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Prcis: In a diverse database (All of Us), we report significant dose-response associations between alcohol use frequency and glaucoma, with alcohol use of 4 or more drinks per week associated with significantly increased odds of glaucoma., Purpose: Current evidence on the association between alcohol use and primary open angle glaucoma (POAG) is mixed. We utilize the diverse All of Us Research Program to further examine this relationship., Methods: This is a retrospective cohort study using the diverse All of Us Research Program, a nationwide effort by the United States National Institutes of Health to recruit those historically under-represented in biomedical research. Electronic health records and survey data from the All of Us program was analyzed. A randomized 1:4 case/control ratio was utilized for POAG patients and randomly selected control patients. Chi-Square, bivariable, and multivariable regression were utilized to examine the associations between alcohol use and POAG., Results: Of the 3876 POAG patients, 2015 (52%) were female, 1943 (50%) were White, 1152 (30%) were Black, 117 (3%) were Asian, and 584 (15%) were Hispanic. Alcohol use of 4 or more drinks per week was significantly higher in the glaucoma cohort relative to controls (15% vs. 12%, P<0.001). On bivariate analysis, diagnosed alcohol misuse was associated with higher odds of POAG [Odds Ratio (OR): 1.20, 95% Confidence Interval (CI): 1.17-1.23, P<0.001]. In multivariable regression, more frequent alcohol use was associated with higher odds of glaucoma; alcohol use with a frequency of 4 or more drinks per week was significantly associated with increased odds of glaucoma (OR: 1.22, 95% CI: 1.03-1.44, P=0.023). This dose-response relationship was also observed and more pronounced for female participants, where alcohol use frequency of monthly or less was already associated with increase odds of glaucoma (OR: 1.21, 95% CI: 1.002-1.46, P=0.048)., Conclusion: In the diverse All of Us database, there was a dose-response relationship between alcohol consumption and POAG risk, which was more pronounced in female participants. Overall, higher frequency of alcohol consumption was associated with increased risk of POAG; 4 or more drinks per week significantly was associated with higher glaucoma risk., Competing Interests: Conflict of Interest: Sally Baxter reports equipment support from Topcon and Optomed, and consulting/speaking fees from Topcon, outside of the submitted work. Robert N. Weinreb reports grants from National Eye Institute, National Institute of Minority Health and Health Disparities, and Research to Prevent Blindness (New York, NY); Consultant for AbbVie, Alcon, Allergan, Amydis, Balance,Editas, Eyenovia, Iantrek, Implandata, iSTAR Medical, Nicox, Santen, and Topcon; Patents licensed to Toromedes from UCSD and licensed to Carl Zeiss Meditec from UCSD; non-financial support (research instruments) from Carl Zeiss Meditec, Centervue, Optovue, Topcon, co-Founder -Toromedes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To evaluate the impact of testing frequency on the time required to detect statistically significant glaucoma progression for ganglion cell complex (GCC) with optical coherence tomography (OCT)., Materials and Methods: From multicentre glaucoma registries, 332 eyes of 201 glaucoma patients were enrolled over an average of 4.4 years. Patients with 4 or more OCT tests were selected to calculate the longitudinal rates of GCC thickness change over time by linear regression. A computer simulation was then used to generate real-world GCC data and assess the time required to detect progression at different loss rates and testing frequencies based on variability estimates. Time and accuracy to detect worsening of progression were calculated., Results: As testing frequency increased, the time required to detect a statistically significant negative GCC slope decreased, but not proportionally. All eyes with a GCC loss of -1 µm/year progressed after 3.8, 2.6 and 2.2 years on average when testing was conducted one, two and three times per year, respectively. For eyes with a GCC loss of -1.5 µm/year, progression was identified after 3.3, 2.2, and 1.8 years on average, respectively., Conclusion: Increasing the frequency of macular OCT testing to three times per year more sensitively detects progression compared with two times per year. However, two times per year testing may be sufficient in clinical settings to detect progression and also to reduce the healthcare burden., Trial Registration Numbers: NCT00221897, NCT00221923., Competing Interests: Competing interests: GM: None; SM: None; KL: None; NB: None; EW: None; TN: None; KD: None; GG: None; JHW: None; JML: C: Allergan, Genentech, Thea, Bausch & Lomb; F: Novartis, Research to Prevent Blindness; MF: F: National Eye Institute, EyeSight Foundation of Alabama, Research to Prevent Blindness, Heidelberg Engineering GmbH, Topcon and Wolfram Research; CAG: F: National Eye Institute, Heidelberg Engineering and Topcon, EyeSight Foundation of Alabama, Research to Prevent Blindness, Heidelberg Engineering GmbH, C: iridex; LMZ: C: Abbvie Inc. Topcon F: National Eye Institute, Carl Zeiss Meditec Inc., Heidelberg Engineering GmbH, Optovue Inc., Topcon Medical Systems Inc., P: Carl Zeiss Meditec, AISight Health; C: Abbvie, Aerie Alcon, Amydis, Balance, Iantrek, Implandata, Spinogenix, Topcon Medical, F: Topcon Medical, Centervue, Vasoptic, Visionix, P: Toromedes, Carl Zeiss Meditec., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Keratoconus (KC) is a chronic corneal disease that typically presents in early adulthood, and may potentially result in poor mental health in affected individuals. The evidence regarding the association of depression with KC is controversial. Hence, we investigated the association between depression and KC via a systematic review and meta-analysis., Methods: Five electronic medical databases (PubMed, Scopus, PsycINFO, Web of Science, and CINAHL Complete) were systematically queried for English-language records from their inception to January 8, 2024. We include observational studies that measured the risk of depression or compared depression scores in KC patients in comparison to healthy ones. The Newcastle-Ottawa Quality Assessment Scale was utilized to assess bias risk in the included studies. Random-effect modeling was applied for meta-analysis (STATA-17)., Results: Out of the 159 documents retrieved, seven articles were deemed relevant after screening. An analysis involving 83 KC patients and 3,186 controls indicated that KC participants had significantly higher depression scores [SMD: 0.71 [0.31, 1.11]; p < 0.01, I 2 : 52.7%]. However, a meta-analysis of four studies comparing depression rates in KC patients ( n = 23,838) to control groups ( n = 73,482) found no increased risk of depression among KC patients compared to controls [OR: 1.13 [0.66, 1.94]; p = 0.65, I 2 : 95.35%]., Conclusion: While KC patients exhibit significantly higher depression scores compared to controls, a meta-analysis indicates no increased overall risk of depression among KC patients. These findings highlight the complexity of the relationship between keratoconus and mental health, warranting further investigation., Systematic Review Registration: PROSPERO, identifier, CRD42024502247, available at: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42024502247., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Moshfeghinia, Arman, Sobhi, Mahmoudinezhad and Molavi Vardanjani.)

Background/aims: To design a deep learning (DL) model for the detection of glaucoma progression with a longitudinal series of macular optical coherence tomography angiography (OCTA) images., Methods: 202 eyes of 134 patients with open-angle glaucoma with ≥4 OCTA visits were followed for an average of 3.5 years. Glaucoma progression was defined as having a statistically significant negative 24-2 visual field (VF) mean deviation (MD) rate. The baseline and final macular OCTA images were aligned according to centre of fovea avascular zone automatically, by checking the highest value of correlation between the two images. A customised convolutional neural network (CNN) was designed for classification. A comparison of the CNN to logistic regression model for whole image vessel density (wiVD) loss on detection of glaucoma progression was performed. The performance of the model was defined based on the confusion matrix of the validation dataset and the area under receiver operating characteristics (AUC)., Results: The average (95% CI) baseline VF MD was -3.4 (-4.1 to -2.7) dB. 28 (14%) eyes demonstrated glaucoma progression. The AUC (95% CI) of the DL model for the detection of glaucoma progression was 0.81 (0.59 to 0.93). The sensitivity, specificity and accuracy (95% CI) of DL model were 67% (34% to 78%), 83% (42% to 97%) and 80% (52% to 95%), respectively. The AUC (95% CI) for the detection of glaucoma progression based on the logistic regression model was lower than the DL model (0.69 (0.50 to 0.88))., Conclusion: The optimised DL model detected glaucoma progression based on longitudinal macular OCTA images showed good performance. With external validation, it could enhance detection of glaucoma progression., Trial Registration Number: NCT00221897., Competing Interests: Competing interests: VM: None; YL: None; SM: F: National Eye Institute; PX: None; TN: C: Topcon; GM: None; ME: None; EW: None; AK: F: Fight for Sight; EM: None; J-HW: None:, MC: F: National Eye Institute; LMZ: C: Abbvie Inc., Topcon; F: National Eye Institute, Carl Zeiss Meditec Inc., Heidelberg Engineering GmbH, Optovue Inc., Topcon Medical Systems Inc.; P: Zeiss Meditec, AISight Health (founder); TJ: None; RNW: C: Abbvie, Aerie Pharmaceuticals, Allergan, Amydis, Editas, Equinox, Eyenovia, Iantrek, Implandata, IOPtic, iSTAR Medical, Nicox, Santen, Tenpoint and Topcon; F: National Eye Institute, National Institute of Minority Health and Health Disparities, Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Zilia, Centervue, and Topcon; P: Toromedes, Carl Zeiss Meditec., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Prcis: Increased oxygen saturation (StO 2 ) was significantly associated with the severity of visual field (VF) damage in patients with glaucoma., Objective: To investigate the association between retinal StO 2 percentage and the severity of VF loss in glaucoma., Methods: A total of 198 eyes from 131 patients with glaucoma were included in this cross-sectional study. Participants underwent imaging using ocular oximetry (Zilia) and 24-2 Swedish Interactive Threshold Algorithm standard VF (Carl Zeiss-Meditec). StO 2 (%) was measured at 2 locations of the peripapillary optic nerve head (superotemporal, and inferotemporal). Measurements were reported as the mean of at least 5 measurements in each location. Associations between the severity of VF loss, reported as mean deviation, and StO 2 (%) were calculated., Results: A total of 198 eyes of 131 patients (mean (95% CI) age, 71.1 (68.9,73.3) years, 68 females (51.9%), and 63 males (48.1%) were analyzed. In univariable analysis, higher StO 2 -0.06 (-0.12, 0.00) was associated with severity in all hemifields ( P = 0.047). Multivariate regression analysis showed that each 1% increase in StO 2 was associated with -0.06 (-0.12, -0.00) dB loss in mean deviation in all hemifields ( P = 0.043). In multivariate regression analysis in the superior hemifields, higher StO 2 -0.07 (-0.16, 0.01) tended to be associated with superior hemifield severity ( P = 0.09)., Conclusions: Retinal oximetry enabled the continuous quantitative measurement of retinal StO 2. Increased StO 2 was significantly associated with the severity of VF damage in patients with glaucoma., Competing Interests: Disclosure: R.N.W.: C: Abbvie, Aerie Pharmaceuticals, Alcon, Allergan, Iantrek, Implandata, IOPtic, Nicox, Santen, Topcon Medical; F: Topcon Medical, Heidelberg Engineering, Carl Zeiss Meditec, Optovue, Centervue, Zilia; P: Toromedes, Carl Zeiss Meditec. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Animal-induced ocular injuries represent an under-documented health problem that may pose significant visual complications. This study aimed to investigate the clinical characteristics and outcomes of ocular injuries caused by animals., Methods: This multicenter prospective study enrolled patients with a history of animal-induced ocular injuries presenting to the ophthalmology departments of two tertiary hospitals over a one-year period. All participants underwent comprehensive assessments by ophthalmologists, and the following data were collected: demographic information, animal species involved, injury details, pre- and post-treatment visual data, management strategies, and follow-up outcomes., Results: Seventy-two patients (62.5% male) were included in the study. Insects were the most common species, causing 37.5% of ocular injuries. The type of animal involved was significantly associated with injury patterns ( p  < 0.0001), visual impairments at presentation ( p  < 0.05), and need for surgery ( p  < 0.001). Insects predominantly caused periorbital soft tissue injuries; birds primarily affected the anterior segment; dogs and cats mainly led to adnexal injuries; and equines often involved both anterior and posterior segments. Equine-related injuries resulted in the most severe visual impairments, requiring surgical interventions in all cases. At the same time, the majority of cases involved with other animal species experienced no visual impairment. The number of patients without visual impairment increased from 46 cases (63.9%) at the time of presentation to 58 (80.6%) at discharge after treatment. At follow-up, eight patients (11.1%) experienced complications, including traumatic cataract ( n  = 6, 8.3%), endophthalmitis ( n  = 3, 4.2%), corneal scarring ( n  = 1, 1.4%), and retinal detachment ( n  = 1, 1.4%). Rooster pecking was the leading cause of complications, including endophthalmitis and traumatic cataract., Conclusion: This study revealed that depending on the type of animal causing the injury, animal-induced ocular injuries present with diverse characteristics, requiring appropriate treatment approaches and potentially resulting in different outcomes. These findings may promote public awareness and improve preventive strategies and clinical guidelines development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mohammadi, Attar, Mahmoudinezhad, Shahesmaeilinejad, Zhu, Fowler, Farsi, Shirvani and Gohari.)

Purpose: To evaluate the association of mean intraocular pressure (IOP) and IOP variability (IOP fluctuation [SD of IOP] and the IOP range) with the rate of ganglion cell complex (GCC) layer thinning over time in patients with glaucoma., Design: Prospective cohort study., Methods: Participants with at least 4 visits and 2 years of follow-up of optical coherence tomography tests were included. A linear mixed-effect model was used to investigate the association of IOP parameters with the rates of GCC thinning. Subgroup analyses were conducted for eyes with early (MD ≥ -6 dB), and moderate to advanced stage (MD < -6 dB) at baseline., Results: The cohort consisted of 369 eyes of 249 glaucoma patients (282 early glaucoma and 87 moderate to advanced glaucoma) with mean (standard deviation [SD]) age of 68.2 (10.7) years over 5.1 years of follow-up. The mean rate of GCC change was -0.59 (95% confidence interval [CI], -0.67 to -0.52) µm per year. In multivariable models, faster annual rate of GCC thinning was associated with a higher IOP fluctuation (-0.17 [95% CI, -0.23 to -0.11] µm per 1-mmHg higher, P < .001) or higher IOP range (-0.07 [95% CI, -0.09 to -0.05] µm per 1-mmHg higher, P < .001) after adjustment for mean IOP and other confounding factors. Similar results were found for early and moderate to advanced stages of glaucoma., Conclusions: IOP variability showed an independent association with macular change in patients with glaucoma regardless of severity at baseline, even after adjustment for mean IOP, supporting its potential value as a therapeutic target for clinical decision-making., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/aims: To investigate the association between longitudinal changes of foveal avascular zone (FAZ) area and the rate of structural and functional progression in glaucoma., Methods: A longitudinal cohort included 115 eyes (46 glaucoma suspect and 66 primary open-angle glaucoma) of 81 patients having ≥2 year follow-up, and ≥4 visits with optical coherence tomography angiography and visual field (VF). Eyes in the longitudinal cohort with a slope greater than that found in 95 percentile of separate healthy test-retest series for FAZ area were categorised into FAZ progressors; all other eyes were defined as FAZ non-progressors. A generalised linear mixed-effect model was used to investigate the association of FAZ progressors with demographic and clinical characteristics., Results: Faster ganglion cell complex (GCC) thinning and faster VF mean deviation (MD) loss were found in eyes with FAZ progressors compared with FAZ non-progressors (mean difference: -0.7 (95% CI, -1.4 to -0.1) µm/y; p=0.026, -0.3 (-0.5 to -0.1) dB/y; p=0.017, respectively), while whole image vessel density was not associated with FAZ progressors (p=0.929). SD of intraocular pressure (IOP) and IOP range were also associated with FAZ progressors in separate multivariable models (OR: 1.54 (1.02 to 2.32) per 1 mm Hg higher, p=0.041; OR: 1.20 (1.01 to 1.41) per 1 mm Hg higher; p=0.035, respectively)., Conclusions: Significant FAZ increase was weakly associated with moderately faster rates of both GCC thinning and VF MD loss, but not macular vessel density change in glaucoma eyes. Additional studies are needed to elucidate the pathophysiological associations between macula GCC thinning and FAZ area increases in glaucoma., Competing Interests: Competing interests: TN: consultant—Topcon; SM: consultant—Topcon; EW: none; GG: none; J-HW: none; AK: Fight for sight, LMZ: consultant—Topcon, Abbvie; financial support—Carl Zeiss Meditec, Heidelberg Engineering, OptoVue. Patent: AISight Health (co-founder), RNW: consultant—Abbvie, Aerie Pharmaceuticals, Allergan, Amydis, Editas, Equinox, Eyenovia, Iantrek, IOPtic, Implandata, iSTAR Medical, Nicox, Santen, Tenpoint and Topcon; financial support—Heidelberg Engineering, Carl Zeiss Meditec, Optovue, Centervue, Zilia and Topcon., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Rapid initial optic nerve head capillary density loss may be used to assess the risk of glaucoma visual field progression., Objective: To investigate the association between the rate of initial optic nerve head capillary density loss from optical coherence tomography angiography (OCTA) and visual field progression., Design, Setting, Participants: This was a retrospective study of a longitudinal cohort at a glaucoma referral center. A total of 167 eyes (96 with primary open-angle glaucoma and 71 with glaucoma suspect) of 109 patients were monitored for a mean (SD) of 5.7 (1.4) years from January 2015 to December 2022. Data analysis was undertaken in April 2023., Main Outcomes and Measures: The rates of initial capillary density and average retinal nerve fiber layer loss were calculated from the first 3 optic nerve head OCTA and OCT scans, respectively, during the initial follow-up (mean [SD], 2.0 [1.0] years). Based on the median rate, eyes were categorized into fast and slow progressor groups. The association between initial capillary density change or retinal nerve fiber layer thinning and visual field progression was evaluated using linear-mixed and time-varying Cox models., Results: A total of 167 eyes of 109 patients (mean [SD] age, 69.0 [11.1] years; 56 [51.4%] female and 53 [48.6%] male) were assessed. Eighty-three eyes were slow OCTA progressors, while 84 eyes were fast with mean capillary density loss of -0.45% per year and -1.17% per year, respectively (mean difference, -0.72%/year; 95% CI,-0.84 to -0.60; P < .001). Similarly, 83 eyes were slow OCT progressors, while 84 eyes were fast with mean retinal nerve fiber layer thinning of -0.09 μm per year and -0.60 μm per year, respectively (mean difference, -0.51 μm/year; 95% CI,-0.59 to -0.43; P < .001). The fast OCTA and OCT progressors were associated with more rapid visual field loss (mean difference, -0.18 dB/year; 95% CI,-0.30 to -0.06; P = .004 and -0.17 dB/year; 95% CI,-0.29 to -0.06; P = .002, respectively). Fast OCTA progressing eyes were more likely to have visual field progression (hazard ratio, 1.96; 95% CI, 1.04-3.69; P = .04). Seventeen of 52 eyes (32.7%; 95% CI, 32.5-32.8) with fast OCTA and OCT progression developed subsequent visual field likely progression., Conclusion and Relevance: Rapid initial optic nerve head capillary density loss from OCTA was associated with a faster rate of visual field progression and a doubling of the risk of developing event progression in this study. These findings may support clinical use of OCTA and OCT optic nerve head measurements for risk assessment of glaucoma progression.

Prcis: A lifetime history of greater smoking consumption was associated with faster vessel density loss over time. Smoking intensity should be considered when assessing the risk of glaucoma progression, as well as its management., Purpose: To investigate the relationship of smoking and smoking intensity, with the rate of optic nerve head (ONH) whole image capillary density (wiCD) loss in primary open angle glaucoma (POAG) and glaucoma suspect patients., Methods: In this longitudinal study, patients with POAG who had at least 2 years of follow-up and optical coherence tomography angiography (OCTA) performed at a minimum of 4 visits were selected for study. The smoking intensity was calculated as the pack-year at the baseline OCTA. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of wiCD loss over time. Nonlinear least-squares estimation with piecewise regression model was used to investigate the cutoff point for the relationship between wiCD loss and smoking intensity., Results: One hundred sixty-four eyes (69 glaucoma suspect and 95 POAG) of 110 patients were included with a mean (95% CI) follow-up of 4.0 (3.9 to 4.1) years. Of the 110 patients, 50 (45.5%) had a reported history of smoking. Greater smoking intensity was associated with faster wiCD loss [-0.11 (-0.23 to 0.00)] %/year per 10 pack-year higher; P =0.048) after adjusting for covariates. The wiCD thinning became significantly faster when smoking intensity was greater than 22.2 pack-years. Smoking had no effect on the rate of wiCD thinning in patients who smoked <22.2 pack-years during their lifetime., Conclusions: A history of greater smoking consumption was associated with faster vessel density loss, suggesting smoking intensity as a potential risk factor for glaucoma., Competing Interests: Disclosure: T.N. is a consultant in Topcon. R.N.W. is a consultant in Abbvie, Alcon, Allergan, Amydis, Editas, Equinox, Eyenovia, Iantrek, Implandata, IOPtic, Nicox, Santen, Topcon Medical; and received research support from Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Centervue, and Topcon; and patent in Toromedes, Carl Zeiss Meditec. S.M. received research support from the National Eye Institute, the University of California Tobacco-Related Disease Research Program, and an unrestricted grant from Topcon Medical. The sponsor or funding organization had no role in the design or conduct of this research. Research instrument from Topcon Medical. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To examine the time to detectable retinal nerve fiber layer thickness (RNFLT) progression by optical coherence tomography (OCT) among glaucoma patients of African descent (AD) and European descent (ED)., Design: Retrospective cohort study., Methods: AD and ED glaucoma eyes from the Diagnostic Innovations in Glaucoma Study (DIGS)/African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2 years/4 visits of optic nerve head RNFLT measurements were included after homogenization on age, diagnosis, and baseline visual field (VF) measurement. RNFLT variability estimates based on linear mixed-effects models were used to simulate longitudinal RNFLT data for both races. Times to trend-based RNFLT progression detection were calculated under standardized scenarios (same RNFLT baseline/thinning rates for both races) and real-world scenarios (AD and ED cohort-specific RNFLT baseline/thinning rates)., Results: We included 332 and 542 eyes (216 and 317 participants) of AD and ED, respectively. In standardized scenarios, the time to detect RNFLT progression appeared to be similar (difference, <0.2 years) for AD and ED across different assumed RNFLT thinning rates/baseline. In real-world scenarios, compared to ED, AD had a faster RNFLT thinning rate (-0.8 vs -0.6 µm/y) and thicker baseline RNFLT (84.6 vs 81.8 µm). With a faster thinning rate, the mean (SD) time to progression detection was shorter in AD (4.8 [2.0] vs ED: 5.4 [2.4] years), and the 5-year progression rate appeared to be higher (AD: 59% vs ED: 47%)., Conclusions: Time to progression detection was similar for both races when assuming identical RNFLT baseline/thinning rates, and shorter in AD eyes under real-world simulation when AD had faster RNFLT thinning. In contrast to prior results on VF, which detected progression later in AD eyes than in ED eyes, OCT may detect progression more consistently across these races., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine event-based glaucoma progression using optical coherence tomography (OCT) and OCT angiography (OCTA)., Methods: In this retrospective study, glaucoma eyes with ≥2-year and 4-visits of OCT/OCTA imaging were included. Peripapillary capillary density (CD) and retinal nerve fibre layer thickness (RNFL) were obtained from 4.5 mm × 4.5 mm optic nerve head (ONH) scans. Event-based OCT/OCTA progression was defined as decreases in ONH measurements exceeding test-retest variability on ≥2 consecutive visits. Visual field (VF) progression was defined as significant VF mean deviation worsening rates on ≥2 consecutive visits. Inter-instrument agreement on progression detection was compared using kappa(κ) statistics., Results: Among 147 eyes (89 participants), OCTA and OCT identified 33(22%) and 25(17%) progressors, respectively. They showed slight agreement (κ = 0.06), with 7(5%) eyes categorized as progressors by both. When incorporating both instruments, the rate of progressors identified increased to 34%. Similar agreement was observed in diagnosis- and severity-stratified analyses (κ < 0.10). Compared to progressors identified only by OCT, progressors identified only by OCTA tended to have thinner baseline RNFL and worse baseline VF. VF progression was identified in 11(7%) eyes. OCT and VF showed fair agreement (κ = 0.26), with 6(4%) eyes categorized as progressors by both. OCTA and VF showed slight agreement (κ = 0.08), with 4(3%) eyes categorized as progressors by both., Conclusions: OCT and OCTA showed limited agreement on event-based progression detection, with OCT showing better agreement with VF. Both OCT and OCTA detected more progressors than VF. OCT and OCTA may provide valuable, yet different and complementary, information about glaucoma progression., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose of Review: Assessing whether lifestyle related factors play a role in causing primary open-angle glaucoma (POAG) is of great value to clinicians, public health experts and policy makers. Smoking is a major global public health concern and contributes to ocular diseases such as cataracts, and age-related macular degeneration through ischemic and oxidative mechanisms. Recently, smoking has been investigated as a modifiable risk factor for glaucoma. In the presence of an association with glaucoma, provision of advice and information regarding smoking to patients may help reduce the burden of disease caused by POAG. Therefore, the aim of this review is to summarize the current evidence regarding the effect of smoking in the pathogenesis of glaucoma and its incidence, progression as well as the benefits of smoking cessation., Recent Findings: While the association between glaucoma development and smoking history is controversial, in the last decade, several recent studies have helped to identify possible effects of smoking, especially heavy smoking, in regard to glaucomatous progression. Smoking cessation may possibly be protective against glaucoma progression., Summary: Smoking may play a role in glaucoma progression and long-term smoking cessation may be associated with lower glaucoma progression. The dose-response relationship between smoking and glaucoma as well as therapeutic potential of smoking cessation needs to be further validated with both preclinical and rigorous clinical studies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate and compare the diagnostic accuracy of macular vessel density (VD) measured by OCT angiography (OCTA) in individuals of African descent (AD) and European descent (ED) with open-angle glaucoma., Design: Observational, cross sectional study., Participants: A total of 176 eyes of 123 patients with glaucoma and 140 eyes of 88 healthy participants from the Diagnostic Innovations in Glaucoma Study., Methods: Whole-image ganglion cell complex (wiGCC) thickness and macular VD (parafoveal VD and perifoveal VD) were obtained from 6 × 6 macula scans. Area under the receiver operating characteristic (AUROC) curves were used to evaluate the diagnostic accuracy of macular VD and ganglion cell complex (GCC) thickness in AD and ED participants after adjusting for confounders such as age, visual field mean deviation (VF MD), signal strength index, axial length, self-reported hypertension and diabetes., Main Outcome Measures: Macular VD and wiGCC measurements., Results: Parafoveal and perifoveal VD were significantly lower in ED than AD patients with glaucoma. Parafoveal and perifoveal VD performed significantly worse in AD participants compared with ED participants for detection of glaucoma (adjusted AUROC, 0.75 [95% confidence interval (CI), 0.62, 0.87], 0.85 [95% CI, 0.79, 0.90], P = 0.035; and 0.82 [95% CI, 0.70, 0.92], 0.91 [95% CI, 0.87, 0.94], respectively; P = 0.020). In contrast to VD, diagnostic accuracy of GCC thickness was similar in AD and ED individuals (adjusted AUROC, 0.89 [95% CI, 0.79, 0.96], 0.92 [95% CI, 0.86, 0.96], respectively; P = 0.313). The diagnostic accuracies of both macular VD and GCC thickness for differentiating between glaucoma and healthy eyes increased with increasing VF MD in both AD and ED participants., Conclusions: Diagnostic performance of OCTA macular VD, but not GCC thickness, for glaucoma detection varies by race. Moreover, macular VD parameters had lower accuracy for detecting glaucoma in AD individuals than in ED individuals. The diagnostic performance of macular VD is race-dependent, and, therefore, race should be taken into consideration when interpreting macular OCTA results., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/aims: To assess the long-term variability of macular optical coherence tomography (OCT)/OCT angiography (OCTA) and visual field (VF) parameters., Methods: Healthy and glaucoma eyes with ≥1-year follow-up were included. 24-2 VF and macular OCT/OCTA parameters, including VF mean deviation (MD), whole-image vessel density (wiVD) and ganglion cell complex thickness (wiGCC) were analysed. Intraclass correlation coefficient (ICC), root mean squared error (RMSE), within-subject test-retest SD (Sw) and test-retest variability were calculated for stable eye cohort (max follow-up=1.5 years). Rates of change and RMSE were evaluated in the extended cohort including all eyes (unlimited follow-up)., Results: From a total of 230 eyes (150 participants; age=67.7 years), 86 eyes (37%, 62 participants) were stable. In stable eyes, OCT parameters showed the highest mean (95%) ICC (wiGCC=0.99 (0.99, 0.99)), followed by VF (VF MD=0.91 (0.88, 0.93)) and OCTA (wiVD=0.82 (0.75, 0.87)). RMSE and Sw for VF MD were 0.92 dB and 0.81 dB, respectively, for wiVD were 1.64% and 1.48%, respectively, and for wiGCC, 0.91 µm and 0.78 µm, respectively. The long-term test-rest variability of VF MD, wiVD and wiGCC was 2.2 dB, 4.1% and 2.2 µm, respectively. In the extended cohort (mean follow-up=3.0 years), all parameters had significant rates of change (p<0.001), and compared with the stable cohort, only slightly higher RMSE (VF MD=1.07 dB; wiGCC=2.03 µm; wiVD=2.57%) were found., Conclusions: VF and macular OCT/OCTA, particularly OCT parameters, showed small long-term variability in all eyes, including stable ones, supporting the use of these instruments in glaucoma follow-up. Changes in macular VD and GCC greater than 4%-5% and 2 µm, respectively, indicate possible progression., Trial Registration Number: NCT00221897., Competing Interests: Competing interests: Acknowledgements/Financial Disclosures. Commercial Disclosures: LMZ reported grants from the National Eye Institute and Heidelberg Engineering; non-financial support from Carl Zeiss Meditec, Optovue, Heidelberg Engineering and Topcon; consultant of Abbvie and patents from Carl Zeiss Meditec. RNW is a consultant of Abbvie, Aerie Pharmaceuticals, Allergan, Amydis, Equinox, Eyenovia, Iantrek, IOPtic, Implandata, Nicox, and Topcon. RNW reported nonfinancial support from Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Centervue and Topcon; grants from the National Eye Institute; patents from Toromedes, Carl Zeiss Meditec; all outside the submitted work. No other disclosures were reported. Other acknowledgements: None.b. Grant information/Funding/Support: This work is supported by National Institutes of Health/National Eye Institute Grants R01EY029058, R01EY011008, R01EY019869, R01EY027510, R01EY026574, R01EY018926, P30EY022589; University of California Tobacco Related Disease Research Program (T31IP1511); and an Unrestricted Grant from Research to Prevent Blindness (New York, New York, USA)., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To evaluate the relationship over time between intraocular pressure (IOP) and the rate of macula whole image vessel density (wiVD) loss and whole image ganglion cell complex (wiGCC) thinning in glaucoma METHODS: From 62 patients in the Diagnostic Innovations in Glaucoma Study, 59 Primary open-angle glaucoma and 27 glaucoma suspect eyes with mean follow-up of 3.2 years were followed. Optical coherence tomography angiography (OCT-A)-based vessel density and OCT-based structural thickness of the same 6×6 mm GCC scan slab were evaluated. Univariable and multivariable linear mixed models were performed for all eyes and also a subset of them in which peak IOP <18 mm Hg to investigate the effect of IOP parameters on the rate of wiVD and wiGCC change., Results: The mean baseline visual field mean deviation (95% CI) was -3.3 dB (-4.4 to -2.1). Higher mean IOP (-0.07%/year per 1 mm Hg (-0.14 to -0.01), p=0.033), peak IOP (-0.07%/year per 1 mm Hg (-0.13 to -0.02), p=0.004) and IOP fluctuation (IOP SD) (-0.17%/year per 1 mm Hg (-0.32 to 0.02), p=0.026) were associated with faster macular vessel density loss. Faster wiGCC thinning was associated with higher mean IOP (-0.05 µm/year per 1 mm Hg (-0.10 to -0.01), p=0.015), peak IOP (-0.05 µm/year per 1 mm Hg (-0.08 to -0.02), p=0.003) and IOP fluctuation (-0.12 µm/year per 1 mm Hg (-0.22 to -0.01), p=0.032). In eyes with peak <18 mm Hg, faster wiVD progression was associated with higher mean IOP (p=0.042). Faster wiGCC progression was associated with higher mean IOP in these eyes (p=0.025)., Conclusion: IOP metrics were associated with faster rates of overall macular microvascular loss and also in the eyes with peak IOP <18 mm Hg. Future studies are needed to examine whether additional IOP lowering reduces the rate of microvascular loss in patients with glaucoma., Trial Registration Number: NCT00221897., Competing Interests: Competing interests: RNW: Financial support—National Eye Institute; Research instruments: Carl Zeiss Meditec, Centervue, Heidelberg Engineering, Konan, Optovue, Topcon; Consultant—Abbvie, Aerie Pharmaceuticals, Allergan, Amydis, Eyenovia, Implandata, Ioptic, Nicox, Topcon., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To develop deep learning (DL) models estimating the central visual field (VF) from optical coherence tomography angiography (OCTA) vessel density (VD) measurements., Design: Development and validation of a deep learning model., Methods: A total of 1051 10-2 VF OCTA pairs from healthy, glaucoma suspects, and glaucoma eyes were included. DL models were trained on en face macula VD images from OCTA to estimate 10-2 mean deviation (MD), pattern standard deviation (PSD), 68 total deviation (TD) and pattern deviation (PD) values and compared with a linear regression (LR) model with the same input. Accuracy of the models was evaluated by calculating the average mean absolute error (MAE) and the R 2 (squared Pearson correlation coefficients) of the estimated and actual VF values., Results: DL models predicting 10-2 MD achieved R 2 of 0.85 (95% confidence interval [CI], 74-0.92) for 10-2 MD and MAEs of 1.76 dB (95% CI, 1.39-2.17 dB) for MD. This was significantly better than mean linear estimates for 10-2 MD. The DL model outperformed the LR model for the estimation of pointwise TD values with an average MAE of 2.48 dB (95% CI, 1.99-3.02) and R 2 of 0.69 (95% CI, 0.57-0.76) over all test points. The DL model outperformed the LR model for the estimation of all sectors., Conclusions: DL models enable the estimation of VF loss from OCTA images with high accuracy. Applying DL to the OCTA images may enhance clinical decision making. It also may improve individualized patient care and risk stratification of patients who are at risk for central VF damage., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate the prevalence of cataracts, refractive disorders, age-related macular disease (AMD), and glaucoma, as well as their trends from 1990 to 2019 in Iran, in comparison with high-middle socio-demographic index (HMSDI) countries and the world, using the Global Burden of Disease (GBD) 2019 study., Methods: The GBD study provided data on the prevalence of blindness and visual impairment (VI), as well as four of their causes including cataracts, refractive disorders, age-related macular disease (AMD), and glaucoma. Using Joinpoint analysis, the annual percent change (APC) was calculated to assess the trend of change in prevalence in each category of diseases from 1990 to 2019, stratified by sex and age, for Iran, HMSDI countries, and the world., Results: In 2019, refractive errors and cataracts were the most common causes of blindness and VI for both genders in Iran, HMSDI countries and the world. Iran had a higher age-standardized prevalence in all four categories of ophthalmologic disorders compared to HMSDI countries and the world for both genders in 2019. Additionally, the age-specific prevalence of all four disorders in 2019 was higher in Iran compared to HMSDI countries. However, in terms of trends of prevalence from 1990 to 2019, the rate of reduction for the four ophthalmologic disorders in Iran was higher than in HMSDI and the world for both males and females. Furthermore, Iran had a greater percentage of reduction in prevalence for all age groups in all four disorders compared to HMSDI countries., Conclusion: The prevalence of cataracts, refractive errors, AMD, and glaucoma in Iran was higher compared to HMSDI countries in 2019 for both sexes and all age groups, but the trends of prevalence for all four disorders from 1990 to 2019 in Iran had a higher slope of reduction compared to HMSDI countries for all ages and sexes., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background/aims: To evaluate the association of macular vessel density (VD) and ganglion cell complex (GCC) thickness with 10-2 central visual field (CVF) progression in glaucoma., Methods: In this retrospective cohort study, patients with glaucoma from Diagnostic Innovation in Glaucoma Study with≥five 10-2 visual field (VF) tests and 3-year follow-up before optical coherence tomography (OCT) and OCT angiography (OCTA) imaging were included. Whole-image GCC thickness (wiGCC) and superficial VD (wiVD) were obtained from 6*6 macula scans. The association of wiVD and wiGCC with past rate of 10-2 VF mean deviation worsening, and with past CVF progression (defined using clustered linear regression criteria) was evaluated using linear mixed models after adjusting for confounders., Results: From 238 eyes (141 patients), 25 eyes (11%) of 16 patients were CVF progressors. In the multivariable analysis of the association between OCT/OCTA parameters and past rate of 10-2 CVF worsening, lower wiVD (β=-0.04 (-0.05, -0.02); p<0.001; R 2 =0.32) and wiGCC (β=-0.01 (-0.01, 0.00); p=0.004; R 2 =0.21) were significantly associated with faster CVF worsening. For the association between OCT/OCTA parameters and past CVF progression, the multivariable analysis showed that a lower wiVD was significantly associated with increased odds of past CVF progression (OR=1.23 (1.06, 1.44) per 1% lower; p=0.008), while wiGCC did not show correlation., Conclusions: Lower macular VD and GCC were associated with faster worsening of CVF, and lower macular VD was associated with increased odds of CVF progression. Assessment of macular OCT and OCTA may help detect glaucoma eyes with CVF progression., Competing Interests: Competing interests: LZ is a consultant of Abbvie. LZ reported grants from the National Eye Institute; grants and non-financial support from Carl Zeiss Meditec, Optovue, Heidelberg Engineering, and Topcon. RNW is a consultant of Aerie Pharmaceuticals, Allergan, Equinox, Eyenovia, Iantrek, IOPtic, Implandata, Nicox, and Topcon. RNW reported non-financial support from Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Centervue, and Topcon; grants from the National Eye Institute, patents from Toromedes, Carl Zeiss Meditec; all outside the submitted work. No other disclosures were reported., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To investigate the relationship between smoking and smoking intensity, and the rate of retinal nerve fibre layer (RNFL) thinning in patients with primary open angle glaucoma (POAG)., Methods: In this longitudinal study, patients with POAG who had at least 3 years of follow-up with a minimum of 5 visits of optical coherence tomography (OCT) were enrolled. The smoking intensity was calculated as the pack-year at the baseline OCT. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of RNFL thinning over time. Non-linear least-squares estimation with piecewise regression model was used to investigate the cut-off point for the relationship between circumpapillary RNFL thinning and smoking intensity., Results: A total of 466 eyes of 314 patients were included over the mean (95% CI) follow-up of 6.6 (6.4 to 6.7) years. Of the 314 patients, 121 (39%) had reported any history of smoking. Greater smoking intensity was associated with faster RNFL thinning (-0.06 (95% CI -0.11 to 0.00) µm/year per 10 pack-year higher; p=0.031) after adjusted for confounding factors. RNFL thinning became significantly faster when smoking intensity was >8 pack-year., Conclusions: Smoking intensity is associated with faster rates of RNFL thinning. Evaluation of smoking intensity might add information to the assessment of risk of glaucoma progression. Future studies are required to explore if withdrawing smoking as a modifiable risk factor can decrease progression in patients with glaucoma., Competing Interests: Competing interests: RW: financial support—National Eye Institute. Research instruments: Carl Zeiss Meditec, Centervue, Heidelberg Engineering, Konan, Optovue, Consultant—Aerie Pharmaceuticals, Allergan, Eyenovia, Nicox, Novartis; JML: research support—Carl Zeiss Meditec, Heidelberg Engineering, National Eye Institute, Optovue; Consultant—Alcon, Allergan, Carl Zeiss Meditec, Heidelberg Engineering; CAG: financial support—EyeSight Foundation of Alabama; National Eye Institute; Research to Prevent Blindness; MAF: financial support—EyeSight Foundation of Alabama; National Eye Institute; Research to Prevent Blindness; LMZ: research support—Carl Zeiss Meditec, Heidelberg Engineering, National Eye Institute, Topcon, Optovue., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Predict central 10° global and local visual field (VF) measurements from macular optical coherence tomography (OCT) volume scans with deep learning (DL)., Methods: This study included 1121 OCT volume scans and 10-2 VFs from 289 eyes (257 patients). Macular scans were used to estimate 10-2 VF mean deviation (MD), threshold sensitivities (TS), and total deviation (TD) values at 68 locations. A three-dimensional (3D) convolutional neural network based on the 3D DenseNet121 architecture was used for prediction. We compared DL predictions to those from baseline linear models. We carried out 10-fold stratified cross-validation to optimize generalizability. The performance of the DL and baseline models was compared based on correlations between ground truth and predicted VF measures and mean absolute error (MAE; ground truth - predicted values)., Results: Average (SD) MD was -9.3 (7.7) dB. Average (SD) correlations between predicted and ground truth MD and MD MAE were 0.74 (0.09) and 3.5 (0.4) dB, respectively. Estimation accuracy deteriorated with worsening MD. Average (SD) Pearson correlations between predicted and ground truth TS and MAEs for DL and baseline model were 0.71 (0.05) and 0.52 (0.05) (P < 0.001) and 6.5 (0.6) and 7.5 (0.5) dB (P < 0.001), respectively. For TD, correlation (SD) and MAE (SD) for DL and baseline models were 0.69 (0.02) and 0.48 (0.05) (P < 0.001) and 6.1 (0.5) and 7.8 (0.5) dB (P < 0.001), respectively., Conclusions: Macular OCT volume scans can be used to predict global central VF parameters with clinically relevant accuracy., Translational Relevance: Macular OCT imaging may be used to confirm and supplement central VF findings using deep learning.

Objectives: To investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma., Design: A retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES)., Setting: Three tertiary glaucoma centres in the USA., Participants: 825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies., Outcome Measures: Development of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time., Results: VF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years)., Conclusion: Alcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people., Trial Registration Number: NCT00221897 and NCT00221923., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: In eyes with suspected glaucoma, it is clinically relevant to find diagnostic tests for the risk of development of perimetric glaucoma., Objective: To investigate the association between rates of ganglion cell/inner plexiform layer (GCIPL) and circumpapillary retinal nerve fiber layer (cpRNFL) thinning and the development of perimetric glaucoma in eyes with suspected glaucoma., Design, Setting, and Participants: This observational cohort study used data collected in December 2021 from a tertiary center study and a multicenter study. Participants with suspected glaucoma were followed up for 3.1 years. The study was designed in December 2021 and finalized in August 2022., Exposures: Development of perimetric glaucoma was defined as having 3 consecutive results showing abnormal visual fields. Using linear mixed-effect models, rates of GCIPL were compared between eyes with suspected glaucoma that did and did not develop perimetric glaucoma. A joint longitudinal multivariable survival model was used to investigate the performance of rates of GCIPL and cpRNFL thinning in predicting the risk of developing perimetric glaucoma., Main Outcomes and Measures: Rates of GCIPL thinning and hazard ratio (HR) of developing perimetric glaucoma., Results: Among a total of 462 participants, the mean (SD) age was 63.3 (11.1) years, and 275 patients (60%) were female. Of 658 eyes, 153 eyes (23%) developed perimetric glaucoma. The mean rates of GCIPL thinning were faster in eyes that developed perimetric glaucoma (-1.28 vs -0.66 μm/y for minimum GCIPL thinning; difference, -0.62; 95% CI, -1.07 to -0.16; P = .02). Based on the joint longitudinal survival model, every 1-μm/y faster rate of minimum GCIPL and rate of global cpRNFL thinning were associated with a 2.4 and 1.9 higher risk of developing perimetric glaucoma, respectively (HR, 2.4; 95% CI, 1.8 to 3.2, and HR, 1.99; 95% CI, 1.76 to 2.22, respectively; P < .001). Among the predictive factors, African American race (HR, 1.56; 95% CI, 1.05 to 2.34; P = .02), male sex (HR, 1.47; 95% CI, 1.02 to 2.15; P = .03), 1-dB higher baseline visual field pattern standard deviation (HR, 1.73; 95% CI, 1.56 to 1.91; P < .001), and 1-mm Hg higher mean intraocular pressure during follow-up (HR, 1.11; 95% CI, 1.05 to 1.17; P < .001) were associated with higher risk of developing perimetric glaucoma., Conclusions and Relevance: This study found that faster rates of GCIPL and cpRNFL thinning were associated with higher risks of developing perimetric glaucoma. Rates of cpRNFL thinning and specifically GCIPL thinning may be useful measures for monitoring eyes with suspected glaucoma.

Background/aims: To identify clinical characteristics and factors associated with microcystic macular edema (MME) in patients with primary open-angle glaucoma (POAG)., Methods: We included 315 POAG eyes between 2010 and 2019 with good-quality macular volume scans that had reliable visual fields (VF) available within 6 months in this observational retrospective cohort study. Eyes with retinal pathologies except for epiretinal membrane (ERM) were excluded. The inner nuclear layer was qualitatively assessed for the presence of MME. Global mean deviation (MD) and Visual Field Index (VFI) decay rates, superior and inferior MD rates and pointwise total deviation rates of change were estimated with linear regression. Logistic regression was performed to identify baseline factors associated with the presence of MME and to determine whether MME is associated with progressive VF loss., Results: 25 out of 315 eyes (7.9%) demonstrated MME. The average (±SD) age and MD in eyes with and without MME was 57.2 (±8.7) versus 62.0 (±9.9) years (p=0.02) and -9.8 (±5.7) versus -4.9 (±5.3) dB (p<0.001), respectively. Worse global MD at baseline (p=0.001) and younger age (p=0.02) were associated with presence of MME. ERM was not associated with the presence of MME (p=0.84) in this cohort. MME was not associated with MD and VFI decay rates (p>0.49)., Conclusions: More severe glaucoma and younger age were associated with MME. MME was not associated with faster global VF decay in this cohort. MME may confound monitoring of glaucoma with full macular thickness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the association of vision-related quality of life (VRQOL) with the central visual field and macular ganglion cell complex (GCC) thickness in healthy control participants, patients with preperimetric glaucoma, and patients with perimetric glaucoma., Design: Retrospective cross-sectional study., Methods: A total of 39 healthy, 34 preperimetric glaucoma, and 145 perimetric glaucoma patients completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). A linear mixed-effect models was used to investigate the association between the glaucoma stage as measured by binocular 10-2 visual field mean sensitivity (VFMS) and GCC thickness with the Rasch-calibrated NEI-VFQ score., Results: A total of 436 eyes from 218 participants (mean age = 67.2 [95% CI = 65.1 to 69.2] years) were enrolled. VRQOL calculated by the NEI-VFQ Rasch-calibrated score was worst for patients with perimetric glaucoma (50.7 [95% CI = 47.2 to 54.2]), followed by patients with preperimetric glaucoma (41.2 [95% CI = 34.5 to 47.9]) and healthy controls (29.3 [95% CI = 24.0 to 34.7]. Worse VRQOL had a moderate association with a worse global binocular 10-2 VFMS (-3.4 [95% CI = -5.0 to -1.9] dB per 1 score; P < .001; adjusted R 2  = 0.27), but not with a thinner global GCC in the better eye (-0.1 [95% CI = -0.2 to 0.1] µm per 1 score; P =.0485; adjusted R 2  = 0.17)., Conclusions: These findings suggest that patients with perimetric and preperimetric glaucoma have worse VRQOL than patients with healthy eyes. As compared to macular thickness measurements, the central visual field is more strongly associated with VRQOL and may better help to identify patients in need of intervention., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To investigate the association between corneal hysteresis (CH) and rates of optic nerve head whole image capillary density (wiCD) loss over time in open-angle glaucoma (OAG)., Design: Observational cohort., Participants: One hundred seventy-four eyes (122 OAG and 52 glaucoma suspect eyes) from 112 patients over more than 2 years and 4 visits or more., Methods: Baseline CH measurements were acquired with the Ocular Response Analyzer. Linear mixed-effect models were designed to investigate the effect of CH, average intraocular pressure (IOP) during follow-up, and baseline visual field (VF) mean deviation (MD) on the rates of wiCD loss and circumpapillary retinal nerve fiber layer (cpRNFL) thinning over time, while adjusting for confounders. Interaction between CH or baseline MD and average IOP during follow-up were included in final models to evaluate the effect of baseline MD or average IOP during follow-up on structural changes for different values of CH., Main Outcome Measure: Effect of CH, IOP, and baseline MD on the rates of wiCD loss and cpRNFL thinning over time., Results: The average follow-up time was 3.9 years. In the multivariable model, non-Black race, higher average IOP during follow-up, lower baseline CH, lower baseline VF MD, and higher numbers of IOP-lowering medications were associated with faster rates of wiCD loss over time. For CH values 6 mmHg and 12 mmHg, every 1-mmHg increase in average IOP during follow-up was associated with 0.23% per year faster and 0.07% per year slower rates of wiCD loss over time, respectively. While every 1-mmHg decrease in CH was associated with 1.89% per year faster rate of wiCD loss for MD of -12 dB, it was associated with 0.81% per year faster rate of wiCD loss for MD of -3 dB., Conclusion: Lower CH values were significantly associated with faster rates of wiCD loss over time. In eyes with lower CH, both higher average IOP during follow-up and more severe glaucoma damage at baseline were associated with faster rates of wiCD loss and cpRNFL thinning. These results support CH as a useful parameter for risk assessment of glaucoma progression., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To estimate central 10-degree visual field (VF) map from spectral-domain optical coherence tomography (SD-OCT) retinal nerve fiber layer thickness (RNFL) measurements in glaucoma with artificial intelligence., Design: Artificial intelligence (convolutional neural networks) study., Methods: This study included 5352 SD-OCT scans and 10-2 VF pairs from 1365 eyes of 724 healthy patients, patients with suspected glaucoma, and patients with glaucoma. Convolutional neural networks (CNNs) were developed to estimate the 68 individual sensitivity thresholds of 10-2 VF map using all-sectors (CNN A ) and temporal-sectors (CNN T ) RNFL thickness information of the SD-OCT circle scan (768 thickness points). 10-2 indices including pointwise total deviation (TD) values, mean deviation (MD), and pattern standard deviation (PSD) were generated using the CNN-estimated sensitivity thresholds at individual test locations. Linear regression (LR) models with the same input were used for comparison., Results: The CNN A model achieved an average pointwise mean absolute error of 4.04 dB (95% confidence interval [CI] 3.76-4.35) and correlation coefficient (r) of 0.59 (95% CI 0.52-0.64) over 10-2 map and the mean absolute error and r of 2.88 dB (95% CI 2.63-3.15) and 0.74 (95% CI 0.67-0.80) for MD, and 2.31 dB (95% CI 2.03-2.61) and 0.59 (95% CI 0.51-0.65) for PSD estimations, respectively, significantly outperforming the LR A model., Conclusions: The proposed CNN A model improved the estimation of 10-2 VF map based on circumpapillary SD-OCT RNFL thickness measurements. These artificial intelligence methods using SD-OCT structural data show promise to individualize the frequency of central VF assessment in patients with glaucoma and would enable the reallocation of resources from patients at lowest risk to those at highest risk of central VF damage., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To use longitudinal optical coherence tomography (OCT) and OCT angiography (OCTA) data to detect glaucomatous visual field (VF) progression with a supervised machine learning approach., Design: Prospective cohort study., Methods: One hundred ten eyes of patients with suspected glaucoma (33.6%) and patients with glaucoma (66.4%) with a minimum of 5 24-2 VF tests and 3 optic nerve head and macula images over an average follow-up duration of 4.1 years were included. VF progression was defined using a composite measure including either a "likely progression event" on Guided Progression Analysis, a statistically significant negative slope of VF mean deviation or VF index, or a positive pointwise linear regression event. Feature-based gradient boosting classifiers were developed using different subsets of baseline and longitudinal OCT and OCTA summary parameters. The area under the receiver operating characteristic curve (AUROC) was used to compare the classification performance of different models., Results: VF progression was detected in 28 eyes (25.5%). The model with combined baseline and longitudinal OCT and OCTA parameters at the global and hemifield levels had the best classification accuracy to detect VF progression (AUROC = 0.89). Models including combined OCT and OCTA parameters had higher classification accuracy compared with those with individual subsets of OCT or OCTA features alone. Including hemifield measurements significantly improved the models' classification accuracy compared with using global measurements alone. Including longitudinal rates of change of OCT and OCTA parameters (AUROCs = 0.80-0.89) considerably increased the classification accuracy of the models with baseline measurements alone (AUROCs = 0.60-0.63)., Conclusions: Longitudinal OCTA measurements complement OCT-derived structural metrics for the evaluation of functional VF loss in patients with glaucoma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To test the hypothesis that macular ganglion cell layer (GCL) measurements detect early glaucoma with higher accuracy than ganglion cell/inner plexiform layer (GCIPL) thickness measurements., Design: Cross-sectional study., Participants: The first cohort included 58 glaucomatous eyes with visual field mean deviation (MD) ≥ -6 dB and 125 normal eyes. The second cohort included 72 glaucomatous and 73 normal/glaucoma suspect (GS) eyes with scans able to create GCL/GCIPL deviation maps., Methods: In the first cohort, 8 × 8 GCL and GCIPL grids were exported and 5 superior and inferior sectors were defined. Global and sectoral GCL and GCIPL measures were used to predict glaucoma. In the second cohort, proportions of scan areas with abnormal (< 5% and < 1% cutoffs) and supernormal (> 95% and > 99% cutoffs) thicknesses on deviation maps were calculated. The extents of GCL and GCIPL abnormal areas were used to predict glaucoma., Main Outcome Measures: Extents of abnormal GCL/GCIPL regions and areas under receiver operating characteristic curves (AUROC) for prediction of glaucoma were compared between GCL or GCIPL measures., Results: The average ± standard deviation MDs were -3.7 ± 1.6 dB and -2.7 ± 1.8 dB in glaucomatous eyes in the first and second cohorts, respectively. Global GCIPL thickness measures (central 18° × 18° macular region) performed better than GCL for early detection of glaucoma (AUROC, 0.928 vs. 0.884, respectively; P = 0.004). Superior and inferior sector 3 thickness measures provided the best discrimination with both GCL and GCIPL (inferior GCL AUROC, 0.860 vs. GCIPL AUROC, 0.916 [P = 0.001]; superior GCL AUROC, 0.916 vs. GCIPL AUROC, 0.900 [P = 0.24]). The extents of abnormal GCL regions at a 1% cutoff in the central elliptical area were 17.5 ± 22.2% and 6.4 ± 10.8% in glaucomatous and normal/GS eyes, respectively, versus 17.0 ± 22.2% and 5.7 ± 10.5%, respectively, for GCIPL (P = 0.06 for GCL and 0.002 for GCIPL). The extents of GCL and GCIPL supernormal regions were mostly similar in glaucomatous and normal eyes. The best performance for prediction of glaucoma in the second cohort was detected at a P value of < 1% within the entire scan for both GCL and GCIPL (AUC, 0.681 vs. 0.668, respectively; P = 0.29)., Conclusions: Macular GCL and GCIPL thicknesses are equivalent for identifying early glaucoma with current OCT technology. This is likely explained by limitations of inner macular layer segmentation and concurrent changes within the inner plexiform layer in early glaucoma., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine how the frequency of testing affects the time required to detect statistically significant glaucoma progression for circumpapillary retinal nerve fiber layer (cpRNFL) with optical coherence tomography (OCT) and circumpapillary capillary density (cpCD) with OCT angiography (OCTA)., Design: Retrospective, observational cohort study., Methods: In this longitudinal study, 156 eyes of 98 patients with glaucoma followed up over an average of 3.5 years were enrolled. Participants with 4 or more OCT and OCTA tests were included to measure the longitudinal rates of cpRNFL thickness and cpCD change over time using linear regression. Estimates of variability were then used to re-create real-world cpRNFL and cpCD data by computer simulation to evaluate the time required to detect progression for various loss rates and different testing frequencies., Results: The time required to detect a statistically significant negative cpRNFL and cpCD slope decreased as the testing frequency increased, albeit not proportionally. cpCD detected progression slightly earlier than cpRNFL. Eighty percent of eyes with a cpCD loss of -1%/y were detected after 6.0, 4.2, and 4 years when testing was performed 1, 2, and 3 times per year, respectively. Progression in 80% of eyes with a cpRNFL loss of -1 µm/y was detected after 6.3, 5.0, and 4.2 years, respectively., Conclusions: cpRNFL and cpCD are comparable in detecting progression. As there were only small changes in the time to detect progression when testing increased from 2 to 3 times per year, testing twice per year may provide sufficient information for detecting progression with either OCT or OCTA in clinical settings., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Whether rapid ganglion cell complex (GCC) thinning during an initial follow-up period is associated with rates of central visual field loss over time is unclear but important to understand because risk of glaucoma progression can help guide treatment intensity., Objective: To investigate the association between the rate of GCC thinning during initial follow-up and the rate of central visual field loss., Design, Setting, and Participants: This retrospective cohort study assessed patients older than 18 years with glaucoma at a tertiary glaucoma center who were followed up from June 18, 2014, to January 11, 2019. Data analysis for the current study was undertaken in March 2022., Main Outcomes and Measures: Initial rates of GCC thinning were obtained from global GCC thickness values of the first 3 optical coherence tomography (OCT) scans. Rates of central visual field loss were assessed as the change in central (10-2) visual field mean deviation during the 4.7-year follow-up period by univariable and multivariable linear mixed-effects models. Eyes were categorized as slow (>-1 μm/y) or fast (≤-1 μm/y) progressors based on rates of GCC thinning., Results: The cohort consisted of 202 eyes of 139 patients (mean [SD] age, 68.7 [10.0] years; 72 male [51.8%]); 44 African American patients (31.7%), 13 Asian patients (9.4%), 80 White patients (57.6%), and 2 patients who identified as other race and ethnicity (1.4%) were analyzed. The rate of GCC change was -0.56 μm/y (95% CI, -0.66 to -0.46 μm/y) during a mean initial follow-up of 1.8 years (95% CI, 1.7-2.0 years). A total of 163 eyes (80.7%) were slow OCT progressors, and 39 (19.3%) were fast OCT progressors, with rates of GCC thinning of -0.3 μm/y (95% CI, -0.4 to -0.2 μm/y) and -1.6 μm/y (-1.8 to -1.3 μm/y), respectively. The rates of 10-2 visual field mean deviation worsening among slow and fast OCT progressors were -0.10 dB/y (95% CI, -0.16 to 0.00 dB/y) and -0.34 dB/y (95% CI, -0.51 to -0.16 dB/y), respectively (difference, -0.26 dB/y; 95% CI, -0.45 to -0.07 dB/y; P = .008)., Conclusions and Relevance: In this cohort study, rapid GCC thinning during an initial follow-up period was associated with faster rates of central visual field decline. These findings support use of longitudinal macular OCT scans assisting clinical decision-making for glaucoma and also may guide possible intensification of therapy in high-risk patients.

Purpose: To evaluate the effects of pressure changes induced by a multipressure dial (MPD) on circumpapillary retinal nerve fiber layer (RNFL) and capillary density (CD) measurements in patients with glaucoma using OCT angiography (OCTA)., Design: Prospective interventional study., Participants: Twenty-four patients with primary open-angle glaucoma., Methods: One eye of each patient underwent negative pressure application with the MPD. The MPD alters intraocular pressure (IOP) relative to atmospheric pressure by generating a negative pressure vacuum within a goggle chamber that is placed over the eye. Each participant underwent serial high density OCTA imaging (AngioVue) of the optic nerve head at different negative pressure increments of -5 mmHg, starting from 0 mmHg, ending at -20 mmHg, and then returning to baseline. Images were acquired after 2 minutes of sustained negative pressure at each target pressure to allow for stabilization of the retinal structures and microvasculature. The RNFL thickness and CD measurements were automatically calculated using the native AngioVue software, and then exported for analysis., Main Outcome Measures: The influence of different levels of negative pressure on circumpapillary RNFL thickness and CD measurements, assessed by a linear mixed-effects model with repeated measures., Results: The mean (± SD) age was 71.0 years (± 7.8 years), the baseline IOP was 17.5 mmHg (± 3.6 mmHg), and there was a mean 24-2 mean deviation of -2.80 dB (± 2.55 dB). Serial circumpapillary CD measurements showed a statistically significant dose-dependent increase from baseline, without negative pressure application, to the maximum negative pressure application of -20 mmHg (difference, 2.27%; P = 0.010). Capillary density measurements then decreased symmetrically when lowering the negative pressure to baseline. Circumpapillary CD measurements at target negative pressures of -10 mmHg, -15 mmHg, and -20 mmHg were significantly higher than the baseline measurements (all P values < 0.05). Circumpapillary RNFL thickness remained the same throughout different levels of negative pressure., Conclusions: Circumpapillary CD measurements showed a dose-dependent increase with the induction of negative pressure, while RNFL thickness measurements remained unchanged., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the effect of smoking on rates of progressive visual field (VF) damage over time in glaucoma., Design: Retrospective cohort study., Participants: Five hundred eleven eyes of 354 patients with glaucoma followed up from multicenter glaucoma registries., Methods: In this longitudinal study, 354 patients with primary open-angle glaucoma with a minimum of 3 years of follow-up and 5 VF tests were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Univariate and multivariate linear mixed models were used to investigate the effects of smoking on rates of 24-2 VF mean deviation loss. Visual field progression was defined using pointwise linear and significant negative VF mean deviation loss. Logistic regression was used to identify baseline factors and whether different levels of smoking intensity were associated with VF progression. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between smoker and never smoker groups., Main Outcome Measures: Visual field progression., Results: Five hundred eleven eyes of 354 patients were included over the median follow-up of 12.5 years. Median baseline age was 64.8 years. Of the 354 patients, 124 (35%) were Black, and 149 (42.1%) and 168 (59.8%) had reported a history of smoking or alcohol consumption, respectively. In a multivariate model, higher smoking intensity was associated with faster VF loss (coefficient, -0.05 decibels (dB)/year per 10 pack-years; 95% confidence interval [CI], -0.08 to -0.01 dB/year per 10 pack-years; P = 0.010). Developing VF progression in eyes of heavy smokers (≥ 20 pack-years) was 2.2 times more than in eyes of patients without smoking history (odds ratio, 2.21; 95% CI, 1.02-4.76; P = 0.044). Statistically significant differences were found between heavy smokers (≥ 20 pack-years) and never smokers by Kaplan-Meier analysis (P = 0.011, log-rank test)., Conclusions: Heavy smokers are more likely to sustain VF loss in eyes with glaucoma. The prospective longitudinal design of this study supports the hypothesis that levels of smoking may be a significant predictor for glaucoma progression. Additionally, this information can be used for clinically relevant tobacco prevention and intervention messages., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Prcis: The earlier a person quits smoking the more likely is the optic nerve be spared from damage., Purpose: To investigate the effect of smoking cessation on visual field (VF) progression in glaucoma., Methods: Primary open angle glaucoma patients with a minimum of 3 years follow-up and 5 VFs were included. Linear mixed models were used to investigate the effects of smoking on the rates of 24-2 VF mean deviation loss after adjusting for confounding factors. Cox proportional hazard regression was used to identify whether different levels of smoking intensity were associated with VF progression with respect to different duration of quitting., Results: Five hundred eleven eyes of 354 patients were included over the mean follow-up of 12.4 years. Mean baseline age (95% confidence interval) was 62.3 (61.2, 63.4) years. One hundred forty nine (42.1%) patients were smokers. In a multivariable model, smoking intensity was associated with faster VF loss (-0.06, 95% confidence interval (-0.10, -0.01) dB/year per 10 pack-years, P =0.01) among smokers. Heavy smokers (≥20 pack-years) who had quit ˂25 years prior had significantly greater odds of VF progression compared with never smokers (odds ratio=2.49 (1.01, 6.08); P =0.046). There was no significant difference in odds of VF progression in heavy smokers who had quit smoking more than 25 years compared with never smokers ( P =0.43). A significantly higher proportion of VF progression was found in heavy smokers who quit < 25 years compared with heavy smokers who quit ≥25 years by Kaplan-Meier analysis ( P =<0.001)., Conclusions: After ≥25 years of smoking cessation, the risk of VF progression in former heavy smokers becomes similar to never smokers. Long-term smoking cessation may be associated with lower VF progression in glaucoma patients., Competing Interests: Disclosure: R.N.W. has received financial support from C: Aerie Pharmaceuticals, Allergan, Equinox, Eyenovia, Nicox, Topcon; F: Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Centervue, Bausch&Lomb, Topcon; P: Toromedes, Carl Zeiss Meditec, Topcon. C.A.G. has received financial support from National Eye Institute, EyeSight Foundation of Alabama, Research to Prevent Blindness, Heidelberg Engineering, GmbH. J.M.L. has received financial support from C: Alcon, Allergan, Bausch & Lomb, Carl Zeiss Meditec, Heidelberg Engineering, Reichert, Valeant Pharmaceuticals; F: Bausch & Lomb, Carl Zeiss Meditec, Heidelberg Engineering, National Eye Institute, Novartis, Optovue, Reichert Technologies, Research to Prevent Blindness. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the association between rates of choroidal microvasculature dropout (MvD) change and rates of circumpapillary retinal nerve fiber layer (cpRNFL) loss in primary open-angle glaucoma (POAG) eyes., Design: Cohort study from clinical trial data., Methods: A total of 91 eyes of 68 POAG patients with and without localized MvD at baseline with at least 4 visits and 2 years of follow-up with optical coherence tomography angiography (OCT-A) and OCT scans were included. Area and angular circumference of MvD were evaluated on OCT-A en face and B-scan choroidal vessel density images during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in MvD area or angular circumference and RNFL thickness. Univariable and multivariable regressions were completed to identify the factors contributing to cpRNFL thinning., Results: MvD was identified in 53 eyes (58.2%) at baseline. Seventeen eyes (18.6%) that did not show MvD at baseline developed it over the follow-up period. Over a mean follow-up of 4.0 years, the mean rates of change in MvD area and angular circumference (95% CI) were 0.05 (0.04, 0.06) mm 2 per year and 13.2° (10.7°, 15.8°) per year, respectively. In multivariable models, the rate of cpRNFL thinning was significantly associated with the rates of change in MvD area and angular circumference (P = .008 and P = .009, respectively)., Conclusions: Rates of MvD area and angular circumference change over time were associated with concurrent rates of cpRNFL loss in POAG eyes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Prcis: Decreased superficial whole image capillary density was observed in open angle glaucoma (OAG) patients with high smoking intensity., Purpose: To investigate the effects of smoking on optic nerve head capillary density measured by optical coherence tomography angiography in patients with OAG., Methods: In this retrospective cross-sectional study, perimetric and preperimetric glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optical coherence tomography angiography follow-up were included. Univariable and multivariable linear mixed analysis were performed to determine the effects of different variables on the superficial whole image capillary density., Results: A total of 432 eyes of 271 glaucoma patients comprising 63 preperimetric (106 eyes) and 208 perimetric OAG (326 eyes) were included. A history of tobacco consumption was reported in 105 (38.8%). Among smokers, mean (95% confidence interval) smoking intensity was 12.8 (10.2, 15.5) pack-years. After adjusting for age, glaucoma severity and other confounders, each 10 pack-year increase in smoking intensity (95% confidence interval) was associated with -0.54 (-1.06, -0.02) % lower whole image capillary density ( P =0.041)., Conclusions: Smoking intensity is associated with reduced optic nerve vessel density in glaucoma., Competing Interests: Disclosure: R.N.W. has received financial support from C: Aerie Pharmaceuticals, Allergan, Equinox, Eyenovia, Nicox, Topcon; F: Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Centervue, Bausch & Lomb, Topcon; P: Toromedes, Carl Zeiss Meditec, Topcon. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Faster structural changes may be associated with worse vision-related quality of life in patients with glaucoma., Objectives: To evaluate the association between the rate of ganglion cell complex thinning and the Vision Function Questionnaire in glaucoma., Design, Setting, and Participants: This retrospective analysis of a longitudinal cohort was designed in October 2021. Patients were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Two hundred thirty-six eyes of 118 patients with diagnosed or suspected glaucoma were followed up with imaging for a mean of 4.1 years from September 2014 to March 2020., Main Outcomes and Measures: The Vision Function Questionnaire was evaluated using the 25-item National Eye Institute Visual Function at the last follow-up visit. Ganglion cell complex thickness was derived from macular optical coherence tomography scans and averaged within 3 circular areas (3.4°, 5.6°, and 6.8° from the fovea) and superior and inferior hemiregions. Linear mixed-effects models were used to investigate the association between the rate of ganglion cell complex thinning and Rasch-calibrated Vision Function Questionnaire score., Results: The mean (SD) age was 73.2 (8.7) years, 65 participants (55.1%) were female, and 53 participants (44.9%) were African American. Race was self-reported by the participants. Mean composite Rasch-calibrated National Eye Institute Visual Function Questionnaire score was 50.3 (95% CI, 45.9-54.6). A faster annual rate of global ganglion cell complex thinning in the better eye was associated with a higher disability reflected by the composite National Eye Institute Visual Function Questionnaire score (-15.0 [95% CI, -28.4 to -1.7] per 1 μm faster; P = .03). When stratified by degrees from the fovea, the 5.6° and 6.8° areas were associated with the composite National Eye Institute Visual Function Questionnaire Rasch-calibrated score (-14.5 [95% CI, -27.0 to -2.0] per 1 μm faster; R2 = 0.201; P = .03; and -23.7 [95% CI, -45.5 to -1.9] per 1 μm faster; R2 = 0.196; P = .02, respectively), and -8.0 (95% CI, -16.8 to 0.8) per 1 μm faster for the 3.4° area (R2 = 0.184; P = .07) after adjusting for confounding factors., Conclusions and Relevance: These findings suggest that faster and sectoral central location of ganglion cell complex thinning provides useful information in determining the risk of vision-related quality of life in glaucoma. Monitoring macular structure may be useful for determining the risk of functional impairment in glaucoma.

Purpose: We compared rates of change of macular ganglion cell/inner plexiform (GCIPL) thickness and proportion of worsening and improving rates from 2 optical coherence tomography (OCT) devices in a cohort of eyes with glaucoma., Design: Longitudinal cohort study., Methods: In a tertiary glaucoma clinic we evaluated 68 glaucoma eyes with ≥2 years of follow-up and ≥4 OCT images. Macular volume scans from 2 OCT devices were exported, coregistered, and segmented. Global and sectoral GCIPL data from the central 4.8 × 4.0-mm region were extracted. GCIPL rates of change were estimated with linear regression. Permutation analyses were used to control specificity with the 2.5 percentile cutoff point used to define "true" worsening. Main outcome measures included differences in global/sectoral GCIPL rates of change between 2 OCT devices and the proportion of negative vs positive rates of change (P < .05)., Results: Average (standard deviation) 24-2 visual field mean deviation, median (interquartile range) follow-up time, and number of OCT images were -9.4 (6.1) dB, 3.8 (3.3-4.2) years, and 6 (5-8), respectively. GCIPL rates of thinning from Spectralis OCT were faster (more negative) compared with Cirrus OCT; differences were significant in superonasal (P = .03) and superotemporal (P = .04) sectors. A higher proportion of significant negative rates was observed with Spectralis OCT both globally and in inferotemporal/superotemporal sectors (P < .04). Permutation analyses confirmed the higher proportion of global and sectoral negative rates of change with Spectralis OCT (P < .001)., Conclusions: Changes in macular GCIPL were detected more frequently on Spectralis' longitudinal volume scans than those of Cirrus OCT. OCT devices are not interchangeable with regard to detection of macular structural progression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To compare local ganglion cell-inner plexiform layer (GCIPL) thickness measurements between 2 OCT devices and to explore factors that may influence the difference in measurements., Design: Cross-sectional study., Participants: Sixty-nine glaucoma eyes (63 patients) with evidence of central damage or mean deviation (MD) of -6.0 dB or worse on a 24-2 visual field (VF)., Methods: Cirrus and Spectralis OCT macular volume scans were exported, data from the central 20° of both OCT devices were centered and aligned, and 50 × 50 arrays of 0.4° × 0.4° superpixels were created. We estimated nonparametric (Spearman's) correlations and used Bland-Altman plots to compare GCIPL thickness measurements between the two OCTs at the superpixel level. Factors that may have influenced the differences between thickness measurements between the two devices were explored with linear mixed models., Main Outcome Measures: Pooled and individual-eye Spearman's correlation and agreement between thickness measurements from the two devices., Results: The median 24-2 VF MD was -6.8 dB (interquartile range [IQR], -4.9 to -12.3 dB). The overall pooled Spearman's correlation between the two devices for all superpixels and eyes was 0.97 (P < 0.001). The median within-eye correlation coefficient was 0.72 (IQR, 0.59-0.79). Bland-Altman plots demonstrated a systematic bias in most individual eyes, with Spectralis GCIPL measurements becoming larger than Cirrus measurements with increasing superpixel thickness. The average superpixel thickness and distance to the fovea influenced the thickness difference between the two devices in multivariate models (P < 0.001)., Conclusions: Local macular thickness measurements from the Spectralis and Cirrus devices are highly correlated, but not interchangeable. Differences in thickness measurements between the two devices are influenced by the location of superpixels and their thickness., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the relationship between the presence of an acquired pit of the optic nerve (APON) and the rate of visual field (VF) decay in primary open-angle glaucoma (POAG)., Methods: Consecutive patients with POAG were screened for APON by three glaucoma specialists. A control group of POAG eyes without APON were matched with the APON group for factors such as age, gender, baseline intraocular pressure and baseline mean deviation (MD). The pointwise rate of change (PRC) was used for pointwise comparisons between the two groups. MD rate, Visual Field Index (VFI) rate and Glaucoma Rate Index (GRI) were used for global rate comparisons. We compared the proportions of eyes progressing in the groups with event-based guided progression analysis (GPA), MD, VFI and GRI criteria., Results: Mean (SD) PRC was faster in the APON group -1.00 (±2.57) %/year compared with the control group -0.25 (±2.19) %/year; p<0.001. MD rate (-0.22 (±0.27) dB/year vs 0.03 (±0.41) dB/year; p=0.009), VFI rate (-0.81 (±0.86) %/year vs -0.05 (±1.0) %/year; p=0.04) and GRI (-12.27 (±16.27) vs -3.75 (±10.6); p=0.052) were all faster in the APON group compared with controls. The proportion of progressing eyes with GPA, MD, VFI and GRI was not significantly different between the two groups (p>0.1)., Conclusions: The presence of APON in patients with POAG is associated with focal, fast rates of VF decay. Identification of patients with APON should alert clinicians to the possibility of a fast rate of functional progression and to consider appropriately aggressive treatment of their glaucoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)