Search Results (644)

Background/Objectives: The objective of this study was to clarify changes in the antimicrobial susceptibility of commensal bacteria in the conjunctival sac and nasal cavity associated with repeated use of prophylactic antimicrobial eye drops during intravitreal anti-vascular endothelial growth factor injections. Methods: Patients were divided into Group A, comprising 21 patients before the first use of prophylactic antimicrobial eye drops, and Group B, comprising 26 patients after receiving 20 or more injections. Minimum inhibitory concentration and susceptibility testing were performed on bacteria isolated from the conjunctival sac and nasal cavity using cefmenoxime, ceftazidime, levofloxacin, gatifloxacin, and moxifloxacin. Genetic mutations in the quinolone resistance-determining region of Staphylococcus epidermidis, phylogenetic relationships, and the nasal microbiome were also analyzed. Results: Corynebacterium, S. epidermidis, and Cutibacterium acnes were detected in both sites. In Group B, S. epidermidis and Corynebacterium showed reduced susceptibility to quinolones, whereas C. acnes did not. GyrA_S84 and ParC_S80 mutation rates in S. epidermidis were higher in Group B than in Group A. Among the patients with quinolone-resistant S. epidermidis isolated from both sites, 4 out of 10 patients had paired conjunctival and nasal isolates with the same ST type, suggesting that isolates from the two anatomical sites may be genetically related. The nasal microbiome α- and β-diversity did not differ significantly between groups, although exploratory LEfSe analysis suggested candidate taxon-level differences. Conclusions: Repeated prophylactic use of antibiotic eye drops was associated with reduced susceptibility in both the conjunctival sac and nasal cavity. Full article

Menthol is an agonist of TRPM8 receptors that activates tear secretion. Objectives: The hypothesis was that menthol delivered to the cornea in vapor form could stimulate tear secretion without irritation. Methods: This was a randomized, placebo-controlled, double-blind clinical trial of menthol vapor. Thirty generally healthy participants were randomized to the treatment or placebo group. Results: Median age was 58 (43, 73 IQR) years, 18 participants (60%) were female; 12 (40%) were male. Tear weight exceeded 5 mg in 2 (13.3%) of the placebo group, versus 13 (86.7%) of the menthol group (p = 0.020). Median weight of tears wiped from below the eye in the placebo group was 3 (−1, 8 IQR) mg versus 13 (8, 35 IQR) mg in the menthol group (p = 0.002). Nasolacrimal drainage in the placebo group weighed 10 (4,12 IQR) mg versus 56 (22, 173 IQR) mg in the menthol group (p < 0.001). The treated right eye felt qualitatively moister than the untreated left eye in 7 (47%) of the placebo group, versus 15 (100%) of the menthol group (p = 0.002). No participant reported eye irritation or any adverse effects at the one-week follow-up. Conclusions: Menthol delivered to the eye as vapor evoked tear secretion without eye irritation. Menthol vapor warrants further study as a complementary treatment or an alternative to eye drops for dry eye disease. Full article

Background/Objectives: Foot arch status and muscular strength may influence balance and physical performance. However, evidence regarding their associations with unilateral balance performance, walking performance, and lower limb functional capacity in healthy young adults, particularly in Saudi Arabia, remains limited. This study investigated the associations of foot arch status and handgrip strength with these outcomes in healthy young Saudi adults. Methods: In this cross-sectional study, 104 healthy young adults (mean age: 21.1 ± 1.2 years; 52.9% female) underwent assessment of foot arch status using the sit-to-stand navicular drop test (SSNDT) and of muscular strength using a digital hand dynamometer. Unilateral balance performance was assessed using the single-leg stance test (SLST) under eyes open and eyes closed conditions. Walking performance and lower limb functional capacity were assessed using the 10 m walk test (10-MWT) and the 30 s chair stand test (30 s-CST), respectively. Generalised estimating equations and multivariable linear regression models were used to examine adjusted associations. Results: Greater SSNDT scores were independently associated with shorter SLST duration for both the right (β = −0.46, p = 0.003) and left feet (β = −0.25, p = 0.048). Greater handgrip strength was independently associated with longer SLST duration for the right foot only (β = 0.17, p = 0.019). Neither SSNDT score nor handgrip strength was independently associated with 10-MWT or 30 s-CST outcomes after adjustment. Athletic participants demonstrated superior balance and chair-stand performance, while the male sex was associated with longer SLST duration. Conclusions: Greater functional lowering of the medial longitudinal arch was independently associated with poorer unilateral balance performance, whereas handgrip strength demonstrated a more limited association. These findings suggest that foot arch behaviour is more strongly related to balance performance than to walking performance or lower limb functional capacity. Full article

Eye diseases are common in veterinary clinical practice and are most often treated with topical ophthalmic preparations. Increasing resistance to antimicrobial agents is driving the search for safe and effective alternatives to traditional treatment methods. The aim of this study was to develop and evaluate gel-based ophthalmic formulations based on poloxamer 407 and sodium carboxymethylcellulose, containing propolis extracts and diclofenac sodium, by assessing their physical and chemical properties, antimicrobial activity, and cytotoxicity in vitro. Propolis extracts were prepared using a solvent consisting of ethanol and choline chloride, and the developed formulations were evaluated for pH, viscosity, refractive index, gelation temperature, SIRC cell viability and apoptosis, and antimicrobial activity against clinical and reference bacterial strains. The developed formulations exhibited physicochemical properties suitable for ophthalmic preparations and antimicrobial activity, particularly against Gram-positive bacteria. Most of the concentrations of the active ingredients tested were well tolerated by SIRC cells, although higher concentrations of the ethanol propolis extract caused a greater cytotoxic effect. The results obtained indicate that gelled ophthalmic formulations based on propolis extracts and diclofenac sodium are promising for the further development of topically acting ophthalmic preparations; however, their biological efficacy and safety must be confirmed. The results obtained indicate that gelled ophthalmic formulations based on propolis extracts and diclofenac sodium are promising for the further development of topical ophthalmic preparations; however, their bioavailability and safety must be confirmed by further in vivo studies. Full article

Objective: Myopia has reached epidemic proportions globally, with approximately 50% of the world population projected to be affected by 2050. Low-concentration atropine eye drops (0.01%, 0.025%, 0.05%) have emerged as a primary intervention for myopia control. Several meta-analyses on this topic have been published; however, none have included the most recent trials nor separately analyzed premyopia prevention outcomes. This systematic review and meta-analysis evaluates the efficacy and safety of these concentrations for myopia progression control and premyopia prevention. Methods: We searched PubMed, Web of Science, Embase, and Cochrane CENTRAL from database inception through April 2026. Randomized controlled trials (RCTs) comparing 0.01%, 0.025%, or 0.05% atropine with placebo or no treatment in children were included. Studies were screened using PICOS criteria (Population, Intervention, Comparison, Outcomes, Study design). Meta-analysis was performed using DerSimonian–Laird random-effects models. Subgroup analyses were conducted by concentration, follow-up duration, and population (myopia progression vs. premyopia prevention). Results: Of 18 full-text articles assessed, 8 RCTs (n = 1756) met all PICOS criteria and were included in the quantitative synthesis. For myopia progression, 0.01% atropine demonstrated significant efficacy at 1 year (pooled MD = +0.291 D, 95% CI: 0.199 to 0.384; p < 0.0001; I² = 29.1%) and at 2 years (pooled MD = +0.174 D, 95% CI: 0.056 to 0.291; p = 0.0038; I² = 0%). The 0.05% concentration showed the largest effect (pooled MD = +0.520 D, 95% CI: 0.409 to 0.630; p < 0.0001; I² = 0%). Clinically, a 0.25 D difference over 1–2 years may translate to approximately 0.50 D cumulative benefit over a typical 5-year treatment course, potentially reducing the risk of high myopia. For premyopia prevention, a narrative synthesis was performed due to extreme heterogeneity between studies (I² = 99.2%). All concentrations showed an excellent safety profile with no serious adverse events. Conclusions: Low-concentration atropine is effective for myopia progression control at all three concentrations, with a concentration-dependent gradient (0.05% > 0.025% > 0.01%). The 0.01% concentration offers a reasonable balance of efficacy and tolerability. Further independent validation of the 0.05% concentration is warranted. The premyopia prevention indication requires additional well-designed RCTs. Full article

Automatic inspection of small, irregular stamped parts remains challenging due to their compact size, random orientation on conveyors, and susceptible metallic surface reflections, coupled with local, weak, and densely distributed defects. This study presents an integrated vision-based dynamic defect detection and robotic sorting system to address these issues. The framework seamlessly unifies conveyor-based image acquisition, YOLO-CGMS-based defect recognition, hand–eye coordinate mapping, and Delta robot trajectory planning. To drive real-time visual perception, the YOLO-CGMS architecture modifies the YOLOv8n baseline by incorporating C2f-CRM, GRF-SPPF, MCA, and Inner-GIoU modules, optimizing small-defect feature extraction and bounding-box regression. Evaluated on a factory-collected dataset, YOLO-CGMS achieved an mAP50 of 88.7% and an inference speed of 236.23 frames/s, using only 2.8 M parameters and 7.3 GFLOPs. Compared with YOLOv8n, mAP and execution speed increased by 5.1 percentage points and 12.18 frames/s, respectively, while the parameter size and computational cost dropped by 0.2 M and 0.8 GFLOPs. Furthermore, physical sorting capability was validated on a developed prototype platform, yielding a mean hand–eye positioning error of 2.66 mm. Across 200 dynamic trials, the system successfully sorted 161 defective workpieces, translating to an 80.5% success rate and a mean cycle time of 2.6 s per part. These findings confirm that the proposed system reliably links closed-loop visual perception with physical execution, providing a practical foundation for the automated quality control of complex stamped components. Full article

Background: Dry Eye Disease (DED) is a multifactorial condition with an impact on quality of life and an often suboptimal response to conventional lubricants. This study aimed at evaluating the real-world efficacy, tolerability, and patient adherence of a therapy with a novel ophthalmic solution containing Ribohyal, a riboflavin–hyaluronic acid complex, used in patients with DED. Methods: This national survey included data from adult patients with clinically diagnosed DED treated with Lacrinova eye drops (4 times/day for 3 months) whose data were collected from 82 Italian ophthalmologists. Patients were assessed before (T0) and after treatment (T1). Outcomes included patient-reported symptoms for 9 domains (0–10 numerical rating scale), objective clinical parameters (best-corrected visual acuity [BCVA], break-up time [BUT], and corneal fluorescein staining [CFS]), and treatment acceptability. Results: Data from 2993 patients (5986 eyes) were analyzed. Improvements were observed across all 9 symptom domains, with reductions ranging from 53% to 60% (all p < 0.001). BCVA and BUT significantly improved (from 0.08 ± 0.22 at T0 to 0.06 ± 0.19 logMAR at T1 and from 9.20 ± 4.49 to 11.85 ± 4.66 s at T1, respectively, both p < 0.001). The prevalence of CFS decreased from 42.0% to 23.4% (p < 0.001). Treatment acceptability was high, with mean scores of 8.88± 1.49 for tolerability, 8.55 ± 1.63 for adherence, and 8.62 ± 1.55 for perceived efficacy. No relevant adverse events were reported. Conclusions: Lacrinova eye drops demonstrated significant improvements in both symptoms and clinical signs of DED, with excellent tolerability and adherence. These findings support its use as an effective therapeutic option in routine clinical practice, although controlled studies are warranted to confirm the efficacy. Full article

Background: Conventional ophthalmic eye drops have low bioavailability (<5%) and poor patient adherence, driving the development of sustained-release ophthalmic drug delivery systems. The lacrimal drainage system represents a unique anatomical site for minimally invasive depot formulations. Objective: To summarize and critically appraise punctal and intracanalicular drug delivery systems, occlusive devices, and in situ-forming hydrogels with respect to composition, release mechanisms, clinical efficacy, safety, and critical quality attributes (CQAs). Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov, and patent/regulatory sources, including FDA materials and Google Patents, covering 2001–2026. Anatomical features, materials, active pharmaceutical ingredients, release profiles, and adverse events were analyzed. Results: Seventy-one sources were included. Occlusive plugs without an active pharmaceutical ingredient demonstrate premature expulsion in up to 57.4% of cases and bacterial colonization in 44%. Drug delivery systems provide release from 7 days (PEGDA hydrogels) to 3 months (Eximore, Ocular Therapeutix™). DEXTENZA^® (dexamethasone) is FDA-approved for postoperative inflammation, whereas pivotal trials of travoprost (OTX-TP) and latanoprost systems (L-PPDS, EXP-LP) did not demonstrate superiority over placebo or eye drops. In situ systems eliminate size-fitting requirements but face challenges related to gelation control and biodegradation. Conclusions: We propose the following candidate CQAs: retention (>80% over 4 weeks), swelling degree (30–60%), controlled burst release (<40% within 24 h), and mechanical compatibility. The proposed QTPP matrices for punctal, intracanalicular, and in situ systems may guide the development of ophthalmic drug delivery platforms. Full article

Clozapine-induced hypersalivation (CIH) affects 30–80% of patients on clozapine and is a major contributor of non-adherence. Current managements, largely based on systemic anticholinergics, can worsen other clozapine-related side effects. Here sublingual tropicamide 1% eye drops can be a low-cost alternative worth evaluating. We report a case series of seven patients with schizophrenia treated with sublingual tropicamide 1% ophthalmic solution (4–8 drops/day) for CIH. Treatment response was assessed by patient-reported percentage reduction in salivation. All seven patients reported improvement (25–80%). One patient reported a transient bitter taste; no systemic anticholinergic effects occurred. Sublingual tropicamide was associated with patient-reported improvement in CIH and was well tolerated in this small, uncontrolled series. Its short duration of action and local administration may offer practical advantages over systemic anticholinergics, though the mechanism remains unproven. Randomised trials with validated outcome measures are needed to establish its efficacy and safety. Full article

Background/Objectives: Glaucoma medication adherence is influenced by multiple factors, including treatment-related knowledge, eye drop instillation technique, cognitive function, and systemic health status. However, the relationships between comprehensive geriatric assessment (CGA) results and specific adherence-related problems remain poorly understood. This study investigated the associations between CGA results and glaucoma eye drop adherence-related problems using the newly developed Shimane University Glaucoma Eye Drop Adherence Questionnaire (SU-GAQ). Methods: This retrospective study included 187 consecutive glaucoma patients who underwent CGA and completed the SU-GAQ at Shimane University Hospital. The SU-GAQ consists of Knowledge (Q1–Q5) and Technique (Q6–Q15) domains. CGA included the Mini-Cog, G8, and Age-Adjusted Charlson Comorbidity Index (ACCI). Associations between questionnaire responses and CGA results were evaluated using Spearman’s rank correlation and generalized regression analyses. Exploratory factor analysis (EFA) based on tetrachoric correlations was performed to evaluate the questionnaire structure. Results: Lower Mini-Cog scores were significantly associated with higher Knowledge-domain scores (ρ = −0.27, p = 0.0002) and higher overall questionnaire scores (ρ = −0.23, p = 0.002). In multivariate analysis, Mini-Cog remained independently associated with the Knowledge domain (estimate = −0.31, p < 0.0001) and total score (estimate = −0.44, p = 0.002). Higher ACCI scores were associated with higher Technique-domain scores (ρ = 0.19, p = 0.009) and remained significant in multivariate analysis (estimate = 0.16, p = 0.02). G8 scores were not significantly associated with questionnaire outcomes. EFA identified a two-factor structure corresponding to the predefined Knowledge and Technique domains, accounting for 71.2% of the total variance. Conclusions: Lower cognitive function was primarily associated with knowledge-related barriers to glaucoma medication adherence, whereas greater comorbidity burden was associated with technical difficulties in eye drop instillation. The SU-GAQ demonstrated a clinically meaningful two-domain structure and may facilitate identification of specific adherence-related barriers in glaucoma patients. Full article

Background/Objectives: Despite available treatment options, glaucoma continues to be a leading cause of irreversible blindness. Current medications have multiple limitations, including rapid drainage, ocular irritation, requirement for multiple daily dosings, and systemic side effects. The current study was designed to engineer and characterize a pregabalin-containing enhanced delivery formulation (PRG-EDF) to directly address these inadequacies. Methods: PRG-EDF eye drops were prepared using ingredients that are either U.S. Food and Drug Administration (FDA)-approved for ophthalmic use or have established safety profiles. The formulation was characterized using multiple evaluations, including pH, zetasizer analyses, viscosity, in vitro drug release, transcorneal permeability, determination of dose concentration and volume, systemic exposure, and potential for tachyphylaxis. Efficacy was evaluated using both Dutch belted rabbits and baboons. Results: PRG-EDF provides extended release for up to 24 h. Ex vivo data reveal that PRG-EDF does not alter the inherent high PRG corneal permeability. An intraocular pressure (IOP) study using DB rabbits demonstrates that 40 µL of PRG-EDF, 0.6%, is the optimum dose of our formulation. Comparison of the efficacy of PRG-EDF with commercial products demonstrated its superiority in overall IOP-lowering efficacy. An extended in vivo assessment demonstrated that the potency of PRG-EDF reached maximum IOP-lowering amplitude after 4 weeks of daily dosing. Moreover, an in vivo bioadhesion assay demonstrated that EDF remained on the ocular surface for up to 24 h. Impressively, PRG-EDF is as effective in baboons as in rabbits. Conclusions: We have successfully engineered a highly promising once-daily glaucoma medication with superior efficacy, as illustrated by higher IOP-lowering ability and prolonged duration of action. Full article

Non-invasive drug delivery for ocular diseases remains a significant challenge in ophthalmology, as conventional eye drops offer less than 5% bioavailability due to pre-corneal barriers and the corneal epithelium. This review explores the intranasal (IN) route as a promising strategy for targeting both the anterior and posterior segments of the eye. The IN route leverages several distinct pathways: the nasolacrimal reflex for remote physiological stimulation; the “neural bridge” through the cribriform plate, allowing direct perineural and vascular transport via the olfactory and trigeminal nerves to bypass the blood–retinal barrier; and systemic absorption that avoids hepatic first-pass metabolism. Pre-clinical evidence indicates that IN administration of agents such as erythropoietin, nerve growth factor, and insulin achieves superior retinal concentrations compared to topical or systemic dosing, offering neuroprotection in models of retinal degeneration and glaucoma. Clinically, varenicline nasal spray is already FDA-approved for dry eye disease, while intranasal steroids demonstrate a favorable ocular safety profile without significantly increasing intraocular pressure. Although limited by mucociliary clearance and small delivery volumes, the IN route offers a painless, non-invasive alternative to intraocular injections, potentially enhancing patient compliance. Future advancements in mucoadhesive nanocarriers are essential to optimize drug residence time and realize the full potential of nose-to-eye delivery in chronic ophthalmic care. Full article

Background/Objectives: Corneal epithelial defects and ulcers remain a significant clinical challenge, often leading to vision impairment and requiring prolonged treatment. In this context, topical insulin has recently gained attention in ophthalmic research. However, conventional eye drops suffer from short residence time and poor bioavailability. To overcome these limitations, the present study evaluates, for the first time in vitro, multiple commercially available soft contact lenses as sustained insulin delivery platforms, analyzing how protein loading influences the essential physicochemical and optical properties of these materials. Methods: The physicochemical properties of eight different commercially available soft contact lens materials, including light transmittance, wettability, and central thickness, were examined before and after insulin loading via a soaking method. Loading efficiency and in vitro release profiles were assessed over time. Corneal cytotoxicity and permeability were evaluated using a human epithelial cell-based model (HCE-2). Results: Among the eight commercial materials screened, Nesofilcon A, Stenfilcon A, and Delefilcon A were selected due to their superior physicochemical performance after insulin loading. At initial concentrations of 1750 and 875 μg/mL, drug loading efficiency reached maximum values of up to 69.3% and 63.1%, with cumulative release values reaching up to 32.4% and 55.1% after 24 h, respectively. Permeability studies confirmed effective insulin diffusion across the HCE-2 cell layer, while cell viability assays indicated no significant cytotoxicity at the lower loading concentration. Conclusions: Insulin-loaded commercial soft contact lenses represent a promising drug–device combination product for the management of persistent epithelial defects and refractory corneal ulcers. These in vitro findings suggest that this approach may enhance drug performance by prolonging residence time and improving corneal bioavailability, while maintaining essential lens properties. However, further in vivo and clinical studies are required to confirm these potential benefits and establish therapeutic efficacy for the management of persistent epithelial defects. Full article

Background and Clinical Significanc: Neuropathic corneal pain is a debilitating condition characterized by ocular pain disproportionate to clinical signs, often resulting from peripheral and central sensitization of the corneal somatosensory pathway. Emerging evidence suggests that chronic involuntary muscle contraction in blepharospasm may lead to irritation of trigeminal afferents and corneal neurogenic inflammation, potentially predisposing patients to neuropathic corneal pain. Given its debilitating nature, early recognition can prevent the progression of neuropathic sequelae. This study examines the potential role of blepharospasm as a predisposing factor contributing to neuropathic corneal pain. Case Presentation: This retrospective case series describes three cases (median age: 50 years) of neuropathic corneal pain in association with blepharospasm and their clinical course following multimodal treatment over a median follow-up period of one year. Ocular surface was evaluated using slit-lamp biomicroscopy, while corneal nerve structure and morphology were assessed with in vivo confocal microscopy. All the three subjects presented with minimal ocular surface staining but disproportionate ocular pain characterized by burning sensation and photophobia. Proparacaine challenge testing was performed to determine the subtype of neuropathic corneal pain. Pain symptoms and quality of life were evaluated using the Ocular Pain Assessment Survey and Ocular Surface Disease Index questionnaires. In vivo confocal microscopy demonstrated characteristic corneal nerve abnormalities including reduced corneal nerve density, increased nerve tortuosity, and the presence of microneuromas. Treatment included oral Pregabalin or Gabapentin, topical lubricants, Cyclosporine 0.05% (1 case), and 20% autologous serum eye drops (1 case). Two of the three cases received four to five injections of botulinum toxin for blepharospasm, whereas one had undergone a single injection prior to review. All patients also received weekly periorbital quantum molecular resonance electrotherapy for two months. Improvements were observed across multiple domains of the Ocular Pain Assessment Survey and Ocular Surface Disease Index evaluation, including ocular pain, photophobia, non-ocular pain, and quality-of-life measures following multimodal treatment. The co-existence of blepharospasm and neuropathic corneal pain observed in our cases supports a possible association between chronic periocular muscle hyperactivity and corneal nociceptor sensitization. Proposed mechanisms include chronic trigeminal nerve irritation, neurogenic inflammation, and sensitization mediated by pro-inflammatory neuropeptides. Multimodal treatment targeting both motor hyperactivity and neuropathic pain pathways appeared to provide symptomatic relief, including the use of quantum molecular resonance electrotherapy, which might modulate pain pathways, block nociceptor neurotransmission, and accelerate corneal nerve regeneration. Given the complexity of the neural pathways responsible for ocular discomfort, further studies are required to elucidate the relationship between neuropathic corneal pain and blepharospasm in larger cohorts, as well as refine existing therapeutic approaches, including evaluating the therapeutic role of electrotherapy. Conclusions: Blepharospasm may represent a potential predisposing factor of neuropathic corneal pain. Early recognition and concurrent treatment of blepharospasm and neuropathic corneal pain can effectively relieve symptoms and improve quality of life. Adopting a multimodal treatment approach is therefore recommended. Full article

Acanthamoeba keratitis (AK) and mycotic keratitis (MK) are severe infectious diseases of the cornea. A major challenge to treatment is the poor bioavailability of conventional eye drop formulations, resulting in significant loss of the therapeutic compound. The present study describes the preparation of self-nanoemulsifying drug delivery systems (SNEDDSs) utilizing 3D-molded inserts as a vehicle for the co-delivery of voriconazole (VOR) and diclofenac sodium (DIC). Characterization of the SNEDDS and the 3D-molded inserts involved analysis of droplet size, polydispersity index (PDI), and zeta potential (ZP), followed by an ex vivo transcorneal permeation. Careful optimization of the SNEDDS composition was fundamental for obtaining a nanoemulsion with a droplet size under 100 nm, a PDI below 0.35, and a variable ZP (ranging from −14.6 ± 0.1 to 16.3 ± 2.4 mV). These properties facilitated a marked improvement in voriconazole’s solubility and subsequent transcorneal permeability. The investigation of the inserts revealed that the in vitro drug release could be tailored for immediate release or extended release. Moreover, ex vivo permeation studies demonstrated that the inserts delivered voriconazole to the cornea at concentrations more than the minimum inhibitory concentration. This work successfully demonstrates the formulation of a patient-centric, personalized drug delivery platform for the treatment of AK and MK. Full article