Central Visual Field Testing in Early Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the current published literature on the utility of the 10-2 visual field (VF) testing strategy for the evaluation and management of early glaucoma, defined here as mean deviation (MD) better than -6 decibels (dB). METHODS: A search of the peer-reviewed literature was last conducted in June 2023 in the PubMed database. Abstracts of 986 articles were examined to exclude reviews and non-English-language articles. After inclusion and exclusion criteria were applied, 26 articles were selected, and the panel methodologist rated them for strength of evidence. Thirteen articles were rated level I, and 8 articles were rated level II. The 5 level III articles were excluded. Data from the 21 included articles were abstracted and reviewed. RESULTS: The central 12 locations on the 24-2 VF test grid lie within the central 10 degrees covered by the 10-2 VF test. In early glaucoma, defects detected within the central 10 degrees generally agree between the 2 tests. Defects within the central 10 degrees of the 24-2 VF test can predict defects on the 10-2 VF test, although the 24-2 may miss defects detected on the 10-2 VF test. In addition, results from the 10-2 VF test show better association with findings from OCT scans of the macular ganglion cell complex. Modifications of the 24-2 test that include extra test locations within the central 10 degrees improve detection of central defects found on 10-2 VF testing. CONCLUSIONS: Evidence to date does not support routine testing using 10-2 VF for patients with early glaucoma. However, early 10-2 VF testing may provide sufficient additional information for some patients, particularly those with a repeatable defect within the central 12 locations of the standard 24-2 VF test or who have inner retinal layer thinning on OCT scans of the macula. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Aqueous Shunts with Extraocular Reservoir for Open-Angle Adult Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the recently published literature on the efficacy and safety of the use of aqueous shunts with extraocular reservoir for the management of adult open-angle glaucomas (OAGs). METHODS: A search of peer-reviewed literature was last conducted in April 2023 of the PubMed database and included only articles published since the last aqueous shunt Ophthalmic Technology Assessment, which assessed articles published before 2008. The abstracts of these 419 articles were examined, and 58 studies were selected for full-text analysis. After inclusion and exclusion criteria were applied, 28 articles were selected and assigned ratings by the panel methodologist according to the level of evidence. Twenty-five articles were rated level I and 3 articles were rated level II. There were no level III articles. RESULTS: Implantation of aqueous shunts with extraocular reservoir can lower intraocular pressure (IOP) by between one-third and one-half of baseline IOP, depending on whether it is undertaken as the primary or secondary glaucoma surgery. Success rates for aqueous shunts were found to be better than for trabeculectomies in eyes with prior incisional surgery. Conversely, in eyes without prior incisional surgery, implantation of aqueous shunts was found to have an overall lower success rate as the primary glaucoma procedure compared with trabeculectomy. Although both valved and nonvalved aqueous shunts with extraocular reservoir were effective, the nonvalved device generally achieved slightly lower long-term IOPs with fewer glaucoma medications and less need for additional glaucoma surgery. Both devices slow the rates of visual field progression with efficacy comparable with that of trabeculectomy. Early aqueous humor suppression after aqueous shunt implantation is recommended for the management of the postoperative hypertensive phase and long-term IOP control. No strong evidence supports the routine use of mitomycin C with aqueous shunt implantation for OAG. CONCLUSIONS: Implantation of aqueous shunts with extraocular reservoir, including valved or nonvalved devices, has been shown to be an effective strategy to lower IOP. Strong level I evidence supports the use of aqueous shunts with extraocular reservoir by clinicians for the management of adult OAG. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Trabecular Procedures Combined with Cataract Surgery for Open-Angle Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To determine the intraocular pressure (IOP) reduction of various trabecular procedures (a form of minimally invasive glaucoma surgery [MIGS]) combined with cataract surgery compared with cataract surgery alone, to compare the safety of the various trabecular procedures, and to highlight patient characteristics that may favor one trabecular procedure over another. METHODS: A search of English-language peer-reviewed literature in the PubMed database was initially conducted in February 2021 and updated in April 2023. This yielded 279 articles. Twenty studies met initial inclusion and exclusion criteria and were assessed for quality by the panel methodologist. Of these, 10 were rated level I, 3 were rated level II, and 7 were rated level III. Only the 10 level I randomized controlled trials (RCTs) were included in this assessment, and all were subject to potential industry-sponsorship bias. RESULTS: The current analysis focuses on the amount of IOP reduction (in studies that involved medication washout) and on IOP reduction with concurrent medication reduction (in studies that did not involve medication washout). Based on studies that performed a medication washout, adding a trabecular procedure to cataract surgery provided an additional 1.6 to 2.3 mmHg IOP reduction in subjects with hypertensive, mild to moderate open-angle glaucoma (OAG) at 2 years over cataract surgery alone, which itself provided approximately 5.4 to 7.6 mmHg IOP reduction. In other words, adding a trabecular procedure provided an additional 3.8% to 8.9% IOP reduction over cataract surgery alone, which itself provided 21% to 28% IOP reduction. There was no clear benefit of one trabecular procedure over another. Patient-specific considerations that can guide procedure selection include uveitis predisposition, bleeding risk, metal allergy, and narrowing of Schlemm's canal. There are no level I data on the efficacy of trabecular procedures in subjects with pretreatment IOP of 21 mmHg or less. CONCLUSIONS: Trabecular procedures combined with cataract surgery provide an additional mild IOP reduction over cataract surgery alone in hypertensive OAG subjects. Additional research should standardize outcome definitions, avoid industry sponsorship bias, and study the efficacy of these procedures in normotensive OAG. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Corneal Hysteresis for the Diagnosis of Glaucoma and Assessment of Progression Risk: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the current published literature on the utility of corneal hysteresis (CH) to assist the clinician in the diagnosis of glaucoma or in the assessment of risk for disease progression in existing glaucoma patients. METHODS: Searches of the peer-reviewed literature in the PubMed database were performed through July 2022. The abstracts of 423 identified articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 19 articles were selected, and the panel methodologist rated them for level of evidence. Eight articles were rated level I, and 5 articles were rated level II. The 6 articles rated level III were excluded. RESULTS: Corneal hysteresis is lower in patients with primary open-angle glaucoma, primary angle-closure glaucoma, pseudoexfoliative glaucoma, and pseudoexfoliation syndrome compared with normal subjects. Interpretation of low CH in patients with high intraocular pressure (IOP) or on topical hypotensive medications is complicated by the influence of these parameters on CH measurements. However, CH is also lower in treatment-naïve, normal-tension glaucoma patients compared with normal subjects who have a similar IOP. In addition, lower CH is associated with an increased risk of progression of glaucoma based on visual fields or structural markers in open-angle glaucoma patients, including those with apparently well-controlled IOP. CONCLUSIONS: Corneal hysteresis is lower in glaucoma patients compared with normal subjects, and lower CH is associated with an increased risk of disease progression. However, a causal relationship remains to be demonstrated. Nevertheless, measurement of CH complements current structural and functional assessments in determining disease risk in glaucoma suspects and patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Ocular and systemic determinants of perifoveal and macular vessel parameters in healthy African Americans.

PURPOSE: To determine the relationship of various systemic and ocular characteristics with perifoveal and macular vessel density in healthy African American eyes. DESIGN: A population-based cross-sectional study of prospectively recruited African Americans ≥40 years of age. Participants underwent 3×3 mm and 6×6 mm macula scans using spectral-domain optical coherence tomography angiography (OCTA), clinical examinations and clinical questionnaires. Participants with glaucoma, severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and macular oedema were excluded. Custom MATLAB based software quantified vessel area density (VAD) and vessel skeleton density (VSD) in the superficial retinal layer of the macula. Multivariable regression analysis, controlling for inter-eye correlation, was performed to determine systemic and ocular determinants of macular vessel metrics using stepwise selection. Candidate variables included: age, gender, body mass index, history of smoking, history of diabetes, diabetes duration, history of stroke or brain haemorrhage, systolic blood pressure, diastolic blood pressure (DBP), pulse pressure, mean arterial pressure, central subfield thickness (CSFT), visual field mean deviation, intraocular pressure, axial length (AL), mean ocular perfusion pressure and signal strength (SS). RESULTS: A total of 2221 OCTA imaged eyes from 1472 participants were included in this study. Reduced perifoveal and macular VAD and VSD were independently associated with longer AL, reduced SS, reduced CSFT and older age. Male gender and lower DBP were also associated with reduced perifoveal and macular VSD. CONCLUSIONS: When interpreting OCTA images in a clinical setting, it is important to consider the effects ocular and systemic characteristics may have on the macular microcirculation.

Optimal number and orientation of anterior segment OCT images to measure ocular biometric parameters in angle closure eyes: the Chinese American Eye Study.

PURPOSE: To assess the optimal number and orientation of anterior segment optical coherence tomography (AS-OCT) images for accurately measuring ocular biometric parameters in angle closure eyes. METHODS: Subjects with angle closure, defined as >3 quadrants of non-visible pigmented trabecular meshwork on static gonioscopy, were selected from the Chinese American Eye Study. Mean angle opening distance (AOD500) was calculated using four images (0°-180°, 45°-225°, 90°-270° and 135°-315° meridians) from one eye per subject. Ten eyes from each quartile of AOD500 measurements were randomly selected for detailed 32-image analysis of 10 biometric parameters, including AOD500, iris curvature (IC), anterior chamber depth (ACD), lens vault (LV), and anterior chamber area (ACA). Mean and range of measurements from 1, 2, 4, 8 or 16 images were compared with 32-image values for all parameters. RESULTS: 40 out of 335 eyes with angle closure were selected for 32-image analysis. Deviation from the 32-image mean was between 0.44% and 19.31% with one image, decreasing to 0.08% to 4.21% with two images for all parameters. Deviation from the 32-image range of measurements was between 54.67% to 88.94% with one image, decreasing to <7.00% with eight images for all parameters except ACD and ACA. Orienting the first image analysed along the 25°-205° meridian better approximated the range of measurements when four or fewer images were analysed. CONCLUSIONS: Sectoral anatomical variations in angle closure eyes are easily misrepresented based on current AS-OCT imaging conventions. A revised multi-image approach can better capture the mean and range of biometric measurements.

Repeatability and Reproducibility of 4.5 by 4.5 mm Peripapillary Optical Coherence Tomography Angiography Scans in Glaucoma and Non-Glaucoma Eyes.

PRCIS: Peripapillary vessel parameters from optical coherence tomography angiography (OCTA) 4.5×4.5 mm scans in nonglaucomatous and glaucomatous eyes showed high repeatability and reproducibility, with higher reliability for commercially developed OCTA parameters compared with custom OCTA parameters. PURPOSE: The purpose of this study was to assess intrasession repeatability versus intersession reproducibility of peripapillary vessel parameters from 4.5×4.5 mm OCTA scans in nonglaucomatous eyes and glaucomatous eyes. MATERIALS AND METHODS: In a longitudinal study, peripapillary OCTA scans were quantified using research-oriented custom quantification software that calculated vessel area density (VAD) and flux and clinic-oriented commercially developed software (Cirrus 11.0) that calculated perfusion density (PD) and flux index (FI). Intrasession repeatability and intersession reproducibility were evaluated using within-eye coefficient of variation (CV W ) and intraclass correlation coefficient (ICC). RESULTS: With 127 nonglaucomatous eyes, intrasession CV W for VAD, PD, flux, and FI were 1.900%, 1.174%, 2.787%, and 1.425%, respectively. The intersession CV W were 2.039%, 1.606%, 4.053%, and 2.798%, respectively. Intrasession ICC ranged from 0.903 to 0.956, and intersession ICC ranged from 0.850 to 0.896. Among 144 glaucomatous eyes, intrasession CV W for VAD, PD, flux, and FI were: 3.841%, 1.493%, 5.009%, and 2.432%, respectively. The intersession CV W were 4.991%, 2.155%, 6.360%, and 3.458%, respectively. Intrasession ICC ranged from 0.956 to 0.969, and intersession ICC ranged from 0.918 to 0.964. CONCLUSIONS: Among nonglaucomatous and glaucomatous eyes, the majority of peripapillary OCTA vessel parameters from 4.5×4.5 mm scans had greater intrasession repeatability than intersession reproducibility. There was a greater agreement for the commercially developed quantification parameters than for their custom quantification counterparts.

Wedge Defects on Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma: Prevalence and Associated Clinical Factors.

PRCIS: Among subjects with glaucoma, wedge-shaped defects on optical coherence tomography angiography (OCTA) were associated with disc hemorrhages (DH), paracentral visual field (VF) defects, increased cup-to-disc ratio (CDR), and thinner retinal nerve fiber layer (RNFL). PURPOSE: To examine determinants of wedge defects on peripapillary OCTA in glaucoma. MATERIALS AND METHODS: A total of 278 eyes of 186 subjects with mild to severe primary open-angle glaucoma underwent 6×6 spectral-domain OCTA imaging of the superficial peripapillary retina from 2016 to 2020 at an academic practice. Wedge defects were defined as focal microvasculature loss that extends outward from the optic nerve in an arcuate, wedge shape. Logistic regression models controlling for intereye correlation identified variables significantly associated with wedge defects. Eyes with profound microvasculature loss in both hemispheres were excluded. Candidate variables included: age, sex, race or ethnicity, diabetes, hypertension, follow-up duration, baseline untreated intraocular pressure, intraocular pressure at time of imaging, DH history, paracentral VF defects, CDR, central corneal thickness, spherical equivalent, VF mean deviation, RNFL thickness, and glaucoma stage. RESULTS: Of 278 eyes, 126 (45.3%) had wedge defects in at least 1 hemisphere. In our multivariable logistic regression model, wedge defects were associated with DH history [odds ratio (OR): 3.19, 95% confidence interval (CI): 1.05-9.69, P=0.041], paracentral VF defects [OR: 4.38 (95% CI: 2.11-9.11), P<0.0001], larger CDR [OR: 1.27 (95% CI: 1.03-1.56), P=0.024, per 0.1 increase], and thinner RNFL [OR: 1.71 (95% CI: 1.25-2.34), P=0.0009, per 10 µm decrease]. CONCLUSION: DH history and paracentral VF defects were independently associated with wedge defects on OCTA, which was present in 45.3% of primary open-angle glaucoma patients. These findings may provide insight into glaucoma pathogenesis.

Longer Axial Length Potentiates Relationship of Intraocular Pressure and Peripapillary Vessel Density in Glaucoma Patients.

Purpose: The purpose of this study was to investigate how axial length (AL) changes the relationship of intraocular pressure (IOP) with peripapillary vessel density (pVD) in glaucoma versus non-glaucomatous eyes. Methods: A population-based, cross-sectional study of 2127 African Americans aged 40 years and older in Inglewood, California, were imaged with 6 × 6-mm optic disc optical coherence tomography angiography scans. There were 1028 healthy subjects (1539 eyes) and 65 subjects with glaucoma (86 eyes) who met inclusion criteria. A multivariable linear mixed effects regression model investigated the relationship of IOP on pVD after controlling for signal strength, retinal nerve fiber layer thickness, and age. These results were stratified by AL groups. Results: Higher IOP was a significant predictor of lower pVD among subjects with glaucoma (P = 0.009), but not among healthy subjects (P = 0.26). After stratifying by the sample median AL (23.46 mm), higher IOP was associated with lower pVD among subjects with glaucoma with longer AL (≥ 23.46 mm, P = 0.005), but not among those in the shorter AL (< 23.46 mm, P = 0.45). IOP was not significantly associated with pVD among healthy subjects in either AL stratum. Conclusions: Among subjects with glaucoma with longer AL, IOP was significantly associated with pVD. This relationship was not seen among subjects with glaucoma with shorter AL or non-glaucomatous subjects in either AL group. These findings support the hypothesis that disturbed retinal autoregulation may be present in subjects with glaucoma with longer AL. Longitudinal studies are needed to further investigate whether axial elongation increases glaucoma risk by compromising retinal autoregulation.

Hemiretinal Asymmetry in Peripapillary Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

PURPOSE: To investigate hemiretinal asymmetry in radial peripapillary capillary vessel area density (VAD) of healthy, glaucoma suspect, and glaucoma eyes of varying severity and its diagnostic utility for glaucoma. DESIGN: Population-based, cross-sectional study. METHODS: Optic disc scans (6 × 6 mm) were collected on optical coherence tomography angiography (OCTA) to obtain VAD and on optical coherence tomography (OCT) to measure circumpapillary retinal nerve fiber layer (RNFL) thickness. Hemiretinal difference in VAD (hdVAD) was defined as the absolute difference between superior and inferior hemiretinal VAD. Age-adjusted multivariable linear regression of hdVAD on glaucoma severity was performed. Areas under curves (AUCs) were calculated from predicted probabilities generated by multiple logistic regression of glaucoma severity on age-adjusted single and combined parameters. RESULTS: A total of 1,043 eyes of 1,043 participants (587 healthy, 270 suspect, 67 mild, 54 moderate, 65 severe glaucoma) were included. After age adjustment, mean hdVAD was similar between healthy and suspect (P = .225), higher in mild vs suspect (P < .001), and higher in moderate vs mild (P = .018), but lower in severe vs moderate (P = .001). AUCs of hdVAD were highest for discriminating mild (0.685) and moderate (0.681) glaucoma from healthy. Combining hdVAD and global RNFL (gRNFL) yielded the highest AUCs of all parameters for mild (0.818) and any POAG (0.859) and resulted in significantly better diagnostic accuracy than either hdVAD or gRNFL alone (P < .05 for all comparisons). CONCLUSIONS: hdVAD is higher in early glaucoma and may help with early detection when damage is focal, but its diagnostic ability appears less robust in advanced glaucoma when damage is diffuse.

Steps to Measurement Floor of an Optical Microangiography Device in Glaucoma.

PURPOSE: To compare dynamic ranges and steps to measurement floors of peripapillary and macular metrics from a complex signal-based optical microangiography (OMAGC) optical coherence tomography angiography (OCTA) device for glaucoma with those of OCT measurements. DESIGN: Cross-sectional study. METHODS: Imaging of 252 eyes from 173 patients with glaucoma and 123 eyes from 92 subjects without glaucoma from a glaucoma clinic was quantified using custom and commercial software. Metrics from OCT (retinal nerve fiber layer [RNFL], ganglion cell/inner plexiform layer [GCIPL]) and OCTA (custom: peripapillary vessel area density [pVAD], macular vessel area density [mVAD], and macular vessel skeleton density [mVSD]; commercial: peripapillary perfusion density [pPDZ], macular perfusion density [mPDZ], and macular vessel density [mVDZ]) were plotted against visual field mean deviation (MD) with linear change-point analyses, measurement floors, and steps to floors. RESULTS: Mean MD (dB) for glaucomatous eyes was -5.77 (-6.45 to -5.10). The number of eyes with mild glaucoma (MD >-6), moderate glaucoma (MD -6 to -12), and severe glaucoma (MD <-12) were 164, 50, and 38, respectively. pPDZ yielded the lowest estimated floor at -26.6 dB (standard error [SE] 1.53), followed by OCTA macular metrics (-25 to -21 dB; SE 1.03) and pVAD (-17.6 dB, SE 1.06). RNFL and GCIPL produced floors at -17.8 (SE 0.927) and -23.6 dB (SE 1.14). The highest number of steps to measurement floor belonged to RNFL (7.20) and GCIPL (7.33), followed by pPDZ (4.25), mVAD (3.87), and mVSD (3.81), with 2.5 or fewer steps for pVAD, mPDZ, and mVDZ. CONCLUSIONS: pPDZ, mVAD, and mVSD had approximately 4 steps within their dynamic ranges, without true measurement floors, and thus may be useful in evaluating advanced glaucomatous progression. Improving OCTA test-retest repeatability could augment number of steps for OCTA metrics, increasing their clinical utility.

Relationship Between Macular Vessel Density and Total Retinal Blood Flow in Primary Open-angle Glaucoma.

PRECIS: An association between macular vessel density (VD) and total retinal blood flow (TRBF) was demonstrated in subjects with primary open-angle glaucoma (POAG) and visual field (VF) loss. PURPOSE: The purpose of this study was to report relationships of macular VD metrics and TRBF in POAG. MATERIALS AND METHODS: A total of 24 POAG and 19 healthy control subjects participated in the study. Subjects underwent optical coherence tomography and angiography for measurements of inner retinal thickness (IRT), VD, and spacing between large vessels (SLV) and small vessels (SSV). Doppler optical coherence tomography imaging was performed for TRBF measurement. In POAG subjects, automated perimetry was performed and VF loss expressed as mean deviation was measured. RESULTS: Compared with the control group, POAG group had decreased VD, TRBF, IRT, and increased SLV (P<0.0001). Decreased VD (Pearson correlation, r=0.51; P<0.0001; N=43) and increased SLV (Spearman correlation, rs=-0.47; P=0.001) were correlated with decreased TRBF. Decreased VD and SSV (r≥0.39; P≤0.001; N=43) and increased SLV (rs=-0.71; P<0.0001) were associated with decreased IRT. Decreased VF mean deviation was correlated with decreased VD, SSV, IRT (r≥0.53; P≤0.001; N=24), and with increased SLV (rs=-0.84; P<0.0001). CONCLUSIONS: The finding of an association between macular VD and TRBF supports the role of vascular factors in the pathophysiology of POAG and potential conduct of future studies aimed at identifying multiple image-based vascular metrics for disease diagnosis.

Intrasession repeatability and intersession reproducibility of peripapillary OCTA vessel parameters in non-glaucomatous and glaucomatous eyes.

OBJECTIVE: To compare intrasession repeatability versus intersession reproducibility of the peripapillary vessel parameters using optical microangiography-based optical coherence tomography angiography (OCTA) in non-glaucomatous and glaucomatous eyes. METHODS: In an observational, longitudinal study, peripapillary OCTA scans were collected to evaluate intrasession repeatability and intersession reproducibility using within-eye coefficient of variation (CVW) and intraclass correlation coefficient (ICC). Images were quantified using a custom research-oriented quantification software calculating vessel area density (VAD) and flux and a commercially developed, clinic-oriented quantification software (Cirrus 11.0, Carl Zeiss Meditec) calculating perfusion density (PD) and flux index (FI). Effect of signal strength on the reliability of OCTA parameters was also evaluated. RESULTS: Among 120 non-glaucomatous eyes, intrasession CVW were 4.2% for VAD, 5.3% for flux, 1.5% for PD and 2.0% for FI. The intersession CVW were 6.5% for VAD, 8.0% for flux, 2.0% for PD and 3.2% for FI. The intrasession ICC ranged from 0.928 to 0.945, and intersession ICC ranged from 0.811 to 0.866. From 118 glaucomatous eyes, intrasession CVW was 9.0% for VAD, 10.3% for flux, 1.7% for PD and 2.3% for FI. The intersession CVW was 12.1% for VAD, 14.2% for flux, 2.3% for PD and 3.5% for FI. The intrasession ICC ranged from 0.904 to 0.972, and intersession ICC ranged from 0.855 to 0.955. Signal strength was significantly positively associated with OCTA vessel parameters (p<0.0001) for both groups. CONCLUSION: Peripapillary OCTA vessel parameters had greater intrasession repeatability compared to intersession reproducibility in both non-glaucomatous and glaucomatous eyes. The built-in commercially developed quantification software demonstrated greater agreement than the custom research-oriented quantification software.

Retinal Nerve Fiber Layer Thickness in Healthy Eyes of Black, Chinese, and Latino Americans: A Population-Based Multiethnic Study.

PURPOSE: To compare peripapillary retinal nerve fiber layer (RNFL) thickness among healthy adults by race and ethnicity and to identify determinants of RNFL thickness. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Data from 6133 individuals (11 585 eyes) from 3 population-based studies in Los Angeles County, California, 50 years of age or older and of self-described African, Chinese, or Latin American ancestry. METHODS: We measured RNFL thickness and optic nerve head parameters using the Cirrus HD-OCT 4000. Multivariate linear mixed regression was used to evaluate factors associated with RNFL thickness among participants without ocular diseases. MAIN OUTCOME MEASURES: Determinants and modifiers of RNFL thickness. RESULTS: The mean age of the participants was 60.1 years (standard deviation, 7.4 years). Black Americans showed the lowest RNFL thickness and smallest cup-to-disc ratio (CDR), and Chinese Americans showed the largest CDR and disc area after adjusting for age and gender (all P < 0.05). Per each 10-year older age group, the average RNFL thickness was 2.5 µm (95% confidence interval [CI], 1.8-3.1 µm), 2.8 µm (95% CI, 2.3-3.3 µm), and 3.5 µm (95% CI, 2.9-4.1 µm) thinner for Black, Chinese, and Latino Americans, respectively (age trend P < 0.05 and interaction P = 0.041). Black Americans compared with Chinese Americans, older age, male gender, hypertension, diabetes, greater axial length (AL), bigger disc area, and lower scan signal strength were associated with thinner average RNFL. Race, age, AL, disc area, and scan signal strength consistently were associated with RNFL thickness in all quadrants, whereas gender, hypertension, and diabetes were associated with RNFL thickness in select quadrants. Age and race explained the greatest proportion of variance of RNFL thickness. CONCLUSIONS: Clinically important differences in RNFL thickness are present in healthy adults 50 years of age or older from different racial and ethnic groups of the same age, with the thinnest measures observed in Black Americans. This difference remains after accounting for disc size and AL. Furthermore, age-related RNFL thinning differs by race and ethnicity. Longitudinal studies are needed to verify our findings and to assess the influence of race and ethnicity in the clinical application of RNFL thickness.

Ocular Biometric Determinants of Anterior Chamber Angle Width in Chinese Americans: The Chinese American Eye Study.

PURPOSE: We sought to investigate anatomic mechanisms of angle narrowing by assessing ocular biometric determinants of anterior chamber angle width. DESIGN: Population-based cross-sectional study. METHODS: Subjects ≥50 years of age from the Chinese American Eye Study underwent a comprehensive ocular examination, including anterior segment optical coherence tomography imaging and ultrasound A-scan. Independent variables, including anterior chamber depth (ACD), lens vault (LV), iris curvature (IC), anterior chamber width, lens thickness, vitreous cavity depth, and axial length, and dependent variables, including angle opening distance, were measured in 1 randomly selected eye per subject. Univariable and multivariable regression models with standardized regression coefficients (SRCs) and semipartial correlation coefficients squares (SPCC2) were used to assess relative and unique contributions by independent variables to angle width. RESULTS: Two thousand two hundred twenty-five subjects (1433 women and 834 men) were included in the analysis. All biometric parameters except lens thickness differed between men and women (age-adjusted P < .001). In model 1A (R2 = 0.66), which included ACD, lens thickness, and vitreous cavity depth, ACD (SRC = 0.64, SPCC2 = 0.19) and IC (SRC = -0.26, SPCC2 = 0.041) were the strongest determinants of angle opening distance. In model 1B (R2 = 0.58), which included LV and axial length, LV (SRC = -0.46, SPCC2 = 0.1) and IC (SRC = -0.3, SPCC2 = 0.047) were the strongest determinants of angle opening distance. Determinants of angle width were similar in separate multivariable models for men and women. CONCLUSIONS: ACD, LV, and IC are the strongest determinants of angle width in Chinese Americans. Sex-related differences in angle width are explained by differences among biometric measurements. These results provide insights into anatomic mechanisms of angle narrowing and have important implications for quantitative assessments of angle closure eyes.

Clinical Utility of Triplicate En Face Image Averaging for Optical Coherence Tomography Angiography in Glaucoma and Glaucoma Suspects.

PRéCIS:: Averaging triplicate en face angiograms of the radial peripapillary capillary (RPC) plexus with optical coherence tomography angiography (OCTA) improves vessel visualization, reduces vessel density parameters, and increases the diagnostic accuracy for glaucoma of one such parameter. PURPOSE: The purpose of this study was to test the hypothesis that triplicate averaging of the RPC layer improves visualization and diagnostic accuracy of OCTA for glaucoma. MATERIALS AND METHODS: This is a cross-sectional study involving 63 primary open-angle glaucoma patients and 70 age-matched glaucoma suspects. Triplicate 6×6 mm OCTA scans of the optic nerve head were acquired, and the RPC layer was extracted. RPC en face images were registered and averaged. Parameters of global entropy, global standard deviation, local texture correlation, local homogeneity, signal-to-noise ratio, and intercapillary distance were used to measure the change in visualization with averaging. Vessel area density (VAD), vessel skeleton density (VSD), and flux parameters were calculated in a 2.8 mm annulus excluding the optic disc. The diagnostic accuracy of these parameters for glaucoma was assessed by calculating the area under the receiver operating curve (AUC) values. RESULTS: Three-frame averaging resulted in decreased global entropy and global standard deviation (Ps<0.001), and increased local texture correlation, local homogeneity, signal-to-noise ratio, and intercapillary distance (Ps<0.001). Averaged images also had reduced VAD, VSD, and flux (Ps<0.001). AUC was significantly increased for VSD after image averaging (P=0.018), while no significant change in AUC was observed for VAD (P=0.229) or flux (P=0.193). CONCLUSIONS: Triplicate averaging improves visualization of the RPC layer and the diagnostic accuracy of VSD for glaucoma. The impact of image averaging on OCTA diagnostic performance and other potential applications warrants further exploration.

Systemic Determinants of Peripapillary Vessel Density in Healthy African Americans: The African American Eye Disease Study.

PURPOSE: To determine the relationship between systemic factors and radial peripapillary capillary (RPC) vessel density (VD) in healthy African American (AA) participants of the African American Eye Disease Study. DESIGN: A population-based, cross-sectional study. METHODS: A total of 4135 eyes from 2127 AA participants aged 40 years and older in Inglewood, California, were imaged for 6×6-mm optic disc scans on a spectral-domain optical coherence tomography angiography (OCTA) device. Of these, 1029 eyes from 1029 participants who met the inclusion and exclusion criteria were analyzed, including only 1 eye per participant. Custom software was used to quantify RPC VD. Multivariate linear regression was used to identify systemic factors associated with RPC VD with a significance level set at 0.05. The contribution of each variable to the final model was estimated with the magnitude of standardized regression coefficients (SRCs). The fit of the final model was measured by R2. RESULTS: The average RPC VD was 0.346±0.045. Controlling for signal strength, the systemic variables in the final multivariate model associated with reduced RPC VD were older age (ß = -0.0123 per decade; SRC = -0.2733; P < .0001), male sex (ß = -0.0067; SRC = -0.0716; P = .0060), and longer diabetes duration (ß = -0.0022 per 5 years; SRC = -0.0527; P = .0427). The model R2 was 0.3689. CONCLUSIONS: Age, sex, and systemic influences, such as diabetes duration, need to be considered when assessing changes in RPC VD in glaucoma and other ocular diseases. Longitudinal studies are needed to investigate whether reduced RPC VD and the factors that affect it are associated with an increased risk of developing glaucomatous nerve damage.

Differences in Anterior Chamber Angle Assessments Between Gonioscopy, EyeCam, and Anterior Segment OCT: The Chinese American Eye Study.

PURPOSE: To quantify interquadrant differences in anterior chamber angle (ACA) configuration assessed on gonioscopy, EyeCam, and anterior segment optical coherence tomography (AS-OCT) in a cohort of Chinese Americans. METHODS: Subjects aged 50 years or older were recruited from the Chinese American Eye Study (CHES), a population-based epidemiologic study in Los Angeles, CA. Each subject underwent a complete ocular exam, including gonioscopy, EyeCam, and AS-OCT, under dark ambient lighting. Gonioscopy and AS-OCT imaging and EyeCam image grading were performed by trained ophthalmologists. RESULTS: Seven hundred nine eyes from 709 subjects were analyzed. Less anatomic variation among the quadrants was detected on gonioscopy and EyeCam compared with AS-OCT (P < 0.05). The mean gonioscopy grade, EyeCam grade, and AS-OCT measurement for each quadrant varied by up to 10.3%, 6.4%, and 46.2% of the superior quadrant value, respectively. There were significant interquadrant differences (P < 0.05) among mean AOD750 measurements when grouping by quadrant and gonioscopy or EyeCam grade. Mean AOD750 measurements were smallest for the superior quadrant by between 14.3% and 38.1% and 17.4% and 37.9% on gonioscopy and EyeCam, respectively, compared with other quadrants. CONCLUSIONS: Gonioscopy and EyeCam significantly underrepresent anatomic variations of the ACA compared with AS-OCT. Gonioscopy or EyeCam grades from different quadrants do not appear to be comparable or interchangeable, which supports reconsideration of current definitions and methods used to diagnose and manage primary angle closure disease. TRANSLATIONAL RELEVANCE: AS-OCT imaging raises concerns about current clinical definitions and methods that rely gonioscopy or EyeCam to assess the ACA.

Effect of Scan Size on Glaucoma Diagnostic Performance Using OCT Angiography En Face Images of the Radial Peripapillary Capillaries.

PRECIS: When comparing 4.5×4.5 mm to 6.0×6.0 mm optical coherence tomography angiography scans of the radial peripapillary capillaries (RPCs) for glaucoma diagnostic capability, there was a trend of 4.5 scans outperforming 6.0 scans, especially for inferior, nasal, and superior quadrants. OBJECTIVES: The main purpose of this study was to compare diagnostic ability of peripapillary vessel parameters from 4.5×4.5 mm (4.5) and 6.0×6.0 mm (6.0) spectral-domain optical coherence tomography angiography scans of the RPC in detecting primary open-angle glaucoma from nonglaucoma eyes. METHODS: Consecutive patients from an academic glaucoma clinic underwent 4.5 and 6.0 scans (CIRRUS HD-OCT 5000 with AngioPlex OCT Angiography; ZEISS, Dublin, CA). Automatic segmentation created en face RPC images. Vessel area density, vessel skeleton density, and flux were calculated using custom quantification software, and perfusion density and flux index (FI) using automated quantification software. Area under the curve statistics included age and hypertension in the analysis. RESULTS: Of 173 eyes from 123 patients who underwent both 4.5 and 6.0 imaging, 32 primary open-angle glaucoma eyes from 32 patients and 95 nonglaucoma eyes from 95 patients were studied. For the global region of 4.5 versus 6.0 scans, area under the curve was 0.940 and 0.916 for vessel area density (P=0.286); 0.941 and 0.921 for vessel skeleton density (P=0.385); 0.942 and 0.916 for flux (P=0.239); 0.912 and 0.884 for perfusion density (P=0.103); and 0.913 and 0.865 for FI (P=0.159), respectively. For the quadrant regions, 4.5 images significantly outperformed 6.0 images for the superior and inferior quadrants for flux and superior and nasal quadrants for FI (P-values=0.007, 0.047, 0.011, 0.007, respectively); other quadrant differences were not significant. CONCLUSIONS: Parameters from 4.5 scans generally outperformed those from 6.0 scans in the global and quadrant regions, suggesting greater digital resolution in 4.5 scans of the immediate peripapillary RPC is important in detecting glaucomatous changes.

Machine Learning Models for Diagnosing Glaucoma from Retinal Nerve Fiber Layer Thickness Maps.

PURPOSE: To assess the diagnostic accuracy of multiple machine learning models using full retinal nerve fiber layer (RNFL) thickness maps in detecting glaucoma. DESIGN: Case-control study. PARTICIPANTS: A total of 93 eyes from 69 patients with glaucoma and 128 eyes from 128 age- and sex-matched healthy controls from the Los Angeles Latino Eye Study (LALES), a large population-based, longitudinal cohort study consisting of Latino participants aged ≥40 years residing in El Puente, California. METHODS: The 6×6-mm RNFL thickness maps centered on the optic nerve head (Cirrus 4000; Zeiss, Dublin, CA) were supplied to 4 different machine learning algorithms. These models included 2 conventional machine learning algorithms, Support Vector Machine (SVM) and K-Nearest Neighbor (KNN), and 2 convolutional neural nets, ResNet-18 and GlaucomaNet, which was a custom-made deep learning network. All models were tested with 5-fold cross validation. MAIN OUTCOME MEASURES: Area under the curve (AUC) statistics to assess diagnostic accuracy of each model compared with conventional average circumpapillary RNFL thickness. RESULTS: All 4 models achieved similarly high diagnostic accuracies, with AUC values ranging from 0.91 to 0.92. These values were significantly higher than those for average circumpapillary RNFL thickness, which had an AUC of 0.76 in the same patient population. CONCLUSIONS: Superior diagnostic performance was achieved with both conventional machine learning and convolutional neural net models compared with circumpapillary RNFL thickness. This supports the importance of the spatial structure of RNFL thickness map data in diagnosing glaucoma and further efforts to optimize our use of this data.