Reference Database for a Novel Binocular Visual Function Perimeter: A Randomized Clinical Trial.

Purpose: To construct a comprehensive reference database (RDB) for a novel binocular automated perimeter. Design: A four-site prospective randomized clinical trial. Subjects and Controls: Three hundred fifty-six healthy subjects without ocular conditions that might affect visual function were categorized into 7 age groups. Methods: Subjects underwent comprehensive ocular examination of both eyes before enrollment. Using the TEMPO/IMOvifa automated perimeter (Topcon Healthcare/CREWT Medical Systems), each subject completed 4 binocular threshold visual field (VF) tests during a single visit: First, practice 24-2 and 10-2 tests were obtained from both eyes. Next, study 24-2 and 10-2 tests were obtained from both eyes. Test order of each sequence was randomized, and the tests were conducted under standard automated perimetry testing conditions: Goldmann stimulus size III, 3183 cd/m2 maximum stimulus intensity, and background intensity of 10 cd/m2, using AIZE-Rapid test strategy. Standard VF reliability indices were assessed. For each subject, 24-2 and 10-2 test results from 1 randomly selected eye were analyzed. Main Outcome Measures: Perimetric threshold sensitivity and reference limits for each test analysis parameter. Results: The ages of the study cohort were widely distributed, with a mean age (standard deviation [SD]) of 52.3 (18.5) years. Sex assignment was 44.0% male and 56.0% female. The majority of subjects self-identified as White (67.4%), followed by Black or African American (13.5%) and Asian (8.7%), with 14.6% self-identified as Hispanic or Latino ethnicity. Mean sensitivity (SD) was 29.1 (1.3) decibels (dB) for the 24-2 and 32.4 (1.0) dB for the 10-2 test. For the 24-2 and 10-2, mean sensitivity (SD) age-related changes averaged -0.06 (0.01) dB and -0.05 (0.01) dB per year, respectively. The normal range of pointwise threshold sensitivity increased with eccentricity and showed asymmetry around the mean, particularly notable in the 24-2 test. Mean (SD) binocular test duration was 3.18 (0.38) minutes (1 minute 35 seconds per eye) for the 24-2 test and 3.58 (0.43) minutes (1 minute 47 seconds per eye) for the 10-2 test. Conclusions: An RDB for the TEMPO/IMOvifa perimeter was established, highlighting the significance of considering both age and stimulus eccentricity in interpreting threshold VF test results. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Analysis of immune checkpoint inhibitors for advanced non-small cell lung cancer in patients receiving antacids.

BACKGROUND: Proton pump inhibitors (PPIs) are reported to decrease the efficacy of immune checkpoint inhibitors (ICIs), but there are few reports on the association between ICI efficacy and antacids other than PPIs, and simultaneous examination of the effects of antacids, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) on ICI therapy. METHODS: We conducted a retrospective study of 381 patients with non-small cell lung cancer who received ICI therapy from January 1, 2016 to December 31, 2022. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Antacids included histamine type 2 receptor antagonists (H2RAs), PPIs, and potassium-competitive acid blockers (P-CABs). RESULTS: Antacids were administered to 218 patients, including 168 with PPIs, 37 with P-CABs, and 13 with H2RAs. Patients with antacids had worse median PFS and OS than those without antacids (PFS, 2.9 vs. 6.2 months; OS, 12.3 vs. 24.0 months), and those with PPIs, P-CABs, or H2RAs had similar results. However, there were no significant differences between patients with and without antacids when stratified by corticosteroid and NSAID use. Multivariate analyses showed that corticosteroids and NSAIDs administered for cancer-associated symptoms were related to poor prognosis, but antacids including PPIs, P-CABs, or H2RAs were not related. CONCLUSIONS: Antacids were not related to ICI efficacy when NSAIDs or corticosteroids were taken into consideration. This may be because the most frequent reason for administering NSAIDs and corticosteroids was cancer-associated symptoms, which are a poor prognostic factor, and most of the patients treated with these medications also received antacids.

Time to glaucoma progression detection by optical coherence tomography and visual field in glaucoma individuals of African descent.

PURPOSE: To examine the time to glaucoma progression detection by retinal nerve fiber layer thickness (RNFLT) and visual field (VF) among African descent (AD) individuals. DESIGN: Retrospective cohort study. METHODS: Setting: Multi-center. STUDY POPULATION: We included AD glaucoma eyes from DIGS/ADAGES with ≥2-year/5-visits of optic nerve head RNFLT and 24-2 VF examinations. Intervention or Observation Procedure: Rates of VF mean deviation (MD) and RNFLT worsening were analyzed using linear mixed-effects models, and longitudinal data was simulated using the variability estimates. MAIN OUTCOME MEASURE: The simulated time to detect trend-based glaucoma progression was assessed with assumed rates of VF MD and RNFLT change derived from the cohort (25th, 50th, 75th percentile [p25, median, p75] slopes and mean slopes). Severity-stratified analyses were also performed. RESULTS: We included 184 eyes from 128 AD subjects (mean baseline age: 63.4 years; VF MD: -4.2 dB, RNFLT: 80.2 µm). The p25, median, mean and p75 rates of change were -0.43, -1.01, -1.15 and -1.64 µm/year for RNFLT, and 0.00, -0.21, -0.30 and -0.51 dB/year for VF MD, respectively. Compared to VF MD, RNFLT showed an overall shorter mean time to progression detection (time difference: 0.4-1.7 years), with the mean rates showing the largest difference (RNFLT: 5.2 years vs. VF MD: 6.9 years). Similarly, we found an overall shorter time to detect RNFLT progression, compared to that of VF MD progression, in mild glaucoma eyes (≥1 year earlier) and in moderate-advanced glaucoma eyes (∼0.5 year earlier). CONCLUSIONS: Computer simulation showed potentially shorter time to detect RNFLT progression than VF MD progression in AD eyes. Our findings support the importance of using RNFLT to detect progressive glaucoma in AD individuals.

Detection of glaucoma progression on longitudinal series of en-face macular optical coherence tomography angiography images with a deep learning model.

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.

Rates of Choriocapillaris Microvascular Dropout and Macular Structural Changes in Glaucomatous Optic Neuropathy With and Without Myopia.

PURPOSE: To evaluate the association between rates of juxtapapillary choriocapillaris microvasculature dropout (MvD) change and rates of ganglion cell inner plexiform layer (GCIPL) loss in primary open-angle glaucoma (POAG) and glaucoma suspect eyes with and without myopia. DESIGN: Cohort study from clinical trial data. METHODS: 238 eyes from 155 POAG and glaucoma suspect patients were stratified into no-myopia (axial length (AL) ≤ 24 mm; n = 78 eyes), mild myopia (24 mm < AL ≤ 26 mm; n = 114 eyes), and high myopia (AL > 26 mm; n = 46 eyes). Eyes with a minimum of 3 visits and 1.5 years of follow-up with both optical coherence tomography angiography (OCT-A) and OCT macula scans were included. Presence, area, and angular circumference of juxtapapillary MvD were evaluated on en face choroidal images and horizontal B-scans obtained from OCT-A imaging. RESULTS: Over the mean follow-up of 4.4 years, the mean MvD area rates of change (95% CI) were largest in high and mild myopia group (0.04 [0.03, 0.05] mm2/year in both groups), followed by the no-myopia group (0.03 [0.02, 0.04] mm2/year). The mean MvD angular circumference rates of change (95% CI) were highest in mild myopia group (8.7° [6.9°, 10.5°]/year) followed by the high myopia and no-myopia groups (8.1° [5.3°, 10.9°]/year, and 7.4° [5.3°, 9.6°]/year, respectively). While the mean global GCIPL thinning rates between eyes with MvD at baseline compared to eyes without were similar in all myopia groups, the rates of MvD area change were significantly faster in all myopia groups with baseline MvD (all p ≤ 0.004). Significant faster rates of MvD angular circumference change were found in the mild myopia group with baseline MvD (P < .001) only. In multivariable models, the rates of GCIPL thinning over time were significantly associated with rates of MvD angular circumference change and MvD area change (R2 = 0.33, P < .001 and R2 = 0.32, P = .006, respectively). CONCLUSIONS: Rates of GCIPL thinning were associated with rates of MvD area and angular circumference change over time in myopic POAG eyes. Utilizing OCT-A to detect MvD may provide an additional tool for monitoring macular structural changes in glaucomatous eyes with myopia.

Association between metformin use with circumpapillary retinal nerve fibre layer thickness and capillary vessel density in glaucoma.

BACKGROUND/AIMS: To investigate the association between use of metformin and circumpapillary retinal nerve fibre layer (cpRNFL) thickness, as well as whole image capillary density (wiCD), in patients with glaucoma. METHODS: This cross-sectional study included patients with glaucoma suspect or primary open-angle glaucoma (POAG) underwent optical coherence tomography angiography imaging. Use and duration of antidiabetic medications were assessed at the time of imaging. Multivariable linear mixed-effect modelling was used to estimate the effect of diabetes medication on wiCD and cpRNFL while controlling for covariates including age, race, body mass index, diagnosis, 24-2 visual field mean deviation, and intraocular pressure, average signal strength index as well as any variables that showed a p <0.1 in the univariable analysis. RESULTS: A total of 577 eyes (330 POAG and 247 glaucoma suspect) of 346 patients were included. Sixty-five patients (23%) had diabetes, of whom 55 (78.5%) used metformin, and 17 (26.2%) used insulin. After adjusting for covariates, the association between metformin use and wiCD (1.56 (95% CI 0.40 to 2.71); p=0.008), duration of metformin use and wiCD (0.12 (95% CI 0.02 to 0.22) per 1 year longer; p=0.037), and metformin use and cpRNFL thickness (5.17 (95% CI 1.24 to 9.10) µm; p=0.010) had statistically significant associations in each model. CONCLUSIONS: Metformin use was associated with higher wiCD and thicker cpRNFL. These findings indicate a potential association, underscoring the need for longitudinal studies to determine if metformin plays a role in the retinal conditions of patients with glaucoma. TRIAL REGISTRATION NUMBER: NCT00221897.

Retinal Nerve Fiber Layer Optical Texture Analysis and 10-2 Visual Field Assessment in Glaucoma.

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.

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.

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

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.

Long-term variability of retinal nerve fibre layer thickness measurement in patients with glaucoma of African and European descents.

BACKGROUND: To examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma. METHODS: This retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races. RESULTS: There were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p<0.05). In both races, intervening CE was most strongly correlated with higher RNFLT variability (ß: 0.24-0.92, p<0.05). After excluding eyes with intervening CE, RNFLT variability was reduced and the small racial difference was no longer significant (AD: 1.40 (1.31, 1.48) µm vs ED: 1.34 (1.27, 1.40) µm; p=0.280). CONCLUSIONS: Although some predictors were identified, long-term RNFLT variability appeared small for both AD and ED eyes. Moreover, the racial difference did not remain once intervening CE, the strongest predictor of variability, was eliminated. Our findings inform on strategies to optimise structural assessment and suggest that, when accounting for relevant factors, RNFLT is reliable across races.

Association of foveal avascular zone change and glaucoma progression.

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.

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.

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.

Central visual field damage in glaucoma eyes with choroidal microvasculature dropout with and without high axial myopia.

PURPOSE: To characterise the relationship between a deep-layer microvasculature dropout (MvD) and central visual field (VF) damage in primary open-angle glaucoma (POAG) patients with and without high axial myopia. DESIGN: Cross-sectional study. METHODS: Seventy-one eyes (49 patients) with high axial myopia and POAG and 125 non-highly myopic POAG eyes (97 patients) were enrolled. Presence, area and angular circumference of juxtapapillary MvD were evaluated on optical coherence tomography angiography B-scans and en-face choroidal images. RESULTS: Juxtapapillary MvD was detected more often in the highly myopic POAG eyes (43 eyes, 86%) than in the non-highly myopic eyes (73 eyes, 61.9%; p=0.002). In eyes with MvD, MvD area and angular circumference (95% CI) were significantly larger in the highly myopic eyes compared with the non-highly myopic eyes (area: (0.69 (0.40, 0.98) mm2 vs 0.31 (0.19, 0.42) mm2, p=0.011) and (angular circumference: 84.3 (62.9, 105.8) vs 74.5 (58.3, 90.9) degrees, p<0.001), respectively. 24-2 VF mean deviation (MD) was significantly worse in eyes with MvD compared with eyes without MvD in both groups (p<0.001). After adjusting for 24-2 MD VF, central VF defects were more frequently found in eyes with MvD compared with eyes without MvD (82.7% vs 60.9%, p<0.001). In multivariable analysis, higher intraocular pressure, worse 24-2 VF MD, longer axial length and greater MvD area and angular circumference were associated with worse 10-2 VF MD. CONCLUSIONS: MvD was more prevalent and larger in POAG eyes with high myopia than in non-highly myopic POAG eyes. In both groups, eyes with MvD showed worse glaucoma severity and more central VF defects.

Relationship of Choroidal Microvasculature Dropout and Beta Zone Parapapillary Area With Visual Field Changes in Glaucoma.

PURPOSE: To evaluate the association between rates of choroidal microvasculature dropout (MvD) change, beta zone parapapillary atrophy (ß-PPA) area change, and visual field (VF) changes in eyes with primary open-angle glaucoma (POAG). DESIGN: Retrospective, observational cohort study. METHODS: In a tertiary glaucoma clinic, we included 76 eyes from 58 patients with POAG with and without localized MvD, who had ≥2 years of follow-up with a minimum of 4 visits with optical coherence tomography angiography and optical coherence tomography scans. ß-PPA area was evaluated using scanning laser ophthalmoscopy-like images and compared with the area of MvD on an en face choroidal vessel density map during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in ß-PPA area or MvD area and VF mean deviation (MD). RESULTS: Mean rates of change in ß-PPA and MvD area were 0.037 mm2 (95% confidence interval [CI] 0.030-0.043 mm2) per year and 0.039 mm2 (95% CI 0.029-0.048 mm2) per year, respectively, over the mean follow-up of 4.1 years. In multivariable models, MvD area enlargement was significantly associated with faster rates of VF MD loss (0.03 mm2 [95% CI 0.02-0.04 mm2] per 1-dB worse, P < .001) but not ß-PPA area enlargement (0.04 mm2 [95% CI 0.03-0.05 mm2] per 1-dB worse, P = .252). CONCLUSION: MvD area rates, but not ß-PPA area rates, were associated with VF MD loss changes in eyes with POAG. Assessment of MvD is useful for the detection of patients with glaucoma who are at an increased risk of faster VF loss.

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.

Comparison of the TEMPO binocular perimeter and Humphrey field analyzer.

This study compared between TEMPO, a new binocular perimeter, with the Humphrey Field Analyzer (HFA). Patients were tested with both TEMPO 24-2 Ambient Interactive Zippy Estimated by Sequential Testing (AIZE)-Rapid and HFA 24-2 Swedish Interactive Threshold Algorithm (SITA)-Fast in a randomized sequence on the same day. Using a mixed-effects model, visual field (VF) parameters and reliability indices were compared. Retinal nerve fiber layer (RNFL) thickness was measured using Cirrus optical coherence tomography (OCT), and coefficient of determinations for VF and OCT parameters were calculated and compared using Akaike information criteria. 740 eyes (including 68 healthy, 262 glaucoma suspects, and 410 glaucoma) of 370 participants were evaluated. No significant differences were seen in mean deviation and visual field index between the two perimeters (P > 0.05). A stronger association between VF mean sensitivity (dB or 1/L) and circumpapillary RNFL was found for TEMPO (adjusted R2 = 0.25; Akaike information criteria [AIC] = 5235.5 for dB, and adjusted R2 = 0.29; AIC = 5200.8 for 1/L, respectively) compared to HFA (adjusted R2 = 0.22; AIC = 5263.9 for dB, and adjusted R2 = 0.22; AIC = 5262.7 for 1/L, respectively). Measurement time was faster for TEMPO compared to HFA (261 s vs. 429 s, P < 0.001). Further investigations are needed to assess the long-term monitoring potential of this binocular VF test.