他莫昔芬相关眼部病变的研究进展

本文回顾总结了近年来他莫昔芬应用于乳腺癌、神经胶质瘤治疗时出现的相关眼部病变的文献,将他莫昔芬导致眼部病变出现的发生率、发病机制、相关眼部病变特征性表现（角膜病变、白内障、视网膜病变、视神经病变以及其他一些少见病变）进行综述,为眼科医师对他莫昔芬眼部病变的识别和眼部病变的监测提供指导。 （中华眼科杂志,20...     

应用DiI染色晶体对人胚胎视神经发育过程的初步研究

目的：应用Dil(1,1′-dioctadecyl-3,3′,3′-tertamethylin-docarbocyanine perchlorate,一种羰花青染料)染色晶体研究人胚胎视网膜、外侧膝状体、上丘及视皮质间连接的形态学特征和动态发育过程。方法：对不同胎龄的7个胎儿眼球标本进行灌注固定后,分别于标本的视束、上丘臂和视皮质下板层植入Dil染色晶体,以标记来自视网膜和外侧膝状体的轴突。于室温下放置4-10周,等待Dil染色晶体扩散,再根据神经走向切片,通过激光共焦扫描显微镜观察并记录植入Dil染色晶体12-28周的结果。结果：植入Dil染色晶体12周时,胎儿标本的视网膜神经纤维投射已经到达外侧膝状体,但尚未出现分层现象;视网膜神经投射也已达到上丘,纤维位于上丘臂的背侧;视皮质下已出现板层结构。植入22周时视皮质下仍存在板层结构。结论：植入Dil染色晶体12周前,视网膜神经纤维投射已达到外侧膝状体和上丘,视皮质下的板层也已经形成,22周后消失。Dil染色技术能有效地用于研究胚胎期视神经的连续发育过程。     

玻璃体腔注射内皮素-1诱导猫视盘慢性缺血的实验研究

目的猫眼玻璃体腔注射内皮素-1（endothelin-1，ET-1）诱导视盘慢性缺血动物模型，研究慢性缺血对视神经的影响。方法将13只猫随机分为A组7只和B组6只。右眼为实验眼，左眼为对照眼。实验开始时（术前）行眼部检查和眼压测量，海德堡共焦扫描激光多普勒视网膜地形图（heidelberg retina tomography，HRT）分析视盘形态，海德堡共焦扫描激光多普勒视网膜血流分析仪（heidelberg retina flowmeter，HRF）分析视盘筛板微循环。实验眼注入10μL ET-1溶液，A组浓度为10^-6mol／L，B组为10^-5mol／L，对照眼注入10μL相应赋形剂。每周注射2次，连续4周。每次注药前后均行眼部检查、眼压测量。实验结束后检查同术前。取视神经标本进行视神经轴突计数。结果B组实验眼注药前后眼压与术前眼压比较，部分检测点差异有统计学意义；实验眼术后视盘筛板血流量降低33．80％，血流速降低57．73％，红细胞移动速率降低57．70％；术后实验眼较对照眼视神经轴突数减少10．70％。A组中实验眼和对照眼术前、术后各研究参数差异均无统计学意义。结论猫眼玻璃体腔多次微量注射10^-5mol／LET-1可诱导视盘缺血，损害视神经。     

大鼠视神经部分损伤后视神经纤维再生的形态学观察

目的探讨大鼠视神经不同程度损伤后视网膜神经节细胞（RGC）和轴突的变化规律及神经再生能力。方法用夹持力为148g的反向镊夹持大鼠视神经3、6、12、30、60S建立不同程度视神经损伤的动物模型,计数视神经损伤后0．5、1、2、3、7个月RGC和损伤后1、2、3个月轴突随时间的变化规律,透射电镜观察损伤的再生反应,在银染的视神经纵切片上计数后计算视神经横断面上纤维数目,根据横断面的纤维数目计算损伤视神经的再生指数以衡量不同程度视神经损伤后的再生能力。再生指数的计算为（损伤点后0．5mm纤维数-损伤点后2．5唧纤维数）／（球后0．5唧纤维数-损伤点后2．5mm纤维数）。结果视神经部分损伤后RGC和轴突持续丢失,这种丢失可分为伤后2周内的急性丢失和其后的缓慢丢失两个时期,并呈指数形式下降。随着致伤程度的加重,RGC的丢失率上升而存活率降低,RGC和轴突的丢失率随致伤程度的加重而增高,轻度损伤时这种继发损伤具有自限性。视神经损伤后,有大量丛状聚集、区域化分布的无髓再生纤维。视神经夹持损伤3、6、12、30、60s后,再生指数分别为1．409、1．490、0．916、1．119、1．224（χ^2=281．2,P〈0．01）,不同程度损伤后神经的再生能力可能不同,轻度损伤的再生能力较强。结论不同程度视神经部分损伤后继发反应和再生能力不同,轻度损伤后的继发损伤具有自限性并具有更强的再生能力,在一定程度的损伤下修复与损伤可能达到某种平衡而导致成功再生。     

兔视神经间接损伤后视觉电生理及视神经超微结构观察

目的 :视神经间接损伤在闭合性颅脑外伤中占到 5 % ,但是有关其临床治疗仍存在较大分歧。因此探讨视神经间接损伤后形态学的演变 ,为临床治疗提供相关的理论依据 ,具有重要的意义。方法 :在成年兔的视神经间接损伤模型上 ,动态观察视觉电生理 (F -VEP)的变化 ,同时结合视神经的超微结构变化了解视神经间接损伤后形态学的演变。结果 :间接损伤后损伤眼的F -VEP的P1峰幅值比对照眼下降 47 3 8% ,峰潜时延长 ,伤后 1～ 2周时变化更为明显 ,伤后 4周时F -VEP开始恢复 ,8周时P1峰幅值明显提高 ,峰潜时缩短 ,12周时稳定 ,接近正常水平。间接损伤后视神经的超微结构变化主要表现为轴突肿胀 ,髓鞘疏松 ,板层脱离 ,毛细血管破裂出血 ,胶质细胞核内染色质浓缩 ,胶质细丝溶解。这些改变 2周时最重 ,4周时部分轴突开始修复 ,8～ 12周时部分轴突明显修复 ,同时有大量胶质纤维填补变性坏死的轴突留下的空隙。结论 :本实验条件下间接损伤后的视神经其视功能可以逐渐恢复 ,超微结构的观察证明间接损伤的视神经有一定的修复能力 ,这构成视功能恢复的基础。     

Melanocytoma of the optic nerve head: a review

The melanocytoma of the optic disc is a deeply-pigmented tumor located on the optic nerve head. In contrast to malignant melanoma, it appears to occur in equal frequency in whites and non-whites. Histologically, it consists of deeply-pigmented plump nevus cells with benign characteristics. No treatment is usually necessary and the prognosis is excellent.Supported in part by the Retina Research and Development Foundation, Philadelphia, and the Lions Club of Pennsylvania.     

Bilateral retrobulbar hemorrhage and visual loss following traumatic asphyxia

Retrobulbar hemorrhage and permanent visual loss are rare presentations following traumatic asphyxia. In this case, bilateral permanent visual disturbance developed in a woman after chest-crushing trauma without direct trauma to the orbits. A computed tomography scan confirmed bilateral retrobulbar hemorrhages. An ophthalmologic exam revealed bilateral subconjunctival hemorrhages and severe lid edema. Despite high-dose steroid therapy, visual recovery was limited, and optic nerve atrophy developed. Ischemia of the optic nerve associated with retrobulbar hemorrhage may be postulated as one of the causes of permanent visual impairment following traumatic asphyxia.     

视神经吸断伤动物模型的制作

目的 探索一种简便易行并可用于研究影响视神经再生外加因素的新型视神经损伤模型。方法 实验研究。成年SD大鼠20只,行腹腔麻醉,经眶上缘切口分离至左眼球后极部,暴露视神经,用微波管在球后离视盘2.0 mm处完全吸除视神经纤维0.5 mm,在吸断处注入PBS溶液,继而逐层缝合眶上缘切口。另选5只大鼠不造模,作为正常组。于损伤后15 h,在相同测量条件下行造模眼和正常眼视网膜电图（ERG）和视觉诱发电位（VEP）检测。结果 通过视神经纵行冰冻切片观察,视神经纤维损伤量较为一致、准确;造模眼ERG和VEP图像仅为基线,均无正常眼ERG和VEP图像的波峰及波谷出现;视神经冰冻切片拍照证明,视神经鞘膜保留完整,轴突轴浆已中断,可见2个断端。结论 采用视神经吸断方法制作动物模型,造模眼视神经轴突已被吸断,无电传导功能,视神经损伤模型造模成功。     

Electrophysiological monitoring in a patient with an optic nerve glioma

Purpose To report a case illustrating the value of pattern VEP and pattern ERG (PERG) in monitoring optic nerve gliomata (OG). Case report A 15-year-old girl presented with a 3-year history of frontal headaches and a 5-month history of blurred vision in the right eye. MRI scanning revealed a thickened, right optic nerve extending to the cranial opening of the optic canal, consistent with an optic nerve glioma. Pattern VEP showed a mildly delayed major positive component consistent with optic nerve dysfunction. The PERG N95:P50 ratio was subnormal in keeping with retinal ganglion cell involvement. Visual acuity decreased over the following 2 years and repeat VEP objectively demonstrated marked deterioration in optic nerve function despite neuroradiology showing no significant change in the tumour. Conclusions Pattern VEPs and pattern ERGs can provide early objective evidence of optic nerve/retinal ganglion cell dysfunction in optic nerve gliomata. Serial recordings can objectively demonstrate worsening function in the absence of significant neuroradiological change.     

源自视神经的畸胎性恶性髓上皮瘤一例

髓上皮瘤是源自神经系统的一种少见的恶性肿瘤,多发生在中枢神经系统和睫状体,而源自视神经的恶性髓上皮瘤则很少见,国内尚未有病例报道.此病早期类似胶质瘤,易造成误诊.本文报道了1例3岁10个月的男性患儿.经部分肿物切除活检发现肿瘤具有典型恶性髓上皮瘤的病理特点,部分瘤细胞向软骨细胞分化,并逐渐形成透明软骨岛.NSE及S-100表达阳性,病理诊断为源自视神经的畸胎性恶性髓上皮瘤.     

Reducing noise in suspected glaucomatous visual fields by using a new spatial filter

Visual field testing with automated perimetry is hampered by the amount of noise present in the readings. Here, we derive a physiologically accurate spatial filter to be applied to the data after patient examination. The filter was tested by a Virtual Eye computer simulation. By simulating series of stable fields it was shown that specificity of determining visual field changes was improved; while simulating progressing fields (based on a map of the optic nerve head) it was shown that sensitivity was also improved. The filter appears to reduce the noise in glaucomatous visual field data and may be clinically useful.     

How to Handle Benign Optic Glioma of Childhood: A Short Overview

Optic glioma is a rare benign tumour predominantly occurring in childhood, frequently associated with Neurofibromatosis Type 1 (NF1). It threatens vision and—if extending suprachiasmatically—the life of the patient. Symptoms are visual loss, orbital signs including motility disorders and/or nystagmus in suprachiasmatic lesions. There is no therapy approved in studies with highest evidence. Radiotherapy is most effective in stopping tumour progression but has serious side effects, such as brain developmental anomalies, moya moya syndrome and secondary tumours. Therefore in children younger than 9 and patients with NF1, chemotherapy with vincristine and carboplatine is preferred. Surgery plays only a role in the debulking of large tumours, cosmetic correction or definitive removal if visual function is lost. Therapeutic decisions should be based on reliable function testing.     

Successful Surgical Treatment of a Primary Optic Nerve Sheath Meningioma

We report the case of a 54-year-old female patient, who underwent lateral orbitotomy for a right retrobulbar mass. A cavernous hemangioma was suspected on imaging; however, the histological examination unexpectedly revealed a WHO I° meningioma. Visual function, motility, and pupillary and fundus changes fully recovered within a three-month period after surgery. At the five-year follow-up, there was no evidence of local recurrence. Our case adds to the small number of cases with full recovery of visual function after surgery for optic nerve sheath meningioma reported in the literature to date.     

青光眼视神经保护离我们有多远

尽管在基础研究中,Memantine、Calpain、促红细胞生成素等药物均显现出喜人的青光眼视神经保护潜能,但随着Memantine等Ⅲ期临床试验的失败,目前仍无一种视神经保护药物能够通过美国食品药品管理局的审核批准并投入临床应用,使临床青光眼视神经保护的研究面临近乎尴尬的困境.青光眼视神经保护的迫切性要求我们必须从新的视角审视问题,充分利用人类基因组计划、蛋白质组计划、干细胞和转基因动物研究成果,对其实施分期靶点干预,以使青光眼视神经保护的梦想变成现实.     

CT三维重建和导航下内镜视神经管减压的解剖学研究

目的 为CT三维重建和导航下内镜视神经管减压手术提供解剖学依据.方法 实验研究.对8例(16侧)成人湿性尸头视神经管及其重要毗邻结构进行解剖和测量,比较分析内镜下CT三维重建和导航定位的视神经管结构与实体解剖下视神经管结构的差异.采用配对t检验.结果 内镜下视神经管隆起、颈内动脉隆起和视神经-颈内动脉隐窝出现率分别为62.5％、75％和75％,与实体解剖结果完全吻合.内镜下视神经管眶口内壁中点到鼻小柱基底前缘的距离为(71.19±4.00)mm、视神经管颅口内壁中点到鼻小柱基底前缘的距离为(79.69±3.65)mm、视神经管内侧壁长度为(10.00±1.71)mm、视神经管眶口直径为(4.46±0.56)mm、视神经管颅口直径为(4.71±0.42)mm,与实体解剖测量结果比较差异无统计学意义.结论 CT三维重建和导航技术可以准确定位视神经管,为安全有效的内镜视神经管减压手术提供保障.     

Onchocerciasis as a Risk Factor for Night Blindness

Purpose: In the Kaduna State Nigeria Onchocerciasis focus, the prevalence of reported night blindness (RNB ) was 12.9%, higher than the national average (1%), and a control non-onchocercal community (0.83%, P?<?0.0001). Risk factors for RNB were explored.

Methods: This was an analysis of baseline data from the phase three ivermectin trials in Kaduna (1988–1995). 6831 subjects in the onchocercal zone and 1563 in the control zone were examined. Ordinal logistic regression was used to assess the relationship between microfilaria load (uninfected, low (<10 mf/mg), moderate (10–49 mf/mg) and high (50+ mf/mg)) and likelihood of RNB.

Results: Ocular evidence of vitamin A deficiency (Bitot spots or xerophthalmia) was absent in both populations. The excess risk of nightblindness attributable to domicile in this onchocerciasis-endemic area was 11.9% with a population attributable fraction of 92.2%. The prevalence of RNB and age-adjusted odds ratio increased with higher microfilaria load (P?<?0.0027.) Subjects with onchocerciasis-related ocular lesions such as optic nerve disease (OND; age-adjusted OR 2.29, 95% confidence interval, CI, 1.86–2.83), sclerosing keratitis (OR 2.75, 95% CI 2.10–3.50), and onchocercal chorioretinitis (OR 1.66, 95% CI 1.22–2.26) were significantly more likely to report night blindness.

Overall, subjects with a primary diagnosis of ‘ocular onchocerciasis’ were 50% more likely to report night blindness. OND, cataract and trachoma together accounted for 52% of all RNB but OND (onchocerciasis-related in 80% of cases) emerged as the single most common associated pathology in 30% of cases.

Conclusions: Onchocercal infection probably accounted for the excess of RNB in this focus.     

两种常用大鼠视神经钳夹伤模型造模效果的比较

背景 视神经钳夹伤(ONC)动物模型是外伤性视神经损伤致病机制及治疗方法相关基础研究的主要工具,目前常用的造模方法有经眼眶上缘开神经鞘膜视神经钳夹法和经球结膜外眦部夹伤视神经法,但关于2种模型优劣评价的研究很少. 目的 比较2种常用大鼠ONC模型的造模效果,为相关的实验研究中造模方法的选择提供依据.方法 采用随机分配方法将8～10周龄健康成年雄性SD大鼠24只分为经眶上缘开神经鞘膜ONC组和经眶上缘开神经鞘膜ONC 20 s、40 s、60 s组,分别采用经眶上缘开神经鞘膜视神经夹伤法(20 s)及经球结膜外眦部夹伤视神经法在大鼠的一侧眼建立ONC动物模型,各组大鼠的正常对侧眼作为对照.于造模后14 d记录各组大鼠闪光视觉诱发电位(F-VEP)P1波;制备大鼠视神经组织切片,采用苏木精-伊红染色法观察大鼠视神经的组织病理学改变;采用免疫荧光法观察并计数大鼠视网膜组织中Brn-3α阳性视网膜神经节细胞(RGCs).对2种造模方法的造模过程和检测结果进行比较.结果 造模后14d,经眶上缘开神经鞘ONC组和经球结膜ONC 20 s组、40 s组、60 s组大鼠的F-VEP P1波潜伏期较各自的正常对侧眼均明显延长,差异均有统计学意义(t=-11.64、-8.04、-6.50、-10.84,均P＜0.01);经眶上缘开神经鞘ONC组大鼠P1波潜伏期与经球结膜ONC 20 s、40 s、60 s组大鼠比较均明显延长,差异均有统计学意义(P=0.01、0.02、0.05);各组大鼠术眼P1波振幅与其正常对侧眼比较差异均无统计学意义(均P＞0.05).造模后14 d,免疫荧光检测显示各组大鼠模型眼视网膜上Brn-3α表达阳性RGCs数均较正常对侧眼明显减少,经眶上缘开神经鞘ONC组大鼠视网膜上Brn-3α表达阳性RGCs数为(13.60±2.14)个/视野,为其正常对侧眼的47.49％,经球结膜ONC 20 s、40 s和60 s组中Brn-3α阳性RGCs数分别为(18.74±3.61)、(15.84±2.31)和(14.58±3.23)个/视野,分别为其正常对侧眼的67.70％、56.69％和50.17％,经眶上缘开神经鞘ONC组大鼠视网膜中Brn-3α阳性RGCs数与经球结膜ONC 40 s和60 s组比较,差异均无统计学意义(均P＞0.05).组织病理学检查显示,各组大鼠造模眼神经胶质细胞核排列紊乱,细胞基质空泡化,可见大量炎性细胞浸润,以眶上缘开神经鞘ONC组更为严重.结论 与经球结膜ONC模型鼠比较,经眶上缘开视神经鞘ONC模型大鼠视神经形态结构损害更为严重,视神经的传导功能更为迟缓,RGCs的存活率更低.     

大鼠视神经损伤后Toll样受体4在视网膜中的表达

背景Toll样受体4（TLR4）是一种重要的免疫相关受体,在多种疾病的发生中起致炎作用。研究发现,视神经损伤后继发的炎症反应可进一步引起视网膜损伤,因此视神经损伤后TLR4的表达及其效应值得研究。目的研究大鼠视神经损伤后视网膜TLR4的表达情况。方法选取成年健康SPF级SD大鼠24只,按随机数字表法随机分为视神经损伤3d组和视神经损伤7d组。取大鼠右眼用视神经钳夹法制备视神经损伤模型,左眼不予处理为对照组。分别于视神经损伤后3d和7d用过量麻醉法处死大鼠并分离视网膜,采用免疫荧光法检测各组大鼠视网膜中TLR4的表达;分别采用逆转录PCR法（RT—PCR）和Westernblot法检测大鼠视网膜中TLR4mRNA及其蛋白的表达;采用TUNEL染色法观察各组大鼠视网膜神经节细胞（RGCs）的凋亡情况。结果视网膜免疫荧光法检测结果显示,TLR4在大鼠视网膜中呈绿色荧光,视神经损伤3d组和视神经损伤7d组造模眼视网膜中的荧光强度较对照组左眼均明显增强,绿色荧光主要分布在视网膜内层。RT—PCR法检测表明,模型眼视网膜损伤后3d和7d视网膜中TLR4mRNA相对表达量分别为2．92±0．06和3．92±0．12,对照眼TLR4mRNA的相对表达量分别为2．87±0．12和3．44±0．17,大鼠模型眼TLR4mRNA表达的灰度值较对照眼明显增加,差异均有统计学意义（t3d=-12．888,P〈0．001;t7d=-4．669,P=0．010）。Westernblot法检测显示,大鼠模型眼视网膜损伤3d和7d视网膜中TLR4蛋白的相对表达量分别为1．14±0．05和1．49±0．03,对照眼TLR4蛋白的相对表达量分别为0．99±0．09和1．38±0．07,模型眼视网膜中TLR4蛋白表达量明显高于对照眼,差异均有统计学意义（t3d=-11．324,P〈0．001;t7d=-5．638,P=0．005）。TUNEL染色显示,模型眼RGCs凋亡数较对照眼增多。结论TLR4在视神经损伤大鼠视网膜内层的表达明显上调,提示TLR4通路可能参与RGCs的损伤。     

A mathematical description of nerve fiber bundle trajectories and their variability in the human retina

We developed a mathematical model wherein retinal nerve fiber trajectories can be described and the corresponding inter-subject variability analyzed. The model was based on traced nerve fiber bundle trajectories extracted from 55 fundus photographs of 55 human subjects. The model resembled the typical retinal nerve fiber layer course within 20° eccentricity. Depending on the location of the visual field test point, the standard deviation of the calculated corresponding angular location at the optic nerve head circumference ranged from less than 1° to 18°, with an average of 8.8°.