Purpose

To evaluate whether automated assessment of beta zone parapapillary atrophy (βPPA) area can differentiate between glaucomatous and healthy eyes of varying axial lengths (AL).

Design

Cross-sectional study.

Methods

βPPA 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 βPPA 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 βPPA 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 βPPA area. The age- and AL-adjusted area under the receiver operating characteristic curve (95% confidence interval) of βPPA 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 βPPA 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.

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.

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.

Purpose

To determine if OCT angiography (OCTA)-derived vessel density measurements can extend the available dynamic range for detecting glaucoma compared with spectral-domain (SD) OCT-derived thickness measurements.

Design

Observational, cross-sectional study.

Participants

A total of 509 eyes from 38 healthy participants, 63 glaucoma suspects, and 193 glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study.

Methods

Relative vessel density and tissue thickness measurement floors of perifoveal vessel density (pfVD), circumpapillary capillary density (cpCD), circumpapillary retinal nerve fiber (cpRNFL) thickness, ganglion cell complex (GCC) thickness, and visual field (VF) mean deviation (MD) were investigated and compared with a previously reported linear change point model (CPM) and locally weighted scatterplot smoothing curves.

Main outcome measures

Estimated vessel density and tissue thickness measurement floors and corresponding dynamic ranges.

Results

Visual field MD ranged from -30.1 to 2.8 decibels (dB). No measurement floor was found for pfVD, which continued to decrease constantly until very advanced disease. A true floor (i.e., slope of approximately 0 after observed CPM change point) was detected for cpRNFL thickness only. The post-CPM estimated floors were 49.5±2.6 μm for cpRNFL thickness, 70.7±1.0 μm for GCC thickness, and 31.2±1.1% for cpCD. Perifoveal vessel density reached the post-CPM estimated floor later in the disease (VF MD, -25.8±3.8 dB) than cpCD (VF MD, -19.3±2.4 dB), cpRNFL thickness (VF MD, -17.5±3.3 dB), and GCC thickness (VF MD, -13.9±1.8 dB; P < 0.001). The number of available measurement steps from normal values to the CPM estimated floor was greatest for cpRNFL thickness (8.9), followed by GCC thickness (7.4), cpCD (4.5), and pfVD (3.8).

Conclusions

In late-stage glaucoma, particularly when VF MD is worse than -14 dB, OCTA-measured pfVD is a promising tool for monitoring progression because it does not have a detectable measurement floor. However, the number of steps within the dynamic range of a parameter also needs to be considered. Although thickness parameters reached the floor earlier than OCTA-measured pfVD, there are more such steps with thickness than OCTA parameters.

PURPOSE:To evaluate whether automated assessment of beta zone parapapillary atrophy (βPPA) area can differentiate between glaucomatous and healthy eyes of varying axial lengths (AL). DESIGN:Cross-sectional study. METHODS:βPPA 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 βPPA 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 βPPA 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 βPPA area. The age- and AL-adjusted area under the receiver operating characteristic curve (95% confidence interval) of βPPA 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 βPPA 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.

Purpose

To investigate inter-eye retinal vessel density asymmetry in healthy, glaucoma suspect, and mild-to-moderate glaucoma subjects, and its potential utility for early detection of glaucomatous damage.

Design

Cross-sectional study.

Methods

In 153 subjects including 55 healthy, 32 glaucoma suspect, and 66 glaucoma subjects enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS), vessel density was obtained from optical coherence tomography angiography (OCT-A) macular and optic nerve head scans. Thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (mGCC) was measured with spectral-domain optical coherence tomography (SD-OCT) scans. Inter-eye asymmetry was calculated by taking the absolute value of difference in vessel density and thickness between the right and left eyes.

Results

Inter-eye retinal vessel density asymmetry parameters were significantly different among the 3 groups. Glaucoma suspects had significantly higher peripapillary and macular inter-eye vessel density asymmetries compared to healthy groups in univariate (1.1% vs 2.0%, P = .014 and 1.2% vs 2.5%, P = .027, respectively) and multivariate analyses (P = .007 and P = .038, respectively). No significant differences in asymmetry of thickness parameters were found between glaucoma suspect and healthy groups (all P > .718). However, significant differences in asymmetry of thickness parameters between glaucoma suspects and glaucoma patients (P < .01) were found for all parameters.

Conclusion

Inter-eye vessel density asymmetry can be quantified by OCT-A measurement. Glaucoma suspects have significantly greater vessel density asymmetry than healthy eyes. Longitudinal studies are needed to better characterize the relationship of vessel density asymmetry with the development and progression of glaucoma.

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 1 year with optical coherence tomography angiography (OCT-A) imaging on at least 2 visits were included. Vessel density was calculated in the macula superficial layer. The rate of change was compared across diagnostic groups using a multivariate linear mixed-effects model.

Results

Baseline macula vessel density was highest in healthy eyes, followed by glaucoma-suspect and POAG eyes (P < .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%/y) than in glaucoma-suspect (0.87%/y, P = .001) or healthy eyes (0.29%/y, P = .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.

Purpose

To investigate inter-eye retinal vessel density asymmetry in healthy, glaucoma suspect, and mild-to-moderate glaucoma subjects, and its potential utility for early detection of glaucomatous damage.

Design

Cross-sectional study.

Methods

In 153 subjects including 55 healthy, 32 glaucoma suspect, and 66 glaucoma subjects enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS), vessel density was obtained from optical coherence tomography angiography (OCT-A) macular and optic nerve head scans. Thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (mGCC) was measured with spectral-domain optical coherence tomography (SD-OCT) scans. Inter-eye asymmetry was calculated by taking the absolute value of difference in vessel density and thickness between the right and left eyes.

Results

Inter-eye retinal vessel density asymmetry parameters were significantly different among the 3 groups. Glaucoma suspects had significantly higher peripapillary and macular inter-eye vessel density asymmetries compared to healthy groups in univariate (1.1% vs 2.0%, P = .014 and 1.2% vs 2.5%, P = .027, respectively) and multivariate analyses (P = .007 and P = .038, respectively). No significant differences in asymmetry of thickness parameters were found between glaucoma suspect and healthy groups (all P > .718). However, significant differences in asymmetry of thickness parameters between glaucoma suspects and glaucoma patients (P < .01) were found for all parameters.

Conclusion

Inter-eye vessel density asymmetry can be quantified by OCT-A measurement. Glaucoma suspects have significantly greater vessel density asymmetry than healthy eyes. Longitudinal studies are needed to better characterize the relationship of vessel density asymmetry with the development and progression of 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 (β, 1.007; P = 0.005), visual field mean deviation (β, 0.066; P = 0.049), and difference in intraocular pressure before and after DH (β, -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.

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.