Search Results (60)

This narrative review of rapid eye movement (REM) focuses on its primary etiology and how it fits into the larger framework of neurophysiology and general physiology. Arterial blood flow in the retina may be sensitive to the full overlying ‘weight’ of its adjacent and contiguous vitreous humor caused by the humoral mass effect in the Earth’s gravitational field. During waking hours of the day, this ‘weight’ is continuously shifted in position due to changing head position and eye movements associated with ordinary environmental observations. This reduces its impact on any one point on the retinal field. However, during sleep, the head may maintain a relatively constant position (often supine), and observational eye movements are minimal, leaving essentially one retinal area exposed at the ‘bottom’ of each eye, relative to gravity. During sleep, REM may provide a mechanism for frequently repositioning the retina with respect to the weight it incurs from its adjacent (overlying) vitreous humor. Our findings were consistent with the intermittent terrestrial nocturnal development of ‘gravitational ischemia’ in the retina, wherein the decreased blood flow is accompanied metabolically by decreased oxygen tension, a critically important metric, with a detrimental influence on nerve-related tissue generally. However, the natural mechanisms for releasing and resolving gravitational ischemia, which likely involve glymphatics and cerebrospinal fluid shifts, as well as REM, may gradually fail in old age. Concurrently associated with old age in some individuals is the deposition of alpha-synuclein and/or tau in the retina, together with similar deposition in the brain, and it is also associated with the development of Parkinson’s disease and/or Alzheimer’s disease, possibly as a maladaptive attempt to release and resolve gravitational ischemia. This suggests that a key metabolic parameter of Parkinson’s disease and Alzheimer’s disease may be a lack of oxygen in some neural tissues. There is some evidence that oxygen therapy (hyperbaric oxygen) may be an effective supplemental treatment. Many of the cardinal features of spaceflight-associated neuro-ocular syndrome (SANS) may potentially be explained as features of gravity opposition physiology, which becomes unopposed by gravity during spaceflight. Gravity opposition physiology may, in fact, create significant challenges for humans involved in long-duration space travel (long-term microgravity). Possible solutions may include the use of artificial gravitational fields in space, such as centrifuges. Full article

Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H₂O₂) or by subjecting retinal neuronal cells to 8 h of oxygen–glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties. Full article

Background/Objectives: Retinal ischemia–reperfusion (I/R) injury is a common mechanism in glaucoma, diabetic retinopathy, and retinal vein occlusion, leading to progressive loss of retinal ganglion cells (RGCs). This study investigates the regulatory role of miR-21-5p and its interaction with Signal Transducer and Activator of Transcription 3 (STAT3) in retinal I/R injury. Methods: An acute intraocular hypertension (AIH) rat model was used to induce retinal I/R. The interaction between miR-21-5p and STAT3 was examined by dual-luciferase reporter assays. miR-21-5p and STAT3 expression were quantified by qRT-PCR and Western blotting. Retinal morphology, microglial polarization, and RGC survival were assessed by H&E staining and immunofluorescence. In vitro, microglia and RGCs were subjected to oxygen–glucose deprivation/reperfusion (OGD/R), and microglial-conditioned media (MCM) were applied to RGCs. Results: (1) miR-21-5p ameliorated AIH-induced retinal damage in vivo. (2) Overexpression of miR-21-5p inhibits M1 polarization of RM cultured in vitro. (3) MCM from miR-21-5p-overexpressing microglia attenuated OGD/R-induced RGC death. (4) miR-21-5p downregulates STAT3 expression to inhibit RM M1 polarization. (5) miR-21-5p down-regulation of STAT3 levels inhibits M1 polarization and reduces apoptosis of RGCs in retinal microglia of AIH rats. Conclusions: miR-21-5p alleviates retinal I/R injury by restraining microglial M1 polarization through direct repression of STAT3, thereby promoting RGC survival. These findings identify the miR-21-5p/STAT3 axis as a potential therapeutic target for ischemic retinal diseases. Full article

Dengue virus infection frequently involves the eye, manifesting with hemorrhages, uveal inflammation, retinal vascular changes and maculopathy. These ocular manifestations may arise during the acute febrile phase or emerge weeks later. Studies from endemic regions report that up to one-quarter of hospitalized patients develop eye-related symptoms. Furthermore, studies confirm a higher risk of new uveitis cases following dengue infection. Breakdown of the blood–ocular barrier—driven by antibody-mediated enhancement, complement activation and release of inflammatory mediators—leads to vascular leakage, tissue injury and ischemia. Diagnosis relies on clinical examination supplemented by imaging (OCT, angiography) and laboratory confirmation of dengue. Mild anterior inflammation often responds to topical steroids, while sight-threatening posterior disease requires systemic corticosteroids and, in refractory cases, immunomodulatory agents. Visual outcomes depend on the initial severity; anterior uveitis typically resolves without sequelae, whereas vasculitis or foveal involvement may leave lasting deficits. This review integrates the current understanding of dengue-related eye disease, emphasizing its varied presentations and the importance of early recognition. Further research into targeted, mechanism-based therapies is needed to optimize visual outcomes. Full article

Background: Chemical eye burns are a serious ophthalmic emergency that can lead to permanent vision loss in severe cases. This study aims to evaluate structural changes in the posterior segment of the eye in individuals who have experienced chemical burns. Methods: The study included 64 eyes from 54 patients with chemical burns (chemical burn group) and 87 healthy eyes from 87 subjects (control group), matched by age and sex. Patients had confirmed burns with limbal ischemia, no glaucoma, normal intraocular pressure, and no major ocular or systemic diseases. Burned eyes were examined during the acute phase and again at 3 months, with some followed up at 6 months if significant retinal asymmetry was detected. Retinal nerve fiber layer (RNFL) thickness was assessed in four quadrants, and ganglion cell complex (GCL++) thickness was analyzed using automated segmentation of optical coherence tomography (OCT) maps. Results: This study compared measurements between the burn group, the control group, and timepoints. OCT analysis revealed no significant difference in total RNFL thickness between burn patients and controls (mean difference: −1.14 µm, 95% CI: −3.92 to 1.64). Similarly, GCL++ thickness did not differ significantly between groups (mean difference: −0.97 µm, 95% CI: −3.31 to 1.37). At 6-month follow-up, a non-significant decline in both RNFL and GCL++ thicknesses was observed. Logistic regression identified higher Dua grade as an independent predictor of RNFL thinning (OR: 4.816, 95% CI: 1.103–21.030; p = 0.037). Patients with severe ocular chemical burns (Dua grade ≥ 3) demonstrated reduced RNFL thickness in all quadrants compared to healthy controls. The most pronounced reductions were observed in the nasal and superior quadrants (p = 0.007 and p = 0.069, respectively); however, after applying Bonferroni correction for multiple comparisons, only the difference in the nasal quadrant remained statistically significant (adjusted p = 0.035). Conclusions: Although overall RNFL and GCL++ thicknesses did not differ significantly between burn patients and healthy controls, patients with severe ocular chemical burns (Dua grade ≥ 3) showed a significant reduction in RNFL thickness, in the nasal quadrant. Higher Dua grade was identified as an independent predictor of RNFL thinning. These findings suggest a potential association between burn severity and posterior segment changes, highlighting the need for further longitudinal studies with larger cohorts. Full article

Retinal ischemia is implicated in ocular diseases involving aberrant neovessel proliferation that characterizes proliferative retinopathies. Their therapy still remains confined to the intravitreal administration of anti-vascular endothelial growth factor (VEGF) medication, which is limited by side effects and progressive reduction in efficacy. Mimicking neovascular diseases in rodents, although of great help for translating fundamental mechanistic findings and assessing therapeutic potential in humans, is limited by the rodent’s short life span, which prevents retinal vessel proliferation over time. However, the oxygen-induced retinopathy (OIR) model, which mimics retinopathy of prematurity, seems to meet some criteria that are common to proliferative retinopathies. The present review provides insight into preclinical models and their suitability to mimic proliferative retinopathies. Further considerations will be applied to emerging approaches and advanced methodologies for the management of proliferative retinopathies, leading to the identification of new therapeutic targets, including our contribution in the field. Major emphasis is given to the possibility of using systemic therapies either alone or in combination with intravitreal anti-VEGF administration to maximize clinical benefits by combining drugs with different modes of action. This review is concluded by an in-depth discussion on future advancements and a critical view of preclinical finding translatability. Despite the major effort of preclinical and clinical research to develop novel therapies, the blockade of VEGF activity still remains the only treatment for proliferative retinopathies for more than twenty years since its first therapeutic application. Full article

Background: Intra-arterial chemotherapy (IAC) is increasingly useful for treating intraocular retinoblastoma (Rb). It offers targeted delivery of chemotherapy with reduced systemic exposure. In this study, we evaluate management outcomes and identify predictive factors for globe salvage following IAC in children with Rb. Methods: This retrospective study included 20 eyes of 20 melphalan-based IAC-treated patients (67 sessions) between 2015 and 2023 in a tertiary cancer center (King Hussein Cancer Center) in Jordan. Data collection included patients’ demographics, tumor staging, eye salvage, complications, and survival, followed by statistical comparisons between eye salvage rates and clinical factors. Results: The median age of IAC initiation was 38 months (range: 6–78 months). IAC was used as a primary treatment in 35% (7/20) of eyes and as a secondary treatment following systemic chemotherapy in 65% (13/20) of eyes. Nineteen (95%) eyes showed initial tumor regression, 15 (75%) eyes showed short term tumor control, and long-term eye salvage was achieved in 11 (55%) eyes. Poor prognostic factors for eye salvage included advanced tumor stage (Group D/E: 43% salvage rate vs. Group C: 83%; p = 0.047), vitreous seeding at the time of IAC (38% with seeding vs. 75% without; p = 0.046), use of IAC as a secondary rather than a primary treatment (46% vs. 71%; p = 0.047), and the need for >3 IAC cycles (20% success with >3 cycles vs. 67% with ≤3 cycles; p = 0.034). Complications were notable: systemic adverse effects were seen in five (25%) patients, including neutropenia (20%) and bronchospasm (6%). Procedure-related complications were seen with 22% of injections, including failure of the procedure (7%), ophthalmic artery spasm (6%), and intra-procedural stroke (3%). Five (25%) eyes developed ocular complications, including vitreous hemorrhage (15%), retinal detachment (10%), optic atrophy (10%), and retinal or choroidal ischemia (10%). Notably, all infants under 12 months of age (4/4) developed complications, including the two events of stroke. At a median follow-up of 60 months, eye salvage was achieved in 11 (55%) eyes, and none of the 9 (45%) enucleated eyes showed high-risk pathological features. There was no orbital recurrence, and one (5%) child developed CNS metastasis and passed away. Conclusion: IAC achieves long-term globe salvage in 55% of Rb cases; however, outcomes are poorer with Group D/E tumors, vitreous seeds, prior IVC failure, or requiring >3 IAC cycles. While reducing systemic chemotherapy toxicity, IAC carries significant risks of vision- and life-threatening complications. Infants and single-eyed patients require particularly cautious consideration. Though IAC remains crucial for globe preservation, optimal implementation demands improved patient selection criteria, multicenter collaboration, and long-term outcome studies to maximize safety and efficacy. Full article

Retina, a light-sensitive layer of tissue of the eye, requires high levels of oxygen for its physiology. Retinal ischemia occurs due to inadequate supply of blood to the retina and choroid. Retinal ischemia is implicated in the development or progression of many ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). To date, anti-vascular endothelial growth factor (VEGF) treatment has been widely used to manage neovascular diseases associated with retinal ischemia. Nonetheless, a substantial number of patients with DR or AMD still suffer from incomplete response and adverse effects related to its therapy with limitations. Therefore, research scientists have been developing and finding novel treatments to protect against or prevent vision loss in those diseases. In this review article, we summarize the recent novel therapeutic approaches for the treatment of ischemic retinopathy (e.g., cell therapy, advanced molecular targeting, or drug delivery). This summary enables further research to obtain more solid evidence of novel effective drug development in retinal ischemic diseases. Full article

Neovascular glaucoma is a rare and serious condition typically associated with advanced ocular or systemic vascular diseases such as central retinal vein occlusion or diabetic retinopathy. This report describes a unique case of neovascular glaucoma presenting for the first time as an initial symptom of bilateral occlusive retinal vasculitis (ORV) in a generally healthy 4-year-old girl. The patient presented with symptoms of pain and redness in the left eye, accompanied by high intraocular pressure. These symptoms were particularly distressing and uncharacteristic for such a young child. Clinical examination revealed significant findings, including elevated intraocular pressure, corneal edema, and iris neovascularization in the left eye. Additional imaging studies, including fluorescein angiography, demonstrated extensive retinal ischemia with peripheral capillary nonperfusion, confirming the diagnosis of occlusive vasculitis. The management of this case was challenging due to the progressive and aggressive nature of the disease in a 4-year-old patient. This article aims to present the diagnostic and therapeutic strategies for the management of this condition. This report highlights a rare case of neovascular glaucoma as the first manifestation of bilateral ORV in a young child. The unusual presentation emphasizes the need for a high index of suspicion and comprehensive evaluation in cases of pediatric neovascular glaucoma. Early diagnosis and prompt, multimodal treatment are crucial in preventing irreversible vision loss in such cases. Full article

This comprehensive review examines the ocular vascular complications of cocaine use, focusing on its effects on retinal vasculature and inflammation. A rare case of bilateral frosted branch angiitis (FBA) in a 48-year-old man with a history of intranasal cocaine abuse is presented as an illustrative example to stimulate discussion. The case highlights severe retinal ischemia and vascular sheathing, with no identifiable infectious or autoimmune cause, ultimately complicated by systemic vascular events. Integrating this case with a review of the literature, we discuss cocaine’s vasoconstrictive and immunomodulatory effects and their role in retinal pathology, including vasculitis, vascular occlusions, hemorrhages, and optic neuropathy. Although often a diagnosis of exclusion, and with rare and poorly understood consequences, this review underscores the importance of considering cocaine abuse in the differential diagnosis of complex retinal presentations. Full article

Glaucoma is a main cause of irreversible blindness worldwide, with a high impact on productivity and quality of life. The mechanical and ischemic theories are currently the most recognized pathophysiological pathways that explain the neurodegeneration of retinal nerve fibers in glaucoma. In this narrative review, aspects of ischemia in glaucoma are discussed, including vascular dysregulation, retinal ischemia signaling pathways, roles of vascular endothelial growth factors, and future research and therapeutic directions. In conclusion, a better understanding of the ischemic processes in glaucoma may lead to innovative treatment options and improved management and follow-up of our patients. Full article

Background: Corneal degeneration is a form of progressive cell death caused by multiple factors, such as diabetic retinopathy. It is the most well-known neural degenerative disease caused by macular degeneration in the aged and those with retinitis pigmentosa. Myocardial infarction is becoming a more common burden, causing cardiomyocyte degeneration, ischemia, and heart tissue death. This study examined the preventive effects of rutin on isoproterenol (ISO)-induced oxidative damage (that is, inflammation) on rabbit corneal epithelial cells and mouse heart injuries. Methods: These investigations involved a cytotoxicity test, biochemical analysis, qRT-PCR, Western blotting, and mouse cardiac histopathology. Results: The results showed that rutin enhanced ADH7 and ALDH1A1, retinoic acid signaling components in SIRC1 rabbit corneal cell lines. The production of NO by ocular epithelial cells was significantly reduced. It reduced cTnT and cTnI, CK-MB, and LDH contents in mouse cardiac tissue. The nuclear expressions of Nrf2, Sirt, and HO-1 were all increased by rutin. Docking studies revealed a good interaction between rutin and the Keap protein, enhancing Nrf2 nuclear activity. Conclusions: This showed that rutin can potentially enhance ADH7 and ALDH1A1 corneal signaling components, preventing corneal degeneration and mitigating ISO-induced myocardial infarction (MI) via Keap/Nrf2 expressions. 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: Carotenoids are present throughout retina and body its dense deposition leads to an identifiable yellow spot in the macula. Macular pigment optical density (MPOD) measured in the macula is vital to macular well-being and high-resolution visual acuity. MPOD has also been associated with various health and disease states. We sought to review the literature on this topic and summarize MPODs role as a measurable modifiable clinical biomarker, particularly as a measure of the eye’s antioxidant capacity in the context of oxidative damage and retinal ischemia. Methods: A literature review collated the articles relevant to MPOD, carotenoid intake or supplementation, and their influence on various health and disease states. Results: Literature reveals that MPOD can serve as a reliable biomarker for assessing the retinal defense mechanisms against oxidative stress and the deleterious effects of excessive light exposure. Elevated MPOD levels offer robust protection against the onset and progression of age-related macular degeneration (AMD), a prevalent cause of vision impairment among the elderly population. MPOD’s implications in diverse ocular conditions, including diabetic retinopathy and glaucoma, have been explored, underscoring the real need for clinical measurement of MPOD. The integration of MPOD measurement into routine eye examinations presents an unparalleled opportunity for early disease detection, precise treatment planning, and longitudinal disease monitoring. Conclusions: Longitudinal investigations underscore the significance of MPOD in the context of age-related ocular diseases. These studies show promise and elucidate the dynamic nuances of MPOD’s status and importance as a measurable, modifiable clinical biomarker. Full article

Coronavirus disease 2019 (COVID-19) is associated with increased risk of microvascular complications; however, reports of ophthalmic manifestations associated with retinal vascular occlusion associated with COVID-19 are limited. In this report, we describe two middle-aged female patients who were admitted for acute hypoxic respiratory failure secondary to COVID-19-induced pneumonia. Following prolonged intensive care unit admission requiring mechanical ventilation and critical care interventions, both patients reported substantially reduced vision upon regaining consciousness. Dilated funduscopic exam showed multiple blot hemorrhages in all quadrants of the posterior pole, bilateral retinal hemorrhage, macular edema, and retinal vascular tortuosity. Both patients were diagnosed with retinal ischemic events owing to bilateral ophthalmic artery occlusion in the first patient, and bilateral central retinal vein occlusion (CRVO) in the second individual. While uncommon, retinal microvascular complications associated with COVID-19 leading to vision loss require prompt evaluation and referral given their potential long-term impact following acute illness. Full article