Early Manifest Glaucoma Trial Research Articles

The need for more pragmatic trials in glaucoma research.

There have been a number of clinical trials in glaucoma research published in the past two decades. Most of these trials were designed to evaluate very specific issues in selected populations placing them in the explanatory end of the pragmatic-explanatory continuum. The purpose of this study was to assess the level of pragmatism of published randomized controlled trials in glaucoma. A PubMed search using 'glaucoma' from 1995 to 2022 and randomized controlled trial (RCT) article type was done. Each study was assessed by three independent examiners using the Pragmatic-Explanatory Continuum Indicator Summary version 2 (PRECIS-2) toolkit. Scores were calculated for each study to determine the level of pragmatism. A summed score ≥36 was indicative of a very pragmatic study. Thirty-two different articles were included in the analysis. These papers represented 13 different landmark trials. The median PRECIS-2 score was 32 (range, 25 for the Early Manifest Glaucoma Trial (EMGT) to 34 to the Collaborative Normal Tension Glaucoma Study (CNTGS) and the Ocular Hypertension Treatment Study). The Treatment of Advanced Glaucoma Study (TAGS), was considered very pragmatic and scored 33 points. Despite the number of RCTs in glaucoma, there is still a need for more pragmatic studies.

Long-term Impact of Immediate Versus Delayed Treatment of Early Glaucoma: Results From the Early Manifest Glaucoma Trial

To compare long-term visual outcomes in the 2 arms of the Early Manifest Glaucoma Trial (EMGT) and determine if delayed treatment was associated with a penalty in terms of visual function. Long-term follow-up of a prospective, randomized controlled clinical trial. EMGT was carried out at 2 centers in Sweden; 255 subjects with newly detected, untreated glaucoma were randomized to immediate treatment with topical betaxolol and argon laser trabeculoplasty or to no initial treatment as long as no progression was detected. Subjects were followed prospectively with standard automated perimetry, visual acuity measurements, and tonometry for up to 21 years. Outcomes included vision impairment (VI), the perimetric mean deviation (MD) index and rate of progression, and visual acuity. At study end, percentages of eyes with VI or blindness were slightly higher in the treated group than in the untreated control group, 12.1% vs 11.0%, and 9.4.% vs 6.1% respectively, as were subjects with VI in at least one eye, 19.5% vs 18.7%. The differences were not statistically significant, nor were cumulative incidences of VI in at least one eye. The control group had more field loss than the treatment group, with median MD in the worse eye of -14.73 dB vs -12.85 dB, and rate of progression of -0.74 vs -0.60 dB/y, which was not statistically significant. Differences in visual acuity were minimal. Delaying treatment did not result in serious penalties. VI occurred at similar proportions in both treatment arms with a slight preponderance in the treatment group, whereas visual field damage was slightly higher in the control group.

Cost-Effectiveness Analysis of Minimally Invasive Trabecular Meshwork Stents with Phacoemulsification

To investigate the costs and effects of implanting trabecular meshwork bypass stents during cataract surgery from a societal perspective in the United States. Cost-utility analysis using Markov models and efficacy/safety data from published pivotal or randomized control trials (RCTs) of devices investigated. Patients aged 65 years and older with mild to moderate primary open-angle glaucoma with or without visually significant cataract. With the use of Markov models, glaucoma progression through 4 glaucoma states (mild, moderate, advanced, severe/blind) and death were simulated over 35 years. The cohort with cataract entered the model and received cataract surgery with or without device implantation. We included a medication management only reference group to calculate total costs and outcomes for those without cataract. Intraocular pressure (IOP) reductions from RCTs were converted to glaucoma state transition probabilities using visual field (VF) mean deviation (MD) decline rates from the Early Manifest Glaucoma Trial. Progressive thinning of the retinal nerve fiber layer (RNFL) on OCT imaging related to IOP control warranted further intervention, including adding medication, selective laser trabeculoplasty (SLT), or incisional glaucoma surgery. We estimated whole costs at Medicare rates and obtained utility values for glaucoma states from previous studies. Incremental costs per quality-adjusted life-year (QALY) gained were evaluated at a QALY threshold of $50 000. One-way deterministic sensitivity analysis, scenario analyses, and probabilistic sensitivity analyses addressed parameter uncertainty and demonstrated model robustness. Total costs, QALY, and incremental cost-effectiveness ratio (ICER). Over 35 years in the base case, the Hydrus (Ivantis, Inc.) implanted with cataract surgery arm cost $48 026.13 and gained 12.26 QALYs. The iStent inject (Glaukos Corp.) implanted with cataract surgery arm cost $49 599.86 and gained 12.21 QALYs. Cataract surgery alone cost $54 409.25 and gained 12.04 QALYs. Initial nonsurgical management cost $57 931.22 and gained 11.74 QALY. The device arms dominated or were cost-effective compared with cataract surgery alone within 5 years and throughout sensitivity analyses. The iStent inject arm was cost-effective in 94.19% of iterations in probabilistic sensitivity analyses, whereas the Hydrus arm was cost-effective in 94.69% of iterations. Implanting the Hydrus Microstent or iStent inject during cataract surgery is cost-effective at a conservative QALY threshold.

Infographic of the Early Manifest Glaucoma Trial (EMGT).

Infographic of the Early Manifest Glaucoma Trial (EMGT).

Sympathetic context of the disease - a new era in glaucoma management.

Primary open angle glaucoma (POAG) is a multifactorial optic neuropathy, which progresses in a chronic manner. Several etiological factors are involved, including genetic factors, race, age, IOP or vascular, systemic factors. IOP has an established role in the initiation and evolution of glaucoma, but its interactions with additional risk factors are complex. We propose the notion of the Glaucoma Etiological Area (GEA), as a representation of all the elements acting in collaboration in the physiopathology of each glaucoma case. When combined in different proportions, these elements may trigger the typical glaucomatous optic neuropathy (GON). We know that the statistical values of IOP are valid for normal eyes, but the glaucoma eye is not a normal eye. The notion of GEA can open a new perspective to interpret IOP values and to assess the true value of IOP control as a treatment for glaucoma. Applying the GEA theory allows us to tune the role of IOP. Additional factors, such as ocular properties (RGCL status, CCT, IOP fluctuation curve), ocular comorbidities (PEX, PDS), systemic comorbidities (arterial hypertension, vasospastic diseases such as migraines or Reynaud’s syndrome) or patient’s attitude towards glaucoma management (treatment compliance, access to follow-up and treatment) may greatly influence the evolution of GON and should be viewed holistically when developing a management plan for each patient. Applying the notion of GEA in clinical practice allows a more realistic approach of the pathophysiology of the disease and for a glaucoma treatment that is tailored to each patient.Abbreviations: AG = advanced glaucoma, BP = blood pressure, CCT = central corneal thickness, CIGTS = Collaborative Initial Glaucoma Treatment Study, CNTGS = Collaborative Normal-Tension Glaucoma Study, EMGT = Early Manifest Glaucoma Trial, GEA = glaucoma etiological area, GON = glaucomatous optic neuropathy, IOP = intraocular pressure, NTG = Normal Tension Glaucoma, OHTS = Ocular Hypertension Study, PDS = Pigmentary dispersion syndrome, PEX = Pseudoexfoliation syndrome, POAG - primary open-angle glaucoma, RGCL = retinal ganglion cell layer, VFL = visual field loss

Risk Factors for Visual Field Deterioration in the United Kingdom Glaucoma Treatment Study

The United Kingdom Glaucoma Treatment Study (UKGTS) investigated the visual field (VF)-preserving effect of medical treatment in open-angle glaucoma (OAG). The objective of this analysis was to identify risk factors associated with VF deterioration. Randomized, double-masked, placebo-controlled multicenter trial. Five hundred sixteen participants with previously untreated OAG were recruited prospectively in 10 United Kingdom centers. Eligibility criteria were modeled on those for the Early Manifest Glaucoma Trial. Study participants were randomized to either latanoprost 0.005% or placebo eye drops. The observation period was 2 years and involved, among other procedures, VF testing and intraocular pressure (IOP) measurement at 11 scheduled visits, with clustering of tests at baseline, 18 months, and 24 months. Guided progression analysis pattern deviation maps were used to determine VF deterioration. Cox regression was used to compute the hazard ratios (HRs) and respective 95% confidence intervals (CIs) while accounting for the correlation within sites. Model selection was guided by backward stepwise selection conducted on the model containing all variables that were significant at the 0.2 level in the univariate analysis. Follow-up variables that showed collinearity with baseline values were not retained in the final model. Time to VF deterioration. Treatment with latanoprost reduced the HR, for VF deterioration by 58% (HR, 0.42; 95% CI, 0.27-0.67; P= 0.001). Factors associated with deterioration were bilateral disease (HR, 1.59 for yes vs. no; 95% CI, 1.02-2.50; P= 0.041), higher baseline IOP (HR, 1.07 per mmHg; 95% CI, 1.02-1.12; P= 0.008), and disc hemorrhage at visit 1 (HR, 2.08; 95% CI, 1.07-4.04; P= 0.030). Smoking (current or previous) was associated with a reduced HR, for VF deterioration (HR, 0.59; 95% CI, 0.37-0.93; P= 0.023). No other evaluated factors were found to be statistically significant in the multivariable analysis. In the UKGTS, treatment with latanoprost halved VF deterioration risk. Bilateral disease, higher IOP, and disc hemorrhage were confirmed as risk factors for deterioration; smoking history seemed to be protective against VF deterioration.

Gene Therapy for Glaucoma by Ciliary Body Aquaporin 1 Disruption Using CRISPR-Cas9.

Glaucoma is a common cause of blindness, yet current therapeutic options are imperfect. Clinical trials have invariably shown that reduction in intraocular pressure (IOP) regardless of disease subtype prevents visual loss. Reducing ciliary body aqueous humor production can lower IOP, and the adeno-associated virus ShH10 serotype was identified as able to transduce mouse ciliary body epithelium following intravitreal injection. Using ShH10 to deliver a single vector CRISPR-Cas9 system disrupting Aquaporin 1 resulted in reduced IOP in treated eyes (10.4 ± 2.4 mmHg) compared with control (13.2 ± 2.0 mmHg) or non-injected eyes (13.1 ± 2.8 mmHg; p < 0.001; n = 12). Editing in the aquaporin 1 gene could be detected in ciliary body, and no off-target increases in corneal or retinal thickness were identified. In experimental mouse models of corticosteroid and microbead-induced ocular hypertension, IOP could be reduced to prevent ganglion cell loss (32 ± 4 /mm2) compared with untreated eyes (25 ± 5/mm2; p < 0.01). ShH10 could transduce human ciliary body from post-mortem donor eyes in ex vivo culture with indel formation detectable in the Aquaporin 1 locus. Clinical translation of this approach to patients with glaucoma may permit long-term reduction of IOP following a single injection.

Making a Correct Diagnosis of Glaucoma: Data From the EMGT.

Précis:A correct diagnosis of glaucoma established at initial visits.Purpose:It has been suggested that a diagnosis of glaucoma cannot be certain until progression has been demonstrated. Our aim was to evaluate the correctness of a glaucoma diagnosis established after 2 initial visits.Patients and Methods:Patients included in the Early Manifest Glaucoma Trial (EMGT) who had continued follow-up for at least 15 years were included in this analysis. The patients had been recruited primarily through a population screening and were diagnosed with glaucoma if the Glaucoma Hemifield Test was outside normal limits in the same sector at two consecutive visits. A Glaucoma Hemifield Test classification of borderline was also diagnostic if corresponding optic disc findings were present. At least one of the following criteria had to be fulfilled during follow-up to confirm the initial diagnosis: (1) visual field progression in at least one eye according to the EMGT criterion; (2) development of manifest glaucoma in an initially ineligible fellow eye; (3) optic disc progression in at least one eye; (4) optic disc hemorrhages in at least 1 eye.Results:Of the 255 patients included in the EMGT, 117 were followed for at least 15 years, representing 147 eyes eligible for our study. During follow-up, 134 eyes (91%) showed visual field progression, and, of the remaining 13 eyes, only 4 (3%) did not fulfill any of the criteria to confirm the diagnosis.Conclusions:A diagnosis made applying strict criteria to 2 initial visual field tests, supported by optic disc findings if visual field findings were borderline, was almost always correct.

Trend-Based Progression Analysis for Examination of the Topography of Rates of Retinal Nerve Fiber Layer Thinning in Glaucoma

Measurement of the rates of retinal nerve fiber layer (RNFL) thinning has consisted primarily of the circumpapillary RNFL profile. This study reports the rates of RNFL thinning over the 6 × 6 mm2 RNFL thickness map and their application for indication of visual field (VF) worsening in patients with glaucoma. To investigate the association between the rates of RNFL thinning and the risk of VF worsening in patients with glaucoma. This prospective study included 117 eyes of 89 Chinese patients with primary open-angle glaucoma followed up at approximate 4-month intervals for 5 or more years between July 1, 2007, and October 30, 2015, with progressive RNFL thinning detected by optical coherence tomography trend-based progression analysis (TPA). The mean and the peak rates of RNFL thinning and the area of progressive RNFL thinning were measured by the rates of change of RNFL thickness map. Visual field worsening was determined by the Early Manifest Glaucoma Trial and pointwise linear regression criteria. Hazard ratios (HRs) for indication of VF worsening determined by time-varying Weibull survival models. Of 89 patients (117 eyes) included in the study, 53 (59.6%) were men; mean (SD) age was 54.0 (13.8) years. At the time that progressive RNFL thinning was confirmed by TPA, the mean and the peak rates of RNFL thinning were 9.06 (8.05) µm/y and 4.52 (3.19) µm/y, respectively, and the area of progressive RNFL thinning was 1.54 (1.83) mm2. The inferotemporal meridians at 268° to 288° and the superotemporal meridians at 40° to 60° were the most frequent locations where progressive RNFL thinning was observed; 41.9% of the eyes had progressive RNFL thinning at these locations. After controlling for baseline covariates, the peak and the mean rates of RNFL thinning, but not the area of progressive RNFL thinning, were indicative of VF worsening. For each micrometer-per-year increase in the peak and the mean rates of RNFL thinning, the hazard ratios were 1.12 (95% CI, 1.04-1.19) for the peak rate and 1.39 (95% CI, 1.19-1.62) for the mean rate by the Early Manifest Glaucoma Trial criteria, and 1.07 (95% CI, 1.03-1.10) for the peak rate and 1.18 (95% CI, 1.09-1.28) for the mean rate by the pointwise linear regression criteria. Topographic measurement of the rates of RNFL thinning by optical coherence tomography TPA is informative for risk assessment of VF loss in glaucoma. Although progressive RNFL thinning may not necessarily be associated with VF worsening, faster rates of RNFL thinning were associated with a higher risk of subsequent decline in VF.

Detection of glaucoma progression by perimetry and optic disc photography at different stages of the disease: results from the Early Manifest Glaucoma Trial.

PurposeTo compare the earliest detection of progression in visual fields and monoscopic optic disc photographs at different stages of manifest glaucoma.MethodsThis study evaluated 306 eyes in 249 patients with manifest open‐angle glaucoma included in the Early Manifest Glaucoma Trial (EMGT). All patients in the trial were followed up regularly by standard automated perimetry and monoscopic optic disc photography, and the median follow‐up time was 8 years. Progression was assessed in series of optic disc photographs and in series of visual fields using glaucoma change probability maps and the predefined EMGT progression criterion. The proportion of progressions detected first in visual fields and the proportion detected first in optic disc photographs were compared at different stages of glaucoma severity defined by the perimetric mean deviation (MD) of the baseline visual field.ResultsAssessment of 210 eyes with early visual field loss, 83 eyes with moderate field loss, and 13 eyes with advanced field loss showed that, among the eyes exhibiting progression, the progression was detected first in the visual field in 80%, 79% and 100%, respectively. The predominance of visual field progressions at all stages was still apparent when using narrower (3‐dB) MD intervals for staging.ConclusionIn the EMGT material on eyes with manifest open‐angle glaucoma, the initial progression was detected much more often in the visual field series than in the optic disc photographs at all stages of disease.

Lack of Visual Field Improvement After Initiation of Intraocular Pressure Reducing Treatment in the Early Manifest Glaucoma Trial

PurposeWe evaluate how visual fields are affected by the initiation of IOP-reducing therapy in previously untreated glaucoma individuals.MethodsQualifying individuals with newly diagnosed glaucoma having normal to moderately elevated IOP were prospectively randomized either to IOP-reducing therapy or to no treatment. Before randomization, individuals underwent repeatedly Standard Automated Perimetry (SAP) testing and Goldmann tonometry. Three months after randomization, patients again underwent SAP and tonometry. Changes between baseline and the 3-month follow-up visit in the perimetric summary index, mean deviation (MD), and total deviation values at significantly depressed test points were compared between the treated and untreated groups.ResultsOf 255 individuals studied, 129 were randomized to treatment and 126 to no treatment. Intraocular pressure decreased by an average of 24% among treated and by 0.6% in the untreated patients. Mean deviation deteriorated slightly in both groups; mean change was −0.15 and −0.44 dB in the treated and untreated groups, respectively; the difference was not statistically significant, (P = 0.16). No association was seen between IOP reduction and change in MD. Sensitivities decreased slightly in significantly depressed test points, mean change was −0.45 dB in the untreated and −0.38 dB in the treated groups (P = 0.88).ConclusionsObserved visual field changes among glaucoma patients receiving initial IOP-reducing therapy were not significantly different to changes seen in patients who received no treatment. Thus, our results did not support the idea that visual field status improves after initiation of IOP- reducing therapy in glaucoma individuals, at least not in individuals with initially normal to moderately elevated IOPs.

Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinning: A 5-Year Prospective Study

To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma. Prospective study. A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for ≥5 years. Retinal nerve fiber layer imaging and VF testing were performed at ∼4-month intervals. Progressive RNFL thinning was determined by event analysis (Guided Progression Analysis [GPA]) and trend analysis (Trend-based Progression Analysis [TPA]) of serial registered RNFL thickness maps. VF progression was detected according to the Early Manifest Glaucoma Trial (EMGT) ("likely progression") and pointwise linear regression (PLR) criteria (≥3 contiguous locations with sensitivity change <0 decibels [dB]/year at P < 0.01). Hazard ratios (HRs) for predicting VF progression were calculated by Cox proportional hazard modeling with progressive RNFL thinning as a time-dependent covariate. The specificity of GPA/TPA for detection of RNFL changes was determined by the proportion of eyes with significant RNFL thinning/thickening in 25 normal subjects followed weekly for 8 consecutive weeks and the proportion with significant RNFL thickening in the glaucoma group. The HRs of VF progression. A total of 65 (27.1%) and 117 eyes (48.8%) had progressive RNFL thinning based on GPA and TPA, respectively, and 30 (12.5%) and 39 eyes (16.3%) had VF progression per the EMGT and PLR criteria, respectively, during follow-up. Eyes with progressive RNFL thinning had lower VF survival estimates and a faster decline of visual field index than eyes without. Progressive RNFL thinning predicted the development of VF progression with HRs of 8.44 (95% confidence interval, 3.30-21.61) (EMGT criteria) and 5.11 (2.51-10.42) (PLR criteria) for TPA and 3.95 (1.74-8.93) (EMGT criteria) and 3.81 (1.83-7.92) (PLR criteria) for GPA after controlling for baseline covariates. The specificities of GPA and TPA were 100% (83.4%-100.0%) in the normal group and 81.7% (76.2%-86.4%) and 84.2% (78.9%-88.6%), respectively, in the glaucoma group. Progressive RNFL thinning determined by GPA and TPA is predictive of detectable functional decline in glaucoma. This finding underscores the significance of detecting progressive RNFL thinning and itsrelevance to initiate or augment treatment for glaucoma patients. Regulatory authorities may consider progressive RNFL thinning as an outcome measure in clinical trials for evaluation of glaucoma treatment.

Structural and Functional Progression in the Early Manifest Glaucoma Trial

To elucidate the temporal relationship between detection of glaucomatous optic disc progression, as assessed by fundus photography, and visual field progression. Prospective, randomized, longitudinal trial. Three hundred six study eyes with manifest glaucoma with field loss and 192 fellow eyes without any field defect at the start of the trial, from a total of 249 subjects included in the Early Manifest Glaucoma Trial (EMGT), were assessed. Evaluation of visual field progression and optic disc progression during an 8-year follow-up period. Three graders independently assessed optic disc progression in optic disc photographs. Visual field progression was assessed using glaucoma change probability maps and the EMGT progression criterion. Time to detection of visual field progression and optic disc progression. Among study eyes with manifest glaucoma, progression was detected in the visual field first in 163 eyes (52%) and in the optic disc first in 39 eyes (12%); in 1 eye (0%), it was found simultaneously with both methods. Among fellow eyes with normal fields, progression was detected in the visual field first in 28 eyes (15%) and in the optic disc first in 34 eyes (18%); in 1 eye (1%), it occurred simultaneously. In eyes with manifest glaucoma, progression in the visual field was detected first more than 4 times as often as progression in the optic disc. Among fellow eyes without visual field loss at baseline, progression was detected first as frequently in the optic disc as in the visual field.

Visual impairment and vision-related quality of life in the Early Manifest Glaucoma Trial after 20years of follow-up.

PurposeTo determine the association between vision‐related quality of life (VRQOL) and levels of visual function loss in the Early Manifest Glaucoma Trial (EMGT).MethodsTwo hundred and fifty‐five patients were included in the EMGT between 1993 and 1997 and followed regularly by ophthalmic examinations. A Swedish translation of the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ‐25) was self‐administered at several follow‐up visits until 2014. We analysed the association between Rasch‐calibrated NEI VFQ‐25 scores and visual function in the best eye at the final follow‐up visit.ResultsNinety‐one per cent (233/255) of all participants completed the NEI VFQ‐25 at least once. In univariate logistic regression analysis, NEI VFQ‐25 scores were modestly associated with visual acuity (VA) (r 2 = 0.330, p < 0.001), visual field index (VFI) (r 2 = 0.200, p < 0.001) and perimetric mean deviation (MD) (r 2 = 0.193, p < 0.001). In multivariate analysis, VA and VFI together accounted for approximately 40% (r 2 = 0.380) of the NEI VFQ‐25 scores. NEI VFQ‐25 scores were significantly higher for patients with no visual impairment (mean 73 ± 22) than for visually impaired patients (mean 31 ± 15, p < 0.001). VFI worse than 50% or MD worse than −18 dB was significantly associated with low VRQOL scores (p < 0.001).ConclusionsOur results support the widespread, albeit arbitrary, use of a better‐eye visual field of <50% as an important threshold for a significant reduction in VRQOL.

Clinical Impact of 8 Prospective, Randomized, Multicenter Glaucoma Trials

To determine the impact of 8 multicenter randomized clinical trials (RCTs) on glaucoma practice. An electronic survey was distributed to the members of the American Glaucoma Society (AGS). Each participant was asked 2 study-specific questions and 1 standard question common to all 8 RCTs assessing the study's impact on clinical practice. RCTs included in the survey were the Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CIGTS), Collaborative Normal Tension Glaucoma (CNTG) Study, European Glaucoma Prevention Study (EGPS), Early Manifest Glaucoma Trial (EMGT), Glaucoma Laser Trial (GLT), Ocular Hypertension Treatment Study (OHTS), and Tube Versus Trabeculectomy (TVT) Study. A 5-point Likert scale was used for rating all responses. The practice setting and duration of glaucoma practice was determined for all AGS members who responded. A total of 206 (23.0%) of 894 AGS members participated in the survey. Among those who responded, 46.4% were self classified as academic practitioners and 53.6% worked in a private practice setting. Mean Likert scores for the standard question evaluating the overall impact of the RCT were OHTS 4.47, CNTG Study 4.13, AGIS 3.78, TVT Study 3.53, EMGT 3.48, CIGTS 3.44, GLT 3.39, and 2.69 EGPS. Substantial differences were observed in the clinical impact of several RCTs in glaucoma. The reported impact of each study likely reflects several factors including study timing, design, conduct, and interpretation of results.

Assessment methods of visual field defects of patients with glaucoma

Glaucoma is a common eye disease which may cause irreversible blindness.This ocular degenerative disease affects retinal ganglion cells (RGCs) and eventually causes optic nerve dysfunction by way of axonal loss.Patients with glaucoma may show characteristic changes of optic disc,damages of visual field and impairment of vision.Detection and evaluation of the impairment of visual field in patients with glaucoma are essential for the diagnosis and estimation of progression of this disease.Numerous techniques have been developed to detect field progression,but no standard has been widely accepted.Assessment Methods including visual field indices,glaucoma hemifield test (GHT),Advanced Glaucoma Intervention Study (AGIS),Early Manifest Glaucoma Trial (EMGT),Collaborative Initial Glaucoma Treatment Study(CIGTS),as well as the strength and limitation of each method were reviewed in this article in order to find out suitable ways to evaluate visual field defects in patients with glaucoma in clinical works and researches. Key words: Glaucoma; Visual field defect; Assessment

Comparison of Treated Mean Intraocular Pressure in Stable Glaucoma with Different Severity in Vietnam.

ABSTRACTPurpose: To compare stable glaucoma with different severity in a Vietnamese population in regard to mean intraocular pressure (IOP) and number of medications used.Materials and methods: A total of 116 eyes from 68 patients with medically treated glaucoma were prospectively enrolled at a single center and subjected to automated perimetry every 3 months for at least 9 months. Glaucoma progression was identifed according to early manifest glaucoma trial criterion using glaucoma progression analysis software. Eyes in which no progression was identifed were staged for glaucoma severity using field criteria (mild MD ≥ 6 dB, moderate MD –6 to –12 dB, advanced MD ≥ 12 dB, end-stage central island only). Groups were compared in terms of mean IOP and number of medications used. Statistical analysis was performed using SPSS v16.0.Results: A total of 109 eyes displayed no evidence of pro gres-sion during the study period. Pretreatment mean IOP for mild, moderate, severe and end-stage glaucoma was 28.2 ± 1.4, 28.8 ± 1.6, 29.1 ± 1.8, and 28.6 ± 0.8 mm Hg. The mean IOP of all 109 eyes during follow-up was 16.8 ± 1.4 mm Hg (95% conf dence interval = 15.4 ± 18.2 mm Hg). Mild, moderate, advan ced, and end-stage glaucoma had mean IOP of 17.5 ± 1.2, 16.9 ± 1.3, 15.8 ± 0.9 and 15.5 ± 1.1 mm Hg. The mean IOP of mild stage was significantly higher than advanced and end-stage (t-test, p < 0.001). Also, the mean IOP of moderate glaucoma was significantly higher than advanced and end-stage glaucoma (t-test, p < 0.05). Number of medications had no signi ficant difference among these glaucoma stages (chi-square test, p > 0.05).Conclusion: Reached IOP lowering contributes to glaucoma stabilization especially in late stages. To maintain stable glaucoma, there was no difference in medical procedure of glaucoma stages.How to cite this article: Thanh NTH. Comparison of Treated Mean Intraocular Pressure in Stable Glaucoma with Different Severity in Vietnam. J Current Glau Prac 2014;8(1):7-9.

Medikamentöse Glaukomtherapie

The prospective multicenter randomized controlled clinical trials (RCTs) Ocular Hypertension Glaucoma Treatment Study (OHTS), Early Manifest Glaucoma Trial (EMGT), Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CITGS) and Collaborative Normal Tension Glaucoma Study (CNGTS) are often named as landmarks for glaucoma management as the results of these studies provided the evidence for numerous therapeutic decisions in clinical practice. The studies confirmed the consensus that reduction of intraocular pressure reduces the risk of glaucoma progression covering the whole spectrum of glaucoma from ocular hypertension to advanced glaucoma. Furthermore, the identification of new risk factors allows a higher precision of assessment of the risk of progression. The RCTs achieved the main goal of high level of evidence, thus making progress in the understanding of glaucoma and its treatment and bridging consensus-based and evidence-based decisions. However, the implementation of the results into clinical practice needs adequate and accurate interpretation of the results.

The United Kingdom Glaucoma Treatment Study: A Multicenter, Randomized, Double-masked, Placebo-controlled Trial: Baseline Characteristics

The United Kingdom Glaucoma Treatment Study (UKGTS) tests the hypothesis that treatment with a topical prostaglandin analog, compared with placebo, reduces the frequency of visual field (VF) deterioration events in patients with open-angle glaucoma (OAG) by 50% over a 2-year period. Additional goals are to evaluate study power with novel clinical trial outcomes: (1) VF deterioration velocity and (2) VF and quantitative imaging measurements modeled as joint outcomes. The UKGTS is a randomized, double-masked, placebo-controlled, multicenter treatment trial for OAG. A total of 516 patients with newly diagnosed (previously untreated) OAG were prospectively recruited at 10 UK centers between 2007 and 2010. Eligible patients were randomly assigned to treatment with latanoprost 0.005% or placebo. The observation period was 2 years, with subjects monitored by VF testing, quantitative imaging, optic disc photography, and tonometry at 11 visits. The primary outcome measure is time to VF deterioration within 24 months. Secondary outcomes include the deterioration velocity of VF and quantitative imaging measures. The main source of referrals was optometrists (88%). A total of 777 subjects were assessed for eligibility, and 261 were excluded because they did not meet the inclusion criteria or declined to participate. The mean age of the 516 participants was 66 years, and 52.9% were male; 90.1% of the participants were white, and approximately one third (32.2%) reported a family history of glaucoma. A total of 777 eyes were eligible at initial assessment. Both eyes were eligible for 265 participants. Mean (standard deviation) intraocular pressure (IOP) at baseline for the eyes with better versus worse mean deviation (MD) was 18.9 (4.1) and 19.9 (4.7) mmHg, respectively (P = 0.0053). Some 56.1% of all eligible eyes had IOP <20 mmHg at baseline. The median (interquartile range) VF MD for all eligible eyes was -2.9 dB (-1.6 to -4.8 dB). This is the first randomized, placebo-controlled trial to evaluate the efficacy of medical treatment in reducing VF deterioration in OAG. The baseline characteristics for eligible patients and eyes from this cohort are presented and compared with those of previous trials. The baseline characteristics are similar to those of the largely population-based Early Manifest Glaucoma Trial. The early stage of the glaucoma and relatively low IOP at diagnosis suggest remarkably sensitive case findings by community optometrists in the United Kingdom.

Effect of Intraocular Pressure on the Bayesian Estimation of Rates of Visual Field Progression in Glaucoma

I read, with great interest, the study by Anderson and Johnson on the use of population information to modify estimates of rates of visual field progression in glaucoma through Bayesian analysis.1 I was surprised, however, to verify that the authors omitted previous work on this subject, which was actually the first to investigate this issue.2,3 Using real data from a large cohort of 352 eyes of 250 glaucoma patients, my colleagues and myself showed that incorporating risk factors into the estimation of rates of visual field change using Bayesian analysis resulted in significant improvement over the ordinary least squares approach.2 We showed that incorporating information about IOP during follow up, along with corneal thickness and presence/absence of progressive disc damage, resulted in more accurate and precise slopes, with better prediction of future standard automated perimetry mean deviation (MD) values. In contrast to our results, Anderson and Johnson concluded that failure to consider information on IOP did not alter the performance of a Bayesian estimator of visual field progression.1 They also suggest that because of a lack of significant influence of IOP, efforts of considering other risk factors would have even smaller significance.1 However, there are simple explanations for the lack of significance of the results presented by Anderson and Johnson and they are mostly related to the poor definition and characterization of the priors used in their study. The authors evaluated whether two different priors, representing the distributions of slopes of change in treated versus untreated glaucomatous populations, would differently influence the estimates of rates of visual field progression.1 The priors used in their study, however, were derived from previously published data from two widely different populations followed as part of the Canadian Glaucoma Study (the treated group) and Early Manifest Glaucoma Trial (EMGT, the untreated group).4,5 This approach, however, has major limitations. It would have been more appropriate to obtain the two distributions from a homogenous population randomized to treatment versus no treatment. By using widely different populations from different geographic areas and clinical settings, the authors are ignoring potentially confounding factors that could be important in determining the distribution of rates of change in these populations. Even more importantly, to evaluate the effect of IOP by simply using two prior distributions of rates of change categorized as “treated” versus “untreated” is largely inappropriate. This essentially ignores the continuous effect of IOP on the risk of glaucoma progression, as shown by several major clinical trials.4–6 For example, while the distribution of rates of change for a population of treated glaucomatous eyes with IOP of 12 mm Hg will be largely different than that of an untreated population with IOP of 30 mm Hg, such differences will be largely missed by simply considering these eyes as part of broad groups of treated versus untreated eyes. In the treated group from the Canadian Glaucoma Study there were many eyes with IOPs that overlapped with those of the untreated group from the EMGT. Additionally, within each one of these two groups there are major differences in the IOPs of the included eyes. As another example, one should not expect that the distribution of rates of change for eyes with a mean IOP of 10 mm Hg would be the same as that for eyes with a mean IOP of 20 mm Hg, even if these eyes were both treated over time.6 In essence, the methodology used by Anderson and Johnson was not able to capture the effect of IOP on estimation of rates of change.1 In contrast to their analysis, our method allowed prior distributions that would vary according to each level of IOP, providing a much better way of assessing the impact of IOP on the estimation of rates of change using Bayesian analysis.2 In conclusion, I congratulate the authors for their effort in evaluating the complex issue of estimating rates of change in glaucoma. However, the conclusions of their work are the result of improper prior design and do not seem to be justifiable. I hope that their results will not adversely impact the promising use of Bayesian techniques to incorporate risk factor information into the assessment of rates of progression in glaucoma.