Search Results (453)

Glaucoma is recognized as a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) is considered the only modifiable risk factor, current medical treatments are challenged by issues such as inadequate IOP control and ocular side effects. Rho kinase (ROCK) inhibitors have been developed as a novel pharmacologic class targeting the trabecular meshwork to enhance conventional aqueous humor outflow. In this review, the pharmacokinetics and IOP-lowering efficacy of key ROCK inhibitors are summarized. Beyond IOP reduction, ROCK inhibitors exhibit neuroprotective, anti-inflammatory, antifibrotic, and ocular perfusion-enhancing effects. Finally, we analyzed the limitations and future prospects of ROCK inhibitors in the management of glaucoma. Full article

Background/Objectives: This study investigates adaptive changes in long-lasting pattern electroretinogram (PERG) responses in ocular hypertension (OHT) and open-angle glaucoma (OAG) patients, and in healthy subjects. Methods: Sixty consecutive individuals were recruited, including 20 OHT, 20 OAG, and 20 normal subjects. All participants underwent comprehensive ophthalmologic examination, 30–2 perimetry, and retinal nerve fiber layer imaging. Steady-state (7.5 Hz) PERGs were recorded over approximately 2 min, in response to 90% contrast alternating gratings within a large field size. The recordings were acquired into a sequence of 10 averages (packets), lasting 10 s each, following a standardized adaptation paradigm (Next Generation PERG, PERGx). Key outcome measures included PERGx parameters reflecting response amplitude and phase changes over time. Results: The PERGx grand average scalar amplitude, a surrogate of ordinary PERG, was significantly reduced in both OHT and OAG groups compared to normal subjects (p < 0.01). In contrast, minimal adaptation changes were noted in PERGx amplitude among all groups. The PERGx phase exhibited a progressive decline over time, with consistent delays of approximately 20 degrees across all groups. Angular dispersion of the PERGx phase increased significantly in OHT patients compared to normal subjects (p < 0.05). An inverse relationship was observed between PERGx angular dispersion and treated intraocular pressure, specifically in OHT patients. Conclusions: The findings suggest that both OHT and OAG eyes may exhibit temporal abnormalities in PERG adaptation, potentially indicating early dysfunction in retinal ganglion cell activity. Translational Relevance: PERGx phase changes may have significant implications for glaucoma early detection and management. Full article

Trabeculectomy with mitomycin C is a key surgical intervention for managing glaucoma when conservative treatments fail. The success of trabeculectomy is influenced by various factors, including preoperative ocular characteristics like conjunctival vascularity. This study aims to explore the relationship between the preoperative conjunctival vascular area and post-trabeculectomy outcomes in glaucoma patients. By analyzing the conjunctival vascular density, intraocular pressure (IOP), bleb morphology, laser suture lysis (LSL) frequency, and postoperative eye drops, this research sheds light on the impact of preoperative vascularity on surgical success. Results show that lower preoperative conjunctival vessel density is associated with favorable outcomes, such as better bleb formation and reduced need for postoperative interventions, while higher conjunctival vessel density correlates with complications like hyphema. These findings emphasize the importance of assessing preoperative conjunctival vascularity to optimize trabeculectomy outcomes and personalize treatment strategies for glaucoma patients. Full article

Obstructive sleep apnoea (OSA) is a prevalent condition characterised by intermittent upper airway obstruction during sleep, resulting in recurrent hypoxia and sleep fragmentation. Emerging evidence highlights the significant impact of OSA on neuro-ophthalmological health, linking it to conditions such as glaucoma, optic neuropathy, papilledema, and visual field defects. These associations emphasise the importance of understanding the mechanisms connecting OSA to neuro-ophthalmological disorders to enhance early diagnosis and management. This review explores the pathophysiological pathways, including hypoxia-induced vascular dysregulation, oxidative stress, inflammation, and intracranial pressure fluctuations, that contribute to ocular and neurological impairments in OSA patients. Advanced diagnostic tools, such as optical coherence tomography and polysomnography, offer promising avenues for detecting subclinical neuro-ophthalmological changes, enabling timely intervention. Management strategies, primarily centred on continuous positive airway pressure therapy, have shown efficacy in mitigating OSA-related neuro-ophthalmological complications. However, surgical and pharmacological interventions and lifestyle modifications remain vital components of a multidisciplinary approach to care. Despite advancements, significant research gaps persist, particularly in understanding the long-term impact of OSA treatment on neuro-ophthalmological outcomes and identifying specific biomarkers for early detection. Future research should prioritise longitudinal studies, interdisciplinary collaborations, and personalised medicine approaches to address these challenges. Recognising and treating neuro-ophthalmological disorders in OSA patients is imperative for improving quality of life and preventing irreversible visual and neurological damage. Full article

Background: An acute angle-closure attack (AAC) is an ocular emergency that results from a rapid increase in intraocular pressure (IOP). Sustained IOP elevation induces severe degeneration of retinal ganglion cells (RGCs) without treatment. Overactivated microglia, key participants in innate immune responses, have critical roles in the pathogenesis of IOP-induced RGC death, although precise mechanisms remain unclear. In the present study, we used a rat ex vivo acute glaucoma model to investigate the role of microglial signaling in RGC death and examined whether pharmacological depletion of microglia using a CSF-1R inhibitor, PLX5622, exerts neuroprotection against pressure-induced retinal injury. Methods: Ex vivo rat retinas were exposed to hydrostatic pressure (10 mmHg or 75 mmHg) for 24 h. Pressure-dependent changes in retinal microglia and RGCs were detected by immunofluorescence. Morphological changes in the retina and RGC apoptosis were examined using light microscopy and TUNEL staining, respectively. The expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β were examined using Western blotting. Effects of PLX5622, an agent that depletes microglia, were examined in morphology, apoptosis, and protein expression assays, while TAK-242, a TLR4 inhibitor, was examined against protein expression. Results: Pressure loading at 75 mmHg markedly increased activated microglia and apoptotic RGCs in the isolated retinas. Western blotting revealed increases in expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β at 75 mmHg compared to 10 mmHg. Inhibition of pressure-induced increases in NLRP3 by TAK-242 indicates that pressure elevation induces RGC death via activation of the TLR4–NLRP3 inflammasome cascade. PLX5622 depleted microglia at 75 mmHg and significantly decreased expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β at 75 mmHg, resulting in preservation of RGCs. Conclusions: These results indicate that pressure elevation induces proliferation of inflammatory microglia and promotes IL-1β production via activation of the TLR4–NLRP3 inflammasome cascade, resulting in RGC death. Pharmacological depletion of microglia with PLX5622 could be a potential neuroprotective approach to preserve RGCs from inflammatory cytokines in AAC eyes. Full article

Objective: To conduct a comparative analysis of layer-by-layer macular thickness, peripapillary retinal nerve fiber layer (pRNFL), and minimum rim width (MRW) between the eyes of patients with prostate cancer undergoing treatment with androgen receptor pathway inhibitors (ARPIs) and those of age- and sex-matched healthy controls, with the aim of assessing the potential effects of ARPIs on retinal structure. Methods: In this prospective cross-sectional study, 80 eyes of 80 patients with ARPI-treated metastatic prostate cancer and 80 eyes of 80 age-matched healthy controls were evaluated using Heidelberg Spectralis optical coherence tomography (OCT). Layer-by-layer macular thickness, pRNFL, and MRW were measured and compared between groups. Results: Thickness in most segments of retinal layers and pRNFL, as well as all MRW values, were significantly lower in the ARPI-treated group than in the controls (p < 0.05). No significant differences were observed between groups in terms of age, visual acuity, intraocular pressure, central corneal thickness, or lens status. Conclusions: This study is the first to evaluate layer-by-layer macular thickness in patients with metastatic prostate cancer treated with ARPIs, revealing significant thinning in nearly all macular layers, pRNFL, and MRW. These findings suggest that ARPI therapy may induce neurodegenerative changes in retinal and optic nerve structures. Therefore, further research is warranted to assess the ocular safety of these therapeutic agents. Full article

Background/Objectives: The relationship between upper trapezius muscle stiffness and choroidal circulatory dynamics remains unclear. This study aimed to examine changes in upper trapezius muscle stiffness and choroidal circulatory dynamics before and after trapezius muscle self-stretching. Methods: Eighteen healthy adults in their 20s (median age ± standard error: 21.0 ± 4.9 years) and eight healthy adults in their 40s (age: 43.0 ± 15.2 years) were included. Intraocular pressure (IOP); systolic, diastolic, and mean blood pressure (BP); heart rate (HR); ocular perfusion pressure (OPP); and salivary alpha-amylase (sAA) activity—as an indicator of autonomic nervous system function—were measured at baseline and after trapezius muscle self-stretching. Upper trapezius muscle stiffness was assessed using ultrasound strain elastography, whereas choroidal circulation was evaluated using laser speckle flowgraphy to determine the mean blur rate (MBR), a relative measure of macular blood flow velocity. Results: Significant reductions in systolic and mean BP; OPP; sAA activity; and MBR were observed after trapezius muscle self-stretching in both groups; however, no significant changes were found in IOP and HR. A significant decrease in upper trapezius muscle stiffness was observed after self-stretching only in the 20-year-old group. Conclusions: In healthy adults in their 20s and 40s, trapezius muscle self-stretching may enhance parasympathetic nervous system activity, resulting in decreased systemic and choroidal circulatory parameters. However, the reduction in muscle stiffness observed only in younger participants suggests that short-term self-stretching may be less effective in reducing trapezius muscle stiffness with advancing age. Full article

Ocular diseases including glaucoma, diabetic retinopathy and age-related macular degeneration represent a growing global health burden, with current treatments often providing only symptomatic relief. Through an integrated approach combining preclinical models, molecular biology, and clinical insights, this review synthesizes 25 years of my translational research to advance therapeutic strategies for these conditions. Key findings demonstrate the following: (1) the dual neuroprotective and intraocular pressure-lowering effects of natural compounds (EGCG, forskolin) in glaucoma models; (2) successful development of Uparant, a first-in-class peptide inhibitor of pathological angiogenesis with efficacy in retinal disease models; and (3) innovative drug delivery systems (melatonin nanomicelles, liposomal sprays) that enhance ocular bioavailability. Notably, some of these approaches have progressed to early-phase clinical trials, demonstrating translational potential. Significant challenges remain in optimizing sustained drug delivery and addressing the heterogeneity of ocular diseases through personalized approaches. Future directions include combinatorial therapies and the application of artificial intelligence for treatment optimization. Collectively, this work establishes a framework for developing multi-target therapies that address both the molecular mechanisms and clinical needs in ophthalmology. Full article

Background: The biomechanical properties of ocular tissues are critical to physiological processes that span ocular development, aging, and disease. The structural integrity of these tissues is important in mediating how the eye responds to strain and stress that pose challenges to physiological homeostasis. In the posterior segment, the peripapillary sclera and lamina separate the intraocular chamber and the fluid-filled subarachnoid space. Degradation of each contribute to pathogenic progression in multiple conditions and are largely determined by the integrity and architecture of collagen fibers, especially type I collagen. Methods: We used atomic force microscopy to measure how stress induced by elevations in intraocular pressure impacts stiffness of the peripapillary sclera and glial lamina in the rat eye and whether changes in stiffness could be influenced by topical treatment of a reparative mimetic of type I collagen. Results: Four weeks of elevated intraocular pressure reduced Young’s modulus in peripapillary sclera and glial lamina, coincident with reduced anterograde transport along the optic projection to the brain. Reduction in tissue stiffness correlated with an increase in fragmented collagen. Topical application of collagen mimetic peptide during the period of elevation countered both. Conclusions: Collagen remodeling occurs in many ocular conditions that influence the peripapillary sclera and glial lamina, including glaucoma and myopia. Our results suggest that topical application of collagen mimetic peptides that intercalate with and repair collagen damaged by disease processes could serve to mitigate changes in tissue stiffness and integrity due to degraded collagen. Full article

Objective: The aim of this study was to evaluate the clinical outcomes of sutureless scleral-fixated (SSF) Soleko Fil Carlevale intraocular lens (SC-IOL) implants associated with pars plana vitrectomy (PPV) in patients with aphakia secondary to complicated cataract surgery or IOL luxation nationwide. Methods: A multicenter, national, retrospective study of 268 eyes (268 patients) which underwent simultaneous PPV and SC-IOL implantation was conducted. Demographics; ocular data; pre-surgical, surgical and post-surgical details; and refractive results were collected. Intra- and postoperative complications and management details were described. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) and central retinal thickness (CRT) were collected at 1 week and at 1, 3, 6 and 12 months post-surgery. Kaplan–Meier curves were constructed to assess the cumulative probability of postoperative BCVA, IOP levels, macular edema (ME) and corneal decompensation. Results: The cumulative probability of final VA ≤ 0.3 logMAR was 64.4% at 12 months follow-up. The probability of IOP > 21, ≥25 and ≥30 mmHg was 29.8%, 16.9% and 10.1%, respectively, and the cumulative probability of IOP-lowering treatment was 42.3% at 12 months. Glaucoma surgery was required in 3.7% of the eyes (10/268). The cumulative probability of postoperative ME development was 26.6% at 12 months, managed with topical treatment alone (73.5%) and intravitreal injections (26.5%). Corneal transplantation was required in 3.7% of the eyes (10/268). Conclusions: Sutureless scleral-fixated SC-IOL is an adequate therapeutic alternative in the management of aphakia with good visual results and an acceptable safety profile in routine clinical care. Longer-term studies are needed to evaluate its results and complications compared to other therapeutic alternatives. Full article

(1) Aim: To evaluate early real-world outcomes of switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD) in the United Kingdom. (2) Methods: This retrospective, observational study included 59 eyes from 50 patients with treatment-refractory nAMD previously treated with multiple anti-vascular endothelial growth factor (anti-VEGF) agents. Eyes were switched to aflibercept 8 mg without loading doses and treated using a treat-and-extend regimen. Functional, anatomical, and safety outcomes were evaluated over a mean (SD) follow-up of 33.5 (10.4) weeks. (3) Results: The mean (SD) age was 80.2 (6.3) years, and 28 (56.0%) of 50 patients were male. At baseline, the mean (SD) best corrected visual acuity (BCVA) was 66.0 (14.4) letters, with 33 (55.9%) eyes achieving ≥70 letters. The mean (SD) baseline central subfield thickness (CST) was 367.2 (100.7) µm. Prior to switching to aflibercept 8 mg, the mean (SD) number of injections for each eye was 26.9 (19.0), with the most recent mean (SD) treatment interval of 7.7 (1.7) weeks. Switching to aflibercept 8 mg resulted in extension of the mean (SD) injection interval from 7.7 (1.7) weeks to 8.7 (2.2) weeks (p < 0.01). BCVA and CST remained stable, with a significant reduction in pigment epithelial detachment (PED) height (232.5 µm to 211.6 µm, p < 0.01). No serious ocular adverse events or intraocular pressure (IOP) elevations requiring treatment were reported. (4) Conclusion: Aflibercept 8 mg demonstrated early treatment durability, anatomical benefit, and a favourable short-term safety profile in eyes with treatment-refractory nAMD. Further prospective studies are warranted. Full article

Previous models of extraocular mechanics have often assumed isotropic properties for ocular tissues, despite evidence indicating anisotropy in the optic nerve sheath (ONS). To investigate this further, we developed a finite element model (FEM) of horizontal eye rotation using MRI data from a living subject with normal tension glaucoma. Mechanical properties were derived from tensile tests on 17 post-mortem human eyes, revealing previously unrecognized anisotropic characteristics in the ONS. We simulated ±32° horizontal eye rotations and compared isotropic versus anisotropic ONS properties using the Holzapfel model. Strain distributions in the optic nerve (ON) were analyzed using ABAQUS 2024 software. During 32° adduction, stress and strain were concentrated at the ONS-sclera junction, reaching 8 MPa and 40% with isotropic properties, and 15 MPa and 30% with anisotropic properties. In contrast, during 32° abduction, stress was lower and strain was higher in the isotropic case (6 MPa and 30%) compared to the anisotropic case (12 MPa and 25%). Increased intraocular and intracranial pressures had minimal impact on the mechanical responses. These findings suggest that the anisotropic properties of the ONS increase stress concentration at the optic disc while reducing strain during eye movements, offering new insights into ocular biomechanics. A novel phenomenon emerged from the simulations: during larger ductions, the peripapillary Bruch’s membrane is predicted to wrinkle, forming undulations with an approximately 20 μm amplitude and 100 μm wavelength at its interface with the retina and choroid. Full article

Background/Objectives: Glaucoma and Alzheimer’s disease (AD) are neurodegenerative conditions with vascular underpinnings. This study aimed to explore the relationship between blood pressure parameters such as mean arterial pressure (MAP), pulse pressure (PP), and cerebral perfusion pressure (CPP) and cognitive performance in patients with AD, normal-tension glaucoma (NTG), and healthy controls. We hypothesized that NTG patients, like those with mild cognitive impairment (MCI), may experience subtle cognitive changes related to vascular dysregulation. Methods: Ninety-eight participants (35 NTG, 17 AD, 46 controls) were assessed for CPP, MAP, OPP, and cognitive performance. Statistical analyses compared groups and examined correlations. Results: AD patients showed lower CPP and MAP (p < 0.001), indicating systemic vascular dysfunction, while NTG patients had higher ocular perfusion pressure (OPP) (p = 0.008), suggesting compensatory mechanisms. CPP correlated with visuospatial abilities in AD (r = 0.492, p = 0.045). MAP correlated with the Clock drawing test (CDT) scores in the NTG group (r = 0.378, p = 0.025). PP negatively correlated with cognition in AD (r = −0.527, p = 0.016 for CDT scores) and controls (r = −0.440, p = 0.002 for verbal fluency and r = −0.348, p = 0.019 for total ACE scores). Conclusions: The study highlights distinct hemodynamic profiles: systemic dysfunction in AD and localized dysregulation in NTG. These findings emphasize the role of vascular dysregulation in neurodegeneration, with implications for personalized treatment approaches targeting vascular health in neurodegenerative conditions. Full article

Vestibular atelectasis (VA) is a rare clinical entity characterized by a collapse of the endolymphatic space resulting in vestibular loss with the possible onset of positional and/or sound/pressure-induced vertigo. It could be idiopathic or secondary to other inner-ear diseases including Meniere’s disease (MD). A collapse of the membranous labyrinth involving the semicircular canals (SCs) and the utricle represents its distinctive histopathological feature. While specific radiological patterns consistent with VA have been described on contrast-enhanced MRI with delayed acquisitions, an impairment of the blood–labyrinthine barrier (BLB) could be detected in several disorders leading to vestibular loss. We conducted a narrative review of the literature on VA focusing on the putative pathomechanisms accounting for positional and sound/pressure-induced nystagmus despite unilateral vestibular loss (UVL) in this condition, providing two novel cases of VA. Both patients presented with a clinical picture consistent with unilateral MD that rapidly turned into progressive UVL and positional and/or sound/pressure-induced vertigo. In both cases, the posterior SC was initially impaired at the video-head impulse test (vHIT) and both cervical and ocular VEMPs were initially reduced. Progressively, they developed unsteadiness with paretic spontaneous nystagmus, an impairment also for the lateral and anterior SCs, caloric hypo/areflexia and VEMPs areflexia. They both exhibited ipsilesional nystagmus to sound/pressure stimuli and in one case a persistent geotropic direction-changing positional nystagmus consistent with a “light cupula” mechanism involving the lateral SC of the affected side. A collapse of the membranous labyrinthine walls resulting in contact between the vestibular sensors and the stapes footplate could explain the onset of nystagmus to loud sounds and/or pressure changes despite no responses to high- and low-frequency inputs as detected by caloric irrigations, vHIT and VEMPs. On the other hand, the onset of positional nystagmus despite UVL could be explained with the theory of the “floating labyrinth”. Both patients received contrast-enhanced brain MRI with delayed acquisition exhibiting increased contrast uptake in the pars superior of the labyrinth, suggesting an impairment of the BLB likely resulting in secondary VA. A small intralabyrinthine schwannoma was detected in one case. VA should always be considered in case of positional and/or sound/pressure-induced vertigo despite UVL. Full article

Background: Glaucoma is a leading cause of irreversible visual loss worldwide, characterized by progressive retinal ganglion cell (RGC) degeneration and optic nerve damage. Current therapies mainly focus on lowering intraocular pressure (IOP), yet fail to address pressure-independent neurodegenerative mechanisms. Melatonin, an endogenously produced indoleamine, has gained attention for its potential in modulating both IOP and neurodegeneration through diverse cellular pathways. This review evaluates the therapeutic relevance of melatonin in glaucoma by examining its mechanistic actions and emerging delivery approaches. Methods: A comprehensive literature search was conducted via PubMed and Medline to identify studies published between 2000 and 2025 on melatonin’s roles in glaucoma. Included articles discussed its effects on IOP regulation, RGC survival, oxidative stress, mitochondrial integrity, and inflammation. Results: Evidence supports melatonin’s involvement in IOP reduction via MT receptor activation and its synergism with adrenergic and enzymatic regulators. Moreover, it protects RGCs by mitigating oxidative stress, preventing mitochondrial dysfunction, and inhibiting apoptotic and inflammatory cascades. Recent advances in ocular drug delivery systems enhance its bioavailability and therapeutic potential. Conclusions: Melatonin represents a multi-target candidate for glaucoma treatment. Further clinical studies are necessary to establish optimal dosing strategies, delivery methods, and long-term safety in patients. Full article