Search Results (343)

Personalizing the management of neovascular age-related macular degeneration (nAMD) poses significant challenges for practicing retina specialists and their patients. This commentary addresses some of these complexities, particularly those that arise in the context of an expanding array of intravitreal agents targeting vascular endothelial growth factor (VEGF) and related retinal disease targets. Many of these newer agents approved by the Food and Drug Administration (FDA) for the treatment of nAMD have labeling that indicates that they can provide non-inferior visual outcomes when compared head-to-head with previously available treatments and can be used at significantly extended dosing intervals in some patients. It can be difficult to know if patients should be transitioned to these agents, especially those who are doing well on existing therapies. Although offering extended intervals may be appropriate for some patients with excellent disease control, retina specialists know that undertreatment risks the loss of visual acuity (VA). It can also be challenging for clinicians to interpret the results delivered by clinical trial treatment protocols compared with what is likely to occur in real-world office settings. Many retina specialists use less liberal treatment paradigms than employed in clinical study protocols and consequently many patients experience shorter injection intervals. Since VA is most closely linked to quality of life, it should be prioritized compared with other endpoints. The authors advocate for maintaining consistent treatment schedules dictated by disease control instead of switching therapies even in the presence of small amounts of macular fluid that may occur with longer injection intervals. Full article

Omega-3 fatty acids are critical components of cell membranes, including those in the retina. Specifically, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the primary omega-3 fatty acids that have been studied for their potential benefits in retinal health, preventing the progression of retinopathy. Several studies have shown that a higher intake of omega-3 fatty acids is associated with a lower risk of developing diabetic retinopathy and age-related macular degeneration (AMD). Reviewing clinical trials and observational studies that support the protective role of omega-3s in retinal disorders is essential. This comprehensive review aims to evaluate the current literature on the role of omega-3 fatty acids, exploring their mechanisms of action and anti-inflammatory, anti-angiogenic, and neuroprotective roles in the retina. Omega-3s have been shown to inhibit abnormal blood vessel growth in the retina, which is a significant factor in proliferative diabetic retinopathy and neovascular AMD. Furthermore, omega-3 fatty acids are often studied with other nutrients, such as lutein, zeaxanthin, and vitamins, for their synergistic effects on retinal health. Reviewing these combinations can help understand how omega-3s can be part of a comprehensive approach to preventing or treating retinopathies, especially in diabetic patients. This review emphasizes the preventive function of EPA and DHA in alleviating oxidative stress-related damage in retinal diseases, concentrating on their antioxidative mechanisms. Full article

Functional cell death pathways are essential for normal ocular vascular development and tissue homeostasis. As our understanding of necrosis-based cell death pathways has expanded, the inclusion of regulated forms, including necroptosis, ferroptosis, and oxytosis, has occurred. Although the existence of these pathways is well described, our understanding of their role during vascular development and pathological neovascularization is very limited. Here, we examined the role of receptor-interacting protein kinase-3 (Ripk3), a key regulator of necroptosis, in postnatal retinal vascularization and retinal and choroidal neovascularization under pathological conditions. Postnatal vascularization of the retinal superficial layer in the absence of Ripk3 (Ripk3^−/−) was not significantly different from wild-type mice. However, we noted decreased retinal endothelial cells and pericyte numbers at 3 weeks of age when the formation of the retinal primary vascular plexus was complete. In contrast, choroidal and retinal neovascularization following laser treatment and oxygen-induced ischemic retinopathy increased in the absence of Ripk3 expression, respectively. In addition, the inhibition of RIPK1/3 activity suppressed choroidal neovascularization. Thus, Ripk3 expression and/or activity may have unique roles during normal and pathological ocular vascularization through its interactions with Caspase 8 and modulation of cell death processes. Full article

Proliferative diabetic retinopathy (PDR) is the most severe complication of chronic hyperglycaemi stimulates oxidative stress that changes the retinal basement membrane function and provokes neovascularization, macular edema and retinal detachment. But an oxidative–antioxidant biomarker assessment in ocular matrices, such as aqueous humor (AH) and vitreous, might show the oxidative stress (OS) status in the posterior segment. Here, we show a cross-sectional analytical study of 39 patients who had a vitrectomy and assess the levels of different oxidative–antioxidant biomarkers in blood, aqueous and vitreous humor in three groups: diabetes mellitus 2 (DM2) with PDR [DM(+)PDR(+)] (n =13), DM2 without PDR [DM(+)PDR(−)] (n = 13) and non-DM2 non-PDR [DM(−)PDR(−)] as the control group (n = 13). Our finding suggests the presence of oxidative stress in diabetic retinopathy, as evidenced by increased levels of 8-isoprostanes and decreased levels of total antioxidant capacity from stages before the development of diabetic retinopathy. Our results reveal a notable increment in catalase levels in the DM(+)PDR(+) group in blood and vitreous humor. Likewise, we identified that the DM(+)PDR(−) group presents significant levels in 8-IP and SOD in vitreous humor and blood versus aqueous humor. These finding suggest the role of antioxidant enzymes in compensating oxidative stress mechanisms in PDR development. Full article

Retinopathy of prematurity (ROP) is primarily caused by the exposure of preterm infants with underdeveloped blood vessels to high oxygen concentrations. This damages the astrocytes that promote normal vascular development, leading to avascularity, pathological neovascularization, and retinal detachment, and even blindness as the disease progresses. In this study, the aim was to investigate the differences in the characteristics of astrocytes and blood vessels between wild-type (WT) and genetically modified mice overexpressing platelet-derived growth factor subunit A (PDGF-A) in the retina immediately after high oxygen exposure, a protocol in the oxygen-induced retinopathy (OIR) model of ROP. Our results showed that PDGF-A mice exhibited an increased population of astrocytes and higher vascular density than WT mice and that PDGF-A strengthened the resistance to hyperoxic conditions. In the OIR model, PDGF-A mice had reduced avascular zone areas following hyperoxia exposure. Furthermore, immunostaining for NG2 and CD31 showed that pericytes tended to regress earlier than endothelial cells, particularly at the vessel edges in both WT and transgenic mice, indicating relatively higher susceptibility to hyperoxia-induced damage. These findings suggest that PDGF-A plays a crucial role in stabilizing retinal vessels and may serve as a novel therapeutic target for ROP, highlighting the potential significance of PDGF-A in the pathological mechanisms of retinal diseases. Full article

Background: Age-related macular degeneration (AMD) is a multifactorial disorder, and there is growing evidence of immunological involvement in its pathogenesis. To address this, we aimed to identify biomarker candidates related to retinal antigens in patients with neovascular AMD treated with ranibizumab and healthy subjects. Materials and Methods: This study was designed as a prospective, open, parallel-group, interventional, single-center phase IV trial. Fifty subjects with neovascular AMD and twenty healthy volunteers were enrolled. The primary objective was to assess the efficacy of intravitreally (IVT) administered ranibizumab in terms of the change in best-corrected visual acuity in subjects with all subtypes of neovascular AMD and in a subgroup of pretreated AMD subjects. A secondary objective was to assess the efficacy of the same in terms of the change in central retinal thickness (CRT) in the same subjects. Another secondary objective was to identify antibodies against retinal antigens in patients with neovascular AMD treated with ranibizumab and healthy subjects. The last secondary objective was to correlate functional and structural parameters with the identified biomarker candidates to differentiate between initial and deferred responders to IVT administered ranibizumab. Serum was analyzed using customized antigen microarrays containing 58 antigens. Results: After 12 weeks of ranibizumab treatment, treated patients gained 4.02 letters on average. The central retinal thickness (CRT) measured in the complete AMD study population was significantly (p < 0.001) decreased at Week 24 compared to the baseline measurement, and the mean CRT dropped from 393.4 to 296.8 µm. A significant increase in the following autoantibodies was detected between the control group and AMD group at Week 24, as well as in the AMD group between baseline and Week 24: antibodies targeting the proteins serotransferrin, opioid growth factor receptor, 60 kDa chaperonin 2, neurotrophin-4, dermcidin, clusterin and vascular endothelial growth factor. Conclusions: The present trial was able to confirm the efficacy of ranibizumab treatment in neovascular AMD, and treatment-naïve patients benefitted the most. Up- and downregulations of antibodies were observed over the course of treatment with ranibizumab. Some antibodies seemed to have a fair correlation with the classification of initial and deferred responders. Full article

Background/Objectives: Neovascular age-related macular degeneration (nAMD) is a retinal disorder leading to irreversible central vision loss. The pro-re-nata (PRN) treatment for nAMD involves frequent intravitreal injections of anti-VEGF medications, placing a burden on patients and healthcare systems. Predicting injections needs at each monitoring session could optimize treatment outcomes and reduce unnecessary interventions. Methods: To achieve these aims, machine learning (ML) models were evaluated using different combinations of clinical variables, including retinal thickness and volume, best-corrected visual acuity, and features derived from macular optical coherence tomography (OCT). A “Leave Some Subjects Out” (LSSO) nested cross-validation approach ensured robust evaluation. Moreover, the SHapley Additive exPlanations (SHAP) analysis was employed to quantify the contribution of each feature to model predictions. Results: Results demonstrated that models incorporating both structural and functional features achieved high classification accuracy in predicting injection necessity (AUC = 0.747 ± 0.046, MCC = 0.541 ± 0.073). Moreover, the explainability analysis identified as key predictors both subretinal and intraretinal fluid, alongside central retinal thickness. Conclusions: These findings suggest that session-by-session prediction of injection needs in nAMD patients is feasible, even without processing the entire OCT image. The proposed ML framework has the potential to be integrated into routine clinical workflows, thereby optimizing nAMD therapeutic management. Full article

Retinal vascular diseases encompass several retinal disorders, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and retinal vascular occlusion; these disorders are classified as similar groups of disorders due to impaired retinal vascularization. The aim of this review is to address the main signaling pathways involved in the pathogenesis of retinal vascular diseases and to identify crucial molecules and the importance of their interactions. Vascular endothelial growth factor (VEGF) is recognized as a crucial and central molecule in abnormal neovascularization and a key phenomenon in retinal vascular occlusion; thus, anti-VEGF therapy is now the most successful form of treatment for these disorders. Interaction between angiopoietin 2 and the Tie2 receptor results in aberrant Tie2 signaling, resulting in loss of pericytes, neovascularization, and inflammation. Notch signaling and hypoxia-inducible factors in ischemic conditions induce pathological neovascularization and disruption of the blood–retina barrier. An increase in the pro-inflammatory cytokines—TNF-α, IL-1β, and IL-6—and activation of microglia create a persistent inflammatory milieu that promotes breakage of the blood–retinal barrier and neovascularization. Toll-like receptor signaling and nuclear factor-kappa B are important factors in the dysregulation of the immune response in retinal vascular diseases. Increased production of reactive oxygen species and oxidative damage follow inflammation and together create a vicious cycle because each factor amplifies the other. Understanding the complex interplay among various signaling pathways, signaling cascades, and molecules enables the development of new and more successful therapeutic options. Full article

Neovascular age-related macular degeneration (nAMD) is one of the major causes of vision impairment that affect millions of people worldwide. Early detection of nAMD is crucial because, if untreated, it can lead to blindness. Software and algorithms that utilize artificial intelligence (AI) have become valuable tools for early detection, assisting doctors in diagnosing and facilitating differential diagnosis. AI is particularly important for remote or isolated communities, as it allows patients to endure tests and receive rapid initial diagnoses without the necessity of extensive travel and long wait times for medical consultations. Similarly, AI is notable also in big hubs because cutting-edge technologies and networking help and speed processes such as detection, diagnosis, and follow-up times. The automatic detection of retinal changes might be optimized by AI, allowing one to choose the most effective treatment for nAMD. The complex retinal tissue is well-suited for scanning and easily accessible by modern AI-assisted multi-imaging techniques. AI enables us to enhance patient management by effectively evaluating extensive data, facilitating timely diagnosis and long-term prognosis. Novel applications of AI to nAMD have focused on image analysis, specifically for the automated segmentation, extraction, and quantification of imaging-based features included within optical coherence tomography (OCT) pictures. To date, we cannot state that AI could accurately forecast the therapy that would be necessary for a single patient to achieve the best visual outcome. A small number of large datasets with high-quality OCT, lack of data about alternative treatment strategies, and absence of OCT standards are the challenges for the development of AI models for nAMD. Full article

Neovascular age-related macular degeneration (nAMD), a leading cause of blindness in older adults, presents a challenging pathophysiology involving choroidal neovascularization (CNV) and retinal degeneration. Current treatments relying on intravitreal (IVT) administration of anti-angiogenic agents are costly and of moderate effectiveness. Metformin, the common anti-diabetic drug, has been associated with decreased odds of developing AMD. Studies have shown that metformin can mitigate cellular aging, neoangiogenesis, and inflammation across multiple diseases. This preclinical study assessed metformin’s impact on vessel growth using choroidal explants before exploring IVT metformin’s effects on laser-induced CNV and light-induced retinal degeneration in C57BL/6J and BALB/cJ mice, respectively. Metformin reduced new vessel growth in choroidal explants in a dose-dependent relationship. Following laser induction, IVT metformin suppressed CNV and decreased peripheral infiltration of IBA1⁺ macrophages/microglia. Furthermore, IVT metformin protected against retinal thinning in response to light-induced degeneration. IVT metformin downregulated genes in the choroid and retinal pigment epithelium which are associated with angiogenesis and inflammation, two key processes that drive nAMD progression. These findings underscore metformin’s capacity as an anti-angiogenic and neuroprotective agent, demonstrating this drug’s potential as an accessible option to help manage nAMD. Full article

Background/Objectives: Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular age-related macular degeneration (nvAMD). While proactive and adequate treatment generally leads to better visual outcomes, various factors, including the disease type, ocular findings, lifestyle, and systemic status, affect the visual prognosis in clinical settings. This study aimed to identify the factors that affect the visual prognosis in patients with nvAMD treated with anti-VEGF therapy. Methods: We conducted a multicenter retrospective cohort study at eight tertiary referral centers in Japan, where we reviewed the medical records of patients newly diagnosed with nvAMD between January 2014 and December 2019. These patients had started treatment with either ranibizumab (0.5 mg) or aflibercept (2.0 mg) and were followed for at least 1 year. We evaluated the impact of the disease type, systemic factors, and initial fundus findings on the best-corrected visual acuity (BCVA) at 1 year. Results: This study included 182 patients (129 men, 53 women), with a mean age of 75.0 ± 8.6 years. The disease types were categorized as typical AMD (53%), polypoidal choroidal vasculopathy (PCV) (43%), and retinal angiomatous proliferation (RAP) (4%). Univariate analysis identified age, the baseline logarithm of the minimum angle of resolution BCVA, intraretinal fluid (IRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM). Multivariate analysis identified the following significant risk factors associated with vision worsening: age, smoking history, diabetes, and the presence of IRF and PED. Conclusions: The presence of IRF, PED, and SHRM at the start of treatment and a history of smoking and diabetes may be associated with a poor visual prognosis in patients with nvAMD. Full article

Owing to its promiscuous roles, poly (ADP-ribose) polymerase-1 (PARP-1) is involved in various neurological disorders including several retinal pathologies. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus affecting the retina. In the present review, we highlight the importance of PARP-1 participation in pathophysiology of DR and discuss promising potential inhibitors for treatment. A high glucose level enhances PARP-1 expression; PARP inhibitors have gained attention due to their potential therapeutic effects in DR. They target different checkpoints (blocking nuclear transcription factor (NF-κB) activation; oxidative stress protection, influence on vascular endothelial growth factor (VEGF) expression, impacting neovascularization). Nowadays, there are several improved clinical PARP-1 inhibitors with different allosteric effects. Combining PARP-1 inhibitors with other compounds is another promising option in DR treatments. Besides pharmacological inhibition, genetic disruption of the PARP-1 gene is another approach in PARP-1-initiated therapies. In terms of future treatments, the limitations of single-target approaches shift the focus onto combined therapies. We emphasize the importance of multi-targeted therapies, which could be effective not only in DR, but also in other ischemic conditions. Full article

Background: Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions. Methods: A comprehensive literature search was conducted in major medical databases through July 2024. Relevant studies on monoclonal antibodies for intraocular diseases were included. Two independent researchers screened the literature, extracted data, and assessed study quality. Cost-effectiveness analyses were also reviewed. Results: Anti-vascular endothelial growth factor (VEGF) antibodies, such as bevacizumab, ranibizumab, and aflibercept, showed significant therapeutic effects in neovascular age-related macular degeneration (NVAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Tumor necrosis factor-alpha (TNF-α) inhibitors demonstrated promising results in treating noninfectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios. Conclusions: Monoclonal antibodies are vital for treating intraocular diseases, but continuous innovation and rigorous clinical evaluation are essential. Future research should focus on developing novel delivery systems, exploring combination therapies, conducting long-term follow-up studies, and investigating personalized treatment strategies to provide safer, more effective, and cost-effective therapeutic solutions. Full article

Dye-based angiography is the main imaging modality in evaluating the vasculature of the eye. Although most commonly used to assess retinal vasculature, it can also delineate normal and abnormal blood vessels in the anterior segment diseases—but is limited due to its invasive, time-consuming methods. Thus, anterior segment optical coherence tomography angiography (AS-OCTA) is a useful non-invasive modality capable of producing high-resolution images to evaluate the cornea and ocular surface vasculature. AS-OCTA has demonstrated the potential to detect and delineate blood vessels in the anterior segment with quality images comparable to dye-based angiography. AS-OCTA has a diverse range of applications for the cornea and ocular surface, such as objective assessment of corneal neovascularization and response to various treatments; diagnosis and evaluation of ocular surface squamous neoplasia; and evaluation of ocular surface disease including limbal stem cell deficiency and ischemia. Our review aims to summarize the new developments and clinical applications of AS-OCTA for the cornea and ocular surface. Full article

Background/Objectives: This study evaluates the impact of anti-vascular endothelial growth factor (anti-VEGF) treatment on neovascular age-related macular degeneration (nAMD) with and without pigment epithelial detachment (PED) over a one-year period. Methods: Conducted at a tertiary referral center in Taiwan, this retrospective analysis included 88 eyes treated with intravitreal aflibercept injections. Patients were categorized into four groups based on the presence or absence of PED at baseline and 12 months post-treatment. Results: Significant reductions in central macular thickness (CMT) and PED height were observed, although no statistical difference was found in best-corrected visual acuity (BCVA). The presence or type of PED did not negatively impact visual outcomes. Among nAMD patients with persistent PED throughout the first year of anti-VEGF treatment, linear regression analysis showed that mixed-type PED revealed poor final BCVA compared to those with serous PED. The analysis also identified older age and poorer initial BCVA as predictors of less favorable visual outcomes. Conclusions: This study highlights the effectiveness of anti-VEGF therapy in real-world settings and offers insights into factors influencing visual outcomes for nAMD patients with PED. Full article