Decreased Macular Choriocapillaris Perfusion Correlates with Contrast Sensitivity Function in Dry Age-related Macular Degeneration.

PURPOSE: To investigate the relationships between contrast sensitivity (CS), choriocapillaris perfusion and other structural optical coherence tomography (OCT) biomarkers in dry age-related macular degeneration (AMD). DESIGN: Cross-sectional, observational study. PARTICIPANTS: One hundred AMD eyes (22 early, 52 intermediate and 26 late) from 74 patients and 45 control eyes from 37 age-similar subjects. METHODS: All participants had visual acuity (VA) assessment, quantitative contrast sensitivity function (qCSF) testing, macular OCT, and 6x6-mm swept-source OCT angiography (OCTA) scans on the same day. OCT volumes were analyzed for subretinal drusenoid deposits and hyporeflective drusen cores, and to measure thickness of the outer nuclear layer (ONL). OCTA scans were utilized to calculate drusen volume, inner choroid flow deficit percentage (IC-FD%), and to measure the area of choroidal hypertransmission defects (HTD). IC-FD% was measured from a 16 µm-thick choriocapillaris slab after compensation and binarization with Phansalkar's method. Generalized linear mixed-effects models were used to evaluate the associations between functional and structural variables. MAIN OUTCOME MEASURES: To explore the associations between qCSF-measured CS, ICFD% and various AMD imaging biomarkers. RESULTS: AMD exhibited significantly reduced qCSF metrics eyes across all stages compared to controls. Univariate analysis revealed significant associations between various imaging biomarkers, reduced qCSF metrics and VA in both groups. Multivariate analysis confirmed that higher IC-FD% in the central 5 mm was significantly associated with decreases in all qCSF metrics in AMD eyes (ß= -0.74 to -0.25, all p<0.05), but not with VA (p>0.05). ONL thickness in the central 3 mm correlated with both VA (ß= 2.85, p<0.001) and several qCSF metrics (ß= 0.01-0.90, all p<0.05), especially in AMD eyes. Further, larger HTD areas were associated with decreased VA (ß=-0.89, p<0.001) and reduced CS at low-intermediate frequencies across AMD stages (ß= -0.30 to -0.29, p<0.001). CONCLUSIONS: The significant association between IC-FD% in the central 5 mm and qCSF-measured CS reinforces the hypothesis that decreased macular choriocapillaris perfusion contributes to visual function changes in AMD, which are more pronounced in CS than in VA.

Contrast Sensitivity Better Reflects Wide-Field Swept-Source Optical Coherence Tomography Angiography Vascular Metrics Among Healthy Eyes Compared to Visual Acuity.

BACKGROUND AND OBJECTIVE: To evaluate the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) and visual function in healthy eyes. PATIENTS AND METHODS: Fifty-seven eyes of 45 patients were evaluated with visual acuity (VA), contrast sensitivity (CS), and WF SS-OCTA (3 × 3, 6 × 6, and 12 × 12 mm images) on the same day. Mixed-effects multivariable regression analyses were performed. RESULTS: Contrast sensitivity metrics, including CS between 6 to 18 cycles per degree (cpd) and area under the logarithm CS function, were significantly associated with vessel density (VD) and vessel skeletonized density (VSD), whereas VA was not. The largest effect size was between CS at 18 cpd and VD (ß = 0.41, P = 0.007) and VSD (ß = 0.42, P = 0.006) on 12 × 12 mm images. CONCLUSIONS: Reduced VSD and VD on WF SSOCTA was significantly associated with decreased CS, whereas VA was not. These results suggest CS could serve as a screening tool for early stage retinal and neurologic disorders. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

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.

En Face Depth Resolved OCTA Monitoring of Macular Outer Retinal Deposits in a Case of Multifocal Choroiditis Mimicking Syphilitic Uveitis.

PURPOSE: Multifocal choroiditis (MFC) is a rare inflammatory condition characterized by retinal and choroidal lesions that may present similarly to ocular pathology of various etiologies. Here we present a case of MFC mimicking syphilitic uveitis with unique en face optical coherence tomography angiography (OCTA) imaging characteristics. METHODS: Case report. RESULTS: A 61-year-old woman presented with blurry vision, floaters and multiple whitish subretinal deposits on en face swept-source OCTA in the left eye. Fluorescent treponemal antibody test absorption was positive which led to the initial diagnosis of syphilitic uveitis and subsequent treatment with intravenous penicillin. During follow-up, OCTA of the left eye revealed the development of new choroidal neovascular membrane and new punched-out lesions in the posterior pole. The patient was eventually diagnosed with MFC and treated with aflibercept injections. CONCLUSIONS: Immune-mediated uveitis can simulate infectious and neoplastic uveitis. En face OCTA is unique imaging modality that allowed for the complete characterization and monitoring of the sub-macular deposits. This expands the clinical spectrum of multifocal choroiditis.

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 as Predictors of Anti-VEGF Treatment in Retinal Vein Occlusions.

BACKGROUND AND OBJECTIVE: Our objective was to assess baseline widefield swept-source optical coherence tomography angiography (WF SSOCTA) microvascular metrics as predictors for the number of anti-vascular endothelial growth factor (VEGF) injections and visual acuity (VA) at 12-months follow-up in patients with retinal vein occlusion (RVO). PATIENTS AND METHODS: This was a prospective study including 49 RVO eyes from 49 patients who had not received an anti-VEGF injection for at least 3 months prior to imaging. Microvascular metrics from 6×6-mm and 12×12-mm angiograms were assessed using linear regression models, adjusting for age. RESULTS: Reductions in the vessel density (VD) and vessel skeletonized density (VSD) vascular metrics were associated both with a higher number of anti-VEGF injections at all follow-up time points and reduced VA 12 months after imaging in all RVO eyes. CONCLUSIONS: WF SS-OCTA VD and VSD micro-vascular metrics at baseline can prognosticate VA and number of anti-VEGF injections required at 3, 6, and 12 months in RVO eyes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:xx-xx.].

Quantitative Contrast Sensitivity Function and the Effect of Aging in Healthy Adult Eyes: A Normative Database.

BACKGROUND AND OBJECTIVE: We sought to establish normative quantitative contrast sensitivity function (qCSF) values in healthy adult eyes and investigate the effect of age on qCSF. PATIENTS AND METHODS: Healthy eyes underwent qCSF testing (adaptive sensory technology) and Snellen's visual acuity (VA). Descriptive statistics and mixed-effects multivariable linear regressions were evaluated. RESULTS: A total of 334 eyes (290 patients) with median age 61 years (range 21 to 88) had qCSF values as follows: area under the log contrast sensitivity function curve: 1.18; contrast acuity: 1.32; contrast sensitivity (CS) at 1 cycle per degree (cpd): 1.32; CS at 1.5 cpd: 1.37; CS at 3 cpd: 1.38; CS at 6 cpd: 1.20; CS at 12 cpd: 0.69; CS at 18 cpd: 0.22. Linear reductions in qCSF values per decade of age ranged from -0.02 to -0.07 vs 0.01 for visual acuity (VA). Age had a greater effect on the majority of qCSF values than VA (beta standardized regression coefficient ranged from -0.309 to -0.141 for qCSF values vs 0.177 for VA). CONCLUSIONS: We herein establish a normative database for qCSF and quantify the effect of age on qCSF values, adding evidence towards the validation of qCSF as a clinical endpoint. [Ophthalmic Surg Lasers Imaging Retina 2024;55:212-219.].

Changes in wider field swept-source OCT angiography vascular metrics with anti-vascular endothelial growth factor therapy in central retinal vein occlusion.

PURPOSE: To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). METHODS: We included 23 eyes with macular edema associated with non-ischemic CRVO from 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. RESULTS: Median CST decreased significantly from 369 µm (305-531) to 267 µm (243-300, p < 0.001). VD and VSD parameters in 12 × 12 mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 × 12 mm images (p < 0.05). Notably, the reductions in VSD and VD on 12 × 12 mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). CONCLUSION: Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.

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.

Associations of quantitative contrast sensitivity with wide-field swept-source optical coherence tomography angiography in retinal vein occlusion.

PURPOSE: To investigate associations between contrast sensitivity (CS) and vascular metrics on wide-field swept-source optical coherence tomography angiography (WF-SS-OCTA) in patients with retinal vein occlusion (RVO). METHODS: This prospectively recruited, cross-sectional observational study included RVO patients who underwent quantitative CS function (qCSF) testing and WF-SS-OCTA using 3 × 3, 6 × 6, and 12 × 12 mm angiograms on the same day. The study measured several qCSF outcomes and WF-SS-OCTA vascular metrics, including vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ). The data were analyzed using multivariable regression analysis controlling for age and central subfield thickness (CST). RESULTS: A total of 43 RVO eyes of 43 patients and 30 fellow eyes were included. In RVO eyes, multiple vascular metrics were associated with CS outcomes but not visual acuity (VA). On 12 × 12 images, CS thresholds at 1 cpd, 1.5 cpd, and 3 cpd were significantly associated with VD and VSD, but VA was not. When comparing standardized regression coefficients, we found that vascular metrics had a larger effect size on CS than on VA. For instance, the standardized beta coefficient for FAZ area and CS at 6 cpd (ß* = - 0.46, p = 0.007) was larger than logMAR VA (ß* = 0.40, p = 0.011). CONCLUSION: Microvascular changes on WF-SS-OCTA in RVO had a larger effect size on CS than VA. This suggests CS may better reflect the microvascular changes of RVO compared to VA. qCSF-measured CS might be a valuable adjunct functional metric in evaluating RVO patients.

WIDEFIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN WAGNER SYNDROME.

PURPOSE: To describe novel clinical and angiographic findings in Wagner syndrome. METHODS: A retrospective case series of three related patients with Wagner syndrome. Patients underwent standard optical coherence tomography (OCT), B-scan ultrasonography, and fluorescein angiography in addition to wide field swept-source OCT angiography (WF SS-OCTA) (PLEX Elite 9000, Carl Zeiss Meditec Inc). Patients underwent genetic testing for a panel of hereditary vitreoretinopathies. RESULTS: Three related patients with Wagner syndrome were identified. All were found to have prominent vitreous strands, abnormal vitreoretinal adhesions, peripheral retinal holes, and varying degrees of myopia. A mid-peripheral tractional ridge was identified in all six eyes. All patients were positive for a known pathologic intron variant in the VCAN gene (4004-5T-A). Wide field swept-source OCT angiography (12 mm × 12 mm) was performed in two patients and demonstrated perivascular capillary loss in the superficial capillary plexus along the arcades bilaterally. One patient demonstrated associated retinal atrophy within the area of capillary loss. The capillary loss extended beyond the margin of retinal atrophy. CONCLUSION: The unusual finding of a mid-peripheral tractional ridge of the retina associated with myopia led to a genetic diagnosis of Wagner syndrome. Widefield swept-source OCT angiography demonstrated a novel feature of perivascular loss of the superficial retinal capillary plexus. This result suggests that vitreous traction may cause localized microvasculature dysfunction and subsequent retinal atrophy in Wagner syndrome. This is the first known evaluation of Wagner syndrome using OCT angiography.

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.

Comparative study of widefield swept-source optical coherence tomography angiography in eyes with concomitant age-related macular degeneration and diabetic retinopathy.

BACKGROUND/AIMS: We sought to evaluate widefield swept-source optical coherence tomography angiography (WF SS-OCTA) among eyes with concomitant age-related macular degeneration (AMD) and diabetes mellitus or diabetic retinopathy (DM/DR). METHODS: This cross-sectional, comparative study consisted of three study groups: eyes with (1) AMD and DM/DR, (2) AMD alone and (3) DM/DR alone. WF SS-OCTA (3×3, 6×6 and 12×12 mm) images were captured. Vascular metrics included foveal avascular zone (FAZ), vessel density (VD) and vessel skeletonised density (VSD). Mixed-effects multivariable regression models adjusted for age were performed by cohort and subgroup based on AMD and DR stages. RESULTS: Our cohort included 287 eyes from 186 patients with an average age of 64±14.0 years old. Results revealed significantly reduced vascular metrics in concomitant AMD and DM/DR eyes (N=68) compared with AMD-only eyes (N=71) on all angiograms but not compared with DM/DR-only eyes (N=148). For example, when compared with AMD-only eyes, AMD and DM/DR eyes had significantly reduced VD (ß=-0.03, p=0.016) and VSD (ß=-1.09, p=0.022) on 12×12 mm angiograms, increased FAZ perimeter (ß=0.51, p=0.025) and FAZ area (ß=0.11, p=0.015) on 6×6 mm angiogram, and reductions in all VD and VSD metrics on 3×3 and 6×6 mm angiograms. However, only 3×3 mm angiogram FAZ metrics were significantly different when comparing DM/DR eyes with concomitant AMD and DM/DR eyes. CONCLUSION: WF SS-OCTA revealed significant reductions in retinal microvasculature metrics in AMD and DM/DR eyes compared with AMD-only eyes but not compared with DM/DR-only eyes.

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.

Semi-automated algorithm using directional filter for the precise quantification of non-perfusion area on widefield swept-source optical coherence tomography angiograms.

Background: The clinical application of optical coherence tomography angiography (OCTA) has been well documented in literature with its promising potential in dye-less evaluation of various retinal vascular pathologies. Recent advances in OCTA help us gather wider field of view with 12 mm × 12 mm and montage compared to the standard dye-based scans, which has a higher accuracy and sensitivity in detection of peripheral pathologies. The aim of this study is to build a semi-automated algorithm to precisely quantify the non-perfusion areas (NPAs) on widefield swept-source optical coherence tomography angiography (WF SS-OCTA). Methods: All subjects underwent imaging on 100 kHz SS-OCTA device acquiring 12 mm × 12 mm angiograms centered on fovea and optic disc. After a comprehensive literature review, a novel algorithm using FIJI (ImageJ) was designed to calculate the NPAs (mm2) after excluding the threshold and segmentation artifact areas from the total field of view. Segmentation and threshold artifacts were first removed from enface structure images using the spatial variance and mean filter respectively. Vessel enhancement was achieved by using 'Subtract Background' followed by directional filter. The cut off for Huang's fuzzy black and white thresholding was defined from the pixel values based of the foveal avascular zone. Then, the NPAs were calculated using the 'Analyze Particles' command with a minimum size of ~0.15 mm2. Finally, the artifact area was subtracted from to give the corrected NPAs. Results: Our cohort had 44 eyes of 30 control patients and 107 eyes of 73 patients with diabetes mellitus (both median age 55 years, P=0.89). Of 107 eyes, 21 eyes had no evidence of diabetic retinopathy (DR), 50 eyes had non-proliferative DR and 36 eyes had proliferative DR. The median NPA was 0.20 (0.07-0.40) in controls, 0.28 (0.12-0.72) in no DR, 5.54 (3.12-9.10) in non-proliferative DR and 13.38 (8.73-26.32) in proliferative DR eyes. Using mixed effects-multiple linear regression analysis adjusting for age, there was significant progressive increase in NPA with increasing DR severity. Conclusions: This is one of the first study to use the directional filter for WFSS-OCTA image processing which is known to be superior to other Hessian based multiscale, linear, and non-linear filters especially for vascular analysis. Our method could greatly refine and streamline the calculation of signal void area proportion, while being much quicker and accurate than manual delineation of NPAs and subsequent estimation. This combined with the wide field of view can have a great prognostic and diagnostic clinical impact for future applications in DR and other ischemic retinal pathologies.

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.

Vitreous Humor Biomarkers Reflect Pathological Changes in the Brain for Alzheimer's Disease and Chronic Traumatic Encephalopathy.

BACKGROUND: Patients with eye disease have an increased risk for developing neurodegenerative disease. Neurodegenerative proteins can be measured in the eye; however, correlations between biomarker levels in eye fluid and neuropathological diagnoses have not been established. OBJECTIVE: This exploratory, retrospective study examined vitreous humor from 41 postmortem eyes and brain tissue with neuropathological diagnoses of Alzheimer's disease (AD, n = 7), chronic traumatic encephalopathy (CTE, n = 15), both AD + CTE (n = 10), and without significant neuropathology (controls, n = 9). METHODS: Protein biomarkers i.e., amyloid-ß (Aß40,42), total tau (tTau), phosphorylated tau (pTau181,231), neurofilament light chain (NfL), and eotaxin-1 were quantitatively measured by immunoassay. Non-parametric tests were used to compare vitreous biomarker levels between groups. Spearman's rank correlation tests were used to correlate biomarker levels in vitreous and cortical tissue. The level of significance was set to α= 0.10. RESULTS: In pairwise comparisons, tTau levels were significantly increased in AD and CTE groups versus controls (p = 0.08 for both) as well as AD versus AD+CTE group and CTE versus AD+CTE group (p = 0.049 for both). Vitreous NfL levels were significantly increased in low CTE (Stage I/II) versus no CTE (p = 0.096) and in low CTE versus high CTE stage (p = 0.03). Vitreous and cortical tissue levels of pTau 231 (p = 0.02, r = 0.38) and t-Tau (p = 0.04, r = -0.34) were significantly correlated. CONCLUSION: The postmortem vitreous humor biomarker levels significantly correlate with AD and CTE pathology in corresponding brains, while vitreous NfL was correlated with the CTE staging. This exploratory study indicates that biomarkers in the vitreous humor may serve as a proxy for neuropathological disease.

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.

A normative database of wide-field swept-source optical coherence tomography angiography quantitative metrics in a large cohort of healthy adults.

PURPOSE: Data from healthy eyes is needed to interpret optical coherence tomography angiography (OCTA) findings. However, very little normative data is available for wide-field swept-source OCTA (WF SS-OCTA), particularly 12 × 12-mm and disc-centered angiograms. Therefore, we aim to report quantitative metrics in a large sample of control eyes. METHODS: In this cross-sectional observational study, 482 eyes of 375 healthy adults were imaged on the 100 kHz Zeiss PLEX® Elite 9000 using protocols centered on the fovea (3 × 3, 6 × 6, and 12 × 12-mm) and optic disc (6 × 6 and 12 × 12-mm) between December 2018 and January 2022. The ARI Network (Zeiss Portal v5.4) was used to calculate vessel density (VD) and vessel skeletonized density (VSD) in the superficial capillary plexus, deep capillary plexus, and whole retina, as well as foveal avascular zone (FAZ) parameters. Mixed-effect multiple linear regression models were used for statistical analysis. RESULTS: The subjects' median age was 55 (38-63) years, and 201 (53.6%) were female. Greater age and worse best-corrected visual acuity (BCVA) were associated with significantly lower VD and VSD (p < 0.05). VD and VSD differed based on race and cataract status, but not sex, on some scan protocols (p < 0.05). FAZ circularity decreased with age, and FAZ dimensions differed based on race and ethnicity in certain scan protocols. CONCLUSIONS: We report a large database of parafoveal and peripapillary vascular metrics in several angiogram sizes. In referencing these values, researchers must consider characteristics such as age, race, and BCVA, but will have a valuable point of comparison for OCTA measurements in pathologic settings.