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.

Smoking Intensity is Associated with Progressive Optic Nerve Head Vessel Density loss in Glaucoma.

PURPOSE: To investigate the relationship of smoking and smoking intensity, with the rate of optic nerve head (ONH) whole image capillary density (wiCD) loss in primary open angle glaucoma (POAG) and glaucoma suspect patients. METHODS: In this longitudinal study, POAG patients who had at least 2 years of follow-up and optical coherence tomography angiography (OCTA) performed at a minimum of 4 visits were selected for study. The smoking intensity was calculated as the pack-year at the baseline OCTA. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of wiCD loss over time. Nonlinear least-squares estimation with piecewise regression model was used to investigate the cutoff point for the relationship between wiCD loss and smoking intensity. RESULTS: 164 eyes (69 glaucoma suspect and 95 POAG) of 110 patients were included with a mean (95% CI) follow-up of 4.0 (3.9 to 4.1) years. Of the 110 patients, 50 (45.5%) had a reported history of smoking. Greater smoking intensity was associated with faster wiCD loss (-0.11 (-0.23 to 0.00)) %/year per 10 pack-year higher; P=0.048) after adjusting for covariates. The wiCD thinning became significantly faster when smoking intensity was greater than 22.2 pack-years. Smoking had no effect on the rate of wiCD thinning in patients who smoked < 22.2 pack-years during their lifetime. CONCLUSIONS: A history of greater smoking consumption was associated with faster vessel density loss, suggesting smoking intensity as a potential risk factor for glaucoma.

Association of Long-Term Intraocular Pressure Variability and Rate of Ganglion Complex Thinning in Patients With Glaucoma.

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

Time to Glaucoma Progression Detection by Optical Coherence Tomography in Individuals of African and European Descents.

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

Detection and agreement of event-based OCT and OCTA analysis for glaucoma progression.

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

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.

Impact of smoking on glaucoma.

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

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.

Prediction of Central Visual Field Measures From Macular OCT Volume Scans With Deep Learning.

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

Associations of smoking and alcohol consumption with the development of open angle glaucoma: a retrospective cohort study.

OBJECTIVES: To investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma. DESIGN: A retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). SETTING: Three tertiary glaucoma centres in the USA. PARTICIPANTS: 825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies. OUTCOME MEASURES: Development of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time. RESULTS: VF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years). CONCLUSION: Alcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people. TRIAL REGISTRATION NUMBER: NCT00221897 and NCT00221923.

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.

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.

Comparison of Ganglion Cell Layer and Ganglion Cell/Inner Plexiform Layer Measures for Detection of Early Glaucoma.

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

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.

Risk factors for microcystic macular oedema in glaucoma.

BACKGROUND/AIMS: To identify clinical characteristics and factors associated with microcystic macular edema (MME) in patients with primary open-angle glaucoma (POAG). METHODS: We included 315 POAG eyes between 2010 and 2019 with good-quality macular volume scans that had reliable visual fields (VF) available within 6 months in this observational retrospective cohort study. Eyes with retinal pathologies except for epiretinal membrane (ERM) were excluded. The inner nuclear layer was qualitatively assessed for the presence of MME. Global mean deviation (MD) and Visual Field Index (VFI) decay rates, superior and inferior MD rates and pointwise total deviation rates of change were estimated with linear regression. Logistic regression was performed to identify baseline factors associated with the presence of MME and to determine whether MME is associated with progressive VF loss. RESULTS: 25 out of 315 eyes (7.9%) demonstrated MME. The average (±SD) age and MD in eyes with and without MME was 57.2 (±8.7) versus 62.0 (±9.9) years (p=0.02) and -9.8 (±5.7) versus -4.9 (±5.3) dB (p<0.001), respectively. Worse global MD at baseline (p=0.001) and younger age (p=0.02) were associated with presence of MME. ERM was not associated with the presence of MME (p=0.84) in this cohort. MME was not associated with MD and VFI decay rates (p>0.49). CONCLUSIONS: More severe glaucoma and younger age were associated with MME. MME was not associated with faster global VF decay in this cohort. MME may confound monitoring of glaucoma with full macular thickness.

Effect of Corneal Hysteresis on the Rates of Microvasculature Loss in Glaucoma.

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.