Uric acid and glaucoma: a systematic review and meta-analysis.

Background: Glaucoma, the leading cause of irreversible blindness, is a common disorder that contributes to gradual optic nerve degeneration. The beneficial impacts of uric acid (UA) have been reported in some neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. But the results of current studies about the association between serum UA level and glaucoma are conflicting. The present meta-analysis was conducted to provide a better understanding of the association between serum UA level and glaucoma. Methods: We searched the databases of PubMed, Scopus, Web of Science, and Google Scholar systematically until November 20, 2022 to identify case-control studies, comparing the serum UA concentrations of the patients with glaucoma and controls. The mean ± standard division difference was used to assess the difference in serum UA concentrations between the glaucoma patients and controls. Results: Six studies involving 1,221 glaucoma patients and 1,342 control group were included in the present meta-analysis. This meta-analysis using a random effect model indicated that the mean UA level in glaucoma patients was 0.13 (I2 = 91.92%, 95% CI = -0.42 to 0.68) higher than the controls; however, it was not statistically significant. Conclusions: Our findings provide evidence that glaucoma patients have a higher serum UA level compared to the controls, but this difference is not statistically significant. Prospective studies are needed to determine the possible association between increased UA and glaucoma pathogenesis. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364055, identifier: CRD42022364055.

Retinal Ischemic Perivascular Lesions in Individuals With Atrial Fibrillation.

Background We previously demonstrated that retinal ischemic perivascular lesions (RIPLs), which are indicative of ischemia in the middle retina, may be a biomarker of ischemic cardiovascular disease. In this study, we sought to determine the relationship between RIPLs and atrial fibrillation, a common source of cardiac emboli. Methods and Results In this case-control study, we identified individuals between the ages of 50 and 90 years who had undergone macular spectral domain optical coherence tomography imaging. Individuals with atrial fibrillation were identified, and age- and sex-matched individuals from the same pool, but without a diagnosis of atrial fibrillation, were selected as controls. Spectral domain optical coherence tomography scans were reviewed by 3 independent and masked observers for presence of RIPLs. The relationship between RIPLs and atrial fibrillation was analyzed using multivariable logistic regression models. There were 106 and 91 subjects with and without atrial fibrillation, respectively. The percentage of subjects with RIPLs was higher in the atrial fibrillation group compared with the control group (57.5% versus 37.4%; P=0.005). After adjusting for age, sex, smoking history, hypertension, diabetes, coronary artery disease, carotid stenosis, stroke, and myocardial infarction, the presence of RIPLs was significantly associated with atrial fibrillation, with an odds ratio of 1.91 (95% CI, 1.01-3.59). Conclusions RIPLs are significantly associated with atrial fibrillation, independent of underlying ischemic heart disease or cardiovascular risk factors. This association may inform the diagnostic cardiovascular workup for individuals with RIPLs incidentally detected on optical coherence tomography scan of the macula.

Effect of Testing Frequency on the Time to Detect Glaucoma Progression With Optical Coherence Tomography (OCT) and OCT Angiography.

PURPOSE: To determine how the frequency of testing affects the time required to detect statistically significant glaucoma progression for circumpapillary retinal nerve fiber layer (cpRNFL) with optical coherence tomography (OCT) and circumpapillary capillary density (cpCD) with OCT angiography (OCTA). DESIGN: Retrospective, observational cohort study. METHODS: In this longitudinal study, 156 eyes of 98 patients with glaucoma followed up over an average of 3.5 years were enrolled. Participants with 4 or more OCT and OCTA tests were included to measure the longitudinal rates of cpRNFL thickness and cpCD change over time using linear regression. Estimates of variability were then used to re-create real-world cpRNFL and cpCD data by computer simulation to evaluate the time required to detect progression for various loss rates and different testing frequencies. RESULTS: The time required to detect a statistically significant negative cpRNFL and cpCD slope decreased as the testing frequency increased, albeit not proportionally. cpCD detected progression slightly earlier than cpRNFL. Eighty percent of eyes with a cpCD loss of -1%/y were detected after 6.0, 4.2, and 4 years when testing was performed 1, 2, and 3 times per year, respectively. Progression in 80% of eyes with a cpRNFL loss of -1 µm/y was detected after 6.3, 5.0, and 4.2 years, respectively. CONCLUSIONS: cpRNFL and cpCD are comparable in detecting progression. As there were only small changes in the time to detect progression when testing increased from 2 to 3 times per year, testing twice per year may provide sufficient information for detecting progression with either OCT or OCTA in clinical settings.

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.

Effects of Smoking on Optic Nerve Head Microvasculature Density in Glaucoma.

PRCIS: Decreased superficial whole image capillary density was observed in open angle glaucoma (OAG) patients with high smoking intensity. PURPOSE: To investigate the effects of smoking on optic nerve head capillary density measured by optical coherence tomography angiography in patients with OAG. METHODS: In this retrospective cross-sectional study, perimetric and preperimetric glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optical coherence tomography angiography follow-up were included. Univariable and multivariable linear mixed analysis were performed to determine the effects of different variables on the superficial whole image capillary density. RESULTS: A total of 432 eyes of 271 glaucoma patients comprising 63 preperimetric (106 eyes) and 208 perimetric OAG (326 eyes) were included. A history of tobacco consumption was reported in 105 (38.8%). Among smokers, mean (95% confidence interval) smoking intensity was 12.8 (10.2, 15.5) pack-years. After adjusting for age, glaucoma severity and other confounders, each 10 pack-year increase in smoking intensity (95% confidence interval) was associated with -0.54 (-1.06, -0.02) % lower whole image capillary density ( P =0.041). CONCLUSIONS: Smoking intensity is associated with reduced optic nerve vessel density in glaucoma.

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.

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.

Superficial and Deep Macula Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

PRECIS: Macular superficial capillary plexus (SCP) vessel density is more informative than deep capillary plexus (DCP) vessel density for the detection of glaucoma. PURPOSE: The purpose of this study was to characterize optical coherence tomography angiography macular SCP and projection-resolved DCP vessel densities and compare their diagnostic accuracies with ganglion cell complex (GCC) thickness in healthy, glaucoma suspect, and glaucoma eyes. MATERIALS AND METHODS: Sixty-eight eyes of 44 healthy subjects, 26 eyes of 16 preperimetric glaucoma suspects, and 161 eyes of 124 glaucoma patients from the Diagnostics Innovations in Glaucoma Study with good quality high-density 6×6 mm2 macula optical coherence tomography angiography images were included. The diagnostic accuracy of SCP vessel density, projection-resolved DCP vessel density and GCC thickness were compared among groups. RESULTS: Mean whole image vessel density (wiVD; % of area occupied by vessels containing flowing blood) in the SCP layer was highest in healthy eyes (49.7%), followed by glaucoma suspect eyes (46.0%), and glaucoma eyes (40.9%) (P<0.001). Mean wiVD in the DCP layer was similar in healthy (50.6%), glaucoma suspect (47.3%), and glaucoma eyes (45.7%) (P=0.925). Diagnostic accuracy of both GCC thickness and SCP wiVD was significantly higher than DCP wiVD for classifying healthy and glaucoma eyes [adjusted area under the receiver operating characteristic curve (95% confidence interval): GCC=0.86 (0.72, 0.94), SCP=0.80 (0.66, 0.91) and DCP=0.44 (0.30, 0.57)] (P<0.001). CONCLUSIONS: SCP vessel densities have better diagnostic accuracy for detecting glaucoma than DCP vessel densities. Although the diagnostic accuracy of the macula SCP is relatively modest, it is more informative than the DCP.

Case report 68Ga-DOTATATE of optic nerve sheath meningioma.

We report a patient with an optic nerve sheath meningioma whose diagnosis and management were guided by using Gallium-68 DOTA-Tyr3-octreotatate (68Ga-DOTATATE). Positron Emission Tomography-Computed Tomography (PET-CT).

Macular imaging with optical coherence tomography in glaucoma.

With the advent of spectral-domain optical coherence tomography, imaging of the posterior segment of the eye can be carried out rapidly at multiple anatomical locations, including the optic nerve head, circumpapillary retinal nerve fiber layer, and macula. There is now ample evidence to support the role of spectral-domain optical coherence tomography imaging of the macula for detection of early glaucoma. Macular spectral-domain optical coherence tomography measurements demonstrate high reproducibility, and evidence on its utility for detection of glaucoma progression is accumulating. We present a comprehensive review of macular spectral-domain optical coherence tomography imaging emerging as an essential diagnostic tool in glaucoma.

Prediction of Glaucoma Progression with Structural Parameters: Comparison of Optical Coherence Tomography and Clinical Disc Parameters.

PURPOSE: To test the hypothesis that baseline optical coherence tomography (OCT) measures predict visual field (VF) progression in a cohort of patients with suspected or established glaucoma and to compare their performance to semiquantitative optic disc measures. DESIGN: This was an observational cohort study. METHODS: The setting of this study was an academic institution. The study population included 171 eyes of 95 patients with good-quality baseline retinal nerve fiber layer (RNFL) and macular OCT images and disc photographs with >2 years of follow-up and ≥5 VFs. The observation procedures were baseline macular and RNFL OCT measures and cup-to-disc ratio and disc damage likelihood score. The main outcome measure was prediction of glaucomatous VF deterioration according to trend and event analyses. RESULTS: Median (interquartile range) baseline mean deviation and follow-up were -2.9 (-6.4 to -1.1) dB and 54 (44-65) months, respectively. Seventeen and 25 eyes progressed by final visit based on pointwise event analysis and trend analysis of visual field index (VFI), respectively. Thinner central corneal thickness (P = .005), female gender (P = .015), and thinner average peripapillary RNFL (P = .001) predicted VF progression on proportional hazard models. Thinner RNFL at baseline (P = .006) or thinner average ganglion cell-inner plexiform layer (P = .028) along with higher baseline VFI (P = .018 and .048, respectively) predicted VFI progression. Neither optic disc measures predicted VF progression in any of the explored models. CONCLUSIONS: Baseline structural OCT measures predicted subsequent VF progression in contrast to semi-quantitative optic disc measures. OCT-based structural measures should be included in prognostic models of glaucomatous VF deterioration.

Association of Macular and Circumpapillary Microvasculature with Visual Field Sensitivity in Advanced Glaucoma.

PURPOSE: To evaluate the association between optical coherence tomography angiography (OCTA) macular and circumpapillary vessel density and visual field mean deviation (MD) in advanced primary open angle glaucoma. DESIGN: Cross-sectional study. METHODS: Macula (superficial layer) and optic nerve head (ONH) with capillary density (CD) and without vessel density (VD) automated removal of large vessels OCTA of 34 eyes (34 patients, MD < -10 dB) were investigated as macula whole image VD (wiVD), parafoveal VD (pfVD), ONH wiVD, wiCD, circumpapillary VD, and cpCD. Spectral domain OCT circumpapillary retinal nerve fiber layer, macular ganglion cell complex, and ganglion cell inner plexiform layer were also analyzed. RESULTS: Macular and ONH VD decreased significantly with worsening MD. Each 1-dB decrease in MD was associated with a reduction of 0.43% and 0.46% for macular wiVD and pfVD with R2 of 0.28 and 0.27, respectively (all P < .01). The association between MD and VD was strongest for measures of ONH with large vessels removed, wiCD, and cpCD, followed by wiVD and circumpapillary VD with R2 of 0.26, 0.22, 0.17, 0.14, and a VD reduction of 0.43%, 0.51%, 0.33%, and 0.40%, respectively (all P < .02). There was a reduction of 1.19 µm in Avanti parafoveal ganglion cell complex, 1.13 µm in Spectralis ganglion cell inner plexiform layer, and 1.01 µm in Spectralis circumpapillary retinal nerve fiber layer, with R2 of 0.19 (P = .006), 0.23 (P = .002), and 0.24 (P = .002), respectively. CONCLUSIONS: ONH and macula OCTA VD and thickness are associated with the severity of visual field damage in advanced primary open angle glaucoma.

Optic disc microvasculature dropout in primary open-angle glaucoma measured with optical coherence tomography angiography.

PURPOSE: To evaluate microvasculature dropout in the optic disc (Mvd-D) using optical coherence tomography angiography (OCTA) and investigate factors associated with Mvd-D in primary open-angle glaucoma (POAG) eyes. METHODS: One hundred twenty-three eyes of 123 POAG patients were included from the Diagnostic Innovations in Glaucoma Study. The 3.0×3.0-mm optic nerve head OCTA scans were acquired using a spectral-domain OCT instrument. Images with whole-signal-mode were evaluated. Eyes were classified into 3 categories (Mvd-D, pseudo-Mvd-D, and no Mvd-D). Mvd-D and pseudo-Mvd-D had complete loss of OCTA signals on the temporal side of the optic disc on the en face projection image. They were distinguished base on the visualization of the anterior lamina cribrosa in the horizontal B-scans of that area. No Mvd-D was defined when no complete signal loss of OCTA signals was observed. Covariates including focal lamina cribrosa defects assessed by swept-source OCT and microvasculature dropout in the parapapillary region (Mvd-P) were analyzed. RESULTS: Forty-two, 37, and 44 eyes were identified as having Mvd-D, pseudo-Mvd-D, and no Mvd-D, respectively. The eyes with Mvd-D showed significantly lower intraocular pressure, worse visual field mean deviation, larger cup-to-disc ratio, thinner circumpapillary retinal nerve fiber layer (cpRNFL), and lower circumpapillary vessel density within the RNFL than the eyes with pseudo-Mvd-D or the eyes without Mvd-D. Multivariable logistic regression analysis showed significant associations of Mvd-D with larger cup-to-disc ratio (OR, 1.08; P = 0.001), worse visual field mean deviation (OR, 1.09; P = 0.048), higher prevalence of focal lamina cribrosa defect (OR, 9.05; P = 0.002), and higher prevalence of Mvd-P (OR, 10.33; P <0.001). CONCLUSIONS: OCTA-derived Mvd-D was strongly associated with the presences of Mvd-P and focal lamina cribrosa defects, and these 3 findings were topographically associated with each other.

Macular and Optic Nerve Head Vessel Density and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma.

PURPOSE: To investigate prospectively the relationship between macular and peripapillary vessel density and progressive retinal nerve fiber layer (RNFL) loss in patients with mild to moderate primary open-angle glaucoma. DESIGN: Prospective, observational study. PARTICIPANTS: One hundred thirty-two eyes of 83 patients with glaucoma followed up for at least 2 years (average: 27.3±3.36 months). METHODS: Measurements of macular whole image vessel density (m-wiVD) and optic nerve head whole image vessel density (onh-wiVD) were acquired at baseline using OCT angiography. RNFL, minimum rim width (MRW), and ganglion cell plus inner plexiform layer (GCIPL) thickness were obtained semiannually using spectral-domain OCT. Random-effects models were used to investigate the relationship between baseline vessel density parameters and rates of RNFL loss after adjusting for the following confounding factors: baseline visual field mean deviation, MRW, GCIPL thickness, central corneal thickness (CCT), and mean intraocular pressure during follow-up and disc hemorrhage, with or without including baseline RNFL. MAIN OUTCOME MEASURES: Effects of m-wiVD and onh-wiVD on rates of RNFL loss over time. RESULTS: Average baseline RNFL thickness was 79.5±14.8 µm, which declined with a mean slope of -1.07 µm/year (95% confidence interval, -1.28 to -0.85). In the univariate model, including only a predictive factor and time and their interaction, each 1% lower m-wiVD and onh-wiVD was associated with a 0.11-µm/year (P < 0.001) and 0.06-µm/year (P = 0.031) faster rate of RNFL decline, respectively. A similar relationship between low m-wiVD and onh-wiVD and faster rates of RNFL loss was found using different multivariate models. The association between vessel density measurements and rate of RNFL loss was weak (r2 = 0.125 and r2 = 0.033 for m-wiVD and onh-wiVD, respectively). Average CCT also was a predictor for faster RNFL decline in both the univariate (0.11 µm/year; P < 0.001) and multivariate models. CONCLUSIONS: Lower baseline macular and optic nerve head (ONH) vessel density are associated with a faster rate of RNFL progression in mild to moderate glaucoma. Assessment of ONH and macular vessel density may add significant information to the evaluation of the risk of glaucoma progression and prediction of rates of disease worsening.

Automated Beta Zone Parapapillary Area Measurement to Differentiate Between Healthy and Glaucoma Eyes.

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

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.

Deep-Layer Microvasculature Dropout by Optical Coherence Tomography Angiography and Microstructure of Parapapillary Atrophy.

Purpose: To investigate the association between the microstructure of ß-zone parapapillary atrophy (ßPPA) and parapapillary deep-layer microvasculature dropout assessed by optical coherence tomography angiography (OCT-A). Methods: Thirty-seven eyes with ßPPA devoid of the Bruch's membrane (BM) (γPPA) ranging between completely absent and discontinuous BM were matched by severity of the visual field (VF) damage with 37 eyes with fully intact BM (ßPPA+BM) based on the spectral-domain (SD) OCT imaging. Parapapillary deep-layer microvasculature dropout was defined as a dropout of the microvasculature within choroid or scleral flange in the ßPPA on the OCT-A. The widths of ßPPA, γPPA, and ßPPA+BM were measured on six radial SD-OCT images. Prevalence of the dropout was compared between eyes with and without γPPA. Logistic regression was performed for evaluating association of the dropout with the width of ßPPA, γPPA, and ßPPA+BM, and the γPPA presence. Results: Eyes with γPPA had significantly higher prevalence of the dropout than did those without γPPA (75.7% versus 40.8%; P = 0.004). In logistic regression, presence and longer width of the γPPA, worse VF mean deviation, and presence of focal lamina cribrosa defects were significantly associated with the dropout (P < 0.05), whereas width of the ßPPA and ßPPA+BM, axial length, and choroidal thickness were not (P > 0.10). Conclusions: Parapapillary deep-layer microvasculature dropout was associated with the presence and larger width of γPPA, but not with the ßPPA+BM width. Presence and width of the exposed scleral flange, rather than the retinal pigmented epithelium atrophy, may be associated with deep-layer microvasculature dropout.

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.