Search Results (6,193)

Autophagy is a fundamental catabolic process that degrades and recycles intracellular components, serving as a key survival mechanism in neurons. In glaucomatous optic neuropathy, autophagy has been linked to both protection of retinal ganglion cells (RGCs) and their accelerated loss, yet its precise impact remains unresolved. In this study, we established and validated a straightforward rat model of retinal ischemia/reperfusion (I/R) using double circumlimbal sutures, which reliably produced RGC apoptosis, retinal thinning, and axonal degeneration compared with controls. Early after reperfusion (1–6 h), robust induction of the autophagy marker LC3B was observed, but this activation diminished within 48 h. Other autophagy-related proteins, including ATG4, ATG7, Beclin-1, and p62, followed similar temporal patterns, while components of the mammalian target of rapamycin (mTOR) pathway displayed an inverse time course. Pharmacologic suppression of mTOR with intravitreal rapamycin administered prior to ischemia provided the most significant neuroprotection, whereas post-injury treatment yielded minimal benefit. Collectively, these findings indicate that timely stimulation of autophagy before retinal ischemic injury can enhance RGC survival and may represent a therapeutic potential for glaucoma management. Full article

This study evaluated the early structural and functional effects of combined citicoline and coenzyme Q10 (CoQ10) (CitiQ10) treatment in a laser-induced ocular hypertension (OHT) model in Swiss albino mice, focusing on retinal inflammation and neuroprotection. Sixty male CD-1 mice were assigned to four groups: vehicle, CitiQ10, OHT, and OHT + CitiQ10. OHT was induced by laser photocoagulation of limbal and episcleral veins, and CitiQ10 was administered orally starting 15 days before induction. Intraocular pressure (IOP) was measured by rebound tonometry, retinal structure was assessed by spectral domain optical coherence tomography (SD-OCT), and function was evaluated using full-field electroretinography (ffERG). At 3 days post-induction, OHT eyes exhibited significant retinal nerve fiber layer (RNFL) thickening, increased vitreous particles, and early functional impairment, particularly reduced scotopic b-wave and oscillatory potentials. CitiQ10 treatment mitigated these changes, reducing vitreous particles, moderating RNFL alterations, and not exhibiting significant changes in ERG amplitudes. At 7 days post-induction, structural and functional deficits persisted but were less pronounced in treated eyes. These findings suggest that CitiQ10 treatment may attenuate early retinal damage in glaucoma, with OCT and ffERG serving as reliable monitoring tools, supporting the therapeutic potential of this approach in early stage disease. Full article

Background and Clinical Significance: Macular holes are rare in pediatric patients and most often result from blunt trauma, commonly from soccer-related injuries. These cases present unique challenges due to delayed presentation, tightly adherent hyaloid layers, and difficulties with postoperative positioning. Larger, chronic macular holes have low spontaneous closure rates and poorer surgical outcomes, necessitating advanced surgical approaches. Herein we report a case of chronic traumatic macular hole in a pediatric patient that closed with an internal limiting membrane (ILM) flap surgical technique with silicone oil tamponade. Case Presentation: A 15-year-old male patient presented with a history of blunt ocular trauma from a soccer ball one year prior, resulting in a large chronic macular hole. The decision was made to perform pars plana vitrectomy with an inverted ILM flap technique and silicone oil tamponade. To stabilize the ILM flap and prevent displacement, a novel technique involving the placement of a single drop of silicone oil on the retinal surface prior to complete silicone oil fill was employed. This “silicone oil drop” technique allowed for smoother propagation of the oil over the flap, effectively securing it without the need for additional manipulation or perfluorocarbon liquid. Postoperatively, the macular hole was closed, and the patient’s vision improved. Conclusions: This case highlights the potential benefits of the ILM flap technique in treating pediatric macular holes with utilization of silicone oil as not only a tamponade but as a method to stabilize the flap. Full article

Geographic atrophy (GA) is a progressive cause of central vision loss with limited rehabilitation options. This prospective case series aimed to evaluate the effects of biofeedback fixation training (BFT) on visual function and vision-related quality of life (QoL) in patients with GA. Eighteen patients with total central vision loss in one eye underwent BFT on the fellow eye (study eye) using the Macular Integrity Assessment (MAIA) system, which was used to select a new, previously chosen preferred retinal locus (PRL) to stabilize fixation or adopt a new fixation locus. Patients were followed for an average of 13.2 months (range 3–26 months). Functional outcomes included best corrected visual acuity (ETDRS chart), reading performance (Radner test), and contrast sensitivity (Spot Checks test). MAIA parameters comprised average retinal sensitivity, fixation distance and stability (P1, P2), and changes in the bivariate contour ellipse area (BCEA). Vision-related quality of life was assessed using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). Following BFT, visual acuity, reading ability and contrast sensitivity improved significantly (p value: p < 0.02), and fixation stability and NEI-VFQ-25 scores showed a positive trend. These findings indicate that BFT is a feasible and promising rehabilitation approach for patients with GA. Full article

The current study investigates the influence of intersubject variability in ocular characteristics on the mapping of visual field (VF) sites to the pointwise directional angles in retinal nerve fiber layer (RNFL) bundle traces. In addition, the performance efficacy on the mapping of VF sites to the optic nerve head (ONH) was compared to ground truth baselines. Fundus photographs of 546 eyes of 546 healthy subjects (with no history of ocular disease or diabetic retinopathy) were enhanced digitally and RNFL bundle traces were segmented based on the Personalized Estimated Segmentation (PES) algorithm’s core technique. A 24-2 VF grid pattern was overlaid onto the photographs in order to relate VF test points to intersecting RNFL bundles. The PES algorithm effectively traced RNFL bundles in fundus images, achieving an average accuracy of 97.6% relative to the Jansonius map through the application of 10th-order Bezier curves. The PES algorithm assembled an average of 4726 RNFL bundles per fundus image based on 4975 sampling points, obtaining a total of 2,580,505 RNFL bundles based on 2,716,321 sampling points. The influence of ocular parameters could be evaluated for 34 out of 52 VF locations. The ONH-fovea angle and the ONH position in relation to the fovea were the most prominent predictors for variations in the mapping of retinal locations to the pointwise directional angle (p < 0.001). The variation explained by the model (R² value) ranges from 27.6% for visual field location 15 to 77.8% in location 22, with a mean of 56%. Significant individual variability was found in the mapping of VF sites to the ONH, with a mean standard deviation (95% limit) of 16.55° (median 17.68°) for 50 out of 52 VF locations, ranging from less than 1° to 44.05°. The mean entry angles differed from previous baselines by a range of less than 1° to 23.9° (average difference of 10.6° ± 5.53°), and RMSE of 11.94. Full article

Aim: To report on the clinical and genetic spectrum of retinopathy associated with CDHR1 variants in a Hungarian cohort. Methods: A retrospective cohort study was conducted at a single tertiary care referral center. The study enrolled nine patients harboring biallelic variants in the CDHR1 gene. Detailed clinical history, multimodal imaging, electroretinography, and molecular genetics are presented. Results: We identified four CDHR1 variants predicted to cause loss-of-function and five phenotypes (cone dystrophy, central areolar choroidal dystrophy, cone-rod dystrophy, rod-cone dystrophy, and late-onset macular dystrophy). The most frequent variant was the synonymous CDHR1 c.783G>A (p.Pro261=) variant (10/18 alleles, 55.6%). A novel splice acceptor site variant, CDHR1 c.349-1G>A, and a novel intronic variant, CDHR1 c.1168-10A>G, were also detected. Fundus examination revealed macular atrophy with or without peripheral retinal changes. Full-field electroretinography, available in seven patients, demonstrated decreased light-adapted and extinguished dark-adapted responses in both the rod-cone dystrophy group and patients with macular involvement. OCT imaging indicated ellipsoid zone disruption with foveal sparing in two out of nine patients and severe retinal damage in rod-cone dystrophy cases. Conclusions: The predominant clinical manifestations of cone dystrophy, cone-rod dystrophy, and macular dystrophy in the Hungarian patient cohort showed heterogeneity, with a rod-cone dystrophy phenotype observed in five of nine cases (55.6%). The natural history of CDHR1-associated retinopathy typically follows a slow progression, providing a therapeutic window, which makes the disease a candidate for gene therapy. Full article

Major traumas result from the application of multiple force components that, in adulthood, can lead to high mortality and morbidity. In forensic practice, pathological consequences arising from the rapid flexion–extension of an adult victim’s soma are observed, with typical intracranial and ophthalmological findings. The totality of these findings allows for a contribution to the definition of the Shaken Adult Syndrome (SAS). A comprehensive review, employing the PRISMA methodology, was conducted on international works pertaining to SAS. This resulted in the identification of six scientific papers, which were analyzed separately. It emerged that, for the diagnosis of SAS, the same diagnostic triad as Shaken Baby Syndrome is valid, comprising subdural hemorrhages, retinal hemorrhages, and encephalopathy. This syndrome appears to encompass a broad spectrum of pathological conditions, ranging from whiplash to diffuse axonal injury (DAI). At the conclusion of this work, we proposed a diagnostic flowchart that allows for suspected predictive diagnosis of SAS, both in live patients presenting to emergency medical services and in post-mortem cadavers. For this purpose, the collection of anamnesis and circumstantial data, the detection of external injuries, and the execution of cranial CT scans will be essential. Ultimately, microscopic examinations of the brain with specific immunomarkers and of ocular structures will enable the identification of pathognomonic findings for SAS. Full article

This pilot study assessed the effectiveness of the intravitreal dexamethasone implant (Ozurdex) in retinal vein occlusion (RVO) patients and explored potential pre-treatment biomarkers to improve management and prognosis. Eighteen patients with branch RVO (BRVO) and twenty-four with central RVO (CRVO) receiving two intravitreal injections of Ozurdex (at baseline and between 4 and 6 months) were included. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded at baseline and after 3, 6, and 12 months. Retinal morphology was assessed using optical coherence tomography (OCT), and serum biomarkers were analyzed by ELISAs. No significant BCVA improvement was observed in RVO patients, while CRT significantly decreased from 3 to 12 months. Patients without defects of the retinal inner layers, ellipsoid zone, and external limiting membrane showed significantly higher BCVA at 6 and 12 months. Both BRVO and CRVO groups demonstrated significant BCVA improvement and CRT reduction at 6 and 12 months, with better outcomes in BRVO patients. These patients exhibited lower baseline serum levels of xanthine oxidase (XO) and thrombospondin-1 (TSP-1), which inversely correlated with BCVA at 12 months. Ozurdex was effective in real-life RVO treatment, particularly in BRVO. Serum XO and TSP-1 may serve as prognostic biomarkers for RVO. Full article

Cataracts remain the leading cause of blindness worldwide, and surgery is currently the only effective clinical treatment, as no pharmacological therapy has yet been validated. Here, we explore Fullerenol, a hydroxylated fullerene derivative formulated as eye drops, as a potential nanomedicine for delaying cataract onset and progression. In UVB-induced mouse cataract models, topical Fullerenol preserved the lens transparency and histological structure. In human lens epithelial cells, Fullerenol reduced the oxidative stress, restored the mitochondrial function, alleviated the DNA damage, and suppressed the cellular senescence. RNA sequencing and pathway enrichment analyses further indicated that Fullerenol modulated the oxidative stress- and senescence-associated signaling pathways, including MAPK and TGF-β cascades, while downregulating the p53–CDKN1A (p21) axis. These findings provide new evidence that Fullerenol can mitigate photo-oxidative damage and age-related cellular dysfunction, highlighting its promise as a non-invasive and clinically translatable nanomedicine strategy for cataract management. Full article

Vitamin A in the form of 11-cis-retinaldehyde is the chromophore essential to vision. Thus, deficiencies in vitamin A necessitate the implementation of vitamin A supplementation. Moreover, some vitamin A is lost from the visual cycle due to random reactions that generate diretinaldehyde (bisretinoid) molecules; the latter are photoreactive and contribute to retinal disease. Here, we measured the systemic and ocular uptake of vitamin A along with bisretinoid as a function of vitamin A availability when supplied in the diet or by weekly i.p. injection in light- and dark-reared mice. Retinyl palmitate delivered as an i.p. bolus served to elevate plasma ROL but an associated increase in ocular 11-cisRAL was not observed in light- or dark-reared mice. In dark-reared mice, 11-cisRAL was more abundant when retinyl palmitate was provided in chow versus weekly i.p. injection; moreover, by the latter route, retinyl acetate was more effective. Conversely in dark-reared mice given retinyl palmitate by weekly i.p. injection versus chow, ocular atRAL was elevated. Liver atRE was elevated by increased retinyl palmitate in chow; the latter also favored elevated 11-cisRAL in dark-reared mice. In cyclic light-reared mice, ocular stores of atRE were increased by i.p. retinyl palmitate. With dark-rearing, there was no difference in bisretinoid (A2E) with retinyl palmitate in chow, nor by weekly i.p. injection; notably, bisretinoid levels were lower in cyclic light-reared mice due to photooxidative loss. In summary, light modulates the ocular retinoid, plasma atROL does not predict ocular levels of retinoid or bisretinoid and atRAL is elevated with sustained darkness. Full article

Diabetic retinopathy (DR) has been classically considered a microvascular disease with all diagnostic and therapeutic resources focusing on its vascular components. However, during the past years, the obtained evidence highlighted the critical pathogenic role of early neuronal impairment redefining DR as a neurovascular complication. Retinal neurodegeneration is triggered by chronic hyperglycemia, which activates harmful biochemical pathways that lead to oxidative stress, metabolic overload, glutamate excitotoxicity, inflammation, and neurotrophic factor deficiency. These drivers of neurodegeneration can precede detectable vascular abnormalities. Simultaneously, endothelial injury, pericyte loss, and breakdown of the blood–retinal barrier compromise neurovascular unit integrity and establish a damaging cyclic loop in which neuronal and vascular dysfunctions reinforce each other. The interindividual variability of these processes highlights the need to properly redefine patient phenotyping by using advanced imaging and functional biomarkers. This would allow early detection of neurodegeneration and patient subtype classification. Nonetheless, translation of therapies based on neuroprotection has been limited by classical focus on vascular impairment. To meet this need, several strategies are emerging, with the most promising being those delivered through innovative ocular routes such as topical formulations, sustained-release implants, or nanocarriers. Future advances will depend on proper guidance of these therapies by integrating personalized medicine with multimodal biomarkers. Full article

Effective and transparent medical diagnosis relies on accurate and interpretable classification of medical images across multiple modalities. This paper introduces an explainable multi-modal image analysis framework based on a dual-stream architecture that fuses handcrafted descriptors with deep features extracted from a custom MobileNet. Handcrafted descriptors include frequency-domain and texture features, while deep features are summarized using 26 statistical metrics to enhance interpretability. In the fusion stage, complementary features are combined at both the feature and decision levels. Decision-level integration combines calibrated soft voting, weighted voting, and stacking ensembles with optimized classifiers, including decision trees, random forests, gradient boosting, and logistic regression. To further refine performance, a hybrid class-specific feature selection strategy is proposed, combining mutual information, recursive elimination, and random forest importance to select the most discriminative features for each class. This hybrid selection approach eliminates redundancy, improves computational efficiency, and ensures robust classification. Explainability is provided through Local Interpretable Model-Agnostic Explanations, which offer transparent details about the ensemble model’s predictions and link influential handcrafted features to clinically meaningful image characteristics. The framework is validated on three benchmark datasets, i.e., BTTypes (brain MRI), Ultrasound Breast Images, and ACRIMA Retinal Fundus Images, demonstrating generalizability across modalities (MRI, ultrasound, retinal fundus) and disease categories (brain tumor, breast cancer, glaucoma). Full article

Background: Nuclear cataracts cause visual degradation through light scattering by aggregated proteins and particles within the crystalline lens. Existing computational models mainly consider submicron scatterers, while the optical impact of micrometer-scale particles observed in human nuclear cataracts remains underexplored. Objective: This study extends a LOCS III–based computational cataract model by incorporating micrometer-scale particles and quantitatively evaluates their effects on forward and backward light scattering across nuclear cataract grades. Methods: A physics-based scattering model was implemented using optical simulation software (LightTools). Three particle populations—nanometer-scale (S-type), submicron-scale (M-type), and micrometer-scale (L-type)—were uniformly distributed within the lens. Retinal luminance reduction was analyzed for forward scattering, while slit-lamp-based backward scattering simulations were used to evaluate luminance distributions and chromaticity changes. Particle concentrations were varied within clinically reported ranges corresponding to LOCS III grades. Results: Micrometer-scale particles had minimal impact in early nuclear cataract grades but significantly increased forward scattering and luminance loss in advanced grades (NO5–NO6). Backward scattering simulations revealed pronounced luminance enhancement and yellow chromaticity shifts with increasing micrometer-scale particle concentration. One micrometer-scale particle produced a luminance-reduction effect equivalent to approximately 6–7 submicron particles, depending on cataract severity. Conclusions: Including micrometer-scale particles enables a more complete optical representation of nuclear cataracts, linking retinal image degradation with slit-lamp appearance. The model provides a physically grounded framework for offline analysis and reference data generation to support clinical interpretation of cataract grading. Full article

Background/Objectives: Retinitis pigmentosa is a degenerative retinal disease and a major cause of inherited blindness globally. The pro-survival kinase AKT is downregulated in degenerating photoreceptors in retinitis pigmentosa, and its activation has shown neuroprotective effects in retinitis pigmentosa and other neurodegenerative disorders. In this study, we evaluated the therapeutic potential of SC79, a pharmaceutical AKT activator, in two mouse models of retinitis pigmentosa, rd1.GFP and RhoP23H.GFP. Methods: SC79 was administered intravitreally at postnatal day 12 (P12) and analysis was conducted at P16. Results: SC79 at 10 µM was well tolerated in wildtype mice, with no reduction in retinal function or thickness. In rd1.GFP mice, SC79 partially preserved peripheral outer nuclear layer (ONL) thickness, improved rod photoreceptor-driven optomotor contrast sensitivity responses, and improved cone photoreceptor morphology. Immunohistochemistry of retinal sections indicated AKT-related protein expression changes in both sham and SC79-treated rd1.GFP retinas, with sham injections leading to decreases in this pathway and SC79 injections restoring this back to uninjected protein levels or higher, indicating the damage from intravitreal injections can induce AKT-related protein expression changes. In RhoP23H.GFP mice, changes to the visual response from the therapeutic effects of SC79 were not detectable. An increased dosage of SC79 at 100 µM was evaluated in wildtype mice and showed no major toxic effects, although it did not confer neuroprotective benefits in either disease model. Conclusions: These results demonstrate the potential therapeutic effect of AKT pathway modulation for preserving photoreceptors in recessive retinitis pigmentosa, with further optimisation of treatment delivery required. Full article

Hypoxic eye diseases represent a pivotal yet often underappreciated contributor to the onset and progression of many retinal disorders. When hypoxia persists or exceeds the tissue’s compensatory capacity, it triggers pathological retinal neovascularization, blood–retinal barrier disruption, and neuronal apoptosis, ultimately resulting in irreversible visual impairment. Connexins (Cxs) form gap junction channels and hemichannels and regulate retinal cell proliferation, differentiation, and survival, thereby playing a central regulatory role in the pathogenesis of hypoxic ocular diseases. In addition to gap junctions, Cx hemichannels promote transmission of molecules between intra- and extracellular environments, further influencing retinal homeostasis under hypoxic stress. This review synthesizes recent progress in understanding connexins in localized and systemic hypoxic eye diseases. We focus on the molecular mechanisms underlying the development and progression of hypoxia-induced ocular pathology, with particular emphasis on the emerging potential of Cxs as novel therapeutic targets for hypoxic ocular diseases. Following a systematic literature search, the electronic databases PubMed and EMBASE were consulted, with the search deadline set at December 2025. The search terms employed were as follows: hypoxia, connexin, gap junctions, hemichannels. Full article