Ocular surface toxicity of depatuxizumab mafoditin (ABT-414): case reports / Toxicidade do depatuxizumabe mafodotina (ABT-414) na superfície ocular: relatos de casos

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.

Primary malignant melanoma of the uterine cervix treated with pembrolizumab after radical surgery: a case report and literature review

Malignant melanoma of the genital tract is a rare disease that is usually diagnosed by chance. When a definite diagnosis is delayed, the prognosis is very poor without standardized treatment. Herein, we describe a 40-year-old patient who presented with a history of bloody vaginal discharge for 7 months. Gynecological examination showed an exophytic, hard and pigmented cervical mass involving the upper vagina. The patient was diagnosed with cervical melanoma after a punch biopsy and underwent a radical hysterectomy, upper vaginectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. After surgeries, the patient underwent 2-cycles of adjuvant immunotherapy with pembrolizumab, but died within 8 months. In this report, treatment with pembrolizumab after radical surgery was not effective for this patient who had a primary cervical melanoma that metastasized to bone and lung tissue. We do not know why pembrolizumab was ineffective for this patient, but there are several possible explanations; further research is needed.

Progresses in the treatment of exudative age-related macular degeneration with anti-vascular endothelial growth factor drugs / 中华眼底病杂志

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.

Efficacy and safety of omalizumab on the treatment of chronic spontaneous urticaria: a meta-analysis / 中华皮肤科杂志

Objective To evaluate the efficacy and safety of omalizumab on the treatment of chronic spontaneous urticaria (CSU) by systemic review and meta-analysis.Methods Electronic databases,such as PubMed,Clinicaltrials.gov,the Cochrane Database of Systematic Reviews,and the Cochrane Central Register of Controlled Trials,were searched to collect randomized controlled trials (RCTs) about the efficacy and safety of omalizumab in the treatment of CSU.Two reviewers independently screened RCTs according to the inclusion and exclusion criteria,extracted data,and assessed the quality of the included RCTs.And then,a meta-analysis was carried out by using RevMan 5.3 software for comparisons of the efficacy and safety of the 75-,150-,300-,600-mg omalizumab groups versus the placebo group after 1-month treatment,as well as the total omalizumab group versus the placebo group.Results A total of 7 RCTs involving 1 365 patients were included in this meta-analysis.The results showed that the total omalizumab group and different omalizumab subgroups were superior in improving the urticaria activity score of 7 days (UAS7) and wheal number score of 7 days to the placebo group (all P ＜ 0.05).For the improvement in the itch severity score (ISS) of 7 days and complete response rate for main symptoms (UAS7 =0),the total omalizumab group,75-,150-and 300-mg omalizumab groups were superior to the placebo group (all P ＜ 0.05),but there were no significant differences between the 600-mg omalizumab group and the placebo group (P =0.07).The dermatology life quality index (DLQI) was better in the total omalizumab group,150-and 300-mg omalizumab groups than in the placebo group (all P ＜ 0.05),but no significant difference was observed between the 75-mg omalizumab group and the placebo group (P =0.50).There were no significant differences in the incidence of common adverse events or serious adverse events between the total omalizumab group as well as the 75-,150-and 300-mg omalizumab subgroups and the placebo subgroup (all P ＞ 0.05).Conclusions Omalizumab can improve clinical symptoms and life quality of patients with CSU,and is effective in improving the UAS,ISS,wheal number score,DLQI and complete response rate for main symptoms (UAS =0) with high safety.Subcutaneous injection of omalizumab at a dose of 150 or 300 mg/month shows the best efficacy in improving the clinical symptoms and life quality of patients with CSU.

Therapeutic efficacy and significance of intravitreal injection of ranibizumab for age-related macular degeneration with subfoveal scarring and active lesion / 中华实验眼科杂志

Background Intravitreal injection of ranibizumab is a primary approach to the treatment of wet age-related macular degeneration (wAMD),but whether it is necessary for wAMD with subfoveal scarring and active lesion to receive the intravitreal injection of ranibizumab is in dispute.Objective This study was to evaluate the possible therapeutic effect of intravitreal injection of ranibizumab on wAMD with subfoveal scarring and active lesion.Methods The clinical data of the patients with wAMD with subfoveal scarring and active lesion were retrospectively analyzed,including 89 eyes of 89 cases who received diagnoses and treatments in Second Hospital of Yunnan Province from February 2013 to May 2015.Sixty-eight patients who received intravitreal injections of ranibizumab were treated group,and 21 patients who received clinical observations only served as the untreated group.Intravitreal injection of ranibizumab was carried out following the 3+prn principle,and all of the patients were followed-up for 6-24 months.Best corrected visual acuity (BCVA) of the patients were examined with ETDRS chart.The fundus findings was examined by fundus color photography and fundus fluoresceinangiography (FFA).The subjective assessment of visual improvements was obtained from each patient,and the recession of retinal active lesions was assessed by OCT,including the absorbing state of subretinal fluid,the change of central retinal thickness (CRT) and subfoveal scarring.Results The mean injection times were (4.1 ± 1.2) for each eye.The BCVA at the end of following-up was evidently improved in both groups,and no significant difference was found among various time points (P＞0.05).However,the patient rate of BCVA improvement was 69.12％ in the treated group,which was signnificantly higher than 28.58％ of the untreated group (P =0.016).In the treated group,subretinal fluid was gradually absorbed in all eyes in the treating duration,however,in the untreated group,the fluid was completely absorbed in 7 eyes,unchanged in 8 eyes and increased in 6 eyes.The CRT reduced by (220.16±34.76) μm in treated group,and that in the untreated group was (101.56±31.59) μm,showing significant difference between them (P =0.004).The patient rate of perceived improvement of vision was 91.12％ and 42.85％ in the treated group and untreated group respectively,with significant difference between the two groups (P=0.008).Conclusions Intravitreal injection of ranibizumab can make active lesion recess in end-stage wAMD with subfoveal scarring and active lesion and improve the life quality of the patients.

Influence of repetitive intravitreal ranibizumab for neovascular age-related macular degeneration on retinal pigment epithelium and choroidal thickness / 中华实验眼科杂志

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.

Recent advances in biomarkers for the targeted therapy of metastatic colorectal cancer / 中华检验医学杂志

Colorectal Cancer (CRC) is a kind of molecular diversified neoplasm.For nonmetastatic early CRC patients who received surgery based systemic treatment,the 5 years survival rate is as high as 50％-80％.However,only chemotherapy is available for majority of metastatic advanced CRC patients.The effect of chemotherapy is disappointing.Numerous studies have demonstrated that some patients with metastatic advanced CRC can benefit from anti-EGFR and anti-VEGF monoclonal antibodies.Here,we give a brief overview about the clinical research of the detection of KRAS,BRAF,MSI and HER2in guiding treatment with targeted drugs in metastatic advanced CRC

Alemtuzumab in refractory Sézary syndrome

Abstract: Sézary syndrome is a primary cutaneous T-cell lymphoma characterized by the triad of erythroderma, lymphadenopathy and circulating atypical cells. The emergence of new molecular targets has enabled the development of drugs such as alemtuzumab, an anti-CD52 monoclonal antibody, which has shown promising results in the treatment of this entity. We report the case of a 70-year-old male with refractory Sézary syndrome in whom treatment with alemtuzumab achieved an 80% skin lesion clearance with complete haematologic and radiologic response. The treatment was discontinued after 4 months due to adverse effects, with the patient showing a sustained response without disease progression after 13 months of follow-up.

A comparative study on conbercept and triamcinolone acetoinde intravitreal injection for macular edema secondary to central retinal vein occlusion / 中华实验眼科杂志

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.

Inhibitory effects of bevacizumab on filtering bleb scarring following trabeculectomy in rabbits / 中华实验眼科杂志

Background The primary reason to trabeculectomy failure is fibrosis of conjunctiva and episclera because of progressive fibroblast proliferation and collagen deposition of the filtration bleb.Conventional methods of inhibiting bleb scarring was intraoperative application of mitomycin C (MMC),but many complications occured after surgery.Researches showed that bevacizumab was an antifibrotic agent,and whether it can suppress scarring of filtering bleb after trabeculectomy is concerned.Objective The aim of this study was to evaluate the antifibrotic efficacy of bevacizumab after trabeculectomy in rabbits.Methods Forty New Zealand rabbits were randomly divided into four groups.Trabeculectomy was performed on the right eyes of each rabbits.The rabbits received subconjunctival injection of 0.05 ml bevacizumab (25 mg/ml) at the end of operation in the bevacizumab single injection group.The same dose of bevacizumab was respectively injected at the end of operation as well as 3 days and 7 days after operation in the bevacizumab repitition injection group,and 0.05 ml normal saline solution was used in the same way in the normal saline group.In the MMC group,MMC cotton patch with 0.2 mg/ml was placed under the Tenon caplsule and scleral flap for 3 minutes during operation.The intraocular pressure (IOP),bleb area and shape were evaluated during the 28-day period.The animals were sacrificed on postoperative day 14 and 28,respectively for the histopathologic examination of bleb.The expression of CD31 in the bleb was detected by immunohistochemistry for the calculation of microvessels.All experiments were performed in accordance with the ethics code for animal experimentation and approved by the Institutional Review Board of Tianjin Eye Hospital.Results No significant difference was found in the postoperative IOP among the groups (F =0.88,P =0.47).Compared with the bevacizumab single injection group,MMC group and normal saline group,the shape of bleb was higher and much diffuse with sparse vessels 7 days after operation in the bevacizumab repitition injection group.The survival time of bleb was 27 days,19 days and 13 days in the bevacizumab repitition injection group,the bevacizumab single injection group,MMC group and normal saline group,respectively.The percentage of collagen deposition area was (49.18±1.54)％,(26.41±1.23)％,(50.68±1.87)％ and (70.63±1.81)％ at day 14 postoperative in the bevacizumab single injection group,bevacizumab repitition injection group,MMC group and normal saline group,respectively,with the largest area in the normal saline group,and percentage of collagen deposition area was significantly reduced in the bevacizumab repitition injection group compared with the bevacizumab single injection group (all at P＜0.05).The percentage of collagen deposition area was (66.82±1.53)％ at day 28 postoperative in the bevacizumab repitition injection group,while complete scarring was seen in other 3 groups.The number of microvessels was least at postoperative day 14 in the bevacizumab repitition injection group compared with the bevacizumab single injection group,MMC group and normal saline group (all at P ＜ 0.05).The number of microvessels was more in postoperative day 28 in the bevacizumab repitition injection group (3.51 ±0.31) compared with other groups (all at P ＜ 0.05).Conclusions Subconjunctival injection of bevacizumab following trabeculectomy can improve the successful rate of surgery by remaining the survival time of filtering bleb,inhibiting the bleb scarring in rabbits.

The relationship between central retinal thickness relative change and visual prognosis in diabetic macular edema patients following intravitreal injection of ranibizumab / 中华实验眼科杂志

Background The studies on intravitreal ranibizumab for diabetic macular edema (DME) primarily focuses on the absolute change of central retinal thickness, while the affection of the relative change of central retinal thickness (RCRT) or relative change of central retinal thickening (RCRTing) on visual prognosis has not been elucidated completely.Objective This study aimed to evaluate the effect of RCRT and RCRTing in assessing visual prognosis in DME patients following intravitreal injection of ranibizumab.Methods A self-controlled observational study was designed.Thirty eyes of thirty patients with clinically significant DME (CSDME) were recruited in Beijing 401 Hospital of China Nuclear Industry from November 2013 to October 2014.Ranibizumab of 0.05 ml (10 mg/ml) was intravitreally injected by 30G syringe needle at 3.5 mm posterior corneal limbus.Best corrected visual acuity (BCVA) far 2.5 meters away modified ETDRs visual chart was examined before injection and 3 and 6 months after injection,and the BCVA difference value between before injection and 6 months after injection was calculated as the absolusion BCVA (ABCVA).Spectral domian optical coherence tomography (SD-OCT) system was employed to measure the central retinal thickness (CRT) and to calculate the RCRT and RCRTing value.The correlations of RCRT or RCRTing with ABCVA was analyzed.Results The LogMAR values were (0.66±0.20) ,(0.40±0.25) BCVA and (0.37±0.25) before injection and 3,6 months after injection respectively in the CSDME patients,with a significant difference among them (F =36.79,P＜0.05).The values were obviously improved 3 and 6 months after injection compared with before injection (both at P＜0.05).The mean ABCVA (LogMar) of the patients was (0.30±0.21).The CRT 3,6 ,pmyjd sgyrt omkrvyopm values were (508.63±130.44), (331.07±71.84) and (311.77±64.47)μm before injection and respectively in the CSDME patients, showing a significant difference among them (F=49.78,P＜0.05).The CRT values were evidently reduced 3 and 6 months after injection in comparison with before injection (both at P＜0.05) ,and the mean ACRT value was (196.87±140.59) μm.The ABCVA values were (0.13±0.13),(0.44±0.14),(0.07±0.09) and (0.41±0.15) LogMAR in the RCRT＜35％ group,RCRT≥ 35％ group,RCRTing＜69％ group and RCRTing ≥ 69％ group, respectively.Significant differences were found in ABCVA between the RCRT＜35％ group and RCRT≥35％ group (t=-6.27,-8.65,both at P＜0.05).RCRT and RCRTing showed the positive correlations with ABCVA in the CSDME patients (r =0.86,0.79, P ＜ 0.05).Conclusions RCRT and RCRTing can identify well the optimal responders to intravitreal ranibizumab and predict BCVA improvement after treatment.RCRT has better association with ABCVA than RCRTing.RCRTing may be preferable when retinal thickening is more severe.

Macular choroidal thickness changes following intravitreal injection of ranibizumab for central retinal vein occlusion / 中华实验眼科杂志

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.

Influence factors and strategies of anti-VEGF therapy for wet AMD / 中华实验眼科杂志

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.

Drastic effect of ranibizumab on choroidal neovascularization in idiopathic angioid streaks / Efeito dramático do ranibizumabe na neovascularização de coroide em estrias angióides idiopáticas

ABSTRACTA 28-year-old man presented with bilateral vision loss. His best-corrected visual acuity (BCVA) was 0.3 in the right eye (OD) and 0.6 in the left eye (OS). Fundoscopy and fluorescein angiography showed angioid streaks encircling the optic discs of both eyes (OU). Spectral Domain Optical Coherence Tomography (SD-OCT) showed bilateral macular serous detachment. Systemic and ocular screening tests showed no specific cause for the angioid streaks. The patient had previously received pegaptanib sodium injection on three occasions, photodynamic therapy in OS, and no treatment in OD. Upon intravitreal injection of ranibizumab (twice in OU), subretinal fluid was nearly eliminated in OU. BCVA increased to 0.6 in OD and 0.9 in OS, and remained improved until 6 months after treatment.

RESUMOUm homem de 28 anos apresentou-se com perda de visão bilateral. A melhor acuidade visual corrigida (BCVA) era 0,3 no olho direito (OD) e 0,6 no olho esquerdo (OS). A fundoscopia e a angiofluoresceinografia demonstraram estrias angióides ao redor dos discos ópticos em ambos os olhos (OU). A tomografia de coerência óptica de domínio espectral (SD-OCT) demonstrou descolamento seroso macular bilateral. Testes de triagem sistêmicas e oculares não mostraram causa específica para estrias angióides. O paciente tinha um historia de três tratamentos com injeção de pegaptanibe sódico e terapia fotodinâmica em OS e nenhum tratamento em OD. Após a injeção intravítrea de ranibizumabe (duas vezes em OU), fluido sub-retiniano quase desapareceu em OU. BCVA melhorou para 0,6 em OD e 0,9 em OS e não se alterou até o sexto mês de tratamento.

Safety and feasibility of the use of a bevacizumab-methylcellulose mixture as an adjunct to glaucoma surgery: a pilot study / Segurança e viabilidade do uso de uma mistura de bevacizumabe-metilcelulose como terapia adjuvante à cirurgia anti-glaucomatosa: um estudo piloto

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.

Anatomical and visual outcomes of ranibizumab injections in retinal pigment epithelium tears / Resultados anatômicos e visuais de injeções de ranibizumab em roturas do epitélio pigmentado da retina

ABSTRACT Purpose: To report the anatomical and visual results in patients diagnosed as having retinal pigment epithelium (RPE) tears after receiving ranibizumab injections. Methods: Eyes diagnosed as having RPE tears with a minimum 6-month follow-up were retrospectively evaluated. Each eye was treated with at least three doses of ranibizumab at monthly intervals. Best-corrected visual acuity (BCVA), anterior segment findings, intraocular pressure, and fundus examination results were evaluated during control visits. Color fundus photography, fundus fluorescein angiographies, fundus autofluorescence, and spectral domain optical coherence tomography (SD-OCT) images were obtained. The height of pigment epithelial detachment (PED) was measured by SD-OCT. Results: Twelve eyes with RPE tears were studied. Nine eyes (75%) developed RPE tears during ranibizumab injections for choroidal neovascularization (eight eyes with vascularized PED and one eye with choroidal osteoma), and tears occurred in three eyes before any injections. The median number of ranibizumab injections after diagnosis of RPE tears was 3 (min 2, max 5). In the most recent follow-up visit, there was no statistically significant correlation between the grade of RPE and logMAR of BCVA (p>0.05, r=0.112). Eight of twelve eyes had PED, and seven of these had irregular PED contours before injection therapy. The mean PED height was 447 ± 122 µm. Conclusions: In this series, RPE tears developed mostly after intravitreal anti-VEGF injections for vascularized PED. Increased vertical height and irregular contours of the PEDs can be risk factors for the formation of RPE tears. The continuation of anti-VEGF therapy after tear formation is beneficial for vision improvement in eyes with RPE tears. .

RESUMO Objetivo: Apresentar os resultados anatômicos e visuais de injeções de ranibizumab em pacientes que foram diagnosticados com roturas do epitélio pigmentado da retina (RPE). Métodos: Olhos com um mínimo de seis meses de acompanhamento após diagnóstico de roturas do RPE foram avaliados retrospectivamente. Cada olho foi tratado com, pelo menos, três doses de ranibizumab em intervalos mensais. Acuidade visual com a melhor correção (BCVA), achados do segmento anterior, pressão intraocular e exames de fundo de olho foram avaliados nas visitas de controle. Retinografia colorida, angiografias fluoresceínicas, autofluorescência de polo posterior e tomografia de coerência óptica imagens de domínio espectral (SD-OCT) foram obtidos. A altura do descolamento do epitélio pigmentado (PED) foi medida com SD-OCT. Resultados: Doze olhos com roturas do epitélio pigmentado da retina foram incluídos no estudo. Nove olhos (75%) desenvolveram roturas do epitélio pigmentado da retina durante as injeções ranibizumab para neovascularização de coroide (oito olhos com descolamento do epitélio pigmentado vascularizado e um olho com osteoma de coroide), a rotura ocorreu em três olhos antes de quaisquer injeções. A mediana do número de injeções de ranibizumab após o diagnóstico da rotura do RPE foi de 3 (mínimo 2, máximo 5). Na visita de acompanhamento mais recente, não houve correlação estatisticamente significante entre o grau de RPE e logMAR de BCVA (p>0,05, r=0,112). Oito dos doze olhos tinham descolamento do epitélio pigmentado, desses, 7 olhos tinham PEDs com contornos irregulares antes da injeção. A altura média do PED foi 447 ± 122 µm. Conclusões: Nesta série, as roturas de epitélio pigmentado da retina aconteceram principalmente após a injeção intravítrea anti-VEGF para descolamento do epitélio pigmentado vascularizado. O aumento da altura vertical e contornos irregulares dos PEDs podem ser considerados fatores de risco para a formação da rotura ...

Therapeutic effect and safety of 23G pars plana vitrectomy assisted by ranibizumab for severe proliferative diabetic retinopathy / 中华实验眼科杂志

Background Pars plana vitrectomy (PPV) is a main method of treating severe proliferative diabetic retinopathy (PDR) , but intraoperative bleeding often occurs, which affects the intraoperative process and final prognosis.Intravitreal injection of ranibizumab (IVR), a vascular endothelial growth factor (VEGF) monoclonal antibody,has been used in PPV,so the evaluation of therapeutic effect and safety of PPV associated by IVR is very important.Objective This study was to evaluate the effect of IVR-assisted 23G PPV on patients with severe PDR.Methods The clinical data of 82 eyes of 77 patients with severe PDR who received 23G PPV from August 2012 to December 2013 were respectively analyzed,including 49 eyes undergone IV R-assisted 23G PPV (IVR combined with PPV group) and 33 eyes undergone 23G PPV only (simple PPV group).IVR (0.5 mg/0.05 ml) was performed on the eyes 5-7 days before PPV in the IVR combined with PPV group,and only PPV was carried out in the simple PPV group.Operative duration, endodiathermy times, incidence of iatrogenic retinal holes, best corrected visual acuity (BCVA) (LogMAR), postoperative bleeding, re-operation rate, Ⅰ phase attached rate of retinas, occurrence rate of neovascular glaucoma and temporary ocular hypertension rate were compared between the two groups.Results The average operation duration was (71.90-± 26.42) minutes in the IVR combined with PPV group, which was significantly shorter than (96.76±25.15) minutes in the simple PPV group (t =-4.300, P＜0.05).Endodiathermy time in the IVR combined with PPV group was significantly less than that in the simple PPV group (0.76±0.14 versus 2.18±1.64) (x2 =-4.284,P＜0.01).The BCVA at postoperative 3 months was (0.70±0.50) and (0.74±0.50) in the IVR combined with PPV group and simple PPV group,which was significantly improved in comparison with before operation (1.73±0.50,1.70±0.470) respectively (t=-0.151,0.118,both at P＜0.01),but no significant difference in the postoperative BCVA between the two groups (t =-0.318, P =0.758).The incidence of iatrogenic retinal holes was significantly lower in the IVR combined with PPV group than that in the simple PPV group (6.12％ versus 21.20％) (x2 =4.193 ,P=0.041).In addition,the postoperative bleeding rate was also significantly different between the IVR combined with PPV group and the simple PPV group (2.04％ versus 15.15％) (x2=6.580, P=0.010).No significant differences were seen in the incidence of re-operation rate, I phase attached rate of retinas,occurrence rate of neovascular glaucoma and temporary ocular hypertension rate between two groups (all at P＞O.05).Conclusions IVR before 23G PPV can reduce the risk of intravitreal bleeding during operation and after surgery,shorten operation duration and lessen the incidence of iatrogenic retinal break.The BCVA after IVR-assisted PPV improves as good as simple PPV.

Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis / Doença pulmonar intersticial aguda induzida por adalimumabe em paciente com artrite reumatoide

The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.

O uso de imunobiológicos no tratamento das doenças autoimunes é cada vez mais frequente na prática médica. Terapias anti-TNF têm sido cada vez mais utilizadas nas doenças autoimunes refratárias, especialmente na artrite reumatoide, com resultados promissores. Entretanto, o uso dessas terapias está relacionado ao aumento do risco do desenvolvimento de outras doenças autoimunes. Adicionalmente, o uso de agentes anti-TNF pode determinar repercussões pulmonares, como a reativação de infecções por micobactérias e fungos e o desenvolvimento de sarcoidose e de outras doenças pulmonares intersticiais (DPIs). A associação de DPI e uso dos agentes anti-TNF, em especial infliximabe e etanercepte, já foi descrita. O adalimumabe é a mais nova droga dessa classe, e algumas publicações sugerem que seu uso pode determinar a indução ou mesmo a exacerbação de DPIs preexistentes. Neste estudo, relatamos o primeiro caso de DPI aguda secundária à utilização de adalimumabe, em uma paciente portadora de artrite reumatoide sem DPI prévia no Brasil.

Intravitreal ranibizumab and bevacizumab therapy for choroidal neovascularization in age-related macular degeneration with extensive pre-existing geographic atrophy / Avaliação da resposta da injeção intravítrea de ranibizumab e bevacizumab em pacientes com neovascularização de coroide da degeneração macular relacionada à idade com atrofia geográfica extensa pré-existente

PURPOSE: To report the response of choroidal neovascularization to intravitreal ranibizumab or bevacizumab treatment in the setting of age-related macular degeneration with extensive pre-existing geographic atrophy of the retinal pigment epithelium. METHODS: This is a retrospective case series of 11 eyes in ten consecutive patients retrieved from a photographic database. The patients were treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration with pre-existing geographic atrophy. Patients were included if they had geographic atrophy at or adjacent to the foveal center of at least 1 disc area in size that was present before the development of choroidal neovascularization. The best corrected visual acuity and optical coherence tomography analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab or bevacizumab were administered until there was complete resolution of subretinal fluid on optical coherence tomography. Data over the entire follow-up period were analyzed for overall visual and optical coherence tomography changes. RESULTS: The patients received an average of 7 ± 3 intravitreal injections over the treatment period. Seven of 11 eyes had reduced retinal thickening on optical coherence tomography. On average, the central macular thickness was reduced by 72 ± 115 µm. Six of these 7 eyes had improvement of one or more lines of vision and one had no change. The average acuity change for all patients was -0.04 ± 0.46 logMAR units, which corresponded to a gain of 0.2 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with resolution of the subretinal fluid and overall stable visual acuity. CONCLUSIONS: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF) agent (ranibizumab or bevacizumab) for choroidal neovascularization in age-related macular degeneration with pre-existing geographic atrophy is effective. Our results are not as striking as published results from large-scale trials of anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization, presumably due to the limitation in the baseline visual acuity caused by the underlying geographic atrophy. The favorable anatomic response with the resolution of subretinal fluid and stable acuity were consistent with other ranibizumab and bevacizumab studies.

OBJETIVO: Avaliação dos resultados da injeção intravítrea de ranibizumab e bevacizumab em pacientes com neovascularização de coróide da degeneração macular relacionada a idade, com atrofia geográfica extensa, pré-existente. MÉTODOS: Este é um estudo retrospectivo de 10 pacientes, 11 olhos com neovascularização de coroide da degeneração macular relacionada à idade, com atrofia geográfica extensa, pré-existente. Os pacientes incluídos apresentaram atrofia geográfica, envolvendo a fóvea ou adjacência, antes do desenvolvimento da neovascularização de coroide. A melhor correção visual e o exame de tomografia de coerência óptica com análise da espessura macular foram registrados em cada visita. As injeções de ranibizumab e bevacizumab intravítrea foram feitas até a resolução do líquido sub-retiniano pela tomografia de coerência óptica e clinicamente. Todos os pacientes tinham seguimento de 6 meses do diagnóstico a 2 anos, com média de 16 meses. RESULTADOS: Onze olhos de 10 pacientes incluídos receberam uma média de 7 ± 3 injeções intravítreas de ranibizumab e bevacizumab, sendo que 7 apresentaram redução do espessamento macular pelo tomografia de coerência óptica. A mácula teve o espessamento reduzido entre 72 ± 115 µm, 6 olhos tiveram melhora de 1 ou mais linhas de visão, um olho teve acentuada diminuição da visão e um outro não teve alteração. A média do resultado do tratamento em logMAR era -0,04 ± 0,46 correlacionando um ganho de visão na tabela de Snellen entre 0,2 ± 4,4 linhas de visão. CONCLUSÕES: Estes resultados sugerem que o uso do ranibizumab e bevacizumab intravítrea para neovascularização de coroide da degeneração macular relacionada à idade em extensa atrofia geográfica pré-existente é eficaz. Há, entretanto dificuldades na avaliação da acuidade visual destes pacientes em virtude da extensa atrofia geográfica que apresentavam e sobre esta ainda a neovascularização de coroide, se comparados a casos em que a neovascularização de coroide não ocorre em atrofia geográfica pré-existente.

Sarcoidosis Induced by Adalimumab in Rheumatoid Arthritis / 결핵및호흡기질환

Adalimumab is a full human monoclonal antibody that inhibits tumor necrosis factor-alpha (TNF-alpha). This has recently been shown to be effective in the treatment of rheumatoid arthritis (RA), ankylosing spondylitis, and other conditions. Sacoidosis is known to be the target for adalimumab but we describe a patient who has developed sarcoidosis with lung involvement during adalimumab therapy for RA. A 48-year-old woman, who was treated with adalimumab for 5 months, was admitted because of chronic cough and both hilar lymphadenopathy on chest radiography. Chest computed tomography revealed the enlargement of multiple lymph nodes in the right supraclavicular, subcarinal, both hilar and right axillary area. She was diagnosed with sarcoidosis based on the biopsy of supraclavicular lymph node, skin and lung through video-associated thoracoscopic surgery, which was non-caseating epitheloid cell granuloma and excluded from a similar disease. She was treated for sarcoidosis with prednisolone and methotrexate instead of adalimumab.