Cost of Medical Treatment for Primary Open-Angle Glaucoma in Relation to Patients’ Income and Its Impact on the Prognosis of the Disease, in Bouaké University Hospital

Introduction: Medical treatment for POAG is continuous and lifelong treatment. The aim of this study was to evaluate the relationship between the cost of this treatment and patients’ income and the impact of this relationship on treatment compliance. Materials and Methods: Prospective cross-sectional study with a descriptive aim covering sociodemographic data, average incomes, and direct and indirect costs of treatment of 57 patients followed for POAG during the period from January 1, 2012, to December 31, 2016 (5 years). Results: The patients were aged 25 to 77 years (mean = 54.4 years) with a male predominance (sex ratio = 1.5). Retirees were the most represented (26.32%), followed by workers in the informal sector (14.04%) and housewives (12.28%). Patients who had an annual income less than or equal to 900,000 CFA francs (€1370.83) per year represented 56.14% and those who did not have health coverage represented 57.89%. The treatment was monotherapy (64.91%), dual therapy (31.58%) or triple therapy (3.05%) and the average ratio of “annual cost of treatment to annual income” was 0.56 with for maximum 2.23 and 0.02 as minimum. Patients who considered the cost of treatment unbearable for their income represented 78.95%. Conclusion: Prevention of blindness due to glaucoma requires early detection but also the establishment of health coverage mechanisms to improve compliance with medical treatment. In addition, consideration should be given to the development of glaucoma surgery in our country, the indication of which could be the first intention in certain patients, considering for those patients, the geographical and financial accessibility of medical treatment. .

Epidemiological, Clinical, Therapeutic and Evolutive Profile of Primary Open-Angle Glaucoma in a Cameroonian Population

Background: Sub-Saharan Africa has the highest prevalence of primary open-angle glaucoma (POAG), at 4.2%. The efficacy of medical treatment has been demonstrated and remains one of the treatments of choice for POAG. However, in sub-Saharan Africa, its effectiveness has many challenges, due to multiple factors, including cost and access to care. Thus, the present study aimed to determine the epidemiological, clinical, therapeutic and evolutive profile of primary open-angle glaucoma patients. Methodology: A descriptive cross-sectional study was carried out in two hospitals in western Cameroon. Epidemiological, clinical, therapeutic, and evolutionary data on intraocular pressure at one year after medical treatment were analyzed. SPSS version 23 software was used for statistical analysis, with a significant p-value set at 5%. Results: A total of 201 patients with POAG were included in the study. The population comprised 100 men and 101 women, with a mean age of 54 ± 12 years. At diagnosis, the mean intraocular pressure was 23.9 ± 8.70 mmHg for the right eye and 25.5 ± 9.57 mmHg for the left eye. The mean cup/disc ratio was 0.64 ± 0.2 [0.2-1] and 0.67 ± 0.19 [02-1] in the right and left eyes, respectively. Monotherapy was the most prescribed treatment [59.2%]. After one year of treatment, intraocular pressure was reduced by 15.5% with beta-blockers, 23.66% with prostaglandins, 19.11% with carbonic anhydrase inhibitors, 35, 92% with beta-blockers and carbonic anhydrase inhibitors, 25.92% with beta-blockers and prostaglandins, 48.03% with carbonic anhydrase inhibitors and prostaglandin agonists, and 38.77% with triple therapy. Taking glaucoma severity into account, a significant reduction in intraocular pressure at one year was observed in all participants [p 0.05]. However, the target pressure was obtained in 47%, 20% and 14% of eyes suffering of mild, moderate, and severe grade of POAG respectively. Conclusion: In the present study, there was a significant reduction in intraocular pressure after one year of medical treatment. However, the reduction in intraocular pressure does not allow the target pressure to be reached in severe forms. Thus, alternatives to the medical treatment of POAG should be discussed early in the present context. .

Coinheritance of OLFM2 and SIX6 variants in a Chinese family with juvenile-onset primary open-angle glaucoma: A case report

BACKGROUND Juvenile-onset primary open-angle glaucoma(JOAG),characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40,is a rare subtype of primary open-angle glaucoma.Several genetic mutations have been associated with JOAG.CASE SUMMARY The proband patient was a young male,diagnosed with primary open-angle glaucoma at the age of 27.The patient and his unaffected parents who have been excluded from classic genetic mutations for primary open-angle glaucoma were included to explore for other possible genetic variants through whole genome sequencing and bioinformatics analysis.In this trio,we found two heterozygous variants inherited from the parents in the proband:c.281G>A,p.Arg94His in OLFM2 and c.177C>G,p.Ile59Met in SIX6.Both genetic mutations are predicted through bioinformatics analysis to replace evolutionary conserved amino acids,therefore rendering a pathogenic effect on proteins.In contrast,very low frequencies for these genetic mutations were recorded in most common control databases.CONCLUSION This is the first report on coinherited mutations of OLFM2 and SIX6 in a JOAG family,which shows the complexity of JOAG inheritance.Large-scale clinical screening and molecular functional investigations on these coinherited mutations are imperative to improve our understanding of the development of JOAG.

Abnormal Systemic and Ocular Responses to the Valsalva Manoeuvre in Primary Open-Angle Glaucoma:A Case for Autonomic Failure?

Objective This study aimed to examine the association of primary open-angle glaucoma(POAG)with autonomic dysfunction by assessing the differences in systemic and ocular responses to an autonomic provocation test,the Valsalva manoeuvre(VM),between POAG patients and normal subjects.Methods Forty POAG and forty control subjects were subjected to the VM.Systemic and ocular parameters were measured at baseline,phase 2,and phase 4 of the VM(VM2 and VM4),where VM2 and VM4 are sympathetic and parasympathetic nervous activation states,respectively.Heart rate variability was used to assess the autonomic nervous activity,among which the high-frequency component(HF)and the low-frequency(LF)/HF ratio were used as indices of parasympathetic and sympathetic activation,respectively.Results POAG patients demonstrated higher sympathetic activation(LF/HF ratio median:2.17 vs.1.53,P=0.000)than controls at baseline and exhibited attenuated sympathetic and parasympathetic responses(a smaller change in LF/HF and HF values)during the VM than controls.During VM,the intraocular pressure(IOP),mean blood pressure(MAP),mean ocular perfusion pressure(MOPP),and the Schlemm’s canal area(SCAR)increased from baseline to VM2 and then decreased from VM2 to VM4 in both the POAG and control groups(all P<0.05).However,when we compared the changes above,the fluctuations in IOP,MAP,and MOPP were more pronounced in POAG than in controls(all P<0.05),while the changes in amplitudes of SCAR were smaller in POAG(P<0.05).Furthermore,from VM2 to VM4,the choroid thickness(ChT)in the POAG group was significantly decreased,while it was unchanged in normal subjects(P=0.258).A regression analysis showed a significant correlation of the baseline LF/HF with IOP change values(ΔIOP)from baseline to VM2 in POAG(R^(2)=0.147,P=0.014).Conclusion Patients with POAG showed more pronounced fluctuations in IOP,MAP,MOPP and ChT during the VM than controls.These reactions could be associated with autonomic dysfunction in POAG.

Incidence of Primary Open-Angle Glaucoma at the Flamboyants Communal Medical Center of Conakry, Guinea

Background: Primary Open-Angle Glaucoma (POAG) is a chronic, progressive optic neuropathy of multifactorial origin defined by alterations in the visual field, progressive loss of optic nerve fibers and ganglion cells, and an open iridocorneal angle in gonioscopy. It is the world’s leading cause of irreversible blindness. There is no epidemiological study in Guinea that allows us to locate the real level of the problem. The objective of this study is to determine the hospital incidence of POAG at the Centre Médical Communal (CMC) in the Flamboyants. Patients and Method: This was a descriptive cross-sectional study with a prospective collection for one year, from April 1, 2020 to March 31, 2021, in patients aged at least 40 years, received in consultation at the CMC in the Flamboyants. The diagnostic criterion for a new case of glaucoma was the presence in a patient of the following two signs: (excavation of the optical disc C/D ≥ 0.5 and alteration of the visual field) with an open angle at least stage 4 of the Shaffer and Etienne classification associated or not with ocular hypertonia and having never received anti glaucoma treatment. We described variables related to sociodemographic characteristics, visual acuity, intraocular pressures, papillary excavations, and visual field surveys. Informed consent from patients was sought and obtained. The confidentiality of the files was guaranteed. Results: 68 new cases of POAG were diagnosed out of 3220 consultations, an incidence rate of 2.11%. The average age was 58.2 years (10.64 with a male predominance of 63.23%. A family history of glaucoma was present in 11.36% of cases. Visual acuity was poor Conclusion: This study has shown us that POAG in our environment is relatively common, early onset, and rapidly evolving. The implementation of a rapid and reliable screening strategy by the Eye Health Program will make it possible to manage glaucoma from the earliest stages.

Prevalence of Open-angle Glaucoma in Southwestern China: the Yongchuan Glaucoma Study

This study examined the prevalence of primary open-angle glaucoma（POAG） among residents aged ≥50 years living in Yongchuan district of Chongqing. Stratified cluster sampling was employed in random selection to estimate the prevalence of glaucoma from April to June, 2005. Twenty-nine villages or neighborhood communities were randomly selected in urban area（Zhongshan Road）, suburban area（Shanjiao Town） and exurban area（Zhutuo Town） of this district. All the respondents underwent detailed ophthalmic examinations. The examinations included questionnaire investigation, visual acuity test, naked-eye examination, measurement of peripheral anterior chamber depth（Van Herrick＇s technique）, detection of intraocluar pressure（IOP） with a Perkins hand-held applanation tonometer（HA-2） and examination of the optic disc by using a 78 diopters（D） lens（including the cup-disc ratio, cup/disc ratio asymmetries, horizontal and vertical diameter, notching and optic disc hemorrhages）. A total of 5938 residents were actually examined, and the response rate was 85.19%. The crude prevalence of POAG was 0.86%（n=51/5938, 95% CI 0.64%–1.11%）. There were 24 males and 27 females in the glaucoma group. The glaucoma prevalence was not significant different in case number between the male and female subjects（P=0.4900）. Furthermore, no association between age or schooling and POAG was noted（P=0.8030, 0.0734）. Out of 51 subjects with POAG, unilateral glaucoma-related blindness occurred in 38 subjects（74.5%） and bilateral glaucoma-related blindness was found in 7 subjects（13.7%）. This study exhibited that the prevalence of POAG was 0.86% among residents aged ≥50 years living in Yongchuan District of Chongqing. The vision loss caused by POAG in this population was obviously higher than that previously reported in other studies. Glaucoma management, detection of affected persons and handling of the burden of glaucoma should be the priorities of the agenda of local health authorities of Western China.

The Study of Relationships between the Damage of Visual Function and Hemorrheology, Ocular Rheography, as well as Other Related Factors in Patients with Primary Open Angle Glaucoma (POAG)

Researches of glaucoma visual function damage, hemorrheololgy, ocular rheography and other related multiplex factors, with computed multifactorial stepwise regresion analysis, indicate that the elevation of intraocular pressure (IOP) is not the only factor to induce visual impairment. POAG patients are shown to have markedly reduced diastolic purfussion pressure in ophthalmic artery, besides prolonged filling time of the retinal artery and vein, diminished erythrocyte deformability and increased platele...

SEQUENTIAL INTRAOCULAR PRESSURE MEASUREMENTS IN SUSPECTED OPEN-ANGLE GLAUCOMA

Objective To evaluate the variations of intraocular pressure （lOP） in suspected open-angle glaucoma （OAG） patients. Methods The variations of lOP were measured in 216 eyes of suspected OAG patients at 4-hour intervals for 48 h. Based on the results of the serial lOP measurements, optic disc changed and visual field defected, the patients were diagnosed as primary OAG （ POAG ）, normal tension glaucoma （NTG）, ocular hypertension （ OHT） , or physiologic cup （PC）. Results After the serial lOP measurements, 16. 7% of the suspected OAG patients were diagnosed as POAG, 32. 4% as NTG, 24. 5% as OHT, and 26. 4% as PC. The highest percentages of the POAG group had peak lOP at 8 AM （19. 4% ） and their trough lOP at 10 PM （27. 8% ） ; the NTG group had peak lOP at 12 AM （18. 6% ） and their trough lOP at 12 PM （22. 9% ） ; the OHT group had peak lOP at 4 AM （22. 6% ） and their trough lOP at 10 PM （26. 4% ） ; and the PC group had peak lOP at 4 AM （ 21. 1% ） and their trough lOP at 12 PM （ 21. 1% ）. The percentages of peak lOP outside clinic （ 8 AM - 4 PM） in the POAG, NTG, OHT and PC groups were 55. 6%, 50. 0%, 58. 4% and 45. 7%, respectively. The mean magnitude of variance was 5. 1 - 6. 7 mmHg in those suspected OAG patients. There was a strong positive correlation in lOP between both eyes at each time point of measurement and the variation curves of the right and left eyes had parallel profiles in those suspected OAG patients. Conclusion Serial measurement of lOP is still needed, in order not to miss the peak and the trough lOP readings in suspected OAG patients, which helps in better management of glaucoma.

Clinical relevance of the glucocorticoid receptor gene polymorphisms in glucocorticoid-induced ocular hypertension and primary open angle glaucoma

AIM: To avoid the side effects of ocular hypertension of glucocorticoid(GC) usage in eye, we must identify susceptible individuals, which exists in about one-third of all population. Further, the majority of all primary open angle glaucoma(POAG) patients show this phenotype.Glucocorticoid receptor(GR) regulates C responsiveness in trabecular meshwork(TM) cells. In this study, single nucleotide polymorphism(SNP) genotyping was used to determine whether there are differences in the Bcl I(rs41423247) and N363S(rs6195) polymorphisms of the GR gene in healthy and POAG patients, and glucocorticoid-induced ocular hypertension(GIOH)populations.METHODS: Three hundred and twenty-seven unrelated Chinese adults, including 111 normal controls, 117 GIOH subjects and 99 POAG patients, were recruited. DNA samples were prepared and the Bcl I and N363 S polymorphisms were screened using real-time polymerase chain reaction(RT-PCR)-restriction fragment length polymorphism(RFLP) analysis. Frequencies of the Bcl I and N363 S polymorphisms were determined and compared using Fisher’s exact test and the Chi-squared test.RESULTS: Only the Bcl I polymorphism was identified in the Chinese Han population. The frequency of the G allele was 21.6 % in normal controls, 18.3% in GIOH patients, and 13.64% in the POAG patients. There was no significant difference in polymorphism or allele frequency in the 3 groups. Furthermore, no N363 S polymorphism was found in the study subjects.CONCLUSION: The Bcl I polymorphisms in GR gene had no association with GIOH and POAG patients, and N363 S polymorphism might not exist in the Chinese Han population. Therefore, the Bcl I polymorphism might not be responsible for the development of GC-induced ocular hypertension or POAG.

A Study of Motion Perception in Primary Open Angle Glaucoma

Purpose: To study the features of the motion perception (MP) and explore the worth of the clinical application of MP test in primary open angle glaucoma (POAG).Methods: MPs were recorded from 41 patients (67 eyes) with POAG ang 56 normal subjects (112 eyes) by the MP software in PC compatible computer. Meanwhile , the MP ways and MP sites were analyzed and MP abnormal rate was compared to the clinical parameters and the visual function indices related to glaucoma. . Results: The results showed that the total abnormal rate of MP was 89. 5% in POAG, and the abnormal rate was 81. 6% in early stage of POAG, and MP abnormal degree had positive correlation with C/D, ocular tension and corrected loss variance (CLV), and negative correlation with visual acuity and mean sensitivity (MS), and no correlation with age and short-term fluctuation (SF) in the patients with POAG.Concusion: These results suggest that the MP test provides a newly effctive examination method in diagnosing the early POAG. Eye Science 1996;

Association between the M98K variant of the OPTN gene and the risk for primary open angle glaucoma:an updated meta-analysis

Background:The association between optineurin(OPTN)M98K variant and primary open angle glaucoma(POAG)has been widely investigated.However,the results remain controversial among published meta-analyses.Therefore,we conducted an updated meta-analysis to further explore the association between M98K and POAG and its subgroups.Methods:PubMed,Embase,Web of Science,and China National Knowledge Infrastructure(CNKI)databases were searched to find all articles describing the relationships between the M98K variant and POAG,which were published from the inception to 31 December,2019.The associations between M98K and overall POAG,normal tension glaucoma(NTG),high tension glaucoma(HTG),POAG in Asian and non-Asian populations,juvenile open angle glaucoma(JOAG)and adult-onset POAG were evaluated by calculating the pooled odds ratio(OR)and 95%confidence interval(CI).The Bonferroni correction was used to determine the statistically significant genetic models.Results:A total of 34 eligible articles involving 7,310 POAG patients and 5,173 controls were identified in the present meta-analysis.The articles achieved an average of 6.21 stars for quality assessment by the Newcastle-Ottawa Scale(NOS).Evidence from the pooled results indicated significant association between M98K and overall POAG susceptibility under the dominant model(OR=1.30,95%CI,1.12-1.52;P<0.001).In the subgroup analyses,no significant associations were found between M98K and the risks of NTG,HTG,JOAG,adult-onset POAG,Asian POAG or non-Asian POAG.Conclusions:The updated meta-analysis revealed that OPTN M98K was significantly associated with the susceptibility to overall POAG.

肠道菌群与POAG因果关系的两样本孟德尔随机化研究

目的:利用两样本孟德尔随机化(MR)的研究方法探究肠道菌群(GM)与原发性开角型青光眼(POAG)的潜在因果关系。方法:利用英国布里斯托尔大学的GM的全基因组关联研究数据(GWAS)作为暴露和IEU Open GWAS数据库中POAG的GWAS数据作为结局,采用逆方差加权(IVW)、MR Egger、加权中位数(WM)、Simple Mode、Weighted Mode方法分析POAG与GM之间存在的潜在关系,其中IVW为主要分析方法。敏感性分析检测该MR分析结果是否可靠。结果:IVW分析显示,Butyrivibrio(OR=1.170,95%CI:1.057-1.295,P=0.002)、Howardella(OR=1.188,95%CI:1.043-1.355,P=0.010)、LachnospiraceaeUCG001(OR=1.229,95%CI:1.016-1.485,P=0.033)增加了POAG的发病风险;而Candidatus Soleaferrea(OR=0.810,95%CI:0.670-0.981,P=0.031)、Ruminococcustorquesgroup(OR=0.656,95%CI:0.453-0.950,P=0.026)、Ruminococcaceae-UCG013(OR=0.770,95%CI:0.598-0.990,P=0.041)降低了POAG的发病风险。敏感性分析结果表明以上结果不存在异质性和多效性,分析结果具有可靠性。结论:GM与POAG存在潜在的因果关系,由于POAG具有致盲性,早期诊断和早期干预POAG的相关因素对该病的临床预后具有重要意义。

The Characteristics of Interaction between Color and Motion Perception in PrimaryOpen Angle Glaucoma

Purpose: To investigate the characteristics of interaction between color and motion perception in primary open angle glaucoma (POAG) and measure motion perception of B,G and R cones, thus find a more sensitive method to diagnose the visual nerve damage in POAG. Methods : Motion perceptions of B,G and R cones were isolated by blue , green and red vertical line stimulus displayed on the yellow , purple and blue background respectively, then measured the displacement threshold and flicking threshold of motion perception from each cones in POAG, and compared it with the age-match normals.Results:The displacement threshold and flicking threshold of motion perception from B,G and R cones were all damaged in POAG compared with the normals, and the motion perception of G and B cones was deficits more obviously than the R cones.Conclusion: These findings support the suggestion that color provides an input to human motion perception. Magnocellular and parvocellular pathway may be significandy damaged in POAG,

Ex-PRESS implantation versus trabeculectomy in Chinese patients with POAG:fellow eye pilot study

AIM： To compare the outcomes of Ex-PRESS implantation in one eye versus trabeculectomy with mitomycin C in the fellow eye in Chinese patients with primary open-angle glaucoma （POAG）. METHODS： This was a prospective, non-randomized comparative study. Forty-eight eyes of 24 patients with bilateral POAG necessitating surgery were included and underwent Ex-PRESS implantation under the scleral flap in one eye and trabeculectomy in the other eye according to patients’ choice. Primary outcome measures included mean intraocular pressure （IOP） and success rate. Secondary outcome measures were aqueous flare, postoperative medication use, visual acuity, and incidence of complications.RESULTS： All 24 patients finished a 1-year follow-up. Both groups maintained significant reductions in IOP after surgery throughout the follow-up period. At any point in time, the IOP of the two groups did not differ significantly. The Kaplan-Meier survival curve analysis showed no significant differences in success between the two groups （P=0.289）. The mean number of anti-glaucoma medicines and visual acuity in both groups were not significantly different. Eyes with Ex-PRESS implantation had lower aqueous flare values on days 1 and 3 （both P〈0.05）. Instances of early postoperative hypotony and choroidal effusion were significantly fewer in frequency after Ex-PRESS implantation under the scleral flap compared with those after trabeculectomy （P〈0.001）. CONCLUSION： Ex-PRESS is comparable to trabeculectomy in terms of IOP, success rate, number of glaucoma medications used, and visual acuity. However, Ex-PRESS resulted in fewer cases of inflammation and a lower rate of complications.

Retinal nerve fiber layer in primary open-angle glaucoma with high myopia determined by optical coherence tomography and scanning laser polarimetry

Background Fundus changes associated with high myopia （HM） may mask those associated with primary open-angle glaucoma （POAG）. This study aim to determine the characteristics of RNFL thickness changes in patients with both POAG and HM and compare these to changes in patients with only HM. The diagnostic capabilities of both OCT and GDxVCC in this subset of patients are also evaluated. Methods Twenty-two eyes with POAG and HM （spherical equivalent （SE） between -6.0 and -12.0 D） were evaluated, and 22 eyes with HM were used for comparison. Characteristic retinal nerve fiber layer （RNFL） thickness profiles in patients with POAG and HM were examined using optical coherence tomography （OCT） and scanning laser polarimetry with variable corneal compensation （GDxVCC）, and the diagnostic capabilities of these imaging modalities were compared. RNFL parameters evaluated included superior average （Savg-GDx）, inferior average （lavg-GDx）, temporal-superior-nasal- inferior-temporal （TSNIT） average, and nerve fiber indicator （NFI） on GDxVCC and superior average （Savg-OCT）, inferior average （lavg-OCT）, nasal average （Navg-OCT）, temporal average （Tavg-OCT）, and average thickness （AvgThick-OCT） on OCT （fast RNFL scan）. Visual field testing was performed and defects were evaluated using mean defect （MD） and pattern standard deviation （PSD）. Results The RNFL parameters （P 〈0.05） significantly different between groups included Savg-GDx, lavg-GDx, TSNIT average, NFI, Savg-OCT, lavg-OCT, Tavg-OCT, and AvgThick-OCT. Significant correlations existed between TSNIT average and AvgThick-OCT （r=0.778）, TSNIT average and MD （r=0.749）, AvgThick-OCT and MD （r=0.647）, TSNIT average and PSD （r=-0.756）, and AvgThick-OCT and PSD （r=-0.784）. The area under the receiver operating characteristic curve （AUROC） values of TSNIT average, Savg-GDx, lavg-GDx, NFI, Savg-OCT, lavg-OCT, Navg-OCT, Tavg-OCT, and AvgThick-OCT were 0.947, 0.962, 0.973, 0.994, 0.909, 0.917, 0.511, 0.906, and 0.913, respectively. The NFI AUROC was the highest value. Conclusions RNFL thickness was significantly lower in all but the nasal quadrant in patients with POAG and HM, compared to patients with only HM. Measurements with OCT and GDxVCC were well-correlated, and both modalities detected RNFL thickness chanaes. However. GDxVCC was better than OCT in detectina POAG in HM Datients.

Central visual function and inner retinal structure in primary open-angle glaucoma

To investigate associations between central visual function and inner retinal structure in primary open-angle glaucoma(POAG). This study enrolled 78 POAG patients and 58 healthy controls. POAG was classified into early glaucoma and moderate to advanced glaucoma. The following tests were performed on all participants: isolated-check visual evoked potential(ic VEP) testing, 24-2 standard automated perimetry(SAP), and Cirrus optical coherence tomography(OCT) examinations. Signal-to-noise ratio(SNR) measures obtained from ic VEP responses to isolated checks presented at four depths of modulation(DOMs;8%, 14%, 22%, and 32%) were explored. Mean macular sensitivity(mMS) was assessed by calculating the mean sensitivities of central 12 SAP points. Ganglion cell layer+ inner plexiform layer thickness(GCL+IPLT) and peripapillary retinal nerve fiber layer thickness(pRNFLT) were measured by OCT scanning. For each group of subjects, linear relationships among the following measures were analyzed: SNR, mMS, GCL+IPLT, and pRNFLT. SNR, mMS, GCL+IPLT, and pRNFLT were all more significantly decreased in glaucoma than in controls(P<0.001). A significant positive association was found between SNR at 14% DOM and GCL+IPLT at the inferior sector in early glaucoma(r=0.465, P=0.004). In moderate to advanced glaucoma, significant correlations were found between SNR at 32% DOM and mean GCL+IPLT(r=0.364, P=0.023), superior GCL+IPLT(r=0.358, P=0.025), and mean p RNFLT(r=0.396, P=0.025). In addition, in moderate to advanced glaucoma, there were significant correlations between mMS and all relevant measures of retinal thickness(r=0.330–0.663, P< 0.010). In early glaucoma, significant correlations were found between mean mMS and minimum GCL+IPLT(r=0.373, P=0.023), and between inferior mMS and superior GCL+IPLT(r=0.470, P=0.003). Linear models provided a good explanation for the relationship between SNR and inner retinal thickness(IRT), whereas nonlinear models better explained the relationship between mMS and IRT. In early glaucoma, both SNR and mMS were related moderately and significantly to IRT, whereas in moderate to advanced glaucoma, mMS was more strongly correlated with IRT than SNR.

Identification of Mutations in Myocilin and Beta-1,4-galactosyltransferase 3 Genes in a Chinese Family with Primary Open-angle Glaucoma

Background： Glaucoma is a major cause of irreversible blindness worldwide. There is evidence showing that a subset of the disease is genetically determined. In this study, we screened for mutations in chromosome lq-linked open-angle glaucoma （GLC1A） in a Chinese family with primary open-angle glaucoma （POAG）. Methods： A total of 23 members from five generations of a family were enrolled and underwent thorough ophthalmologic examinations. In addition, 200 unrelated healthy Chinese controls were also recruited as normal control. GLC1A gene was amplified by polymerase chain reaction, and DNA sequencing was performed to screen for mutations. Results： Six members were diagnosed as POAG, with severe clinical manifestations, and history of high intraocular pressures. The mean age of disease onset was 26.3 years. However, the others were asymptomatic. In six affected and three asymptomatic members, gene sequencing revealed a mutation c.C1456T in exon 3 of myocilin gene （MYOC）. Furthermore, we also identified a novel mutation c.G322A in beta- 1,4-galactosyltransferase 3 （B4GALT3） gene in all six affected and three asymptomatic members, which was not reported previously in POAG patients. The two newly identified variants were absent in other family members as well as controls. Conclusion： The mutations c.1456C〈T （p.L486F） in MYOC and c.322G〈A （p.V1081） in B4GALT3 are likely responsible for the pathogenesis of POAG in this family.

Comparison of corneal biomechanics among primary open-angle glaucoma with normal tension or hypertension and controls

Background:Normal tension glaucoma(NTG)is a less pressure-dependent type of glaucoma with characteristic optic neuropathy.Recently,the biomechanical mechanism has been thought to account for glaucomatous optic neuropathy to some degree.We intended to compare dynamic corneal response parameters(DCRs)among patients with primary open-angle glaucoma with normal tension or hypertension and controls.The correlations between DCRs and known risk factors for glaucoma were also analyzed.Methods:In this cross-sectional study,49 NTG subjects,45 hypertension glaucoma(HTG)subjects,and 50 control subjects were enrolled.We compared the differences in DCRs using corneal visualization Scheimpflug technology among the NTG,HTG,and control groups.We also analyzed the correlations between DCRs and known risk factors for glaucoma(eg,central corneal thickness[CCT],intraocular pressure[IOP],etc).Results:The maximum inverse concave radius(NTG:0.18[0.17,0.20]mm-1;control:0.17[0.16,0.18]mm-1;P=0.033),deformation amplitude ratio of 2 mm(DAR 2 mm,NTG:4.87[4.33,5.39];control:4.37[4.07,4.88];P<0.001),and DAR 1 mm(NTG:1.62[1.58,1.65];control:1.58[1.54,1.61];P<0.001)were significantly higher in NTG than in the controls.The integrated radius(IR,NTG:8.40±1.07 mm-1;HTG:7.64±1.31 mm-1;P=0.026)and DAR 2 mm(NTG:4.87[4.33,5.39];HTG:4.44[4.12,5.02];P<0.007)were significantly higher,whereas the stiffness parameter at the first applanation(SP-A1,NTG:91.23[77.45,107.45];HTG:102.36[85.77,125.12];P=0.007)was lower in NTG than in HTG.There were no significant differences in the DCRs between HTG and control groups(P>0.05).In the univariate and multivariate analyses,some of the DCRs,such as IR,were negatively correlated with CCT and IOP,whereas SP-A1 was positively correlated with CCT and IOP.Conclusions:The cornea was more deformable in NTG than in HTG or controls.There were no significant differences in corneal deformability between HTG and controls.The cornea was more deformable with the thinner cornea and lower IOP.

POAG和高眼压症患者24h眼压与饮水试验的临床特点和相关性分析

目的:总结原发性开角型青光眼(POAG)和高眼压症(OHT)患者24h眼压和饮水试验(WDT)的临床特点并分析其相关性。方法:收集2019-12/2022-03于深圳大学总医院眼科行24h眼压(每2h测量1次)和WDT(按1000mL饮水量,5min内饮完,之后1h内每15min测量1次)的POAG和OHT患者87例174眼,共分为三组:高眼压性开角型青光眼(HTG组)33例66眼,正常眼压性青光眼(NTG组)28例56眼,OHT组26例52眼。总结三组患者24h眼压和WDT临床特点,并对各组眼压峰值、波动值进行Spearman相关分析。结果:三组患者临床特点:(1)24h眼压HTG组、NTG组、OHT组眼压峰值比例:凌晨(2∶00~6∶00):40.9%、23.2%、26.9%;上午(8∶00~12∶00):34.8%、46.4%、55.8%;下午(14∶00~18∶00):18.2%、21.4%、11.5%;夜间(20∶00~24∶00):6.1%、8.9%、5.8%。各组谷值比例:凌晨:21.2%、25.0%、30.8%;上午:22.7%、10.7%、13.5%;下午:19.7%、17.9%、17.3%;夜间:36.4%、46.4%、38.5%。各组24h眼压波动<6mmHg的比例:9.1%、62.5%、17.3%;6~<8mmHg:24.2%、32.1%、40.4%;≥8mmHg:66.7%、5.4%、42.3%。(2)WDT:三组30min内可达到眼压高峰比例分别为81.8%、76.8%、80.8%。三组WDT眼压波动<6mmHg的比例:10.6%、78.6%、38.5%;6~<8mmHg:22.7%、16.1%、28.8%;≥8mmHg:66.7%、5.4%、32.7%。(3)三组WDT峰值高于24h眼压峰值的比例分别为:80.3%、80.4%、80.8%。相关性:三组24h眼压峰值与WDT峰值存在显著正相关(均P<0.01),HTG组和OHT组24h眼压波动值与WDT波动值存在正相关(P<0.01,P<0.05),NTG组二者眼压波动值无明显相关(P>0.05)。结论:仅在工作时间(08∶00~18∶00)监测眼压可能会遗漏峰值,低估眼压波动值,24h眼压波动值≥8mmHg中HTG组>OHT组>NTG组。超过75%患者WDT在30min内达峰值,大于80%患者WDT峰值高于24h眼压峰值。HTG和OHT患者24h眼压波动值与WDT波动值存在正相关性。WDT在评估患者眼压的波动有一定临床意义。

Identification and validation of key biomarkers and potential therapeutic targets for primary open-angle glaucoma

Primary open-angle glaucoma(POAG)is a prevalent cause of blindness worldwide,resulting in degeneration of retinal ganglion cells and permanent damage to the optic nerve.However,the underlying pathogenetic mechanisms of POAG are currently indistinct,and there has been no effective nonsurgical treatment regimen.The objective of this study is to identify novel biomarkers and potential therapeutic targets for POAG.The mRNA expression microarray datasets GSE27276 and GSE138125,as well as the single-cell high-throughput RNA sequencing(sc RNA-seq)dataset GSE148371 were utilized to screen POAGrelated differentially expressed genes(DEGs).Functional enrichment analyses,protein-protein interaction(PPI)analysis,and weighted gene co-expression network analysis(WGCNA)of the DEGs were performed.Subsequently,the hub genes were validated at a single-cell level,where trabecular cells were annotated,and the mRNA expression levels of target genes in different cell clusters were analyzed.Immunofluorescence and quantitative real-time PCR(q PCR)were performed for further validation.DEGs analysis identified 43 downregulated and 32 upregulated genes in POAG,which were mainly enriched in immune-related pathways,oxidative stress,and endoplasmic reticulum(ER)stress.PPI networks showed that FN1 and DUSP1 were the central hub nodes,while GPX3 and VAV3 were screened out as hub genes through WGCNA and subsequently validated by q PCR.Finally,FN1,GPX3,and VAV3 were determined to be pivotal core genes via single-cell validation.The relevant biomarkers involved in the pathogenesis of POAG,may serve as potential therapeutic targets.Further studies are necessary to unveil the mechanisms underlying the expression variations of these genes in POAG.