Development and validation of a simple and practical model for early detection of diabetic macular edema in patients with type 2 diabetes mellitus using easily accessible systemic variables.

OBJECTIVE: Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. METHODS: In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People's Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People's Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. RESULTS: The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. CONCLUSION: The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

APTAnet: an atom-level peptide-TCR interaction affinity prediction model.

The prediction of affinity between TCRs and peptides is crucial for the further development of TIL (Tumor-Infiltrating Lymphocytes) immunotherapy. Inspired by the broader research of drug-protein interaction (DPI), we propose an atom-level peptide-TCR interaction (PTI) affinity prediction model APTAnet using natural language processing methods. APTAnet model achieved an average ROC-AUC and PR-AUC of 0.893 and 0.877, respectively, in ten-fold cross-validation on 25,675 pairs of PTI data. Furthermore, experimental results on an independent test set from the McPAS database showed that APTAnet outperformed the current mainstream models. Finally, through the validation on 11 cases of real tumor patient data, we found that the APTAnet model can effectively identify tumor peptides and screen tumor-specific TCRs.

Comprehensive assessment of ocular parameters for identifying diagnostic indicators of diabetic peripheral neuropathy.

PURPOSE: To explore variations in systemic and ocular parameters among patients with diabetes, both with and without diabetic peripheral neuropathy (DPN) and to identify sensitive indicators for DPN diagnosis. METHODS: Ninty-five patients with type 2 diabetes mellitus (T2DM) were involved in this cross-sectional study, including 49 without DPN and 46 with DPN. Ocular parameters were obtained using optical coherence tomography angiography (OCTA) and corneal confocal microscopy (CCM). RESULT: Patients with DPN presented with significantly higher HbA1c (p < 0.05) and glycated albumin (GA, p < 0.01) levels, increased prevalence of diabetic retinopathy (DR, p < 0.05), and lower serum albumin (ALB, p < 0.01) and red blood cell (RBC, p < 0.05) levels. Ocular assessments revealed reduced corneal nerve fiber length (CNFL, p < 0.001) and enlarged foveal avascular zone (FAZ) area (p < 0.05) in DPN group. Logistic regression analysis indicated a significant association of presence of DR, RBC, GA, ALB, CNFL and DPN (p < 0.05, respectively). In the binary logistic regression for DPN risk, all three models including the presence of DR and CNFL exhibited the area under the curve (AUC) exceeding 0.8. CONCLUSION: The study establishes a strong correlation between ocular parameters and DPN, highlighting CCM's role in early diagnosis. Combining systemic and ocular indicators improves DPN risk assessment and early management.

A Novel Risk Stratification-Based Immunomodulatory Treatment Strategy for Vogt-Koyanagi-Harada Disease.

PURPOSE: To develop a more tailored immunomodulatory treatment (IMT) strategy based on a novel 2-arm risk stratification system in Vogt-Koyanagi-Harada (VKH) patients. DESIGN: A retrospective clinical cohort study. METHODS: Seventy-nine VKH patients in the acute stage were stratified into low- (n = 58) and high-risk (n = 21) groups based on their exposure to risk factors. They were treated with oral glucocorticoids (GCs) plus as-needed (PRN) or first-line IMT. Best corrected visual acuity (BCVA), sunset glow fundus (SGF) occurrence, relapse rate, and systemic adverse events were evaluated during follow-up. RESULTS: Compared with the low-risk group, the high-risk group showed poorer BCVA at baseline (estimated difference 0.51, 95% CI 0.30-0.78; P < .001) and 6-month follow-up (estimated difference 0.08, 95% CI 0.00-0.08; P = .006), higher incidence of SGF at 12 months (52% vs 28%; RR 1.9, 95% CI 1.1-3.4; P = .040), and higher relapse rate at 6 months (24% vs 5%; RR 4.6, 95% CI 1.2-17.5; P = .028) and 12 months (52% vs 12%; RR 4.4, 95% CI 1.9-9.7; P < .001). In the low-risk cohort, no significant difference between the 2 IMT strategies was observed in primary outcomes. In the high-risk cohort, patients with the immediate IMT showed better BCVA (estimated difference -0.20, 95% CI -0.3 to -0.08; P = .007), lower incidence of SGF (27% vs 80%; RR 0.3, 95% CI 0.1-0.9; P = .030), and lower relapse rate (27% vs 80%; RR 0.3, 95% CI 0.1-0.9; P = .030) compared with the PRN regimen. Moreover, the immediate IMT regimen had a higher frequency of systemic adverse events than the PRN regimen (47% vs 7%; RR 7.1, 95% CI 2.5-20.4; P < .001). CONCLUSIONS: High-risk stratification at baseline was associated with poor prognosis. The immediate IMT regimen was only beneficial for high-risk VKH patients regarding visual outcome, SGF, and relapse rate. This study suggests a potential need for a customized IMT strategy for VKH patients.

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.

Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα.

Nanobodies and chemical cross-linking were used to gain information on the identity and positions of flexible domains of PI3Kα. The application of chemical cross-linking mass spectrometry (CXMS) facilitated the identification of the p85 domains BH, cSH2, and SH3 as well as their docking positions on the PI3Kα catalytic core. Binding of individual nanobodies to PI3Kα induced activation or inhibition of enzyme activity and caused conformational changes that could be correlated with enzyme function. Binding of nanobody Nb3-126 to the BH domain of p85α substantially improved resolution for parts of the PI3Kα complex, and binding of nanobody Nb3-159 induced a conformation of PI3Kα that is distinct from known PI3Kα structures. The analysis of CXMS data also provided mechanistic insights into the molecular underpinning of the flexibility of PI3Kα.

Methotrexate for chronic non-necrotizing anterior scleritis in Chinese patients.

AIM: To evaluate the effectiveness and corticosteroid-sparing capabilities of methotrexate (MTX) in the treatment of chronic non-necrotizing anterior scleritis in Chinese patients. METHODS: A retrospective chart review of all patients with active anterior scleritis between January 2015 and June 2019 was conducted. All patients received 10 to 15 mg/wk MTX orally, and corticosteroids (10 to 40 mg/d prednisolone or equivalent methylprednisolone) with slow tapering. Topical corticosteroid eye drops (1% prednisolone actate, 0.1% dexmathosone or 0.1% fluoromethalone) were applied to control comorbid anterior uveitis at presentation or during follow up. The main outcomes were inflammation control and corticosteroid-sparing success, and secondary outcomes were reduction of immunosuppression load and best-corrected visual acuity (BCVA). RESULTS: Thirty-two eyes (22 patients) were included. The proportion of patients who achieved corticosteroid-sparing success was 50.0% at 3mo and 77.3% at 12mo [8 (36.4%) patients discontinued corticosteroid]. The proportion of eyes that achieved inflammation control was 59.4% at 3mo and 78.1% at 12mo. The immunosuppression load was 5.14±0.87 at presentation and 2.76±2.34 at 12mo (P<0.01). BCVA maintained unchanged or improved in 29 (90.6%) of all affected eyes. One patient discontinued MTX treatment because of an abnormal liver function test, and no other serious adverse effects were observed. CONCLUSION: According to this pilot study, low dose MTX appear to be a well-tolerated and effective treatment for chronic non-necrotizing anterior scleritis patients in the Chinese population.

A Case of Refractory Childhood Glaucoma Secondary to Weill-Marchesani Syndrome: Management with Combined CO2 Laser-Assisted Sclerectomy Surgery and Trabeculectomy.

A 2-year-old girl was diagnosed as Weill-Marchesani syndrome with typical systemic features of short stature, short and stubby hands and feet, language disorders and mental retardation. He developed bilateral angle closure glaucoma, ectopia lentis and suffered visual loss from the ocular features of Weill-Marchesani syndrome. The child was successfully treated by combined CO2 laser-assisted sclerectomy surgery and trabeculectomy.

Structural basis of peptidomimetic agonism revealed by small- molecule GLP-1R agonists Boc5 and WB4-24.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective in treating type 2 diabetes and obesity with proven cardiovascular benefits. However, most of these agonists are peptides and require subcutaneous injection except for orally available semaglutide. Boc5 was identified as the first orthosteric nonpeptidic agonist of GLP-1R that mimics a broad spectrum of bioactivities of GLP-1 in vitro and in vivo. Here, we report the cryoelectron microscopy structures of Boc5 and its analog WB4-24 in complex with the human GLP-1R and Gs protein. Bound to the extracellular domain, extracellular loop 2, and transmembrane (TM) helices 1, 2, 3, and 7, one arm of both compounds was inserted deeply into the bottom of the orthosteric binding pocket that is usually accessible by peptidic agonists, thereby partially overlapping with the residues A8 to D15 in GLP-1. The other three arms, meanwhile, extended to the TM1-TM7, TM1-TM2, and TM2-TM3 clefts, showing an interaction feature substantially similar to the previously known small-molecule agonist LY3502970. Such a unique binding mode creates a distinct conformation that confers both peptidomimetic agonism and biased signaling induced by nonpeptidic modulators at GLP-1R. Further, the conformational difference between Boc5 and WB4-24, two closed related compounds, provides a structural framework for fine-tuning of pharmacological efficacy in the development of future small-molecule therapeutics targeting GLP-1R.

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.

A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2.

Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is expressed in the central and peripheral nervous systems and involved in a number of pathophysiological conditions, including pulmonary arterial hypertension, autoimmune and psychiatric disorders, in which it is thus a valuable drug target. Here, we report the cryo-electron microscopy structure of the human VIP2R bound to its endogenous ligand PACAP27 and the stimulatory G protein. Different from all reported peptide-bound class B1 GPCR structures, the N-terminal α-helix of VIP2R adopts a unique conformation that deeply inserts into a cleft between PACAP27 and the extracellular loop 1, thereby stabilizing the peptide-receptor interface. Its truncation or extension significantly decreased VIP2R-mediated cAMP accumulation. Our results provide additional information on peptide recognition and receptor activation among class B1 GPCRs and may facilitate the design of better therapeutics.

Abnormal global alternative RNA splicing in COVID-19 patients.

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.

Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors.

Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dual agonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their multiplexed pharmacological actions over monoagonists such as semaglutide, we determine cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR. The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the near-atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility of tirzepatide and peptide 20.

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.

Anterior Segment Inflammation in Pediatric Uveitis Is Associated with Reduced Retinal Vascular Density as Quantified by Optical Coherence Tomography Angiography.

PURPOSE: To analyze the retinal capillary vascular density (VD) as quantified by optical coherence tomography angiography (OCTA) in patients with pediatric uveitis. METHODS: OCTA images of 32 pediatric uveitis patients and 30 normal controls (NC) were obtained retrospectively. The foveal avascular zone (FAZ) area, VDs in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the central macular thickness (CMT), and subfoveal choroidal thickness (SFCT) were analyzed and compared between active and quiescent uveitic eyes, contralateral eyes and NC eyes. RESULTS: Compared with NCs, the VDs in the SCP and DCP were significantly reduced in eyes with both active and quiescent pediatric uveitis (P < .05).The SFCT was increased significantly in the active group relative to the quiescent group and NC groups (P < .05). In contrast, no significant differences were observed in the FAZ and CMT (all P > .05). CONCLUSIONS: Our quantitative OCTA findings suggest that the posterior segment is affected during anterior segment recurrence in patients with pediatric uveitis.

Results of modified CO2 laser-assisted sclerectomy monotherapy versus trabeculectomy combination therapy in the eyes with uveitic glaucoma.

This study compared the efficacy of modified CO2 laser-assisted sclerectomy surgery (CLASS) with combined CLASS and trabeculectomy (CLASS-TRAB) in patients with uveitic glaucoma (UG). UG patients who underwent CLASS-TRAB between August 2015 and April 2019 were retrospectively compared with a control group who underwent a modified CLASS standalone procedure during the same period. Visual acuity, intraocular pressure (IOP), use of supplemental medical therapy and postoperative complications were recorded at baseline, 1 week, 3 months, 6 months and 12 months. Forty patients (40 eyes) were enrolled, and each group had 20 patients (20 eyes). The age and sex distribution were matched between groups (P > 0.05). Both the preoperative IOP (CLASS: 34.9 ± 9.3 mmHg, CLASS-TRAB: 36.8 ± 8.7 mmHg; P > 0.05) and number of glaucoma medications (CLASS: 3.3 ± 0.4, CLASS-TRAB: 3.5 ± 0.5; P > 0.05) were relatively higher in the CLASS-TRAB group than in the CLASS group. At the final follow-up, the IOP (CLASS: 12.9 ± 3.4 mmHg, CLASS-TRAB: 11.2 ± 2.5 mmHg) and number of glaucoma medications (CLASS: 0.4 ± 0.7 and CLASS-TRAB: 0.2 ± 0.5) significantly decreased in both groups (P < 0.01). Both the complete success rate and qualified success rate were comparable between the two groups (CLASS versus CLASS-TRAB: 55% versus 80%, P = 0.09; 80% versus 95%, P = 0.34). CLASS-TRAB is as efficient as modified CLASS in terms of the IOP-lowering effect, providing a new option for patients with UG that is severe and ineligible for other treatments.

Surgical Outcomes of Modified CO2 Laser-assisted Sclerectomy for Uveitic Glaucoma.

PURPOSE: To evaluate the clinical safety and efficacy of modified CO2 laser-assisted sclerectomy surgery (CLASS) in patients with uveitic glaucoma (UG) using primary open-angle glaucoma (POAG) patients for a comparison. METHODS: This retrospective study included UG and POAG patients from the modified CLASS Study Group database. Intraocular pressure (IOP) and the number of glaucoma medications were compared between groups by the Wilcoxon test. The Kaplan-Meier method was used for survival analysis; complete success was defined as 5≤ IOP≤18 mmHg and a ≥ 20% reduction in IOP from baseline without medication. RESULTS: Twenty-three and 25 eyes in UG and POAG groups were included. At the 12-month visit in both groups, the mean IOP and mean number of IOP-lowering medications were significantly reduced compared to baseline, with complete success rates of 60.9% and 64.0% in the UG and POAG groups (P = .859). CONCLUSIONS: Modified CLASS yields similar outcomes for patients with UG and POAG.

Efficacy and safety of non-penetrating glaucoma surgery with phacoemulsification versus non-penetrating glaucoma surgery: a Meta-analysis.

AIM: To compare the clinical efficacy and safety of non-penetrating glaucoma surgery (NPGS) plus phacoemulsification (Phaco-NPGS) and NPGS-alone. METHODS: We systematically searched various databases and reviewed studies that had evaluated the effects of Phaco-NPGS or NPGS-alone for patients with glaucoma. Primary outcomes included postoperative intraocular pressure (IOP) and the number of postoperative antiglaucoma medications. Secondary outcomes were the prevalence of complications, incidence of needling or goniopuncture, and surgical success rate. RESULTS: In total, 380 and 424 eyes in NPGS-alone and Phaco-NPGS groups respectively were included. Both postoperative IOP and number of medications were significantly lowered in the Phaco-NPGS group than that in the NPDS-alone group [weighted mean difference (WMD)=-1.12, 95% confidence interval (CI): -2.11 to -0.12, P=0.03; WMD=-0.31, 95%CI: -0.53 to -0.09, P=0.006]. Moreover, Phaco-NPGS had a significantly lower prevalence of complications and postoperative procedures compared to NPGS-alone, while no significant difference existed for surgical success. CONCLUSION: Phaco-NPGS superior to NPGS-alone in the reduction of IOP and medications. Phaco-NPGS can be recommended for glaucoma patients with coexisting cataracts owing to its superior efficacy, fewer complications, and postoperative procedures.

Widefield Swept-Source Optical Coherence Tomography Angiography Assessment of Choroidal Changes in Vogt-Koyanagi-Harada Disease.

Purpose: To investigate choroidal changes in patients with Vogt-Koyanagi-Harada disease (VKH) using widefield swept-source optical coherence tomography angiography (SS-OCTA). Methods: In this cross-sectional study, 133 eyes of 69 patients with VKH (52 eyes of 28 active VKH patients and 81 eyes of 41 inactive VKH patients) and 104 eyes of 52 age and sex matched healthy volunteers were imaged using a widefield SS-OCTA instrument. On 12 mm × 12 mm OCTA scans, mean choroidal thickness (MCT), choroidal vascularity index (CVI), choriocapillaris (CC) flow area, and mean retinal thickness (MRT) were separately calculated in the fovea (diameter of 1 mm) and in concentric rings with different radii (1-3, 3-6, 6-9, and 9-12 mm). Results: Eyes with active VKH showed significant increases in MCT, CVI, and MRT, and decreased CC flow area in all central and peripheral regions (0-1, 1-3, 3-6, 6-9, and 9-12 mm) than in the healthy eyes (p ≤ 0.01) and inactive VKH eyes (p < 0.05). Inactive VKH eyes only showed marked decrease in CC flow area in all regions compared with controls (p < 0.05). Flow voids were observed in 51 of 52 (98.1%) active VKH eyes and 50 of 81 (61.7%) inactive VKH eyes on 12 mm × 12 mm OCTA. The MCT of all regions was significantly correlated with age, disease duration, and disease activity, whereas CVI was associated with age and disease activity. The CC flow void was related to visual acuity in all regions (p < 0.05). Conclusion: Widefield SS-OCTA enables a more comprehensive evaluation of chorioretinal changes in patients with VKH disease. Structural and vascular abnormalities are observed in both the central and peripheral choroid and are closely correlated with disease activity.