Associations of quantitative contrast sensitivity with vascular metrics on widefield swept-source OCT angiography across stages of diabetic retinopathy.

PURPOSE: To investigate structure-function associations between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics across stages of non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR), without diabetic macular oedema. METHODS: Prospective cross-sectional study in 140 eyes of 99 patients: 33 mild NPDR, 24 moderate/severe NPDR, 15 PDR, 33 diabetic without DR (DMnoDR) and 46 control eyes. Mixed-effects multivariable regression models to evaluate associations between quantitative contrast sensitivity function (Adaptive Sensory Technology) and vessel density (VD) and vessel skeletonised density (VSD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) on same-day imaging with WF SS-OCTA (Plex Elite 9000, Carl Zeiss Meditec). RESULTS: Standardised ß coefficients for area under the logarithm of contrast sensitivity function curve (AULCSF) versus visual acuity (VA) at 3×3 mm scans: SCP VSD (ß=0.32, p<0.001 vs -0.18, p=0.044), DCP VSD (ß=0.30, p<0.001 vs -0.21, p=0.02), SCP VD (ß=0.25, p=0.004 vs -0.13, p=0.129), DCP VD (ß=0.26, p=0.003 vs -0.19, p=0.034). AULCSF was significantly reduced in mild NPDR (ß=-0.28, p<0.001) and DMnoDR (ß=-0.19, p=0.005) versus controls, while VA was not significantly different. AULCSF performed better than VA in differentiating between controls and DMnoDR (0.69 vs 0.50), controls and mild NPDR (0.76 vs 0.61) and controls and moderate/severe NPDR (0.89 vs 0.73). CONCLUSIONS: DR-induced microvascular changes on OCTA are associated with larger changes on CS than in VA. CS is affected earlier than VA in the course of DR and performed better in discriminating between controls, DMnoDR and across DR stages.

Assessment of Microvascular Changes After Rhegmatogenous Retinal Detachment Repair Using Wide-Field Swept-Source Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: Our objective was to evaluate retinal microvascular changes and visual outcomes following rhegmatogenous retinal detachment (RRD) repair using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA). PATIENTS AND METHODS: The study included 116 eyes of 111 patients with macula-off (n = 68) or macula-on (n = 48) RRD treated with a single successful procedure, 79 fellow eyes, and 183 eyes of control patients imaged with WF SS-OCTA (3 ×3, 6 ×6, and 12 ×12 mm images). Mixed-effects multiple linear regression models were used for statistical analysis. RESULTS: Vessel density (VD) and vessel skeletonized density (VSD) of the superficial capillary plexus (3 ×3 mm scans) and full-thickness retina (12 ×12 mm) were significantly reduced in RRD eyes compared to fellow and control eyes. Decreased VSD and VD in all layers (3 ×3 mm and 6 ×6 mm) were significantly associated with greater preoperative extent of retinal detachment (P < 0.05) and poorer postoperative best-corrected visual acuity (BCVA) in RRD eyes (P < 0.05). Macula-off status was associated with increased foveal avascular zone irregularity (12 ×12 mm, P = 0.02). CONCLUSIONS: Decreased VD on WF SS-OCTA is associated with poorer postoperative BCVA following RRD repair. [Ophthalmic Surg Lasers Imaging Retina 2024;55:310-317.].

Widefield swept-source optical coherence tomography angiography metrics associated with neovascular glaucoma in patients with proliferative diabetic retinopathy.

PURPOSE: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth's bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. RESULTS: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth's bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95% confidence interval [CI]:5.3-30.7, P<0.001) and BCVA (OR=5.8, 95%CI:1.2-28.8, P<0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. CONCLUSIONS: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG.

Plasma Metabolites Associated with OCT Features of Age-Related Macular Degeneration.

Purpose: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD. Design: Prospectively designed, cross-sectional study. Participants: Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal. Methods: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons. Main Outcome Measures: Plasma metabolite levels associated with OCT features. Results: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed. Conclusions: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Characterizing Macular Neovascularization in Myopic Macular Degeneration and Age-Related Macular Degeneration Using Swept Source OCTA.

Purpose: Visual prognosis and treatment burden for macular neovascularization (MNV) can differ between myopic macular degeneration (MMD) and age-related macular degeneration (AMD). We describe and compare MNV associated with MMD and AMD using swept-source (SS)-OCTA. Patients and Methods: Adult patients with documented MNV associated with MMD or AMD were consecutively recruited. Qualitative and quantitative features were assessed from 6x6mm angiograms, including the MNV area and vessel density (VD). Descriptive statistics and linear regression analyses were carried out. Results: Out of 75 enrolled eyes with diagnosed MNV (30 MMD-MNV and 45 AMD-MNV; mean age 55±19 and 75±8 years, respectively), 44 eyes had discernible MNV (11 MMD-MNV and 33 AMD-MNV) on SS-OCTA at the time of the study and were included in the analysis. The MMD-MNV group exhibited a three-fold smaller sized MNV (p=0.001), lower greatest linear dimension (p=0.009) and greatest vascular caliber (p<0.001) compared to AMD-MNVs, and had a higher prevalence of tree-in-bud pattern. Eyes with AMD showed a higher prevalence of type 1 MNVs with medusa pattern. There was no difference in the location of the MNV, shape's regularity, margins, presence of core vessel, capillary fringe, peripheral loops, or perilesional dark halo (p>0.05) between both conditions. After adjustment, decreased MNV area and increased VD were associated with the tree-in-bud pattern, whereas the diagnosis did not significantly influence those parameters. Conclusion: While larger studies are warranted, this study is the first to describe and compare MMD-MNV and AMD-MNV using SS-OCTA, providing relevant clinical insight on MNV secondary to MMD and AMD. These findings also further validate OCTA as a powerful tool to detect and characterize MNV non-invasively.

Quantitative Wide-Field Swept-Source Optical Coherence Tomography Angiography and Visual Outcomes in RAO.

Purpose: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcomes and is associated with an increased risk of stroke and cardiovascular events. Wide-field swept-source OCT-A (WF SS-OCTA) can provide quick and non-invasive angiographic information with a wide field of view. Here, we looked for associations between OCT-A vascular imaging metrics and vision in RAO patients. Methods: Patients with diagnoses of central (CRAO) or branched retinal artery occlusion (BRAO) were included. 6mm × 6mm Angio and 15mm × 15mm AngioPlex Montage OCT-A images were obtained for both eyes in each patient using Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm × 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Non-perfusion area (NPA) was manually measured using 15mm × 15mm images. A linear regression model was utilized to identify correlation between imaging metrics and vision. P-values less than 0.05 were considered as statistically significant. Results: Twenty-five subjects were included. For RAO eyes, there was a statistically significant inverse correlation between retinal thickness as well as superficial capillary plexus (SCP) vessel density (VD) and vision. An inverse correlation was found between deep capillary plexus (DCP) VD and vision without statistical significance. There was a positive correlation between choroidal thickness as well as choroidal volume and vision without statistical significance. No significant correlation was found between the metrics and vision in contralateral eyes. For NPA and vision, no significant correlation was identified. Conclusion: This is the first study to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between retinal vascular imaging metrics and visual outcomes. The results of this study provide a basis to understand the structural changes involved in vision in RAO and may guide management of RAO and prevention of cerebral stroke and cardiovascular accidents.

Structure-function associations between contrast sensitivity and widefield swept-source optical coherence tomography angiography in diabetic macular edema.

PURPOSE: To evaluate the relationship between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics in diabetic macular edema (DME) was the purpose. METHODS: This prospectively enrolled cross-sectional observational study included 61 eyes of 48 patients that were tested with the quantitative CS function (qCSF) test on the same day as imaging with WF SS-OCTA (PLEX® Elite 9000, Carl Zeiss Meditec) 3 × 3, 6 × 6, and 12 × 12 mm scans. Outcomes included visual acuity (VA) and multiple qCSF metrics. Vascular metrics included vessel density (VD) and vessel skeletonized density (VSD) in the superficial (SCP) and deep capillary plexus (DCP) and whole retina (WR) and foveal avascular zone (FAZ) parameters. Mixed effects multivariable linear regression models controlling for age, lens status, and diabetic retinopathy stage were performed. Standardized beta coefficients were calculated by refitting the standardized data. RESULTS: SS-OCTA metrics had a significant association with CS and VA. The effect size of OCTA metrics was larger on CS compared to VA. For example, the standardized beta coefficients for VSD and CS at 3 cpd (ßSCP = 0.76, ßDCP = 0.71, ßWR = 0.72, p < 0.001) were larger than those for VA (ßSCP = - 0.55, p < 0.001; ßDCP = - 0.43, p = 0.004; ßWR = - 0.50, p < 0.001). On 6 × 6 mm images, AULCSF, CS at 3 cpd, and CS at 6 cpd were significantly associated with VD and VSD in all three slab types (SCP, DCP, and WR), while VA was not. CONCLUSION: Structure-function associations in patients with DME leveraging the qCSF device suggest microvascular changes on WF SS-OCTA are associated with larger changes in contrast sensitivity than VA.

Association Between Contrast Sensitivity and Central Subfield Thickness in Center-Involving Diabetic Macular Edema.

Purpose: To evaluate the association between contrast sensitivity (CS) and central subfield thickness (CST) in diabetic macular edema (DME). Methods: This prospectively recruited, cross-sectional study included eyes with DME evaluated from November 2018 to March 2021. CST was measured using spectral-domain optical coherence tomography on the same day as CS testing. Only eyes with center-involving DME (CST >305 µm for women; >320 µm for men) were included. CS was evaluated using the quantitative CS function (qCSF) test. Outcomes included visual acuity (VA) and the following qCSF metrics: area under the log CS function, contrast acuity (CA), and CS thresholds at 1 to 18 cycles per degree (cpd). Pearson correlation and mixed-effects regression analyses were performed. Results: The cohort included 52 eyes of 43 patients. Pearson correlation analysis showed a stronger association between CST and CS thresholds at 6 cpd (r = -0.422, P = 0.002) than CST and VA (r = 0.293, P = 0.035). Mixed-effects univariate and multivariate regression analyses showed significant associations between CST and CA (ß = -0.001, P = .030), CS at 6 cpd (ß = -0.002, P = .008), and CS at 12 cpd (ß = -0.001, P = .049) but no significant associations between CST and VA. Among the visual function metrics, the effect size of CST was largest on CS at 6 cpd (ßStandardized = -0.37, P = .008). Conclusions: In patients with DME, CS may be more strongly associated with CST than VA. Including CS as an adjunct visual function outcome measure in eyes with DME may prove clinically valuable.

Prevalence of venous loops and association with retinal ischemia in diabetic retinopathy using widefield swept-source OCT angiography.

PURPOSE: To investigate the prevalence and clinical characteristics of diabetic patients with retinal venous loops (RVLs) and to assess the association with retinal ischemia using widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: In this retrospective, cross-sectional study, a total of 195 eyes of 132 diabetic patients (31 eyes with no diabetic retinopathy (DR), 76 eyes with nonproliferative DR (NPDR), and 88 eyes with proliferative DR (PDR)) were imaged with WF SS-OCTA using Angio 6 × 6 mm and Montage 15 × 15 mm scans. Quantitative ischemia-related parameters, including ischemia index (ratio of nonperfusion area to total retinal area), foveal avascular zone (FAZ), and neovascularization features, were evaluated. RVLs were classified as type I or type II according to the branching level of the feeder vessel. A multivariate generalized estimating equations (GEE) logistic regression model was used to analyze the association of systemic parameters and ischemia-related metrics with RVLs in PDR eyes. RESULTS: Forty-eight RVLs were identified in 22 eyes (11.28%). The prevalence of RVLs was higher in PDR compared to NPDR eyes (21.59% vs. 3.95%, P < 0.05). Type II RVLs accounted for a higher proportion than type I (89.58% vs. 10.42%, P < 0.001). RVLs were more likely to originate from superior (vs. inferior) and temporal (vs. nasal) veins (P < 0.05). The GEE model showed that neovascularization (NV) flow area and diastolic blood pressure were associated with RVLs in the PDR group (P < 0.05). CONCLUSION: WF SS-OCTA is useful for the identification of RVLs in patients with DR. NV flow area and diastolic blood pressure were associated with the presence of RVLs in eyes with PDR. Ischemia index, FAZ, and other WF SS-OCTA parameters were not associated with RVLs. Further longitudinal studies are needed to identify the role of RVLs in DR progression.

Wide-field swept-source optical coherence tomography angiography in the assessment of retinal microvasculature and choroidal thickness in patients with myopia.

BACKGROUND/AIMS: Pathological myopia (PM) is a leading cause of blindness worldwide. We aimed to evaluate microvascular and chorioretinal changes in different stages of myopia with wide-field (WF) swept-source (SS) optical coherence tomography angiography (OCTA). METHODS: This prospective cross-sectional observational study included 186 eyes of 122 patients who had undergone imaging between November 2018 and October 2020. Vessel density (VD) and vessel skeletonised density (VSD) of superficial capillary plexus, deep capillary plexus and whole retina, as well as foveal avascular zone parameters, retinal thickness (RT) and choroidal thickness (CT), were calculated. RESULTS: This study evaluated 75 eyes of 48 patients with high myopia (HM), 43 eyes of 31 patients with mild to moderate myopia and 68 eyes of 53 age-matched controls. Controlling for age and the presence of systemic hypertension, we found that HM was associated with decrease in VD and VSD in all layers on 12×12 mm² scans. Furthermore, HM was associated with a VD and VSD decrease in every Early Treatment Diabetic Retinopathy Study grid, with a larger decrease temporally (ßVD=-0.39, ßVSD=-10.25, p<0.01). HM was associated with decreased RT and CT. Reduction in RT was outside the macular region, while reduction in CT was in the macular region. CONCLUSION: Using WF SS-OCTA, we identified reduction in microvasculature and structural changes associated with myopia. Decrease in VD and VSD was greater in the temporal quadrant, and reductions in RT and CT were uneven across the retina. Further work may help identify risk factors for the progression of PM and associated vision-threatening complications.

Structure-function association between contrast sensitivity and retinal thickness (total, regional, and individual retinal layer) in patients with idiopathic epiretinal membrane.

PURPOSE: To investigate structure-function associations between retinal thickness, visual acuity (VA), and contrast sensitivity (CS), using the quantitative contrast sensitivity function (qCSF) method in patients with idiopathic epiretinal membrane (ERM). METHODS: Retrospective, cross-sectional observational study. Patients with a diagnosis of idiopathic ERM were included. Patients underwent complete ophthalmic examination, spectral-domain optical coherence tomography imaging (SD-OCT) (SPECTRALIS® Heidelberg), and CS testing using the qCSF method. Outcomes included area under the log CSF (AULCSF), contrast acuity (CA), and CS thresholds at 1, 1.5, 3, 6, 12, and 18 cycles per degree (cpd). RESULTS: A total of 102 eyes of 79 patients were included. Comparing standardized regression coefficients, retinal thickness in most ETDRS sectors was associated with larger reductions in AULCSF, CA, and CS thresholds at 3 and 6 cpd than those in logMAR VA. These differences in effect on VA and CS metrics were more pronounced in the central subfield and inner ETDRS sectors. Among the retinal layers, increased INL thickness had the most detrimental effect on visual function, being significantly associated with reductions in logMAR VA, AULCSF, CA, and CS thresholds at 3 and 6 cpd (all p < .01), as well as at 1.5 and 12 cpd (p < .05). CONCLUSION: Retinal thickness seems to be associated with larger reductions in contrast sensitivity than VA in patients with ERM. Measured with the qCSF method, contrast sensitivity may serve as a valuable adjunct visual function metric for patients with ERM.

Visualization of retinal breaks on ultra-widefield fundus imaging using a digital green filter.

PURPOSE: We compare the ability of resident physicians to identify retinal breaks on ultra-widefield color fundus photos using the traditional image compared to an image with a green filter overlay. METHODS: Residents were shown fundus photos of 10 eyes with either a retinal tear or hole. Participants were shown each photo twice-once with traditional color settings and once with a green filter overlay. Participants were scored on whether the break was correctly identified and timed on how long it took to identify the pathology. RESULTS: Residents were able to correctly identify more retinal breaks on fundus photos with a green filter overlay compared to photos with traditional settings (P = 0.02). Residents were also able to identify breaks on fundus photos more quickly on images with a green filter overlay compared to the traditional images (P < 0.001). CONCLUSIONS: The application of a green filter overlay may help in identifying retinal breaks.

Characterising collateral vessels in eyes with branch retinal vein occlusions using widefield swept-source optical coherence tomography angiography.

BACKGROUND/AIMS: To characterise the morphology, location and functional significance of both macular and extramacular collateral vessels (CVs) in patients with a history of branch retinal vein occlusion (BRVO) using widefield swept-source optical coherence tomography angiography (WF SS OCTA). METHODS: Patients with a history of BRVO underwent WF SS OCTA testing to acquire 12×12 mm images, which were evaluated for CVs and non-perfusion area (NPA). Region of interest analysis of individual CVs was performed to identify correlations between CV size, depth and retinal location. Mixed effects multivariate regression analyses of factors associated with NPA and visual acuity (VA) were performed. RESULTS: Fifty-five CVs were identified in 28 BRVO eyes from 27 patients. CVs were identified in 42.9% (12/28) of eyes with a history of BRVO, and of these, 45.5% (25/55) were extramacular. The majority of CVs (87.3%, 48/55) coursed through both the superficial and the deep capillary plexus (DCP), while a subset (12.7%, 7/55) were strictly superficial. No CVs were found to course strictly through the DCP alone. CV depth increased with distance from the optic disc (p=0.011) and CV size increased with distance from the fovea (p=0.005). There were no statistically significant associations between CVs and NPA, or between CVs and VA. CONCLUSIONS: WF SS OCTA revealed that a large fraction of CVs that form after BRVO are extramacular, and the morphology of CVs varies as a function of retinal location. Depth-resolved study of CVs may offer valuable insights on the pathophysiological mechanisms leading to the development of macular oedema.

Active Learning to Characterize the Full Contrast Sensitivity Function in Cataracts.

Background: To characterize contrast sensitivity function (CSF) in cataractous and pseudophakic eyes compared to healthy control eyes using a novel quantitative CSF test with active learning algorithms. Methods: This is a prospective observational study at an academic medical center. CSF was measured in eyes with visually significant cataract, at least 2+ nuclear sclerosis (NS) and visual acuity (VA) ≥ 20/50, in pseudophakic eyes and in healthy controls with no more than 1+ NS and no visual complaints, using the Manifold Contrast Vision Meter. Outcomes included Area under the Log CSF (AULCSF) and CS thresholds at 1, 1.5, 3, 6, 12, and 18 cycles per degree (cpd). A subgroup analysis as performed on cataract eyes with VA ≥ 20/25. Results: A total of 167 eyes were included, 58 eyes in the cataract group, 77 controls, and 32 pseudophakic eyes with respective median AULCSF of 1.053 (0.352) vs 1.228 (0.318) vs 1.256 (0.360). In our multivariate regression model, cataract was associated with significantly reduced AULCSF (P= 0.04, ß= -0.11) and contrast threshold at 6 cpd (P= 0.01, ß= -0.16) compared to controls. Contrast threshold at 6 cpd was significantly reduced even in the subgroup of cataractous eyes with VA ≥ 20/25 (P=0.02, ß=-0.16). Conclusion: The novel qCSF test detected disproportionate significant contrast deficits at 6 cpd in cataract eyes; this remained significant even in the cataractous eyes with VA ≥ 20/25. CSF testing may enhance cataract evaluation and surgical decision-making, particularly in patients with subjective visual complaints despite good VA.

Sex-Specific Changes in Choroid Vasculature Among Patients with Schizophrenia and Bipolar Disorder.

Purpose: While structural changes within the retina of psychosis patients have been established, no detailed studies of choroidal microvasculature in these patients have been performed. Given evidence of microvascular disruption in psychosis patients, this study sought to determine whether there exists evidence of microvascular disruption in the choroids in these patients. Methods: Fifty-six subjects (20 controls and 36 psychosis patients) were recruited from April 2018 to February 2020. Five were excluded due to imaging artifact or missing demographic information. Swept-source optical coherence tomography angiography (SS-OCTA) images were obtained. Choroid vascular enface images (12 mm × 9mm) were exported every 2.6 µm from Bruch's membrane to the choroid-scleral interface from Topcon to ImageJ. The images were binarized using Otsu's method, signal from the optic disk and retinal vasculature was removed, and average choroid vascular density (CVD) was calculated as the average of percent area occupied by choroidal vasculature across images in the stack. Choroid vascular volume (CVV) was calculated as the CVD multiplied by maximum CT and image area. During image analysis, study staff were blinded to the phenotype of the study subjects. Results: Compared with same-sex controls, male psychiatric patients had significantly lower CVD. Compared with same-sex controls, female psychiatric patients had significantly lower maximum CT with correspondingly decreased CVV, after adjusting for age. When all psychiatric patients were compared with all healthy controls, no significant differences in CT, CVD, or CVV were noted. Conclusion: These results suggest that the pathogenesis of psychotic illness affects choroidal microvasculature in a sex-specific manner.

Nonperfusion Area and Other Vascular Metrics by Wider Field Swept-Source OCT Angiography as Biomarkers of Diabetic Retinopathy Severity.

Purpose: To study the wider field swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, especially non-perfusion area (NPA), in the diagnosing and staging of DR. Design: Cross-sectional observational study (November 2018-September 2020). Participants: 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients). Methods: We imaged using 6mm×6mm and 12mm×12mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operator characteristic analysis was used for statistical analyses. Main Outcome Measures: Quantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading. Results: Among patients with diabetes (median age 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had non-proliferative DR (NPDR); and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. NPA was the best parameter to diagnose DR (AUC:0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC:0.97) and differentiated between DR stages (AUC range:0.83-0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas an increased VD and VSD in SCP among moderate-severe NPDR group. Conclusions: Our work highlights the importance of NPA, which can be more readily and easily measured with WF SS-OCTA compared to fluorescein angiography. It is additionally quick and non-invasive, and hence can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6mm×6mm and 12mm×12mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.

Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography.

PURPOSE: To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA). METHODS: Patients with and without a diagnosis of HTN were included in this cross-sectional observational study. All eyes were imaged with SD-OCTA using 3 mm × 3 mm and 6 mm × 6 mm centered on both the fovea and optic disk. A second 6 mm × 6 mm scan was taken after a 30 s breath-hold. Vessel density (VD), vessel skeletonized density (VSD), and fractal dimension (FD) were calculated using customized MATLAB scripts. Vessel diameter index (VDI) was obtained by taking the ratio of VD to VSD. Vasoreactivity was measured by subtracting the VD or VSD before and after breath-hold (∆VD, ∆VSD). RESULTS: Twenty-three eyes with HTN (17 patients) and 17 control eyes (15 patients) were included. In the 6 mm × 6 mm angiogram centered on fovea, the superficial capillary plexus (SCP) VD (ß = - 0.029, p = 0.012), VSD (ß = - 0.004, p = 0.043) and the choriocapillaris VD (ß = - 0.021, p = 0.030) were significantly decreased in HTN compared to control eyes. Similarly, FD was decreased in both the SCP (ß = - 0.012, p = 0.013) and choriocapillaris (ß = - 0.009, p = 0.030). In the 3 mm × 3 mm angiogram centered on optic disk, SCP VDI (ß = - 0.364, p = 0.034) was decreased. ∆VD and ∆VSD were both reduced in the DCP (ß = - 0.034, p = 0.032; ß = - 0.013, p = 0.043) and ∆VSD was elevated in the choriocapillaris of HTN eyes (ß = 0.004, p = 0.032). CONCLUSIONS: The study used SD-OCTA to show significant differences in the retinal vasculature of hypertensive patients. It was also the first to demonstrate the potential of OCT-A to investigate retinal vascular reactivity in patients with HTN.

Remote Imaging Capture with Widefield Swept-Source OCT Angiography During the COVID-19 Pandemic.

Purpose: The COVID-19 pandemic has had a widespread impact on the health sector worldwide, both in the clinical and research subsector. This has necessitated for the invention of protocols compliant with social distancing policies to efficiently tackle the current needs. Our aim is to describe a novel remote imaging technique, which helped us continue our research with widefield swept-source optical coherence tomography angiography (WF SS-OCTA). Patients and Methods: As a part of this cross-sectional observational study from August 2020 to September 2020 at Massachusetts Eye and Ear (MEE), we used our institute approved remote desktop, outside of MEE, to gain full access to the on-site WF SS-OCTA device in the imaging room for the purpose of remote imaging. With only the patient being in the imaging room, effective communication was established via video conferencing on an encrypted tablet computer device for the entire procedure. Results: We imaged four patients with various retinal pathologies, aged 32-69 years. All images obtained were of high quality and signal strength (median score 9/10 for both) and all patients reported a highly satisfactory, comfortable, and safe experience amidst the COVID-19 pandemic. Conclusion: This novel method is better for remote imaging compared to the previously described techniques as it is time and cost effective, requires limited resources without compromising the image quality or patient satisfaction and adheres to the various guidelines for infection control, most importantly social distancing. As a paradigm shift, this can also be employed in future for setups with limited staff like busy emergency departments or a rural setup with limited access or difficult commute, in the "new-normal" era.

Plasma Metabolomic Profiles Associated with Three-Year Progression of Age-Related Macular Degeneration.

Plasma metabolomic profiles have been shown to be associated with age-related macular degeneration (AMD) and its severity stages. However, all studies performed to date have been cross-sectional and have not assessed progression of AMD. This prospective, longitudinal, pilot study analyzes, for the first time, the association between plasma metabolomic profiles and progression of AMD over a 3-year period. At baseline and 3 years later, subjects with AMD (n = 108 eyes) and controls (n = 45 eyes) were imaged with color fundus photos for AMD staging and tested for retinal function with dark adaptation (DA). Fasting plasma samples were also collected for metabolomic profiling. AMD progression was considered present if AMD stage at 3 years was more advanced than at baseline (n = 26 eyes, 17%). Results showed that, of the metabolites measured at baseline, eight were associated with 3-year AMD progression (p < 0.01) and 19 (p < 0.01) with changes in DA. Additionally, changes in the levels (i.e., between 3 years and baseline) of 6 and 17 metabolites demonstrated significant associations (p < 0.01) with AMD progression and DA, respectively. In conclusion, plasma metabolomic profiles are associated with clinical and functional progression of AMD at 3 years. These findings contribute to our understanding of mechanisms of AMD progression and the identification of potential therapeutics for this blinding disease.