Search Results (154)

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

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

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

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. Full article

Bardet–Biedl syndrome (BBS) is a rare multisystem ciliopathy characterized by early-onset retinal degeneration and other vision-threatening ophthalmologic manifestations. This review synthesizes current knowledge on the ocular phenotype of BBS as well as emerging therapeutic approaches aimed at preserving visual function. Retinal degeneration, particularly early macular involvement and rod–cone dystrophy, remains the hallmark of BBS-related vision loss. Additional ocular manifestations, such as refractive errors, nystagmus, optic nerve abnormalities, and cataracts further contribute to visual morbidity. Experimental therapies—including gene-based interventions and pharmacologic strategies such as nonsense suppression and antioxidant approaches—have shown promise in preclinical models but require further validation. Early ophthalmologic care, including routine visual assessments, refractive correction, and low-vision rehabilitation, remains the standard of management. However, there are currently no effective therapies to halt or reverse retinal degeneration, which underscores the importance of emerging molecular and genetic interventions. Timely recognition and comprehensive ophthalmologic evaluation are essential to mitigate visual decline in BBS. Future efforts should focus on translating these approaches into clinical practice, enhancing early diagnosis, and promoting multidisciplinary collaboration to improve long-term outcomes for patients with BBS. Full article

Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the integrity of the blood–retinal barrier, and contribute to angiogenesis. Recent advancements in molecular and cellular biology have revealed the heterogeneity of pericytes and their critical involvement in ocular physiology and pathology. This review provides a comprehensive analysis of pericyte functions in ocular health and their implications in diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusion. Pericyte dysfunction is implicated in vascular instability, neurovascular coupling failure, inflammation, and pathological neovascularization, contributing to vision-threatening disorders. The review further explores recent findings on pericyte-targeted therapies, including pharmacological agents, gene therapy, and cell-based approaches, aiming to restore pericyte function and preserve ocular health. Full article

Background/Objectives: The corneal epithelium plays a vital role in maintaining corneal transparency and ocular surface integrity. Chronic topical use of antiglaucoma medications may induce epithelial changes, especially with the concurrent use of multiple agents. This study aimed to evaluate the association between the number and class of antiglaucoma medications and central corneal epithelial thickness (CET), measured using a spectral-domain optical coherence tomography (SD-OCT) device. Methods: This cross-sectional study included 456 eyes from 242 adults (median age 72 years), grouped by the number of antiglaucoma agents used (0–4 medications). All pharmacologically treated participants had received the same regimen for ≥6 months. CET was measured using SD-OCT (SOLIX, Optovue). Generalized estimating equations (GEEs) accounted for inter-eye correlation. Two models were constructed: one evaluating specific medication effects and another assessing CET reduction per additional drug used. Age and sex were included as covariates. Results: CET progressively decreased with the number of medications, ranging from 53 µm in controls to 48 µm with quadruple therapy. Multivariable GEE analysis confirmed a cumulative thinning effect, with each additional medication associated with further CET reduction (β = −2.83 to −9.17 µm, p < 0.001). Latanoprost exerted the most pronounced single-drug effect (β = −3.01 µm, p < 0.001). Age was a modest negative predictor, while sex showed no significant effect. Conclusions: The cumulative number and specific class of antiglaucoma medications have a significant impact on corneal epithelial thickness. These results emphasize the need for vigilant ocular surface evaluation in patients on multi-drug regimens and propose CET as a surrogate marker for the burden of topical therapy. Full article

The integrated stress response (ISR) is a key regulator of cell survival, promoting apoptosis through the effector protein CHOP in instances of prolonged or severe stress. The ISR’s role in the initiation and progression of epithelial malignancies has been investigated; however, the ISR has not been evaluated in ocular adnexal sebaceous carcinoma (SebCA). Though uncommon, mortality rates of up to 40% have been reported, and the mechanisms underlying SebCA tumorigenesis remain unresolved; however, c-MYC upregulation has been documented. Our objective was to determine the role of MYC in modulating the ISR in the Meibomian gland. Human Meibomian gland epithelial cells (HMGECs) were subject to both pharmacologic and genetic manipulations of MYC expression. Cytotoxicity, proliferation, and changes in protein and gene expression were assessed. Conditionally MYC-overexpressing mice were subject to topical 4-hydroxytamoxifen (4-OHT) induction of the eyelids prior to tissue harvest for histology, immunohistochemistry, immunoblotting, and qPCR. MYC-inhibited HMGECs exhibited dose-dependent decreased proliferation, increased CHOP expression, and increased apoptosis. Conversely, MYC-overexpressing HMGECs and Meibomian glands from 4-OHT-induced mice demonstrated suppressed CHOP expression, reduced apoptosis, and upregulated fatty acid synthase expression. These results suggest that MYC inhibition induces the ISR and promotes apoptosis, while MYC induction suppresses CHOP expression. High MYC expression may, therefore, serve as a mechanism for SebCA to elude cell death by promoting lipogenesis. Full article

Nociceptors respond to noxious stimuli and transmit pain signals to the central nervous system. In the cornea, the nociceptors located in the most external layer provide a myriad of sensation modalities. Damage to these corneal nerve fibers can induce neuropathic pain. In response, corneal nerves become sensitized to previously non-noxious stimuli. Assessing corneal pain origin is a complex ophthalmic challenge due to variations in its causes and manifestations. Current FDA-approved therapies for corneal nociceptive pain, such as acetaminophen and NSAIDs, provide only broad-acting relief with unwanted side effects, highlighting the need for precision medicine for corneal nociceptive pain. A few targeted treatments, including perfluorohexyloctane (F6H8) eye drops and Optive Plus (TRPV1 antagonist), are FDA-approved, while others are in preclinical development. Treatments that target signaling pathways related to neurotrophic factors, such as nerve growth factors and ion channels, such as the transient receptor potential (TRP) family or tropomyosin receptor kinase A, may provide a potential combinatory therapeutic approach. This review describes the roles of nociceptors in corneal pain. In addition, it evaluates molecules within nociceptor signaling pathways for their potential to serve as targets for efficient therapeutic strategies for corneal nociceptive pain aimed at modulating neurotrophic factors and nociceptive channel sensitivity. Full article

Background: Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, and frequently severe allergic ocular condition predominantly impacting children and adolescents in tropical and subtropical areas. It profoundly affects patients’ quality of life owing to its chronic symptoms and possible vision-threatening effects. Notwithstanding progress in comprehending VKC, its ocular symptoms and therapeutic approaches necessitate ongoing assessment. Aims: This review summarizes the main factors to consider when diagnosing, treating, and managing patients with VKC based on the current literature in this field. Methods: This comprehensive review examined peer-reviewed literature from 2010 to 2024 obtained from PubMed. The selection criteria encompassed research addressing the clinical presentation, diagnostic difficulties, and therapy of visual symptoms in pediatric patients with VKC. The publications chosen were those focusing on those that elucidate the pathophysiology, consequences, and innovations in treatment methodologies. Results: The ocular manifestations of VKC are varied and characterized by prominent symptoms such as severe itching, photophobia, lacrimation, and a viscous mucoid discharge. Clinical manifestations range from conjunctival hyperemia and limbal thickening to severe consequences that jeopardize vision, including shield ulcers and keratoconus. Improvements in imaging techniques such as anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy have enhanced diagnostic accuracy. The pharmacological approach has transitioned to steroid-sparing techniques, prioritizing mast cell stabilizers, antihistamines, and immunomodulators such as cyclosporine. Novel therapies, including biologics that target interleukin pathways, demonstrate potential in refractory instances. Nonetheless, access to modern medicines is restricted in resource-limited environments. Conclusions: VKC poses considerable diagnostic and treatment difficulties due to its chronic nature and possible consequences. This review emphasizes the necessity for prompt diagnosis and customized management approaches to avert vision impairment. Despite considerable advancements in comprehending VKC’s etiology and therapy, inequalities in access to sophisticated care highlight the necessity for global activities to guarantee equitable treatment alternatives. Full article

Diquafosol sodium is a purinergic P2Y₂ receptor agonist that is garnering much interest for its potential therapeutic benefits in ocular surface management. This review provides a comprehensive analysis of diquafosol’s pharmacology, clinical effectiveness, and role in the evolving landscape of ocular surface management. Future research should focus on optimising formulations, treatment duration, and exploring potential combination therapies to maximise therapeutic outcomes. By targeting underlying pathophysiological mechanisms, diquafosol represents a significant advancement in ocular surface management and a valuable addition to existing therapies. Full article

Filtration bleb (FB) fibrosis represents the primary risk factor for glaucoma filtration surgery (GFS) failure. We reviewed the most recent literature on post-GFS fibrosis in humans, focusing on novel molecular pathways and antifibrotic treatments. Three main literature searches were conducted. First, we performed a narrative review of two models of extra-ocular fibrosis, idiopathic pulmonary fibrosis and skin fibrosis, to improve the comprehension of ocular fibrosis. Second, we conducted a systematic review of failed FB features in the PubMed, Embase, and Cochrane Library databases. Selected studies were screened based on the functional state and morphological features of FB. Third, we carried out a narrative review of novel potential antifibrotic molecules. In the systematic review, 11 studies met the criteria for analysis. Immunohistochemistry and genomics deemed SPARC and transglutaminases to be important for tissue remodeling and attributed pivotal roles to TGFβ and M2c macrophages in promoting FB fibrosis. Four major mechanisms were identified in the FB failure process: inflammation, fibroblast proliferation and myofibroblast conversion, vascularization, and tissue remodeling. On this basis, an updated model of FB fibrosis was described. Among the pharmacological options, particular attention was given to nintedanib, pirfenidone, and rapamycin, which are used in skin and pulmonary fibrosis, since their promising effects are demonstrated in experimental models of FB fibrosis. Based on the most recent literature, modern patho-physiological models of FB fibrosis should consider TGFβ and M2c macrophages as pivotal players and favorite targets for therapy, while research on antifibrotic strategies should clinically investigate medications utilized in the management of extra-ocular fibrosis. Full article

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and a leading cause of blindness in the working-age population. Current pharmacological treatments counteract DR’s later stages without targeting the earlier disease phases. Using computational approaches, our group previously identified the α1D and α2C adrenoceptors (α1DR and α2CR) as new putative drug targets for DR. Therefore, the aim of this work was to validate the role of these receptors in an in vitro model of DR, i.e., retinal pigmented epithelial cells (ARPE-19) challenged with high glucose (HG, 50 mM). We examined the effects of selective α1DR and α2CR agonists and antagonists on hyperglycemia-induced mitochondrial dysfunction and blood retinal barrier breakdown. Seahorse XFe was employed to assess the oxygen consumption rate and extracellular acidification rate. The integrity of the ARPE-19 barrier was evaluated through transepithelial electrical resistance measurements and a sodium fluorescein permeability test. α1DR pharmacological modulation through the α1DR antagonist BMY 7378 (0.1–1 µM, 24 h), but not α2CR, significantly attenuated HG-induced mitochondrial dysfunction. BMY 7378 (0.1–1 µM, 48 h) also prevented HG-mediated damage to retinal epithelial integrity. In contrast, the α1DR agonist phenylephrine (1–10 μM, 24 h) further reduced ARPE-19 mitochondrial activity compared to HG, indicating that α1D activation is directly implicated in DR-mediated mitochondrial dysfunction. In conclusion, the current in vitro study validated α1DR as a pharmacological target for DR. Full article

Endometriosis afflicts 10% of women in their reproductive years and nearly half of women with infertility, and its etiology is not yet clear. Pharmacological therapy is generally based on progestins like progestogen. This drug binds to progesterone receptors with many known side effects. Here, we describe the case of a 33-year-old woman surgically treated for endometriosis who continued with drug therapy based on estradiol valerate and dienogest. Approximately 21 months after treatment, she reported ocular symptoms with vision alteration, diplopia, and metamorphopsia related to central serous chorioretinopathy (CSC). After the discontinuation of combined progestin-based treatment, the CSC fully subsided. Semeiological, clinical, and laboratory approaches were adopted, and urinary steroids were measured. A slight increase in prolactinemia in the absence of macro-prolactinemia was reported. The steroidal profile appeared without abnormalities, although a slight alteration of estrogen balance was noted. Considering the pharmacodynamics of dienogest versus selective progesterone receptor modulators, it can be assumed that patients’ clinical events are related to specific site response to steroids that bind the progesterone receptor. Dienogest may have induced the CSC as a not yet characterized side effect of the drug. Undoubtedly, further specific studies are needed concerning the metabolic and pharmacodynamic aspects that cannot be exhaustively covered here. Full article