Glaucoma

Glaucoma Publications

Seto B, Singh MK, Lemire CA, Arroyo JG. Anterior versus posterior endoscopic cyclophotocoagulation: comparison of indications, populations, and outcomes. Int Ophthalmol 2021;Abstract
PURPOSE: To examine how indications, patient characteristics, and outcomes differ between anterior and posterior approaches of endoscopic cyclophotocoagulation (ECP) in the treatment of glaucoma. METHODS: This is a retrospective chart review of 9 anterior and 20 posterior ECP cases (n = 29). RESULTS: Posterior ECP cases were typically associated with a dramatic increase in intraocular pressure (IOP), whereas the anterior ECP was associated with chronically elevated pressures. The initial IOPs in mm Hg of posterior ECP cases (26.8 non-NVG; 35.2 NVG) were much greater than anterior ECP cases (17.8), and a greater overall reduction in IOP was observed in the posterior versus anterior ECP cases (10.3 posterior non-NVG; 21.3 posterior NVG; 3.6 anterior, P < .001). With procedural success defined as 6-month post-operative IOP falling within normal ranges and a decrease in either IOP or number of prescribed glaucoma medications, the success rate of ECP was 92% for posterior NVG, 89% for anterior and 75% for posterior non-NVG cases (P = .34), similar to the previous literature. Of the four unsuccessful cases, two resulted in a normal IOP but lacked a drop in pressure or reduction in medication burden, one resulted in a 6-point drop in IOP but remained at 23 mm Hg, and one resulted in phthisis bulbi (3%) from an initial pressure above 40 mm Hg. CONCLUSION: Endoscopic cyclophotocoagulation is an effective and safe procedure for severe glaucoma cases from both an anterior and posterior approach. Ophthalmologists should consider this procedure as part of their glaucoma treatment arsenal.
Shuldiner SR, Boland MV, Ramulu PY, De Moraes GC, Elze T, Myers J, Pasquale L, Wellik S, Yohannan J. Predicting eyes at risk for rapid glaucoma progression based on an initial visual field test using machine learning. PLoS One 2021;16(4):e0249856.Abstract
OBJECTIVE: To assess whether machine learning algorithms (MLA) can predict eyes that will undergo rapid glaucoma progression based on an initial visual field (VF) test. DESIGN: Retrospective analysis of longitudinal data. SUBJECTS: 175,786 VFs (22,925 initial VFs) from 14,217 patients who completed ≥5 reliable VFs at academic glaucoma centers were included. METHODS: Summary measures and reliability metrics from the initial VF and age were used to train MLA designed to predict the likelihood of rapid progression. Additionally, the neural network model was trained with point-wise threshold data in addition to summary measures, reliability metrics and age. 80% of eyes were used for a training set and 20% were used as a test set. MLA test set performance was assessed using the area under the receiver operating curve (AUC). Performance of models trained on initial VF data alone was compared to performance of models trained on data from the first two VFs. MAIN OUTCOME MEASURES: Accuracy in predicting future rapid progression defined as MD worsening more than 1 dB/year. RESULTS: 1,968 eyes (8.6%) underwent rapid progression. The support vector machine model (AUC 0.72 [95% CI 0.70-0.75]) most accurately predicted rapid progression when trained on initial VF data. Artificial neural network, random forest, logistic regression and naïve Bayes classifiers produced AUC of 0.72, 0.70, 0.69, 0.68 respectively. Models trained on data from the first two VFs performed no better than top models trained on the initial VF alone. Based on the odds ratio (OR) from logistic regression and variable importance plots from the random forest model, older age (OR: 1.41 per 10 year increment [95% CI: 1.34 to 1.08]) and higher pattern standard deviation (OR: 1.31 per 5-dB increment [95% CI: 1.18 to 1.46]) were the variables in the initial VF most strongly associated with rapid progression. CONCLUSIONS: MLA can be used to predict eyes at risk for rapid progression with modest accuracy based on an initial VF test. Incorporating additional clinical data to the current model may offer opportunities to predict patients most likely to rapidly progress with even greater accuracy.
Elhusseiny AM, VanderVeen DK. Early Experience with Ahmed Clear Path Glaucoma Drainage Device in Childhood Glaucoma. J Glaucoma 2021;Abstract
PURPOSE: To evaluate the short-term outcomes of Ahmed Clear Path (ACP) valveless glaucoma drainage device in childhood glaucoma. METHODS: Retrospective chart review of all patients ≤16 years with childhood glaucoma who had ACP implantation at Boston Children's Hospital from December 2019 to June 2020 with at least 6 months follow-up period. RESULTS: The study included 7 eyes of 5 patients implanted by a single surgeon. The median follow-up was 12 months. The mean IOP was reduced from 36±3.5▒mmHg on a mean of 2.7±0.6 glaucoma medications preoperatively to a mean IOP of 12.4±2.8▒mmHg (P<0.001) on a mean of 0.7±0.8 medications postoperatively at final follow-up (P=0.0009). Complete success was achieved in 4 eyes while qualified success was achieved in 3 eyes. CONCLUSION: The ACP GDD provided good short term IOP control and technical advantages for implantation for pediatric eyes were observed.
Yang S-A, Mitchell W, Hall N, Elze T, Lorch AC, Miller JW, Zebardast N, Zebardast N. Trends and Usage Patterns of Minimally Invasive Glaucoma Surgery (MIGS) in the US: IRIS Registry Analysis 2013-2018. Ophthalmol Glaucoma 2021;Abstract
OBJECTIVE: Understanding trends and patterns in the use of minimally invasive glaucoma surgery (MIGS) and patient profiles undergoing each procedure is important given their relative expense and unknown long-term safety and effectiveness. DESIGN: Retrospective analysis SUBJECTS: MIGS and standard glaucoma surgeries recorded in the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS®) Registry. METHODS: We used the data from IRIS® Registry between 2013-2018 (inclusive) to measure annual number of MIGS and standard surgical techniques (trabeculectomy or glaucoma drainage device (GDD)) performed in the US, stratified by demographic characteristics. Secondary analyses of concurrent surgeries and of subsequent surgeries for MIGS and standard surgical technique were also conducted. MAIN OUTCOME MEASURES: Trends and sociodemographic characteristics of MIGS usage in the US. RESULTS: 203,332 eyes and 232,537 unique procedures had associated, documented International Statistical Classification of Diseases and Related Health Problems (ICD) 9/10 codes for glaucoma and were included in final analyses. Among eyes with documented glaucoma diagnoses, there was a substantial increase in annual MIGS procedures over the study period (from 7,586 in 2013 to 39,677), and a smaller decrease in standard glaucoma procedures (from 16,215 to 13,701). The proportion of iStent procedures almost tripled during the study period (from 14% to 40%), and by 2017 accounted for almost half (43.7%) of all glaucoma surgeries in the US. 21,025 (10.3%) of all eyes received multiple procedures; 7,638 (36.3%) on the same day and 13,387 (63.7%) on subsequent days. ECP and iStent were the most common concurrent procedures (55.4% of all concurrent procedures). Trabeculectomy and GDD were most commonly followed by another standard glaucoma surgery, but when followed by sequential MIGS, ECP and goniotomy were the most common procedures performed (33.0%, 21.9%, respectively). CONCLUSIONS: There was a significant increase in MIGS use over the recent six-year period despite limited evidence of their long-term safety or effectiveness, highlighting the need for trials comparing safety and outcomes of novel MIGS vs traditional surgical treatments for glaucoma.
Qiu M, Woreta F, Boland MV. Microinvasive Glaucoma Surgery in United States Ophthalmology Residency: Surgical Case Log Cross-sectional Analysis and Proposal for New Glaucoma Procedure Classification. J Glaucoma 2021;Abstract
PRECIS: A cross-sectional sample of the United States ophthalmology residency graduating class of 2018 revealed that 18.4% of residents logged less than 5 traditional glaucoma surgeries, and 63.4% logged at least one microinvasive glaucoma surgery. PURPOSE: Describe the state of microinvasive glaucoma surgery in United States ophthalmology residency training and propose a glaucoma procedure classification system for residents' surgical case logs. METHODS: Deidentified case logs from residents graduating in 2018 were requested from United States residency program directors. RESULTS: Case logs were received for 152/488 (31%) residents from 36/115 (31%) programs. The mean number of traditional glaucoma surgeries per resident was 9.0±5.9 (range 0-31). The mean number of microinvasive glaucoma surgery per resident was 5.2±8.9 cases (range 0-58). There were 28/152 (18.4%) residents from 16/36 (44.4%) programs who logged <5 traditional glaucoma surgeries, and 3/152 (2.0%) residents from 3/36 (8.3%) programs who logged zero traditional glaucoma surgeries. There were 98/152 (64.5%) residents from 32/36 (88.8%) programs who logged <5 microinvasive glaucoma surgery as primary surgeon, and 48/152 (31.6%) residents from 25 of 36 (69.4%) programs who logged zero microinvasive glaucoma surgery. There were 104/152 (63.4%) residents from 33/36 (91.6%) programs who logged at least 1 microinvasive glaucoma surgery; there were 3/36 (8.3%) residency programs where no resident logged any microinvasive glaucoma surgery. CONCLUSIONS: United States ophthalmology residents' microinvasive glaucoma surgery experience varies widely. Residents can satisfy glaucoma surgery requirements with some microinvasive glaucoma surgery, even in the absence of adequate traditional glaucoma surgeries. We propose a residency case log classification system that better reflects the growing role of microinvasive glaucoma surgery in clinical practice and helps ophthalmic educators more accurately track procedures requiring related skills.
Chang EK, Gupta S, Chachanidze M, Hall N, Chang TC, Solá-Del Valle D. Safety and efficacy of microinvasive glaucoma surgery with cataract extraction in patients with normal-tension glaucoma. Sci Rep 2021;11(1):8910.Abstract
This study assesses the safety and efficacy of microinvasive glaucoma surgery (MIGS) with cataract extraction in patients with normal-tension glaucoma (NTG). In our sample of 45 NTG patients, mean intraocular pressure (IOP) decreased from 13.7 to 12.3 mmHg at 2.5 years, and mean medication burden decreased from 2.0 to 1.1 at 1.5 years. For success defined as IOP reduction ≥ 30% from baseline IOP with medication burden reduction from preoperative levels, success probability was 5.4% at 1.5 years. For success defined as medication burden reduction with an IOP reaching goal IOP as determined by the glaucoma specialist, success probabilities were 67.2% at 1.5 years and 29.4% at 2.5 years. At the last follow-up visit, eyes with two MIGS procedures with different mechanisms of action achieved successful medication reduction 68.8% of the time versus 35.7% achieved by a single MIGS procedure (p = 0.052). At their last visit, visual acuity was unchanged or improved in all eyes (100%). MIGS with cataract surgery results in modest reductions in IOP and medication burden in NTG patients, which may lead to lower costs and better therapeutic compliance. A combination of two MIGS procedures with different mechanisms of action may potentially be more effective in reducing medication burden than a single MIGS procedure in NTG patients. Further research is necessary to ascertain whether MIGS for NTG patients may help decrease medication burden while helping achieve goal IOP.
Soh ZD, Yu M, Betzler BK, Majithia S, Thakur S, Tham YC, Wong TY, Aung T, Friedman DS, Cheng C-Y. The global extent of undetected glaucoma in adults: a systematic review and meta-analysis. Ophthalmology 2021;Abstract
TOPIC: Glaucoma is the leading cause of irreversible blindness despite having good prognosis with early treatment. We evaluated the global extent of undetected glaucoma and the factors associated with it in this systematic review and meta-analysis of population-based epidemiological studies. CLINICAL RELEVANCE: Undetected glaucoma increases the risk of vision impairment, which leads to detrimental effects on the quality-of-life and socio-economic well-being of those affected. Detailed information on the extent and factors associated with undetected glaucoma aid in the development of public health interventions. METHODS: We conducted a systematic review and meta-analysis of population-based studies published between January 1, 1990 to June 1, 2020. Article search was conducted in online databases (PubMED, Web-of-Science), grey literatures (opengrey) and non-government organization (NGOs) reports. Our outcome measure was the proportion of glaucoma cases that were undetected previously. Manifest glaucoma included any form of glaucoma reported in the respective study and may include primary-open-angle-glaucoma (POAG), primary-angle-closure-glaucoma (PACG), and/or secondary glaucoma. Undetected glaucoma was defined as glaucoma cases that were undetected prior to diagnosis in the respective study. Random-effect meta-analysis was used to estimate the pooled proportion and factors associated with undetected glaucoma. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines in our study. RESULTS: We identified 61 articles from 55 population-based studies (N= 189,359 participants; N= 6,949 manifest glaucoma; N= 5,558 undetected glaucoma). Globally, more than half of all glaucoma cases were previously undetected in each geographical region. Regionally, Africa (OR 12.70, 95% CI 4.91, 32.86) and Asia (OR 3.41, 95% CI 1.63, 7.16) had higher odds of undetected glaucoma as compared to Europe. Countries with low human development index (HDI, <0.55) had higher proportion of undetected manifest glaucoma as compared to countries of medium to very high HDI (≥0.55, all P <0.001). In 2020, 43.78 million POAG cases were undetected, of which 76.7% reside in Africa and Asia. CONCLUSION: Undetected glaucoma is highly prevalent across diverse communities worldwide, and more common in Africa and Asia. Strategies to improve detection are needed to prevent excess visual disability and blindness due to glaucoma.
Susanna FN, Melchior B, Paula JS, Boland MV, Myers JS, Wellik SR, Elze T, Pasquale LR, Shen LQ, Ritch R, Susanna R, Hood DC, Liebmann JM, De Moraes CG. Variability and Power to Detect Progression of Different Visual Field Patterns. Ophthalmol Glaucoma 2021;Abstract
PURPOSE: To compare the variability and ability to detect visual field progression of 24-2, central 12 locations of the 24-2 and 10-2 visual field (VF) tests in eyes with abnormal VFs. DESIGN: Retrospective, multisite cohort. PARTICIPANTS: A total of 52,806 24-2 and 11,966 10-2 VF tests from 7,307 eyes from the Glaucoma Research Network database were analyzed. Only eyes with ≥ 5 visits and ≥ 2 years of follow-up were included. METHODS: Linear regression models were used to calculate the rates of MD (Mean Deviation) change (slopes) while their residuals were used to assess variability across the entire MD range. Computer simulations (n=10,000) based upon real MD residuals of our sample were performed to estimate power to detect significant progression (P < 5%) at various rates of MD change. MAIN OUTCOME MEASURES: Time required to detect progression. RESULTS: For all 3 patterns, the MD variability was highest within the -5 to -20 dB range and consistently lower with the 10-2 compared to 24-2 or Central 24-2. Overall, time to detect confirmed significant progression at 80% power was the lowest with 10-2 VF, with a decrease of 14.6% to 18.5% when compared to 24-2 and a decrease of 22.9% to 26.5% when compared to Central 24-2. CONCLUSION: Time to detect central VF progression was reduced with 10-2 MD compared with 24-2 and C24-2 MD in glaucoma eyes in this large dataset, in part because 10-2 tests had lower variability. These findings contribute to current evidence of the potential value of 10-2 testing in the clinical management of glaucoma patients and in clinical trial design.
Zebardast N, Sekimitsu S, Wang J, Elze T, Gharahkhani P, Cole BS, Lin MM, Segrè AV, Wiggs JL, Wiggs JL. Characteristics of Gln368Ter Myocilin variant and influence of polygenic risk on glaucoma penetrance in the UK Biobank. Ophthalmology 2021;Abstract
OBJECTIVE: MYOC (myocilin) mutations account for 3-5% of primary open angle glaucoma (POAG). We aimed to understand the true population-wide penetrance and characteristics of glaucoma among individuals with the most common MYOC variant (p.Gln368Ter) and the impact of a POAG polygenic risk score (PRS) in this population. DESIGN: Cross-sectional population-based METHODS: Individuals with the p.Gln368Ter variant were identified among 77,959 UK Biobank participants with fundus photographs (FPs). A genome-wide POAG PRS was computed and two masked graders reviewed FPs for disc-defined glaucoma (DDG). MAIN OUTCOME MEASURES: Penetrance of glaucoma RESULTS: 200 individuals carried the p.Gln368Ter heterozygous genotype, and 177 had gradable FPs. 132 had no evidence of glaucoma, 45 (25.4%) had probable/definite glaucoma in at least one eye and 19 (10.7%) had bilateral glaucoma. There were no differences in age, race/ethnicity, or gender among groups (p>0.05). Of those with DDG, 31% self-reported or had ICD 9/10 code for glaucoma, while 69% were undiagnosed. Subjects with DDG had higher medication-adjusted cornea-corrected intraocular pressure (IOPcc) (p<0.001) vs. those without glaucoma. This difference in IOPcc was larger in DDG with prior glaucoma diagnosis vs. those not diagnosed (p<0.001). Majority of p.Gln368Ter carriers had IOP in the normal range (<=21 mmHg), though this proportion was lower in those with DDG (p<0.02) and those with prior glaucoma diagnosis (p<0.03). Prevalence of DDG increased with each decile of the POAG PRS. Subjects with DDG had significantly higher PRS compared to those without glaucoma (0.37 ± 0.97 vs 0.01 ± 0.90, p=0.03). Of those with DDG, individuals with prior diagnosis of glaucoma had higher PRS compared to undiagnosed individuals (1.31 ± 0.64 vs 0.00 ± 0.81, p<0.001) and had 27.5 times (95%CI 2.5-306.6) adjusted odds of being in the top decile of PRS for POAG. CONCLUSION: 1 in 4 individuals with MYOC p.Gln368Ter mutation had evidence of glaucoma, a substantially higher penetrance than previously estimated, with 69% of cases undetected. A large portion of p.Gln368Ter carriers have IOP in the normal range, despite similar age, including those with DDG. PRS increases disease penetrance and severity of disease, supporting the utility of PRS in optimizing risk stratification among MYOC p.Gln368Ter carriers.
Aboobakar IF, Friedman DS. Home Monitoring for Glaucoma: Current Applications and Future Directions. Semin Ophthalmol 2021;:1-5.Abstract
Technological advances provide a number of options for glaucoma monitoring outside the office setting, including home-based tonometry and perimetry. This has the potential to revolutionize management of this chronic disease, improve access to care, and enhance patient engagement. Here, we provide an overview of existing technologies for home-based glaucoma monitoring. We also discuss areas for future research and the potential applications of these technologies to telemedicine, which has been brought to the forefront during the ongoing COVID-19 pandemic.
Ong AY, Ng SM, Vedula SS, Friedman DS. Lens extraction for chronic angle-closure glaucoma. Cochrane Database Syst Rev 2021;3:CD005555.Abstract
BACKGROUND: Primary angle-closure glaucoma (PACG) is characterized by a rise in intraocular pressure (IOP) secondary to aqueous outflow obstruction, with relative pupillary block being the most common underlying mechanism. There is increasing evidence that lens extraction may relieve pupillary block and thereby improve IOP control. As such, comparing the effectiveness of lens extraction against other commonly used treatment modalities can help inform the decision-making process. OBJECTIVES: To assess the effectiveness of lens extraction compared with other interventions in the treatment of chronic PACG in people without previous acute angle-closure attacks. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and two trials registers (December 2019). We also screened the reference lists of included studies and the Science Citation Index database. We had no date or language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing lens extraction with other treatment modalities for chronic PACG. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We identified eight RCTs with 914 eyes. We obtained data for participants meeting our inclusion criteria for these studies (PACG only, no previous acute angle-closure attacks), resulting in 513 eyes included in this review. The participants were recruited from a diverse range of countries. We were unable to conduct meta-analyses due to different follow-up periods and insufficient data. One study compared phacoemulsification with laser peripheral iridotomy (LPI) as standard care. Participants in the phacoemulsification group were less likely to experience progression of visual field loss (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.13 to 0.91; 216 eyes; moderate certainty evidence), and required fewer IOP-lowering medications (mean difference [MD] -0.70, 95% CI -0.89 to -0.51; 263 eyes; moderate certainty evidence) compared with standard care at 12 months. Moderate certainty evidence also suggested that phacoemulsification improved gonioscopic findings at 12 months or later (MD -84.93, 95% CI -131.25 to -38.61; 106 eyes). There was little to no difference in health-related quality of life measures (MD 0.04, 95% CI -0.16 to 0.24; 254 eyes; moderate certainty evidence), and visual acuity (VA) (MD 2.03 ETDRS letter, 95% CI -0.77 to 4.84; 242 eyes) at 12 months, and no observable difference in mean IOP (MD -0.03mmHg, 95% CI -2.34 to 2.32; 257 eyes; moderate certainty evidence) compared to standard care. Irreversible loss of vision was observed in one participant in the phacoemulsification group, and three participants in standard care at 36 months (moderate-certainty evidence). One study (91 eyes) compared phacoemulsification with phaco-viscogonioplasty (phaco-VGP). Low-certainty evidence suggested that fewer IOP-lowering medications were needed at 12 months with phacoemulsification (MD -0.30, 95% CI -0.55 to -0.05). Low-certainty evidence also suggested that phacoemulsification may have improved gonioscopic findings at 12 months or later compared to phaco-VGP (angle grading MD -0.60, 95% CI -0.91 to -0.29; TISA500 MD -0.03, 95% CI -0.06 to -0.01; TISA750 MD -0.03, 95% CI -0.06 to -0.01; 91 eyes). Phacoemulsification may result in little to no difference in best corrected VA at 12 months (MD -0.01 log MAR units, 95% CI -0.10 to 0.08; low certainty evidence), and the evidence is very uncertain about its effect on IOP at 12 months (MD 0.50 mmHg, 95% CI -2.64 to 3.64; very low certainty evidence). Postoperative fibrin reaction was observed in two participants in the phacoemulsification group and four in the phaco-VGP group. Three participants in the phaco-VGP group experienced hyphema. No data were available for progression of visual field loss and quality of life measurements at 12 months. Two studies compared phacoemulsification with phaco-goniosynechialysis (phaco-GSL). Low-certainty evidence suggested that there may be little to no difference in mean IOP at 12 months (MD -0.12 mmHg, 95% CI -4.72 to 4.48; 1 study, 32 eyes) between the interventions. Phacoemulsification did not reduce the number of IOP-lowering medications compared to phaco-GSL at 12 months (MD -0.38, 95% CI -1.23 to 0.47; 1 study, 32 eyes; moderate certainty evidence). Three eyes in the phaco-GSL group developed hyphemas. No data were available at 12 months for progression of visual field loss, gonioscopic findings, visual acuity, and quality of life measures. Three studies compared phacoemulsification with combined phaco-trabeculectomy, but the data were only available for one study (63 eyes). In this study, low-certainty evidence suggested that there was little to no difference between groups in mean change in IOP from baseline (MD -0.60 mmHg, 95% CI -1.99 to 0.79), number of IOP-lowering medications at 12 months (MD 0.00, 95% CI -0.42 to 0.42), and VA measured by the Snellen chart (MD -0.03, 95% CI -0.18 to 0.12). Participants in the phacoemulsification group had fewer complications (risk ratio [RR] 0.59, 95% CI 0.34 to 1.04), and the phaco-trabeculectomy group required more IOP-lowering procedures (RR 5.81, 95% CI 1.41 to 23.88), but the evidence was very uncertain. No data were available for other outcomes. AUTHORS' CONCLUSIONS: Moderate certainty evidence showed that lens extraction has an advantage over LPI in treating chronic PACG with clear crystalline lenses over three years of follow-up; ultimately, the decision for intervention should be part of a shared decision-making process between the clinician and the patient. For people with chronic PACG and visually significant cataracts, low certainty evidence suggested that combining phacoemulsification with either viscogonioplasty or goniosynechialysis does not confer any additional benefit over phacoemulsification alone. There was insufficient evidence to draw any meaningful conclusions regarding phacoemulsification versus trabeculectomy. Low certainty evidence suggested that combining phacoemulsification with trabeculectomy does not confer any additional benefit over phacoemulsification alone, and may cause more complications instead. These conclusions only apply to short- to medium-term outcomes; studies with longer follow-up periods can help assess whether these effects persist in the long term.
Ratanawongphaibul K, Tsikata E, Zemplenyi M, Lee H, Margeta MA, Ondeck CL, Kim J, Pan BX, Petrakos P, Coleman AL, Yu F, de Boer JF, Chen TC. Earlier Detection of Glaucoma Progression Using High-Density 3D Spectral-Domain Optical Coherence Tomography Optic Nerve Volume Scans. Ophthalmol Glaucoma 2021;Abstract
PURPOSE: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, two-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) neuroretinal rim measurements. DESIGN: Prospective longitudinal cohort study PARTICIPANTS: One hundred and twenty-four eyes of 124 open angle glaucoma patients METHODS: Over a 5-year period, 124 open angle glaucoma patients had yearly DP, VFs, SD-OCT RNFL thickness scans, and optic nerve volume scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or non-glaucoma progressors using event-based analysis. Progression by DP and VF occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if there was change greater than test-retest variability. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa coefficients were used to measure agreement of progressing eyes among modalities. MAIN OUTCOME MEASURES: Time to glaucoma progression among all 4 modalities RESULTS: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared to DP (16.1%, P<0.001), and global RNFL thickness (15.3%, P<0.001) respectively. Global MDB thickness detected glaucoma progression earlier than either DP (23 versus 44 months; P<0.001) or global RNFL thickness (23 versus 33 months; P<0.001). Among MDB progressing eyes, 46.2% were simultaneously or later confirmed by other conventional modalities. Agreement of glaucoma progressing eyes for all 4 modalities in paired fashion were slight to fair (k=0.095-0.300). CONCLUSION: High-density 3D SD-OCT neuroretinal rim measurements detected glaucoma progression approximately 1-2 years earlier compared to current clinically available structural tests (i.e. disc photos and 2D RNFL thickness measurements).
Gharahkhani P, Jorgenson E, Hysi P, Khawaja AP, Pendergrass S, Han X, Ong JS, Hewitt AW, Segrè AV, Rouhana JM, Hamel AR, Igo RP, Choquet H, Qassim A, Josyula NS, Cooke Bailey JN, Bonnemaijer PWM, Iglesias A, Siggs OM, Young TL, Vitart V, Thiadens AAHJ, Karjalainen J, Uebe S, Melles RB, Nair SK, Luben R, Simcoe M, Amersinghe N, Cree AJ, Hohn R, Poplawski A, Chen LJ, Rong S-S, Aung T, Vithana EN, Vithana EN, Vithana EN, Vithana EN, Vithana EN, and Consortium UKBEV, and Consortium UKBEV, and Consortium UKBEV, Tamiya G, Shiga Y, Yamamoto M, Nakazawa T, Currant H, Birney E, Wang X, Auton A, Lupton MK, Martin NG, Ashaye A, Olawoye O, Williams SE, Akafo S, Ramsay M, Hashimoto K, Kamatani Y, Akiyama M, Momozawa Y, Foster PJ, Khaw PT, Morgan JE, Strouthidis NG, Kraft P, Kang JH, Pang CP, Pasutto F, Mitchell P, Lotery AJ, Palotie A, van Duijn C, Haines JL, Hammond C, Pasquale LR, Klaver CCW, Hauser M, Khor CC, Mackey DA, Kubo M, Cheng C-Y, Craig JE, Macgregor S, Wiggs JL. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nat Commun 2021;12(1):1258.Abstract
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
Chang EK, Gupta S, Chachanidze M, Miller JB, Chang TC, Solá-Del Valle DA. Combined pars plana glaucoma drainage device placement and vitrectomy using a vitrectomy sclerotomy site for tube placement: a case series. BMC Ophthalmol 2021;21(1):106.Abstract
PURPOSE: The purpose of this study is to report the safety and efficacy of pars plana glaucoma drainage devices with pars plana vitrectomy using one of the vitrectomy sclerotomy sites for tube placement in patients with refractory glaucoma. METHODS: Retrospective case series of 28 eyes of 28 patients who underwent combined pars plana glaucoma drainage device and pars plana vitrectomy between November 2016 and September 2019 at Massachusetts Eye and Ear. Main outcome measures were intraocular pressure (IOP), glaucoma medication burden, best corrected visual acuity, and complications. Statistical tests were performed with R and included Kaplan-Meier analyses, Wilcoxon paired signed-rank tests, and Fisher tests. RESULTS: Mean IOP decreased from 22.8 mmHg to 11.8 mmHg at 1.5 years (p = 0.002), and mean medication burden decreased from 4.3 to 2.1 at 1.5 years (p = 0.004). Both IOP and medication burden were significantly lower at all follow-up time points. The probability of achieving 5 < IOP ≤ 18 mmHg with at least 20% IOP reduction from preoperative levels was 86.4% at 1 year and 59.8% at 1.5 years. At their last visit, three eyes (10.7%) achieved complete success with IOP reduction as above without medications, and 14 eyes (50.0%) achieved qualified success with medications. Hypotony was observed in 1 eye (3.6%) prior to 3 months postoperatively and 0 eyes after 3 months. Visual acuity was unchanged or improved in 23 eyes (82.1%) at their last follow-up. Two patients had a visual acuity decrease of > 2 lines. Two eyes required subsequent pars plana vitrectomies for tube obstruction, and one eye had transient hypotony. CONCLUSIONS: The results of pars plana glaucoma drainage device and pars plana vitrectomy using one of the vitrectomy sclerotomy sites for tube placement are promising, resulting in significant IOP and medication-burden reductions through postoperative year 1.5 without additional risk of postoperative complications. Inserting glaucoma drainage devices into an existing vitrectomy sclerotomy site may potentially save surgical time by obviating the need to create another sclerotomy for tube placement and suture one of the vitrectomy ports.
Waksmunski AR, Song YE, Kinzy TG, Laux RA, Sewell J, Fuzzell D, Fuzzell S, Miller S, Wiggs JL, Pasquale LR, Skarie JM, Haines JL, Cooke Bailey JN. The GGLEAM Study: Understanding Glaucoma in the Ohio Amish. Int J Environ Res Public Health 2021;18(4)Abstract
Glaucoma leads to millions of cases of visual impairment and blindness around the world. Its susceptibility is shaped by both environmental and genetic risk factors. Although over 120 risk loci have been identified for glaucoma, a large portion of its heritability is still unexplained. Here we describe the foundation of the Genetics of GLaucoma Evaluation in the AMish (GGLEAM) study to investigate the genetic architecture of glaucoma in the Ohio Amish, which exhibits lower genetic and environmental heterogeneity compared to the general population. To date, we have enrolled 81 Amish individuals in our study from Holmes County, Ohio. As a part of our enrollment process, 62 GGLEAM study participants (42 glaucoma-affected and 20 unaffected individuals) received comprehensive eye examinations and glaucoma evaluations. Using the data from the Anabaptist Genealogy Database, we found that 80 of the GGLEAM study participants were related to one another through a large, multigenerational pedigree containing 1586 people. We plan to integrate the health and kinship data obtained for the GGLEAM study to interrogate glaucoma genetics and pathophysiology in this unique population.

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