年龄相关性黄斑变性的研究进展

年龄相关性黄斑变性(AMD)严重威胁老年人视力健康,视网膜色素上皮细胞(RPE)功能障碍是其关键环节。年龄增长导致RPE复制性衰老,光暴露、香烟暴露等导致RPE压力性早衰,衰老的RPE细胞溶酶体消化能力下降导致脂褐素积累,触发早期AMD的发生。老化的视网膜内细胞衰老-更新失衡、氧化压力-抗氧化失衡、慢性炎性反应-抗炎失衡、肠道屏障和肠道微生态失衡、促血管生成-抗血管生成失衡一系列内稳态失衡进一步促进AMD的发展。

Blue light induced retinal oxidative stress:Implications for macular degeneration

A number of studies have shown that oxidative stress can be harmful for the retina. The real causal circumstances that lead to degenerative diseases like age related macular degeneration remain obscure. Whether light induced radical stress is a direct interaction of light with photoreceptors or a secondary mechanism within the pigment epithelium or choroid is in discussion. Among the molecular mechanisms involved are production of reactive oxygen species(ROS), secondary lipid peroxidation, protein oxidation and DNA-damage. The initial trigger to write this review was first a recent finding of our group that the photoreceptor outer segments produce great amounts of ROS and second the detection of ectopic enzymes of the respiratory chainlocalized there- in addition to the hitherto known ROS sources like the visual pigments with their intermediates and the photoreceptor mitochondria harbouring the respiratory chain.

肠-视网膜轴机制及其与眼科疾病的相互作用

肠道菌群是维持机体稳态的重要组成部分,近年来,随着16S rRNA和宏基因组等测序技术的快速发展,人们对微生物有了更加深入而全面的认识,在动物和人类中的研究证实肠道菌群不仅参与免疫性、代谢性和神经系统等全身性疾病的病变过程,还与眼病的发生密切相关。宿主高血糖、免疫异常、衰老和高眼压等因素可引起肠道菌群失调,肠-血屏障通透性增加。肠道菌群相关的脂多糖和肽聚糖等病原相关分子模式穿过受损的肠道屏障进入体循环,最终沉积到视网膜和葡萄膜组织中,参与免疫及炎症反应过程,而肠道来源的宿主免疫细胞或损伤相关的分子模式又可加重眼部炎症的级联反应。同时,包括饮食和环境诱导在内的肠道菌群代谢产物,如胆红素、胆汁酸和短链脂肪酸等,通过调节免疫T细胞平衡、miRNA表达和视网膜细胞炎性活化等参与视网膜疾病的进展。本文拟对近年来国内外关于肠道菌群与糖尿病视网膜病变、葡萄膜炎、年龄相关性黄斑变性和青光眼的相关研究进行综述,探讨肠道菌群通过肠-视网膜轴参与眼科疾病的可能机制,为眼部疾病的机理研究和防治提供一些新的思路。

基于OCTA技术的单侧RVO患者健侧眼黄斑区微血管血流密度、视网膜和脉络膜厚度变化

目的基于光学相干断层扫描血管成像(OCTA)技术,观察单侧视网膜静脉阻塞(RVO)患者健侧眼黄斑区微血管血流密度、视网膜和脉络膜厚度变化。方法单侧RVO患者38例共76只眼,其中患眼38只记为患侧眼组,健侧眼38只记为健侧眼组。另选取同期体检健康者25例的25只正常眼作为对照组。采用美国光视公司RTVue XR 100光学相干断层扫描仪进行黄斑区微血管血流密度、视网膜和脉络膜厚度测量,包括浅层毛细血管丛(SCP)全层、上半侧、下半侧、中心凹、旁中心凹、旁中心凹上半侧、旁中心凹下半侧、旁中心凹颞侧、旁中心凹上方、旁中心凹鼻侧、旁中心凹下方的血流密度(VD),深层毛细血管丛(DCP)全层、上半侧、下半侧、中心凹、旁中心凹、旁中心凹上半侧、旁中心凹下半侧、旁中心凹颞侧、旁中心凹上方、旁中心凹鼻侧、旁中心凹下方的VD,黄斑中心凹无血管区(FAZ)面积和周长、非圆度指数(AI),黄斑中心凹为中心周围300µm区域的视网膜(FD300)的VD,黄斑区视网膜厚度(CMT),黄斑中心凹下脉络膜厚度(SFCT)。结果与对照组组相比,健侧眼组SCP上半侧VD、SCP旁中心凹上半侧VD、DCP旁中心凹VD、DCP旁中心凹上方VD均降低(P均<0.05);与患侧眼组相比,健侧眼组SCP全层VD、SCP上半侧VD、SCP下半侧VD、SCP旁中心凹VD、SCP旁中心凹上半侧VD、SCP旁中心凹下半侧VD、SCP旁中心凹颞侧VD、SCP旁中心凹上方VD、SCP旁中心凹鼻侧VD、SCP旁中心凹下方VD、DCP全层VD、DCP上半侧VD、DCP下半侧VD、DCP旁中心凹VD、DCP旁中心凹上半侧VD、DCP旁中心凹下半侧VD、DCP旁中心凹颞侧VD、DCP旁中心凹上方VD、DCP旁中心凹鼻侧VD、DCP旁中心凹下方VD均升高,SCP中心凹VD、DCP中心凹VD、AI、CMT均降低(P均<0.05)。结论基于OCTA技术观察到单侧RVO患者的健侧眼黄斑区部分微血管血流密度已发生下降,但降低程度不及患侧眼,且健侧眼视网膜和脉络膜厚度变化不明显。

B类1型清道夫受体介导的高密度脂蛋白在年龄相关性黄斑变性中的研究进展

随着年龄的增长,机体胆固醇代谢失调和叶黄素水平异常易导致视网膜异常脂质沉积和玻璃膜疣,进而增加年龄相关性黄斑变性(age-related macular degeneration,AMD)的患病风险。视网膜细胞上的B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)在脂质代谢和视网膜保护中至关重要。组织细胞表面的SR-B1通过识别并结合细胞外的高密度脂蛋白(high-density lipoprotein,HDL),将游离胆固醇逆向转运至肝脏,对维持全身包括视网膜的脂质代谢平衡与避免脂质沉积至关重要。此外,HDL同样作为转运体参与叶黄素的视网膜转运过程。叶黄素,以其独特的蓝光过滤和抗氧化功能,减少蓝光对视网膜的潜在损伤并清除有害的氧自由基,发挥保护视网膜的作用。本综述将详细探讨SR-B1在视网膜中的作用,尤其是在协助胆固醇清除和叶黄素抗氧化防御方面的重要性,并评述SR-B1以及携带的有益成分如HDL和叶黄素对缓解AMD发病的机制与最新研究进展。

双眼电焊弧光黄斑损伤1例

电焊在日常工作中广泛使用,但操作工人常常会受到电焊弧光的照射,导致眼部损伤,影响视力。因此,工作中对眼部的保护非常重要。本院曾收治1例因焊接工作时未采取眼部防护措施而导致双眼黄斑光损伤的患者。在此患者就诊期间,使用了激光扫描检眼镜(SLO)、光学相干断层扫描血管成像(OCTA)和光学相干断层扫描成像(OCT)等设备,监测其视网膜黄斑的变化情况,及时了解病情发展并评估预后。根据检查结果和视网膜黄斑损伤的情况,积极调整治疗方案,实现了早发现和早治疗,避免了病情加重对视力的进一步损害。当发现患者的双眼黄斑区出现脉络膜新生血管后,及时采取了玻璃体腔内抗血管内皮生长因子(VEGF)药物注射的方法进行治疗,成功挽救了患者的视力。在治疗过程中,使用OCTA记录了注射后黄斑区脉络膜新生血管的密度、面积变化及波动情况,这些数据为治疗带来了明显的帮助和收益。因此,OCTA和OCT在视网膜黄斑病变类疾病的治疗中具有重要的指导意义。

Intravitreal dexamethasone implants for diabetic macular edema

AIM： To evaluate the safety and efficacy of a dexamethasone（DEX） intravitreal implant for diabetic macular edema（DME）.METHODS： Totally 113 eyes of 84 patients were divided in three subgroups： naive patients（n=11）, pseudophakic patients（n=72） and phakic patients（n=30）. Inclusive criterion comprised adult diabetic patients with central fovea thickening and impaired visual acuity resulting from DME for whom previous standard treatments showed no improvement in both central macular thickness（CMT） and best corrected visual acuity（BCVA） after at least 3 mo of treatment. Outcome data were obtained from patient visits at baseline and at months 1, 3, 5, 9 and 12 after the first DEX implant injection. At each of these visits, patients underwent measurement of BCVA, a complete eye examination and measurement of CMT and macular volume（MV） carried out with optical coherence tomography（OCT） images. RESULTS： Seventy-three eyes（64.5%） received a single implant, 30（26.5%） received two implants and 10（9%） received three implants. At baseline, average in BCVA, CMT and MV were 43.5±20.8, 462.8±145 and 12.6±2.5 respectively. These values improved significantly at 1 mo（BCVA： 47.2±19.5, CMT： 339.6±120, MV： 11.11±1.4） and 3 mo（BCVA： 53.2±18.1, CMT： 353.8±141, MV： 11.3±1.3）（P≤0.05）. At 5 mo（BCVA： 50.9±19.8, CMT： 425±150, MV： 12.27±2.3）, 9 mo（BCVA： 48.4±17.6, CMT： 445.5±170, MV： 12.5±2.3） and 12 mo（BCVA： 47.7±18.8, CMT： 413.2±149, MV： 12.03±2.5）, improvements in the three parameters were no longer statistically significant and decreased progressively but did not reach baseline values. There were no clinical differences between subgroups. Ocular complications were minimal.CONCLUSION： Patients with DEX implants show maximum efficacy at 3 mo which then declined progressively, but is still better than baseline values at the end of follow-up.

视网膜内界膜翻转填塞联合自体血覆盖与空气填充对大孔径特发性黄斑裂孔的疗效对比

目的对比分析视网膜内界膜翻转填塞联合自体血覆盖与空气填充治疗大孔径特发性黄斑裂孔(IMH)的临床效果。方法前瞻性选取2022年1月至2024年2月西安市人民医院眼科收治的120例大孔径(裂孔直径>400µm)IMH患者,采用随机数字表法随机分为对照组和观察组,每组60例。对照组行视网膜内界膜翻转填塞+空气填充治疗,观察组行视网膜内界膜翻转填塞+自体血覆盖治疗,比较两组的术后裂孔闭合率,术前和术后1个月、3个月的最佳矫正视力(BCVA),术前和术后3个月的视网膜外界膜(ELM)缺损直径、椭圆体带(EZ)缺损直径、黄斑裂孔(MH)直径,以及术后并发症发生情况。结果观察组术后裂孔闭合率(98.33%)高于对照组(85.00%),差异有统计学意义(P<0.05)。术前两组BCVA比较差异无统计学意义(P>0.05);术后1个月和3个月,两组BCVA均明显优于术前,且观察组明显优于对照组,差异有统计学意义(P<0.05)。术前两组ELM缺损直径、EZ缺损直径、MH直径比较差异无统计学意义(P>0.05);术后两组ELM缺损直径、EZ缺损直径、MH直径均明显低于术前,且观察组明显低于对照组,差异有统计学意义(P<0.05)。两组术后并发症发生率比较差异无统计学意义(P>0.05)。结论采用视网膜内界膜翻转填塞联合自体血覆盖治疗大孔径IMH具有较好的临床效果,可改善患者视力,促进黄斑裂孔愈合。

Macular integrity assessment to determine the association between macular microstructure and functional parameters in diabetic macular edema

AIM： To respectively evaluate macular morphological features and functional parameters by using spectraldomain optical coherence tomography（SD-OCT） and macular integrity assessment（MAIA） in patients with diabetic macular edema（DME）. METHODS： This prospective, non-controlled, open study included 61 eyes of 38 consecutive patients with DME. All patients underwent best-corrected visual acuity（BCVA） measurement, MAIA microperimetry, and SDOCT. DME morphology, including central retinal thickness（CRT） and central retinal volume（CRV）; integrity of the external limiting membrane（ELM） and photoreceptor inner segment/outer segment（IS/OS） junction; and the deposition of hard macular exudates were assessed within a 1000-μm central subfield area. MAIA microperimetry parameters evaluated were average threshold（AT）-retinal sensitivity, macular integrity index（MI）, fixation points within a circle of radius 1°（P1） and 2°（P2）, and bivariate contour ellipse area considering 63% and 95% of the fixation points（A63 and A95, respectively）. RESULTS： MI was significantly higher in eyes with disrupted ELM or IS/OS, compared with eyes with intact ELM and IS/OS. Values of BCVA（log MAR）, total AT, AT within 1000-μm diameter, P2, A63, A95, and CRT were significantly worse in eyes with disrupted IS/OS, compared with eyes with intact IS/OS. The values of BCVA（log MAR）, AT within 1000-μm diameter, and CRT were significantly worse in eyes with disrupted ELM, compared with eyes with intact ELM. These parameters were not significantly different between eyes with or without hard macular exudate deposition. CRV was not significantly different in the presence or absence of the integrity of ELM, IS/OS, or deposition of hard macular exudates. At the center, nasal and temporal sectors of the fovea, significant negative correlations were observed between retinal thickness and AT of the corresponding area. At the inferior and superior sectors of the fovea, no correlations were observed between retinal thickness and AT of the corresponding area. In the intact IS/OS group, significant negative correlations were observed between CRT and central AT. There was no correlation between retinal sensitivity and thickness when the IS/OS layer was disrupted. Multiple linear regression analyses revealed that IS/OS integrity was an independent factor affecting MI. CONCLUSION： Functional（BCVA and visual field） and morphological parameters（retinal thickness） were significantly associated with an intact IS/OS. Local photoreceptor integrity was a strong predictor of local visual function throughout the retina. MI revealed the functional status in DME, reflecting the IS/OS juction status in the macula.

Modified Vitreous Surgery for Subretinal Neovascularization and Hemorrhage

Purpose:To modify vitreous surgery for subretinal neovascularization(SRNV)and to detrmine the effects of this operation.Methods:Six patients with SRNV were performed with this operation,The meth-ods of examination before and after operation included;testing the best-corrected visual acuity before operation and 1,3or6months after operation;30degrees and visual acuity before operation and 1,3or6months after operation;30degrees and macular 10degrees Humphrey visual field examination:FFA examination preop-eratively and 1,3or6months postoperatiely.Modified surgery procedureis;a preventive buckling;pars plana vitrectomy;peeling the vitreous cortical;no in-traocular diathermy;small retinotomy;subretinal surgery;air-fluid exchang.Results:SRNV was taken off in4cases.Subretinal hemorrhage was washed in2cases.After4to7months follow-up,the visual acuity was improved in 4cases,unchanged in 2cases.The visual field was improved in 4cases.unchanged in 1case,decraesed in 1case,The complications included macular hole due to surgery in lcase and subretinal hemorrage in 1case.Conclusion;The surgery criteria were:1)massive subretinal hemorrhage;2)some patients of SRN V included;FFA evidence they showed the membrane is beneath fovea,the bestV.Ais20/100orlower.and can't be treated by laser and the pa-tient consent.This modified subretinal operation is safe,and effective for massive hemorrhage and some SRNVS.

The complexities underlying age-related macular degeneration： could amyloid beta play an important role？

e-related macular degeneration （AMD） causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognized, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarize the literature describing how the Alzheimer＇s-linked amyloid beta （Aβ） group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer＇s disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that Aβ fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of Aβ were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of Aβ accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of Aβ-mediated retinopathy. Furthermore, we discuss our findings revealing how Aβ behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose Aβ as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for latestage AMD.

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 agerelated 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 24 mo 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 24 mo. 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 24 mo 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.

Amyloid beta deposition related retinal pigment epithelium cell impairment and subretinal microglia activation in aged APPswePS1 transgenic mice

AIM：To identify the pathological role of amyloid beta（Aβ） deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells（RPE） layer and the associated structural and functional changes in Alzheimer＇s disease transgenic mice.METHODS：RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic（NTG） mice over 20 months old were examined.Histological changes were investigated via hematoxylin and eosin（H＆E） staining and transmission electron microscopy（TEM） examination,whereas the expression of amyloid precursor protein（APP）,Aβ,Zonula occludens-1（ZO-1） and Ionized calcium binding adaptor molecule-1（IBA-1） were investigated using immunohistochemistry and immunofluorescence techniques.All of the obtained results were quantitatively and statistically analyzed.RESULTS：In aged transgenic mice,an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice.The RPE demonstrated some vacuole changes,shortened basal infoldings and basal deposition in histopathological examination and TEM tests,wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence.Furthermore,IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch＇s membrane（Br M） complex,which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice.The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts.CONCLUSION：The observed Aβ deposition in the RPE layer may cause RPE dysfunction,which is associated with microglia cells infiltration into the retina of aged transgenic mice,suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.

六味地黄汤对碘酸钠诱导的干性年龄相关性黄斑变性大鼠视网膜组织色素上皮衍生因子的表达及氧化应激水平的影响

目的 观察六味地黄汤对碘酸钠(NaIO3)腹腔注射致干性年龄相关性黄斑变性(Dry AMD,dAMD)模型大鼠视网膜结构及色素上皮衍生因子(Pigment Epithelium-derived Factor,PEDF)、活性氧(Reactiveoxygenspecies,ROS)、丙二醛(Malonicdialdehyde,MDA)和还原型谷胱甘肽(Glutathione,GSH)表达水平的影响,探讨六味地黄汤对dAMD模型大鼠视网膜保护作用的机制。方法 将45只SPF级雌性SD大鼠采用随机数字表法分为空白组15只和dAMD组30只,空白组腹腔注射生理盐水(60 mg/kg),dAMD组腹腔注射NaIO3(60 mg/kg)。再将dAMD组随机分为模型组和中药组,每组各15只。空白组、模型组灌服生理盐水6.75 g/(kg·d),中药组灌服六味地黄汤6.75 g/(kg·d),连续14 d。末次给药后2 h时,通过眼底彩照观察各组大鼠眼底情况后取材,通过HE染色观察各组大鼠视网膜病理改变情况;通过免疫组化法、Western-blot法检测各组大鼠视网膜PEDF表达情况;通过Elisa法检测各组大鼠视网膜GSH、MDA、ROS的表达水平。结果 dAMD模型大鼠视网膜组织中MDA、ROS表达程度增高,差异有统计学意义(P<0.05);PEDF、GSH表达程度降低,差异有统计学意义(P<0.05)。六味地黄汤通过降低MDA、ROS表达水平、提高PEDF、GSH表达水平而达到保护视网膜的作用。结论 六味地黄汤对dAMD模型大鼠视网膜具有保护作用,其机制可能与调控PEDF及氧化应激水平相关。

Acetylcholinesterase function in apoptotic retina pigment epithelial cells induced by H_2O_2

AIM:To investigate the acetylcholinesterase（AChE）expression involved in retina pigment epithelial（RPE）apoptosis induced by higher concentrations H2O2.METHODS:The human retinal pigment epithelium cell line ARPE-19 was from ATCC（Rockville,MD）.Cultured ARPE-19 cells were treated with H2O2 at 0,250,500,1000,2 000μmol/L and cell viability was measured with MTT assay.AChE expression and DNA fragments were analyzed by immunocytochemistry,TUNEL and PARP-1Western blotting.RESULTS:Immunofluorescence detected AChE exist in the normal human retinal tissue.When H2O2】500μmol/L,AChE expression showed an increase after 2h,and this concentration was selected for the present study.RPE cell was induced with 1 000μmoI/L H2O2 for 2h,compared to the control group,cell activity decline detected by MTT,AChE and PARP-1 protein expression was significantly increased detected by Western blotting.AChE immunofluorescence staining was positive in RPE cell after HO2 incubate 2h.In addition,pretreatment with100|jmol/L epigallocatechin gallate（EGCG）,cell viability increased from 31.20%±3.90%to 70.23%±12.96%.CONCLUSION:AChE is weakly expressed in normal human RPE cells.Stimulation with H2O2 caused the stable increase of AChE expression in RPE cells,which may indicate that AChE may be an important role in AMD.

Nanotechnology in retinal drug delivery

Retinal diseases, including age-related macular degeneration （AMD） and diabetic retinopathy （DR） are the leading causes of blindness in adults over the age of 50 years in the US. While most of those conditions do not have a cure, currently available treatment options attempt to prevent further vision loss. For many ophthalmic drugs, an efficient delivery system to provide maximum therapeutic efficacy and promote patient compliance remains an unmet medical need. An exploration of literature via PubMed spanning from 2007 to 2017 was conducted to identify studies that have evaluated nanotechnology as platforms for delivering therapeutic agents to the posterior segment of the eye where the retina is located. Until now, four routes that have been utilized for retinal drug delivery are the intravitreal, periocular, subretinal, and systemic routes. Intravitreal injections are now widely used in clinical practice due to their ability to directly target the back of the eye but are highly invasive procedures that may cause several complications, particularly with repeated uses over a short timespan. Nanotechnology shows great promise to revolutionize retinal drug delivery, offering many advantages such as a targeted delivery system towards the specific site of the retina as well as sustained delivery of therapeutic agents. In this review, specific eye anatomy and constraints on ocular drug administration are illustrated. Further, we list and highlight several examples of nanosystems, such as hydrogels, liposomes, dendrimers, and micelles, used via different drug delivery routes to treat various retinal diseases.

雷珠单抗对脉络膜新生血管模型大鼠视网膜氧化应激的抑制作用及其机制

目的研究雷珠单抗对脉络膜新生血管(CNV)模型大鼠视网膜氧化应激的作用及其机制。方法选取10周龄SPF级雄性SD大鼠60只,按照随机数字表法随机分为正常对照组、模型对照组、雷珠单抗组、转录因子核因子E2相关因子2(Nrf2)抑制剂(ML385)组、雷珠单抗+ML385组,每组12只。除正常对照组外,其余各组以氪激光诱导CNV模型。雷珠单抗组、ML385组和雷珠单抗+ML385组分别玻璃体腔内注射1μl雷珠单抗、ML385、雷珠单抗+ML385,模型对照组、正常对照组分别给予玻璃体腔内注射等体积生理盐水。脉络膜铺片法检测CNV面积;苏木精-伊红染色观察视网膜病理学变化;实时荧光定量PCR及Western blot检测视网膜组织中Nrf2、超氧化物歧化酶(SOD)、醌氧化还原酶(NQO1)mRNA及蛋白表达水平。结果模型对照组、ML385组和雷珠单抗+ML385组CNV面积分别为(23.01±1.52)×10^(3)、(30.23±2.01)×10^(3)和(18.56±1.85)×10^(3)μm^(2),明显高于雷珠单抗组的(12.35±1.22)×10^(3)μm^(2),雷珠单抗+ML385组CNV面积小于模型对照组和ML385组,ML385组CNV面积大于模型对照组,差异均有统计学意义(均P<0.001)。苏木精-伊红染色结果显示,雷珠单抗组RPE-脉络膜-巩膜复合体结构损害程度较模型对照组轻;雷珠单抗+ML385组RPE-脉络膜-巩膜复合体结构损害程度较雷珠单抗组重,但较模型对照组轻;ML385组RPE-脉络膜-巩膜复合体结构损害较模型对照组严重。雷珠单抗组Nrf2、SOD和NQO1 mRNA及蛋白相对表达量均低于正常对照组,但高于模型对照组、ML385组和雷珠单抗+ML385组,且雷珠单抗+ML385组Nrf2、SOD和NQO1 mRNA及蛋白相对表达量高于模型对照组和ML385组,差异均有统计学意义(均P<0.05)。结论雷珠单抗可抑制氪激光诱导的CNV生长,减轻RPE氧化应激损伤,其机制与Nrf2/ARE通路的激活有关。

康柏西普注射液玻璃体腔内注射联合网膜一号方治疗黄斑水肿的疗效

目的观察康柏西普注射液玻璃体腔内注射联合网膜一号方治疗黄斑水肿(ME)的疗效。方法选取2018年7月—2021年12月三明市中西医结合医院收治的ME患者100例为研究对象,按照随机数字表法分为单一治疗组与联合治疗组,各50例。2组患者均予以康柏西普注射液玻璃体腔内注射治疗,联合治疗组加用中药网膜一号方口服治疗。2组均持续治疗3个月。比较2组临床疗效,治疗前后黄斑区视网膜最大厚度、视力,水肿情况,不良反应。结果联合治疗组治疗总有效率为100.00%,高于单一治疗组的88.00%(χ^(2)=4.433,P=0.035)。治疗3个月后,2组黄斑区视网膜最大厚度较治疗前降低,且联合治疗组较单一治疗组低(P<0.01)。治疗3个月后,联合治疗组视力优于单一治疗组,3种半径的轮廓线中信号点平均水肿均小于单一治疗组(P<0.05或P<0.01)。联合治疗组不良反应总发生率为4.00%,低于单一治疗组的22.00%(χ^(2)=7.162,P=0.007)。结论康柏西普注射液玻璃体腔内注射联合网膜一号方治疗ME的疗效确切,可有效降低黄斑区视网膜最大厚度,提高视力,减轻水肿,且安全性较高。

局灶视网膜激光光凝术联合阿柏西普眼内注射溶液经玻璃体腔注射治疗局灶型糖尿病性黄斑水肿的疗效

目的 探讨局灶视网膜激光光凝术联合阿柏西普眼内注射溶液经玻璃体腔注射治疗局灶型糖尿病性黄斑水肿(DME)的临床效果。方法 选取惠州市第一人民医院2020年1月至2021年12月收治的48例局灶型DME患者,按随机数字表法分为两组,各24例。对照组予以阿柏西普眼内注射溶液经玻璃体腔注射治疗,试验组在对照组基础上加用局灶视网膜激光光凝术治疗,均随访36周,比较两组最佳矫正视力(BCVA)、黄斑情况、玻璃体腔药物注射次数及生命质量变化。结果 试验组治疗后BCVA、黄斑中心厚度(CMT)、黄斑区视网膜平均厚度(CAT)、黄斑总体积(TMV)、玻璃体腔药物注射次数为分别为(0.59±0.11)、(289.63±25.41)μm、(302.41±36.52)μm、(9.25±1.02)mm3、(5.36±1.02)次,均低于对照组的(0.75±0.19)、(342.47±31.52)μm、(341.14±38.41)μm、(10.37±1.42)mm3、(7.52±1.24)次,差异有统计学意义(P <0.05);试验组治疗后视功能损害眼病患者生命质量量表(SQOL-DVI)的临床症状和视功能、社会活动、身体机能、精神心理评分及总分分别为(55.63±5.12)分、(27.89±2.04)分、(30.14±2.78)分、(28.41±2.35)分、(142.05±12.13)分,均高于对照组的(50.41±5.05)分、(24.15±1.89)分、(27.69±2.25)分、(25.05±2.24)分、(127.31±10.52)分,差异有统计学意义(P<0.05)。结论 局灶视网膜激光光凝术联合阿柏西普眼内注射溶液经玻璃体腔注射可提高局灶型DME患者治疗效果,加快BCVA复常,改善黄斑水肿情况,减少玻璃体腔药物注射次数,降低疾病对患者生命质量的影响。

玻璃体腔注射抗血管内皮生长因子药物治疗视网膜分支静脉阻塞继发黄斑水肿的代谢组学分析

目的:探讨视网膜分支静脉阻塞(BRVO)继发黄斑水肿(ME)患者通过玻璃体内注射血管内皮生长因子拮抗剂(anti-VEGF)治疗后眼内代谢的变化。方法:收集2021年1月至2021年6月温州医科大学附属眼视光医院20例BRVO继发ME患者抗VEGF治疗前及治疗后1个月的房水样本,采用液相色谱/质谱(LC-MS/MS)技术进行代谢物的检测,并通过主成分分析(PCA)、差异表达分析和通路富集分析等方法对代谢物进行筛选和功能注释。结果:抗VEGF治疗1个月后,所有BRVO继发ME患者的黄斑中心厚度均显著下降,差异有统计学意义(P<0.05)。PCA和OPLS-DA分析结果显示,BRVO继发ME患者房水的代谢产物与治疗前存在显著差异。通过差异表达分析发现,与治疗前相比,治疗后患者房水中的4-Oxo-2-壬烯醛含量显著升高(P<0.05),而棕榈酰溶血磷脂酰胆碱PC(16:0)、7-烯胆(甾)烷醇和PC[20:4(8Z、11Z、14Z、17Z)/P-18:0]等代谢物的含量显著降低(P<0.05)。通路富集分析结果表明,含量降低的代谢物主要富集在甘油磷脂代谢、α-亚油酸代谢和亚麻酸代谢等通路(P<0.05)。结论:抗VEGF治疗后的BRVO继发ME患者眼内代谢发生了显著变化,脂类代谢物水平明显降低。