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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.

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.

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.

PURPOSE To examine the impact of surgical intraocular pressure (IOP) reduction on visual function using various methods to define visual field (VF) progression. METHODS A retrospective chart review was conducted on consecutive glaucoma patients who underwent surgical IOP reduction between January 1, 2002 and December 31, 2007. All subjects had glaucomatous optic neuropathy, a minimum of 5 preoperative and 5 postoperative VFs, and were followed for a minimum of 2 years both before and after surgery. VF progression was determined using guided progression analysis, linear regression analysis of the visual field index, and individual sensitivity values using Progressor software. RESULTS Seventeen eyes of 17 patients (mean age 77.9±9.9 y) were enrolled. Subjects were followed for a mean 5.8±2.4 years before surgery and 4.5±1.5 years after surgery. The mean postoperative IOP (11.3±4.2 mm Hg) and medications (1.3±1.3) were significantly (P

International audience; Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

Purpose To determine the diagnostic performance of macular ganglion cell–inner plexiform layer (GCIPL) thickness measured with the Cirrus high-definition optical coherence tomography (HD-OCT) ganglion cell analysis (GCA) algorithm (Carl Zeiss Meditec, Dublin, CA) to discriminate normal eyes and eyes with early glaucoma and to compare it with that of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements. Design Evaluation of diagnostic test or technology. Participants Fifty-eight patients with early glaucoma and 99 age-matched normal subjects. Methods Macular GCIPL and peripapillary RNFL thicknesses and ONH parameters were measured in each participant, and their diagnostic abilities were compared. Main Outcome Measures Area under the curve (AUC) of the receiver operating characteristic. Results The GCIPL parameters with the best AUCs were the minimum (0.959), inferotemporal (0.956), average (0.935), superotemporal (0.919), and inferior sector (0.918). There were no significant differences between these AUCs and those of inferior quadrant (0.939), average (0.936), and superior quadrant RNFL (0.933); vertical cup-to-disc diameter ratio (0.962); cup-to-disc area ratio (0.933); and rim area (0.910), all P >0.05. Conclusions The ability of macular GCIPL parameters to discriminate normal eyes and eyes with early glaucoma is high and comparable to that of the best peripapillary RNFL and ONH parameters. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Medicare claims data and surveys of the American Glaucoma Society membership show that aqueous shunts are being increasingly utilized in the surgical management of glaucoma. New clinical trials data have identified differences in the efficacy and safety of shunts in common use. Recent studies have reported comparable results with trabeculectomy and aqueous shunts in similar patient groups. Intraoperative and postoperative complications may develop with aqueous shunt surgery related to the implantation of a foreign material. Several modifications in surgical technique have been directed toward improving surgical success, reducing complications, and optimizing efficiency and cost.

Objective To evaluate a new automated analysis of optic disc images obtained by spectral-domain optical coherence tomography (SD OCT). Areas of the optic disc, cup, and neural rim in SD OCT images were compared with these areas from stereoscopic photographs to represent the current traditional optic nerve evaluation. The repeatability of measurements by each method was determined and compared. Design Evaluation of diagnostic technology. Participants One hundred nineteen healthy eyes, 23 eyes with glaucoma, and 7 glaucoma suspect eyes. Methods Optic disc and cup margins were traced from stereoscopic photographs by 3 individuals independently. Optic disc margins and rim widths were determined automatically in SD OCT. A subset of photographs was examined and traced a second time, and duplicate SD OCT images also were analyzed. Main Outcome Measures Agreement among photograph readers, between duplicate readings, and between SD OCT and photographs were quantified by the intraclass correlation coefficient (ICC), by the root mean square, and by the standard deviation of the differences. Results Optic disc areas tended to be slightly larger when judged in photographs than by SD OCT, whereas cup areas were similar. Cup and optic disc areas showed good correlation (0.8) between the average photographic reading and SD OCT, but only fair correlation of rim areas (0.4). The SD OCT was highly reproducible (ICC, 0.96–0.99). Each reader also was consistent with himself on duplicate readings of 21 photographs (ICC, 0.80–0.88 for rim area and 0.95–0.98 for all other measurements), but reproducibility was not as good as SD OCT. Measurements derived from SD OCT did not differ from photographic readings more than the readings of photographs by different readers differed from each other. Conclusions Designation of the cup and optic disc boundaries by an automated analysis of SD OCT was within the range of variable designations by different readers from color stereoscopic photographs, but use of different landmarks typically made the designation of the optic disc size somewhat smaller in the automated analysis. There was better repeatability among measurements from SD OCT than from among readers of photographs. The repeatability of automated measurement of SD OCT images is promising for use both in diagnosis and in monitoring of progression. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

BACKGROUND AND OBJECTIVE: To determine the amount of interoperator and interinstrument variability introduced into retinal nerve fiber layer (RNFL) thickness measured with Stratus OCT and Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) in normal and glaucomatous eyes. PATIENTS AND METHODS: Thirty-seven eyes from 37 subjects (20 normal and 17 with glaucoma) were included in the study. Each eye was scanned with one Stratus OCT and one Cirrus OCT by two operators. The eyes were then scanned with a different Stratus OCT and Cirrus OCT by one of the operators. Average, quadrant, and clock-hour RNFL measurements were compared between operators and between instruments after determining the proportion of variance due to subjects, operators, and instruments by means of variance component analysis. RESULTS: Significant differences were observed between Stratus OCT instruments, but not between Cirrus OCT instruments, in average ( P = .01), inferior ( P = .006), and nasal ( P < .001) quadrant RNFL thickness in glaucomatous eyes. Interoperator differences in RNFL thickness measured with both types of instruments were non-significant. The interoperator variability ranged from 0% to 1% on Stratus OCT and was 0% on Cirrus OCT, whereas the interinstrument variability ranged from 0% to 3% for Stratus OCT and from 0% to 1% for Cirrus OCT. CONCLUSION: The interoperator variability of RNFL thickness measured with Stratus OCT and Cirrus OCT, as well as the interinstrument variability of measurements obtained with Cirrus OCT, are non-significant. However, there is significant variability between RNFL measurements performed on two different Stratus OCT instruments.

Purpose The Ahmed Baerveldt Comparison (ABC) Study compares the long-term outcomes and complications of the Ahmed glaucoma valve (AGV; model FP7; New World Medical, Los Ranchos, CA) and the Baerveldt glaucoma implant (BGI; model 101-350; Abbott Medical Optics, Abbott Park, IL). Design Multicenter, randomized, controlled clinical trial. Participants Two hundred seventy-six glaucoma patients at 16 clinical centers worldwide who were 18 to 85 years of age with inadequately controlled intraocular pressure (IOP; ≥18 mmHg) in whom placement of an aqueous shunt was planned. Methods Study patients were randomized to undergo implantation of an AGV or a BGI. Main Outcome Measures Failure, defined as IOP >21 mmHg or not reduced by 20% less than baseline or IOP ≤5 mmHg (2 consecutive visits after 3 months), additional glaucoma surgery, removal of the implant, or loss of light perception vision. Results A total of 276 patients were enrolled between October 2006 and April 2008, including 143 in the AGV group and 133 in the BGI group. The mean age±standard deviation (SD) of patients enrolled was 63±14 years, and 52% were male. The mean baseline IOP±SD was 31.5±11.8 mmHg. Except for a 13% higher prevalence of hypertension in the AGV group, no significant differences in baseline demographic or ocular characteristics were observed between the study groups. Intraoperative complications occurred in 11 (8%) patients in the AGV group and in 16 (12%) patients in the BGI group ( P = 0.31). Conclusions The ABC Study should yield valuable prospective data comparing 2 commonly used aqueous shunts in clinical practice. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose To study optic nerve head (ONH) topography parameters measured by Stratus optical coherence tomography (OCT) in normal subjects and to analyze ONH data for differences in relation to disc size, ethnicity, and age. Methods Three hundred sixty-seven normal subjects underwent Stratus optical coherence tomography ONH measurement using the fast optic disc scan protocol software package 3.0. Only ONH scans meeting specific qualification criteria were included for data analysis ensuring appropriate scan quality and reliability. ONH topographic parameters of qualified scans were analyzed for differences in regards to optic disc size, age, and ethnicity. Results Two hundred and twelve qualified ONH scans were included for data analysis. Mean disc area was 2.27+/-0.41 mm and optic cup area, rim area, and horizontal integrated rim width increased with disc size, whereas vertical integrated rim area did not. Vertical integrated rim area, horizontal integrated rim width, and rim area decreased and cup area increased with age. Mean optic disc area was larger in African-Americans as compared with Hispanics or Whites and this difference was statistically significant. Conclusions Optic cup area, rim area, and horizontal integrated rim width correlated to disc size. Vertical integrated rim area, horizontal integrated rim width, rim area, and cup area, changed with age. African-American optic discs had larger disc area measurements as compared with Whites optic discs and this difference was statistically significant.

To determine the prevalence of ocular surface disease (OSD) in patients with glaucoma using topical intraocular pressure (IOP)-lowering therapy.This prospective observational study enrolled patients with primary open-angle glaucoma or ocular hypertension who were on a topical IOP-lowering medication regimen. Enrolled patients completed the ocular surface disease index (OSDI) and OSDI scores (0-100, with 0 representing no symptoms) were calculated for each patient. Medical history, demographics, and concomitant medication information were also collected.Overall, 630 patients from 10 sites participated. Of these, 305 patients (48.4%) had an OSDI score indicating either mild (n = 134, 21.3%), moderate (n = 84, 13.3%), or severe (n = 87, 13.8%) OSD symptoms. OSDI scores were significantly different between patients with and without a prior diagnosis of dry eye syndrome (25.2 +/- 15.4 vs 15.4 +/- 15.8, respectively; P = 0.0036) and between patients who did and did not use artificial tears at the time of study participation (23.0 +/- 15.6 vs 15.3 +/- 15.8, respectively; P = 0.0046). Mean OSDI scores varied significantly with the number of topical IOP-lowering medications used, with higher (more severe) OSDI scores in patients using multiple IOP-lowering medications. Specifically, patients on a single medication had a mean OSDI score of 12.9 +/- 13.1, which was significantly lower than those of patients on 2 (16.7 +/- 17.0; P = 0.007) or 3 medications (19.4 +/- 18.1; P = 0.0001).OSD is prevalent among medically treated patients with glaucoma. The severity of OSD symptoms is positively correlated to the number of IOP-lowering medications used.

Purpose To evaluate the sensitivity and specificity of measurements of retinal nerve fiber layer (RNFL) thickness in early to moderate glaucoma using Stratus time-domain and Cirrus spectral-domain optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA). Design Evaluation of diagnostic test or technology. Participants Fifty-four glaucoma subjects with early to moderate visual field defects and 50 age-matched normal subjects. Testing Three peripapillary RNFL scans of 1 eye of each subject using Stratus and Cirrus OCT. Main Outcome Measures Sensitivity and specificity of average, quadrant, and clock-hour RNFL thickness. Results The average age±standard deviation in the normal and glaucoma groups was 62.9±12.7 years (range, 40–84 years) and 67.6±11.4 (range, 42–85 years), respectively ( P = 0.05). The glaucoma group consisted of 34 early (average mean deviation, −3.20±1.22 dB) and 20 moderate (average mean deviation, −8.05±1.87 dB) glaucomas. Cirrus OCT sensitivity and specificity for average RNFL abnormal at the 5% level were 83% and 88%, respectively, and at the 1% level were 65% and 100%, respectively. Stratus OCT sensitivity and specificity for average RNFL abnormal at the 5% level were 80% and 94%, respectively, and at the 1% level were 61% and 100%, respectively. For 1 or more abnormal quadrants at the 5% level, the sensitivity and specificity for Cirrus OCT were 98% and 80%, respectively, and at the 1% level were 87% and 92%, respectively. For 1 or more quadrants abnormal at the 5% level, the sensitivity and specificity for Stratus OCT were 96% and 76%, respectively, and at the 1% level were 74% and 94%, respectively. Cirrus OCT sensitivity and specificity using a criterion of 1 or more abnormal clock hours at the 5% level were 100% and 72%, respectively, and at the 1% level were 85% and 94%, respectively. Stratus OCT sensitivity and specificity for 1 or more abnormal clock hours at the 5% level were 98% and 66%, respectively, and at the 1% level were 85% and 90%, respectively. Conclusions The sensitivity and specificity of various RNFL parameters using the Cirrus OCT for glaucoma with early to moderate visual field defects are excellent and are equivalent to Stratus OCT. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose To report 3-year results of the Tube Versus Trabeculectomy (TVT) Study. Design Multicenter randomized clinical trial. Methods setting: Seventeen clinical centers. study population: Patients 18 to 85 years of age who had previous trabeculectomy, cataract extraction with intraocular lens implantation, or both and uncontrolled glaucoma with intraocular pressure (IOP) ≥18 mm Hg and ≤40 mm Hg on maximum tolerated medical therapy. interventions: A 350-mm2 Baerveldt glaucoma implant or trabeculectomy with mitomycin C (MMC 0.4 mg/ml for 4 minutes). main outcome measures: IOP, visual acuity, use of supplemental medical therapy, surgical complications, and failure (IOP >21 mm Hg or not reduced by 20%, IOP ≤5 mm Hg, reoperation for glaucoma, or loss of light perception vision). Results A total of 212 eyes of 212 patients were enrolled, including 107 in the tube group and 105 in the trabeculectomy group. At 3 years, IOP (mean ± standard deviation [SD]) was 13.0 ± 4.9 mm Hg in the tube group and 13.3 ± 6.8 mm Hg in the trabeculectomy group (P = .78). The number of glaucoma medications (mean ± SD) was 1.3 ± 1.3 in the tube group and 1.0 ± 1.5 in the trabeculectomy group (P = .30). The cumulative probability of failure during the first 3 years of follow-up was 15.1% in the tube group and 30.7% in the trabeculectomy group (P = .010; hazards ratio, 2.2; 95% confidence interval, 1.2 to 4.1). Postoperative complications developed in 42 patients (39%) in the tube group and 63 patients (60%) in the trabeculectomy group (P = .004). Surgical complications were associated with reoperation and/or loss of ≥2 Snellen lines in 24 patients (22%) in the tube group and 28 patients (27%) in the trabeculectomy group (P = .58). Conclusions Tube shunt surgery had a higher success rate compared to trabeculectomy with MMC during the first 3 years of follow-up in the TVT Study. Both procedures were associated with similar IOP reduction and use of supplemental medical therapy at 3 years. While the incidence of postoperative complications was higher following trabeculectomy with MMC relative to tube shunt surgery, most complications were transient and self-limited.

Author(s): Liu, Yutao; Bailey, Jessica Cooke; Helwa, Inas; Dismuke, W Michael; Cai, Jingwen; Drewry, Michelle; Brilliant, Murray H; Budenz, Donald L; Christen, William G; Chasman, Daniel I; Fingert, John H; Gaasterland, Douglas; Gaasterland, Terry; Gordon, Mae O; Igo, Robert P; Kang, Jae H; Kass, Michael A; Kraft, Peter; Lee, Richard K; Lichter, Paul; Moroi, Sayoko E; Realini, Anthony; Richards, Julia E; Ritch, Robert; Schuman, Joel S; Scott, William K; Singh, Kuldev; Sit, Arthur J; Song, Yeunjoo E; Vollrath, Douglas; Weinreb, Robert; Medeiros, Felipe; Wollstein, Gadi; Zack, Donald J; Zhang, Kang; Pericak-Vance, Margaret A; Gonzalez, Pedro; Stamer, W Daniel; Kuchtey, John; Kuchtey, Rachel W; Allingham, R Rand; Hauser, Michael A; Pasquale, Louis R; Haines, Jonathan L; Wiggs, Janey L | Abstract: PurposeNoncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG).MethodsUsing the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls.ResultsOnly rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11-1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08-1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment.ConclusionsOur integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.

To assess, with optical coherence tomography (OCT), any changes in peripapillary retinal nerve fiber layer (RNFL) thickness in glaucoma patients after reduction of intraocular pressure (IOP).Prospective observational case series.Twenty-one eyes of 21 glaucoma patients who underwent medical or surgical intervention to lower IOP.Patients with elevated IOP underwent fast peripapillary RNFL measurements with the Stratus OCT (model 3000, software version 4.04; Carl Zeiss Meditec, Dublin, CA) before and after the IOP was lowered by medical or surgical therapy.Changes in overall and quadrant RNFL thickness with respect to change in IOP.The OCT scans were performed before intervention (range, 0-38 days before; mean+/-standard deviation [SD], 9.8+/-9.3 days) and after intervention (range, 32-74 days; mean+/-SD, 46.8+/-11.2 days) to measure peripapillary RNFL thickness. Mean IOP (mean+/-SD) decreased from 31.5+/-8.2 mmHg to 12.8+/-4.6 mmHg with the intervention (P0.001). Twenty of 21 eyes had an IOP reduction of more than 30%. There was no significant change in the overall RNFL thickness associated with the lowering of IOP (mean+/-SD, 1.02+/-10.3 microm; P = 0.653). Quadrant analysis did not show a significant change in the RNFL thickness of any of the 4 quadrants (superior, -1.71+/-14.5 microm, P = 0.593; inferior, 2.38+/-16.8 microm, P = 0.523; temporal, 2.19+/-9.50 microm, P = 0.303; and nasal, 1.24+/-12.5 microm, P = 0.655). No relationship was found between any of the changes in OCT parameters or percent change in OCT parameters and the extent of IOP reduction, or whether IOP was lowered medically or surgically, with or without adjusting for preintervention OCT measurements as an indication of disease severity (P values ranged from 0.331 to 0.985).No significant change in the RNFL thickness was associated with the lowering of IOP by medical or surgical therapy, as measured by OCT.

Optical coherence tomography (OCT) aids in the diagnosis and long-term monitoring of various ocular diseases, including glaucoma. Initially, the retinal nerve fiber layer was the only OCT structural parameter used in glaucoma. Subsequent research has resulted in more retinal and optic nerve head parameters. In addition, OCT is being investigated for its ability to assess ocular hemodynamics. This review summarizes these spectral domain-optical coherence tomography (SDOCT) parameters in the context of glaucoma.Several new SDOCT retinal nerve fiber layer, optic nerve head, and macular parameters with good glaucoma diagnostic ability have been added to existing ones recently. The combination of SDOCT and Doppler or angiography has also resulted in hemodynamic parameters that may prove to be useful in the functional assessment in glaucoma.OCT technology is advancing not only as a tool for structural assessment, but also as a multimodality tool to assess both structure and function to enhance our understanding of glaucoma, and ultimately clinical decisions.