视网膜色素变性97例的眼电图研究

目的：研究视网膜色素变性的超微结构及病理性改变与眼电图之间的关系。方法：采用视觉电生理技术，对97例视网膜色素变性患进行眼电图（EOG）检测，观察光峰电位等十项指标，并与47名健康进行比较，结果：视网膜色素变性患的色素上皮层功能明显损害，97例视网膜色素变性患的眼电图检测表现为三种类型：（1）光波明显降低（低波型）54例，占55．67％；（2）光峰暗谷消失（无波型）14例，占14．43％；（3）暗谷光峰倒转（倒置型）29例，占29．90％，低波型提示色素上皮功能轻度损害，无波型提示色素上皮严重受损，倒置波提示锥体细胞受损较杆细胞为重，明适应阶段锥体细胞反应低下，结论：眼电图的检测有助于视网膜色素变性患的诊断及判断病程进展情况。     

視網膜色素變性97例的眼電圖研究

目的研究視網膜色素變性的超微結構及病理性改變與眼電圖之間的關系.方法采用視覺電生理技術,封97例視網膜色素變性患者進行眼電圖(EOG)檢測,觀察光峰電位等十項指標,并與47名健康者進行比較.結果視網膜色素變性患者的色素上皮層功能明顯損害,97例視網膜色素變性患者的眼電圖檢測表现爲三種類型(①光波明顯降低(低波型)54例,占55.67%;(②光峰暗谷消失(無波型)14例,占14.43%;③暗谷光峰倒轉(倒置型)29例,占29.90%.低波型者提示色素上皮功能輕度損害;無波型者提示色素上皮嚴重受損,倒置波提示錐髓细胞受損較杆细胞爲重,明通應階段锥髓细胞反應低下.結論眼電圖的檢測有助于視網膜色素變性患者的診斷及判斷病程進展情况.     

原发性视网膜色素变性光感受器细胞损害的临床分析

目的：用视网膜电图(ERG)与暗适应(DA)检测评价视网膜色素变性(RP)患者视杆细胞和视锥细胞的功能改变。 方法：100例RP患者(198眼)和正常人30例(60眼)对照研究，应用Nicolet compact Ⅳ电生理仪和Fridmann视野计(FVFA)MK₂程序分析分别作ERG和暗适应(DA)检查。 结果：93例RP患者184眼ERG正常者4眼(2.1%)，b波近消失者120眼(65.2%)，b波降低者60眼(32.6%)．后者多数呈杆-锥型损害，少数呈锥杆型攒害。89例170眼DA检查发现84.7%光敏感阈值升高，68.8%严重升高. 结论：大多数RP患者杆体细胞最先受损，部分病例锥体细胞似乎活性损害在前，其次是锥，杆细胞广泛损害。 （中华眼底病杂志，1995，11：147-150）     

视网膜色素变性患者三项视功能检测指标分析

视网膜色素变性患者的闪光视网膜电图 (ｆｌａｓｈｅｌｅｃｔｒｏｒｅｔｉｎｏｇｒａｍ ,Ｆ ＥＲＧ)明显异常 ,与患者的视网膜色素上皮和第一级光感受器细胞受损有关。由于本病逐渐累及黄斑区的视锥细胞 ,常导致患者的视力显著下降 ,中央视野检测所记录到图形视诱发电位 (ｐａｔｔｅｒｎｖｉｓｕａｌｅｖｏｋｅｄｐｏｔｅｎｔｉａｌ,Ｐ ＶＥＰ) ,可反映出黄斑区视网膜受累的程度。夜盲患者的暗视功能严重受损 ,采用眼电图 (ｅｌｅｃｔｒｏｏｃｕｌｏｇｒａｐｈｙ,ＥＯＧ)测定患者明、暗适应机能具有临床意义。我们对视网膜色素变性患者进行…     

视网膜色素变性的ERGs观察

目的：为研究视网膜色素变性的视网膜电图（ＥＲＧｓ）,测定了７５例１５０眼视网膜色素变性病人的ＥＲＧｓ,分析了其ｂ波振幅情况。方法：用视觉电生理仪测量ＥＲＧｓ的ｂ波振幅。分析从５个月到７０岁的７５例１５０多膜色素变性病人的ＥＲＧｓ的ｂ波振幅情况。结果：（１）ｂ波振重度降低或记录不到波形者１３０眼,占８７％,平均年龄２５岁,其最好视力达１．５,最低右无光感。（２）ｂ波振幅轻度或中度降低者１０例２０眼,     

复发性CSC的FFA特征

目的：探讨复发性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy，CSC)的荧光眼底血管造影(fluorescein fundus angiography，FFA)特征。方法：对26例(38只眼)CSC患者进行FFA检查。结果：在26例复发性CSC患者中有神经上皮脱离者13只眼，色素上皮脱离者11只眼，窗样缺损者9只眼，色素上皮带状萎缩4只眼。病灶位于黄斑区30只眼，黄斑颞侧7只眼，鼻侧仅有1只眼。色素上皮和神经上皮脱离范围小于1／2PD者占50．9％，大于2PD者占8．9％，二者之间者占30．1％。结论：对于复发性CSC，FFA仍然是最有诊断意义的检查，其特征性改变提示视网膜色素上皮代偿失调与脉络膜毛细血管循环障碍有联系。     

视网膜色素变性的多焦视网膜电图分析

测试并比较视网膜色素变性患者和正常人多焦视网膜电图。方法 :应用美国EDI公司生产的VERISScience 4 2多焦视网膜电图检查仪对 8例视网膜色素变性患者 8只眼 ,12例正常人 12只眼进行检测 ,分析其 6个环形视网膜区域的反应。结果 :视网膜色素变性患者 6个环形视网膜区域的反应密度均低于正常人 ,5环和 6环的潜伏期显著延长。结论 :视网膜色素变性患者多焦视网膜电图的反应密度下降 ,周边视网膜潜伏期延长 ,这种改变主要是由于视网膜感受器功能受损并且周边视网膜首先受累所致。     

原发性视网膜色素变性合并血管闭塞的临床特点分析

目的探讨原发性视网膜色素变性(RP)合并视网膜血管闭塞患者的临床特点及预后。方法回顾性分析18例(36只眼)原发性RP合并视网膜血管闭塞患者的临床资料,包括眼底检查、荧光素眼底血管造影、吲哚氰绿血管造影、视网膜电图及视诱发电位等检查结果。对3例患者进行基因筛选。结果原发性RP合并视网膜血管闭塞患者的临床表现有视乳头萎缩、视网膜血管变细、广泛视网膜色素上皮萎缩。视网膜电图检查显示a、b波为无波型或近无波型。患者多有夜盲史。既符合原发性RP的临床表现,又具有血管闭塞的自身特征,如晚期血管可完全或近完全闭塞、视神经明显萎缩、脉络膜血管受累,最终致盲速度较原发性RP快,且无有效疗法。3例患者经基因筛查,在RHO及RLBPI两基因编码区中,未发现基因突变。结论原发性RP合并视网膜血管闭塞可能属于毯层视网膜变性范畴,血管进行性闭塞可能是其合并的临床表现。     

脉络膜再血管化术联合药物综合治疗视网膜色素变性

目的:探讨治疗原发性视网膜色素变性的有效方法。方法:选择符合诊断及入选标准的原发性视网膜色素变性患者60例120眼,采用脉络膜再血管化术联合药物综合治疗,12mo后观察患者视力、视野、视网膜电图(ERG)。结果:患者60例120眼中,视力下降者2眼(1.6%),视力无提高者15眼(12.5%),视力提高0.02～0.20者80眼(66.7%),视力提高>0.20者23眼(19.2%)。56例112眼做了周边视野(60°)和中心视野(30°)检查,治疗前45眼可检测到周边视野敏感度,治疗后56眼可检测到,检出率为50%,56眼经过12mo观察后,其中47眼周边视野和中心视野无变化,有效率为83.9%。59例患者110眼行ERG检查(8眼初期未见异常,未作检查),治疗前100眼记录不到a波与b波,治疗前后无变化。30Hz闪烁反应治疗前59例患者110眼中54例97眼可记录到波形,检出率为88.2%;治疗后100眼可记录到波形,检出率为90.9%。结论:脉络膜再血管化术联合药物综合治疗能延缓或控制原发性视网膜色素变性病情发展,提升视力,改善视功能,值得临床推广应用。     

酒精中毒眼部损害视觉电生理检测

目的 对急性慢性酒精中毒眼部损害者进行视觉电生理观察,了解酒精中毒性视力损害的机制。方法 对急性酒精中毒眼部损害者3例6眼和慢性中毒者6例12眼行暗适应视网膜电图（ERG）,视觉诱发电位（VEP）和视野,眼底荧光造影等检查并进行1月－2年的随访。结果 显示急性中毒3例6眼中暗适应ERG正常,F－VEP或P－VEPP100波严重下降,2例4眼治疗后完全恢复（66．7％）,1例成为永久性损害。经证实未恢复的1例2眼呈弥漫性色素上皮损害,眼底荧光血管造影显示全部眼底的透见荧光和色素游离的遮蔽荧光相间造影像,黄斑区视网膜尤甚。经2年随访无明显改善。慢性中毒6例12眼有不同程度的视野缺损,暗适应ERGa,b波、P－VEPP100波潜伏值均出现永久性异常,眼底荧光血管造影证实视网膜后极部数簇遮荧光和透见荧光像。结论 认为急慢性酒精中毒可首称造成视网膜色素上皮的弥漫性或黄斑区的损害,而视神经损伤可能发生于上述改变之后;视觉电生理检测可对其损害提供可靠的诊断和跟踪随访依据。     

Effect of alcohol and light on the retinal pigment epithelium of normal subjects and patients with retinal dystrophies

BACKGROUND: Light absorbed by photoreceptors causes oscillations in the voltage across the retinal pigment epithelium (RPE). This is the basis of the clinical test, electro-oculography (EOG). We have previously shown that alcohol causes a sequence of voltage changes which are so precisely the same as those caused by light that they must be produced by the same RPE machinery. There is good evidence that alcohol produces its effect by a direct action on the RPE. Consequently, in diseases associated with loss of photoreceptors, alcohol should continue to produce the voltage changes of the EOG unless secondary changes have occurred in the RPE. METHODS: The alcohol response in patients with retinitis pigmentosa (RP) was investigated using EOG. RESULTS: In no patient with RP was there any alcohol rise. CONCLUSION: In patients with RP secondary abnormalities of function of the RPE must occur.     

Fundus autofluorescence in patients with leber congenital amaurosis

PURPOSE: Fundus autofluorescence (FAF), as an index of lipofuscin accumulation in the retinal pigment epithelium (RPE), provides indirect information on the level of metabolic activity of the RPE and thus the integrity of the RPE/photoreceptor complex. To investigate whether the photoreceptor/RPE complex is still viable in patients with Leber congenital amaurosis (LCA), FAF imaging was performed. METHODS: Three patients with LCA (patients A, B, and C; ages, 24, 15, and 37 years, respectively) were enrolled and one patient with RP with preserved visual acuity (age, 28 years) was included as a control. The diagnosis was based on history, visual function, and Ganzfeld electroretinography (International Society for Clinical Electrophysiology of Vision [ISCEV] standard). FAF was recorded with a confocal scanning laser ophthalmoscope (cSLO; Heidelberg Retina Angiograph; Heidelberg Engineering, Heidelberg, Germany). RESULTS: All patients with LCA had vision reduced to perception of light and had undetectable ERGs. FAF was normal in patient A. In patient B, there was a parafoveal ring of mildly increased FAF. The midperiphery showed mildly decreased FAF. Patient C showed a parafoveal ring of moderately increased FAF. FAF was moderately decreased along the arcades and the midperiphery. The patient with RP showed a parafoveal ring of moderately increased FAF and severely decreased FAF eccentric to the macula including the periphery. CONCLUSIONS: The FAF findings in these patients with LCA suggest that there is continuous metabolic demand from the photoreceptors and that the RPE/photoreceptor complex is, at least in part, anatomically intact, but the photoreceptors have lost function. These findings may have implications for future treatment. It is notable that more than 20 years of severe visual impairment associated with LCA can be associated with normal FAF, indicating that photoreceptor function may be rescuable.     

Activated retinitis pigmentosa peripheral lymphocytes adhere to and alter cultured human retinal pigment epithelial cells.

Interleukin-2 receptor (IL-2R) is an activation molecule that, when expressed on peripheral blood lymphocyte (PBL) membranes, indicates the secretion of IL-2 and initiation of an immune system activation cascade. Comparing the average of IL-2R expression in 34 patients with retinitis pigmentosa (RP) syndrome (561 +/- 282 cells/mm3; mean +/- standard deviation) with 35 age-matched normal subjects (194 +/- 39 cells/mm3), it was found that those with RP had greater numbers of IL-2R-positive cells (P less than 0.001). The increased amounts of IL-2R on PBL of 29 RP and the homotypic self-aggregation of RP PBL by phase and scanning electron microscopy led to the study of the interaction of RP PBL with cultured human postmortem retinal pigment epithelial cells (RPE). A direct correlation was found between the amount of IL-2R expression and the numbers of RP lymphocytes adhering to RPE monolayers. However, the adherence effect was not unique to RP syndrome but appeared to be a nonspecific result of lymphocyte activation. Greater adherence to RPE than normal also was observed in PBL from disease control subjects with elevated IL-2R values and in PBL stimulated by the mitogen, concanavalin A (Con-A). In addition, RPE monolayers were destroyed by Con-A-stimulated PBL that showed 95-98% IL-2R expression. Similar, but less serious effects, occurring in RPE cells after 1 wk's cocultivation with RP PBL, suggested that activated RP lymphocytes can be cytotoxic to RPE during prolonged contact. Because macrophage-like cells and class II major histocompatibility complex expression have been found in RP-affected retinas, immune-mediated cytopathologic effects may contribute to retinal degeneration in RP.     

Screening genes of the visual cycle RGR, RBP1 and RBP3 identifies rare sequence variations

The visual cycle is essential for vision and several genes encoding proteins of the cycle have been found mutated in various forms of inherited retinal dystrophy. We screened 3 genes of the visual cycle. RGR, encoding the retinal pigment epithelium (RPE) G protein-coupled receptor acting in vitro as a photoisomerase; RBP1, encoding the ubiquitous cellular retinol binding protein carrying intracellular all-trans retinoids; RBP3, encoding the interphotoreceptor retinoid binding protein, a retinal-specific protein which shuttles all-trans retinol from photoreceptors to RPE and 11-cis retinal from RPE to photoreceptors. We used denaturing high performance liquid chromatography (D-HPLC) and direct sequencing to screen 216 patients (134 with autosomal recessive or sporadic retinitis pigmentosa (RP) and 82 with other retinal dystrophies) for RBP1 and RBP3, and 331 patients for RGR (79 cases with autosomal dominant RP and 36 RP cases with undetermined inheritance were added to the 216 previous patients). Several variants were found in the 3 genes, including unique amino acid changes, but none of them showed evidence of pathogenicity. It is likely that mutations in RGR, RBP3, and possibly RBP1 occur rarely in inherited retinal dystrophies.     

Function of the Retinal Pigment Epithelium in Patients With Neurofibromatosis Type 1

PurposeRetinal and choroidal abnormalities in neurofibromatosis type 1 (NF1) remain poorly studied. It has been reported, however, that the function of the retinal pigment epithelium (RPE) in NF1 was abnormal, with a supra-normal Arden ratio of the electro-oculogram (EOG). This study aims to evaluate the function of the RPE, using EOG, first in patients with NF1 compared to controls and second in patients with NF1 with choroidal abnormalities compared to patients with NF1 without choroidal abnormalities.MethodsThis prospective case-control study included 20 patients with NF1 (10 patients with choroidal abnormalities and 10 patients without) and 10 healthy patients, matched for age. A complete ophthalmologic assessment with multimodal imaging, an EOG, and a full-field electroretinogram were performed for each included patient. The main outcome measured was the EOG light peak (LP)/dark trough (DT) ratio.ResultsThe LP/DT ratio was 3.02 ± 0.52 in patients with NF1 and 2.63 ± 0.31 in controls (P = 0.02). DT values were significantly lower in patients with NF1 than in controls (240 vs. 325 µV, P = 0.02), while light peak values were not significantly different (P = 0.26). No difference was found for peak latencies. No significant correlation between the surface and number of choroidal abnormalities and EOG parameters was demonstrated.ConclusionsThis study confirms the dysfunction of the RPE in patients with NF1, involving a lower DT and a corresponding higher LP/DT ratio. We hypothesize that this pattern may be due to a dysregulation of the melanocytogenesis, inducing a disruption in Ca2⁺ ion flux and an abnormal polarization of the RPE.     

A model of best vitelliform macular dystrophy in rats

PURPOSE: The VMD2 gene, mutated in Best macular dystrophy (BMD) encodes bestrophin, a 68-kDa basolateral plasma membrane protein expressed in retinal pigment epithelial (RPE) cells. BMD is characterized by a depressed light peak (LP) in the electro-oculogram. Bestrophin is thought to be the Cl channel that generates the LP. The goal was to generate an animal model of BMD and to determine the effects of bestrophin overexpression on the RPE-generated components of the ERG. METHODS: Bestrophin or bestrophin mutants (W93C or R218C) were overexpressed in the RPE of rats by injection of replication-defective adenovirus. Immunofluorescence microscopy and ERG recordings were used to study subsequent effects. RESULTS: Bestrophin was confined to the basolateral plasma membrane of the RPE. Neither wild-type (wt) nor mutant bestrophin affected the a- or b-waves of the ERG. Wt bestrophin, however, increased the c-wave and fast oscillation (FO), but not the LP. In contrast, both mutants had little or no effect on the c-wave and FO, but did reduce LP amplitude. LP amplitudes across a range of stimuli were not altered by wt bestrophin, though the luminance response function was desensitized. LP response functions were unaffected by bestrophin R218C but were significantly altered by bestrophin W93C. CONCLUSIONS: A model of BMD was developed in the present study. Because overexpression of wt bestrophin shifted luminance response but did not alter the range of LP response amplitudes, the authors conclude that the rate-limiting step for generating LP amplitude occurs before activation of bestrophin or that bestrophin does not directly generate the LP conductance.     

两种波长自发荧光联合频域光学相干断层扫描对视网膜色素变性微结构与功能的再认识

目的 分析视网膜色素变性(RP)中两种波长眼底自发荧光(FAF)和多焦视网膜电图(mf-ERG)的临床特征,应用频域光学相干断层扫描(Spectralis OCT)观察相应的视网膜微结构改变,进一步探讨两者联合应用在RP诊断中的价值.方法 非干预性、观察性研究.应用激光共焦扫描检眼镜(德国Heidelberg公司)对8例(15眼)RP患者进行蓝光自发荧光(BL-FAF,激发光488 nm,滤光片＞500 nm)、近红外波长自发荧光(NIR-FAF,激发光787 nm,滤光片＞800 nm)及Spectralis OCT检查.5例进行了荧光素眼底血管造影(FFA)检查,其中3例同时接受了吲哚青绿血管造影(ICGA)检查;7例进行了眼底照相;4例患者接受了mf-ERG检查.分析RP病例FAF分布特征及Spectralis OCT所示视网膜微结构与mf-ERG中反应振幅密度的对应改变.结果 在视网膜色素上皮(RPE)和光感受器(PR)萎缩及骨细胞沉着部位,BL-FAF与NIR-FAF均为低荧光,mf-ERG反应强度降低,中心反应区正常尖峰消失.正常FAF区域内Spectralis OCT提示视网膜PR、RPE保存完整,外界膜(OLM)部分断裂.部分病例NIR-FAF高荧光区域小于BL-FAF.FFA早期出现典型的"窗样缺损"现象,提示RPE受损:早期ICGA表现为脉络膜毛细血管萎缩.结论 两种波长FAF联合Spectralis OCT及mf-ERG是诊断RP十分有用的非侵入性工具,其特征性改变提示PR和RPE细胞拥有共同的退化途径,而BL-FAF和NIR-FAF提示该途径所累及的脂褐索和非脂褐素的荧光性物质分别存在不同的病理生理变化.     

Preserved para-arteriole retinal pigment epithelium (PPRPE) in retinitis pigmentosa.

Five patients with retinitis pigmentosa (RP) with probable autosomal recessive inheritance have been identified in whom there is relative preservation of retinal pigment epithelium adjacent to and under retinal arterioles despite a panretinal degenerative process. All the patients were hypermetropic, though patients with RP tend to be myopic. This implies that there is a factor associated with retinal arterioles which locally retards the RP process in these patients. It may be appropriate to look for the PPRPE pattern in hypermetropic RP patients.     

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments.