Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). METHODS: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. RESULTS: Fifty-three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6 microm (P < 0.001). CONCLUSION: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.     

Combined intravitreal bevacizumab and photodynamic therapy for neovascular age-related macular degeneration

Background Our aim was to evaluate the short-term safety and efficacy of combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab in neovascular age-related macular degeneration (AMD). Methods A prospective non-randomized interventional case series of 30 eyes of 30 patients with choroidal neovascularization (CNV) caused by AMD was studied. All patients were treated with PDT followed by an intravitreal injection of bevacizumab (1.5 mg) on the same day. Ophthalmic evaluations included determination of best-corrected visual acuity by using ETDRS charts. CNV lesion characteristics were determined by fluorescein angiography, and retinal morphology by optical coherence tomography. Review examinations were performed 1, 4, and 12 weeks following treatment. Results The median ETDRS letter scores increased by 3 letters after 4 weeks and 4.3 letters after 12 weeks. Median central retinal thickness decreased from the baseline by 145 μm (week 1), 205 μm (week 4), and 171 μm (week 12), respectively (P < 0.0001, for all comparisons). One patient experienced a transient moderate vision loss after 4 weeks post treatment. Leakage on fluorescein angiography was resolved in all patients at week 12. No significant ocular or systemic side-effects were observed. Conclusions Short-term results suggest that a single PDT in combination with intravitreal bevacizumab is safe and associated with stabilization of visual acuity and decrease of intraretinal and subretinal fluid accumulation in the macula. Further evaluation of this treatment strategy for neovascular AMD appears warranted. None of the authors has a financial interest in the subject matter of the article.     

RPE tears after pegaptanib treatment in age-related macular degeneration

PURPOSE: To describe retinal pigment epithelial (RPE) tears in patients with age-related macular degeneration (AMD) status post pegaptanib (Macugen) injection. METHODS: Six eyes from six patients who developed RPE tears while undergoing treatment with pegaptanib for AMD-related fibrovascular pigment epithelial detachment (PED) and occult choroidal neovascularization (CNV) were identified retrospectively. Diagnosis of pre-pegaptanib fibrovascular PED and post-pegaptanib RPE tears were made by clinical examination, fluorescein angiography (FA), and optical coherence tomography (OCT) imaging of the macula. RESULTS: Four patients developed an RPE tear within 8 weeks after the first pegaptanib injection, while RPE tears were found in two patients following a second injection. Only one of the patients reported acute vision loss, although three of six eyes had a decrease in objective visual acuity in the affected eye to the count fingers level. All six cases displayed the classic clinical and angiographic appearance of RPE tears. In addition, OCT imaging showed an irregular, hyperreflective RPE layer with a focal defect. CONCLUSIONS: RPE tears are known to occur in the setting of PED spontaneously or after laser treatment, but have only recently been described in association with intravitreal pegaptanib. OCT imaging of eyes status post pegaptanib therapy may be helpful in identifying this complication. Patients with AMD, especially those with occult CNV and fibrovascular PED, receiving pegaptanib therapy should be monitored for RPE tears, which may warrant deferral of further injections.     

Treatment of neovascular age-related macular degeneration with pegaptanib and boosting with bevacizumab or ranibizumab as needed

BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration presents a therapeutic challenge. The efficacy of pegaptanib sodium, a selective inhibitor of vascular endothelial growth factor 165, was examined as a therapeutic mainstay combined with "as needed" boosts of nonselective vascular endothelial growth factor blockade with bevacizumab or ranibizumab. PATIENTS AND METHODS: A retrospective chart review of outcomes of patients treated with pegaptanib and later boosted with bevacizumab or ranibizumab was conducted. Visual acuity, optical coherence tomography, and fluorescein angiography findings were recorded and assessed. RESULTS: During a mean follow-up of 12.1 months, an average of 7.8 injections of pegaptanib 0.3 mg, 1.4 injections of bevacizumab 1.25 mg, and 0.9 injections of ranibizumab 0.5 mg were administered to 17 eyes. In all, 47% of eyes gained 3 or more lines of visual acuity and 76% gained 0 or more lines. CONCLUSION: Pegaptanib as a mainstay of neovascular age-related macular degeneration therapy with an occasional boost of bevacizumab or ranibizumab appears to be an effective treatment option.     

Predictors of response after intravitreal bevacizumab injection for neovascular age-related macular degeneration

Purpose  

To identify fluorescein angiography (FA) and optical coherence tomography (OCT) characteristics predicting responses to intravitreal bevacizumab therapy in patients with neovascular age-related macular degeneration (AMD).     

年龄相关性黄斑变性患者玻璃体内注射bevacizumab期间的视功能变化

目的 观察湿性年龄相关性黄斑变性(age-related macular degeneration,AMD)患者在接受玻璃体内注射bevacizumab治疗期间的视功能变化.方法 对18例(21眼)经荧光素眼底血管造影、光学相干断层扫描检查确诊存在黄斑中心凹下脉络膜新生血管的AMD患者行玻璃体内注射bevacizumab,每6周注射1次,每次剂量为1.25mg(0.05 mL),共3次.研究治疗期间患者的EDTRS视力得分、闪光视网膜电图的a、b波振幅值、对比敏感度及视野平均视敏度的变化情况.结果 患者的平均视力EDTRS得分提高,第3次注射后第3天较第1次注射前1 d平均得分提高5.1分(P=0.001);3次注射前1 d,闪光视网膜电图中a、b波振幅值分别为(160.00±47.63)μV、(263.84±65.81)μV;(159.79±55.07)μV、(273.47±92.56)μV;(164.05±57.94)μV、(282.26±96.55)μV;后2次注射前1 d数据与第1次相比,差异无统计学意义(P>0.05);对比敏感度及视野平均视敏感度无明显变化.结论 湿性AMD患者在接受玻璃体内注射bevacizumab后,治疗期间各项视功能指标稳定,多次注射后EDTRS视力得分有所提高.     

Retinal pigment epithelium tear after intravitreal bevacizumab for exudative age-related macular degeneration

PURPOSE: To report on the development of retinal pigment epithelium tears after intravitreal injections of bevacizumab as treatment of exudative age-related macular degeneration (AMD). DESIGN: Interventional case series. METHODS: The study included 63 patients who received an intravitreal injection of 1.5 mg bevacizumab as treatment of a detachment of the retinal pigment epithelium attributable to AMD and who had a follow-up of at least two months. RESULTS: Four patients (6%) developed a tear of the retinal pigment epithelium in the parafoveal region. Compared with the baseline value, visual acuity at the end of follow-up remained stable in three patients and declined in the fourth patient. CONCLUSIONS: Intravitreal injections of bevacizumab may be followed by a tear of the retinal pigment epithelium in eyes with exudative AMD and a retinal pigment epithelium detachment.     

玻璃体腔注射bevacizumab治疗年龄相关性黄斑变性的初步临床观察

目的初步探讨玻璃体腔内注射bevacizumab（Avastin）治疗湿性年龄相关性黄斑变性（ARMD）的临床效果。方法采用单中心非随机对照临床研究方法。收集经荧光素眼底血管造影检查（FFA）、相干光断层成像术（OCT）确诊存在黄斑中心凹下脉络膜新生血管（CNV）的ARMD患者5例,患眼最佳矫正视力均〈0．1,无全身和局部手术禁忌证。患眼行bevacizumab玻璃体腔内注射术,用量为1．5mg（0．06ml）,记录手术前、后患眼的视力、眼压、FFA和OCT的检查结果。术后随访时间4～6个月。结果全部患者均未出现眼内和全身不良反应。1例患者术后第3天出现一过性眼压升高,局部给予降眼压药物治疗后症状得到控制。1例患者术后1周视力由0．1上升至0．4;4例患者术后2个月视力提高1—6行,其中3例于术后4—6个月时视力保持稳定,1例视力下降。3例患者术后1个月黄斑水肿明显改善,黄斑中心凹视网膜厚度较术前减少5．9％～41．4％,3例患者FFA显示CNV渗漏较术前减轻。结论玻璃体腔内注射bevacizumab治疗湿性ARMD安全,副作用少,可改善患者的视功能,减轻黄斑水肿,减少CNV渗漏,有望成为药物治疗ARMD的新方法,但尚需进行多中心大样本临床随机对照研究。     

Single-session photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration

PURPOSE: To evaluate the efficacy of combined single-session photodynamic therapy (PDT) and intravitreal bevacizumab (IVB) for treatment of neovascular age-related macular degeneration (AMD). METHODS: In a prospective interventional case series, patients with subfoveal choroidal neovascularization (CNV) underwent PDT followed by 1.25 mg IVB injection. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were repeated at 6-week intervals and fluorescein angiography was performed after 12 weeks and when considered necessary thereafter. Repeat injections of IVB were performed based on fluorescein angiographic evidence of CNV leakage. RESULTS: Fourteen eyes were included in this study. Mean follow-up was 52.4+/-15.2 weeks (range: 26-74 weeks). Initially, mean BCVA was 0.80+/-0.42 logMAR and mean central macular thickness (CMT) was 308+/88 microm. At week 12, BCVA improved to 0.62+/-0.47 logMAR (p=0.006) and CMT reduced to 186+/-53 microm (p=0.003). Corresponding results were 0.53+/-0.52 logMAR (p=0.02) and 193+/-78 microm (p=0.002) after 24 weeks. A second IVB injection was performed in 13 eyes with a mean interval of 16.3+/-5.9 weeks. CONCLUSIONS: Combination therapy with single-session PDT and IVB can improve vision and reduce CMT in neovascular AMD. Repeat IVB injections may maintain the visual gain from the initial combination therapy.     

Treatment of neovascular age-related macular degeneration with intravitreal bevacizumab: efficacy of three consecutive monthly injections

PURPOSE: To report the efficacy of treatment of neovascular age-related macular degeneration (AMD) with intravitreal bevacizumab (Avastin; Genentech, Inc, South San Francisco, California, USA) when administered in a series of three monthly injections followed by a period of observation. DESIGN: Retrospective case series. METHODS: Retrospective review of consecutive eyes with all choroidal neovascular lesion subtypes resulting from neovascular AMD treated with intravitreal bevacizumab. Treatment consisted of a pars plana injection of 1.25 mg Avastin (0.05 ml bevacizumab at a concentration of 25 mg/ml). Evaluation consisted of a complete ophthalmologic examination, including best-corrected visual acuity (VA) measurement, ophthalmoscopy, and optical coherence tomography. Eyes received a series of three monthly injections followed by a three-month period of observation. RESULTS: A total of 36 patients (37 eyes) received a series of three consecutive monthly intravitreal injections of bevacizumab. Twenty (54%) of 37 eyes had no previous treatments for neovascular AMD in the eye that received bevacizumab. Seventeen (46%) of 37 eyes had received some previous treatment before initiation of bevacizumab therapy. Intravitreal Avastin therapy produced an improvement in foveal thickness over time in eyes with neovascular AMD. This improvement was sustained during the series of three monthly injections. All eyes experienced worsening after three months without treatment. No statistically significant effect on VA was demonstrated in this series. CONCLUSION: Intravitreal bevacizumab therapy produced an improvement in foveal thickness over time in eyes with neovascular AMD when one injection was given each month for three consecutive months. All eyes experienced increased foveal thickening during the subsequent three months without treatment.     

Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration

PURPOSE: To study retinal pigment epithelium (RPE) tears after off-label intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) injection for neovascular age-related macular degeneration. Eyes with a vascularized pigment epithelial detachment (PED) that developed an RPE tear were compared with eyes with a vascularized PED but without an RPE tear. METHODS: Nine retina specialists across the United States and in Europe participated in this retrospective case series. All eyes that received intravitreal bevacizumab injection for choroidal neovascularization (CNV) over 12 months (October 2005 to September 2006) were included. Eyes without all three confirmed tests (fluorescein angiography, fundus photography, and optical coherence tomography) were excluded from analysis. Statistical analyses were performed on multiple characteristics of eyes with a vascularized PED that did and did not develop an RPE tear. RESULTS: Among 2,785 intravitreal bevacizumab injections for 1,064 eyes, RPE tears were found in 22 eyes in 22 patients (2.2%). A vascularized PED was present in 21 of 22 eyes that developed an RPE tear (17.1% of PED eyes; 15, 100% occult CNV; 6, predominantly occult CNV). Mean interval from bevacizumab injections to RPE tears was 37.3 days. Mean follow-up time was 124.9 days. Mean subfoveal PED size was larger for eyes with tears than for those without tears (13.97 mm vs 9.9 mm, respectively; P = 0.01; odds ratio, 1.09). There was substantially smaller mean ratio of CNV size to PED size for eyes with tears than for those without tears (27.9% vs 67.6%, respectively; P = 0.005). Mean pre-bevacizumab injection best-corrected Snellen visual acuity was 20/162, and mean post-RPE tear best-corrected visual acuity was 20/160 (P = 0.48). CONCLUSION: Large PED size is a predictor for RPE tears, and a small ratio of CNV size to PED size (<50%) is more common in eyes with RPE tears. Vision may be preserved despite RPE tears.     

Concentration of cytokines in age-related macular degeneration after consecutive intravitreal bevacizumab injection

Background  

To evaluate the changes in aqueous humor cytokine levels following consecutive intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA) injections in eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).     

Visual hallucinations after intravitreal injection of bevacizumab in vascular age-related macular degeneration

PURPOSE: To describe transient structured visual hallucinations in a patient with vascular age-related macular degeneration (AMD), following an intravitreal Avastin-injection. DESIGN: Interventional case reports. METHODS: A fully alert 83-year-old woman with disciform scar right eye (OD) and occult choroidal neovascularization (CNV) left eye (OS) experienced a progressive visual loss to 20/800 OD and 20/400 OS. A coherent 84-year-old woman with occult CNV both eyes (OU) experienced decreased vision of 20/800 OU. After both patients gave informed consent, an uneventful intravitreal injection of 1.25 mg Avastin was performed in the left eyes. RESULTS: One day and three days after an uneventful intravitreal injection both patients experienced structured hallucinations including trees, faces, and water for approximately 15 to 30 minutes. CONCLUSIONS: We report a typical symptoms of Charles-Bonnet syndrome (CBS) in patients with severe AMD after intravitreal Avastin-injections. The reduced retinal edema and realignment of the photoreceptors may promote the release phenomenon and trigger hallucinatory episodes.     

Retinal pigment epithelial tears after intravitreal bevacizumab injection for exudative age-related macular degeneration

We report a series of retinal pigment epithelial (RPE) tears after intravitreal bevacizumab therapy for choroidal neovascularization associated with age-related macular degeneration (ARMD). Retinal pigment epithelial tears were estimated to occur at an incidence of 1.6% in this patient population at our institution. Ophthalmologists should be aware of this rare but serious finding associated with exudative macular degeneration therapy.