Impact of Pupil Dilation on Optical Coherence Tomography Angiography Retinal Microvasculature in Healthy Eyes.

PRéCIS:: Small but significant decreases in optical coherence tomography angiography (OCTA)-measured circumpapillary capillary density (cpCD) were observed in healthy eyes dilated with 2.5% phenylephrine/0.5% tropicamide. Although likely clinically insignificant, ophthalmologists should consider these changes when interpreting OCTA results from dilated eyes. PURPOSE: The purpose of this study was to investigate the effect of pupil dilation using 2.5% phenylephrine and 0.5% tropicamide on quantitative assessment of retinal microvasculature using OCTA. METHODS: OptoVue AngioVue high density (HD) and non-HD OCTA macula and optic nerve head (ONH) images were obtained at 15-minute intervals predilation and postdilation in 26 healthy participants (mean age: 40.0; 95% confidence interval=33.9, 46.1 y). Superficial macular vessel density (VD) was measured in the whole image VD and the parafoveal region VD. ONH capillary density was measured in the whole image capillary density and the cpCD region. Differences between predilation and postdilation densities were assessed using linear mixed effects models to account for within-patient correlation. RESULTS: Instillation of dilating drops resulted in a small but statistically significant reduction in non-HD ONH whole image capillary density of 0.6%, from a mean of 45.2% (95% confidence interval=41.9%, 48.4%) to 44.6% (41.4%, 47.8%) (P=0.046). A similar reduction in non-HD ONH cpCD of 0.8% also was observed, from a mean of 49.3% (45.3%, 53.3%) to 48.5% (44.5%, 52.4%) (P=0.025). No postdilation decreases in macular VD or HD ONH capillary density were observed. CONCLUSIONS: Pupil dilation using topical 2.5% phenylephrine and 0.5% tropicamide results in a small but statistically significant reduction in non-HD ONH whole image and cpCD in healthy eyes. The observed reduction likely is not clinically significant because the observed reduction was within the previously reported range of measurement variability. Further studies should consider investigating these effects in nonhealthy eyes with glaucoma and media opacities, as well as older individuals.

Diagnostic Ability of Optical Coherence Tomography Angiography Macula Vessel Density for the Diagnosis of Glaucoma Using Difference Scan Sizes.

PRéCIS:: There is diagnostic information in the outer region of optical coherence tomography angiography (OCT-A) macula scans not available in the inner region, and this information is especially useful in the early stages of glaucoma. PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of 3×3 and 6×6 mm macula OCT-A scans for classifying healthy, mild glaucoma, and moderate to severe glaucoma eyes. METHODS: Participants enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality 3×3 and 6×6 mm OCT-A images of the macula acquired on the same day were included in this cross-sectional study. The area under the receiver operating characteristic (AUC) curves were calculated to assess the diagnostic accuracy of vessel density (VD) of both scan sizes for differentiating between 3 diagnostic groups. RESULTS: Two hundred seventy-nine eyes (89 healthy, 127 with mild glaucoma, and 63 with moderate to severe glaucoma) from 190 subjects were included in this study. The VD of the outer area of the 6×6 mm scan size had higher diagnostic accuracy compared with the VD of the inner area of the 3×3 mm scan when differentiating between healthy and mild glaucoma (3×3 mm AUC=0.71 and 6×6 mm AUC=0.79, P=0.032). The VD of the outer area of the 6×6 mm scans had only similar diagnostic accuracy compared with the inner area of the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes (AUC=0.90 for 3×3 mm and 0.92 for 6×6 mm, P=0.279). The VD of the inner area of the 6×6 mm scan size had similar diagnostic accuracy to the corresponding area of the 3×3 mm scan in both diagnostic categories. CONCLUSION: The diagnostic accuracy of VD using the 6×6 mm macula OCT-A scan was better than the 3×3 mm scan when differentiating between healthy and mild glaucoma eyes, and similar to the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes.

Optical Coherence Tomography Angiography Macular Vascular Density Measurements and the Central 10-2 Visual Field in Glaucoma.

PURPOSE: To evaluate the association between macula vascular density assessed by optical coherence tomography angiography (OCT-A) and central visual field (VF) threshold sensitivities in healthy, glaucoma suspect, and glaucoma patients. METHODS: A total of 185 eyes from 38 healthy participants, 31 glaucoma suspects, 72 mild glaucoma patients, and 44 moderate/severe glaucoma patients from the Diagnostic Innovations in Glaucoma Study who underwent OCT-A images of the macula and 10-2 VF testing were enrolled in this observational cross-sectional study. The relationship between central VF mean sensitivity (MS) and superficial macula whole-image vessel density (wiVD), and the relationship between the MS of the 4 central points of the 10-2 VF (MS4) and parafoveal vessel density (pfVD), were assessed using linear regression models. RESULTS: Mean wiVD (52.5%, 49.8%, 49.4% and 45.2%, respectively) and mean pfVD (54.9%, 52.1%, 51.8% and 47.7%, respectively) were found to be significantly higher in healthy eyes and glaucoma suspect eyes compared with glaucoma eyes with mild and moderate/severe disease [analysis of covariance (ANCOVA) P<0.001]. The univariate associations between 10-2 MS and wiVD (R=26.9%) and between 10-2 MS4 and pfVD (R=16.8%) were statistically significant (P<0.001 for both). After adjusting for scan quality, age, sex and intraocular pressure, superficial macula wiVD and pfVD were still independently associated with central VF loss. Macula wiVD performed better [area under the receiver operator characteristic (AUROC)=0.70] than ganglion cell complex thickness (AUROC=0.50) for differentiating between glaucoma suspect and healthy eyes (P=0.010). CONCLUSIONS: Loss of OCT-A macula vessel density is associated with central 10-2 VF defects. Macula vessel density is a clinically relevant parameter that may enhance monitoring of glaucoma suspects and patients.

Macular Vessel Density in Glaucomatous Eyes With Focal Lamina Cribrosa Defects.

PURPOSE: To compare optical coherence tomography angiography (OCTA) measured macular vessel density and spectral domain optical coherence tomography (SDOCT) measured macular ganglion cell complex (GCC) thickness in primary open-angle glaucoma eyes with and without focal lamina cribrosa (LC) defects. METHODS: In this cross-sectional, case-control study of patients with primary open-angle glaucoma, 46 eyes of 46 patients with LC defects and 54 eyes of 54 patients without observable LC defects were included. OCTA and SDOCT imaging were performed on the same day by the same operator. Perimetry and swept-source OCT testing used to identify LC defects were conducted within 6 months of OCTA and SDOCT testing. Global and local parafoveal vessel density and macular GCC thickness were compared between study groups. RESULTS: Glaucoma severity was similar between groups (SAP mean deviation=-5.63 and -4.64 dB for eyes with and without LC defects, respectively; P=0.40). Global and local measured parafoveal vessel density was similar between groups (all P≥0.11). GCC focal loss volume was higher in eyes with LC defects than eyes without LC defects (7.2% and 4.97%, respectively; P=0.03). In addition, GCC focal loss volume was topographically related to defect location in LC defect eyes. CONCLUSIONS: Although OCTA macular vessel density was not significantly different between eyes with and without LC defects, focal GCC loss in eyes with LC defects was different. This highlights the importance of not relying solely on vessel density measurements for determining macular changes for diagnosing and detecting glaucomatous progression.

The Association Between Macula and ONH Optical Coherence Tomography Angiography (OCT-A) Vessel Densities in Glaucoma, Glaucoma Suspect, and Healthy Eyes.

PURPOSE: To evaluate strength of associations between optical coherence tomography (OCT)-angiography vessel density (VD) measurements in the macula and peripapillary region of the optic nerve head (ONH) with standard structural OCT thickness measures. MATERIALS AND METHODS: This cross-sectional study included 333 eyes of 219 primary open-angle glaucoma patients, 41 glaucoma suspects, and 73 healthy participants from the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality OCT angiography images. The strength of associations between microvasculature measures in the ONH retinal nerve fiber layer (RNFL) and superficial macula layer was assessed using linear regression models. Associations between ONH and macula VD, and circumpapillary (cp) RNFL thickness and macular ganglion cell complex (mGCC) measures were also evaluated. RESULTS: The strength (r) of associations among VD and thickness measures of ONH and macula ranged from 14.1% to 69.4%; all were statistically significant (P<0.001). The association between ONH and macula whole-image VD (r=41.0%) was significantly weaker than the relationship between mGCC and cpRNFL thickness (r=69.4%, P<0.001). Although both cpRNFL and mGCC thicknesses tended to be more strongly associated with ONH VD (r=39.2% and 26.7%, respectively) than macula VD (r=27.5% and 17.7%, respectively), differences did not reach statistical significance (P=0.050 and P=0.113, respectively). CONCLUSIONS: The strength of the association of VD with cpRNFL and mGCC thicknesses varies by retinal layer. The weaker association of macula VD compared with ONH VD with tissue thickness may be due to differences in micorovasculature between the macula and ONH.

Reproducibility of Optical Coherence Tomography Angiography Macular and Optic Nerve Head Vascular Density in Glaucoma and Healthy Eyes.

PURPOSE: Optical coherence tomography angiography (OCT-A) is a noninvasive technology that allows visualization of retinal blood vessels. It is important to determine reproducibility of measurements as low precision can impair its diagnostic capabilities. The purpose of this study is to determine intravisit and intervisit reproducibility of optic nerve head (ONH) and macular vessel density measurements with OCT-A. PATIENTS AND METHODS: Fifteen healthy volunteers and 14 glaucoma patients completed 2 OCT-A (AngioVue; Optovue Inc.) scanning sessions on each of 2 separate days to assess intravisit and intervisit reproducibility. A series of ONH and macula scans were acquired at each session. Vessel density (%), the proportion of vessel area over the total measurement area was calculated. Reproducibility was summarized using coefficients of variation (CV) and intraclass correlation coefficients calculated from variance component models. RESULTS: In healthy eyes, the CV of intravisit and intervisit global vessel density measures ranged from 1.8% to 3.2% in ONH scans and 2.5% to 9.0% in macular scans. In glaucoma eyes, the CV of intravisit and intervisit global vessel density measures ranged from 2.3% to 4.1% in ONH scans and 3.2% to 7.9% in macular scans. CVs were lower for global than sectorial measures. Global OCT-A ONH intraclass correlation measurements for the retinal nerve fiber layer in healthy eyes were lower (range: 0.65 to 0.85) than in glaucoma eyes (range: 0.89 to 0.94). Scan size did not make large differences in measurement CVs. CONCLUSIONS: Reproducibility of OCT-A ONH and macula vessel density measurements is good. Moreover, glaucoma patients have sparser vessel density with poorer reproducibility than healthy subjects.

REPRODUCIBILITY OF VESSEL DENSITY MEASUREMENT WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN EYES WITH AND WITHOUT RETINOPATHY.

PURPOSE: To determine the intravisit and intervisit reproducibility of optical coherence tomography angiography measurements of macular vessel density in eyes with and without retinal diseases. METHODS: Fifteen healthy volunteers and 22 patients with retinal diseases underwent repeated optical coherence tomography angiography (Angiovue Imaging System, Optovue Inc) scans after pupil dilation on 2 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. Intravisit and intervisit reproducibility were summarized as coefficient of variations and intraclass correlation coefficients were calculated from variance component models. RESULTS: The coefficient of variations representing the intravisit reproducibility of the superficial macular vessel density measurements for different quadrants on 3 mm × 3-mm scans varied from 2.1% to 4.9% and 3.4% to 6.8% for healthy and diseased eyes, respectively, and for the intervisit it was 2.9% to 5.1% and 4.0% to 6.8%, respectively. The coefficient of variations were lower in healthy eyes than in diseased eyes, lower for intravisit than for intervisit, lower on 3 mm × 3-mm scans than on 6 mm × 6-mm scans, and lower for paracentral subfields than for central subfield. CONCLUSION: The evidence presented here demonstrates good reproducibility of optical coherence tomography angiography for measurement of superficial macula vessel density in both healthy eyes and eyes with diabetic retinopathy without diabetic macular edema.