Search Results (58)

Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and laser therapy, are frequently hampered by limited drug bioavailability, rapid clearance, and treatment-related complications, primarily due to the eye’s unique anatomical and physiological barriers. Hydrogels, characterized by their three-dimensional network structure, high water content, excellent biocompatibility, and tunable physicochemical properties, have emerged as promising platforms for ophthalmic drug delivery. This review summarizes the classification, fabrication strategies, and essential properties of hydrogels, and highlights recent advances in their application to ocular diseases, including keratitis management, corneal wound repair, intraocular pressure regulation and neuroprotection in glaucoma, sustained drug delivery for AMD and DR, vitreous substitutes for retinal detachment, and therapies for DED. In particular, we highlight recent advances in stimuli-responsive hydrogels that enable spatiotemporally controlled drug release in response to ocular cues such as temperature, pH, redox state, and enzyme activity, thereby enhancing therapeutic precision and efficacy. Furthermore, this review critically evaluates translational aspects, including long-term ocular safety, clinical feasibility, manufacturing scalability, and regulatory challenges, which are often underrepresented in existing reviews. By integrating material science, ocular pathology, and translational considerations, this review aims to provide a comprehensive framework for the rational design of next-generation hydrogel systems and to facilitate their clinical translation in ophthalmic therapy. Full article

Background/Objectives: The influence of the vitreoretinal interface on neovascular age-related macular degeneration (nAMD) remains poorly characterized. Most previous studies relied solely on macular optical coherence tomography (OCT), which provides limited information about global posterior vitreous detachment (PVD). This study evaluated (1) whether ultrasonography-defined PVD status differs between nAMD eyes and healthy controls, and (2) whether baseline PVD influences macular neovascularization (MNV) phenotype and functional outcomes following anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: In this prospective longitudinal study, treatment-naïve nAMD eyes and population-based healthy controls underwent dynamic B-scan ultrasonography and spectral-domain OCT. PVD was categorized as absent, partial, or complete. nAMD eyes received intravitreal aflibercept according to a treat-and-extend protocol and were followed for 12 months. Structural parameters—including subretinal fluid (SRF), intraretinal fluid (IRF), and central foveal thickness—along with best-corrected visual acuity (BCVA) were recorded. A multivariable linear regression model was performed to assess whether PVD independently predicted BCVA gain after adjusting for age, baseline BCVA, MNV subtype, SRF, atrophy, and number of injections. Results: Absence of PVD was significantly more frequent in nAMD eyes than in controls (p < 0.001), whereas complete PVD prevalence was comparable. In nAMD, absence of PVD was associated with a higher prevalence of MNV type 2 (p = 0.032), while partial/complete PVD correlated with type 1 lesions. After 12 months, eyes without PVD achieved the greatest visual improvement (mean BCVA gain +0.34 ± 0.26), outperforming eyes with complete PVD (p = 0.026). A multivariable model confirmed that absence of PVD was an independent predictor of greater BCVA gain (β = −0.27; 95% CI −0.42 to −0.12; p = 0.0008). Eyes with complete PVD required more injections (p = 0.046). SRF and foveal-thickness reductions occurred across groups, whereas IRF changes were similar. Conclusions: Ultrasonography-defined PVD status differs markedly between nAMD and healthy eyes and independently influences neovascular phenotype and functional response to anti-VEGF therapy. These findings underscore the physiological importance of the vitreoretinal interface and support the use of ocular ultrasonography as an adjunct tool for assessing global vitreous status in selected nAMD settings. Full article

Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants’ in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial–mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28–42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment. Full article

Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Case Presentation: An 89-year-old woman with bilateral neovascular age-related macular degeneration (nAMD) developed blurred vision and mild ocular pain in both eyes four days after receiving aflibercept 8 mg injections in both of her eyes. Examination revealed a marked anterior chamber reaction with Descemet’s folds, 2+ vitreous cells, and 3+ vitreous haze bilaterally. Intraocular pressures were normal, and B-scan ultrasonography confirmed attached retinas with bilateral vitreous opacities. The clinical presentation initially raised concern for infectious endophthalmitis; however, the bilateral presentation, quiet conjunctivae, and prior history of sterile inflammation after aflibercept 2 mg supported a diagnosis of sterile intraocular inflammation. The patient was hospitalized and treated with intensive topical corticosteroids, antibiotics, and cycloplegics, resulting in rapid improvement and complete resolution of symptoms within four days with recovery of baseline vision. Conclusions: Intravitreal aflibercept 8 mg can be associated with bilateral sterile intraocular inflammation, even in patients who previously tolerated standard-dose aflibercept. Awareness of this potential adverse event is essential to avoid unnecessary interventions and to guide appropriate management. Full article

Background/Objectives: The purpose of this study was to evaluate the implementation of ultra-widefield swept-source optical coherence tomography (SS-OCT) in characterizing peripheral retinal degenerations and rhegmatogenous lesions, and to assess its potential implications for clinical management. These lesions are often challenging to visualize with conventional techniques, highlighting the need for advanced imaging modalities to improve detection and characterization. Methods: We conducted a retrospective observational study involving patients diagnosed with peripheral retinal degenerations and/or rhegmatogenous lesions referred to our center. All participants underwent comprehensive ophthalmological evaluation, including slit-lamp biomicroscopy, dilated fundus examination, and peripheral SS-OCT imaging. Key parameters assessed included the presence of vitreoretinal attachment, vitreous traction, full-thickness retinal defects, and subretinal fluid associated with the peripheral lesions under investigation. Results: A total of 107 eyes from 95 patients were included. The mean spherical equivalent was −2.18 ± 2.5 diopters, and mean BCVA was 0.03 ± 0.11. Peripheral SS-OCT imaging successfully captured and characterized 130 retinal lesions, including retinal tears (n = 34), lattice degeneration (n = 25), retinal holes (n = 21), peripheral retinoschisis (n = 17), and schisis/detachment (n = 7). Less commonly observed lesions were snail track degeneration (n = 4), white without pressure (n = 4) microcystic degeneration (n = 2), dialysis (n = 2), condensed vitreous (n = 2), and paving stone degeneration (n = 1). SS-OCT provided high-resolution visualization of the peripheral retina and vitreoretinal interface, revealing findings such as vitreous traction, everted edges in retinal holes, and associated subretinal fluid, some of which were not clinically detectable and, in several cases, directly influenced management decisions. Conclusions: Ultra-widefield SS-OCT significantly enhanced the visualization of peripheral retinal degenerations and rhegmatogenous lesions, providing clinically meaningful details that may influence diagnosis and clinical decision-making. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss. Its pathogenesis is complex and multifactorial, involving genetic predisposition, inflammation, oxidative stress, and environmental influences, which underscores the need to better understand biomarkers associated with the disease. This review provides a comprehensive translational overview of biomarkers linked to both dry and wet forms of AMD by integrating findings from human studies and preclinical mouse models, including chemical, genetic, and laser-induced paradigms. It outlines key tissue, fluid, and systemic biomarkers related to oxidative stress, inflammation, complement activation, extracellular matrix remodeling, angiogenesis, and gut microbiota alterations. The main findings highlight similarities and differences between human AMD and animal models, identify challenges in biomarker validation, and emphasize the potential of combining biomarker profiles from ocular tissues, blood, tear fluid, aqueous and vitreous humor, and gut microbiome samples to improve early diagnosis, therapeutic monitoring, and personalized treatment strategies. These insights suggest that integrating experimental and clinical biomarker data could advance precision medicine in AMD, facilitating better early detection and individualized therapies. Future research should aim to bridge these datasets to optimize biomarker-driven approaches for AMD management. Full article

Background: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the developed world, and the approved products for geographic atrophy (GA), a late-stage form of dry AMD, have shown limited efficacy and require frequent administration. Therefore, longer-lasting therapies with improved efficacy would be a welcome addition to AMD treatment. One potential therapeutic is ONL1204, a small peptide inhibitor of the Fas receptor that has prevented cell death and inflammation in retinal disease models. This study characterizes the pharmacokinetics (PK) and durability of protection conferred by ONL1204. Methods: Ocular pharmacokinetic profiles were generated over 3 months in rabbit and minipig following a single intravitreal (IVT) injection of ONL1204 at multiple doses. Ocular pharmacodynamics were evaluated in two models: a rabbit model using a single IVT injection of ONL1204 with a delayed sodium iodate challenge coupled with fluorescein angiography to quantify RPE loss, and a chronic mouse model that reflects key features of dry AMD disease pathology to assess the efficacy of repeat IVT administrations of ONL1204. Results: ONL1204 had prolonged residence in the ocular tissues of rabbit and minipig, with a vitreous humor half-life of over 100 days. ONL1204 demonstrated significant protection of the retinal pigment epithelium (RPE) in the rabbit sodium iodate model. In the chronic mouse model, two administrations of ONL1204 preserved RPE morphology, reduced caspase-8 activity, and decreased inflammation. Conclusions: These data represent key characteristics of ONL1204, highlighting its clinical potential as a therapeutic for chronic retinal diseases, including GA. Full article

Introduction: This study aimed to determine the frequency of posterior vitreous detachment (PVD) in dry and wet age-related macular degeneration (AMD) patients compared with healthy eyes via ultrawide field optical coherence tomography (UWF–OCT). Additionally, the retinal thicknesses in the central and peripheral zones of AMD patients and the control group were compared. Methods: We included 123 eyes from 83 participants with dry AMD, 123 from 87 participants with wet AMD, and 85 from 53 healthy controls. All three study groups were compared according to age, sex, best corrected visual acuity (BCVA), PVD stage, axial length, and retinal thickness in the central, perifoveal, and peripheral zones. Additional analyses included correlations between the BCVA and PVD stage and between retinal thickness and the PVD stage. Results: Complete separation of the vitreous from the macula was significantly more common in AMD patients than in the control group, as noted in 47 eyes (55.29%) in the control group, 92 eyes (74.80%) in the wet AMD group, and 93 eyes (75.61%) in the dry AMD group. The PVD stage did not significantly influence retinal thickness. BCVA in AMD patients did not correlate with the PVD stage. Conclusions: Complete PVD is more common in AMD patients than in healthy controls, as evaluated by UWF–OCT. No relationship between the PVD stage and AMD type or BCVA was observed. Full article

Background/Objectives: Submacular hemorrhage (SMH) associated with neovascular age-related macular degeneration (nAMD) can lead to significant vision loss, and the optimal management strategy remains uncertain. This study aimed to evaluate the efficacy and safety of pneumatic displacement (PD) without tissue plasminogen activator (t-PA) for SMH secondary to nAMD. Methods: A retrospective analysis was conducted on 22 eyes with SMH secondary to nAMD treated with PD without t-PA. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of intravitreal injections, and postoperative complications were assessed at baseline and follow-up. Multiple logistic regression analyses were used to identify factors associated with visual outcomes. Results: In the 22 eyes that completed the 6-month follow-up, BCVA (logMAR) was 0.88 ± 0.46 at baseline and 0.76 ± 0.63 at 6 months (p = 0.24). In the 15 eyes with 12-month follow-up, BCVA improved significantly from 0.92 ± 0.47 at baseline to 0.56 ± 0.51 at 12 months (p = 0.01). CRT significantly decreased at 3 months (p < 0.01). During this period, patients received an average of 8.13 ± 2.90 intravitreal anti-vascular endothelial growth factor (VEGF) injections. A shorter duration from symptom onset to treatment was associated with better visual outcomes (p = 0.02). Postoperative vitreous hemorrhage occurred in 31.8% of cases. Conclusions: PD without t-PA, in combination with anti-VEGF therapy, improved visual outcomes over 12 months. Early intervention and continuous anti-VEGF administration appear to be key factors in optimizing treatment outcomes. Further studies are needed to establish standardized treatment protocols for SMH associated with nAMD. Full article

Background: Bacterial endophthalmitis is a rare but serious complication of intravitreal injections (IVIs). Prefilled syringes have been introduced to reduce contamination risk during drug preparation. However, whether they lower the incidence of bacterial endophthalmitis compared to vials remains unclear. Methods: This retrospective cohort study analyzed aflibercept IVIs performed at 17 clinical centers in Japan between 2015 and 2022. Patients aged ≥20 years who received aflibercept IVIs (vial or prefilled syringe) for age-related macular degeneration, diabetic macular edema, retinal vein occlusion, or myopic choroidal neovascularization were included. Bacterial endophthalmitis was diagnosed based on clinical signs (e.g., rapid vision loss, pain, hypopyon, vitreous opacity). Incidence rates were compared using Fisher’s exact test. Results: Among 152,039 injections (43,684 prefilled syringes; 108,355 vials), 12 cases of bacterial endophthalmitis were identified (0.0046% vs. 0.0092%, p = 0.53). Poor visual outcomes were associated with Enterococcus faecalis, Streptococcus spp., and diabetes. Conclusions: Although incidence was lower in the prefilled syringe group, the difference was not statistically significant. Detecting a significant difference requires a larger sample. Further studies are needed to confirm the potential benefits of prefilled syringes in reducing endophthalmitis risk. Full article

Goldmann–Favre syndrome (GFS) is a rare vitreoretinal degenerative disorder caused by mutations in the NR2E3 gene located on the short arm of chromosome 15. This condition, inherited in an autosomal recessive manner, was first described by Favre in two siblings, with Ricci later confirming its hereditary pattern. In GFS, rod photoreceptors are essentially replaced by S-cone photoreceptors. Enhanced S-Cone Syndrome (ESCS) and Goldmann–Favre syndrome are two distinct entities within the spectrum of retinal degenerative diseases, both caused by mutations in the NR2E3 gene. Despite sharing a common genetic basis, these conditions exhibit significantly different clinical phenotypes. ESCS is characterized by an excessive number of S-cones (blue-sensitive cones) with degeneration of rods and L-/M-cones, leading to increased sensitivity to blue light and early-onset night blindness. In contrast, GFS is considered a more severe form of ESCS, involving additional features such as retinal schisis, vitreous degeneration, and more pronounced visual impairment. GFS typically manifests in the first decade of life as night blindness (nyctalopia) and progressive visual acuity impairment. The clinical features include degenerative vitreous changes such as liquefaction, strands, and bands, along with macular and peripheral retinoschisis, posterior subcapsular cataract, atypical pigmentary dystrophy, and markedly abnormal or nondetectable electroretinograms (ERGs). Although peripheral retinoschisis is more common in GFS, central retinoschisis may also occur. Despite the consistent genetic basis, the phenotype of GFS can vary significantly among individuals. The differential diagnosis should consider diseases within the retinal degenerative spectrum, including retinitis pigmentosa, congenital retinoschisis, and secondary pigmentary retinopathy. Full article

Objectives: This study aimed to predict the unknown etiology of fundus-obscuring vitreous hemorrhage (FOVH) based on preoperative conditions using machine learning (ML) and to identify key preoperative factors. Methods: Medical records of 223 eyes from 204 patients who underwent vitrectomy for FOVH of unknown etiology between January 2012 and July 2022 were retrospectively reviewed. Preoperative data, including demographic information, systemic disease, ophthalmic history, and retinal status of the unaffected eye, were collected. The postoperatively identified etiologies of FOVH were categorized into six groups: proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO) or rupture of retinal arterial macroaneurysm, neovascular age-related macular degeneration (nAMD), retinal tear, Terson syndrome, and other causes. Four ML algorithms were trained and evaluated using seven-fold cross-validation. Results: The ML algorithms achieved mean accuracies of 76.2% for artificial neural network, 74.5% for XG-Boost, 74.4% for LASSO logistic regression, and 68.5% for decision tree. Key predictive factors commonly selected by the ML algorithms included PDR in the fellow eye, underlying diabetes mellitus, subarachnoid hemorrhage, and a history of retinal tear, RVO, or nAMD in the affected eye. Conclusions: The unknown etiology of FOVH could be predicted preoperatively with considerable accuracy by ML algorithms. Previous ophthalmic conditions in the affected eye and the condition of the fellow eye were important variables for prediction. This approach might assist in determining appropriate treatment plans. Full article

Background: Observational studies have noted that patients with certain retinal degenerative diseases exhibit iron disturbances in the retina or vitreous compared to healthy controls. However, the connection between serum iron status and these diseases remains unclear. This study aims to explore the potential causal relationship between serum iron status biomarkers and the development of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Methods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between serum iron status and several retinal degenerative diseases. Genome-wide association study (GWAS) summary-level data were extracted from public GWAS databases. Inverse-variance weighting (IVW), MR-Egger regressions, Simple model, Weighted median, and Weight mode were used as MR methods. Sensitivity analysis was conducted to confirm the robustness of the results by examining horizontal pleiotropy and heterogeneity through MR-Egger intercept and leave-one-out analysis. Results: The MR analysis revealed causal relationships between genetically predicted serum iron status biomarkers and various retinal diseases. Transferrin was positively associated with the odds of AMD (whether dry or wet) (OR = 1.167, 95% CI = 1.045–1.304, p = 0.006) and wet AMD (OR = 1.194, 95% CI = 1.018–1.402, p = 0.030). Ferritin was negatively associated with the odds of wet AMD (OR = 0.555, 95% CI = 0.333–0.927, p = 0.024). Serum iron (OR = 0.508, 95% CI = 0.260–0.993, p = 0.048) and transferrin saturation (OR = 0.508, 95% CI = 0.260–0.993, p = 0.048) were negatively associated with the odds of RP. Conclusions: These findings provide evidence supporting a potential causal relationship between serum iron status and various retinal degenerative diseases, highlighting a direction for future research into the underlying mechanisms of these diseases. Full article

Background: The aim of this paper was to investigate the protein concentrations of high-temperature requirement A 1 (HTRA1) and transforming growth factor-$\mathsf{\beta }$ (TGF-$\mathsf{\beta }$) in the vitreous humor of patients with chorioretinal vascular diseases. Methods: This study measured protein concentrations of HTRA1, TGF-${\mathsf{\beta }}_{1-3}$, and vascular endothelial growth factor A (hereinafter called VEGF) in the vitreous humor from seven eyes of patients with chorioretinal vascular diseases (age-related macular degeneration, diabetic macular edema, and retinal vein occlusion) and six control eyes (idiopathic epiretinal membrane and macular hole). We analyzed the mutual relationship among the protein levels. Results: The protein levels of HTRA1 and VEGF were significantly increased in the chorioretinal vascular disease group compared with the control group (1.57 ± 0.79 $\times {10}^{-9}$ mol/mL vs. 0.68 ± 0.79 $\times {10}^{-9}$ mol/mL, p = 0.039; 3447.00 ± 3423.47 pg/mL vs. 35.33 ± 79.01 pg/mL, p = 0.046, respectively). TGF-${\mathsf{\beta }}_2$ levels were not significantly different between groups (2222.71 ± 1151.25 pg/mL for the chorioretinal vascular disease group vs. 1918.83 ± 744.01 pg/mL for the control group, p = 0.62). The concentration of HTRA1 was strongly associated with TGF-${\mathsf{\beta }}_2$ levels in the vitreous humor, independent of VEGF (r = 0.80, p = 0.0010). Conclusions: We revealed that vitreous HTRA1 was increased in patients with chorioretinal vascular diseases and strongly correlated with TGF-${\mathsf{\beta }}_2$. Full article

Photoreceptor degeneration is a major cause of untreatable blindness worldwide and has recently been targeted by emerging technologies, including cell- and gene-based therapies. Cell types of neural lineage have shown promise for replacing either photoreceptors or retinal pigment epithelial cells following delivery to the subretinal space, while cells of bone marrow lineage have been tested for retinal trophic effects following delivery to the vitreous cavity. Here we explore an alternate approach in which cells from the immature neural retinal are delivered to the vitreous cavity with the goal of providing trophic support for degenerating photoreceptors. Rat and human retinal progenitor cells were transplanted to the vitreous of rats with a well-studied photoreceptor dystrophy, resulting in substantial anatomical preservation and functional rescue of vision. This work provides scientific proof-of-principle for a novel therapeutic approach to photoreceptor degeneration that is currently being evaluated in clinical trials. Full article