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.
“六要素,三个一”是眼底影像基础阅片工作中进行眼底疾病临床创新性研究的模式要点,即在眼底阅片过程中捕捉到1个异常的病例后,通过积累病例、提炼特征、文献检索、寻同查异,进而扩展到1组病例,最后通过思辨创新,提出或完善1种新的疾病或疾病表征。近二十年来,在此模式的指导下,团队在眼底疾病研究工作中取得了一些原创性的成果:比如息肉状脉络膜血管病变的认识及其在国人新生血管性年龄相关性黄斑变性中发病比例第一,提出点状内层脉络膜病变病灶国际分期和命名新亚型,年龄相关的吲哚菁绿血管造影晚期散在弱荧光点揭示潴留性视网膜色素上皮脱离的发病机制,发现急性黄斑神经视网膜病变是登革热患者视力下降的主要原因,在全球最大的持续性鳞状黄斑病变的病例系列中明确病灶层次等创新性成果。“六要素”框架规范眼底影像研究流程,强调研究过程的严谨性与渐进性,且多次循环后衍生发散出更多研究线索和思路,极大拓展研究深度和广度。“三个一”路径体现了研究的层次性,从个体现象(点)到群体规律(线),最终构建疾病认知的立体网络(面);指导眼底异常影像征象、罕见病、新病种研究,加速疾病谱系完善。以“六要素”为纲,以“三个一”为略,将继续推动眼底疾病临床研究的创新与突破。
The "6 Elements, 3 Ones" constitutes a methodological framework for conducting innovative clinical research of ocular fundus diseases in foundational fundus imaging interpretation. This model emphasizes: 1) identifying a single abnormal case during routine fundus evaluation; 2) systematically expanding this observation into a case series through case accumulation, feature extraction, literature review, and comparative analysis; and 3) ultimately proposing or refining novel disease entities or manifestations through critical thinking and innovation. Over the past two decades, guided by this paradigm, our research team has achieved several original breakthroughs in fundus imaging studies, including: establishing polypoidal choroidal vasculopathy as the predominant subtype of neovascular age-related macular degeneration in Chinese populations; proposing an international staging system and novel subtypes for punctate inner choroidopathy; elucidating the pathogenesis of retentional retinal pigment epithelial detachment through the sign of age-related scattered hypofluorescent spots on late-phase indocyanine green angiography; identifying acute macular neuroretinopathy as the primary cause of vision loss in dengue fever patients; and precisely localizing lesion in the world's largest case series of persistent placoid maculopathy. The "6 Elements" framework standardizes fundus disease research protocols, emphasizing methodological rigor and progressive investigation while generating multiple research trajectories through iterative cycles, thereby expanding both the depth and breadth of scientific inquiry. The "3 Ones" pathway embodies hierarchical research progression - transitioning from individual phenomena (point observations) to population-level patterns (linear correlations), ultimately constructing a multidimensional disease cognition network (planar integration). This approach guides investigations ranging from signs of common disease to rare disorders and novel disease entities, accelerating the refinement of disease taxonomies. By adhering to the "6 Elements" as the structural framework and implementing the "3 Ones" as the strategic pathway, we will continue to advance innovation and achieve breakthroughs in clinical fundus disease researches.
目的:观察急性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)的自然病程中渗漏点的形态及变化。方法:本研究为前瞻性研究,使用光学相干断层扫描(optical coherence tomography,OCT)观察从发病到发病后5~13个月的CSC患者的渗漏点的OCT形态,测量并计算Hall层、脉络膜全层各自厚度及比值,并进行比较。结果:共20例患者[男14例,女6例,年龄33~59(中位数41)岁]纳入研究。随访时间为5~13个月。在19例患者中观察到微小视网膜色素上皮脱离(pigment epithelium detachment,PED)。1例患者可见视网膜色素上皮(retinal pigment epithelium, RPE)小凸起。在随访期间,仅1例患者的PED完全恢复,其他19例患者在视网膜下液被完全吸收时,RPE和Bruch膜之间仍存在微小分离。渗漏点处的Haller层/脉络膜厚度显著高于中央凹处(初诊时0.806±0.08 vs 0.863±0.06,P=0.003;最后1次随访时为0.801±0.07 vs 0.851±0.06,P=0.004)。结论:本研究观察到在急性CSC患者自然病程中,即使视网膜下液吸收,OCT显示渗漏点处仍存在持续的PED,更厚的Haller层及更薄的内层脉络膜,这些发现为CSC的发病机制提供了更多线索。
Objective: To observe the morphology and changes of leakage points in the natural course of acute central serous chorioretinopathy (CSC). Methods: This study was a prospective study, using optical coherence tomography to observe the OCT morphology of leakage points in CSC patients from onset to 5 to 13 months after onset, measuring the thickness and ratio of Hall layer and the whole choroid, and then compare them. Results: A total of 20 patients were included in the study, including 14 males and 6 females, aged from 33 to 59, with the median being 41 years old. The follow-up time ranged from 5 months to 13 months. Minute retinal pigment epithelial detachments (PED) were observed in 19 patients. A small bulge of retinal pigment epithelium (RPE) was observed in 1 patient. During the follow-up, only one patient totally recovered. Small separation between RPE and Bruch membrane still exit even subretinal fluid were absorbed completely in the other 19 patients. The thickness of Haller layer or choroid at the leakage point was significantly higher than that of the fovea (0.806±0.08 vs 0.863±0.06, P=0.003, at the first visit; 0.801±0.07 vs 0.851±0.06, P=0.004, at the last follow-up). Conclusion: This study observed that in the natural course of acute CSC patients, even if the subretinal fluid was absorbed, OCT still showed that there was persistent PED at the leakage point, thicker Haller layer and thinner inner choroid layer. These findings provided more clues to the pathogenesis of CSC.
目的:观察急性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)的自然病程中渗漏点的形态及变化。方法:本研究为前瞻性研究,使用光学相干断层扫描(optical coherence tomography,OCT)观察从发病到发病后5~13个月的CSC患者的渗漏点的OCT形态,测量并计算Hall层、脉络膜全层各自厚度及比值,并进行比较。结果:共20例患者[男14例,女6例,年龄33~59(中位数41)岁]纳入研究。随访时间为5~13个月。在19例患者中观察到微小视网膜色素上皮脱离(pigment epithelium detachment,PED)。1例患者可见视网膜色素上皮(retinal pigment epithelium,RPE)小凸起。在随访期间,仅1例患者的PED完全恢复,其他19例患者在视网膜下液被完全吸收时,RPE和Bruch膜之间仍存在微小分离。渗漏点处的Haller层/脉络膜厚度显著高于中央凹处(初诊时0.806±0.08 vs 0.863±0.06,P=0.003;最后1次随访时为0.801±0.07 vs 0.851±0.06,P=0.004)。结论:本研究观察到在急性CSC患者自然病程中,即使视网膜下液吸收,OCT显示渗漏点处仍存在持续的PED,更厚的Haller层及更薄的内层脉络膜,这些发现为CSC的发病机制提供了更多线索。
Objective: To observe the morphology and changes of leakage points in the natural course of acute central serous chorioretinopathy (CSC). Methods: This study was a prospective study, using optical coherence tomography to observe the OCT morphology of leakage points in CSC patients from onset to 5 to 13 months after onset, measuring the thickness and ratio of Hall layer and the whole choroid, and then compare them. Results: A total of 20 patients were included in the study, including 14 males and 6 females, aged from 33 to 59, with the median being 41 years old. The follow-up time ranged from 5 months to 13 months. Minute retinal pigment epithelial detachments (PED) were observed in 19 patients. A small bulge of retinal pigment epithelium (RPE) was observed in 1 patient. During the follow-up, only one patient totally recovered. Small separation between RPE and Bruch membrane still exit even subretinal fluid were absorbed completely in the other 19 patients. The thickness of Haller layer or choroid at the leakage point was significantly higher than that of the fovea (0.806±0.08 vs 0.863±0.06, P=0.003, at the first visit; 0.801±0.07 vs 0.851±0.06, P=0.004, at the last follow-up). Conclusion: This study observed that in the natural course of acute CSC patients, even if the subretinal fluid was absorbed, OCT still showed that there was persistent PED at the leakage point, thicker Haller layer and thinner inner choroid layer. These findings provided more clues to the pathogenesis of CSC.