PurposeThe purpose of this study was to compare retinal nerve fiber layer (RNFL) thickness and optical coherence tomography angiography (OCT-A) retinal vasculature measurements in healthy, glaucoma suspect, and glaucoma patients.MethodsTwo hundred sixty-one eyes of 164 healthy, glaucoma suspect, and open-angle glaucoma (OAG) participants from the Diagnostic Innovations in Glaucoma Study with good quality OCT-A images were included. Retinal vasculature information was summarized as a vessel density map and as vessel density (%), which is the proportion of flowing vessel area over the total area evaluated. Two vessel density measurements extracted from the RNFL were analyzed: (1) circumpapillary vessel density (cpVD) measured in a 750-μm-wide elliptical annulus around the disc and (2) whole image vessel density (wiVD) measured over the entire image. Areas under the receiver operating characteristic curves (AUROC) were used to evaluate diagnostic accuracy.ResultsAge-adjusted mean vessel density was significantly lower in OAG eyes compared with glaucoma suspects and healthy eyes. (cpVD: 55.1 ± 7%, 60.3 ± 5%, and 64.2 ± 3%, respectively; P < 0.001; and wiVD: 46.2 ± 6%, 51.3 ± 5%, and 56.6 ± 3%, respectively; P < 0.001). For differentiating between glaucoma and healthy eyes, the age-adjusted AUROC was highest for wiVD (0.94), followed by RNFL thickness (0.92) and cpVD (0.83). The AUROCs for differentiating between healthy and glaucoma suspect eyes were highest for wiVD (0.70), followed by cpVD (0.65) and RNFL thickness (0.65).ConclusionsOptical coherence tomography angiography vessel density had similar diagnostic accuracy to RNFL thickness measurements for differentiating between healthy and glaucoma eyes. These results suggest that OCT-A measurements reflect damage to tissues relevant to the pathophysiology of OAG.

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 (POAG) Design Observational cross-sectional study Participants One hundred and fifty three eyes from 31 healthy, 48 glaucoma suspects, and 74 glaucoma participants enrolled in the Diagnostic Innovations in Glaucoma Study Methods All eyes underwent imaging using an OCT-A (Angiovue, Optovue; Fremont, CA) and a spectral domain OCT (Avanti, Optovue; Fremont, CA), along with standard automated perimetry (SAP). Retinal vasculature information was summarized as vessel density, the percent of area occupied by flowing blood vessels in the selected region. Two measurements from the retinal nerve fiber layer (RNFL) were utilized: 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 severity of visual field loss, reported as SAP mean deviation (MD) and OCT-A vessel density Results Compared to POAG 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, 41.7% respectively) and for cpVD (62.8, 61.0, 57.5, 49.6% respectively) (P<0.001 for both). The association between the severity of visual field damage (MD) with cpVD and wiVD was stronger (R2=0.54, and R2=0.51 respectively) than the association between visual field MD and RNFL (R2=0.36) and rim area (R2=0.19) (P<0.05 for all). Multivariate regression analysis, adjusted for confounders, showed that each 1% decrease in cpVD was associated with 0.64 dB loss in MD and each 1% decrease in wiVD, was associated with 0.66 dB loss in MD. In addition, the association between vessel density and the 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 severity of visual field damage independent of the structural loss. OCT-A is a promising technology in glaucoma management, potentially enhancing the understanding of vascular role in the pathophysiology of the disease

Purpose To investigate factors associated with dropout of the deep retinal layer microvasculature within the β-zone parapapillary atrophy (βPPA) assessed by optical coherence tomography angiography (OCT-A) in glaucomatous eyes. Design Cross-sectional study. Participants Seventy-one eyes from 71 primary open angle glaucoma (POAG) patients with βPPA enrolled in the Diagnostic Innovations in Glaucoma Study. Methods βPPA deep layer microvasculature dropout was defined as a complete loss of the microvasculature located within deep retinal layer of the βPPA from OCT-A-derived optic nerve head vessel density maps by standardized qualitative assessment. Circumpapillary vessel density (cpVD) within the retinal nerve fiber layer (RNFL) was also calculated using OCT-A. Choroidal thickness and presence of the focal lamina cribrosa (LC) defect were determined using swept-source OCT. Main Outcome Measures Presence of the βPPA 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 defect, βPPA area, and choroidal thickness were analyzed. Results βPPA deep layer microvasculature dropout was detected in 37 eyes (52.1%) of eyes with POAG. Eyes with dropouts had a higher prevalence of LC defect (70.3 vs. 32.4%), lower cpVD (52.7 vs. 58.8%), worse VF MD (-9.06 vs. -3.83dB), thinner total choroidal thickness (126.5 vs. 169.1/μm), longer axial length (24.7 vs. 24.0mm), larger βPPA (1.2 vs. 0.76mm2) and lower diastolic blood pressure (74.7 vs. 81.7mmHg) than those without dropouts (P< 0.05, respectively). In the multivariate logistic regression, higher prevalence of focal LC defect (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 significantly associated with the dropout. Conclusions Certain systemic and ocular factors such as focal LC defect, more advanced disease status, reduced RNFL vessel density, thinner choroidal thickness, and lower diastolic blood pressure were factors associated with the βPPA deep layer microvasculature dropout in glaucomatous eyes. Longitudinal studies are required to elucidate the temporal relationship between βPPA deep layer dropout and these factors.

Purpose To compare hemifield differences in the vessel density of the optic nerve head and macula in open-angle glaucoma (OAG) eyes with visual field (VF) defect confined to one hemifield using optical coherence tomography angiography (OCT-A). Design Cross-sectional study. Participants Fifty-eight eyes of 58 glaucoma patients 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 also calculated using spectral domain OCT. Paired and unpaired t-tests were utilized 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 OAG eyes (59.0% and 51.1%) were higher than the affected hemiretinae (54.7% and 48.3%; p<0.001) but lower than healthy eyes (62.4% and 53.8%; 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 found to be higher (r = 0.450 and 0.403) than the correlations between MS and cpRNFL and mGCC thickness measurements (r = 0.340 and 0.290; all 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. Moreover vessel density attenuation in both affected and intact hemiretinae was associated with the extent of VF damage in the corresponding hemifields. OCT-A potentially shows promise for identifying glaucomatous damage before focal VF defects are detectable.

Purpose To characterize the rate of macula vessel density loss in primary open angle glaucoma (POAG), glaucoma suspect, and healthy eyes. Design Longitudinal, observational cohort from the Diagnostic Innovations in Glaucoma Study. Methods One hundred eyes (32 POAG, 30 glaucoma suspect and 38 healthy) followed for at least one year with optical coherence tomography angiography (OCT-A) imaging on at least two visits were included. Vessel density was calculated in the macula superficial layer. The rate of change was compared across diagnostic groups using multivariate linear mixed-effects model. Results Baseline macula vessel density was highest in healthy eyes, followed by glaucoma-suspect and POAG eyes (P < 0.01). The rate of vessel density loss was significantly different from zero in the POAG, but not in the glaucoma suspect or healthy eyes. The mean rate of change in macula whole en-face vessel density was significantly faster in glaucoma eyes (−2.23 %/yr) than in glaucoma suspect (0.87%/yr, P = 0.001) or healthy eyes (0.29 %/yr, P = 0.004). Conversely, the rate of change in ganglion cell complex (GCC) thickness was not significantly different from zero in any diagnostic group, and no significant differences in the rate of GCC change among diagnostic groups were found. Conclusions With a mean follow-up of less than 14 months, eyes with POAG had significantly faster loss of macula vessel density than either glaucoma suspect or healthy eyes. Serial OCT-A measurements also detected glaucomatous change in macula vessel density in eyes without evidence of change in GCC thickness.

This modeling exercise indicates that most patients in glaucoma clinics are not at high risk of progressing to statutory blindness. The likelihood of patients suffering impairment in their lifetimes is linked to VF loss at presentation, which illuminates the importance of reliably detecting significant VF defects in primary care.

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.

Purpose To determine the intra-visit and inter-visit reproducibility of optical coherence tomography angiography (OCTA) measurements of macular vessel density in eyes with and without retinal diseases. Methods Fifteen healthy volunteers and 22 patients with retinal diseases underwent repeated OCTA (Angiovue Imaging System, Optovue Inc.) scans after pupil dilation on two separate visit days. For each visit day, the eyes were scanned twice. Vessel density defined as the proportion of vessel area with flowing blood over the total measurement area was calculated using Angiovue software. Intra-visit and inter-visit reproducibility were summarized as coefficients of variation (CV) and intra-class correlation coefficients (ICC) calculated from variance component models. Results The CVs representing the intra-visit reproducibility of the superficial macular vessel density measurements for different quadrants on 3 × 3 mm scans varied from 2.1–4.9% and 3.4–6.8% for healthy and diseased eyes respectively, and for the inter-visit it was 2.9–5.1% and 4.0–6.8% respectively. The CVs were lower in healthy eyes than in diseased eyes, lower for intra-visit than for inter-visit, lower on 3 × 3 mm scans than on 6 × 6 mm scans, and lower for paracentral subfields than for central subfield. Conclusion The evidence presented here demonstrates good reproducibility of OCTA for measurement of superficial macula vessel density in both healthy eyes and eyes with diabetic retinopathy without diabetic macular edema.