Early Manifest Glaucoma 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.

Association Between Optic Disc Perfusion Determined by Swept-Source Optical Coherence Tomography Angiography and Visual Field Progression in Glaucoma.

Reduced optic disc vessel density determined by swept-source optical coherence tomography angiography (SS-OCTA) was associated with visual field (VF) deterioration in glaucomatous eyes, which suggested that this parameter can be a potential biomarker that correlates well with functional deterioration. The purpose of this study was to identify the association between optic disc perfusion evaluated by SS-OCTA and VF progression in primary open angle glaucoma (POAG) eyes. A total of 266 POAG eyes of 266 patients (5.4y of mean follow-up) were included. Optic nerve head SS-OCTA was performed to evaluate the optic disc vessel density (dVD), parapapillary choroidal vessel density (pcVD), choroidal microvascular dropout (cMvD), and optic disc microvascular dropout (dMvD). VF progression was defined using Early Manifest Glaucoma Trial criteria. Factors associated with VF worsening were assessed by Cox proportional hazard analysis. Eighty (30.1%) out of the 266 POAG eyes showed VF progression. The progression group showed a significantly higher proportion of disc hemorrhage, cMvD, and dMvD but lower dVD and pcVD than the stable group (all P <0.05). Considering the strong association between the parameters [dMvD vs. dVD ( r = -0.757, P =0.010], cMvD vs. pcVD ( r = -0.745, P =0.012), dMvD vs. cMvD ( r = 0.802, P <0.001], dVD vs. pcVD ( r = 0.862, P <0.001), CMvD vs. dVD ( r = -0.698, P =0.031), and dMvD vs. pcVD ( r = -0.688, P =0.034)], 6 models with different combinations of covariates compensating for multicollinearity were developed. Younger age, presence of disc hemorrhage, and lower dVD were consistently associated with progression in all models that included these parameters. Optic disc perfusion, represented as dVD, may be a useful biomarker that correlates well with functional deterioration in POAG eyes.

Morning Blood Pressure Surge and Glaucomatous Visual Field Progression in Normal-Tension Glaucoma Patients With Systemic Hypertension

To investigate the impact of a morning blood pressure surge (MBPS) at baseline on subsequent visual field (VF) progression in hypertensive, normal-tension glaucoma (NTG) patients receiving oral anti-hypertensive treatment. Retrospective cohort study. A total of 127 eyes from 127 newly diagnosed NTG patients treated for systemic hypertension and followed up for at least 2 years were analyzed. All patients underwent baseline 24-hour ambulatory blood pressure monitoring (ABPM) and at least 5 serial VF examinations during the follow-up period. VF progression was defined according to the Early Manifest Glaucoma Trial criteria. The associations of VF progression with 24-hour ABPM-based blood pressure (BP) parameters (including MBPS) and other clinical variables were analyzed using Cox regression analyses. Kaplan-Meier survival analysis was used to compare VF survival estimates in patients with and without MBPS. VF progression was detected in 38 eyes (29.9%) over a 5.2-year mean follow-up. In the multivariate Cox regression model, a greater MBPS (hazard ratio [HR]=1.033; P=.024) and lower nighttime mean arterial pressure (MAP) trough (HR=0.965; P=.031) at baseline were significant independent predictors of subsequent VF progression. The likelihood of VF progression was significantly greater in patients with higher MBPS (P=.021) at baseline according to Kaplan-Meier survival analysis. An increased MBPS at baseline is a significant independent predictor of subsequent VF progression in NTG patients with systemic hypertension. This may be another relevant BP parameter associated with VF progression in hypertensive NTG patients receiving oral anti-hypertensive treatment.

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.

Pattern Electroretinogram in Ocular Hypertension, Glaucoma Suspect and Early Manifest Glaucoma Eyes: A Systematic Review and Meta-analysis

To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes. The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators. The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups' eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive). Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies. The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. Steady state PERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses. Proprietary or commercial disclosure may be found after the references.

Structural and vascular changes in glaucoma with single-hemifield defect: predictors of opposite hemifield visual field progression.

To investigate longitudinal changes in optic nerve head (ONH) superficial vessel density (VD), macular VD, circumpapillary retinal nerve fiber layer (RNFL) thickness, and macular ganglion cell-inner plexiform layer (GCIPL) thickness, and their associations with future VF defects in unaffected hemifields of primary open angle glaucoma (POAG) eyes with baseline VF defect confined to a single hemifield. This retrospective observational study included 61 POAG eyes with VF defect confined to a single hemifield monitored over a mean follow-up time of 2.7years. Development of VF defect in opposite hemifield was defined based the Early Manifest Glaucoma Trail criteria. Each eye was classified into either "conversion" or "no conversion" groups according to development of VF defect in the unaffected hemifield. The rates of longitudinal changes in VD and structure parameters in each hemiretina were compared between the two groups. A Cox proportional hazard model was used to identify potential risk factors for VF conversion in the unaffected hemifield. Among 61 eyes, 17 eyes (27.9%) were classified as "conversion" and 44 eyes (72.1%) were classified as "non-conversion" groups. The conversion group exhibited significantly greater rates of both VD and structural changes in both hemiretinas. In Cox proportional hazard model, greater rate of change in GCIPL thickness, ONH superficial VD, and macular VD of both hemiretinas and greater rate of change in RNFL thickness of the unaffected hemiretina were identified as risk factors for VF conversion in the unaffected hemifield. Monitoring progressive changes in VD and structural parameters effectively predict future VF defect in the opposite hemifields of POAG eyes with single-hemifield defects.

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.

Population-based associations between progression of normal-tension glaucoma and Yang-deficient constitution among Chinese persons

PurposeTo explore the association between constitution types as defined by traditional Chinese medicine (TCM) and risk for normal-tension glaucoma (NTG).DesignPopulation-based cohort study.MethodsPersons were identified in a population cohort aged ≥30...

Infographic of the Early Manifest Glaucoma Trial (EMGT).

Infographic of the Early Manifest Glaucoma Trial (EMGT).

Baseline Choroidal Microvasculature Dropout as a Predictor of Subsequent Visual Field Progression in Open-angle Glaucoma.

Choroidal microvasculature dropout (CMvD) is an independent predictor for overall and central visual field (VF) progression in open-angle glaucoma (OAG) eyes. The purpose of this study was to investigate the impact of CMvD identified by optical coherence tomography angiography (OCT-A) at baseline on subsequent VF progression in eyes with OAG. This retrospective observational study included 80 OAG eyes with CMvD [CMvD(+)] and without CMvD [(CMvD(-)] at baseline [40 of each matched for both age (10 y and below) and baseline VF severity (≤1 dB)]. The patients were followed regularly at 6-month intervals. VF progression was defined according to the Early Manifest Glaucoma Trial criteria. Associations of overall VF progression with baseline clinical factors, including the presence of CMvD and other variables, were analyzed by logistic regression with a generalized estimating equation in the entire OAG cohort. Linear mixed models were used to determine the differences in visual field mean sensitivity (VFMS) between the CMvD(+) and CMvD(-) groups globally and regionally at each follow-up point. During a mean follow-up of 35.91±2.51 months, a significant difference was evident in the VF progression rate between the CMvD(-) and CMvD(+) groups (22.5% vs. 70%, P<0.001). CMvD at baseline and a higher visit-to-visit intraocular pressure fluctuation were significant predictors of VF progression. The VFMS differed significantly between the 2 groups at the central and superior central VF regions after 2 years of follow-up. The presence of CMvD at baseline is an independent predictor of subsequent VF progression. CMvD(+) eyes show a faster rate of VFMS loss at the central and superior central VF regions.

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.

Wide-field Trend-based Progression Analysis of Combined Retinal Nerve Fiber Layer and Ganglion Cell Inner Plexiform Layer Thickness: A New Paradigm to Improve Glaucoma Progression Detection

Evaluation of glaucoma progression with OCT has been centered on the analysis of progressive retinal nerve fiber layer (RNFL) thinning over the parapapillary region and/or progressive ganglion cell inner plexiform layer (GCIPL) thinning over the macula. We investigated (1) whether combining the RNFL and GCIPL as a single layer (i.e., RNFL-GCIPL) for wide-field progression analysis outperforms wide-field progression analysis of the RNFL or the GCIPL, and (2) whether eyes with progressive RNFL-GCIPL thinning are at risk of visual field (VF) progression. Prospective, longitudinal study. A total of 440 eyes from 236 glaucoma patients; 98 eyes from 49 healthy individuals. OCT RNFL/GCIPL/RNFL-GCIPL thickness and VF measurements were obtained at ∼4-month intervals for ≥3 years. Progressive changes of the RNFL/GCIPL/RNFL-GCIPL thicknesses were analyzed over a wide field (12×9 mm2) covering the parapapillary region and the macula with trend-based progression analysis (TPA) controlled at a false discovery rate of 5%. VF progression was determined by the Early Manifest Glaucoma Trial criteria. Proportions of eyes with progressive RNFL/GCIPL/RNFL-GCIPL thinning; hazard ratios (HRs) for development of VF progression. More eyes showed progressive RNFL-GCIPL thinning (127 eyes; 28.9%, 95% confidence interval [CI]: 23.9%-33.8%) than progressive RNFL thinning (74 eyes; 16.8%, 95% CI: 13.1%-20.6%) and progressive GCIPL thinning (26 eyes; 5.9%, 95% CI: 3.7%-8.1%) in the glaucoma group over the study follow-up. Progressive RNFL-GCIPL thinning was almost always detected before or simultaneously with progressive RNFL thinning or progressive GCIPL thinning. The specificity of TPA (estimated from the healthy group) for detection of progressive RNFL-GCIPL thinning, progressive RNFL thinning, and progressive GCIPL thinning was 83.7% (95% CI: 74.9%-92.4%), 94.9% (95% CI: 90.6%-99.2%), and 96.9% (95% CI: 93.5%-100.0%), respectively. Eyes with progressive RNFL-GCIPL thinning had a higher risk to develop possible (HR: 2.4, 95% CI: 1.2-5.0) or likely (HR: 4.6, 95% CI: 1.5-14.0) VF progression, with adjustment of covariates, compared with eyes without progressive RNFL-GCIPL thinning. Progression analysis of RNFL-GCIPL thickness reveals a significant portion of progressing eyes that neither progression analysis of RNFL thickness nor GCIPL thickness would identify. Wide-field progression analysis of RNFL-GCIPL thickness is effective to inform the risk of VF progression in glaucoma patients.

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.

Impact of Posterior Sclera on Glaucoma Progression in Treated Myopic Normal-Tension Glaucoma Using Reconstructed Optical Coherence Tomographic Images.

To investigate factors associated with visual field (VF) progression in treated myopic normal-tension glaucoma (NTG) using a novel posterior sclera reconstruction method involving swept-source optical coherence tomography (OCT). Fifty-six myopic patients on ocular hypotensive therapy with the diagnose NTG had five or more VF tests during a period of 72.63 ± 20.46 months in clinical follow-up. Glaucomatous VF progression was decided by the standards of Early Manifest Glaucoma Trial criteria. Coronally reconstructed OCT images were used to obtain the position of the deepest point of the eye (DPE), and parameterized the distance (Disc-DPE distance), depth (Disc-DPE depth) and angle (Disc-DPE angle) of the posterior sclera. The Cox proportional hazards model and Kaplan-Meier curves were used to determine the risk factors for VF progression. Among 56 eyes, 28 showed VF progression. Eyes with progression had significantly different distance, depth, and angle of the DPE position (P = 0.049, P = 0.032, and P = 0.006, respectively). A multivariate Cox proportional hazard model revealed that the vertical tilt angle (hazard ratio [HR] 0.835, P = 0.026) and the DPE positioned temporal to fovea (HR 4.314, P = 0.001) were associated with VF progression. Among eyes with DPE positioned temporal to fovea, in addition to percentage reduction in IOP from baseline (HR 0.915, P = 0.012), shorter axial length (HR 0.542, P = 0.044) was found to be associated with VF progression. Eyes with a particular posterior sclera structure are at increased risk for glaucoma progression in treated myopic NTG patients. This finding highlights the significance of investigating posterior sclera structure and its relevance to initiate or augment treatment for myopic glaucoma patients.

Baseline Systolic versus Diastolic Blood Pressure Dip and Subsequent Visual Field Progression in Normal-Tension Glaucoma

To investigate the impact of systolic and diastolic blood pressure (DBP) dip at baseline on subsequent visual field (VF) progression in eyes with normal-tension glaucoma (NTG). Prospective cohort study. This study included 119 eyes of 119 newly diagnosed NTG patients followed up for at least 2 years (average, 40.4±16.9 months). All participants underwent baseline 24-hour ambulatory blood pressure (BP) monitoring and measurements of intraocular pressure (IOP) and at least 5 serial VF examinations. Participants were followed up as outpatients at 4- to 6-month intervals. Visual field progression was defined according to Early Manifest Glaucoma Trial criteria. The associations of VF progression with systolic BP (SBP) and DBP measured during the day and at night and other clinical variables were analyzed. Factors associated with VF progression over time. During follow-up, 41 eyes (34%) showed VF progression. In the multivariate Cox regression model, lower nighttime trough DBP (hazard ratio, 0.953; P= 0.023) and greater nighttime DBP dip area (time multiplied by nighttime DBP > 10 mmHg less than mean daytime DBP; hazard ratio, 1.017; P= 0.003) at baseline were significant predictors of subsequent VF progression. None of the SBP parameters was associated with VF progression. Nocturnal DBP dip showed a greater association with VF progression than SBP dip. Nocturnal trough DBP and DBP dip area at baseline are significant predictors of subsequent VF progression in NTG. Nocturnal DBP dip may be more relevant to future VF progression than SBP dip in NTG eyes.

Patterns of Progressive Ganglion Cell–Inner Plexiform Layer Thinning in Glaucoma Detected by OCT

To investigate the spatial characteristics and patterns of progressive macular ganglion cell-inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). Longitudinal, retrospective, observational study. Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2-8.1 years) were included. Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. Spatial characteristics and patterns of progressive GCIPL thinning. Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°-339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression.

Integrating Macular Ganglion Cell Inner Plexiform Layer and Parapapillary Retinal Nerve Fiber Layer Measurements to Detect Glaucoma Progression

To investigate the temporal relationship among progressive macular ganglion cell inner plexiform layer (GCIPL) thinning, progressive parapapillary retinal nerve fiber layer (RNFL) thinning, and visual field (VF) progression in patients with primary open-angle glaucoma (POAG). Prospective study. One hundred thirty-six POAG patients (231 eyes) followed up for ≥5 years. OCT imaging of the macular GCIPL and parapapillary RNFL and perimetry were performed at ∼ 4-month intervals. Progressive GCIPL and RNFL thinning were determined by Guided Progression Analysis (GPA) of serial GCIPL and RNFL thickness maps. The specificities of GPA were calculated from the proportions of eyes with progressive GCIPL or RNFL thinning in 67 eyes of 36 healthy individuals followed up for ≥5 years. Visual field progression (likely or possible) was determined by the Early Manifest Glaucoma Trial criteria. Hazard ratios for VF progression, progressive RNFL thinning, and progressive GCIPL thinning, as determined by time-varying Cox models. GPA detected 57 eyes (24.7%) with progressive GCIPL thinning and 66 eyes (28.6%) with progressive RNFL thinning at a specificity of 95.5% and 91.0%, respectively. Thirty-five eyes (15.2%) demonstrated progressive RNFL and GCIPL thinning, whereas 53 eyes (22.9%) demonstrated progressive RNFL or GCIPL thinning. Eyes with progressive GCIPL thinning had a higher risk for progressive RNFL thinning (HR, 5.27; 95% confidence interval [CI], 2.89-9.62), whereas eyes with progressive RNFL thinning were also at a higher risk for progressive GCIPL thinning (HR, 2.99; 95% CI, 1.48-6.02), after adjusting for baseline covariates. The HRs for likely and possible VF progression were 3.48 (95% CI, 1.51-8.01) and 2.74 (95% CI, 1.26-5.98), respectively, on detection of progressive GCIPL thinning and 3.66 (95% CI, 1.68-7.97) and 2.54 (95% CI, 1.23-5.21), respectively, on detection of progressive RNFL thinning after adjusting for baseline covariates. Eyes with VF progression were not at risk of progressive RNFL or GCIPL thinning (P ≥ 0.493). Progressive macular GCIPL thinning and progressive parapapillary RNFL thinning are mutually predictive. Because progressive RNFL thinning and progressive GCIPL thinning are both indicative of VF progression, integrating macular GCIPL and parapapillary RNFL measurements is relevant to facilitate early detection of disease deterioration in glaucoma patients.

Relationship between Progressive Changes in Lamina Cribrosa Depth and Deterioration of Visual Field Loss in Glaucomatous Eyes.

PurposeTo investigate the relationship between the progression of visual field (VF) loss and changes in lamina cribrosa depth (LCD) as determined by spectral-domain optical coherence tomography (SD-OCT) enhanced depth imaging in patients with primary open angle glaucoma (POAG).MethodsData from 60 POAG patients (mean follow-up, 3.5 ± 0.7 years) were included in this retrospective study. The LCD was measured in the optic disc image using SD-OCT enhanced depth imaging scanning at each visit. Change in the LCD was considered to either ‘increase’ or ‘decrease’ when the differences between baseline and the latest two consecutive follow-up visits were greater than the corresponding reproducibility coefficient value (23.08 µm, as determined in a preliminary reproducibility study). All participants were divided into three groups: increased LCD (ILCD), decreased LCD (DLCD), and no LCD change (NLCD). The Early Manifest Glaucoma Trial criteria were used to define VF deterioration. Kaplan-Meier survival analysis and Cox's proportional hazard models were performed to explore the relationship between VF progression and LCD change.ResultsOf the 60 eyes examined, 35.0% (21 eyes), 28.3% (17 eyes), and 36.7% (22 eyes) were classified as the ILCD, DLCD, and NLCD groups, respectively. Kaplan-Meier survival analysis showed a greater cumulative probability of VF progression in the ILCD group than in the NLCD (p < 0.001) or DLCD groups (p = 0.018). Increased LCD was identified as the only risk factor for VF progression in the Cox proportional hazard models (hazard ratio, 1.008; 95% confidence interval, 1.000 to 1.015; p = 0.047).ConclusionsIncreased LCD was associated with a greater possibility of VF progression. The quantitative measurement of LCD changes, determined by SD-OCT, is a potential biomarker for the prediction of VF deterioration in patients with POAG.

Impact of Rates of Change of Lamina Cribrosa and Optic Nerve Head Surface Depths on Visual Field Progression in Glaucoma.

To investigate the impact of the rates of change of anterior lamina cribrosa surface depth (ALCSD) and optic nerve head surface depth (ONHSD) on visual field (VF) progression in glaucoma. One hundred forty-six eyes of 95 glaucoma patients had optical coherence tomography ONH imaging and VF testing at approximately 4-month intervals for greater than or equal to 5 years. Anterior lamina cribrosa surface depth and ONHSD were measured with reference to (1) Bruch's membrane opening (BMO), and (2) choroid-sclera interface (CSI). The rates of change of ALCSD and ONHSD of individual eyes were measured with linear regression analysis. The hazard ratios (HRs) of the rates of change of ALCSD/ONHSD for prediction of VF progression as per Early Manifest Glaucoma Trial criteria were determined by joint longitudinal and survival models. Using the BMO reference, 23.3% and 28.1% of eyes showed a significant positive trend (posterior displacement), whereas 29.5% and 24.0% showed a significant negative trend (anterior displacement) of ALCSD and ONHSD, respectively. Using the CSI reference, the proportions with a significant negative trend decreased to 11.6% and 14.4%, respectively; and the proportions with a significant positive trend increased to 37.7% and 38.4%, respectively. The HRs of VF progression were 1.06 and 1.11 for each micrometer per year increase in the rates of change of ALCSDBMO and ONHSDBMO, respectively; and 1.07 and 1.09 for each micrometer per year increase in the rates of change of ALCSDCSI and ONHSDCSI, respectively. Identifying fast progressors of posterior ALCS/ONHS displacement is relevant to the management of glaucoma patients as they have a higher risk of VF progression.