Search Results (237)

Background/Objectives:Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Protocol was registered with Open Science Framework. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials, spanning 1996–2024. Local anesthetics were the most frequent drug class, followed by opioids, corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, most of the studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited, but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies. Full article

Background: Antibody-drug conjugates (ADCs) have ushered in a new era of precision oncology by combining the targeting specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs. However, the cellular and molecular mechanisms underlying their dose-limiting ocular toxicity remain unclear. Elahere™, the first FDA-approved ADC targeting folate receptor α (FRα), demonstrates remarkable efficacy in platinum-resistant ovarian cancer but causes keratitis and other ocular toxicities in some patients. Notably, FRα is not expressed in the corneal epithelium—the primary site of damage—highlighting the urgent need to elucidate its underlying mechanisms. The aim of this study was to identify the cell-type-specific molecular mechanisms underlying Elahere-induced ocular toxicity. Methods: Sprague-Dawley rats were treated with intravenous Elahere (20 mg/kg) or vehicle weekly for five weeks. Ocular toxicity was determined by clinical examination and histopathology. Corneal single-cell suspensions were analyzed using the BD Rhapsody single-cell RNA sequencing (scRNA-seq) platform. Bioinformatic analyses to characterize changes in corneal cell populations, gene expression, and signaling pathways included cell clustering, differential gene expression, pseudotime trajectory inference, and cell-cell interaction modeling. Results: scRNA-seq profiling of 47,606 corneal cells revealed significant damage to the ocular surface and corneal epithelia in the Elahere group. Twenty distinct cell types were identified. Elahere depleted myeloid immune cells; in particular, homeostatic gene expression was suppressed in phagocytic macrophages. Progenitor populations (limbal stem cells and basal cells) accumulated (e.g., a ~2.6-fold expansion of limbal stem cells), while terminally differentiated cells decreased in corneal epithelium, indicating differentiation blockade. Endothelial cells exhibited signs of injury and inflammation, including reduced angiogenic subtypes and heightened stress responses. Folate receptor alpha, the target of Elahere, was expressed in endothelial and stromal cells, potentially driving stromal cells toward a pro-fibrotic phenotype. Fc receptor genes were predominantly expressed in myeloid cells, suggesting a potential mechanism underlying their depletion. Conclusions: Elahere induces complex, multi-compartmental ocular toxicity characterized by initial perturbations in vascular endothelial and immune cell populations followed by the arrest of epithelial differentiation and stromal remodeling. These findings reveal a cascade of cellular disruptions and provide mechanistic insights into mitigating Elahere-associated ocular side effects. Full article

Iron is an essential micronutrient integral to ocular physiology, supporting biochemical processes such as mitochondrial respiration, DNA synthesis and phototransduction. Disruptions in systemic or local iron homeostasis, whether due to overload or deficiency, have been increasingly implicated in the pathogenesis of a broad range of anterior and posterior segment ocular disorders. Iron deficiency may compromise retinal bioenergetics, impair cellular repair, and increase susceptibility to oxidative stress, while iron overload facilitates the generation of reactive oxygen species, contributing to lipid peroxidation, mitochondrial dysfunction, and ferroptosis. Dysregulated iron metabolism has been associated with several ocular pathologies, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinal detachment, cataracts, and anemic retinopathy. The eye possesses specialized iron regulatory mechanisms involving proteins such as transferrin, ferritin, ferroportin, and hepcidin that govern iron transport, storage, and export across ocular barriers. Aberrations in these pathways are now recognized as contributing factors in disease progression. This narrative review explores the complex dual role of iron overload and deficiency in ocular diseases. It highlights the molecular mechanisms underlying iron-mediated pathologies in both the posterior and anterior segments of the eye, along with the clinical manifestations of iron imbalance. Current therapeutic approaches are discussed, including oral and parenteral iron supplementation for deficiency and emerging chelation-based or antioxidant strategies to address iron overload, while highlighting their limitations. Key challenges remain in developing targeted ocular delivery systems that optimize bioavailability and minimize systemic toxicity. Hence, maintaining iron homeostasis is critical for visual function, and further research is needed to refine therapeutic interventions and clarify the mechanistic role of iron in ocular health and disease. Full article

Background/Objectives: We report the development of a novel intraocular sustained-release implantable pharmaceutical formulation, designed to be placed in the anterior chamber of the eye after cataract surgery. The device is intended to reduce postoperative inflammation, and to prevent opportunistic bacterial infections that may lead to endophthalmitis. Methods: The implants were produced via hot-melt extrusion, using a twin-screw extruder to process a homogeneous mixture of polylactide-co-glycolic acid, moxifloxacin hydrochloride (MOX HCl) and dexamethasone (DEX). Quality control tests included drug content determination, release rate profile evaluation, and several instrumental characterization techniques (scanning electron microscopy (SEM), confocal Raman microscopy, differential scanning calorimetry, and X-ray diffraction). Long-term and accelerated stability tests were also performed, following ICH guidelines. Sterilization was achieved by exposing samples to gamma radiation. In vivo exploratory studies were carried out in healthy rabbits to evaluate the safety and overall performance of the implantable formulation. Results: In terms of quality control, drug content was found to be homogeneously distributed throughout the implants, and it also met the label claim. In vitro release rate was constant for MOX HCl, but non-linear for DEX, increasing over time. In vivo preliminary tests showed that the inserts completely biodegraded within approximately 20 days. No clinical signs of anterior segment toxic syndrome or statistically significant intraocular pressure differences were found between treatment and control groups. Conclusions: The implants developed in this study can act as sustained-release depots for the delivery of both DEX and MOX HCl, and are biocompatible with ocular structures. Full article

Background: Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare, life-threatening mucocutaneous disorders often associated with severe ophthalmic complications. Ocular involvement occurs in 50–68% of cases and can result in permanent vision loss. Despite this, optimal management strategies remain unclear, and treatment practices vary widely. Methods: A systematic review was conducted in accordance with PRISMA guidelines and prospectively registered on PROSPERO (CRD420251022655). Medline, Embase, and CENTRAL were searched from 1998 to 2024 for English-language studies reporting treatment outcomes for ocular SJS/TEN. Results: A total of 194 studies encompassing 6698 treated eyes were included. Best-corrected visual acuity (BCVA) improved in 52.2% of eyes, epithelial regeneration occurred in 16.8%, and symptom relief was reported in 26.3%. Common treatments included topical therapy (n = 1424), mucosal grafts (n = 1220), contact lenses (n = 1134), amniotic membrane transplantation (AMT) (n = 889), systemic medical therapy (n = 524), and punctal occlusion (n = 456). Emerging therapies included TNF-alpha inhibitors, anti-VEGF agents, photodynamic therapy, and 5-fluorouracil. Conclusions: Disease-stage-specific therapy is crucial in ocular SJS/TEN. Acute interventions such as AMT may prevent long-term complications, while chronic care targets structural and tear-film abnormalities. Further prospective studies are needed to standardize care and optimize visual outcomes. Full article

Polyhexamethylene guanidine phosphate (PHMG-p), a widely used disinfectant component in household humidifiers, has been implicated in various health issues, including pulmonary toxicity. Many people use humidifiers to improve dry eye disease (DED). The current study was performed to elucidate the effect of PHMG-p on eye dryness in a rat model using metabolomics. Male Sprague Dawley rats were exposed to PHMG-p (0.1% and 0.3%) following a previously established DED induction model using scopolamine hydrobromide and desiccation stress. Ocular surface damage was assessed using corneal fluorescein staining, tear volume measurement, and tear break-up time (TBUT). Plasma and urine samples were analyzed using ¹H-NMR-based metabolomics to identify metabolic alterations associated with PHMG-P-p exposure and DED pathogenesis. PHMG-p exposure exacerbated DED symptoms, as evidenced by a significant reduction in tear volume, shorter TBUT, and increased corneal damage compared to the control group. Metabolomic profiling identified distinct metabolic changes in PHMG-p-exposed groups, including alterations in glutamate, glycine, citrate, and succinate metabolism. These metabolic changes correlated with increased levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α in the corneal and lacrimal gland tissues. Our findings suggest that PHMG-p exposure contributes to DED pathophysiology by inducing metabolic disturbances and inflammatory responses in the ocular surface. This study highlights the need for further investigation into the potential risks of PHMG-p exposure on ocular health and provides novel insights into the metabolic underpinnings of DED. Full article

Background/Objectives: Oxidative stress plays a critical role in the development of ocular diseases such as cataracts. Selenium nanoparticles (SeNPs) offer antioxidant benefits with low toxicity. This study aimed to evaluate the antioxidant activity of SeNPs coated with D-α-tocopheryl polyethylene glycol succinate (TPGS) in human lens epithelial (HLE) cells. Methods: SeNPs were synthesised by reducing sodium selenite with ascorbic acid in the presence of TPGS. Physicochemical characterisation was carried out using dynamic light scattering to assess size and surface charge. Antioxidant activity was measured by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Cytocompatibility was assessed on adult retinal pigment epithelial (ARPE-19) and HLE cells using PrestoBlue. Functional antioxidant performance was determined through enzymatic assays for glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and glutathione (GSH), and lipid peroxidation was assessed using malondialdehyde (MDA) quantification. Catalase mimicry was evaluated under 3-amino-1,2,4-triazole (3-AT)-induced inhibition. Results: The optimal SeNP formulation had an average hydrodynamic diameter of 44 ± 3 nm, low PDI (<0.1), and a surface charge of −15 ± 3 mV. These TPGS-SeNPs demonstrated strong radical scavenging (EC₅₀ ≈ 1.55 µg/mL) and were well tolerated by ARPE-19 cells (IC₅₀ = 524 µg/mL), whereas HLE cells had a narrower biocompatibility window (≤0.4 µg/mL, IC₅₀ = 2.2 µg/mL). Under oxidative stress, SeNPs significantly enhanced GPx and TrxR activity but did not affect GSH or MDA levels. No catalase-mimetic activity was observed. Conclusions: TPGS-SeNPs exhibit potent antioxidant enzyme modulation under stress conditions in HLE cells. Although not affecting all oxidative markers, these nanoparticles show promise for non-invasive strategies targeting lens-associated oxidative damage, including cataract prevention. Full article

Background/Objectives: Ultra-low-dose radiotherapy (ULD-RT), an ultra-low-dose regimen delivering 4 Gy in two fractions, has emerged as a promising treatment for indolent ocular adnexal lymphoma (OAL), offering disease control with minimal toxicity. However, the clinical outcomes and safety profile of ULD-RT remain inconsistently reported across studies. Methods: We conducted a systematic review of peer-reviewed studies evaluating ULD-RT in patients with OAL, including prospective, retrospective, and comparative cohorts published between 2000 and 2025. A comprehensive search was performed in PubMed, Embase, and Scopus. Eligible studies reported clinical outcomes (e.g., response rates, local control, progression-free survival) and safety data (acute and late toxicities). Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Results: Ten studies comprising 591 patients met the inclusion criteria. The overall response rate to ULD-RT ranged from 88% to 100%, with complete response rates of 50% to 95%. Local control rates ranged from 63% to 100%, and 2-year progression-free survival exceeded 85% in most studies. Importantly, no grade ≥ 3 toxicities were observed following the regimen of 4 Gy in two fractions. Acute toxicities occurred in up to 42% of patients, typically grade 1 dry eye or conjunctivitis. Late toxicities were uncommon (16–33%), with cataracts rarely requiring surgery. All included studies were rated as good quality (NOS score ≥ 7), indicating low risk of bias. Conclusions: ULD-RT is a highly effective and safe treatment modality for OAL, providing excellent local control with a favorable toxicity profile. These findings support the adoption of ULD-RT as a first-line radiotherapy strategy for indolent OAL. Future prospective trials with longer follow-up and standardized toxicity reporting are warranted to confirm and refine its clinical role. Full article

Background and Clinical Significance: Central serous chorioretinopathy (CSCR) and hydroxychloroquine (HCQ) retinopathy can both cause outer retinal changes in systemic lupus erythematosus (SLE) patients treated with HCQ and corticosteroids. Differentiating between transient steroid-induced CSCR and irreversible HCQ toxicity is critical to avoid unnecessary discontinuation of essential therapy. Case Presentation: Three female SLE patients (ages 47, 41, and 37) on long-term HCQ (25, 9, and 6 years, respectively) and recent or ongoing low-dose prednisolone presented with unilateral OCT findings, parafoveal or pericentral photoreceptor defects, with the fellow eye unaffected. Review of clinical history and serial imaging revealed transient subretinal fluid in all cases, associated with recent corticosteroid use or dose escalation. Subsequent tapering or cessation of steroids led to resolution of the fluid, and earlier OCT scans confirmed normal outer retinal morphology, indicating that these changes were residual effects of resolved CSCR rather than HCQ toxicity. In Cases 1 and 2, the best-corrected visual acuity (BCVA) in the affected eye declined from 20/22 to 20/40 during the CSCR episode and improved to 20/30 and 20/25, respectively, after subretinal fluid resolution. In Case 3, by contrast, BCVA remained stable at 20/20 throughout the pre-, during-, and post-CSCR periods. Conclusions: Resolved CSCR can mimic HCQ retinopathy. These cases emphasize the importance of detailed medication history, serial multimodal retinal imaging, and comparison with prior and fellow-eye scans to distinguish resolved CSCR from HCQ retinopathy. Such thorough evaluation and careful differential diagnosis help ensure appropriate management—avoiding unnecessary HCQ discontinuation while protecting both ocular and systemic health. Full article

Background: RMS is the most common soft tissue sarcoma in children. Pencil beam scanning proton therapy (PBS PT) enables highly conformal dose delivery with reduced exposure to surrounding healthy structures, making it particularly suited for RMS in critical anatomical regions. Long-term clinical outcome data for this new radiation technique are scarce. Purpose: This study reports long-term outcomes and quality of life after PBS PT in children and adolescents with rhabdomyosarcoma (RMS). Methods and Materials: We retrospectively reviewed 114 children and adolescents with RMS (mostly embryonal, n = 100; 87.7%) treated between 2000 and 2020. Their median age was 4.6 years (range, 0.3–18). All received systemic chemotherapy according to prospective protocols. The median total PT dose delivered was 52 Gy (RBE; range, 41.4–64.8). Results: After a median follow-up period of 7.1 years (range, 0.3 to 17 years), we observed 26 failures overall; 21 (80.8%) occurred in-field. The 5-year local control and overall survival were 81.2% and 81%, respectively. The composite endpoint (non-ocular grade ≥3 toxicity- and failure-free survival) counting the first occurrence of any failure (local or distant), death, or non-ocular CTCAE v5.0 grade ≥3 toxicity was 77.3% at 5 years. At the start of PT, parents and children reported a quality of life significantly worse than that of a German normative group, but during the follow-up period, their scores improved to normal values in nearly all domains within two years. Conclusions: Our two decades of experience with PBS PT provide data that reflect good local control rates and minimal late non-ocular grade 3 toxicity. We also show that quality of life returned to normal scores in nearly all domains within 2 years. Children and adolescents with RMS seem to benefit from PBS PT in terms of toxicity and quality of life, but further prospective, multi-institutional comparative trials are needed. Full article

The efficacy of topical drug delivery via eye drops is often achieved at the expense of tolerability, and consequently, efforts are being made to design strategies that minimize the adverse effects associated with the passage of active pharmaceutical ingredients (APIs) across the ocular surface. Many of these approaches are too complex, costly and challenging to implement on an industrial scale, yet there is increasing evidence that hylan A, a very high molecular weight hyaluronic acid (≥3.0 MDa), may be a promising vehicle for topical drug delivery of ocular therapies. In this review, we explore how the mucoadhesive and viscoelastic properties of eye drop formulations based on hylan A help extend the residence time of APIs at the ocular surface, while maintaining patient comfort. Moreover, we examine how hylan A facilitates the dissolution and stabilization of APIs, as well as their transport across the ocular epithelial barrier, without the need to use toxic penetration enhancers, thereby preserving ocular surface health. Finally, we present evidence indicating that the intrinsic biological properties of hylan A, including its anti-inflammatory effects, help mitigate side effects commonly associated with certain APIs. To illustrate these advantages, we examine the pioneering use of a hylan A-based aqueous eye drop formulation as a vehicle to deliver latanoprost, a prostaglandin analogue widely used in the treatment of glaucoma. This case study demonstrates the potential of hylan A-based eye drops to offer safer and more effective topical drug delivery, especially for long-term ocular therapies where tolerability and biocompatibility are critical. Full article

Background and Clinical Significance: Immune checkpoint inhibitors (ICIs) ushered in a new era in cancer treatment, but alongside their efficacy is an adverse event profile that involves the immune system as a whole and may impact several organs. Case Presentation: We present the case of a 68-year-old woman with a diagnosis of cervical cancer treated with pembrolizumab who developed progressively steroid-refractory chronic diarrhea and ensuing visual problems. Topical antibiotics failed to heal a corneal ulcer in the left eye, necessitating evisceration. Imaging showed intestinal pneumatosis without ischemia, and there was immediate clinical improvement after initiation of corticosteroid therapy. This clinical picture—steroid-dependent colitis and immune-mediated uveitis associated with secondary bacterial infection—was coded as an immune-related adverse event (irAE) resulting from ICI treatment. Because of the prompt and complete regression of the symptoms upon corticosteroid therapy, this was considered as a criterion for the final diagnosis. Conclusions: The case highlights the complexity and potential severity of irAEs that need to be appropriately identified and promptly managed by multidisciplinary teams. Full article

Aluminium (Al) is a widespread environmental contaminant known to induce oxidative stress and genotoxic effects in aquatic organisms. While its neurotoxic properties are well documented, the molecular impact of Al on the visual system remains poorly understood. In this study, adult zebrafish (Danio rerio) were exposed to 11 mg/L Al for 10, 15, and 20 days to investigate the oxidative and genotoxic responses in ocular tissue. Activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were measured in eye supernatants to detect oxidative stress. Additionally, the activities of poly (ADP-ribose) polymerase (PARP) and poly (ADP-ribose) glycohydrolase (PARG) were assessed in tissue homogenates to evaluate oxidative DNA damage and repair processes. The results indicate that these enzymes respond to counteract the increased reactive oxygen species (ROS) induced by aluminium exposure. However, their activity may not sufficiently reduce ROS levels to fully prevent oxidative DNA damage, as evidenced by a significant rise in PARP activity during short exposure times. Over longer exposures, PARP activity returned to baseline, suggesting ocular cells may adapt to aluminium toxicity. We propose that this reduction in PARP activity is a cellular survival mechanism, as sustained activation can deplete energy reserves and trigger cell death. Finally, thin-layer chromatography confirmed that PARG facilitates the breakdown of poly (ADP-ribose) (PAR) into ADP-ribose, demonstrating the dynamic regulation of the PAR cycle, which is crucial to preventing parthanatos. Full article

Radiation-induced keratoconjunctivitis sicca (KCS) is a significant late complication in dogs receiving radiation therapy for intranasal tumors, particularly with hypofractionated intensity-modulated radiation therapy (IMRT). This retrospective case-control study was performed to identify anatomical and dosimetric risk factors for KCS in 15 canine patients treated with IMRT delivered in 4–6 weekly fractions of 8 Gy. Orbital structures were retrospectively contoured, and dose–volume metrics (D50) were calculated. Receiver operating characteristic (ROC) curve analysis and odds ratios were used to evaluate the associations between radiation dose and KCS development. Six dogs (33%) developed KCS within three months post-treatment. Statistically significant dose differences were observed between affected and unaffected eyes for the eyeball, cornea, and retina. ROC analyses identified dose thresholds predictive of KCS: 13.8 Gy (eyeball), 14.9 Gy (cornea), and 17.0 Gy (retina), with the retina showing the highest odds ratio (28.33). To ensure clinical relevance, KCS was diagnosed based on decreased tear production combined with corneal damage to ensure clinical relevance. This study proposes dose thresholds for ocular structures that may guide treatment planning and reduce the risk of KCS in canine patients undergoing IMRT. Further prospective studies are warranted to validate these thresholds and explore mitigation strategies for high-risk cases. Full article

Background: Previous research has demonstrated that 20 kHz probe or 37 kHz bath sonication of poloxamers comprising polypropylene glycol (PPG) and polyethylene glycol (PEG) blocks can generate degradation byproducts that are toxic to mammalian cells and organisms. Herein, an investigation of a PEGylated phospholipid micelle was undertaken to identify low-molecular-weight sonolytic degradation byproducts that could be cytotoxic. The concern here lies with the fact that sonication is a frequently employed step in drug delivery manufacturing processes, during which PEGylated phospholipids can be subjected to shear forces and other extreme oxidative and thermal conditions. Methods: Control and 20 kHz-sonicated micelles of DSPE-mPEG2000 were analyzed using dynamic light scattering (DLS) and zeta potential analyses to study colloidal properties, matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) mass spectroscopy (MS) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy to study the structural integrity of DSPE-mPEG2000, and ¹H-NMR spectroscopy and high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection to quantitate the formation of low-molecular-weight degradation byproducts. Results: MALDI-TOF-MS analyses of 20 kHz-sonicated DSPE-mPEG2000 revealed the loss of ethylene glycol moieties in accordance with depolymerization of the PEG chain; ¹H-NMR spectroscopy showed the presence of formate, a known oxidative/thermal degradation product of PEG; and HPLC-UV showed that the generation of formate was dependent on 20 kHz probe sonication time between 5 and 60 min. Conclusions: It was found that 20 kHz sonication can degrade the PEG chain of DSPE-mPEG2000, altering the micelle’s PEG corona and generating formate, a known ocular toxicant. Full article