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Keywords = choriocapillaris

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30 pages, 3329 KB  
Article
Foveal Density and Multi-Domain OCTA Biomarkers May Help Identify Preclinical Diabetic Microvasculopathy in Type 2 Diabetes Mellitus
by Marko Zlatanović, Maja L. J. Živković, Nevena Zlatanović, Mladen Brzaković and Mihailo Jovanović
Medicina 2026, 62(6), 1153; https://doi.org/10.3390/medicina62061153 - 13 Jun 2026
Viewed by 204
Abstract
Background and Objectives: Type 2 diabetes mellitus (T2DM) causes retinal microvascular changes that precede clinically apparent diabetic retinopathy (DR). We aimed to identify which optical coherence tomography angiography (OCTA) biomarkers best distinguish eyes with T2DM without clinical DR from healthy controls and [...] Read more.
Background and Objectives: Type 2 diabetes mellitus (T2DM) causes retinal microvascular changes that precede clinically apparent diabetic retinopathy (DR). We aimed to identify which optical coherence tomography angiography (OCTA) biomarkers best distinguish eyes with T2DM without clinical DR from healthy controls and to evaluate machine learning classifiers trained on a comprehensive 68-parameter OCTA panel. Materials and Methods: In this prospective case–control study, 80 patients with T2DM without clinical DR and 33 controls underwent 3 × 3 mm macular OCTA using an Optovue RTVue Avanti System. After outlier screening, 221 eyes (155 T2DM, 66 controls) were analyzed. Sixty-eight OCTA parameters were extracted, covering FAZ morphometry (including foveal density FD-300), SCP and DCP vessel density and layer thickness, outer-retina and choriocapillaris flow, and a full retinal-thickness map. Between-group comparisons used the Mann–Whitney U test with Benjamini–Hochberg FDR correction. Logistic regression, random forest, and XGBoost classifiers were evaluated with patient-grouped 10-fold cross-validation; feature importance was quantified via SHAP. Results: Forty-two of 68 parameters reached FDR significance (q < 0.05). Deep capillary plexus vessel density was the most discriminative family (whole image rb = −0.66, q = 2.5 × 10−13; parafovea rb = −0.64). FD-300 was reduced in T2DM (median 47.55% vs. 51.86%; rb = −0.57; q = 1.0 × 10−10) and emerged as the top SHAP feature (mean |SHAP| = 0.81). FAZ circularity decreased without FAZ-area enlargement, and outer-retina flow was paradoxically elevated (rb = +0.39), consistent with a projection artifact. XGBoost using all 68 features achieved a patient-grouped cross-validated AUC of approximately 0.91, compared with 0.85 for conventional SCP + DCP whole-image density. No parameter correlated with current HbA1c in T2DM (all q > 0.98), and the well-controlled (<7%) and poorly controlled (≥7%) subgroups were indistinguishable across five of six principal biomarkers, consistent with metabolic memory. FD-300 remained independent after adjustment for hypertension, hyperlipidemia, and age (OR = 0.76; 95% CI 0.69–0.84; p < 0.001). Conclusions: A multi-compartment OCTA panel outperforms conventional two-layer vessel-density metrics in detecting preclinical diabetic microvasculopathy, although external validation is required before clinical use. FD-300 is the single most informative biomarker, while choriocapillaris and retinal thickness measures provide complementary, compartment-specific signals. Because the OCTA signature is decoupled from the current HbA1c, screening should not be deferred in well-controlled T2DM. Full article
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15 pages, 5826 KB  
Review
Non-Infectious Choroiditis Subdivided into Its Diverse Pathophysiological Sub-Groups Is the Best-Known and Most Appropriate Nomenclature to Date for the Reclassification and Diagnosis of Former White Dot Entities
by Carl P. Herbort Jr, Sukhum Silpa-archa, Ioannis Papasavvas, Nadia Bouchenaki, Anna Byszewska, Oleksandra Dorokhova, Christine Fardeau, Alireza Hedayatfar, De-Kuang Hwang, Vânia Lages, Wen-Jung Lo, Marina Papadia, Masaru Takeuchi, Yoshihiko Usui, Ryoji Yanai and Oleksandra Zborovska
Diagnostics 2026, 16(11), 1735; https://doi.org/10.3390/diagnostics16111735 - 4 Jun 2026
Viewed by 336
Abstract
White dot syndromes (WDS), a purely descriptive term formulated in 1995, grouped inflammatory conditions primarily affecting the choroid that shared the clinical appearance of white dots on fundus examination, thus presenting similar white dots on fundus examination, which, however, had diverse pathophysiologies and [...] Read more.
White dot syndromes (WDS), a purely descriptive term formulated in 1995, grouped inflammatory conditions primarily affecting the choroid that shared the clinical appearance of white dots on fundus examination, thus presenting similar white dots on fundus examination, which, however, had diverse pathophysiologies and different primary localizations of inflammation that did not warrant their association. Some of them, including birdshot retinochoroiditis (BRC) and sympathetic ophthalmia, produced predominant inflammation in the choroidal stroma, while others, including multiple evanescent white dot syndrome (MEWDS) and acute posterior multifocal placoid pigment epitheliopathy (APMPPE), caused inflammatory non-perfusion of the choriocapillaris. The aim of this review is to build upon a pathophysiology-based classification framework that groups these entities under the broader concept of non-infectious choroiditis and subdivides them according to their predominant inflammatory mechanisms and anatomical localization. This framework distinguishes diseases characterized by inflammatory occlusion of the choriocapillaris with consequent perfusion dysfunction, including MEWDS, APMPPE, multifocal choroiditis (MFC), and serpiginous choroiditis, from conditions primarily involving inflammatory infiltration of the choroidal stroma, such as birdshot retinochoroiditis (BRC), Vogt-Koyanagi-Harada disease (VKH), and sympathetic ophthalmia. Moreover, the review raises the question of how such an inadequate term, based on unscientific assumptions, could gain such quick access to ophthalmic practice and literature, be immediately adopted in major textbooks, and persist for so long being unrecognized as a misnomer. The slow and progressive reevaluation of this nomenclature over more than two decades is related and contextualized. Full article
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15 pages, 10588 KB  
Article
Comparison of Choroidal Morphological Changes Between Aflibercept 8 mg and Faricimab-svoa in Treatment-Naïve Polypoidal Choroidal Vasculopathy and Pachychoroid Neovasculopathy
by Seongyong Jeong, Seung Hyeon Seong and Min Sagong
J. Clin. Med. 2026, 15(11), 4355; https://doi.org/10.3390/jcm15114355 - 4 Jun 2026
Viewed by 370
Abstract
Background/Objectives: This study compared choroidal morphological changes, including choroidal vascularity index (CVI) and layer-specific choroidal thickness, between aflibercept 8 mg and faricimab-svoa in treatment-naïve polypoidal choroidal vasculopathy (PCV) and pachychoroid neovasculopathy (PNV). Methods: This retrospective study included 66 eyes treated with [...] Read more.
Background/Objectives: This study compared choroidal morphological changes, including choroidal vascularity index (CVI) and layer-specific choroidal thickness, between aflibercept 8 mg and faricimab-svoa in treatment-naïve polypoidal choroidal vasculopathy (PCV) and pachychoroid neovasculopathy (PNV). Methods: This retrospective study included 66 eyes treated with aflibercept 8 mg (n = 32) or faricimab-svoa (n = 34). Following three monthly loading injections, a pro re nata regimen was employed for 6 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED) height, and CVI were assessed. Results: Both groups demonstrated significant improvements in BCVA, CMT, SFCT, and PED height at 6 months (all p < 0.05), with no between-group differences. Dry macula rates were 75.0% and 79.4%, respectively. Faricimab-svoa was associated with a significantly greater CVI increase (0.037 vs. 0.018, p = 0.003), driven by a numerically greater reduction in choriocapillaris/Sattler’s layer thickness (−18.9 ± 16.4 μm vs. −13.8 ± 15.8 μm, p = 0.153). Conclusions: Both agents achieved comparable functional and anatomical outcomes in treatment-naïve PCV and PNV. Faricimab-svoa was associated with a greater CVI increase, reflecting differential choroidal remodeling. CVI may serve as a biomarker for differentiating the choroidal effects of second-generation anti-VEGF therapies in pachychoroid spectrum disease. Full article
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16 pages, 1465 KB  
Article
Choriocapillaris Flow-Enriched Prediction of Retinal Sensitivity Using OCT-Derived Biomarkers in Intermediate Age-Related Macular Degeneration
by Johannes Schrittwieser, Lukas Kuchernig, Virginia Mares, Irene Steiner, Klaudia Birner, Florian Frommlet, Enrico Borrelli, Hrvoje Bogunović, Stefan Sacu and Gregor S. Reiter
J. Clin. Med. 2026, 15(9), 3392; https://doi.org/10.3390/jcm15093392 - 29 Apr 2026
Viewed by 382
Abstract
Objectives: To assess the association of structural biomarkers derived from optical coherence tomography (OCT) and choriocapillaris (CC) flow information with point-wise retinal sensitivity (PWS) measured by microperimetry (MP) in intermediate age-related macular degeneration (iAMD). Methods: Patients with iAMD received imaging with spectral-domain [...] Read more.
Objectives: To assess the association of structural biomarkers derived from optical coherence tomography (OCT) and choriocapillaris (CC) flow information with point-wise retinal sensitivity (PWS) measured by microperimetry (MP) in intermediate age-related macular degeneration (iAMD). Methods: Patients with iAMD received imaging with spectral-domain (SD)-OCT (Spectralis, Heidelberg Engineering) and OCT-angiography (OCT-A) (PLEX Elite 9000, ZEISS). In addition, MP examinations in photopic setting (MP-3, NIDEK) and mesopic background illumination (MAIA2, ICare) were performed. The thickness of the ellipsoid-zone (EZ) and the outer nuclear layer (ONL), as well as the volume of drusen and HRF, were segmented using deep-learning (DL)-based approaches. CC flow deficit percentage (FD%) was extracted from OCT-A slabs using a novel binarization method. Semiautomatic co-registration of MP examinations, OCT-A slabs, and OCT volumes was performed. Three exploratory models were calculated using multivariable mixed-effects models: (1) structure–function (SF) using structural OCT biomarkers, (2) flow–function (FF) utilizing OCT-A derived flow information, and (3) structure–flow–function (SFF) incorporating both OCT and OCT-A data. Model performance was evaluated using AIC and BIC criterion. Results: 19 eyes of 19 patients were evaluated, totalling 3297 MP-stimuli, 1873 B-scans, and 19 OCT-A slabs. Mean (SD) age was 76 (7) years, and sensitivity was 26.0 (3.36) dB in the MP-3 and 22.42 (3.64) dB in the MAIA2. Mesopic MAIA2 examinations showed significantly lower PWS values (−3.56 to −3.63 dB; p < 0.001). Drusen and HRF volume decreased PWS (−0.6 [95% CI: −1.04; −0.16] dB/nL; p = 0.007 and −9.56 [95% CI: −12.86; −6.26] dB/nL; p < 0.001), while ONL was positively associated with PWS (0.06 [0.05; 0.07] at an eccentricity of 5.2°; p < 0.001) in the SF model. CC FD% was not significantly associated with PWS in the FF and the SFF model (p > 0.05 in both cases). In the SFF model drusen volume (−1.69 [95% CI: −2.09; −1.29] dB/nL; p < 0.001), EZ (0.04 [95% CI: 0.02; 0.06] dB/µm; p < 0.001), and ONL thickness (0.03 [95% CI: 0.02; 0.04] dB/µm; p < 0.001) were significant predictors for PWS. The SF model exhibited the lowest AIC and BIC indicating best model performance. Conclusions: Structural parameters derived from SD-OCT such as HRF, drusen volume, and outer retinal layer thickness may be more closely associated with PWS, with CC FD% as an OCT-A-derived metric contributing limited additional explanatory benefit in cross-sectional analyses. Full article
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10 pages, 612 KB  
Article
Automated Longitudinal Quantification of Retinal and Choroidal Vascular Changes After Phacoemulsification
by Seung Hoon Lee, Phil Kyu Lee, Se Eun Park, Ho Ra and Jiwon Baek
Tomography 2026, 12(3), 42; https://doi.org/10.3390/tomography12030042 - 19 Mar 2026
Viewed by 462
Abstract
Background/Objectives: To comprehensively evaluate longitudinal retinal and choroidal vascular changes after phacoemulsification using automated optical coherence tomography angiography (OCTA) analysis and to investigate clinical factors influencing these changes. Methods: This retrospective study included 26 subjects (31 eyes) who underwent uncomplicated phacoemulsification. OCTA was [...] Read more.
Background/Objectives: To comprehensively evaluate longitudinal retinal and choroidal vascular changes after phacoemulsification using automated optical coherence tomography angiography (OCTA) analysis and to investigate clinical factors influencing these changes. Methods: This retrospective study included 26 subjects (31 eyes) who underwent uncomplicated phacoemulsification. OCTA was performed at baseline and at 1 day, 1 week, 1 month, and 2 months postoperatively. Automated quantitative analysis was applied to assess vessel density- and structure-related parameters in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris, and Haller layer. Longitudinal changes were analyzed using repeated-measures analysis of variance, with time × clinical factor interactions evaluated for diabetes mellitus, anesthesia method, and sex. Inter-layer associations were assessed using Spearman correlation analysis. Results: Significant longitudinal changes were observed in retinal layers. In the SCP, vessel density increased from 42.59 ± 1.46 at baseline to 44.10 ± 1.44 at 2 months (p = 0.002), accompanied by increases in vessel length and node counts (all p < 0.001). In the DCP, vessel density increased from 34.66 ± 5.98 to 38.65 ± 4.83 (p < 0.001). In contrast, choriocapillaris-related parameters showed no significant overall time effect. In the Haller layer, mean vessel diameter decreased significantly over time (p < 0.001), while density-related metrics remained unchanged. ΔVAD demonstrated positive correlations between adjacent layers (SCP–DCP and DCP–choriocapillaris) and a negative correlation between choriocapillaris and Haller layers. Diabetes mellitus showed no significant longitudinal effect, whereas retrobulbar anesthesia and sex significantly modified selected choroidal trajectories. Conclusions: Automated and integrated OCTA analysis revealed layer-dependent retinal and choroidal vascular responses after phacoemulsification, with coordinated changes confined mainly to anatomically adjacent layers and selective modulation by clinical factors. Full article
(This article belongs to the Section Artificial Intelligence in Medical Imaging)
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12 pages, 2947 KB  
Case Report
MEWDS-like Presentation Unmasking Sequential Bilateral Multifocal Choroiditis: Insights from Longitudinal Multimodal Imaging
by Blerta Lang, Annekatrin Rickmann, Karl Thomas Boden, Stefanie Behnke and Peter Szurman
Biomedicines 2026, 14(3), 649; https://doi.org/10.3390/biomedicines14030649 - 13 Mar 2026
Cited by 1 | Viewed by 687
Abstract
Background: Multiple evanescent white dot syndrome (MEWDS) is usually acute and self-limited, whereas multifocal choroiditis (MFC)/punctate inner choroidopathy (PIC) is relapsing; overlap can obscure early diagnosis and requires longitudinal multimodal imaging. Methods: We report a 4-year follow-up of a 31-year-old woman with fundus [...] Read more.
Background: Multiple evanescent white dot syndrome (MEWDS) is usually acute and self-limited, whereas multifocal choroiditis (MFC)/punctate inner choroidopathy (PIC) is relapsing; overlap can obscure early diagnosis and requires longitudinal multimodal imaging. Methods: We report a 4-year follow-up of a 31-year-old woman with fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT), plus a systemic/neurologic/rheumatologic work-up. Treatment included intravenous methylprednisolone for presumed optic neuritis, followed by topical, periocular, intravitreal, and systemic corticosteroids, later escalated to adalimumab and an intravitreal dexamethasone implant. Because foveal granularity could not be documented, baseline was termed “MEWDS-like”. Diagnostic labelling was benchmarked against Standardization of Uveitis Nomenclature (SUN) criteria, and choroidal neovascularization (CNV) was assessed at each relapse by OCT and FA. Results: The right eye initially showed a MEWDS-like pattern with wreath-like FA lesions and disc leakage, hyperautofluorescent FAF lesions, focal ellipsoid zone disruption on SD-OCT, and multifocal ICGA hypofluorescent spots. A relapse at 6 months with peripapillary inflammatory foci and recurrent cystoid macular edema supported reclassification to a unilateral MFC/PIC-spectrum phenotype. At 2 years, the fellow eye developed mild vitritis, peripapillary hyperautofluorescence, peripapillary/arcade leakage on FA, delayed peripapillary filling on ICGA, and cystoid macular edema, establishing sequential bilateral MFC; no CNV developed and anti-vascular endothelial growth factor (anti-VEGF) therapy was not required. Complications included steroid-induced ocular hypertension and cataract surgery. Conclusions: The purpose of this report is to highlight longitudinal imaging “red flags” that supported reclassification from a MEWDS-like phenotype to a sequential bilateral MFC/PIC-spectrum disease. Full article
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12 pages, 693 KB  
Article
Correlations Between OCTA Parameters and Clinical Changes in Patients Newly Diagnosed with Multiple Sclerosis
by Ion Iulian Enache, Vlad Eugen Tiu, Cătălina Andreea Anghel, Alina Popa Cherecheanu, Mihai Bostan, Jacqueline Chua, Chi Li, Jia Wei Cheong, Leopold Schmetterer and Cristina Tiu
Diagnostics 2026, 16(6), 828; https://doi.org/10.3390/diagnostics16060828 - 11 Mar 2026
Viewed by 567
Abstract
Background: The eye has shown potential as a reliable, readily accessible and clinically relevant site for investigating patients with multiple sclerosis (pwMS). Optical coherence tomography angiography (OCTA) shows promise in revealing new metabolic and vascular elements driving multiple sclerosis (MS) disease pathology. This [...] Read more.
Background: The eye has shown potential as a reliable, readily accessible and clinically relevant site for investigating patients with multiple sclerosis (pwMS). Optical coherence tomography angiography (OCTA) shows promise in revealing new metabolic and vascular elements driving multiple sclerosis (MS) disease pathology. This study aimed to explore correlations between OCTA parameters and clinical characteristics in newly diagnosed relapsing–remitting MS (RRMS) patients. Methods: In this cross-sectional study, forty-one newly diagnosed RRMS patients underwent comprehensive evaluations, including neurological examinations, functional and cognitive tests (9-Hole Peg Test, Montreal Cognitive Assessment), and OCT/OCTA scans. Multiple regression analyses assessed correlations between OCT/OCTA parameters and baseline clinical characteristics. Results: Lower superficial capillary plexus (SCP) vessel density was associated with longer disease duration, higher EDSS scores (visual, pyramidal, cerebellar, ambulation), and impaired 9-Hole Peg Test performance, especially in the non-dominant hand. Higher values of choriocapillaris (CC) flow voids correlated with worse cognitive performance (MoCA). Structural OCT parameters showed limited clinical correlations. Conclusions: OCTA-derived parameters are associated with disability, fine motor function, and cognitive performance in newly diagnosed RRMS patients without prior ON. These findings suggest that retinal vascular alterations may reflect early neurodegenerative processes and provide complementary information beyond structural OCT metrics. OCTA may represent a sensitive, non-invasive imaging biomarker for patient assessment in early MS. Full article
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11 pages, 746 KB  
Article
Optical Coherence Tomography Angiography in Patients with Mixed Connective Tissue Disease
by Magdalena Szeretucha, Katarzyna Paczwa, Katarzyna Romanowska-Próchnicka, Sylwia Ornowska, Radosław Różycki and Joanna Gołębiewska
Biomedicines 2026, 14(3), 612; https://doi.org/10.3390/biomedicines14030612 - 9 Mar 2026
Viewed by 725
Abstract
Background: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease which presents with clinical features that overlap with at least two connective tissue disorders, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM), dermatomyositis (DM), and rheumatoid arthritis (RA). [...] Read more.
Background: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease which presents with clinical features that overlap with at least two connective tissue disorders, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM), dermatomyositis (DM), and rheumatoid arthritis (RA). It is characterized by the presence of anti-ribonucleoprotein (anti-U1RNP) antibodies. The mechanism of the vasculopathy associated with MCTD remains largely unknown. Optical coherence tomography angiography (OCTA) is a non-invasive imaging method of the microvasculature of the retina and choroid, providing the assessment of retinal perfusion. Objectives: The aim of the study was to evaluate the optical coherence tomography angiography (OCTA) parameters in patients with mixed connective tissue disease compared to healthy individuals. Methods: In this study, we compared the following parameters between patients with MCTD and healthy subjects: foveal avascular zone (FAZ), FAZ perimeter (PERIM), flow density (FD), choriocapillaris flow area (CCFA), outer retina flow area (ORFA), and foveal and parafoveal mean superficial and deep vessel density. Results: Parafoveal mean superficial vessel density and parafoveal mean deep vessel density were significantly lower in the MCTD group than in controls. The FAZ, FAZ PERIM, and FD values in the patients with MCTD were lower than in the control group and statistically significant for all parameters. Conclusions: The present study’s findings suggest the presence of ocular vascular abnormalities in patients suffering from MCTD. These abnormalities are characterized by decreased retinal vessel density and lower choriocapillaris flow. The results of the study demonstrate the significant role of OCTA in the diagnosis and monitoring of microvascular changes in patients with MCTD. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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10 pages, 1248 KB  
Article
Normative Database and Determinants of Retinal and Choroidal Vessel Density in Tibetan Children
by Zhaojun Meng, Yao Yao, Lei Li, Weiwei Chen and Jing Fu
Children 2026, 13(2), 284; https://doi.org/10.3390/children13020284 - 19 Feb 2026
Viewed by 413
Abstract
Background/Objectives: This study investigates the normative data and determinants of retinal and choroidal vessel density (VD) in Tibetan children using optical coherence tomography angiography (OCTA). Methods: This study recruited students from primary schools in Lhasa who underwent OCTA encompassing VD in the superficial [...] Read more.
Background/Objectives: This study investigates the normative data and determinants of retinal and choroidal vessel density (VD) in Tibetan children using optical coherence tomography angiography (OCTA). Methods: This study recruited students from primary schools in Lhasa who underwent OCTA encompassing VD in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) and choriocapillaris (CC) in the macular region, as well as refractive status, axial length, and systemic examinations. Results: This study included a total of 645 children who met the criteria. The results showed that VD in the fovea was significantly higher in the SCP than in the DCP, while CC had the highest VD in the fovea. Correlation analysis revealed strong correlations in VD among all quadrants of the SCP, DCP, and CC, as well as significant correlations between corresponding regions of the SCP and DCP. VD showed no significant association with age, sex, axial length, or spherical equivalent. Foveal VD in both the SCP and DCP was positively correlated with oxygen saturation. No consistent correlation was found between choroidal or retinal thickness and VD in any layer. Conclusions: The identified link between systemic oxygen saturation and foveal vascular density offers a novel perspective on human adaptation to chronic hypoxia, positioning the retinal microcirculation as a sensitive indicator of systemic oxygen homeostasis. Full article
(This article belongs to the Section Pediatric Ophthalmology)
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15 pages, 270 KB  
Article
Haemodialysis-Induced Stress Influences Ocular Microcirculation
by Joanna Roskal-Wałek, Sylwia Terpiłowska, Joanna Gołębiewska, Jerzy Mackiewicz, Kamila Bołtuć-Dziugieł, Agnieszka Bociek, Paweł Wałek, Michał Biskup, Dominik Odrobina and Andrzej Jaroszyński
Biomedicines 2026, 14(2), 454; https://doi.org/10.3390/biomedicines14020454 - 18 Feb 2026
Viewed by 786
Abstract
Background: Haemodialysis (HD) superimposes additional circulatory stress on the microvasculature, leading to endothelial dysfunction, which plays a key role in the development of haemodialysis-associated multiorgan dysfunction. This study was undertaken to evaluate the effect of a single HD session on retinal and choroidal [...] Read more.
Background: Haemodialysis (HD) superimposes additional circulatory stress on the microvasculature, leading to endothelial dysfunction, which plays a key role in the development of haemodialysis-associated multiorgan dysfunction. This study was undertaken to evaluate the effect of a single HD session on retinal and choroidal microcirculation, using optical coherence tomography angiography (OCTA) in relation to changes in the blood levels of selected biochemical modulators of endothelial function. Methods: The vessel density (VD) of 35 patients was evaluated before and after a single HD session, using OCTA in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC). Retinal thickness (RT) and choroidal thickness (CT) were also assessed. Asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1) and malondialdehyde (MDA) levels, oxidative stress (OS) status and systemic parameters were assessed before and after a single HD session. The correlation between changes in these parameters and changes in selected OCTA parameters was tested. Results: A single HD session resulted in a significant increase in RT and a decrease in CT. In addition to increased oxidative and osmotic stress resulting from a significant reduction in plasma osmolality, the HD session was associated with a significant increase in ET-1 levels and a decrease in ADMA levels. These biochemical changes correlated with changes in RT and CT, as well as with changes in VD in the retinal capillary plexuses and the CC. Increased ET-1 levels and decreased plasma osmolality were identified as predictors of RT increase, whereas increased MDA levels corrected serum creatinine-predicted CT reduction. Conclusions: Changes in ADMA and ET-1 and OS, as well as osmotic stress induced by a single HD session, affect the eye microcirculation and morphology of the retina and choroid. OCTA examination is a promising method for assessing microcirculation in HD patients. Full article
(This article belongs to the Section Molecular and Translational Medicine)
12 pages, 1554 KB  
Article
Choriocapillaris Flow and Retinal Vascular Fractal Dimension in Dry Age-Related Macular Degeneration
by Mine Ozturk and Abdullah Ağın
Diagnostics 2026, 16(3), 422; https://doi.org/10.3390/diagnostics16030422 - 1 Feb 2026
Cited by 1 | Viewed by 450
Abstract
Background/Objective: To evaluate the association between optical coherence tomography angiography (OCTA)-derived choriocapillaris flow (CCflow), retinal vascular fractal dimension (FD), and drusen burden in eyes with dry age-related macular degeneration (AMD). Methods: This retrospective study included 113 eyes from 73 patients with dry AMD. [...] Read more.
Background/Objective: To evaluate the association between optical coherence tomography angiography (OCTA)-derived choriocapillaris flow (CCflow), retinal vascular fractal dimension (FD), and drusen burden in eyes with dry age-related macular degeneration (AMD). Methods: This retrospective study included 113 eyes from 73 patients with dry AMD. Eyes were classified into large and small drusen groups based on median drusen area. OCTA-derived CCflow and FD indices of the superficial and deep capillary plexuses were analyzed. Patient-level clustered analyses were performed using linear mixed-effects and generalized estimating equation models to account for inter-eye correlation. Results: Eyes with large drusen showed significantly lower CCflow compared with those with small drusen (p < 0.001), whereas FDsup did not differ between groups, and FDdeep demonstrated only a near-significant trend toward higher values. CCflow was moderately and negatively correlated with drusen area (ρ = −0.452, p < 0.001), whereas FDdeep showed no significant correlation in unadjusted analyses (ρ = 0.137, p = 0.148). In patient-level age-adjusted multivariable models accounting for inter-eye dependency, CCflow remained independently associated with drusen burden, while FDdeep demonstrated an independent association only after adjustment for age. Conclusions: Reduced CCflow is independently associated with increased drusen burden in dry AMD. FD metrics provide complementary descriptive information regarding microvascular remodeling but do not function as independent biomarkers. CCflow may serve as a robust quantitative indicator of early choroidal compromise in dry AMD. Full article
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24 pages, 4157 KB  
Article
Caffeine Mitigates Adenosine-Mediated Angiogenic Properties of Choroidal Endothelial Cells Through Antagonism of A1 Adenosine Receptor and PI3K-AKT Axis
by SunYoung Park, Yong-Seok Song, Xuan Feng, Christine M. Sorenson and Nader Sheibani
Cells 2026, 15(1), 87; https://doi.org/10.3390/cells15010087 - 5 Jan 2026
Viewed by 1378
Abstract
Aging reduces the tissue regenerative capacity, promotes chronic inflammation, and contributes to neurodegenerative diseases, including age-related macular degeneration (AMD). AMD is a leading cause of vision loss in older adults and manifests as dry (atrophic) or wet (neovascular) disease. Although dry AMD is [...] Read more.
Aging reduces the tissue regenerative capacity, promotes chronic inflammation, and contributes to neurodegenerative diseases, including age-related macular degeneration (AMD). AMD is a leading cause of vision loss in older adults and manifests as dry (atrophic) or wet (neovascular) disease. Although dry AMD is more prevalent, neovascular AMD (nAMD) causes the most severe vision impairment and remains a major public health burden. Oxidative stress-mediated inflammation and dysfunction of retinal pigment epithelium (RPE) cells and choriocapillaris drive early AMD. Neovascular AMD is marked by pathologic choroidal neovascularization (CNV), driven largely by dysregulated VEGF signaling. Anti-VEGF therapies are the current standard of care for nAMD but require frequent intravitreal injections, carry procedure-related risks, and are ineffective in a substantial subset of patients, underscoring the need for new therapeutic approaches. Caffeine, a widely consumed and well-tolerated adenosine receptor antagonist, has emerging relevance in vascular regulation and inflammatory signaling. Extracellular ATP and its metabolites, including adenosine, accumulate under stress and act through purinergic receptors to influence angioinflammatory processes. We recently showed that systemic caffeine administration suppressed CNV in vivo, an effect partly reproduced by the adenosine receptor A2A antagonist Istradefylline. Here, we investigated the cell-autonomous effects of caffeine on mouse choroidal endothelial cells, focusing on its role as an adenosine receptor antagonist and its potential to inhibit pathological neovascularization. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Vascular-Related Diseases)
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15 pages, 1934 KB  
Article
Changes in Choroidal Structure Associated with Idiopathic Macular Hole Border Morphology
by Hiroaki Endo, Hiroto Terasaki, Shozo Sonoda, Yuki Ito, Satoshi Katsuta and Satoru Kase
J. Clin. Med. 2025, 14(18), 6362; https://doi.org/10.3390/jcm14186362 - 9 Sep 2025
Viewed by 1544
Abstract
Objectives: To investigate the association between the hole border morphology and choroidal structure in idiopathic macular hole (IMH) patients and its impact on visual outcomes. Methods: A retrospective case–control study of 34 IMH eyes and 34 control eyes was conducted. Spectral-domain [...] Read more.
Objectives: To investigate the association between the hole border morphology and choroidal structure in idiopathic macular hole (IMH) patients and its impact on visual outcomes. Methods: A retrospective case–control study of 34 IMH eyes and 34 control eyes was conducted. Spectral-domain optical coherence tomography (SD-OCT) was used to categorize the patients into groups with smooth or bumpy hole borders. Based on this classification, a further evaluation was conducted of MH morphology and choroidal structure, both before a vitrectomy and at 1 and 2 months post-surgery. The choriocapillaris, Sattler’s layer, and Haller’s layer were the divisions of each choroidal vascular layer. Then, binarization techniques were employed to calculate the choroidal area (CA), luminal area (LA), stromal area (SA), and central choroidal thickness (CCT). The L/C ratio was established as the ratio of LA to CA. Results: In the patients with IMH, the choroidal structure was associated with the morphology of the hole border. In particular, the eyes with bumpy hole borders were significantly correlated with reduced choroidal thickness and total choroidal area, as well as a reduced L/C ratio in the choriocapillaris. After surgery, visual acuity improved in both groups, but the patients with smooth hole borders achieved earlier and higher levels of visual recovery. The multivariate analysis suggested that a bumpy hole border and the basal hole diameter were independent predictors of postoperative choriocapillaris recovery. Conclusions: Bumpy idiopathic macular hole borders are associated with impaired choroidal vasculatures, particularly in the choriocapillaris, which may be a contributing factor to delayed visual acuity recovery post-surgery. Full article
(This article belongs to the Section Ophthalmology)
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14 pages, 7335 KB  
Article
Retinal Vessel Coronal Displacement in Intermediate Age-Related Macular Degeneration
by Mariacristina Parravano, Serena Fragiotta, Maria Sole Polito, Monica Varano, Giorgio Querzoli and Tommaso Rossi
J. Clin. Med. 2025, 14(17), 6030; https://doi.org/10.3390/jcm14176030 - 26 Aug 2025
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Abstract
Introduction: This pilot study aimed to test the feasibility of a novel vectorial image analysis method to quantify coronal microvascular displacement in different retinal plexuses in intermediate age-related macular degeneration (iAMD) over 6 months. Material and methods: A retrospective series of [...] Read more.
Introduction: This pilot study aimed to test the feasibility of a novel vectorial image analysis method to quantify coronal microvascular displacement in different retinal plexuses in intermediate age-related macular degeneration (iAMD) over 6 months. Material and methods: A retrospective series of iAMD patients with at least 6-month follow-up was included if they had complete medical records, best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and OCT angiography (OCTA). En-face (coronal) vascular displacement between baseline and 6 months was assessed in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) using the Farneback motion tracking algorithm applied to consecutive OCTA scans. Results: Eighteen eyes of 18 iAMD patients met the inclusion criteria. Average coronal vascular displacement (T0–T6) was 13.7 ± 7.72 µm for the SCP, 15.11 ± 10.06 µm for the DCP, and 19.02 ± 12.25 µm for the CC slab. Reticular pseudodrusen (RPD) was associated with greater displacement in the DCP (p = 0.047), but not in the SCP (p = 0.980) or CC (p = 0.473). Quantitative analysis confirmed the highest DCP displacement in RPD eyes (66.7%, p = 0.02), while drusenoid pigment epithelial detachment showed the greatest reorganization in the CC (100%, p = 0.02). Discussion: Retinal vessels undergo significant tangential displacement in iAMD, suggesting a structural reorganization of the microvasculature. Such remodeling may constitute a compensatory response to ultrastructural alterations resulting in ischemia. Full article
(This article belongs to the Special Issue New Advances in Age-Related Macular Degeneration)
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15 pages, 1025 KB  
Article
Ocular Structural and Vascular Changes in Patients with Severe Asymptomatic Carotid Disease After Undergoing Carotid Endarterectomy (CEA) and Carotid Artery Stenting (CAS)
by Foteini Xanthou, Anna Dastiridou, Athanasios Giannoukas, Miltiadis Matsagkas, Chara Tzavara, Athanasios Chaidoulis, Sofia Androudi and Evangelia E. Tsironi
Diagnostics 2025, 15(14), 1826; https://doi.org/10.3390/diagnostics15141826 - 21 Jul 2025
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Abstract
Background/Objectives: This study aimed to prospectively assess the incidence of retinal embolization and to evaluate the vascular and structural changes in the retina and choroid in 52 patients with asymptomatic severe carotid artery disease who underwent carotid artery revascularization. Methods: In [...] Read more.
Background/Objectives: This study aimed to prospectively assess the incidence of retinal embolization and to evaluate the vascular and structural changes in the retina and choroid in 52 patients with asymptomatic severe carotid artery disease who underwent carotid artery revascularization. Methods: In our study, 35 patients underwent carotid endarterectomy (CEA) and 17 underwent carotid artery stenting (CAS). Biomicroscopy, fundoscopy, optical coherence tomography (OCT), and OCT-angiography (OCTA) were performed at baseline and 1 month after revascularization. Results: The subfoveal choroidal thickness (SFCT), peripapillary choroidal thickness inferior to the optic nerve head (ppCTi), total overall average retinal vascular density (rVDtot), and total overall average choriocapillaris vascular density (ccVDtot) of the eyes ipsilateral to the operated carotid artery increased significantly after revascularization, whereas a statistically significant increase was also found in the SFCT, rVDtot, and ccVDtot of the contralateral eyes in the overall cohort. Comparing the two study groups, we found that the SFCT, superior and inferior peripapillary choroidal thicknesses (ppCTs, ppCTi), rVDtot, and ccVDtot increased in both groups after revascularization, but significantly only in the CEA group. Furthermore, the temporal choriocapillaris vascular density (ccVDt) increased significantly after revascularization in both groups to a similar degree. Conclusions: Carotid artery revascularization led to a statistically significant increase in retinal and choroidal vascular densities, which indicates significantly improved ocular perfusion. The analysis of the findings of the two study groups suggests the superiority of CEA in terms of improving ocular perfusion in asymptomatic severe carotid artery disease. The rate of retinal embolization was similar in both surgical groups. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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