Quantitative evaluation of choroidal and retinal microvasculature post-alcohol consumption: A pilot study.

PURPOSE: The aim of this study was to assess the impact of acute, heavy alcohol consumption on the ocular microvasculature, providing insight into the largely unexplored response of microvascular structures to excessive drinking. METHODS: Healthy volunteers in this prospective pilot study were tasked with consuming spirits, wine, and water at different times. Alcohol intake was measured according to body weight (g/kg). The ocular microvascular parameters primarily including choroidal volume (CV) and choroidal vessel volume (CVV) reflecting arteriolovenularity, and choroidal capillary density (CCD) reflecting capillary, were evaluated using swept-source optical coherence tomography angiography at baseline and 0.5-, 1-, 2-, and 3-hour post-consumption. RESULTS: A total of 34 eyes underwent 170 successful examinations in this study. After consuming spirits or wine, we observed significant decreases in CV and CVV values (all P < 0.01 for 0.5-, 1-, 2-, and 3-hour post-consumption), along with significant increase in CCD (P < 0.05 at 0.5-, 1-, 2-hour post-spirits consumption and 1-hour post-wine consumption). The most pronounced changes occurred 1-hour after spirits or wine consumption (all P < 0.001 in both univariate and multivariate model). However, post-consumption changes in the ocular microvasculature showed no significant differences between spirits and wine (P > 0.05). Additionally, no significant differences were observed in any parameters after water intake (all P > 0.05). CONCLUSIONS: Excessive alcohol consumption leads to ocular arteriolovenular vasoconstriction and capillary vasodilation, most evident 1-hour post-consumption of spirits and wine. Our research provides insight into alcohol's immediate ocular microvascular effects, hinting at systemic microvascular effects.

Association between three-dimensional morphological features and functional indicators of neovascular age-related macular degeneration.

PURPOSE: To investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD). METHODS: This was a prospective observational study of treatment-naïve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm3) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm2) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL). RESULTS: Sixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all P < 0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (ß = 0.377, P < 0.001), avascular SHRM (ß = 0.306, P = 0.032), and ELM impairment area (ß = 0.301, P = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (ß = 0.374, p = 0.003; ß = 0.388, P < 0.001, respectively), while ONL impairment primarily associated with MNV (ß = 0.475, P < 0.001). CONCLUSION: The utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.

EPIRETINAL MACROPHAGE-LIKE CELLS ON OPTICAL COHERENCE TOMOGRAPHY: Potential Inflammatory Imaging Biomarker of Severity in Diabetic Retinopathy.

PURPOSE: To investigate the clinical value of epiretinal macrophage-like cells (eMLCs) in different stages of diabetic retinopathy (DR), including diabetic macular edema (DME). METHODS: One hundred and seventy-six eyes of 176 patients, including 31 diabetes eyes without retinopathy, 24 with mild nonproliferative DR (NPDR), 37 with moderate NPDR, 32 with severe NPDR, and 52 with proliferative DR, were compared with 30 healthy controls. The optic nerve head and macular region were examined using en face optical coherence tomography and optical coherence tomography angiography. A previously described technique was employed to measure the eMLCs on the inner limiting membrane. RESULTS: The optic nerve head and macular eMLC densities increased with worsening DR stage and were higher in moderate, severe NPDR, and proliferative DR, especially in eyes with DME (all adjusted P < 0.01). The optic nerve head and macular eMLC densities in the DME groups were higher than those in their corresponding non-DME groups at the same DR stage (all P < 0.05). The average macular thickness was correlated with macular eMLC density (standardized ß = 0.661, P < 0.001) in patients with diabetes. The proportion of eyes with larger and plumper eMLCs increased with worsening DR and was higher in moderate, severe NPDR, proliferative DR, and eyes with DME ( P = 0.018, P < 0.001, P < 0.001, and P < 0.001, respectively). CONCLUSION: Increased density along with morphological changes of eMLCs is observed beginning with moderate NPDR and correlates with the progression of DR, including DME.

Natural course of age-related retentional avascular pigment epithelial detachment: Support for the lipid barrier hypothesis.

PURPOSE: Retentional pigment epithelial detachment (PED) associated with age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) is hypothesized to be caused by Bruch's membrane's lipid barrier. This study aimed to report the natural course of retentional PED and evaluate the relationship between retentional PED evolution and ASHS-LIA. METHODS: Patients with treatment-naïve retentional PED were enrolled and observed every 3 months for at least 12 months. Treatment was not performed except for secondary macular neovascularization. RESULTS: In 55 studied eyes with a median follow-up of 18.0 (range: 12-36) months, 87.3% (48/55) of the retentional PEDs persisted, 7.3% (4/55) resolved, and 5.5% (3/55) progressed to polypoidal choroidal vasculopathy. The mean PED area significantly increased during the follow-up (P <0.001) and with the ASHS-LIA grade at each follow-up point (all P <0.05), especially during the first 6 months before approaching the edge of confluent ASHS-LIA. Persistent PEDs were mostly stable (52.1%) or enlarged (45.8%) but reduced in only 1 case (2.1%) due to RPE microrip at the edge of PED. The persistent PEDs were all within the ASHS-LIA region, especially the macular confluence region. The resolved PEDs all had grade 1 ASHS-LIA and resolved after gradual expansion of PED beyond the confluent ASHS-LIA region. PEDs that progressed to MNV all had confluent grade 2 or 3 ASHS-LIA. RPE breaks or apertures within PED did not affect the progression of the PED. CONCLUSION: The natural course of retentional PED is closely related to the features of ASHS-LIA and supports its lipid-barrier hypothesis.

SOLITARY PUNCTATE CHORIORETINITIS: A Unique Subtype of Punctate Inner Choroidopathy.

PURPOSE: To describe a case series of a special subtype of punctate inner choroidopathy with solitary lesions in the macular area and named solitary punctate chorioretinitis. METHODS: This retrospective observational study clinically evaluated 12 eyes from 12 patients diagnosed as punctate inner choroidopathy with solitary lesions. Demographic data and multimodal imaging features were analyzed for the included patients. RESULTS: All the included patients were Chinese and of Han ethnicity. The median age of the included patients was 29.5 years (range: 25-40 years). Most patients (11/12, 91.67%) were myopic, with median refraction errors of -4.4 diopters (D) (range: -8.5 to 0 D). Solitary chorioretinitis lesions were yellow‒white and appeared hyperfluorescent during the entire phase of fundus fluorescein angiography without leakage (9/12, 75%) and hypofluorescent on indocyanine green angiography (11/11, 100%). On spectral domain optical coherence tomography, active inflammatory lesions appeared as isolated, heterogeneous, moderately reflective material at the outer retina (10/12, 83.33%) in the fovea or parafoveal region with disruption of the outer retinal layers. When the inflammatory lesions regressed, the moderately reflective materials in the outer retina were absorbed or regressed with outer retinal tissue loss. Additional sequelae of lesion regression included focal choroidal excavation and intraretinal cystoid space. Secondary choroidal neovascularization was noticed in 2 eyes (2/12, 16.67%). CONCLUSION: Solitary punctate chorioretinitis is a rare and unique subtype of punctate inner choroidopathy. Solitary punctate chorioretinitis may also be an unrecognized etiology of some forms of focal choroidal excavation and idiopathic choroidal neovascularization.

Screening for diabetic retinopathy in diabetic patients with a mydriasis-free, full-field flicker electroretinogram recording device.

PURPOSE: To investigate the accuracy of the RETeval full-field flicker ERG in the screening of diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) and to determine a suitable range of DR diagnostic reference for patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study involving 172 subjects with T2DM, including 71 subjects without clinically detectable DR (NDR), 25 subjects with mild non-proliferative diabetic retinopathy (NPDR), 24 subjects with moderate NPDR, 27 subjects with severe NPDR and 25 subjects with proliferative diabetic retinopathy (PDR). All the subjects underwent a full-field flicker ERG using the RETeval device (DR assessment protocol), which is a mydriasis-free, full-field electroretinogram (ERG) recording system. The performance of the DR assessment protocol in detecting the DR (including mild NPDR, moderate NPDR, severe NPDR and PDR) and VTDR was analyzed with the receiver operating characteristic (ROC) curve. RESULTS: For the detection of DR (mild NPDR, moderate NPDR, severe NPDR, PDR), the area under the ROC curve was 0.867 (p < 0.001, 95% CI 0.814-0.920), and the best cutoff value for DR was determined to be 20.75, with a sensitivity of 80.2% and specificity of 81.7%. Meanwhile, for the detection of VTDR, the area under the ROC curve was 0.965 (p < 0.001, 95% CI 0.941-0.989), and the best cutoff value was set to 23.05, with a sensitivity of 94.6% and a specificity of 88.8%. CONCLUSION: The DR assessment protocol in RETeval device was effective in screening for DR (mild NPDR, moderate NPDR, severe NPDR, PDR) and VTDR in patients with diabetes. It could be helpful in referring and managing patients with T2DM in primary healthcare setting. However, caution should be taken that optimal cutoff value of DR assessment protocol may vary in different ethnic populations.

Retinal vasculature-function correlation in non-proliferative diabetic retinopathy.

PURPOSE: To compare and correlate retinal microcirculation and function in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: Thirty-three healthy controls (33 eyes), 36 diabetic patients with no clinically detectable retinopathy (NDR, 36 eyes) and 101 patients (101 eyes) with NPDR (35 mild NPDR, 34 moderate NPDR, 32 severe NPDR) were involved in the study. We used optical coherence tomography angiography (OCTA) to quantify the macular vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP) and foveal density in a 300 µm region around foveal avascular zone. Retinal function was assessed by a mydriasis-free, full-field flicker electroretinogram (FERG) recording device, and the amplitudes and implicit time were recorded. The association between microvascular parameters and FERG results was analyzed with stepwise multiple linear regression model. RESULTS: Decreased amplitudes and delayed implicit time, as well as lower parafoveal/perifoveal VD in both SCP and DCP, were found in NDR group and NPDR groups compared with the control group (all p < 0.05). Specifically, the FERG parameters and microvascular indices were comparable between NDR group and mild NPDR group (all p > 0.05). However, compared to mild NPDR, the reduction in FERG amplitude was more pronounced than the reduction in parafoveal VD (both SCP and DCP) in severe NPDR. Stepwise multiple linear regression analyses showed that delayed implicit time was significantly correlated with increased age and decreased VD of parafoveal region in both SCP and DCP in patients with NPDR. Meanwhile, decreased amplitude was significantly associated with decreased VD of parafoveal region in both SCP and DCP in patients with NPDR. CONCLUSION: Macular VD in both superficial and deep capillary plexus correlated with ERG implicit time and amplitude in mild-to-severe NPDR. OCTA and FERG may both be useful in detection of preclinical DR and early DR, but once the disease deteriorates, FERG may be more sensitive to discern progression of DR.

Comprehensive analysis of vitreous chemokines involved in ischemic retinal vein occlusion.

Purpose: To investigate vitreous levels of chemokines in eyes with ischemic retinal vein occlusion (RVO). Methods: The vitreous humor was collected at the start of 23-gauge pars plana vitrectomy from patients with ischemic RVO and patients with idiopathic preretinal membranes (PRMs) and idiopathic macular holes (IMHs). The levels of 40 different chemokines were measured using magnetic color-bead-based multiplex assay. The chi-square test was performed for clinical variables such as sex, and the Mann-Whitney U test was performed to evaluate the differences in the chemokine levels between the RVO group and the control group. Results: Vitreous humor was collected from 20 controls and 25 subjects with ischemic RVO. C-C motif ligand 17 (CCL17) was unmeasurable in more than 70% of the samples. The levels of 29 of 39 chemokines were statistically significantly elevated in the RVO group compared with the control group, including CCL21, C-X-C motif ligand (CXCL) 13, CCL27, CCL24, CX3CL1, CXCL6, interferon-gamma (IFN-γ), interleukin (IL) 1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-16, CXCL10, CXCL11, CCL8, CCL7, CCL13, CCL22, macrophage migration inhibitory factor (MIF), CXCL9, CCL3, CCL15, CCL20, CCL19, CCL23, CCL25, and tumor necrosis factor-alpha (TNF-α). Among the 29 elevated chemokines, we found that the levels of three chemokines (IL-8, CXCL9, and TNF-α) showed a more than six-fold increase in the RVO eyes versus controls, and CXCL9 expression showed the greatest change of all tested chemokines. Conclusions: Dozens of chemokines were found to be elevated in the vitreous of RVO eyes complicated with vitreous hemorrhage, suggesting that inflammation is severe in the ischemic retina. The knowledge of specific upregulation of chemokines in ischemic RVO could allow more targeted future therapies.

Incidence and multimodal imaging characteristics of macular neovascularisation subtypes in Chinese neovascular age-related macular degeneration patients.

AIMS: To investigate the incidence of macular neovascularisation (MNV) subtypes of neovascular age-related macular degeneration (nAMD) and summarise these subtypes' clinical features in the Chinese population using multimodal imaging. METHODS: We retrospectively analysed 506 consecutive treatment-naïve nAMD patients (582 eyes). Incidence of MNV subtypes and clinical features were recorded based on their multimodal images. The classification of MNV subtypes in nAMD patients were referred to Consensus on Neovascular Age-related Macular Degeneration Nonmenclature (CONAN) study group classifications. RESULTS: 460 eyes of 389 nAMD patients were included in our study. 68.5% (315/460) of nAMD eyes were from male. According to CONAN, we identified type 1 macular neovascularisation (MNV) in 61.1% of eyes (281/460), type 2 MNV in 16.3% of eyes (75/460), type 3 MNV in 2.0% of eyes (9/460), mixed type 1 and type 2 MNV in 20.6% of eyes (95/460). 58% of eyes (267/460) were diagnosed as polypoidal choroidal vasculopathy lesions (PCV). 45.2% of eyes (208/460) with PCV lesions were type 1 MNV and 12.8% of eyes (59/460) with PCV lesions were co-occurred with type 2 MNV. CONCLUSION: Based on the consensus anatomical classification system developed by the CONAN Study Group, we updated the incidence of MNV subtypes and found that PCV was the most common subtype and type 3 MNV was the least common subtype among Chinese nAMD patients. In addition, the co-occurrence of PCV and type 2 MNV was typically observed, and its frequency was reported in our study.

Analyzing Formation and Absorption of Avascular Subretinal Hyperreflective Material in nAMD From OCTA-Based Insights.

PURPOSE: To investigate the formation and absorption of avascular subretinal hyperreflective material (avSHRM) in neovascular age-related macular degeneration (nAMD) based on optical coherence tomography angiography (OCTA) characteristics. DESIGN: Prospective cohort study. METHODS: This study included patients with treatment-naive nAMD who were followed up for 3 months. Subjects were classified into an avSHRM group and a non-avSHRM group based on the presence of avSHRM at baseline. Quantitative OCTA characteristics including explant area, perimeter, vessel area, density, length, junctions, endpoints, lacunarity, maximum vessel caliber, vessel dispersion, and fractal dimension were assessed, and 3-dimensional volume and optical density ratio (ODR) of avSHRM were measured. Comparison analyses, correlation coefficients, and regression models were applied to explore factors associated with avSHRM formation and absorption. RESULTS: A total of 88 eyes from 88 patients (39 female) were enrolled. Compared to the non-avSHRM group, the avSHRM group exhibited a more intricate vasculature, characterized by higher values of macular neovascularization (MNV) perimeter, vessel area, total vessel length, total number of junctions, and total number of endpoints (all P < .05), as well as the maximum vessel caliber (P < .001). In the multivariate model, which was adjusted for age, sex, and types of medications, avSHRM absorption was correlated with baseline average vessel length, maximum vessel caliber, and avSHRM ODR (standardized ß = 0.274, -0.367, and -0.334; P = .049, .010, and .018, respectively), with an adjusted R² of 0.453. CONCLUSIONS: Quantitative OCTA measurements can be used for assessing the dynamics of avSHRM in nAMD. Patients with more complex vasculature are at higher risk for avSHRM formation. Average vessel length, maximum vessel diameter, and avSHRM ODR play a role in its absorption.

A Novel Exploration of the Choroidal Vortex Vein System: Incidence and Characteristics of Posterior Vortex Veins in Healthy Eyes.

Purpose: The purpose of this study was to investigate the incidence and characteristics of posterior vortex veins (PVVs) in healthy eyes and explore their relationship with age and refractive status. Methods: This retrospective cross-sectional analysis encompassed 510 eyes from 255 consecutive healthy participants. Wide-field optical coherence tomography angiography (WF-OCTA) imaging was used to assess the presence of PVVs. Eyes were classified according to refractive status (emmetropia, low and moderate myopia, and high myopia) and age (minors and adults). The incidence and characteristics of eyes with PVVs were analyzed. Results: Participants (mean age = 30.60 ± 21.12 years, 47.4% men) showed a mean refractive error of -2.83 ± 3.10 diopters (D; range = -12.00 to +0.75). PVVs were observed in 16.1% (82/510) of eyes. Of these, 39% (32/82) had PVVs in one eye and 61% (50/82) in both eyes. The mean number of PVVs per eye was 1.65 ± 1.05 (range = 1-6). PVVs are mainly around the optic disc (78%, 64/82) of eyes with PVVs and less in the macular area (6.1%, 5/82) or elsewhere (15.9%, 13/82). PVV incidence correlated with refractive status: 10.3% (22/213) in emmetropia, 16.6% (31/187) in low and moderate myopia, and 26.4% (29/110) in high myopia (P = 0.001), but not with age. Refractive status was the key predictor of PVV occurrence (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.02-2.06, P = 0.038). Conclusions: This study confirms PVVs' presence in healthy eyes, highlighting their inherent existence and susceptibility to alterations due to refractive conditions. These findings enhance our understanding of the vortex vein system and its distribution within the eyes.

Diurnal Variation in Choroidal Parameters Among Healthy Subjects Using Wide-Field Swept-Source Optical Coherence Tomography Angiography.

Purpose: The purpose of this study was to evaluate the diurnal variation in choroidal parameters in a wide field area among healthy subjects and to identify correlations between choroidal luminal area and stromal area and various systemic factors. Methods: In this cross-sectional study, 42 eyes from 21 healthy participants (mean age = 32.4 ± 8.8 years) were examined using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA, 24 mm × 20 mm). Measurements of choroidal parameters, including choroidal volume (CV), choroidal thickness (CT), choroidal vessel volume (CVV), and choroidal stromal volume (CSV), were taken at 8:00, 12:00, 18:00, and 22:00. Systemic factors, such as blood pressure and heart rate, were concurrently monitored. Results: Our study observed significant diurnal variations in the mean total CV, CT, CVV, and CSV, with minimum measurements around 12:00 (P < 0.001) and peak values at 22:00 (P < 0.001). Furthermore, changes in CV in specific regions were more closely associated with fluctuations in CVV than CSV in the same regions. No significant diurnal variations were found in systolic (P = 0.137) or diastolic blood pressure (P = 0.236), whereas significant variations were observed in the heart rate (P = 0.001). Conclusions: Our study reveals diurnal variations in choroidal parameters and their associations, emphasizing that changes in choroidal volume relate more to the luminal than the stromal area in vessel-rich regions. This enhances our understanding of choroidal-related ocular diseases. Translational Relevance: Regions with higher choroidal vasculature observed greater choroidal volume changes.

A prospective observation of influence of anti-VEGF on optic disc vasculature in nAMD patients.

BACKGROUND: This study aims to investigate the short-term changes in relatively normal retinal vessels following anti-vascular endothelial growth factor (anti-VEGF) therapy in nAMD patients, an area that currently represents a research gap. METHODS: In this prospective study, we enrolled patients newly diagnosed with neovascular age-related macular degeneration (nAMD) and received standardized monthly anti-VEGF therapy for three months. Follow-ups were conducted at baseline and 1-week, 1-month, 2-months and 3-months post first injection. Assessment indicators included radial peripapillary capillary vascular density (RPC-VD) and retinal nerve fiber layer (RNFL) thickness in different optic disk regions using optical coherence tomography angiography, as well as intraocular pressure (IOP). RESULTS: 68 nAMD patients (68 eyes) were included in this study. Significant reductions of RPC-VD and increases of RNFL thickness primarily in the nasal regions were observed 1-week post anti-VEGF (adjusted P < 0.05). Significant negative correlations were found between 1-week changes in RPC-VD and RNFL thickness in the nasal sectors (P < 0.05). From 1 to 3 months post-injection, RPC-VD and RNFL thickness essentially returned to baseline levels. Throughout the follow-up periods, IOP remained stable (P > 0.05). CONCLUSION: Anti-VEGF treatments transiently influence the relatively normal retinal vessels, which might lead to nerve fiber edema, predominantly on the nasal side of the optic disk.

Molecular Responses of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration: Integrative Insights From Multi-Omics and Clinical Imaging.

Purpose: The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements. Methods: In this prospective study, 54 treatment-naive patients with nAMD underwent "3+ pro re nata" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas. Results: There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material. Conclusions: This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.

Macrophage-like Cells Characterized by En Face Optical Coherence Tomography was Associated with Fluorescein Vascular Leakage in Behçet's Uveitis.

PURPOSE: To investigate the features of macrophage-like cell (MLC) characterized by en face optical coherence tomography (OCT) in Behçet's uveitis (BU). METHODS: The extent of fluorescein vascular leakage (FVL) was graded on a scale of 0-3 (0=none, 1=mild, 2=moderate, 3=severe) for the optic nerve head (ONH), macula and peripheral retina. The 3µm en face OCT slabs on inner limiting membrane of ONH or macular region was used to visualize the MLCs. RESULTS: The MLC densities of BU group in ONH and macular region were significantly higher than the control group (both p<0.001). The ONH and macular MLC density were significantly higher in eyes with higher FVL grade and they were positively correlated with FVL score (all p<0.001). CONCLUSION: MLC density was elevated in Behçet's uveitis and it may serve as a noninvasive indicator for the severity of fluorescein leakage and retinal inflammation in Behcet's uveitis.

Multimodal imaging analysis for the impact of retinal peripheral lesions on central neurovascular structure and retinal function in type 2 diabetes with diabetic retinopathy.

OBJECTIVES: To explore the possible role of peripheral lesions (PLs) detected by ultrawide field (UWF) imaging system on central neurovascular structure and retinal function. METHODS: Ninety-seven diabetic patients were included in this cross-sectional study using UWF pseudocolour colour imaging with Optos Daytona (Optos, PLC). UWF images were graded as with predominantly peripheral lesions (PPLs) and without PPL. Macular neurovascular alterations and retinal function were measured by optical coherence tomography angiography (OCTA) and RETeval device, respectively. Central microcirculation and retinal function were compared between eyes with and without PPL. RESULTS: The study evaluated 186 eyes (97 patients; 43 females (44.3%)), including 92 eyes without PPL and 94 eyes with PPL. Central retinal vessel density was comparable between eyes with and without PPL. Delayed implicit time and decreased pupil area ratio were found in the PPL group compared with eyes without PPL, and this difference remained unchanged after adjusting for systemic factors (all p＜0.01). CONCLUSIONS: Our study suggests that retinal function is worse in diabetic eyes with PPL. These findings challenged the conventional ETDRS protocols which ignored peripheral retina in determining DR severity. Furthermore, combining UWF imaging with RETeval system to detect more retinal abnormalities may be helpful in DR management.

Choroidal Vein Alterations in Pachychoroid Disease With Choroidal Vascular Hyperpermeability: Evaluated by Wide-Field Indocyanine Green Angiography.

Purpose: The purpose of this study was to investigate choroidal vein (ChV) morphological features in pachychoroid disease (PCD) with choroidal vascular hyperpermeability (CVH). Methods: This retrospective study assessed subfoveal choroidal thickness (SFCT) and CVH area numbers and locations of recruited patients with PCD using multimodal images. ChV alteration patterns, including fusiform, bulbosity, sausaging, confluence, and anastomoses, as well as asymmetric ChVs, dominant ChVs, and non-dominant ChVs, were evaluated using wide-field indocyanine green angiograms. Results: Of 68 PCD eyes from 35 patients (mean age: 46.16 ± 6.28 years, 71.4% men), 2.9% had uncomplicated pachychoroid, 32.4% had pachychoroid pigment epitheliopathy (PPE), 55.9% central serous chorioretinopathy (CSC), and 8.8% pachychoroid neovasculopathy (PNV). Mean SFCT was 468.65 ± 131.40 µm. Among 419 CVH areas, ChV fusiform, ChV bulbosity, and ChV sausaging accounted for 35.8%, 35.1%, and 29.1%, respectively; 21.2% had ChV confluence and 11.9% had ChV anastomoses. At CVH areas, 13.1% had retinal pigment epithelium (RPE) leakage. ChV fusiform is steadily declining (37.4%, 36.8%, and 22.9%, respectively), and ChV sausaging, ChV anastomoses, and ChV confluence are increased gradually in the PPE, CSC, and PNV groups (21.4%, 30.0%, and 37.1%; 11.4%, 11.1%, and 20.0%; and 19.8%, 20.9%, and 28.6%, respectively). Dominant ChVs had higher CVH area numbers than non-dominant ChVs in the PPE and CSC groups (P = 0.010, P = 0.001). Conclusions: Different patterns of ChV alterations, including the newly identified ChV confluence, are commonly present at CVH areas in PCD. The CVH areas in PCD eyes are primarily located within the dominant ChVs. These findings provide crucial evidence for advancing our understanding of the underlying mechanisms of PCD pathogenesis.

Fluorescein Leakage and Optical Coherence Tomography Angiography Features of Microaneurysms in Diabetic Retinopathy.

RESULTS: Thirty-six, fifty-two, and seventy-nine MAs showed no, mild, and severe leakage on FA, respectively. Most MAs (61.7%) were centered in the inner nuclear layer. Cystoid spaces were observed adjacent to 60 (35.9%) MAs. MAs with severe leakage had a statistically higher flow proportion compared to MAs with no or mild leakage (both P < 0.001). Only 112 MAs (67.1%) were visualized in the OCTA en face images, while 165 MAs (98.8%) could be visualized in the OCT en face images. The location of MAs did not associate significantly with FA leakage status. The presence of nearby cystoid spaces and higher flow proportion by OCT B-scan with flow overlay correlated significantly with FA leakage status. CONCLUSION: The flow proportion of MAs observed on OCT B-scans with flow overlay might be a potential biomarker to identify leaking MAs. A combination of OCT B-scan, OCT en face, and OCTA en face images increased the detection rate of diabetic MAs in a noninvasive way.

Clinical Relevance of Body Fluid Volume Status in Diabetic Patients With Macular Edema.

Objective: To investigate body fluid status in diabetic macular edema (DME) patients and the extent to which it is affected by renal function. Methods: One hundred and thirty-two eyes from 132 patients with diabetes mellitus (DM) were prospectively collected in this cross-sectional, observational study. Thirty-five were DM patients without diabetic retinopathy (DR), 31 were DR patients without DME, and 66 were DME patients. The fluid status of each participant was quantified with extracellular water-to-total body water ratio (ECW/TBW) using a body composition monitor. Central subfield thickness (CST) and macular volume (MV) were obtained using optical coherence tomography (OCT). Urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and albumin was obtained using serum and urine laboratory data. Results: ECW/TBW was significantly increased in DME patients (39.2 ± 0.9, %) compared to DM (38.1 ± 0.7, %, P = 0.003) and DR patients without DME (38.7 ± 0.9, %, P < 0.001). In multilinear regression, fluid overload was positively related to DME and UACR (DME vs. DM: ß = 2.418, P < 0.001; DME vs. DR: ß = 1.641, P = 0.001; UACR, per 102, ß = 1.017, P = 0.01). In the binary logistic regression for DME risk, the area under the receiver operating characteristic curve (AUROC) increased significantly by adding ECW/TBW along with UACR and age (AUC: 0.826 vs. 0.768). Conclusion: DME patients had elevated body fluid volume independent of kidney functions. The assessment of extracellular fluid status may help in the management of DME.

Diabetic Retinopathy May Be a Predictor of Stroke in Patients With Diabetes Mellitus.

Background: It is unclear whether diabetic retinopathy (DR) can be a predictor of stroke. In this research context, the objective of our study was to investigate whether there is a significant association between DR and stroke in diabetic patients by meta-analysis. Methods: After a systematic search of studies in electronic databases, we screened all studies reporting the risk of DR status and stroke incidence and calculated their odds ratios (ORs) and hazard ratios (HRs). The effects of type of diabetes and severity of DR were also considered for subgroup analysis. Results: We included 19 studies involving 45 495 patients. A pooled HR = 1.62 (1.28-2.06) were found for the risk of DR and stroke in diabetic patients. In a subgroup analysis performed on the type of diabetes, the results showed a significant association between stroke incidence and DR status in patients with type 2 diabetes (T2D) (OR: 1.78; 95% CI, 1.53-2.08), but this association was not conclusive in type 1 diabetes (T1D) (OR: 1.77; 95% CI, 0.48-6.61). The results of the subgroup analysis with diabetes severity showed that both mild and moderate nonproliferative diabetic retinopathy (NPDR) status and severe NPDR and worse status significantly increased the risk of stroke with HRs of 2.01 (1.45-2.78) and 2.27 (1.52-3.39), respectively. Conclusion: DR status in diabetic patients is associated with an increased risk of stroke. This correlation was robust in patients with T2D, but uncertain in T1D. Based on this result, we have perhaps found the new factor for stroke management, so we analyzed the necessity and advantages of considering DR as a factor for stroke screening and risk management in our studies.