泪膜,眼表面异常与干眼症

干眼症与泪膜和眼表面有密切的关系。本文阐述了正常泪膜和眼表面的作用，分析了干眼症的发病机理，并讨论了Ｓｊｏｇｒｅｎ氏综合征泪腺的病理变化和病变机制。     

眼表粘蛋白的研究进展

眼表粘蛋白是泪膜的重要成分，在维持眼表生理功能和预防眼表病变方面起着重要作用。目前已证实存在于眼表的粘蛋白有MUCl、MUC2、MUCA、MUC5AC、MUC5B、MUC7和MUCl6。对眼表粘蛋白的功能和调节机制的研究将为干眼症的治疗提供新的有效途径。     

人眼表微生物群与眼表疾病研究进展

眼表微生物群是人体眼表微环境的一部分,在维持其稳定中占据重要作用。许多研究对于健康与疾病状态下眼表微生物群的组成进行探究,但研究结果基于内外因素的不同而存在差异,且微生物失调与疾病之间的关系也尚未明确。近年来,随着肠道微生物与全身性疾病的研究不断深入,眼科研究者们也从中获得了一些启发,对眼表微生物群与眼表非感染性疾病的关系有了更进一步的探讨。本文将对正常眼表核心微生物群、眼部及全身性疾病眼表微生物群的变化进行综述,并讨论微生物失调引起疾病的可能机制,希望对未来眼表微生物群的进一步研究提供参考依据。     

眼表粘蛋白的研究进展

眼表粘蛋白是泪膜的重要成分,在维持眼表生理功能和预防眼表病变方面起着重要作用。目前已证实存在于眼表的粘蛋白有MUC1、MUC3、MUC4、MUC5AC、MUC5B、MUC7和MUC16。对眼表粘蛋白的功能和调节机制的研究将为干眼症的治疗提供新的有效途径。     

角膜神经调控眼表微环境的研究进展

角膜是眼前段透明的外层结构,由高密度的神经组织支配。在角膜神经支配过程中,三叉神经节起源的角膜神经穿过上皮层和基质层中不同类型的角膜细胞。角膜基质细胞、上皮细胞、免疫细胞等多种细胞和角膜神经之间发生密切的相互作用,共同维持角膜微环境稳态。此外,角膜神经参与许多眼表疾病的发生发展过程。角膜神经释放多种活性肽物质,参与调控角膜感觉、维持上皮完整性和增殖、促进伤口愈合及调控角膜局部炎症和免疫反应等。本文对角膜神经在眼表微环境调控作用的研究进展进行综述,为角膜神经相关疾病的研究及治疗提供新的思路。     

角膜塑形镜对青少年眼表和泪膜的影响

目的：观察夜戴型角膜塑形镜矫正青少年近视对眼表和泪膜的影响及眼表不适症状。

方法：前瞻性研究。选取12～18岁近视患者69例138眼,其中使用框架眼镜者31例,使用角膜塑形镜者38例。分别于戴镜1、3、6、12mo时进行眼表疾病指数(OSDI)和眼表染色评分(Oxford法),检测泪膜破裂时间(TBUT)、非接触性泪膜破裂时间(NIBUT)及基础泪液分泌量。

结果：与框架眼镜组和戴镜前比较,戴镜后各时间点角膜塑形镜组患者OSDI评分升高,TBUT和NIBUT均降低,且戴镜6、12mo时角膜塑型镜组患者眼表染色评分均高于框架眼镜组(均P<0.05),但戴镜前后两组患者基础泪液分泌量无明显差异(P>0.05)。

结论：角膜塑形镜会导致OSDI和眼表染色评分轻度升高,影响泪膜稳定性,应加强眼表和泪膜情况的戴镜前检查和随访,重视患者的不适主诉。     

夜戴型非球面角膜塑形镜对眼表微环境的影响

夜戴型非球面角膜塑形镜(night-wear aspheric orthokeratology lens),以下简称OK镜,利用夜间睡眠时间矫正视力,是目前为数不多的可以让近视的孩子白天不戴眼镜的方法,所以经常作为8～16岁近视人群临床上首选推荐。OK镜通过对眼表面产生逆向几何作用力的压迫作用,使得角膜曲率降低,从而达到暂时性的矫正近视的作用。目前作为一种公认的治疗青少年近视的非手术方法之一,非球面角膜塑形镜的镜片材质和验配水平一直在不断的创新和升级。OK镜片直接覆盖于眼表,长期配戴会对眼表微环境造成一定影响,比如睑板腺、泪膜、结膜、角膜以及眼表微生物等,甚至可能造成眼表微环境的失衡,从而导致眼表疾病的发生和发展。本文旨在分析配戴非球面角膜塑形镜对眼表睑板腺形态、泪膜的形态与功能、结膜微循环、角膜细胞形态、眼表微生物等因素的影响,以指导临床医生对青少年配戴角膜塑形镜时给予全面考量,增加夜戴型非球面角膜塑形镜的安全性和有效性。     

切开式重睑术后眼表泪膜变化的研究

目的：探讨切开式重睑术前后眼表泪膜的变化。

方法：该研究为前瞻性研究。选取2017-10/2018-07在我科行切开式重睑术者17例34眼,分别于术前和术后1、7、14d,1、3mo行眼表疾病指数问卷调查(OSDI)、基础泪液分泌试验(SⅠt)、泪膜破裂时间(BUT)、角膜荧光素染色、泪液羊齿状结晶试验(TFT)、结膜印迹细胞学检查,以评价患者手术前后的眼表泪膜功能。

结果：患者术后1、7、14d眼部不适感较术前加重,OSDI评分高于术前(P<0.001),术后1、3mo眼部不适感较术后1、7、14d明显缓解,OSDI评分与术前无明显差异(P>0.05); 术后1d角膜荧光素染色点明显增多(P=0.008),术后7、14d,1、3mo角膜荧光色染色与术前无差异(P>0.05); 术后1、7、14d时SⅠt值明显增高(P<0.001),术后1、3mo时SⅠt值与术前无差异(P>0.05); 术后1d结膜杯状细胞个数较术前下降(P<0.001),余各时间点结膜杯状细胞数无明显差异,而术后BUT、TFT值与术前无差异(P>0.05)。

结论：切开式重睑术后早期患者出现明显的不适感和刺激症状,角膜、结膜上皮受到损害,拆除缝线后,随着眼表微环境的重新建立,术后1mo各项指标恢复至术前水平。     

芳香化酶抑制剂对眼表微环境影响的分析

目的：分析芳香化酶抑制剂(AIs)对服用者眼表微环境的影响。

方法：横断面观察性研究。研究对象为2022-11/2023-05我院乳腺科就诊的接受AIs治疗的药物绝经后的女性,根据AIs的种类分为甾体组和非甾体组。对照组为年龄相匹配的职业健康体检女性。所有参与者都进行了眼表疾病指数(OSDI)问卷评分,详细的眼科检查包括：最佳矫正视力、眼压、眼轴、角膜曲率、泪河弯曲面的曲率半径、泪液渗透压、泪膜破裂时间、角膜荧光素钠染色评分、泪液分泌试验(SchirmerⅠ试验)、睑板腺红外线评分。

结果：对照组与甾体组、非甾体组的年龄、最佳矫正视力、眼压、眼轴、角膜曲率比较均无差异(P>0.05); 甾体组和非甾体组的药物服药时长比较无差异(P>0.05)。对照组与甾体组、非甾体组的OSDI评分、泪河弯曲面的曲率半径、泪液渗透压、泪膜破裂时间、角膜荧光素钠染色评分、SchirmerⅠ试验、睑板腺红外线评分比较均有差异(P<0.05); 甾体组和非甾体组SchirmerⅠ试验结果比较有差异(P<0.05),其余数据之间均无差异(P>0.05)。

结论：接受AIs治疗的药物绝经后女性患者,眼表微环境改变明显,干眼的发生既有泪液分泌不足,也存在泪液蒸发过强。特别是接受非甾体类AIs者主泪腺分泌减少更明显。     

Tear Film and Ocular Surface Evaluation in Gestational Diabetes Mellitus

Background: Dry eye syndrome is one of the complaints of diabetic patients. The aim of the present study was to evaluate the tear functions in pregnant women with gestational diabetes mellitus (GDM) using tests: Schirmer, tear break-up time (TBUT), and tear film osmolarity (TFO) tests and the Ocular Surface Disease Index score (OSDI). Methods: Pregnant women with GDM (Group 1, n=46) and healthy pregnant women (Group 2, n=36) were enrolled. Initially, all participants were asked to answer the OSDI and then they underwent a detailed ophthalmic examination including Schirmer, TBUT, and TFO tests. The individuals with ocular or systemic disorders that might affect the tear function tests and who were using topical medications were excluded. Results: The results of Schirmer, TBUT, TFO tests and OSDI scores were 11.20±4.93 mm, 5.59±2.16 sec, 309.65±14.80 mOsm/L, and 9.59 ± 9.69 in Group 1, respectively, and 12.33±5.33 mm, 5.67±2.68 sec, 308.36±16.00 mOsm/L, and 10.62±8.66 in Group 2, respectively. There was no significant difference in any of the tear function tests and OSDI scores between the study groups (p>0.05). Conclusion: GDM seems to have no negative effects on tear function tests. This may be due to a lack of duration of hyperglycemia long enough to affect the tear function tests of pregnant women.     

Understanding the Interactions Between the Ocular Surface Microbiome and the Tear Proteome

PurposeThe purpose of this study was to explore the interplay between the ocular surface microbiome and the tear proteome in humans in order to better understand the pathogenesis of ocular surface-associated diseases.MethodsTwenty eyes from 20 participants were included in the study. The ocular surface microbiome was sequenced by whole-metagenome shotgun sequencing using lid and conjunctival swabs. Furthermore, the tear proteome was identified using chromatography tandem mass spectrometry. After compositional and functional profiling of the metagenome and functional characterization of the proteome by gene ontology, association studies between the ocular microbiome and tear proteome were assessed.ResultsTwo hundred twenty-nine taxa were identified with Actinobacteria and Proteobacteria being the most abundant phyla with significantly more Propionibacterium acnes and Staphylococcus epidermidis in lid compared to conjunctival swabs. The lid metagenomes were enriched in genes of the glycolysis lll and adenosine nucleotides de novo and L-isoleucine biosynthesis. Correlations between the phylum Firmicutes and fatty acid metabolism, between the genus Agrobacterium as well as vitamin B1 synthesis and antimicrobial activity, and between biosynthesis of heme, L-arginine, as well as L-citrulline and human vision were detected.ConclusionsThe ocular surface microbiome was found to be associated with the tear proteome with a role in human immune defense. This study has a potential impact on the development of treatment strategies for ocular surface-associated diseases.     

Increased Tear Film Osmolarity in Systemic Lupus Erythematosus

Purpose: To evaluate tear film osmolarity in patients with systemic lupus erythematosus (SLE). Methods: A total of 55 eyes from 55 patients with SLE and 47 eyes from 47 age- and gender-matched healthy individuals were included in this study. Tear film osmolarity was evaluated with a lab-on-a-chip technique (TearLab; TearLab Corporation, San Diego, CA) in SLE patients in comparison with healthy individuals, and results were correlated to clinically available diagnostic tests for dry eye, such as tear ?lm break-up time (BUT), Schirmer’s test, and Ocular Surface Disease Index (OSDI). Results: The mean tear film osmolarity in the SLE patients and healthy individuals was 306.02 ± 13.27 mOsm/L and 300.74 ± 9.11 mOsm/L, respectively, which made for a statistically significant difference (p = 0.020). In the SLE group, tear film osmolarity was negatively correlated with the Schirmer’s test score and the BUT value (r = ?0.295 p = 0.029 and r = 0.347 p = 0.009, respectively), whereas tear film osmolarity was not correlated with OSDI score (r = ?0.182 p = 0.183). Conclusions: This study revealed that tear film hyperosmolarity and abnormal tear film function are associated with SLE.     

Ocular surface microbiota in patients with varying degrees of dry eye severity

AIM: To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye (DE).METHODS: The single-center, prospective, case-control, observational study categorized all participants into three distinct groups: 1) control group (n=61), 2) mild DE group (n=56), and 3) moderate-to-severe DE group (n=82). Schirmer’s tear secretion strips were used, and the bacterial microbiota was analyzed using 16S ribosomal ribonucleic acid gene sequencing.RESULTS: The three groups had significant differences in alpha diversity: the control group had the highest richness (Chao1, Faith’s phylogenetic diversity), the mild DE group showed the highest diversity (Shannon, Simpson), and the moderate-to-severe DE group had the lowest of the above-mentioned indices. DE severity was positively correlated with a reduction in beta diversity of the microbial community, with the moderate-to-severe DE group exhibiting the lowest beta diversity. Linear discriminant analysis effect size presented distinct dominant taxa that significantly differed between each. Furthermore, the exacerbation of DE corresponded with the enrichment of certain pathogenic bacteria, as determined by random forest analysis.CONCLUSION: As DE severity worsens, microbial community diversity tends to decrease. DE development corresponds with changes in microbial constituents, primarily characterized by reduced microbial diversity and a more homogenous species composition.     

Tear diluents in the treatment of keratoconjunctivitis sicca

To determine the optimum solution concentration for lowering elevated tear film osmolarity in keratoconjunctivitis sicca (KCS), tear osmolarity was measured in four KCS patients before and after instillation of either an isotonic saline solution or one of four hypotonic saline solutions (range, 75-225 mOsm/L). Average tear osmolarity one minute after instillation was significantly lower with the hypotonic solutions than with the isotonic saline (mean +/- SEM, 290 +/- 3 mOsm/L vs. 317 +/- 1 mOsm/L, P less than 0.0005). Solutions 150 mOsm/L or less were most effective in lowering osmolarity; the 75 mOsm/L solution was occasionally associated with irritation. In 16 KCS patients, we then compared the therapeutic efficacy of the 150 mOsm/L solution with that of an otherwise identical isotonic solution in a two-week, double-masked, crossover study. The 150 mOsm/L solution was superior for symptom relief by nearly 2:1 (P = 0.01).     

The Precorneal Tear Film as a Fluid Shell: The Effect of Blinking and Saccades on Tear Film Distribution and Dynamics

We conducted a series of experiments to elucidate the behavior of the human precorneal tear film (PCTF) during blinking and horizontal and vertical saccades. Methodology included video-interferometry with subsequent image cross-correlation (tear film lipid layer [TFLL]) and video-microscopy (mucoaqueous subphase [MAS]). We observed that the TFLL interference pattern deteriorates rapidly with successive blinks and degrades slowly with repeated horizontal saccades during blink suppression when dark arcs of thinning appear in the fluorescein-stained PCTF. Furthermore, after full downgaze and a return to the primary position, a transient horizontal bright band appears, deep to the spreading TFLL. It may be followed by local disturbances in the interference pattern. Two horizontal dark bands form in the stained PCTF after the return saccade. PCTF disruption may occur below the lower band during blink suppression. We concluded that shearing during horizontal saccades is insufficient to disturb the tear film structure greatly. The MAS and TFLL move together as a fluid shell. The dark arcs/bands are caused by meniscus-induced thinning, imprinted onto the PCTF at the lid margin. Their stability during blink suppression suggests that the MAS has gel-like properties. The horizontal bright bands are probably due to transient corneal indentation in downgaze. In downgaze, the disturbance of the TFLL and MAS below the dark bands is possibly due to shearing across the MAS in the return phase. This could cause desiccating stress in everyday activities, such as working at a computer.     

The Effect of Closed-Eye Tear Film Conditions on Blood-Isolated Neutrophils,In Vitro

Purpose: Eyelid closure results in influx of neutrophils onto the ocular surface, which are non-responsive to inflammatory stimuli. This investigation examined whether incubation of blood-isolated neutrophils in closed-eye conditions induce a tear-film neutrophil phenotype.

Methods: Blood-isolated neutrophils were incubated combining various conditions: hypoxia, corneal epithelial cells (HCEC), artificial tear solution (ATS).

Results: A hypoxic environment induced no differential effect on membrane receptor expression. Incubation in the presence of HCEC resulted in membrane receptor upregulation and increase in caspase activation.

Conclusions: Hypoxia, corneal epithelial cell exposure, or artificial tear fluid are insufficient to replicate a tear-film neutrophil phenotype using blood-isolated neutrophils.     

糖尿病2型患者的眼表改变

目的:探讨2型糖尿病患者的眼表改变。方法:2型糖尿病患者50例100眼及非糖尿病对照者30例60眼,分别进行常规眼科检查、角膜荧光素染色、角膜知觉检查、基础泪液分泌试验(SchirmerⅠ)、泪膜破裂时间检查(BUT)、结膜印记细胞学检查。采用Mann-WhitneyU检验和χ2检验进行统计学分析。结果:糖尿病组与对照组相比:①角膜染色程度增加:糖尿病组阳性率为60.0%,高于对照组25.0%,两者差异有统计学意义(χ2=18.447,P<0.05);②角膜知觉下降:糖尿病组为36.0%,高于对照组10%,两者差异有统计学意义(χ2=44.434,P<0.05);③BUT值缩短:糖尿病组BUT值<10s者为64.0%,高于对照组6.7%,两者差异有统计学意义(χ2=19.489,P<0.05);Shirmer值降低:糖尿病组Shirmer值<5mm者为24.0%,而对照组均大于5mm(χ2=8.471,P<0.05);④结膜上皮鳞状化生程度增加:两者差异有统计学意义(u=-4.366,P<0.05)。结论:2型糖尿病可以导致泪膜稳定性下降,角结膜上皮损害。     

Interfacial Phenomena and the Ocular Surface

Ocular surface disorders, such as dry eye disease, ocular rosacea, and allergic conjunctivitis, are a heterogeneous group of diseases that require an interdisciplinary approach to establish underlying causes and develop effective therapeutic strategies. These diverse disorders share a common thread in that they involve direct changes in ocular surface chemistry as well as the rheological properties of the tear film and topographical attributes of the cellular elements of the ocular surface. Knowledge of these properties is crucial to understand the formation and stability of the preocular tear film. The study of interfacial phenomena of the ocular surface flourished during the 1970s and 1980s, but after a series of lively debates in the literature concerning distinctions between the epithelial and the glandular origin of ocular surface disorders during the 1990s, research into this important topic has declined. In the meantime, new tools and techniques for the characterization and functionalization of biological surfaces have been developed. This review summarizes the available literature regarding the physicochemical attributes of the ocular surface, analyzes the role of interfacial phenomena in the pathobiology of ocular surface disease, identifies critical knowledge gaps concerning interfacial phenomena of the ocular surface, and discusses the opportunities for the exploitation of these phenomena to develop improved therapeutics for the treatment of ocular surface disorders.     

穿透性角膜移植术后泪膜稳定性的临床观察

目的 探讨穿透性角膜移植术后泪膜稳定性的变化规律.方法 对20例行部分穿透性角膜移植术后的患者分别观察术后6、9、12个月主观感觉、泪膜破裂时间(BUT)、泪液分泌值、泪河高度值、角膜荧光素染色,并与健眼对照观察.将结果作统计学分析.结果 穿透性角膜移植术后12个月内,术眼泪膜破裂时间低于健眼(P＜0.01),但患者无明显眼部干涩等症状;泪液分泌值在6个月时,比较健眼有统计学意义(P＜0.01),9、12个月时与健眼相比无统计学意义(P＞0.05);泪河高度值在6个月时比较健眼有统计学意义(P＜0.01),9、12个月时术眼与健眼无统计学意义(P＞0.05);荧光素染色在6个月时评分为7.89,与健眼比较有统计学意义(P＜0.01),9、12月时评分为4.62、3.03,与健眼比较无统计学意义(P＞0.05).结论 穿透性角膜移植术后6～12月的时间内,术跟的泪膜稳定性仍未恢复到正常水平,特别是泪膜破裂时间的缩短较健眼有显著差异(P＜0.01),提示穿透性角膜移植术后12个月时间内,存在泪膜不稳定和干眼症,需要定期复查泪膜变化,根据情况使用不含防腐剂的人工泪液和角膜营养,神经营养药物.