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基于光学相干断层成像的剥脱综合征和剥脱性青光眼眼底病变研究进展

阅读量：5054
DOI：10.12419/24010801
发布日期：2024-01-28
作者：
张荣沛 #,陈荣新 #,黄丹平
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关键词

剥脱综合征
剥脱性青光眼
光学相干断层扫描
光学相干断层扫描血管成像
眼底病变

摘要

剥脱综合征(exfoliation syndrome,XFS)以眼内异常纤维样物质沉积为特征，临床典型表现为裂隙灯下瞳孔缘和(或)晶状体前囊膜存在灰白色粉末状的剥脱物(exfoliation material,XFM)。XFM可阻塞小梁网引起剥脱性青光眼(exfoliaiton glaucoma,XFG)，并可通过房水循环进入血液，引起血管性损害。眼底病变视力损伤通常不可逆，XFM可进入眼底微血管及毛细血管，引起眼底结构和血管异常。基于光学相干断层成像技术的光学相干断层扫描(optical coherence tomography,OCT)及光学相干断层扫描血管成像(optical coherence tomography angiography,OCTA)以实时、非侵入性、高分辨率等优势，已广泛应用于眼底组织结构及血管病变检查。文章对XFS眼底病变在OCT和OCTA上的表现进行综述。

全文

剥脱综合征(exfoliation syndrome,XFS)最早发现于1917年[1]，主要表现为裂隙灯下可见瞳孔缘和晶状体前表面细小、粉末状的灰白色剥脱物质(pseudoexfoliation material,XFM)。XFS是基因和环境共同作用的疾病，赖氨酰氧化酶样1(lysyl oxidase-like 1, LOXL1)是XFS的主要致病基因[2]。XFS患病率在不同地区和不同民族中存在差异[3]，研究表明XFS存在典型高发区，如希腊[3]、冰岛[4]和我国新疆维吾尔自治区[5]。XFS是年龄相关性疾病[2]，据统计，世界范围内60岁以上人群中30%患有XFS[6]。当前研究认为，XFM可由角膜内皮细胞、晶状体上皮细胞和小梁网细胞等多种组织细胞产生[7]。释放入眼内的XFM一方面破坏血房水屏障增加白内障发病风险[5]，另一方面沉积在房角阻碍房水流出导致剥脱性青光眼(exfoliation glaucoma,XFG)[8]。值得注意的是，XFM十分细小，早期XFS仅在电镜下才能观察到[9]，XFS患者可能存在临床难以察觉的潜在病变。XFM可随房水循环进入血液循环，从而进入眼外组织。结膜、心血管等均可发现XFM的存在[6]。
进入血管的XFM不仅可引起外周血炎性指标升高[10]，沉积在眼内细小血管的XFM容易引起眼底供血不足，进而损害黄斑、视盘及周边视网膜。组织病理学研究发现，XFS患者CRA和睫状后短动脉存在XFM沉积[9]，彩色多普勒成像(color Doppler imaging,CDI)[11]也表明XFS患者视网膜中央动脉(central retinal artery,CRA)和睫状后短动脉出现灌注不足。视网膜血流计测量结果显示，眼前段未观察到XFM的单眼XFS对侧眼眼底同样存在灌注不足[12]。XFS眼底病变还包括发展成为XFG后的青光眼视神经损害。据统计，约40%的XFS最终进展成为XFG[8]，造成永久性视力损伤和不可逆性眼底病变。XFS眼底病变以不易发觉、不可逆等特点，越来越受到关注。光学相干断层成像技术可获得实时的活体二维及三维图像，广泛应用于眼科的光学相干断层扫描(optical coherence tomography,OCT)及光学相干断层扫描血管成像(optical coherence tomography angiography,OCTA)分别着重显示组织结构和血管病变。本文拟对XFS眼底病变，包括XFS和XFG在OCT和OCTA上的表现做一综述。

1 XFS和XFG黄斑区的结构及血管异常

黄斑区由CRA发出视网膜颞侧上、下小动脉供血，其中黄斑中心凹通常由脉络膜毛细血管层供血，中心凹周围的毛细血管弓共同形成无血管区(foveal avascular area,FAZ)。黄斑区正常结构对良好的中心视力十分关键，现广域OCT可扫描到黄斑周围24 mm范围内的图像，OCTA可扫描到黄斑区24 mm×20 mm的范围。目前黄斑区OCTA微小病变扫描多采用8 mm以内的扫描范围。

1.1 黄斑区视网膜神经节细胞是XFS主要病变部位

研究表明，单眼XFS患者的患眼和对侧眼黄斑中心凹下视网膜厚度分别为(243.1±5.3)μm和(249.3±4.8)μm，与健康眼的(249.9±5.4)μm相比差异无统计学意义；而单眼XFS患眼和对侧眼的黄斑中心凹下脉络膜厚度分别为(301.1±9.8)μm和(308.0±10.4)μm，均较正常眼(323.0±10.7)μm变薄，但仅单眼XFS患眼的黄斑中心凹下脉络膜厚度与正常眼之间比较差异有统计学意义[13]。另有研究显示，单眼XFG患者的患眼和对侧眼黄斑中心凹处的脉络膜厚度分别为(201.8±71.3)μm和(216.7±79.1)μm，较正常眼(232.9±50.2)μm变薄，且单眼XFG患者的患眼中心凹处脉络膜厚度较对侧眼和正常眼显著变薄，而单眼XFG患者对侧眼的中心凹处脉络膜厚度与正常眼相比差异无统计学意义[14]。以上提示，单眼PXS和单眼PXG患者的双眼可能处于PXS进展的不同阶段，即使单眼XFS和单眼XFG患者的对侧眼也存在黄斑区脉络膜厚度变薄。另有研究测量了年龄、性别和眼轴相匹配的XFG、XFS和正常眼的黄斑区中心凹处脉络膜厚度，分别为(182.5±56.4)μm、(198.6±62.1)μm和(223.3±54.2)μm，XFS眼和XFG眼均较正常眼变薄，XFG眼较XFS眼更薄[15]。该研究中，仅XFG眼黄斑中心凹处脉络膜厚度变薄与正常眼相比差异存在统计学意义，XFS眼并未出现之前研究[13]差异的统计学意义。近来研究者测量结果显示，XFG、XFS和对照组的中心凹下脉络膜厚度分别为(238.7±12.2)μm、(267.2±12.4)μm和(270.1±16.7)μm，虽然呈现厚度XFG＜XFS＜对照组(Control)的趋势，其差异并无统计学意义[16]。脉络膜厚度存在昼夜波动，且部分研究XFS的黄斑区脉络膜厚度变薄差异并无统计学意义，故黄斑区脉络膜厚度尚不能成为评估XFS眼底病变的临床可靠指标。
黄斑区中心凹视网膜主要包括感光细胞核层，有研究对黄斑区中心凹附近的视网膜各层厚度进行了测量。部分OCT的神经节细胞复合体(ganglion cell complex, GCC)分析模式包含视网膜内丛状层(inner plexiform layer, IPL)、神经节细胞层(ganglion cell layer,GCL)和视网膜神经纤维层(retinal nerve fiber layer,RNFL)，分别对应视网膜神经节细胞(retinal ganglion cell,RGC)的树突、胞体和轴突。RGC具有将信号输出到视神经，产生动作电位的独有功能，大约50%的RGC分布在黄斑区[17]。Lim等[17]的研究表明，单眼XFS患者患眼眼压(17.2±2.8) mmHg，对侧眼眼压(16.8±2.2) mmHg，虽在正常范围，但显著高于健康对照组(14.5±2.3) mmHg。该研究还发现，单眼XFS患者的患眼和对侧眼GCC厚度分别为(86.2±6.4)μm和(87.5±6.9)μm，与对照组(93.5±6.0)μm相比出现显著变薄。XFS与青光眼密切相关，Beni等[18]进一步测量了XFG的黄斑区GCC平均厚度为(80.2±14.9)μm，较健康对照组(101.7±6.0)μm显著变薄；且该研究发现中晚期XFG的黄斑区GCC平均厚度较早期XFG显著变薄。另有研究发现XFS的黄斑区GCC厚度与眼动脉阻力指数呈显著负相关[19]，体现XFS黄斑区结构异常与血流异常的相关性。XFS是年龄相关性疾病，有研究通过OCT的GCL+IPL厚度分析模式，发现XFS引起的XFG黄斑区GCL+IPL厚度随年龄增长显著下降，且XFG黄斑区GCL+IPL厚度下降速度较原发性开角型青光眼(primary open-angle glaucoma, POAG)更快[20]。黄斑区GCL+IPL厚度在诊断青光眼中的作用越来越得到重视[21]，黄斑区GCC厚度在诊断早期青光眼中同视盘区RNFL厚度均呈现较高的灵敏度和特异度[22]。因此，黄斑区GCC相关指标在评估PXS青光眼相关眼底病变中具有良好的临床应用前景。

1.2 黄斑区血流密度的变化有助于监测青光眼病变

OCTA可根据眼底解剖结构和血管网分布，定量评估不同层面的血管异常。视网膜主要分为包含GCL和IPL浅层的浅层毛细血管网(superficial capillary plexus,SCP)或浅层血管复合体(superficial vascular complex, SVC)，包含内核层的深层毛细血管网(deep capillary plexus,DCP)或深层血管复合体(deep vascular complex, DVC)，以及无血管分布的外核层以外的外层视网膜。此外，OCTA可单独分析脉络膜中的毛细血管层。青光眼的发病机制是视网膜RGC的不可逆损害[23]，黄斑区是RGC高度集中的区域[24]。黄斑区RGC对应OCTA分层下的SCP或SVC，研究表明青光眼黄斑区SVC的血管密度(vessel density,VD)呈进展性下降[25]，黄斑区SVC的VD下降与青光眼患者视野缺损进展密切相关[26]。研究发现视盘区RNFL厚度和视盘周围VD尚无异常的XFS眼，其黄斑区SCP的VD为(45.4±5.8)%，较视力、年龄和性别相匹配的健康眼黄斑区SCP的VD(48.3±5.8)%显著下降[27]。另有研究发现，XFG黄斑区SVC的VD较青光眼病情程度相匹配的POAG显著降低[28]。如前所述，黄斑区GCC相关指标有助于评估PXS青光眼相关眼底改变，该研究还发现XFS的黄斑区SCP的VD变化与GCL+IPL厚度呈显著正相关[27]，从而将结构与血流变化相结合。目前认为，XFS的眼底结构变化是由于XFM沉积在眼底血管内影响血流所致，故XFS的眼底血管异常可能发生在结构异常之前。研究显示[13]，XFS眼的黄斑区视网膜厚度无异常时，黄斑区SCP的VD即显著下降。以上研究表明，黄斑区SCP的VD有望成为评估XFS青光眼相关改变的可靠指标。
先前CDI已发现XFG眼动脉血流速度较XFS显著降低[11]，说明XFG的眼底血管损害可能较XFS更重。有研究纳入经药物控制眼压在正常范围的XFG和POAG，发现XFG无论黄斑SCP的VD还是DCP的VD均较POAG显著下降[29]。另有研究纳入视野损害程度相匹配的POAG和XFG，同样发现XFG黄斑区SCP的VD和DCP的VD均较POAG显著下降[30]。视野检查是青光眼诊断的金标准之一，其结果作为青光眼的病情分级依据。另有研究显示，XFG黄斑区SCP的VD下降无论在青光眼早期还是中晚期，均与视野病变进展呈现出一致的趋势[24]，体现出黄斑区SCP的VD作为XFG病情评估指标的潜力。关于XFG的脉络膜VD报道很少，现有XFG脉络膜血管直径和脉络膜血管指数(choroidal vascularity index,CVI)反映黄斑区脉络膜血流异常。Sarrafpour等[31]报道了单眼XFG患眼脉络膜血管平均直径为45.7 μm，较对侧眼58.6 μm显著变细。Simsek等[32]测得单眼XFG患眼和对侧眼黄斑区平均CVI分别为(62.2±2.3)%和(67.5±2.4)%，较对照组(69.3±2.5)%显著下降，且患眼CVI较对侧眼显著降低。

2 XFS和XFG视盘区的结构及血管异常

如前所述，RGC对于视觉传导至关重要。视盘是RGC轴突纤维汇聚穿出筛板与视神经连接，并向视觉中枢传递的结构，眼动脉的重要分支视网膜中央动脉(central retinal artery,CRA)和视网膜中央静脉(central retinal vein,CRV)，由视盘进入眼内。视盘处无感光细胞，为生理盲点，其功能结构决定了眼睛可见的空间范围。青光眼视野这一主观指标动态变化，与视盘区组织结构的病变具有一定程度的对应关系。OCT和OCTA最大可扫描视盘区直径6 mm的区域。

2.1 XFS视盘区出现青光眼相关结构改变

视盘区RGC分布较少，但为RGC轴突纤维汇聚之处。RGC轴突纤维对应RNFL，其厚度的测定对反映视神经受损程度具有良好价值，与黄斑区GCC厚度同为青光眼的OCT评估指标[20]。临床上通常将眼底检查视盘区形态正常、视野无异常缺损以及视盘RNFL无异常变薄判定为无青光眼相关视神经病变。XFG的血管损害机制提示，即使是无青光眼相关视神经病变的XFS患者也很可能因为血管中XFM的累积引起视神经血供不足，从而造成视盘区组织结构的异常。研究表明，单眼XFS患者的患眼和对侧眼视盘区RNFL平均厚度分别为(93.4±10.4)μm和(94.2±9.3)μm，均较对照组视盘区RNFL平均厚度(96.3±12.2)μm变薄，但仅单眼XFS患眼的视盘区RNFL平均厚度与对照组比较差异有统计学意义[17]。单眼XFG患者的患眼及对侧眼视盘RNFL平均厚度分别为(97.1±18.6)μm和(120.0±23.0)μm，均较正常眼(122.1±22.4)μm变薄，但仅单眼XFG患眼视盘RNFL平均厚度与正常眼之间比较差异存在统计学意义[33]。研究表明，单眼XFS的患眼和对侧眼的视盘区RNFL平均厚度之间比较差异无统计学意义[17]，而单眼XFG患眼和对侧眼之间视盘区RNFL平均厚度之间比较差异存在统计学意义[33]。以上研究结果表明，单眼XFS和XFG患者存在双眼视盘区RNFL厚度异常，且单眼XFS和XFG患者的双眼可能处于XFS的不同病变阶段。
视盘区脉络膜与内1/3巩膜形成筛板(laminacribrosa,LC)，包绕RGC和CRA，LC损伤可阻碍RGC轴浆运输和减少CRA血流[34]，从而损害视神经。青光眼的特征之一是筛板损伤，主要机制为高眼压对筛板的压迫[35]以及筛板细胞外基质(extracellular matrix,ECM)重塑[34]。OCT可通过测量LC厚度和LC弯曲指数显示青光眼的筛板损害。研究表明，POAG的LC厚度为(225.3±27.4)μm，较正常眼的LC厚度(248.5±26.8)μm显著变薄，且POAG的LC厚度变薄与视盘区RNFL厚度变薄呈显著正相关[36]。此外，POAG的LC弯曲指数为11.0±2.6，较正常眼的LC弯曲指数6.8±1.4显著变薄，且LC弯曲指数对青光眼诊断的受试者操作特征(receiver operating characteristic,ROC)曲线下面积(area under the curve,AUC)为0.9。XFG具有眼压高及眼压波动范围大的特点[37]，且XFS的重要致病基因LOXL1与ECM重塑和纤维化有关[38]，从而引起XFS和XFG的LC相关异常。研究表明XFG眼和XFS眼LC厚度分别为(151.1±51.2)μm和(158.8±49.6)μm，均较对照组的LC厚度(181.0±39.1)μm显著变薄，但XFG眼和XFS眼的LC厚度比较差异无统计学意义[39]。该研究发现，仅XFG的LC厚度变薄与视盘区RNFL厚度变薄呈显著正相关，XFS的LC厚度与视盘区RNFL厚度无显著相关性[39]。另有研究[37]纳入的XFG和POAG视盘区RNFL厚度比较差异无统计学意义，而XFG视盘区LC弯曲指数为8.8±2.9，较POAG视盘区的LC弯曲指数6.6±1.9显著增加。视盘区生物力学指标可体现青光眼LC的ECM重塑，研究表明XFG，POAG和正常眼的眶脂肪到巩膜-脉络膜-视网膜复合体的应变比率(the strain ratios of orbital fat to scleral-choroidal-retinal complex,ROFSCR)分别为2.6±1.1、4.0±1.7和1.8±0.4，XFG和POAG的ROFSCR均较正常眼显著增加[40]。

2.2 XFS存在视盘区血管的损害

RGC轴突位于视盘区RNFL层，对应OCTA的视盘周围放射状毛细血管(radial peripapillary capillary,RPC)层。研究显示，视盘区RNFL厚度尚无异常的XFS眼，其RPC的VD为(48.4±2.6)%，较年龄和性别相匹配的健康对照组的(50.9±2.6)%显著下降[41]。 此外，单眼XFS患者的患眼和对侧眼，以及正常眼RPC的VD分别为(47.2±3.8)%、(49.9±2.5)%和(50.2±2.3)%；单眼XFS患者的患眼和对侧眼RPC的VD较正常眼下降，单眼XFS的患眼RPC的VD与对侧眼和正常眼相比差异均存在统计学意义[42]。该研究纳入的单眼XFS双眼视盘区RNFL均较正常眼显著变薄[42]，说明XFS进展为XFG之前，可能已经存在眼底视盘区结构和血管的异常。另有研究表明，单眼XFG患者的患眼和对侧眼，以及对照组RPC的VD分别为(48.1±2.0)%、(51.2±2.3)%和(53.4±2.4)%，单眼XFG患者的患眼和对侧眼RPC的VD均较正常眼显著下降；而单眼XFG患者的对侧眼视盘RNFL厚度和视野与正常眼相比尚未见异常[33]。研究表明，70%的单眼PXS患者在12年内进展为双眼[43]，以上说明XFS视盘区血管异常可能先于结构异常出现，且单眼XFS和XFG的对侧眼的眼底病变可能属于XFS眼底病变的早期阶段。对于青光眼病变程度相同的XFG和POAG，早期XFG和早期POAG的RPC层VD均较正常眼显著下降，但早期XFG和早期POAG的RPC层VD之间比较差异无统计学意义[44]；此外，中期XFG和POAG的RPC层VD差异也无统计学意义[45]。值得注意的是，视网膜和脉络膜血流存在日波动[32]，研究表明青光眼病变程度相匹配的XFG和POAG以及对照组，三组内不同时间点的RPC层VD比较差异无统计学意义[45]。以上说RPC层VD可显示XFS不同阶段的视盘区血管异常，但未能像黄斑区SVC层VD显示出XFG和POAG的不同。
XFS存在视盘区脉络膜血流异常。有研究纳入双眼视盘区RNFL厚度尚无异常的单眼XFS，其患眼和对侧眼视盘区CVI分别为(59.5±2.9)%和(61.0±2.9)%，均较对照组(62.0±2.8)%显著下降[46]。另有研究发现，XFG视盘区CVI为(64.1±2.1)%，XFS为(65.2±2.5)%，均较对照组(67.0±1.5)%显著下降，而XFG和XFS的视盘区CVI比较差异无统计学意义[47]。CVI每次测量仅能反映单个切面的脉络膜血流情况，而OCTA可观察特定层面内的三维VD，较CVI测量结果更准确。有研究将视盘脉络膜血管进一步分为视盘边界外宽度0.5 mm的内环区和内环外宽度0.5 mm的外环区；XFS和XFG视盘区内环脉络膜VD分别为(16.1±6.6)%和(14.1±6.7)%，均较正常眼的24.7%显著下降，而XFS和XFG的视盘区内环脉络膜VD比较差异无统计学意义；XFS和XFG视盘区外环脉络膜VD分别为13.2%和11.1%，同样均较正常眼的18.6%显著下降，且XFG视盘区外环脉络膜VD较XFS显著下降[48]。此外，OCTA可通过定量描述青光眼患者的视盘周围脉络膜微血管丢失(peripapillary choroidal microvascular dropout,CMvD)，反映青光眼视盘缺血的严重程度[49]。研究表明早期原发性闭角型青光眼(primary angle-closure glaucoma,PACG)，早期XFG和早期POAG的CMvD分别为7.5%、25.0%和46.3%，三者之间的CMvD差异存在统计学意义，组间两两比较仅早期PACG和POAG的CMvD比较差异存在统计学意义；中晚期PACG，XFG和POAG的CMvD分别为59.1%、68.2%和81.0%，三者之间的CMvD比较差异无统计学意义[49]。

3 XFS与其他眼底病变的关系

XFS可与其他眼底病变同时存在，但目前研究集中于提取XFS相关眼底病变特征，近年来对伴有XFS的眼底病变患者的研究较少。Chiras等[50]总结了干性年龄相关性黄斑变性(age-related macular degeneration, AMD)和XFS的发病机制，认为干性AMD和XFS均与氧化应激有关。Zengin等[51]分析了76例双眼AMD且仅单眼XFS的患者，发现XFS眼中干性AMD比例为88.16%较非XFS眼22.37%更高，而湿性AMD比例11.84%较非XFS眼77.63%更低。但XFS和AMD的因果关系仍需进一步研究。糖尿病引起的糖尿病视网膜病变(diabetic retinopathy,DR)和视网膜静脉阻塞(retinal vein occlusion, RVO)是常见的致盲性视网膜血管病，均与血管阻塞有关。研究表明XFS与糖尿病和RVO有关。一项横断面研究表明糖尿病对XFS的OR值为1.6，说明糖尿病可能是XFS的危险因素[52]。研究表明，XFG对RVO的OR值为3.1，说明XFG可能是RVO的危险因素[53]。RVO根据阻塞位置分为视网膜中央静脉阻塞(central retinal vein occlusion,CRVO)和视网膜分支静脉阻塞(branch retinal vein occlusion,BRVO)。视盘区是CRV进入眼内发出分支的部位，睑板病变、血流受阻均是CRVO常见的致病原因，也是XFS造成眼底损害的机制。一项回顾性研究结果显示，CRVO中XFS的患病率为29.0%，远高于BRVO中XFS患病率8.5%和对照组中XFS患病率8.6%[54]。该研究进一步分析了缺血型CRVO中XFS患病率高达48.0%，远高于非缺血型CRVO中XFS的患病率4.8%，说明XFS很可能是缺血型CRVO发生的危险因素之一。

4 总结与展望

OCT和OCTA均属于眼科无创性影像学检查，具有操作简便、无创等优势，配合OCT和OCTA的后期软件分析、算法自动分析和手动测算，能够对XFS眼底主要结构黄斑区和视盘区进行结构和血管情况的分析。OCT和OCTA对黄斑区和视盘区结构参数及VD的测量可进一步细分不同象限和层面，发现与解剖结构和临床表现相对应的结构和血管变化。目前OCT和OCTA扫描分辨率越来越清晰，扫描范围越来越大，扫描模式越来越精确，近年来描述XFS眼底病变特征的研究越来越多。作为光学检查项目，OCT和OCTA均要求受检者具有良好的屈光介质清晰度，否则获取的图像质量欠佳，影响分析结果的可靠性。
XFS是青光眼的确切病因之一，对于XFS和XFG，黄斑区结构和血管异常主要由XFM在血管中的沉积导致，而视盘区血管异常同时受到XFM在血管中沉积以及XFS改变LC结构的影响。结果表明，XFS即使未确诊青光眼时，眼底已存在青光眼相关眼底结构和血管异常；且XFG的眼底结构和血管异常较XFS更明显。因此，OCT和OCTA，对早期发现XFS的青光眼相关眼底改变，以及XFS和XFG的眼底病变病情随访，均具有重要的临床意义。一方面，对于可观察到XFM的XFS和XFG患者，OCT和OCTA可定量评估XFM异常沉积造成的具体损害及病变程度。其中OCT的黄斑区GCC相关指标和OCTA的黄斑区SCP的VD有助于评估XFS相关青光眼眼底改变。另一方面，即使临床未观察到XFM的单眼XFS和单眼XFG的对侧眼也已出现眼底结构和血管改变。OCT发现单眼XFS和单眼XFG的对侧眼出现视盘区RNFL厚度变薄；OCTA则发现单眼XFS和单眼XFG的对侧眼出现视盘区RPC的VD下降。因此OCT和OCTA有助于定量描述XFS和XFG不同病变阶段的眼底结构和血管特征。需要注意的是，光学相干断层成像的结果与机器的不同算法有关，必要时需手动检验分层[44]。目前OCT和OCTA多种指标都可显示XFS眼底病变(表1)，寻找一种客观性比较强的指标是下一步工作的重点。

表1 目前用于定量评估XFS眼底病变的OCT及OCTA指标
Table 1 Current OCT and OCTA indicators for quantitative assessment of XFS fundus lesion

20240507103712_5124.png
综上所述，XFS是年龄相关性系统性进展性疾病，单眼XFS患者的对侧眼可能处于XFS的早期阶段。XFS患者尚未确诊青光眼时即可出现青光眼相关眼底结构和血管异常。基于光学相干断层成像技术的OCT和OCTA有助于显示XFS的早期结构和血管异常，并可提供XFS向XFG进展的临床依据。

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基金

1、广东省基础与应用基础研究基金项目

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59、Won HJ, Sung KR, Shin JW, et al. Comparison of lamina cribrosa curvature in pseudoexfoliation and primary open-angle glaucoma[ J]. Am J Ophthalmol, 2021, 223: 1-8. DOI: 10.1016/j.ajo.2020.09.028.
60、Wirostko BM, Curtin K, Taylor SC, et al. Risk of atrial fibrillation is increased in patients with exfoliation syndrome: the Utah Project on exfoliation syndrome (UPEXS)[ J]. Acta Ophthalmol, 2022, 100(4): e1002-e1009. DOI: 10.1111/aos.15017.
61、Topcu H, Altan C, Cakmak S, et al. Comparison of the lamina cribrosa parameters in eyes with exfoliation syndrome, exfoliation glaucoma and healthy subjects[ J]. Photodiagnosis Photodyn Ther, 2020, 31: 101832. DOI: 10.1016/j.pdpdt.2020.101832.
62、Incekalan TK, Peköz BÇ. Usability of real-time elastography for the diagnosis of primary open angle and pseudoexfoliation glaucoma[ J]. J Ultrasound Med, 2023, 42(7): 1471-1480. DOI: 10.1002/jum.16157.
63、Hondur G, Ucgul Atilgan C, Hondur AM. Sectorwise analysis of peripapillary vessel density and retinal nerve fiber layer thickness in exfoliation syndrome[ J]. Int Ophthalmol, 2021, 41(11): 3805-3813. DOI: 10.1007/s10792-021-01950-7.
64、Goker YS, Kızıltoprak H. Quantitative analysis of radial peripapillary capillary plexuses in patients with clinically unilateral pseudoexfoliation syndrome[ J]. Graefes Arch Clin Exp Ophthalmol, 2020, 258(6): 1217- 1225. DOI: 10.1007/s00417-020-04643-6.
65、Arnarsson A, Sasaki H, Jonasson F. Twelve-year incidence of exfoliation syndrome in the Reykjavik eye study[ J]. Acta Ophthalmol, 2013, 91(2): 157-162. DOI: 10.1111/j.1755-3768.2011.02334.x.
66、Onur IU, Acar OPA, Cavusoglu E, et al. Vessel density in early-stage primary open angle glaucoma and pseudoexfoliation glaucoma: a comparative controlled optical coherence tomography angiography study[ J]. Arq Bras Of talmol, 2021, 84(4): 352-360. D OI: 10.5935/0004-2749.20210051.
67、Demirtaş AA, Karahan M, Ava S, et al. Evaluation of diurnal fluctuation in parafoveal and peripapillary vascular density using optical coherence tomography angiography in patients with exfoliative glaucoma and primary open-angle glaucoma[ J]. Curr Eye Res, 2021, 46(1): 96-106. DOI: 10.1080/02713683.2020.1784437.
68、Simsek M, Inam O, Sen E, et al. Peripapillary and macular choroidal vascularity index in patients with clinically unilateral pseudoexfoliation syndrome[ J]. Eye, 2021, 35(6): 1712-1720. DOI: 10.1038/s41433- 020-01171-9.
69、Karslioglu MZ, Kesim C, Yucel O, et al. Choroidal vascularity index in pseudoexfoliative glaucoma[ J]. Int Ophthalmol, 2021, 41(12): 4197- 4208. DOI: 10.1007/s10792-021-01990-z.
70、Aghsaei Fard M, Safizadeh M, Shaabani A, et al. Automated evaluation of parapapillary choroidal microvasculature in pseudoexfoliation syndrome and pseudoexfoliation glaucoma[ J]. Am J Ophthalmol, 2021, 224: 178-184. DOI: 10.1016/j.ajo.2020.12.002.
71、Jo YH, Sung KR, Shin JW. Comparison of peripapillary choroidal microvasculature dropout in primary open-angle, primary angle-closure, and pseudoexfoliation glaucoma[ J]. J Glaucoma, 2020, 29(12): 1152-1157. DOI: 10.1097/IJG.0000000000001650.
72、Chiras D, Kitsos G, Petersen MB, et al. Oxidative stress in dry age-related macular degeneration and exfoliation syndrome[J]. Crit Rev Clin Lab Sci, 2015, 52(1): 12-27. DOI: 10.3109/10408363.2014.968703.
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76、 广东省基础与应用基础研究基金项目(2023A1515010306)。
This work was supported by the GuangDong Basic and Applied Basic Research Foundation(2023A1515010306).
77、Karagiannis D, Kontadakis GA, Klados NE, et al. Central retinal vein occlusion and pseudoexfoliation syndrome[ J]. Clin Interv Aging, 2015, 10: 879-883. DOI: 10.2147/CIA.S776.

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