Peripapillary and Macular Vessel Density in Patients with Primary Open-Angle Glaucoma and Unilateral Visual Field Loss.

PURPOSE: To characterize OCT angiography (OCT-A) vessel density of patients with primary open-angle glaucoma (POAG) with unilateral visual field (VF) loss. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 33 patients with POAG with a VF defect in 1 eye (mean VF mean deviation [MD], -3.9±3.1 decibels [dB]) and normal VF in the other eye (mean VF MD, -0.2±0.9 dB) and 33 healthy eyes. METHODS: All subjects underwent OCT-A imaging, spectral-domain (SD)-OCT imaging, and VF testing. OCT-A retinal vascular measurements were summarized as whole image vessel density (wiVD), circumpapillary vessel density (cpVD), and parafoveal vessel density (pfVD). Inter-eye differences in vascular measures, as well as SD OCT retinal nerve fiber layer (RNFL), macular ganglion cell complex (mGCC) thickness, and rim area measurements in glaucoma and healthy eyes were compared. Areas under the receiver operating characteristic curves (AUROCs) were used to evaluate diagnostic accuracy for differentiating between unaffected eyes of patients with POAG and healthy eyes. MAIN OUTCOME MEASURES: Difference in OCT-A vessel density and SD OCT structural parameters between unaffected eyes of patients with POAG with the fellow affected eyes and healthy controls. RESULTS: Mean wiVD in unaffected eyes of patients with POAG (52.0%) was higher than in their fellow affected eyes (48.8%) but lower than in healthy eyes (55.9%; P < 0.001). Mean circumpapillary RNFL (cpRNFL) thickness, mGCC thickness, and rim area measurement in unaffected eyes of patients with POAG (87.5 µm, 87.7 µm, and 1.0 mm2) were also higher than those measurements in their fellow eyes (76.5 µm, 79.5 µm, and 0.8 mm2; P < 0.001) and lower than in healthy eyes (98.0 µm, 94.5 µm, and 1.4 mm2; P < 0.001). The AUROCs for differentiating unaffected eyes of patients with POAG from healthy eyes were highest for wiVD (0.84), followed by mGCC (0.78), cpRNFL (0.77), and pfVD (0.69). CONCLUSIONS: OCT-A measures detect changes in retinal microvasculature before VF damage is detectable in patients with POAG, and these changes may reflect damage to tissues relevant to the pathophysiology of glaucoma. Longitudinal studies are needed to determine whether OCT-A measures can improve the detection or prediction of the onset and progression of glaucoma.

Rates of Local Retinal Nerve Fiber Layer Thinning before and after Disc Hemorrhage in Glaucoma.

PURPOSE: To investigate longitudinal temporal and spatial associations between disc hemorrhage (DH) and rates of local retinal nerve fiber layer (RNFL) thinning before and after DHs. DESIGN: Longitudinal, observational cohort study. PARTICIPANTS: Forty eyes of 37 participants (23 with glaucoma and 17 with suspect glaucoma at baseline) with DH episodes during follow-up from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. METHODS: All subjects underwent optic disc photography annually and spectral-domain optical coherence tomography (OCT) RNFL thickness measurements every 6 months. The rates of RNFL thinning were calculated using multivariate linear mixed-effects models before and after DH. MAIN OUTCOME MEASURES: Rates of global and local RNFL thinning. RESULTS: Thirty-six eyes of 33 participants with inferior or superior DHs were analyzed. The rates of RNFL thinning were significantly faster in DH quadrants than in non-DH quadrants after DH (-2.25 and -0.69 µm/year; P < 0.001). In the 18 eyes with intensified treatment after DH, the mean rate of RNFL thinning significantly slowed after treatment compared with before treatment in the non-DH quadrants (-2.89 and -0.31 µm/year; P < 0.001), but not in the DH quadrants (-2.64 and -2.12 µm/year; P = 0.19). In 18 eyes with unchanged treatment, the rate of RNFL thinning in the DH quadrant was faster after DH than before DH (P = 0.008). Moreover, compared with eyes without a treatment change, intensification of glaucoma treatment after DH significantly reduced the global, non-DH quadrants, and DH quadrant rates of RNFL thinning after DH compared with before DH (global, P = 0.004; non-DH quadrant, P < 0.001; DH quadrant, P = 0.005). In the multiple linear regression analysis, treatment intensification (ß, 1.007; P = 0.005), visual field mean deviation (ß, 0.066; P = 0.049), and difference in intraocular pressure before and after DH (ß, -0.176; P = 0.034) were associated significantly with the difference of global RNFL slope values before and after DH. CONCLUSIONS: Although the rate of RNFL thinning worsened in a DH quadrant after DH, glaucoma treatment intensification may have a beneficial effect in reducing this rate of thinning.

Peripapillary and Macular Vessel Density in Patients with Glaucoma and Single-Hemifield Visual Field Defect.

PURPOSE: To compare hemifield differences in the vessel density of the peripapillary and macula in open-angle glaucoma eyes with visual field (VF) defect confined to one hemifield using optical coherence tomography angiography (OCT-A). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 58 eyes of 58 patients with glaucoma with VF loss confined to a single hemifield and 28 healthy eyes. METHODS: Retinal vasculature information was summarized as circumpapillary vessel density (cpVD) and perifoveal vessel density (pfVD). Circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thickness were calculated using spectral domain optical coherence tomography (SD OCT). Paired and unpaired t tests were used to evaluate differences between the perimetrically affected and intact hemiretinae and healthy hemiretinae. Linear regression analyses were performed to evaluate the associations between VF measures with vascular and structural measurements. MAIN OUTCOME MEASURES: Total and hemispheric cpVD, pfVD, cpRNFL, mGCC, and mean sensitivity (MS). RESULTS: Mean cpVD and pfVD in the intact hemiretinae of glaucoma eyes (59.0% and 51.1%, respectively) were higher than in the affected hemiretinae (54.7% and 48.3%, respectively; P < 0.001) but lower than in healthy eyes (62.4% and 53.8%, respectively; P < 0.001). Similar results were noted with cpRNFL and mGCC thickness measurements (P < 0.05 for both). The strongest associations between MS in the affected hemifields were found for cpVD (r = 0.707), followed by pfVD (r = 0.615), cpRNFL (r = 0.496), and mGCC (r = 0.482) in the corresponding hemiretinae (P < 0.001 for all). Moreover, the correlations in the intact hemifields between MS with cpVD and pfVD were higher (r = 0.450 and 0.403) than the correlations between MS and cpRNFL and mGCC thickness measurements (r = 0.340 and 0.290; P values <0.05 for all). CONCLUSIONS: Reduced peripapillary and macular vessel density was detectable in the perimetrically intact hemiretinae of glaucoma eyes with a single-hemifield defect. Vessel density attenuation in both affected and intact hemiretinae was associated with the extent of VF damage in the corresponding hemifields. Optical coherence tomography angiography potentially shows promise for identifying glaucomatous damage before focal VF defects are detectable.

Deep Retinal Layer Microvasculature Dropout Detected by the Optical Coherence Tomography Angiography in Glaucoma.

PURPOSE: To investigate factors associated with dropout of the parapapillary deep retinal layer microvasculature assessed by optical coherence tomography angiography (OCTA) in glaucomatous eyes. DESIGN: Cross-sectional study. PARTICIPANTS: Seventy-one eyes from 71 primary open-angle glaucoma (POAG) patients with ß-zone parapapillary atrophy (ßPPA) enrolled in the Diagnostic Innovations in Glaucoma Study. METHODS: Parapapillary deep-layer microvasculature dropout was defined as a complete loss of the microvasculature located within the deep retinal layer of the ßPPA from OCTA-derived optic nerve head vessel density maps by standardized qualitative assessment. Circumpapillary vessel density (cpVD) within the retinal nerve fiber layer (RNFL) also was calculated using OCTA. Choroidal thickness and presence of focal lamina cribrosa (LC) defects were determined using swept-source optical coherence tomography. MAIN OUTCOME MEASURES: Presence of parapapillary deep-layer microvasculature dropout. Parameters including age, systolic and diastolic blood pressure, axial length, intraocular pressure, disc hemorrhage, cpVD, visual field (VF) mean deviation (MD), focal LC defects ßPPA area, and choroidal thickness were analyzed. RESULTS: Parapapillary deep-layer microvasculature dropout was detected in 37 POAG eyes (52.1%). Eyes with microvasculature dropout had a higher prevalence of LC defects (70.3% vs. 32.4%), lower cpVD (52.7% vs. 58.8%), worse VF MD (-9.06 dB vs. -3.83 dB), thinner total choroidal thickness (126.5 µm vs. 169.1 µm), longer axial length (24.7 mm vs. 24.0 mm), larger ßPPA (1.2 mm2 vs. 0.76 mm2), and lower diastolic blood pressure (74.7 mmHg vs. 81.7 mmHg) than those without dropout (P < 0.05, respectively). In the multivariate logistic regression analysis, higher prevalence of focal LC defects (odds ratio [OR], 6.27; P = 0.012), reduced cpVD (OR, 1.27; P = 0.002), worse VF MD (OR, 1.27; P = 0.001), thinner choroidal thickness (OR, 1.02; P = 0.014), and lower diastolic blood pressure (OR, 1.16; P = 0.003) were associated significantly with the dropout. CONCLUSIONS: Systemic and ocular factors including focal LC defects more advanced glaucoma, reduced RNFL vessel density, thinner choroidal thickness, and lower diastolic blood pressure were factors associated with the parapapillary deep-layer microvasculature dropout in glaucomatous eyes. Longitudinal studies are required to elucidate the temporal relationship between parapapillary deep-layer microvasculature dropout and systemic and ocular factors.

Relationship between Optical Coherence Tomography Angiography Vessel Density and Severity of Visual Field Loss in Glaucoma.

PURPOSE: To evaluate the association between vessel density measurements using optical coherence tomography angiography (OCT-A) and severity of visual field loss in primary open-angle glaucoma. DESIGN: Observational, cross-sectional study. PARTICIPANTS: A total of 153 eyes from 31 healthy participants, 48 glaucoma suspects, and 74 glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study. METHODS: All eyes underwent imaging using OCT-A (Angiovue; Optovue, Fremont, CA), spectral-domain OCT (Avanti; Optovue), and standard automated perimetry (SAP). Retinal vasculature information was summarized as vessel density, the percentage of area occupied by flowing blood vessels in the selected region. Two measurements from the retinal nerve fiber layer (RNFL) were used: circumpapillary vessel density (cpVD) (750-µm-wide elliptical annulus around the optic disc) and whole-image vessel density (wiVD) (entire 4.5×4.5-mm scan field). MAIN OUTCOME MEASURES: Associations between the severity of visual field loss, reported as SAP mean deviation (MD), and OCT-A vessel density. RESULTS: Compared with glaucoma eyes, normal eyes demonstrated a denser microvascular network within the RNFL. Vessel density was higher in normal eyes followed by glaucoma suspects, mild glaucoma, and moderate to severe glaucoma eyes for wiVD (55.5%, 51.3%, 48.3%, and 41.7%, respectively) and for cpVD (62.8%, 61.0%, 57.5%, 49.6%, respectively) (P < 0.001 for both). The association between SAP MD with cpVD and wiVD was stronger (R2 = 0.54 and R2 = 0.51, respectively) than the association between SAP MD with RNFL (R2 = 0.36) and rim area (R2 = 0.19) (P < 0.05 for all). Multivariate regression analysis showed that each 1% decrease in wiVD was associated with 0.66 decibel (dB) loss in MD and each 1% decrease in cpVD was associated with 0.64 dB loss in MD. In addition, the association between vessel density and severity of visual field damage was found to be significant even after controlling for the effect of structural loss. CONCLUSIONS: Decreased vessel density was significantly associated with the severity of visual field damage independent of the structural loss. Optical coherence tomography angiography is a promising technology in glaucoma management, potentially enhancing the understanding of the role of vasculature in the pathophysiology of the disease.

Optical Coherence Tomography Angiography Vessel Density in Glaucomatous Eyes with Focal Lamina Cribrosa Defects.

PURPOSE: To investigate whether vessel density assessed by optical coherence tomography angiography (OCT-A) is reduced in glaucomatous eyes with focal lamina cribrosa (LC) defects. DESIGN: Cross-sectional, case-control study. PARTICIPANTS: A total of 82 patients with primary open-angle glaucoma (POAG) from the Diagnostic Innovations in Glaucoma Study (DIGS) with and without focal LC defects (41 eyes of 41 patients in each group) matched by severity of visual field (VF) damage. METHODS: Optical coherence tomography (OCT) angiography-derived circumpapillary vessel density (cpVD) was calculated as the percentage area occupied by vessels in the measured region extracted from the retinal nerve fiber layer (RNFL) in a 750-µm-wide elliptical annulus around the disc. Focal LC defects were detected using swept-source OCT images. MAIN OUTCOME MEASURES: Comparison of global and sectoral (eight 45-degree sectors) cpVDs and circumpapillary RNFL (cpRNFL) thicknesses in eyes with and without LC defects. RESULTS: Age, global, and sectoral cpRNFL thicknesses, VF mean deviation (MD) and pattern standard deviation, presence of optic disc hemorrhage, and mean ocular perfusion pressure did not differ between patients with and without LC defects (P > 0.05 for all comparisons). Mean cpVDs of eyes with LC defects were significantly lower than in eyes without a defect globally (52.9%±5.6% vs. 56.8%±7.7%; P = 0.013) and in the inferotemporal (IT) (49.5%±10.3% vs. 56.8%±12.2%; P = 0.004), superotemporal (ST) (54.3%±8.8% vs. 58.8%±9.6%; P = 0.030), and inferonasal (IN) (52.4%±9.0% vs. 57.6%±9.1%; P = 0.009) sectors. Eyes with LC defects in the IT sector (n = 33) had significantly lower cpVDs than eyes without a defect in the corresponding IT and IN sectors (P < 0.05 for all). Eyes with LC defects in the ST sector (n = 19) had lower cpVDs in the ST, IT, and IN sectors (P < 0.05 for all). CONCLUSIONS: In eyes with similar severity of glaucoma, OCT-A-measured vessel density was significantly lower in POAG eyes with focal LC defects than in eyes without an LC defect. Moreover, reduction of vessel density was spatially correlated with the location of the LC defect.

Correlation between depth and area of retinal nerve fiber layer defect as measured by spectral domain optical coherence tomography.

BACKGROUND: To evaluate the correlation between the depth and area of retinal nerve fiber layer (RNFL) defect, as measured on an RNFL map of spectral-domain optical coherence tomography (SD-OCT). METHODS: The RNFL of 472 glaucoma subjects and of 217 healthy subjects was imaged by an SD-OCT. RNFL defect depth and area on the RNFL map were expressed as an RNFL defect depth percentage index (RDPI) and an RNFL defect area index (RDAI), respectively, according to the following two formulas: 100×[1-{summation of thicknesses of RNFL defects/summation of thicknesses of upper 95th percentile range of age-matched healthy subjects in areas corresponding to defects}]; 100×[number of superpixels of RNFL defects/(46 × 46-superpixels inside optic disc or ß zone parapapillary atrophy)]. The best-fitting model describing the relationship between the two parameters was derived by fractional polynomial analysis. RESULTS: Logarithmic fit was determined to be the best-fitting model in describing the relationship of the RDPI against the RDAI (y = 53.4 + 3.7 ln(x) and y = 50.9 + 5.9 ln(x) in superior and inferior hemifields, respectively). The expected RDAIs at the point where the RDPI and RDAI rates of change were the same were 3.7 and 5.9 %; the corresponding upper 95 % confidence interval limits of the RDPI 59.0 and 61.8 % in the superior and inferior hemifields, respectively. CONCLUSIONS: The correlation between the RNFL defect depth and area, as derived from the RNFL map, was best described by the logarithmic fit. Changes were more marked in depth than in area, especially for mild localized defects.

Quantitative assessment of retinal nerve fiber layer defect depth using spectral-domain optical coherence tomography.

PURPOSE: To assess quantitatively the depth of retinal nerve fiber layer (RNFL) defects using a Cirrus high-definition (HD) optical coherence tomography (OCT)-derived RNFL thickness deviation map. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Three-hundred fifteen eyes with localized and diffuse RNFL defects of 315 glaucoma patients and 217 eyes of 217 healthy subjects. METHODS: For the glaucoma subjects, the severity of the RNFL defect was graded on red-free fundus photographs by 2 observers using a standardized protocol with a 3-level grading system. The RNFL defect depth on the RNFL thickness deviation map was expressed as an RNFL defect depth percentage index (RDPI): 100×(1-[summation of thicknesses of RNFL defects {red or yellow superpixels}/summation of RNFL thicknesses of upper 95th percentile range of age-matched healthy subjects in areas corresponding to RNFL defects]). MAIN OUTCOME MEASURES: Retinal nerve fiber layer defect depth percentage index, average and segmental (4 quadrants and 12 clock-hour sectors) circumpapillary RNFL (cpRNFL) thicknesses according to the RNFL defect severity, and the area under the receiver operating characteristic curves (AUROCs) for various OCT parameters. RESULTS: The RDPIs increased with the increasing severity of the RNFL defect in both the superior and inferior hemifields (P <0.05, 1-way analysis of variance test with Bonferroni correction). The AUROCs of the RDPIs (0.969 and 0.975 in the superior and inferior hemifields, respectively) were larger than those of all of the cpRNFL thicknesses in discriminating the mild from the moderate RNFL defects (P <0.05). Meanwhile, in discriminating the moderate from the severe RNFL defects, the AUROCs of the RDPIs (0.961 and 0.891 in the superior and inferior hemifields, respectively) were larger than those of the cpRNFL thicknesses in all areas except the inferior quadrant and the 6-, 7-, and 11-o'clock sectors (P <0.05). CONCLUSIONS: The RDPI, a new parameter using a Cirrus HD OCT-derived RNFL thickness deviation map, can be a useful adjunct tool for objective quantification of RNFL defect depth. This parameter has an advantage over cpRNFL thickness in discriminating between mild and moderate RNFL defects, not in discriminating between moderate and severe defects.

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).

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.

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.

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.

Lamina cribrosa thickness is not correlated with central corneal thickness or axial length in healthy eyes: central corneal thickness, axial length, and lamina cribrosa thickness.

BACKGROUND: The aim of this study was to determine the relationship of the central corneal thickness (CCT) and axial length (AXL) with the central lamina cribrosa thickness (LCT) in healthy human eyes. METHODS: This was a prospective observational case series. The optic discs of 189 eyes from 100 healthy subjects with a refractive error smaller than -8 diopters were scanned using enhanced-depth imaging spectral-domain optical coherence tomography (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). The thickness of the lamina cribrosa (LC) was measured on B-scan images obtained at the center of the optic nerve head. A linear mixed-effects model was used to determine the factors associated with LCT, taking into account clustering of eyes within subjects. RESULTS: The thickness of the central LC was 273.19 ± 34.74 µm (mean ± SD; range, 173.73-367.94 µm). Multivariate analysis revealed a significant influence of older age on increased central LCT (p = 0.001). There was no significant association between central LCT and either CCT or AXL. CONCLUSIONS: In this study, the central LCT increased significantly with older age in healthy human eyes. Neither CCT nor AXL was significantly associated with the central LCT in healthy human eyes with a spherical equivalent within the range from -7.0 to +3.0 diopters.

Combination of optic disc rim area and retinal nerve fiber layer thickness for early glaucoma detection by using spectral domain OCT.

BACKGROUND: To compare the diagnostic ability of optic disc rim area (RA), retinal nerve fiber layer thickness (RNFLT), and their combination on sector-based analysis of spectral domain optical coherence tomography (Cirrus OCT) in discriminating subjects with early-stage open angle glaucoma (OAG) from normal subjects. METHODS: RA and RNFLT of 78 early OAG and 80 normal subjects were measured on Cirrus OCT at the global area, 4 quadrants, 12 clock hours, and 7 + 11 o'clock (a sector that includes 7 and 11 o'clock). A new parameter, RR (a multiplication of the RA and RNFLT) was derived to identify the best combination of the two parameters. Areas under the receiver operating characteristics curves (AUCs) of RA, RNFLT, and RR were compared. RESULTS: AUCs of RA were larger than those of RNFLT at nasal quadrant, at 1-5 o'clock on Cirrus OCT (all P values < 0.05). At the remaining areas, the two parameters were not significantly different on both devices (all P values > 0.05). RR had significantly larger AUCs than those of both RA and RNFLT at 7 + 11 o'clock (0.931 for RA, 0.933 for RNFLT, and 0.968 for RR) and global area (0.914 for RA, 0.905 for RNFLT, and 0.935 for RR), which were the two areas with largest AUCs. CONCLUSIONS: RR outperformed both RA and RNFLT of the Cirrus OCT, especially at areas with diagnostic importance. This suggests that combinations of RA and RNFLT by sector-based analysis of Cirrus OCT would be promising to determine early glaucoma.

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.

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.

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.

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.