Glaucoma

Glaucoma Publications

Wang Z, Wiggs JL, Aung T, Khawaja AP, Khor CC. The genetic basis for adult onset glaucoma: Recent advances and future directions. Prog Retin Eye Res 2022;:101066.Abstract
Glaucoma, a diverse group of eye disorders that results in the degeneration of retinal ganglion cells, is the world's leading cause of irreversible blindness. Apart from age and ancestry, the major risk factor for glaucoma is increased intraocular pressure (IOP). In primary open-angle glaucoma (POAG), the anterior chamber angle is open but there is resistance to aqueous outflow. In primary angle-closure glaucoma (PACG), crowding of the anterior chamber angle due to anatomical alterations impede aqueous drainage through the angle. In exfoliation syndrome and exfoliation glaucoma, deposition of white flaky material throughout the anterior chamber directly interfere with aqueous outflow. Observational studies have established that there is a strong hereditable component for glaucoma onset and progression. Indeed, a succession of genome wide association studies (GWAS) that were centered upon single nucleotide polymorphisms (SNP) have yielded more than a hundred genetic markers associated with glaucoma risk. However, a shortcoming of GWAS studies is the difficulty in identifying the actual effector genes responsible for disease pathogenesis. Building on the foundation laid by GWAS studies, research groups have recently begun to perform whole exome-sequencing to evaluate the contribution of protein-changing, coding sequence genetic variants to glaucoma risk. The adoption of this technology in both large population-based studies as well as family studies are revealing the presence of novel, protein-changing genetic variants that could enrich our understanding of the pathogenesis of glaucoma. This review will cover recent advances in the genetics of primary open-angle glaucoma, primary angle-closure glaucoma and exfoliation glaucoma, which collectively make up the vast majority of all glaucoma cases in the world today. We will discuss how recent advances in research methodology have uncovered new risk genes, and how follow up biological investigations could be undertaken in order to define how the risk encoded by a genetic sequence variant comes into play in patients. We will also hypothesise how data arising from characterising these genetic variants could be utilized to predict glaucoma risk and the manner in which new therapeutic strategies might be informed.
Friedman DS, Chang DS, Jiang Y, Huang S, Kim JA, Munoz B, Aung T, He M, Foster PJ. Acute Angle Closure Attacks Are Uncommon in Primary Angle-Closure Suspects: The Zhongshan Angle Closure Prevention Trial. Ophthalmol Glaucoma 2022;Abstract
PURPOSE: Angle-closure glaucoma is a major cause of blindness worldwide that carries an excess risk of severe, bilateral visual impairment. A common concern among clinicians is precipitating acute angle closure (AAC) attacks by mydriasis. We evaluated the risk of AAC after pharmacologic dilation in Chinese individuals classified as bilateral primary angle-closure suspects (PACS). DESIGN: Randomized interventional controlled trial. PARTICIPANTS: A total of 889 bilateral PACS aged between 50 and 70 years were identified through community screening in Guangzhou, China and enrolled in the study. METHODS: In the Zhongshan Angle Closure Prevention (ZAP) Trial, bilateral PACS were treated by laser peripheral iridotomy (LPI) in one randomly selected eye, with the fellow eye serving as an untreated control. Over 72 months of follow-up, participants had their pupils pharmacologically dilated six times with 5% phenylephrine and 0.5% tropicamide. MAIN OUTCOME MEASURES: Incidence and risk of post-mydriasis AAC in LPI-treated and untreated control PACS eyes. RESULTS: One bilateral AAC attack occurred after mydriasis at the two-week post-LPI visit. No other AAC events occurred in LPI-treated eyes. In untreated eyes, four additional attacks occurred: two after dilation (one at 54- and one at 72-months follow-up) and two spontaneously. The risk of post-mydriasis AAC in untreated eyes was one attack in 1,587 dilations. The risk of spontaneous AAC in untreated eyes was 0.44 per 1000 eye-years (95% CI: 0.11-1.77 per 1000 eye-years). CONCLUSIONS: The risk of an incident AAC attack in PACS eyes was extremely low, even in a higher-risk group with repeated pharmacologic pupillary dilation over six years of follow-up. Prophylactic LPI reduced this small but real risk.
Chang DS-T, Jiang Y, Kim JA, Huang S, Munoz B, Aung T, He M, Foster PJ, Friedman D. Cataract progression after Nd:YAG laser iridotomy in primary angle-closure suspect eyes. Br J Ophthalmol 2022;Abstract
BACKGROUND/AIMS: Prophylactic laser peripheral iridotomy (LPI) is performed in primary angle-closure suspect (PACS) eyes to prevent acute angle-closure attacks. However, accelerated cataractogenesis is a potential risk of the procedure that may result in decreased visual acuity. We aimed to assess the long-term impact of LPI on cataract formation in Chinese PACS. METHODS: In the Zhongshan Angle Closure Prevention Trial, eligible bilateral PACS participants received LPI in one randomly selected eye, while the fellow eye remained untreated. Cataract was graded using the Lens Opacity Classification System III, and progression was defined as an increase in grade by at least two units in any category or cataract surgery. RESULTS: In total, 889 participants were randomly assigned to LPI in one eye only (mean age 59±5 years, 83% female). At 72 months, treated eyes had slightly higher average nuclear grades (p<0.001). However, there were no differences between eyes for predefined cataract progression (cumulative probability at 72 months: 21.2% in LPI vs 19.4% in control, p=0.401) or cataract surgery (1% for both). While LPI-treated eyes had a 10% higher risk of progression over 6 years (HR=1.10 (95% CI 0.88 to 1.36)), this was not statistically significant. Visual acuity at 72 months was similar in treated and untreated eyes (p=0.43). CONCLUSION: Although lenses were graded on average as slightly more opaque in laser-treated eyes, prophylactic neodymium:yttrium-aluminum-garnet LPI did not cause significant cataract progression. Our results suggest that LPI treatment of asymptomatic narrow angles does not increase the risk of developing clinically meaningful cataract worsening over time. TRIAL REGISTRATION NUMBER: ISRCTN45213099.
Halawa OA, Roldan AM, Meshkin RS, Zebardast N, Fenwick EK, Lamoureux EL, Friedman DS. Factors associated with glaucoma-specific quality of life in a US glaucoma clinic in a pilot implementation of an online computerised adaptive test (GlauCAT). Br J Ophthalmol 2022;Abstract
OBJECTIVES: Measure quality of life (QoL) outcomes using a novel computerised adaptive test in a clinical setting, and determine the social and demographic factors associated with specific QoL domains in patients with glaucoma. DESIGN: Cross-sectional study between July 2020 and April 2021. PARTICIPANTS: English-speaking adults presenting to glaucoma clinic. Patients with cognitive impairment on a six-item cognitive impairment screen or with intraocular surgery within 90 days prior to presentation were excluded. RESULTS: Of 206 patients surveyed, mean age was 64.8 years (SD 15.2), 122 (56.7%) were female and 159 (74.7%) were white. On multivariable regression, visual acuity was associated with greater activity limitation (β=-2.8 points, 95% CI -3.8 to -1.8, p<0.001) and worse mobility (β=-2.1 points, 95% CI -3.2 to -0.9, p<0.001), while poorer visual field (VF) mean deviation was associated with lower scores on the emotional well-being domain (β=-2.4 points, 95% CI -4.6 to -0.3, p=0.03). Glaucoma suspects and those with early VF defects had higher QoL scores than those with severe glaucoma in the following domains: activity limitation (88.5±14.6 vs 74.3±21.9, respectively, p<0.001), mobility (91.0±12.5 vs 80.0±25.3, respectively, p=0.005) and concerns domains (82.2±13.9 vs 72.5 5±18.9, respectively, p=0.01). CONCLUSIONS: In a busy glaucoma clinic where QoL was measured with online adaptive tests for glaucoma, we found that several demographic and clinical variables are associated with lower domain scores, suggesting that patients with predisposing demographic and clinical factors are at a higher risk of worse QoL.
Mitchell WG, Azuara-Blanco A, Foster PJ, Halawa O, Burr J, Ramsay CR, Cooper D, Cochran C, Norrie J, Friedman D, Chang D. Predictors of long-term intraocular pressure control after lens extraction in primary angle closure glaucoma: results from the EAGLE trial. Br J Ophthalmol 2022;Abstract
BACKGROUND/AIMS: To assess baseline ocular parameters in the prediction of long-term intraocular pressure (IOP) control after clear lens extraction (CLE) or laser peripheral iridotomy (LPI) in patients with primary angle closure (PAC) disease using data from the Effectiveness of Early Lens Extraction for the treatment of primary angle-closure glaucoma (EAGLE) tria. METHODS: This study is a secondary analysis of EAGLE data where we define the primary outcome of 'good responders' as those with IOP<21 mm Hg without requiring additional surgery and 'optimal responders' as those who in addition were medication free, at 36-month follow-up. Primary analysis was conducted using a multivariate logistic regression model to assess how randomised interventions and ocular parameters predict treatment response. RESULTS: A total of 369 patients (182 in CLE arm and 187 in LPI arm) completed the 36-month follow-up examination. After CLE, 90% met our predefined 'good response' criterion compared with 67% in the LPI arm, and 66% met 'optimal response' criterion compared with 18% in the LPI arm, with significantly longer drops/surgery-free survival time (p<0.05 for all). Patients randomised to CLE (OR=10.1 (6.1 to 16.8)), Chinese (OR=2.3 (1.3 to 3.9)), and those who had not previously used glaucoma drops (OR=2.8 (1.6 to 4.8)) were more likely to maintain long-term optimal IOP response over 36 months. CONCLUSION: Patients with primary angle closure glaucoma/PAC are 10 times more likely to maintain drop-free good IOP control with initial CLE surgery than LPI. Non-Chinese ethnicity, higher baseline IOP and using glaucoma drops prior to randomisation are predictors of worse long-term IOP response.
Hall NE, Chang EK, Samuel S, Gupta S, Klug E, Elze T, Lorch AC, Miller JW, Solá-Del Valle D. Risk factors for glaucoma drainage device revision or removal using the IRIS Registry. Am J Ophthalmol 2022;Abstract
PURPOSE: To elucidate risk factors for revision or removal of glaucoma drainage devices (GDD) in glaucoma patients in the United States. DESIGN: Retrospective cohort study. METHODS: IRIS® Registry (Intelligent Research in Sight) patients who underwent GDD insertion between 01/01/2013 and 12/31/2018 were included. Various demographic and clinical factors were collected. Kaplan-Meier (KM) survival plots, Cox proportional-hazard models utilizing Firth's Penalized Likelihood (CRFPL), and multivariate linear regression models were used. The main outcome measures were hazard ratios (HRs) and beta coefficient (β) estimates. RESULTS: 44,330 distinct patients underwent at least one GDD implantation, and 3,354 of these underwent subsequent GDD revision or removal surgery. With failure defined as GDD revision/removal, factors significantly associated with decreased failure included unknown race (HR=0.83; p=0.004) and unknown ethnicity (HR=0.68; p<0.001). Factors associated with increased risk of GDD revision/removal surgery included presence of chronic angle closure glaucoma (HR=1.32; p<0.001) and dry eye disease (HR=1.30; p=0.007). Additionally, factors associated with a decreased average time (in days) to GDD revision/removal included male sex (β=-25.96; p=0.044), unknown race (β=-55.28; p=0.013), and right-eye laterality (β=-38.67; p=0.026). Factors associated with an increased average time to GDD revision/removal included having a history of a past eye procedure (β=104.83; p<0.001) and being an active smoker (β=38.15; p=0.024). CONCLUSIONS: The size and scope of the IRIS Registry allows for detection of subtle associations between risk factors and GDD revision or removal surgery. Aforementioned demographic and clinical factors may all have an impact on GDD longevity and can inform the treatment options available for glaucoma patients.
Tam EK, Elhusseiny AM, Shah AS, Mantagos IS, VanderVeen DK. Etiology and outcomes of childhood glaucoma at a tertiary referral center. J AAPOS 2022;Abstract
PURPOSE: To describe the etiology, clinical features, and outcomes for a large contemporary cohort of children presenting with glaucoma at a tertiary referral center. METHODS: The medical records of patients presenting to Boston Children's Hospital from January 2014 to July 2019 with a diagnosis of childhood glaucoma were retrospectively reviewed. Data regarding etiology, treatment, and visual and anatomic outcomes were collected; visual acuity outcomes were analyzed by laterality and diagnosis categories, using the Childhood Glaucoma Research Network (CGRN) classifications. RESULTS: A total of 373 eyes of 246 patients (51% males) diagnosed with glaucoma before 18 years of age were identified. Mean follow-up was 7.04 ± 5.61 years; 137 cases were bilateral. The mean age at diagnosis was 4.55 ± 5.20 years. The most common diagnoses were glaucoma following cataract surgery (GFCS, 36.5%) and primary congenital glaucoma (PCG, 29.0%). Overall, 164 eyes (44.0%) underwent at least one glaucoma surgery. Intraocular pressure (IOP) was ≤21 mm Hg with or without glaucoma medications in 300 eyes (80.4%) at the last follow-up visit. Poor final best-corrected visual acuity (≤20/200) was found in 110 eyes; patients with poor final visual acuity tended to have poor visual acuity at presentation. The most common reason for poor vision was amblyopia. Uncontrolled IOP was an uncommon cause for vision loss. CONCLUSIONS: Childhood glaucoma can be challenging to manage, but poor vision usually results from amblyopia or presence of other ocular abnormalities or syndromes rather than glaucomatous optic neuropathy.
Huang JJ, Geduldig JE, Jacobs EB, Tai TYT, Ahmad S, Chadha N, Buxton DF, Vinod K, Wirostko BM, Kang JH, Wiggs JL, Ritch R, Pasquale LR. Head and neck region dermatological UV-related cancers are associated with exfoliation syndrome in a clinic-based population. Ophthalmol Glaucoma 2022;Abstract
OBJECTIVE: We assessed the relation between UV-associated dermatological carcinomas (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) and exfoliation syndrome with or without glaucoma (XFS/XFG). DESIGN: Case-control study. Subjects, participants, and controls:321 participants with XFS/XFG, primary open angle glaucoma (POAG), and control subjects (XFS/XFG = 98, POAG = 117, control = 106, ages 50-90) were recruited between 2019-2021. METHODS: Subjects were recruited for a cross-sectional survey assessing medical history, maximum known intraocular pressure, cup-to-disc ratio, Humphrey Visual Field 24-2 (HVF), propensity to tan or burn in early life, history of BCC and/or SCC and XFS/XFG diagnosis. We generated multivariable models adjusting for age, sex, medical history, eye color, hair color, and likeliness of tanning vs burning at a young age. MAIN OUTCOME MEASURES: History of diagnosed XFS/XFG. RESULTS: Any history of BCC/SCC in the head and neck region was associated with a 2-fold higher risk for having XFS/XFG versus having POAG or being a control subject (odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.04 - 3.89) in multivariable-adjusted analysis. Additionally, we observed a dose-response association where the chance of having XFS/XFG was higher by 67% per head and neck BCC/SCC occurrence (OR = 1.67, 95% CI = 1.09 - 2.56). When we excluded POAG participants, head and neck BCC/SCC was associated with 2.8-fold higher risk of XFS/XFG (OR = 2.80, 95% CI = 1.12 - 7.02) and each additional occurrence of head and neck BCC/SCC had a 2-fold higher risk for XFS/XFG (OR = 1.97, 95% CI = 1.09 - 3.58). The association between head and neck region BCC/SCC and POAG compared to control subjects was null (OR = 1.42, 95% CI = 0.58 - 3.48). When BCC/SCC located anywhere on the body was considered, there was a non-significant higher risk of XFS/XFG compared to having POAG or being a control subject (OR = 1.65, 95% CI = 0.88 - 3.09). CONCLUSIONS: Head and neck region BCC/SCCs are associated with a higher risk for having XFS/XFG. These findings support prior evidence that head and neck UV exposure may be a risk factor for XFS.
Gardiner SK, Kinast RM, De Moraes CG, Budenz DL, Jeoung JW, Lind JT, Myers JS, Nouri-Mahdavi K, Rhodes LA, Strouthidis NG, Chen TC, Mansberger SL. Clinicians' Use of Quantitative Information when Assessing the Rate of Functional Progression in Glaucoma. Ophthalmol Glaucoma 2022;Abstract
PURPOSE: Clinicians use both global and pointwise information from visual fields to assess the rate of glaucomatous functional progression. We asked which objective, quantitative measures best correlate with the subjective assessment by glaucoma experts. In particular, we aimed to determine how much that judgment was based on localized rates of change, versus the global indices reported by the perimeter. DESIGN: Prospective cohort study. PARTICIPANTS: Eleven academic expert glaucoma specialists independently scored the rate of functional progression from 1 (improvement) to 7 (very rapid progression), for series of 5 biannual clinical printouts from 100 glaucoma or glaucoma suspect eyes of 51 participants, 20 of which were scored twice to assess repeatability. METHODS: Regression models were used to predict the average of the 11 clinicians' scores from the objective rates of change of Mean Deviation (MD), Visual Field Index (VFI), Pattern Standard Deviation (PSD), the Nth fastest progressing location, and the Nth fastest progressing of ten anatomically-defined clusters of locations after weighting by eccentricity. MAIN OUTCOME MEASURES: The correlation between objective rates of change and the average of the 11 clinicians' scores. RESULTS: The average MD of study eyes was -2.4dB (range -16.8 to +2.8dB). The mean clinician score was highly repeatable, with intraclass correlation coefficient 0.95. It correlated better with the rate of change of VFI (pseudo-R2=0.73, 95% confidence interval [0.60, 0.83]) than MD (0.63 [0.45, 0.76]) or PSD (0.41 [0.26, 0.55]). Using pointwise information, the highest correlations were with the 5th fastest progressing location (pseudo-R2=0.71 [0.56, 0.80]), or the fastest progressing cluster after eccentricity weighting (0.61 [0.48, 0.72]). Among 25 eyes with average VFI>99%, the highest observed pseudo-R2 values was 0.34 [0.16 to 0.61] for PSD. CONCLUSIONS: Expert academic glaucoma specialists' assessment of rate of change correlated best with VFI rates, except in eyes near VFI's ceiling of 100%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but expert opinions more closely correlated to global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.
Ichhpujani P, Thakur S, Singh T, Singh RB, Kumar S. Effect of laser peripheral iridotomy on contrast sensitivity using Spaeth/Richman Contrast Sensitivity test. Ther Adv Ophthalmol 2022;14:25158414221078142.Abstract
Background: Laser peripheral iridotomy (LPI) is the current standard of care for primary angle-closure glaucoma. The existing literature lacks evidence regarding the effects of LPI on contrast sensitivity (CS) after the procedure. Objective: This study evaluates central and peripheral CS in patients undergoing LPI using the computer-based, Spaeth/Richman Contrast Sensitivity (SPARCS) test. Methods: We performed a pilot, prospective, interventional cohort study including 30 patients of primary angle-closure suspect (PACS) or primary angle closure (PAC) in both eyes. LPI was performed after a detailed history and clinical examination using standard procedure in all eyes. Intraocular pressure (IOP) and CS testing using SPARCS was performed before, 2 weeks and 3 months after LPI. Results: Data analyses revealed female predominance (66.67%, 20/30); the mean age of enrolled patients was 49.93 ± 10.43 years, and presenting acuity was 0.02 ± 0.06 (Log of Minimum Angle of Resolution [LogMAR]). The mean vertical cup-to-disc ratio (VCDR), mean deviation (MD in dB) and pattern standard deviation (PSD in dB) were 0.34 ± 0.09, -2.36 ± 1.72 and 2.34 ± 0.81, respectively. There was a statistically significant decrease between the pre- (15.17 ± 3.83 mmHg) and 2 weeks post-LPI (11.70 ± 1.53 mmHg) IOP (p < 0.001). However, CS in the pre- (73.47 ± 9.88) and 3 months post-LPI (75.20 ± 11.98) SPARCS scores did not reveal any statistical difference. The group-wise analysis showed a similar trend between PAC and PACS patients. Conclusion: LPI does not affect central as well as peripheral CS assessment in patients with the primary angle-closure disease.
Fenwick EK, Roldan AM, Halawa OA, Meshkin RS, Zebardast N, Popov V, Lis P, Friedman DS, Lamoureux EL. Implementation of an Online Glaucoma-Specific Quality of Life Computerized Adaptive Test System in a US Glaucoma Hospital. Transl Vis Sci Technol 2022;11(2):24.Abstract
Purpose: The feasibility of implementing a computerized adaptive test (CAT) system in routine clinical care in ophthalmology has not been assessed. We evaluated the implementation of a glaucoma-specific CAT (GlauCAT) in outpatients at Massachusetts Eye and Ear Institute. Methods: In this implementation study (July 2020-April 2021), 216 adults (mean ± SD age 64.8 ± 15.3 years; 56.0% women) completed six adaptive GlauCAT quality of life (QOL) tests on an internet-enabled tablet at the clinic. A real-time printable report summarizing domain scores was shared with physicians prior to consultation. The implementation was evaluated using Proctor's outcomes: acceptability (patient satisfaction); appropriateness (independent complete rate [%]); feasibility (acceptance rate [%]; completion time); and fidelity (percentage of patients discussing GlauCAT results with their physician). Physician barriers/facilitators were explored using open-ended questions. Results: Patients' mean ± SD satisfaction score was 3.5 ± 0.5 of 4, with >95% of patients willing to recommend it to others. Of the 216 (89.2%) patients accepting to participate, 173 (80%) completed GlauCAT independently. Patients took 8 minutes and 5 seconds (median) to complete all 6 GlauCAT tests. Almost two-thirds (n = 136/216) of the patients reported discussing their GlauCAT results with their doctor. Physicians described the GlauCAT summary report as helpful and user-friendly, although lack of time and uncertainty about how to action information were reported. Conclusions: Pilot implementation of six GlauCAT QOL tests in glaucoma outpatient clinics was feasible and acceptable. Integration of GlauCAT with electronic medical records (EMRs) and evaluation of long-term implementation outcomes are needed. Translational Relevance: GlauCAT's multiple outcomes and low test-taking burden makes it attractive for measuring glaucoma-specific QOL in routine clinical care.

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