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甲状腺相关性眼病 (thyroid-associated ophthalmopathy, TAO)是成年人最常见的一种眼眶疾病,目前尚无直接有效的治疗方法能够改变其病程,临床治疗策略的制定与该病的活动性密切相关。有关该病活动期的诊断,目前临床中广泛采用欧洲Graves眼病专家组指南中的临床活动性评分(clinical activity score,CAS)进行评价[1],但其在临床应用时存在一定的局限性。99Tcm-DTPA SPECT/CT眼眶显像融合了功能、代谢和解剖等多方面信息,提供了客观的眼眶病变组织炎症程度和解剖改变程度的信息,逐渐被证明是一种相对客观的评价方法。我们对近年来该领域的研究进展进行综述。
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TAO又称Graves眼病,是Graves病中最常见的甲状腺外临床表现,其发病率在成年人眼眶病中居于首位。TAO主要与Graves甲状腺功能亢进有关,少数也可能伴有甲状腺功能正常或甲状腺功能减退[2]。目前,TAO具体的发病机制尚不清楚,可能与甲状腺上皮细胞、眼眶前脂肪细胞、成纤维细胞及眼外肌细胞表达共同靶抗原相关[3-4],在环境、遗传等危险因素影响下触发自身免疫反应,产生多种促炎性细胞因子、生长因子和趋化剂,造成眼外肌、眼眶脂肪及其他结缔组织的炎性水肿、增生和纤维化。
TAO对患者的生活质量、心理健康以及社会经济都造成了严重的负面影响[5-6],一经确诊应立即开始治疗。但由于对该病发病机制的了解有限,目前治疗上主要依据对TAO的临床活动性和严重程度的评估,以及对病程持续时间和患者生活质量的评估,治疗的目的是抑制眼眶炎症,减少永久性眼眶重塑。
TAO的自然病程遵循“Rundle曲线”,包括早期炎症活动期、中期持续平台期、晚期非活动缓解期[7]。在疾病的早期炎症活动期应给予免疫抑制治疗,疗效通常较好,可明显缩短病程并减轻TAO的严重程度,而晚期非活动缓解期给予抗炎和(或)免疫抑制治疗的效果明显较差,一般应在病情至少稳定6个月以上时,考虑行康复手术[1]。早期干预有助于改善TAO患者的预后,减少重症患者的比例和提高患者的生活质量。
由此可见,TAO的病程分期对临床治疗具有关键的指导作用,目前TAO活动性分期主要采用CAS评分进行评价。CAS评分中有7项指标与炎症的主要特征相关(表1中1~7项),3项与严重程度随着时间的推移变化相关(表1中8~10项)。CAS评分是最便捷和最常用的评估TAO活动性的工具,但由于其主要基于患者的主诉和临床医师的经验和观察来进行评分,主观性较强[8],而且对炎症特征进行二元评分,难以精确衡量炎症的变化过程,较易受到眼前节变化的影响,高估或低估疾病的活动性,这使得CAS评分结果虽然特异度高,但灵敏度低,较低的CAS评分并不能断定使用免疫抑制治疗不能获得良好的治疗效果[9]。另外,活动期和非活动期TAO都可能伴随严重的眼部症状,因此,为了弥补CAS评分的不足,需要采用更准确的成像技术,以便更有效地区分TAO患者所处的疾病阶段与状态,作出正确的临床决策。
序号 评分项目 评分 1 自发性眼球后疼痛 1分 2 眼球向上或向下注视痛 1分 3 眼睑红斑(充血) 1分 4 结膜充血 1分 5 结膜水肿 1分 6 眼睑炎性肿胀 1分 7 泪阜或皱襞肿胀 1分 8 最近1~3个月眼球突出增加≥2 mm 1分 9 最近1~3个月眼球运动减少≥8° 1分 10 最近1~3个月视力下降1行(Snellen视力表) 1分 注:对于初诊TAO患者,采用表中前7项进行评分,评分≥3分表明TAO处于活动期;对于随访期(前1~3个月)TAO患者,采用表中所有10项进行评分,评分≥ 4分表明TAO处于活动期。TAO为甲状腺相关性眼病 表 1 甲状腺相关性眼病临床活动性评分标准
Table 1. Clinical activity score for thyroid-associated ophthalmopathy
较早应用于TAO的辅助检查方法是超声探查,通过测量眼外肌的厚度、肌肉内回声或反射、眼动脉流速等判断TAO的活动性,但由于精确度不高,其临床使用受限。CT扫描能够从多层面成像,较好地分辨眼眶组织的解剖结构,分析各条眼外肌的厚度和密度、眼眶脂肪含量、泪腺大小、视神经受压情况等改变,检查速度快,价格相对低,但其较难显示炎症过程的变化。MRI可以比CT更精细地显示眼眶内软组织的解剖结构,不仅可以显示眼睑、泪腺等软组织增厚、内部结构改变和水肿情况,还可以定量研究T1和T2成像的改变,对炎症活动性和组织纤维化程度都能提供良好的信息,并且无辐射危害,因此得到了越来越多的关注。但其由于操作时间长、图像分析较为复杂、需要经验丰富的医师进行判读、检查价格昂贵等,在临床中的应用也受到一定的限制。光学相干断层扫描技术在TAO引起的视神经病变的早期诊断中具有一定的价值,其血流成像技术还能进一步监测TAO患者血管密度的定量变化,反映疾病进程。眼眶核素显像采用67Ga 、99Tcm、111In等标记的显像剂,不仅能提供眼眶组织大小、位置、形态和结构方面的信息,还能提供血流、功能及代谢情况的信息,显像设备由原始的扫描仪发展到今天的SPECT、PET及融合设备SPECT/CT、PET/CT,大大提高了局部病变的分辨率和定量诊断的准确性,是一种无创、易被患者接受的检查方法,其中放射性核素99Tcm兼具良好的显像物理性能和较易获得的优势,应用前景更加广阔。
99Tcm-DTPA SPECT/CT眼眶显像在甲状腺相关性眼病诊疗中的应用进展
Application advances of orbital 99Tcm-DTPA SPECT/CT in the diagnosis and treatment of thyroid-associated ophthalmopathy
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摘要: 甲状腺相关性眼病(TAO)对患者的生活质量、心理健康以及社会经济都造成了严重的负面影响,在该病的早期活动期进行治疗的效果较好,目前该病的活动性分期主要采用临床活动性评分(CAS),其存在较多不足之处。近年来,99Tcm-二亚乙基三胺五乙酸(DTPA) SPECT/CT眼眶显像在TAO的早期诊断、治疗和随访中都显示出重要价值,其可以与CAS互相补充,应用前景广阔。笔者总结了目前该领域的研究进展,提出未来需要更多的研究以期建立标准化的采集和结果分析共识,进一步研究一种新的TAO筛选工具,将99Tcm-DTPA SPECT/CT眼眶显像与人工智能技术相结合,以便更加精准便捷地指导临床。
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关键词:
- Graves眼病 /
- 99m锝五乙酸盐 /
- 体层摄影术,发射型计算机,单光子 /
- 体层摄影术,X线计算机 /
- 眼眶
Abstract: Thyroid-associated ophthalmopathy (TAO) leads a significant negative impact on patients' quality of life, mental health and community economy. Treatment in the early active stage of the disease will achieve better efficacy. At present clinical activity score (CAS) is the mainly method of judging disease activity, but it has many shortcomings. Recent studies have suggested that 99Tcm-diethylene triamine pentaacetic acid (DTPA) orbital SPECT/CT shows important value in the early diagnosis, treatment and follow-up of TAO. It can complement with CAS and has a broad application prospect. The authors summarize the current research progress in this field and highlight the need for more research to establish a standardized consensus on collection method and result analysis. Investigating a new tool to judge disease activity which can combine 99Tcm-DTPA orbital SPECT/CT with the artificial intelligence will more accurately and conveniently guide the clinical practice. -
表 1 甲状腺相关性眼病临床活动性评分标准
Table 1. Clinical activity score for thyroid-associated ophthalmopathy
序号 评分项目 评分 1 自发性眼球后疼痛 1分 2 眼球向上或向下注视痛 1分 3 眼睑红斑(充血) 1分 4 结膜充血 1分 5 结膜水肿 1分 6 眼睑炎性肿胀 1分 7 泪阜或皱襞肿胀 1分 8 最近1~3个月眼球突出增加≥2 mm 1分 9 最近1~3个月眼球运动减少≥8° 1分 10 最近1~3个月视力下降1行(Snellen视力表) 1分 注:对于初诊TAO患者,采用表中前7项进行评分,评分≥3分表明TAO处于活动期;对于随访期(前1~3个月)TAO患者,采用表中所有10项进行评分,评分≥ 4分表明TAO处于活动期。TAO为甲状腺相关性眼病 -
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