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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.)

Polypharmacy, defined here as the concomitant use of five or more medications, is a significant health issue, particularly affecting individuals with chronic diseases like hypertension (HTN). To compare individuals with and without HTN in term of polypharmacy, and to investigate correlates of polypharmacy and medication use patterns in individuals with HTN in southwest Iran. This cross-sectional study used the baseline data of 9270 participants of the Pars Cohort Study (PCS) with a mean age of 52.6 ± 9.7 years. Poisson multivariable modeling was applied to identify correlates of polypharmacy, and Lexicomp® was used to assess drug-drug interactions. Anatomical Therapeutic Chemical classification was used to describe the pattern of medication use. The prevalence of polypharmacy in individuals without hypertension was 4.7 % (4.2%-5.2 %) vs. 23.7 % (22.1%-25.3 %) in individuals with hypertension (P < 0.001). Individuals with hypertension from middle-high socioeconomic status (SES) had a 1.51-fold higher prevalence of polypharmacy than vs. low SES. Those with more than three comorbidities had a 5.18 times higher prevalence of polypharmacy than those with isolated hypertension. Calcium channel blockers were the most common antihypertensives (20.9 %). In terms of drug-drug interactions, type C interactions were most prevalent among participants with hypertension and polypharmacy (76.0 %). Our findings imply a fairly high prevalence of polypharmacy and drug-drug interactions among individuals with hypertension; to tackle this issue, we recommend a national pharmacovigilance system, training programs for primary care physicians, public education and awareness campaigns, drug-checking campaigns, targeted screenings to alter modifiable risk factors, and the use of safe combination pills., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/aims: To examine longitudinal optical coherence tomography angiography (OCTA) changes in macula and optic nerve head (ONH) in healthy, glaucoma suspect (GS) and primary open-angle glaucoma (POAG) eyes., Methods: Healthy, GS and POAG eyes from Diagnostic Innovations in Glaucoma Study with ≥2 years follow-up and four visits of macular/ONH OCTA imaging were included. Rates of macular wiVD (whole-image vessel density) and ONH wiCD (whole-image capillary density) changes were calculated for each diagnosis group using join mixed-effect modelling. Differences in wiVD/wiCD change rates across diagnoses were examined through pairwise comparison. Relationships of baseline 24-2 visual field (VF) mean deviation (MD) with wiVD/wiCD change rates were evaluated for POAG eyes., Results: There were 36, 57 and 79 eyes (25, 38 and 50 subjects) in healthy, GS and POAG groups, respectively. Rates of wiVD (range:-0.72 to -0.92 %/year) and wiCD (range:-0.28 to -0.66 %/year) loss were different from zero in all groups (p<0.05). The rates of wiCD loss differed across all diagnosis groups (p<0.001), while wiVD change rates did not increase when comparing healthy to GS eyes (p=0.167). Baseline VF MD showed a significant but modest correlation with the rates of both wiVD and wiCD loss (p<0.05), and the correlation with wiCD change rate was slightly stronger (R 2 =0.27 vs 0.16)., Conclusions: In glaucoma, there is earlier microvasculature loss in the ONH than in the macula. Moreover, ONH VD loss shows a slightly stronger association with baseline VF than macular VD. Observing ONH VD loss with OCTA may help to monitor early glaucoma, which should be confirmed by future larger studies., Competing Interests: Competing interests: SM reported grants from the National Eye Institute. TN is a consultant for Topcon. LMZ reported grants from the National Institutes of Health, National Eye Institute; grants from Heidelberg Engineering and nonfinancial support from Carl Zeiss Meditec, Optovue, Heidelberg Engineering and Topcon; and patents from Carl Zeiss Meditec and AiSight Health; cofounder and board member AiSight Health. LMZ is a consultant for Abbvie and Topcon Medical Systems. RNW is a consultant for Abbvie, Alcon, Allergan, Amydis, Editas, Equinox, Eyenovia, Iantrek, IOPtic, Implandata, iSTAR Medical, Nicox, Santen, Ten Point and Topcon. He receives grants from the National Eye Institute and National Institute of Minority Health Disparities and Research to Prevent Blindness (New York, NY). He reports patents licensed by UCSD to Toromedes and Carl Zeiss Meditec from UCSD; founder of Toromedes; all outside the submitted work. No other disclosures were reported., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to 1) investigate the association between papillomacular and papillofoveal bundle defects with 10-2 visual field (VF) sensitivity abnormalities, and 2) integrate the information from RNFL bundle defect and 24-2 VF central test locations to determine the likelihood of 10-2 VF sensitivity abnormalities., Design: Cross-sectional., Methods: A total of 841 eyes (144 healthy, 317 glaucoma suspect, and 380 glaucoma) of 442 participants were included. Eyes underwent 24-2, and 10-2 VF testing and OCT for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate, papillomacular, and papillofoveal bundles was determined for each eye. Multilevel logistic regression analysis was applied to evaluate the structure-function association., Results: Papillomacular (92.1%) and papillofoveal (37.9%) RNFL bundle defects were prevalent in eyes with glaucoma. A 10-2 VF location that was projected onto a papillomacular or a papillofoveal RNFL bundle defect had a significantly increased likelihood of reduced sensitivity (ORs of 18.61 at PDP < 5%, and 20.17 at TDP < 5%, respectively, P < .001 for both). When predicting the likelihood of VF abnormality in a 10-2 test location, noticeably higher odds ratios were observed when overlapping with an RNFL bundle defect, compared to when an abnormal corresponding 24-2 central point was present., Conclusions: Papillomacular and papillofoveal RNFL bundle defects are present in a considerable proportion of eyes with glaucoma. When detected, they significantly increase the likelihood of abnormality in the corresponding central VF test locations assessed by the 10-2 test., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Evaluation of central vision in glaucoma is important due to its impact on patients' quality of life and activities of daily living such as reading, driving, and walking. The 10-2 visual field (VF) assessment remains a mainstay in the functional analysis of central vision in glaucoma diagnosis and progression. However, it may be underutilized in clinical practice. Monitoring of disease progression especially in advanced cases, glaucoma evaluation in certain ocular disorders such as high myopia, disc hemorrhage, low corneal hysteresis, and certain optic disc phenotypes, as well as earlier detection of central VF damage, are certain conditions where additional monitoring with the 10-2 pattern may provide complementary clinical information to the commonly utilized 24-2 pattern. In addition, the development of artificial intelligence techniques may assist clinicians to most effectively allocate limited resources by identifying more risk factors to central VF damage. In this study, we aimed to determine specific patient characteristics that make central VF damage more likely and to assess the benefit of incorporating the 10-2 VF in various clinical settings., Competing Interests: Sasan Moghimi reported grants from the National Eye Institute. No other disclosures were reported., (Copyright: © 2024 Taiwan J Ophthalmol.)

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.

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.)

Background: Gastroesophageal Reflux Disease (GERD) is a common chronic condition. Its chronic nature may affect the pattern of medication use. This study aimed to investigate the prevalence, associated factors, and patterns of polypharmacy and medication use among GERD patients in southwestern Iran., Methods: We used data from the Pars Cohort Study. We classified drugs using the Anatomical Therapeutic Chemical classification system. The Lexicomp® database was used to assess potential drug-drug interactions. Multivariable Poisson regression was applied. Adjusted prevalence ratio (PR) and its 95% confidence interval (CI) were estimated., Results: A total of 9262 participants were included. Among 2,325 patients with GERD, age-standardized prevalence of polypharmacy was 9.5% (95% CI: 7.5%, 11.6%) in males, and 19.3% (95% CI: 17.2%, 21.4%) in females. The PR of experiencing Polypharmacy by GERD patients compared to non-GERD patients was 1.82 (95% CI: 1.61, 2.05%). Multimorbidity (PR: 3.33; CI: 2.66, 4.15), gender (PR: 1.68; CI: 1.30, 2.18), and metabolic syndrome (PR: 1.77; CI: 1.45, 2.15) were associated with polypharmacy among GERD patients. Drugs for acid-related disorders were the most common used drugs among men, women and elders. We found that 13.9%, 4.2%, and 1.1% of GERD patients had type C, D and X drug interactions, respectively., Conclusion: GERD is correlated with a higher prevalence of polypharmacy. Among GERD patients, females, those with multi-morbidities, and those with metabolic syndrome may be affected more by polypharmacy. Considering the fairly high rate of interactions identified, a review of the medication list is essential when approaching GERD patients, and physicians must check for medications that may worsen GERD., (© 2023. The Author(s).)

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 investigate the association of macular optical coherence tomography (OCT)/OCT angiography (OCTA) parameters with visual acuity (VA) in glaucoma., Methods: 144 pseudophakic primary open-angle glaucoma eyes were included. Foveal (fVD), parafoveal (pf), perifoveal (perifVD) and whole-image vessel densities (wiVD) of superficial and deep layers, and their corresponding ganglion cell complex (GCC) thicknesses were obtained from OCTA 6×6 mm 2 macula scans. Foveal avascular zone (FAZ) area, FAZ circumference and foveal density-300 (FD300) were measured. Correlation between OCT/OCTA parameters and Logarithm of the Minimum Angle of Resolution VA (logMAR VA) in early and moderate-advanced glaucoma was evaluated with age and Signal Strength Index-adjusted mixed models. Area under receiver operating characteristic (AUC) was used to evaluate discriminative power of OCT/OCTA for decreased VA (<20/25)., Results: In early glaucoma (80 eyes), no parameter correlated with VA. In moderate-advanced glaucoma (64 eyes), greater FAZ area (β=0.228) and circumference (β=0.063) correlated with worse VA (p<0.05), but not FD300. fThinner sectoral and global GCC was associated with worse VA (β=0.002-0.003, p<0.05), except for inferior hemifield perifGCC and wiGCC. For VD, lower superior hemifield superficial perifVD and wiVD (β=0.007-0.008) and deep fVD (β=0.004) correlated with worse VA (p<0.05). OCT/OCTA parameters showed modest ability to discriminate decreased VA, with the superior hemifield performing better than the inferior hemifield. In early glaucoma, GCC and VD showed similar discrimination (AUC=0.67-0.77). In moderate-advanced glaucoma, fGCC and pfGCC yielded higher AUC (0.75-0.81) than VD (AUC=0.63-0.72)., Conclusions: Some macular OCT/OCTA parameters were associated with VA in moderate-advanced, but not early glaucoma. These structural parameters may help identify glaucoma patients with impaired vision and reduced quality of life., Trial Registration Number: NCT00221897., Competing Interests: Competing interests: LMZ reported grants from the National Eye Institute; grants and nonfinancial support from Heidelberg Engineering, non-financial support from Carl Zeiss Meditec, Optovue and Topcon. RNW reported nonfinancial support from Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Centervue and Topcon; grants from the National Eye Institute; personal fees from Abbvie, Aerie Pharmaceuticals, Allergan, Equinox, Nicox, and Topcon; 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 factors associated with choroidal microvasculature drop-out (MvD) enlargement detected by optical coherence tomography angiography (OCT-A) in glaucomatous eyes., Methods: Ninety-one eyes of 68 primary open-angle glaucoma patients were enrolled. Only eyes with a minimum of four good quality OCT-A and OCT scans of the optic nerve head acquired at least and with a minimum of 2 years follow-up were included. Area and angular circumference of MvD were analysed on en face images. Univariable and multivariable mixed effects models were constructed to identify the factors contributing to MvD area and angular circumference change over time., Results: Peripapillary MvD was detected in 53 (58.2%) eyes at baseline and in an additional 17 (18.6%) eyes during follow-up, whereas MvD was not detected in 21 (23.0 %) eyes during the entire follow-up period. In multivariable analysis, worse baseline visual field (VF) mean deviation (MD) (ß=0.27, 95% CI 0.10 to 0.44, p=0.002), greater intraocular pressure (IOP) fluctuations (ß=0.86, 95% CI 0.24 to 1.48, p=0.007), higher peak IOP (ß=0.17, 95% CI -0.01 to 0.35, p=0.067) and greater number of IOP lowering medications (ß=1.36, 95% CI 0.67 to 2.05, p<0.001) were associated with faster MvD area enlargement. Worse baseline VF MD and greater IOP fluctuation were also associated with significantly faster MvD circumferential enlargement in multivariable models., Conclusion: Greater IOP fluctuation, higher peak IOP, worse baseline VF MD and greater number of glaucoma medications were significantly associated with MvD enlargement in glaucomatous eyes. The identification of factors associated with MvD enlargement may improve our understanding of the role of choroidal vasculature in glaucoma., Competing Interests: Competing interests: LMZ: National Eye Institute (F), Carl Zeiss Meditec (F), Heidelberg Engineering (F), OptoVue (F, R), Topcon Medical Systems (F, R) Merck (C); Robert N. Weinreb: Allergan (C), Eyenovia (C), Topcon (C), Heidelberg Engineering (F), Carl Zeiss Meditec (F), Konan (F), OptoVue (F), Topcon (F), Centervue (F)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the association between baseline severity of visual field (VF) damage and the initial rates of VF progression with quality of life (QOL) outcomes over an extended follow-up in glaucoma., Design: Retrospective cohort study., Methods: Both eyes of 167 glaucoma or suspected glaucoma patients were followed for 10.0±0.3 years. The National Eye Institute Visual Function Questionnaire (NEI-VFQ)-25 was performed at the end of the follow-up. Separate linear regression models included the VF parameters of the better eye, the worse eye, and the central and peripheral points of the integrated binocular VF to evaluate the association of baseline and initial rates of change of VF parameters (first half of the follow-up) with NEI-VFQ-25 Rasch-calibrated disability scores over an extended follow-up., Results: All models demonstrated association of worse baseline severity of VF damage with worse subsequent NEI-VFQ-25 scores. Faster rates of decline in VF mean deviation of the better eye and the mean sensitivity of the central and peripheral test locations of the integrated binocular VF were significantly associated with worse subsequent NEI-VFQ-25 scores. VF parameters of the better eye performed better than those of the worse eye (R 2 of 0.21, and 0.15, respectively), and the VF parameters of the central test locations performed better than those of the peripheral test locations (R 2 of 0.25, and 0.20, respectively)., Conclusions: Baseline severity and initial rates of change of VF damage are associated with QOL outcomes over an extended follow-up. Assessment of longitudinal VF changes, especially in better eye, provides prognostic utility to identify glaucoma patients at a higher risk for developing disease-related disability., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To compare visual acuity (VA) changes using standardized ETDRS best-corrected visual acuity (BCVA) and nonstandardized Snellen VA among subjects enrolled in clinical trials., Design: Retrospective study., Participants: Patients enrolled in prospective clinical trials at 3 urban retina practices., Methods: Best available Snellen VA at the clinic visit before study entry and after exit were compared with the ETDRS BCVA at trial entry and exit. The correlation and discrepancies between Snellen VA and ETDRS methods as well as the VA changes from trial entry to exit were evaluated., Main Outcome Measures: The discrepancy between VA change from trial entry to exit using Snellen VA versus ETDRS BCVA methods., Results: A total of 273 eyes were included. The mean (standard deviation [SD]) Snellen VA was 58.1 (20) ETDRS-equivalent letters (Snellen 20/69) at the clinic visit before trial entry and 61.6 (21) ETDRS-equivalent letters (Snellen 20/59) at the visit after trial exit. The mean (SD) ETDRS BCVA was 65.5 (16) letters (Snellen 20/49) at trial entry and 70.5 (17) letters (Snellen 20/39) at trial exit. The mean VA change from trial entry to exit was not significantly different for ETDRS (5 letters of vision gain) compared with Snellen (3.6 letters of vision gain) methods ( P  = 0.061). Eyes with baseline Snellen VA 20/50 or worse gained significantly more letters using Snellen (9.3 ± 22.3 letters) compared with ETDRS (5.2 ± 18.7 letters; P  = 0.012). Among eyes with baseline Snellen VA of > 20/50, VA gain was significantly greater with the ETDRS method (4.9 ± 12.3 letters) compared with Snellen (-1.5 ± 12.3 letters; P < 0.001)., Conclusions: The mean VA change from clinical trial entry to exit was similar between the ETDRS and Snellen methods. However, among patients with worse baseline Snellen vision, the magnitude of VA change was greater with Snellen compared with ETDRS, whereas among those with better baseline vision, this magnitude was greater with the ETDRS method. Understanding the proportion of the study population with varying VA levels may have implications for interpreting VA outcomes from retrospective clinic-based studies compared with those reported in clinical trials., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2023 by the American Academy of Ophthalmology.)

Background/aims: To investigate the relationship between ganglion cell complex (GCC) thinning and baseline deep and superficial macular vessel density (VD) in glaucoma., Methods: 97 eyes of 69 primary open-angle glaucoma (POAG) and glaucoma suspect patients from the Diagnostics Innovations in Glaucoma Study with a minimum of 4 visits and 2 years of follow-up after baseline optical coherence tomography angiography (OCTA) examination were included. OCTA 3×3 mm 2 macular scans were acquired at each visit and used to calculate superficial and deep parafoveal VD (pfVD) and OCT-based parafoveal GCC (pfGCC) thickness. Association of baseline superficial and deep pfVD with pfGCC thinning rate was evaluated using linear mixed model., Results: The included subjects had a baseline mean visual field mean deviation (95% CI) of -2.9 (-3.7 to -2.1) dB and a mean follow-up period of 3.6 years. In the univariable model, lower baseline superficial pfVD and higher mean intraocular pressure (IOP) during follow-up were significantly associated with a faster pfGCC thinning rate (p<0.05 for all), while deep pfVD was not (p=0.177). In the multivariable model, faster pfGCC thinning was correlated with higher mean IOP during follow-up (β=-0.05, p=0.002) and lower baseline superficial pfVD (β=-0.04, p=0.011). Eyes with a baseline superficial pfVD in the lowest tertile (≤46%) had significantly faster pfGCC loss compared with eyes with baseline superficial pfVD greater than 46% (p=0.015)., Conclusion: Lower baseline superficial pfVD, but not deep pfVD, was associated with faster pfGCC thinning in glaucoma. Moreover, superficial macular VD may help predict central macula thinning in patients with glaucoma., Competing Interests: Competing interests: LMZ reported grants from the National Eye Institute; grants and nonfinancial support from Heidelberg Engineering, non-financial support from Carl Zeiss Meditec, Optovue, and Topcon. RNW reported nonfinancial support from Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Centervue and Topcon; grants from the National Eye Institute; personal fees from Allergan, Equinox, Nicox and Topcon; all outside the submitted work., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Prcis: Faster worsening of 10-2 visual field (VF) was associated with the development of visual acuity (VA) loss in mild-to-moderate glaucoma, suggesting longitudinal 10-2 VF change is associated with the risk of VA impairment., Purpose: To examine whether longitudinal 10-2 central VF change is associated with the risk of VA loss in glaucoma., Patients and Methods: Primary open angle glaucoma and glaucoma suspect eyes with ≥3 years and 5 visits of 10-2 VF examinations were included. Cox proportional hazard modeling with shared frailty was used to evaluate the hazard ratio (HR) of 10-2 VF mean deviation (MD), superior hemifield mean sensitivity (hemi-MS), and inferior hemi-MS worsening rates for developing VA loss, defined as a change in logMAR VA ≥95% test-retest variability., Results: Among the 252 eyes (148 participants, mean follow-up = 5.8 y), 30 eyes (21 participants, mean follow-up = 4.9 y) developed VA loss. There was no difference in baseline VF between eyes with and without VA loss ( P > 0.05). Eyes with VA loss showed faster 10-2 VF MD worsening [-0.39 (95% CI: -0.60, -0.18) dB/y] and hemi-MS decrease (range: -0.42~-0.38 dB/y), as compared with no-VA loss eyes [10-2 VF MD change = -0.11 (-0.16, -0.07) dB/y; hemi-MS change: -0.12~-0.07 dB/y; P < 0.05]. In the multivariable model, faster 10-2 VF MD worsening [HR (95% CI) = 4.05 (1.61, 10.22), per 1 dB/y faster], superior hemi-MS decrease [HR (95% CI) = 7.07 (2.48, 20.14), per 1 dB/y faster], and inferior hemi-MS decrease [HR (95% CI) = 8.32 (1.99, 34.91), per 1 dB/y faster] were all associated with increased risk of developing VA loss ( P < 0.05)., Conclusions: Faster 10-2 VF MD and hemifield MS worsening are associated with the development of VA loss. Monitoring the longitudinal central 10-degree VF change may suggest that there is impending VA impairment in glaucoma., Competing Interests: Disclosure: S.M. reported grants from the National Eye Institute. Takashi Nishida is a consultant for Topcon. J.M.L. is a consultant to Alcon, Allergan, Thea, Genetech. AdvanceSight, and Carl Zeiss Meditech. M.F. reported grants from the National Eye Institute; grants from Heidelberg Engineering and Topcon; nonfinancial support from Wolfram Research. C.A.G. reported research support from Heidelberg Engineering and Topcon. L.M.Z. reported grants from the National Eye Institute; grants from Heidelberg Engineering and nonfinancial support from Carl Zeiss Meditec, Optovue, Heidelberg Engineering, and Topcon; and patents from Carl Zeiss Meditec and AiSight Health. L.M.Z. is a consultant of Abbvie and Topcon. R.N.W. is a consultant of Abbvie, Allergan, Amydis, Equinox, Eyenovia, Iantrek, IOPtic, Implandata, Nicox, and Topcon. R.N.W. reported nonfinancial support from Heidelberg Engineering, Carl Zeiss Meditec, Optovue, Centervue, and Topcon; grants from the National Eye Institute, National Institute of Minority Health Disparities, and Research to Prevent Blindness, patents from Toromedes, Carl Zeiss Meditec to UCSD; all outside the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: To investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD)., Methods: POAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models., Results: Thirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes with MvD than in those without MvD (mean differences: -0.50 (95% CI -0.83 to -0.17) µm/year; p=0.003)). Presence of MvD, area and angular circumference of MvD were independently associated with a faster rate of thinning (p=0.002, p=0.031 and p=0.013, respectively)., Conclusion: In POAG eyes, GCC thinning is faster in eyes with MvD. Detection of MvD in OCT-A images can assist clinicians to identify patients who are at higher risk for central macula thinning and glaucomatous progression and may require more intensive management., Competing Interests: Competing interests: Acknowledgment/financial support: National Institutes of Health/National Eye Institute Grants R01EY029058, R01EY011008, R01EY026574, R01EY019869 and R01EY027510; Core Grant P30EY022589; by the donors of the National Glaucoma Research Program (no grant number); a programme of the BrightFocus Foundation Grant (G2017122); an Unrestricted Grant from Research to Prevent Blindness (New York, NY); UC Tobacco Related Disease Research Program (T31IP1511); and grants for participants’ glaucoma medications from Alcon, Allergan, Pfizer, Merck, and Santen. Financial Disclosures: Eleonora Micheletti: none; SM: none; TN: none; NE-N: none; MHS: none ; JAP: none ; AK: none; LMZ: National Eye Institute (F), Carl Zeiss Meditec (F), Heidelberg Engineering(F), OptoVue (F, R), Topcon Medical Systems Inc. (F, R) Merck (C); Robert N. Weinreb: Allergan (C), Eyenovia (C), Topcon (C), Heidelberg Engineering (F), Carl Zeiss Meditec (F), Konan (F), OptoVue (F), Topcon (F), Centervue (F)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To assess and compare long-term reproducibility of optic nerve head (ONH) and macula optical coherence tomography angiography (OCTA) vascular parameters and optical coherence tomography (OCT) thickness parameters in stable primary open-angle glaucoma (POAG), glaucoma suspect and healthy eyes., Methods: Eighty-eight eyes (15 healthy, 38 glaucoma suspect and 35 non-progressing POAG) of 68 subjects who had at least three visits within 1-1.5 years with OCTA and OCT imaging (Angiovue; Optovue, Fremont, California, USA) on the same day were included. A series of vascular and thickness parameters were measured including macular parafoveal vessel density (pfVD), ONH circumpapillary capillary density (cpCD), macular parafoveal ganglion cell complex (pfGCC) and ONH circumpapillary retinal nerve fibre layer (cpRNFL). A random effects analysis of variance model was used to estimate intraclass correlation (ICC) coefficients and long-term variability estimates., Results: ICC was lower for OCTA (pfVD 0.823 (95% CI 0.736 to 0.888) and cpCD 0.871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test-retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities., Conclusions: OCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change., Trial Registration Number: NCT00221897., 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 examine the epidemiology and factors of cannabis use among open-angle glaucoma (OAG) patients., Methods: In this cross-sectional study, OAG participants in the All of Us database were included. Cannabis ever-users were defined based on record of cannabis use. Demographic and socioeconomic data were collected and compared between cannabis ever-users and never-users using Chi-Square tests and logistic regression. Odds ratios (OR) of potential factors associated with cannabis use were examined in univariable and multivariable models., Results: Among 3723 OAG participants, 1436 (39%) were cannabis ever-users. The mean (SD) age of never-users and ever-users was 72.9 (10.4) and 69.2 (9.6) years, respectively (P < 0.001). Compared to never-users, Black (34%) and male (55%) participants were better represented in ever-users, while Hispanic or Latino participants (6%) were less represented (P < 0.001). Diversity was also observed in s ocioeconomic characteristics including marital status, housing security, and income/education levels. A higher percentage of ever-users had a degree ≥12 grades (91%), salaried employment (26%), housing insecurity (12%), and history of cigar smoking (48%), alcohol consumption (96%), and other substance use (47%) (P < 0.001). In the multivariable analysis, Black race (OR [95% CI] = 1.33 [1.06, 1.68]), higher education (OR = 1.19 [1.07, 1.32]), and history of nicotine product smoking (OR: 2.04-2.83), other substance use (OR = 8.14 [6.63, 10.04]), and alcohol consumption (OR = 6.80 [4.45, 10.79]) were significant factors associated with cannabis use. Increased age (OR = 0.96 [0.95, 0.97]), Asian race (OR = 0.18 [0.09, 0.33]), and Hispanic/Latino ethnicity (OR = 0.43 [0.27, 0.68]) were associated with decreased odds of use (P < 0.02)., Conclusions: This study elucidated the previously uncharacterized epidemiology and factors associated with cannabis use among OAG patients, which may help to identify patients requiring additional outreach on unsupervised marijuana use., (© 2023 The Authors.)

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.

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.)

Background: Although polypharmacy is considered a major predictor of irrational use of drugs, little is known about polypharmacy in developing regions. We aimed to indicate the prevalence and correlates of polypharmacy and to determine the medication profile at the population level in southern Iran., Methods: In this cross-sectional study, we analyzed data from participants of the Pars Cohort Study (PCS) (aged above 40 years, N=9269). Polypharmacy was defined as using five or more medications concurrently. A Poisson multivariable model was applied to estimate the adjusted prevalence ratios (APRs) of various risk factors. The Anatomical Therapeutic Chemical (ATC) classification system was used for classifying medications., Results: Prevalence of polypharmacy was 10.4%, (95% CI: 9.75; 11.08) and it was higher among females (15.0%), older adults (age≥65 years) (16.0%), and individuals with more than two chronic conditions (31%). Being female, educated, married, and not having a low socio-economic class were independently associated with a higher likelihood of polypharmacy. The most prevalent medications among female participants were sex hormones and modulators of the genital system (58.4%), drugs for acid-related disorders (14.6%), and anti-anemic preparations (13.6%,). On the other hand, males were using acid-related disorders (14.6%), anti-inflammatory and anti-rheumatic products (7.8%), and beta-blocking agents (6.3%)., Conclusion: The prevalence of polypharmacy in our sample was relatively low, especially among males. Cardiovascular drugs, acid suppressants, hormonal contraceptives, and anti-anemic preparations are drug classes with the highest contribution to polypharmacy., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

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.)

Background/aims: To investigate the relationship between the foveal avascular zone (FAZ) parameters assessed by optical coherence tomography angiography (OCTA) and central visual field parameters in glaucoma and healthy subjects., Methods: One hundred and eighty-eight subjects (248 eyes), including 24 healthy (38 eyes), 37 glaucoma suspect (42 eyes, and 127 primary open angle glaucoma (POAG) patients (168 eyes), underwent imaging using OCTA and standard automated perimetry using the 24-2 and 10-2 Swedish Interactive Thresholding Algorithm. OCTA-based and OCT-based FAZ parameters (superficial FAZ area, FAZ circumference), foveal vessel density (FD300) and foveal thickness were measured. The correlation between FAZ parameters and visual field parameters was assessed using linear mixed model., Results: Axial length adjusted-FAZ area was not different among the three groups (mean (95% CI)): in healthy 0.31 (0.27 to 0.36) mm 2 , glaucoma suspect 0.29 (0.26 to 0.31) mm 2 and POAG eyes 0.28 (0.27 to 0.30) mm 2 (p=0.578). FD300 was lower in glaucoma suspect 49.1% (47.9% to 50.4%) and POAG eyes 48.7% (48.1% to 49.4%) than healthy eyes 50.5% (49.3% to 51.7%) though the difference was not statistically significant (p=0.071). Lower FD300 was associated with worse 24-2 and 10-2 visual field mean deviation and foveal threshold in multivariable linear mixed models (all p<0.05). In addition, a smaller FAZ area was associated with lower intraocular pressure (IOP) (p=0.026)., Conclusions: The FD300, but not the FAZ area was correlated with 10° central visual field mean deviation and foveal threshold in healthy, glaucoma suspect and POAG eyes. In contrast, a smaller FAZ area was associated with lower IOP., Competing Interests: Competing interests: LMZ: Financial support (research instruments)—Heidelberg Engineering, Carl Zeiss Meditec, Optovue, Topcon; Robert N. Weinreb: Financial support (research instruments)—Heidelberg Engineering, Carl Zeiss Meditec, Konan Medical, Optovue, Centervue, Bausch & Lomb; Consultant—Aerie Pharmaceuticals, Allergan, Equinox, Eyenovia; Patent—Toromedes, Carl Zeiss Meditec., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in postmortem ocular specimens of patients with severe COVID-19 disease., Patients and Methods: Postmortem conjunctival (28 samples), aqueous humor (30 samples) and vitreous humor (30 samples) specimens were obtained bilaterally from the eyes of 15 deceased COVID-19 patients within one hour of death. The presence of viral RNA was evaluated in samples using Real-time reverse transcriptase-polymerase chain reaction (RT-PCR)., Results: Positive RT-PCR SARS-COV-2 results were found in one conjunctival and 2 vitreous humor samples. All aqueous humor samples tested negative for the presence of SARS-COV-2 RNA. Of note, three positive samples were obtained from three different patients. The overall prevalence of positive RT-PCR ocular samples was 3.4% among all samples and 20% at the patient level., Conclusion: SARS-CoV-2 RNA is detectable in postmortem conjunctival and vitreous humor samples of patients with severe COVID-19.

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.

Most studies aiming at unraveling the molecular events associated with cardiac congenital heart disease (CHD) have focused on the effect of mutations occurring in the nuclear genome. In recent years, a significant role has been attributed to mitochondria for correct heart development and maturation of cardiomyocytes. Moreover, numerous heart defects have been associated with nucleotide variations occurring in the mitochondrial genome, affecting mitochondrial functions and cardiac energy metabolism, including genes encoding for subunits of respiratory chain complexes. Therefore, mutations in the mitochondrial genome may be a major cause of heart disease, including CHD, and their identification and characterization can shed light on pathological mechanisms occurring during heart development. Here, we have analyzed mitochondrial genetic variants in previously reported mutational genome hotspots and the flanking regions of mt-ND1, mt-ND2, mt-COXI, mt-COXII, mt-ATPase8, mt-ATPase6, mt-COXIII, and mt-tRNAs ( Ile, Gln, Met, Trp, Ala, Asn, Cys, Tyr, Ser, Asp, and Lys ) encoding genes by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) in 200 patients with CHD, undergoing cardiac surgery. A total of 23 mitochondrial variations (5 missense mutations, 8 synonymous variations, and 10 nucleotide changes in tRNA encoding genes) were identified and included 16 novel variants. Additionally, we showed that intracellular ATP was significantly reduced ( P =0.002) in CHD patients compared with healthy controls, suggesting that the mutations have an impact on mitochondrial energy production. Functional and structural alterations caused by the mitochondrial nucleotide variations in the gene products were studied in-silico and predicted to convey a predisposing risk factor for CHD. Further studies are necessary to better understand the mechanisms by which the alterations identified in the present study contribute to the development of CHD in patients., (Copyright © 2022 Heidari et al.)

Patients with β-thalassemia major (β-TM) face a wide range of complications as a result of excess iron in vital organs, including the heart and liver. Our aim was to find the best predictive machine learning (ML) model for assessing heart and liver iron overload in patients with β-TM. Data from 624 β-TM patients were entered into three ML models using random forest (RF), gradient boost model (GBM), and logistic regression (LR). The data were classified and analyzed by R software. Four evaluation metrics of predictive performance were measured: sensitivity, specificity, accuracy, and area under the curve (AUC), operating characteristic curve. For heart iron overload, the LR had the highest predictive performance based on AUC: 0.68 [95% CI (95% confidence interval): 0.60, 0.75]. The GBM also had the highest specificity (69.0%) and accuracy (67.0%). Most sensitivity is also acquired with LR (75.0%). For liver iron overload, the highest performance based on AUC was observed with RF, AUC: 0.68 (95% CI: 0.59, 0.76). The RF showed the highest accuracy (66.0%) and specificity (66.0%), while the LR had the highest sensitivity (84.0%). Ferritin, duration of transfusion, and age were determined as the most effective predictors of iron overload in both heart and liver. Logistic regression LR was determined to be the strongest method to predict cardiac and RF values for liver iron overload in patients with β-TM. Older thalassemia patients with a high serum ferritin (SF) level and a longer duration of transfusion therapy were more prone to heart and liver iron overload.

Purpose: To investigate the relationship of longitudinal changes in macular vessel density (VD) from OCT angiography and in ganglion cell complex (GCC) from OCT with central visual field (VF) in eyes with early glaucoma., Design: Observational cohort., Participants: A total of 95 eyes, 37 preperimetric and 58 with early glaucoma (24-2 VF mean deviation [MD] ≥ -6 decibels), with an average follow-up of 3.8 years and 5.3 visits, were included., Methods: Whole-image VD (wiVD) and whole-image GCC (wiGCC) and parafoveal scans, as well as localized regions of interest (LROIs), hemiretinae of whole images, and superior, inferior, temporal, and nasal sectors of parafoveal maps, were matched with central VF locations. Age-adjusted rates of change of VD, GCC, mean sensitivity of VF locations, and 10-2 VF MD were calculated using linear mixed-effect models. Normalized rates of change were calculated for comparison of change rates in wiVD and wiGCC., Main Outcome Measures: Structure-function (SF) correlations of VD and GCC with central VF measurement change rates and comparison of different correlations of SF relationships after bootstrapping the difference of the correlation coefficients., Results: Vessel density loss and GCC thinning demonstrated significant correlations with central VF damage, globally and with most LROIs. The SF correlation (r, 95% confidence interval [CI]) between wiVD and 10-2 VF MD change rates was 0.42 [0.24, 0.58], whereas it was 0.27 [0.08, 0.45] between wiGCC and 10-2 VF MD changes rates (all P < 0.05). In contrast to GCC thinning, VD loss in the parafoveal sectors demonstrated significant correlations with central VF damage in inferior and temporal sectors. Differences in the relationship of SF with central VF damage were not significant between VD loss and GCC thinning. The mean (95% CI) normalized change rates of wiVD (-7.40 [-7.71 to 7.09] %/year) was faster than that of wiGCC (-2.39 [-2.94 to 1.84] %/year) (P < 0.05)., Conclusions: Rates of VD loss and GCC thinning are associated with central VF loss over time. Assessment of both macular VD and GCC thickness should be considered for evaluation of glaucoma progression., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.)

Background: Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran., Method: We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated., Results: Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57-4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07-2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00-1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30-1.53), high physical activity (PR: 0.66; 95% CI 0.45-0.95), use of opiate ever (PR: 0.46; 95% CI 0.26-0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12-0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs., Conclusion: Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial., (© 2022. The Author(s).)

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: To evaluate the role of corneal hysteresis (CH) as a risk factor of central visual field (VF) progression in a cohort of glaucoma suspect and glaucoma patients., Design: Prospective cohort study., Methods: Two hundred forty-eight eyes of 143 subjects who were followed for an average of 4.8 years with a minimum of 5 visits with 10-2 and 24-2 VF tests were included. Univariable and multivariable linear mixed-effects models were used to identify characteristics associated with the rate of change over time in 10-2 and 24-2 mean deviation (MD). Mixed-effects logistic regression was used to evaluate characteristics associated with an increased likelihood of event-based 10-2 VF progression based on the clustered pointwise linear regression criterion., Results: CH was significantly associated with 10-2 and 24-2 VF progression in the univariable trend-based analysis. In multivariable trend-based analyses, lower CH was associated with a faster rate of decline in 10-2 MD (0.07 dB/y per 1 mm Hg, P < .001) but not with 24-2 MD (P = .490). In multivariable event-based analysis, lower CH was associated with an increased likelihood of 10-2 VF progression (odds ratio = 1.35 per 1 mm Hg lower, P = .025). Similar results were found in eyes with early glaucomatous damage at the baseline (baseline: 24-2 MD ≥ -6 dB)., Conclusions: Lower CH was associated with a statistically significant, but relatively small, increased risk of central VF progression on the 10-2 test grid. Given the substantial influence of central VF impairment on the quality of life, clinicians should consider using CH to assess the risk of progression in patients with primary open-angle glaucoma including those with early disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Prcis: Face mask wearing has no significant effects on artifacts or vessel density measurements in optic nerve head (ONH) and macular optical coherence tomography-angiography (OCT-A) scans., Purpose: The aim was to assess the difference in area of artifacts observed in optical OCT-A scans with and without face mask wear and to verify if mask wear interferes with OCT-A vessel density measurements., Subjects and Controls: A total of 64 eyes of 10 healthy subjects, 4 ocular hypertensive, 8 glaucoma suspects, and 17 glaucoma patients were included., Materials and Methods: High-density ONH and macula OCT-A scans were obtained in patients with and without surgical masks. Seven different artifacts (motion, decentration, defocus, shadow, segmentation failure, blink, and Z-offset) were quantitatively evaluated by 2 trained graders. The changes in the area (% of scan area) of artifacts, without and with mask wearing, and differences of vessel density were evaluated., Results: Trends of increasing motion artifact area for the ONH scans [4.23 (-0.52, 8.98) %, P=0.08] and defocus artifact area for the macular scans [1.06 (-0.14, 2.26) %, P=0.08] were found with face mask wear. However, there were no significant differences in the mean % area of any artifacts (P>0.05 for all). Further, the estimated mean difference in vessel density in images acquired without and with masks was not significant for any type of artifact., Conclusion: Face mask wearing had no significant effect on area of artifacts or vessel density measurements. OCT-A vessel density measurements can be acquired reliably with face mask wear during the pandemic., Competing Interests: Disclosure: N.W.E.-N.: current employment at Topcon Healthcare, but all work related to the current manuscript was done before employment. L.M.Z.: F: National Eye Institute, Carl Zeiss Meditec Inc., Heidelberg Engineering GmbH, Optovue Inc., Topcon Medical Systems Inc. R.N.W.: F: National Eye Institute, Heidelberg Engineering, Carl Zeiss Meditec, Konan, Optovue, Topcon, Centervue. C: Aerie Pharmaceuticals, Alcon, Allergan, Bausch & Lomb, Equinox, Eyenovia. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Abdominal obesity is associated with increased risk of myocardial infarction and death events. Thus, obtaining data on the status of abdominal obesity is important in risk factor assessment and prevention of non-communicable diseases. This study aimed to evaluate the validity of using pictograms to classify abdominal obesity indices (waist circumference [WC], waist-hip ratio [WHR], and waist-height ratio [WHtR]) into normal and at-risk categories and determine the effects of demographic characteristics on this validity., Methods: This cross-sectional study used data from Pars Cohort Study (PCS). Participants chose the most similar pictogram scores to their body size at 15, 30 years, and current age. Optimal normal/at-risk cut-off values for pictograms were calculated using sensitivity/specificity plots. Receiver operating characteristic curves were used to evaluate the validity of pictograms. Validity measures were analyzed across different subgroups of demographic characteristics., Results: A total of 9263 participants (46% males) were included in the study. The estimated area under the curves were 84% for WC, 77% for WHR, and 89% for WHtR in males, and 84% for WC, 73% for WHR, and 90% for WHtR in females. Optimal pictogram cutoffs to classify central obesity for WC, WHR, and WHtR were 4, 4, and 5 in males and 4, 4, and 6 in females, respectively. The majority of demographic characteristics were not associated with the validity of pictograms., Conclusion: Using pictograms to determine normal and at-risk categories of abdominal obesity indices is valid among adult population with a wide range of demographic characteristics. However, the results need to be interpreted with caution in those with a positive history of weight fluctuation., (© 2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Purpose: To compare measurements of global and regional circumpapillary capillary density (cpCD) with retinal nerve fiber layer (RNFL) thickness and characterize their relationship with visual function in early primary open-angle glaucoma (POAG)., Design: Cross-sectional study., Participants: Eighty healthy eyes, 64 preperimetric eyes, and 184 mild POAG eyes from the Diagnostic Innovations in Glaucoma Study., Methods: Global and regional RNFL thickness and cpCD measurements were obtained using OCT and OCT angiography (OCTA). For direct comparison at the individual and diagnostic group level, RNFL thickness and capillary density values were converted to a normalized relative loss scale., Main Outcome Measures: Retinal nerve fiber layer thickness and cpCD normalized loss at the individual level and diagnostic group. Global and regional areas under the receiver operating characteristic curve (AUROC) for RNFL thickness and cpCD to detect preperimetric glaucoma and glaucoma, R 2 for the strength of associations between RNFL thickness function and capillary density function in diagnostic groups., Results: Both global and regional RNFL thickness and cpCD decreased progressively with increasing glaucoma severity (P < 0.05, except for temporal RNFL thickness). Global and regional cpCD relative loss values were higher than those of RNFL thickness (P < 0.05) in preperimetric glaucoma (except for the superonasal region) and glaucoma (except for the inferonasal and superonasal regions) eyes. Race, intraocular pressure (IOP), and cpCD were associated with greater cpCD than RNFL thickness loss in early glaucoma at the individual level (P < 0.05). Global measurements of capillary density (whole image capillary density and cpCD) had higher diagnostic accuracies than RNFL thickness in detecting preperimetric glaucoma and glaucoma (P < 0.05; except for cpCD/RNFL thickness comparison in glaucoma [P = 0.059]). Visual function was significantly associated with RNFL thickness and cpCD globally and in all regions (P < 0.05, except for temporal RNFL thickness-function association [P = 0.070])., Conclusions: Associations between capillary density and visual function were found in the regions known to be at highest risk for damage in preperimetric glaucoma eyes and all regions of mild glaucoma eyes. In early glaucoma, capillary density loss was more pronounced than RNFL thickness loss. Individual characteristics influence the relative magnitudes of capillary density loss compared with RNFL thickness loss. Retinal nerve fiber layer thickness and microvascular assessments are complementary and yield valuable information for the detection of early damages seen in POAG., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association of macular superficial vessel density (SVD) and projection-resolved deep vessel density (DVD) with past visual field (VF) progression in patients with primary open-angle glaucoma., Design: Retrospective cohort., Methods: In this longitudinal study, 208 eyes of 147 patients with glaucoma from the Diagnostics Innovations in Glaucoma Study were included. Eligible participants were required to have at least five 24-2 VF tests over a minimum follow-up period of 3 years before macular optical coherence tomography angiography imaging. VF progression was defined based on both event-based pointwise linear regression and trend-based methods. The association of macular SVD and DVD with the probability and rate of past VF progression was evaluated using a linear mixed effects model., Results: Fifty-two (25%) eyes had VF progression based on the pointwise linear regression based criterion at the end of a mean ± standard deviation follow-up duration of 6.9 ± 1.2 years. In the event-based multivariable analysis, a lower baseline SVD was associated with a higher likelihood of past VF progression (odds ratio per 1% lower. 1.28; 95% confidence interval, 1.02-1.59). Similarly, in the trend-based multivariable analysis, lower macular SVD was associated with a faster past rate of mean deviation decline (coefficient = -0.03 dB/year; 95% confidence interval, -0.04 to -0.01). Event-based and trend-based analyses found no significant associations for macular DVD with the likelihood/rate of past VF progression (P > .05)., Conclusions: Lower macular SVD, and not DVD, was associated with a higher probability of past VF progression. Macular optical coherence tomography angiography imaging shows promise for identifying eyes at risk of VF progression in patients with glaucoma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Rapid vessel density loss during an initial follow-up period may be associated with the rates of visual field loss over time., Objectives: To evaluate the association between the rate of vessel density loss during initial follow-up and the rate of visual field loss during an extended follow-up period in patients suspected of having glaucoma and patients with primary open-angle glaucoma., Design, Setting, and Participants: This retrospective cohort study assessed 124 eyes (86 with primary open-angle glaucoma and 38 suspected of having glaucoma) of 82 patients who were followed up at a tertiary glaucoma center for a mean of 4.0 years (95% CI, 3.9-4.1 years) from January 1, 2015, to February 29, 2020. Data analysis for the current study was undertaken in March 2021., Main Outcomes and Measures: The rate of vessel density loss was derived from macular whole-image vessel density values from 3 optical coherence tomography angiography scans early during the study. The rate of visual field loss was calculated from visual field mean deviation during the entire follow-up period after the first optical coherence tomography angiography visit. Linear mixed-effects models were used to estimate rates of change., Results: A total of 124 eyes from 82 patients (mean [SD] age, 69.2 [10.9] years; 41 female [50.0%] and 41 male [50.0%]; and 20 African American [24.4%], 10 Asian [12.2%], 50 White [61.0%], and 2 other race or ethnicity [2.4%]) were assessed. The annual rate of vessel density change was -0.80% (95% CI, -0.88% to -0.72%) during a mean initial follow-up of 2.1 years (95% CI, 1.9-2.3 years). Eyes with annual rates of vessel density loss of -0.75% or greater (n = 62) were categorized as fast progressors, and eyes with annual rates of less than -0.75% (n = 62) were categorized as slow progressors. The annual rate of visual field loss was -0.15 dB (95% CI, -0.29 to -0.01 dB) for the slow optical coherence tomography angiography progressors and -0.43 dB (95% CI, -0.58 to -0.29 dB) for the fast optical coherence tomography angiography progressors (difference, -0.28 dB; 95% CI, -0.48 to -0.08 dB; P = .006). The fast optical coherence tomography angiography progressor group was associated with the faster overall rate of visual field loss in a multivariable model after adjusting to include concurrent visual field mean deviation rate (-0.17 dB; 95% CI, -0.33 to -0.01 dB; P = .04)., Conclusions and Relevance: The findings of this cohort study suggest that faster vessel density loss during an initial follow-up period was associated with faster concurrent and subsequent rates of visual field loss during an extended period.

Purpose: To compare convolutional neural network (CNN) analysis of en face vessel density images to gradient boosting classifier (GBC) analysis of instrument-provided, feature-based optical coherence tomography angiography (OCTA) vessel density measurements and OCT retinal nerve fiber layer (RNFL) thickness measurements for classifying healthy and glaucomatous eyes., Design: Comparison of diagnostic approaches., Methods: A total of 130 eyes of 80 healthy individuals and 275 eyes of 185 glaucoma patients with optic nerve head (ONH) OCTA and OCT imaging were included. Classification performance of a VGG16 CNN trained and tested on entire en face 4.5 × 4.5-mm radial peripapillary capillary OCTA ONH images was compared to the performance of separate GBC models trained and tested on standard OCTA and OCT measurements. Five-fold cross-validation was used to test predictions for CNNs and GBCs. Areas under the precision recall curves (AUPRC) were calculated to control for training/test set size imbalance and were compared., Results: Adjusted AUPRCs for GBC models were 0.89 (95% CI = 0.82, 0.92) for whole image vessel density GBC, 0.89 (0.83, 0.92) for whole image capillary density GBC, 0.91 (0.88, 0.93) for combined whole image vessel and whole image capillary density GBC, and 0.93 (0.91, 095) for RNFL thickness GBC. The adjusted AUPRC using CNN analysis of en face vessel density images was 0.97 (0.95, 0.99) resulting in significantly improved classification compared to GBC OCTA-based results and GBC OCT-based results (P ≤ 0.01 for all comparisons)., Conclusion: Deep learning en face image analysis improves on feature-based GBC models for classifying healthy and glaucoma eyes., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To investigate longitudinal changes in rates of optic nerve head circumpapillary retinal nerve fiber layer (cpRNFL) thinning and vessel density loss in patients with primary open-angle glaucoma with or without a history of disc hemorrhage (DH)., Design: Observational cohort., Methods: In this longitudinal study, 34 eyes with DH and 134 eyes without DH that had ≥1.5 years of follow-up and 3 optical coherence tomography and optical coherence tomography angiography follow-up scans were enrolled. A linear mixed-effects model was used to compare the rates of cpRNFL thinning and vessel density loss between DH and non-DH eyes., Results: Rates of whole image capillary density loss were faster in the DH group compared with the non-DH group (mean difference [95% confidence interval] -0.32% [-0.59% to -0.04%] per year; P = .027). Faster mean rates of vessel density loss were found in the inferotemporal, inferonasal, and nasal sectors in eyes with DH than without DH (P < .05). There was no statistically significant difference in the global rate of cpRNFL thinning between the 2 groups (P = .679). The mean rate of cpRNFL thinning was faster in the DH group compared with the non-DH group only in the inferotemporal sector (mean difference [95% confidence interval] -1.01 μm (-1.62 μm to -0.40 μm) per year; P = .001)., Conclusions: Mean rates of vessel density loss between DH and non-DH eyes were different not only in the affected area but also in the other regions. In contrast, a significant difference in cpRNFL thinning between the 2 groups was detected only in the inferotemporal sector. Disc hemorrhage is an independent predictor of faster vessel density loss in glaucoma suspects and patients with primary open-angle glaucoma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To characterize the change of ganglion cell complex (GCC) thickness and macular vessel density in glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON)., Design: Prospective, longitudinal study., Participants: Eight-three eyes (24 healthy, 30 OHT, and 29 GON) of 65 patients who underwent at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years., Methods: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3 × 3-mm 1 GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using a linear mixed-effects model., Main Outcome Measures: Change rates of macula GCC thickness and superficial vessel density., Results: Significant mean rates of both GCC thinning and vessel density loss were detectable in OHT and GON groups. Of the individual suspect eyes, 49.1% showed significant loss (P < 0.05) with either vessel density or GCC thickness. Of the GON eyes, 31.0% showed both significant GCC loss and vessel density loss, 51.7% showed only significant GCC loss, whereas 17.2% showed only significant vessel density loss. Vessel density loss was faster than GCC thinning in half of the suspect eyes based on percent loss analysis. The age and scan quality-adjusted GCC thinning rates of the OHT group (-0.59 μm/year; P = 0.025) and GON group (-0.79 μm/year; P = 0.058) were faster than those of the healthy group (-0.11 μm/year), whereas the rate of vessel density loss was not significantly different among the diagnostic groups (all P > 0.2). Higher mean intraocular pressure during follow-up was associated with faster GCC thinning in the OHT group (P = 0.065) and GON groups (P = 0.015), but was not associated with the rate of vessel density decrease., Conclusions: Whereas the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes showed significant loss of vessel density and faster vessel density loss than GCC thinning. OCT and OCTA are complementary and useful for evaluating eyes with OHT or GON., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the superficial vascular density of the optic nerve head in different stages of pseudoexfoliation disease using optical coherence tomography angiography (OCTA)., Methods: In this cross-sectional study, 57 normal eyes, 41 eyes with pseudoexfoliation syndrome (PXS), 82 eyes with pseudoexfoliation glaucoma (PXG) and 27 non-glaucomatous fellow eyes of PXG (NL-PXG) that had OCTA were included. Circumpapillary RNFL (cpRNFL) thickness and circumpapillary capillary density (cpCD) were compared among the groups after adjusting for confounders using linear-mixed model., Results: PXG eyes had thinner global RNFL and lower cpCD (74.2±14.3 µm and 36.7±10.0%) than control (103.3±8.6 µm and 52.5±2.3%), PXS (96.8±8.8 µm and 51.5±2.3%), and NL-PXG eyes (96.3±11.1 µm and 50.1±3.9%) (p<0.001). After adjustment for age, gender and signal strength index, global cpRNFL thickness was comparable among control, PXS and NL-PXG. NL-PXG had the lowest cpCD (p=0.045) and sectoral cpCD compared to PXS and control eyes. Although cpCD was comparable between control and PXS (p=0.425) eyes, sectoral differences (p=0.009 and 0.004, for inferonasal and temporal-inferior cpCD, respectively) were detectable between the two groups. AUROC for differentiating NL-PXG eyes from normal were better for cpCD (0.78) compared to cpRNLF (0.69)., Conclusions: OCTA can detect reduced capillary density before significant changes in cpRNFL in fellow eyes of PXG patients. This can enable earlier detection of glaucomatous loss in pseudoexfoliation disease and enhance management of the disease., Competing Interests: Competing interests: Weinreb: Aerie Pharmaceuticals (C), Alcon (C), Allergan (C), Bausch & Lomb (C), Eyenovia (C), Unity (C), Heidelberg Engineering (F), Carl Zeiss Meditec (F), Genentech (F), Konan (F), OptoVue (F), Topcon (F), Optos (F), Centervue (F). Rao HL: Santen (C), Carl Zeiss Meditec (C), Allergan (C). Others: none., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)