Journal of Ocular Pharmacology and Therapeutics最新文献

Objective: To describe the clinical effects of a novel, combined ocular lubricant for treating patients with dry eye disease. Methods: A noncomparative, retrospective cohort of 67 eyes (67 patients) with a confirmed diagnosis of dry eye disease using the ocular surface disease index (>12), tear osmolarity, and ocular surface parameters (noninvasive break-up time, meniscus height, and meibography) evaluated using the Cornea550 were included. All patients were treated with a combination of 0.5% carboxymethylcellulose, glycerin 0.9%, and trehalose 3% with a dosing regimen of one drop four times a day for 1 month with a final evaluation of the same parameters. Results: We included 67 eyes (80.6% females) with a mean age of 48.3 ± 16.2 years (standard deviation [SD]). In total, 37% of the subjects had comorbidities such as hypothyroidism (9%), ocular rosacea (4%), Sjogren's syndrome (4%), and arterial hypertension (4%). Of these, 34% were taking systemic medications and 56.7% had previous ocular surgery. The mean ocular surface disease index score before treatment was 57.6 ± 17.2 (SD) and 22.2 ± 12.9 points (SD) after treatment (P < 0.05). Other parameters such as noninvasive break-up time, meniscus height, and meibography improved without a statistically significant difference. Conclusion: Cristal Tears Plus is a novel, combined, and multipurpose treatment for dry eye disease.

In 2023, Xdemvy® (0.25% lotilaner ophthalmic solution) was approved by the U.S. FDA for treating Demodex blepharitis in humans. This article reviews lotilaner's history, physicochemical properties, pharmacokinetics, pharmacology, clinical outcomes, and other indications for which it is being evaluated clinically. Furthermore, the article discusses Demodex blepharitis, alternative treatments used in the clinic to ameliorate its symptoms, and other drugs in development. Prior to its approval in humans, lotilaner found extensive application in treating parasitic infections in cats and dogs. Lotilaner was previously approved in 2017 as an oral veterinary medicine (Credelio®) for canines to treat demodicosis, other mite infections, and tick infections. Lotilaner belongs to the isoxazoline class of drugs and is a potent arthropod-selective gamma-aminobutyric acid-gated chloride ion channel inhibitor. Like several other drugs in the isoxazoline class, lotilaner has a long plasma half-life and high plasma protein binding of about 99.9%. When used as indicated, lotilaner treats infested Demodex blepharitis in 42 days, with its antiparasitic action starting within 24 h. Furthermore, lotilaner is also being evaluated for its efficacy in other conditions such as Lyme disease and dry eye disease. Other products evaluated for treating Demodex blepharitis include ivermectin eye ointment, ivermectin-metronidazole gel, permethrin cream, terpinen-4-ol wipes, and hypochlorous acid spray. Along with these, azithromycin eye drop, azithromycin/loteprednol eye drop, and other treatments are being evaluated for treating blepharitis. Other drugs from the isoxazoline drug class including afoxolaner, sarolaner, and fluralaner, could also be potentially explored for human use.

Purpose: Cyclosporine A (CsA) is a primary treatment for dry eye disease (DED). Ophthalmic solutions containing CsA are available in concentrations of 0.05%, 0.09%, and 0.1%. While 0.1% CsA solutions have been used to treat DED, their safety and effectiveness remains somewhat uncertain. Therefore, we conducted a meta-analysis to evaluate their safety and efficacy. Methods: We searched PubMed, Cochrane Database, Embase, and Web of Science for randomized controlled trials (RCTs) that compared 0.1% CsA solutions with their vehicle. Statistical analysis was performed using Review Manager 5.4.1. Results: We included six RCTs (2,170 patients) with follow-up periods ranging from 4 weeks to 6 months. A total of 1,119 patients (51.56%) with DED were treated with 0.1% CsA. The mean age of patients was 57.9 ± 4.8 years, with 79.7% being female. The total corneal fluorescein staining (tCFS) at last follow-up [mean differences (MD) -0.49; 95% confidence interval (CI) (-0.73, -0.24); P < 0.0001], at 4 weeks [MD -0.64; 95% CI (-1.07, -0.22); P = 0.003], and central corneal fluorescein staining (cCFS) [MD -0.19; 95% CI (-0.35, -0.03); P = 0.02] scores were lower in patients treated with 0.1% CsA compared with vehicle. The Lissamine Green conjunctival staining (LGCS) [MD -0.51; 95% CI (-0.78, -0.24); P = 0.0002] and ocular surface disease index (OSDI) scores [MD -3.04; 95% CI (-5.84, -0.23); P = 0.03] were lower in the 0.1% CsA group compared with vehicle. Adverse events associated with 0.1% CsA solution in the treatment of DED varied across studies, but were generally mild to moderate. Notably, similar events were also significantly present in the vehicle group, supporting the safety profile of this treatment. Conclusion: Ophthalmic 0.1% CsA seems safe for treating DED, and significantly reduced tCFS, cCFS, LGCS, and OSDI scores compared with vehicle solutions.

Age-related macular degeneration (AMD) poses a significant threat to visual health among the elderly, necessitating urgent preventive measures as the global population ages. Extensive research has implicated oxidative stress (OS)-induced retinal damage as a primary contributor to AMD pathogenesis, prompting investigations into potential therapeutic interventions. Among the various nutrients studied for their potential in AMD risk reduction, antioxidants have shown promise, with initial findings from the Age-Related Eye Disease Study suggesting a correlation between antioxidant supplementation and decreased AMD progression. This article explores the scientific foundation supporting the therapeutic efficacy of tocotrienol-rich fraction (TRF) as a viable candidate for slowing AMD progression, based on interventional studies. AMD is characterized by OS, inflammation, dysregulated lipid metabolism, and angiogenesis, all of which TRF purportedly addresses through its potent anti-inflammatory, lipid-lowering, antiangiogenic, and antioxidant properties. The review underscores TRF's promising attributes, aiming to deepen understanding of AMD pathogenesis and advocate for TRF-based pharmacological interventions to enhance therapeutic outcomes. Given the pressing need for effective AMD treatments, TRF represents a promising avenue for intervention, offering hope for improved vision outcomes and enhanced quality of life for individuals affected by this debilitating condition.

Purpose: Keratoconus is a progressive corneal ectasia characterized by irregular astigmatism, leading to corneal scarring and decreased vision. Corneal cross-linking (CXL) is the standard treatment to halt disease progression, but its effectiveness in transepithelial (epithelium-on, epi-on) approaches is limited by the low permeability of the corneal epithelium to riboflavin (Rb). This study aimed to enhance transepithelial Rb penetration in ex vivo bovine corneas using Rb-modified tannic acid-coated superparamagnetic iron oxide nanoparticles (Rb-TA-SPIONs) under an external magnetic field. Methods: SPIONs were synthesized via co-precipitation, modified with TA and Rb, and characterized by physicochemical techniques. The average size of the Rb-TA-SPIONs was 46 ± 5.3 nm, with a saturation magnetization of 55.9 emu/g. Ex vivo experiments involved the application of 0.1% Rb to bovine corneas, and penetration was evaluated under epi-on conditions with iontophoresis (1-5 mA, 5 min). In addition, a 0.1% Rb-containing nanocarrier solution was tested under magnetic fields of 1-300 Gauss. Results: Results showed increased Rb penetration with rising electric current density and Rb-TA-SPION penetration with stronger magnetic fields, compared with epi-on control groups. Specifically, Rb penetration increased from 0.036% (P ≤ 0.01) at 1 mA to 0.059% (P ≤ 0.001) at 5 mA in the iontophoresis group and from 0.035% (P ≤ 0.001) at 1 G to 0.054% (P ≤ 0.001) at 300 G in the magnetic group. Conclusion: These findings indicate that magnetic nanoparticle-assisted Rb delivery, guided by an external magnetic field, could improve potential CXL efficacy by enhancing Rb penetration and corneal permeability.

Introduction: Povidone-iodine (PI) is the standard antiseptic for intravitreal injections (IVIs), while chlorhexidine (CHX) is a potential alternative. The efficacy of PI versus CHX in preventing endophthalmitis remains debated, with studies showing mixed results. Objective: To compare the effectiveness of using PI compared with CHX in IVI procedures regarding endophthalmitis rates, culture-positive endophthalmitis rates, and changes in visual acuity. Methods: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched the PubMed, EMBASE, Cochrane, and Web of Science databases for studies using PI compared with CHX in the IVI procedure. Statistical analysis was done using R software. Results: Four studies encompassing 453,340 eyes were included. The pooled results showed no statistical differences in endophthalmitis rates [odds ratio (OR): 1.26; 95% confidence interval (CI): 0.53-3.00]. In those who received the CHX group, there was no decrease in the rates of culture-positive endophthalmitis (OR: 2.04; 95% CI: 0.76-5.47), and the pooled results revealed no statistical differences in the mean change in visual acuity between the CHX and PI groups at final follow-up [mean difference: -0.02; 95% CI: -0.40 to 0.36]. Significant heterogeneity was identified in the post-procedure endophthalmitis rate and culture-positive endophthalmitis rate. Conclusions: Despite finding a trend toward higher rates of endophthalmitis with CHX, there are no statistical differences in using PI compared with CHX. However, our results are limited due to high heterogeneity. PI remains the gold standard, and a widespread shift to CHX cannot be justified based on the findings of this analysis.

Purpose: To evaluate the efficacy of human placental extract (HPE) eye drops compared to that of carboxymethylcellulose (CMC) and human peripheral blood serum (HPBS) eye drops in a mouse model of experimental dry eye (EDE) and corneal alkali burns. Methods: EDE and alkali burn models were induced in C57BL/6 mice using desiccating stress and NaOH, respectively. In both the EDE and alkali burn models, treatment groups received CMC, HPBS, or HPE eye drops. In EDE model, tear volume, tear break-up time (TBUT), and total corneal fluorescein staining score (CFSS) were measured. ROS were detected with 2',7'-dichlorodihydrofluorescein diacetate. Conjunctiva goblet cells were identified by periodic acid-Schiff staining, and corneal epithelial apoptosis was detected by TUNEL assay. In alkali burn model, the area and diameter of epithelial defects were assessed in each group. Results: In the EDE model, tear volume, CFSS, and epithelial apoptosis were significantly improved in all treatment groups. Compared to the CMC group, the HPE group showed a better improvement in the production of tear volume, TBUT, CFSS, ROS, and conjunctiva goblet cell density. There were no significant differences in parameters between the HPBS and HPE groups except for TBUT at 14 days. In the alkali burn model, the HPE group had a smaller area compared to the control and CMC groups and a shorter diameter compared to the control group. Conclusion: HPE eye drops were as effective as HPBS eye drops in improving the clinical signs and ocular surface oxidative damage of EDE and in promoting corneal epithelialization after alkali burn.

Posterior segment ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion, are leading causes of vision impairment and blindness worldwide. Effective management of these conditions remains a formidable challenge due to the unique anatomical and physiological barriers of the eye, including the blood-retinal barrier and rapid drug clearance mechanisms. To address these hurdles, nanostructured drug delivery systems are proposed to overcome ocular barriers, target the retina, and enhance permeation while ensuring controlled release. Traditional therapeutic approaches, such as intravitreal injections, pose significant drawbacks, including patient discomfort, poor compliance, and potential complications. Therefore, understanding the physiology and clearance mechanism of eye could aid in the design of novel formulations that could be noninvasive and deliver drugs to reach the target site is pivotal for effective treatment strategies. This review focuses on recent advances in formulation strategies for posterior segment ocular drug delivery, highlighting their potential to overcome these limitations. Furthermore, the potential of nanocarrier systems such as in-situ gel, niosomes, hydrogels, dendrimers, liposomes, nanoparticles, and nanoemulsions for drug delivery more effectively and selectively is explored, and supplemented with illustrative examples, figures, and tables. This review aims to provide insights into the current state of posterior segment drug delivery, emphasizing the need for interdisciplinary approaches to develop patient-centric, minimally invasive, and effective therapeutic solutions.