Search

Introduction: Lotilaner ophthalmic solution (0.25%) is the first United States Food and Drug Administration (US FDA)-approved drug for treating Demodex blepharitis. In pivotal trials, it was found to be well tolerated and demonstrated a significant reduction in collarettes and mite density after a 6-week treatment regimen. This study aimed to report the safety and efficacy profile of lotilaner ophthalmic solution (0.25%) from a pooled analysis of two pivotal trials in patients with Demodex blepharitis. Methods: Pooled data were analyzed from two randomized, double-masked, vehicle-controlled clinical trials [phase 2b/3 Saturn-1 (NCT04475432) and phase 3 Saturn-2 (NCT04784091)] in which patients with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution (0.25%) (study group) or the vehicle formulation without lotilaner (control group), twice daily for 6 weeks. The outcome measures were the proportion of patients with 0–2 collarettes (grade 0 collarettes), mite eradication, erythema cure, and the proportion of patients with ≤ 10 collarettes (grade 0 or 1 collarettes) at day 43. Results: Overall, 833 participants were randomized to receive either the study drug (N = 415) or vehicle (N = 418). On day 43, 49.8% of patients in the study group vs. 9.9% in the control group (p < 0.0001) had collarette grade 0 (0–2 collarettes). A reduction to ≤ 10 collarettes (grade 0 or 1 collarettes) was achieved in 85.1% of patients in study group vs. 28.0% in control group (p < 0.0001). The proportion of patients achieving mite eradication (60.2% vs. 16.1%, p < 0.0001) and erythema cure (24.9% vs. 7.9%, p < 0.0001) were also statistically significantly higher in the study group compared to the control group. The rates of adverse events were low in both studies, with no serious drug-related ocular adverse events reported. As many as 92% of patients rated the study drop as neutral to very comfortable. Conclusions: Twice-daily treatment with lotilaner ophthalmic solution (0.25%) for 6 weeks demonstrated statistical significance for all outcome measures compared to the vehicle control, with low rates of adverse events and a high rate of drop comfort. [ABSTRACT FROM AUTHOR]

Background/Objectives: A novel ophthalmic formulation, XanterDES, containing 0.2% xanthan gum and 0.025% desonide sodium phosphate (DES), was developed to alleviate ocular surface discomfort and irritation. This study aimed to evaluate its pharmacodynamic properties and to characterize its rheological behavior and mucoadhesive characteristics, compared to another formulation containing 0.2% hyaluronic acid and 0.001% hydrocortisone (HYD). Methods: A rabbit (New Zealand White) model of LPS-induced uveitis was used to test different concentrations of DES on ocular markers of inflammation. The efficacy of XanterDES and HYD on induced dry eye was evaluated by assessing tear volume and corneal damage in C57BL/6 mice exposed to a controlled environmental chamber. The rheological and mucoadhesive properties of XanterDES and HYD were assessed using a HAAKE RheoStress RS600 rheometer and a TA-XT2 texture analyzer, respectively. Results: In the uveitis model, unlike DES 0.25%, a low concentration of 0.025% DES showed a significant inhibitory activity localized to the eye surface and effectively reduced corneal edema. In the dry eye model, XanterDES demonstrated superior efficacy compared to HYD, effectively preventing both tear volume reduction and corneal damage. XanterDES also demonstrated pseudoplastic and enhanced mucoadhesive properties compared to HYD. Conclusions: The ancillary anti-inflammatory effects of a low dose of DES combined with the biophysical properties of xanthan gum are supportive of a favorable therapeutic profile, promoting the maintenance or restoration of ocular surface homeostasis while minimizing the risk of adverse effects typically associated with standard-dose corticosteroids. The comparison with another low-dose corticosteroid highlights the superiority of XanterDES in pharmacodynamic and biophysical performance. [ABSTRACT FROM AUTHOR]

Perfluorohexyloctane ophthalmic solution (Miebo) and water-free cyclosporine ophthalmic solution 0.1% (Vevye) are recently approved treatments for dry eye disease (DED). Perfluorohexyloctane (PFHO) uses a novel approach to treat evaporative DED, whereas water-free cyclosporine (CsA 0.1%) is formulated to increase ocular delivery of its active ingredient to improve tear production. The two medications utilize the distinctive properties of two different semifluorinated alkanes (SFAs) to elicit their therapeutic effects. PFHO consists of 100% active ingredient and forms a monolayer on the surface of the tear film to inhibit evaporation. CsA 0.1% utilizes a vehicle consisting of perfluorobutylpentane (PFBP) and ethanol to facilitate delivery of cyclosporine to ocular tissues. The structure of these SFAs determines their differing behaviors and functions. The longer chain length of PFHO results in a slower evaporation rate and facilitates formation of a stable monolayer on the ocular surface. In vitro, PFHO demonstrated a substantially lower evaporation rate versus PFBP or human meibum, as well as a significantly longer ocular surface residence time. Ex vivo, PFHO demonstrated a longer ocular surface residence time than PFBP. The shorter chain length of PFBP enables it to better solubilize cyclosporine and improve drug delivery to ocular tissues. Although both of these ophthalmic drops utilize SFAs, their differences—in physicochemical properties and the mechanisms by which they are understood to intervene in the DED cycle—are important considerations in treatment selection for patients with DED. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the usage of oxymetazoline hydrochloride ophthalmic solution, 0.1% in the treatment of Graves' disease to improve lid symmetry. Methods: Fourteen patients were identified with unilateral upper eyelid retraction, secondary to Graves' disease. A phenylephrine test was performed to evaluate whether treating the unaffected (non-retracted) side would result in improved symmetry using Hering's law. Patients were prescribed oxymetazoline hydrochloride ophthalmic solution, 0.1% to instill into the unaffected eye. Marginal reflex distance 1 (MRD1) measurements were taken pre- and post-treatment and patient satisfaction surveys were completed. Results: The average pre-treatment MRD1 difference between the right eye (OD) and the left eye (OS) was 2.46 [range 1.50–4.00]. The average post-treatment MRD1 difference between OD and OS was 0.39 [range 0.00–1.00]. One hundred percent of patients were satisfied or very satisfied with the improvement in symmetry. Conclusions: Oxymetazoline hydrochloride ophthalmic solution, 0.1% is a potential method to improve symmetry in patients with Graves' disease and unilateral upper eyelid retraction via Hering's law, especially for non-surgical candidates or those who prefer non-surgical treatment. Our results indicate improved MRD1 differences between fellow eyes and patient satisfaction regarding the symmetry of the upper eyelids. [ABSTRACT FROM AUTHOR]

Background: TearCare is an in-office procedure indicated to treat MGD and relieve DED signs and symptoms. MGD is a major cause of DED, a high-prevalence condition currently treated with medical therapies including over-the-counter and prescription drops. The BIA assessed the budget impact of increasing the TearCare market share against prescription drops in treating moderate to severe MGD-associated DED in US patients ≥ 18 years over 2 years. Research Design and Methods: Prescription drops used twice daily were compared to TearCare (used once per year for patients with moderate disease and twice for severe disease). The BIA assumed a health plan population with 1 million lives and incorporated population characteristics, treatment allocation, market share, and treatment persistence. Assuming a 20% increase in TearCare market share, the model calculated total per member per year/cost (PMPY/PMPM). Results: Results showed PMPY and PMPM savings of $34.47 and $2.87, respectively. Sensitivity analysis indicated sensitivity to the proportion of moderate DED patients using prescription drops, moderate to severe DED incidence, and cyclosporine 0.05% costs. If 10% of patients did not switch to TearCare, notable savings were still observed with PMPY and PMPM savings of $30.11 and $2.51 over 2 years. Conclusion: Results show cost savings with a TearCare market share increase in treating MGD-associated DED. [ABSTRACT FROM AUTHOR]

To evaluate the safety and efficacy of 0.75% phentolamine ophthalmic solution (POS), an α-adrenergic antagonist, in reversal of pharmacologically induced mydriasis. Two phase 3, multicenter, placebo-controlled, randomized, double-masked clinical trials in healthy participants. Five hundred fifty-three healthy 12- to 80-year-old participants were randomized 1:1 (MIRA 2) and 2:1 (MIRA 3) to receive either POS or placebo eye drops in both eyes. Participants received POS or placebo administered 1 hour after mydriasis, induced by instillation of either 2.5% phenylephrine, 1% tropicamide, or 1% hydroxyamphetamine / 0.25% tropicamide. Percent of participants returning to within 0.2 mm of baseline pupil diameter in study eye 90 minutes after POS administration. Safety measures included treatment-emergent adverse events and tolerability measures, including conjunctival hyperemia. A total of 553 participants were randomized to treatment with placebo (n = 215) or POS (n = 338). A statistically significant greater percentage of participants treated with POS showed reversal of mydriasis at 90 minutes compared to placebo (MIRA 2: 48.9% vs. 6.6% [ P < 0.0001]; MIRA 3: 58% vs. 6% [ P < 0.0001]) and as early as 60 minutes (MIRA 2: 27.7% vs. 2.2% [ P < 0.0001]; MIRA 3: 42% vs. 2% [ P < 0.0001]). Between 28% and 34% of participants receiving placebo did not returned to baseline PD at 24 hours after pharmacologic dilation compared with 8% to 11% of patients treated with POS (P < 0.0001). Treatment with POS reduced PD within 60 to 90 minutes, with a statistically significant time savings of 5 to 6 hours to return to baseline PD compared with placebo. One or 2 drops of POS rapidly reversed mydriasis in all participants regardless of mydriatic agent or iris color. More participants receiving POS reported a benefit in the resolution of visual symptoms caused by pharmacologically induced mydriasis compared with placebo, with statistically significant differences noted as early as 1 hour. The safety profile was favorable, with the most common adverse effects being mild transient conjunctival hyperemia (11.2%), instillation site discomfort (10.9%), and dysgeusia (3.6%). Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diabetes is a well-recognised factor inducing a plethora of corneal alterations ranging from dry eye to reduced corneal sensibility, epithelial defects, and reduced cicatrisation. This cohort study aimed to assess the efficacy of a novel ophthalmic solution combining cross-linked hyaluronic acid (CHA), chondroitin sulfate (CS), and inositol (INS) in managing diabetes-induced corneal alterations. Specifically, it evaluated the solution's impact on the tear breakup time (TBUT), the ocular surface disease index (OSDI), and corneal sensitivity after three months of treatment. Additionally, the solution's potential to promote wound healing was examined. Methods: Two different populations were retrieved from the database; the first one was composed of 20 diabetic subjects treated for three months with the ophthalmic CAH-CS (OPHTAGON srl, Rome, Italy), while the second group was composed of 20 diabetic subjects who did not want to use any eye lubricant or other treatment. The outcome measures were the TBUT, the OSDI score, and the corneal sensitivity measured using a Cochet–Bonnet aesthesiometer. To investigate the wound-healing properties, in vitro tests were conducted using two cell lines, comparing the results of scratch tests with and without the solution. Results: The results indicate that CHA-CS significantly improved the tear film stability, as evidenced by an increased TBUT and a reduction in dry eye symptoms reflected by lower OSDI scores. Moreover, the solution was associated with an enhanced corneal sensitivity in treated patients. In wound-healing assays, CHA-CS promoted cell motility, suggesting a supportive role in tissue repair compared to untreated cells. Conclusions: Collectively, the results suggest that CHA-CS could serve as an innovative tool for the treatment of diabetic patients with corneal alterations and delayed corneal sensitivity. Clinical trial registration number: Clinical Trial.gov NCT06573606. [ABSTRACT FROM AUTHOR]

Aims Methods and Results Conclusion With the growing evidence of cardiovascular risks associated with diclofenac use, regulatory measures governing its application and sales have intensified since 2008. We evaluated the association between central regulatory actions and trends in diclofenac use in Denmark from 1999 to 2023, according to different dosage forms and routes of administration.Data on diclofenac sales in Denmark from 1999 to 2023 were retrieved from the publicly available web database MEDSTAT, based on the Danish Register of Medicinal Products Statistics. The annual sales of various diclofenac dosage forms, including systemic (tablets, modified‐release dosage forms, and suppositories) and topical (nonspecific and ophthalmic) dosage forms, were calculated and displayed by sales unit.From 1999 to 2008, sales of all systemically administered diclofenac forms increased: tablets by 51% (2000–2008), modified‐release dosage forms by 40% (2003–2007), and suppositories by 44% (1999–2008). Thereafter, sales of tablets declined by 86% and modified‐release dosage forms by 90% through 2023. The sales of suppositories declined somewhat lesser, by 34%, during 2008 to 2018 and then increased by 67% through 2023. Sales of nonspecific topical diclofenac increased by several thousandfold from 2005, although with brief periods of decline.Sales of systemically administered diclofenac dosage forms, particularly tablets and modified‐release drugs, declined by approximately 90% from about 2008 to 2023, indicating compliance with Danish and international regulatory actions. Conversely, sales of topically administered diclofenac increased heavily from 2005 to 2023, denoting a policy‐driven shift toward these lower risk dosage forms. [ABSTRACT FROM AUTHOR]

This study aims to develop and implement an ergonomic intervention program at the workplace of knowledge workers, and to evaluate its impact on the reduction of Computer Vision Syndrome (CVS) and musculoskeletal symptoms. 84 workers were part of the study (mean age 43.2 ± 9.7 years). The intervention included training, delivery of a packaging of artificial tears, and adjustments in workstations. It was conducted intensively along 6 weeks. Data was collected on-site, with questionnaires administered pre-intervention, 2 months after, and 4 months after. Participants exhibited behavioural changes, especially in workplace adjustments and visual rest. By the intervention's end, over 90% had correctly adjusted screens and adopted appropriate postures, while 42.7% adhered to the 20x20x20 rule. CVS severity and prevalence decreased, but not significantly across the three time points. Significant improvements were observed in upper back and neck musculoskeletal symptoms at the end of workdays. Findings suggest that an ergonomic intervention program can benefit employees by reducing visual and musculoskeletal symptoms. PRACTITIONER SUMMARY: This study addresses CVS and MSDs, commonly experienced by individuals working with display screen equipment. It was emphasised the significance of ergonomic interventions in reducing musculoskeletal discomfort. The major finding was the positive behavioural changes, such as improved workplace adjustments and visual rest practices. [ABSTRACT FROM AUTHOR]

This study proposed a novel electrochemical sensor for the sensitive measurement of the eye medication ofloxacin (OFX), which is based on a NiO@C-dot nanocomposite. The NiO@C-dot nanocomposite was synthesized using the sol-gel method, which was then applied to alter a glassy carbon electrode (GCE). With regard to OFX, the modified GCE shown outstanding electrochemical activity along with good sensitivity, selectivity, and stability. With OFX concentrations ranging from 5 µM to 975 µM, the NiO@C-dot/GCE showed a linear relationship with a sensitivity of 0.63994 µA/µM. The limit of detection (LOD) was 0.023 µM. The response to 50 µM OFX was measured, and the electrode was stored at 4°C after each test in order to evaluate the sensor's long-term stability and repeatability. After 20 days, the peak current response was still 97.89 % of its initial value. After 40 days of prolonged storage, 93.78 % of the electrode's original responsiveness was retained. The sensor showed a recovery rate of 97.37–99.70 % in all sample types when it was used to detect OFX in human urine, tap water, and food samples. These findings highlight the NiO@C-dot/GCE's outstanding selectivity, dependability, and longevity as solid platforms for OFX detection in complicated samples for a range of applications.

Introduction: Retinal vein occlusion (RVO) often causes irreversible visual impairment, making early prevention crucial. This study aims to identify associations between different medications and RVO and provide information for clinical practice. Method: This study included reports of RVO from the FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2023. The reported drugs were analyzed for adverse drug reaction (ADR) signals using four disproportionality algorithms. Kaplan-Meier curves and median time to onset were used to evaluate the drugs. Results: From 2004 to 2023, the FAERS database recorded 6,151 reports associated with RVO. Disproportionality analyses identified 25 drugs significantly associated with RVO. Mirabegron showed the highest risk signal, followed by Raloxifene, Tadalafil, Fingolimod, and Bimatoprost. These high-risk drugs are distributed across different therapeutic areas, including urogenital system and sex hormones, ophthalmic drugs, nervous system drugs, musculoskeletal system drugs, anti-tumor and immune-modulating drugs, and anti-parasitic drugs. Specific drug targets such as adrenergic receptor agonists, hormone regulators, and PDE5 inhibitors were identified as high risk. Ophthalmic drugs exhibited the longest median time to adverse ocular reactions at 532.01 days, followed by anti-parasitic drugs, nervous system drugs, urogenital system and sex hormone drugs, anti-tumor and immune-modulating drugs, and musculoskeletal system drugs. Conclusion: This study provides an overview of drug-induced RVO, identifying potential culprit drugs and their distribution characteristics. These findings enhance understanding of medication safety and help optimize clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique. Methods: Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo. Results: Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye. Conclusions: SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies. Translational Relevance: Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and efficacy of Lotilaner ophthalmic solution 0.25% in the treatment of demodex blepharitis. Methods: PubMed, Web of Science, Scopus, and Embase databases were searched. RCTs comparing lotilaner with placebo or any other standard treatments were included. Outcomes of mean collarette grade (MCG), mite density (Md), meaningful collarette reduction (MCR), mite eradication (ME), were pooled as mean difference (MD), and the outcomes of erythema cure (EC), collarette cure (CC) adverse events (AE) as risk ratio (RR) with their 95% confidence interval (CI) between the two groups from baseline to the endpoint. Review Manager (Version 5.4.1) software was used to conduct all statistical analyses. Results: Four RCTs (947 patients) were included in this study. The overall effect favored the lotilaner group in terms of mean collarette grade upper lid (MD −0.99, 95% CI [−1.26, −0.72]), MCG lower lid (MD −0.57, 95% CI [−1.03, −0.11]), Md (MD −1.13, 95% CI [−1.47, −0.79]), MCR (MD 2.07, 95% CI [2.27, 3.21]), ME (MD 3.46, 95% CI [2.96, 4.04]). EC (RR 3.16, 95% CI [2.18 to 4.59]) and CC (RR 4.17, 95% CI [2.97 to 5.85]). No significant difference between the two groups in terms of AE (RR 1.25, 95% CI [0.75 to 2.06]). However, these findings are limited by significant heterogeneity in some of the reported outcomes. Conclusions: Our findings show that lotilaner might effectively treat Demodex blepharitis. However, further RCTs with larger and more diverse populations are needed to confirm these findings as some outcomes show significant heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Anterior blepharitis (AB) is a chronic eyelid inflammation with no definitive cure. Objectives: To assess the safety and efficacy of a 1% povidone-iodine (PVI) ophthalmic solution lid scrub compared to formulated eyelid wipes in treating AB. Design: A prospective, randomized, controlled, observer-masked, paired-eye trial. Methods: Sixty-three AB patients were randomly assigned to a 30-day treatment in which one eye underwent a daily lid scrub with 1% PVI solution (1% PVI group), while the fellow eye was treated with formulated eyelid wipes (control group). Clinical outcomes, such as blepharitis signs, tear breakup time, and corneal staining, were evaluated at study enrollment and exit visits. Symptom assessments utilized the visual analog scale (VAS) per eye and the ocular surface disease index (OSDI) questionnaire. Results: Fifty-two patients (mean age 62.3 years, 53.8% females) completed the treatment, while seven patients were lost to follow-up, three were non-compliant, and one sustained an eye trauma. After 30 days, both the 1% PVI and control groups exhibited significant improvements in symptoms, blepharitis signs, and corneal staining (p < 0.05). The 1% PVI scrubs were equally effective as eyelid wipes in most outcomes (p = 0.480) and superior in alleviating eyelid erythema (p = 0.007). Only the 1% PVI group showed a positive correlation between OSDI and VAS score improvements (r (52) = 0.353, p = 0.01). No adverse events related to either treatment modality were reported. Conclusions: A 1% PVI solution is an effective, safe, and well-tolerated treatment option for AB and is superior to formulated eyelid wipes in several subjective and objective measures. [ABSTRACT FROM AUTHOR]

The facilitation of targeted drug delivery within the ocular region presents a formidable challenge owing to its intricate physiological structure, which confers a biological barrier. This barrier is characterised by short retention times, diminished drug accumulation, and suboptimal bioavailability. To overcome these limitations, this study aimed to develop a hyaluronic acid-based nanoparticulate system encapsulating curcumin (CUR) and ranibizumab (RAN), designated as CUR-RAN@NPs with a uniform distribution of particle size and exhibited the capacity for sustained release of both CUR and RAN. The evaluation of biosafety and biocompatibility using cytotoxicity assays indicated that CUR-RAN@NPs are non-toxic and biologically compatible. Consequently, the CUR-RAN@NPs have promising potential for the advancement of ocular drug delivery systems. Finally, CUR-RAN@NPs demonstrated exceptional antibacterial activity and inhibition of neovascularization, thereby underscoring their therapeutic potential in ophthalmic applications. [ABSTRACT FROM AUTHOR]

In this meta-analysis, our aim was to systematically evaluate the efficacy and safety of lotilaner ophthalmic solution in treating Demodex Blepharitis (DB), with the goal of providing evidence for clinical practice. PubMed, Embase, Web of Science, The Cochrane Library, CNKI, Wanfang, and CBM were searched from inception to November 28, 2023. Randomized controlled trials (RCTs) comparing lotilaner ophthalmic solution (experimental group) with placebo (control group) for the treatment of DB were included. Two researchers independently screened the literature, extracted the data, and assessed the quality of the included studies. Meta-analysis was conducted using RevMan 5.4 software. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to evaluate the evidence quality of outcomes. Publication bias was assessed using a funnel plot. Four RCTs involving 947 patients were included. Meta-analysis revealed that compared to placebo, lotilaner ophthalmic solution significantly increased the rate of mite eradication (RR = 3.61, 95% CI (2.90, 4.49), P < 0.00001). Additionally, lotilaner treatment resulted in higher rates of collarette cure, erythema cure, composite erythema/collarette cure, and clinically meaningful collarette cure; the differences were statistically significant, with effect sizes (RR = 5.74, 95% CI (4.27, 7.72), P < 0.00001), (RR = 3.16, 95% CI (2.18, 4.58), P < 0.00001), (RR = 6.75, 95% CI (3.75, 12.16), P < 0.00001), and (RR = 3.09, 95% CI (2.65, 3.60), P < 0.00001), respectively. Mite density (MD = -1.42, 95% CI (-2.09, -0.74), P < 0.0001) and collarette grade (MD = -1.51, 95% CI (-1.77, -1.25), P < 0.00001) were significantly reduced. Indeed, no discernible discrepancies in the comfort levels experienced with eye drops emerged between the two groups. Although the experimental group did exhibit a slightly higher occurrence of treatment-related adverse events, ranging from instillation site discomfort to eye discharge and eyelid swelling, these variances did not attain statistical significance. Notably, upon GRADE evaluation, the study's evidence quality was deemed moderate, while scrutiny for publication bias revealed minimal indications thereof. In the realm of treatment, lotilaner ophthalmic solution shined as a beacon of efficacy, effectively combating mite infections and bolstering cure rates among patients with DB. Moreover, its administration was met with commendable compliance and upheld safety standards. [ABSTRACT FROM AUTHOR]

Light Density Polyethylene (LDPE) bottles with a specific resin were chosen as container closure system (CCS) to fill "Latanoprost ophthalmic solution" (a generic drug product). As an alternative packaging component, additional manufacturer of LDPE bottles with the same characteristics as the previously selected LDPE bottles was chosen. The appropriateness of both packaging components was evaluated using an extractables and leachable (E&L) study and a formal stability programme that monitored quality of latanoprost ophthalmic solution. The results of relevant quality attributes in stability samples of latanoprost ophthalmic solution packed in both LDPE bottles were compared. It noticed that an unknown impurity in latanoprost ophthalmic solution packaged in LDPE bottles manufactured by an additional manufacturer. Further study revealed that this unknown impurity is Epsilon-caprolactam, a leachable of plastic used in the transportation of LDPE bottles. The leachability was validated through an extraction analysis of a plastic bag used for transportation. Thus, in certain cases, when the source of leachable is not identifiable by an E&L examination of primary, secondary, and tertiary packaging components, the assessment could be extended to include packaging components utilized throughout the supply chain. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) have gained attention in medicine for their potent antibacterial, antiviral, and anti-inflammatory properties. The use of silver nanoparticles in ophthalmic solutions raises concerns regarding potential toxicity of nanoparticles to ocular tissues, such as the cornea, conjunctiva, and retina, which necessitates further toxicity assessments aiding in the development of safer ophthalmic solutions. This study investigates the impact of AgNPs on corneal tissue using ophthalmic investigations, Fourier transform infrared (FTIR) spectroscopy, and chemometric analyses. Three concentrations of AgNPs (0.48 µg/mL, 7.2 µg/mL, and 15.5 µg/mL) were topically applied twice daily for 10 days, synthesized biologically by reducing silver nitrate with almond kernels water extract. Corneas, obtained by cutting 2–3 mm below the ora serrata, were analyzed with FTIR spectroscopy and subjected to chemometric analyses. Results reveal AgNPs' influence on constituents with OH and NH groups, affecting corneal lipids and reducing the lipid saturation index. AgNPs alter both bulk and interfacial water, leading to changes in corneal hydration thus modifying corneal physico-chemical properties. The influence extends to the water environment around proteins and lipids, releasing bound water from phospholipids and disrupting hydrogen bonding networks around proteins. In conclusion, the applied AgNPs concentrations can be linked to dry eye onset. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy of 0.05% cyclosporine A (CsA) eye drops (II) and 3% Diquafosol ophthalmic solution (DQS) in the treatment of dry eye (DE) after cataract surgery (CS). Methods: Clinical data of 123 patients with DE after CS treated at the Fourth Hospital of Hebei Medical University from June 2022 to August 2023 were retrospectively analyzed. Patients were divided into three groups based on the treatment: Conventional group (tobramycin & dexamethasone eye drops combined with pranoprofen eye drops, n=41), DQS group (3% DQS based on the conventional treatment, n=42), and CsA group (0.05% CsA eye drops(II) based on the conventional treatment, n=40). The therapeutic effects; Schirmer I test (SIt), tear film breakup time (TBUT), levels of serum inflammatory factors, and tear cytokine levels before and after treatment were compared between the groups. Results: Chief complaint score, conjunctival congestion score, corneal fluorescein staining score, and ocular surface disease index score of the DQS group and the CsA groups were significantly lower than those of the conventional group (P<0.05). After treatment, the improvement in SIt, TBUT, serum inflammatory factors, and tear cytokine levels in the DQS group and the CsA group was significantly better than that in the conventional group (P<0.05). However, these indexes were comparable in the DQS and the CsA group (P>0.05). Conclusions: Compared to the conventional treatment alone, the addition of 3% DQS or 0.05% CsA eye drops (II) to the conventional treatment both are effective and might more effectively alleviate DE in patients undergoing CS. [ABSTRACT FROM AUTHOR]

Dry eye disease is characterized by impaired tear film homeostasis and ocular surface inflammation. Topical ocular medications for moderate-to-severe dry eye disease include hyaluronic acid (HA), cyclosporine A (CsA), serum eyedrops, and lifitegrast. Effective HA-based formulations and regimens include topical aqueous HA 0.15% and 0.18%, HA gel 0.30%, sequential administration of HA 0.30% and 0.15%, a combination of HA 0.15% and polyethylene glycol, and multi-agent eyedrops containing 0.15% HA. Preservative-free hydrocortisone and loteprednol, known as soft steroids, are effective and have a reduced risk of steroid-related adverse effects. Effective CsA formulations include 0.05% CsA gel, CsA nanoemulsions, water-free CsA, and CsA combinations with lubricants (eg, HA). Autologous, allogeneic, and umbilical cord serum eyedrops, as well as the novel lymphocyte function-associated antigen-1 antagonist lifitegrast, are also effective. Various treatment options may improve treatment adherence. Long-term and large-scale studies are required to confirm the therapeutic efficacies of these treatments. [ABSTRACT FROM AUTHOR]

Background: Despite advances in glaucoma management, topical eyedrop treatment has been paramount, with prostaglandin analogues (PGAs) being first-line agents. While late presentation is linked with deprivation, there is no recent research examining associations between deprivation and prescribing within primary care. Aim: To explore PGA prescribing in general practice over a 6-year timeline, assessing associations with deprivation. Design & setting: Analysis of NHS Business Services Authority (NHSBSA) data for general practice prescribing in England from April 2016-March 2022. Method: Glaucoma treatments by GP prescribers were extracted, identifying ~9.11-9.58 million prescriptions/annum. Data were linked to Index of Multiple Deprivation (IMD) quintiles of GP practices. Crude rates per 1000 population were calculated using population data from NHS Digital. Time-series analyses facilitated comparison in prescribing nationally and in deprived areas. Autoregressive Integrated Moving Average (ARIMA) modelling facilitated measurement of synchrony between time series using cross correlation. Results: PGAs and fixed combination eyedrops accounted for approximately two-thirds of glaucoma-related prescribing. Prescriptions per month increased slightly over a 6-year timeline, but rates per 1000 population reduced in 2020-2021 during the COVID-19 pandemic. The number of PGA prescriptions dispensed in deprived areas was lower than all other quintiles. Cross-correlation analysis indicates a lag of ~12 months between average PGA prescribing nationally versus more deprived areas. Conclusion: The rate of PGA prescribing in primary care was substantially lower in deprived versus affluent areas, with delayed uptake of PGAs in more deprived areas of ~12 months. Further research is needed to explore reasons for this discrepancy, permitting strategies to be developed to reduce unwarranted variation. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Dry eye disease (DED) is a very frequently encountered ocular disease, making it a growing public health burden. However, current treatments for DED present unmet medical needs owing to their side effects or ineffectiveness. Therefore, an effective and safe therapeutic agent to manage DED is needed. Method and Analysis: We planned a phase 2, dose-finding, double-blind, randomized placebo-controlled trial to evaluate the efficacy and safety of two different doses of USL (Useul), the extract of Achyranthis Radix, compared with placebo, for DED. USL has been found to protect against DED by inducing tear secretion and improving corneal irregularity via anti-inflammatory effects, which will provide new therapeutic options. One hundred and twenty participants will be enrolled, after assessing the inclusion/exclusion criteria, at Daejeon University Daejeon Korean Medicine Hospital. Enrolled participants will be allocated to standard-dose USL, high-dose USL, or placebo groups in a 1:1:1 ratio and will be required to administer the trial medication twice a day for 12 weeks and visit the clinic five times. For efficacy outcomes, objective endpoints of fluorescein corneal staining score, tear break-up time, Schirmer's test, and meibomian test and subjective endpoints of Ocular Surface Disease Index, visual analog scale, Standard Patient Evaluation for Eye Dryness-II, and biomarkers will be assessed throughout the trial. Safety will be assessed based on adverse events, vital signs, laboratory tests, visual acuity, and intraocular pressure. Discussion: Our study results are expected to provide clinical evidence for the use of DED as an effective and safe agent for DED. [ABSTRACT FROM AUTHOR]

The document discusses the issue of shortages of essential generic drugs in the USA, which hinders patient access to medications like antibiotics and cancer treatments. It highlights the Affordable Drug Manufacturing Act of 2023 as a proposed solution to establish a federal Office of Drug Manufacturing for public production of off-patent drugs with limited competition. The study identifies 24 essential generic drugs with limited competition that were in shortage for a median of 16 months, emphasizing the need for policy reforms to address drug shortages effectively. The research was funded by Arnold Ventures and the Commonwealth Fund, with data availability upon request from the authors. [Extracted from the article]

Glaucoma is one of the major causes of irreversible blindness worldwide. Increased intraocular pressure (IOP) is a key factor in the onset and progression of this disease. The drugs used to treat glaucoma influence a variety of biological targets. Azolopyrimidine derivatives have attracted significant attention as potential agents for the treatment of glaucoma because they presumed to be analogs of adenosine receptor (AR) agonists and antagonists. In this study, a series of novel 3(4)‐alkyl‐[1,2,4]triazolo[1,5‐a]pyrimidin‐7‐amines were synthesized to develop promising ophthalmic hypotensive drugs. The synthesized compounds demonstrated significant hypotensive activity against IOP, which opens new possibilities for glaucoma therapy. [ABSTRACT FROM AUTHOR]

Glaucoma, a leading cause of blindness due to elevated intraocular pressure (IOP), is managed with medications like latanoprost (LAT), a prostaglandin analogue, to enhance aqueous outflow. Despite the challenge posed by eye anatomy and tear dynamics, effective ocular bioavailability via topical administration remains elusive. This study aims to optimize self-assembled nanomicelles incorporating LAT, an anti-glaucoma drug, belonging to BCS Class II (low solubility and high permeability) via a two-level, two-factor full factorial design, the nanomicelles were formulated via direct dissolution method and validated using design of expert. The optimized nanomicelles exhibited a spherical morphology, with a size of 69 nm and encapsulation efficiency of 77.5%, demonstrating a sustained LAT release over 12 h. In normotensive rabbits, the nanomicelles elicited a substantial reduction in intraocular pressure (IOP) by up to 40% for a duration of three days, that was significantly longer than the IOP-lowering efficacy of XALATAN eye drops (24 h). These findings indicated that self-assembled nanomicelles hold promise for enhancing the ocular bioavailability and extending the therapeutic duration of LAT, while providing the physical stability. [ABSTRACT FROM AUTHOR]

In situ gels have been developed as an innovative strategy to prolong corneal residence time and enhance drug absorption compared to traditional eye drops. Our study aimed to formulate an ophthalmic in situ gel with a combination of two thermosensitive poloxamers, P407 and P188, in an optimal ratio not only to increase the time of action but also to increase the solubility of selected antibiotics for the treatment of ophthalmic infections. Two BSC II class substances, Azithromycin and Ofloxacin, with different mechanisms of action, have been incorporated into the in situ gel system after determining their solubility. The antibiotics-loaded in situ gel formulation was evaluated for its clarity, pH, rheological properties, and gel characteristics of gelling time, temperature, and capacity. The formulation demonstrated satisfactory clarity, appropriate pH, effective gelation properties in simulated tear fluid, and suitable rheological characteristics. In addition, APIs release insight has been studied through a dissolution test, and the effectivity against sensitive and resistant bacterial strains has been proved through the antimicrobial study. Therefore, our in situ gel system based on thermosensitive poloxamers, with two hydrophobic antibiotics, AZM and OFX, can be considered a valuable approach for ophthalmic drug delivery with an enhancement of the antibiotics bioavailability through increasing the contact time with the ocular surface and enhancing patient compliance. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease is one of the most common disorders we see in practice today. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO®) (©Bausch + Lomb) is a novel, non-aqueous, single entity, preservative-free ophthalmic drop recently approved by the FDA for treatment of the signs and symptoms of dry eye disease. Purpose: While the safety and efficacy of PFHO has been demonstrated in non-contact lens wearers, its safety and potential benefits in habitual contact lens wearers have not been explored. This report presents the results of a trial designed to evaluate the safety of PFHO and its effect on contact lens comfort, specifically in established contact lens wearers. Patients and methods: The study included 47 patients who were adjusted contact lens wearers with a best corrected visual acuity of 20/25 or better at distance. All the patients were healthy contact lens wearers with no dry eye symptoms. Results: A significant improvement in comfort scoring was observed without any significant changes in osmolarity, meibography scores, and total fluorescein staining. Conclusion: These findings suggest that PCHO is safe for contact lens wearers to use and shows promise to reduce contact lens dropout. [ABSTRACT FROM AUTHOR]

Background: The enhancement of ocular drug delivery is achieved by using biopolymer carriers in liquid ophthalmic preparations. Using natural polysaccharides to formulate ocular medications is attractive because they are economical and readily available. The primary goal of the study was to assess the safety and effectiveness of Tamarind seed polysaccharide (TSP)/Hyaluronic acid (HA) containing Rohto eye drops (TSP/HA drops) in alleviating the signs and symptoms of dry eye disease (DED) under dry environmental conditions using controlled environmental chamber (CEC). Methods: 12 participants were subjected to harsh environmental conditions in a CEC with a relative humidity (RH) of 5% and an ambient temperature of 21°C. TSP/HA drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment and relief (drops instilled after exposure to the dry environment. Before and after administering drops, patients undergo screening for ocular symptoms, tear osmolarity, ocular surface temperature (OST), and tear production using the ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and phenol red test (PRT) respectively. Tear production was calculated by the Tear Function Index test (TFI). Results: Before (protection) and after (relief) exposure to the dry environment, TSP/HA resulted in a mean tear osmolarity of 296.0 mOsm/L and 292.0 mOsm/L, with no significant statistical difference. The presence of TSP/HA in both protection and relief modes led to an increase in tear production. TSP/HA drops did not significantly affect OST compared to the absence of TSP/HA drops at 5% RH. There was a significant increase in mean symptom score from 14 at 40% RH to 128 at 5% RH (p=0.003). A substantial reduction in symptoms was found in both protection (before exposure) (35) (p=0.003) and relief (after exposure) (50) (p=0.005) compared to when no drop was used. Conclusion: It was apparent that using TSP/HA for protection was superior to relief for osmolarity and eye comfort. To optimise the therapeutic efficacy of TSP/HA, it is advisable to instruct patients to administer it before exposure to dry atmospheric conditions. The small sample size limits the ability to generalize the findings. Future studies should evaluate the tear supplement with a larger sample to improve statistical power. [ABSTRACT FROM AUTHOR]

Background: The treatment of vitiligo is a persistent challenge in dermatology. New treatments are being offered and studied in this field for those resistant to or intolerant of classical therapies. Aims: In this systematic review, we study the use of prostaglandin analogues (PGAs) and phosphodiesterase inhibitors (PDEIs) in the treatment of vitiligo, as they are known for their pigmentation inducing effects through activating melanocytes. Methods: We searched four main online databases with the keywords "Vitiligo", "Prostaglandin analogue" and "Phosphodiesterase inhibitor". Results: A total of 42 articles were included, with 1027 cases, studying drugs like bimatoprost, latanoprost, travoprost, dinoprostone, apremilast, crisaborole, etc. Among the included studies, the treatment regimens are commonly once or twice daily for 12–48 weeks, with a mean of 20.61 weeks, and the routes of administration are mainly topical gels or ophthalmic solutions and oral tablets. Side effects are mild and tolerable, namely erythema, itching or burning sensations at application site for topicals, or gastrointestinal problems with apremilast. Repigmentation results are significant in both adult and pediatric patients and progressive or stable vitiligo. PGAs and PDEIs outperform many classical therapies, for example, narrowband ultraviolet B phototherapy (NB‐UVB), tacrolimus, mometasone or methylprednisolone mini‐pulse. PGAs or PDEIs are usually used in combination therapies to either cause synergism or increase drug delivery, and almost always enhance repigmentation, for example, with NB‐UVB, fractional CO2 laser, microneedling, and mometasone. Conclusion: Monotherapy or add‐on PGAs and PDEIs can be considered effective treatments for vitiligo and promising last resorts for those resistant to other therapies. [ABSTRACT FROM AUTHOR]

Lotilaner ophthalmic solution 0.25% (XDEMVY®; henceforth referred to as lotilaner 0.25%) is a novel prescription eye drop indicated for the treatment of Demodex blepharitis. It is the first and currently the only US FDA-approved treatment for this condition. One drop of lotilaner 0.25% instilled in each eye twice daily for 6 weeks was associated with significantly higher rates of collarette reduction to ≤ 2 collarettes (primary endpoint), mite eradication and erythema cure compared to the vehicle control. Lotilaner 0.25% is generally well tolerated, with the most common ocular adverse reaction being instillation site stinging and burning (incidence 10%). The 6-week treatment remained durable with no safety issues during the observational period for up to a year. The eye drop was generally neutral or very comfortable for most patients. Plain Language Summary: Demodex blepharitis is a common eyelid margin disease caused by an infestation of Demodex mites. It is characterized by persistent cylindrical waxy dandruff (collarettes) in the eyelashes, eyelid margin inflammation, redness and eye irritation. Lotilaner ophthalmic solution 0.25% (XDEMVY®; henceforth referred to as lotilaner 0.25%) is a novel prescription eye drop that eradicates Demodex mites. It is FDA-approved in the USA for the treatment of Demodex blepharitis. One drop of lotilaner 0.25% in each eye twice daily for 6 weeks significantly reduces collarettes, decreases or eradicates Demodex mites and reduces eyelid redness in patients with Demodex blepharitis. The treatment is generally well tolerated, with the most common ocular adverse reactions being installation site stinging and burning (incidence 10%). Currently, lotilaner 0.25% is the only US FDA-approved treatment for Demodex blepharitis. [ABSTRACT FROM AUTHOR]

Ophthalmic treatment demands precision and consistency in delivering therapeutic agents over extended periods to address many conditions, from common eye disorders to complex diseases. This diversity necessitates a range of delivery strategies, each tailored to specific needs. We delve into various delivery cargos that are pivotal in ophthalmic care. These cargos encompass biodegradable implants that gradually release medication, nonbiodegradable implants for sustained drug delivery, refillable tools allowing flexibility in treatment, hydrogels capable of retaining substances while maintaining ocular comfort, and advanced nanotechnology devices that precisely target eye tissues. Within each cargo category, we explore cutting-edge research-level approaches and FDA-approved methods, providing a thorough overview of the current state of ophthalmic drug delivery. In particular, our focus on nanotechnology reveals the promising potential for gene delivery, cell therapy administration, and the implantation of active devices directly into the retina. These advancements hold the key to more effective, personalized, and minimally- invasive ophthalmic treatments, revolutionizing the field of eye care. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ocular and systemic pharmacokinetics of lotilaner ophthalmic solution, 0.25%, following bilateral topical ocular administration of single and repeated doses in rabbits. Methods: Dutch-belted rabbits (n = 34) were administered lotilaner ophthalmic solution, 0.25%, eye drops, either in a single bilateral dose (Group 1) or twice a day bilaterally for 7 days and once on Day 8 (Group 2). The pharmacokinetics and tissue distribution levels of lotilaner were assessed following the single dose in Group 1 and the last dose in Group 2. The drug levels were examined in various ocular tissues and whole blood. The maximal concentration of the drug (Cmax), time to maximal concentration, the terminal phase elimination half-life, the area under the concentration–time curve (AUC), and total clearance of the drug were determined. Results: In the eyelid margins, lotilaner exhibited the highest observed concentrations at 0.25 hour (h), presenting a mean Cmax of 14,600 ng/mL in Group 1 and 20,100 ng/mL in Group 2. The highest AUC was in the eyelid margin at 242,000 h×ng/mL in Group 1 and 535,000 h×ng/mL in Group 2. In the eyelid margin, the observed clearance rate (0.634 mL/h in single dose, 0.288 mL/h in repeat dose) was the slowest among all ocular tissues in both groups, with the longest half-life of 152 h (∼6.3 days) observed in the repeat dose group. Conclusions: Lotilaner ophthalmic solution, 0.25%, demonstrated rapid ocular tissue absorption into the eyelid margin tissue with a long half-life of almost a week. No adverse effects were observed following topical ocular administration in Dutch-belted rabbits. [ABSTRACT FROM AUTHOR]

There are many possible differential diagnoses for the patient with a red eye. This article provides a pragmatic approach to the diagnosis and management of red eye, the most common eye problem presenting to primary care.1,2 The authors describe how to take a history and examine a red eye in primary care, highlighting the red flag symptoms and signs that indicate an urgent ophthalmology referral is required. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion This study aims to assess the risk of drug‐associated glaucoma and track its epidemiological characteristics using real‐world data.Adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2023 were analysed. Disproportionality analysis and the Bayesian Confidence Propagation Neural Network algorithm were used. The study classified drugs associated with glaucoma, assessed risk levels, and compared drug‐induced times across different categories.Eight hundred and five drugs were linked to glaucoma in the FAERS database. Disproportionality analysis identified 46 drugs with significant risk, mainly adrenergic medications (clobetasol propionate, fluocinolone acetonide), antihypertensives (hydrochlorothiazide), insulin (insulin human), anticholinergics (umeclidinium, darifenacin), VEGF inhibitors (brolucizumab, faricimab), and psychotropics (topiramate, ziprasidone). The top three high‐risk drugs were clobetasol propionate, umeclidinium, and fluocinolone acetonide. The shortest drug‐induced times were observed with indacaterol, salmeterol, and umeclidinium. Anticholinergic medications had the shortest drug‐induced time among all categories. Females (62.5%) and the elderly (average age 63.5 ± 16.8 years) were predominantly affected. Reports of drug‐associated glaucoma increased over the years.Preventing drug‐associated glaucoma is more effective than treatment. Identifying the risk and drug‐induced times of systemic and ophthalmic drugs can reduce occurrence risk. Clinical practitioners should be vigilant and inform patients of these risks. [ABSTRACT FROM AUTHOR]

Background: No consensus has been reached on the adequate dose of mitomycin C (MMC) in XEN45 gel stent implantation. Lower doses have the potential to reduce MMC‐linked side effects. This study aimed to evaluate treatment efficacy of ab interno XEN45 gel stent in primary open‐angle glaucoma (POAG) with three different MMC doses. Methods: This retrospective single‐centre nonrandomised trail included 54 patients (56 eyes) who underwent XEN45 gel stent implantation for POAG with above‐target intraocular pressure (IOP) under medical therapy. Eyes were grouped according to the received MMC dose: Group 1 (20 μg; n = 21), Group 2 (10 μg; n = 14) and Group 3 (5 μg; n = 21). The primary endpoint was the mean IOP change in the three MMC dose groups after 6, 12 and 24 months. Secondary endpoints included the success rate defined as lowering of baseline IOP ≥ 20% and below a cut‐off IOP set at three different levels: ≤ 18, ≤ 16 and ≤ 14 mmHg (Criteriums 1, 2 and 3), the mean number of ocular hypotensive medications and the frequency of needling procedures. Results: After 24 months, the overall mean (standard error) IOP was significantly reduced from 24.7 (0.9) mmHg to 15.2 (0.7) mmHg (p < 0.0001). The average IOP change (standard error) in MMC dose groups 1, 2 and 3 was −8.6 (2) mmHg, −10.1 (2.1) mmHg and −10.4 (2.8) mmHg. Complete success (Criterium 1) was achieved in 50%, 62% and 43% of the eyes in groups 1, 2 and 3. No statistically significant difference was found within the first 24 months between the three MMC dose groups for IOP change, success rate, number of ocular hypotensive medications and the frequency of needling procedures. Conclusions: XE45 was effective in all three dose groups. As the success rate did not significantly differ between the MMC doses, these results may support the use of the lowest dose. Trial Registration: ClinicalTrials.gov identifier: 559/2016BO2 [ABSTRACT FROM AUTHOR]

This study proposed a novel electrochemical sensor for the sensitive measurement of the eye medication ofloxacin (OFX), which is based on a NiO@C-dot nanocomposite. The NiO@C-dot nanocomposite was synthesized using the sol-gel method, which was then applied to alter a glassy carbon electrode (GCE). With regard to OFX, the modified GCE shown outstanding electrochemical activity along with good sensitivity, selectivity, and stability. With OFX concentrations ranging from 5 µM to 975 µM, the NiO@C-dot/GCE showed a linear relationship with a sensitivity of 0.63994 µA/µM. The limit of detection (LOD) was 0.023 µM. The response to 50 µM OFX was measured, and the electrode was stored at 4°C after each test in order to evaluate the sensor's long-term stability and repeatability. After 20 days, the peak current response was still 97.89 % of its initial value. After 40 days of prolonged storage, 93.78 % of the electrode's original responsiveness was retained. The sensor showed a recovery rate of 97.37–99.70 % in all sample types when it was used to detect OFX in human urine, tap water, and food samples. These findings highlight the NiO@C-dot/GCE's outstanding selectivity, dependability, and longevity as solid platforms for OFX detection in complicated samples for a range of applications. [ABSTRACT FROM AUTHOR]

Introduction: This was a prospective study to investigate the antimicrobial efficacy of a novel ophthalmic solution comprising ozonated sunflower oil in liposomes plus hypromellose in conjunction with liposomal foam (BlefOX), in patients undergoing intravitreal injection, in comparison to povidone iodine 5%. Methods: The study employed a paired-eye design with n = 195 patients and a total of n = 390 eyes divided into two groups. Conjunctival swabs were collected from both eyes of each patient at baseline (T0—3 days before the injection). The study group underwent home therapy, which included instilling two drops of an isotonic ophthalmic solution containing 0.5% ozonated sunflower oil in liposomes plus hypromellose (Ozodrop) four times daily and applying liposomal foam twice daily to the eye undergoing intravitreal injections. In contrast, the control group (contralateral eyes) received treatment with povidone iodine 5%. This treatment regimen was maintained for 3 days. At T1 (10 min before injection), all patients instilled one drop of a topical solution of povidone iodine 5% into the conjunctival sac of both eyes. After 30 seconds had elapsed, a conjunctival swab was obtained for each eye in both study groups. Results: The results, derived from conjunctival swabs, exhibited a significant reduction in the microbial load of the study group on both chocolate agar and blood agar (p ≤ 0.007). The study demonstrated that the combination of povidone iodine 5% + Ozodrop + BlefOX provides a greater reduction in microbial load than povidone iodine 5% alone on both chocolate agar (141 [72.31%] vs. 98 [50.26%], p < 0.0001) and blood agar (130 [66.67%] vs. 97 [49.74%], p = 0.0007). The combination of povidone iodine 5% + Ozodrop + BlefOX resulted in the killing of approximately 41% to 49% of bacteria compared to povidone iodine 5% alone on the chocolate agar and blood agar, respectively. Conclusions: Liposomal ozonated oil treatment, coupled with liposomal foam, in patients undergoing intravitreal injection led to a substantial reduction in conjunctival microbial load compared to eyes treated solely with povidone iodine 5%. [ABSTRACT FROM AUTHOR]

Introduction: Patients with dry eye disease (DED) complain of a multitude of symptoms that affect their visual function and quality of life (QoL). This clinical investigation assessed the performance, tolerance, and safety of a novel preservative-free ophthalmic solution containing xanthan gum 0.2% and desonide sodium phosphate 0.025%. Methods: This was an observational, prospective, multicentric, and post-market clinical investigation to assess the effect of three times a day instillation of the study formulation in patients suffering from DED. The primary objective was to achieve a 50% reduction in conjunctival hyperemia index as assessed with the OCULUS Keratograph after 1 month of treatment compared to baseline values. The secondary objectives included patient-reported outcomes, clinical performance, and safety. Results: Thirty patients were enrolled (21 women, 9 men) with a mean age of 61.10 ± 14.53 years. The instillation of the study formulation was associated with a significant reduction in redness scores after 1 month of treatment compared to baseline (mean − 0.51 ± 0.51; p ≤ 0.0001). Although the primary endpoint was not completely met, a 50% reduction in the conjunctival hyperemia index was achieved in 23% of the participants, and 77% showed a reduction of 26% of the same index. In addition, the ophthalmic solution significantly increased tear film break-up time, and a significant reduction of corneal and conjunctival staining with fluorescein was achieved. It also reduced DED symptoms and had a very good safety profile. Conclusions: the study formulation produced a significant improvement in the signs, symptoms, and QoL of patients with mild to moderate DED with a good safety profile after 1 month of treatment. [ABSTRACT FROM AUTHOR]

Ocular surface disease (OSD) is a frequent disabling challenge among patients with glaucoma who use benzalkonium chloride (BAK)-containing topical glaucoma medications for prolonged periods. In this comprehensive review, we evaluated the prevalence of OSD and its management, focusing on both current and future alternatives. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used to assess a) the impact of active ingredients and preservatives on the ocular surface and b) the efficacy of preservative-free (PF) alternatives and adjunctive therapies. BAK-containing glaucoma medications were found to significantly contribute to OSD by increasing corneal staining, reducing tear film stability, and elevating ocular surface disease index (OSDI) scores. Transitioning to PF formulations or those with less cytotoxic preservatives, such as Polyquad® and SofZia®, demonstrated a marked improvement in OSD symptoms. In particular, the use of adjunct cyclosporine A, through its anti-inflammatory and enhanced tear film stability actions, was shown to be very beneficial to the ocular surface. Therefore, the most effective management of OSD is multi-factorial, consisting of switching to PF or less cytotoxic medications, adjunct use of cyclosporine A, and early incorporation of glaucoma surgical treatments such as laser trabeculoplasty, trabeculectomy, glaucoma drainage devices, or minimally invasive glaucoma surgery (MIGS). [ABSTRACT FROM AUTHOR]

Eye disorders affect a substantial portion of the global population, yet the availability of efficacious ophthalmic drug products remains limited. This can be partly ascribed to a number of factors: (1) inadequate understanding of physiological barriers, treatment strategies, drug and polymer properties, and delivery systems; (2) challenges in effectively delivering drugs to the anterior and posterior segments of the eye due to anatomical and physiological constraints; and (3) manufacturing and regulatory hurdles in ocular drug product development. The present review discusses innovative ocular delivery and treatments, encompassing implants, liposomes, nanoparticles, nanomicelles, microparticles, iontophoresis, in situ gels, contact lenses, microneedles, hydrogels, bispecific antibodies, and gene delivery strategies. Furthermore, this review also introduces advanced manufacturing technologies such as 3D printing and hot-melt extrusion (HME), aimed at improving bioavailability, reducing therapeutic dosages and side effects, facilitating the design of personalized ophthalmic dosage forms, as well as enhancing patient compliance. This comprehensive review lastly offers insights into digital healthcare, market trends, and industry and regulatory perspectives pertaining to ocular product development. [ABSTRACT FROM AUTHOR]

Nanoemulsions (NEs) are submicron-sized heterogeneous biphasic liquid systems stabilized by surfactants. They are physically transparent or translucent, optically isotropic, and kinetically stable, with droplet sizes ranging from 20 to 500 nm. Their unique properties, such as high surface area, small droplet size, enhanced bioavailability, excellent physical stability, and rapid digestibility, make them ideal for encapsulating various active substances. This review focuses on recent advancements, future prospects, and challenges in the field of NEs, particularly in oral, parenteral, and ophthalmic delivery. It also discusses recent clinical trials and patents. Different types of in vitro and in vivo NE characterization techniques are summarized. High-energy and low-energy preparation methods are briefly described with diagrams. Formulation considerations and commonly used excipients for oral, ocular, and ophthalmic drug delivery are presented. The review emphasizes the need for new functional excipients to improve the permeation of large molecular weight unstable proteins, oligonucleotides, and hydrophilic drugs to advance drug delivery rapidly. [ABSTRACT FROM AUTHOR]

Introduction: We sought to streamline cataract surgery post-operative care when COVID-19 hit by discontinuing the 1-day post-operative visit. We wanted to know if this change was safe and beneficial to our patients by reducing patients' time and transportation burden, opening appointment slots allowing providers to see more patients and reducing greenhouse gas emissions. By minimising intraoperative use of dispersive viscoelastic, increasing irrigation/aspiration time at the end of the surgery and using intraocular pressure (IOP) lowering medications such as carbachol, brimonidine and acetazolamide routinely, we posit that post-operative day 1 IOP spikes can be avoided, thereby eliminating the need for the 1st post-operative day visit. We also sought to show the positive environmental impact of eliminating that 1st day. Methods: We retrospectively reviewed cataract surgeries performed before COVID-19 to determine the incidence of serious pathology discovered at the post-operative day 1 visit. Subsequently, we examined all the cataract surgeries performed in 2023 by our practice. Results: One hundred and ninety-three cataract surgeries performed before COVID-19 and 832 performed in 2023 were reviewed. We found that the post-operative day 1 visit after cataract surgery is unnecessary in most routine uncomplicated cases. Conclusion: By eliminating hundreds of post-operative day 1 visits for a busy rural practice annually, patients, their friends and relatives are spared an extra trip to the office (that can be 100 km each way), the office schedule is open to accommodate more patients, and the patients' carbon footprint of travel to the office is reduced. Introduction: Nous avons cherché à rationaliser les soins postopératoires de la chirurgie de la cataracte lors de l'arrivée de la Covid en supprimant la visite postopératoire d'un jour. Nous voulions savoir si ce changement était sécuritaire et bénéfique pour nos patients en réduisant le temps et la charge de transport des patients, en ouvrant des créneaux de rendez-vous permettant aux prestataires de voir plus de patients et en réduisant les émissions de gaz à effet de serre. En minimisant l'utilisation peropératoire de viscoélastique dispersif, en augmentant le temps d'irrigation/aspiration à la fin de l'opération et en utilisant systématiquement des médicaments abaissant la PIO, tels que le carbachol, la brimonidine et l'acétazolamide, nous pensons que les PIO postopératoire du premier jour peuvent être évitées, éliminant ainsi la nécessité d'une première visite de jour postopératoire. Nous avons également cherché à démontrer l'impact environnemental positif de l'élimination de ce premier jour. Méthodes: Nous avons examiné rétrospectivement opérations de la cataracte réalisées avant la Covid afin de déterminer l'incidence des pathologies graves découvertes lors de la visite postopératoire du premier jour. Par la suite, nous avons examiné toutes les opérations de la cataracte réalisées en 2023 par notre cabinet. Résultats: 193 opérations de la cataracte réalisées avant la Covid et 832 réalisées en 2023 ont été examinées. Nous avons constaté que la visite postopératoire du premier jour après la chirurgie de la cataracte n'est pas nécessaire dans la plupart des cas de routine sans complications. Conclusion: En éliminant des centaines de visites postopératoires du premier jour dans une région rural, les patients, leurs amis et leurs proches n'ont pas à SE rendre au cabinet (ce qui peut représenter des centaines de kilomètres aller-retour). L'emploi du temps du cabinet est libéré pour accueillir davantage de patients et l'empreinte carbone des patients liée à leur déplacement au cabinet est réduite. [ABSTRACT FROM AUTHOR]

Background: Allergic conjunctivitis is increasing with the rise in the levels of allergens. Drug therapy is usually needed in addition to avoidance of general allergens to treat this condition. Both bepotastine besilate and olopatadine hydrochloride ophthalmic solutions are newer additions in the treatment of allergic conjunctivitis having dual properties of second-generation antihistaminics along with mast cell stabilizing activity. Aims and Objectives: The aim of the study was to compare the efficacy and tolerability of bepotastine besilate (1.5%) and olopatadine hydrochloride (0.1%) eye drops in patients presenting with allergic conjunctivitis in a tertiary care hospital of Southern part of India. Materials and Methods: Sixty patients who were clinically diagnosed to be suffering from allergic conjunctivitis were selected as participants for the study. They were randomly distributed into two groups consisting of 30 patients each. One group received eye drop bepotastine (1.5%) and the other group received eye drop olopatadine (0.1%), with each patient receiving the medication twice daily for a duration of 2 weeks. During the first visit, all the patients were assessed for the signs and symptoms and subsequently re-assessed at weekly intervals for a period of 2 weeks. They were also advised to report occurrence of any unwanted drug reaction during the weekly follow-up visits. Results: The above study showed the effectiveness of both bepotastine and olopatadine eye drops in decreasing the signs and symptoms of allergic conjunctivitis. Significant clinical improvement was found in all participants, whereas deterioration was found in none of them. Statistically significant improvement of itching and redness of eyes was observed with use of both the study drugs mentioned beforehand. Both the drugs were well tolerated by the patients. Statistically significant reduction of itching and foreign body sensation was found to be more in patients using bepotastine eye drops compared to those using olopatadine eye drops. Only two patients using bepotastine eye drops complained of having a mild burning sensation in eyes. Conclusion: From this study, bepotastine and olopatadine eye drops have been observed to be safe and efficacious in allergic conjunctivitis. Bepotastine eye drop was found to be more efficacious to relieve itching and foreign body sensation compared to that of olopatadine eye drops. [ABSTRACT FROM AUTHOR]

Topical ophthalmic drug product development is a niche research domain as the drug formulations need to be designed to perform in the unique ocular physiological conditions. The most common array of small molecule drug formulations intended for topical ophthalmic administration include solutions, suspensions, emulsions, gels, and ointments. The formulation components such as excipients and container closure are unique to serve the needs of topical ophthalmic delivery compared to other parenteral products. The selection of appropriate formulation platform, excipients, and container closure for delivery of drugs by topical ophthalmic route is influenced by a combination of factors like physicochemical properties of the drug molecule, intended dose, pharmacological indication as well as the market trends influenced by the patient population. In this review, data from literature and packaging inserts of 118 reference listed topical ophthalmic medications marketed in the US are collected and analyzed to identify trends that would serve as a guidance for topical ophthalmic formulation development for small molecule drugs. Specifically, the topics reviewed include current landscape of the available small molecule topical ophthalmic drug products in the US, physicochemical properties of the active pharmaceutical ingredients (APIs), formulation platforms, excipients, and container closure systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Trabeculectomy is a primary surgical procedure used to reduce intraocular pressure (IOP) in patients with glaucoma. Despite its effectiveness, it can lead to significant complications, including hypotony, choroidal effusion, blebitis, and bleb leaks. Bleb leaks require prompt medical or surgical intervention to prevent severe complications such as blebitis and bleb-associated endophthalmitis. In recent years, the indications for collagen cross-linking (CCL) have expanded beyond corneal ectatic diseases to include various ocular conditions such as keratitis and leaking blebs. Here, we present the case of a 70-year-old male patient with a leaking avascular cystic bleb. Following treatment with a combination of conjunctival CCL, topical gentamicin, a dorzolamide/timolol combination, and a therapeutic contact lens, the patient experienced cessation of bleb leakage and an increase in IOP. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical characteristics and treatment strategies of limbal stem cell deficiency (LSCD) patients managed with medical therapy. Materials and Methods: The study included 29 eyes of 21 patients with LSCD who were managed medically at Ege University Faculty of Medicine, Department of Ophthalmology between May 2013 and May 2023. LSCD stages before and after medical treatment were recorded according to the LSCD staging system published by the International LSCD Working Group. The medical records of patients showing improvement in LSCD stage with medical treatment without surgical intervention were evaluated. Results: The mean age was 35.5±23.8 years (range, 5-71 years) with a male-to-female ratio of 6:15. The primary etiology of LSCD was ocular rosacea in 12 patients (57.1%), marginal keratitis in the setting of blepharitis in 8 patients (38.1%), and topical medication toxicity in 1 patient (4.8%). The mean baseline best corrected visual acuity (BCVA) was 0.25±0.26 logarithm of the minimum angle of resolution (logMAR) (range, 0-1 logMAR). Pre-treatment LSCD stage was stage 1A in 5 eyes (17.2%), stage 1B in 12 eyes (41.4%), stage 1C in 4 eyes (13.8%), stage 2A in 4 eyes (13.8%), and stage 2B in 4 eyes (13.8%). Complete regression of LSCD was achieved in 6 eyes (20.7%) with medical treatment addressing the primary etiology. In the remaining eyes, after medical treatment, the severity of LSCD decreased below the surgical threshold, which is considered stage 2B. The mean final BCVA was 0.07±0.1 logMAR (range, 0-0.4 logMAR). Conclusion: This study highlights that LSCD can be completely or partially reversible with appropriate management, especially in cases with underlying limbal niche dysfunction, where inflammation plays a significant role. Although limbal stem cell transplantation is considered the main treatment approach for LSCD, localized and early-stage LSCD can be effectively managed medically without the need for surgical intervention. [ABSTRACT FROM AUTHOR]

• The OphtalMimic device offers a precise simulation of human ocular conditions for improved ophthalmic drug product evaluation. • A novel hydrogel-based hybrid membrane closely replicates the human cornea's water content and morphology. • The device successfully differentiated between the drainage profiles of various ophthalmic formulations. • The system demonstrated its potential as a reliable platform for the high-throughput screening of ophthalmic drugs. • This advancement aligns with ethical mandates to reduce animal testing and accelerate the development of safer and more effective ophthalmic drugs. Envisaging to improve the evaluation of ophthalmic drug products while minimizing the need for animal testing, our group developed the OphthalMimic device, a 3D-printed device that incorporates an artificial lacrimal flow, a cul-de-sac area, a moving eyelid, and a surface that interacts effectively with ophthalmic formulations, thereby providing a close representation of human ocular conditions. An important application of such a device would be its use as a platform for dissolution/release tests that closely mimic in vivo conditions. However, the surface that artificially simulates the cornea should have a higher resistance (10 min) than the previously described polymeric films (5 min). For this key assay upgrade, we describe the process of obtaining and thoroughly characterizing a hydrogel-based hybrid membrane to be used as a platform base to simulate the cornea artificially. Also, the OphthalMimic device suffered design improvements to fit the new membrane and incorporate the moving eyelid. The results confirmed the successful synthesis of the hydrogel components. The membrane's water content (86.25 ± 0.35 %) closely mirrored the human cornea (72 to 85 %). Furthermore, morphological analysis supported the membrane's comparability to the natural cornea. Finally, the performance of different formulations was analysed, demonstrating that the device could differentiate their drainage profile through the viscosity of PLX 14 (79 ± 5 %), PLX 16 (72 ± 4 %), and PLX 20 (57 ± 14 %), and mucoadhesion of PLXCS0.5 (69 ± 1 %), PLX16CS1.0 (65 ± 3 %), PLX16CS1.25 (67 ± 3 %), and the solution (97 ± 8 %). In conclusion, using the hydrogel-based hybrid membrane in the OphthalMimic device represents a significant advancement in the field of ophthalmic drug evaluation, providing a valuable platform for dissolution/release tests. Such a platform aligns with the ethical mandate to reduce animal testing and promises to accelerate the development of safer and more effective ophthalmic drugs. [ABSTRACT FROM AUTHOR]

Background: Allergic conjunctivitis, causing eye inflammation and redness, requires effective treatment with alcaftadine 0.25% and olopatadine 0.2% eye drops. Aims and Objectives: The aim of the study was to compare the efficacy and safety of alcaftadine and olopatadine ophthalmic medications in mild-to-moderate allergic conjunctivitis. Materials and Methods: A prospective, open-label, comparative study of 60 patients randomized into two study groups of 30 patients each. Each group was assigned to receive either olopatadine or alcaftadine ophthalmic solutions. Patients were followed through at regular intervals with a reduction of signs and symptoms documented using total ocular symptom scoring (TOSS) and hyperemia scale systems. Results: Baseline (1st visit) mean TOSS scores for the alcaftadine group and olopatadine groups were (6.12±1.92) and (6.32±1.80), respectively, as compared to the corresponding TOSS scores on 14th Day (4th visit) which were (0.5±0.11) and (0.9±0.40), respectively. The resolution of conjunctival symptoms in the alcaftadine group was significantly profoundly as comparison to olopatadine group (P = 0.004). Baseline (1st visit) mean hyperemia scores for alcaftadine group and olopatadine groups were (2.1±1.71) and (2.2±1.52), respectively, as comparison to the corresponding hyperemia scores on 14th day (4th visit) which were (0.08±0.01) and (0.6±0.32), respectively. The resolution of hyperemia symptoms in the alcaftadine group was significantly profound as compared to the olopatadine group (P = 0.002). Conclusion: Two topical medications utilized in the study were effective and safe for the therapy of allergic conjunctivitis. However, alcaftadine appears to surpass olopatadine in alleviating the symptoms of allergic conjunctivitis while having a lower side effect pro [ABSTRACT FROM AUTHOR]