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 (8.7o (6.9o, 10.5o)/year) followed by the high myopia and no-myopia groups (8.1o (5.3o, 10.9o)/year, and 7.4o (5.3o, 9.6o)/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<0.001) 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<0.001 and R2=0.32, p=0.006, 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.

Wide-Field Optical Coherence Tomography Imaging Improves Rate of Change Detection in Progressing Glaucomatous Eyes Compared With Standard-Field Imaging.

Purpose: To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images. Methods: Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included. Results: Thirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27). Conclusions: In this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high 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.

Reduction of Optic Disc Microvasculature and Retinal Nerve Fiber Layer Thinning in Patients With Glaucoma.

PURPOSE: To assess the relationship between the change of optic disc vessel density (ODVD) and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective case series. METHODS: For 105 POAG patients, ≥5 consecutive optical coherence tomography (OCT) and OCT angiography images were obtained during ≥2 years of follow-up. Based on enface OCT angiography imaging, ODVD was calculated as the ratio of pixels occupied by vessels below the internal limiting membrane within the temporal area of the optic cup, and ODVD reduction was determined when there was a statistically significant negative slope (P < .05) for any of the global, superior, or inferior sectors. The association between the rates of ODVD change and RNFL thinning was assessed by a multivariable longitudinal linear mixed-effects model versus time. RESULTS: During 2.9 ± 0.3 years of follow-up on the 105 participants with visual field mean deviation at baseline of -5.7 ± 4.8 dB, 46 (43.8%) showed ODVD reduction. Faster global RNFL thinning was associated with the smaller Bruch's membrane opening area (ß = 0.381; 95% confidence interval [CI], 0.120-0.646; P = .006), optic disc hemorrhage (ß = -0.567; 95% CI, -0.909 to -0.228; P = .002), and faster rate of global ODVD change (ß = -0.090; 95% CI, -0.139 to -0.042; P = .001). CONCLUSIONS: Reduction of optic disc microvasculature was associated with rapid RNFL thinning in POAG. This suggests a role for deep optic nerve head circulation in the glaucoma pathogenesis.

Diagnostic Accuracy of Optic Nerve Head and Macula OCT Parameters for Detecting Glaucoma in Eyes With and Without High Axial Myopia.

PURPOSE: To characterize structural differences and assess the diagnostic accuracy of optic nerve head (ONH) and macula optical coherence tomography (OCT) parameters to detect glaucoma in eyes with and without high axial myopia. DESIGN: Cross-sectional study. METHODS: Three hundred sixty-eight glaucoma and 411 healthy eyes with no axial myopia, 393 glaucoma and 271 healthy eyes with mild axial myopia and 124 glaucoma and 85 healthy eyes with high axial myopia were included. Global and sectoral peripapillary retinal nerve fiber layer thickness (pRNFLT), Bruch's membrane opening minimum rim width (BMO-MRW), ganglion cell inner plexiform layer thickness (GCIPLT), and macula RNFLT (mRNFLT) were compared and the diagnostic accuracy for glaucoma detection was evaluated using the adjusted area under the receiver operating characteristic curve (AUC). RESULTS: Diagnostic accuracy for ONH and macula parameters to detect glaucoma was generally high and differed by myopia group. For ONH parameters the diagnostic accuracy was highest for global (AUC = 0.95) and inferotemporal (AUC = 0.91) pRNFLT for high myopes and global BMO-MRW for nonmyopes (AUC = 1.0) and mild myopes (AUC = 0.97). For macula parameters, the diagnostic accuracy was higher in high myopes with 6 of the 11 GCIPLT global/sectors having adjusted AUCs > 0.90 compared to nonhigh myopes with no AUCs > 0.90. In all myopia groups, mRNFLT had lower AUCs than GCIPLT. CONCLUSIONS: The diagnostic accuracy for pRNFL and GCIPL was high for high axial myopic eyes and shows promise for glaucoma detection in high myopes. Further analysis is needed to determine whether the high diagnostic accuracy can be confirmed in other populations.

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 Diagnostic Accuracy of Retinal Nerve Fiber Layer Thickness in Primary Open-Angle Glaucoma.

Purpose: To evaluate the diagnostic accuracy of retinal nerve fiber layer thickness (RNFLT) by spectral-domain optical coherence tomography (OCT) in primary open-angle glaucoma (POAG) in eyes of African (AD) and European descent (ED). Design: Comparative diagnostic accuracy analysis by race. Participants: 379 healthy eyes (125 AD and 254 ED) and 442 glaucomatous eyes (226 AD and 216 ED) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Methods: Spectralis (Heidelberg Engineering GmbH) and Cirrus (Carl Zeiss Meditec) OCT scans were taken within one year from each other. Main Outcome Measures: Diagnostic accuracy of RNFLT measurements. Results: Diagnostic accuracy for Spectralis-RNFLT was significantly lower in eyes of AD compared to those of ED (area under the receiver operating curve [AUROC]: 0.85 and 0.91, respectively, P=0.04). Results for Cirrus-RNFLT were similar but did not reach statistical significance (AUROC: 0.86 and 0.90 in AD and ED, respectively, P =0.33). Adjustments for age, central corneal thickness, axial length, disc area, visual field mean deviation, and intraocular pressure yielded similar results. Conclusions: OCT-RNFLT has lower diagnostic accuracy in eyes of AD compared to those of ED. This finding was generally robust across two OCT instruments and remained after adjustment for many potential confounders. Further studies are needed to explore the potential sources of this difference.

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.

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.

Optic Disc Microvasculature Dropout in Preperimetric Glaucoma.

PRCIS: Optic disc microvasculature dropout (MvD-D) was associated with worse disease severity in pre-perimetric glaucoma. MvD-D was not accompanied by focal lamina cribrosa defect or parapapillary deep-layer microvasculature dropout in 62.3% and 71.0% of eyes, respectively. PURPOSE: To investigate factors associated with optic disc microvasculature dropout (MvD-D) in patients with preperimetric primary open angle glaucoma (PPG). METHODS: One hundred thirty nine eyes of PPG patients were categorized according to the presence of MvD-D with optical coherence tomography angiography (OCTA). Factors including visual field (VF) mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, focal lamina cribrosa (LC) defect, optic disc hemorrhage (DH), and parapapillary deep-layer microvasculature dropout (MvD-P) were compared between eyes with and without MvD-D. RESULTS: MvD-D was observed in 69 PPG eyes (49.6%). Compared with eyes without MvD-D, the ones with MvD-D had a significantly thinner RNFL in all areas except the nasal sector, worse VF MD, and a focal LC defect and MvD-P ( P <0.05): male gender also was more highly prevalent. A considerable number of eyes with MvD-D lacked focal LC defect (62.3% [43/69]) or MvD-P (71.0% [49/69]), while a few eyes without MvD-D had focal LC defect (10.0% [7/70]) or MvD-P (2.9% [2/70]). In a multivariable logistic regression analysis, male gender (odds ratio [OR], 3.96; P <0.001), worse VF MD (OR, 1.44; P =0.019), thinner global RNFL (OR, 1.13; P <0.001), higher prevalence of focal LC defect (OR, 3.71; P =0.014) and MvD-P (OR, 7.85; P <0.001) were significantly associated with MvD-D. CONCLUSIONS: MvD-D was related to worse disease severity in patients with PPG, and often was not accompanied by focal LC defect or MvD-P. This suggests that impaired optic disc circulation can be an early sign of glaucoma without noticeable changes in functional or structural features (i.e., VF, focal LC defect, MvD-P).

OCT Optic Nerve Head Morphology in Myopia IV: Neural Canal Scleral Flange Remodeling in Highly Myopic Eyes.

PURPOSE: To compare the prevalence, location and magnitude of optic nerve head (ONH) OCT-detected, exposed neural canal (ENC), externally oblique choroidal border tissue (EOCBT) and exposed scleral flange (ESF) regions in 122 highly myopic (Hi-Myo) versus 362 nonhighly myopic healthy (Non-Hi-Myo-Healthy) eyes. DESIGN: Cross-sectional study. METHODS: After OCT radial B-scan, ONH imaging, Bruch's membrane opening (BMO), the anterior scleral canal opening (ASCO), and the scleral flange opening (SFO) were manually segmented in each B-scan and projected to BMO reference plane. The direction and magnitude of BMO/ASCO offset and BMO/SFO offset as well as the location and magnitude of ENC, EOCBT and ESF regions, perineural canal (pNC) retinal nerve fiber layer thickness (RNFLT) and pNC choroidal thickness (CT) were calculated within 30° sectors relative to the Foveal-BMO (FoBMO) axis. Hi-ESF eyes were defined to be those with an ESF region ≥100 µms in at least 1 sector. RESULTS: Hi-Myo eyes more frequently demonstrated Hi-ESF regions (87/122) than Non-Hi-myo-Healthy eyes (73/362) and contained significantly larger ENC, EOCBT, and ESF regions (P < .001) which were greatest in magnitude and prevalence within the inferior-temporal FoBMO sectors where Hi-Myo pNC-RNFLT and pNCCT were thinnest. BMO/ASCO offset and the BMO/SFO offset were both significantly increased (P < .001) in the Hi-Myo eyes, with the latter demonstrating a greater increase. CONCLUSIONS: ENC region tissue remodeling that includes the scleral flange is enhanced in Hi-Myo compared to Non-Hi-Myo-Healthy eyes. Longitudinal studies are necessary to determine whether the presence of an ENC region influences ONH susceptibility to aging and/or glaucoma.

Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Proactive Decision Support for Glaucoma Treatment: Predicting Surgical Interventions with Clinically Available Data.

A longitudinal ophthalmic dataset was used to investigate multi-modal machine learning (ML) models incorporating patient demographics and history, clinical measurements, optical coherence tomography (OCT), and visual field (VF) testing in predicting glaucoma surgical interventions. The cohort included 369 patients who underwent glaucoma surgery and 592 patients who did not undergo surgery. The data types used for prediction included patient demographics, history of systemic conditions, medication history, ophthalmic measurements, 24-2 VF results, and thickness measurements from OCT imaging. The ML models were trained to predict surgical interventions and evaluated on independent data collected at a separate study site. The models were evaluated based on their ability to predict surgeries at varying lengths of time prior to surgical intervention. The highest performing predictions achieved an AUC of 0.93, 0.92, and 0.93 in predicting surgical intervention at 1 year, 2 years, and 3 years, respectively. The models were also able to achieve high sensitivity (0.89, 0.77, 0.86 at 1, 2, and 3 years, respectively) and specificity (0.85, 0.90, and 0.91 at 1, 2, and 3 years, respectively) at an 0.80 level of precision. The multi-modal models trained on a combination of data types predicted surgical interventions with high accuracy up to three years prior to surgery and could provide an important tool to predict the need for glaucoma intervention.

Deep Learning Identifies High-Quality Fundus Photographs and Increases Accuracy in Automated Primary Open Angle Glaucoma Detection.

Purpose: To develop and evaluate a deep learning (DL) model to assess fundus photograph quality, and quantitatively measure its impact on automated POAG detection in independent study populations. Methods: Image quality ground truth was determined by manual review of 2815 fundus photographs of healthy and POAG eyes from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study (DIGS/ADAGES), as well as 11,350 from the Ocular Hypertension Treatment Study (OHTS). Human experts assessed a photograph as high quality if of sufficient quality to determine POAG status and poor quality if not. A DL quality model was trained on photographs from DIGS/ADAGES and tested on OHTS. The effect of DL quality assessment on DL POAG detection was measured using area under the receiver operating characteristic (AUROC). Results: The DL quality model yielded an AUROC of 0.97 for differentiating between high- and low-quality photographs; qualitative human review affirmed high model performance. Diagnostic accuracy of the DL POAG model was significantly greater (P < 0.001) in good (AUROC, 0.87; 95% CI, 0.80-0.92) compared with poor quality photographs (AUROC, 0.77; 95% CI, 0.67-0.88). Conclusions: The DL quality model was able to accurately assess fundus photograph quality. Using automated quality assessment to filter out low-quality photographs increased the accuracy of a DL POAG detection model. Translational Relevance: Incorporating DL quality assessment into automated review of fundus photographs can help to decrease the burden of manual review and improve accuracy for automated DL POAG detection.

Optic neuropathy in high myopia: Glaucoma or high myopia or both?

Due to the increasing prevalence of high myopia around the world, structural and functional damages to the optic nerve in high myopia has recently attracted much attention. Evidence has shown that high myopia is related to the development of glaucomatous or glaucoma-like optic neuropathy, and that both have many common features. These similarities often pose a diagnostic challenge that will affect the future management of glaucoma suspects in high myopia. In this review, we summarize similarities and differences in optic neuropathy arising from non-pathologic high myopia and glaucoma by considering their respective structural and functional characteristics on fundus photography, optical coherence tomography scanning, and visual field tests. These features may also help to distinguish the underlying mechanisms of the optic neuropathies and to determine management strategies for patients with high myopia and glaucoma.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

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.

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.