Intravitreal conbercept injection for neovascular age-related macular degeneration

AIM: To evaluate the efficacy and safety of intravitreal injection of conbercept in patients with neovascular age-related macular degeneration (AMD). METHODS: Retrospective review of 66 eyes of 63 patients with neovascular AMD. All patients received 0.5 mg intravitreal injections of conbercept monthly for 3 consecutive months, and then pro re nata treatment was performed. The changes of best-corrected visual acuity (BCVA) and central macular thickness (CMT) were observed before and after treatments. Minimum follow-up time was 12mo. SPSS 22.0 statistical software was used for statistical analysis. RESULTS: The mean BCVA and CMT of 66 eyes (63 patients) were 1.11±0.60, 533.20±219.95 μm at baseline, and were 0.68±0.38, 310.28±125.60 μm at 3mo. No subjects were lost during the first three months, the improvements were all significantly (P<0.05). During the whole follow-up time of 12mo, 15 subjects (18 eyes) were lost. The mean BCVA and CMT of the rest 48 eyes with the follow-up time at least 1y were 0.83±0.46 and 547.59±196.77 μm at baseline, after 3mo and 12mo of conbercept injections became 0.55±0.41, 318.24±141.29 μm and 0.55±0.51, 333.87±173.25 μm. The differences were significant (P<0.05). No serious complications were observed. CONCLUSION: Intravitreal injection of conbercept appears to significantly improve visual acuity and anatomical outcomes in patients with neovascular AMD, no serious adverse reactions and complications are observed.     

One-year outcome after intravitreal ranibizumab for large, serous pigment epithelial detachment secondary to age-related macular degeneration

Aim

To report the effects of intravitreal ranibizumab therapy for large, serous pigment epithelial detachment (PED), secondary to age-related macular degeneration, and occupying more than 50% of the total lesion area.

Materials and methods

In a retrospective case series, visual acuity, ocular coherence tomography (OCT), and safety data were collected for 19 eyes of 19 patients, with serous PED and evidence of disease progression. Intravitreal ranibizumab of 0.5 mg was given with a loading phase of three consecutive monthly injections, followed by monthly review with further treatment, as indicated according to visual acuity and OCT findings. The change in visual acuity and maximum PED height from baseline to month 12 was determined.

Results

Moderate visual loss was avoided in 18/19 eyes (95%) at the 12-month examination. In all, 12 eyes (63%) had an increase in ETDRS letter score from baseline, and five eyes (26%) had a gain of 15 or more letters. Although there was a trend for the PED height to reduce with treatment, in none of the cases was the PED seen to resolve completely. There was no difference in functional or anatomical outcome between the avascular and vascularised serous PED. A single eye developed a retinal pigment epithelium rip, complicated by extensive sub-retinal haemorrhage, during the study period.

Conclusions

Visual acuity outcomes of intravitreal ranibizumab for large serous PED are comparable to those seen in multicentre, phase 3 trials of other lesion types, and were obtained without the need for either monthly, fixed treatment, or for continued treatment until the PED resolves.     

干性年龄相关性黄斑变性患者视网膜色素上皮细胞损伤机制

年龄相关性黄斑变性(age-related macular degeneration,AMD)是中老年人视力障碍的重要原因之一。AMD分为2型:萎缩型(干性)和渗出型(湿性)。本文从光照损伤、脂褐素积累、氧化损伤、内质网应激4个方面,综述了干性AMD研究中基于视网膜色素上皮细胞损伤的相关研究进展,为进一步探索其发病机制提供依据和方向。     

AMD并发视网膜色素上皮脱离的研究现状及治疗进展

视网膜色素上皮脱离伴随许多脉络膜视网膜病的疾病进程,尤其常见于AMD.了解AMD并发视网膜色素上皮脱离的发病机制以及脱离类型,不仅有助于预测疾病进程,更可以帮助医生选择合适的治疗方案,改善患者预后.     

玻璃体腔注射康柏西普治疗渗出性年龄相关性黄斑变性

目的：观察玻璃体腔注射康柏西普治疗渗出性年龄相关性黄斑变性(age-related macular degeneration,ARMD)的临床疗效。

方法：回顾性研究我院2015-07/2016-01确诊的渗出性ARMD患者45例45眼,采取每月1次玻璃体腔注射康柏西普(0.5mg/0.05mL),连续治疗3mo,之后按需给药(3+PRN),随访2a。分别观察治疗前和治疗后最佳矫正视力(best corrected visual acuity,BCVA)、黄斑中心凹厚度(central macular thickness,CMT)变化情况。

结果：治疗后第1、2、3mo,1、2a后的BCVA较治疗前显著提高,差异有统计学意义(t=5.208、5.111、4.323、4.701、5.156,P<0.05),CMT较治疗前显著减低,差异有统计学意义(t=3.807、4.556、2.841、2.707、3.145,P<0.05)。

结论：康柏西普眼用注射液3+PRN方案治疗渗出性ARMD可以有效提高视力、减轻黄斑水肿。     

Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration

Purpose

There is evidence for complement dysfunction in age-related macular degeneration (AMD). Complement activation leads to formation of the membrane attack complex (MAC), known to assemble on retinal pigment epithelial (RPE) cells. Therefore, the effect of sub-lytic MAC on RPE cells was examined with regard to pro-inflammatory or pro-angiogenic mediators relevant in AMD.

Methods

For sub-lytic MAC induction, RPE cells were incubated with an antiserum to complement regulatory protein CD59, followed by normal human serum (NHS) to induce 5% cell death, measured by a viability assay. MAC formation was evaluated by immunofluorescence and FACS analysis. Interleukin (IL)-6, -8, monocytic chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Intracellular MCP-1 was analysed by immunofluorescence, vitronectin by western blotting, and gelatinolytic matrix metalloproteinases (MMPs) by zymography.

Results

Incubation of RPE cells with the CD59 antiserum followed by 5% NHS induced sub-lytic amounts of MAC, verified by FACS and immunofluorescence. This treatment stimulated the cells to release IL-6, -8, MCP-1, and VEGF. MCP-1 staining, production of vitronectin, and gelatinolytic MMPs were also elevated in response to sub-lytic MAC.

Conclusions

MAC assembly on RPE cells increases the IL-6, -8, and MCP-1 production. Therefore, sub-lytic MAC might have a significant role in generating a pro-inflammatory microenvironment, contributing to the development of AMD. Enhanced vitronectin might be a protective mechanism against MAC deposition. In addition, the increased expression of gelatinolytic MMPs and pro-angiogenic VEGF may be associated with neovascular processes and late AMD.     

miRNA-146a在视网膜色素上皮细胞老化及老年性黄斑变性中的功能研究

目的 检测miRNA-146a(miR-146a)在视网膜色素上皮细胞(retinal pigment epithelial cells,RPE)衰老及老年性黄斑变性(age-related macular degeneration,AMD)中的表达水平,并探讨其通过抑制VEGF-A表达,参与调控AMD病变进程的机制.方法 qRT-PCR检测年龄为2个月、8个月、12个月、18个月和24个月小鼠的RPE及75岁晚期“湿”性AMD患者眼球中miR-146以及VEGF-A的mRNA表达水平.Western Blotting检测VEGF-A蛋白表达水平.在ARPE-19细胞系中转染miR-146a,通过qRT-PCR及Western Blotting检测miR-146a对VEGF-A mRNA及蛋白水平的影响.结果 在自然衰老的RPE中,miR-146的表达呈现随年龄增加逐渐上升的趋势,与2个月的小鼠相比,在18个月及24个月的小鼠中miR-146a水平上升约8倍及24倍.而VEGF-A的表达呈现下降趋势,与对照相比,24个月的小鼠RPE中的VEGF-A相对水平由2个月时的1.5倍降为0.8倍.但是在AMD患者中,病灶部位的miR-146a较病灶旁侧表达下降14.5倍,VEGF-A表达上升.在ARPE-19细胞中过表达miR-146a抑制了VEGF-A的mRNA及蛋白表达水平.结论 本实验结果将miR-146a与RPE衰老及AMD的发生联系在一起,未来有可能成为RPE衰老及AMD早期诊断的新的分子标记物,为制定临床治疗策略提供参考.     

康柏西普玻璃体腔注射治疗渗出型老年性黄斑变性的疗效

目的：观察玻璃体腔内注射康柏西普治疗渗出型老年黄斑变性的临床疗效。
　　方法：前瞻性研究。渗出型老年黄斑变性患者112例112眼,随机分为研究组和对照组,各56例56眼,研究组患者采用玻璃体腔内注射康柏西普治疗,对照组采用保守治疗,观察治疗前后两组患者裸眼视力及黄斑中心凹视网膜厚度。
　　结果：研究组患者治疗后视力明显提高,且治疗后6mo 提高最明显。研究组患者治疗后黄斑中心凹视网膜厚度均减低,且治疗后6mo 减低最明显。
　　结论：玻璃体腔内注射康柏西普能有效提高渗出型老年黄斑变性患者视力,降低黄斑中心凹厚度。     

Influence of pigment epithelial detachment on visual acuity in neovascular age-related macular degeneration

Pigment epithelial detachment (PED), the anatomical separation of the retinal pigment epithelium from the Bruch membrane, is common in many chorioretinal diseases, including neovascular age-related macular degeneration. PED is present in about 30% to 80% of neovascular age-related macular degeneration patients based on the CATT, EXCITE, and VIEW studies. The influence of PED on visual acuity is controversial as a result of inconsistent results reported by various studies. With advances in imaging technologies, it is possible to evaluate not only the presence or absence of PED, but also detailed quantitative parameters, such as height, width, greatest linear diameter, area, volume, and reflectivity within the PED. We performed a comprehensive literature review to evaluate the relationship of PED with visual acuity. In summary, the presence or persistence of a PED may still be compatible with relatively good visual acuity. There is no strong evidence that the presence of a PED or aspects of its morphology has a significant impact on visual acuity. The presence of a PED may be predictive of the need for more regular treatment. More well-designed studies with standardized PED definitions and classifications are needed to evaluate the relationship between PED and visual acuity.     

Interleukin-13 and age-related macular degeneration

AIM: To identify the effects of interleukin (IL)-13 on retinal pigment epithelial (RPE) cells and the IL-13 level in aqueous humor of age-related macular degeneration (AMD) patients. METHODS: IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA). ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot respectively. The expression of tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) were assessed by ELISA. RESULTS: IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33±17.64 vs 27.12±5.65 pg/mL; P<0.01). In vitro, IL-13 of high concentrations (10, 15, and 20 ng/mL) inhibited ARPE-19 cell proliferation. α-SMA mRNA in ARPE-19 cell were increased (1.017±0.112 vs 1.476±0.168; P<0.001) and ZO-1 decreased (1.051±0.136 vs 0.702±0.069; P<0.001) after treated with 10 ng/mL IL-13 for 48h. The protein expression of α-SMA and ZO-1 also showed the same tendency (α-SMA: P=0.038; ZO-1: P=0.008). IL-13 significantly reduced the level of TNF-α (44.70±1.67 vs 31.79±3.53 pg/mL; P=0.005) at 48h, but the level of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/mL at 24h (P=0.004) and from 61.26±1.11 to 86.91±3.59 pg/mL at 48h (P<0.001). While expressions of VEGF didn’t change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.     

Change of retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in exudative age-related macular degeneration

Purpose:The study aimed to investigate the quantitative changes of retinal pigment epithelial (RPE) atrophy during a 24-month follow-up period of anti-vascular endothelial growth factor (VEGF) for exudative age-related macular degeneration (AMD).Results:The mean number of anti-VEGF treatments was 9.18. RPE atrophic area was 1.293 ± 1.298 mm² at baseline and enlarged to 2.394 ± 1.940 mm² after 24 months, which differed significantly (P = 0.001). Multiple regression analysis revealed that larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF treatments were associated with increased RPE atrophic areas.Conclusions:RPE atrophy progresses in eyes with exudative AMD during anti-VEGF treatment. Larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF injections were associated with an increased risk of progression of RPE atrophy the following treatment. These findings may be useful to clinicians using intravitreal anti-VEGF for the treatment of exudative AMD, both for selecting an appropriate treatment plan and for predicting the progression of RPE atrophy.     

丛生蛋白参与年龄相关性黄斑变性的作用机制

丛生蛋白是玻璃膜疣的主要蛋白成分之一。近年来研究发现丛生蛋白与衰老密切相关,不仅通过对补体系统的调节参与年龄相关性黄斑变性（ａｇｅ-ｒｅｌａｔｅｄｍａｃｕｌａｒｄｅｇｅｎ-ｅｒａｔｉｏｎ,ＡＭＤ）炎症反应发生机制,也与氧化还原反应密切相关,是ＡＭＤ发生过程中氧化应激反应的感受器。本文就丛生蛋白参与ＡＭＤ作用机制的研究进展进行综述。     

康柏西普玻璃体腔注射治疗湿性年龄相关性黄斑变性

目的：观察康柏西普玻璃体腔注射治疗湿性年龄相关性黄斑变性的临床疗效。

方法：将确诊的60例湿性年龄相关性黄斑变性的患者,根据随机数字表法分为治疗组和对照组各30例。治疗组注射康柏西普0.05mL,对照组注射曲安奈德0.1mL。在治疗前及治疗后1d,1、3mo采用标准视力表对患者进行最佳矫正视力(BCVA)检查; 用光学相干断层扫描仪(OCT)检测黄斑中心凹视网膜厚度。并观察患者治疗后1d,1、3mo内出现的并发症情况,包括前房炎性反应、角膜水肿、高眼压等。

结果：治疗组治疗后1d,1、3mo视力提高明显好于对照组(P<0.05)。治疗组治疗后1d,1、3mo的黄斑中心凹视网膜厚度明显低于对照组(P<0.05)。治疗组和对照组治疗后1d,1、3mo均未出现眼部严重并发症。

结论：康柏西普玻璃体腔注射治疗湿性年龄相关性黄斑变性可以提高疗效。     

玻璃体内注射雷珠单抗对年龄相关性黄斑变性患者眼表的影响

目的探究玻璃体内注射药物对年龄相关性黄斑变性(age-related macular degeneration,AMD)患者眼表的影响。方法选取南昌大学第一附属医院眼科住院部18例(均单眼患病)被诊断为AMD且需进行玻璃体内注射雷珠单抗治疗的患者为研究对象,其中,患眼作为A组进行3次玻璃体内注射雷珠单抗治疗;对侧健康眼作为B组不进行任何治疗。双眼均在治疗前及3次治疗结束后6 h进行相关检测。对比两组患者治疗前后泪液分泌测试(Schirmer I test,SIT)、泪膜破裂时间(break-up time,BUT)、角膜荧光素染色(corneal fluorescein staining,CSF)及眼部症状和体征评分情况。结果两组治疗前泪河高度相比,差异无统计学意义(P>0.05);A组治疗前和治疗后的最佳矫正视力和治疗后的泪河高度均低于B组,差异均有统计学意义(均为P<0.05);与治疗前相比,A组治疗后的最佳矫正视力明显上升,泪河高度明显下降,差异均具有统计学意义(均为P<0.05);B组最佳矫正视力、泪河高度改变均不明显,差异均无统计学意义(均为P>0.0...     

Assessment of the long-term visual and anatomical outcomes of ranibizumab to treat neovascular age-related macular degeneration

AIM: To investigate the long-term visual and anatomical outcomes of patients who underwent intravitreal ranibizumab monotherapy to treat neovascular age-related macular degeneration (AMD) and followed-up for at least 2y. METHODS: A total of 74 eyes of 74 patients who underwent ranibizumab monotherapy for neovascular AMD were included in this retrospective study. RESULTS: The average patient age was 72.1±6.5 (range, 57-85)y, the average follow-up time 46.2±13.1 (range, 24-75)mo, and the average number of visits 24.1±9.5 (range, 8-48). The mean number of injections in year 1 was 4.5, 1.6 in year 2, 0.9 in year 3, 0.4 on year 4, and 0.1 in the following years. Within the entire follow-up period, the mean number of injections was 7.6±4.4 (range, 2-21). The mean visual acuity was 48.1±15 (range, 15-76) letters at baseline and 45.7±19 (range, 7-75) at year 5. The mean central macular thickness was 303±78 (range, 178-552) μm at baseline and 251±51 (range, 138-359) μm at year 5. Scars developed in 47 (63.5%) eyes at the end of the follow-up period, and atrophy was evident in 6 (8.1%) eyes. CONCLUSION: Ranibizumab monotherapy can stabilize visual acuity for a mean period of 4y in patients with neovascular AMD.     

Spontaneous or secondary to intravitreal injections of anti-angiogenic agents retinal pigment epithelial tears in age-related macular degeneration

AIM:To evaluate the visual function evolution of retinal pigment epithelial (RPE) tears in patients with age-related macular degeneration (AMD) according to type of occurrence [spontaneous or secondary to anti-vascular endothelial growth factor (anti-VEGF) injection] and the topographic location of the tear after a two-year follow-up period.METHODS:A total of 15 eyes of 14 patients with RPE tears in exudative AMD were analyzed retrospectively at the University Eye Clinic of Trieste. Inclusion criteria were:patient age of 50 or older with AMD and RPE tears both spontaneous occurring or post anti-VEGF treatment. Screening included:careful medical history, complete ophthalmological examination, fluorescein angiography (FA), indocyanine green angiography (ICG), autofluorescence and infrared imaging and optical coherence tomography (OCT). Patients were evaluated every month for visual acuity (VA), fundus examination and OCT. Other data reported were:presence of PED, number of injections before the tear, location of the lesion.RESULTS: Mean follow-up was 24wk (SD±4wk). A total of 15 eyes were studied for RPE tear. In 6 cases (40%), the RPE tears occurred within two years of anti-VEGF injections the others occurred spontaneously. In 13 cases (86.6%), the RPE tear was associated with pigment epithelial detachment (PED). In 7 cases (46.6%), the RPE tear occurred in the central area of the retina and involved the fovea. Two lesions were found in the parafoveal region, six in the extra-macular area. In all cases visual acuity decreased at the end of the follow-up period (P<0.01) independently of the type or the topographical location of the lesion.CONCLUSION:RPE tear occurs in exudative AMD as a spontaneous complication or in relation to anti-VEGF injections. Visual acuity decreased significantly and gradually in the follow-up period in all cases. No correlation was found between visual loss and the type of onset or the topographic location of the tears.     

玻璃体腔注射Ranibizumab联合经瞳孔温热疗法治疗年龄相关性黄斑变性

目的：观察玻璃体腔注射Ranibizumab联合经瞳孔温热疗法( TTT)治疗渗出型年龄相关性黄斑变性的临床疗效及安全性。方法：选取来我院就诊并通过病史、临床症状及眼底血管照影(FFA/ICGA)和光学相干断层扫描(OCT)等辅助检查确诊的渗出型年龄相关性黄斑变性的患者160例(160眼),随机分为联合组和对照组,联合组给予单次行玻璃体腔注射Ranibizumab,7d后行TTT治疗,对照组仅行TTT治疗,随访1a,分别于治疗后1wk;1,6mo;1a,观察患者的最佳矫正视力、散瞳后眼底的变化及眼底血管照影( FFA/ICGA)及OCT的检查。
　　结果：观察期末,联合组最佳矫正视力提高34例(42.50%),对照组最佳矫正视力提高16例(20.00%),差异具有统计学意义(P<0.05)。治疗后1wk;1,6mo;1a联合组和对照组的荧光渗透有效率分别为(88.75%,62.50%);(91.25%,65.00%);(86.25%,61.25%);(78.75%,51.25%)。治疗后1 wk;1,6 mo;1 a联合组和对照组黄斑中心厚度分别为：(347.43±36.96)μm 和(423.58±29.03)μm;(287.78±34.16)μm和(387.14±32.98)μm;(301.75±37.21)μm和(415.40±31.38)μm;(326.17±27.39)μm 和(436.44±35.49)μm,两组相比,差异具有统计学意义(P<0.05)。结论：玻璃体腔注射Ranibizumab联合经瞳孔温热疗法治疗渗出型年龄相关性黄斑变性,能够使患者的视力得到改善,病灶渗漏停止或减轻,促进黄斑区出血、水肿及渗出的吸收,安全、疗效可靠,是一种有效的临床治疗方法。     

Vascular endothelial growth factor and its inhibitor in age-related macular degeneration

Intraocular angiogenesis is considered the leading cause for severe loss of vision, and contributes to many ocular diseases such as neovascular age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, the main causes of blindness in developed countries.¹ An enormous body of work has demonstrated that vascular endothelial growth factor (VEGF) plays a prominent role as mediator in the procedure of pathological angiogenesis. This makes VEGF a potential target for the medical therapies of retinal angiogenesis and some clinical trials have proved the efficacy of anti-VEGF strategies. This review evaluates the role of VEGF in the pathogenesis of age-related macular degeneration and provides an overview of recent developments in therapeutic modalities.     

Measurement of macular pigment optical density among healthy Chinese people and patients with early-stage age-related macular degeneration

AIM: To measure the macular pigment optical density (MPOD) in healthy Chinese people and patients with early age-related macular degeneration (AMD). METHODS: Cross-sectional population based study. Demographic and lifestyle characteristics were ascertained by questionnaire. A food frequency questionnaire was completed for all participants. Participants underwent general physical and ophthalmic examinations and MPOD was measured by heterochromatic flicker photometry. Foveal architecture was measured by optical coherence tomography. RESULTS: MPOD of 225 participants (122 healthy and 103 early AMD) was 0.48±0.18. Patients with early AMD (0.52±0.19) tended to have higher MPOD levels than healthy people (0.47±0.17), but the difference was not statistically significant (P=0.06). Participants with carrot or corn oil intake every week tended to have higher levels of MPOD (P=0.002 and 0.008 respectively) while those with corn intake had relatively lower level of MPOD (P=0.01). MPOD increased with the center foveal thickness (P=0.01). CONCLUSION: Our findings show that there is no statistically significant association between MPOD and early AMD in the studied population. MPOD is related to center foveal thickness and diets would influence MPOD levels.