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. .

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.

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.

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.

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.

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.

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.

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〉

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.

Changes in corneal endothelial cell density in patients with primary open-angle glaucoma

BACKGROUND Glaucoma is a group of diseases characterized by a specific pattern of optic nerve neuropathy and retinopathy.Increasing evidence demonstrates glaucoma associated corneal endothelium loss.Direct-compression mechanism due to elevated intraocular pressure(IOP),cell toxicity after long term exposure to preservatives and glaucoma surgery have been reported to be the possible mechanism.Herein,we compare the specular endothelial microscopy in primary open-angle glaucoma(POAG)patients and healthy controls of the same age group to observe the corneal endothelium changes and the correlations to the mean IOP in a Chinese case control study.AIM To investigate corneal endothelial cell density in Chinese patients with POAG.METHODS A case control study was performed on 60 eyes of 60 patients with POAG.Exclusion criteria included history of corneal diseases,intraocular diseases,contact lens use,ocular trauma or surgery(including intraocular surgery and laser treatment),congenital abnormalities or systemic diseases such as diabetes.Intraocular pressure was measured using Goldmann tonometry.Indirect specular microscopy(TOPCON SP-2000P)was performed on central corneas and endothelial images were acquired.Endothelial cell density,area and cell counts were analyzed.RESULTS Endothelial cell density was 2959±236 cells/mm2 in healthy controls and 2757±262 cells/mm2 in patients with POAG.The POAG eyes had significantly lower endothelial cell density compared to healthy control eyes(P<0.001).In the POAG group,endothelial cell density was 2686±233 cells/mm2 in the patients receiving medication and 2856±272 cells/mm2 in the untreated subgroup.The eyes receiving medication had significantly lower endothelial cell density compared to untreated eyes.There was a negative correlation between cell density and mean IOP(r=-0.286,P=0.004),positive correlation between the average cell area and mean IOP(r=0.228,P=0.022),maximum cell area and mean IOP(r=0.218,P=0.029)and minimum cell area and mean IOP(r=0.290,P=0.003).The percentage of hexagonal cells was not correlated with mean IOP.CONCLUSION Patients with POAG have lower corneal endothelial cell density than healthy controls of the same age.This may be attributed to mechanical damage from elevated IOP and toxicity of glaucoma medications.

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.

Association of apolipoprotein E-219T>G promoter polymorphism with primary open angle glaucoma in Turkish population

AIM:To investigate the association between apolipoprotein E(APOE)-219 T>G promoter polymorphism and primary open angle glaucoma(POAG).METHODS:Patients and healthy subjects were genotyped with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Genotype/allele frequencies were compared between 122 healthy subjects and in 75 POAG patients using Chi-square test.RESULTS:Although the frequency of APOE-219 GG genotype was higher in POAG group(13.3%)than in control group(6.6%),this finding was not statistically significant(P=0.09).In glaucoma patients carrying GG genotype,mean linear C/D ratio was higher and progression was more compared to glaucoma patients with GT genotype.CONCLUSION:APOE-219 T>G polymorphism does not seem to be a risk factor for the presence of glaucoma,but might play a role in deterioration of the disease,which needs further evaluation.

A new diagnostic model of primary open angle glaucoma based on FD-OCT parameters

AIM： To build a clinical diagnostic model of primary open angle glaucoma （POAG） using the normal probability chart of frequency-domain optical coherence tomography （FD-OCT）. METHODS： This is a cross-sectional study. Total 133 eyes from 133 healthy subjects and 99 eyes from 99 early POAG patients were included in the study. The retinal nerve fibre layer （RNFL） thickness parameters of optic nerve head （ONH） and RNFL3.45 scan were measured in one randomly selected eye of each subject using RTVue-100 FD-OCT. Then, we used these parameters to establish the diagnostic models. Four different diagnostic models based on two different area partition strategies on ONH and RNFL3.45 parameters, including ONH traditional area partition model （ONH-T）, ONH new area partition model （ONH-N）, RNFL3.45 traditional area partition model （RNFL3.45-T） and RNFL3.45 new area partition model （RNFL3.45-N）, were built and tested by cross-validation. RESULTS： The new area partition models had higher area under the receiver operating characteristic （AROC; ONH-N： 0.990; RNFL3.45-N： 0.939） than corresponding traditional area partition models （ONH-T： 0.979; RNFL3.45-T： 0.881）. There was no statistical difference among AROC of ONH-T, ONH-N, and RNFL3.45-N. Nevertheless, ONH-N was the simplest model. CONCLUSION： The new area partition models had higher diagnostic accuracy than corresponding traditional area partition models, which can improve the diagnostic ability of early POAG. In particular, the simplest ONH-N diagnostic model may be convenient for clinical application.

Comparison of long-term results of trabeculectomy to treat pseudoexfoliative glaucoma and primary open angle glaucoma

AIM： To compare the long term outcome of trabeculectomy in patients with pseudoexfoliative glaucoma（PEG） and primary open angle glaucoma（POAG） in terms of surgical success. METHODS： The success of the trabeculectomy was evaluated by three criteria. Criterion A： intraocular pressure（IOP） ≤21 mm Hg and decrease in IOP ≥20%; Criterion B： IOP ≤18 mm Hg and decrease in IOP ≥30%; Criterion C： IOP ≤15 mm Hg and decrease in IOP ≥50%. Patients that met these criteria without medical treatment were considered to be completely successful, while those that met these criteria with medical treatment were considered partially successful. Significance levels of differences between the POAG and PEG groups in the Kaplan-Meier survival curves were calculated with the log-rank test. RESULTS： Sixty-four eyes from 64 patients with PEG and 51 eyes from 51 patients with POAG were evaluated. No significant differences were detected between the PEG and POAG groups according to full or partial success relative to each of the three criteria（A： P=0.73, 0.32; B： P=0.73, 0.31; C：P=0.90, 0.27）. CONCLUSION： There is no difference in the long-term success of trabeculectomy between PEG and POAG patients whose clinical characteristics are otherwise the same.

GSTM1-null and GSTT1-active genotypes as risk determinants of primary open angle glaucoma among smokers

AIM： To evaluate glutathione transferase theta 1 and mu 1（GSTT1 and GSTM1） polymorphisms as determinants of primary open angle glaucoma（POAG） risk, independently or in combination with cigarette smoking, hypertension and diabetes mellitus.METHODS： A case-control study with 102 POAG patients and 202 age and gender-matched controls was carried out. Multiplex-polymerase chain reaction method was used for the analysis of GSTM1 and GSTT1 polymorphisms. The differences between two groups were tested by the t-test or χ~2 test. Logistic regression analysis was used for assessing the risk for disease development.RESULTS： The presence of GSTM1-null genotype did not contribute independently towards the risk of POAG. However, individuals with GSTT1-active genotype were at almost two-fold increased risk to develop glaucoma（P=0.044） which increased up to 4.36 when combined with GSTM1-null carriers（P=0.024）. When glutathione transferase（GST） genotypes were analyzed in association with cigarette smoking, hypertension and diabetes, only carriers of GSTT1-active genotype had significantly increased risk of POAG development in comparison with GSTT1-null genotype individuals with no history of smoking, hypertension and diabetes, respectively （OR=3.52, P=0.003; OR=10.02, P〈0.001; OR=4.53, P=0.002）. CONCLUSION： The results obtained indicate that both GSTM1-null and GSTT1-active genotypes are associated with increased POAG risk among smokers, suggesting potential gene-environment interaction in glaucoma development.