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In both pre-perimetric and early perimetric glaucoma, the diagnostic agreements between optic disc, retinal nerve fiber layer and ganglion cell inner plexiform layer parameters based on Cirrus HD-OCT normative database classification were mostly fair, suggesting that abnormal classification in one anatomic area may suffice for the diagnosis of glaucoma in early stages.To evaluate the agreement of normative database diagnostic classification between optic disc, retinal nerve fiber layer (RNFL), and ganglion cell-inner plexiform layer (GCIPL) in patients with early glaucoma.Retrospective cross-sectional study involving 66 eyes (66 patients) with pre-perimetric and 97 eyes (97 patients) with early perimetric glaucoma. Normative database diagnostic classifications were retrieved from Cirrus HD-OCT scans of one eye per participant. An eye was considered abnormal if any of the optic disc, RNFL, or GCIPL was abnormal (yellow or red color-coded classification). For combined parameters, the eye had to be flagged as abnormal by both classifications, regardless of the parameters that were abnormal (global or sectorial). Agreement was assessed with Cohen's Kappa statistics.The agreement between RNFL and GCIPL was fair in both pre-perimetric (κ=0.25) and perimetric glaucoma (κ=0.21). Agreements between RNFL or GCIPL and ONH parameters (rim area and vertical cup-to-disc ratio; VCDR) were inconclusive due to insufficient date (P0.05). Combining GCIPL and rim area agreed fairly with RNFL both in pre-perimetric (κ=0.21) and perimetric glaucoma (κ=0.33). The best classification agreement (moderate) was achieved with the comparison RNFL-rim area versus VCDR (κ=0.48 in pre-perimetric, 0.45 in perimetric glaucoma). There were no significant differences between pre-perimetric and perimetric glaucoma coefficients of classification agreement.The normative database diagnostic agreements between optic disc, RNFL, and GCIPL were mostly fair in both pre-perimetric and early perimetric glaucoma. Clinicians should not wait for multiple structures to show abnormality on OCT to diagnose early glaucoma.

The annual incidence of glaucoma progression (9.7%) and rates of visual field mean deviation (MD) change in progressors (-1.02±0.06 dB/y) are high in a small cohort of urban Ghanaians.To report the incidence of glaucoma progression and the rate of visual field deterioration in a small cohort of Ghanaians.One hundred ten subjects (204 eyes) diagnosed with glaucoma at a baseline population-based screening examination were re-examined a mean of 8.3±0.8 years later. Eyes were classified as having progressed if the optic disc alone, visual field alone or both showed significant glaucomatous changes on follow-up. Visual field MD was used to calculate the rate of visual field progression.Progression was observed in 89 (80.9%, 9.7%/year) subjects (130 eyes). Progression occurred in 32 (31.7%, 3.8%/year) subjects by optic disc alone (46 eyes), 38 (44.7%, 5.4%/year) subjects by visual field alone (58 eyes), and 19 (25.0%, 3.0%/year) subjects by both modalities (26 eyes). The average rate of change in MD differed significantly between progressors (-1.02±1.06 dB/y) and nonprogressors (+0.089±0.49 dB/y), P =0.001. The rate of visual field worsening was greater among those who were classified as having progressed by both structure and function (-1.29±0.68 dB/y) and by function alone (-1.21±1.20 dB/y) than by structure alone (-0.55±0.76 dB/y). Progression was significantly associated with older age [odds ratio (OR), 1.42; P0.001] and higher baseline intraocular pressure (OR, 1.18; P =0.002). Factors associated with rate of MD change were baseline older age (OR, 1.66; P =0.003), higher intraocular pressure (OR, 2.81; P =0.007), better visual field MD (OR, 1.41; P =0.004), and systemic hypertension (OR, 1.15; P =0.029).The incidence and rate of visual field progression are high in this longitudinal study of Ghanaian subjects with glaucoma. The findings may have important clinical and public health policy ramifications.

The glaucoma question prompt list/video intervention was well received by patients. Eighty-seven percent of patients recommended that other patients should watch the educational video before their visits, and 89% said that other patients should complete the question prompt list before visits.The objectives of this study were to (a) describe patient feedback on a glaucoma question prompt list/video intervention designed to motivate African American patients to be more engaged during visits and (b) examine patient demographics associated with acceptance of the intervention.We are conducting a randomized controlled trial of a glaucoma question prompt list/video intervention. African American patients with glaucoma were enrolled and assigned to a control group or an intervention group where they watched a video emphasizing the importance of asking questions and received a prompt list to complete before visits. All patients were interviewed after visits and are being followed up for 12 months.One hundred eighty-nine African American patients with glaucoma were enrolled into the larger trial. Of the 93 patients randomized to the intervention group, 89% said that patients should complete the prompt lists before visits, and 87% recommended that patients should watch the video before visits. Older patients were significantly less likely to believe that other patients should watch the video before their visits (t = -3.7, P = .04). Patients with fewer years of education were significantly more likely to rate the video as being more useful than patients with more years of education (Pearson correlation, -0.27; P = .01). Patients who reported being less adherent on the visual analog scale were more likely to rate the video as being more useful (Pearson correlation, -0.23; P = .03).This study demonstrates that the question prompt list/video was accepted by the majority of African American patients who received the intervention.

To identify the risk factors associated with failure of tube shunt surgery.Pooled analysis of 3 prospective multicenter, randomized clinical trials.A total of 621 patients with medically uncontrolled glaucoma were enrolled, including 276 from the Ahmed Baerveldt Comparison Study, 238 from the Ahmed Versus Baerveldt Study, and 107 from the tube group of the Tube Versus Trabeculectomy Study. Patients were randomized to treatment with an Ahmed glaucoma valve (model FP7) or Baerveldt glaucoma implant (model 101-350). The associations between baseline risk factors and tube shunt failure were assessed using a Cox proportional hazards regression model. The primary outcome measure was the rate of surgical failure defined as intraocular pressure (IOP)21 mmHg or reduced 20% from baseline, IOP ≤ 5 mmHg, loss of light perception vision, reoperation for glaucoma, or removal of implant.The cumulative probability of failure after tube shunt surgery was 38.3% after 5 years. In multivariable analyses, baseline factors that predicted tube shunt failure included preoperative IOP (≤ 21 mmHg compared to IOP21 and ≤ 25 mmHg; HR, 2.34; 95% CI, 1.52-3.61; P.001), neovascular glaucoma (HR, 1.79; 95% CI, 1.28-2.52; P = .001), randomized treatment (for Ahmed glaucoma valve; HR, 1.36; 95% CI, 1.04-1.78; P = .025), and age (for 10 year decrease in age; HR, 1.19; 95% CI, 1.09-1.31; P.001).Lower preoperative IOP, neovascular glaucoma, Ahmed implantation, and younger age were predictors of tube shunt failure. This Study provides the largest prospectively collected dataset on tube shunt surgery.

Clinicians use both global and point-wise information from visual fields to assess the rate of glaucomatous functional progression. We asked which objective, quantitative measures best correlated with subjective assessment by glaucoma experts. In particular, we aimed to determine how much that judgment was based on localized rates of change vs. on global indices reported by the perimeter.Prospective cohort study.Eleven academic, expert glaucoma specialists independently scored the rate of functional progression, from 1 (improvement) to 7 (very rapid progression), for a series of 5 biannual clinical printouts from 100 glaucoma or glaucoma suspect eyes of 51 participants, 20 of which were scored twice to assess repeatability.Regression models were used to predict the average of the 11 clinicians' scores based on objective rates of change of mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), the Nth fastest progressing location, and the Nth fastest progressing of 10 anatomically defined clusters of locations after weighting by eccentricity.Correlation between the objective rates of change and the average of the 11 clinicians' scores.The average MD of the study eyes was -2.4 dB (range, -16.8 to +2.8 dB). The mean clinician score was highly repeatable, with an intraclass correlation coefficient of 0.95. It correlated better with the rate of change of VFI (pseudo-RExpert academic glaucoma specialists' assessment of the rate of change correlated best with VFI rates, except in eyes with a VFI near the ceiling of 100%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but the experts' opinions correlated more closely with global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.

OCT scans contain large amounts of information, but clinicians often rely on reported layer thicknesses when assessing the rate of glaucomatous progression. We sought to determine which of these quantifications most closely relate to the subjective assessment of glaucoma experts who had all the diagnostic information available.Prospective cohort study.Eleven glaucoma specialists independently scored the rate of structural progression from a series of 5 biannual clinical OCT printouts.A total of 100 glaucoma or glaucoma suspect eyes of 51 participants were included; 20 were scored twice to assess repeatability. Scores ranged from 1 (improvement) to 7 (very rapid progression). Generalized estimating equation linear models were used to predict the mean clinician score from the rates of change of retinal nerve fiber layer thickness (RNFLT) or minimum rim width (MRW) globally or in the most rapidly thinning of the 6 sectors.The correlation between the objective rates of change and the average of the 11 clinicians' scores.Average RNFLT within the series of study eyes was 79.3 μm (range, 41.4-126.6). Some 95% of individual clinician scores varied by ≤ 1 point when repeated. The mean clinician score was more strongly correlated with the rate of change of RNFLT in the most rapidly changing sector in %/year (pseudo-RThe rate of change of RNFLT in the most rapidly changing sector predicted experts' assessment of the rate of structural progression better than global rates or MRW. Sectoral rates may be a useful addition to current clinical printouts.

PURPOSE: Describe a new method to analyze retinal nerve fiber layer (RNFL) thickness maps. DESIGN: Cross-sectional study. SUBJECTS: RNFL thickness maps of healthy and glaucomatous eyes. METHODS: Optical coherence tomography (OCT) RNFL raster scans from 98 healthy and 50 glaucomatous eyes were analyzed. The RNFL thickness maps were separated into superficial (SNFL) and deep (DNFL) slabs through a partial thickness plane set at the modal thickness (mode). Association between mode and OCT signal strength (SS), age, axial length, and visual field mean deviation (VFMD) was tested (Pearson coefficient, r). Thicknesses of inferior and superior SNFL regions (i-,s-SNFL), and inferior, superior, nasal, and temporal DNFL regions (i-,s-,n-,t-DNFL) were calculated. The regions thicknesses were compared between healthy and glaucomatous eyes (t-test) and between glaucomatous eyes with early, moderate, and severe disease (ANOVA and linear regressions of thickness on VFMD). Diagnostic accuracy and correlation with VFMD of RNFL regions thicknesses were calculated as the area under the receiver operating characteristic curve (AUC) and Pearson r, respectively. P

Globalization is a comprehensive phenomenon with significant implications for global health. The globalization of minimally invasive glaucoma surgery (MIGS) is currently still a work in progress, with these devices slowly making inroads into Asia, Australasia, South America, and South Africa. Although MIGS companies can enjoy a quantum leap in economies of scale by serving global markets rather than only a confined domestic market, there are considerable economic, logistical, training, legal, and regulatory challenges that they need to overcome. The globalization of MIGS may benefit glaucoma patients worldwide, by reducing medication burden, improving the quality of life, and potentially decreasing the global incidence of glaucoma-related blindness.

BACKGROUND: The use of monoscopic cameras for glaucoma screening is increasing due to their portability, lower cost, and non-mydriatic capabilities. However, it is important to compare the accuracy of such devices with stereoscopic cameras that are used clinically and are considered the gold standard in optic disc assessment. The aim of this study is to compare vertical cup-to-disc ratio (VCDR) estimates obtained using images taken with a monoscopic and stereoscopic camera. METHODS: Participants were selected from the Tema Eye Survey. Eligible subjects had images of at least one eye taken with two cameras. They were classified as meeting the glaucoma threshold if an eye had a VCDR estimate >97.5th percentile, corresponding to >0.725 for this population. Hence, we used 0.725 as the cutoff to group eyes into two categories: positive and negative. We calculated sensitivity, specificity, and predictive values of VCDR assessed by expert readers at a reading center for monoscopic photos using stereoscopic photos as the gold standard. RESULTS: Three hundred and seventy-nine eyes of 206 participants were included in the study. Most participants were female (60.2%) and the most common age group was 50–59 years (36.4%). Sixteen eyes met the glaucoma threshold (VCDR > 0.725). Of these, the VCDR estimates of 14 eyes (87.5%) disagreed on the glaucoma threshold from the two cameras. The sensitivity to detect glaucoma with the monoscopic camera was 14.3% (95% CI: 4.0, 40.3). CONCLUSIONS: The low sensitivity of monoscopic photos suggests that stereoscopic photos are more useful in the diagnosis of glaucoma.

Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders.Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma.Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma.Exposures: Genetic variants associated with primary open-angle glaucoma.Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10−8 in the discovery stage and in the meta-analysis of combined discovery and validation data.Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10−8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10−13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry.Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P

Timely detection of glaucomatous progression is crucial in the delivery of glaucoma care. Clinical judgment may be used to make this assessment, but relatively modest agreement among practitioners supports the use of complementary methods. Event-based analyses take into account expected localized test-retest variabilities in sensitivity, and trend-based analyses are helpful for determining and predicting overall visual function. Landmark clinical trials have used various visual field progression criteria as end points with variable performances. Short- and long-term fluctuations as well as inadequate testing frequency are limitations in visual field analysis for glaucomatous progression. Ongoing improvements in statistical techniques as well as incorporation of functional and structural measures into a single model likely will lead to an enhanced ability to detect glaucomatous progression and will allow for more timely and appropriate therapy.

To compare the vertical and horizontal cup-to-disc ratio (VCDR, HCDR) by an updated optical coherence tomography (OCT) Bruch membrane opening (BMO) algorithm and stereoscopic optic disc photograph readings by glaucoma specialists.Reliability analysis.A total of 195 eyes (116 glaucoma and 79 glaucoma suspect) of 99 patients with stereoscopic photographs and OCT scans of the optic discs taken during the same visit were compared. Optic disc photographs were read by 2 masked glaucoma specialists for VCDR and HCDR estimation. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess the agreement between photograph reading and OCT in estimating CDR.OCT images computed significantly larger VCDR and HCDR than photograph reading before and after stratifying eyes based on disc size (P.001). The difference in CDR estimates between the 2 methods was equal to or greater than 0.2 in 29% and 35% of the eyes for VCDR and HCDR, respectively, with a mean difference of 0.3 in each case. The ICCs between the readers and OCT ranged between 0.50 and 0.63. The size of disagreement in VCDR correlated weakly with cup area in eyes with medium (rOCT and photograph reading by clinicians agree poorly in CDR assessment. The difference in VCDR between the 2 methods was depended on cup area in medium and large discs. These differences should be considered when making conclusions regarding CDRs in clinical practice.

To determine the relative efficacy of the Ahmed-FP7 and Baerveldt BG101-350 implants.Pooled analysis of 2 multicenter, randomized clinical trials.A total of 514 patients aged 18 or older with uncontrolled glaucoma that had failed or were at high risk of failing trabeculectomy were randomized to receive an Ahmed implant (n = 267) or Baerveldt implant (n = 247). Cumulative failure rates (using an intraocular pressure [IOP] target of 6-18 mm Hg inclusive), de novo glaucoma surgery rates, mean IOP, mean glaucoma medication use, and visual acuity were compared.Baseline characteristics were similar between groups. Mean preoperative IOP of the study population was 31.5 ± 11.3 mm Hg on an average of 3.3 ± 1.1 glaucoma medications. At 5 years, mean IOP was 15.8 ± 5.2 mm Hg in the Ahmed group and 13.2 ± 4.7 mm Hg in the Baerveldt group (P.001). Mean glaucoma medication use was 1.9 ± 1.5 in the Ahmed group and 1.5 ± 1.4 in the Baerveldt group (P = .007). The cumulative failure rate at 5 years was 49% in the Ahmed group and 37% in the Baerveldt group (P = .007). High IOP was the most common reason for failure in both groups, and de novo glaucoma surgery was required in 16% of the Ahmed group and 8% of the Baerveldt group (P = .006). Failure owing to hypotony occurred in 0.4% of the Ahmed group and 4.5% of the Baerveldt group (P = .002). Visual outcomes were similar between groups (P = .90).The Baerveldt group had a lower failure rate, lower rate of de novo glaucoma surgery, and lower mean IOP on fewer medications than the Ahmed group. Baerveldt implantation carried a higher risk of hypotony.

Spectral-domain optical coherence tomography (SD-OCT) is a key tool in the diagnosis and evaluation of glaucoma. On OCT printouts, measurements of the retinal nerve fiber layer (RNFL), macula, and optic nerve are compared to a normative database of age-matched normals and then color-coded. A color-coding of green (“within normal limits”) suggests that the patient is normal and has nerve tissue values similar to age-matched normals. Yellow (“borderline”) is a warning and suggests that the patient’s values may be slightly thinner than normal. Red (“outside normal limits”) indicates that the patient has glaucoma and has very thin nerve tissue.

Optical coherence tomographt (OCT) is now used daily for the diagnosis, therapeutic decision-making, and follow-up of glaucoma. In order for OCT to serve its purpose efficiently, correct interpretation of its output requires good knowledge of what constitutes a good and bad scan. A good scan is characterized by the absence of any artifact whereas a bad scan has one or multiple artifacts that must be recognized. Failure to identify the artifacts can lead to misdiagnosis and inappropriate management. This chapter presents the various types of scan artifacts obtained with different OCT devices in glaucoma clinics and explains how to identify them.

In glaucoma, optical coherence tomography (OCT) allows high-resolution imaging of the optic nerve head (ONH) and inner retinal layers and provides both qualitative and highly reproducible quantitative information on these structures. This set of information assists the clinician in the diagnosis of glaucoma and detection of its progression. This chapter focuses on OCT as a tool for ONH evaluation for glaucoma detection. Specifically, it informs the reader what the best ONH parameters are and then presents actual clinical cases showing how ONH parameters can be used effectively to diagnose prepreimetric and perimetric glaucoma.

Significance Glaucoma patients express a strong need for practical instruction on instilling eye drops correctly. To maximize the benefit of a video intervention to improve eye drop technique, patients recommend that video education be provided both in the clinic setting and online. Purpose The purposes of this study were to (1) describe glaucoma patients' perspectives on how to improve an online eye drop technique video and how to disseminate it to other glaucoma patients and (2) examine how these perspectives differ across demographics. Methods Glaucoma patients (N = 43) who viewed an online eye drop technique educational video as part of a randomized controlled trial were interviewed to assess their overall rating of the video on a 4-point scale, with whom they had watched the video, whether they would recommend the video to others, how the video helped them, how they would recommend improving the video, and how they would like the video to be disseminated to other glaucoma patients. Results Patients' mean (SD) rating of the video was 3.4 (0.8), with a higher mean rating of 3.8 among African Americans (P = .02). All 43 patients said that they would recommend that others watch the video. Patients most commonly said that the video helped them learn to block the tear duct correctly, put the cap down on its side, mix the medication correctly, and close the eye after instillation. Patients preferred viewing the video in the doctor's office examination room and a website. Conclusions Eye drop technique videos should be disseminated in the doctor's office and online. Health systems that integrate educational videos into their everyday practice may be able to use technique videos to improve patient technique at low cost and little time burden to the provider.

Glaucoma is the leading cause of irreversible blindness worldwide and requires regular monitoring upon diagnosis to ascertain whether the disease is stable or progressing. However, making this determination remains a difficult clinical task. Recently, a novel spatiotemporal boundary detection predictor of glaucomatous visual field (VF) progression (STBound) was developed. In this work, we explore the ability of STBound to differentiate progressing and non-progressing glaucoma patients in comparison to existing methods. STBound, Spatial PROGgression, and traditional trend-based progression methods (global index (GI) regression, mean regression slope, point-wise linear regression, permutation of pointwise linear regression) were applied to longitudinal VF data from 191 eyes of 91 glaucoma patients. The ability of each method to identify progression was compared using Akaike information criterion (AIC), full/partial area under the receiver operating characteristic curve (AUC/pAUC), sensitivity, and specificity. STBound offered improved diagnostic ability (AIC: 197.77 vs. 204.11–217.55; AUC: 0.74 vs. 0.63–0.70) and showed no correlation (r: −0.01–0.11; p-values: 0.11–0.93) with the competing methods. STBound combined with GI (the top performing competitor) provided improved performance over all individual metrics and compared to all metrics combined with GI (all p-values

Item does not contain fulltext Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 x 10(-27)) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 x 10(-5)); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.

To assess the associations of central corneal thickness (CCT) with ocular and systemic factors in a West African population.Population-based cross-sectional study.Participants aged ≥40 years in the Tema Eye Survey who had clinically normal corneas were included in this study. CCT was determined bilaterally using handheld ultrasound pachymetry. The association between CCT and ocular or systemic factors was analyzed with univariable linear regression. Multivariable linear regression analysis was performed for variables significantly associated with CCT in the univariable analysis. Main outcome measures were CCT (μm) and its associations with age, sex, IOP, cup-to-disc ratio (CDR), glaucoma, hypertension, and diabetes.A total of 6806 eligible subjects were identified, of whom 5603 (82.3%) participated in the Tema Eye Survey. A total of 4737 participants (84.5% of participants) of West African descent and clinically normal corneas were included. The mean age ± standard deviation (SD) of participants was 51.2 ± 9.7 years and 38.7% were male. The mean ± SD CCT in the population was 533.9 ± 34.0 μm. In the multivariable linear regression analysis, increased CCT was significantly associated with younger age, male sex, and higher IOP (all P.001). There were no significant associations between CCT and CDR, glaucoma, hypertension, and diabetes.This population-based cross-sectional survey of West African adults found a significant association between increased CCT and younger age, male sex, and higher IOP but not glaucoma or CDR. Variations in corneal thickness may influence the accuracy of IOP measurements in African persons.

Objective To determine the effectiveness of an online video intervention in improving self-efficacy and eye drop application technique in glaucoma patients. Methods We randomized ninety-two patients with primary open-angle glaucoma, all who self-administer their eye drops, to either watch the 4-minute Meducation® eye drop technique video in the intervention group, or a nutrition video in the control group. We assessed five eye drop technique steps using objective video recordings at baseline, immediately after watching the video, and 1 month later. We used linear regression models to determine whether the intervention group had better self-efficacy and technique than the control group. Results Adjusted for baseline technique and other covariates, eye drop technique averaged 0.73 steps better in intervention patients than controls immediately after the video (p = 0.003) and 0.63 steps better at 1 month (p = 0.01). Adjusted for baseline self-efficacy, intervention patients had better eye drop technique self-efficacy than controls immediately after the video (p = 0.02) and at 1 month (p = 0.02). Conclusion A short educational video can significantly improve glaucoma patients’ short-term self-efficacy and eye drop technique. Practice implications Videos may provide an inexpensive, convenient way to deliver eye drop technique education in any provider’s office or online.

To determine the incidence of open-angle glaucoma (OAG) and its risk factors in the Tema Eye Survey in Ghana, West Africa.Longitudinal, observational population-based study.One thousand two hundred five of 1500 participants 40 years of age or older selected randomly from 5603 participants originally drawn from the population and who had undergone a baseline examination.All participants underwent baseline and follow-up ophthalmologic examinations 8 years apart. Glaucoma diagnosis was determined based on the International Society for Geographical and Epidemiologic Ophthalmology criteria.Incidence and odds ratio (OR).The response rate was 80.3%. Of 1101 nonglaucomatous participants at baseline who had complete follow-up data, 4.6% (95% confidence interval [CI], 3.7%-5.2%) demonstrated OAG over the 8-year period, or 0.58% (95% CI, 0.4%-0.8%) per year. The 8-year incidence increased with age from 3.1% in those 40 to 49 years old to 7.0% in those 60 to 69 years old. Baseline risk factors for incident OAG were male gender (OR, 2.1; 95% CI, 1.1-4.0; P = 0.025), older age relative to those 40 to 49 years old (those 50-50 years old: OR, 2.6; 95% CI, 1.2-5.7; those 60-69 years old: OR, 4.3; 95% CI, 2.0-8.8; and for those 70 years of age and older: OR, 6.3; 95% CI, 2.6-15.4; all P0.001), higher intraocular pressure (IOP; OR, 1.4; 95% CI, 1.1-1.8; P 0.001), larger vertical cup-to-disc ratio (OR, 5.8; 95% CI, 5.2-6.6; P0.001), and thinner central cornea (OR, 1.2; 95% CI, 1.03-1.5; P = 0.013). A separate analysis performed with central corneal thickness-based IOP correction did not change the outcome of the associative model of incident glaucoma.The incidence of OAG is higher in this population than reported in nonblack populations outside Africa. This is important not only in Ghana and probably other West African countries but also wherever people of the West African diaspora reside. These data enhance our understanding of the epidemiologic factors of OAG in this setting and may serve as reference for public health policy and planning.

Author(s): Mwanza, Jean-Claude; Lee, Gary; Budenz, Donald L; Warren, Joshua L; Wall, Michael; Artes, Paul H; Callan, Thomas M; Flanagan, John G | Abstract: Purpose:To independently validate the performance of the University of North Carolina Optical Coherence Tomography (UNC OCT) Index in diagnosing and predicting early glaucoma. Methods:Data of 118 normal subjects (118 eyes) and 96 subjects (96 eyes) with early glaucoma defined as visual field mean deviation (MD) greater than -4 decibels (dB), aged 40 to 80 years, and who were enrolled in the Full-Threshold Testing Size III, V, VI comparison study were used in this study. CIRRUS OCT average and quadrants' retinal nerve fiber layer (RNFL); optic disc vertical cup-to-disc ratio (VCDR), cup-to-disc area ratio, and rim area; and average, minimum, and six sectoral ganglion cell-inner plexiform layer (GCIPL) measurements were run through the UNC OCT Index algorithm. Area under the receiver operating characteristic curve (AUC) and sensitivities at 95% and 99% specificity were calculated and compared between single parameters and the UNC OCT Index. Results:Mean age was 60.1 ± 11.0 years for normal subjects and 66.5 ± 8.1 years for glaucoma patients (P l 0.001). MD was 0.29 ± 1.04 dB and -1.30 ± 1.35 dB in normal and glaucomatous eyes (P l 0.001), respectively. The AUC of the UNC OCT Index was 0.96. The best single metrics when compared to the UNC OCT Index were VCDR (0.93, P = 0.054), average RNFL (0.92, P = 0.014), and minimum GCIPL (0.91, P = 0.009). The sensitivities at 95% and 99% specificity were 85.4% and 76.0% (UNC OCT Index), 71.9% and 62.5% (VCDR, all P l 0.001), 64.6% and 53.1% (average RNFL, all P l 0.001), and 66.7% and 58.3% (minimum GCIPL, all P l 0.001), respectively. Conclusions:The findings confirm that the UNC OCT Index may provide improved diagnostic perforce over that of single OCT parameters and may be a good tool for detection of early glaucoma. Translational Relevance:The UNC OCT Index algorithm may be incorporated easily into routine clinical practice and be useful for detecting early glaucoma.

PURPOSE OF REVIEW: To describe the current state of knowledge regarding glaucoma patients’ eye drop technique, interventions attempting to improve eye drop technique, and methods for assessing eye drop technique. RECENT FINDINGS: In observational studies, between 18.2 and 80% of patients contaminate their eye drop bottle by touching their eye or face, 11.3–60.6% do not instill exactly one drop, and 6.8–37.3% miss the eye with the drop. Factors significantly associated with poorer technique include older age, lack of instruction on eye drop technique, female sex, arthritis, more severe visual field defect, lack of positive reinforcement to take eye drops, lower educational level, low self-efficacy, and being seen at a clinic rather than a private practice. Among intervention studies, four of five studies using a mechanical device and three of four studies using educational interventions to improve technique showed positive results, but none of the studies were randomized controlled trials. SUMMARY: Poor eye drop technique is a significant impediment to achieving good control of intraocular pressure in glaucoma. Both mechanical device interventions and educational interventions offer promise to improve patients’ technique, but studies with stronger designs need to be done followed by introduction into clinical practice.

Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - “response to fluid shear stress” and “abnormal retina morphology” - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

Author(s): Bailey, Jessica N Cooke; Gharahkhani, Puya; Kang, Jae H; Butkiewicz, Mariusz; Sullivan, David A; Weinreb, Robert N; Aschard, Hugues; Allingham, R Rand; Ashley-Koch, Allison; Lee, Richard K; Moroi, Sayoko E; Brilliant, Murray H; Wollstein, Gadi; Schuman, Joel S; Fingert, John H; Budenz, Donald L; Realini, Tony; Gaasterland, Terry; Scott, William K; Singh, Kuldev; Sit, Arthur J; Igo, Robert P; Song, Yeunjoo E; Hark, Lisa; Ritch, Robert; Rhee, Douglas J; Vollrath, Douglas; Zack, Donald J; Medeiros, Felipe; Vajaranant, Thasarat S; Chasman, Daniel I; Christen, William G; Pericak-Vance, Margaret A; Liu, Yutao; Kraft, Peter; Richards, Julia E; Rosner, Bernard A; Hauser, Michael A; Craig, Jamie E; Burdon, Kathryn P; Hewitt, Alex W; Mackey, David A; Haines, Jonathan L; MacGregor, Stuart; Wiggs, Janey L; Pasquale, Louis R; Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) Consortium | Abstract: Purpose:Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods:We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results:In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions:Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.

© 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved. PURPOSE. Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. METHODS. We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure. RESULTS. We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010). CONCLUSIONS. We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important.

To study the performance of the Matrix perimeter compared with the Humphrey Field Analyzer II (HFA) with the Swedish Interactive Thresholding Algorithm over the range of contrast sensitivities each machine could estimate.Fifty stable glaucoma subjects at various stages of disease and three normal subjects had visual fields testing done on five different days within 8 weeks with both perimeters. Intraclass correlation coefficient of mean deviation, pattern standard deviation, and the SD of repeat measurements were evaluated. The repeatability of the sensitivity estimates at individual locations and global indices was quantified, as well as their dependence on disease severity. The relationship between sensitivity determinations with the two instruments was explored (principal curve analysis).Mean deviation on the HFA ranged from -31 to +2.5 dB. The mean deviation and pattern standard deviation had intraclass correlation coefficients above 0.90 for both instruments. Over most of the useful range (above 20 dB on the HFA), a difference of 1 dB for the Matrix corresponded to a difference of 2 dB for the HFA. The SD of repeat measurements increased with disease severity with HFA, but not with Matrix, except that values of 12 or 34 dB were highly variable on repeat. Variability was reduced for both HFA and Matrix when duplicate sensitivity values were used. A single Matrix test provided only 15 possible sensitivity values, unevenly spaced, but the average of duplicate measurements provided more numerous sensitivity values. A learning effect was detected for Matrix.The decibel values reported by the two machines are not equivalent. Variability of sensitivity determinations is affected more by the sensitivity level with HFA than with Matrix. Duplicate measurements for baseline and follow-up evaluation could be important, especially for Matrix. Further information on learning effects is needed, as is commercially available progression software for Matrix.

Optical coherence tomography (OCT) has moved to the forefront of imaging modalities in the management of glaucoma and retinal diseases. It is modifying how glaucoma and glaucoma progression are diagnosed clinically and augmenting our understanding of the disease. OCT provides multiple parameters from various anatomic areas for glaucoma diagnosis, evaluation of treatment efficacy, and progression monitoring. While the use of multiple parameters has increased the likelihood of detecting early structural changes, diagnosing glaucoma in early stages is often challenging when the damages are subtle and not apparent on OCT scans, in addition to the fact that assessment of OCT parameters often yields conflicting findings. One promising approach is to combine multiple individual parameters into a composite parameter from the same test to improve diagnostic accuracy, sensitivity, and specificity. This review presents current evidence regarding the value of spectral domain OCT composite parameters in diagnosing early glaucoma.

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = −0.62, P = 5.30 × 10−5) but not between CCT and primary open-angle glaucoma (r = −0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Purpose To explore the association between peripapillary atrophy (PPA) area and conversion from ocular hypertension (OHT) to glaucoma. Design Prospective, longitudinal cohort study of cases and controls. Participants We included 279 age-matched and follow-up time–matched eyes with OHT that converted to glaucoma and 279 eyes with OHT that did not convert to glaucoma. Methods Initial and last acceptable optic disc photos were analyzed. Disc, α-zone, and β-zone PPA were traced independently by 2 trained readers and their areas were measured with Photoshop. The α-zone and β-zone areas were expressed as a percentage of optic disc area. Main Outcome Measures α-Zone and β-zone PPA size over time. Results Intraclass correlation coefficients (ICCs) demonstrated that readers had good agreement on disc area (ICC = 0.97) and β-zone (ICC = 0.82), but not α-zone (ICC = 0.48). The s-zone, as a percentage of disc area, increased in size ( P P = 0.82). Enlargement of the β-zone was not correlated with follow-up time ( P = 0.39). Conclusions The results did not show a difference in size of the β-zone at baseline between eyes that proceed to develop glaucoma and those that do not. Moreover, the β-zone enlarges equally in case and control eyes during follow-up.

Since its introduction in ophthalmology, optical coherence tomography (OCT) has undergone significant advances in imaging protocols, algorithms, and addition of new parameters which have maximized its potential for diagnosing, evaluating the response to treatment, and assessing the progression of various ocular diseases, including glaucoma. This review provides an update on recent developments in OCT with respect to the management of glaucoma.Most recent notable developments include the introduction of the minimum distance band, which is a three-dimensional optic nerve head parameter, and Swept-Source OCT with its single wide-field scanning capability. The introduction of OCT angiography provides additional structural and functional measures for glaucoma management. Adaptive optics helps visualize individual RNFL bundles and measure their widths.Continued improvements in OCT technology is both enhancing our understanding of glaucoma and improving our ability to manage the disease.

To determine the change and rate of change in central corneal thickness (CCT) and their determinants.Longitudinal observational population-based study.A total of 758 normal and 58 glaucomatous subjects underwent complete eye examination, with CCT measurements at 2 separate visits. Change and rate of change in CCT were determined. Univariate and multivariate linear regression analyses were performed to determine the factors associated with change and rate of change.The mean follow-up duration was 8.4 ± 0.7 years. The overall change was -8.9 ± 16.7 μm in OD and -9.8 ± 16.2 μm in OS, both P.0001. Changes in glaucomatous and normal subjects were -14.1 ± 2.2 μm vs -8.6 ± 0.6 μm in OD (P = .02) and -14.5 ± 2.2 μm vs -9.5 ± 0.6 μm in OS (P = .03), respectively. The overall rate of thinning was -1.1 μm/year (OD) and -1.2 μm/year (OS). Rates in glaucomatous and normal eyes were -1.7 ± 0.3 μm/year vs -1.0 ± 0.1 μm/year in OD (P = .02) and -1.7 ± 0.3 μm/year vs -1.1 ± 0.1 μm/year in OS (P = .03), respectively. Change and rate of change were associated with baseline CCT (ß = -0.1 to -0.09 and -0.011, respectively, all P.001) and glaucoma (ß = -6.8 to -5.6, P ≤ .009, and -0.75 to -0.69, P ≤ .007, respectively).CCT decreased significantly over time. The change and rate of change were greater in glaucomatous than normal eyes, and were greater than described in cross-sectional studies.

PurposeTo determine if there are systematic differences in cup-to-disc ratio (CDR) grading using fundus biomicroscopy compared to stereoscopic disc photograph reading.MethodsThe vertical cup-to-disc ratio (VCDR) and horizontal cup-to-disc ratio (HCDR) of 2200 eyes (testing set) were graded by glaucoma subspecialists through fundus biomicroscopy and by a reading center using stereoscopic disc photos. For validation, the glaucoma experts also estimated VCDR and HCDR using stereoscopic disc photos in a subset of 505 eyes that they had assessed biomicroscopically. Agreement between grading methods was assessed with Bland-Altman plots.ResultsIn both sets, photo reading tended to yield small CDRs marginally larger, but read large CDRs marginally smaller than fundus biomicroscopy. The mean differences in VCDR and HCDR were 0.006±0.18 and 0.05±0.18 (testing set), and -0.053±0.23 and -0.028±0.21 (validation set), respectively. The limits of agreement were ~0.4, which is twice as large as the cutoff of clinically significant CDR difference between methods. CDR estimates differed by 0.2 or more in 33.8-48.7% between methods.ConclusionsThe differences in CDR estimates between fundus biomicroscopy and stereoscopic optic disc photo reading showed a wide variation, and reached clinically significance threshold in a large proportion of patients, suggesting a poor agreement. Thus, glaucoma should be monitored by comparing baseline and subsequent CDR estimates using the same method rather than comparing photographs to fundus biomicroscopy.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p&nbsp

PURPOSE: To evaluate the glaucoma diagnostic performance of ganglion cell inner-plexiform layer (GCIPL) parameters used individually and in combination with retinal nerve fiber layer (RNFL) or optic nerve head (ONH) parameters measured with Cirrus HD-OCT (Carl Zeiss Meditec, Inc, Dublin, CA). DESIGN: Prospective cross-sectional study. PARTICIPANTS: Fifty patients with early perimetric glaucoma and 49 age-matched healthy subjects. METHODS: Three peripapillary RNFL and 3 macular GCIPL scans were obtained in 1 eye of each participant. A patient was considered glaucomatous if at least 2 of the 3 RNFL or GCIPL scans had the average or at least 1 sector measurement flagged at 1% to 5% or less than 1%. The diagnostic performance was determined for each GCIPL, RNFL, and ONH parameter as well as for binary or-logic and and-logic combinations of GCIPL with RNFL or ONH parameters. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). RESULTS: Among GCIPL parameters, the minimum had the best diagnostic performance (sensitivity, 82.0%; specificity, 87.8%; PLR, 6.69; and NLR, 0.21). Inferior quadrant was the best RNFL parameter (sensitivity, 74%; specificity, 95.9%; PLR, 18.13; and NLR, 0.27), as was rim area (sensitivity, 68%; specificity, 98%; PLR, 33.3; and NLR, 0.33) among ONH parameters. The or-logic combination of minimum GCIPL and average RNFL provided the overall best diagnostic performance (sensitivity, 94%; specificity, 85.7%; PRL, 6.58; and NLR, 0.07) as compared with the best RNFL, best ONH, and best and-logic combination (minimum GCIPL and inferior quadrant RNFL; sensitivity, 64%; specificity, 100%; PLR, infinity; and NPR, 0.36). CONCLUSIONS: The binary or-logic combination of minimum GCIPL and average RNFL or rim area provides better diagnostic performances than those of and-logic combinations or best single GCIPL, RNFL, or ONH parameters. This finding may be clinically valuable for the diagnosis of early glaucoma.

IMPORTANCE: Genetic variants associated with primary open-angle glaucoma (POAG) are known to influence disease risk. However, the clinical effect of associated variants individually or in aggregate is not known. Genetic risk scores (GRS) examine the cumulative genetic load by combining individual genetic variants into a single measure, which is assumed to have a larger effect and increased power to detect relevant disease-related associations. OBJECTIVE: To investigate if a GRS that comprised 12 POAG genetic risk variants is associated with age at disease diagnosis. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study included individuals with POAG and controls from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study. A GRS was formulated using 12 variants known to be associated with POAG, and the alleles associated with increasing risk of POAG were aligned in the case-control sets. In case-only analyses, the association of the GRS with age at diagnosis was analyzed as an estimate of disease onset. Results from cohort-specific analyses were combined with meta-analysis. Data collection started in August 2012 for the NEIGHBOR cohort and in July 2008 for the GLAUGEN cohort and were analyzed starting in March 2018. MAIN OUTCOMES AND MEASURES: Association of a 12 single-nucleotide polymorphism POAG GRS with age at diagnosis in individuals with POAG using linear regression. RESULTS: The GLAUGEN study included 976 individuals with POAG and 1140 controls. The NEIGHBOR study included 2132 individuals with POAG and 2290 controls. For individuals with POAG, the mean (SD) age at diagnosis was 63.6 (9.8) years in the GLAUGEN cohort and 66.0 (13.7) years in the NEIGHBOR cohort. For controls, the mean (SD) age at enrollment was 65.5 (9.2) years in the GLAUGEN cohort and 68.9 (11.4) years in the NEIGHBOR cohort. All study participants were European white. The GRS was strongly associated with POAG risk in case-control analysis (odds ratio per 1-point increase in score = 1.24; 95% CI, 1.21-1.27; P = 3.4 × 10(−66)). In case-only analyses, each higher GRS unit was associated with a 0.36-year earlier age at diagnosis (β = −0.36; 95% CI, −0.56 to −0.16; P = 4.0 × 10(−4)). Individuals in the top 5% of the GRS had a mean (SD) age at diagnosis of 5.2 (12.8) years earlier than those in the bottom 5% GRS (61.4 [12.7] vs 66.6 [12.9] years; P = 5.0 × 10(−4)). CONCLUSIONS AND RELEVANCE: A higher dose of POAG risk alleles was associated with an earlier age at glaucoma diagnosis. On average, individuals with POAG with the highest GRS had 5.2-year earlier age at diagnosis of disease. These results suggest that a GRS that comprised genetic variants associated with POAG could help identify patients with risk of earlier disease onset impacting screening and therapeutic strategies.

PURPOSE To evaluate and compare the diagnostic specificities of peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell-inner plexiform layer (GC-IPL) thickness, and optic nerve head (ONH) measurements in nonglaucomatous myopic individuals. METHODS In a prospective, cross-sectional study, participants underwent a complete ophthalmic examination, a screening automated visual field test, and axial length measurement. The study eye then underwent optic nerve head and macular scanning using spectral-domain optical coherence tomography (OCT) instrumentation to determine RNFL thickness, GC-IPL thickness, and ONH measurements. False-positive rates for each of the OCT-derived parameters, using predefined criteria for an abnormal test, were calculated. Comparative analysis was performed using the McNemar test. RESULTS Data from 43 eligible subjects were analyzed. The mean age was 30±6.8 years (range, 22 to 50 y) with an average axial length of 25.26±1.21 mm (range, 23.06 to 29.07 mm) and mean spherical equivalent of -4.50±1.93 D (range, -1.00 to -9.00 D). The false-positive rate was higher when using RNFL parameters compared with both ONH (47% vs. 7%, respectively; P

To determine the cumulative incidence of optic disc hemorrhage (ODH) before and after development of primary open-angle glaucoma (POAG); determine the prognostic significance of ODH for the development of POAG; and identify predictive factors for ODH.Prospective cohort study.ODHs were evaluated in 3236 eyes of 1618 Ocular Hypertension Treatment Study (OHTS) participants annually using stereoscopic optic disc photographs. The incidence of ODH before and after the development of POAG, the risk of ODH for POAG, and risk factors for ODH were determined using a multivariate proportional hazards regression model.After a median follow-up of 13 years, 1 or more ODHs were detected in 179 eyes of 169 participants. The incidence of ODH was 0.5% per year during an average of 13 years before the development of POAG and 1.2% per year during an average of 6 years after the development of POAG. The cumulative incidence of POAG in eyes with ODH was 25.6% compared with 12.9% in eyes without ODH. The occurrence of an ODH increased the risk of developing POAG 2.6-fold in the multivariate analysis (95% confidence interval, 1.7-4.0; P.0001). Randomization to the observation group, older age, thinner central corneal thickness, larger vertical cup-to-disc ratio, higher intraocular pressure, and self-reported black race were identified as risk factors for ODH.ODH is an independent predictive factor for the development of POAG in patients with ocular hypertension (OHT) and the predictive factors for ODH are very similar to those for POAG in OHT patients.

Glaucoma drainage implant (GDI) surgery represents a significant advance in the treatment of refractory glaucomas. Recent randomized clinical trials have compared the efficacy and safety of this technique to standard trabeculectomy. Several types of implants are currently available and differ in surface area, shape, composition, and presence or absence of a flow-restricting valve. A prospective, randomized clinical trial comparing two types of GDIs is ongoing. GDIs may be placed in the anterior chamber, ciliary sulcus, or pars plana. Several types of patch graft material may be utilized to prevent tube erosion. Potential complications of GDI surgery may relate to immediate or late-onset hypotony, motility disturbances, corneal decompensation, or tube erosion.