Longitudinal Assessment of Intraretinal Microvascular Abnormalities in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: To longitudinally investigate the changes in intraretinal microvascular abnormalities (IRMAs) over time, employing swept-source optical coherence tomography angiography in eyes with diabetic retinopathy. Methods: In this retrospective, longitudinal study, we evaluated 12 × 12-mm swept-source optical coherence tomography angiography centered on the macula at baseline and last available follow-up visit for (1) IRMA changes during follow-up, defined as (a) stable, (b) regressed, (c) obliterated, and (d) progressed; and the (2) development of new neovascularization (NV) and their origins. Competing-risk survival analysis was used to assess the factors associated with these changes. Results: In total, 195 eyes from 131 participants with diabetic retinopathy were included. Stable, regressed, obliterated, and progressed IRMA were observed in 65.1%, 12.8%, 11.3%, and 19% of eyes with diabetic retinopathy, respectively. Anti-VEGF injections during the follow-up periods and a slower increase of foveal avascular zone were associated with IRMA regression (P < 0.001 and P = 0.039). Obliterated IRMA were correlated with previous panretinal photocoagulation (P < 0.001) and a lower deep capillary plexus vessel density at baseline (P = 0.007), as well as with follow-up anti-VEGF injections (P = 0.025). A higher baseline ischemia index (ISI) and panretinal photocoagulation during the follow-up periods were associated with IRMA progression (P = 0.049 and P < 0.001). A faster increase in ISI predicted the development of NV elsewhere (NVE) from veins (P < 0.001). No significant factors were found to be associated with NVE originating from IRMA. Conclusions: Changes in IRMA closely correlated with the severity of retinal ischemia and treatment. Notably, our study confirmed the potential, yet relatively rare, development of NVE from IRMA in a large cohort; however, the risk factors associated with this transformation require further exploration.

Progressive Choriocapillaris Changes on Optical Coherence Tomography Angiography Correlate With Stage Progression in AMD.

Purpose: We investigated the association between inner choroid flow deficit percentage (IC-FD%) using swept-source optical coherence tomography angiography (SS-OCTA) and progression of AMD. Methods: Retrospective, observational study including 64 eyes (42 participants) with early or intermediate AMD at baseline. Participants had two or more consecutive swept-source optical coherence tomography angiography covering a period of at least 18 months. Demographics, visual acuity, and AMD staging based on Beckman classification were reviewed. OCT was analyzed for hyperreflective foci, subretinal drusenoid deposits, hyporeflective drusen cores, and subfoveal choroidal thickness. IC-FD% was measured within the central 3- and 6-mm using a 16-µm slab, after compensation and binarization (Phansalkar method). Mixed-effects Cox regression models assessed the association between imaging biomarkers and AMD progression. Results: During follow-up (37 ± 9 months), 4 eyes with early AMD (31%) progressed to intermediate AMD and 30 (59%) eyes with intermediate AMD developed late AMD (19 geographic atrophy; 11 wet AMD). Baseline hyporeflective drusen core was associated with geographic atrophy development (P < 0.01), whereas greater IC-FD% (3-mm) was associated with wet AMD (P = 0.03). Time-varying analysis showed that faster subfoveal choroidal thickness reduction and IC-FD% (6-mm) increase were associated with geographic atrophy onset (P < 0.05), whereas IC-FD% (3-mm) increase was associated with wet AMD (P = 0.03). Notably, greater IC-FD% increases in the 3 mm (area under the curve = 0.72) and 6 mm (area under the curve = 0.89) were better predictive of wet AMD and geographic atrophy development, respectively. Conclusions: Our longitudinal IC-FD% assessment emphasizes the role of progressive choriocapillaris changes as a biomarker for AMD progression. Our findings support that widespread choriocapillaris alterations (6 mm) may precede progression to geographic atrophy, whereas more central choriocapillaris loss (3 mm) may provide an ischemic stimulus for wet AMD.

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.].

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.

Workshop report - interdisciplinary metabolomic epidemiology: the pathway to clinical translation.

Metabolomic epidemiology studies are complex and require a broad array of domain expertise. Although many metabolite-phenotype associations have been identified; to date, few findings have been translated to the clinic. Bridging this gap requires understanding of both the underlying biology of these associations and their potential clinical implications, necessitating an interdisciplinary team approach. To address this need in metabolomic epidemiology, a workshop was held at Metabolomics 2023 in Niagara Falls, Ontario, Canada that highlighted the domain expertise needed to effectively conduct these studies -- biochemistry, clinical science, epidemiology, and assay development for biomarker validation -- and emphasized the role of interdisciplinary teams to move findings towards clinical translation.

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.

Metabolomic-derived endotypes of age-related macular degeneration (AMD): a step towards identification of disease subgroups.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a complex pathophysiology and phenotypic diversity. Here, we apply Similarity Network Fusion (SNF) to cluster AMD patients into putative metabolomics-derived endotypes. Using a discovery cohort of 163 AMD patients from Boston, US, and a validation cohort of 214 patients from Coimbra, Portugal, we identified four distinct metabolomics-derived endotypes with varying retinal structural and functional characteristics, confirmed across both cohorts. Patients clustered into Endotype 1 exhibited a milder form of AMD and were characterized by low levels of amino acids in specific metabolic pathways. Meanwhile, patients clustered into both Endotype 3 and 4 were associated with more severe AMD and exhibited low levels of fatty acid metabolites and elevated levels of sphingomyelins and fatty acid metabolites, respectively. These preliminary findings indicate that metabolomics-derived endotyping may offer a refined strategy for categorizing AMD patients based on their specific pathophysiological underpinnings, rather than relying solely on traditional observational clinical indicators.

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.].

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.

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.].

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.

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.

Evaluation of a mobile app for dark adaptation measurement in individuals with age-related macular degeneration.

We present clinical evaluation of a mobile app for dark adaptation (DA) measurement in age-related macular degeneration (AMD) patients and in older adults (age > 50 years) without AMD or other retinal disorders (NV). The outcome measures were the area under dark adaptation curve (AUDAC) and the time for visual sensitivity to recover by 3 log units (TR). Larger AUDAC and TR values indicated worse DA response. The association of AUDAC with AMD was analyzed using linear regression, while time-to-event analysis was used for TR. 32 AMD patients (mean ± SD; age:72 ± 6.3 years, VA:0.09 ± 0.08 logMAR) and 25 NV subjects (mean ± sd; age:65 ± 8.7 years, VA:0.049 ± 0.07 logMAR) were measured with the app. Controlling for age, VA, and cataract severity, the AMD presence was significantly associated with higher AUDAC (ß = 0.41, 95% CI 0.18-0.64, p = 0.001) and with slower sensitivity recovery (ß = 0.32, 95% CI 0.15-0.69, p = 0.004). DA measurements with the app were highly correlated with those obtained with AdaptDx-an established clinical device (n = 18, ρ = 0.87, p < 0.001). AMD classification accuracy using the app was 72%, which was comparable to the 71% accuracy of AdaptDx. Our findings indicate that the mobile app provided reliable and clinically meaningful DA measurements that were strongly correlated with the current standard of care in AMD.

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.

RP2 X-LINKED RETINITIS PIGMENTOSA CARRIER STATE PRESENTING WITH VASCULAR LEAKAGE AND UNILATERAL MACULAR ATROPHY.

PURPOSE: We describe the unusual clinical presentation of a 33-year-old woman subsequently identified as a carrier of RP2-associated X-linked retinitis pigmentosa. METHODS: Case report. RESULTS: A 33-year-old woman without a known family history of retinal disease presented with unilateral reduced visual acuity and central scotoma in the left eye. Examination showed underlying macular atrophy in the left eye and a bilateral tapetal-like reflex. Full-field electroretinogram was abnormal in the left eye but normal in the right eye. Notable findings on wide-field imaging included bilateral peripheral vascular leakage on fluorescein angiography and a bilaterally symmetric radial pattern of hyperfluorescence on fundus autofluorescence. Genetic testing demonstrated a pathogenic variant in the gene RP2 confirming that she was a carrier of X-linked retinitis pigmentosa. CONCLUSION: We describe clinical features of the carrier state of RP2-XLRP and expand potential findings to include peripheral vascular leakage. This case highlights the importance of awareness of the carrier state, particularly if a family history cannot be provided.

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.

Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.