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.     

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。     

雷珠单抗治疗渗出型AMD伴浆液性视网膜色素上皮脱离的效果分析

目的:探讨渗出型老年性黄斑变性(AMD)伴浆液性视网膜色素上皮脱离(serous retinal pigment epithelial detachment,SPED)患者应用雷珠单抗的治疗效果.方法:选取2015-02/2016-02在我院治疗的渗出型AMD伴SPED患者60例60眼,给予玻璃体腔注射雷珠单抗(intravitreal injection of ranibizumab,IVR)治疗,检查患者治疗前后最佳视力矫正(bestcorrected visual acuity,BCVA)、PED高度和容积、黄斑中心凹视网膜厚度(central fovea thickness,CFT)以及房水中血管内皮生长因子(vascular endothelial growth factor,VEGF).结果:患者治疗后1、3、6 mo BCVA分别为0.6±0.1、0.4±0.1和0.3±0.1,均明显较治疗前改善,差异均有统计学意义(P<0.05);患者治疗后1、3、6mo PED高度和容积均较治疗前降低,差异均有统计学意义(P<0.05),其中治疗后6mo患者PED高度和容积分别为240.02±35.10μm和0.310±0.120mm3;患者治疗后6mo CFT为290.02±33.10μm,明显低于治疗前及治疗后1mo,差异均有统计学意义(P<0.05);患者治疗后1、3、6 mo房水VEGF均较治疗前降低,差异均有统计学意义(P<0.05),其中治疗后6 mo患者房水VEGF为149.11±28.89 pg/mL;治疗期间未发现有眼内炎、葡萄膜炎等不良反应发生.结论:IVR治疗渗出型AMD伴SPED有较好的效果,能有效提高患者视力,降低PED高度和容积以及房水VEGF浓度,且安全可靠.     

康柏西普两种给药方案治疗新生血管性年龄相关性黄斑变性48周的效果比较

目的 比较康柏西普两种给药方案治疗新生血管性年龄相关性黄斑变性(nAMD)48周的效果。设计随机对照临床试验。研究对象兰州大学第二医院眼科nAMD患者30例。方法 30例(30眼)患者以简单随机抽样法分为两组,治疗延长组(3+T&E组)16例和按需给药组(3+PRN组)14例。患眼进行康柏西普0.05 ml玻璃体注射,按治疗方案随访48周。主要指标最佳矫正视力(BCVA)、中央视网膜厚度(CRT)变化、脉络膜新生血管(CNV)变化及玻璃体注药次数。结果 失访4例,随访完成的26例患者中3+T&E组和3+PRN组分别为15例(15眼)和11例(11眼)。与基线相比,治疗后4、16、20、32、48周,3+T&E组平均BCVA提高,但差异均无统计学意义(P均>0.05);3+PRN组平均BCVA提高,与基线相比,在治疗后4、16、20周,差异无统计学意义(P=0.378、0.097、0.090),第32、48周,差异有统计学意义(P=0.034、0.025);两组治疗后平均CRT与基线相比,差异均有统计学意义(P均<0.01)。治疗后4、16、20、32...     

年龄相关性黄斑变性中隐匿性脉络膜新生血管伴色素上皮脱离的光动力学疗法

目的：研究新生血管性年龄相关性黄斑变性(AMD)伴有色素上皮脱离(PED)采用光动力学疗法后的视力和血管造影的结果。     

单次注射康柏西普治疗渗出型AMD患者RPE隆起面积与容积变化

目的　观察单次玻璃体内注射康柏西普治疗渗出型年龄相关性黄斑变性（ａｇｅ-ｒｅｌａｔｅｄｍａｃｕｌａｒｄｅｇｅｎｅｒａｔｉｏｎ,ＡＭＤ）患者的视网膜色素上皮（ｒｅｔｉｎａｌｐｉｇｍｅｎｔｅｐｉｔｈｅｌｉｕｍ,ＲＰＥ）隆起的面积及容积变化,以评价康柏西普治疗ＡＭＤ的短期疗效及安全性。方法　选取渗出型ＡＭＤ患者４０例（４５眼）,所有患者均行玻璃体内注射康柏西普０．０５ｍＬ（０．５ｍｇ）治疗。术前、术后１周、１个月及３个月复诊行Ｃｉｒｒｕｓ５０００ＯＣＴ检查,比较治疗前后最佳矫正视力（ｂｅｓｔｃｏｒｒｅｃｔｅｄｖｉｓｕａｌａｃｕｉｔｙ,ＢＶＣＡ）、黄斑中心凹厚度及ＲＰＥ隆起的面积、容积。结果　术后１周、１个月,ＢＣＶＡ（ｌｏｇＭＡＲ）由术前１．２５±０．７９分别提升至０．９２±０．６６（Ｐ＜０．００１）和０．９４±０．６１（Ｐ＜０．００１）,３ｍｍ圆内ＲＰＥ隆起面积及容积由术前的（２．９１±１．７３）ｍｍ２、（０．５０±０．７３）ｍｍ３分别降至（２．７５±１．８２）ｍｍ２（Ｐ＝０．０２４）、（０．４２±０．７１）ｍｍ３（Ｐ＝０．０２０）和（２．３３±１．８５）ｍｍ２（Ｐ＝０．００２）、（０．３２±０．０９）ｍｍ３（Ｐ＝０．０４６）。术后３个月时ＢＣＶＡ下降至１．３０±０．８２,与术前差异无统计学意义（Ｐ＞０．０５）;３ｍｍ圆内ＲＰＥ隆起面积及容积增加到（２．７３±１．８１）ｍｍ２、（０．５１±０．７９）ｍｍ３,与术前相比差异均无统计学意义（均为Ｐ＞０．０５）。术后１周、１个月、３个月５ｍｍ圆内ＲＰＥ隆起面积及容积与术前差异均无统计学意义（均为Ｐ＞０．０５）。黄斑中心凹厚度仅在术后１个月由术前（２４４．５６±２５．３７）μｍ降至（２３４．９１±２１．５０）μｍ（Ｐ＝０．０４４）。所有患者均未出现严重眼部并发症及全身不良反应。结论　康柏西普短期内治疗渗出型ＡＭＤ可显著提高视力,恢复视网膜结构,具有良好的安全性。     

年龄相关性黄斑变性中隐匿性脉络膜新生血管 伴色素上皮脱离的光动力学疗法

目的：研究新生血管性年龄相关性黄斑变性(AMD)伴有色素上皮脱离(PED)采用光动力学疗法后的视力和血管造影的结果。方法：回顾自2000年1月1日-002年8月31日，患有AMD伴脉络膜新生血管和至少一个视盘直径的浆液性PED，接受过光动力学疗法所有连续患者的荧光素和吲哚青绿血管造影照片和医疗图表。结果：30例(34只眼)符合研究标准。每例进行了1—8次治疗(平均4次)；随访12—36个月(平均19个月)。19只眼(56％)丧失了Snellen表3行或3行以上视力，7只眼(21％)丧失1—2行视力，6只眼(18％)保持原有视力，2只眼(6％)增进1—2行视力。5只眼发生了视网膜下出血，4只眼视网膜色素上皮破裂。有4只眼视力下降至数指、手动或光感。结论：在AMD和PED的34只眼中，尽管有44％丧失了少于3行的Snellen视力，但视力严重丧失至数指或更少的有4只眼，其中3只眼PED内有脉络膜新生血管形成。需要进一步的研究和治疗程式以改善新生血管性AMD伴浆液性PED的预后。     

雷珠单抗治疗新生血管性年龄相关性黄斑变性的长期疗效

目的：研究就诊于我院新生血管性年龄相关性黄斑变性(NV-AMD)患者使用雷珠单抗治疗后3年的疗效。

方法：回顾性研究。共纳入73例(101眼)患者。根据入组时视力情况(ETDRS chart),患者被分为3组。第1组：视力≤ 35; 第2组：视力36～54; 第3组：视力≥55字母。患者接受3次,每次0.5 mg的雷珠单抗负荷剂量,之后根据病情决定是否再次注射。对患者每月进行一次随访,进行视力、详细的眼前节及眼底的生物显微镜,以及光学相干断层扫描(OCT)检查。对最接近12、24、36mo的视力检查结果进行分析。

结果：纳入的101眼中,男性57眼,女性44眼。患者平均年龄75.1岁。治疗24mo和36mo时,三组患者之间视力变化情况差异均有统计学意义(P=0.002, 0.0001)。治疗36mo后,第2组视力较入组时显著改善(P=0.001),第3组患者视力改善不显著。随访12、24、36mo时,第1组视力无明显变化的患者人数最多。所有患者平均注射雷珠单抗7.3次,随访次数23.9次。

结论：入组时视力情况尚可的患者视力改善最明显。视力较差和视力较好的患者视力改变不明显。最终视力与注射次数无明显关系。     

雷珠单抗联合光动力疗法治疗wAMD的效果

目的：探讨湿性年龄相关性黄斑变性(wAMD)患者采用雷珠单抗联合光动力疗法的临床效果及对患者血清新生血管调控因子的影响。

方法：回顾性分析。选取2014-01/2016-06我院治疗的wAMD患者68例68眼进行分析,其中采取光动力疗法治疗(对照组)34眼、采用雷珠单抗联合光动力疗法治疗(治疗组)34眼,对比两组患者治疗前后BCVA、视网膜平均厚度、黄斑中心凹视网膜厚度(CMT)值及血清新生血管调控因子情况。

结果：治疗前,两组患者的BCVA、视网膜平均厚度、CMT值比较差异无统计学意义(P>0.05); 治疗后3、6、12mo,两组患者的BCVA值、视网膜平均厚度、CMT值较本组治疗前均显著降低,差异有统计学意义(P<0.05); 治疗组患者的BCVA值、视网膜平均厚度、CMT值均显著低于对照组,差异有统计学意义(P<0.05)。治疗前,两组患者血清中VEGF、PDGF、TIMP-1、ES值差异无统计学意义(P>0.05); 治疗后3mo,两组患者血清中的VEGF、PDGF、ES值较本组治疗前均显著降低,差异有统计学意义(P<0.05); 治疗组患者的VEGF、PDGF、ES值均显著低于对照组,差异有统计学意义(P<0.05)。

结论：雷珠单抗联合光动力疗法治疗wAMD患者能取得更加显著的临床效果,更有效地降低血清中新生血管调控因子水平。     

Retinal pigment epithelial detachment

Detachment of the retinal pigment epithelium is a prominent feature of many chorio-retinal disease processes, the most prevalent of which is age-related macular degeneration (AMD). Detachment of the retinal pigment epithelium may or may not be associated with choroidal neovascularization and may be caused by different types of pathogenesis, each associated with distinct angiographic features, natural course, visual prognosis, and response to treatment. The phrase "detachment of the retinal pigment epithelium" is used quite often, not always in the correct association and with no clear differentiation between its various types. It is important to identify the specific nature of detachment of the retinal pigment epithelium, and to establish an accurate diagnosis and treatment plan. Therefore, we present a review of the existing types of detachment of the retinal pigment epithelium with what we propose as being appropriate nomenclature and classification, and potential treatment recommendations.     

Long-term visual outcome of pigment epithelial tears in association with anti-VEGF therapy of pigment epithelial detachment in AMD

Purpose

Retinal pigment epithelium (RPE) tears may develop as a complication after anti-VEGF (vascular endothelial growth factor) treatment for pigment epithelial detachments (PEDs) in exudative age-related macular degeneration (AMD). This retrospective study analyses best-corrected visual acuity (BCVA) and foveal involvement after RPE tears that are associated with anti-VEGF therapy due to PED in exudative AMD.

Methods

A total of 37 patients with RPE tears during anti-VEGF therapy (bevacizumab 12, ranibizumab 21 and pegaptanib 4 eyes) for progressive PED in AMD (PED with occult choroidal neovascularization 25 eyes and PED with retinal angiomatous proliferation 12 eyes) were included in this study. We analyzed BCVA and different morphologic aspects by means of appearance on fluorescein angiography and optical coherence tomography. Mean follow-up was 88 weeks.

Results

RPE tears were diagnosed a mean of 56 days after the first injection. BCVA deteriorated after RPE tear and during follow-up significantly (P<0.001), with 53.2% of eyes being legally blind (WHO, world health organization) at 12 months. RPE-free foveal area, foveal wrinkling of the RPE, and fibrotic scar development were significantly associated with worse visual acuity.

Discussion

RPE tears can be observed in 12–15% of treated eyes during anti-VEGF therapy for PED in exudative AMD. Owing to the close time relationship with the therapy, this complication must be taken into consideration. Visual prognosis is associated with a decrease in vision in the long term, often resulting in a severe visual disability. Relevant factors for a negative visual prognosis were the potential foveal involvement of the central RPE and morphologic fibrovascular transformation of the RPE tear.     

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.     

High-dose ranibizumab therapy for vascularized pigment epithelial detachment

Purpose

The conventional dose of anti-vascular endothelial growth factor treatment may slowly reduce the subretinal fluid and height of a vascularized pigment epithelial detachment (vPED), but rarely leads to its complete resolution. We report a dramatic outcome involving a high dose (2 mg) of ranibizumab for treating vPED.

Methods

This report describes three eyes with vPED that received 2 mg in 0.05 ml of ranibizumab injections on a monthly basis and were followed prospectively. Each patient received a complete ocular examination, including best-corrected standardized ETDRS testing, fundus photography (FP), fluorescein angiography (FA), optical coherent tomography (OCT), and indocyanine-green angiography at baseline. ETDRS and OCT testing were repeated monthly, while FP and FA were performed every 3 months.

Results

Following a single intravitreal injection of 2 mg ranibizumab, there was rapid resolution of the subretinal fluid, haemorrhage, exudates, and flattening of the vPED within 10 days for Case 1, and within 1 month for Case 2 and Case 3.

Conclusion

Rapid and dramatic decrease in the exudative changes and collapse of the vPED may develop after a single injection of high-dose (2 mg) ranibizumab in certain eyes with a vPED. The improvement was maintained with additional monthly injections to 12 months.     

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.     

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment*

Objective: To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Design: Retrospective, consecutive, interventional case series. Participants: Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Methods: Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Results: Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455?µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p?p?=?0.029). In patients with PED, there was a mean 27.9% reduction in height (p?=?0.046) at eight weeks’ follow-up. Conclusions: Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.     

Retinal pigment epithelium and endothelial cell interaction causes retinal pigment epithelial barrier dysfunction via a soluble VEGF-dependent mechanism

PURPOSE: To investigate the effect of endothelial cells (EC) on the barrier function of the retinal pigment epithelium (RPE). METHODS: Primary bovine RPE were grown in solo culture or in coculture with bovine EC. Culture media of RPE were varied to develop a monolayer with stable barrier properties determined by transepithelial electrical resistance (TER) and permeability to sodium fluorescein. The effect of EC on the barrier properties of RPE was tested in contacting and non-contacting cocultures of RPE and EC. The conditioned media of cocultures were analysed for soluble vascular endothelial growth factor (VEGF) by ELISA. A neutralizing antibody to VEGF(165) was added to cocultures of RPE and EC and the TER was measured. RESULTS: RPE had maximal barrier properties (high TER, low permeability, positive staining for barrier proteins) at day 10 that persisted until day 20. Compared to solo RPE culture, cocultivation of RPE with EC reduced RPE barrier function significantly and led to a greater release of soluble VEGF into the conditioned media (p<0.05). Neutralizing VEGF with antibody led to partial recovery of barrier properties in the coculture conditions (p<0.03). CONCLUSIONS: Coculture of RPE with EC reduces RPE barrier properties and the reduction is, in part, mediated by soluble VEGF. EC-RPE contact-induced disruption of barrier properties occurs in ocular pathologies such as choroidal neovascularization, where EC move through Bruch's membrane and contact the RPE, leading to further exacerbation of the already compromised blood-retinal barrier.     

玻璃体腔注射雷珠单抗和康柏西普治疗渗出型年龄相关性黄斑变性疗效比较

目的：探讨玻璃体腔注射雷珠单抗和康柏西普治疗渗出型年龄相关性黄斑变性(ARMD)疗效,并分析对患者最佳矫正视力(BCVA)、中心凹视网膜厚度(CRT)和并发症的影响。

方法：回顾性分析。收集2017-01/2020-01我院收治的渗出型ARMD患者60例60眼临床资料,按治疗药物不同分为玻璃体腔注射雷珠单抗组30眼和玻璃体腔注射康柏西普组30眼。比较两组患者治疗前,治疗1、2、3mo时患者BCVA、CRT、脉络膜新生血管变化和并发症发生情况。

结果：治疗后1、2、3mo,两组患者BCVA(LogMAR)较治疗前显著改善(P<0.05),CRT较治疗前显著降低(P<0.05),且玻璃体腔注射康柏西普组治疗1、2、3mo的CRT显著低于玻璃体腔注射雷珠单抗组(P<0.05); 两组脉络膜新生血管恢复情况和并发症发生情况比较无明显差异(P>0.05)。

结论：玻璃体腔注射雷珠单抗和康柏西普治疗渗出型ARMD均可取得较好的疗效,二者在改善视力方面无明显差异,但康柏西普治疗渗出型ARMD在降低CRT方面更具有明显优势。     

盐酸甲氯芬酯对人视网膜色素上皮细胞增生的影响

目的观察盐酸甲氯芬酯对体外培养的人视网膜色素上皮细胞增生的影响。方法通过MTT比色法和核仁嗜银蛋白染色分析,观察盐酸甲氯芬酯对人视网膜色素上皮细胞增生的影响。结果不同浓度盐酸甲氯芬酯可以促进人视网膜色素上皮细胞增生,在10~1000mg·L-1的范围内呈剂量效应关系,并随时间的延长,促进效应增强。嗜银蛋白染色结果:10mg·L-1盐酸甲氯芬酯作用24h后其胞核内AgNORs的数量增加,平均数为2.0(P=0.029);100mg·L-1盐酸甲氯芬酯作用12h即有胞核内AgNORs的增多,平均数为2.0(P=0.029)。随剂量的增加和时间的延长,胞核内AgNORs的数量增加。结论盐酸甲氯芬酯可以促进人视网膜色素上皮细胞增生,并与剂量和作用时间有一定的关系。     

Flicker perimetry and retinal pigment epithelial detachment

We report a case of a 71-year-old man with a retinal pigment epithelial detachment (PED) and occult subretinal neovascularisation. Automatic perimetry was performed with a non-flickering stimulus and an 18 Hz flickering stimulus (flicker perimetry). The addition of flicker to the perimetric task enhanced the detection of the PED. It appears that testing the ability of the visual system to process temporally encoded information can enable detection of a deficit in visual function where there is a minimal defect for conventional increment thresholds. Furthermore, given the known athophysiology of PED, it appears that flicker perimetry can enable detection of a defect of photoreceptor function. Flicker perimetry may prove December to be a useful tool for assessing retinal disease.