Analysis of SMOC2 gene variants in familial and nonfamilial primary open angle glaucoma Pakistani patients

AIM:To find out the association of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 2(SMOC2)gene variants rs2255680 and rs13208776 with genotypic and phenotypic characteristics in both familial and non-familial primary open angle glaucoma(POAG)patients.METHODS:A total of 212 POAG patients,comprising 124 familial and 88 non-familial,were enrolled.For genotyping the SMOC2 variant rs2255680,amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)method and PCR-restriction fragment length polymorphism(PCR-RFLP)were utilized for analyzing rs13208776 variant.RESULTS:The mean age of familial POAG patients was 50.92±9.12y,with 78 males and 46 females.The mean age of non-familial POAG patients was 53.14±13.44y,with 52 males and 36 females.The SMOC2 gene variant rs13208776 showed the significant association with POAG between familial and non-familial groups.The homozygous G/G variant was frequent among non-familial(60.2%)whereas the heterozygous G/A variant was more frequent in familial POAG patients(46%).There were significant differences in G/A variant between familial and non-familial glaucoma patients,and the risk was decreased to 0.53-fold in non-familial glaucoma patients[odds ratio(OR):0.53;95%confidence interval(CI):0.29-0.94;P=0.033]in codominant model.The risk was further reduced to 0.49-fold(95%CI:0.28-0.86;P=0.012)in dominant model for non-familial patients.No significant association of SMOC2 gene variant rs2255680 between familial and non-familial glaucoma patients was found in our population.The haplotype analysis showed the decreased risk for TA[OR:0.48(95%CI:0.29-0.79);P=0.004]and an increased risk for TG[OR=2.28(95%CI:1.22-4.25);P=0.01]haplotypes.CONCLUSION:Current findings show significant association of SMOC2 gene variant rs13208776 with POAG between familial and non-familial Pakistani patients.

A highly sensitive fluorescent probe RN-NA reveals peroxynitrite as a novel biomarker for primary open angle glaucoma

AIM:To directly quantify peroxynitrite(ONOO-)using a highly sensitive fluorescence resonance energy transfer probe RN-NA,investigate the association between ONOOand primary open angle glaucoma(POAG),and clarify whether RN-NA could be used as a potential tool for POAG diagnosis.METHODS:Plasma and aqueous humor(AH)samples were collected from POAG patients(n=100,age:59.70±6.87y)and age-related cataract(ARC)patients(n=100,age:61.15±4.60y)admitted to our hospital.Next,RN-NA was used to detect ONOO-in plasma and AH samples,and the relationship between ONOO-level and POAG was analyzed using binary logistic regression.Besides,Pearson correlation analysis was applied to characterize the correlation of the levels of ONOO-with the patients’age,intraocular pressure(IOP),and mean deviation of visual field testing.The ONOO-scavenger MnTMPyP was employed to treat the 3-morpholinosyndnomine(SIN-1)-induced ocular hypertension in mice(n=7,6-8wk).Finally,the IOP and ONOO-in both eyes were measured 30min after the last drug treatment.RESULTS:ONOO-levels of AH and plasma were significantly higher in the POAG group than in the ARC group(P<0.01).Additionally,ONOO-levels were closely correlated with POAG in a binary logistic regression analysis[odds ratio(OR)=1.008,95%confidence interval(CI):1.002-1.013,P<0.01 for AH;OR=1.004,95%CI:1.002-1.006,P<0.001 for plasma].Pearson correlation analysis showed that ONOO-levels in AH or plasma were positively associated with visual field defects(R=0.51,P<0.01 for AH;R=0.45,P<0.001 for plasma),and ONOO-levels in plasma and AH were correlated in the POAG group(R=0.69,P<0.001).However,administering MnTMPyP to mouse eyes reversed the elevated IOP caused by SIN-1(P<0.05).CONCLUSION:ONOO-levels in AH and plasma,detected by RN-NA,are significantly related to POAG and positively correlated with visual field defects in POAG patients.Hence,ONOO-is a potential biomarker of POAG,especially advanced POAG.Besides,anti-nitration compounds may be novel ocular hypotensive agents based on the animal study.

MP-3 microperimeter in early primary open angle glaucoma with a new pattern

AIM:To investigate macular microperimetry in patients with early primary open angle glaucoma(POAG)using a new custom-made pattern,and analyze the characteristics of macular sensitivity.METHODS:This case-control study included 38 patients with POAG,who were divided into pre-perimetric glaucoma(18 eyes of 18 patients),early-stage(20 eyes of 20 patients),and control(20 eyes of 20 patients)groups.All subjects underwent standard 24-2 humphrey visual field test.An MP-3 microperimeter with a new custom-made pattern(28 testing points distributed in four quadrants,covering the central 10°of the retina)was used to evaluate macular sensitivity.Ganglion cell complex(GCC)thicknesses were examined using an RS-3000 Advance OCT system.The features of structure and function were analysed per quadrant.RESULTS:The pre-perimetric glaucoma group had significantly lower inferior hemifield macular sensitivity compared to controls(P<0.05).The early-stage POAG group had significantly lower average,inferior hemifield,inferonasal,and inferotemporal mean sensitivities compared to the pre-perimetric glaucoma group(P<0.05),and lower macular sensitivity in all sectors compared to controls(P<0.05).Regarding GCC thickness,all sectors in the early-stage POAG group became thinner compared to those in controls(P<0.05);whereas all sectors in the early-stage POAG group,except the superonasal quadrant,became thinner compared to those in the pre-perimetric glaucoma group(P<0.05).Macular sensitivity and GCC thickness were significantly associated in each sector.The inferotemporal quadrant had the highest correlation coefficients(0.840).The structure-function relationship for the inferonasal and inferotemporal sectors was stronger compared to the corresponding superior sectors.CONCLUSION:Microperimetry reveals variations in macular sensitivity in patients with early glaucoma earlier than conventional perimetry,particularly in pre-perimetric glaucoma cases in which it might be undetectable by conventional methods.The new custom-made pattern may improve the accuracy of microperimetry by enhancing point arrangement and reducing fatigue effects.Macular sensitivity measured by MP-3 with this pattern shows statistically significant structural and functional associations with the thicknesses of the GCC.

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. .

Efficacy and safety of latanoprost/timolol fixed combination dosed twice daily compared to once daily in patients with primary open angle glaucoma

AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,randomized,prospective crossover study on fourty primary open angle glaucoma patients.Two weeks of washout period were followed by randomization to either once daily(OD,group A)or twice daily dosing(BD,group B)of LTFC for 4wk.After another 2-week washout period,the patients’treatment dose was crossed-over for another 4wk.IOP reduction alongside ocular and systemic side effects were evaluated.RESULTS:Mean baseline IOP was 18.57±2.93 and 17.8±3.01 mm Hg before OD and BD dose respectively,(P=0.27).Mean IOP after BD dose was statistically lower(12.49±1.59 mm Hg)compared to OD(13.48±1.81 mm Hg,P=0.017).Although IOP reduction after BD dose was more(5.32±3.24 mm Hg,29.89%)than after OD dosing(5.04 mm Hg,27.14%),it did not reach statistical significance(P=0.68).Patients switched from OD to BD(group A)showed mean IOP reduction by 0.69 mm Hg[95%confidence interval(CI):-0.09 to 1.48 mm Hg,P=0.078];but patients switched from BD to OD(group B)had significantly higher mean IOP by 1.25 mm Hg(95%CI:-2.04 to-0.46 mm Hg,P=0.006).BD dose had more ocular side effects albeit mild.CONCLUSION:Mean IOP after LTFC dosed twice daily is statistically lower,with additional mild side effects.

Prevalence of Myocilin Gene Mutation in Adult-Onset Primary Open Angle Glaucoma and Non-Glaucoma Subjects Who Are Indigenes of Rivers State, Nigeria

Background: Glaucoma is the leading cause of irreversible blindness incapacitating over 80 million people worldwide. Several pathogenetic mechanisms have been postulated to explain the optic nerve damage that occur in POAG among which genetic predisposition is prominent. Gene-Linkage-based studies have identified genes associated with POAG: Myocilin, Optineurin, WDR36, Tank-Binding Kinase (TBK1) and APbb-2. Objective: To investigate the prevalence of myocilin gene mutation in adult-onset POAG patients and non-glaucoma subjects who are indigenes of Rivers State. Methodology: In this comparative cross-sectional study, 393 POAG patients attending the Glaucoma Clinic of UPTH were compared with 393 age and sex-matched phenotypically normal participants. Clinical assessment combined with findings from clinical records was used. Venous blood was obtained for genomic analyses. Extracted DNA was sequenced with specific primers for myocilin and polymerase chain reaction. Zymo-Bead Genomic DNA kit protocol was used to detect allelic differences. Results: Total of 786 participants participated in the study. The mean age was 59.8 ± 11.8 years. The prevalence of myocilin gene mutation (MYOC) in the study population was 5.3%, in the POAG group was 8.4%, and 2.3% in the non-glaucoma group. This observed difference was statistically significant (p = 0.001). Location of the mutant myocilin gene was in GLC1A 171638779, 171638703, 171638610 and 171638608. Conclusion: Mutations in myocilin gene are associated with adult-onset POAG in Rivers State. Its relevance as a biomarker for diagnosis of adult-onset POAG needs further investigations.

Effect of phacoemulsification on intraocular pressure in patients with primary open angle glaucoma and pseudoexfoliation glaucoma

AIM：To compare the effect of phacoemulsification on intraocular pressure（IOP）in patients with primary open angle glaucoma（POAG）and pseudoexfoliation glaucoma（PXG）.METHODS：A retrospective comparative case series conducted at the Glaucoma Department at the Association to Prevent Blindness in Mexico.The study enrolled consecutive patients having phacoemulsification with intraocular lens（IOL）implantation and a diagnosis of POAG or PXG.Data about IOP values and number of glaucoma medications used was collected at baseline,1,3,6 and12mo postoperatively.RESULTS：The study enrolled 88 patients（88 eyes）.After phacoemulsification,there was a statistically significant reduction in IOP values and glaucoma medications use compared to baseline in both POAG and PXG patients（P〈0.001）.In the POAG group,a 20%decrease in IOP values was evidenced,and a 56.5%reduction in the number of medications used at the one-year follow-up.The PXG group showed a 20.39%,and a 34.46%decrease in IOP and number of medications used,respectively.A significant difference in the meanΔIOP（postoperative changes in IOP）was evidenced between groups（P=0.005）.The reduction of the postsurgical IOP mean values in both groups,the POAG group showed a greater reduction in IOP values compared to the PXG group.CONCLUSION：In both types of glaucoma,phacoemulsification cataract surgery can result in a significant IOP reduction（20%）over a 12mo follow-up period.The number of medications used is also significantly reduced up to 12mo after surgery,especially in the PXG group.

High myopia as a risk factor in primary open angle glaucoma

Glaucoma, one of the leading causes of irreversible blindness in the adult population worldwide, is a progressive optic neuropathy. Primary open angle glaucoma (POAG) is the most commonly reported type of glaucoma in population based prevalence studies worldwide. Elevated intraocular pressure is a well-known major risk factor for POAG. In addition, there is growing evidence that other risk factors like age, gender, race, refractive error, heredity and systemic factors may play a role in glaucoma pathogenesis. Many studies found that high myopia has been associated with POAG, however, direct and convincing evidences are still lacking. The aim of this review is to summarize the evidences implicating high myopia as a risk factor in the pathogenesis of POAG.

Two-year outcomes of ab interno trabeculectomy with the Trabectome for Chinese primary open angle glaucoma： a retrospective multicenter study

AIM： To evaluate the 2-year efficacy and safety of ab interno trabeculectomy with the Trabectome in Chinese primary open angle glaucoma （POAG） patients. METHODS： This was a multicenter, retrospective, observational study and included POAG patients with or without visually-significant cataracts. The Chinese patients were enrolled from three glaucoma centers and a group of comparable Japanese POAG patients was analyzed from our international Trabectome database. The patients received Trabectome or a combined surgery with phacoemulsification and intraocular lens implantation. The primary outcome was intraocular pressure （IOP） reduction. Secondary outcomes included reduction of glaucoma medications, surgical complications, and success at 2y. Success was defined as： 1） IOP≤21 mm Hg and at least 20% IOP reduction from baseline after 3mo at any two consecutive visits; 2） no additional glaucoma surgery required. RESULTS： A total of 42 Chinese POAG patients from three glaucoma centers were enrolled. Twelve patients underwent Trabectome surgery combined with phacoemulsification and intraocular lens implantation while the remainder underwent Trabectome surgery alone. Thirteen patients had a history of failed glaucoma surgery and were considered as complicated cases. In China data, the mean preoperative IOP was 21.4±1.23 mm Hg. The Trabectome lowered IOP to 17.9±1.8 mm Hg at 2y （P=0.05）. The number of glaucoma medications also decreased significantly from a baseline of 2.0±0.9 to 1.1±0.8 at 2y post-surgery （P=0.04）. The overall 2-year success rate was 78%, with patients undergoing combined surgery having a higher success rate compared with those undergoing Trabectome surgery alone （100% vs 76%）. In Japan data, the mean preoperative IOP was 20.8±7.7 mm Hg. The Trabectome lowered IOP to 12.20±2.0 mm Hg at 2y. The number of glaucoma medications also decreased significantly from a baseline of 2.1±0.9 to 3.4±0.6 at 2y post-surgery. In all patients, no major complications were seen. CONCLUSION： Surgery with the Trabectome appears to be an efficient and safe procedure in Chinese POAG patients in the long-term.

Comparison of total/active ghrelin levels in primary open angle glaucoma,pseudoexfoliation glaucoma and pseudoexfoliation syndrome

AIM：To investigate the levels of ghrelin（Gh）,acylated ghrelin（AGh） and AGh/Gh ratio in the humor aqueous（HA） of cases with pseudoexfoliation syndrome（PXS）,pseudoexfoliation glaucoma（PXG）,primary open angle glaucoma（POAG） and to compare these with control subjects.METHODS：A prospective examination was made of the total Gh,and AGh levels in HA of 67 patients undergoing cataract surgery.Patients were divided into 4 groups.HA samples were aspirated at the beginning of the surgery,stored at -70℃.Gh and AGh quantification was performed with ELISA kits and the AGh/total-Gh ratios were calculated.ANOVA,Kruskal-Wallis,Chi-square and post-hoc tests were used for statistical analysis.RESULTS：Total Gh levels in HA were 189.2±45.6 pg/mL in the control group,199.2±32.9 pg/mL in PXS,180.6±20.9 pg/mL in PXG and 176.8±21.4 pg/mL in POAG groups（P〉0.05）.AGh levels in HA were 23.09±5.01 pg/mL in the control group,24.13±5.22 pg/mL in PXS,22.29±1.55 pg/m L in PXG and 19.69±2.93 pg/mL in POAG groups（P〉0.05）.The ratio of AGh/Gh was 10.3%±2.34% in the control group,13.03%±2.58% in PXS,12.3%±1.54% in PXG and 11.79%±1.41% in POAG groups（P=0.044）.The difference between the PXS and control groups was significant（P=0.03）.CONCLUSION：In spite of statistically insignificant results,the HA total Gh levels were lower than those of the control subjects but not parallel with the AGh levels in glaucoma patients.The relative increase in the AGh/Gh ratio in glaucoma cases supports the view that proportional increases of AGh might play a role in the pathogenesis of glaucoma.

Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

AIM:To evaluate intraocular pressure(IOP)-lowering effect and ocular tolerability of brimonidine/timolol,dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma.· METHODS:Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer.Ocular discomfort(conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale.RESULTS:Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2ndmo IOP measurements, and mean(%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels.· CONCLUSION:Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.

Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension:a systematic review and meta-analysis

AIM:To assess the effects of the fixed combination of0.005% latanoprost and 0.5% timolol(FCLT) vs their individual components for primary open angle glaucoma(POAG) and ocular hypertension(OHT).· METHODS:After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials(RCTs) and cross-over studies were included. The control groups were the monotherapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure(IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software.RESULTS:Thepost-interventionmeanIOPofFCLTwas significantly lower compared to timolol [mean difference(MD)-2.92, 95%CI-3.28 to-2.55, P 【0.00001] and latanoprost(MD-1.11, 95%CI-1.51 to-0.72, P 【0.00001). The postintervention IOP fluctuation was also significantly lower compared to timolol(MD-0.88, 95%CI-1.23 to-0.53, P 【0. 00001) and latanoprost( MD- 0. 63, 95 % CI- 1. 04to-0.22, P =0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol(UFCLT)(MD1.10, 95% CI 0.81 to 1.39, P 【0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT(MD 0.34, 95% CI-0.01 to 0.69, P =0.06).There was no statistical difference for the incidence ofvisual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.visual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.

Efficacy of low-energy selective laser trabeculoplasty on the treatment of primary open angle glaucoma

AIM: To investigate the efficacy of low-energy selective laser trabeculoplasty(SLT) on the treatment of primary open angle glaucoma(POAG) patients.METHODS: Outpatients with POAG who underwent 360-degree SLT using an initial energy of 0.3 mJ(total energy of 30-40 mJ) were reviewed retrospectively from September 2011 to January 2018.RESULTS: Eight-six eyes of 44 POAG patients underwent 360-degree SLT using initial energy of 0.3 mJ and were followed up regularly. The total energy used was 32.5±2.5 mJ(23-40 mJ, 105±6 spots). The average pretreatment intraocular pressure(IOP) was 19.8±3.9 mm Hg. At 1, 3, 6 mo, 1, and 2 y, the post-SLT IOPs(mm Hg) were 16.9±3.3, 16.5±3.3, 17.1±3.4, 16.6±3.5, 16.5±2.8, which were significantly lower than that before treatment(P<0.001). The patients in the SLT success group were found to be younger than those in the SLT failure group. After SLT, 59 eyes that maintained pretreatment medications were defined as the drug retention group. The pre-SLT IOP was 20.1±3.7 mm Hg.At 1, 3, 6 mo, 1, and 2 y, the post-SLT IOPs(mm Hg) were 17.3±3.6, 16.6±3.5, 17.2±3.6, 16.9±3.8 and 16.5±2.9, respectively. Twenty-seven eyes that required reduced drugs were defined as the drug reduction group. The pre-SLT IOP was 19.2±4.4 mm Hg. At 1, 3, 6 mo, 1, and 2 y, the post-SLT IOPs(mm Hg) were 16.1±2.6, 16.5±3.1, 16.8±2.9, 16.0±2.6 and 16.3±2.4, respectively. Compared with the pretreatment IOPs, the post-SLT IOPs were significantly lower in drug retention group and drug reduction group. The patients in the drug reduction group were found to be younger than those in the drug retention group.CONCLUSION: Low-energy SLT is safe and effective for POAG patients during a 2-year follow-up. Younger POAG patients may obtain better results after low-energy SLT treatment.

Efficacy and safety of micropulse laser trabeculoplasty for primary open angle glaucoma

AIM: To evaluate the efficiency and safety of micropulse laser trabeculoplasty(MLT) for primary open angle glaucoma(POAG) patients. METHODS: Retrospective study. POAG patients undergoing MLT in Peking University Third Hospital from June 2016 to November 2017. Seventy-two eyes of 72 POAG patients were enrolled. Only one eye of each patient was treated by MLT. The intraocular pressure(IOP) before MLT and at 1 d, 1, 4, 12 and 24 wk and glaucoma medication before and after treatment were compared.RESULTS: The IOP was 20.6±5.9 mm Hg before MLT and 20.8±6.8 mm Hg at 2 h after MTL. The IOP at 1 d, 1, 4, 12 and 24 wk was 17.9±4.4, 18.0±4.3, 17.5±3.4, 17.0±2.7, and 16.5±2.9 mm Hg, respectively. The IOP before and after MLT demonstrated a statistically significant difference by ANOVA analyses(F=5.797, P<0.001). Least significant difference t-tests showed there was no statistically significant difference between pre-MLT IOP within 2 h after MLT(P=0.207). The statistically significant difference was confirmed between the pre-MLT IOP at 1 d, 1, 4, 12 and 24 wk after MLT(P=0.006, 0.009, 0.001, <0.001, <0.001, respectively). The number of glaucoma medications before MLT was 1.7±1.4 and 1.5±1.4 24 wk after MLT with a significantly statistical difference(t=2.219, P=0.031)CONCLUSION: MLT is effective and safe for POAG patients. No patient experienced IOP spikes after MLT. The IOP 6 mo after treatment decreased significantly with less glaucoma medication.

Association between interleukin-10 genetic polymorphisms and risk of primary open angle glaucoma in a Chinese Han population: a case-control study

AIM: To investigate the association between interleukin-10(IL-10) genetic polymorphisms and risk of POAG through a case-control study in a Han population of China.METHODS: A total of 210 patients with POAG and 420 normal subjects were recruited during the period from Dec. 2013 to Dec. 2016. The IL-10-1082 A>G(rs1800870),-819 T>C(rs1800871) and-592 C>A(rs1800872) polymorphisms were determined using iPlex GOLD SNP genotyping analysis(the SequenomMassARRAY? System, Sequenom, San Diego, USA). The association between IL-10-1082 A>G(rs1800870),-819 T>C(rs1800871), and-592 C>A(rs1800872) polymorphisms and risk of POAG was assessed by singlelogistic regression analysis.RESULTS: We observed that those carrying the CC genotype of rs1800871 was associated with an increased risk of POAG when compared with those harboring the TT genotype(OR=1.84, 95%CI=1.01-3.38). Those with AA genotype of rs1800872 had a 10.62 fold risk of POAG in comparison to the CC genotype(OR=10.62, 95%CI, 3.41-33.09). A completely linkage disequilibrium was found between IL-10 rs1800871-rs1800872(D’=1.00, r2=0.16). The A-C-A(OR=2.60, 95%CI, 1.48-4.58) and G-T-A(OR=2.34, 95%CI, 1.42-3.86) haplotypes were associated with an increased risk of POAG, while the A-T-C haplotype showed a decreased risk of POAG(OR=0.63, 95%CI, 0.49-0.81). CONCLUSION: Our data suggest that IL-10 rs1800871 and rs1800872 can be predictive factors for the pathogenesis of POAG in the Chinese population.

Elevated urine formaldehyde in elderly patients with primary open angle glaucoma

AIM：To investigate the risk factor of primary open angle glaucoma（POAG）,which is the leading cause of irreversible blindness worldwide.An abnormally high level of endogenous formaldehyde（FA） has recently been found correlated with cell death and neurodegenerative disease,raising the possibility of a putative correlation of abnormal endogenous FA with POAG.· METHODS：Thirty-four elderly patients with POAG and sixteen healthy controls were enrolled.Glaucomatous visual defects were present at both the functional（visual field） and structural[retinal nerve fiber layer（RNFL）thickness]levels.Morning urine samples were obtained and were analyzed by high-performance liquid chromatography（HPLC） to detect the endogenous FA level in a double blind manner.· RESULTS：Patients with POAG（P 〈0.05） had significantly higher urine FA levels.The urine FA level of patients with severe visual field defects[mean deviation（MD）≥12 dB]was significantly（P〈0.001） greater than that of patients with mild to moderate defects（MD〈12 dB）.By optical coherence tomography（OCT）,the superior and inferior RNFL thickness of POAG group was significantly（P〈0.001） thinner than in controls.Furthermore,the superior and inferior thinning of the RNFL was correlated with the elevation of urine FA concentration.CONCLUSION：Endogenous FA level is positively correlated with the neuronal defects of POAG.

Inflammatory model in patients with primary open angle glaucoma and diabetes

AIM: To assess the inflammatory cytokines expression in aqueous humor in diabetic primary open angle glaucoma(POAG) patients. METHODS: A cross-sectional study on 87 eyes, distributed as following: 26 eyes from diabetic patients, 16 eyes with POAG and 21 eyes from diabetic POAG patients; healthy controls(24 eyes) were recruited from patients undergoing conventional cataract surgery. A volume of 100 μL of aqueous humor(AH) was collected during phacoemulsification and 21 inflammatory markers were quantified using a Luminex~? cytometric bead assay: IL-1 Ra, IL-1α, IL-1β, IL-5, IL-6, IL-10, IL-17, GM-CSF, IFNγ, CCL2, CCL3, CCL4, CXCL5, CXCL8, bFGF, VEGF, TNFα. Main changes in cytokine profile were analyzed and compared between groups. Data on demographics, duration of glaucoma, intraocular pressure(IOP), number of anti-glaucoma substances were recorded for correlation analysis and prediction models. RESULTS: Significant differences in cytokine expression between groups were detected for CXCL5(P<0.001), CXCL8(P=0.004), IL-1α(P<0.001), IL-2(P<0.001), CCL4(P=0.003), CCL5(P<0.001) and TNFα(P=0.05). Post-hoc analysis identified IL-2(P=0.009) and CXCL5(P<0.001) as "separation markers" between POAG and diabetic POAG eyes. In POAG patients, the "separation markers" could highly predict the TNFα levels F(1, 16)=14.639, P<0.001, whereas in diabetic patients F(1, 24)=4.844, P=0.006 and diabetic POAG patients F(1, 19)=2.358, P=0.05 the level of prediction was inferior.CONCLUSION: Our results reveal an inflammatory model based on increased TNFα levels in POAG eyes.Simultaneous co-stimulatory molecules and additional inflammatory pathways need to be further explored in diabetic POAG cases, since the prediction model could only partially explain the increased TNFα level in this category of patients.

Single nucleotide polymorphism of MYOC affected the severity of primary open angle glaucoma

AIM: To detect the mutations in two candidate genes, myocilin (MYOC ) and cytochrome P450 1B1 (CYP1B1 ), in a Chinese family with primary open angle glaucoma (POAG). ·METHODS:Thefamilywascomposedofthreemembers, the parents and a daughter. All members of the family underwent complete ophthalmologic examinations. Exons of MYOC and CYP1B1 genes were screened for sequence alterations by polymerase chain reaction (PCR) and direct DNA sequencing. ·RESULTS: The mother was the proband, she was diagnosed as POAG in both eyes. Her daughter was diagnosed as juvenile -onset POAG. The father was asymptomatic. One MYOC heterozygous mutation c.1150 G 】A (D384N) in exon 3 was identified in the mother, another MYOC heterozygous variation c.1058 C】T (T353I) in exon 3 was identified in the father, and the daughter inherited both of the variations. Meanwhile, three single nucleotide polymorphisms (SNPs) in CYP1B1 gene were found in the family. ·CONCLUSION: The D384N mutation of MYOC has been reported as one of disease-causing mutations in POAG, whereas T353I variation of MYOC was thought as a high risk factor for POAG. The two variations of MYOC were first reported in one juvenile -onset POAG patient whopresented with more severe clinical manifestations, suggesting that T353I polymorphism of MYOC may be associated with the severity of POAG.

Proteome alterations in aqueous humour of primary open angle glaucoma patients

AIM: To unravel the primary open angle glaucoma(POAG) related proteomic changes in aqueous humour(AH).METHODS: Totally 35 patients listed for cataract surgery(controls: n=12, age: 67.4±13.6 y) or trabeculectomy for POAG(n=23, age: 72.5±8.3 y) were included. AH samples of those patients were obtained during cataract surgery or trabeculectomy. AH samples were subsequently pooled into the experimental groups under equal contribution in terms of protein amount of each individual patient. Protein samples were analyzed by a linear trap quadrupol Orbitrap Mass Spectrometry device with an upstream liquid chromatography system. The obtained raw data were analyzed using the Maxquant proteome software and compared. Proteins with a fold-change ratio higher than a cut-off of 2 were considered as noticeably altered.RESULTS: A total number of 175 proteins could be identified out of the AH from POAG and cataract by means of quantitative mass spectrometric analysis. Apolipoprotein D(fold change, 3.16 times), complement C3(2.96), pigment epithelium-derived factor(2.86), dickkopf-related protein 3(2.18) and wingless-related integration(Wnt) inhibitory factor 1(2.35) were significantly upregulated within the AH of glaucoma compared to cataract serving as controls.CONCLUSION: AH provides a tool to analyze changes in glaucoma and shows striking changes in Wnt signaling inhibitory molecules and other proteins.