Search Results (135)

Diabetic retinopathy (DR), a leading cause of blindness in working-age adults, arises from chronic hyperglycemia-induced oxidative stress, inflammation, and vascular dysfunction. Current therapies such as laser photocoagulation, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and steroids target advanced stages but fail to prevent early neuronal and microvascular damage. Emerging evidence highlights oxidative stress as a key driver of DR pathogenesis, disrupting the blood-retinal barrier (BRB), promoting neurodegeneration and angiogenesis. Advances in imaging, particularly optical coherence tomography angiography (OCTA), enable earlier detection of neurodegeneration and microvascular changes, underscoring DR as a neurovascular disorder. Polyphenols, such as resveratrol, curcumin, and pterostilbene, exhibit multitarget antioxidant, anti-inflammatory, and anti-angiogenic effects, showing promise in preclinical and limited clinical studies. However, their low bioavailability limits therapeutic efficacy. Nanotechnology-based delivery systems enhance drug stability, tissue targeting, and sustained release, offering potential for early intervention. Future strategies should integrate antioxidant therapies and precision diagnostics to prevent early irreversible retinal damage in diabetic patients. Full article

Retinal diseases can result in blindness and visual impairment. They represent a significant medical burden and adversely affect life expectancy. Recently, antibody- and nucleic acid-based pharmaceuticals have increasingly been used to treat retinal diseases, with improvement or cure as the goal; however, these drugs are currently only administered by intravitreal injection. In this study, we present a novel approach to treating retinal diseases using eye drops that contain PnkRNA, a single-stranded RNA nucleic acid. PnkRNA-loaded liposomes were shown to effectively deliver retinal drugs and significantly inhibit retinal thickening in a mouse retinal-vein occlusion model. Cationic modification of the liposome surface enhanced the delivery of nucleic acids and therapeutic efficacy. Moreover, to reduce the frequency of eye-drop administration, liposomes were incorporated into the thermoresponsive gels. This formulation provided sustained retinal delivery and exhibited superior therapeutic efficacy compared with liposomal eye drops. This nucleic acid retinal delivery technology represents a significant advancement in drug-delivery technology, offering a safe and simple treatment for retinal diseases. 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/Objectives: The management of ocular tumours is faced with the challenge of developing a suitable treatment strategy with consideration of the anatomical and physiological protective barriers of the eye. Interferon alpha has been employed to treat patients with ocular tumours for decades; however, its short half-life and poor tolerability necessitate frequent administration. This study focuses on the design of an injectable pH-responsive and protective nanoparticle system dispersed into a thermo-responsive hydrogel for site-specific sustained delivery of interferon alpha (IFN-α2b) in the treatment of ocular surface tumours. Methods: The synthesis of a poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymer (PECE) was undertaken. The IFN-α2b was encapsulated in poly(β-amino ester) (PBAE) nanoparticles (NP) with pH-responsive characteristics to proposedly release the IFNα-2b in response to the acidic nature of the tumour microenvironment. This was followed by characterisation via Fourier transform infrared spectroscopy (FT-IR), ¹H-nuclear magnetic resonance (¹H-NMR) analysis, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) analysis, thermogravimetric analysis (TGA), and thermal-transition analysis of the PECE hydrogels. Results: Release studies demonstrated that the PBAE nanoparticulate PEG-PCL-PEG hydrogel was both pH-responsive, while providing controlled release of IFN-α2b, and thermo-responsive. Release analysis highlighted that IFN-α2b-loaded NP dispersed into the hydrogel (IFNH) further prolonged the release of IFN-α2b with a pH-responsive yet controlled release rate in an acidic environment simulating a tumour microenvironment. The developed system proved to be biocompatible with human retinal pigment epithelial cells and the released IFN-α demonstrated bioactivity in the presence of an A172 glioblastoma cell line. Conclusions: In conclusion, the PECE hydrogel has promising potential for application as an ocular drug delivery system for the treatment of ocular tumours and could potentially overcome and prevent the drawbacks associated with the commercially available IFN-α2b injection. Full article

Age-related macular degeneration (AMD) is a multifactorial retinal disease influenced by complex molecular mechanisms, including genetic susceptibility, inflammation, oxidative stress, and metabolic dysregulation. While substantial progress has been made in understanding its pathogenesis, the full molecular underpinnings of AMD remain unclear, impeding the effectiveness of current therapeutic strategies. This study provides an in-depth exploration of the molecular interactions involved in AMD progression, particularly focusing on genetic predispositions (such as CFH, ARMS2/HTRA1, and APOE), inflammatory pathways (including complement system dysregulation and cytokine responses), lipid metabolism (e.g., cholesterol homeostasis and drusen formation), and angiogenesis (VEGF signaling). Through a systematic review and bibliometric analysis of literature published between 2015 and 2025, the study identifies emerging research trends, existing gaps, and promising future therapeutic directions. It further investigates innovative precision medicine approaches, including gene editing (CRISPR), RNA therapeutics (siRNA, antisense oligonucleotides), immunomodulatory therapies, and nanotechnology-based drug delivery systems. Additionally, the study examines the role of metabolic disorders such as diabetes and dyslipidemia in AMD progression, highlighting the influence of systemic health factors on disease onset. Finally, the potential of artificial intelligence (AI) in enhancing AMD management through biomarker-based risk stratification, predictive modeling, and personalized treatment optimization is assessed. By mapping the intricate molecular networks underlying AMD and evaluating novel therapeutic strategies, this research aims to contribute to the development of more effective, individualized treatment protocols for patients with AMD. 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

Complex anatomical and physiological barriers make the eye a challenging organ to treat from a drug delivery perspective. Currently available treatment methods (topical eyedrops) for anterior segment diseases pose several limitations in terms of bioavailability and patient compliance. Conventional drug delivery methods to treat posterior segment ocular diseases are primarily intravitreal injection (IVT) of solutions. IVT is highly invasive and leads to retinal toxicity, endophthalmitis, and intraocular inflammation, frequently requiring professional administration and frequent clinical visits. Advanced drug delivery treatment strategies could improve patient compliance and convenience. Long-acting drug delivery platforms (biodegradable or nonbiodegradable) provide sustained/controlled release of drugs for at least four to six months. Smart drug delivery alternatives, for instance, in situ forming implants, are injectable formulations that form semisolid-to-solid implants in response to the various stimuli of pH, light, osmolarity, and temperature. Additionally, nanoparticulate drug delivery systems, contact lenses, electrospun patches, and microneedle-based drug delivery systems provide minimally invasive treatment options for ocular disorders. This comprehensive review focuses on advanced drug delivery options for the management of ocular disorders. 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

Over 2.2 billion people across the globe face significant barriers to accessing essential ophthalmic care, with elderly, rural, and refugee populations being disproportionately affected, deepening existing disparities in eye care. Three-dimensional printing is a novel technology that has the potential to transform the field and improve access by alleviating many patient-specific barriers. This article delves into the evolution of 3D printing within ophthalmology, highlighting its current applications and future potential. It explores various 3D printing techniques and numerous biomaterials discussing their effectiveness in creating advanced solutions such as bioengineered corneas, ocular prosthetics, and innovative treatments for dry eye syndrome, from punctal plugs to lacrimal gland models. Additionally, 3D printing has revolutionized drug delivery systems for conditions like glaucoma, retinal diseases, and ocular brachytherapy. Whether through 3D printed contact lens-based drug delivery systems or polycaprolactone implants that biodegrade and provide sustained drug release without adverse effects, these systems hold immense potential in the field. Despite its promise, the integration of 3D printing into clinical practice presents challenges, which the article addresses alongside strategies for overcoming them. By mapping out the technological advancements and challenges, this review offers a roadmap for enhancing global eye care accessibility and improving patient outcomes on a global scale. Full article

Nanomedicine is emerging as a groundbreaking strategy for the management of the neuro-visual symptoms of neuroinflammatory and neurodegenerative diseases. This innovative field of study leverages nanoscale materials and technologies to improve drug delivery, enabling targeted treatments to reach the affected ocular tissues. By facilitating the transport of therapeutic agents across the blood–retinal barrier and boosting their bioavailability, nanomedicine holds the potential to significantly mitigate the symptoms of conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), etc. This review summarizes the latest developments in nanomedicine applications for the management of these ocular conditions, highlighting their capacity to foster more effective disease diagnosis and treatment. Full article

Background: Sirtuin-1 (SIRT1), a histone deacetylase enzyme expressed in ocular tissues with intracellular localization, plays a critical protective role against various degenerative ocular diseases. The link between reduced SIRT1 levels and diabetic retinopathy (DR) has prompted the exploration of natural therapeutic compounds that act as SIRT1 agonists. Curcumin (CUR), which has been shown to upregulate SIRT1 expression, is one such promising compound. However, effective delivery of CUR to the deeper ocular tissues, particularly the retina, remains a challenge due to its poor solubility and limited ocular penetration following topical administration. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for CUR topical ocular delivery represents a novel approach. Methods: In accordance with our prior research, optimized SNEDDS loaded with CUR were developed and characterized post-reconstitution with simulated tear fluid (STF) at a 1:10 ratio, showing suitable physicochemical and technological parameters for ocular delivery. Results: An entrapment efficiency (EE%) of approximately 99% and an absence of drug precipitation were noticed upon resuspension with STF. CUR-SNEDDS resulted in a better stability and release profile than free CUR under simulated ocular conditions. In vitro analysis of mucoadhesive properties revealed that CUR-SNEDDS, modified with a cationic lipid, demonstrated enhanced interactions with mucin, indicating the potential for improved ocular retention. Cytotoxicity tests demonstrated that CUR-SNEDDS did not affect the viability of human corneal epithelial (HCE) cells up to concentrations of 3 μM and displayed superior antioxidant activity compared to free CUR in an oxidative stress model using retinal pigment epithelial (ARPE-19) cells exposed to hydroquinone (HQ). Cell uptake studies confirmed an enhanced accumulation of CUR within the retinal cells following exposure to CUR-SNEDDS compared to neat CUR. CUR-SNEDDS, at lower concentrations, were found to effectively induce SIRT1 expression. Conclusions: The cytocompatibility, antioxidant properties, and enhanced cellular uptake suggest that these developed systems hold promise as formulations for the delivery of CUR to the retina. Full article

Age-related macular degeneration (AMD) is a predominant cause of vision loss, posing significant challenges in its management despite advancements such as anti-vascular endothelial growth factor (anti-VEGF) therapy. Nanomedicine, with its novel properties and capabilities, offers promising potential to transform the treatment paradigm for AMD. This review reports the significant advancements in the use of diverse nanoparticles (NPs) for AMD in vitro, in vivo, and ex vivo, including liposomes, lipid nanoparticles, nanoceria, nanofibers, magnetic nanoparticles, quantum dots, dendrimers, and polymer nanoparticles delivered in forms such as gels, eye drops, intravitreally, or intravenously. Drug delivery was the most common use of NPs for AMD, followed by photodynamic therapy dose enhancement, antioxidant function for nanoceria, biomimetic activity, and immune modulation. Innovative approaches arising included nanotechnology-based photodynamic therapy and light-responsive nanoparticles for controlled drug release, as well as gene therapy transfer. Nanomedicine offers a transformative approach to the treatment and management of AMD, with diverse applications. The integration of nanotechnology in AMD management not only provides innovative solutions to overcome current therapeutic limitations but also shows potential in enhancing outcomes and patient quality of life. Full article

This review aims to examine existing research on the development of ocular drug delivery devices utilizing hyaluronic acid (HA). Renowned for its exceptional biocompatibility, viscoelastic properties, and ability to enhance drug bioavailability, HA is a naturally occurring biopolymer. The review discussed specific mechanisms by which HA enhances drug delivery, including prolonging drug residence time on ocular surfaces, facilitating controlled drug release, and improving drug penetration through ocular tissues. By focusing on these unique functionalities, this review highlights the potential of HA-based systems to revolutionize ocular treatment. Various fabrication techniques for HA-based ocular drug delivery systems, including hydrogels, nanoparticles, and microneedles, are discussed, highlighting their respective advantages and limitations. Additionally, this review explores the clinical applications of HA-based devices in treating a range of ocular diseases, such as dry eye syndrome, glaucoma, retinal disorders, and ocular infections. By comparing the efficacy and safety profiles of these devices with traditional ocular drug delivery methods, this review aims to provide a comprehensive understanding of the potential benefits and challenges associated with HA-based systems. Moreover, this review discusses current limitations and future directions in the field, such as the need for standardized fabrication protocols, long-term biocompatibility studies, and large-scale clinical trials. The insights and advancements presented in this review aim to guide future research and development efforts, ultimately enhancing the effectiveness of ocular drug delivery and improving patient outcomes. Full article

Background: Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions. Methods: A comprehensive literature search was conducted in major medical databases through July 2024. Relevant studies on monoclonal antibodies for intraocular diseases were included. Two independent researchers screened the literature, extracted data, and assessed study quality. Cost-effectiveness analyses were also reviewed. Results: Anti-vascular endothelial growth factor (VEGF) antibodies, such as bevacizumab, ranibizumab, and aflibercept, showed significant therapeutic effects in neovascular age-related macular degeneration (NVAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Tumor necrosis factor-alpha (TNF-α) inhibitors demonstrated promising results in treating noninfectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios. Conclusions: Monoclonal antibodies are vital for treating intraocular diseases, but continuous innovation and rigorous clinical evaluation are essential. Future research should focus on developing novel delivery systems, exploring combination therapies, conducting long-term follow-up studies, and investigating personalized treatment strategies to provide safer, more effective, and cost-effective therapeutic solutions. Full article

The most prevalent reason for vision impairment in aging inhabitants is age-related macular degeneration (AMD), a posterior ocular disease with a poor understanding of the anatomic, genetic, and pathophysiological progression of the disease. Recently, new insights exploring the role of atrophic changes in the retinal pigment epithelium, extracellular drusen deposits, lysosomal lipofuscin, and various genes have been investigated in the progression of AMD. Hence, this review explores the incidence and risk factors for AMD, such as oxidative stress, inflammation, the complement system, and the involvement of bioactive lipids and their role in angiogenesis. In addition to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and other therapeutic interventions such as oral kinase inhibitors, photodynamic, gene, and antioxidant therapy, as well as their benefits and drawbacks as AMD treatment options, strategic drug delivery methods, including drug delivery routes with a focus on intravitreal pharmacokinetics, are investigated. Further, the recent advancements in nanoformulations such as polymeric and lipid nanocarriers, liposomes, etc., intended for ocular drug delivery with pros and cons are too summarized. Therefore, the purpose of this review is to give new researchers an understanding of AMD pathophysiology, with an emphasis on angiogenesis, inflammation, the function of bioactive lipids, and therapy options. Additionally, drug delivery options that focus on the development of drug delivery system(s) via several routes of delivery can aid in the advancement of therapeutic choices. Full article