Optic Nerve Head Capillary Network Quantified by Optical Coherence Tomography Angiography and Decline of Renal Function in Type 2 Diabetes: A Three-Year Prospective Study.

PURPOSE: To assess the association of optic capillary perfusion with decline in the estimated glomerular filtration rate (eGFR) and to clarify its added value. DESIGN: Prospective, observational cohort study. METHODS: Patients with type 2 diabetes mellitus without diabetic retinopathy (non-DR) underwent standardized examinations annually during a 3-year follow-up period. The superficial capillary plexus (SCP), deep capillary plexus (DCP), and radial peripapillary plexus (RPC) of optic nerve head (ONH) were visualized using optical coherence tomography angiography (OCTA), and the perfusion density (PD) and vascular density were quantified for the whole image and circumpapillary regions of the ONH.  The lowest tercile of annual eGFR slope was defined as the rapidly progressive group, and the highest tercile was considered the stable group. RESULTS: A total of 906 patients were included for 3-mm × 3-mm OCTA analysis. After adjusting for other confounders, each 1% decrease in baseline whole en face PD in SCP and RPC was associated with accelerated rates of decline in eGFR by -0.53 mL/min/1.73/m2 per year (95% confidence interval [CI] -0.17 to -0.90; P = .004) and -0.60 mL/min/1.73/m2 per year (95% CI 0.28-0.91), respectively. Adding both whole-image PD in SCP and whole-image PD in RPC to the conventional model increased the area under the curve from 0.696 (95% CI 0.654-0.737) to 0.725 (95% CI 0.685-0.765; P = .031). Another cohort of 400 eligible patients with 6-mm × 6 mm OCTA imaging validated the significant associations between ONH perfusion and rate of eGFR decline (P < .05). CONCLUSIONS: Reduced capillary perfusion of ONH in patients with type 2 diabetes mellitus is associated with a greater eGFR decline, and it has additional predictive value for detecting an early stage and progression.

The association of homocysteine level with the risk of diabetic nephropathy and diabetic retinopathy in NHANES.

AIMS: To examine the association of homocysteine (Hcy) with diabetic nephropathy (DN) and diabetic retinopathy (DR) in a representative United States population. METHODS: This was a cross-sectional study using data from participants in the National Health and Nutrition Examination Survey 2005-2006. Metrics including Hcy level, urinary albumin to creatinine ratio, estimated glomerular filtration rate, and retinopathy grading were collected. Multiple logistic regression models were employed to assess the association of Hcy with DN and DR. RESULTS: 630 participants were included in this study. The Hcy level was significantly higher in those with DN and DR than those without DN and DR. Hcy was associated with an increased risk of DN (OR = 1.31, 95% CI 1.18-1.46; P < 0.001). In the fully adjusted model of DN (model II), compared to participants in quartiles 1 of Hcy, the adjusted ORs for participants in quartiles 2-4 were 1.49 (95% CI 0.52-4.26; P = 0.426), 3.81 (95% CI 1.35-10.73; P = 0.015), and 14.08 (95% CI 3.84-51.66; P = 0.001), respectively. Hcy was also associated with an increased risk of DR (OR = 2.260, 95% CI 1.212-4.216; P = 0.014), but this association was non-significant in the fully adjusted model of DR (model II). CONCLUSIONS: In diabetic patients, Hcy was associated with increased risk of DN in a non-linear manner. In addition, Hcy was associated with the risk of DR, but the association was attenuated after adjusting for confounders. In the future, Hcy can potentially be used as an early screening indicator for diabetic microvascular complications.

Longitudinal Choriocapillaris Vascular Density Changes in Different Types of Primary Open-Angle Glaucoma.

Purpose: To evaluate longitudinal changes in choriocapillaris perfusion in patients with glaucoma with four phenotypes of optic disc damage and to explore associated factors with decreased choriocapillaris vessel density (CVD). Methods: This prospective longitudinal study included 96 eyes of 96 patients with primary open-angle glaucoma (POAG). Patients with POAG was differentiated into the optic disc phenotypes of focal ischemic type (FI), myopic type (MY), senile sclerotic type (SS), and generalized enlargement type (GE). Patients were followed up every three months. Simple linear regression was used to investigate the factors associated with a reduction in CVD. Results: The median follow-up time was 2.5 years (range, 2.0-3.0 years). Choriocapillaris perfusion tended to decrease over time, with CVD decreasing significantly faster in the FI type than in the other three types (P < 0.001). The percentage decrease in the FI type was 7.85%, 10.89%, and 8.88% faster than MY, SS and GE, respectively, after correcting for age, gender, axial length, intraocular pressure, mean deviation, retinal nerve fiber layer (RNFL), and image quality score. In multivariate regression, decreased CVD was independently associated with the rate of RNFL thinning. Conclusions: FI type had the fastest rate of CVD decline in the four phenotypes of optic disc damage, and decreased CVD was positively correlated with the rate of RNFL thinning. Translational Relevance: The role of the choriocapillaris in the pathogenesis and therapeutic potential of glaucoma require further attention to facilitate better management of glaucoma patients.

Choriocapillaris Flow Deficit as a Biomarker for Diabetic Retinopathy and Diabetic Macular Edema: 3-Year Longitudinal Cohort.

PURPOSE: To investigate the relationship between choriocapillaris flow deficit percentage (CC FD%) by swept-source optical coherence tomography angiography (SS-OCTA) and 3-year risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. DESIGN: Prospective, observational cohort study. METHODS: A total of 903 participants with type 2 diabetes mellitus (T2DM) without DR or with mild nonproliferative DR (NPDR) free of DME at baseline were followed up annually for 3 years. All participants underwent standard 7-field fundus photography and spectral-domain OCT. SS-OCTA was used for retinal and choriocapillaris imaging and 3 × 3-mm2 macular CC FD% was quantified. Univariate and multivariate logistic models were used to evaluate the association between CC FD% and 2 or more steps of DR progression and DME development. The additional predictive value of CC FD% for outcome events was assessed using C statistic, net reclassification index (NRI), and integrated discrimination improvement index (IDI). RESULTS: Over 3 years, 295 of 1805 eyes (16.34%) developed DR progression, and 118 eyes (6.54%) developed DME. A higher average CC FD% was correlated with DR progression (odds ratio [OR], 3.41 per SD increase, 95% CI: 2.65-4.39, P < .001) and DME development (OR, 1.37 per SD increase, 95% CI: 1.06-1.77, P = .016) after adjusting for confounders. In the ETDRS regions, increased CC FD% in all fields was associated with DR progression; however, increased CC FD% in the inferior field was associated with DME development. Compared with the models based on established risk factors, the addition of average CC FD% significantly improved the C statistics for DR progression (0.712 to 0.777, P < .001) and DME occurrence (0.743 to 0.773, P = .044). The estimated NRIs and IDIs (all >0) indicated that the addition of CC FD% led to a significant improvement in the discriminative performance for end points. CONCLUSION: CC FD% is independently associated with DR progression and DME development in the Chinese T2DM population and provides incremental predictive value beyond traditional risk factors and retinal microvascular parameters. Further inclusion of CC FD% in DR prediction models helps guide population-based screening and personalized management.

Macular and submacular choroidal microvasculature in patients with primary open-angle glaucoma and high myopia.

AIMS: To characterise the influence of primary open-angle glaucoma (POAG) and high myopia (HM) on the macular and choroidal capillary density (CD). METHODS: Two hundred and seven eyes were enrolled, including 80 POAG without HM, 50 POAG with HM, 31 HM without POAG and 46 normal controls. A fovea-centred 6×6 mm optical coherence tomography angiography scan was performed to obtain the CD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris. Macular and choroidal CDs were compared among the groups and the association of CDs with visual field mean deviation (MD) was determined using linear regression models. RESULTS: Compared with normal eyes, SCP CD was decreased in the POAG without HM group (p<0.05), while DCP CD was significantly decreased in the HM without POAG group (p<0.05). Both SCP and DCP CDs were significantly decreased in the POAG with HM group (p<0.05). CD reduction occurred mainly in the outer rather than inner ring of the 6×6 mm scan size. In multivariate regression analysis, worse MD was associated with lower CD in the outer ring of the SCP in all the HM eyes (p<0.05). CONCLUSIONS: POAG and HM reduced macular CD in different layers of the retinal capillary plexus and both particularly in the outer ring of the 6×6 mm scans. Furthermore, assessment of the CD in the outer ring of the SCP may facilitate the diagnosis of glaucoma in eyes with HM.

Choriocapillaris flow deficit and the risk of referable diabetic retinopathy: a longitudinal SS-OCTA study.

AIMS: To investigate the association between the choriocapillaris flow deficit percentage (CC FD%) and the 1-year incidence of referable diabetic retinopathy (RDR) in participants with type 2 diabetes mellitus (DM). METHODS: This prospective cohort study included participants with type 2 DM. The DR status was graded based on the ETDRS-7 photography. The CC FD% in the central 1 mm area, inner circle (1.5 mm to 2.5 mm), outer circle (2.5 mm to 5.0 mm) and the entire area in the macular region were measured using swept-source optical coherence tomography angiography (SS-OCTA). Logistic regression analysis was used to examine the association between baseline CC FD% and 1-year incident RDR. RESULTS: A total of 1222 patients (1222 eyes, mean age: 65.1±7.4 years) with complete baseline and 1-year follow-up data were included. Each 1% increase in baseline CC FD% was significantly associated with a 1.69 times (relative risk 2.69; 95% CI 1.53 to 4.71; p=0.001) higher odds for development of RDR after 1-year follow-up, after adjusting for other confounding factors. CONCLUSIONS: A greater baseline CC FD% detected by SS-OCTA reliably predicted higher risks of RDR in participants with type 2 DM. Thus, CC FD% may act as a novel biomarker for predicting the onset and progression of DR.

Choriocapillaris and progressive ganglion cell-inner plexiform layer loss in non-glaucomatous eyes.

AIMS: To explore the relationship between choriocapillaris (CC) flow deficit percentage (FD%) and ganglion cell-inner plexiform layer (GCIPL) thickness in a population-based sample of non-glaucomatous eyes. METHODS: This is a longitudinal cohort study and prospective cross-sectional study. Non-glaucoma Chinese subjects aged 18 years or older were enrolled. All participants underwent a detailed ophthalmic examination, including swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography. Average, inner average, outer average and nine Early Treatment Diabetic Retinopathy Study sub-regions of GCIPL thickness and CC FD% were measured. The correlation between CC FD% and GCIPL was assessed using a linear regression model, and the relationship between the rate of change of GCIPL thickness and CC FD% was further validated in a 2year longitudinal study. RESULTS: In the cross-sectional study including 3514 participants (3514 non-glaucoma eyes), a higher CC FD% was significantly associated with a thinner GCIPL (ß=-0.32; 95% CI -0.43 to -0.21; p<0.001). Further, in a longitudinal study (453 eyes of 453 participants), a faster increase in CC FD% was found to be significantly associated with a faster decrease in GCIPL thickness (ß=-0.10; 95% CI -0.17 to -0.03; p=0.004) after adjusting for age, sex, axial length and image quality score. CONCLUSIONS: This is the first time to show that CC FD% and GCIPL thickness were correlated in both cross-sectional and longitudinal studies of non-glaucomatous individuals, which may potentially provide further insights on the role of CC perfusion in glaucoma development and progression.

Quantitative analysis of choriocapillaris flow deficits and choroidal thickness in children with Marfan syndrome.

PURPOSE: To evaluate the characteristics and associated factors of choroidal thickness (ChT) and choriocapillaris flow deficit percentage (CC FD%) in children with Marfan syndrome (MFS). METHODS: This is a cross-sectional study. The ChT of the subfoveal area and other areas 0.5, 1.5, and 2.5 mm away from the fovea were assessed. The CC FD% of quadrant and circular regions with diameters of 0.5, 1.5 and 2.5 mm were assessed with 3×3 mm macular choriocapillaris images. Best-corrected visual acuity (BCVA) and cardiac function factor such as Z score were measured to analyse the associations with ChT and CC FD%. RESULTS: 51 MFS children and 50 healthy controls were enrolled in this study. Compared with the healthy controls, the ChT in the MFS group was thinner in the subfoveal area, temporal 0.5, 1.5 and 2.5 mm (all p<0.001). The CC FD% was higher in circle 0.5, 1.5 and 2.5 mm (all p<0.001). Multivariate regression analysis showed that CC FD% in the circle 2.5 mm when the Z score ≥2 was associated with BCVA (ß=9.08 (95% CI 3.96 to 14.20); p=0.005) and Z score (ß=4.19 (95% CI 1.28 to 12.00); p=0.012). CONCLUSIONS: Thinner ChT and a higher CC FD% were observed in children with MFS, and an increased CC FD% in circle 2.5 mm was significantly associated with worse BCVA and cardiac function. These findings may help identify future visual impairment and early cardiac events in MFS children.

Genome-wide DNA methylation analysis of extreme phenotypes in the identification of novel epigenetic modifications in diabetic retinopathy.

BACKGROUND: Aberrant epigenetic modifications such as DNA methylation may contribute to the pathogenesis of DR. We aimed at elucidating the role of novel DNA methylation modifications in diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) using an extreme phenotypic design. METHODS/RESULTS: Two consecutive studies were conducted. A cross-sectional study using an extreme phenotypic design was conducted to identify rare methylation modifications that might contribute to DR pathogenesis. A 2-year longitudinal nested case-control study was conducted to validate the results and assess whether these novel methylation modifications could be used as biomarkers for predicting DR onset. A large number of differentially methylated CpG sites were identified in the cross-sectional study, and two (cg12869254 and cg04026387) corresponding to known genes were replicated in the longitudinal study. Higher methylation of cg12869254 significantly correlated with macular RNFL thinning in the superior and nasal subregions, and that of cg04026387 correlated with reduced deep capillary plexus VD in the superior and inferior subregions after adjusting for covariates. CONCLUSIONS: Cg12869254 and cg04026387 hypermethylation may complement the known risk factors that contribute to the pathogenesis of DR and as novel biomarkers for disease prediction.

Axial Length and Choriocapillaris Flow Deficits in Non-pathological High Myopia.

PURPOSE: To examine the relationship between axial length (AL) and choriocapillaris (CC) flow deficits percentage (FD%) in non-pathological highly myopic eyes. DESIGN: Prospective cross-sectional study. METHODS: This study included Chinese patients with non-pathological high myopia, which was defined by an AL of > 26 mm and a META-PM classification grade of <2. Swept-source optical coherence tomography angiography was used to obtain 6 × 6 mm images of the macular CC. The CC FD% was measured in the fovea, parafovea, and perifovea subfields. RESULTS: A total of 1017 individuals (1017 eyes) with a mean age of 35.95 ± 14.11 years were included. After adjusting for age, sex, intraocular pressure, body mass index, systolic blood pressure, and image quality score, the overall CC FD% increased by 0.27% (95% CI 0.02, 0.52; P = .034) for each mm increase in AL. Among subfields, longer AL was associated with a higher CC FD% in the perifovea (ß = 0.53, 95% CI 0.30, 0.77; P < .001), and was not associated with a higher CC FD% in the parafovea (ß = 0.08, 95% CI -0.26, 0.42; P = .652) and fovea (ß = 0.001, 95% CI -0.50, 0.50; P = .999). CONCLUSIONS: The CC FD% increased with a longer AL in high myopia in the perifovea region but not in the fovea and parafovea fields. These findings may be of interest in elucidating the etiology of myopic axial elongation.

Ocular Factors of Fractal Dimension and Blood Vessel Tortuosity Derived From OCTA in a Healthy Chinese Population.

Purpose: To identify the ocular factors of microvascular fractal dimension (FD) and blood vessel tortuosity (BVT) of macula measured with optical coherence tomography angiography (OCTA) in a healthy Chinese population. Methods: Healthy subjects without ocular disorders were recruited at Zhongshan Ophthalmic Center. The FD and BVT in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at the macula were obtained from OCTA images. The FD was calculated using the box-counting method, and the BVT was defined as the ratio of the actual distance between two points to the straight distance on the skeletonized image. Univariate and stepwise multivariate linear regression analyses were performed to identify the ocular factors of FD and BVT, and the results are presented as coefficients and 95% confidence intervals (CIs). Only the right eye of each subject was included. Results: A total of 2189 healthy individuals (2189 eyes) were included with a mean age of 49.9 ± 13.2 years; 54.4% were female. In the multivariate model, the FD in the SCP was significantly associated with higher intraocular pressure (IOP) (ß = 0.204; 95% CI, 0.073-0.335; P < 0.001), axial length (AL) (ß = -0.875; 95% CI, -1.197 to -0.552; P < 0.001; R2 = 0.26; root mean square error [RMSE] = 7.78). The FD in the DCP was significantly associated with best-corrected visual acuity (ß = -6.170; 95% CI, -10.175 to -2.166; P = 0.003) and anterior chamber depth (ß = -0.348; 95% CI, -0.673 to -0.023; P = 0.036; R2 = 0.10; RMSE = 2.58). Superficial BVT was independently associated with IOP (ß = -0.044; 95% CI, -0.079 to -0.009; P = 0.012) and AL (ß = 0.097; 95% CI, 0.014-0.181; P = 0.022; R2 = 0.15; RMSE = 2.02). Deep BVT was independently associated with IOP (ß = -0.004; 95% CI, -0.009 to -0.0005; P = 0.028) and lens thickness (ß = 0.036, 95% CI, 0.003-0.060; P = 0.028; R2 = 0.07, RMSE = 0.25). Conclusions: The IOP and AL were dependent ocular parameters variables of FD and BVT in the SCP in this healthy population. The FD in the DCP was also influenced by visual acuity and anterior chamber depth. These factors should be considered when microvascular geometrics are used in the future studies. Translational Relevance: This work discovered the influence factors of OCTA geometrics parameters for further establishment of diagnostic model or method for glaucoma and other microvasculature-related ocular diseases.

Comparison of Non-contact Tonometry and Goldmann Applanation Tonometry Measurements in Non-pathologic High Myopia.

Purpose: To compare intraocular pressure (IOP) values obtained using Goldmann applanation tonometry (IOPGAT) and non-contact tonometry (IOPNCT) in a non-pathologic high myopia population. Methods: A total of 720 eyes from 720 Chinese adults with non-pathologic high myopia were enrolled in this cross-sectional study. Demographic and ocular characteristics, including axial length, refractive error, central corneal thickness (CCT), and corneal curvature (CC) were recorded. Each patient was successively treated with IOPNCT and IOPGAT. Univariate and multivariable linear regression analyses were conducted to detect factors associated with IOPNCT and IOPGAT, as well as the measurement difference between the two devices (IOPNCT-GAT). Results: In this non-pathologic high myopia population, the mean IOPNCT and IOPGAT values were 17.60 ± 2.76 mmHg and 13.85 ± 2.43 mmHg, respectively. The IOP measurements of the two devices were significantly correlated (r = 0.681, P < 0.001), however, IOPNCT overestimated IOPGAT with a mean difference of 3.75 mmHg (95% confidence interval: 3.60-3.91 mmHg). In multivariate regression, IOPNCT was significantly associated with body mass index (standardized ß = 0.075, p = 0.033), systolic blood pressure (SBP) (standardized ß = 0.170, p < 0.001), and CCT (standardized ß = 0.526, p < 0.001). As for IOPGAT, only SBP (standardized ß = 0.162, p < 0.001), CCT (standardized ß = 0.259, p < 0.001), and CC (standardized ß = 0.156, p < 0.001) were significantly correlated. The mean IOPNCT-GAT difference increased with younger age (standardized ß = -0.134, p < 0.001), higher body mass index (standardized ß = 0.091, p = 0.009), higher SBP (standardized ß = 0.074, p = 0.027), thicker CCT (standardized ß = 0.506, p < 0.001), and lower IOPGAT (standardized ß = -0.409, p < 0.001). Conclusion: In the non-pathologic high myopia population, IOPNCT overestimated IOPGAT at 3.75 ± 2.10 mmHg. This study suggests that the difference between the values obtained by the two devices, and their respective influencing factors, should be considered in the clinical evaluation and management of highly myopic populations.

Assessment of Artifacts in Swept-Source Optical Coherence Tomography Angiography for Glaucomatous and Normal Eyes.

Purpose: To evaluate the frequency of and identify the factors that influence the artifacts of swept-source optical coherence tomography angiography (SS-OCTA) in glaucomatous and normal eyes. Methods: Artifacts of OCTA images of open-angle glaucoma (OAG) and normal subjects were analyzed using SS-OCTA. Univariate and multivariate logistic regression analyses were performed to evaluate the association of age, sex, best-corrected visual acuity, axial length (AL), intraocular pressure, presence and severity of OAG, and image quality score (IQS) with the presence of artifacts. Results: Images from 4426 subjects were included in the study. At least one type of artifact was present in 24.54% of the images. The most common artifacts were occurrence of motion (705 eyes, 15.93%), followed by defocus (628 eyes, 14.19%), decentration (134 eyes, 3.03%), masking (62 eyes,1.40%), and segmentation errors (23 eyes, 0.52%). Multivariate logistic analyses showed that the presence of OAG (odds ratio [OR] = 2.71; 95% confidence interval [CI], 2.09-3.51; P < 0.001), female sex (OR = 1.34; 95% CI, 1.12-1.61; P = 0.001), longer AL (OR = 1.09; 95% CI, 1.02-1.17; P = 0.017), and IQS < 40 (OR = 3.75; 95% CI, 3.15-4.48; P < 0.001) were significantly associated with higher odds for the presence of any artifact. The IQS had poor performance for detecting artifacts, with an area under the curve of 0.723, sensitivity of 73.04%, and specificity of 62.53%. Conclusions: OAG eyes had more SS-OCTA image artifacts than normal eyes. IQS is an imperfect tool for identifying artifacts. Translational Relevance: Special attention should be paid to the effect of artifacts when using SS-OCTA in the clinical setting to assess vascular parameters in patients with glaucoma.

Digital Gonioscopy Based on Three-dimensional Anterior-Segment OCT: An International Multicenter Study.

PURPOSE: To develop and evaluate the performance of a 3-dimensional (3D) deep-learning-based automated digital gonioscopy system (DGS) in detecting 2 major characteristics in eyes with suspected primary angle-closure glaucoma (PACG): (1) narrow iridocorneal angles (static gonioscopy, Task I) and (2) peripheral anterior synechiae (PAS) (dynamic gonioscopy, Task II) on OCT scans. DESIGN: International, cross-sectional, multicenter study. PARTICIPANTS: A total of 1.112 million images of 8694 volume scans (2294 patients) from 3 centers were included in this study (Task I, training/internal validation/external testing: 4515, 1101, and 2222 volume scans, respectively; Task II, training/internal validation/external testing: 378, 376, and 102 volume scans, respectively). METHODS: For Task I, a narrow angle was defined as an eye in which the posterior pigmented trabecular meshwork was not visible in more than 180° without indentation in the primary position captured in the dark room from the scans. For Task II, PAS was defined as the adhesion of the iris to the trabecular meshwork. The diagnostic performance of the 3D DGS was evaluated in both tasks with gonioscopic records as reference. MAIN OUTCOME MEASURES: The area under the curve (AUC), sensitivity, and specificity of the 3D DGS were calculated. RESULTS: In Task I, 29.4% of patients had a narrow angle. The AUC, sensitivity, and specificity of 3D DGS on the external testing datasets were 0.943 (0.933-0.953), 0.867 (0.838-0.895), and 0.878 (0.859-0.896), respectively. For Task II, 13.8% of patients had PAS. The AUC, sensitivity, and specificity of 3D DGS were 0.902 (0.818-0.985), 0.900 (0.714-1.000), and 0.890 (0.841-0.938), respectively, on the external testing set at quadrant level following normal clinical practice; and 0.885 (0.836-0.933), 0.912 (0.816-1.000), and 0.700 (0.660-0.741), respectively, on the external testing set at clock-hour level. CONCLUSIONS: The 3D DGS is effective in detecting eyes with suspected PACG. It has the potential to be used widely in the primary eye care community for screening of subjects at high risk of developing PACG.

Multimodal Machine Learning Using Visual Fields and Peripapillary Circular OCT Scans in Detection of Glaucomatous Optic Neuropathy.

PURPOSE: To develop and validate a multimodal artificial intelligence algorithm, FusionNet, using the pattern deviation probability plots from visual field (VF) reports and circular peripapillary OCT scans to detect glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. SUBJECTS: Two thousand four hundred sixty-three pairs of VF and OCT images from 1083 patients. METHODS: FusionNet based on bimodal input of VF and OCT paired data was developed to detect GON. Visual field data were collected using the Humphrey Field Analyzer (HFA). OCT images were collected from 3 types of devices (DRI-OCT, Cirrus OCT, and Spectralis). Two thousand four hundred sixty-three pairs of VF and OCT images were divided into 4 datasets: 1567 for training (HFA and DRI-OCT), 441 for primary validation (HFA and DRI-OCT), 255 for the internal test (HFA and Cirrus OCT), and 200 for the external test set (HFA and Spectralis). GON was defined as retinal nerve fiber layer thinning with corresponding VF defects. MAIN OUTCOME MEASURES: Diagnostic performance of FusionNet compared with that of VFNet (with VF data as input) and OCTNet (with OCT data as input). RESULTS: FusionNet achieved an area under the receiver operating characteristic curve (AUC) of 0.950 (0.931-0.968) and outperformed VFNet (AUC, 0.868 [95% confidence interval (CI), 0.834-0.902]), OCTNet (AUC, 0.809 [95% CI, 0.768-0.850]), and 2 glaucoma specialists (glaucoma specialist 1: AUC, 0.882 [95% CI, 0.847-0.917]; glaucoma specialist 2: AUC, 0.883 [95% CI, 0.849-0.918]) in the primary validation set. In the internal and external test sets, the performances of FusionNet were also superior to VFNet and OCTNet (FusionNet vs VFNet vs OCTNet: internal test set 0.917 vs 0.854 vs 0.811; external test set 0.873 vs 0.772 vs 0.785). No significant difference was found between the 2 glaucoma specialists and FusionNet in the internal and external test sets, except for glaucoma specialist 2 (AUC, 0.858 [95% CI, 0.805-0.912]) in the internal test set. CONCLUSIONS: FusionNet, developed using paired VF and OCT data, demonstrated superior performance to both VFNet and OCTNet in detecting GON, suggesting that multimodal machine learning models are valuable in detecting GON.

Association of foveal avascular zone area withstructural and functional progression in glaucoma patients.

BACKGROUND: To investigate whether quantitative optical coherence tomography angiography (OCTA) metrics of the superficial/deep macular retina and optic disc are associated with glaucoma progression risk. METHODS: A total of 238 eyes from 119 patients with open angle glaucoma or ocular hypertension, and no history of systemic hypertension or diabetes mellitus were included. All participants underwent OCTA imaging with a swept-source OCT (DRI-OCT 1, Topcon, Japan). OCTA metrics of superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the macular region, and radial peripapillary capillary network of the optic disc were measured by a customised MATLAB program to obtain foveal avascular zone (FAZ) area, FAZ circularity and capillary density of SCP/DCP, and capillary density of the peripapillary region. Relationships between baseline OCTA metrics, visual field (VF) metrics, intraocular pressure fluctuation and risk of glaucoma progression were analysed with the Cox proportional hazards model. A frailty model was used to adjust for intereye correlation. RESULTS: During a mean follow-up duration of 29.39 months (range 12-56 months), 50, 48 and 16 eyes were determined to have retinal nerve fibre layer (RNFL), ganglion cell-inner plexiform layer (GC-IPL) and VF progression respectively. FAZ area per SD increase at baseline were significantly associated with both RNFL thinning (HR 1.73 95% CI 1.04 to 2.90); p=0.036) and GC-IPL thinning (HR 2.62, 95% CI 1.59 to 4.31; p<0.001), after adjusting for age, axial length and other potential confounding factors. VF progression was associated with age (HR 1.05, 95% CI 1.02 to 1.08; p<0.001) and mean deviation value (HR 0.91, 95% CI 0.84 to 0.98; p=0.010), but not with any OCTA metrics. CONCLUSION: Enlarged FAZ area measured by OCTA was associated with a higher risk of RNFL and GC-IPL thinning associated with glaucoma, but not with functional deterioration in glaucoma.

Choriocapillaris Flow Deficits in Normal Chinese Imaged by Swept-Source Optical Coherence Tomographic Angiography.

PURPOSE: To evaluate the ocular and systemic determinants of the choriocapillaris flow deficits percentage (CC FD%) in normal eyes. DESIGN: Observational cross-sectional study. METHODS: Healthy Chinese participants without ocular or systemic diseases underwent detailed ophthalmic evaluations, including swept-source optical coherence tomography angiography (SS-OCTA) with 6- × 6-mm macular choriocapillaris images. The CC FD% was assessed in circular regions with diameters of 1.0 and 5.0 mm, rings with 1.0- to 2.5-mm diameters, and rings with 2.5- to 5.0-mm diameters. RESULTS: The study included 830 individuals (mean ± SD age 58.66 ± 8.75 years). CC FD% (mean ± SD 22.05% ± 1.13%) was the lowest in the 2.5- to 5.0-mm ring, followed by the 1.0- to 2.5-mm ring, and highest in the 1.0-mm circle. In multivariable analysis, a higher CC FD% was associated with older age (ß = 0.16 [95% confidence interval {CI}] 0.08-0.24, P < .001), higher intraocular pressure (ß = 0.34 [95% CI 0.25-0.42], P < .001), higher serum concentrations of high-density lipoprotein cholesterol (ß = 0.24 [95% CI 0.17-0.32], P < .001), and lower image quality score (ß = -0.22 [95% CI -0.30 to -0.14], P < .001). CC FD% was also independent of axial length. CONCLUSIONS: In healthy adult Chinese individuals, a higher CC FD% was associated with older age, higher intraocular pressure, and higher high-density lipoprotein cholesterol serum concentration. These factors may influence clinical assessments of the choriocapillaris. The lack of an association between CC FD% and axial length is consistent with similar findings for Bruch membrane thickness, macular retinal thickness, and macular retinal pigment epithelium cell density.

Longitudinal Macular Retinal and Choroidal Microvasculature Changes in High Myopia.

Purpose: The purpose of this study was to determine the longitudinal changes in macular retinal and choroidal microvasculature in normal healthy and highly myopic eyes. Methods: Seventy-one eyes, including 32 eyes with high myopia and 39 healthy control eyes, followed for at least 12 months and examined using optical coherence tomography angiography imaging in at least 3 visits, were included in this study. Fovea-centered 6 × 6 mm scans were performed to measure capillary density (CD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC). The rates of CD changes in both groups were estimated using a linear mixed model. Results: Over a mean 14-month follow-up period, highly myopic eyes exhibited a faster rate of whole image CD (wiCD) loss (-1.44%/year vs. -0.11%/year, P = 0.001) and CD loss in the outer ring of the DCP (-1.67%/year vs. -0.14%/year, P < 0.001) than healthy eyes. In multivariate regression analysis, baseline axial length (AL) was negatively correlated with the rate of wiCD loss (estimate = -0.27, 95% confidence interval [CI] = -0.48 to -0.06, P = 0.012) and CD loss in the outer ring (estimate = -0.33, 95% CI = -0.56 to -0.11, P = 0.005), of the DCP. The CD reduction rates in the SCP and CC were comparable in both groups (all P values > 0.05). Conclusions: The rate of CD loss in the DCP is significantly faster in highly myopic eyes than in healthy eyes and is related to baseline AL. The CD in the outer ring reduces faster in eyes with longer baseline AL.