Aflibercept more effectively weans patients with neovascular age-related macular degeneration off therapy compared with bevacizumab

BACKGROUNDStudies assessing the efficacy of therapies for neovascular age-related macular degeneration (nvAMD) have demonstrated that aflibercept may have a longer treatment interval than its less-expensive alternative, bevacizumab. However, whether this benefit justifies the additional cost of aflibercept remains under debate. We have recently reported that a treat-and-extend-pause/monitor approach can be used to successfully wean 31% of patients with nvAMD off anti-VEGF therapy. Here, we examined whether the choice of therapy influences the outcomes of this approach.METHODSIn this retrospective analysis, 122 eyes of 106 patients with nvAMD underwent 3 consecutive monthly injections with either aflibercept (n = 70) or bevacizumab (n = 52), followed by a treat-and-extend protocol, in which the decision to extend the interval between treatments was based on visual acuity, clinical exam, and the presence or absence of fluid on optical coherence tomography. Eyes that remained stable 12 weeks from their prior treatment were given a 6-week trial of holding further treatment, followed by quarterly monitoring. Treatment was resumed for worsening vision, clinical exam, or optical coherence tomography findings.RESULTSAt the end of 1 year, eyes receiving bevacizumab had similar vision but required more injections (8.7 ± 0.3 treatments vs. 7.2 ± 0.3 treatments) compared with eyes receiving aflibercept. However, eyes treated with aflibercept were almost 3 times more likely to be weaned off treatment (43% vs. 15%) compared with eyes treated with bevacizumab at the end of 1 year.CONCLUSIONThese observations expose an advantage of aflibercept over bevacizumab and have important clinical implications for the selection of therapy for patients with nvAMD.FUNDINGThis work was supported by the National Eye Institute, NIH grants R01EY029750 and R01EY025705, Research to Prevent Blindness, the Alcon Young Investigator Award from the Alcon Research Institute, and the Branna and Irving Sisenwein Professorship in Ophthalmology.     

Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration

Introduction: The consistent association between choroid neovascularization (CNV) and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular age-related macular degeneration (AMD). The authors report the systemic side effects secondary to intravitreal administration of these compounds, that is, the main cardiovascular effects, as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thromboflebitis.

Areas covered: The authors reviewed major Clinical Trials and publications concerning systemic adverse events of anti-VEGF drugs in order to identify the main thromboembolic events related to the use of these agents and their occurrence. Anti-VEGF efficacy, safety and tolerability are also discussed.

Expert opinion: Three compounds (pegaptanib, ranibizumab and aflibercept) have been approved for the treatment of AMD; a fourth agent, bevacizumab, is used off-label. Anti-VEGF therapy has not shown the ability to fully eradicate the CNV, so that recurrences are common when the intravitreal injections are suspended. Although no evident rise in anti-VEGF-induced thromboembolic side effects was reported, more data are required to evaluate hemodynamic and pharmacokinetics of these compounds. Since only few studies have focused on these aspects, further researches are mandatory to determine distribution, effects and duration of these substances.     

Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration

Introduction: The consistent association between choroid neovascularization (CNV) and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular age-related macular degeneration (AMD). The authors report the systemic side effects secondary to intravitreal administration of these compounds, that is, the main cardiovascular effects, as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thromboflebitis. Areas covered: The authors reviewed major Clinical Trials and publications concerning systemic adverse events of anti-VEGF drugs in order to identify the main thromboembolic events related to the use of these agents and their occurrence. Anti-VEGF efficacy, safety and tolerability are also discussed. Expert opinion: Three compounds (pegaptanib, ranibizumab and aflibercept) have been approved for the treatment of AMD; a fourth agent, bevacizumab, is used off-label. Anti-VEGF therapy has not shown the ability to fully eradicate the CNV, so that recurrences are common when the intravitreal injections are suspended. Although no evident rise in anti-VEGF-induced thromboembolic side effects was reported, more data are required to evaluate hemodynamic and pharmacokinetics of these compounds. Since only few studies have focused on these aspects, further researches are mandatory to determine distribution, effects and duration of these substances.     

Ranibizumab: treatment in patients with neovascular age-related macular degeneration

Vascular endothelial growth factor (VEGF)-A is a major regulator of angiogenesis and vascular permeability implicated in the development of diseases involving pathological angiogenesis and increased vascular permeability, such as neovascular age-related macular degeneration (AMD). LUCENTIS (ranibizumab), a humanized antigen-binding fragment (Fab) that neutralizes all VEGF-A isoforms and their biologically active degradation products, was recently approved by the FDA. Ranibizumab is the first FDA-approved treatment for neovascular AMD that maintains or improves vision in > or = 90% patients and provides a > or = 15-letter improvement in visual acuity for a quarter to a third of patients with all choroidal neovascularisation subtypes. Ranibizumab was associated with a < or = 1.7% rate of key serious ocular adverse events, such as endophthalmitis and uveitis, in two pivotal Phase III trials.     

Ranibizumab: treatment in patients with neovascular age-related macular degeneration

Vascular endothelial growth factor (VEGF)-A is a major regulator of angiogenesis and vascular permeability implicated in the development of diseases involving pathological angiogenesis and increased vascular permeability, such as neovascular age-related macular degeneration (AMD). LUCENTIS? (ranibizumab), a humanised antigen-binding fragment (Fab) that neutralises all VEGF-A isoforms and their biologically active degradation products, was recently approved by the FDA. Ranibizumab is the first FDA-approved treatment for neovascular AMD that maintains or improves vision in ≥ 90% patients and provides a ≥ 15-letter improvement in visual acuity for a quarter to a third of patients with all choroidal neovascularisation subtypes. Ranibizumab was associated with a ≤ 1.7% rate of key serious ocular adverse events, such as endophthalmitis and uveitis, in two pivotal Phase III trials.     

抗VEGF药物对湿性老年性黄斑变性视网膜微循环的疗效研究

目的 研究抗血管内皮生长因子(VEGF)药物对湿性老年性黄斑变性(wAMD)视网膜微循环的临床疗效;方法 回顾性分析2018年6月～2020年7月在同济大学附属杨浦医院收治的wAMD患者38例38眼,包括康柏西普治疗组(A组)及雷珠单抗治疗组(B组),每组各19例。收集两组患者治疗前和治疗后1个月最佳矫正视力,黄斑中心凹以及距离黄斑中心凹0.5 mm四个方位的视网膜厚度,视网膜毛细血管密度,以及黄斑中心凹无灌注区面积的差异;结果 与治疗前相比,两组治疗后视网膜厚度均明显降低(P<0.001),黄斑中心凹无灌注区面积均明显减少(P<0.05);两组治疗后视网膜浅层和深层血管密度均显著增加(P<0.05)。两组治疗后的结果相比较,视网膜微循环相关指标均无显著差异(P>0.05)。结论 玻璃体腔注射康柏西普或者雷珠单抗治疗湿性老年性黄斑变性患者可有效改善黄斑部形态以及视网膜微循环。     

Ranibizumab for the treatment of neovascular age-related macular degeneration: a review

BACKGROUND: Choroidal neovascular (wet) age-related macular degeneration (ARMD) is becoming more prevalent worldwide as life expectancy continues to increase. Ranibizumab for intravitreal injection is an inhibitor of human vascular endothelial growth factor A approved by the US Food and Drug Administration for the treatment of ARMD in June 2006. The actions of ranibizumab result in reduced cell proliferation, reduced formation of new blood vessels, and minimization of vascular leakage. OBJECTIVE: This paper reviews the pharmacologic and pharmacokinetic properties, clinical efficacy, and safety profile of ranibizumab, and pharmacoeconomic considerations associated with its use. METHODS: MEDLINE (1966-December 2006) and International Pharmaceutical Abstracts (1970-December 2007) were searched for original research studies (Phase I, II, III, and IIIb), abstracts, and review articles concerning ranibizumab. The search terms were choroidal neovascularization, macular degeneration, Lucentis, ranibizumab, retinal degeneration, and vascular endothelial growth factor. Preference was given to Phase IlfllI studies. Selected information from the manufacturer of ranibizumab was also included. RESULTS: The efficacy of ranibizumab has been studied in 3 large clinical trials having the same primary efficacy end point, the proportion of patients losing <15 letters from baseline at 12 months (Early Treatment of Diabetic Retinopathy Study chart). A multicenter, Phase III, randomized, double-blind, sham-controlled, 24-month clinical trial evaluated ranibizumab 0.3 and 0.5 mg in 716 patients with minimally classic or occult choroidal neovascularization (CNV) associated with ARMD. The results for the primary efficacy end point were 94.5% and 94.6% in the ranibizumab 0.3- and 0.5-mg groups, respectively, compared with 62.2% in the sham-injection group (P < 0.001, both ranibizumab groups vs sham injection); at 24 months, the corresponding proportions were 92.0%, 90.0%, and 52.9% (P < 0.001, both ranibizumab groups vs sham injection). A 2-year, Phase I/II, single-masked (masked patient and visual acuity examiner, unmasked investigator), multicenter trial evaluated the tolerability and efficacy of the combination of ranibizumab 0.5 mg and verteporfin photodynamic therapy (PDT) compared with verteporfin PDT alone in 162 patients with predominantly classic CNV. For the primary efficacy end point, the results were 90.5% for ranibizumab + PDT and 67.9% for PDT alone (P < 0.001). Receipt of ranibizumab + PDT was also associated with improved visual acuity, with 23.8% of patients gaining >15 letters from baseline, compared with 5.4% of those who received PDT alone (P = 0.003). Finally, an international Phase III, double-blind, active-controlled study compared ranibizumab 0.3 and 0.5 mg with verteporfin PDT in 423 patients with predominantly classic lesions associated with CNV secondary to ARMD. For the primary efficacy end point, the results were 35.7% for ranibizumab 0.3 mg, 40.3% for ranibizumab 0.5 mg, and 5.6% for verteporfin PDT (P < 0.001). Serious adverse ocular events, which occurred in association with < 0.1% of intravitreal injections in these trials, included retinal detachment and endophthalmitis. Less serious adverse ocular reactions occurring in < 2% of patients included intraocular inflammation and increased intraocular pressure. CONCLUSION: The findings of these 3 large clinical trials suggest that ranibizumab was effective and well tolerated in patient.     

Pegaptanib sodium for the treatment of neovascular age-related macular degeneration: a review

OBJECTIVE: This article reviews available information on the new selective vascular endothelial growth factor aptamer pegaptanib in the treatment of neovascular age-related macular degeneration (ARMD). The pharmacology, pharmacokinetics, pharmacodynamics, contraindications, and drug-interaction potential of pegaptanib are discussed, and the results of clinical trials evaluating its efficacy and tolerability are summarized. METHODS: Relevant articles were identified through searches of MEDLINE (1966-June 2005) and International Pharmaceutical Abstracts (1970-June 2005). The search terms included pegaptanib sodium, Macugen, age-related macular degeneration, and choroidal neovascularization. The reference lists of identified articles were reviewed for additional publications, and further information was obtained from the manufacturer of pegaptanib. Included studies were review articles and Phase II, III, and IV clinical trials, with preference given to available Phase III studies. RESULTS: Only 1 research group has evaluated the tolerability and efficacy of pegaptanib in patients with neovascular ARMD. The VEGF Inhibition Study in Ocular Neovascularization involved 2 concurrent randomized trials of intravitreous injections of pegaptanib 0.3 mg (n = 294), 1 mg (n = 300), and 3 mg (n = 296) compared with sham injections (n = 296) every 6 weeks for 54 weeks in patients with neovascular ARMD. Assessments were conducted at 6, 12, 18, 24, 30, 42, 48, and 54 weeks. The primary end point was the proportion of patients losing <15 letters on the study eye chart at 54 weeks. This end point was achieved in 70%, 71%, and 65% of patients who received pegaptanib 0.3 (P < 0.001), 1 (P < 0.001), and 3 mg (P = 0.03), respectively, compared with 55% of those receiving the sham injections. Significant improvements in visual acuity with pegaptanib compared with the sham-injection group were seen at all time points (0.3 and 1 mg: P < 0.002; 3 mg: P < 0.05). The sham-injection group was twice as likely to have severe vision loss (loss of > or =30 letters or 6 lines on the eye chart) compared with those receiving pegaptanib 0.3 or 1 mg (P < 0.001). Adverse events reported significantly more often in the pegaptanib group compared with the sham-injection group included vitreous floaters (33% vs 28%, respectively; P < 0.001), vitreous opacities (18% vs 10%; P < 0.001), and anterior-chamber inflammation (14% vs 6%; P = 0.001). Injection-related adverse events during the first year of pegaptanib treatment included endophthalmitis in 12 (1.3%) patients, retinal detachment in 6 (0.7%) patients, and traumatic injury to the lens in 5 (0.6%) patients. CONCLUSIONS: There are few published clinical data on pegaptanib. In 2 clinical comparisons with sham injections, pegaptanib was well tolerated and effective in slowing the decline in visual acuity in patients with neovascular ARMD. This agent may be considered an option for the treatment of neovascular ARMD.     

经瞳孔温热疗法治疗渗出型年龄相关性黄斑变性的疗效观察及护理

目的观察经瞳孔温热疗法（TTT）治疗渗出型年龄相关性黄斑变性（AMD）的临床疗效,探讨其护理要点和方法。方法选择AMD病人65例65眼,分为TTT组和药物组,TTT组运用810nm激光治疗仪,通过封闭脉络膜新生血管（CNV）使黄斑区的出血和渗出得以控制。随访5～25个月观察治疗效果。结果TTT组视力提高及稳定不变者共占78．1％,视力下降者21．9％;CNV总有效率84．4％,无效15．6％。药物组视力提高及稳定不变者共占42．4％,视力下降者57．6%;CNV总有效率9．1％,无效90．9％。结论TTT是治疗渗出型AMD的有效方法,治疗前做好心理护理,治疗后做好健康宣教,对降低AMD的进一步发展有重要意义。     

健康管理模式在年龄相关性黄斑变性患者中的应用

目的探讨健康管理模式在年龄相关性黄斑变性（AMD）患者中的应用效果。方法选择眼科门诊AMD早期患者60例,按随机数字表法分为干预组和对照组各30例。干预组构建健康管理模式,建立患者健康档案,定期应用阿姆斯勒（Amsler）表筛查,进行日常生活和饮食指导;对照组采用常规宣教法。结果应用健康管理模式1年后干预组患者生活习惯改善,定期使用Amsler表的患者占83．3％,对照组仅有26．7％,两组比较差异有统计学意义（Х^2=19．46,P〈0．01）;干预组仅1例玻璃膜疣融合增多,对照组有6例,两组比较差异有统计学意义（Х^2=4．04,P〈0．05）;进展情况与对照组相比,差异具有统计学意义（P〈0．05）。结论健康管理模式可有效改善患者生活习惯,延缓干性黄斑变性向湿性黄斑变性的进展。     

健康教育对老年性黄斑变性患者焦虑心理的影响

目的探讨良好适当的健康教育对老年性黄斑变性患者（AMD）焦虑心理的影响.方法对来我院南楼门诊经吲哚青绿造影和荧光眼底造影确诊的老年性黄斑变性患者进行有针对性的健康教育,同时应用Zung氏焦虑自评量表（SAS）对患者进行心理评估,判断健康教育对患者焦虑的影响.结果健康教育组的患者焦虑心理评分明显降低（P〈0.01）.结论良好适当的健康教育对老年性黄斑变性患者的焦虑心理有明显的影响作用.     

健康教育对老年性黄斑变性患者焦虑心理的影响

目的探讨良好适当的健康教育对老年性黄斑变性患者(AMD)焦虑心理的影响.方法对来我院南楼门诊经吲哚青绿造影和荧光眼底造影确诊的老年性黄斑变性患者进行有针对性的健康教育,同时应用Zung氏焦虑自评量表(SAS)对患者进行心理评估,判断健康教育对患者焦虑的影响.结果健康教育组的患者焦虑心理评分明显降低(P<0.01).结论良好适当的健康教育对老年性黄斑变性患者的焦虑心理有明显的影响作用.     

Optimizing the functionality of clients with age-related macular degeneration.

Age-related macular degeneration (ARMD) is a major cause of severe vision loss and blindness among older people. This condition is progressive, incurable, and significantly compromises central vision. Rehabilitation nurses have a pivotal role in the assessment and management of clients with ARMD. An understanding of incidence and pathophysiology of ARMD, as well as health promotion and a new treatment for ARMD can help rehabilitation nurses design interventions to help clients maintain an acceptable quality of life despite declining vision.     

Evaluation of trans-scleral diode laser using diopexy probe for subfoveal choroidal neovascular membrane in age-related macular degeneration

OBJECTIVE: To evaluate safety and short-term visual and fluorescein angiographic effects of trans-scleral diode laser photocoagulation in patients with subfoveal choroidal neovascularization from age-related macular degeneration (ARMD). BACKGROUND DATA: The visual outcome following treatment of subfoveal choroidal neovascularization in ARMD is still unsatisfactory. Various forms of therapy such as laser treatment, photodynamic therapy, radiation therapy, transpupillary thermotherapy, and surgical excision have been tried with variable results. MATERIALS AND METHODS: Patients with subfoveal choroidal neo-vascularization were treated with trans-scleral diode laser using the diopexy probe under indirect ophthalmoscopic visualization and followed up at 2, 6, and 12 weeks. Standardized protocol refraction, visual acuity testing, reading speed, contrast requirement measurement, ophthalmic examinations, color fundus photographs, and fluorescein angiogram were used to evaluate the results of treatment. RESULTS: Eighteen eyes of 18 patients were included in the study between April 2000 and May 2002. At 12 weeks, 81.5% patients showed stabilization (+/-5 letters) in letter visual acuity score, and one patient showed improvement (gain of more than five letters) in letter visual acuity score. Reading speed levels and contrast requirement were found to be similar to pre-laser level at 3 months followup. At 12 weeks, moderate fluorescein leakage was seen in one eye, minimal leakage was seen in five eyes, absence of leakage was seen in 10 eyes, and progression was seen in two eyes. CONCLUSION: Transcleral diode laser treatment of subfoveal choroidal neovascular membranes in ARMD may be an effective as well as safe alternative in the management of these patients.     

年龄相关性黄斑变性患者营养干预决策辅助方案的构建及应用

目的 探讨营养干预决策辅助方案在年龄相关性黄斑变性患者中的应用效果。方法 通过参考国内外文献、专家函询、课题小组讨论以及预试验,基于共同决策三阶段会谈模型构建年龄相关性黄斑变性患者营养干预决策辅助方案,包括团队会谈、选择会谈、决策会谈3个步骤。2021年3月—12月便利选取重庆市某三级甲等综合医院眼科110例年龄相关性黄斑变性患者,采用随机数字表法分为试验组和对照组各55例。试验组在常规健康教育的基础上实施决策辅助方案,对照组给予常规健康教育。干预后分别使用年龄相关性黄斑变性营养相关知识测评问卷、决策准备量表、决策自我效能量表、决策困境量表、综合医院焦虑/抑郁情绪测定表对两组进行评估。结果 试验组干预后营养相关知识测评问卷得分高于对照组(P<0.001),决策准备量表得分高于对照组(P<0.001);决策自我效能量表得分高于对照组(P<0.001),决策困境量表得分低于对照组(P<0.001);试验组焦虑/抑郁情绪测定表得分低于对照组(P<0.05)。结论 应用该研究制订的患者决策辅助方案,可提高患者营养干预相关知识水平,提高患者的决策准备度和决策自我效能...     

湿性年龄相关性黄斑变性患者共同决策影响因素的质性研究

目的:了解湿性年龄相关性黄斑变性(wet age-related macular degeneration,wAMD)患者共同决策的影响因素。方法:采用目的抽样法,选取23名wAMD患者进行半结构式访谈,应用Colaizzi现象学分析法进行资料分析。结果:提炼出wAMD患者共同决策影响因素的3个主题:患者参与共同决策的能力、共同决策交互因素、医疗系统因素。结论:根据wAMD患者共同决策的影响因素来充分了解疾病治疗过程中患者参与共同决策所面临的难题,为患者有效参与共同决策,并基于个人价值观、最佳循证医学证据和医生治疗经验等选择最适宜证据的治疗决策方案。     

Nutritional supplements in the prevention of age-related macular degeneration

The benefit of the AREDS study and of nutritional supplements in reducing the onset or progression of end-stage AMD in those known to be at risk is a step forward in our understanding of what can be a blinding and debilitating disease. Nutritional supplements are not without risks, and their effects must be diligently and accurately monitored. However, they pose a viable complement in the venue of treating ocular disease and conditions.     

Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial

Twenty-eight patients with advanced neovascular age-related macular degeneration (AMD) were given a single intravitreous injection of an E1-, partial E3-, E4-deleted adenoviral vector expressing human pigment epithelium- derived factor (AdPEDF.11). Doses ranging from 10(6) to 10(9.5) particle units (PU) were investigated. There were no serious adverse events related to AdPEDF.11 and no dose-limiting toxicities. Signs of mild, transient intraocular inflammation occurred in 25% of patients, but there was no severe inflammation. Six patients experienced increased intraocular pressure that was easily controlled by topical medication. All adenoviral cultures were negative. At 3 and 6 months after injection, 55 and 50%, respectively, of patients treated with 10(6)-10(7.5) PU and 94 and 71% of patients treated with 10(8)-10(9.5) PU had no change or improvement in lesion size from baseline. The median increase in lesion size at 6 and 12 months was 0.5 and 1.0 disk areas in the low-dose group compared with 0 and 0 disk areas in the high-dose group. These data suggest the possibility of antiangiogenic activity that may last for several months after a single intravitreous injection of doses greater than 10(8) PU of AdPEDF.11. This study provides evidence that adenoviral vector-mediated ocular gene transfer is a viable approach for the treatment of ocular disorders and that further studies investigating the efficacy of AdPEDF.11 in patients with neovascular AMD should be performed.