Search Results (183)

Retinopathy of Prematurity (ROP) affects preterm infants worldwide, involving abnormal development of retinal blood vessels associated with supplemental oxygen use in neonatal care. Although there have been strides in identifying at-risk infants, implementing early screening, updating disease criteria through the International Classification of Retinopathy of Prematurity (ICROP), and developing new therapies, ROP remains a leading cause of preventable blindness. As preterm birth survival rates rise, the incidence of ROP continues to increase and is projected to rise even in countries with abundant resources and well-established care programs. Improving ROP care requires global standardization of screening, diagnosis, and management to prevent missed diagnoses and minimize outcome variability. Intravitreal anti-vascular endothelial growth factor (VEGF) injections are changing the landscape of ROP management, but longitudinal research is needed to determine their long-term safety in preterm infants. Effective ROP management relies on teamwork across disciplines and open communication with parents. Given that parents are lifelong caregivers of a child who may be affected by ROP-related vision impairment, including them in the care team and encouraging psychosocial support is vital. Socioeconomic disparities and limited access to ROP-trained ophthalmologists exacerbate disease burden, underscoring the need for innovative solutions to improve access to care. This perspective emphasizes the importance of globally standardizing ROP prevention and care, noting that efforts are still incomplete, equitable access has not been realized, and the long-term role of anti-VEGF agents in ROP treatment remains unclear. Full article

Background and Objectives: Myopic choroidal neovascularization (mCNV) is a vision-threatening complication of pathologic myopia. While anti-VEGF monotherapy is the current standard of care, recurrence and suboptimal responses remain challenges. Faricimab is a novel bispecific antibody that targets both vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) to improve vascular stability. This study aims to evaluate the short-term efficacy and safety of a single intravitreal faricimab injection in eyes with active mCNV. Materials and Methods: This retrospective, single-center study included 27 eyes from 24 patients with active mCNV, including both treatment-naïve and previously treated cases. All eyes received a single intravitreal injection of faricimab (6.0 mg/0.05 mL). Best-corrected visual acuity (BCVA) in logMAR and central retinal thickness (CRT) via spectral-domain optical coherence tomography were assessed at baseline and one month post injection. Statistical significance was determined using paired and independent t-tests (p < 0.05). Results: The study population (mean age 55.5 ± 13.9 years; mean axial length 29.3 ± 1.6 mm) showed significant improvements at one month. Mean BCVA improved from 0.77 ± 0.71 logMAR to 0.51 ± 0.52 logMAR (p < 0.005). Mean CRT decreased from 290.2 ± 66.0 μm to 242.5 ± 45.7 μm (p < 0.005). No ocular adverse events, such as intraocular inflammation, retinal detachment, or endophthalmitis, were observed. Conclusions: A single intravitreal injection of faricimab provides significant short-term functional and anatomical improvement in this small retrospective series. Dual inhibition of VEGF-A and Ang-2 appears to be a safe and effective approach for stabilizing retinal vasculature in patients with high myopia. Larger, long-term prospective studies are needed to determine optimal treatment intervals for mCNV. Full article

Fibroblast growth factor 2 (FGF2) is expressed in retinal Müller glia cells, and its expression increases in response to photoreceptor degeneration. To investigate the physiological relevance of FGF2, we analyzed retinal morphology and cellular responses in Fgf2-deficient (Fgf2^−/−) mice. Loss of FGF2 did not affect photoreceptor survival, retinal vasculature, or retinal pigment epithelium (RPE) integrity. To further understand its role in retinal degeneration, Fgf2^−/− mice were crossed with Pde6b^STOP/STOP mice, a model of retinitis pigmentosa (RP). We then analyzed outer nuclear layer thickness, cone number, rod outer segments length, RPE morphology, and microglia number in Fgf2^−/− Pde6b^STOP/STOP and Pde6b^STOP/STOP mice. Although FGF2 was upregulated in degenerating photoreceptor cells in the Pde6b^STOP/STOP retina, its absence did not accelerate photoreceptor loss in Fgf2^−/− Pde6b^STOP/STOP mice. Interestingly, microglia numbers were significantly changed at early disease stages in Fgf2^−/− Pde6b^STOP/STOP retinas compared with Pde6b^STOP/STOP controls, suggesting that FGF2 modulates inflammatory signaling. Together, these results show that loss of FGF2 does not alter photoreceptor degeneration kinetics or retinal morphology, but may contribute to the regulation of early microglial accumulation during degeneration. Full article

The dystrophin gene encodes multiple dystrophin isoforms with tissue-specific functions, including several shorter isoforms expressed in the central nervous system and retina. While Duchenne muscular dystrophy (DMD) has historically been characterized as a primary myopathy resulting from loss of the full-length dystrophin Dp427, increasing clinical evidence indicates that dysfunction of shorter dystrophin isoforms contributes to significant extramuscular pathology, including retinal disease. In particular, loss of the Dp71 isoform has been implicated in retinal inflammation, blood–retinal barrier breakdown, and pathological angiogenesis. In this study, we investigated whether low-level residual expression of Dp71 is sufficient to mitigate retinal inflammation in the mdx3Cv mouse model, which displays reduced—but not absent—expression of multiple dystrophin isoforms. Western blot analysis revealed that mdx3Cv retinas express approximately 4% of wild-type Dp71 protein levels. Despite this marked reduction, mdx3Cv mice did not exhibit the inflammatory phenotype previously observed in Dp71-null mice. Retinal VEGF protein levels and VEGF receptor (FLT-1 and KDR) mRNA expression were preserved, while VEGF mRNA levels were modestly reduced. Furthermore, expression of inflammatory markers ICAM-1 and ALOX5AP, leukocyte adhesion to retinal vasculature, Aquaporin-4 expression, and BRB permeability to albumin were all comparable to wild-type littermates. Together, these findings demonstrate that minimal residual expression of Dp71 is sufficient to preserve retinal vascular homeostasis and prevent inflammatory and permeability defects in the mdx3Cv retina. These results further suggest that partial dystrophin restoration—at levels achievable with current exon-skipping or gene-based therapies—may be adequate to prevent or attenuate retinal pathology in DMD, providing a realistic and clinically relevant therapeutic target. Full article

Background: Our study aimed to evaluate whether OCTA can detect retinal dysfunction in hypertensive patients with atherosclerotic plaque in order to improve early detection of vascular changes and to better adjust treatment protocols. Therefore, we can potentially reduce the rate of ocular, cardiovascular and cerebral complications of hypertension and of dyslipidemia. Methods: We performed a study on hypertensive patients with dyslipidemia undergoing specific treatment. Ten OCTA parameters, the presence of carotid plaque on carotid Doppler ultrasound and three types of antihypertensive drugs were analyzed. An increased carotid intima-media thickness (IMT) (≥1.0 mm) or the presence of carotid plaque was defined as subclinical atherosclerosis. We correlated classes of medication with OCTA parameters and with Doppler assessment. Results: In the final study, we included 196 eyes of 98 patients; 51 subjects had carotid plaques. Three groups were formed: antihypertensive monotherapy, including Angiotensin-converting enzyme inhibitor (ACEI) or Calcium channel blocker (CCB) + statins, and combined antihypertensive therapy, including ACEI/Angiotensin Receptor Blocker (ARB) + statins. We found statistically significant results in the presence of atherosclerotic plaques as follows: increased avascular zone (FAZ) and decreased vascular flow area (VFA) in the ACEI group, increased FAZ Circularity and a reduction in Density Total in the CCB lot, higher values of non-flow area (NFA), FAZ Area and decreased Density Total in the ACEI/ARB group. Conclusions: The strongest correlations we found were between increased hypertension, decreased retinal microcirculation and the presence of atherosclerotic plaques in patients using combined antihypertensive therapy and statins. The results indicate that subjects with multiple therapies, advancing hypertensive retinopathy and atherosclerotic carotid plaques display a deficit in retinal vascularization. OCTA can provide early detection of microvascular changes in hypertension associated with dyslipidemia and carotid plaques. Thus, by correlating OCTA and carotid Doppler ultrasound, antihypertensive and statin therapy can be adjusted and disease risk stratification can be obtained. Full article

The miniature (mini) Ossabaw pigs are proposed as a translational preclinical model for testing and developing novel therapeutics for human diseases, including cystic fibrosis, cancer, and metabolic syndrome (MetS). In recent years, pigs have gained similar attention for studying retinal abnormalities and disorders owing to their close resemblance in size, anatomy, vasculature, and pathology to the human eye compared with their rodent counterparts. In our previous study, Ossabaw minipigs fed a Western diet for 10 weeks and followed for 3.5 months exhibited early signs of retinal degeneration and vascular abnormalities, mimicking the early stages of diabetic retinopathy (DR). To further evaluate pathomorphological alterations across neuronal and non-neuronal cell types, the present study comprehensively investigated individual retinal layers using cell-type-specific immunostaining. We found that the Western diet-fed mini pigs had reduced rhodopsin and blue opsins, changes in bipolar and ganglion cells, and reduced density of pre- and post-synaptic connections. Moreover, the retinas of obese mini pigs showed evidence of gliosis and microglial activation. Our findings suggest that a Western diet-induced metabolic disorder exhibits an early neurodegenerative milieu and further demonstrate the suitability of Ossabaw mini pigs as a model for human retinal diseases associated with MetS, such as DR and diabetic macular edema (DME). Full article

Background/Objectives: Coronary artery disease (CAD) remains one of the leading cardiovascular diseases worldwide. While obstructive CAD is well characterized and managed, identification of patients with non-obstructive CAD (NOCAD) remains challenging. Unlike the coronary vasculature, the eye’s microcirculation can be easily and non-invasively assessed. Therefore, this systematic review summarized the ophthalmological diagnostic methods used to assess microvascular alterations associated with coronary microvascular dysfunction (CMD), angina with non-obstructive coronary arteries (ANOCA), or ischemia with non-obstructive coronary arteries (INOCA). Methods: According to PRISMA guidelines, PubMed/MEDLINE and Embase databases were screened by two independent reviewers from inception to 25 November 2025. Original articles that examined ophthalmological microvascular changes by any method in adults with CMD or its subtypes were included. The quality of the studies was assessed using the JBI Critical Appraisal Checklist. Results: Of 101 identified articles, nine studies met the inclusion criteria, comprising 1894 patients. Optical coherence tomography angiography was the most frequently used imaging modality, followed by optical coherence tomography, slit-lamp smartphone imaging, and fundus photography. Five investigations employed blinded image analysis, three did not, and one study used it partially. Four studies used semi-automated measurements, four employed fully automated methods, and one study applied manual and automated measurements for different parameters. Conclusions: Despite a limited number of studies, retinal and conjunctival microvascular alterations helped differentiate CAD subtypes and may reflect systemic microcirculatory impairment among patients with ANOCA/INOCA. Ophthalmological imaging techniques have the potential to serve as non-invasive tools for detecting microvascular alterations associated with CMD in ANOCA and INOCA patients. PROSPERO Registration Number: CRD420251239875 Full article

Background/Objectives: Multiple sclerosis (MS)-related optic neuritis (ON) results in thinning of the peripapillary nerve fiber layer (pRNFL) which tends to be temporal quadrant-predominant. Optical coherence tomography angiography (OCTA) enables visualization of the retinal vasculature. Prior studies have shown reduced peripapillary vessel density (VD) in MS but data on the quadrantic pattern of peripapillary VD loss are limited. Our objective was to investigate the pattern of OCTA-derived peripapillary VD reduction in MS. Methods: People with MS (PwMS) and healthy controls (HC) underwent optic disc OCTA scans (Solix, Optovue) and VD was derived for the peripapillary region and quadrants. Eyes with ON within six months were excluded. Analyses were performed with generalized estimating equations models and standardized coefficients are presented. Results: We included 50 eyes from 29 PwMS (12 ON, 38 non-ON) and 12 eyes from 6 HC. VD in the peripapillary region was lower in MS ON eyes compared to HC with the largest effect size observed in the temporal quadrant (average: −1.47, p < 0.001; superior: −1.08, p = 0.006; inferior: −0.94; p = 0.017; temporal: −1.55; p < 0.001; nasal: −1.06, p = 0.007). In MS non-ON eyes, only temporal VD was significantly lower compared to HC eyes (temporal: −0.77, p = 0.004). Moderate to strong correlations were observed between OCT and corresponding OCTA metrics from the same regions. Conclusions: Our findings suggest that vascular alterations in the peripapillary region may exhibit a temporal quadrant predominant pattern. Larger studies are needed to further characterize the patterns and temporal evolution of retinal peripapillary vascular injury in MS. Full article

The purpose of this research is to determine whether retinal vasculatures differ between participants with schizophrenia spectrum disorder (SSD) and controls. Ninety participants (51 SSD, mean age 35.8 ± 13.5, and 39 controls, mean age 35.5 ± 11.4) underwent 3 × 3 mm² macular and 6 × 6 mm² optic nerve head (ONH) optical coherence tomography angiography (OCTA) scans. En face macula and ONH region images were divided into quadrants, binarized, and then skeletonized. Skeletonized vessel densities were compared between our two groups. Additionally, the foveal avascular zone (FAZ) size and acircularity index were compared between the two groups. There was significantly decreased vessel density in the temporal region of the ONH in the SSD group compared to controls (p = 0.033). Interestingly, the decreased vessel density was already present in patients with SSD in younger adulthood as compared to the controls (p = 0.006). There were no significant group differences in vessel density in any other region of the ONH, the ONH overall, any region of the macula, or the macula overall. There were also no significant group differences in the FAZ size or acircularity index. These data suggest there may be abnormal peripapillary retinal vasculature in patients with SSD. Whether this is a specific ocular vascular deficit or related to more systemic vascular abnormalities in SSD remains to be determined. Full article

Purpose: Current pediatric ophthalmology practice relies on adult reference values for optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) interpretation due to limited age-appropriate normative data, potentially leading to diagnostic misclassification. Methods: We conducted a prospective, cross-sectional study comparing OCT and OCT-A parameters between 37 healthy Caucasian children (1–17 years) and 28 adults (19–65 years) using identical Zeiss CIRRUS protocols. Parameters included peripapillary retinal nerve fiber layer (RNFL), macular thickness, ganglion cell-inner plexiform layer (GCIPL), optic nerve head (ONH) perfusion, and macular vascular density. Results: Children exhibited significantly thinner parafoveal macular thickness compared to adults (251.67 ± 21.32 vs. 270.36 ± 17.02 μm; p < 0.001) while RNFL thickness remained comparable. OCT-A demonstrated higher ONH perfusion in children across multiple sectors (p < 0.001). Within the pediatric cohort, younger children (1–9 years) showed higher macular vessel and perfusion density than older children (10–17 years). All pediatric scans achieved excellent image quality with no exclusions. Conclusions: Clinically significant age-related differences in retinal structure and vasculature necessitate pediatric-specific reference ranges. The demonstrated technical feasibility supports routine OCT/OCT-A implementation in pediatric practice with age-appropriate interpretation guidelines. Full article

To address the shortcomings of existing anti-VEGF monotherapy in neovascular age-related macular degeneration (nAMD), we investigated the therapeutic capabilities of exosomes obtained from human induced pluripotent stem cell (hiPSC)-derived retinal organoids in a mouse model of laser-induced choroidal neovascularization (CNV). To evaluate Retinal Organoid-derived exosome (RO-Exo) distribution after intravitreal (IVT) injection, calcein-labeled RO-Exo was observed using confocal microscopy. CNV was induced in C57BL/6 J mice by laser photocoagulation. RO-Exo was isolated from retinal organoids (differentiation days 55–65) and injected 5 days post-laser. Therapeutic efficacy was evaluated on day 12. Vascular leakage and CNV size were assessed by angiography and CD31 immunostaining. We also examined HIF-1α/VEGF-A expression (Western blotting), Retinal Pigment Epithelium (RPE) integrity markers (immunofluorescence staining for α-SMA, fibronectin, and ZO-1), and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway (phospho-ERK, -p38, -JNK) in CNV lesions. After IVT injection, RO-Exo migrated to the RPE layer, showing high retinotropic distribution. In the CNV model, RO-Exo significantly reduced vascular leakage and CNV size, with greater suppression of HIF-1α and VEGFA expression than aflibercept, the standard-of-care anti-VEGF drug. CD31-positive vasculature was decreased, accompanied by downregulation of fibronectin (a fibrotic marker) and restoration of RPE hexagonality and integrity. Furthermore, RO-Exo inhibited the activation of ERK, P38, and JNK in CNV lesions. Our study results demonstrate that RO-Exo exhibits multi-target therapeutic effects—including anti-angiogenic, anti-fibrotic, and neuroprotective actions—offering a promising alternative to conventional anti-VEGF therapy for nAMD. Full article

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