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.

Agreement and precision of wide and cube scan measurements between swept-source and spectral-domain OCT in normal and glaucoma eyes.

This study aimed to evaluate agreement of Wide scan measurements from swept-source optical coherence tomography (SS-OCT) Triton and spectral-domain OCT (SD-OCT) Maestro in normal/glaucoma eyes, and to assess the precision of measurements from Wide and Cube scans of both devices. Three Triton and three Maestro operator/device configurations were created by pairing three operators, with study eye and testing order randomized. Three scans were captured for Wide (12 mm × 9 mm), Macular Cube (7 mm × 7 mm-Triton; 6 mm × 6 mm-Maestro), and Optic Disc Cube (6 mm × 6 mm) scans for 25 normal eyes and 25 glaucoma eyes. Parameter measurements included circumpapillary retinal nerve fiber layer(cpRNFL), ganglion cell layer + inner plexiform layer (GCL+), and ganglion cell complex (GCL++). A two-way random effect analysis of variance model was used to estimate the repeatability and reproducibility; agreement was evaluated by Bland-Altman analysis and Deming regression. The precision estimates were low, indicating high precision, for all thickness measurements with the majority of the limits < 5 µm for the macula and < 10 µm for the optic disc. Precision of the Wide and Cube scans were comparable. Excellent agreement between the two devices was found for Wide scans, with the mean difference < 3 µm across all measurements (cpRNFL < 3 µm, GCL+ < 2 µm, GCL ++ < 1 µm), indicating interoperability. A single Wide scan covering the peripapillary and macular regions may be useful for glaucoma diagnosis and management.

Factors associated with choroidal microvascular dropout change.

BACKGROUND/AIMS: To investigate the factors associated with choroidal microvasculature drop-out (MvD) enlargement detected by optical coherence tomography angiography (OCT-A) in glaucomatous eyes. METHODS: Ninety-one eyes of 68 primary open-angle glaucoma patients were enrolled. Only eyes with a minimum of four good quality OCT-A and OCT scans of the optic nerve head acquired at least and with a minimum of 2 years follow-up were included. Area and angular circumference of MvD were analysed on en face images. Univariable and multivariable mixed effects models were constructed to identify the factors contributing to MvD area and angular circumference change over time. RESULTS: Peripapillary MvD was detected in 53 (58.2%) eyes at baseline and in an additional 17 (18.6%) eyes during follow-up, whereas MvD was not detected in 21 (23.0 %) eyes during the entire follow-up period. In multivariable analysis, worse baseline visual field (VF) mean deviation (MD) (ß=0.27, 95% CI 0.10 to 0.44, p=0.002), greater intraocular pressure (IOP) fluctuations (ß=0.86, 95% CI 0.24 to 1.48, p=0.007), higher peak IOP (ß=0.17, 95% CI -0.01 to 0.35, p=0.067) and greater number of IOP lowering medications (ß=1.36, 95% CI 0.67 to 2.05, p<0.001) were associated with faster MvD area enlargement. Worse baseline VF MD and greater IOP fluctuation were also associated with significantly faster MvD circumferential enlargement in multivariable models. CONCLUSION: Greater IOP fluctuation, higher peak IOP, worse baseline VF MD and greater number of glaucoma medications were significantly associated with MvD enlargement in glaucomatous eyes. The identification of factors associated with MvD enlargement may improve our understanding of the role of choroidal vasculature in glaucoma.

Central macular OCTA parameters in glaucoma.

BACKGROUND/AIMS: To investigate the relationship between the foveal avascular zone (FAZ) parameters assessed by optical coherence tomography angiography (OCTA) and central visual field parameters in glaucoma and healthy subjects. METHODS: One hundred and eighty-eight subjects (248 eyes), including 24 healthy (38 eyes), 37 glaucoma suspect (42 eyes, and 127 primary open angle glaucoma (POAG) patients (168 eyes), underwent imaging using OCTA and standard automated perimetry using the 24-2 and 10-2 Swedish Interactive Thresholding Algorithm. OCTA-based and OCT-based FAZ parameters (superficial FAZ area, FAZ circumference), foveal vessel density (FD300) and foveal thickness were measured. The correlation between FAZ parameters and visual field parameters was assessed using linear mixed model. RESULTS: Axial length adjusted-FAZ area was not different among the three groups (mean (95% CI)): in healthy 0.31 (0.27 to 0.36) mm2, glaucoma suspect 0.29 (0.26 to 0.31) mm2 and POAG eyes 0.28 (0.27 to 0.30) mm2 (p=0.578). FD300 was lower in glaucoma suspect 49.1% (47.9% to 50.4%) and POAG eyes 48.7% (48.1% to 49.4%) than healthy eyes 50.5% (49.3% to 51.7%) though the difference was not statistically significant (p=0.071). Lower FD300 was associated with worse 24-2 and 10-2 visual field mean deviation and foveal threshold in multivariable linear mixed models (all p<0.05). In addition, a smaller FAZ area was associated with lower intraocular pressure (IOP) (p=0.026). CONCLUSIONS: The FD300, but not the FAZ area was correlated with 10° central visual field mean deviation and foveal threshold in healthy, glaucoma suspect and POAG eyes. In contrast, a smaller FAZ area was associated with lower IOP.

Macula structural and vascular differences in glaucoma eyes with and without high axial myopia.

AIMS: To identify clinically relevant parameters for identifying glaucoma in highly myopic eyes, an investigation was conducted of the relationship between the thickness of various retinal layers and the superficial vessel density (sVD) of the macula with axial length (AL) and visual field mean deviation (VFMD). METHODS: 270 glaucoma patients (438 eyes) participating in the Diagnostic Innovations in Glaucoma cross-sectional study representing three axial myopia groups (non-myopia: n=163 eyes; mild myopia: n=218 eyes; high myopia (AL>26 mm): n=57 eyes) who completed macular optical coherence tomography (OCT) and OCT-angiography imaging were included. Associations of AL and VFMD with the thickness of the ganglion cell inner plexiform layer (GCIPL), macular retinal nerve fibre layer (mRNFL), ganglion cell complex (GCC), macular choroidal thickness (mCT) and sVD were evaluated. RESULTS: Thinner Global GCIPL and GCC were significantly associated with worse VFMD (R2=34.5% and R2=32.9%; respectively p<0.001), but not with AL (all p>0.1). Thicker mRNFL showed a weak association with increasing AL (R2=2.4%; p=0.005) and a positive association with VFMD (global R2=19.2%; p<0.001). Lower sVD was weakly associated with increasing AL (R2=1.8%; p=0.028) and more strongly associated with more severe glaucoma VFMD (R2=29.6%; p<0.001). Thinner mCT was associated with increasing AL (R2=15.5% p<0.001) and not associated with VFMD (p=0.194). mRNFL was thickest while mCT was thinnest in all sectors of high myopic eyes. CONCLUSIONS: As thinner GCIPL and GCC were associated with increasing severity of glaucoma but were not significantly associated with AL, they may be useful for monitoring glaucoma in highly myopic eyes.

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.

Long-term reproducibility of optical coherence tomography angiography in healthy and stable glaucomatous eyes.

BACKGROUND/AIMS: To assess and compare long-term reproducibility of optic nerve head (ONH) and macula optical coherence tomography angiography (OCTA) vascular parameters and optical coherence tomography (OCT) thickness parameters in stable primary open-angle glaucoma (POAG), glaucoma suspect and healthy eyes. METHODS: Eighty-eight eyes (15 healthy, 38 glaucoma suspect and 35 non-progressing POAG) of 68 subjects who had at least three visits within 1-1.5 years with OCTA and OCT imaging (Angiovue; Optovue, Fremont, California, USA) on the same day were included. A series of vascular and thickness parameters were measured including macular parafoveal vessel density (pfVD), ONH circumpapillary capillary density (cpCD), macular parafoveal ganglion cell complex (pfGCC) and ONH circumpapillary retinal nerve fibre layer (cpRNFL). A random effects analysis of variance model was used to estimate intraclass correlation (ICC) coefficients and long-term variability estimates. RESULTS: ICC was lower for OCTA (pfVD 0.823 (95% CI 0.736 to 0.888) and cpCD 0.871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test-retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities. CONCLUSIONS: OCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change. TRIAL REGISTRATION NUMBER: NCT00221897.

Agreement, repeatability, and reproducibility of quantitative retinal layer assessment using swept-source and spectral-domain optical coherence tomography in eyes with retinal diseases.

Purpose: To evaluate the agreement and precision of retinal thickness measurements obtained using swept-source optical coherence tomography (SS-OCT) and spectral-domain OCT (SD-OCT) in healthy eyes and eyes with retinopathy. Methods: This cross-sectional prospective study involved three DRI-OCT Triton (SS-OCT) and three 3D-OCT-1 Maestro (SD-OCT) devices. One of each device (Maestro and Triton) was paired with a single operator. Healthy subjects and patients with retinal diseases were recruited, with study eye and testing order randomized. At least 3 scans per eye were captured for wide scan (12 mm × 9 mm-Triton and Maestro) and macular cube scan (7 mm × 7 mm-Triton, 6 mm × 6 mm-Maestro). Thickness of the full retina, ganglion cell layer + inner plexiform layer (GCL+), and ganglion cell complex (GCL++) were obtained from wide scan and cube scans. Agreement of the measurements between the Triton and Maestro was evaluated by Bland-Altman analysis and Deming regression for each group. Repeatability and reproducibility were assessed using a two-way random effect analysis of variance (ANOVA) model for each parameter by group. Results: Twenty-five healthy subjects (25 eyes) and 26 patients with retinal diseases (26 eyes), including, but not limited to, age-related macular degeneration, macular hole, and diabetic retinopathy were recruited. Overall, the measurement differences between Triton and Maestro were <6 µm (mean differences of full retina, GCL++, and GCL+ thickness were ≤5.5 µm, 1.3 µm, and 2.8 µm, respectively) and not statistically significant across the parameters. The repeatability and reproducibility estimates indicate high precision in both devices and groups. Across all the parameters, the repeatability limit was ≤7.6 µm for Triton and ≤12.7 µm for Maestro; reproducibility limit was ≤9.2 µm for Triton and ≤14.4 µm for Maestro. In eyes with retinal pathology, the repeatability coefficient of variation (CV)% was ≤2.6% for Triton and ≤3.4% for Maestro; reproducibility CV% was ≤3.3% for Triton and ≤3.5% for Maestro. Conclusion: Both Triton SS-OCT and Maestro SD-OCT provide reliable measurements of retinal thickness in healthy eyes and eyes with retinal diseases. Excellent agreement between the two devices indicates interoperability when testing healthy eyes or eyes with retinal pathology. These findings support the use of thickness measurements from Triton SS-OCT and Maestro SD-OCT in clinical practice.

Relative Stability of Regional Facial and Ocular Temperature Measurements in Healthy Individuals.

Purpose: Non-contact measurement of facial temperature using infrared thermography has been used for mass screening of body temperature during a pandemic. We investigated the relative stability of temperature measurement in different facial regions of healthy individuals. Methods: Twenty healthy subjects underwent two experiments. In the first experiment, subjects washed their faces with a 20°C wet towel for 1 minute. Temperature changes compared to baseline in the forehead, cornea, inner canthus, and outer canthus were determined using an infrared camera for 10 minutes. In the second experiment, lubricating eye drops at 20°C were instilled over one eye. Temperature changes in the same regions of interest were monitored for 5 minutes. Results: Baseline temperatures before face washing in the forehead and cornea, inner canthus, and outer canthus of the right eye were 33.4°C ± 0.8°C (mean ± SD), 33.3°C ± 0.8°C, 34.3°C ± 0.7°C, and 32.8°C ± 0.7°C, respectively. Reductions in temperature due to face washing were most significant for the forehead and least significant for the cornea. One minute after face washing, the corresponding changes were -2.8°C ± 0.6°C, -0.3°C ± 0.6°C, -0.6°C ± 0.7°C, and -0.9°C ± 0.7°C for the forehead, cornea, inner canthus, and outer canthus, respectively. After administering the eye drops, no significant temperature changes were observed. Conclusions: When facial temperature was exogenously cooled, the cornea had the most stable temperature readings. Translational Relevance: When using infrared thermography to screen facial temperature, the measurement of corneal temperature is probably a better representative if the stability of temperature readings is critical.

Effect of topical latanoprost on choroidal thickness and vessel area in Guinea pigs.

The aim of this study was to investigate the effect of latanoprost, an ocular hypotensive agent and prostaglandin analog, on choroidal thickness and structure in young adult guinea pigs. Young (three-month-old) guinea pigs (n = 10) underwent daily monocular treatment with topical 0.005% latanoprost for 2 weeks, followed by a washout period of 2 weeks. Tonometry (iCare) and retinoscopy were undertaken to monitor intraocular pressure (IOP) and refractive error (recorded as spherical equivalent refractive error; SER), respectively. Axial length (AL) and choroidal thickness (ChT) were measured using high frequency A-scan ultrasonography, with additional ChT data, as well as choroidal vessel (ChV) areas obtained from posterior segment imaging using Spectral Domain-Optical Coherence Tomography (SD-OCT). Image J was used to analyze SD-OCT images. As expected, latanoprost significantly reduced IOP in treated eyes. Mean interocular IOP difference (±SE) changed from -0.40 ± 0.31 mmHg at baseline to -2.23 ± 0.43 mmHg after 2 weeks of treatment (p = 0.05). However, SER and AL were unaffected; interocular difference changed from 0.41 ± 0.58 to 0.38 ± 0.43 D and from -0.002 ± 0.02 mm to -0.007 ± 0.01 mm (p > 0.05), respectively. Latanoprost had minimal effect on ChT. Interocular ChT differences were 0.01 ± 0.06 µm at baseline and 0.04 ± 0.06 µm after 2 weeks of treatment (SD-OCT; p > 0.05). However, treated eyes had significant increased ChV areas; interocular differences changed from -0.76 ± 69.2 to 100.78 ± 66.9 µm2 after treatment (p = 0.04). While this study was limited to otherwise untreated young adult guinea pigs, the possibility that choroidal vessel enlargement contributes to the previously reported inhibitory effect of topical latanoprost on myopia progression in young guinea pigs warrants investigation.

Comparison of Optic Disc Ovality Index and Rotation Angle Measurements in Myopic Eyes Using Photography and OCT Based Techniques.

Purpose: To compare optic nerve head (ONH) ovality index and rotation angle measurements based on semi-automated delineation of the clinical ONH margin derived from photographs and automated BMO configuration derived from optical coherence tomography (OCT) images in healthy and glaucomatous eyes with high-, mild- and no axial myopia. Methods: One hundred seventy-five healthy and glaucomatous eyes of 146 study participants enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optic disc photographs and Spectralis OCT ONH scans acquired on the same day were stratified by level of axial myopia (non-myopic [n = 56, axial length (AL) <24 mm], mild-myopic [n = 58, AL 24-26 mm] and high-myopic [n = 32, AL >26 mm]. The clinical disc margin of each photograph was manually annotated, and semi-automated measurements were recorded of the ovality index and rotation angle based on a best-fit ellipse generated using ImageJ software. These semi-automated photograph-based measurements were compared to ovality index and rotation angle generated from custom automated BMO-based analysis using segmented OCT ONH volumes. R 2 values from linear mixed effects models were used to describe the associations between semi-automated, photograph-based and automated OCT-based measurements. Results: Average (95% CI) axial length was 23.3 (23.0, 23.3) mm, 24.8 (24.7, 25.0) mm and 26.8 (26.6, 27.0) mm in non-myopic, mild-myopic and high-myopic eyes, respectively (ANOVA, p ≤ 0.001 for all). The R 2 association (95% CI) between semi-automated photograph-based and automated OCT-based assessment of ONH OI for all eyes was [0.26 (0.16, 0.36); p < 0.001]. This association was weakest in non-myopic eyes [0.09 (0.01, 0.26); p = 0.02], followed by mild-myopic eyes [0.13 (0.02, 0.29); p = 0.004] and strongest in high-myopic eyes [0.40 (0.19, 0.60); p < 0.001]. No significant associations were found between photography- and OCT-based assessment of rotation angle with R 2 values ranging from 0.00 (0.00, 0.08) in non-myopic eyes to 0.03 (0.00, 0.21) in high-myopic eyes (all associations p ≥ 0.33). Conclusions: Agreement between photograph-based and automated OCT-based ONH morphology measurements is limited, suggesting that these methods cannot be used interchangeably for characterizing myopic changes in the ONH.

Longitudinal Structure-Function Relationship between Macular Vessel Density and Thickness and Central Visual Field in Early Glaucoma.

PURPOSE: To investigate the relationship of longitudinal changes in macular vessel density (VD) from OCT angiography and in ganglion cell complex (GCC) from OCT with central visual field (VF) in eyes with early glaucoma. DESIGN: Observational cohort. PARTICIPANTS: A total of 95 eyes, 37 preperimetric and 58 with early glaucoma (24-2 VF mean deviation [MD] ≥ -6 decibels), with an average follow-up of 3.8 years and 5.3 visits, were included. METHODS: Whole-image VD (wiVD) and whole-image GCC (wiGCC) and parafoveal scans, as well as localized regions of interest (LROIs), hemiretinae of whole images, and superior, inferior, temporal, and nasal sectors of parafoveal maps, were matched with central VF locations. Age-adjusted rates of change of VD, GCC, mean sensitivity of VF locations, and 10-2 VF MD were calculated using linear mixed-effect models. Normalized rates of change were calculated for comparison of change rates in wiVD and wiGCC. MAIN OUTCOME MEASURES: Structure-function (SF) correlations of VD and GCC with central VF measurement change rates and comparison of different correlations of SF relationships after bootstrapping the difference of the correlation coefficients. RESULTS: Vessel density loss and GCC thinning demonstrated significant correlations with central VF damage, globally and with most LROIs. The SF correlation (r, 95% confidence interval [CI]) between wiVD and 10-2 VF MD change rates was 0.42 [0.24, 0.58], whereas it was 0.27 [0.08, 0.45] between wiGCC and 10-2 VF MD changes rates (all P < 0.05). In contrast to GCC thinning, VD loss in the parafoveal sectors demonstrated significant correlations with central VF damage in inferior and temporal sectors. Differences in the relationship of SF with central VF damage were not significant between VD loss and GCC thinning. The mean (95% CI) normalized change rates of wiVD (-7.40 [-7.71 to 7.09] %/year) was faster than that of wiGCC (-2.39 [-2.94 to 1.84] %/year) (P < 0.05). CONCLUSIONS: Rates of VD loss and GCC thinning are associated with central VF loss over time. Assessment of both macular VD and GCC thickness should be considered for evaluation of glaucoma progression.

Rates of Choroidal Microvasculature Dropout and Retinal Nerve Fiber Layer Changes in Glaucoma.

PURPOSE: To evaluate the association between rates of choroidal microvasculature dropout (MvD) change and rates of circumpapillary retinal nerve fiber layer (cpRNFL) loss in primary open-angle glaucoma (POAG) eyes. DESIGN: Cohort study from clinical trial data. METHODS: A total of 91 eyes of 68 POAG patients with and without localized MvD at baseline with at least 4 visits and 2 years of follow-up with optical coherence tomography angiography (OCT-A) and OCT scans were included. Area and angular circumference of MvD were evaluated on OCT-A en face and B-scan choroidal vessel density images during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in MvD area or angular circumference and RNFL thickness. Univariable and multivariable regressions were completed to identify the factors contributing to cpRNFL thinning. RESULTS: MvD was identified in 53 eyes (58.2%) at baseline. Seventeen eyes (18.6%) that did not show MvD at baseline developed it over the follow-up period. Over a mean follow-up of 4.0 years, the mean rates of change in MvD area and angular circumference (95% CI) were 0.05 (0.04, 0.06) mm2 per year and 13.2° (10.7°, 15.8°) per year, respectively. In multivariable models, the rate of cpRNFL thinning was significantly associated with the rates of change in MvD area and angular circumference (P = .008 and P = .009, respectively). CONCLUSIONS: Rates of MvD area and angular circumference change over time were associated with concurrent rates of cpRNFL loss in POAG eyes.

Comparison of the Effects of Latanoprostene Bunod and Timolol on Retinal Blood Vessel Density: A Randomized Clinical Trial.

PURPOSE: To compare the differences in retinal vessel density (VD) between topical administration of latanoprostene bunod (LBN) ophthalmic solution 0.024% and timolol maleate 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and normal subjects. DESIGN: Randomized, single center, crossover clinical trial. METHODS: Eligible subjects were examined during 6 study visits over 12 weeks. All subjects were randomized in a 1:1 ratio to LBN dosed once daily or timolol dosed twice daily in both eyes (OU) for a duration of 4 weeks each, separated by a 2-week washout period. A comprehensive eye examination OU was performed at each visit. Testing was performed with optical coherence tomography and optical coherence tomography angiography (optic nerve and macula), as well as visual field examination, on the study eye at baseline and before and after each treatment. RESULTS: One eye from each of 50 patients was enrolled (10 healthy patients, 26 patients with OHT, and 14 patients with OAG). After administration of LBN there was significantly increased macular VD (0.76% [0.20%-1.33%], P = 0.009) and a trend in increasing peripapillary VD in patients with OAG and patients with OHT. In contrast, after administration of timolol, there were no differences in macular VD, and a decrease in peripapillary VD only was observed in the nasal inferior sector (-0.56% [-1.08% to -0.03%], P = .04) in patients with OAG and patients with OHT. No change in peripapillary or macular VD was observed in the normal subjects (P > .05 for all). CONCLUSIONS: Topical administration of LBN enhanced macular VD in patients with OAG or patients with OHT. In contrast, timolol administration did not have any effect on VD.

OCT-Angiography Face Mask-Associated Artifacts During the COVID-19 Pandemic.

PRCIS: Face mask wearing has no significant effects on artifacts or vessel density measurements in optic nerve head (ONH) and macular optical coherence tomography-angiography (OCT-A) scans. PURPOSE: The aim was to assess the difference in area of artifacts observed in optical OCT-A scans with and without face mask wear and to verify if mask wear interferes with OCT-A vessel density measurements. SUBJECTS AND CONTROLS: A total of 64 eyes of 10 healthy subjects, 4 ocular hypertensive, 8 glaucoma suspects, and 17 glaucoma patients were included. MATERIALS AND METHODS: High-density ONH and macula OCT-A scans were obtained in patients with and without surgical masks. Seven different artifacts (motion, decentration, defocus, shadow, segmentation failure, blink, and Z-offset) were quantitatively evaluated by 2 trained graders. The changes in the area (% of scan area) of artifacts, without and with mask wearing, and differences of vessel density were evaluated. RESULTS: Trends of increasing motion artifact area for the ONH scans [4.23 (-0.52, 8.98) %, P=0.08] and defocus artifact area for the macular scans [1.06 (-0.14, 2.26) %, P=0.08] were found with face mask wear. However, there were no significant differences in the mean % area of any artifacts (P>0.05 for all). Further, the estimated mean difference in vessel density in images acquired without and with masks was not significant for any type of artifact. CONCLUSION: Face mask wearing had no significant effect on area of artifacts or vessel density measurements. OCT-A vessel density measurements can be acquired reliably with face mask wear during the pandemic.

Measurements of OCT Angiography Complement OCT for Diagnosing Early Primary Open-Angle Glaucoma.

PURPOSE: To compare measurements of global and regional circumpapillary capillary density (cpCD) with retinal nerve fiber layer (RNFL) thickness and characterize their relationship with visual function in early primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study. PARTICIPANTS: Eighty healthy eyes, 64 preperimetric eyes, and 184 mild POAG eyes from the Diagnostic Innovations in Glaucoma Study. METHODS: Global and regional RNFL thickness and cpCD measurements were obtained using OCT and OCT angiography (OCTA). For direct comparison at the individual and diagnostic group level, RNFL thickness and capillary density values were converted to a normalized relative loss scale. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness and cpCD normalized loss at the individual level and diagnostic group. Global and regional areas under the receiver operating characteristic curve (AUROC) for RNFL thickness and cpCD to detect preperimetric glaucoma and glaucoma, R2 for the strength of associations between RNFL thickness function and capillary density function in diagnostic groups. RESULTS: Both global and regional RNFL thickness and cpCD decreased progressively with increasing glaucoma severity (P < 0.05, except for temporal RNFL thickness). Global and regional cpCD relative loss values were higher than those of RNFL thickness (P < 0.05) in preperimetric glaucoma (except for the superonasal region) and glaucoma (except for the inferonasal and superonasal regions) eyes. Race, intraocular pressure (IOP), and cpCD were associated with greater cpCD than RNFL thickness loss in early glaucoma at the individual level (P < 0.05). Global measurements of capillary density (whole image capillary density and cpCD) had higher diagnostic accuracies than RNFL thickness in detecting preperimetric glaucoma and glaucoma (P < 0.05; except for cpCD/RNFL thickness comparison in glaucoma [P = 0.059]). Visual function was significantly associated with RNFL thickness and cpCD globally and in all regions (P < 0.05, except for temporal RNFL thickness-function association [P = 0.070]). CONCLUSIONS: Associations between capillary density and visual function were found in the regions known to be at highest risk for damage in preperimetric glaucoma eyes and all regions of mild glaucoma eyes. In early glaucoma, capillary density loss was more pronounced than RNFL thickness loss. Individual characteristics influence the relative magnitudes of capillary density loss compared with RNFL thickness loss. Retinal nerve fiber layer thickness and microvascular assessments are complementary and yield valuable information for the detection of early damages seen in POAG.

Rates of Circumpapillary Retinal Nerve Fiber Layer Thinning and Capillary Density Loss in Glaucomatous Eyes with Disc Hemorrhage.

PURPOSE: To investigate longitudinal changes in rates of optic nerve head circumpapillary retinal nerve fiber layer (cpRNFL) thinning and vessel density loss in patients with primary open-angle glaucoma with or without a history of disc hemorrhage (DH). DESIGN: Observational cohort. METHODS: In this longitudinal study, 34 eyes with DH and 134 eyes without DH that had ≥1.5 years of follow-up and 3 optical coherence tomography and optical coherence tomography angiography follow-up scans were enrolled. A linear mixed-effects model was used to compare the rates of cpRNFL thinning and vessel density loss between DH and non-DH eyes. RESULTS: Rates of whole image capillary density loss were faster in the DH group compared with the non-DH group (mean difference [95% confidence interval] -0.32% [-0.59% to -0.04%] per year; P = .027). Faster mean rates of vessel density loss were found in the inferotemporal, inferonasal, and nasal sectors in eyes with DH than without DH (P < .05). There was no statistically significant difference in the global rate of cpRNFL thinning between the 2 groups (P = .679). The mean rate of cpRNFL thinning was faster in the DH group compared with the non-DH group only in the inferotemporal sector (mean difference [95% confidence interval] -1.01 µm (-1.62 µm to -0.40 µm) per year; P = .001). CONCLUSIONS: Mean rates of vessel density loss between DH and non-DH eyes were different not only in the affected area but also in the other regions. In contrast, a significant difference in cpRNFL thinning between the 2 groups was detected only in the inferotemporal sector. Disc hemorrhage is an independent predictor of faster vessel density loss in glaucoma suspects and patients with primary open-angle glaucoma.

Macular Thickness and Microvasculature Loss in Glaucoma Suspect Eyes.

PURPOSE: To characterize the change of ganglion cell complex (GCC) thickness and macular vessel density in glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON). DESIGN: Prospective, longitudinal study. PARTICIPANTS: Eight-three eyes (24 healthy, 30 OHT, and 29 GON) of 65 patients who underwent at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years. METHODS: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3 × 3-mm1 GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using a linear mixed-effects model. MAIN OUTCOME MEASURES: Change rates of macula GCC thickness and superficial vessel density. RESULTS: Significant mean rates of both GCC thinning and vessel density loss were detectable in OHT and GON groups. Of the individual suspect eyes, 49.1% showed significant loss (P < 0.05) with either vessel density or GCC thickness. Of the GON eyes, 31.0% showed both significant GCC loss and vessel density loss, 51.7% showed only significant GCC loss, whereas 17.2% showed only significant vessel density loss. Vessel density loss was faster than GCC thinning in half of the suspect eyes based on percent loss analysis. The age and scan quality-adjusted GCC thinning rates of the OHT group (-0.59 µm/year; P = 0.025) and GON group (-0.79 µm/year; P = 0.058) were faster than those of the healthy group (-0.11 µm/year), whereas the rate of vessel density loss was not significantly different among the diagnostic groups (all P > 0.2). Higher mean intraocular pressure during follow-up was associated with faster GCC thinning in the OHT group (P = 0.065) and GON groups (P = 0.015), but was not associated with the rate of vessel density decrease. CONCLUSIONS: Whereas the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes showed significant loss of vessel density and faster vessel density loss than GCC thinning. OCT and OCTA are complementary and useful for evaluating eyes with OHT or GON.

Agreement between Compass Fundus Perimeter New Grid and 10-2 Testing Protocols for Detecting Central Visual Field Defects.

PURPOSE: To evaluate the agreement between Compass New Grid (NG) and 10-2 test protocols for detecting early glaucomatous defects in the central 10 degrees of the visual field (CVFD). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 123 eyes of 14 healthy individuals, 17 glaucoma suspects, and 32 glaucoma patients were enrolled. METHODS: Subjects performed NG and 10-2 Compass automated perimetry testing within 1 week. For both test protocols, total deviation (TD) and pattern deviation (PD) plot CVFDs were defined by 3 contiguous points with probabilities of <5%, <2%, <2% or <5%, <1%, <1%. Cohen's Kappa statistic was used to assess agreement between NG and 10-2 for identifying CVFDs. The Spectralis GMPE Hood Glaucoma Report (investigational software version) macula deviation analysis obtained within 1 year was used for calculating sensitivities and specificities of test protocols. MAIN OUTCOME MEASURES: Protocols' agreement, sensitivity, and specificity. RESULTS: Fair to moderate agreement was observed between NG and 10-2 protocols for detecting presence of superior CVFDs on TD (k = 0.57) and PD (k = 0.26) plots and for detecting inferior CVFDs on TD (0.49) and PD (0.27) plots. With the use of OCT macula deviation maps, specificity for detecting CVFD was consistently higher with NG than 10-2 tests for TD plots of the superior hemifield (0.82 and 0.65), inferior hemifield (0.92 and 0.84), and PD plots of the superior hemifield (0.81 and 0.36) and inferior hemifield (0.86 and 0.52). Sensitivity of NG was consistently lower than TD plots of the superior hemifield (0.48 and 0.72), inferior hemifield (0.28 and 0.46), and PD plots of the superior hemifield (0.48 and 0.78) and inferior hemifield (0.20 and 0.52). By using pattern standard deviation (PSD) criterion, the mean PSD values for 10-2 and NG VF tests were 1.61 (95% confidence interval [CI], 1.26-1.96) and 1.81 (95% CI, 1.45-2.17) (P < 0.001), respectively. CONCLUSIONS: Although the Compass NG detected fewer CVFDs than the 10-2 test protocol, it did detect CVFDs that were not observed in the Compass 24-2 test in patients with early glaucoma. Therefore, NG may be particularly useful in clinical situations when higher specificity is desired or PSD criterion is used.

Racial Differences in Detection of Glaucoma Using Retinal Nerve Fiber Layer Thickness and Bruch Membrane Opening Minimum Rim Width.

PURPOSE: To compare the sensitivities and specificities of the retinal nerve fiber layer thickness (RNFLT) and Bruch membrane opening minimum rim width (BMO-MRW) reference database-based criteria for detection of glaucoma in individuals of European descent (ED) and individuals of African descent (AD). DESIGN: Comparative diagnostic analysis by race METHODS: 382 eyes of 255 glaucoma patients (ED = 170, AD = 85) and 94 eyes of 50 healthy individuals (ED = 30, AD = 20) with global and sectoral RNFLT and BMO-MRW measured with Spectralis optical coherence tomography (OCT) were included. Six diagnostic criteria were evaluated: global measurement below the 5th or 1st percentile, ≥1 of the 6 sector measurements below the 5th or 1st percentile, and superotemporal (ST) and/or inferotemporal (IT) measurement below the 5th or 1st percentile. The sensitivities and specificities of these measurements for detection of glaucoma were compared using bootstrapping methods. RESULTS: ST and/or IT RNFLT below the 5th percentile has the best performance for detection of glaucoma among RNFLT classifications with a sensitivity (95% CI) of 89.5% (86.1, 92.5) and specificity of 87.2% (77.8, 95.1). In AD individuals, sensitivities of ST and IT RNFLT and BMO-MRW measurements below the 5th percentile criteria were lower than in ED individuals (RNFLT: 83.7% vs 92.5%, and BMO-MRW: 72.1% vs 88.5%, respectively), as well as specificities (AD RNFLT: 73.7% and BMO-MRW: 89.5% vs ED RNFLT: 96.4% and BMO-MRW: 98.2%, respectively). CONCLUSIONS: RNFLT and BMO-MRW had consistently lower diagnostic performance in AD individuals compared with ED individuals. BMO-MRW criteria might fail to detect as many as one-third of eyes with glaucoma, specifically in AD individuals. With the current reference database, RNFLT, and especially BMO-MRW, criteria are not adequate for diagnosing glaucoma in AD individuals.