Rate of Initial Optic Nerve Head Capillary Density Loss and Risk of Visual Field Progression.

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.

Racial Differences in the Diagnostic Accuracy of OCT Angiography Macular Vessel Density for Glaucoma.

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.

Deep Learning Estimation of 10-2 Visual Field Map Based on Macular Optical Coherence Tomography Angiography Measurements.

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 R2 (squared Pearson correlation coefficients) of the estimated and actual VF values. RESULTS: DL models predicting 10-2 MD achieved R2 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 R2 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.

Polypharmacy and pattern of medication use among patients with gastroesophageal reflux disease: results from Pars Cohort study.

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.

Prevalence and secular trends of four causes of blindness and visual impairment in Iran (1990-2019): a comparative study based on the Global Burden of Disease project's data.

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.

Prevalence and Correlates of Polypharmacy, and Drug Utilization Pattern in a Semi-urban Population: Results from the Pars Cohort Study.

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.

Association Between Longitudinal 10-2 Central Visual Field Change and the Risk of Visual Acuity Loss in Mild-to-Moderate Glaucoma.

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.

Epidemiology and factors associated with cannabis use among patients with glaucoma in the All of Us Research Program.

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 socioeconomic 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.

Progressive Visual Field Loss and Subsequent Quality of Life Outcomes in Glaucoma.

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 (R2 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 (R2 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.

Association of Rates of Ganglion Cell and Inner Plexiform Thinning With Development of Glaucoma in Eyes With Suspected Glaucoma.

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.

Association Between Rate of Ganglion Cell Complex Thinning and Rate of Central Visual Field Loss.

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.

Vision-Related Quality of Life Among Healthy, Preperimetric Glaucoma, and Perimetric Glaucoma Patients.

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 R2 = 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 R2 = 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.

Deep Learning Estimation of 10-2 Visual Field Map Based on Circumpapillary Retinal Nerve Fiber Layer Thickness Measurements.

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 (CNNA) and temporal-sectors (CNNT) 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 CNNA 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 LRA model. CONCLUSIONS: The proposed CNNA 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.

Combining Optical Coherence Tomography and Optical Coherence Tomography Angiography Longitudinal Data for the Detection of Visual Field Progression in Glaucoma.

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.

Factors associated with choroidal microvascular dropout change.

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.

Central macular OCTA parameters in glaucoma.

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) mm2, glaucoma suspect 0.29 (0.26 to 0.31) mm2 and POAG eyes 0.28 (0.27 to 0.30) mm2 (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.

Effect of Testing Frequency on the Time to Detect Glaucoma Progression With Optical Coherence Tomography (OCT) and OCT Angiography.

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.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in the Human Eye.

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.

Correlation of ganglion cell complex thinning with baseline deep and superficial macular vessel density in glaucoma.

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 mm2 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 (ß=-0.05, p=0.002) and lower baseline superficial pfVD (ß=-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.

Relationship of macular ganglion cell complex thickness to choroidal microvasculature drop-out in primary open-angle glaucoma.

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.