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.     

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.     

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.     

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.     

康柏西普与雷珠单抗治疗nARMD伴纤维血管性色素上皮脱离的效果比较

目的：比较康柏西普与雷珠单抗治疗新生血管性年龄相关性黄斑变性(nARMD)1型黄斑新生血管(MNV)伴纤维血管性色素上皮脱离(fPED)的疗效。

方法：回顾性临床研究。纳入2019-01/2020-12于我院确诊的nARMD 1型MNV伴fPED患者48例48眼,根据治疗药物分为康柏西普组(26例26眼)和雷珠单抗组(22例22眼),均采用3+PRN的治疗方案。随访12mo,观察两组患者最佳矫正视力(BCVA),并采用光相干断层扫描(OCT)测量黄斑中心凹厚度(CFT)、视网膜色素上皮脱离(PED)的消退程度(高度、面积、体积)。

结果：两组患者治疗前BCVA、CFT及PED高度、面积和体积均无显著差异(P>0.05)。治疗(首次玻璃体内注射)后3、6、12mo两组患者PED高度均较治疗前显著改善(P<0.05),但PED面积和体积均无显著改善(P>0.05)。治疗后两组患者BCVA较治疗前均无显著改善(P>0.05)。治疗后3、6、12mo康柏西普组患者CFT均较治疗前显著改善(P<0.05),雷珠单抗组仅在治疗后3mo较治疗前显著改善(P<0.05)。治疗后3、6、12mo两组间BCVA、CFT及PED高度、面积和体积均无显著差异(P>0.05)。

结论：康柏西普和雷珠单抗治疗nARMD 1型MNV伴fPED均有较好疗效,能降低PED高度及CFT,稳定视力、PED面积和体积,而康柏西普减轻黄斑水肿的持续时间更为持久。     

Real-life experience of ranibizumab therapy for neovascular age-related macular degeneration from Turkey

AIM: To report the real-life experience and clinical results of intravitreal ranibizumab injections to neovascular age-related macular degeneration (nAMD) in a single institution in Turkey. METHODS: A total of 101 eyes of 89 patients with nAMD treated with intravitreal ranibizumab injection, followed up for at least 24mo between 2009 and June 2014, which were evaluated retrospectively. A pro re nata (PRN) treatment protocol was performed after the patients had received three, monthly loading injections. Best corrected visual acuity (BCVA) and central macular thickness measurements were evaluated at baseline and 3, 6, 12, 18, and 24mo. Number of injections and visits were also recorded. RESULTS: Of the 89 patients, 34 (38.2%) were male and 55 (61.8%) were female and the mean age was 74.0±9.5 (52-91)y. The mean follow-up period was 24.82±4.4 (24-29)mo. Mean number of visits was 8.4±1.12 (7-12) in the first year and 6.6±1.33 (4-12) in the second year. The mean number of injections was 5.8±1.6 (3-10) and 4.2±2.2 (0-9) in the first and second year, respectively. The mean BCVA was 59±15.8 letters at baseline by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The mean BCVA at 3, 12, and 24mo was 70.3±15.9, 67.9±14.3 and 67.3±16.9 letters, respectively. Improvement in visual acuity for each of the visits from baseline was found to be statistically significant (P<0.01). Visual acuity in 9 eyes at month 3, 7 eyes at month 12, and 13 eyes at month 24 did not change. The mean central macular thickness (CMT) was 437.99±164.78 μm at baseline. The mean CMT was 348.05±138.47 μm, 349.27±139.79 μm, and 344.13±146.30 μm at months 3, 12, and 24, respectively. The decrease in CMT for each of the visits from baseline was found to be statistically significant (P<0.01). CONCLUSION: Anatomical and functional achievement are obtained in our study, but the mean number of injections and visits are found to be lower than the findings reported in randomized controlled clinical trials in the literature. However, the mean number of injections and visits in our study are compatible with the findings reported in real-life experience studies in the literature.     

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.     

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。     

Prediction of retinal pigment epithelial tear in serous vascularized pigment epithelium detachment

Purpose: The aim of the study was to identify predictive factors for detection of impending retinal pigment epithelium (RPE) tears in patients under anti‐VEGF therapy for treatment of retinal pigment epithelial detachment (PED) due to exudative age‐related macular degeneration (AMD) using near‐infrared reflectance imaging (NIR), spectral‐domain optical coherence tomography (SD‐OCT) and fluorescein angiography (FLA). Methods: We retrospectively evaluated NIR, SD‐OCT and FLA images, number of intravitreal injections as well as demographical data of 103 eyes of 98 patients with vascularized PED [48.5% fibrovascular PED (fPED), 51.5% serous vascularized PED (svPED)] secondary to AMD. Results: Fifteen eyes with svPED of 103 included eyes (14.6%) developed an RPE tear under anti‐VEGF therapy. Prior to RPE tear formation, we could identify radial hyperreflective lines spreading in a funnel‐like pattern across the PED lesion in NIR images in 11 eyes correlating with folds in the RPE on corresponding SD‐OCT scans (mean observation period: 115.4 ± 66.6 days; mean number of injections: 3.2 ± 1.5; mean PED height 828.2 ± 356.5 μm). In nine RPE tears (81.8%), the edge of the tear could be clearly localized on the opposite side of the PED lesion in relation to the origin of hyperreflective lines. None of the fPED patients showed the described signal. Conclusions: Patients under anti‐VEGF therapy for treatment of svPED due to AMD frequently show radial hyperreflective lines in NIR images prior to RPE tear development that correspond to wrinkled changes in the RPE. Hyperreflective lines may serve as an indicator for an impending RPE tear in svPED patients.     

Fixed bimonthly aflibercept in naïve and switched neovascular age-related macular degeneration patients: one year outcomes

AIM: To determine real life clinical outcomes in poorly responsive and treatment-naïve neovascular age related macular degeneration (nvAMD) patients using bimonthly fixed dosing aflibercept regimen. METHODS: This was a retrospective study of 165 eyes with nvAMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata (PRN) ranibizumab/bevacizumab due to poor response (107 eyes), or treatment-naïve (58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline were assessed using the Wilcoxon signed-rank test. The proportion of patients maintaining BCVA (<15 letters loss) at 12mo was also evaluated. RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and naïve aflibercept groups respectively (P<0.01). BCVA was maintained in 95.3% of switched and 96.6% of naïve patients. CRT at month 12 showed a decrease of -6.16 µm in the switched group and -35.36 µm in the naïve group (P<0.01). Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections (naïve group), 7.5 injections (switched group) and 4 clinic visits per year. CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-naïve and poorly responsive nvAMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.     

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.     

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.     

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。     

干性ARMD中视网膜色素上皮细胞的作用及损伤机制

年龄相关性黄斑变性(age-related macular degeneration,ARMD)是导致老年人中心视力不可逆丧失的主要原因。ARMD的典型特征是视网膜色素上皮(retinal pigment epithelium,RPE)和脉络膜毛细血管发生退行性改变及黄斑区出现玻璃膜疣。临床上ARMD分为两种亚型：非渗出型(干性或萎缩型)和渗出型(湿性或新生血管型)。该病的发生是年龄、环境、遗传、吸烟、氧化应激和心血管功能障碍等多种因素相互作用的结果。鉴于RPE细胞在ARMD发病中的重要作用,现以RPE细胞为重点,总结了蓝光、吸烟、氧化应激、脂褐素积累、慢性炎症和蛋白质稳态对干性ARMD发病的作用和可能机制,为认识和预防干性ARMD的发生提供新的帮助。     

雷珠单抗治疗湿性年龄相关性黄斑变性的治疗方案

玻璃体内注射抗血管内皮生长因子药物雷珠单抗（ranibizumab）治疗湿性年龄相关性黄斑变性（AMD）的有效性及安全性已得到多项临床研究证实.目前的研究主要集中在治疗方案的设计与优化方面.从早期的固定治疗模式、按需治疗模式、到近期的稳定性治疗模式和间期延长治疗模式等,治疗方案经历了从仅以视功能为标准到综合考虑视力、疾病活动性、患者依从性和整体医疗耗费等因素的变化,并仍处于不断地改进中.本文回顾了近年来有关雷珠单抗的大规模临床试验结果及相关数据分析,综述了其治疗湿性AMD的治疗方案的研究进展.     

紫外线B照射在抑制人视网膜色素上皮细胞自噬中的作用

目的　探讨紫外线B(ultraviolet B,UVB)照射在抑制人视网膜色素上皮细胞株ARPE-19细胞自噬中的作用。方法　不同剂量UVB照射ARPE-19细胞后不同时间收集细胞,应用MTT法检测UVB照射对细胞存活的影响;Western blot检测细胞中自噬蛋白LC3的表达及LC3-II/LC3-I比率、Beclin-1蛋白表达水平;应用细胞自噬增强剂雷帕霉素（rapamycin,RAPA）和细胞自噬抑制剂氯化铵（NH₄Cl）进一步验证UVB照射对于细胞自噬的调节;采用环氧霉素（epoxomicin,EPO）检测泛素-蛋白酶体系统(ubiquitin-proteasome system,UPS)对于UVB作用的影响。MTT法检测细胞自噬变化对于细胞生存的影响。结果　UVB照射组诱导细胞剂量依赖性的死亡,100 mJ·cm^-2 UVB照射后24 h细胞出现明显死亡,和对照组相比差异具有统计学意义（P<0.05）;200 mJ·cm^-2 UVB照射后24 h和对照组相比差异有显著统计学意义(P<0.01);两种剂量的UVB照射后48 h细胞有一定程度的恢复。和对照组相比,UVB照射组ARPE-19细胞中LC3-II/LC3-I比率和Beclin-1蛋白表达水平均降低（均为P<0.05)。和UVB照射组相比,UVB+RAPA组ARPE-19细胞中明显升高了LC3-II/LC3-I比率,UVB+NH₄Cl组进一步降低了LC3-II/LC3-I比率,RAPA和NH₄Cl在一定程度上恢复了UVB照射降低的Beclin-1蛋白表达水平（均为P<0.05)。和对照组相比,EPO组明显增加了ARPE-19细胞中LC3-II/LC3-I比率、升高了Beclin-1蛋白表达水平（均为P<0.05)。与UVB照射组相比,UVB+EPO组ARPE-19细胞中LC3-II/LC3-I比率无明显改变(P>0.05),而Beclin-1蛋白表达水平差异有统计学意义(P<0.05)。与对照组相比,RAPA组细胞死亡率增多,两组间差异有统计学意义（P<0.05）,NH₄Cl组细胞无明显死亡,与UVB照射组相比,UVB+RAPA组和UVB+NH₄Cl组细胞死亡率均无明显改变（均为P>0.05）。细胞自噬的改变不能逆转UVB诱导的ARPE-19细胞死亡。结论　UVB照射抑制了ARPE-19细胞自噬的启动及自噬流,UPS的改变不影响UVB对于自噬流的抑制。UVB照射可通过减少RPE细胞、损害细胞自噬能力增加RPE细胞变性,增加年龄相关性黄斑变性发生的风险。     

抗血管内皮生长因子(VEGF)治疗与视网膜下纤维化研究进展

视网膜下纤维化是导致年龄相关性黄斑病变视力丧失的原因之一,抗血管内皮生长因子治疗是目前对于湿性年龄相关性黄斑变性标准治疗方案.本文主要探讨视网膜纤维化的影响因素,抗血管内皮生长因子治疗与视网膜纤维化的关系以及抗视网膜下纤维化的研究进展.