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.

Suicide risk in juvenile open angle glaucoma patients

AIM:To investigate the association between juvenile open angle glaucoma(JOAG)and mental health among Koreans.METHODS:This study used nationally representative data from the 8th Korea National Health and Nutrition Examination Survey(KNHANES)2021.Glaucoma diagnosis followed the International Society of Geographical and Epidemiological Ophthalmology criteria based on glaucomatous structural defects,visual field defects,corrected vision,and intraocular pressure.As outcomes,suicidal behaviors,psychiatric counseling,and depression were evaluated through mental health questionnaires.Odds ratios(ORs)with 95%confidence intervals(CIs)were estimated using logistic regression models,adjusting for covariates.RESULTS:Among 7090 participants,3446 met the inclusion criteria for analysis,and 88(2.6%)were diagnosed with open angle glaucoma(OAG).After adjusting for age,sex,and best-corrected visual acuity(VA),participants with OAG were revealed to have significantly higher odds of suicidal behaviors(i.e.,ideation,planning,or attempts)compared with those without OAG(OR:2.70;95%CI:1.12-6.54;P=0.028).This association remained significant after further adjustments for socioeconomic status,lifestyle factors,and presence of chronic conditions(P=0.031 and 0.035,respectively).However,there was no significant difference for the other two outcomes,psychiatric counseling and depression.An age-stratified analysis revealed a stronger association between OAG and suicidal behaviors in younger JOAG participants(<40y)than in older OAG participants(≥40y;OR:3.80 vs 2.22;95%CI:0.79-18.22 vs 0.56-8.80,respectively).CONCLUSION:OAG patients show a higher risk of suicidal behaviors than those without glaucoma particularly in JOAG patients.

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.

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.

Comparisons of ganglion cell-inner plexiform layer loss patterns and its diagnostic performance between normal tension glaucoma and primary open angle glaucoma: a detailed, severity-based study

AIM: To evaluate the patterns of macular ganglion cell-inner plexiform layer(GCIPL) loss in normal tension glaucoma(NTG) and primary open angle glaucoma(POAG) in a detailed, disease severity-matched way;and to assess the diagnostic capabilities of GCIPL thickness parameters in discriminating NTG or POAG from normal subjects.METHODS: A total of 157 eyes of 157 subjects, including 57 normal eyes, 51 eyes with POAG and 49 eyes with NTG were enrolled and strictly matched in age, refraction, and disease severity between POAG and NTG groups. The average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL thickness, and the average, superior, temporal, inferior, and nasal retinal nerve fiber layer(RNFL) thickness were obtained by Cirrus optical coherence tomography(OCT). The diagnostic capabilities of OCT parameters were assessed by area under receiver operating characteristic(AUROC) curves. RESULTS: Among all the OCT thickness parameters, no statistical significant difference between NTG group and POAG group was found(all P>0.05). In discriminating NTG or POAG from normal subjects, the average and inferior RNFL thickness, and the minimum GCIPL thickness had better diagnostic capabilities. There was no significant difference in AUROC curve between the best GCIPL thickness parameter(minimum GCIPL) and the best RNFL thickness parameter in discriminating NTG(inferior RNFL;P=0.076) and indiscriminating POAG(average RNFL;P=0.913) from normal eyes.CONCLUSION: Localized GCIPL loss, especially in the inferior and inferotemporal sectors, is more common in NTG than in POAG. Among all the GCIPL thickness parameters, the minimum GCIPL thickness has the best diagnostic performance in differentiating NTG or POAG from normal subjects, which is comparable to that of the average and inferior RNFL thickness.

Bimatoprost/timolol fixed combination(BTFC) in patients with primary open angle glaucoma or ocular hypertension in Greece

AIM：To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03%and timolol 0.5%（BTFC）in patients in Greece with primary open angle glaucoma（POAG）or ocular hypertension（OHT）whose previous therapy provided insufficient lowering of intraocular pressure（IOP）.·METHODS：A multicenter,prospective,open-label,non-interventional,observational study of the use of BTFC in clinical practice was conducted at 41 sites in Greece.The primary endpoint was the reduction in IOP from baseline at study end,approximately 12wk after initiation of BTFC therapy.·RESULTS：A total of 785 eligible patients were enrolled in the study and 97.6%completed the study.The mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg（=764;〈0.001）.In patients（=680）who replaced their previous IOP-lowering monotherapy（a single drug,or a fixed combination of 2drugs in a single ophthalmic drop）with once-daily BTFC,the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg（〈0.001）.IOP was reduced from baseline in 99.2%of patients,and 58.0%of patients reached or exceeded their target IOP.Substantial mean IOP reductions were observed regardless of the previous therapy.BTFC was well tolerated,with 96.0%of patients who completed the study rating the tolerability of BTFC as＂good＂or＂very good.＂Adverse events were reported in 8.3%of patients;only 0.6%of patients discontinued the study due to adverse events.·C ONCLUSION：In clinical practice in Greece,BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy.

Intraocular retinal thickness asymmetry in early stage of primary open angle glaucoma and normal tension glaucoma

AIM： To investigate the intraocular retinal thickness asymmetry of peripapillary retinal nerve fiber layer（pR NFL） and macular layers measured by spectral-domain optical coherence tomography（SD-OCT） in patients with early stage of primary open angle glaucoma（POAG） and normal tension glaucoma（NTG）.METHODS： A total of 117 patients with early stage of glaucoma（54 patients with POAG and 63 patients with NTG） and 32 normal subjects were recruited for the study. The pR NFL thickness, total macular layer（TML） thickness, and isolated inner macular layer（IML） thickness were measured by SD-OCT. Hemisphere TML thickness asymmetry measured by the posterior pole asymmetry scan was evaluated. Thickness differences of pR NFL and IML between superior and inferior quadrants were calculated. Asymmetry indices（AIs） of the p RNFL, TML and isolated IML were also computed. Areas under the receiver-operating characteristic curves（AROCs） were generated to determine the diagnostic capabilities of different parameters. RESULTS： Intraocular p RNFL thickness differences and AIs between the superior and inferior quadrants were significantly different between normal and NTG groups（P=0.009 and P〈0.001, respectively）. Intraocular p RNFL thickness differences and AIs between the temporal-superior and temporal-inferior sectors were also significantly different between normal and NTG groups（P=0.035 and P〈0.001, respectively）. The thickness differences and AIs of TML between superior and inferior hemispheres were significantly different between normal and NTG groups（P=0.001 and P=0.001, respectively） and between normal and POAG groups（P=0.032 and P=0.020, respectively）. The thickness differences and AIs of macular ganglion cell layer（mG CL） between superior and inferior quadrants were significantly different between normal and NTG groups（P=0.013 and P=0.004, respectively）, and between NTG and POAG groups（P=0.015 and P=0.012, respectively）. The thickness difference of TML between superior and inferior hemispheres showed the highest diagnostic capability for early NTG eyes（AROC=0.832）.CONCLUSION： Intraocular retinal thickness asymmetry in pR NFL, TML and mG CL are found in early stage of NTG. Hemisphere TML thickness asymmetry is also found in POAG eyes. Asymmetry analysis of retinal thickness can be an adjunctive modality for early detection of glaucoma.

Selective laser trabeculoplasty in patients with pseudoexfoliative glaucoma vs primary open angle glaucoma： a one-year comparative study

AIM：To compare the efficacy of single-session 360-degree selective laser trabeculoplasty（SLT） for reduction of intraocular pressure（IOP） in patients with pseudoexfoliative glaucoma（PXFG） and primary open angle glaucoma（POAG）.· METHODS：This is a single-center,prospective,nonrandomized comparative study.Patients older than 18 years of age with uncontrolled PXFG or POAG eyes requiring additional therapy while on maximally tolerated IOP-lowering medications were included.The primary outcome measure changed in IOP from baseline.Success was defined as IOP reduction ≥20%from baseline without any additional IOP-lowering medication.All patients were examined at 1d,1wk,1,3,6,9,12 mo after SLT.· RESULTS：Nineteen patients（20 eyes） with PXFG and27 patients（28 eyes） with POAG were included in the study.In the visual fields mean deviation was-2.88（±1.67）in the POAG and-3.1（±1.69） in the PXFG groups（P=0.3）.The mean（±SD） IOP was 22.9（±3.7） mm Hg in the POAG group and 25.7（±4.4） mm Hg in the PXFG group at baseline and decreased to 18.4（±3.2） and 18.0（±3.9） mm Hg in the POAG group（P〈0.001 and P=0.02）,and to 17.9（±4.0） and 21.0（±6.6） mm Hg in the PXFG group（P〈0.001 and P=0.47） at 6 and 12 mo,respectively.The number of medications was 2.6（±0.8） in the POAG group and 2.5（±0.8） in the PXFG group at baseline,and did not change at all follow-up visits in both groups（P =0.16 in POAG and 0.57 in PXFG）.Based on Kaplan-Meier survival analysis,the success rate was 75%in the POAG group compared to 94.1%in the PXFG group（P=0.08;Log-rank test） at 6mo,and 29.1%and 25.0%at 12 mo,respectively（P=0.9;Log-rank）.· CONCLUSION：The 360-degree SLT is an effective and well-tolerated therapeutic modality in patients with POAG and PXFG by reducing IOP without any change in number of medications.The response was more pronounced early in the postoperative period in patients with PXFG whereas there was no statistically significant difference at 12-month follow-up. 〈/tr〉

Efficacy and safety of XEN 45 gel stent alone or in combination with phacoemulsification in advanced open angle glaucoma patients: 1-year retrospective study

AIM:To assess the effectiveness of the XEN 45 gel stent,either alone or combined with cataract surgery,in advanced stage open angle glaucoma(OAG)patients.METHODS:Retrospective and single-center study conducted on consecutive OAG patients who underwent a XEN 45 gel stent implantation surgery,between July 2017 and September 2018.The primary efficacy end-point was the mean intraocular pressure(IOP)reduction at the end of the follow-up period.Success was defined as an IOP reduction of at least 20%and an IOP value≤18 mm Hg without(complete)or with(qualified)hypotensive medication.RESULTS:Seventy-four patients(80 eyes)were included in the study.In the overall study sample,XEN implant significantly reduced IOP from 21.0(19.8 to 22.1)mm Hg at baseline to 9.3(8.2 to 10.4),10.7(9.6 to 11.9),13.4(12.2 to 14.7),14.5(13.6 to 15.4),14.7(13.8 to 15.6),and 14.7(13.9 to 15.4)mm Hg at 1 d,1 wk,1,3,6,and 12 mo of follow-up,respectively(P<0.0001 each).In the overall study population,at the end of the study the mean IOP reduction was 27.4%(23.3%to 31.5%).Adjusted IOP reduction was similar in XEN and XEN+phacoemulsification groups[30.0(23.4 to 36.4)mm Hg vs 24.8(18.4 to 31.2)mm Hg,respectively,P=0.2939].At the last follow-up visit,52(65.0%)eyes were considered success,29(36.3%)eyes as complete success and 23(28.7%)as qualified success.Mean number of hypotensive medications was significantly reduced from 2.8(2.7 to 3.0)at baseline to 1.1(0.8 to 1.3),P<0.0001.Kaplan-Meier survival analysis did not find any difference in the success rate between XEN and XEN+PHACO,mean hazard ratio 0.56,95%CI 0.26 to 1.23;P=0.1469.Needling was performed in 7(8.8%)eyes at months 1(n=3);3(n=2);4(n=1)and 11(n=1).Eleven(13.8%)eyes presented adverse events.CONCLUSION:XEN implant,either alone or in combination with phacoemulsification,significantly reduced the IOP and the number of hypotensive medications in patients with OAG in advanced stage.

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.

Comparison of canaloplasty and trabeculectomy for open angle glaucoma：a Meta-analysis

AIM： To evaluate the advantage of canaloplasty compared to trabeculectomy for patients with open angle glaucoma.METHODS： Potentially relevant studies were systematically searched using various databases from inception until December 2015. The outcome analyses performed automatically using Revman 5.3 included intraocular pressure reduction （IOPR）, postoperative success rate, anti-glaucoma medications reduction and the incidence of adverse events.RESULTS： We included four qualified studies incorporating a total of 215 eyes for quantitative synthesis. The weighted mean difference （WMD） of IOPR between canaloplasty and trabeculectomy from baseline to 12mo was -2.33 （95%CI： -4.00, -0.66）. There was not significant improvement in the complete or qualified success rate （OR： 0.58, 95%CI： 0.26, 1.31; OR： 0.50, 95%CI： 0.10, 2.44, respectively）. Similarly, no statistically significance was observed in anti-glaucoma mediations reduction （WMD： -0.54, 95%CI： -1.18, 0.09）. Sensitivity analysis of the primary outcome estimate confirmed the stability of the Meta-analysis result.CONCLUSION： Trabeculectomy seems to be more effective in lowering IOP up to 12mo when comparing with canaloplasty. Canaloplasty does not seem to be inferior to trabeculectomy considering the postoperative success rate or the number of postoperative anti-glaucoma medications. Meanwhile, it has an advantage of less bleb related complications.

Meta Analysis of Non-penetrating Trabecular Surgery versus Trabeculectomy for the Treatment of Open Angle Glaucoma

This study compared the efficacy of non-penetrating trabecular surgery and trabeculectomy for the treatment of open angle glaucoma. We searched the Cochrane Library, PUBMED （1966 to 2009）, Embase （1980 to 2009） and CMB-disk （1979 to 2009） for the randomized clinical trials （RCT） concerning the two treatment strategies. The reports, including the papers listed in bibliographies, were evaluated against a set of quality criteria and the RCTs that satisfied the criteria were selected and subjected to Meta analysis by employing the Cochrane Collaboration＇s RevMan 4.5 software package. A total of nine RCTs were included in the study. The analyses of the reports showed that, 12 months after surgery, there was significant difference in the reduction of interocular pressure （IOP） between non-penetrating trabecular surgery and trabeculectomy （Z=6.05 P0.00001）. There also existed statistically significant difference in the reduction of IOP at the censored time between the two procedures （Z=4.92, P0.00001）. Difference in the success rate was also found between the two surgeries （Z=3.82, P=0.0001）. It is concluded that, compared with the non-penetrating trabeculectomy, the traditional trabeculectomy could reduce IOP more and had higher success rate while the non-penetrating trabecular surgery is associated with lower postoperative complications.

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.

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.

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.