Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

Bleb needling outcomes for failed trabeculectomy blebs in Asian eyes: a 2-year follow up

·AIM: To describe the outcomes of bleb needling in primary glaucoma in an Asian tertiary eye centre over a2 y period. To compare the success rates between primary angle-closure glaucoma(PACG) and primary open angle glaucoma(POAG). Lastly, to identify factors associated with success of bleb needling.·METHODS: This was a retrospective review of 227 patients who underwent bleb needling between June2009 and June 2011 in Singapore National Eye Centre.The 5-fluorouracil(5-FU) augmented bleb needling was performed either at the slit lamp or in the operating theatre. Repeat bleb needlings were performed as necessary. Complete success was defined as maintenance of intraocular pressure(IOP) ≥6 mm Hg and ≤21 mm Hg, in the absence of further surgery or use of antiglaucoma medication. Qualified success met the above criteria with or without use of antiglaucoma medications.· RESULTS: One hundred and seventy-five eyes completed the two-year follow up. Sixty-nine percent of participants had POAG and 31% had PACG. The mean interval between filtering surgery and bleb needling was299.9 ±616.4d for POAG and 167.1 ±272.2d for PACG.Mean needling attempts were 1.9±1.4 and 2±1.6 for POAG and PACG respectively. In general, there was a statistically significant reduction of IOP ranging from21.9% to 26.8% from month 1 through to month 24. The complete success rates at month 6 were 70.0% for POAG and 65.7% for PACG. At month 12, this decreased to62.2% for POAG and PACG and at month 24, 57.9% for POAG and 63.0% for PACG respectively. The qualified success rates at month 6 for POAG and PACG were23.8% and 29.9% respectively, 32.2% and 29.2% at month12, and 34.7% and 29.6% at month 24. The success ratesbetween POAG and PACG were not significantly different(P 】0.05 for complete and qualified success at months 6,12 and 24). An increased number of needlings and higher pre-needling IOP were associated with failure.·CONCLUSION: The 5-FU augmented bleb needling within one year of trabeculectomy in Asian eyes can provide clinically significant IOP lowering of more than20% for 2y. POAG and PACG had similar complete success rates(58% and 63% respectively). Factors associated with greater risk of procedure failure included increased number of needlings and higher pre-needling IOP. Asian eyes have a greater propensity for scarring but bleb needling, if performed in a timely manner can rescue bleb function.

Prevalence and associations of non-retinopathy ocular conditions among older Australians with self-reported diabetes:The National Eye Health Survey

AIM:To determine the prevalence and associations of non-retinopathy ocular conditions among older Australian adults with diabetes.METHODS:Multistage random-cluster sampling was used to select 3098 non-indigenous Australians aged 50 y or older(46.4%male)and 1738 indigenous Australians aged 40 y or older(41.1%male)from all levels of geographic remoteness in Australia.Participants underwent a standardised questionnaire to ascertain diabetes history,and a clinical examination to identify eye disease.We determined the prevalence of uncorrected refractive error,visually significant cataract,cataract surgery,age-related macular degeneration,glaucoma,ocular hypertension,retinal vein occlusion and epiretinal membrane among those with and without self-reported diabetes.RESULTS:Participants with self-reported diabetes had a higher prevalence of cataract surgery than those without diabetes(28.8%vs 16.9%,OR 1.78,95%CI:1.35-2.34 among non-indigenous Australians,and 11.3%vs 5.2%,OR 1.62,95%CI:1.22-2.14 among indigenous Australians).Diabetic retinopathy(DR)increased the odds of cataract surgery among self-reported diabetic indigenous and nonindigenous Australians(OR 1.89,P=0.004 and OR 2.33,P<0.001 respectively).Having diabetes for≥20 y and having vision-threatening DR increased the odds of cataract surgery among indigenous Australians with diabetes(OR 3.73,P=0.001 and 7.58,P<0.001,respectively).CONCLUSION:Most non-retinopathy ocular conditions are not associated with self-reported diabetes.However,to account for Australia’s worsening diabetes epidemic,interventions to reduce the impact of diabetes-related blindness should include increased cataract surgery services.

In vitro eye embryogenesis from induced pluripotent stem cells for ocular surface disease treatment

In their letter to Nature,Hayashi et al.describe a new method for the generation of ocular surface epitheliumlike cells by incubating human induced pluripotent stem cells(iPS)into four defined concentric zones mimicking the developing eye,which the authors named as self-formed ectodermal autonomous multi-zone(SEAM)(1).

Clinical associations of corneal neuromas with ocular surface diseases

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Mixed-decomposed convolutional network:A lightweight yet efficient convolutional neural network for ocular disease recognition

Eye health has become a global health concern and attracted broad attention.Over the years,researchers have proposed many state-of-the-art convolutional neural networks(CNNs)to assist ophthalmologists in diagnosing ocular diseases efficiently and precisely.However,most existing methods were dedicated to constructing sophisticated CNNs,inevitably ignoring the trade-off between performance and model complexity.To alleviate this paradox,this paper proposes a lightweight yet efficient network architecture,mixeddecomposed convolutional network(MDNet),to recognise ocular diseases.In MDNet,we introduce a novel mixed-decomposed depthwise convolution method,which takes advantage of depthwise convolution and depthwise dilated convolution operations to capture low-resolution and high-resolution patterns by using fewer computations and fewer parameters.We conduct extensive experiments on the clinical anterior segment optical coherence tomography(AS-OCT),LAG,University of California San Diego,and CIFAR-100 datasets.The results show our MDNet achieves a better trade-off between the performance and model complexity than efficient CNNs including MobileNets and MixNets.Specifically,our MDNet outperforms MobileNets by 2.5%of accuracy by using 22%fewer parameters and 30%fewer computations on the AS-OCT dataset.

rhG-CSF促进体外培养神经干细胞的增殖

目的探讨重组人粒细胞集落刺激因子(rhG-CSF)对小鼠胚胎神经干细胞(NSCs)增殖的作用。方法分离培养小鼠NSCs,通过向培养基中添加G-CSF(10、30、60、100和200μg/L),四甲基偶氮唑蓝(MTT)比色法以及5-溴-2'-脱氧尿苷(BrdU)免疫荧光染色标记检测NSCs的增殖。免疫印迹法检测NSCs增殖时信号转导与转录激活因子3(STAT3)和磷酸化信号转导和转录激活因子3(p-STAT3)的表达。结果神经干细胞表达G-CSF受体,细胞活性随G-CSF的浓度不同表现出一定的剂量依赖性,当G-CSF的浓度为100μg/L时细胞的活性最高。G-CSF处理组的细胞增殖活性明显高于对照组。进一步证实,在G-CSF处理后,p-STAT3的表达则在5 min开始升高,30 min到达峰值,之后开始下降,至75 min接近正常水平。加入G-CSF受体的抗体后,p-STAT3的活化现象消失,并且细胞的增殖也明显低于G-CSF作用组,和对照组接近。结论 rhG-CSF可促进小鼠NSCs的增殖,其作用机制可能是通过细胞表面的G-CSF-R促进STAT3的活化。G-CSF可能作用于内源性NSCs的活化和增殖。

关注和了解人泪液蛋白质组学的研究及其临床意义

泪液是眼表的一种成分复杂的体液,可能含有数千种蛋白质及其他分子,研究已证实这些成分的改变在眼病的发生和发展中具有重要作用.泪液标本相对容易获取,可用于眼表疾病及其他眼科疾病或系统性疾病的研究,也可用于生物标志物的鉴定,因此是临床诊疗和新药研发的重要依据.跟踪和了解泪液蛋白质组学的研究技术和泪液蛋白质组学的研究进展有助于相关研究的深入开展,眼科医师应密切关注眼表疾病泪液蛋白质组分的变化及其临床意义,关注泪液蛋白质组学未来的发展方向,以指导相关眼病的诊疗和研究.

Corneal neuromediator profiles following laser refractive surgery

Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy.Following laser refractive surgery,the corneal nerves,epithelial and stromal cells release neuromediators,including neurotrophins,neuropeptides and neurotransmitters.Notably,nerve growth factor,substance P,calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration.Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced.In this review,we will discuss the(1)Functions of neuromediators and their physiological and clinical significance;(2)Changes in the neuromediators following various laser refractive surgeries;(3)Correlation between neuromediators,ocular surface health and corneal nerve status;and(4)Future directions,including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery,and as adjuncts to aid in corneal regeneration after laser refractive surgery.

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

Corneal re-innervation following refractive surgery treatments

Laser refractive surgery is one of the most performed surgical procedures in the world. Although regarded safe and efficient, it has side effects. All of the laser based refractive surgical procedures invoke corneal nerve injury to some degree. The impact of this denervation can range from mild discomfort to neurotrophic corneas. Currently, three techniques are widely used for laser vision correction: small incision lenticule extraction, laser-assisted keratomileusis in situ and photorefractive keratotomy. Each of these techniques affects corneal innervation differently and has a different pattern of nerve regeneration. The purpose of this review is to summarize the different underlying mechanisms for corneal nerve injury and compare the different patterns of corneal reinnervation.

Analysis of corneal nerve plexus in corneal confocal microscopy images

Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of the trigeminal nerve and enter the cornea at the limbus radially from all directions toward the central cornea at the level of anterior and middle stroma.The subepithelial nerve plexus lies at the interface between the Bowman layer and anterior stroma.They then divide into smaller branches and turn 90°toward Bowman’s layer(Muller et al.,2003),travelling between Bowman’s layer and the basal epithelial layer and forming the sub-basal nerve plexus(Muller et al.,2003).

Iris color and associated pathological ocular complications:a review of epidemiologic studies

AIM:To elucidate the associations of iris color with major eye diseases.· METHODS:A systematic search on Medline with coverage up to August 2013 was conducted. Assessment of the quality of studies based on their levels of evidence was in accordance with the Centre for Evidence-Based Medicine, Oxford, United Kingdom.RESULTS:A relationship between darker iris color and an increased risk of age-related cataract has been reported from cross-sectional studies and prospective cohort studies. There was no consistent evidence supporting a major role of iris color in the development or progression of age-related macular degeneration. The association of iris color with ocular uveal melanoma has been confirmed by a meta-analysis of observational studies previously. The etiologic synergism between light iris color and environmental exposure such as UV the exposure of UV radiation was found. There were no studies evaluating the refractive associations with iris color but there may be a possible link between iris color and myopia.CONCLUSION:Darker iris color is associated with an increased risk of cataract and a reduced risk of ocular uveal melanoma. The association of iris color with agerelated macular degeneration is not confirmed.Ophthalmologists should be aware that the risk of ocular disorders appears to vary by differences in iris color.

Comparison of Dextran Perfusion and GSI-B4 Isolectin Staining in a Mouse Model of Oxygen-induced Retinopathy

Purpose: Oxygen-induced retinopathy(OIR) is a robust and widely used animal model for the study of retinal neovascularization(NV). Dextran perfusion and Griffonia simplicifolia isolectin B4(GSI-B4) staining are two common methods for examining the occurrence and extent of OIR. This study provides a quantitative comparison of the two for OIR detection.Methods: At postnatal day 7(PN7), fifteen C57 BL / 6J mice were exposed to a 75% hyperoxic condition for 5 days and then returned to room air conditions. At PN17, the mice received intravitreal injection of GSI-B4 Alexa Fluor 568 conjugate. After 10 hours, they were infused with FITC-dextran conjugate via the left ventricle. Retinal flat mounts were photographed by confocal microscopy. Areas with fluorescent signals and the total retinal areas were quantified by Image J software.Results:Both GSI-B4 and dextran detected the peripheral neovascular area. The mean hyper fluorescence area was 0.33 ±0.14% of whole retinal area determined by GSI-B4 staining and 0.25±0.28% determined by dextran perfusion. The difference between the two measures was 0.08%(95% CI:-0.59%,0.43%)..The Pearson correlation coefficient between the two methods was 0.386,P =0.035..The mean coincidence rates were 14.3 ±13.4% and 24.9 ±18.5% for GSI-B4 and dextran staining, respectively.Conclusion:.Both methods can complement each other indemonstrating and quantitatively evaluating retinal NV. A poor agreement was found between the two methods;.GSI-B4 isolectin was more effective than FITC-dextran perfusion in evaluating the extent of retinal NV in a mouse model of OIR.

Top 100 cited articles in ophthalmic epidemiology between 2006 and 2016

AIM: To identify the most-cited articles in ophthalmic epidemiology over the last decade.METHODS: We performed a cited reference search on articles that were included in the ISI Web of Science database using the terms "Epidemi*" AND "ophthalm*" AND "population*" during year 2006 to 2016. TOP 100 most cited articles(T100) in ophthalmic epidemiology were short listed and analysed using bibliometrics.RESULTS: These top 100 articles in ophthalmic epidemiology were cited between 61 to 333 times. Of these T100 articles, 36% originated from United States, and 34% were published in the Ophthalmology journal. The three major topics identified were age-related macular degeneration(AMD, n=23), glaucoma(n=16) and visual impairment(n=12). The top-cited article was a study on outdoor activities and its association with the prevalence of myopia in school-aged children, published in 2008. CONCLUSION: This bibliometric analysis provides useful insights into the current development in ophthalmicepidemiology in the past decade and can help recognizing the quality of the researches, discoveries, and trends steering ophthalmic epidemiology.

关注蛋白组学和代谢组学在糖尿病视网膜病变中的临床应用转化研究

糖尿病视网膜病变(DR)是糖尿病的多种并发症之一,是世界范围内主要的致盲眼病,早期发现和早期干预可以减少致盲性DR的发生。近年来随着高通量组学技术的发展,蛋白组学和代谢组学在DR的早期诊断、发病机制研究以及治疗靶点探索等方面展现出强大的应用价值。传统生物标志物如糖尿病病程和糖化血红蛋白等具有较高的预测DR进展的能力,但临床上仍然缺乏能够体现DR病理机制的独立预测因子。人工智能和机器算法等技术推动了蛋白组学和代谢组学对DR新型生物标志物的探索,使得新型生物标志物更加无创,稳健和敏感。在临床实践中,对预后存在差异的患者进行蛋白质和代谢物的检测,可以帮助临床医生从蛋白组学和代谢组学角度理解患者的异质性,推动了DR精准医疗的开展。本文对蛋白组学和代谢组学在DR的新型生物标志物筛选、发病机制探索和精准医疗等方面采取的技术和策略进行阐述以期进一步推动这个领域的临床应用转化研究。

Cost-benefit and discriminant validity of a stepwise dementia case-finding approach in an Asian older adult community

Background Case-finding is a recommended approach for dementia early detection in the community.Aims To investigate the discriminant validity and cost-effectiveness of a stepwise dementia case-finding approach in a Singaporean older adult community.Methods The two-phase study was conducted in the community from 2009 to 2015 in Singapore.A total of 3780 participants(age≥60 years)completed phase I(a brief cognitive screening);918 completed phase II and were included in the final analysis.In phase I,all participants were administered the Abbreviated Mental Test(AMT)and the Progressive Forgetfulness Question(PFQ).Those who screened positive on either test were invited to phase II,whereby the Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and a formal neuropsychological battery were administered,followed by the research diagnosis of no cognitive impairment,cognitive impairment no dementia(CIND)-Mild(≤2 impaired cognitive domains),CIND-Moderate(>2 impaired domains)or dementia.Receiver operating characteristic curve analyses were conducted for the different cognitive instruments.All discriminant indices were calculated,including sensitivity,specificity,positive and negative predictive values(NPV)and accuracy.Cost-effectiveness analysis was conducted by estimating the amount of screening time needed and the number of older adults requiring re-evaluation in two case-finding scenarios,ie,with or without preselection by the PFQ.Results The stepwise case-finding approach(preselection by the PFQ,then MMSE or MoCA or AMT)showed an excellent NPV(>99%)and accuracy(>86%)for excluding dementia-free cases.Without preselection by the PFQ,screening time for the three cognitive tools were 317.5,317.5 and 254 hours,with 159,302 and 175 screen-positive older adults involved in further evaluation.By adopting the stepwise case-finding approach,total screening time were 156.5,156.5 and 126.2 hours,which decreased by 50.7%,50.7% and 50.3% as compared with those without preselection.Furthermore,after preselection,only 98,167 and 145 screen-positive older adults required further evaluation,corresponding to a reduction of 38.4%,44.7% and 17.1% in the numbers compared with those without preselection.Conclusions A stepwise approach for dementia case-finding should be implemented in the community to minimise the time and resources needed for large-scale early detection of dementia.

阿托品治疗近视儿童的多焦视网膜电图

Aim: To assess retinal function by multifocal electroretin-ogram (mfERG) in children on atropine eye drops for the treatment of myopia. Methods: mfERGs were recorded in children receiving atropine eye drops (n=48) once daily for 2 years and in those receiving placebo eye drops (n=57) for a similar time. All recordings were performed between the second and third month of cessation of atropine/placebo treatment by a masked investigator. The amplitude and implicit time of the first order kernel (k1) and first slice of the second order kernel (k21) of mfERG responseswere used to study the outer and inner retinal function, respectively. Results: There was no significant reduction in k1 response amplitudes of the atropine group compared to that of the placebo group (N1, P=0.181; P1, P=0.150). No significant difference in the k1 response implicit times between the groups was found (N1, P=0.767; P1, P=0.849). The differences in the k21 amplitudes and implicit times between the groups were not statistically significant (k21 amplitude, P=0.058; k21 implicit time, P=0.156). Conclusions: Daily atropine usage over 2 years for the treatment of myopia has no significant effect on retinal function as demonstrated by recordings of mfERG.

Neuroaxonal and cellular damage/protection by prostanoid receptor ligands,fatty acid derivatives and associated enzyme inhibitors

Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other stimuli.Prostaglandin D_(2),prostaglandin E_(2),prostaglandin F_(2)α,prostaglandin I_(2)and thromboxane-A_(2)interact with five major receptors(and their sub-types)to elicit specific downstream cellular and tissue actions.In general,prostaglandins have been associated with pain,inflammation,and edema when they are present at high local concentrations and involved on a chronic basis.However,in acute settings,certain endogenous and exogenous prostaglandins have beneficial effects ranging from mediating muscle contraction/relaxation,providing cellular protection,regulating sleep,and enhancing blood flow,to lowering intraocular pressure to prevent the development of glaucoma,a blinding disease.Several classes of prostaglandins are implicated(or are considered beneficial)in certain central nervous system dysfunctions(e.g.,Alzheimer’s,Parkinson’s,and Huntington’s diseases;amyotrophic lateral sclerosis and multiple sclerosis;stroke,traumatic brain injuries and pain)and in ocular disorders(e.g.,ocular hypertension and glaucoma;allergy and inflammation;edematous retinal disorders).This review endeavors to address the physiological/pathological roles of prostaglandins in the central nervous system and ocular function in health and disease,and provides insights towards the therapeutic utility of some prostaglandin agonists and antagonists,polyunsaturated fatty acids,and cyclooxygenase inhibitors.

Effect of Changing Heart Rate on the Ocular Pulse and Optic Nerve Head Deformations

Objective To study the effect of changing heart rate on the ocular pulse and optic nerve head deformations with a viscoelastic lamina cribrosa.Methods An FE model of a healthy eye was reconstructed.The choroid was biphasic and consisted of a solid phase(connective tissues)and a fluid phase(blood).The LC was viscoelastic as characterized by a stress-relaxation test.We applied arterial pressures at 18 entry sites(posterior ciliary arteries)and venous pressures at 4 exit sites(vortex veins).The heart rate was varied from 60 bpm to 120 bpm(increment:20 bpm).We reported the ocular pulse amplitude(OPA),pulse volume,optic nerve head(ONH)deformations and the dynamic modulus of the LC at different heart rates.Results With an increasing heart rate,the OPA decreased by 0.04 mmHg for every 10 bpm increase.The pulse volume also exhibited a linear relationship with heart rate,and decreased by 0.13 L.In addition,the storage modulus and the loss modulus of the LC center increased by 0.014 MPa and 0.04 MPa,respectively for every 10 pm increase in heart rate.Conclusions Our model predicted that the OPA,the pulse volume the ONH deformation decreased at a faster heartrate.We also found that the viscoelastic LC became stiffer with an increasing heart rate.Further studies are required to explore the potential links with the vascular dysregulation and axonal loss in glaucoma.