atrophy area around macula and subfoveal choroidal thickness were measured by a newly developed RPE analysis software spectral-domain optical coherence tomography (OCT) and enhanced depth imaging of SD-OCT (EDI-OCT),respectively,and the RPE atrophy area and choroidal thickness changes were compared before IVR and 3,6 and 12 months after IVR.The correlation between RPE atrophy area and choroidal thickness before and after IVR was analyzed.Results All the patients finished the treating procedure and follow up.The visual acuity (logMAR) after IVR was considerably improved in comparison with before IVR (F=7.631,P＜0.001).The mean subfoveal choroidal thickness value was (264.55 ± 100.95) μm before IVR,and that of 3,6,12 months after IVR was (247.42±105.46),(246.81± 99.85) and (253.97±101.15)μm,respectively,showing a significant difference among different time points (F =2.030,P ＜ 0.05),and the mean subfoveal choroidal thickness values 3,6,12 months after IVR were evidently thinned in comparison with before IVR (all at P＜0.05).No significant difference was found in RPE atrophic area among different time points (F=0.116,P =0.951).Weak linear correlations were seen between RPE atrophy area and choroidal thickness (r =-0.185),the RPE atrophy area change values and choroidal thickness change values between IVR ＞ 6 times and ≤ 6 times (r =0.297,-0.327),but these results were not statistically significant (P =0.248,0.282,0.103).At the end of the follow up,weak linear correlations were seen in RPE atrophy area change values and choroidal thickness change values with IVR times (r,=-0.266,0.342),but these results were not statistically significant (P =0.148,0.060).Conclusions IVR for nAMD can lead to subfoveal choroid atrophy instead of RPE atrophy.IVR does not accelerate the atrophy progression of both RPE and choroid.
ABSTRACT
Neovascular age-related macular degeneration is also known as wet age-related macular degeneration (wAMD) , which is now one of potentially blinding diseases in elder population worldwide.The application of anti-vascular endothelial growth factor (VEGF) drugs is becoming the first-line therapy for wAMD at present.However, during the long-term follow up, we find that the vision of some patients dose not improve even falls after treatment, or the vision is unable to keep for a long term after its improvement.Hence,to find the key factors that affect the therapeutical effect is the focus issue nowadays.There are many factors that affect wAMD curative effect,including the limitation of drug itself, the personal conditions of the patients, the features of the choriodal neovascularization (CNV) , the formulation and implementation of the treatment regimen, etc.Imaging features of CNV and treatment timing can serve as the available indexs to analyze the prognosis.In addition,reasonable and optimized managing regimens for wAMD probably is an approach to improve the treating effect.Understanding of the factors that affect curative effect of wAMD is benefit for us to setup the individualized therapy and achieve the best vision.Ophthalmologists should fully recognize the importance of wAMD individualized treatment and management.
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Background Central retinal vein occlusion (CRVO) is a common retinal vascular disease.Intravitreal injection of ranibizumab, a vascular endothelial growth factor (VEGF) antibody, is being a useful approach to the treatment of macular edema secondary to CRVO.However,little literature about choroidal thickness variations following intravitreal injection of ranibizumab for CRVO is published up to now.Objective This study was to observe the dynamic changes of macular choroidal thickness after intravitreal injection of ranibizumab in CRVO eyes.Methods A self-controlled series cases study was designed.Thirty-one eyes of 31 CRVO patients were included in Tianjin Eye Hospital from June 2013 to November 2014,with the males 19 and females 12 and mean age of (51.13±16.65) years.Ranibizumab (5 mg,5 ml) was intravitreally injected in the CRVO eyes once per month for 3 times by the same operator.A enhanced depth image (EDI) mode of spectral-domain OCT system was employed to measure the choroidal thickness at subfoveal, 1 mm from fovea nasal and 1 mm from fovea temporal before and 1 month,2,3 months after first injection in both CRVO eyes and contralateral healthy eyes, respectively.The best LogMAR vision was recored.This research protocol was approved by the Ethic Committee of this hospital, and written informed consent was obtained from each individual prior to any medical examination.Results Retinal bleeding was exhibited in the CRVO eyes in color photography,and fundus fluorescein angiography showed the fluorescine leakege in the early phase and fluorescine accummulation in the late phase.The mean choroidal theckness value was (325.32±83.04) , (294.83±80.61), (315.95±90.77) and (314.81±84.98) μm before injection and 1,2,3 months after injection,respectively,showing a significantly difference among various time points (F =7.96,P =0.00) , and the choroidal theckness values were evidently reduced in various time points after injection in comparison with before injection (P =0.01,0.01,0.00).The choroidal thickness value at foveal was (314.81±84.98) μm in the CRVO eyes 3 months after injection,and that in the fellow eyes was (260.47±55.90) ,with significant difference between them (t =2.95, P =0.01).The LogMAR vision was 0.17±0.09,0.37±0.23,0.42±0.26 and 0.49±0.21 before and 1,2,3 months after injection,with the significant difference among various time points (F =21.50, P =0.00) and showed considerable improvement after intravitreal injection of ranibizumab(all at P＜0.01).The mean retinal thickness value was (244.14-±23.28) μm in the fellow eyes, and those in 1 month, 2,3 months after injection were (523.81 ± 147.61), (352.13 ± 166.71),(376.39±209.46) and (369.00±225.61) μm in the CRVO eyes, showing obvious reduce after intravitreal injection, with significant difference among different time points (F =7.09, P＜0.01).Conclusions Choroidal thickness at macular fovea is obviously increased in CRVO eyes compared with the contralateral healthy eyes.Intravitreal injection of ranibizumab can reduce choroidal thickness and therefore improve vision.EDI OCT is available in the evaluation of dynamic change of choroidal thickness.Macular choroidal thickness could be used as a predictor of CRVO prognosis following intravitreal ranibizumab.
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Background Macular edema is one of the serious complications of central retinal vein occlusion (CRVO),and the present therapies are laser coagulation and intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs.Conbercept is humanized-monoclonal VEGF antibody and used for the treatment of retinal vascular diseases.However,fewer studies were focused on its application in macular edema secondary to CRVO.Objective The aim of this study was to compare the effectiveness and safety of conbercept with triamcinolone acetonide(TA)by intravitreal injections for macular edema secondary to CRVO. Methods A non-randomized controlled study was carried out under the approval of the informed consent of patients.Sixty eyes of 60 patients with macular edema secondary to CRVO were included in Weifang Yidu Central Hospital from March 2012 to August 2013.The eyes were divided into the conbercept group and TA group with 30 for each group.Conbercept and TA of 0.05 ml were intravitreally injected in different groups,and the best corrected visual acuity(BCVA),central macular thickness(CMT)measured by OCT,intraocular pressure(IOP)and relavant complications were examined before injection and 1 week,1 month,3 months and 6 months after injection.The treatment outcomes were compared intergrouply and along with time. Results The BCVA was evidently better in 1 week,1 month,3 months and 6 months after injection than that before injection both in conbercept group and TA group(all at P＜0.01),and the BCVA of TA group was better than that of conbercept group 1 week after injection(P＜0.05).The CMT values of Conbercept were(572.00± 100.01),(325.12±91.55),(280.00±92.37),(258.65 ±88.65),(300.00±87.64)μm,and those of TA group were(570.00± 102.21),(345.12±89.31),(290.00±80.27),(309.65 ±84.13)and(303.00±90.59)μm,and CMT value after injection was significantly lower in 1 week,1 month,3 months and 6 months after injection than that before injection both in the conbercept group and the TA group(all at P＜0.05),and CMT value was evidently reduced in the conbercept group compared with the TA group 3 months after injection(P＜0.05).The IOP was(15.20±3.52),(21.20±3.80),(26.40±4.00),(23.60±3.73)and(21.50±3.27)mmHg in the TA group before injection and 1 week,1 month,3 months and 6 months after injection,showing significnatly elavation after injection(all at P＜0.05),and the IOP at different time points was higher in the TA group than that in the conbercept group(all at P＜0.05).However,there was no considerable change of IOP before and after injection in conbercept group(all at P＜0.05). Conelutions Both conbercept and TA are effective for macular edema secondary to CRVO by intravtreal injection.Compared with TA,conbercept is much safer because of less risk of IOP rising after intravtreal injection.
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ABSTRACT Bevacizumab, a monoclonal anti-vascular endothelial growth factor antibody, has been suggested as a potential healing therapeutic following glaucoma surgery. Here, we aimed to improve the bioavailability of bevacizumab when used as an adjunct therapy to non-penetrating deep sclerectomy (DS) by using a bevacizumab-methylcellulose mixture (BMM). Ten previously non-operated eyes in ten patients diagnosed with primary open angle glaucoma underwent DS with a subconjunctival injection of 0.3 ml of BMM (bevacizumab 3.75 mg incorporated into 4% methylcellulose) at the surgical site. Bevacizumab release was evaluated in vitro using size-exclusion high performance liquid chromatography (HPLC). Intraocular pressure (IOP), bleb morphology, corneal endothelial cell count (CECC), and complications were evaluated at 6 months after surgery. Using HPLC, bevacizumab was detected in BMM for up to 72 h. Moreover, all surgical blebs remained expanded with hyaline material during the first week. A significant IOP reduction (mean ± SD= -10.3 ± 5.4 mmHg, P<0.001) and diffuse blebs were observed at the final follow-up period. Although CECC was slightly reduced (-7.4%), no complications were observed. In conclusion, bevacizumab was released from BMM, and the use of this innovative mixture yielded good results following DS with no complications. Further studies are required to determine its efficacy prior to establishing BMM as an adjunct treatment for penetrating and non-penetrating glaucoma surgeries.
RESUMO O bevacizumabe (um agente anti-fator de crescimento endotelial vascular) tem sido sugerido como potencial modulador cicatricial na cirurgia do glaucoma. Este estudo objetivou melhorar a biodisponibilidade do bevacizumabe, investigando a viabilidade de uma nova mistura de bevacizumabe-metilcelulose (BMM) como terapia adjuvante para a esclerectomia profunda não-penetrante (DS). Dez olhos sem cirurgias prévias de 10 pacientes com glaucoma primário de ângulo aberto foram submetidos à DS associada à uma injeção subconjuntival de 0,3 ml da mistura de bevacizumabe-metilcelulose (bevacizumabe 3,75 mg incorporado em metilcelulose 4%) no sítio cirúrgico. A liberação de bevacizumabe foi avaliada in vitro através de cromatografia líquida de alta performance por exclusão de tamanho (HPLC). A pressão intraocular (PIO), a morfologia da ampola de filtração, a contagem de células endoteliais da córnea (CECC) e as complicações foram estudadas aos seis meses de seguimento. O bevacizumabe foi detectado a partir da mistura de bevacizumabe-metilcelulose por meio do HPLC até 72 horas. Além disso, todas as ampolas cirúrgicas permaneceram expandidas com material hialino durante a primeira semana. Uma redução significativa da pressão intraocular (média ± DP= -10,3 ± 5,4 mmHg, P<0,001) e ampolas difusas foram observadas ao final do período de seguimento. Embora a contagem de células endoteliais da córnea se mostrou discretamente diminuída (-7,4%), nenhuma complicação foi observada. Neste estudo, o bevacizumabe foi liberado da mistura de bevacizumabe-metilcelulose e o uso desta nova mistura se associou com bons resultados cirúrgicos e nenhuma complicação. Estudos futuros serão necessários para determinar sua eficácia, antes de se estabelecer a mistura de bevacizumabe-metilcelulose como um tratamento adjuvante às cirurgias penetrantes e não-penetrantes para o glaucoma.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Angiogenesis Inhibitors/pharmacology , Bevacizumab/pharmacology , Glaucoma, Open-Angle/surgery , Methylcellulose/pharmacology , Angiogenesis Inhibitors/therapeutic use , Blister , Bevacizumab/therapeutic use , Chemotherapy, Adjuvant/methods , Drug Combinations , Drug Liberation , Feasibility Studies , Follow-Up Studies , Glaucoma, Open-Angle/drug therapy , Intraocular Pressure , Methylcellulose/therapeutic use , Pilot Projects , Prospective Studies , Slit Lamp , Wound Healing/drug effectsABSTRACT
Purpose: To evaluate retinal morphology and function of patients with advanced neovascular age-related macular degeneration (AMD) before, during, and after treatment with ranibizumab. Methods: Twenty-one eyes diagnosed with advanced AMD were studied with optical coherence tomography (OCT) and multifocal electroretinography (mfERG). Three intravitreal injections of ranibizumab were administered at 1-month intervals. Evaluations were performed before the first injection (D0) and at 30 (D30), 60 (D60), and 90 days (D90) after the first injection and compared to an age-matched control group (n=21 eyes). Results: The thickness of macular retinal layers increased before treatment due to the presence of intraretinal fluid. A thick retinal pigment epithelium-choriocapillaris complex (RPE-CC) suggested the presence of choroidal neovascular membrane. Intraretinal edema decreased after treatment (P<0.01), but persisting RPE-CC thickness resulted in a subretinal scar. Three different annular retinal areas were studied with mfERG (from center to periphery: rings R1, R2, and R3). The amplitude of the first negative component (N1) decreased in R1, R2, and R3 at D30, D60, and D90 when compared with that in controls (P<0.05); the N1 implicit time was delayed in R3 at D30 (P<0.05). The amplitude of the first positive component (P1) was reduced in R1 and R2 at D30, D60, and D90 when compared with that in controls (P<0.01); the P1 implicit time was delayed in R1 at D0 and D60 (P<0.05), in R2 at D0, D30, and D90 (P<0.01), and in R3 at D30 and D60 (P<0.05). Conclusion: Ranibizumab reduces intraretinal edema, even in advanced cases. Central macular activity appeared to increase after the initiation of treatment, improving over time. .
Objetivo: Avaliar a morfologia e função da retina em pacientes com doença macular relacionada à idade (DMRI), neovascular avançada, antes, durante e após o tratamento com ranibizumabe. Métodos: Vinte e um olhos com diagnóstico de DMRI avançada foram avaliados pela tomografia de coerência óptica (OCT) e eletrorretinografia multifocal (mfERG). Três injeções intravítreas de ranibizumabe foram administradas em intervalos de 1 mês. As avaliações foram realizadas antes da primeira injeção (D0) e aos 30 (D30), 60 (D60), e 90 dias (D90) após a primeira injeção e comparados com um grupo controle (n=21 olhos). Resultados: A espessura macular estava aumentada antes do tratamento devido à presença de fluido intrarretiniano, e o aumento da espessura do complexo EPR-CC foi compatível com a presença de membrana neovascular coroidal. O edema intrarretiniano diminuiu após o tratamento (P<0,01). Três diferentes áreas retinianas anulares (do centro para a periferia: anéis R1, R2 e R3) foram consideradas no mfERG. A amplitude do componente N1 diminuiu nos anéis R1, R2 e R3 em D30, D60 e D90 comparados com o grupo controle (P<0,05); e o tempo implícito de N1 aumentou no anel R3 em D30 (P<0,05). A amplitude do componente P1 diminuiu em R1 e R2 nos dias D30, D60 e D90 comparados com os controles (P<0,01); o tempo implícito de N1 aumentou no anel R1 em D0 e D60 (P<0,05), no anel R2 em D0, D30 e D90 (P<0,01) e no anel R3 em D30 e D60 (P<0,05). Conclusão: O ranibizumabe reduziu o edema intrarretiniano, mesmo em casos avançados. A atividade central macular parece aumentar após o início do tratamento e melhorar ao longo do tempo. .