Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer's disease:a meta-analysis

AIM:To investigate the difference of retinal nerve fiber layer(RNFL) thickness between Alzheimer's disease patients and normal people,so as to provide clue for the early diagnosis of Alzheimer's disease.· METHODS:The articles on the association of RNFL thickness and Alzheimer's disease were retrieved by searching international and national databases.The qualified articles were assessed by meta analysis with Stata11.0 software.The results were pooled using weighted mean difference(WMD) with a corresponding 95% confidence interval(CI).· RESULTS:Totally 7 studies enrolled 324 eyes were included in the meta-analysis.The results of meta analysis showed that in AD patients,there was a significant average RNFL thickness reduction compared with the control group [WMD=-17.561,95%CI:(-23.971,-11.151)].There were significant differences in superior,inferior,nasal and temporal RNFL thickness between the two groups.WMD with a 95%CI were [-18.829,95%CI:(-25.915,-11.743);P<0.05],[-25.775,95%CI:(-34.304,-17.247);P <0.05],[-16.877,95%CI:(-29.141,-4.613);P<0.001] and [-14.565,95%CI:(-28.002,-1.128);P<0.001] respectively.Begg's test and Egger's test did not show significant difference,funnel plot was basically symmetrical,indicating that there was no publication bias existed.· CONCLUSION:There are significant differences in the RNFL thickness in all quadrants between the two groups.RNFL thickness is reduced in AD patients compared with the control group.·

Quantitative study of peripapillary retinal nerve fiber layer thickness and peripapillary vessel density in patients with different stages of Parkinson's disease

AIM: To observe the changes in the thickness of peripapillary retinal nerve fiber layer(p RNFL) and peripapillary vessel density(pVD) in patients with different stages of Parkinson's disease(PD).METHODS: Totally 47 patients(47 eyes) with primary PD were divided into the mild group and the moderateto-severe group according to Hoehn & Yahr(H&Y) stage. Among them, there were 27 cases(27 eyes) in mild group and 20 cases(20 eyes) in moderate-to-severe group. And 20 cases(20 eyes) who were included in the control group were healthy people who came to our hospital for health screening at the same time. All participants underwent optical coherence tomography angiography(OCTA) examinations. The pRNFL thickness, total vessel density(tVD) and capillary vessel density(cVD) of the optic disc in average, superior half, inferior half, superior nasal(SN), nasal superior(NS), nasal inferior(NI), inferior nasal(IN), inferior temporal(IT), temporal inferior(TI), temporal superior(TS), and superior temporal(ST) were measured. One-way ANOVA was used to compare the differences of optic disc parameters among the three groups, and Pearson and Spearman correlations were used to analyze the correlation between pRNFL, pVD and the disease duration, H&Y stage and UPDRS-Ⅲ score in patients with PD, respectively.RESULTS: There were significant differences in p RNFL thickness in average, superior half, inferior half, SN, NS, IN, IT and ST quadrants among the three groups(P<0.05). In PD group, the pRNFL thickness in average, superior half, inferior half, NS and IT quadrants were negatively correlated with H&Y stage and UPDRS-Ⅲ score, respectively(P<0.05). There were statistically significant differences in the cVD of whole image, inferior half, NI and TS quadrants, the tVD of the whole image, inferior half, and peripapillary among the three groups(P<0.05). In PD group, the tVD of whole image and the c VD of NI and TS quadrants were negatively correlated with the H&Y stage, respectively(P<0.05);the cVD of TS quadrant was negatively correlated with UPDRS-Ⅲ score(P<0.05).CONCLUSION: The thickness of pRNFL in PD patients is significantly decreased, and it is negatively correlated with H&Y stage and UPDRS-Ⅲ score. With the increase of the severity of the disease, the pVD parameters in PD patients increase at first in the mild group, and then decrease in the moderate-to-severe group, and negatively correlate with H&Y stage and UPDRS-Ⅲ score.

Spectral-domain optical coherence tomography in patients with congenital nystagmus

AIM: To study macular features in patients with congenital nystagmus and to assess the utility of spectral-domain optical coherence tomography (SD-OCT) in nystagmus. METHODS: The macular areas of 51 outpatients with congenital nystagmus were examined using SD-OCT. Morphological changes in the retinal layers of the macular area were analysed. RESULTS: Macular images were successfully obtained with SD-OCT from 50 (98%) patients. Patients with ocular albinism mainly have macular hypoplasia, abnormal foveal depression, and increased foveal thickness with persistence of an inner nuclear layer, an inner plexiform layer, a ganglion cell layer and a nerve fiber layer. Macular morphology similar to albinism was observed in three patients with idiopathic macular hypoplasia. The OCT findings of cone dystrophy included unclear, disrupted or invisible photoreceptor outer segment/inner segment in the fovea; fusion, thickening and uneven reflection of the outer segment/inner segment with external limiting membrane. Some patients with congenital idiopathic nystagmus showed normal macular morphology and structure, and others showed indistinct macular external limiting membrane reflection. CONCLUSION: SD-OCT is an effective and reliable method to detect the macular morphology of congenital nystagmus patients. This technique has diagnostic value in particular for patients with macular hypoplasia and cone cell dystrophy with no distinct abnormality on fundoscopy.

Establishing a cat model of chronic optic nerve compression injury

BACKGROUND： An animal model of chronic optic nerve injury is necessary to further understand the pathological mechanisms involved. OBJECTIVE： To establish a stabilized, chronic, optic nerve crush model, which is similar to the clinical situation to explore histopathological and optic electrophysiological changes involved in this injury. DESIGN, TIME AND SETTING： A randomized and controlled animal trial was performed at Shanghai Institute of Neurosurgery from May to October 2004, MATERIALS： A BAL3XRAY undetachable balloon and Magic-BD catheter were provided by BLAT, France; JX-2000 biological signal processing system by Second Military Medical University of Chinese PLA, China; inverted phase contrast microscopy by Olympus, Japan. METHODS： A total of twenty normal adult cats were randomly assigned to control （n = 5） and model （n = 15） groups, according to different doses of contrast agent injected through balloons as follows： 0.2 mL injection, 0.25 mL injection, and 0.35 mL injection, with each group containing 5 animals. Imitating the clinical pterion approach, the optic nerves were exposed using micro-surgical methods. An engorged undetachable balloon was implanted beneath the nerve and connected to a catheter. Balloon size was controlled with a contrast agent injection （0.1 mL/10 min） to form an occupying lesion model similar to sellar tumors. MAIN OUTCOME MEASURES： The visually evoked potential examination was used to study optical electrophysiology changes in pre-post chronic optical nerve injury. Ultrastructural pathological changes to the optic nerve were analyzed by electron microscopy. RESULTS： During the early period （day 11 after modeling）, visually evoked potential demonstrated no significant changes. In the late period （day 51 after modeling）, recorded VEP demonstrated that P1 wave latency was prolonged and P1 wave amplitude was obviously reduced. Following injury, the endoneurium, myelin sheath, lamella, axolemma, and axon appeared disordered. CONCLUSION： Results demonstrated that the chronic, intracranial, optical nerve crush model was stable and could simulate optic nerve lesions induced by sellar tumors. Under the condition of chronic optical nerve crush, visually evoked potentials were aggravated.

Retinal thickness and vascular parameters using optical coherence tomography in Alzheimer's disease:a meta-analysis

Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease.In this metaanalysis,we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to diffe rentiate between Alzheimer’s disease and control subjects.Scientific databases including Google Schola r,Web of Science,and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control subjects.Seventy-three studies(5850 participants,including 2249 Alzheimer’s disease patients and 3601controls) were included in this meta-analysis.Relative to controls,Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness(standardized mean difference [SMD]=-0.79,95% confidence intervals [CI]:-1.03 to-0.54,P <0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus controls.Regarding macular paramete rs,values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness(pooled SMD:-0.44,95% CI:-0.67 to-0.20,P=0.0003),foveal thickness(pooled SMD=-0.39,95% CI:-0.58 to-0.19,P <0.0001),ganglion cell inner plexiform layer(SMD=-1.26,95% CI:-2.24 to-0.27,P=0.01) and macular volume(pooled SMD=-0.41,95% CI-0.76 to-0.07,P=0.02).Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and controls.Superficial vessel density(pooled SMD=-0.42,95% CI:-0.68 to-0.17,P=0.0001) and deep vessel density(pooled SMD=-0.46,95% CI:-0.75 to-0.18,P=0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone(SMD=0.84,95% CI:0.17-1.51,P=0.01) was larger in controls.Vascular density and thickness of various retinal laye rs were decreased in Alzheimer’s disease patients compared to controls.Our results provide evidence for optical coherence tomography technology having the potential to detect retinal and microvascular changes in patients diagnosed with Alzheimer’s disease and aid in monito ring and early diagnosis methods.

The Retinal Nerve Fiber Layer Defects in Patients with Anterior Ischemic Optic Neuropathy

Purpose:To demonstrate the effects of optic nerve ischemia on retinal nerve fiber layer(RNFL)and the associated visual dysfunction.Methods:23patients(25eyes)wits anterior ischemic optic neuropathy(AION)un derwent fundus fluorescein angiography(FFA),and then red-foree light pic-tures were taken via SE-40exceiter filter.All pictures were printed for RNAFL analysis,Humphrey central field analysis was conducted.All dataobtained fromFFA and visual field defects were analysed statistically.Results:The RNFL defects and the corresponding visual field edfects were pre-sented in 23of 25eyes(92%),The optic disc filling defects,RNAL edfects and visual field defects were found to be highly correspondent to each other.The RNFL defects were mainly the local losses of RNFL which were correspondent to the ischemic regions.Conclusion:The poor optic disc filling or ischemia can result in the RNFL defects which cause the associated visual dysfunction.Because RNFLdefects are irrever-siable changes,the potential values in predicting the prognosis of visual field de-fects caused by RNFL damages were suggested.Eye Science1995;11:165-167.

Potential role of retina as a biomarker for progression of Parkinson's disease

Optical coherence tomography (OCT) noninvasively quantifies the thickness of the retinal nerve fiber layer (RNFL). OCT has been studied in several neuro-ophthalmic conditions, including Parkinson’s disease (PD). Recent studies suggest that the quantitative analysis of RNFL can be precisely and noninvasively done by OCT scans and the results suggest that the thickness of RNFL is significantly decreased in patients with PD compared with age-matched controls and the foveal retinal thickness correlates with disease severity in PD. In this article, the application of OCT imaging of the retina in PD was reviewed. Literature survey of PubMed was carried out using the search terms of "Optical Coherence Tomography" combined with "Parkinson’s Disease" and "retinal nerve fiber layer" (without restriction to the year of publication). Some related articles were also included. The search was completed in Jul. 2011 and revised and updated as necessary. The aim of this article is to review the current literatures on the use of optical coherence tomography in patients affected by PD and to enhance its use in clinical practice in neuro-ophthalmology.

Optical coherence tomography of the pulmonary arteries in children with congenital heart diseases:A systematic review

Importance:Optical coherence tomography(OCT)is a high-resolution intravascular imaging tool and has shown promise for providing real-time quantitative and qualitative descriptions of pulmonary vascular structures in vivo in adult pulmonary hypertension(PH),while not popular in pediatric patients with congenital heart diseases(CHD).Objective:The aim of this review is to summarize all the available evidence on the use of OCT for imaging pulmonary vascular remodeling in pediatric patients.Methods:We conducted the systematic literature resources(Cochran Library database,Medline via PubMed,EMBASE,and Web of Knowledge)from January 2010 to December 2021 and the search terms were“PH”,“child”,“children”,“pediatric”,“OCT”,“CHD”,“pulmonary vessels”,“pulmonary artery wall”.Studies in which OCT was used to image the pulmonary vessels in pediatric patients with CHD were considered for inclusion.Results:Five studies met the inclusion criteria.These five papers discussed the study of OCT in the pulmonary vasculature of different types of CHD,including common simple CHD,complex cyanotic CHD,and Williams-Beuren syndrome.In biventricular anatomy,pulmonary vascular remodeling was primarily reflected by pulmonary intima thickening from two-dimensional OCT.In single-ventricle anatomy,due to the state of hypoxia,the morphology of pulmonary vessels was indirectly reflected by the number and shape of nourishing vessels from three-dimensional OCT.Interpretation:OCT may be an adequate imaging procedure for the demonstration of pulmonary vascular structures and provide additional information in pediatric patients.

Stem Cell Ophthalmology Treatment Study (SCOTS)： bone marrow-derived stem cells in the treatment of Leber＇s hereditary optic neuropathy

The Stem Cell Ophthalmology Treatment Study （SCOTS） is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov （identifier： NCT01920867）. SCOTS utilizes autologous bone marrow-derived stem cells （BMSCs） to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber＇s hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study （ETDRS） of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo- gous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber＇s hereditary optic neuropathy may be a viable treatment option.

CHANGES OF THE THICKNESS OF RETINA NERVE FIBER LAYER IN ALZHEIMER'S DISEASE

Objective To determine the changes of retina nerve fiber thickness with optical coherence tomography(OCT) in Alzheimer’s disease(AD) patients.Methods OCT was used to measure the thickness of retinal nerve fiber layer(RNFL) from 38 AD patients and 26 healthy age-matched controls.The corrected visual acuity and intraocular pressure were measured and the dilated fundus examinations were also performed in those subjects.Results Compared with healthy age-matched controls,the RNFL thickness of AD patients(95.40±29.45) were much thinner than the controls(105.91±29.87)(P <().05),especially in superior quadrant,while no difference was found in the other retinal area.Conclusion Retinal nerve degeneration may be present in the retina of AD patients and this degeneration is likely localized preferentially to the superior quadrant.

Optic Neuritis: Hidden Manifestations and Mimickers

Optic neuritis is the most common cause of unilateral visual loss associated with orbital pain on ocular movements and impaired colour vision. It can present with anterior optic neuritis, papillitis, a swollen optic disc, retrobulbar neuritis with a normal optic disc, neuritis with oedema of the optic disc and the macular star or anterior ischemic neuropathy. It may be the only manifestation of a disease such as demyelination or associated with systemic diseases such as systemic lupus, giant cell arteritis, Sjogren’s syndrome, herpes simplex, herpes zoster, Lyme disease, CMV, EBV, HIV, toxoplasmosis, West Nile virus, Chikungunya, dengue fever, Rift Valley fever, mumps, rubella, measles, cat scratch disease, tuberculosis, syphilis, rickettsia illnesses, Q fever, Whipple disease, brucellosis, leptospirosis, leprosy, toxocariasis, malaria, Cryptococcus, candidiasis, histoplasmosis, Aspergillosis, mucormycosis, Bacillus Chalmette-Guerin (BCG) vaccination, ethanol and methanol toxicity, sarcoidosis, neuromyelitis optica and Liber’s hereditary optic neuropathy. A systemic approach to the diagnosis is of paramount importance in confirming, diagnosing and treating optic neuritis and underlying systemic diseases to provide definitive cures. Failure to diagnose optic neuritis and treat the cause may result in optic atrophy and permanent blindness. In this paper, we reviewed the diagnosis and differential diagnoses of optic neuritis, including arteritis, ischemic, neuroretina, and vasculitic causes.

促红细胞生成素在常见视神经和视网膜疾病保护及修复中的研究进展

促红细胞生成素(EPO)和EPO受体不仅存在于造血组织中,在造血外组织中也广泛存在。组织缺血、缺氧以及炎症因子水平升高均可促进EPO表达,并通过抗凋亡、抗炎、抗氧化、抗神经毒性、促进神经再生等一系列复杂机制在中枢神经系统中发挥保护作用,促进神经修复。视神经和视网膜是中枢神经系统的延伸,许多视神经和视网膜疾病本质也由缺血、缺氧所致,因此EPO在视神经和视网膜疾病中也发挥重要作用。深入研究EPO在视神经和视网膜疾病中的保护作用,可以为相关疾病的治疗提供新思路。

视网膜激光光凝术治疗眼底病的临床效果

目的:分析视网膜激光光凝术治疗眼底病的临床效果。方法:选取2022年2月—2023年2月平原县第一人民医院眼科收治的60例眼底病患者作为研究对象,以双盲法分为对照组与试验组,各30例。对照组采用常规药物治疗,试验组实施视网膜激光光凝术治疗。比较两组生活质量、视神经功能、视力改善情况、治疗效果。结果:治疗前,两组物质、躯体、社会、心理、精神评分比较,差异无统计学意义(P>0.05);治疗后,两组物质、躯体、社会、心理、精神评分高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05)。治疗前,两组视野平均光敏度、视网膜神经纤维厚度、视野平均缺损比较,差异无统计学意义(P>0.05);治疗后,两组视野平均光敏度、视网膜神经纤维厚度大于治疗前,且观察组大于对照组,两组视野平均缺损小于治疗前,且观察组小于对照组,差异有统计学意义(P<0.05)。试验组视力改善情况优于对照组,差异有统计学意义(P<0.05)。试验组治疗总有效率高于对照组,差异有统计学意义(P=0.044)。结论:视网膜激光光凝术治疗眼底病的临床效果显著,可改善患者视神经功能,提高视力与生活质量。

经鼻内窥镜视神经管减压术的初步报告

目的探索治疗视神经外伤较好的手术方法。方法开展了经鼻内窥镜视神经管减压术，并与鼻外进路进行比较。结果采用经鼻内窥镜鼻内进路视神经管减压术１４例，其中９例视力分别从术前的无光感、眼前手动、５０ｃｍ指数、眼前手动、无光感、光感、无光感、眼前手动、无光感到术后的０．２、０．３、０．３＋２、０．４、０．０６、０．３、０．１、０．７、０．１２，３例眼球活动障碍恢复正常，随访时间１个月～１年。讨论了经鼻内窥镜视神经管减压术的手术解剖学，术中注意事项，手术进路的优点和不足。结论认为经鼻内窥镜筛蝶窦进路视神经管减压术术中出血少，手术时间明显缩短，具有更大的实用性，是治疗外伤性视神经外伤的较好手术方法。

前部缺血性视神经病变的发生因素及诊断

目的探讨前部缺血性视神经病变的发生因素及诊断。方法回顾性分析前部缺血性视神经病变 95例 (10 3只眼 )的发病特点 ,以及视野和眼底荧光素血管造影的表现。结果平均发病年龄 5 2 .4岁。 8例 (10只眼 )无原发病 ,87例 (93只眼 )伴有糖尿病、高血压和 (或 )眼底动脉硬化。眼底荧光素血管造影早期视盘全部或部分荧光充盈延缓或缺损 ,伴有相应的视野缺损。造影晚期视盘荧光形态有多种表现形式 ,缺血区呈强荧光者 76只眼(73 .79% ) ,呈弱荧光者 2 7只眼 (2 6 .2 1% )。结论中老年的糖尿病、高血压和 (或 )动脉硬化患者是前部缺血性视神经病变的高危人群 ,其诊断应综合考虑临床症状、视野和眼底荧光素血管造影检查结果。

类立克次体侵染中华绒螯蟹神经组织的光镜和电镜观察

对患颤抖病的中华绒螯蟹 (Eriocheirsinensis)神经和肌肉组织进行光镜和电镜观察 ,结果显示类立克次体广泛存在于胸神经节中的神经胶质细胞、结缔组织以及细胞间隙中。在神经细胞与步足肌肉细胞连接处 ,即运动终板部位有大量类立克次体侵染 ,并且侵染方式与在胸神经节中一样 ,均以聚集成团的形式存在。胸神经节是支配步足的神经丛 ,而颤抖病是以步足颤抖为主要病症的疾病。类立克次体大量侵染胸神经节和运动终板部位 ,表明该微生物与病蟹步足颤抖的病症有密切关系 ,进一步证明类立克次体是颤抖病的致病微生物。

长春胺对原发性缺血性视神经视网膜脉络膜病变疗效观察

目的观察长春胺注射液对原发性缺血性视神经视网膜脉络膜病变的疗效和安全性。方法采用随机对照方法,将原发性缺血性视神经视网膜脉络膜病变患者60例随机分为对照组(30例)、治疗组(30例),对照组采用妥拉唑林注射液25 mg患眼颞侧颞浅动脉旁皮下注射,治疗组采用妥拉唑林注射液25 mg患眼颞侧颞浅动脉旁皮下注射同时应用长春胺注射液20 mg+0.9%NS250 ml静滴,1次/d,疗程为20 d。结果有效率治疗组为76.7%,对照组为40.0%,两者比较,差异有显著统计学意义(U=203.5,P<0.01)。治疗组除3例患者有短暂恶心,头昏,2例有短暂腹痛外,与对照组均无严重不良反应。结论长春胺对原发性缺血性视神经视网膜脉络膜病变的治疗是有效和安全的。

外伤性视神经病变外科治疗的意义及疗效

目的 探讨外伤性视神经病变 (traumaticopticneuropathy ,TON)外科治疗的意义及疗效。方法 分析 5 2例 (5 3眼 )经鼻内镜视神经管减压术 (5 3眼 )和眶尖减压术 (8眼 )的治疗效果 ,随访 6个月～ 3年。结果 2 1眼获视力改善 (39 6 % ) ,其中皮质类固醇激素治疗无效进而采取手术者 14眼有效 (14 /37,37 8% ) ,未经激素治疗即手术者 7眼有效 (7/16 ,4 3 8% ) ;无光感者 18眼获视力改善 (18/4 9 ,36 7% ) ,术前有残余视力者 3眼有效 (3/4 ,75 0 % )。结论 外科治疗对提高TON疗效有重要意义。

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ONC20s、40s、60s组，分别采用经眶上缘开神经鞘膜视神经夹伤法（20s）及经球结膜外眦部夹伤视神经法在大鼠的-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14d记录各组大鼠闪光视觉诱发电位（F—VEP）P。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-3a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ONC20s组、40S组、60s组大鼠的F—VEPP。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P．波潜伏期与经球结膜ONC20s、40s、60s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P．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14d，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-3a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ONC20s、40s和60s组中Brn-3a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．3a阳性RGCs数与经球结膜ONC40s和60s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。