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.

Morphological disruption and visual tuning alterations in the primary visual cortex in glaucoma(DBA/2J)mice

Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.

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. .

Structural measurements and vessel density of spectraldomain optic coherence tomography in early,moderate,and severe primary angle-closure glaucoma

AIM:To compare the macular ganglion cell-inner plexiform layer(GCIPL)thickness,retinal nerve fiber layer(RNFL)thickness,optic nerve head(ONH)parameters,and retinal vessel density(VD)measured by spectral-domain optical coherence tomography(SD-OCT)and analyze the correlations between them in the early,moderate,severe primary angle-closure glaucoma(PACG)and normal eyes.METHODS:Totally 70 PACG eyes and 20 normal eyes were recruited for this retrospective analysis.PACG eyes were further separated into early,moderate,or severe PACG eyes using the Enhanced Glaucoma Staging System(GSS2).The GCIPL thickness,RNFL thickness,ONH parameters,and retinal VD were measured by SD-OCT,differences among the groups and correlations within the same group were calculated.RESULTS:The inferior and superotemporal sectors of the GCIPL thickness,rim area of ONH,average and inferior sector of the retinal VD were significantly reduced(all P<0.05)in the early PACG eyes compared to the normal and the optic disc area,cup to disc ratio(C/D),and cup volume were significantly higher(all P<0.05);but the RNFL was not significant changes in early and moderate PACG.In severe group,the GCIPL and RNFL thickness were obvious thinning with retinal VD were decreasing as well as C/D and cup volume increasing than other three groups(all P<0.01).In the early PACG subgroup,there were significant positive correlations between retinal VD and GCIPL thickness(except superonasal and inferonasal sectors,r=0.573 to 0.641,all P<0.05),superior sectors of RNFL thickness(r=0.055,P=0.049).More obvious significant positive correlations were existed in moderate PACG eyes between retinal VD and superior sectors of RNFL thickness(r=0.650,P=0.022),and temporal sectors of RNFL thickness(r=0.740,P=0.006).In the severe PACG eyes,neither GCIPL nor RNFL thickness was associated with retinal VD.CONCLUSION:The ONH damage and retinal VD loss appears earlier than RNFL thickness loss in PACG eyes.As the PACG disease progressed from the early to the moderate stage,the correlations between the retinal VD and RNFL thickness increases.

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.

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.

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.

Three-dimensional choroidal vascularity index and choroidal thickness in fellow eyes of acute and chronic primary angle-closure using swept-source optical coherence tomography

AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.

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.

Diffusion tensor imaging of optic nerve and optic radiation in primary chronic angle-closure glaucoma using 3T magnetic resonance imaging

AIM: To evaluate the value of quantitative diffusion tensor imaging (DTI) in assessing the axonal and myelin damage of the optic nerves and optic radiations in patients with chronic primary angle -closure glaucoma (PACG) by using high -field magnetic resonance (MR) imaging (3T). METHODS: Twenty patients with bilateral chronic PACG and twenty age - and sex matched disease -free control subjects were enrolled. Conventional MRI and DTI were performed on all subjects using 3T MR scanner. Mean diffusivity (MD), fractional anisotropy (FA), axial diffusivities (AD) and radial diffusivities (RD) of each optic nerve and each optic radiation were measured by using post -processing software of DTI studio 2.3, and then compared between left eyes and right eyes and between patients group and control group. The pairedsample t- test were used. RESULTS: There was no abnormality in the shape and signal intensity of the optic nerves and optic radiations in patients group and control group on the conventional MRI. No significant differences were observed in the FA, MD, AD and RD between the right and left optic nerves and optic radiations within patients group and control group (P>0.05). The optic nerves and optic radiations of patients with chronic PACG, as compared with control subjects, had significantly higher MD, AD, RD and significantly lower FA (P<0.05). CONCLUSION: The diffusivity of optic nerves and optic radiations in chronic PACG group showed abnormal and diffusivity parameters could be used markers of axonal and myelin injury in glaucoma.

Surgical treatment for primary angle closure-glaucoma: a Meta analysis

AIM To evaluate the efficacy and safety of trabeculectomy, phacotrabeculectomy plus intraocular lens implantation (phacotrab+IOL group) and phacoemulsification with IOL (phaco+IOL) in primary angle-closure glaucoma(PACG). METHODS: It was a systematic review and meta-analysis, randomized controlled trials(RCT) and clinical controlled trials (CCT) were collected through electronic searches of the Cochrane Library, PubMed, EMbase, Wanfang Database online, Chinese journal Full-text Database, Chinese Scientific Journals Full-text Database (from the date of building the database to October 2010) We also checked the bibliographies of retrieved articles. M the related data that matched our standards were abstracted. The quality of included trials was evaluated according to the Dutch Cochrane Centre. Rev Man 5.0 software was used for Meta-analysis. RESULTS: A total of 5 RCT and 11 CCT involving 1495 eyes were included. The results of meta-analysis showed that phacotrab+IOL group was superior than trabeculectomy(trab group) (MD -3.93,95% CI [-7.31, -0.54]) which was also superior than phaco+IOL group(MD 0.52,95%CI [0.10, 0.95]) in decreasing Intraocular Pressure(IOP). Phacotrab group(MD -1.45,95%CI [-1.68, -1.22])and phaco group (MD-1.12,95% CI [-1.87, -0.37])are both deeper than trab group in the anterior chamber depth. In increasing the coefficient of outflow facility of aqueous humor (C values) there was no statistical difference in the three groups. And there was no statistical difference between phacotrab groups and phaco groups in visual acuity but phacotrab group was superior than phaco group (MD 1.07, 95% CI [0.73, 1.40])in the use of IOP-lowering drugs. There was no statistical difference among three groups. CONCLUSION: Current evidence suggests that phacotrab+IOL group was superior than tab group which was also superior than phaco+IOL group in decreasing IOP. Phacotrab group and phaco group are both deeper than trab group in the anterior chamber depth. Phacotrab group was superior than phaco group in the use of IOP-lowering drugs.

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.

The prognosis of trabeculectomy in primary angleclosure glaucoma patients

AIM: To evaluate whether the level of thrombospondin-1(TSP-1) in aqueous humor can predict the prognosis of trabeculectomy in patients with primary angle-closure glaucoma(PACG). METHODS: This case-control study involved 26 patients with PACG who experienced a failed trabeculectomy(case group) and 78 age-and sex-matched patients with PACG who underwent successful trabeculectomy(control group). Aqueous humor was collected at the time of trabeculectomy and tested for TSP-1 and TGF-β2 levels with an enzyme-linked immunosorbent assay method. Logistic regression modeling was used to assess the risk factors for failed trabeculectomy. RESULTS: The mean TSP-1 aqueous concentrations were significantly higher in the case group(20.67±9.79 ng/mL) than the control group(5.17±2.29 ng/mL)(P<0.001). The transforming growth factor-β2(TGF-β2) aqueous concentrations were significantly different between the case and control group, at 3633.25 and 1090.24 pg/mL, respectively(P<0.001). Logistic regression analysis revealed TSP-1 level as an independent risk factor for a failed trabeculectomy(OR=3.540; 95%CI=1.092-11.482). CONCLUSION: The aqueous humor TSP-1 and TGF-β2 levels are higher in PACG eyes with failed trabeculectomy than with successful trabeculectomy at one year. The aqueous humor TSP-1 level is an independent risk factor associated with failed trabeculectomy.

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.

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.

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.

The association between matrix metalloprotease-9 gene polymorphisms and primary angle-closure glaucoma in a Chinese Han population

AIM:To examine the association between the single nucleotide polymorphisms (SNPs)of matrix metalloprotease-9 (MMP-9) gene and primary angleclosure glaucoma(PACG)in a Chinese Han population.METHODS:DNA samples were extracted from peripheral-blood mononuclear cells of 214 PACG patients and 224 healthy controls.Genotyping of rs3918249,rs3918254,rs17577 and rs3787268 in MMP-9was performed using polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP)analysis and the direct sequencing technique.The association between these genetic polymorphisms and risk of PACG was estimated by χ2 test.RESULTS:The distributions of rs3918249,rs3918254,rs17577 and rs3787268 genotypes among cases and healthy controls were compatible with that from HardyWeinberg equilibrium(HWE,P】0.05).The increased frequency of CC and CT genotypes of rs3918254 were observed in PACG patients compared to healthy controls[P=0.006,P corrected(Pcorr)=0.048].The haplotype analysis showed that the CCGG haplotype was nominal associated with PACG(P=0.015),however,the significant was lost when the Bonferroni correction was used(Pcorr=0.105).CONCLUSION:Our results revealed that rs3918254 in MMP-9 may be a susceptible locus to PACG in China,people with the CC and CT genotypes of rs3918254 are more susceptible to PACG.The susceptibility to PACG inChinese Han patients may be not influenced by SNPs rs3918249,rs3787268 and rs17577 in MMP-9.

Phacoemulsification versus combined phacotrabeculectomy in the treatment of primary angle-closure glaucoma with cataract: a Meta-analysis

AIM： To compare the efficacy and safety of phacoemulsification（Phaco） against combined phacotrabeculectomy（Phacotrabe） in primary angle-closure glaucoma（PACG） with coexisting cataract.·METHODS： By searching electronically the Pub Med,EMBASE, Scientific Citation Index and Cochrane Library published up from inception to January 2014, all randomized controlled trials that matched the predefined criteria were included. The quality of included trials was evaluated according to the guidelines developed by the cochrane collaboration. And the outcomes estimating efficacy and safety of two different surgical treatments were measured and synthesised by Rev Man 5.0.· RESULTS： Five randomized controlled trials were selected and included in Meta-analysis with a total of468 patients（468 eyes） with both PACG and cataract. We found that Phacotrabe had a greater intraocular pressure（IOP） lowing effect [preoperative IOP： weighted mean difference（WMD）=0.58, 95% confidence intervals（95% CI,-0.53 to 1.69）, P =0.31; postoperative IOP： WMD =1.37,95% CI（0.45 to 2.28）, P =0.003], a lower number of antiglaucoma medications [risk ratio（RR）=0.05, 95% CI（0.02 to 0.18）, P 〈0.00001] needed postoperatively and less serious damage of optic nerve [RR =0.48, 95% CI（0.21 to 1.07）, P =0.07], but a higher risk of complications[odds ratio（OR）=0.04, 95% CI（0.01 to 0.16）, P 〈0.00001]compared with Phaco. The rest studies indicated that there had no significantly difference between the two surgical methods for postoperative best-corrected visual acuity（BCVA） [WMD =-0.05, 95% CI（-0.14 to 0.05）, P =0.32] and loss of visual field [RR=1.06, 95% CI（0.61 to1.83）, P =0.83].·CONCLUSION： Phaco alone compared with Phacotrabe had a better effect in IOP reduction, whereas the securitydecline. Considering the number of sample size, our results remains to be further studied.