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.

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.

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).

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.

Temporal Optic Disc Microvasculature Dropout in Glaucoma.

Purpose: To assess the clinical characteristics of focal temporal optic disc microvasculature dropout (MvD-D) in primary open-angle glaucoma (POAG) patients. Methods: One hundred and eighty-seven eyes of 187 POAG patients having MvD-D on Swept-Source optical coherence tomography angiography (SS-OCTA) were enrolled. Three groups were categorized according to the presence of temporal MvD-D within the upper and lower 45° of the fovea-Bruch's membrane (BM) opening axis: focal temporal MvD-D (Group 1, isolated focal temporal MvD-D; 44 eyes), supero/inferotemporal MvD-D (Group 2, MvD-D only in superotemporal or inferotemporal sector; 78 eyes), and diffuse temporal MvD-D (Group 3, MvD-D spanning ≥ 2 consecutive sectors, at least one of which being temporal sector; 65 eyes). Results: Group 1 had a significantly longer axial length and ß-zone parapapillary atrophy without BM. There also was a larger horizontal tilt angle and ovality index than the other two groups (P < 0.001). Group 1 had a significantly thinner retinal nerve fiber layer (RNFL) in the temporal sector than did Group 2 (P < 0.001), despite similar thicknesses in all other areas (P > 0.05). Group 3 had significantly worse visual field mean deviation and thinner RNFL than the other two groups in all areas other than the nasal, temporal, and superotemporal sectors (P < 0.05). Conclusions: Focal temporal MvD-D detected by SS-OCTA was associated with a longer axial length and related subsequent morphological changes of the optic disc and parapapillary area. This suggests that stretching of the optic disc consequent on axial elongation may lead to absence of temporal optic disc microvasculature.

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

BACKGROUND/AIMS: To investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD). METHODS: POAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models. RESULTS: Thirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes with MvD than in those without MvD (mean differences: -0.50 (95% CI -0.83 to -0.17) µm/year; p=0.003)). Presence of MvD, area and angular circumference of MvD were independently associated with a faster rate of thinning (p=0.002, p=0.031 and p=0.013, respectively). CONCLUSION: In POAG eyes, GCC thinning is faster in eyes with MvD. Detection of MvD in OCT-A images can assist clinicians to identify patients who are at higher risk for central macula thinning and glaucomatous progression and may require more intensive management.

Bruch Membrane Opening Detection Accuracy in Healthy Eyes and Eyes With Glaucoma With and Without Axial High Myopia in an American and Korean Cohort.

PURPOSE: To determine the predictors of Bruch membrane opening (BMO) location accuracy and the visibility of the BMO location in glaucoma and healthy individuals with and without axial high myopia. DESIGN: Cross-sectional study. METHODS: Healthy eyes and eyes with glaucoma from an American study and a Korean clinic population were classified into 2 groups: those with no axial high myopia (axial length [AL] <26 mm) and those with axial high myopia (AL ≥26 mm). The accuracy of the automated BMO location on optic nerve head Spectralis optical coherence tomography radial scans was assessed by expert reviewers. RESULTS: Four hundred thirty-eight non-highly myopic eyes (263 subjects) and 113 highly myopic eyes (81 subjects) were included. In healthy eyes with and without axial high myopia, 9.1% and 1.7% had indiscernible BMOs while 54.5% and 87.6% were accurately segmented, respectively. More than a third (36.4%) and 10.7% of eyes with indiscernible BMOs were manually correctable (respectively, P = .017). In eyes with glaucoma with and without high myopia, 15.0% and 3.2% had indiscernible BMOs, 55.0% and 38.2% were manually corrected, and 30.0% and 58.7% were accurately segmented without the need for manual correction (respectively, P = .005). Having axial high myopia, a larger AL, a larger BMO tilt angle, a lower BMO ovality index (more oval), and a glaucoma diagnosis were significant predictors of BMO location inaccuracy in multivariable logistic regression analysis. CONCLUSIONS: As BMO location inaccuracy was 2.4 times more likely in eyes with high axial myopia regardless of diagnosis, optical coherence tomography images of high myopes should be reviewed carefully, and when possible, BMO location should be corrected before using optic nerve head scan results for the clinical management of glaucoma.

Optic Disc Microvasculature Dropout in Glaucoma Detected by Swept-Source Optical Coherence Tomography Angiography.

PURPOSE: To assess the clinical utility of swept-source optical coherence tomography angiography (SS-OCTA) in detecting optic disc microvasculature dropout (MvD-D) in primary open-angle glaucoma (POAG) eyes. DESIGN: Cross-sectional study. METHODS: The study enrolled 197 eyes of 197 patients with POAG with acceptable-quality SS-OCTA (PLEX Elite 9000; Carl Zeiss Meditec) images. A whole-signal-mode 6.0- × 6.0-mm optic disc cube was obtained with projection artifact removal. Three groups were categorized: no MvD-D (group 1), MvD-D (group 2, complete loss of microvasculature within the optic disc), and indiscernible MvD-D (group 3, poor visualization of the anterior lamina cribrosa [LC]). RESULTS: There were 82 (42.1%) and 81 (41.5%) eyes categorized as no MvD-D (group 1) and MvD-D (group 2), respectively. The remaining 32 eyes (16.4%), categorized as indiscernible MvD-D (group 3), had a significantly smaller anterior scleral canal opening (ASCO) area (P < .05). Group 2 had significantly worse visual field (VF) mean deviation (MD), thinner average retinal nerve fiber layer (RNFL), higher prevalence of focal LC defect, and parapapillary deep-layer microvasculature dropout (MvD-P) than the other 2 groups (P < .05). In the multivariable logistic regression analysis, higher prevalence of focal LC defect (odds ratio, 46.91; P < .001) and MvD-P (odds ratio, 48.94; P < .001) remained as factors associated with MvD-D. CONCLUSIONS: The presence of MvD-D could be well determined by SS-OCTA in eyes with POAG. MvD-P and focal LC defects were strongly associated with MvD-D. This suggests that SS-OCTA can serve as a useful tool in detecting optic disc microvasculature damage.

Juxtapapillary Deep-Layer Microvasculature Dropout and Retinal Nerve Fiber Layer Thinning in Glaucoma.

PURPOSE: We sought to characterize juxtapapillary (JP) and non-JP microvasculature dropout in patients with primary open-angle glaucoma and to compare their rate of retinal nerve fiber layer (RNFL) thinning. DESIGN: Retrospective cohort study. METHODS: A total of 141 eyes with primary open-angle glaucoma with ≥4 serial optical coherence tomography (OCT) images after initial OCT angiography for ≥2 years were included. Based on OCT angiography imaging, the 3 groups were matched by age and visual field mean deviation: JP group (parapapillary deep-layer microvasculature dropout in contact with the optic disc boundary, n = 47), non-JP group (dropout not reaching the optic disc boundary, n = 47), and no-dropout group (lacking the dropout, n = 47). The RNFL thinning rate was compared among the 3 groups. RESULTS: The rate of RNFL thinning tended to be fastest in the JP group followed by the non-JP group and no-dropout group in all areas except the temporal and nasal sectors. Post hoc analysis revealed that the JP group had significantly faster RNFL thinning than did the no-dropout group in the global area and the inferotemporal and inferonasal sectors (P < .05). When subgroup analysis was performed for subjects in which the main sector of dropout was the inferotemporal sector, the JP group had significantly faster RNFL thinning than the other 2 groups in the corresponding inferotemporal sector (P < .001). CONCLUSION: Eyes with JP microvasculature dropout showed faster RNFL thinning than eyes without dropout. These findings suggest that deep-layer microvasculature dropout, especially in contact with the optic disc boundary, is associated with rapid glaucoma progression.

Deep-layer Microvasculature Dropout in Preperimetric Glaucoma Patients.

PURPOSE: To compare disease severity between preperimetric primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature dropout. MATERIALS AND METHODS: Ninety-four eyes of 94 preperimetric POAG patients with ß-zone parapapillary atrophy (ßPPA) were categorized according to the presence of deep-layer microvasculature dropout defined as a complete loss of microvasculature within the choroid or scleral flange on optical coherence tomography angiography. Parameters representing disease severity, that is, visual field (VF) mean deviation (MD), global and sectoral (6-sector) retinal nerve fiber layer (RNFL) thickness, and other factors including age, focal lamina cribrosa (LC) defect, width of ßPPA with and without Bruch membrane (BM) (ßPPA+BM and ßPPA-BM), and optic disc hemorrhage were compared between eyes with and without dropout. RESULTS: Deep-layer microvasculature dropout was observed in 33 preperimetric POAG eyes (35.1%). Eyes with dropout had significantly thinner RNFL in all areas except the inferonasal sector, worse VF MD, and higher prevalence of focal LC defect, and larger ßPPA-BM (P<0.05), whereas the 2 groups did not differ in age, disc hemorrhage, or ßPPA+BM width (P>0.05). In the multivariable logistic regression, worse VF MD [odds ratio (OR), 1.485; P=0.045], thinner RNFL (OR, 1.141; P<0.001), and higher prevalence of focal LC defect (OR, 6.673; P<0.001) were significantly associated with dropout. CONCLUSIONS: Deep-layer microvasculature dropout was observed in a considerable number of preperimetric POAG eyes, and worse disease severity was associated with dropout. Future studies elucidating the pathogenic role of deep-layer microvasculature dropout in the development and progression of glaucoma are warranted.

Characteristics of Focal Gamma Zone Parapapillary Atrophy.

Purpose: The purpose of this study was to investigate the characteristics of focal γ-zone parapapillary atrophy (focal γPPA) in patients with primary open-angle glaucoma (POAG) using spectral-domain optical coherence tomography (SD-OCT). Methods: Three groups of POAG eyes (n = 214) were defined according to the circumferential extent of Bruch's membrane (BM) within the ß-zone PPA, as follows: (1) no γPPA (intact BM; n = 81), (2) conventional γPPA (γPPA involving the fovea-BM-opening axis; n = 89), and (3) focal γPPA (γPPA not involving the fovea-BM-opening axis; n = 44). Clinical and ocular characteristics, including age, axial length (AXL), and focal lamina cribrosa (LC) defects were compared among the three groups. Results: The focal γPPA group was significantly older (60.6 ± 11.0 years) and had shorter AXL (24.10 ± 1.34 mm) than those of the conventional γPPA group (46.2 ± 13.8 years and 26.53 ± 1.61 mm, respectively; P < 0.001). These values of the focal γPPA group were similar to those of the no γPPA group (23.73 ± 0.97 mm for AXL and 64.0 ± 13.0 years for age). The focal γPPA group had a significantly higher prevalence of focal LC defects than did the other two groups (70.5% [31/44] for the focal γPPA group versus 46.1% [41/89] for the conventional γPPA group versus 37.0% [30/81] for the no γPPA group; P = 0.002). Conclusions: Focal γPPA was differentiated from conventional γPPA by older age and shorter AXL. Further, focal γPPA was frequently accompanied by focal LC defects. Longitudinal studies elucidating whether focal LC defects and focal γPPA share common pathogenesis are warranted.

Optical Coherence Tomography Angiography in Glaucoma.

Optical coherence tomography angiography (OCTA) is a relatively new, noninvasive, dye-free imaging modality that provides a qualitative and quantitative assessment of the vasculature in the retina and optic nerve head. OCTA also enables visualization of the choriocapillaris, but only in areas of parapapillary atrophy. With OCTA, the movement of red blood cells is used as a contrast to delineate blood vessels from static tissues. The features seen with OCTA in eyes with glaucoma are reduction in the superficial vessel density in the peripapillary and macular areas, and complete loss of choriocapillaris in localized regions of parapapillary atrophy (called deep-layer microvascular dropout). These OCTA changes correlate well topographically with the functional changes seen on visual field examination and structural changes seen on optical coherence tomography (OCT) (ie, parapapillary retinal nerve fiber layer changes and inner retinal layer thickness changes at macula). The OCTA measurements also have acceptable test-retest variability and well differentiate glaucomatous from normal eyes. OCTA measurements can be affected by various subject-related, eye-related, and disease-related factors. Vessel density reduction on OCTA reaches a base level (floor) at a more advanced disease stage than the structural changes on OCT and therefore has the potential to monitor progression in eyes with advanced glaucomatous damage. OCTA also adds information about glaucoma patients at risk of faster progression. OCTA, therefore, complements visual field and OCT examinations to diagnose glaucoma, detect progression, and assess risk of progression.

Exploring choroidal angioarchitecture in health and disease using choroidal vascularity index.

The choroid is one of the most vascularized structures of the human body and plays an irreplaceable role in nourishing photoreceptors. As such, choroidal dysfunction is implicated in a multitude of ocular diseases. Studying the choroid can lead to a better understanding of disease pathogenesis, progression and discovery of novel management strategies. However, current research has produced inconsistent findings, partly due to the physical inaccessibility of the choroid and the lack of reliable biomarkers. With the advancements in optical coherence tomography technology, our group has developed a novel quantitative imaging biomarker known as the choroidal vascularity index (CVI), defined as the ratio of vascular area to the total choroidal area. CVI is a potential tool in establishing early diagnoses, monitoring disease progression and prognosticating patients. CVI has been reported in existing literature as a robust marker in numerous retinal and choroidal diseases. In this review, we will discuss the current role of CVI with reference to existing literature, and make postulations about its potential and future applications.

Peripapillary Choroidal Vascularity Index and Microstructure of Parapapillary Atrophy.

Purpose: To investigate the association between the microstructure of ß-zone parapapillary atrophy (ßPPA) and choroidal vascularity index (CVI) determined by spectral-domain optical coherence tomography (SD-OCT) in glaucomatous eyes. Methods: A total of 160 eyes of 160 primary open-angle glaucoma patients with ßPPA were included. Total choroidal area (TCA), luminal area (LA), and CVI were measured at a 3.5-mm distance from the Bruch's membrane (BM) opening center by image binarization of SD-OCT B-scans. The widths of ßPPA with BM (ßPPA+BM) and without BM (ßPPA-BM), and juxtapapillary choroidal thickness (JPCT) were measured on six radial SD-OCT images. OCT angiography-derived parapapillary deep-layer microvasculature dropout (MvD_P) was also derived. Results: In the multivariate regression analysis, larger ßPPA+BM was significantly associated with smaller TCA and smaller LA (P < 0.05, respectively), but not with CVI and JPCT (P > 0.05, respectively). Meanwhile, ßPPA-BM was not significantly associated with TCA, LA, CVI, or JPCT in the multivariate regression analysis (P > 0.05). Conclusions: Despite significant relationship between the choroidal thinning and larger ßPPA+BM, choroidal vascularity was not associated with the ßPPA+BM width. These findings suggest that the presumed common pathogenic mechanism between RPE atrophy and peripapillary choroidal thinning may not be mediated by the impaired choroidal perfusion in glaucomatous eyes. Future studies on the mechanisms in explaining the relationship between the atrophy of retinal pigment epithelium (RPE) and choroid in glaucoma are needed.

Association Between Lamina Cribrosa Defects and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma.

Importance: Certain features of the lamina cribrosa may be associated with increased risk of glaucoma progression. Objectives: To compare the rates of retinal nerve fiber layer (RNFL) thinning in patients with open-angle glaucoma with or without lamina cribrosa (LC) defects and to evaluate factors associated with the rate of glaucoma progression in eyes with LC defects. Design, Setting, and Participants: This longitudinal cohort study designed in September 2017 and conducted at a tertiary glaucoma center in California included 51 eyes of 43 patients with LC defects and 83 eyes of 68 patients without LC defects followed up for a mean (SD) of 3.5 (0.8) years from April 2012 to May 2017. Main Outcomes and Measures: Focal LC defects were detected using swept-source optical coherence tomographic images. All participants underwent visual field testing and spectral-domain optical coherence tomography for RNFL thickness measurements every 6 months. Univariate and multivariable random-effects models were used to compare the rate of local and global RNFL loss. Results: The mean (95% CI) age at baseline for individuals with LC defects was 69.5 (65.4 to 73.6) years, and for those without LC defects, it was 69.6 (67.2-72.0) years; 18 individuals (41%) with LC defects and 35 individuals (51%) without LC defects were men; 6 individuals (14%) with LC defects and 17 individuals (25%) without were African American. The mean (95% CI) rate of global RNFL loss in eyes with LC defects was 2-fold faster than that in eyes without LC defects (-0.91 [-1.20 to -0.62] vs -0.48 [-0.65 to -0.31] µm/y; difference, -0.43 [-0.76 to -0.09] µm/y; P = .01). The rate of RNFL thinning was faster in the LC defect sectors than that in the unaffected sectors (difference, -0.90 [95% CI, -1.68 to -0.12] µm/y, P = .02). Thinner corneal thickness was the only factor that was associated with a faster rate of RNFL loss in eyes with LC defects (ß2 = -0.09 [95% CI, -0.14 to -0.04], P = .001). No association was found between mean intraocular pressure during follow-up and the mean rate of RNFL thinning in eyes with LC defects (ß2, -0.05 [95% CI, -0.17 to 0.06], P = .36). Conclusions and Relevance: These data suggest that LC defects are an independent risk factor for RNFL thinning and that glaucoma progression may correspond topographically to the LC defect location. Thinner corneal thickness in eyes with LC defects was associated with faster further glaucoma progression. In the management of open-angle glaucoma, LC findings may inform the likelihood and rate of glaucoma progression.

Parapapillary Deep-Layer Microvasculature Dropout and Visual Field Progression in Glaucoma.

PURPOSE: To evaluate the association between optical coherence tomography angiography (OCT-A)-derived parapapillary deep-layer microvasculature dropout and glaucomatous visual field (VF) progression. DESIGN: Retrospective, cohort study. METHODS: A total of 138 eyes of 138 patients with primary open-angle glaucoma (mean follow-up, 5.5 years) and with ≥5 VFs prior to OCT-A imaging were included. VF progression was defined as either a Guided Progression Analysis-based "likely progression" event or a significant VF index (VFI) slope. Microvasculature dropout was defined as parapapillary deep-layer microvasculature dropout based on a qualitative analysis of OCT-A. Prevalence of dropout was compared between eyes with and without VF progression. RESULTS: Fifty-five eyes (39.9%) demonstrated VF progression. A higher proportion of eyes with dropout progressed than those without dropout (50/84 eyes [59.5%] vs 5/54 eyes [9.3%]; P < .001). In multivariable logistic regression analysis, mean and standard deviation intraocular pressure, optic disc hemorrhage, focal lamina cribrosa defect, and dropout were significantly associated with prior VF progression (P < .05). The VFI progression rate was significantly faster in eyes with dropout than in those without dropout (-2.23% ± 3.22%/year vs -0.05% ± 1.24%/year, respectively; P < .001), and the location of dropout and VF progression were spatially correlated. CONCLUSIONS: Eyes with parapapillary deep-layer microvasculature dropout detected by OCT-A had a significantly higher rate of VF progression than eyes without dropout. These findings implicate dropout as a structural parameter suggestive of past glaucomatous VF progression. Further prospective longitudinal studies are needed to elucidate the role of deep-layer microvasculature damage in the pathogenesis of glaucoma.

Optic disc microvasculature dropout in primary open-angle glaucoma measured with optical coherence tomography angiography.

PURPOSE: To evaluate microvasculature dropout in the optic disc (Mvd-D) using optical coherence tomography angiography (OCTA) and investigate factors associated with Mvd-D in primary open-angle glaucoma (POAG) eyes. METHODS: One hundred twenty-three eyes of 123 POAG patients were included from the Diagnostic Innovations in Glaucoma Study. The 3.0×3.0-mm optic nerve head OCTA scans were acquired using a spectral-domain OCT instrument. Images with whole-signal-mode were evaluated. Eyes were classified into 3 categories (Mvd-D, pseudo-Mvd-D, and no Mvd-D). Mvd-D and pseudo-Mvd-D had complete loss of OCTA signals on the temporal side of the optic disc on the en face projection image. They were distinguished base on the visualization of the anterior lamina cribrosa in the horizontal B-scans of that area. No Mvd-D was defined when no complete signal loss of OCTA signals was observed. Covariates including focal lamina cribrosa defects assessed by swept-source OCT and microvasculature dropout in the parapapillary region (Mvd-P) were analyzed. RESULTS: Forty-two, 37, and 44 eyes were identified as having Mvd-D, pseudo-Mvd-D, and no Mvd-D, respectively. The eyes with Mvd-D showed significantly lower intraocular pressure, worse visual field mean deviation, larger cup-to-disc ratio, thinner circumpapillary retinal nerve fiber layer (cpRNFL), and lower circumpapillary vessel density within the RNFL than the eyes with pseudo-Mvd-D or the eyes without Mvd-D. Multivariable logistic regression analysis showed significant associations of Mvd-D with larger cup-to-disc ratio (OR, 1.08; P = 0.001), worse visual field mean deviation (OR, 1.09; P = 0.048), higher prevalence of focal lamina cribrosa defect (OR, 9.05; P = 0.002), and higher prevalence of Mvd-P (OR, 10.33; P <0.001). CONCLUSIONS: OCTA-derived Mvd-D was strongly associated with the presences of Mvd-P and focal lamina cribrosa defects, and these 3 findings were topographically associated with each other.

Peripapillary Choroidal Vascularity Index in Glaucoma-A Comparison Between Spectral-Domain OCT and OCT Angiography.

Purpose: To compare the choroidal vascularity index (CVI) determined by spectral-domain optical coherence tomography (OCT) between eyes with and without parapapillary deep-layer microvasculature dropout (MvD_P) assessed by OCT angiography in glaucomatous eyes. Methods: A total of 100 open-angle glaucoma patients with and without MvD_P (50 eyes of 50 patients in each group) matched by age and visual field mean deviation were included. Total choroidal area (TCA) and CVI were measured by image binarization of spectral-domain OCT B-scans in order to assess the choroidal vasculature outside ß-zone parapapillary atrophy (ßPPA) at a 3.5-mm distance from the Bruch's membrane opening center. MvD_P was determined by OCT angiography as a deep-layer microvasculature dropout within ßPPA. Global and sectoral (six 60° sectors) TCA and CVI were compared between eyes with and without MvD_P. Results: The CVIs of eyes with MvD_P were significantly lower than those without MvD_P, globally (P = 0.010) as well as in the inferotemporal (TI) (P = 0.003), temporal (P = 0.009), and nasal (P = 0.048) sectors. Eyes with MvD_P, of which the largest portion was located only in the TI sector (n = 33), had significantly lower CVI than those without MvD_P in the corresponding TI and temporal sectors (P < 0.05 for all), whereas TCA did not differ in any areas. Conclusions: Eyes with MvD_P had significantly lower CVIs than did those without MvD_P. Furthermore, CVI reduction was spatially correlated with MvD_P. Further studies investigating the influence of MvD_P on the choroidal vasculature outside ßPPA are warranted.

Automated Beta Zone Parapapillary Area Measurement to Differentiate Between Healthy and Glaucoma Eyes.

PURPOSE: To evaluate whether automated assessment of beta zone parapapillary atrophy (ßPPA) area can differentiate between glaucomatous and healthy eyes of varying axial lengths (AL). DESIGN: Cross-sectional study. METHODS: ßPPA was automatically identified in glaucoma and healthy eyes with enhanced-depth imaging optical coherence tomography (OCT) optic nerve head (ONH) radial B-scans. Associations with AL and the presence of glaucoma were assessed. Manually delineated ßPPA on individual OCT ONH B-scans of 35 eyes from the Diagnostic Innovations in Glaucoma Study served to validate the automated method. RESULTS: One hundred fifty-three glaucoma eyes (mean ± standard deviation) (visual field mean deviation, -5.0 ± 6.4 dB and mean AL, 25.1 ± 1.1 mm) and 73 healthy eyes (visual field mean deviation, 0.1 ± 1.4 dB and mean AL, 24.1 ± 1.1 mm) were included. In multivariable analysis, larger ßPPA area was significantly associated with a diagnosis of glaucoma after controlling for age, central corneal thickness, and AL. Moreover, in multivariable analysis, the odds of having glaucoma were doubled for each 0.2 mm2 larger ßPPA area. The age- and AL-adjusted area under the receiver operating characteristic curve (95% confidence interval) of ßPPA area for differentiating between glaucoma and healthy eyes was 0.75 (0.68-0.81). Agreement for the location of the Bruch membrane opening and the location of retinal pigment epithelium tips was stronger between the automated technique and each individual observer than it was between the 2 observers. CONCLUSIONS: Larger ßPPA area, as determined by automated OCT assessment, is significantly associated with a diagnosis of glaucoma, even after adjusting for age and AL, and may aid in differentiating healthy from glaucomatous eyes.

Deep-Layer Microvasculature Dropout by Optical Coherence Tomography Angiography and Microstructure of Parapapillary Atrophy.

Purpose: To investigate the association between the microstructure of ß-zone parapapillary atrophy (ßPPA) and parapapillary deep-layer microvasculature dropout assessed by optical coherence tomography angiography (OCT-A). Methods: Thirty-seven eyes with ßPPA devoid of the Bruch's membrane (BM) (γPPA) ranging between completely absent and discontinuous BM were matched by severity of the visual field (VF) damage with 37 eyes with fully intact BM (ßPPA+BM) based on the spectral-domain (SD) OCT imaging. Parapapillary deep-layer microvasculature dropout was defined as a dropout of the microvasculature within choroid or scleral flange in the ßPPA on the OCT-A. The widths of ßPPA, γPPA, and ßPPA+BM were measured on six radial SD-OCT images. Prevalence of the dropout was compared between eyes with and without γPPA. Logistic regression was performed for evaluating association of the dropout with the width of ßPPA, γPPA, and ßPPA+BM, and the γPPA presence. Results: Eyes with γPPA had significantly higher prevalence of the dropout than did those without γPPA (75.7% versus 40.8%; P = 0.004). In logistic regression, presence and longer width of the γPPA, worse VF mean deviation, and presence of focal lamina cribrosa defects were significantly associated with the dropout (P < 0.05), whereas width of the ßPPA and ßPPA+BM, axial length, and choroidal thickness were not (P > 0.10). Conclusions: Parapapillary deep-layer microvasculature dropout was associated with the presence and larger width of γPPA, but not with the ßPPA+BM width. Presence and width of the exposed scleral flange, rather than the retinal pigmented epithelium atrophy, may be associated with deep-layer microvasculature dropout.