The correlation between keratoconus and eye rubbing: a review

Keratoconus is a non-inflammatory disorder which is gradual in development; corneal thinning and ectatic protrusion characterizes it. Keratoconus prevalence varies between different regions depending on several factors that affecting its prevalence. There are risk factors for developing keratoconus such as demographic and environmental factors. It was suggested that eye rubbing was associated with the development of keratoconus. The main aim of this review was to summarize the literature data about keratoconus and to identify the role of eye-rubbing in the aetiology of the disease. A number of 24 articles was reviewed through the PubMed, Google Scholar and Research Gates. There are many keywords used such as keratoconus, aetiology of keratoconus, eye rubbing, keratoconus prevalence, keratoconus and eye rubbing correlation. We concluded that eye rubbing causes the thinning of keratocyte, and the degree of effect of eye rubbing depends on the period and force of performing eye rubbing. It is recommended to avoid eye rubbing to prevent keratoconus, this can be achieved by avoiding itching and treating dryness of the eye and avoiding wearing eye lenses.     

Keratoconus,allergy, itch,eye‐rubbing and hand‐dominance

Background: One hypothesis for the pathogenesis of keratoconus includes teenage allergy, ocular itch and associated eye‐rubbing. Methods: This study examined the prevalence of these factors for teenage and adult patients. The results for a sample of 53 subjects with bilateral keratoconus were compared with those for a control sample of non‐keratoconus subjects, who also routinely wore RGP contact lenses. The strongest dominant hand and the eye with more advanced keratoconus were also determined, to examine for a relationship between them. Results: The keratoconic sample reported significantly higher levels of allergy, itch and rubbing as teenagers and as adults. However, all distributions were bimodal, consistent with the hypothesis that allergy, itch and rubbing are relevant in the pathogenesis of keratoconus only when the highest levels of these factors are present. For example, a significant relationship between the stronger dominant hand and the more advanced eye was evident only in subjects who reported the most severe rubbing. Conclusions: This finding adds weight to the circumstantial evidence that rubbing contributes to the pathogenesis of keratoconus. Low levels of teenage rubbing by some keratoconic subjects suggest a non‐rubbing pathogenesis and that emphasis on rubbing management is not warranted in these cases. However, high levels of adult rubbing reported by many keratoconic subjects indicate that the standard advice to avoid vigorous and prolonged rubbing is often not effective, even when repeated. There appears to be an indication for the need to improve the management of eye‐rubbing for some patients with keratoconus or at risk of developing this disease.     

圆锥角膜发病的力学因素及其机制

圆锥角膜是一种以角膜进行性变薄前突为特征的角膜扩张性疾病。其发病机制尚不清楚。体外实验表明力学刺激可能通过升高氧化应激水平和炎症因子浓度而损伤角膜基质细胞,造成角膜细胞外基质降解等一系列变化。大量临床研究证实揉眼、由睡姿引起的眼球压迫等力学因素可能在圆锥角膜发生发展的过程中起重要作用。它们可能通过增加泪液炎症因子水平、造成眼压变化、改变角膜生物力学性能以及机械摩擦直接损伤角膜组织、升高角膜上皮温度等机制对角膜造成影响。本文就力学因素对角膜基质细胞、角膜组织的影响及其在圆锥角膜发病机制中可能的作用进行阐述,以期为预防和管理圆锥角膜提供参考。     

干眼的发病机制及治疗研究进展

第二次国际干眼研讨会于2017年夏季报告提出,干眼是一种多因素的眼表疾病,其特征是泪膜稳态丧失,伴有眼部症状,其中泪膜不稳定和高渗透压、眼表炎症和损伤以及神经感觉异常具有致病作用。干眼是一个重要的公共卫生问题,会导致卫生成本增高,阻碍日常活动的开展,从而降低人群生活质量。本文简要介绍干眼的病因、发病机制,并着重介绍近2 a来关于干眼治疗的一些新进展。     

Eye rubbing-induced changes in intraocular pressure and corneal thickness measured at five locations, in subjects with ocular allergy

AIM: To assess the effects of eye rubbing on corneal thickness (CT) and intraocular pressure (IOP) measurements obtained 0-30min after habitual eye rubbing in symptomatic patients. METHODS: Measurements of IOP and CT were obtained at five locations (central, temporal, superior, nasal and inferior) before, and every 5min for 30min interval after 30s of eye rubbing, for 25 randomly selected eyes of 14 subjects with ocular allergy and 11 age-matched normals. Differences in measurements were calculated in each group [Baseline measurements minus measurements recorded at each time interval after eye rubbing (for IOP), and for each corneal location (for CT)] and comparison were then made between groups (allergic versus control) for differences in any observed effects. RESULTS: Within groups, baseline mean IOPs in the allergic patient-group (14.2±3.0 mm Hg) and in the control group (13.1±1.9 mm Hg) were similar at all times, after eye rubbing (P >0.05, for all). The maximum reduction in IOP was 0.8 mm Hg in the control subjects and the maximum increase was also 0.8 mm Hg in the allergic subjects. Between groups (allergic versus control), the changes in IOP remained under 1 mm Hg at all times (P=0.2) after 30min of eye rubbing. Between 0 and 30min of CT measurements after eye rubbing, the mean central CT (CCT), inferior CT (ICT), superior CT (SCT), temporal CT (TCT) and nasal CT (NCT) did not vary significantly from baseline values in the control and allergic-subject groups (P>0.05, for both). Between both groups, changes in CT were similar at all locations (P>0.05) except for the TC which was minimally thinner by about 4.4 μm (P=0.001) in the allergic subjects than in the control subjects, 30min following 30s of eye rubbing. CONCLUSION: IOP measured in allergic subjects after 30s of habitual eye rubbing was comparable with that obtained in normal subjects at all times between 0 and 30min. Although, CT in the allergic subjects were similar to those of the control subjects at all times, it varied between +10 and -7.5 μm following eye rubbing, with the temporal cornea showing consistent reductions in thickness in the subjects with allergy. However, this reduction was minimal and was considered to not be clinically relevant.     

Keratograph对不同阶段圆锥角膜干眼特征参数的检测及各参数对圆锥角膜的诊断价值

目的 应用非侵入式眼表综合分析仪Keratograph比较不同阶段圆锥角膜和正常角膜的干眼特征参数,探讨干眼特征参数在圆锥角膜诊断中的作用.方法 选取2015年5月至2016年12月就诊于我院的圆锥角膜患者35例(44眼)作为圆锥角膜组,另选拟进行激光角膜屈光手术患者45例(45眼)作为正常角膜组.两组患者年龄差异无统计学意义(P＞0.05).根据Amsler-Krumeich分级法将圆锥角膜患者按照严重程度分为轻度圆锥角膜19眼,中度15眼,重度10眼.利用眼表综合分析仪Keratograph检测患者双眼非侵入式首次泪膜破裂时间(tear break-up time,BUT)、平均BUT、泪河高度及眼红指数.采用ROC曲线分析不同指标对圆锥角膜的诊断价值.结果 圆锥角膜组的水平中央曲率、垂直中央曲率、表面变异指数、圆锥角膜指数、角膜后表面高度、眼红指数均高于正常角膜组,差异均有统计学意义(均为P＜0.05).圆锥角膜组的首次BUT、平均BUT、泪河高度均小于正常角膜组,差异均有统计学意义(均为P ＜0.05).不同程度圆锥角膜患者的水平中央曲率、垂直中央曲率、表面变异指数、圆锥角膜指数、角膜后表面高度、首次BUT、平均BUT间差异均有统计学有意义(均为P＜O.05).中度组和重度组首次BUT、平均BUT均低于轻度组,差异均有统计学意义(均为P＜0.05),但中度组和重度组间差异均无统计学意义(均为P＞0.05).平均BUT与水平中央曲率、垂直中央曲率、表面变异指数、圆锥角膜指数、角膜后表面高度均呈负相关关系(均为P＜0.05).而平均BUT与泪河高度和眼红指数间无相关性(均为P＞0.05).分别将平均BUT、泪河高度、眼红指数和圆锥角膜指数作为诊断指标,作ROC诊断曲线.圆锥角膜指数的ROC曲线下面积最大,AUC为0.985,95％置信区间为0.963 ～1.000(P＜0.001).此外,ROC曲线下面积平均BUT＞泪河高度＞眼红指数,诊断效果均差于圆锥角膜指数,差异均有统计学意义(均为P ＜0.001).结论 眼表综合分析仪Keratograph能够有效地测量角膜的干眼特征参数,其测量参数中平均BUT对圆锥角膜的诊断价值最高,对轻度圆锥角膜患者的诊断更有意义.     

Genetic factors influencing the reduction of central corneal thickness in disorders affecting the eye

Background: The aim was to summarize and discuss the current knowledge about genetic factors influencing the reduction of central corneal thickness (CCT) in disorders affecting the eye, such as primary open-angle glaucoma (POAG), brittle cornea syndrome (BCS), keratoconus (KTCN), Ehlers–Danlos syndrome (EDS; types I, II, and VI), osteogenesis imperfecta (OI), and myopia.

Materials and methods: A review of the published literature by use of key databases such as PubMed was undertaken in accordance with PRISMA guidelines and experience based on own research findings was applied.

Results: The differences in CCT measurements among those affected with diverse disorders and healthy individuals were evaluated. Then we considered the influence of genetic factors on CCT reduction. Disorders were compared based on phenotypes and sequence variants found in patients.

Conclusions: Specific sequence variants in COL8A2, PRDM5 and ZNF469, COL5A1 and ZNF469, and COL5A1 and COL5A2 could probably contribute to a CCT reduction in POAG, BCS, KTCN, and EDS, respectively. Similar sequence variants and phenotypes were identified and assessed in more than one disease.     

干燥环境相关性干眼的发病机制研究进展

干燥环境相关性干眼是指由长期处于低湿度环境中引起的干眼,与生活环境密切相关。目前干燥环境相关性干眼的发病机制尚不完全明确。炎症是干眼发病机制的关键一环,暴露于干燥环境在干眼的炎症进程中起着重要的作用,主要表现为干燥应激对眼表各方面产生不利影响,促进炎症,进而引起干眼。本文将从干燥环境出发,从眼表免疫稳态失衡、泪膜稳定性下降、氧化应激、神经调控异常几个方面对干燥环境因素在眼表炎症中的作用进行综述,以期全面认识干燥环境对干眼发病的影响,重视干燥环境因素在干眼诊疗中的作用。     

Polymorphism Analysis of VSX1 and SOD1 Genes in Greek Patients with Keratoconus

Background: A number of mutations in the VSX1 and SOD1 genes have been reported to be associated with keratoconus (KC), however the results from different studies are controversial. In this study, we conducted the genotyping of common polymorphisms [VSX1: D144E, H244R, R166W, G160D; SOD1: intronic 7-base deletion (c.169?+?50delTAAACAG)], in a case–control sample panel of the Greek population.

Materials and methods: A case–control panel, with 33 KC patients and 78 healthy controls, were surveyed. DNA from each individual was tested for the VSX1: D144E, H244R, R166W, G160D and SOD1: intronic 7-base deletion (c.169?+?50delTAAACAG) polymorphisms by direct sequencing.

Results: We observed no polymorphisms of the VSX1 gene in the case–control panel. Concerning the SOD1 intronic 7-base deletion (c.169?+?50delTAAACAG), our findings suggest that heterozygous carriers are over-represented among KC cases compared to healthy controls (p?=?0.002).

Conclusions: We cannot confirm the previously reported association of the polymorphism in the VSX1 gene with KC. Our results suggest a possible causative role of SOD1 in the pathogenesis of KC. Further studies are required to identify other important genetic factors involved in the pathogenesis and progression of KC.     

Autologous serum in the management of recalcitrant dry eye syndrome

Purpose: To evaluate the efficacy and safety of long‐term application of autologous serum eye drops treating recalcitrant dry eye syndrome. Methods: A retrospective chart review was conducted of patients who had serum eye drops between May 2001 and March 2006. The clinical data collected included sex, age, indications for serum eye drops, frequency of lubricant eye drops use before and after serum eye drop treatment, Schirmer tear function test with anaesthesia, fluorescein staining at baseline and at follow up and changes in subjective symptoms. Results: There were 46 eyes of 23 patients (19 female and 4 male) in the study group. The average follow‐up period was 17.3 months (range 6–55 months). Corneal fluorescein staining of 34 eyes (73.9%) showed improvement at follow up. Sixteen patients (32 eyes, 69.6%) reported a decreased frequency of lubricant use including eight patients (16 eyes, 34.8%) who used only serum eye drops for dry eye treatment. Eighteen patients (35 eyes, 76.1%) reported subjective improvement after using serum eye drops. No significant complications were reported in this study. Conclusion: Serum eye drops can be effective in treating recalcitrant dry eye syndrome and should be available as a management option when other treatments have failed. Meticulous attention must be paid to the possible contamination of the bottle to minimize the risk of infection.     

Keratoconus in Asians: demographics, clinical characteristics and visual function in a hospital-based population

Background: To describe the demographics, clinical characteristics and visual function of Asian patients with keratoconus managed in a tertiary eye centre. Design: Prospective cross‐sectional study. Participants: 116 patients with clinically evident or suspected keratoconus (on videokeratography) recruited over 11 months. Methods: A standardised interview, full ophthalmic examination, refraction and corneal topography were performed. Visual function was assessed with the VF‐14 questionnaire. Main Outcome Measures: Demographics, clinical characteristics and visual function. Results: Mean age of our patients was 29.5 ± 9.40 years on enrolment, 62.9% were male, and the ethnic distribution was 60.3% Chinese, 13.8% Malays and 9.5% Indians. Clinically evident keratoconus was present bilaterally in 65 patients (56.0%) and unilateral keratoconus in five patients (4.3%). Five patients (4.3%) had a family history of keratoconus. The majority of patients were managed with contact lenses (60.8%) or glasses (24.5%). Eye rubbing was common (68%) as were asthma (26.3%) and eczema (18.4%). Conical protrusion was the commonest sign (75.3%). The mean cylinder was higher in keratoconus eyes compared with keratoconus suspect eyes (?4.01 vs. ?1.27, P < 0.001), and best‐corrected visual acuity was poorer (0.19 vs. 0.05, P < 0.001). Unaided visual acuity was significantly worse with increasing age (P = 0.016). On the VF‐14, 32% scored 90 or less (out of 100), reflecting difficulties with vision‐related daily activities. Conclusions: Our Asian patients with keratoconus had similar demographic and clinical characteristics to patients in Western populations. Even with apparently good visual acuity, some patients still experience substantial impairment in vision‐related activities.     

Investigation of the Efficacy of the Cone Location and Magnitude Index in the Diagnosis of Keratoconus

Purpose: The aim of this study was to investigate the sensitivity, specificity, and accuracy of The Cone Location and Magnitude Index (CLMI) in keratoconus diagnosis. Methods: 301 eyes of 159 keratoconus patients and 394 eyes of 265 refractive surgery candidates as a control group were enrolled in this retrospective clinical study. CLMI was compared with keratometric corneal topography parameters, wavefront aberrations, and pachymetry data derived from optical coherence tomography using independent sample t-tests and ROC curves. Logistic regression analysis was applied to determine the most accurate parameter in keratoconus diagnosis. Pearson’s correlation analysis was used to determine the correlation between CLMI and the other measurements. Results: Average axial CLMI (aCLMI) was 8.19?±?6.15 D in the keratoconus group and 0.83?±?0.62 D in the control group (p?=?0.001). aCLMI had the greatest sensitivity (89%), specificity (94%), and accuracy (92%) for the keratoconus diagnosis at the best cut-off point of 1.82 according to the ROC curve. Logistic regression analysis selected aCLMI as the most accurate measurement among the other parameters (accuracy 92.8%). aCLMI showed strongest correlations with coma-like aberrations (r?=?0.881), total high-order aberrations (r?=?0.858), and vertical coma (r?=??0.814), respectively. Conclusion: CLMI is a robust index for screening keratoconus with high sensitivity, specificity, and accuracy.     

DNA甲基化在遗传性眼病发病机制中的作用

表观遗传学作为近几年兴起的遗传学分支,受到越来越多关注。表观遗传学指基因序列未改变,通过DNA甲基化,组蛋白修饰,微小RNA等修饰作用使细胞功能发生改变,其中以DNA甲基化的研究较为广泛和深入。现有大量关于眼部遗传疾病的发生机制的研究,除了筛选出越来越多的致病基因外,研究者也发现DNA甲基化在遗传性眼病的发病机制中有着复杂而重要的作用。笔者旨在对各种遗传性眼病发病机制中DNA甲基化的作用做一归纳。     

Th细胞及其相关因子参与干眼发病机制的研究进展

干眼是眼表免疫稳态失衡所致的炎症性疾病.由泪膜、角结膜上皮、睑板腺、泪腺以及联络它们的神经通路共同组成的泪腺功能单位(lacrimal functional unit,LFU)是维持眼表生理稳态的完整系统,任何影响这一系统的因素都可以干扰眼表免疫平衡机制引发炎症反应,并最终导致干眼的发生.研究发现,Th细胞及其相关因子在干眼炎症过程中发挥了重要作用,影响Th细胞分化或Th细胞相关因子的异常表达可以控制眼表炎症反应,有助于恢复眼表免疫稳态,有效抑制干眼病理改变和缓解临床症状.     

巩膜镜矫正圆锥角膜的临床效果观察

目的：探讨临床上巩膜镜治疗圆锥角膜的有效性。方法：回顾性研究。选择2020 年10 月至2021 年3月于南京医科大学眼科医院验配巩膜镜的圆锥角膜患者18例（26眼）。根据圆锥角膜AmeslerKrumeich分级,I级9眼,II级3眼,III级4眼,IV级10眼。所有患者均经规范验配程序试戴硬性透气 性接触镜（RGPCL）,因RGPCL不耐受、RGPCL适配不佳等原因选择验配巩膜镜。所有患者均进行 视力、屈光度、裂隙灯显微镜、眼底和Pentacam检查等。应用巩膜镜试戴片试戴,分别通过裂隙灯 显微镜观察、荧光素染色及眼前节光学相干断层扫描（OCT）进行适配评估。评估镜片与中央角膜和 周边间隙,以及周边着陆区匹配情况,并评估戴镜后的最佳矫正视力（BCVA）及主观舒适度。采用 Friedman检验进行统计学分析。结果：所有圆锥角膜患者初戴巩膜镜时,裂隙灯显微镜观察示巩膜 镜定位良好。通过前节OCT观察初始角膜中央间隙为（212±58）μm;配戴巩膜镜4 h后,角膜中央间隙为 （164±58）μm,鼻侧为（101±38）μm,下方为（224±135）μm,颞侧为（103±72）μm,上方为（89±45）μm, 镜片边缘结膜血管未见异常。裸眼视力（UCVA）、框架眼镜BCVA、RGPCL配戴后BCVA及巩膜镜 配戴后BCVA（LogMAR）分别为1.35（1.00, 2.00）、0.52（0.22, 0.79）、0.15（0, 0.30）、0.10（0, 0.22）, 各视力差异有统计学意义（χ2 =67.11, P<0.001）。巩膜镜配戴后BCVA较UCVA、框架眼镜BCVA明显 改善,差异有统计学意义（χ2 =59.90, P<0.001; χ2 =31.08, P=0.001）;巩膜镜配戴后BCVA与RGPCL配 戴后BCVA差异无统计学意义（P=1.000）。配戴巩膜镜4 h后,22眼（22/26）主诉戴镜后舒适或非常舒 适;24眼（24/26）主诉戴镜视物良好或非常良好。结论：圆锥角膜配戴巩膜镜定位良好,舒适度也良 好,通过配戴巩膜镜可有效提升矫正视力。巩膜镜是圆锥角膜患者一种有效的治疗方式。     

Shotgun Proteomics for the Identification and Profiling of the Tear Proteome of Keratoconus Patients

PurposeThe qualitative approach followed in this study aims to obtain an extensive view of the keratoconus (KC) tear proteome, which could highlight proteins previously undetected and enlarge our knowledge of the disease''s pathophysiology.MethodsTwenty-five patients diagnosed with KC and 25 control subjects were studied in a prospective, cross-sectional study. KC screening examinations, including clinical and tomographic examinations, were performed on all participants. Tear samples were collected using Schirmer strips and analyzed by liquid chromatography-tandem mass spectrometry in a data-dependent workflow. A spectral count was used as a semiquantification tool. The tear proteomes of both groups were identified and profiled, and the functional interactions and biological characterization of differential proteins were analyzed using in silico tools.ResultsWe identified a total of 232 proteins, of whom 133 were expressed in both groups’ samples; 41 were observed only in control samples and 58 were identified just in tears of patients with KC. A semiquantitative analysis showed the dysregulation of 17 proteins in the KC samples. An in silico analysis linked proteins only expressed in KC samples to oxidative stress, skin development, and apoptosis. The dysregulation of proteins involved in iron transport, inflammation, oxidative stress, and protease inhibition was observed in the semiquantitative results.ConclusionsA shotgun analysis showed that the tear proteome of patients with KC differed from controls by more than one-third of the total proteins identified, highlighting the relationship of the proteins only expressed in KC tears with processes of cell death, oxidative damage, and inflammation. The underexpression of proteins involved in iron pathways might support the iron imbalance as a contributing factor to cellular damage and death in KC disease.     

眼手术相关性干眼发病机制的研究进展

随着各类眼科手术的快速发展和广泛开展,术后视觉质量受到了更多的关注。干眼(dry eye)是眼科手术后的常见并发症,常引起眼部不适、视物模糊等症状以及其他干眼体征。眼手术相关性干眼是干眼的一个常见类型,通常由于手术损伤角结膜组织及神经、破坏泪膜稳定性、术后炎症反应以及围术期局部用药等多种因素导致。本文就眼手术相关性干眼的危险因素、不同眼科手术导致干眼的发病机制以及对此类干眼的预防等进行综述,以期眼科医生在临床中能够减少眼手术相关性干眼的发生及发展,提高眼科手术后的视觉质量及生活质量。     

Evaluating the Association between Keratoconus and Reported Genetic Loci in a Han Chinese Population

Background: Keratoconus (KC) is a complex degenerative disorder of the cornea. Genetic, environmental, and lifestyle factors may all contribute to the pathogenesis of KC. Most of the reported KC-associated SNPs have been detected in Caucasians and Australians. To investigate whether the reported associated SNPs can be found in a Chinese population, we performed a replication study of the significantly associated SNPs.

Materials and Methods: A total of 210 unrelated Chinese KC patients and 191 unrelated controls were included in the present study. SNPs rs4954218 (Near RAB3GAP1 (5′)), rs4894535 (FNDC3B), rs2956540 (LOX), rs3735520 (Near HGF (5′)), rs1324183 (MPDZ-NF1B), rs1536482 (RXRA-COL5A1), rs7044529 (COL5A1), rs2721051 (Near FOXO1 (3′)), rs9938149 (BANP-ZNF469) and rs6050307 (VSX1) were assessed for their association with KC. The genotype of each SNP was detected using the Sequenom MassARRAY-Assay.

Results: SNP rs1324183 located in MPDZ-NF1B was associated with an increased risk of KC (OR?=?3.108, 95% CI?=?1.366–7.072, p?=?0.005), and SNP rs2956540 in the LOX gene may confer a reduced risk of KC with a borderline p value in our population (OR?=?0.664, 95% CI?=?0.447–0.986, p?=?0.042). No significant difference was observed between patients and controls in the other eight SNP genotypes and allele frequencies.

Conclusions: The replication association of rs1324183 (MPDZ-NF1B) with KC in our population and the results, which are identical to those in different populations, suggest that rs1324183 (MPDZ-NF1B) is a common genetic risk for KC and should be further investigated.     

Dry eye: an update on clinical diagnosis,management and promising new treatments

Dry eye conditions are prevalent with one in four to five patients presenting to eye care practitioners having dry eye signs and/or symptoms. An intimate relationship exists between the ocular surface and the tear film. The cycle of tear film instability and ocular surface damage characteristic of dry eye conditions suggests that dry eye represents a dysfunction of an integrated ocular surface‐lacrimal gland unit. Therefore, dry eye is a multifactorial condition and an approach based on clinical subtypes is required for diagnosis and management. There is increasing evidence that inflammation is a contributing and exacerbating factor in dry eye conditions and anti‐inflammatory or immunomodulatory therapy for chronic dry eye conditions may facilitate ocular surface healing. Other promising new treatments for dry eye include new generation artificial tear polymers and preservative systems, secretagogues, topical androgen supplements and surgical techniques for ocular surface reconstruction.