Ranibizumab Injection for Corneal Neovascularization Refractory to Bevacizumab Treatment

Vascular endothelial growth factor inhibitor is an emerging therapeutic modality for various ocular diseases with neovascularization (NV). However, for corneal NV, controversy remains regarding whether bevacizumab or ranibizumab is superior. A 32-year-old female diagnosed with herpetic keratoconjunctivitis with refractory corneal NV despite two previous subconjunctival and intrastromal bevacizumab injections, received two subconjunctival and intrastromal ranibizumab injections. Six months postoperatively, there was significant regression of the neovascular area and vessel caliber. Here, the authors report a case of improvement in corneal NV with subconjunctival and intrastromal ranibizumab injections, which was previously refractory to bevacizumab injection. The findings may suggest a new prospect in treating corneal NV.     

The Effect of Bevacizumab on Corneal Neovascularization in Rabbits

Purpose

To determine the efficacy of topical application and subconjunctival injection of bevacizumab in the treatment of corneal neovascularization.

Methods

Corneal neovascularization was induced with a silk suture of the corneal stroma in 12 rabbits (24 eyes). One week after suturing, four rabbits were treated with topical bevacizumab at 5 mg/mL (group A) and another four rabbits were treated with topical bevacizumab 10 mg/mL (group B) in the right eyes twice a day for two weeks. A subconjunctival injection of bevacizumab 1.25 mg/mL was done in the right eyes of four rabbits (group C). All of the left eyes (12 eyes) were used as controls. The area of corneal neovascularization was measured after one and two weeks, and the concentration of vascular endothelial growth factor (VEGF) in corneal tissue was measured after two weeks.

Results

The neovascularized area was smaller in all treated groups than in the control group (p<0.001). Upon analysis of the neovascularized area, there was no significant difference between groups A and B. However, the mean neovascularized area of group B was significantly smaller than that of group C after two weeks of treatment (p=0.043). The histologic examination revealed fewer new corneal vessels in all treated groups than the control group. The concentration of VEGF was significantly lower in all treated groups compared to the control group (p<0.01), but no difference was shown between treated groups.

Conclusions

Topical and subconjunctival bevacizumab application may be useful in the treatment of corneal neovascularization and further study is necessary.     

Intravitreal Bevacizumab for Treatment of Bilateral Candida Chorioretinitis Complicated with Choroidal Neovascularization

ABSTRACT

Purpose: The purpose of this report is to describe a case of bilateral Candida chorioretinitis complicated with choroidal neovascularization (CNV) and effectively treated with combined intravitreal bevacizumab and amphotericin B.

Results: An 83-year-old patient was diagnosed with Candida chorioretinitis in both eyes. Optical coherence tomography and fluorescein angiography revealed CNV. Treatment using combined intravitreal bevacizumab and amphotericin B was initiated followed by a 4-weekly regimen of bevacizumab, eventually resulting in the regression of the subretinal fluid and intraretinal edema.

Conclusion: Our study supports the combined use of intravitreal bevacizumab and amphotericin B in the management of CNV in Candida chorioretinitis.     

Assessment of Patient Pain Experience during Intravitreal 27-Gauge Bevacizumab and 30-Gauge Ranibizumab Injection

PurposeTo compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures.MethodsSeventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome.ResultsThe VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 ± 0.91 (range, 0 to 3) and 1.94 ± 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients <65 and ≥65 years of age in both the ranibizumab and bevacizumab groups were then compared. For patients <65, there was a significant difference in the average VAS pain scores between groups (p = 0.003). However, for patients ≥65 years, there was not a significant difference in the average VAS pain scores between groups (p = 0.238). Female and male patients in both ranibizumab and bevacizumab groups were also compared. For female patients, there was a significant difference in the average VAS pain scores between groups (p = 0.016), although not for male patients (p = 0.078).ConclusionsThirty-gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.     

Intravitreal Administration of Ranibizumab and Bevacizumab for Choroidal Neovascularization Secondary to Ocular Toxocariasis: A Case Report

Purpose: To report a case of a choroidal neovascularization (CNV) secondary to ocular toxocariasis treated with intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents.

Methods: A 66-year-old woman presented with decreased vision (20/40) and metamorphopsia in the right eye. Fundus examination revealed inferotemporal retinal whitish lesion and subretinal hemorrhage in the right eye.

Results: She was diagnosed with ocular toxocariasis based on the clinical features and positive serological anti-toxocara antibody test result. Ophthalmic examination revealed classic CNV formation adjacent to a retinal granuloma. She was treated with intravitreal ranibizumab and bevacizumab injections combined with oral albendazole. Her vision decreased to 20/100 following CNV recurrence. However, after additional bevacizumab treatment, the CNV became inactive and her vision recovered to 20/40.

Conclusions: CNV can be combined with retinal granuloma due to ocular toxocariasis. Repeated intravitreal injections of anti-VEGF agents can be efficacious for regressing toxocariasis-associated CNV and improving vision.     

Intravitreal Ranibizumab for Treatment of Choroidal Neovascularization Secondary to Angioid Streaks in Pseudoxanthoma Elasticum: Five-year Follow-up

Purpose: To report on the five-year follow-up of ranibizumab therapy for choroidal neovascularization (CNV) secondary to angioid streaks (AS) in pseudoxanthoma elasticum (PXE).

Methods: A 51-year-old patient with PXE presenting with macular CNV secondary to AS was treated with a series of intravitreal ranibizumab (0.5 mg) injections and followed for five years with fundoscopy, optical coherence tomography (OCT), and fluorescein angiography (FA).

Results: Fluorescein leakage resolved and OCT evidence of subretinal and intraretinal fluid disappeared one year after presentation following an initial 12 injections. There was mild recurrent neovascular activity on two occasions resulting in two injections in the four years subsequent to resolution. Though peripapillary scar formation occurred, the fovea was preserved with 20/20 visual acuity in the affected eye at five years.

Conclusions: This case provides further evidence for the long-term effectiveness of ranibizumab in the treatment of CNV secondary to AS in PXE. Though multiple initial injections were required to control the disease, once stabilization of the CNV was achieved, recurrent neovascular activity was minimal.     

Pharmacogenetics of the Treatment Response of Age-Related Macular Degeneration with Ranibizumab and Bevacizumab

Abstract

Introduction: Age-related macular degeneration is a major cause of blindness among people aged 50 and older in industrialized countries. Anti-VEGF therapy has been tremendously successful in the treatment of neovascular macular degeneration. Examining the pharmacogenetics of patients’ response to the anti-VEGF molecules could allow for a tailored treatment strategy based on patients’ underlying genetics rather than the “one-size fits all” approach currently used. Methods: Review of the English literature for papers examining the pharmacogenetics of treatment response of neovascular macular degeneration to either ranibizumab or bevacizumab. Polymorphisms in CFH, ARMS2, HTRA1 and VEGF A were examined and reviewed. Results: Patients with the high-risk CC genotype in complement factor H (CFH) had a worse response to therapy with ranibizumab and bevacizumab. No clear trends were found with ARMS2, HTRA1 and VEGF A. Conclusions: The goal of personalized medicine is to craft a treatment program that is ideally suited to an individual patient’s disease and genetic make-up rather than simply what works for a large population who share similar disease characteristics. Continued research is needed to achieve this goal for the treatment of age-related macular degeneration.     

Intravitreal Injection of Bevacizumab in Eales Disease

Purpose: To report a case of presumed Eales disease that showed regression of retinal neovascularization after the use of intravitreal bevacizumab. Design: Retrospective, interventional case report. Methods: Broad retinal neovascularization in a patient with presumed Eales disease did not regressed despite adequate photocoagulation treatment, and bevacizumab (1.25 mg) was injected intravitreally. The patient was followed up for 1 year. Results: One week after injection, fluorescein angiography demonstrated dramatic regression of retinal neovascularization. After 12-months, visual acuity was improved and no signs of recurrence were observed. Conclusion: Intravitreal bevacizumab may be effective as an adjunctive treatment of retinal neovascularization in patients with Eales disease.     

Long-Term Outcome of Punctate Inner Choroidopathy or Multifocal Choroiditis with Active Choroidal Neovascularization Managed with Intravitreal Bevacizumab

ABSTRACT

Purpose: To evaluate the long-term outcome of active choroidal neovascularization (CNV) in punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC) after intravitreal bevacizumab treatment.

Methods: Retrospective study of consecutive patients of PIC/MFC complicated with active CNV. Outcome measures included best-corrected visual acuity (BCVA), total number of intravitreal injections of bevacizumab and recurrence of CNV. Correlation analysis was performed to find the correlation of various clinical factors and final BCVA.

Results: There were 23 eyes in 22 patients with a mean age of 33.22 years included in this study. The mean duration of follow-up was 6.48 years. Improvement of BCVA was noted through the first 3 years and at the final follow-up. BCVA at 1, 6, 12 months and recurrence of CNV were correlated with final BCVA.

Conclusion: Most patients of PIC/MFC complicated with CNV managed with intravitreal bevacizumab had improved BCVA over 4 years.     

碱烧伤大鼠角膜新生血管模型的初步探索

目的:探索相对稳定可靠的碱烧伤大鼠角膜新生血管(CNV)动物模型。方法:随机将48只S-D大鼠分成4组,每组12只,采用浸润1mol/L氢氧化钠的3mm滤纸片,分别制作烧灼时间为15、30、40、60s的碱烧伤鼠眼模型,每天裂隙灯观察角膜新生血管、角膜溃疡及前房积血情况,并在3、7、14、21、28d记录上述指标。结果:伤后3d,新生血管开始侵入角膜;7d,新生血管生长活跃,向中央烧灼区侵入;14d,新生血管达到生长高峰;14d后新生血管逐渐回退。烧伤后7d,15、30、40和60s组CNV诱导率分别为16.7%、75%、100%、100%,各实验组角膜新生血管诱导率随着烧伤时间延长而增加。。15sCNV散在稀疏分布,长度较短。30s组CNV接近烧灼区边缘,分布局限。40s组CNV致密,连接成网状,生长均匀一致。30s组和40s组间CNV长度和面积差异均具有统计学差异(P<0.05)。40s组前房积血率16.7%,表现为虹膜血管点片状渗血;60s组前房积血率83.3%,积血量多严重影响到角膜新生血管观察,两组前房积血发生率具有统计学差异(P<0.05)。60s组角膜溃疡率50%,穿孔率33.3%。结论:采用浸润1mol/L氢氧化钠溶液的3mm滤纸片烧灼中央角膜40s的大鼠模型是研究化学性角膜新生血管较理想的动物模型。     

Intravitreal Bevacizumab for Inflammatory Neovascularization of the Lens after Traumatic Open Globe Injury

ABSTRACT

Purpose

To describe a case of inflammatory neovascularization of the lens after open globe injury.     

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.     

Biometric Risk Factors for Corneal Neovascularization Associated with Hydrogel Soft Contact Lens Wear in Korean Myopic Patients

Purpose

To investigate the biometric risk factors for corneal surface complications associated with hydrogel soft contact lens (SCL) fitting in myopic patients in Korea.

Methods

This is a retrospective case-control study. The records of 124 subjects (124 eyes) who wore SCLs on a daily basis were reviewed. Thirty-one patients (31 eyes) who were diagnosed with corneal neovascularization (NV) while wearing SCLs were included in the complication group. Ninety-three age- and sex-matched patients (93 eyes) who wore SCLs, who did not have corneal NV and who visited our clinic for correction of refractive errors were included in the control group. The degree of spherical equivalent, astigmatism and corneal base curve radius (BCR) were compared in both groups.

Results

Patients with NV exhibited poorer best corrected visual acuity and more myopia than controls (p = 0.008 and 0.006, respectively). In univariate analysis, highly myopic patients (-9 diopters [D] or higher) were more likely to experience NV (odds ratio [OR], 2.232; 95% confidence interval [CI], 1.602 to 3.105). High astigmatism (≥2 D) increased the risk of complications (OR, 2.717; 95% CI, 1.141 to 6.451). Steep cornea, in which BCR was <7.5 mm, also raised the risk of complications (OR, 4.000; 95% CI, 1.661 to 9.804). Flat cornea was not a risk factor for the development of NV.

Conclusions

High myopia, high astigmatism, and steep cornea seemed to be risk factors in the development of corneal NV in SCL wearers.     

贝伐单抗在虹膜新生血管治疗中的应用

虹膜新生血管是眼内新生血管的一种表现,血管内皮生长因子(vascular endothelial growth factor,VEGF)是迄今为止鉴定出来最重要的血管生成因子,与新生血管形成和通透性紧密相关。贝伐单抗是人源化的抗VEGF重组鼠单克隆抗体,可与所有已知VEGF异构体结合,通过抑制其生物学活性来抑制新生血管的生成。临床研究此药治疗虹膜新生血管在短期内取得了良好的疗效、且安全可靠。本文就最近几年国内外有关治疗虹膜新生血管疾病的研究进行综述,评估其在虹膜新生血管治疗方面的应用前景。     

雷珠单抗治疗慢性中心性浆液性脉络膜视网膜病变合并CNV的疗效及其影响因素

目的:应用多模式影像观察玻璃体腔抗血管内皮生长因子(VEGF)注射在慢性中心性浆液性脉络膜视网膜病变(CCSC)合并脉络膜新生血管(CNV)的治疗效果,探讨评估其影响因素。方法:回顾性分析30例30眼确诊为CCSC合并CNV患者的资料。所有患者均行最佳矫正视力(BCVA)、频域相干光断层扫描(SD-OCT)的增强深度成像(EDI)模式,荧光素眼底血管造影(FFA)、吲哚菁绿血管造影(ICGA)及光学相干断层扫描血管成像(OCTA)血流扫描检查。对存在黄斑区视网膜下积液(SRF)以及CNV的患眼行玻璃体腔雷珠单抗(IVR)注射治疗,采取1+PRN方案,随访时间为注药治疗后1wk, 1mo,末次注药治疗后3mo。观察指标为最佳矫正视力(BCVA,LogMAR)、黄斑中心凹厚度(CMT)、黄斑中心凹下脉络膜厚度(SFCT)以及CNV血流面积。结果:所有患眼在基线、眼内注药治疗后1wk, 1mo,末次治疗后3mo时各时间点CMT有差异(F=62.06,P<0.01);治疗后各时间点CMT与治疗前比较均有差异(t=3.08、6.57、4.90,P=0.01、0.02、<0.01),其...     

抗血管内皮生长因子Bevacizumab在眼部新生血管中的应用新进展

眼部新生血管性病变是致盲的主要原因之一,大量的研究证据表明血管内皮生长因子(vascular endothelial growth factor,VEGF)是新生血管形成的关键调控因子。Bevaci-zumab是世界上首个批准上市的血管内皮因子抑制剂由于其强大的抗新生血管作用,在眼科新生血管性疾病治疗中有广泛的应用前景。本文对VEGF的特性、VEGF在眼部新生血管形成中的作用和Bevacizumab作用机制、应用范围进行综述。     

Comparison of Ranibizumab monotherapy versus combination of Ranibizumab with photodynamic therapy with neovascular age‐related macular degeneration

Purpose: Modern therapy of neovascular age‐related macular degeneration consists in intravitreal injections of inhibitors of the vascular endothelial growth factor. An increasing number of these injections is required not only in monthly but also in as‐needed treatment regimen. In this study, it should be examined whether an additional administered photodynamic therapy (PDT) can considerably reduce the number of injection. Methods: In this prospective, randomized study carried out in three large hospitals of Vienna eyes with neovascular age‐related macula degeneration were included. Patients were randomized to either Ranibizumab monotherapy or combined standard fluence PDT and Ranibizumab therapy. All patients received a loading dose of three intravitreal Ranibizumab injections and were thereafter treated in an as‐needed regimen based on distance acuity and retinal thickness values. In the combined treatment group, PDT was administered 1 day after the first Ranibizumab injection. Results: Fifty‐one patients were randomized, 44 were finally included (four screening failures and three withdrawals). Twenty‐four patients were assigned to the monotherapy and 20 patients to the combined treatment group. Fewer injections were required in the combined treatment group (4.7 versus 6.3). Overall the patients lost 0.5 letters; in the combined treatment group, the patients lost mean 7.1 letters; in the monotherapy group, they gained mean 5.1 letters. Retinal thickness decreased significantly in both groups. Conclusion: A significant reduction of the number of required intravitreal injections could be achieved by the additional PDT treatment, but was accompanied by a worse functional outcome in this group.     

贝伐单抗辅助自体角膜缘干细胞移植在复发性翼状胬肉中应用

目的 评价贝伐单抗(Avastin)辅助角膜缘干细胞移植治疗复发性翼状胬肉的临床疗效.方法 回顾分析36只眼复发性翼状胬肉的临床资料,分为治疗组17只眼行角膜缘干细胞移植术联合贝伐单抗术中球结膜下注射及术后局部点眼,对照组19只眼行角膜缘干细胞移植术.结果 随访6个月治疗组与对照组平均视力均较术前明显提高,两者差异无统计学意义(P＞0.05);平均眼压与术前比较均无显著差异(P＞0.05);复发率:治疗组无复发,对照组有5例复发,两者差异有统计学意义(P＜0.05).两组干细胞植片均存活良好,无角膜上皮缺失、糜烂、角膜变薄等并发症发生.结论 贝伐单抗联合角膜缘干细胞移植可有效抑制复发性翼状胬肉的复发,未见明显并发症.     

角膜地形图引导下白内障手术切口构建的变异对角膜散光影响

目的 观察根据角膜地形图选择白内障手术切口位置及其构建变异,以进一步降低术前角膜散光.方法 对白内障患者123例(126只服),术前常规作角膜地形图检查.病人随机分成5组,A组、B组、E组为小切口手法组,A组和B组分别于上方和根据角膜地形图在强子午线方向行反眉形巩膜隧道切口;E组根据角膜地形图在强子午线方向行水平巩膜隧道切口;C组和D组为超声乳化组,分别于上方和根据角膜地形图在强子午线方向行透明角膜隧道切口;观察术后1d及7d后视力、角膜地形图等情况.结果 ①视力:术后7d,发现B组与E组患者差异有统计学意义,余各组间差异无统计学意义,组间裸眼视力≥1.0者差异亦无统计学意义.②术后散光轴向变化:A～D组变化不明显,E有12例散光轴向发生改变.③角膜散光:A组、B组散光变化较小,B组和E组术后7d较术前减少,差异有统计学意义;C组、D组术后1d角膜散光较大,7d后渐回复,但C组仍高于术前水平;A组与B组、C组与D组及A组与C组比较术后差异均无统计学意义;B组与D组术后1d差异有统计学意义,术后7d差异无统计学意义;B组与E组比较,术后1d差异无统计学意义,术后7d差异有统计学意义.结论 通过观察角膜地形图来选择白内障手术切口位置及其构建,可降低手术源性角膜散光或术前存在的角膜散光,明显改善术后早期视力.对进一步提高白内障术后的视觉质量具有临床指导意义.