Bevacizumab as adjuvant therapy in the management of pterygium: a systematic review and Meta-analysis

AIM: To evaluate the clinical effect of bevacizumab in pterygium treatment. METHODS: A systematic review and quantitative Meta-analysis was performed. PubMed, EMBASE, Web of Science and Cochrane database were searched for eligible literatures published in English until June 2016. The endpoint was recurrence rate and pooled risk ratio (RR) was calculated. RESULTS: Nine eligible studies were included and Meta-analysis results showed no significantly difference in patients treated with bevacizumab in short term follow-up [3mo: RR=0.70 (0.34, 1.45); 6mo: RR=0.55 (0.23, 1.32)] compared with control groups. No significant effects were observed in favor of bevacizumab in subgroup analyses: patients with subconjunctival injection of bevacizumab [3mo: RR=0.95 (0.70, 1.29); 6mo: RR=0.83 (0.55, 1.28)], primary pterygium [3mo: RR=0.59 (0.23, 1.54; 6mo: RR=0.59 (0.23, 1.53)], simple pterygium excision [3mo: 0.32 (0.05, 2.04), P=0.23; 6mo: 0.27 (0.05, 1.53)] and excision with conjunctival autograft [3mo: 1.51 (0.25, 9.15); 6mo: 1.11 (0.06, 21.69)]. CONCLUSION: In this Meta-analysis, we did not found the significant effect of bevacizumab in pterygium treatment, at least in short term follow-up (3mo and 6mo).     

Bevacizumab and Neovascular Age Related Macular Degeneration: Pathogenesis and Treatment

The pathogenesis of neovascular age related macular degeneration (AMD) is multifactorial including inflammation and angiogenesis leading to choroidal neovascularization (CNV). Therapy against vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular AMD. Intravitreal off-label use of bevacizumab proved to be safe. This literature review was conducted to study improvement in visual acuity, change in central retinal thickness (CRT), safety, pharmacodynamics, and possible resistance to intravitreal bevacizumab over a one-year period in eyes with neovascular AMD. We reviewed articles between 1997 and January 2010 that included at least 30 patients with AMD who received intravitreal bevacizumab monotherapy for at least 1 year. The mean number of letters gained, decrease in CRT, and number of injections were 8 letters, 125.3?µm, and 4.3 injections, respectively. Further, randomized prospective clinical trials are needed to determine the efficacy and safety of intravitreal bevacizumab in the treatment of neovascular AMD.     

Repeated bevacizumab injections versus mitomycin C in rotational conjunctival flap for prevention of pterygium recurrence

Aims:

To evaluate the efficacy of repeated bevacizumab injection in rotational conjunctival flap surgery versus rotational conjunctival flap with adjunctive mitomycin C (MMC) or rotational conjunctival flap alone.

Materials and Methods:

Ninety eyes of 90 patients who underwent primary pterygium surgery with rotational flap were evaluated. Patients were randomly assigned to undergo conjunctival rotational flap alone (Group A) or conjunctival rotational flap with either 0.02% MMC application (Group B) or adjunctive subconjunctival 2.5 mg/0.1 ml bevacizumab injection (Group C). Each group consisted of 30 eyes. Recurrence rates at 9 months were evaluated.

Results:

There were no statistically significant differences in mean size of the pterygium across the limbus in terms of length (P > 0.5). The recurrence rates at 9 months were 26.6% (n = 8) in Group A, 13.3% (n = 4) in Group B, and 10% (n = 3) in Group C. The recurrence rates in Group B and C were significantly lower than in Group A (P =0.1806). The recurrence rates were similar in Group B and C (P > 0.05).

Conclusions:

Subconjunctival bevacizumab injection may decrease the recurrence rate of primary pterygium surgery with rotational conjunctival flap. Further studies with a larger population and longer follow-up period are needed to supplement this study.     

Intravitreal Bevacizumab Treatment of Macular Edema Due to Optic Disc Vasculitis

Purpose: To report the efficacy of intravitreal bevacizumab injection in treatment of macular edema in a case of optic disc vasculitis. Design: Retrospective case review. Methods: A patient diagnosed with macular edema due to optic disc vasculitis was treated with intravitreal bevacizumab injection. Results: One week after injection, fundus appearance dramatically improved and macular edema regressed. The patient was followed up for 1 year after injection and there was no recurrence of macular edema. Conclusions: This case suggests that intravitreal bevacizumab treatment might be effective in the management of macular edema in patients with optic disc vasculitis.     

The Experiment Research of Subconjunctival Injections with Etoposide for the Treatment of Retinoblastoma Mice

Purpose: To evaluate the efficacy of subconjunctival injections of Etoposide for retinoblastoma(RB) mice. Method: Twenty-five RB mice were divided into 5 groups for the study(G0-G4). GO for control group received 0.9% sodium chloride injection subconjunctival. G1: 5 RB mice for systemic delivery received 6 systemic administration of Etoposide 150 μg and Cyclosporin A (CSA )1.0mg at 3 days intervals, respectively. G2-G4: 5 RB mice in each group received 6 subconjunctival delivery of Etoposide in 50、75、150μg at 3 days intervals, respectively .To observe the changes of the volume of RB in anterior chamber and the part of conjunctiva for injections of chemotherapeutic drugs. All eyes and conjunctiva and scleras of the part for drugs injections were obtained at 6 weeks after experiment for histopathologic examination. The findings under the light microscope were analysed with software to measure the areas of RB in anterior chambers and the tumor inhibition rate. Results:The volume of RB in anterior chambers for G1 and G2 increase quickly and none of the mice exhibited tumor control. The RB volume increase slowly in G3 and exhibit tumor control in G4. The areas of tumors in G0-G4 are 0.710,0.659,0.634, 0.515,0.235 mm2, respectively. The rate for tumor inhibition in G0-G4 are 0.0%, 7.18%, 10.70%,27.43%,66.90%, respectively. There are statistical significant difference between the G1 and G4 for the volumes of tumors and the rate of tumor inhibition. The pathologic examination of subconjunctiva and sclera for the injective sites showed no pathologic changes. Conclusions: There are significant effects for the method of subconjunctival delivery of Etoposide in RB control, demonstrating a positive dose-related relationship. Subconjunctival injection of Etoposide reached better efficacy in controlling and inhibiting RB cells than systemic delivery of Etoposide for the same dose. The pathologic results showed the subconjunctival delivery of etoposide were safety for conjunctiva and sclera. It would be one of effective and safety method of chemotherapy for RB. Eye Science 2005;21:169-174.     

基质金属蛋白酶在翼状胬肉的表达

目的:研究基质金属蛋白酶(matrix metalloproteinases,MMPs)在翼状胬肉中的分布和活性状态,探讨MMPs在翼状胬肉病理过程中的作用。方法:翼状胬肉切除术患者26例27只眼,静止期18只眼,进行期9只眼,正常人球结膜6例,免疫组织化学法和明胶酶谱法分析MMP-2和MMP-9的表达和活性水平。结果:翼状胬肉标本有MMP-2和MMP-9表达,MMB-2主要分布在基底上皮细胞层,MMP-9在炎症细胞和血管内皮细胞有阳性染色,翼状胬肉静止期MMP-2的活性水平[(235±18.17)扫描单位]和进展期[(221±22.53)扫描单位]比较差异无显著意义(P>0.05),MMP-9活性水平在静止期[(46±32.21)扫描单位]和进展期[(159±19.28)扫描单位]比较差异有显著性意义(P<0.05)。结论:翼状胬肉中MMP-2和MMP-9表达增强,MMP-2和MMP-9活性水平升高可能与翼状胬肉的发展有关。     

Topical vs Subconjunctival Treatment of Bacterial Corneal Ulcers

The efficacy of eye drops and subconjunctival injections in the treatment of bacterial corneal ulcers for each of the following combinations were compared: cefazolin for staphylococcal ulcers, gentamicin for staphylococcal ulcers, and gentamicin for pseudomonal ulcers. Topical and subconjunctival therapy were equally effective in reducing the numbers of viable bacteria in experimental corneal ulcers. Subconjunctival injections produced high but transient peaks followed by persistent low troughs. In contrast, eye drops produced moderate but sustained concentrations throughout the treatment period. Under the conditions of this study, it appears that transient high peaks are not needed to eliminate bacteria effectively from a corneal ulcer. Since eye drops and subconjunctival injections are equally effective, other factors should determine the preferred route or routes of therapy.     

玻璃体腔注射贝伐单抗治疗慢性CSC的长期疗效观察

目的：探讨玻璃体腔注射贝伐单抗(IVB)治疗慢性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)的安全性和长期临床疗效。

方法：我们给予6例6眼慢性CSC患者玻璃体腔注射1.25mg/0.05mL IVB治疗。5例患者在第一次注射后3mo接受了第二次相同剂量的注射。注射后1,3,6,12,24mo时随访观察。观察指标包括治疗前后的最佳矫正视力、眼压、OCT、眼底荧光素造影(FFA)。

结果：第一次玻璃体腔注射IVB后,2例患者视网膜下液(SRF)完全吸收,但其中1例在随访至3mo复发; 3例患者SRF有小幅度上升或下降; 1例患者的SRF先上升后明显下降; 再次进行IVB后,3例患者SRF完全吸收,其他的3例患者SRF无明显变化。但是SRF的吸收与视力的变化并不是同步的。治疗前后1,2a患者的视力变化在统计学上没有显著性差异。随访期间所有患者眼压均在正常范围,无一例出现眼内炎。

结论：玻璃体腔注射IVB对于治疗慢性CSC患者是安全的,对促进SRF的吸收有一定效果,但从长期结果来看,IVB对于慢性CSC患者的远期视力预后无明显作用。     

Intravitreal Combination of Triamcinolone Acetonide and Bevacizumab (Kenacort-Avastin) in Diffuse Diabetic Macular Edema

Purpose: To evaluate the effect of intravitreal injection of the combination of Triamcinolone Acetonide and Bevacizumab in patients with diabetic macular edema.

Materials and Methods: Twenty seven eyes of 17 patients with diabetic macular edema were treated with an intravitreal injection of triamcinolone acetonide (2?mg) combined with bevacizumab (1.25?mg).

Results: During the 6 months follow-up period 24 eyes (89%) had to repeat the treatment according to the monthly follow-up examination.The mean visual acuity and the central macular thickness improved significantly (P<0.05) throughout the follow-up period.

Conclusion: Intravitreal combination of Triamcinolone Acetonide and Bevacizumab seems to be effective in improving visual acuity and macular edema in patients with diabetic maculopathy.     

比较雷珠单抗和贝伐珠单抗对新生血管AMD的疗效

目的：比较玻璃体内注射雷珠单抗与贝伐珠单抗对年龄相关性黄斑变性（ age-related macular degeneration, AMD）的疗效,治疗方案必要时采用。 方法：回顾性分析63例63眼（雷珠单抗治疗组35眼,贝伐珠单抗治疗组28眼）新确诊新生血管年龄相关性黄斑变性患者的资料。治疗12 mo后随访,分析比较两组患者的最佳矫正视力（ BCVA）和黄斑中心凹厚度（ CFT）。采用双尾t检验和单因素方差分析比较两组最佳矫正视力和黄斑中心凹厚度的变化。 结果：雷珠单抗治疗组35眼和贝伐珠单抗治疗组28眼均完成12 mo随访,并记录数据。雷珠单抗治疗组最佳矫正视力均值增加0.1 logMAR;相反,贝伐珠单抗治疗组最佳矫正视力均值下降0.06logMAR（P=0.01）。雷珠单抗治疗组13眼（37%）和贝伐珠单抗治疗组4眼（14%）最佳矫正视力至少增加0.3logMAR。雷珠单抗治疗组平均黄斑中心凹厚度减少41.6μm,贝伐珠单抗治疗组减少8.1μm（P=0.003）。两组平均注射次数是4.46次和4.11次（P〉0.05）。 结论：玻璃体内注射雷珠单抗组在视力和消水肿方面疗效优于贝伐珠单抗组。但是,两种药的疗效和安全性还需要随机的长期临床试验来验证。     

Effect of Cauterization on the Subconjunctival Fibrovascular Reaction in Rabbit Eyes

ABSTRACT

Objective: The purpose of our study is to investigate the effect of episcleral cauterization during conjunctival autograft surgery on subconjunctival fibrovascular reaction in rabbit eyes. Methods: Twenty-four healthy male New Zealand white rabbits were divided into Control Group (n?=?12) and Cautery Group (n?=?12). In the Control Group, a 4?×?4?mm free conjunctival graft was elevated, the underlying Tenon’s capsule was excised, and the free graft was sutured back to its original place with 10-0 nylon sutures. In the Cautery Group, in addition to the same surgical steps, the episclera was cauterized with six gentle touches before the conjunctival graft was sutured back to its original place. The scleroconjunctival block of the operated area was excised at the first month. The sections were stained with hematoxylin and eosine and Masson trichrome and were evaluated using light microscopy. Results: Subconjunctival collagen fibers were increased, and the fibroblast density increased more significantly in the Cautery Group than in the Control Group. The groups were similar regarding vascularization, lymphocytic, and plasmocytic infiltration. Macrophage density was normal in all animals in both groups. Conclusion: Our histopathological examinations indicate that cauterization seems to lead to an increase in subconjunctival fibrosis at the first postoperative month in rabbit eyes.     

Therapeutic effect of subconjunctival injection of bevacizumab in the treatment of corneal neovascularization

Purpose: To investigate the efficacy of subconjunctival injection of bevacizumab in the treatment of patients with corneal neovascularization. Methods: Twenty‐nine eyes of 29 patients with corneal neovascularization were treated with subconjunctival injection [1.25 mg/0.05 ml (seven eyes), 2.5 mg/0.1 ml (15 eyes) and 5.0 mg/0.2 ml (seven eyes)] of bevacizumab. Best‐corrected visual acuity, intraocular pressure and area of corneal neovascularization were measured before injection and at 1 week, 1 month and 3 months after treatment. Results: At 1 week, the mean neovascularized corneal area decreased significantly to 85.5 ± 18.0% (p = 0.01) in the eyes treated with 2.5 mg bevacizumab and to 73.1 ± 23.4% (p = 0.02) in the eyes treated with 5.0 mg bevacizumab. At 3 months, the mean neovascularized corneal area was 93.6 ± 10.6% (p = 0.10 compared to baseline; p < 0.01 compared to 1 week) in the eyes treated with 2.5 mg bevacizumab and 83.3 ± 25.8% (p = 0.03 compared to baseline; p = 0.02 compared to 1 week) in the eyes treated with 5.0 mg bevacizumab. However, there were no significant changes in the areas of the eyes injected with 1.25 mg bevacizumab. Conclusion: Subconjunctival injection of bevacizumab can partially reduce corneal neovascularization in the short term, and the efficacy of this treatment correlates with the injection dose.     

Subconjunctival conbercept for the treatment of corneal neovascularization

AIM: To investigate the effectiveness and safety of subconjunctival injection of conbercept in the treatment of corneal neovascularization (CNV). METHODS: The data on 10 consecutively recruited patients with CNV who received a subconjunctival conbercept (1 mg) once, and measured the area, length, and diameter of neovascularization before and after (1d, 1, 2wk, and 1mo) treatment as well as the occurrence of systemic and ocular complications after treatment were analyzed. RESULTS: There was a statistically significant reduction in the area of CNV one day after treatment (mean±SD: 38.46±11.36 mm2), compared with before treatment (42.46±12.80 mm2, P<0.01). There was also a statistically significant reduction in the length (3.86±1.80 mm vs 4.64±1.77 mm, P<0.01) and diameter (0.044±0.022 vs 0.060±0.026, P<0.05) of CNV, one week after treatment comparing to before treatment. The reduction in all three parameters was maximized at two weeks after treatment (area: 29.49±8.83 mm2, P<0.001; length: 3.50±1.88 mm, P<0.001; and diameter: 0.038±0.017 mm, P<0.01). No severe systemic or ocular complication was observed during the study. CONCLUSION: During the observation period of one-month, subconjunctival injection of conbercept is an effective and safe method for the reduction of CNV. It may be effective as a preoperative drug for neovascular corneal transplantation.     

结膜下植入物注射装置设计及应用

目的：设计一种结膜下膜片注射植入装置并进行动物实验测试其性能。方法：实验研究。设计并制 作一种结膜下植入物注射装置,并在兔左眼利用该注射装置将可降解明胶膜片注射植入（作为试验 组）,右眼作为对照组仅重复穿刺、进针动作,不植入膜片,分别于植入后0、1、2、3 d各取2只兔子, 处死后摘除眼球,制备冰冻切片后行HE染色观察伤口愈合情况。结果：设计的注射装置的针头弧度 曲率半径为18 mm,内径截面为1.96 mm×0.38 mm。利用此装置注射明胶膜片如兔眼结膜下注射后 兔眼未见出血,膜片未见移位。试验组和对照组在相同时间段伤口愈合程度相近,未见明显区别。 结论：该注射装置操作简便省时,有效地克服了常规植入手术创伤,为新型药物缓控释制剂的临床 应用提供新的辅助。     

Serous Retinal Detachment Following Combined Photodynamic Therapy and Intravitreal Bevacizumab Injection

We report a case of serous retinal detachment following combined photodynamic therapy (PDT) and intravitreal bevacizumab injection in subfoveal choroidal neovascularization (CNV).A 53-year-old woman was diagnosed with subfoveal CNV secondary to age-related macular degeneration (AMD) and treated with combined PDT and intravitreal bevacizumab injection. One day after treatment, the patient experienced a sudden decline of vision and optical coherence tomography (OCT) showed serous retinal detachment involving the macula. She was managed conservatively with an oral steroid beginning on the second day of the combined treatment and the subretinal fluid started to decrease one week following the initiation of steroids.This case suggests that combined PDT and intravitreal injection of bevacizumab can be associated with serous retinal detachment. Additional studies are needed to establish the safety and complications following this treatment regimen.     

Bevacizumab (Avastin) for the Treatment of Ocular Disease

The use of intravitreal bevacizumab (Avastin) has greatly expanded since its introduction into ophthalmic care 3 years ago. A PubMed search on 1 August 2008 revealed 51 ocular disease processes that have been treated with bevacizumab. The majority of publications consist of case reports or retrospective case series and their number is increasing quickly. It is important to collate the experiences gained to date to properly inform our clinical decision making and improve the design of future clinical trials. Current studies cannot easily be combined in a meta-analysis given the lack of standardized data and the wide variety of disorders studied in small numbers. This paper will describe the attempted uses of intravitreal bevacizumab and its efficacy for each ocular disease in addition to discussing safety. Comments regarding appropriate use of this treatment are based on our current level of knowledge. It is clear that the initial encouraging results described in this paper warrant further study of intravitreal bevacizumab in larger, controlled, randomized trials.     

Prospective Comparison of Low-Fluence Photodynamic Therapy Combined with Intravitreal Bevacizumab versus Bevacizumab Monotherapy for Choroidal Neovascularization in Age-Related Macular Degeneration

Abstract

Purpose: To evaluate combination treatment with reduced-fluence photodynamic therapy (RDPDT) with Verteporfin and intravitreal bevacizumab, compared to bevacizumab alone, for choroidal neovascularization (CNV) in age-related macular degeneration. Methods: This was a prospective, randomized comparative study comprising 95 patients with CNV. 49 patients received RDPDT (25?J/cm²) followed by intravitreal bevacizumab 1.25?mg one hour later, while 46 received intravitreal bevacizumab alone. Patients were followed for 12 months at four-week intervals with visual acuity (VA) assessment and Optical Coherence Tomography (OCT) of the macula. Bevacizumab re-injections were performed as needed. Results: On average, patients were re-injected 4.45 times in the combination group and 6.96 times in the bavacizumab group (p?<?0.001). At 12 months, VA improved by 8.64 letters in the bevacizumab group and by 8.37 letters in the combination group (p?=?0.922). Conclusion: Adding a reduced-fluence PDT arm in combination with bevacizumab offers similar results to those of intravitreal bevacizumab alone with significantly reduced number of injection repetitions.     

Measurement of central corneal thickness and pre-corneal tear film thickness of rabbits using the Scheimpflug system

AIM:To measure central corneal thickness (CCT) and pre-corneal tear film thickness using the Galilei dual-Scheimpflug analyzer (GSA) in New Zealand white rabbits.METHODS:Ten normal New Zealand white rabbits (20 eyes) were included in this study. With the assistance of 0.1% fluorescein, the pre-corneal tear film can be well visualized. Both eyes of each rabbit were scanned once with the GSA pre- and post-instillation of 1μL 0.1% fluorescein. The difference between the two measurements of CCT (4-mm diameter) was recorded as the pachymetric values of the central tear film.RESULTS:The CCT of pre- and post-instillation was 388.8±9.5μm and 407.0±10.5μm, respectively. After a paired t-test analysis, the central pre-corneal tear film thickness of 4mm diameter was 18.2±5.31μm with a 95% confidence interval of (15.7, 20.6)μm (P<0.001).CONCLUSION:GSA can be used to measure CCT and analyze central tear film thickness of rabbits with the help of fluorescein.     

Design and Application of a Subconjunctival Implant Injection Device

Objective: To design a subconjunctival implant injection device; to test its performance on rabbits in vivo as the model animal. Methods: A subconjunctival implant injection device was manufactured. Gelatin film was injected via the device into the left eye of rabbits (as the test group), the right eye as the control group just repeat the puncture and insertion actions without implantation of the film. After the implantation, 2 rabbits were selected to be sacrificed at the time points of 0, 1, 2 and 3 d. The eyeballs were removed and the wound healing was observed with hematoxylin-eosin staining. Results: The device with a curvature radius of the 8 mm needle and an inner diameter section of 1.96 mm×0.38 mm. No bleeding at the injection site and no translocation of the gelatin film were observed after injection with this device. The wound healing degree in the same time period between the experimental group and the control group was almost identical without any obvious difference. Conclusions: The injection device is simple and time-saving during film implantation, effectively overcoming the trauma of conventional implant surgery, which might provide new assistance for the clinical application of novel, sustained drug-release formulations.