PURPOSE: To identify patterns of visual field (VF) loss based on unsupervised machine learning and to identify patterns that are associated with rapid progression. DESIGN: Cross-sectional and longitudinal study. PARTICIPANTS: A total of 2231 abnormal VFs from 205 eyes of 176 OHTS participants followed over approximately 16 years. METHODS: VFs were assessed by an unsupervised deep archetypal analysis algorithm as well as an OHTS certified VF reader to identify prevalent patterns of VF loss. Machine-identified patterns of glaucoma damage were compared against those patterns previously identified (expert-identified) in the OHTS in 2003. Based on the longitudinal VFs of each eye, VF loss patterns that were strongly associated with rapid glaucoma progression were identified. MAIN OUTCOME MEASURES: Machine-expert correspondence and type of patterns of VF loss associated with rapid progression. RESULTS: The average VF mean deviation (MD) at conversion to glaucoma was -2.7 dB (Standard Deviation (SD) = 2.4 dB) while the average MD of the eyes at the last visit was -5.2 dB (SD = 5.5 dB). Fifty out of 205 eyes had MD rate of -1 dB/year or worse and were considered rapid progressors. Eighteen machine-identified patterns of VF loss were compared with expert-identified patterns in which 13 patterns of VF loss were similar. The most prevalent expert-identified patterns included partial arcuate, paracentral, and nasal step defects, and the most prevalent machine-identified patterns included temporal wedge, partial arcuate, nasal step, and paracentral VF defects. One of the machine-identified patterns of VF loss predicted future rapid VF progression after adjustment for age, sex, and initial MD. CONCLUSIONS: An automated machine learning system can identify patterns of VF loss and could provide objective, and reproducible nomenclature for characterizing early signs of visual defects and rapid progression in patients with glaucoma.

Purpose: We evaluated racial/ethnic differences in primary open-angle glaucoma (POAG) defined by machine-learning-derived regional visual field (VF) loss patterns. Methods: Participants (N = 209,036) from the Nurses' Health Study (NHS; 1980-2018), Nurses' Health Study II (NHS2; 1989-2019), and Health Professionals Follow-Up Study (HPFS; 1986-2018) who were ≥40 years of age and free of glaucoma were followed biennially. Incident POAG cases (n = 1946) with reproducible VF loss were confirmed with medical records. Total deviation information from the earliest reliable glaucomatous VF for each POAG eye (n = 2564) was extracted, and machine learning analyses were used to identify optimal solutions ("archetypes") for regional VF loss patterns. Each POAG eye was assigned a VF archetype based on the highest weighting coefficient. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using per-eye Cox proportional hazards models. Results: We identified 14 archetypes: four representing advanced loss patterns, nine of early loss, and one of no VF loss. Compared to non-Hispanic whites, black participants had higher risk of early VF loss archetypes (HR = 1.98; 95% CI, 1.48-2.66) and even higher risk for advanced loss archetypes (HR = 6.17; 95% CI, 3.69-10.32; P-contrast = 0.0002); no differences were observed for Asians or Hispanic whites. Hispanic white participants had significantly higher risks of POAG with paracentral defects and advanced superior loss; black participants had significantly higher risks of all advanced loss archetypes and three early loss patterns, including paracentral defects. Conclusions: Blacks, compared to non-Hispanic whites, had higher risks of POAG with early central and advanced VF loss. Translational Relevance: In POAG, risks of VF loss regional patterns derived from machine learning algorithms showed racial differences.

OBJECTIVE: To determine the effectiveness of trabeculectomy and glaucoma drainage device (GDD) surgery performed with concurrent phacoemulsification compared with stand-alone procedures. DESIGN: Multicenter retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight Registry who underwent trabeculectomy or GDD from 2013 through 2019. METHODS: The Kaplan-Meier survival analysis was used to determine reoperation rates. Reoperation was defined as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine reoperation risk factors. MAIN OUTCOME MEASURES: Reoperation rate, intraocular pressure (IOP), visual acuity, reoperation procedure type, postoperative complications, and predictors of surgical failure. RESULTS: A total of 117 697 eyes undergoing glaucoma surgery alone and 35 657 eyes undergoing surgery with phacoemulsification were included. The cumulative reoperation rates at postoperative years 1 and 3 were 4.9% and 11.5%, respectively, for trabeculectomy alone and 3.0% and 7.3%, respectively, for trabeculectomy combined with phacoemulsification (P < 0.001). The reoperation rates at postoperative 1 and 3 years were 3.8% and 7.8%, respectively, for GDD alone and 2.1% and 5.4%, respectively, for GDD with phacoemulsification (P < 0.001). Stand-alone procedures achieved greater IOP reduction by percentage change from baseline (trabeculectomy alone, 35.3% vs. trabeculectomy with phacoemulsification, 23.1%, P < 0.001; and GDD alone, 36.0% vs. GDD with phacoemulsification, 29.3%; P < 0.001). Visual acuity improved by 0.12 logarithm of the minimum angle of resolution (logMAR) (95% confidence interval [CI], 0.11-0.12) and 0.10 logMAR (95% CI, 0.08-0.11) after trabeculectomy and GDD with phacoemulsification and declined by 0.15 logMAR (95% CI, 0.14-0.15) and 0.12 logMAR (95% CI, 0.11-0.12) after stand-alone trabeculectomy and GDD. The overall documented complication rate was 2.9% for GDD and 1.4% for trabeculectomy. Age, sex, race, ethnicity, baseline IOP, and glaucoma diagnosis and severity were associated with surgical failure risk. The most common reoperation procedure was GDD. CONCLUSIONS: Reoperation rates within the first 3 years after trabeculectomy and GDD with and without phacoemulsification were low. Trabeculectomy and GDD with phacoemulsification had lower reoperation rates than those with stand-alone procedures. However, stand-alone procedures resulted in greater IOP reduction compared with combined procedures. Postoperative complications were uncommon overall. Patient age, sex, race, ethnicity, baseline IOP, and glaucoma diagnosis and severity were associated with surgical success.

Juvenile-onset open-angle glaucoma (JOAG) is a subset of primary open-angle glaucoma that is diagnosed before 40 years of age. The disease may be familial or non-familial, with proportions varying among different populations. Myocilin mutations are the most commonly associated. JOAG is characterized by high intraocular pressures (IOP), with many patients needing surgery. The mean age at diagnosis is in the 3rd decade, with a male preponderance. Myopia is a common association. The pathophysiology underlying the disease is immaturity of the conventional outflow pathways, which may or may not be observed on gonioscopy and anterior segment optical coherence tomography. The unique optic nerve head features include large discs with deep, steep cupping associated with high IOP-induced damage. Progression rates among JOAG patients are comparable to adult primary glaucomas, but as the disease affects younger patients, the projected disability from this disease is higher. Early diagnosis, prompt management, and life-long monitoring play an important role in preventing disease progression. Gene-based therapies currently under investigation offer future hope.

PRCIS: In this prospective interventional case series that included 474 patients, there were no significant differences in visual field (VF) parameters between fields from patients tested one-at-a-time and simultaneously, except for fixation losses. PURPOSE: To test for differences in reliability and performance parameters of patients taking VF tests while using a remote patient monitoring system to supervise 1 or 2 test sessions simultaneously. METHODS: In a prospective interventional case series, 861 eyes of 474 consecutive patients undergoing automated perimetry during a 6-month period were monitored during the test using an audio/video-enabled remote monitoring system. Two patients were simultaneously tested (simultaneous test) by a single technician if they were ready for testing at the same time. Patients were otherwise tested individually (single test). Performance and reliability parameters including false negatives, false positives, fixation losses, mean deviation, pattern standard deviation, VF index, and test duration were compared between patients undergoing simultaneous tests and single tests. Patients undergoing remotely monitored testing, for whom a prior VF could be found, had performance and reliability parameters compared with those prior tests. VFs were analyzed separately for 2 test strategies: SITA Standard 24-2 and SITA Faster 24-2C. RESULTS: No significant parameter differences were observed among SITA Standard 24-2 VFs between single and simultaneous tests, except for fixation losses (single: 16.8±19.7%, simultaneous: 22.5±25.0%, P=0.01). Similarly, there were no significant differences observed among SITA Faster 24-2C tests. Paired analyses comparing remotely monitored VFs with prior traditionally monitored VFs showed no significant differences for any parameters, except for fewer fixation losses with remote monitoring (traditional: 23.6±27.5%, remote 17.7±20.8%, P=0.003). CONCLUSIONS: Remote patient monitoring of VF testing enabled technicians to supervise testing of 2 patients simultaneously with preserved performance and reliability.

PRCIS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery. Both treatments were reasonable options for eyes with inadequately controlled IOP after a single GDD. PURPOSE: The purpose of this study is to compare the implantation of a second glaucoma drainage device (SGDD) and transscleral cyclophotocoagulation (CPC) in eyes with inadequately controlled intraocular pressure (IOP), despite the presence of a preexisting glaucoma drainage device. METHODS: Patients with inadequately controlled IOP, despite the medical therapy and a preexisting glaucoma drainage device, were enrolled at 14 clinical centers and randomly assigned to treatment with a SGDD or CPC. MAIN OUTCOME MEASURES: Surgical failure was defined as: (1) IOP ≤5 mm Hg or >18 mm Hg or <20% reduction below baseline on maximum tolerated topical ocular hypotensive therapy, (2) reoperation for glaucoma, or (3) loss of light perception. The primary outcome measure was overall success with or without adjunctive medical therapy. RESULTS: Forty-two eyes of 42 participants were randomized to SGDD (n=22) or CPC (n=20). Mean duration of follow-up was 18.6 (±12.1; range: 1.1-38.6) months. The cumulative success rate was 79% for SGDD and 88% for CPC at 1 year ( P =0.63). Although the study was underpowered, no significant differences in IOP, postoperative number of IOP-lowering medications, or adverse events were observed. The number of additional glaucoma surgeries ( P =0.003), office visits during the first 3 months ( P <0.001), and office visits per month after month 3 ( P <0.001) were greater in the SGDD group. CONCLUSIONS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery.

Purpose: To assess practice patterns and opinions of glaucoma specialists regarding glaucoma drainage device tube shunt placement and post-operative anti-inflammatory medication use. We also assess the perceived need for a randomized control trial to compare them. Patients and Methods: An online survey was distributed to a group of glaucoma specialists from the American Glaucoma Society via the American Glaucoma Society forum from April to August 2021. Results: One hundred and twenty-eight responses were included. Ninety percent placed tubes in the anterior chamber. Sixty-one percent reported that evidence suggested the superiority of sulcus tube placement over the anterior chamber, whereas 34% reported there was not enough evidence to suggest superiority of either in preventing endothelial cell loss. Comparing these techniques for intraocular pressure control, 49% reported evidence suggested sulcus tube placement superiority whereas 46% reported there was not enough evidence. Over 40% of respondents reported that they were either unfamiliar with literature or that there was not enough evidence to support the superiority of difluprednate 0.05% over prednisolone 1% for post-operative use in preventing endothelial cell loss and for intraocular pressure control. Ninety percent and 81% of respondents respectively would benefit from randomized control trials comparing outcomes of anterior chamber vs sulcus tube placement and post-operative corticosteroid usage. Conclusion: Most glaucoma specialists surveyed place glaucoma drainage device tube in the anterior chamber over the sulcus. A randomized control trial to determine optimal tube placement and post-operative anti-inflammatory medication use for preventing endothelial cell loss would change current glaucoma drainage device practice patterns.

BACKGROUND/AIMS: Psychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure. METHODS: This analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method. RESULTS: Among the 441,054 participants, 959 (0.22%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24±1.03 SD vs. 0.00±1.00 SD, p<0.001) and PACG prevalence increased with each decile of higher PRS. Among individuals using psychotropic medication, those with PACG had higher average PRS (0.31±1.00 SD vs. 0.00±1.00 SD, p<0.001) and were more likely to have a PRS in upper deciles of polygenic risk (p = 0.04). At each decile of PRS, psychotropic medication use was associated with increased risk of PACG. These effects were more pronounced and significant in higher deciles. CONCLUSION: We demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum.

PURPOSE: To test whether the increase in insurance coverage in Massachusetts due to the Affordable Care Act (ACA) is associated with a decrease in glaucoma severity in patients presenting for the first time at a tertiary health system. METHODS: Clinical and billing data of first-time glaucoma patients from a tertiary health system in Massachusetts from 2006 to 2021 was used. Pre-ACA is defined as before 2014 and post-ACA is defined as after 2014. Visual field mean deviation was used to define glaucoma severity: greater than -6 dB, less than -6 dB and greater than -12 dB, and less than -12 dB was classified as "mild," "moderate," and "severe" respectively. Ordinal logistic regression models adjusted for age, race, gender, and insurance type were used to determine the odds of presenting with more severe glaucoma. RESULTS: 2,394 pre-ACA and 3,651 post-ACA first-time glaucoma patients were identified. There was no significant difference in the likelihood of more severe glaucoma at first presentation post-ACA compared to pre-ACA (OR=0.96; 95% CI 0.86-1.08; p=0.49) among the entire population. In stratified analyses, patients who utilized Medicaid for insurance had 52% decreased odds for presenting with more severe glaucoma at first presentation post-ACA compared to pre-ACA (OR=0.48; 95% CI 0.33-0.69; p<0.001). This remained significant after adjustment for age, race, and gender (adjusted OR=0.44; 95% CI 0.29-0.65; p<0.001). CONCLUSION: At a Massachusetts-based tertiary healthcare center, individuals on Medicaid were more likely to have more severe glaucoma at first presentation before the implementation of the ACA, compared to after.

PURPOSE: To develop an internationally standardized and validated tool to assess skill in performing tube shunt surgery. DESIGN: A panel of 6 glaucoma surgeons developed a tool for assessing tube shunt surgery using a modified Dreyfus scale for skill acquisition. The tool was reviewed by a panel of 10 international content experts, and their comments were incorporated into the final rubric. PARTICIPANTS: A different panel of 8 international glaucoma specialists independently graded videos of surgical procedures performed by 6 surgeons at various levels of ophthalmic training. MAIN OUTCOME MEASURES: Inter-rater reliability for each step in the rubric was calculated. RESULTS: The tube shunt rubric contained 13 steps specific to tube shunt surgery and 7 global indices. The Cronbach α statistic, a measure of internal reliability, ranged from 0.75 to 0.97, indicating strong internal reliability for all 13 steps. CONCLUSIONS: The tube shunt assessment tool has face validity, content validity, and interobserver reliability, and can be used to assess tube shunt surgery skills. Further studies are required to determine predictive and construct validity.

OBJECTIVE: To develop an objective and easy-to-use glaucoma staging system based on visual fields (VFs). SUBJECTS AND PARTICIPANTS: A total of 13,231 VFs from 8077 subjects were used to develop models and 8024 VFs from 4445 subjects were used to validate models. METHODS: We developed an unsupervised machine learning model to identify clusters with similar VF values. We annotated the clusters based on their respective mean deviation (MD). We computed optimal MD thresholds that discriminate clusters with highest accuracy based on Bayes minimum error principle. We evaluated the accuracy of the staging system and validated findings based on an independent validation dataset. RESULTS: The unsupervised k-means algorithm discovered four clusters with 6784, 4034, 1541, and 872 VFs and average MDs of 0.0▒dB (±1.4: Standard Deviation), -4.8▒dB (±1.9), -12.2▒dB (±2.9), and -23.0▒dB (±3.8), respectively. The supervised Bayes minimum error classifier identified optimal MD thresholds of -2.2▒dB, -8.0▒dB, and -17.3▒dB for discriminating normal eyes and eyes at the early, moderate, and advanced stages of glaucoma. The accuracy of the glaucoma staging system was 94%, based on identified MD thresholds with respect to the initial k-means clusters. CONCLUSIONS: We discovered that four severity levels based on MD thresholds of -2.2▒dB, -8.0▒dB, and -17.3▒dB, provides the optimal number of severity stages based on unsupervised and supervised machine learning. This glaucoma staging system is unbiased, objective, easy-to-use, and consistent, which makes it highly suitable for use in glaucoma research and for day-to-day clinical practice.

TOPIC: This systematic review summarizes evidence for associations between female reproductive factors (age at menarche, parity, oral contraceptive [OC] use, age at menopause, and postmenopausal hormone [PMH] use) and intraocular pressure (IOP) or open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding the associations between female reproductive factors and glaucoma may shed light on the disease pathogenesis and aid clinical prediction and personalized treatment strategies. Importantly, some factors are modifiable, which may lead to new therapies. METHODS: Two reviewers independently extracted articles in MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases to identify relevant studies. Eligibility criteria included studies with human subjects aged > 18 years; a measured outcome of either IOP or OAG; a cohort, case-control, cross-sectional, or randomized controlled trial design; a reported measure of association, such as the hazard ratio, relative risk, odds ratio, or mean difference, with an associated confidence interval; and a measured exposure of at least 1 of the following variables: age at menarche, parity, OC use, age at menopause, or PMH use. RESULTS: We included a total of 27 studies. Substantial differences in study designs, exposure and treatment levels, treatment durations, and variable reporting precluded a meaningful quantitative synthesis of the identified studies. Overall, relatively consistent associations between PMH use and a lower IOP were identified. Estrogen-only PMH use may be associated with lower OAG risk, which may be modified by race. No significant associations were found with combined estrogen-and-progesterone PMH use. No strong associations between parity or age at menarche and glaucoma were found, but a younger age at menopause was associated with an increased glaucoma risk, and adverse associations were identified with a longer duration of OC use, though no overall association with OC use was found. CONCLUSIONS: The association between PMH use and lower IOP or OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies. Future research should examine associations with IOP specifically and how the relationship between genetic factors and OAG risks may be influenced by female reproductive factors.

TOPIC: This systematic review and meta-analysis summarizes the existing evidence for the association of alcohol use with intraocular pressure (IOP) and open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding and quantifying these associations may aid clinical guidelines or treatment strategies and shed light on disease pathogenesis. The role of alcohol, a modifiable factor, in determining IOP and OAG risk also may be of interest from an individual or public health perspective. METHODS: The study protocol was preregistered in the Open Science Framework Registries (https://osf.io/z7yeg). Eligible articles (as of May 14, 2021) from 3 databases (PubMed, Embase, Scopus) were independently screened and quality assessed by 2 reviewers. All case-control, cross-sectional, and cohort studies reporting a quantitative effect estimate and 95% confidence interval (CI) for the association between alcohol use and either IOP or OAG were included. The evidence for the associations with both IOP and OAG was qualitatively summarized. Effect estimates for the association with OAG were pooled using random effects meta-analysis. Studies not meeting formal inclusion criteria for systematic review, but with pertinent results, were also appraised and discussed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: Thirty-four studies were included in the systematic review. Evidence from 10 studies reporting an association with IOP suggests that habitual alcohol use is associated with higher IOP and prevalence of ocular hypertension (IOP > 21 mmHg), although absolute effect sizes were small. Eleven of 26 studies, comprising 173 058 participants, that tested for an association with OAG met inclusion criteria for meta-analysis. Pooled effect estimates indicated a positive association between any use of alcohol and OAG (1.18; 95% confidence interval [CI], 1.02-1.36; P = 0.03; I2 = 40.5%), with similar estimates for both prevalent and incident OAG. The overall GRADE certainty of evidence was very low. CONCLUSIONS: Although this meta-analysis suggests a harmful association between alcohol use and OAG, our results should be interpreted cautiously given the weakness and heterogeneity of the underlying evidence base, the small absolute effect size, and the borderline statistical significance. Nonetheless, these findings may be clinically relevant, and future research should focus on improving the quality of evidence.

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.

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.

PURPOSE: Angle-closure glaucoma is a major cause of blindness worldwide that carries an excessive risk of severe, bilateral visual impairment. A common concern among clinicians is the precipitation of acute angle-closure (AAC) attacks because of mydriasis. We evaluated the risk of AAC after pharmacologic dilation in Chinese individuals classified as having bilateral primary angle-closure suspects (PACSs). DESIGN: Randomized, interventional, controlled trial. PARTICIPANTS: A total of 889 patients with bilateral PACSs, 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 Trial, bilateral PACSs were treated with laser peripheral iridotomy (LPI) in 1 randomly selected eye, with the fellow eye serving as an untreated control. Over 72 months of follow-up, the participants had their pupils pharmacologically dilated 6 times with 5% phenylephrine and 0.5% tropicamide. MAIN OUTCOME MEASURES: Incidence and risk of post-mydriasis AAC in LPI-treated and untreated, control eyes classified as PACSs. RESULTS: One bilateral AAC attack occurred after mydriasis at the 2-week post-LPI visit. No other AAC events occurred in the LPI-treated eyes. In the untreated eyes, 4 additional attacks occurred: 2 occurred after dilation (1 at 54 months and 1 at 72 months of follow-up) and 2 occurred spontaneously. The risk of post-mydriasis AAC in the untreated eyes was 1 attack in 1587 dilations. The risk of spontaneous AAC in the untreated eyes was 0.44 per 1000 eye-years (95% confidence interval, 0.11-1.77 per 1000 eye-years). CONCLUSIONS: The risk of incident AAC attacks in PACSs was extremely low, even in a higher-risk group that underwent repeated pharmacologic pupillary dilation over 6 years of follow-up. Prophylactic LPI reduced this small but real risk. This trial was registered at ISRCTN.com as ISRCTN45213099.

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.

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.

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.

OBJECTIVE: We assessed the relationship between ultraviolet (UV)-associated dermatological carcinomas (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) and exfoliation syndrome (XFS) or exfoliation glaucoma (XFG). DESIGN: Case-control study. PARTICIPANTS: Between 2019 and 2021, 321 participants and control subjects (XFS or XFG = 98; primary open-angle glaucoma [POAG] = 117; controls = 106; ages 50-90 years) were recruited. METHODS: A cross-sectional survey assessing medical history, maximum known intraocular pressure, cup-to-disc ratio, Humphrey visual field 24-2, the propensity to tan or burn in early life, history of BCC or SCC, and XFS or XFG diagnosis. The multivariable models adjusted for age, sex, medical history, eye color, hair color, and likeliness of tanning versus burning at a young age. MAIN OUTCOME MEASURES: History of diagnosed XFS or XFG. RESULTS: Any history of BCC or SCC in the head and neck region was associated with a 2-fold higher risk of having XFS or XFG versus having POAG or being a control subject (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.04-3.89) in a multivariable-adjusted analysis. We observed a dose-response association in which the chance of having XFS or XFG increased by 67% per head and neck BCC or SCC occurrence (OR, 1.67; 95% CI, 1.09-2.56). When we excluded POAG participants, head and neck BCC or SCC was associated with a 2.8-fold higher risk of XFS or XFG (OR, 2.80; 95% CI, 1.12-7.02), and each additional occurrence had a 2-fold higher risk of XFS or XFG (OR, 1.97; 95% CI, 1.09-3.58). The association between head and neck region BCC or SCC and POAG compared with the control subjects was null (OR, 1.42; 95% CI, 0.58-3.48). With BCC or SCC located anywhere on the body, there was a nonsignificantly higher risk of having XFS or XFG compared with having POAG or being a control subject (OR, 1.65; 95% CI, 0.88-3.09). CONCLUSIONS: Head and neck region BCCs or SCCs are associated with a higher risk of having XFS or XFG. These findings support prior evidence that head and neck UV exposure may be a risk factor for XFS.