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重视全身疾病的眼部表现

Attach importance to ocular manifestations of systemic diseases

来源期刊: 眼科学报 | 2023年5月 第38卷 第5期 365-370 发布时间:2023-05-24 收稿时间:2023/5/24 10:06:22 阅读量:7084
作者:
关键词:
全身系统性疾病视网膜心血管系统性疾病神经系统疾病自身免疫性疾病感染性疾病药物相关的眼病人工智能
systemic disease retina cardiovascular disease neurological disorder autoimmune disease infectious disease drug-related eye disease artificial intelligence
DOI:
10.12419/j.issn.1000-4432.2023.05.01
眼可受全身系统性疾病的累及,通过眼部表现可对心血管系统性疾病、神经系统疾病、自身免疫性疾病、感染性疾病及药物相关眼病等全身疾病进行评估、协助诊断和随访观察。重视全身疾病在眼部的表现,对于眼科及相关专业临床诊疗水平的提升具有重要意义。
Eyes can be affected by systemic diseases. Ocular manifestations can be used to evaluate, help to diagnose and observe systemic diseases including cardiovascular diseases, neurological disorders, autoimmune diseases, infectious diseases and drug-related eye diseases. Paying attention to the manifestations of systemic diseases in the eye is of great significance for the improvement of clinical diagnosis and treatment in ophthalmology and related specialties.
眼是最重要的感觉器官,人体90%的外界信息是通过眼获得的,作为视觉器官,除了发生眼球及其附属器的自身病变之外,还易受全身系统性疾病不同程度的累及;部分情况下,眼部病变也可对全身造成重要影响,甚至危及患者生命。对眼与全身病进行深入探索、重视学科交叉,不仅可以通过这一最重要的感觉器官对潜在全身系统性疾病进行评估、协助诊断和随访观察,还可以提升医务工作者对疾病的认知,更新知识储备,促进眼与全身病整体诊疗质量的提升,推动整合医学体系高质量的发展。重视全身系统性疾病在眼部的表现,在真实世界的诊疗实践中,也有利于加深对眼部和全身健康之间复杂相互作用的理解,有利于早期识别病变、及时转诊和持续监测。本文就常见存在眼部表现的全身疾病进行简单述评。

1 心血管系统疾病

心血管系统疾病通常会导致包括眼球在内的外周器官大血管和小血管的病变,广泛的眼部症状体征与心血管疾病有关。在病理条件下,眼底微血管的变化可能先于系统性血管病变发生或同时发生,眼底微循环可作为观察心血管系统疾病的无创窗口[1]
除了常见的动脉硬化、高血压导致的典型的眼底特征性改变之外,冠状动脉疾病也可表现视网膜动静脉压迹、局灶性动脉狭窄和微动脉瘤,根据视网膜栓塞的大小和位置,冠状动脉疾病等系统性血管疾病的眼部表现可出现从黑蒙到视力丧失的各种症状[2]。成人颈内动脉或椎动脉夹层眼部表现为黑蒙伴或不伴有眼交感神经麻痹[3]。先天性心脏缺陷最常见的眼部表现包括视网膜血管扭曲、视网膜血管扩张和视盘发育不全等[4-5],光学相干断层扫描血流成像(optical coherence tomography angiography,OCTA)定量评估能够揭示先天性心脏病患者视网膜微循环存在灌注不良,并与全身缺氧严重程度相关[6]。未经治疗的感染性心内膜炎患者有眼底Roth斑、视网膜炎、视网膜动脉阻塞等表现,并有内源性眼内炎风险[7]。多发性大动脉炎(Takayasu动脉炎)是主要侵犯大动脉及其分支的进行性慢性炎症性闭塞性疾病,眼部多表现为低灌注性、高血压性或“混合性”视网膜病变[8-9]。巨细胞动脉炎最常见的眼部表现是前部缺血性视神经病变,可导致不逆转的视力丧失[10]。罕见的心脏肿瘤如黏液瘤,会导致继发于视网膜中央或分支动脉闭塞的视力下降[11]。对眼部表现的早期诊断和及时处理,有助对即将发生的不良心血管事件进行早期诊断和管理。

2 神经系统疾病

视网膜及视神经作为中枢神经系统的延续,部分中枢神经系统疾病可存在眼底改变,某些急重症患者可首诊于眼科,需迅速诊断及处理。
多发性硬化是中枢神经系统炎性脱髓鞘疾病,多累及视神经、脊髓和脑干,视神经炎是多发性硬化最常见的眼部表现,可引起眼肌麻痹和眼球震颤等眼球运动障碍,导致复视、视物模糊、立体视丧失和阅读疲劳等症状[12]。中枢神经系统的血管病变也可合并多种眼部症状[13]。颅内动脉瘤根据病灶位置的不同,可出现多组颅神经麻痹及特征性视野缺损。颅内高压患者会出现短暂视物模糊、视盘水肿相关视野缺损或外展神经麻痹导致复视,部分患者主诉闪光感,对于双侧视盘水肿患者必须进行完整的眼科评估及相关科室会诊[14]。出现单侧瞳孔缩小伴头痛的年轻患者,要警惕颈动脉夹层的可能,40%~50%的患者可出现不完全Horner综合征表现,多主诉照镜时发现瞳孔缩小、上睑轻度下垂,需尽快完善CT或磁共振血管造影或成像检查[15]。颈动脉海绵窦瘘和海绵状血管瘤等血管畸形,也会有眼部表现,包括表层巩膜静脉扩张迂曲、突眼、颅神经麻痹等表现,单眼浅层巩膜充血、血管迂曲扩张、长期不消退且无分泌物的“慢性结膜炎”患者,如果眼压偏高,应高度怀疑颈动脉海绵窦瘘的可能[16]。偏头痛也可能以视觉先兆首诊于眼科,可能表现为中心视野亮点、线条或区域性视力丧失[17]。中脑和脑桥部位缺血型脑卒中或创伤性脑损伤会导致包括眼外肌运动障碍,其中动眼神经麻痹的发生率最高[18]。文献报道眼底微血管特征及参数与脑卒中风险相关,可能是脑卒中发作的预测因素[19]。随着人工智能等技术的进展,眼底照相及OCTA技术手段将加深对视网膜和脑微循环的认识,有助于脑血管疾病的筛查及预防。

3 自身免疫性疾病

随着自身免疫性疾病的全球发病率增加,与自身免疫性疾病相关的眼部并发症也有所增加[20]。眼部的表现可由疾病本身或由针对自身免疫疾病的治疗引起。眼部表现可能出现在疾病早期阶段,但也可能发生在疾病活动期或缓解期。
免疫性疾病相关性干眼是最常见的免疫系统疾病并发症,干燥综合征、类风湿关节炎(rheumatoid arthritis,RA)、系统性红斑狼疮、Graves病、慢性移植抗宿主病、黏膜类天疱疮等均可引起泪膜稳定性下降及眼表损伤,以眼表的免疫性损伤及炎症反应为重要特征[21-22]。以干眼症状首诊的患者,应仔细询问病史及全身症状,并进行规范的体格检查,有助于早期发现免疫性疾病,并对潜在疾病进行系统控制。眼部受累是 的关节外并发症之一,也可能作为初始症状,包括巩膜炎、外周溃疡性角膜炎等;幼年类风湿性关节炎和强直性脊柱炎的眼部表现以虹膜炎多见[23]。眼部受累在系统性红斑狼疮中并不罕见,尤其是视网膜或中枢神经系统受累的患者,眼底主要表现为免疫复合物介导的微血管病变,包括微血管病变、血管闭塞、血管炎、Purtscher样视网膜病变等[24]。白塞病是一种多器官累及的慢性、复发性炎性疾病,以复发性口腔溃疡、生殖器溃疡、葡萄膜炎、皮肤损害等为主要临床特征,其中50% ~ 60%累及肠道,称为肠白塞病[25]。白塞病眼部受累的典型形式是复发性双侧葡萄膜炎和视网膜血管炎[26]。克罗恩病患者最常见的是巩膜外层炎,其次是巩膜炎和葡萄膜炎,眼眶肌炎、角膜溃疡、睑缘炎、视网膜血管炎等也有报道。溃疡性结肠炎患者的葡萄膜炎和虹膜炎比克罗恩病更常见,还包括视网膜中央静脉阻塞、血管炎、外周角膜溃疡、角膜浸润、中心性浆液性脉络膜视网膜病变和视网膜脱离、眼眶肌炎等[20]。系统性硬化症有多种不同严重程度的眼部表现,包括眼干燥症、眼睑皮肤僵硬、视网膜血管或微血管病变、脉络膜萎缩或虹膜异常等[27]。甲状腺功能异常可导致眼眶内和眶周软组织炎性反应、眶组织纤维化及脂肪堆积,表现为眼睑退缩、眼球突出、眼外肌功能障碍,严重时导致暴露性角膜炎、压迫性视神经病变等甲状腺相关眼病[28-29]。早期识别自身免疫性疾病及其相关眼部表现的高风险者,可以帮助临床医生更有效地诊断、筛选高危患者和实施治疗。

4 感染性疾病相关眼病

病毒感染可能涉及所有眼部组织,并在短期或长期内影响视力及预后[30]。疱疹病毒引起的眼部感染最为常见,其导致的角膜炎和角膜-葡萄膜炎是西方国家感染性失明的主要原因,单纯疱疹病毒、带状疱疹病毒及巨细胞病毒均可导致视网膜坏死等严重并发症[30]。猴痘病毒感染会导致眼红眼痛,眼周皮损等眼部并发症也有报道[31]。腺病毒及肠道病毒是感染性结膜炎最常见的病因并具有高度传染性[32-33],埃博拉病毒及新型冠状病毒感染等也可能引起结膜炎[34-35]。新型冠状病毒感染患者存在多器官受累,眼部表现并不少见,包括角结膜炎、葡萄膜炎、视神经炎、视网膜血管炎、急性黄斑区神经视网膜病变等,多由新型冠状病毒直接诱发血管炎症或感染诱发原有病变导致;结膜炎有时是新型冠状病毒感染的首发症状,对于早期诊断能够提供帮助,新型冠状病毒疫苗相关眼部并发症也有较多报道[36-38]。除了病毒感染,结核分枝杆菌、梅毒、弓形虫、HIV等病原体感染也经常出现眼部病变。布鲁氏菌病患者眼部受累在流行地区很常见,包括前葡萄膜炎、结膜炎和脉络膜炎等[39]。随着节肢动物传播的传染病在全球范围的传播,包括立克次体病、西尼罗河病毒、登革热、基孔肯雅病、裂谷热和寨卡病毒等,这些病原体可导致一系列眼部并发症,包括前葡萄膜炎、视网膜炎、脉络膜视网膜炎、视网膜血管炎和视神经受累[40]。感染性疾病相关眼病治疗大多需要全身治疗和多学科协作,流行病学病史及眼部对于诊断有帮助,预防感染仍是防控传染性疾病相关眼部并发症的主要手段。

5 药物相关的眼病

不同种类的药物可能引起类似的眼部不良反应,同类药物也可能累及多个眼部结构并导致多种眼部病变。眼部不良反应的严重程度通常与治疗持续时间、剂量和个体患者易感性有关[41]。除了常见的糖皮质激素、羟氯喹等药物相关眼部不良反应,越来越多的药物相关眼部并发症受到关注。
用于治疗心律失常的胺碘酮最常见的眼部症状是光晕和(或)视力下降,常见眼部表现有涡状角膜病变、晶状体浑浊和视神经病变等[42]。西替利嗪等抗组胺药可能导致瞳孔变化、调节能力下降、干燥性角结膜炎和和眼睑痉挛等,还有引起眼周危象的报道[43]。甲磺酸伊马替尼是用于慢性粒细胞白血病和胃肠道间质瘤患者的靶向药物,眼周不良反应包括眶周水肿和溢泪[44]。异维A酸药物能够在视网膜的结合位点与视黄酸和视黄醇竞争性结合,可导致暗适应变差,甚至有造成永久性夜盲症的可能,还可能引起睑缘炎、睑板腺萎缩及干眼等[45]。帕米膦酸二钠和其他双膦酸盐可导致前葡萄膜炎和非特异性结膜炎、浅层巩膜炎、巩膜炎、眼眶炎症等[46]。某些磺胺类药物会导致睫状体肿胀,并导致闭角型青光眼的进展。托吡酯是一种用于各种类型的癫痫、偏头痛、抑郁症和双相情感障碍的磺胺类药物,最常见的眼部不良反应有脉络膜渗漏、闭角型青光眼和近视漂移[47]。临床医生应了解到药物潜在的眼部不良反应,告知患者治疗的潜在风险并及时停药或换药。

6 未来展望

随着数字创新的发展,一个很有前途的研究热点是通过人工智能将系统性疾病与眼底影响相结合。据报道通过人工智能深度学习模型能够帮助预测心血管疾病和其他系统性血管疾病的风险因素[48],深度学习技术通过对视网膜形态的学分析还能够对阿尔茨海默病、创伤性脑损伤、肌肉骨骼疾病及贫血等进行预测和评估,增强对复杂疾病的理解[49]。随着眼科成像设备的日益先进,眼病诊疗水平也得到了快速提升,新型真彩超广角眼底照相机、超广角眼底激光扫描照相机,在免散瞳的情况下即可获得高清大范围(180~230 °)的视网膜信息;光学相干断层扫描(optical coherence tomography,OCT)对视网膜断层扫描的精度已经达到微米级别;OCTA可于不注射造影剂的情况下,在短短数秒内获取高清的视网膜血管信息。眼部成像设备的发展和卷积神经网络的更新迭代将有助于我们在疾病更早期捕捉这些全身疾病的微观改变,在疾病的发生、发展过程中及时跟进并评估其严重程度,甚至有望通过学科交叉改变患者的传统诊疗模式和健康管理模式。

7 结语

眼作为观察全身系统性疾病的重要窗口,可以提供很多有用的诊断信息,重视眼与全身病的相互影响,通过眼科专科检查,包括人工智能筛查等技术手段,可实现早期诊断、智能评估、客观随访。加强多学科协作,提升学科交叉水平,有助于临床整体诊疗水平的提高,避免或减少视功能损失,甚至挽救患者生命。

利益冲突

所有作者均声明不存在利益冲突。

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1、浙江省自然科学基金(LY22H120004)。This work was supported by the Zhejiang Provincial Natural Science Foundation of China (LY22H120004).()
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