Distribution of IOP and its relationship with refractive error and other factors:the Anyang University Students Eye Study

AIM:To investigate the distribution of intraocular pressure(IOP)and its relationship with refractive error and other factors in university students from Anyang,China.METHODS:A university-based study was conducted.Subjects were invited to complete ophthalmic examinations,including visual acuity,noncontact tonometr y(NCT),cycloplegic autorefraction,and ocular biometry.Univariable and multivariable analyses were used to evaluate the associations between IOP and other factors.Only data from right eyes were used in analysis.RESULTS:A total of 7720 subjects aged 16 to 26 years old were included,and 2834(36.4%)of the participants were male.The mean IOP of the right eye for all subjects was 15.52±3.20 mm Hg(95%CI:15.45,15.59).Using multivariate linear regression analysis,IOP was found to correlate significantly with younger age(P<0.001;standardized regression coefficientβ,-0.061;regression coefficientβ,-0.139;95%CI:-0.18,-0.09),higher myopic refractive error(P=0.044;standardizedβ,-0.060;regression coefficientβ,-0.770;95%CI:-0.15,-0.002),higher central corneal thickness(P<0.001;standardizedβ,0.450;regression coefficientβ,0.044;95%CI:0.04,0.05),and shorter axial length(AL;P<0.001;standardizedβ,-0.061;regression coefficientβ,-0.163;95%CI:-0.25,-0.07).CONCLUSION:This study described the normal distribution of IOP.In Chinese university students aged 16-26 y,higherIOP is associated with younger age,higher myopic refractive error,higher thickness of the central cornea,and shorter AL.

Strategies to control myopia in children:a review of the findings from the Anyang Childhood Eye Study

Myopia in children remains a major public health problem worldwide,especially in some Asian countries such as China,Singapore and Japan.Although many interventions have been attempted,few has been proven to be effective in controlling onset and progression of myopia in children.Environmental factors,genetic susceptibility or ethnic differences can affect the efficacy of these interventions.However,many questions remain unclear and even controversial for controlling myopia.China has the biggest population with myopia,especially for children myopia.Thus,it is of importance to present what achievements Chinese scientists have made in the field of myopia control in children.We summarize the current findings on myopia control in children from the Anyang Childhood Eye Study,including epidemiological data,clinical trials,systematic reviews and meta-analyses,and compare them with studies in other countries to find potential clues for controlling myopia in children.

The Handan Offspring Myopia Study

The Handan Offspring Myopia Study(HOMS),whose participants came from 6 villages where all people aged≥30 years had taken part in the Handan Eye Study(HES)in 2006-2007,was designed to obtain the familial associations of myopia between parents and their offspring.From March 2010 to June 2010,of 1,238 eligible individuals,878 children(70.2%;52.6%male)from 541 families were recruited.The mean age of the children was 10.5±2.5 years.All the participants had a detailed eye examination and anthropometry examination.All examinations were performed using the same protocols and equipment in both HES and HOMS.Information of the parents was obtained from the HES.The results of the research showed that the myopic shift from parents to children was estimated to be approximately 1 D at 18 years of age.For near work and myopia,no association was found,except for the high near work subgroup with moderate outdoor activity levels.Besides a weak protective effect of outdoor activity on myopia in these rural children was observed.In the future,we plan to follow up these participants and investigate how the refraction of the children change,how myopia-genic activity changes and what effect does it have on myopia.The information will be important for the design of strategies to prevent and reduce myopia.

Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues

The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle glaucoma.However,the molecular basis and biological significance of the aging process in TM have not been fully elucidated.Here,we established a dynamic single-cell transcriptomic landscape of aged macaque TM,wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging.Furthermore,we divided TM cells into 13 clusters and performed an in-depth analysis on cluster O,which had the highest aging score and the most significant changes in cell proportions between the two groups.Ultimately,we found that the APOE gene was an important differentially expressed gene in cluster O during the aging process,highlighting the close relationship between cell migration and extracellular matrix regulation,and TM function.Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components,thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range.Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

Discovery of a normal-tension glaucoma-suspect rhesus macaque with craniocerebral injury:Hints of elevated translaminar cribrosa pressure difference

To the Editor:Normal-tension glaucoma(NTG)is a progressive optic neuropathy characterized by irreversible blindness with statistically normal intraocular pressure(IOP)(≤21 mmHg),^([1,2])which makes early-stage diagnosis in the clinical practice difficult.Pathophysiological pathways underlying NTG include vascular dysregulation,toxic metabolite accumulation,and elevated translaminar cribrosa pressure difference(TLCPD).^([3])Although various small animal models have provided evidence of different pathophysiological mechanisms,the complicated clinical phenotype cannot be fully imitated by secondary disease models,and the gap between rodents and humans weakens their translational potential.Thus,the pathological changes associated with NTG remain unclear.

Surgical outcomes of XEN45 implantation,trabeculectomy vs.penetrating canaloplasty in open-angle glaucoma:A non-randomized comparative study

To the Editor:Glaucoma is a leading cause of irreversible blindness worldwide.[1]Trabeculectomy with mitomycin C(MMC)has been the standard surgical intervention for reducing intraocular pressure(IOP)and slow down the progression of glaucoma.[2]However,some serious complications with devastating consequences can occur after trabeculectomy,such as bleb-related infections,suprachoroidal hemorrhage,vitreous hemorrhage,and malignant glaucoma.Over the last decade,many novel ophthalmic surgical devices have been used in glaucoma.The XEN45 microstent(Allergan,Dublin,CA,USA)is a hydrophilic cross-linked porcine gelatin stent.It is implanted ab-interno.

Pressure balance and imbalance in the optic nerve chamber： The Beijing Intracranial and Intraocular Pressure (iCOP) Study

To determine the interdependence of intracranial pressure(ICP) and intraocular pressure(IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure(LCP), optic nerve subarachnoid space pressure(ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP(via shunting cerebrospinal fluid(CSF) from the ventricle) were recorded. At baseline, all examined pressures were different(ICP>LCP>ONSP), but correlated(P<0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient(TLPG) remained stable(ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined(ICP-IOP independent zone). The optic nerve pressure gradient(ONPG) and trans-optic nerve pressure gradient(TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.

Changes in retinal and choroidal morphology after cerebrospinal fluid pressure reduction: a Beijing iCOP study

Dear Editor,Glaucoma is a multifunctional neurodegenerative disease and is the leading cause of irreversible blindness. It is characterized by progressive loss of retinal ganglion cells and their axons leading to visual field defects.

Association of three single nucleotide polymorphisms at the SIX1-SIX6 locus with primary open angle glaucoma in the Chinese population

This study investigated the genetic association of three single nucleotide polymorphisms （SNPs; rs 10483727, rs33912345, and rs146737847） at the SIX1-SIX6 locus with primar-y open angle glaucoma （POAG） in the Chinese population. A total of 866 subjects with POAG （685 high-tension glaucoma （HTG） and 181 normal-tension glaucoma （NTG）） and 266 control individu- als were included. Significant genetic association was identified for rs 10483727 in HTG （P=0.02; odds ratio （OR）=l.31）, NTG （P=7.41x10-6; OR=2.71）, and POAG （i.e., HTG and NTG combined; P=0.001; OR=1.44）. rs33912345 was also significantly associated with HTG （P=0.008; OR=1.36）, NTG （P=2.72x10-6; OR=2.27）, and POAG （P=3.84x10-4; OR=1.49）. The rare SIX6 mutation, rs146737847, was not found in the subjects enrolled in this study. Stratification by patient age identified that both rs10483727 and rs33912345 were significantly associated with NTG in patients aged above 40 years （P=2.08x10-5; OR=2.28）, whereas in patients aged between 20-40 years, rs33912345 was significantly associated with NTG （P=0.017; OR=2.06）. In HTG, the genetic associations for both rs10483727 and rs33912345 were significant in patients aged between 20-40 years （P=0.006; OR= 1.56） but not in those aged above 40 years （P=0.118, 0R=1.21 and P=0.042, OR= 1.29, respec- tively）. This study replicated the association of POAG with two SNPs at the SIX1-SIX6 locus and demonstrated that SNPs, rs10483727 and rs33912345, are significantly associated with POAG, especially with NTG in patients aged above 40 years.

Finite element analysis of trans-lamina cribrosa pressure difference on optic nerve head biomechanics: the Beijing Intracranial and Intraocular Pressure Study

The present study aims to assess the potential difference of biomechanical response of the optic nerve head to the same level of trans-lamina cribrosa pressure difference(TLCPD) induced by a reduced cerebrospinal fluid pressure(CSFP) or an elevated intraocular pressure(IOP). A finite element model of optic nerve head tissue(pre-and post-laminar neural tissue, lamina cribrosa, sclera, and pia mater) was constructed. Computed stresses, deformations, and strains were compared at each TLCPD step caused by reduced CSFP or elevated IOP. The results showed that elevating TLCPD increased the strain in optic nerve head,with the largest strains occurring in the neural tissue around the sclera ring. Relative to a baseline TLCPD of 10 mmHg, at a same TLCPD of 18 mmHg, the pre-laminar neural tissue experienced 11.10% first principal strain by reduced CSFP and 13.66% by elevated IOP, respectively. The corresponding values for lamina cribrosa were 6.09% and 6.91%. In conclusion, TLCPD has a significant biomechanical impact on optic nerve head tissue and, more prominently, within the pre-laminar neural tissue and lamina cribrosa. Comparatively, reducing CSFP showed smaller strain than elevating IOP even at a same level of TLCPD on ONH tissue, indicating a different potential role of low CSFP in the pathogenesis of glaucoma.

The association of cerebrospinal fluid pressure with optic nerve head and macular vessel density

The present study aims to investigate the effect of temporary cerebrospinal fluid pressure(CSFP) reduction on optic nerve head(ONH) and macular vessel density(VD) using optical coherence tomography angiography.Forty-four eyes of 44 adults with diagnostic lumbar puncture and CSFP reduction were recruited.Thirty-two eyes of 32 healthy volunteers were controls.ONH and macular VD images were evaluated differences between baseline and after CSFP reduction.The results showed that the mean CSFP decreased from(11.6±2.1) mm Hg to(8.2±3.4) mm Hg(P<0.001).VD in the macular regions decreased significantly after CSFP reduction in the study group(all P<0.05).The control group showed no significant changes in macular VD(all P>0.05).In the study group,decreased VD in the macular parainferior region was associated with CSFP reduction(R^(2)=0.192,P=0.003),the reduction of macular VD in parafoveal(R^(2)=0.098,P=0.018),parainferior(R^(2)=0.104,P=0.021),parasuperior(R^(2)=0.059,P=0.058),paranasal(R^(2)=0.057,P=0.042),paratemporal(R^(2)=0.079,P=0.026) was associated with mean ocular perfusion pressure decrease following CSFP reduction.ONH vessel density did not differ after CSFP reduction(all P>0.05).In conclusion,macular vessel density decreased in association with CSFP reduction.Retinal vessel density in the macular region is more sensitive than that in peripapillary region after CSFP reduction.

Comparison of time-domain,spectral-domain and swept-source OCT in evaluating aqueous cells in vitro

Different optical coherence tomography （OCT）, both tirne-domain OCT and spectral-domain OCT, has been used to evaluate anterior chamber cells in previous studies. Recently, commercial swept-source OCT was available. The comparison among three kinds of OCTs have not been done before. Here, we compared their feasibility in discerning aqueous cells in vitro. The peripheral blood was diluted to eight different cell concentrations and was packed into plastic-film bag. Each sample was test- ed using different scan modes of three OCTs. It was easy to discern aqueous cells from background noise in both Visante AS-OCT and RTVue XR Avanti OCT, but difficult in Casia SS-1000 OCT. The measured blood cell densities in high-resolution corneal cross-sectional scan of Visante AS-OCT, cornea line scan and 3D cornea scan of RTVue XR Avanti OCT were highly correlated with the actual blood cell concentration （Pearson correlation=0.991, 0.989, and 0.993 respective- ly）. The mean adjusted cell densities of cornea line scan （10.46±2.87 spots mm-2） and 3D cornea scan （11.01±2.47 spots mm-2） of RTVue XR Avanti OCT were significantly larger than that of Visante AS-OCT （1.55±1.75 spots mm-2） （P〈0.01）. Our study demonstrated that RTVue XR Avanti OCT, a spectral-domain OCT, is superior to other two OCTs in evaluating aqueous cells.

Long-term follow-up of optic neuropathy in chronic low cerebrospinal fluid pressure monkeys: the Beijing Intracranial and Intraocular Pressure(iCOP) Study

Dear Editor,Clinical and anatomic investigations strongly suggest that a low orbital cerebrospinal fluid pressure (CSFP), parallel to an elevated intraocular pressure (IOP), may have a role in the pathogenesis of optic neuropathy (Ren et al., 2011, Wang et al., 2012). Optic neuropathy including glaucoma demonstrated structural alterations in the optic nerve head (ONH)and retinal nerve fiber layer (RNFL), as well as functional abnormalities such as visual field (VF) that eventually cause severe visual impairment and blindness.

New loci for refractive errors and ocular biometric parameters in young Chinese Han adults

Myopia has become a major public health issue with an increasing prevalence.There are still individuals who experience similar environmental risk factors and,yet,remain non-myopic.Thus,there might be genetic factors protecting people from myopia.Considering the opposite ocular characteristics of primary angle closure glaucoma(PACG)to myopia and possible common pathway between them,we propose that certain risk genes for PACG might act as a protective factor for myopia.In this study,2,678 young adults were genotyped for 37 targeted single nucleotide polymorphisms.Compared with emmetropia,rs1401999(allele C:OR=0.795,P=0.03;genotype in dominant model:OR=0.759,P=0.02)and rs1258267(allele A:OR=0.824,P=0.03;genotype in dominant model:OR=0.603,P=0.01)were associated with low to moderate myopia and high myopia,respectively.Genotype under recessive model of rs11024102 was correlated with myopia(OR=1.456,P=0.01),low to moderate myopia(OR=1.443,P=0.02)and high myopia(OR=1.453,P=0.02).However,these associations did not survive Bonferroni correction.Moreover,rs1401999,rs1258267,and rs11024102 showed associations with certain ocular biometric parameters in different groups.Our study suggests that ABCC5,CHAT and PLEKHA7 might be associated with refractive errors by contributing to the regulation of ocular biometry,in terms of uncorrected results and their biological functions.

Mechanism of the reconstruction of aqueous outflow drainage

Glaucoma is the leading cause of irreversible blindness worldwide. The reconstruction of aqueous outflow drainage (RAOD) has recently been proposed to aid in restoring aqueous outflow drainage in primary open-angle glaucoma. However, the mechanism of RAOD remains to be fully understood. Based on literature review and research studies, the potential mechanisms of RAOD are the following: (i) Circumferential dilation of the Schlemm’s canal (SC) and surrounding collector channels. (ii) Instant formation of microcracks through RAOD procedures. (iii) Formation of more pores, and local detachment between the SC endothelium (SCE) and basement membrane. (iv) Activation of stem cells by constant mechanical stress caused by the tensional suture placed at the anterior part of the SC. (v) Reversal of trabecular meshwork (TM) herniation. (vi) Mobilization of the reserve of the aqueous drainage. (vii) Change of SCE phenotype. (viii) Mechanosensing and mechanotransducing of TM.

A review of trachoma history in China: research, prevention, and control

Trachoma is one of the most widespread blinding eye diseases, which is harmful to human visual health. The efforts to prevent and control trachoma in China can be divided into three periods, i.e., highly epidemic period, research on pathogenesis and control of trachoma, and blinding trachoma elimination and epidemiological evaluation. In 1956, Prof. Feifan Tang and Xiaolou Zhang first discovered and isolated Chlamydia trachomatis, which clarified the cause of trachoma, and kick-started a fresh chapter in trachoma research, prevention, and control around the world. Although, the prevalence of trachoma differed in different areas, the average prevalence once exceeded 50% and was as high as 90% in some areas before and at early liberation of China. Therefore, the government-led efforts were made to comprehensively prevent and control trachoma, including development of National Plan for the Prevention and Control of Trachoma, nationwide screening and treatment of trachoma, implementation of National Patriotic Health Campaign and improvement of water supply and lavatories. After decades of effort, China reached the goal of eliminating blinding trachoma in 2015. China has gained remarkable achievements in the prevention and treatment of trachoma, making outstanding contributions toward the goal of eliminating trachoma worldwide. The research, prevention, and control of trachoma in China were reviewed in this paper.

Molecular characteristics of the omp A gene of serotype B Chlamydia trachomatis in Qinghai Tibetan primary school students

To study the molecular characteristics of Chlamydia trachomatis, the major outer membrane protein gene(omp A) of C. trachomatis from primary school students with trachoma residing in the Qinghai Tibetan area was sequenced and compared with the same serotype in Gen Bank. In Jianshetang Primary School and Galeng Central Primary School in the Galeng Tibetan Township of Qinghai Haidong Sala Autonomous County, scraped samples were collected from the upper tarsal conjunctiva and lower conjunctival sac of both eyes of 45 students with trachoma, stored at 4°C, and transported to Beijing Tongren Hospital by air within 24 h. The samples were screened for C. trachomatis by real-time PCR. The omp A gene from the C. trachomatis-positive samples was amplified by nested PCR. The serotype was confirmed by National Center for Biotechnology Information(NCBI) BLAST search and homology analysis. The entire omp A gene sequence was compared with the corresponding gene sequences of serotype B strains available in Gen Bank. Of the 45 students aged 6–13 years with trachoma, 26 C. trachomatis-positive students were identified by the initial real-time PCR screening(average age,(9.09±1.63) years; sex ratio, 1.0), accounting for 57.78%(26/45). The cycle threshold values for real-time PCR were 16.79–37.77. Half(13/26) of C. trachomatis-positive students had a bacterial copy number of >105. The compliance rate of the omp A gene sequences with the C. trachomatis serotype B strains in Gen Bank was up to 99%. Two novel genetic mutations were found when the omp A gene was compared with those of the 11 serotype B strains in Gen Bank. The two non-synonymous mutations were located at(i) position 271 in the second constant domain, an adenine(A) to guanine(G) substitution(ACT?GCT), changing the amino acid at position 91 from threonine to alanine(Thr?Ala) in all 26 strains; and(ii) position 887 in the fourth variable domain, a cytosine(C) to thymine(T) substitution(GCA?GTA), changing the amino acid at residue 296 from alanine to valine(Ala?Val) in four of the 26 strains. Six mutations were identified relative to ATCC VR-573. The strains could be divided into two gene clusters according to the mutation at nucleotide position 887: CQZ-1(China Qinghai Tibetan-1) and CQZ-2(China Qinghai Tibetan-2). We thus detected two novel serotype B mutant strains of C. trachomatis among study subjects with trachoma.

Etiological characteristics of chlamydia trachoma conjunctivitis of Primary Boarding School students in the Qinghai Tibetan area

The aim of this study was to investigate the etiological characteristics of Chlamydia trachomatis conjunctivitis among resident students at primary schools in the Qinghai Tibetan area in order to understand the distribution of C. trachomatis and other pathogenic microorganisms, to detect the isolation rate of infectious pathogens, and to provide an evidence for further targeted efforts in the prevent of sporadic trachoma efforts. From two primary schools in Qinghai Province, ocular samples from 35 students who were clinically diagnosed as trachoma cases and 60 normal controls were obtained by swabbing their upper eyelids and lower conjunctival sacs. Samples were preserved at 4°C and airlifted to Beijing Tongren Hospital within 24 h. Real-time polymerase chain reaction(RT-PCR) was used to screen for C. trachomatis, and nested PCR was used to amplify a fragment of the omp A gene for serotype confirmation. Bacterial cultivation and sensitivity tests were conducted based on the 2015 version of the Clinical and Laboratory Standards Institute. Adenovirus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were screened by RT-PCR. Among the 35 students with trachoma, 8 came from the Jianshetang Primary School and 27 came from the Central Primary School. Two novel C. trachomatis B serotypes(Gen Bank accession numbers KU737520 and KU737521) were detected based on a sequence analysis of the omp A gene. Single C. trachomatis infections accounted for 42.86%(9/21) of the cases, and infections with multiple bacteria, particularly Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and Streptococcus pneumoniae, accounted for the remaining 57.14%(12/21). Of the 14 C. trachomatis-negative samples, one was positive for adenoviral infection(serotype D) and 13 were positive for bacterial infections(H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus, streptococci other than S. pneumoniae, Staphylococcus epidermidis, Corynebacterium, and Arthrobacterium). In addition to C. trachomatis, the other bacteria and virus that were detected in the boarding students of primary schools in the Qinghai Tibetan area should be emphasized in trachoma prevention and control.

Enlightenment of blinding trachoma elimination in China

Trachoma is a blinding eye disease caused by Chlamydia trachomatis infection.Trachoma was pandemic in the 19th century and rampant around the world,and was a widely prevalent infectious eye disease.

Elimination of blinding trachoma in China: why is further study necessary?

Sixty years ago,Prof.Feifan Tang and Xiaolou Zhang first discovered and isolated Chlamydia trachomatis,a finding that clarified the cause of trachoma and marked the beginning of a fresh chapter on trachoma research,prevention,and control worldwide（Tang et al.,1956;Tang et al.,1957a;Tang et al.,1957b）.