Search Results (172)

Retinal vasculature is essential for maintaining visual function by supporting metabolically active neurons. However, the retina lacks redundant blood supply, rendering it highly susceptible to vascular dysfunction. Understanding mechanisms of retinal vascular abnormalities is critical for therapies that preserve vascular and neuronal integrity, yet progress has been hindered by limited models and genetic diversity. To address this gap, we examined the retinal vasculature in multiple aged strains from the BXD recombinant inbred mouse panel, a genetically diverse, tractable, and physiologically relevant platform for uncovering novel genetic drivers and disease mechanisms. We identified BXD32 as a striking outlier with dramatically reduced vessel density. Using optical coherence tomography, optical coherence tomography angiography, and histological analyses, we comprehensively characterized retinal vasculature and structural integrity of BXD32 mice during aging. We found progressive, age-dependent vascular dysfunction and degeneration, beginning in the deep capillary plexus and advancing to the intermediate and superficial layers. These changes were accompanied by neuronal degeneration, including photoreceptor loss and thinning of the ganglion cell complex. Our findings establish BXD32 as a spontaneous and genetically tractable model of inherited retinal neurovascular degeneration and provide a foundation for future studies to identify causative genetic loci and underlying molecular mechanisms. Full article

Uveal melanoma is the most common primary intraocular malignancy in adults, most frequently arising from the choroid, followed by the ciliary body and iris. Its diagnosis and management require precise characterization of tumor morphology, localization, and associated complications to optimize visual and systemic outcomes. Recent advances in optical coherence tomography (OCT), anterior segment OCT (AS-OCT), and OCT angiography (OCTA) have expanded the ophthalmologist’s ability to non-invasively visualize structural and vascular changes associated with this disease. In fact, enhanced depth imaging (EDI) and swept-source (SS) OCT can provide detailed views of deep ocular structures, enabling early detection of hallmark features such as subretinal fluid, retinal pigment epithelium disruption, and dome- or mushroom-shaped choroidal elevations; AS-OCT improves evaluation of lesions of the anterior segment, revealing iris architecture distortion and angle involvement; OCTA facilitates the visualization of abnormal tumor vasculature and detection of radiation-induced microvascular changes, including capillary dropout and foveal avascular zone enlargement. Moreover, these imaging modalities have demonstrated utility in differentiating uveal melanoma from pseudomelanomas, such as choroidal nevi, hemangiomas, and metastases. The present review aims at objectively assessing the use of OCT and OCTA in the diagnosis, treatment, and follow up of ocular melanoma, emphasizing their crucial role in identifying pathologic biomarkers of this potentially fatal ocular disease. Full article

Pericytes produce vascular endothelial growth factor-A (VEGF-A; hereafter referred to as VEGF). VEGF inhibits pericyte proliferation and migration through enhanced VEGFR2 and PDGFRβ heterodimerization. Heterodimerization of these receptors on perivascular supporting cells, mediated by VEGF in culture, mitigates signaling through these receptors and promotes a quiescent phenotype. However, the detailed cellular mechanisms and the significance of these interactions in vivo require further investigation. The cell-autonomous activities of pericyte VEGF expression during vascular development and neovascularization remain unknown. Here we utilized mice conditionally lacking Vegfa in pericytes (Vegfa^PC) to examine its impact on retinal vascular development and pathological ocular neovascularization. Vascular integrity was also assessed in older mice using fundus imaging and fluorescein angiography. The lack of Vegfa pericyte expression delayed the initial spreading of the superficial layer of the retinal vasculature. Mice lacking Vegfa pericyte expression had similar numbers of retinal endothelial cells and arteries to their wild-type littermates. However, the number of pericytes was significantly reduced in younger Vegfa^PC mice but increased in more mature mice. In addition, pericyte Vegfa deficiency did not impact responses during oxygen-induced ischemic retinopathy and laser-induced choroidal neovascularization. Thus, pericyte VEGF expression plays a role during early stages of retinal vascular development with limited influence on mature retinal vascularization, its integrity, and neovascularization. Full article

This study analyzes retinal fundus images to distinguish healthy retinas from those affected by diabetic retinopathy (DR) and glaucoma using a dual-framework approach: vascular texture analysis and global color distribution analysis. The texture-based approach involved segmenting the retinal vasculature and extracting eight Haralick texture features from the Gray-Level Co-occurrence Matrix. Significant differences in features such as energy, contrast, correlation, and entropy were found between healthy and pathological retinas. Pathological retinas exhibited lower textural complexity and higher uniformity, which correlates with vascular thinning and structural changes observed in DR and glaucoma. In parallel, the global color distribution of the full fundus area was analyzed without segmentation. RGB intensity histograms were calculated for each channel and averaged across groups. Statistical tests revealed significant differences, particularly in the green and blue channels. The Mahalanobis distance quantified the separability of the groups per channel. These results indicate that pathological changes in retinal tissue can also lead to detectable chromatic shifts in the fundus. The findings underscore the potential of both vascular texture and color features as non-invasive biomarkers for early retinal disease detection and classification. Full article

Purpose: To investigate the therapeutic potential of inducible pluripotent stem cell (hiPSC)-based vascular repair, we evaluated two vascular reparative cell populations, CD34⁺ cells derived from hiPSC (hiPSC-CD34⁺) and endothelial colony forming cells (ECFCs) derived from hiPSC (iPS-ECFCs), alone and in combination, in a type 2 diabetic (db/db) mouse model of DR. Methods: hiPSC-CD34⁺ cells (1 × 10⁴) or iPSC- ECFCs (1 × 10⁵) alone or in combination (1.1 × 10⁵) were injected into the vitreous of immunosuppressed db/db mice with six months of established diabetes. One month post-injection, mice underwent electroretinography (ERG) and optical coherence tomography (OCT) to evaluate functional and structural retinal recovery with iPSC administration. Immunohistochemistry (IHC) was used to assess recruitment and incorporation of cells into the retinal vasculature. Retinas from the experimental groups were analyzed using Functional Proteomics via Reverse Phase Protein Array (RPPA). Results: Functional assessment via ERG demonstrated significant improvements in retinal response in the diabetic cohorts treated with either hiPSC-derived CD34⁺ cells or hiPSC-ECFCs. Retinal thickness, assessed by OCT, was restored to near-nondiabetic levels in mice treated with hiPSC-CD34⁺ cells alone and the combination group, whereas hiPSC-ECFCs alone did not significantly affect retinal thickness. One month following intravitreal injection, hiPSC-CD34⁺ cells were localized to perivascular regions, whereas hiPSC-ECFCs were observed to integrate directly into the retinal vasculature. RPPA analysis revealed interaction-significant changes, and this was interpreted as a combination-specific, non-additive host responses (m⁶A, PI3K–AKT–mTOR, glycolysis, endothelial junction pathways). Conclusions: The studies support that injection of hiPSC-CD34⁺ cells and hiPSC-ECFCs, both individually and in combination, showed benefit; however, iPSC combination-specific effects were identified by measurement of retinal thickness and by RPPA. Full article

The retinal vasculature provides a unique and non-invasive window into the health of the circulatory system. Josef Flammer, a pioneer in ocular vascular research, was the first to systematically describe how the state of retinal blood vessels reflects broader cardiovascular health. Because the retina is the only part of the human body where blood vessels can be visualized non-invasively, it serves as a valuable proxy for understanding microvascular conditions elsewhere, including the heart, brain, and lymphatics. Recent work has shown that retinal vasculature can be used as a proxy for microcirculatory dysfunction in other body systems, and that treatment using medical doses of vitamins can restore microcirculation, easing symptoms in disorders as diverse as glaucoma, AMD, and lymphedema without the need of pharmacological agents. The advent of machine learning tools to read retinal images promises both early detection of conditions and simplified monitoring of treatment progression. Full article

Objective: Retinal capillary dropout, characterized by acellular capillaries or “ghost vessels,” is an early pathological sign of diabetic retinopathy (DR) that remains undetectable through standard clinical imaging techniques until visible morphological changes, such as microaneurysms or hemorrhages, occur. This study aims to develop a non-destructive artificial intelligence (AI)-based method using fluorescein angiography (FA) images to detect early-stage, silent retinal capillary dropout. Methods: We utilized 94 FA images and corresponding destructive retinal capillary density measurements obtained through retinal trypsin digestion from 51 Nile rats. Early capillary dropout was defined as having an acellular capillary density of ≥18 counts per mm². A DenseNet based deep learning model was trained to classify images into early capillary dropout or normal. A Bayesian framework incorporating diabetes duration was used to enhance model predictions. RNA sequencing was conducted on retinal vasculature to identify molecular markers associated with capillary early dropout. Results: The AI-based FA imaging model demonstrated an accuracy of 80.85%, sensitivity of 84.21%, specificity of 75.68%, and an AUC of 0.86. Integration of diabetes duration into a Bayesian predictive framework further improved the model’s performance (AUC = 0.90). Transcriptomic analysis identified 43 genes significantly upregulated in retinal tissues preceding capillary dropout. Notably, inflammatory markers such as Bcl2a1, Birc5, and Il20rb were among these genes, indicating that inflammation might play a critical role in early DR pathogenesis. Conclusions: This study demonstrates that AI-enhanced FA imaging can predict silent retinal capillary dropout before conventional clinical signs of DR emerge. Combining AI predictions with diabetes duration data significantly improves diagnostic performance. The identified gene markers further highlight inflammation as a potential driver in early DR, offering novel insights and potential therapeutic targets for preventing DR progression. Full article

Purpose: To review the current literature on the combined use of cataract surgery (or lensectomy) and vitrectomy in pediatric patients, with a focus on clinical indications, surgical techniques, outcomes, and complications across various pediatric ocular pathologies. Methods: A narrative review of published studies addressing the use of combined lensectomy and vitrectomy (LV) in pediatric patients was conducted. Conditions discussed include congenital cataracts, ectopia lentis, retinopathy of prematurity (ROP), retinal detachment (RD), and persistent fetal vasculature (PFV). Key surgical considerations, visual and anatomical outcomes, and postoperative complications were examined. Results: The literature search yielded a total of 160 articles, of which 43 met the inclusion criteria and were included in this review. Although lens-sparing vitrectomy (LSV) is preferred in many pediatric cases to preserve accommodation and reduce complications, combined LV is often necessary in advanced or complex diseases. Studies have shown that combined LV can achieve favorable anatomical outcomes, but functional visual recovery remains variable and is affected by factors such as patient age, baseline ocular anatomy, and disease severity. Postoperative complications such as glaucoma, visual axis opacification (VAO), and intraocular lens (IOL) dislocation are more frequent with combined procedures and require long-term follow-up and rehabilitation. Conclusions: Combined cataract surgery (or lensectomy) and vitrectomy may represent a valuable strategy in the management of complex pediatric ocular conditions, particularly when individualized to the clinical context. Tailored surgical approaches are essential to optimize anatomic and functional outcomes. Further prospective studies and harmonized multicenter registries are needed to develop evidence-based principles that can guide individualized surgical decision-making in this unique patient population. Full article

Background: Our study evaluated the correlation between internal carotid artery stenosis (ICAS) and retinal microvascular changes in patients with hypertensive retinopathy, dyslipidemia and ICAS. We analyzed vascular measurements provided by optical coherence tomography angiography (OCTA) and carotid Doppler ultrasonography (US) and linked OCTA parameters with carotid artery US measurements on the same side. Statistical differences in OCTA analysis among three groups (no stenosis, mild stenosis and moderate stenosis) were evaluated and correlated with carotid Doppler parameters. Our study aimed to evaluate whether OCTA can be proposed as a screening method in patients diagnosed with mild and moderate ICAS in order to improve the early detection of carotid changes, thus potentially reducing the rate of cardiovascular and cerebral complications of ICAS. Methods: We conducted a study on hypertensive patients with ICAS using six OCTA parameters in the analysis of the retinal vasculature and carotid Doppler US velocities of three carotid arteries and the vertebral artery (VA). Kruskal–Wallis and Dunn’s post hoc tests were used to determine whether there were statistically significant differences between the normal, mild and moderate stenosis groups. Spearman and Pearson correlation were used to obtain correlations among OCTA parameters such as the foveal avascular zone (FAZ), non-flow area (NFA), vascular flow area (VFA) and blood flow velocity on carotid Doppler US. Results: In the final analysis, 49 patients were included and 3 groups of stenosis were obtained, comprising 21 subjects with no stenosis, 19 with mild stenosis and 9 with moderate stenosis. Right eye and left eye groups were formed. In the right eye group with right ICAS, we found statistically significant results for FAZ circularity when comparing the normal stenosis group to the mild stenosis group (p = 0.025) and the mild stenosis group to the moderate stenosis group (p = 0.006). Statistically significant results were also observed for NFA when comparing the normal stenosis group to the moderate stenosis group (p = 0.004) and the mild stenosis group to the moderate stenosis group (p = 0.011). When comparing the FAZ area (p = 0.016) and VFA (p = 0.037) for the normal and moderate groups, statistically significant values were obtained. When comparing the normal and moderate stenosis groups with regard to the left eye, we found statistically significant results for VFA (p = 0.041), NFA (p = 0.045) and VFA (p = 0.029). When comparing the mild and moderate carotid artery stenosis groups, we obtained statistically significant results for NFA (p = 0.001), FAZ area (p = 0.007) and VFA (p = 0.013). In the right eye group, correlations between internal carotid artery (ICA) peak systolic velocity (PSV) and VFA (rho = −0.286), ICA end-diastolic velocity (EDV) and NFA (r = 0.365), external carotid artery (ECA) PSV and VFA (r = −0.288; rho = −0.317), common carotid artery (CCA) PSV and NFA (rho = −0.345), CCA EDV and NFA (rho = −0.292) and VA PSV and VFA (r = −0.327; rho = −0.379) were found. When analyzing OCTA parameters, we found statistically significant results for NFA and VFA (r = −0.374; rho = −0.288). Correlations were also found in the left eye group between ICA PSV and NFA (r = −0.351; rho = −0.313), ICA EDV and VFA (r = −0.421; rho = −0.314), ECA PSV and NFA (r = −0.412; rho = −0.457), CCA PSV and NFA (p = −0.288; rho = −0.339), and CCA EDV and NFA (r = −0.404; rho = −0.417). Conclusions: Our study found correlations between carotid Doppler velocities and OCTA vascular flow parameters; thus, OCTA may be used as a tool for monitoring the microvascular changes associated with carotid stenosis. OCTA can provide insights concerning the overall vascular condition of the patient, since it provides subjective data on vessel density and flow; therefore, by monitoring hypertensive patients with both OCTA and carotid Doppler US, we may be able to increase efficiency in screening and diagnosing patients with IACS. Full article

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). Key drivers of DR include mitochondrial dysfunction, oxidative stress, and chronic inflammation, which lead to premature senescence of cells within the retinal vasculature. Senolytics improve outcomes in both animal models and in patients with severe forms of DR. In this review, we discuss (i) the role of endothelial senescence in each stage of DR pathogenesis, (ii) methods for detecting senescence in cultured endothelial cells and retinal vessels, and (iii) potential mechanistic explanations for how cells within retinal vessels resist DM-driven senescence. Full article

Background/Objectives: The aim of the current investigation was to assess the short-term changes in retinal-choroidal vasculature and the morphological complexity of non-exudative macular neovascularization (NE-MNV) using optical coherence tomography angiography (OCTA) and spectral-domain optical coherence tomography (SD-OCT). Methods: Sixteen eyes of 12 patients with NE-MNV underwent baseline and six-month follow-up examinations, including comprehensive ophthalmological assessment and imaging. Central macular thickness, foveal avascular zone, vessel density, flow area, and choroidal vascularity index were analyzed. NE-MNV morphology was quantitatively assessed for area, vessel characteristics, and fractal dimensions. Results: Significant changes in NE-MNV morphology were noted over six months, especially in fractal dimensions, vessel junctions, and vessel length (p-values: 0.01, 0.037, and 0.036, respectively). While there was an increase in the NE-MNV area, it did not reach statistical significance. No significant changes were shown regarding the standard SD-OCT and OCTA output parameters or choroidal measurements. Conclusions: The increase in NE-MNV fractal dimensions suggests rising complexity in the neovascular network and may indicate possible implications for clinical management. The correlation between baseline and follow-up measures underscores a trend toward complexity, pointing to the necessity for closer monitoring of patients with higher NE-MNV fractal dimensions. Full article

Background/Objectives: Diabetic retinopathy (DR) remains a leading cause of preventable blindness, with its global prevalence projected to rise sharply as diabetes incidence increases. Early detection and timely management are critical to reducing DR-related vision loss. Optical Coherence Tomography Angiography (OCTA) now enables non-invasive, layer-specific visualization of the retinal vasculature, facilitating more precise identification of early microvascular changes. Concurrently, advancements in artificial intelligence (AI), particularly deep learning (DL) architectures such as convolutional neural networks (CNNs), attention-based models, and Vision Transformers (ViTs), have revolutionized image analysis. These AI-driven tools substantially enhance the sensitivity, specificity, and interpretability of DR screening. Methods: A systematic review of PubMed, Scopus, WOS, and Embase databases, including quality assessment of published studies, investigating the result of different AI algorithms with OCTA parameters in DR patients was conducted. The variables of interest comprised training databases, type of image, imaging modality, number of images, outcomes, algorithm/model used, and performance metrics. Results: A total of 32 studies were included in this systematic review. In comparison to conventional ML techniques, our results indicated that DL algorithms significantly improve the accuracy, sensitivity, and specificity of DR screening. Multi-branch CNNs, ensemble architectures, and ViTs were among the sophisticated models with remarkable performance metrics. Several studies reported that accuracy and area under the curve (AUC) values were higher than 99%. Conclusions: This systematic review underscores the transformative potential of integrating advanced DL and machine learning (ML) algorithms with OCTA imaging for DR screening. By synthesizing evidence from 32 studies, we highlight the unique capabilities of AI-OCTA systems in improving diagnostic accuracy, enabling early detection, and streamlining clinical workflows. These advancements promise to enhance patient management by facilitating timely interventions and reducing the burden of DR-related vision loss. Furthermore, this review provides critical recommendations for clinical practice, emphasizing the need for robust validation, ethical considerations, and equitable implementation to ensure the widespread adoption of AI-OCTA technologies. Future research should focus on multicenter studies, multimodal integration, and real-world validation to maximize the clinical impact of these innovative tools. Full article

Objectives: The aim of this study was to investigate retinal and choroidal microvascular changes in patients with axial spondyloarthritis (axSpA) treated with long-term anti-TNF therapy and NSAIDs and in healthy control subjects using optical coherence tomography angiography (SS-OCT-A). Methods: A total of 162 eyes from 81 participants were included: 52 eyes from 26 axSpA patients treated with anti-TNF therapy (≥5 years), 44 eyes from 22 axSpA patients treated with NSAIDs, and 66 eyes from 33 healthy control subjects. SS-OCT-A imaging was used to assess retinal thickness, ganglion cell layer thickness, retinal nerve fiber layer thickness, and the vessel densities of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC). Disease activity was assessed with ASDAS-CRP. Results: Both axSpA subgroups showed a significant expansion of the foveal avascular zone and reduced SCP and DCP densities compared to the controls. The CC vessel density was higher in axSpA patients than in healthy subjects. The anti-TNF group had a lower CC vascular density than the NSAIDs group. The disease duration correlated with a decreased central DCP density and increased paracentral SCP and CC densities. Conclusions: SS-OCT-A revealed subclinical retinal and choroidal changes in axSpA patients, highlighting the impact of chronic inflammation on the retinal vasculature. While anti-TNF therapy effectively controls systemic inflammation, it cannot completely prevent microvascular changes. Further studies are needed to assess the clinical relevance of these results. Full article

Purpose: Proton irradiation is used to treat choroidal melanoma of the eye. The impact on non-malignant retinal cells is currently understudied. Therefore, we here report a mouse model to investigate the impact of proton irradiation on the retina. Methods: We performed a proton beam irradiation of 5–15 Cobalt-Gray-Equivalent (CGE) of the eyes of female C57Bl6/J (Cx3cr1^+/+), Cx3cr1^gfp/+ and Cx3cr1^gfp/gfp mice mimicking the clinical situation and evaluated the structure, function and cellular composition of the retina up to 24 weeks after irradiation. Results: Proton beam irradiation of the eye with 15 CGE leads to cataract formation after 24 weeks without affecting the gross anatomy of the retinal vasculature as shown by Fundus imaging in all genotypes respectively. However, 10 and 15 CGE, lead to a significant decrease in NG2 positive cell numbers and all three dosages induced an increase in GFAP immunoreactivity. At 24 weeks a dosage of 15 CGE resulted in functional impairment and a decrease of NG2 positive cells in both WT and Cx3cr1 animals. Iba1 cell immunoreactivity was increased in all genotypes. However, in the Cx3cr1 animals the invasion of Iba1 cells into the deep vascular layer was partially prevented. This was accompanied by a less severe functional impairment in the irradiated Cx3cr1^gfp/gfp vs. WT. Conclusions: Although the gross anatomy of the retina does not seem to be affected by proton beam irradiation, the cellular composition and retinal function changed significantly in both WT and Cx3cr1 mice reflecting the clinical situation. Moreover, cataract formation was one of the major long-term effects of irradiation. We conclude that the murine model (WT and Cx3cr1 genotype) can be used to investigate proton-beam associated side effects in vivo as well as to test prospective interventions. Moreover, the loss of Cx3cr1 seems to be partially protective. Full article

Diabetic retinopathy is the most common diabetic complication of the microvasculature and one of the leading causes of acquired vision loss worldwide. Yet, the current treatments for this blinding disease are futile to many diabetics. Accordingly, new biomarkers and therapeutics for diabetic retinopathy are needed. We discovered that STEAP4 (Six-Transmembrane Epithelial Antigen of the Prostate 4) is significantly increased in peripheral blood mononuclear cells of diabetics. STEAP4 expression was gradiently increased from low levels in diabetics without retinopathy to successively higher levels in diabetics with more severe disease. Although the role of STEAP4 in the diabetic retina is unclear, these results provide strong evidence that this metabolic enzyme could be a potential biomarker for diabetic retinopathy progression. Thus, the central goal of this study was to evaluate if this potential biomarker impacts the intrinsic pathologies that lead to the development of diabetic retinopathy. In diabetic mice, STEAP4 was significantly increased and co-localized with 4-Hydroxy-2-nonenal in the Müller glia and photoreceptor layers of the retina. STEAP4 inhibition significantly decreased reactive oxygen species in murine photoreceptor cells, human Müller glia, and retinas of diabetic mice. Administering an intravitreal injection of anti-STEAP4 to diabetic mice halted Occludin degradation in the retinal vasculature. Similarly, anti-STEAP4 treatment of human retina endothelial cells halted cell death mediated by diabetic donor sera. Collectively, our findings provide strong evidence that STEAP4 impacts the intrinsic pathologies that initiate the development of diabetic retinopathy. Suggesting that STEAP4 could be a novel biomarker and clinically relevant therapeutic target for this diabetic complication and blinding disease. Full article