视网膜是中枢神经系统的一部分。在胚胎起源上，视网膜和大脑均由神经管发育而来。因此，许多发生在大脑的神经退行性疾病往往会同时累及视网膜。而神经退行性疾病过程中相关的特征性病理改变，如病理性蛋白聚集和神经血管单元破坏也常能在视网膜组织中被检测到。在一些神经退行性疾病中，眼部的病理改变甚至在临床症状出现之前就已发生；其次视网膜易于观察且局部治疗操作便捷，因此近年来视网膜在中枢神经退行性疾病发病机制研究、早期诊断和新型治疗方式探究等方面备受关注。该文对常见神经退行性疾病的眼部病理改变进行综述，旨在为大脑和视网膜神经退行疾病的发病机制、诊断以及治疗研究提供新的见解。
The retina is a part of the central nervous system. Developmentally, both retina and brain are derived from the neural tube. Therefore, many neurodegenerative diseases that occur in the brain tend to involve both the retina. In the process of neurodegenerative diseases, related characteristic pathological changes, such as pathological protein aggregation, neurovascular unit impairment can often be detected in retinal tissue. In some neurodegenerative diseases, pathological changes in the eye occur even before clinical symptoms appear. In addition, the retina are easy to observe and local treatments are convenient. In recent years, the manifestations of the retina have attracted much attention in the study of pathogenesis, early diagnosis, and new treatments of systemic central neurodegenerative diseases. In this way, this article reviews the ocular pathological changes of common neurodegenerative diseases, aiming to provide new insights into the pathogenesis, diagnosis, and treatment of brain and retinal neurodegenerative diseases.
息肉状脉络膜血管病变（polypoidal choroidal vasculopathy, PCV）是中国人新生血管性年龄相关性黄斑变性的(age-related macular degeneration, AMD)主要亚型。PCV与典型的新生血管性AMD在流行病学、临床表现、影像学特征和自然病程方面存在一定差异。近年来的研究表明，除了传统的玻璃膜疣驱动机制外，PCV可能与肥厚脉络膜机制相关，后者在亚洲人群中更为常见。深入的病理学探索将有助于揭示PCV的发病机制，并探索PCV与其他脉络膜疾病之间的内在联系。由于PCV患者眼球标本的稀缺，现有的病理学研究较少，且结果之间存在一定差异。文章通过介绍笔者最新的临床病理研究结果，并结合历年来国内外的研究，总结了关于PCV病灶所在的层次、起源及血管内皮生长因子（vascular endothelial growth factor, VEGF）表达水平的争议问题，阐明了PCV的临床病理研究现状。第一，PCV病灶的层次。临床上，OCT成像显示PCV病灶位于视网膜色素上皮（retinal pigment epithelium, RPE）与Bruch膜的高反射线之间，属于I型脉络膜新生血管的特殊亚型。部分病理学研究认为PCV病灶位于Bruch膜内，但实际上PCV病灶更准确地位于RPE基底膜下。第二，异常分支血管网（branching vascular networks, BVN）的起源。尸体眼标本的病理分析表明，BVN起源于脉络膜动脉，且动脉穿过Bruch膜后，转变为薄壁毛细血管形成I型脉络膜新生血管。少数研究指出PCV可能由静脉扩张形成，并存在脉络膜静脉的淤滞。第三，VEGF在PCV病灶中的表达。VEGF是新生血管性AMD的关键致病因子，一些研究表明PCV病灶中VEGF表达升高，提示PCV可能与新生血管性AMD具有相似的发病机制，但也有研究发现PCV病灶中的VEGF表达为阴性，提示PCV的机制可能不完全依赖于VEGF。综上，PCV的病理特征具有复杂性，既有与新生血管性AMD相似的表现，也有肥厚脉络膜的特征。随着眼球捐献意识的提高，未来有望获得更多宝贵的眼球标本，为进一步探索PCV的发病机制提供支持,并为其临床诊断和治疗提供更有效的策略。
Polypoidal choroidal vasculopathy (PCV) is the main subtype of neovascular age-related macular degeneration (AMD) in China. PCV differs from typical neovascular AMD in terms of epidemiology, clinical presentation, imaging features, and natural disease course. Recent studies suggest that, in addition to the traditional drusen-driven mechanism, PCV may also be associated with pachychoroid mechanism, which is particularly more common in Asian populations. In-depth pathological research will help uncover the pathogenesis of PCV and explore the intrinsic connections between PCV and other choroidal diseases. Due to the rarity of eye specimens from PCV patients, there is limited pathological research, and results can vary. Herein, this article summarize the controversial issues regarding the location level, origin, and the vascular endothelial growth factor (VEGF) expression of PCV lesions by introducing our latest clinicopathologic study on PCV and combining with previous studies in China and worldwide. First, the layer of PCV lesions. Clinically, OCT imaging shows that PCV lesions are located between the retinal pigment epithelium (RPE) and the hyperreflective line of Bruch membrane, making them a special subtype of type I choroidal neovascularization. Some pathological studies suggest that PCV lesions are located within Bruch membrane, but in fact, PCV lesions are more accurately located beneath the RPE basement membrane. Second, the origin of the branching vascular networks (BVN). Pathological analysis of postmortem eye specimens indicates that BVN originates from choroidal arteries, and after passing through Bruch membrane, they transform into thin-walled capillaries, forming type I choroidal neovascularization. A few studies suggest that PCV may result from dilation of choroidal vein, accompanied with vein stasis. Third, VEGF expression in PCV lesions. VEGF is a key pathogenic factor in neovascular AMD. Some studies show increased VEGF expression in PCV lesions, suggesting that PCV may share a similar pathogenic mechanism with neovascular AMD. However, other studies have found negative VEGF expression in PCV lesions, indicating that the mechanism of PCV may not be entirely dependent on VEGF. In conclusion, the pathological features of PCV are complex, showing both similarities to neovascular AMD and characteristics of pachychoroid. With the increasing awareness of eye donation, more valuable eye specimens are expected to be obtained in the future, providing support for further ex;ploration of the pathogenesis of PCV and offering more effective strategies for its clinical diagnosis and treatment.
眼底老化是年龄相关性黄斑变性(age-related macular degeneration, AMD)发生和进展的关键因素及病理基础，在组织病理学上主要表现为脉络膜毛细血管萎缩、布鲁赫膜(Bruch's membrane, BrM)增厚以及视网膜色素上皮(retinal pigment epithelium, RPE)异常。BrM增厚可由多种眼底老化沉积物聚集引起，在AMD的病理机制中具有重要作用。其中，基底薄层沉积物(basal laminar deposit, BLamD)代表了RPE基底膜的弥漫性增厚，通常作为一种正常眼底老化改变。而以酯化和未酯化胆固醇等中性脂质为主的RPE基底膜下沉积物，即基底线性沉积物(basal linear deposits, BLinD)和软性玻璃膜疣，均可参与破坏脉络膜与外层视网膜间物质交换稳态，造成外层视网膜缺血、缺氧及氧化应激，是AMD早期重要病理改变。硬性玻璃膜疣主要分布于周边视网膜，多见于正常老化眼底；表皮玻璃膜疣是RPE基底膜局灶性结节状增厚的结果，眼底表现与硬性玻璃膜疣相似，但其主要分布于后极部，数量更多且密度更高。近年来逐渐加深了对视网膜下玻璃膜疣样沉积物(subretinal drusenoid deposit, SDD)的认识和研究，其是位于RPE上方的沉积物，在AMD发病机制中亦具有深刻意义。文章就几种眼底老化相关沉积物(包括硬性玻璃膜及表皮玻璃膜疣)的病理特征和多模态影像学表现进行综述，旨在帮助认识和理解这些沉积物的眼底表现、病理特征和形成机制，以及在AMD发生及进展中的临床意义。
Fundus aging is a key factor and pathological basis for the development and progression of age-related macular degeneration (AMD), which is histopathologically characterized by choroidal capillary atrophy, Bruch’s membrane (BrM) thickening, and abnormalities of retinal pigment epithelium (RPE). BrM thickening can be induced by the aggregation of age-related fundus deposits and plays an essential role in the pathogenesis of AMD. Basal laminar deposits (BLamD) represent diffuse thickening of the basement membrane of RPE, usually considered to be a normal fundus aging. Basal linear deposits (BLinD) and soft drusen, mainly composed of neutral lipids such as esterified and unesterified cholesterol, can disrupt the homeostasis of material exchange between the choroid and the outer retina, resulting in ischemia, hypoxia, and oxidative stress in the outer retina, which are important pathological changes in the early AMD. Hard drusen is mainly distributed in the peripheral retina and is very common in aging fundus; Cuticular drusen are resulted from focal nodular thickening of the basement membrane of RPE, with similar appearance as hard drusen, but mainly distributed in the posterior pole and more numerous and denser. Recently, our understanding of subretinal drusenoid deposits (SDD), deposits above the RPE, has been gradually deepened and it also has profound significance in the pathogenesis of AMD. In this review, we presented the pathologic features and multimodal imaging of age-related fundus deposits (including hard drusen and cuticular drusen), aiming to help recognize and understand the manifestations, pathologic features, and formation mechanisms of these deposits, as well as their clinical significance in the development and progression of AMD.
病理性近视相对高度近视而言，更强调眼底并发症的存在。后巩膜葡萄肿(posterior staphyloma，PS)被认为是病理性近视的标志性特征，是眼球后巩膜壁的局部扩张，通常认为与巩膜变薄和脉络膜萎缩等因素相关。近年来研究认为P S的形成可能与局部炎症、Bruch膜缺失等因素密切相关。伴随OCT等检查技术的快速革新以及P S治疗手段的探索，诊断和治疗更加完善。
Pathological myopia emphasizes the existence of fundus complications. Posterior staphyloma, considered as a hallmark of pathological myopia, is a partial extension of the posterior scleral wall, which is believed to be related to the scleral thinning and choroidal atrophy. In recent years, studies have indicated that the formation of posterior staphyloma may closely connected with localized inflammation and defects of Bruch’s membrane.With the rapid innovation of examination technologies such as optical coherence tomography (OCT) and the exploration of treatment for posterior staphyloma. The diagnosis and therapy will be more comprehensive in the future.
目的：分析发生于眶骨的占位性病变的CT表现及其与组织病理学之间的关系。方法：回顾性收集15例经临床表现、影像学特征、病理证实为发生于眶骨占位病变患者的临床资料，分析其CT检查、组织病理学切片及其他临床表现。结果：在15例患者中，经病理诊断为骨瘤的患者有4例，骨内血管瘤3例，骨样骨瘤和骨化性纤维瘤各2例，嗜酸性肉芽肿3例，尤文肉瘤1例。骨瘤由成熟板层骨构成，对应在CT上呈现为高密度的骨样结节状隆起；骨内血管瘤病理主要表现为骨小梁间的畸形血管，在CT上表现为典型的“栅栏状”“蜂窝状”特征；骨样骨瘤以骨样组织和结缔组织为主，在CT上为类圆形的高密度影，中央为典型的低密度“瘤巢“影，外周为增生的骨密度影；骨化性纤维瘤由增生的纤维组织及骨样组织构成，CT表现为肿瘤表面常有骨壳包绕，病变多呈圆形或椭圆形；嗜酸性肉芽肿主要由大量朗格汉斯细胞组成，对应CT上的软组织肿块影，可伴溶骨性破坏；尤文肉瘤以低分化的小圆细胞为主，CT表现为虫蚀样骨质破坏，破坏的骨组织间有软组织病变。结论：发生于眶骨的各类病变有其特有的病理组成，不同的病理组成在CT上表现出相应的影像特征。
Objective: To analyze computed tomography (CT) manifestations of space-occupying lesions of the orbital bone and their relationship with histopathology. Methods: The clinical data of 15 patients with orbital bone occupying lesions confirmed by clinical manifestations , imaging features and pathological symptoms features were retrospectively collected, and their CT examination, histopathological sections and other clinical manifestations were analyzed. Results: Among the 15 patients, 4 cases were pathologically diagnosed with osteoma, 3 cases of intraosseous hemangioma, 2 cases of osteoid osteoma and 2 cases of ossifying fibroma, 3 cases of eosinophilic granuloma and 1 case of Ewing’s sarcoma. Osteoma was composed of mature lamellar bones, which corresponded to a high-density osteoid nodular protuberance on CT. The pathological features of intraosseous hemangioma were mainly malformed blood vessels between bone trabeculae and typical “fence” and “honeycomb” features on CT. Osteoid osteoma was mainly composed of bone-like tissue and connective tissue, mainly showing round high-density shadow, typical low-density “tumor nest” shadow in the center, and hypertrophic bone density shadow in the periphery. Ossifying fibroma was composed of proliferative fibrous tissue and bone-like tissue. CT showed that the surface of the tumor was often surrounded by bone shell, and the lesions were mostly round or oval. Eosinophilic granuloma was mainly composed of a large number of Langerhans cells, which corresponded to the soft tissue mass on CT and could be accompanied by osteolytic destruction. Ewing’s sarcoma was mainly composed of poorly differentiated small round cells, and CT manifestations were worm-eaten bone destruction with soft tissue lesions between destroyed bone tissues. Conclusion: Various lesions occurring in the orbital bone have their own special pathological composition. Different pathological components show corresponding imaging features on CT.
目的：探讨眼部转移性透明细胞肾细胞癌(clear-cell renal cell carcinoma，CC-RCC)的临床病理特点。方法：选取复旦大学附属眼耳鼻喉科医院2010年1月至2020年12月收治的5例并经病理学检查证实的眼部转移性CC-RCC患者的临床病理资料，包括病史、临床表现、影像学检查、病理形态学特点、免疫表型及随访结果等，并进行回顾分析。结果：5例患者中3例为脉络膜转移性CC-RCC，均为男性，年龄51~62岁，均表现为右眼前黑影伴视力下降，病程为1~6个月，术前检查视力均为眼前手动，眼底见视网膜下隆起肿块伴视网膜脱离。B超显示球内隆起肿物，中等回声，考虑脉络膜黑色素瘤。其中例2在2年前有左侧肾CC-RCC切除病史，术后1年转移至肺。3例患者均行眼球摘除加义眼座植入术。病理学形态及免疫组织化学染色结果提示为球内恶性肿瘤，考虑转移性CC-RCC，建议在肾等处寻找原发灶。术后例1腹部CT检查发现左肾占位，考虑肾癌。胸部CT检查示两下肺多个转移瘤。例3术后PET-CT发现左肾占位，手术切除后证实为左肾CC-RCC。2例为眼眶转移性CC-RCC，例4为女性，56岁，右眼红肿伴眼球突出2个月，2个月前行右肾CC-RCC切除术，PEC-CT提示右侧眼眶转移伴骨质破坏。例5为男性，65岁，左眼眉弓处肿物3年，7年前行左肾癌摘除术，后肺部转移。所有5例患者手术切除标本病理学检查均示肿瘤细胞细胞质透明或颗粒状，呈实性片状和腺样分布，间质血管丰富，免疫组织化学表达CK、VIM、CD10和PAX-8等标记提示CC-RCC转移。结论：CC-RCC可以转移至脉络膜或眼眶，病理学上需要和其他眼部具有透明细胞特征的原发和转移性肿瘤相鉴别。
Objective: To evaluate the clinicopathological features of ocular metastatic clear-cell renal cell carcinoma.Methods: Data of 5 patients (5 eyes) with ocular metastatic clear-cell renal cell carcinoma treated and diagnosed at Eye & ENT Hospital of Fudan University from January 2010 to December 2020 were retrospectively analyzed for medical history, clinical features, imaging examinations, pathomorphological features, immunophenotypes and survival outcomes. Results: There were 3 males of choroidal metastatic clear-cell renal cell carcinoma with age from 51 to 62 years old. They all presented with shadow before the eye and reduced visual acuity of the right eye for 1 to 6 months. On examination the visual acuity was hand movement in front of the affected eye. Fundus examination showed a subretinal elevated mass with retinal detachment. B-scan ultrasound demonstrated an intraocular mass with medium internal reflectivity suspected of choroidal melanoma. Case 2 reported a history of clear-cell renal cell carcinoma treated with a left nephrectomy 2 years ago and developed lung metastasis 1 year ago. Three patients all underwent enucleation and prosthesis implantation. Histopathological and immunohistochemical examinations showed intraocular malignant tumor suggestive of clear-cell renal cell carcinoma which needed further examinations to confirm the primary tumor. Postoperative computed tomography scan of the abdomen for case 1 revealed a mass of the left kidney highly suggestive of a renal cell carcinoma. The computed tomography scan of the chest revealed multiple lesions suggestive of lung metastasis. Postoperative PET-CT scan of case 3 revealed a mass of the left kidney which was confirmed to be clear-cell renal cell carcinoma histopathologically. There were 2 patients of orbital metastatic clear-cell renal cell carcinoma. One 56-year-old female patient (Case 4) presented with swelling, redness and proptosis of the right eye for 2 months. Two months ago, her right kidney was resected for the diagnosis of clear-cell renal cell carcinoma. PEC-CT revealed metastasis to the right orbit with bone destruction. Another 65-year-old male patient (Case 5) presented with palpable mass of the left eyebrow for 3 years. He had left nephrectomy for renal cell carcinoma 7 years earlier and metastasis to the lung later. Histopathology of all 5 cases demonstrated uniform cells with clear or granular cytoplasm in solid and glandular arrangement surrounded by a rich vascular network. Immunohistochemical positivity for the biomarkers CK, Vimentin, CD10 and PAX-8 confirmed the diagnosis of metastatic clear-cell renal cell carcinoma.Conclusion: Clear-cell renal cell carcinoma can metastasize to the choroid or orbit. It should be differentiated from the other ocular primary and metastatic tumors with clear-cell appearance histopathologically.
目的：探讨眼眶黏膜相关淋巴组织(mucosa-associated lymphoid tissue，MALT)结外边缘区B细胞淋巴瘤的临床表现、影像学特征及病理学特点，以期减少眼眶淋巴瘤的误诊，提高生存率。方法：对2020年1月至2020年12月中山大学中山眼科中心诊治的71例眼眶MALT结外边缘区B细胞淋巴瘤的临床、影像及病理学资料进行回顾性分析。结果：71例患者中，男38例，女33例；左侧眼眶31例，右侧眼眶34例，双侧眼眶6例；原发病例67例，复发病例4例；年龄23~84岁，病程为3个月~15年。最常见的临床表现是眼部肿块和不同程度的眼球活动受限；磁共振成像(magnetic resonance imaging，MRI)检查见密度均匀的软组织影，呈“铸造样”，眼球内未见侵犯；组织病理检查可见肿瘤由小至中等大小淋巴样细胞组成，瘤细胞呈弥漫或片状生长，核小到中等、不规则，核仁不明显，部分细胞呈单核样淋巴瘤细胞改变，其中9例可见浆细胞样分化，伴浆细胞分化的病例kappa与lambda的表达不对称。结论：眼眶MALT结外边缘区B细胞淋巴瘤有多种临床表现，影像学检查具有一定的特征，可辅助术前诊断。病理学检查可用于术后的准确诊断及分型，据此制定合适的治疗方案，提高疗效。
Objective: To investigate the clinical, imaging and pathological features of orbital extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT), so as to reduce misdiagnosis and improve survival rate.Methods: The clinical, imaging and histopathological data of 71 patients with orbital extranodal marginal zone B cell lymphoma of MALT who were treated in Zhongshan Ophthalmic Center, Sun Yat-sen University from Jan.2020 to Dec. 2020 were retrospectively analyzed. Results: There were 38 males and 33 females in the 71 patients.There were 31 cases located on the left orbit, 34 cases on the right orbit, and 6 cases were bilateral; there were 67 primary cases and 4 relapsed cases. The age ranged from 23 to 84 years old. The disease course ranged from 3 months to 15 years. The main clinical manifestations included ocular masses and limited eyeball movement.Magnetic resonance imaging showed a “cast-like” soft tissue shadow of uniform density, and no intraocular invasion is observed. Histopathological examination showed that the tumor was composed of small to medium sized lymphocyte-like cells. Tumor cells exhibited diffuse or lamellar growth, with small to medium-sized irregular nuclei, and the nucleoli were inconspicuous. Some of the lymphocyte-like cells showed mononuclear lymphoma cells changes, and plasmacytoid differentiation was observed in 9 cases, in which kappa and lambda expressions were asymmetric.Conclusion: The clinical manifestations of orbital extranodal marginal zone B cell lymphoma of MALT are various, and imaging examination has certain characteristics, which can assist preoperative diagnosis.Pathological examination can be used for accurate diagnosis and classification after operation, based on which appropriate treatment plan can be made and curative effect can be improved.
近年来日益强大的眼内液分子/细胞生物学检测技术因其简便、快捷和高效的特点，使得眼科医生在诊断眼内淋巴瘤时倾向于单纯只依据此类方法而淡化病理诊断的重要性。眼内液分子/细胞生物学技术因其本身只能“间接提示肿瘤细胞存在”的局限性而不能作为眼内淋巴瘤的确诊依据。眼内组织/细胞病理仍然是眼内淋巴瘤诊断的金标准，其价值和地位不能被其他任何分子/细胞生物学检测手段所替代。理解并掌握各种诊断、检测技术的优势和局限性，规范和优化眼内组织/细胞病理标本的采集、保存和送检流程有助于提高眼科临床医生对眼内淋巴瘤的诊断效率和医疗质量。
In recent years, more and more powerful molecular/cellular biological techniques of intraocular fluid have made ophthalmologists tend to only rely on these methods in the diagnosis of intraocular lymphoma because of their features of simplicity, fastness and efficiency. The molecular/cellular biological techniques of intraocular fluid cannot be used as the basis for the diagnosis of intraocular lymphoma because it can only indicate the existence of tumor cells indirectly. Intraocular tissue/cell pathology remains the gold standard for the diagnosis of intraocular lymphoma, and its importance cannot be replaced by any other molecular/cell biological methods. Understanding and mastering the advantages and limitations of various diagnostic techniques, standardizing and optimizing the collection, preservation and submission process of intraocular tissue/cell specimens will help ophthalmologists improve the diagnostic efficiency and medical quality of intraocular lymphoma.
眼附属器淋巴组织增生性疾病作为一类疾病的总称，包括了良性淋巴组织增生、非典型性淋巴组织增生、IgG4相关眼病以及多种恶性淋巴瘤在内的数十种疾病类型。临床诊断此类疾病应将患者眼部体征、影像学检查与病理学检查紧密结合。随着免疫表型及分子病理等检测技术的进步，此类疾病之间的鉴别诊断正逐渐清晰。本文就眼附属器淋巴组织增生性疾病进行系统性描述，并重点探讨该类疾病的病理鉴别诊断。
Ocular adnexal lymphoproliferative disease, as a general term, contains reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, IgG4 related ocular disease and malignant lymphoma. The clinical diagnosis of this kind of disease should integrate patient’s symptoms, imaging features and pathology characteristics. Development of immunophenotyping, molecular pathology and other detection technology will help with the differential diagnosis of ocular adnexal lymphoproliferative disease. This article is going to discuss the etiology, epidemiology,diagnosis and treatment of ocular adnexal lymphoproliferative disease, with a focus on the clinicopathological differential diagnosis of such disease.
白内障是世界范围内失明的主要原因。正常晶状体是富有弹性的形似双凸透镜的透明体，是机体内蛋白质含量最高的组织，由晶状体囊膜、晶状体上皮细胞、晶状体纤维和悬韧带构成。白内障为晶状体透明度下降，表现为晶状体混浊。近年来随着分子生物学、表观遗传学、免疫学、有机化学等学科快速发展，国内外学者对白内障也进行了大量分子水平的研究，探讨了白内障发生发展相关分子机制，为未来基因治疗和靶向药物等治疗白内障提供了理论基础。对白内障分子病理改变的了解，是白内障精准诊治的基础。
Cataract is the main cause of blindness worldwide. The normal crystalline lens is a transparent biconvex disc,with highest protein content in all human tissues. The lens is composed of capsule, lens epithelial cells, lens fiber and zonular ligment. Cataract is a decrease in the transparency of the lens, which is characterized by opacity. In recent years, with the rapid development of molecular biology, epigenetics, immunology and organic chemistry,researchers have conducted a large number of studies on the molecular basis of genetic or targeted therapy of cataract. It is important to know the molecular pathology of cataract, which is the basis of precise diagnosis and treatment of cataract.
