在大力发展精准医疗的时代背景下,北京大学第三医院眼科中心率先建立干眼精准医疗平台。通过规范和优化干眼诊疗流程,为患者提供个性化的治疗方案和预防指导意见,有效提高了干眼诊断的精确性与治疗的有效性,同时提升了干眼门诊接诊效能,改善了患者就诊体验。本文将从干眼精准医疗平台体系的建设内容、标准化的检查流程、个性化的诊疗方案等方面进行阐述,并结合实际临床案例,综合分析北京大学第三医院在干眼精准医疗方面进行的探索,展望干眼精准医疗平台的前景与未来。
In the era of developing precision medicine, the Ophthalmic Center of Peking University Third Hospital has taken the lead in establishing a dry eye precision medical platform. By standardizing and optimizing the diagnosis and treatment process of dry eye, this center provides personalized treatment plan and prevention guidance for patients, effectively improves the accuracy of dry eye diagnosis and the effectiveness of treatment, at the same time,improves the reception efficiency of dry eye clinic, and improves the patient’s clinic experience. In this paper, the construction content, standardized inspection process and personalized diagnosis and treatment scheme of dry eye precision medicine platform system will be described. Combined with the actual clinical cases, the exploration of the Peking University Third Hospital in dry eye precision medicine will be comprehensively analyzed, and the future of dry eye precision medical platform will be prospected.
血源性滴眼液是治疗干眼的一种有效的治疗方法。来源可分为自体、供体,其中供体来源又可分为成人外周血及脐带血,并以血清、富血小板血浆、血小板来源生长因子以及血小板裂解产物的形式制成。由于各种血液制品的原理及适应症不同,本文将对不同血源性滴眼液制品的制备及面临的挑战的共识问题进行解读。
Blood-based eye drops can be used effectively in the treatment of dry eyes. The sources of blood-based eye drops can be divided into autologous and donor, and donor sources can be divided into adult peripheral blood and umbilical cord blood, which are prepared in the form of serum, platelet-rich plasma, platelet-derived growth facters and platelet lysate. Due to the different principles and indications of various blood products, the consensus issues on the preparation and challenges of different blood-based eye drop products are reviewed.
干眼是以泪膜稳态丢失及伴随眼部不适症状为特征的最常见眼表疾病,泪膜不稳定、泪液高渗透性、眼表炎症及感觉神经异常为其主要病因。地夸磷索钠是一种P2Y2受体激动剂,能刺激黏蛋白及泪液分泌,其独特的作用机制为干眼的治疗开辟了新的方向,本文就地夸磷索钠近年的临床及基础研究进展作一综述。
Dry eye is one of the most common ocular surface diseases. It is characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and tear hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities play major etiological roles. Diquafosol tetrasodium is a purinergic P2Y2 receptor agonist that promotes mucin and aqueous tear secretion. The unique pharmacological mechanism of diquafosol tetrasodium opens up a new direction for the medical therapies of dry eye. This article reviews the clinical therapeutic effect and research progress of diquafosol tetrasodium for the past few years.
目的:观察强脉冲光(intense pulse light,IPL)治疗睑板腺功能障碍(meibomian gland dysfunction,MGD)性干眼的临床效果。方法:选取2019年10月至2019年12月在东莞市东南部中心医院眼科门诊就诊的MGD性干眼患者64例(64只右眼),随机分为对照组与观察组,每组32例。对照组采用睑板腺按摩联合常规药物治疗,观察组采用IPL联合睑板腺按摩及常规药物治疗,两组疗程均为6周;观察两组患者治疗前后干眼症状、体征及睑板腺功能变化。结果:治疗后两组干眼症状、体征及睑板腺功能均较治疗前明显改善,差异有统计学意义(P>0.05);观察组治疗后2、4周干眼症状、体征及睑板腺功能评分改善优于对照组,差异有统计学意义(P<0.05);治疗后6周两组各项观察指标差异无统计学意义(P>0.05)。经过6周治疗,观察组有效率为87.5%(28/32),对照组有效率75%(24/32),差异有统计学意义(P=0.021)。治疗期间两组均未发生不良反应。结论:IPL联合睑板腺按摩对MGD性干眼能有效减轻眼部不适症状、改善睑板腺功能,较单纯睑板腺按摩起效更快、效果更佳。
Objective: To observe the clinical effect of intense pulse light (IPL) on MGD dry eyes. Methods: Sixty-four patients(64 right eyes) with MGD dry eye from October 2019 to December 2019 were collected and randomly divided into control group (n=32) and observation group (n=32). The control group was treated with meibomian gland massage combined with conventional medicine, while the observation group was treated with IPL combined with meibomian gland massage and conventional medicine. The course of treatment of both groups was 6 weeks. The dry eye symptoms, dry eye signs and meibomian gland function changes were observed before and after treatment in both groups. Results: The dry eye symptoms, physical signs and meibomian gland function of the two groups after treatment were significantly improved compared with those before treatment (P>0.05). The improvement of dry eye symptoms, physical signs and meibomian gland function in observation group were better than those of the control group at two and four weeks after treatment (P<0.05), while there was no statistically significant difference between the two groups at 6 weeks after treatment (P>0.05). The effective rate in observation group was 87.5% (28/32) after 6 weeks treatment, while control group was 75% (24/32), the difference was statistically significant (P=0.021). No adverse reactions occurred in both groups during the treatment. Conclusion: IPL combined with meibomian gland massage can effectively reduce the ocular discomfort and improve the function of meibomian gland in MGD dry eyes,which is faster and more effective than meibomian gland massage alone.
目的:探讨泪液中前列腺素E2(prostaglandin E2,PGE2)水平与干眼严重程度的关系。方法:选取干眼患者60例,并接受眼表疾病指数(Ocular Surface Disease Index,OSDI)问卷调查及眼科检查,包括泪膜破裂时间(tear film breakup time,BUT)、角膜荧光素染色评分(corneal fuorescein staining score,CFLS)、泪液分泌试验(Schirmer I试验)。使用酶联免疫吸附测定(ELISA)测量泪液中PGE2的水平。分析泪液PGE2水平与干眼临床症状相关指标的关系。结果:干眼患者泪液中的PGE2水平为(446.39±139.34) pg/mL。干眼患者泪液中PGE2水平与OSDI评分呈正相关(r=0.458,P<0.001)。泪液PGE2水平与BUT(r=0.164,P=0.354)、CFLS评分(r=0.265,P=0.086)、Schirmer I试验(r=?0.076,P=0.460)均无明显相关性。应用线性回归分析表明,泪液PGE2水平与OSDI评分呈正相关(95%CI:7.04~20.18,t=4.01,P<0.001)。结论:泪液中PGE2的水平与OSDI评分呈正相关,与BUT、CFLS评分、Schirmer I试验均无明显相关性。
Objective: To investigate the relationship between the level of prostaglandin E2 (PGE2) in tears and the severity of dry eye. Methods: Sixty patients with dry eye were selected and investigated with the Ocular Surface Disease Index (OSDI) questionnaire and ophthalmic examination, including tear film break-up time (BUT), corneal fluorescein staining score (CFLS) and tear secretion test (Schirmer I test). The level of PGE2 in tears was measured by enzyme-linked immunosorbent assay (ELISA). The relationship between the level of PGE2 in tears and related indexes of dry eye clinical symptoms was analyzed. Results: The average level of PGE2 in tears of patients with dry eye was (446.39±139.34) pg/mL. The level of PGE2 in tears of patients with dry eye was positively correlated with the OSDI score (r=0.458, P<0.001). PGE2 levels were not significantly correlated with BUT (r=0.164, P=0.354),Schirmer I score (r=?0.076, P=0.460), and CFLS score (r=0.265, P=0.086). Linear regression analysis showed that the level of PGE2 in tears was positively correlated with OSDI score (95% CI: 7.04–20.18, t=4.01, P<0.001).Conclusion: The level of PGE2 in tears is positively correlated with OSDI score, but has no significant correlation with BUT, the CFLS score and Schirmer I test.
目的:探讨大气污染物NO<sub>2</sub>水平与干眼患病的相关性。方法:选取2014年1月至2018年1月共计75 279例干眼患者的临床资料,进行资料汇总。空气质量和天气数据来自西安市气象局2014—2018年的每日环境空气质量数据。分析中包括的环境空气污染物NO<sub>2</sub>。所有数据均按小时收集。计算每个变量的每日平均值,并计算本研究中使用的每周平均值。本研究中患者均自愿参加,并经南昌大学第一附属医院医学研究伦理委员会批准。结果:干眼的门诊就诊次数与NO<sub>2</sub>水平显著相关。本研究发现不同年龄段的人受到不同的参数变化影响,环境中NO<sub>2</sub>的浓度对于全年龄段的人患干眼有显著相关性,对性别无选择性,男女均会因为NO2在环境中的不同水平而患干眼。较高水平的环境NO<sub>2</sub>会增加门诊患者干眼的概率。我们通过对患者人数的累计与环境中NO<sub>2</sub>浓度进行相关性分析,发现其有显著相关性,因此环境空气污染和天气变化可能导致干眼的恶化。结论:大气污染物NO2与干眼患病有显著相关性。
Objective: To investigate the correlation between NO2 levels in air pollutants and dry eye. Methods: The clinical data of 75 279 patients with dry eye from January 2014 to January 2018 were selected and summarized. The air quality and weather data were from the daily ambient air quality data of Xi’an Meteorological Bureau from 2014 to 2018. Environmental air pollutants NO2 was included in the analysis. All data were collected on an hourly basis. We calculated the daily average for each variable and then calculated the weekly average used in this study.All patients in this study volunteered to participate. , and this study was approved by the Medical Research Ethics Committee of the First Affiliated Hospital of Nanchang University. Results: We found that the number of outpatient visits for dry eye was significantly correlated with NO2 levels. Our study found that people of different ages were affected by different parameter changes. The concentration of NO2 in the environment was significantly correlated with dry eyes in all age groups, and is not selective for gender. Both men and women could develop dry eyes due to different levels of NO2 in the environment. Our results showed that higher levels of environmental NO2 increased the chances of dry eyes in outpatients. By analyzing the correlation between the cumulative number of patients and the NO2 concentration in the environment, we found that the correlation was significant.Therefore, ambient air pollution and weather changes may lead to the deterioration of dry eye. Conclusion: There is a significant correlation between atmospheric pollutant NO2 and dry eye disease.
局部点药是眼部用药最常见的方式,但一般药物通过角膜困难,药物生物利用度低。纳米载体药物于8 0年代开始用于眼部,脂质体和类脂质囊泡(niosomes)与眼表的黏蛋白相互作用,延长药物在眼表的停留时间。纳米乳剂(nanoemulsion)的表面活性剂可以松解角膜上皮细胞紧密连接,形成转运开口,抑制细胞表面糖蛋白酶P(glycoprotein P,Pgp)降解药物活性蛋白。纳米粒子(nanoparticles)通过角膜上皮和结膜上皮而不会引起毒性。纳米胶囊(nanocapsules)更深地内化到角膜上皮(50 μm处)。聚合物胶束(polymeric micelles)自组装成核-壳纳米载体增强药物渗透角膜的能力。阴离子高代聚酰氨基胺(poly-amidoamine,PAMAM)树枝状大分子增强药物通透性,中性和阳离子低代树枝状大分子通过网格蛋白途径介导药物更高的通透性。纳米晶体(nanocrystal),除增强药物溶解度和溶解速率之外,它的高黏附能力帮助药物保留和渗透到眼组织中。纳米结构材料与干眼关联密切,为干眼的治疗、诊断提供手段。
Topical administration is the most common method of ocular medication, but it is generally difficult for the drug to pass through the cornea, and the bioavailability of the drug is low. Nanocarrier drugs were used in eyes in the 1980s, and liposomes and lipoids vesicles (Niosomes) interacted with ocular surface mucins to prolong the residence time of the drug on the ocular surface. Nanoemulsion surfactants can release the tight junctions of corneal epithelial cells, form transport openings, and inhibit the degradation of pharmaceutically active proteins by cell surface glycoprotein P (Pgp). Nanoparticles pass through the corneal and conjunctival epithelium without causing toxicity. Nanocapsules internalize deeper into the corneal epithelium (at 50 μm). Polymeric micelles self-assemble into core-shell nanocarriers to enhance the ability of drugs to penetrate the cornea. Anionic high-generation poly-amidoamine (PAMAM) dendrimers enhance drug permeability. Neutral and cationic low-generation dendrimers mediate higher drug permeability through clathrin pathway. Nanocrystal, in addition to enhancing drug solubility and dissolution rate, its high adhesion ability helps drug retention and penetration into ocular tissues. Nanostructured materials are closely related to dry eye and provide a choice for the treatment and diagnosis of dry eye.
泪膜的不同组成成分通过相互作用共同维持眼球表面的湿润,从而维持眼部健康。当这些组成成分出现病理性改变,将会不同程度的影响泪膜稳态,从而导致干眼的发生。而瞬目运动一定程度上影响着泪膜组成成分的分布,随着对干眼相关机制研究的逐步深入,以泪膜为导向的诊断(tear-film-oriented diagnosis,TFOD)的新概念被提出,并被逐渐被接受。我们可以通过泪膜破裂方式来确定眼球表面所缺乏的组成成分,并在此基础上对干眼进行诊断,从而定向补充泪膜缺失成分,重新恢复泪膜稳态。本文将着重分析瞬目、泪膜形成及泪膜破裂机制之间的关系,从而进一步明确泪膜定向诊断的新概念及发展方向。
Different components of the tear film work together to maintain the wettability of the ocular surface, thus maintaining eye health. When the pathological changes of these components occur, the tear film homeostasis will be affected to varying degrees, leading to dry eye. Blinking movement affects the distribution of tear film components to some extent. With the continuous development of research and understanding of the concept and mechanism of dry eye, new concepts of tear-film-oriented diagnosis (TFOD) have been gradually proposed and widely accepted. We can determine the components lacking on the surface of the eye through the tear film breakup patterns (BUPs). On this basis, dry eye is diagnosed, so as to replenish the lacking components of tear film directionally and restore the stability of tear film. This paper will focus on analyzing the relationship between blinking, tear film formation and tear film break-up mechanism, so as to further clarify the new concept and development direction of tear-film oriented diagnosis.
目的:探讨风筝皮瓣及旋转皮瓣在眼外伤或良性肿物切除术后造成眉眼前层缺损的疗效,评价其预后、修复效果以及美学评分改变。方法:收集2018年5月至2020年5月34例眉/眼外伤或因良性肿物行手术切除患者,其眉眼前层缺损最大直径不超过眼长度1/2,根据创面缺损位置、范围,设计沿皮纹方向的缺损邻接部位局部风筝皮瓣及旋转皮瓣,推进滑行局部转移皮瓣向缺损区移位一期修复缺损。随访6个月观察术后皮瓣愈合情况、缺损的修复效果、并发症、患者满意度,比较手术前后美学评分。结果:所有皮瓣全部成活,切口均为I期甲级愈合,局部皮瓣的皮肤色泽、厚薄、毛发情况、质地以及眉毛走行分布与未手术侧基本一致,皮瓣创周器官组织形态无明显改变,皮瓣上眉毛生长良好,手术切口隐蔽在肌肤纹路处、瘢痕增生不鲜明,所有患者无需再次手术。缺损部无臃肿,双侧连续性以及对称性良好,无眉眼变形、倒睫、睑内外翻、上睑下垂等出现,眉/眼组织形态美观、功能良好。患者对手术效果比较满意。患者术后1d及1、3、6个月的美学评分分别为(73.50±7.79)、(76.97±6.84)、(82.21±6.11)和(87.06±6.07)分,均高于术前的(50.59±9.71)分,比较差异均有统计学意义(均P<0.05)。结论:应用风筝皮瓣及旋转皮瓣I期修复眉/眼皮肤软组织缺损,可较好地恢复眉/眼形态和功能,患者对缺损修复效果满意度高,能取得较高的美学评分,操作简单易行,效果可靠,无明显并发症。
Objective:To investigate the therapeutic efect of kite fap and rotary fap on superfcial tissue defect of eyebrow/eye caused by eyebrow/eye trauma or benign tumor resection, and to evaluate the prognosis, repair effect and aesthetic score changes. Methods: A total of 34 cases of eyebrow/eye trauma or benign tumors who underwent surgical resection were collected between May 2018 and May 2020. Te maximum defect diameter was not more than 1/2 of the length of eyebrow/eye. According to the location and scope of the defect, local kite flaps and rotary flaps were designed at the adjacent along the dermatoglyphic direction, and the sliding local transfer faps were promoted to the defect area to repair the eyebrow and eyelid ocular defects in stage one. Follow up for 6 months to observe the fap healing, defect repair efect, complications, patient satisfaction and aesthetic score. Results:All the skin faps survived, and the wound healing was Grade I A. The skin color, thickness, hair condition, texture and eyebrow shape distribution of the local skin faps were basically similar to the non-surgical side. Tere was no obvious change in the tissue morphology around the faps. Te eyebrows on the skin faps grew well, and the surgical incision was concealed in the skin lines with no distinct scar hyperplasia. All patients did not need operation again. Te defects were not swollen, bilateral continuity and symmetry were good, without eyebrow and eye deformation, without trichiasis, entropion or ptosis, etc. Te eyelid/eyebrow were beautiful and functional. The patients were satisfied with the surgical results. The aesthetic scores of patients at diferent postoperative monitoring times (1 day, 1 month, 3 months and 6 months) afer surgery were (73.50 ± 7.79), (76.97 ± 6.84), (82.21 ± 6.11) and (87.06 ± 6.07) points respectively, which were significantly higher than the preoperative scores (50.59 ± 9.71) points, and the diferences were statistically signifcant (P<0.05). Conclusion: Te kite fap and rotary fap can be used to repair the eyebrow/eye skin and sof tissue defects in Phase I, which can restore the shape and function of the eyebrow/eye well. Te patients are satisfed with the efect of the defect repair, and can obtain a higher aesthetic score. Te operation is simple and easy, the efect is reliable, and there was no obvious complications.
目的:获取眼表图像的综合信息,建立眼表疾病综合诊断和评估。方法:将超高分辨率光学相干断层成像仪(ultra-high resolution optical coherence tomography,UHR-OCT)与基于裂隙灯生物显微镜的微血管成像系统相结合,开发了一种多模态、非接触式的眼科光学成像平台。结果:UHR-OCT模块在组织中实现轴向分辨率约为2 μm 。眼表微血管成像模块在最大放大倍率下横向分辨率约为3.5 μm。通过集成在裂隙灯显微镜成像光学路径的不同模块,多模态成像平台能够执行实时前段OCT结构成像、结膜微血管成像和传统裂隙灯成像功能。利用自主开发的软件,进一步分析结膜血管网络图像和血流图像,获取血管分形维数、血流速度、血管直径等定量形态学和血流动力学参数。结论:通过在健康受试者和角膜炎患者的在体成像测试,表明多模态眼前段成像设备可为眼科临床应用及人工智能提供结构和功能信息数据。
Objective: To obtain the comprehensive information of the anterior eye image, establish complementary information for the diagnosis and evaluation of ocular diseases. Methods: We developed a multi-modal, non-invasive optical imaging platform by combining ultra-high resolution optical coherence tomography (UHR-OCT) with a microvascular imaging system based on slit-lamp biomicroscopy. Results: The uHR-OCT module achieved an axial resolution of approximately 2 μm in tissues. The lateral resolution of the ocular surface microvascular imaging module under maximum magnification was approximately 3.5 μm. By combining the imaging optical paths of different modules, the customized multi-modal eye imaging platform was capable of performing real-time cross-sectional UHR-OCT imaging of the anterior eye, conjunctival vessel network imaging, high-resolution conjunctival blood flow videography, and traditional slit-lamp imaging on a single device. With self-developed software, a conjunctival vessel network image and blood flow videography were further analyzed to acquire quantitative morphological and hemodynamics parameters, including vessel fractal dimensions, blood flow velocity and vessel diameters. Conclusion: The ability of the multi-modal anterior eye imager to provide both structural and functional information for ophthalmic clinical applications can be demonstrated in a healthy human subject and a keratitis patient.