Journal of Ocular Pharmacology and Therapeutics最新文献

Rose bengal-assisted green light photodynamic antimicrobial therapy (RB-PDAT) is a new approach being evaluated for treating infectious keratitis. Preliminary clinical evidence suggests the broad-spectrum antimicrobial activity of RB-PDAT. The therapy potentially exerts its activity by generating reactive oxygen species that inhibit microbial growth. Large clinical trials are underway to further establish a role for RB-PDAT in clinical medicine, especially recalcitrant fungal keratitis that is less responsive to conventional photodynamic therapy with riboflavin. A potential limitation of the therapy includes poor penetration of rose bengal dye into the cornea. This limitation is being addressed by several approaches, including lipophilic prodrugs, nanoparticles, and physical approaches for enhanced delivery, including iontophoresis and ultrasound.

Purpose: To compare the efficacy of topical cyclosporine A (CsA) and steroid treatment in the membranous punctal stenosis (PS). Methods: Forty-eight patients with membranous PS were divided into 2 groups: 23 eyes of 13 patients received topical CsA for 6 months as Group CsA and 25 eyes of 14 patients received topical steroid for 3 months as Group S. Examinations were performed before and at 1, 3, 6, and 9 months after treatment. Clinical evaluations involved the Munk score and the fluorescein dye disappearance test (FDDT). Anterior segment optical coherence tomography was employed to measure tear meniscus height (TMH), tear meniscus area (TMA), and outer punctum diameter (OPD). TMH was also examined with biomicroscopy (TMH-Bio). A questionnaire was administered to assess patient satisfaction. Results: Munk score and FDDT grade decreased in both groups at all follow-ups compared with the pre-treatment. TMH-Bio was lower in the Group CsA at all follow-up visits compared with baseline (P < 0.001). TMA and TMH decreased in the Group CsA compared with pre-treatment at 6 months after treatment, whereas there were no changes in the Group S. OPD was larger at 9 months in both groups compared with baseline. The patients' satisfaction was higher in Group CsA at the 6th month compared with Group S. Conclusions: CsA has demonstrated the potential to be a more effective treatment option for the management of PS, with additional advantages compared with topical steroid, such as higher patient satisfaction and favorable functional outcomes.

Dry eye disease (DED) is a multifactorial disorder characterized by disruption of tear film homeostasis, resulting in ocular surface inflammation and damage. Although several Food and Drug Administration-approved topical treatments are available, direct comparisons of their efficacy and safety are complicated by variability in study designs and corneal staining grading scales. This review systematically evaluates and compares the efficacy and safety of topical therapies approved in the United States, focusing on anti-inflammatory and semi-fluorinated alkane (SFA)-based therapies. A systematic literature review identified 12 randomized controlled trials involving a total of 6,984 patients with varying severity of DED eligible for inclusion, with 8 providing data suitable for quantitative meta-analysis and 5 for exploratory regression analysis. Meta-analysis indicated that cyclosporine 0.1%/SFA showed the most significant early improvement (within ≤4 weeks) in total corneal fluorescein staining, outperforming other treatments. Exploratory regression analysis further supported these findings, demonstrating that cyclosporine 0.1%/SFA had the fastest and most consistent reduction in corneal staining, with the steepest improvement slope and strong predictability (R² = 0.871). Safety analyses highlighted improved local tolerability for SFA-based therapies compared with traditional anti-inflammatory treatments, notably lower instillation site discomfort for both cyclosporine 0.1%/SFA (2.5%-9.9%) and perfluorohexyloctane (≤1%) vs. other cyclosporine formulations. SFA-based therapies, especially cyclosporine 0.1%/SFA, demostrated robust efficacy in improving signs of DED with superior tolerability profiles compared to traditional anti-inflammatory treatments. These findings support the role in effectively managing ocular surface inflammation and optimizing treatment strategies in DED.

Purpose: We evaluated the capacity of rebamipide (REB) to alleviate corneal epithelial damage induced via blue light (BL) exposure. Methods: Eight-week-old C57BL/6 mice were exposed to BL (410 nm, 100 J) twice daily for 10 days. The mice were randomly divided into 5 groups: 1 untreated and 4 groups receiving BL exposure ± different topical treatments: BL exposure alone, carboxymethylcellulose, 5% N-acetylcysteine, and REB. Reactive oxygen species (ROS) levels were assessed, and Bcl-2-associated X protein (BAX) protein was analyzed. Apoptotic cells were detected, inflammatory cytokine levels [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)] were measured using enzyme-linked immunosorbent assay (ELISA), and histopathological changes in the cornea were evaluated using hematoxylin and eosin (H&E) staining. Results: The REB group demonstrated significantly lower BL exposure-induced ROS levels (P < 0.01) and BAX expression (P < 0.01) than the BL group. The number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells were lower in the REB group than in the BL group (P < 0.01). Furthermore, ELISA analysis revealed significantly reduced TNF-α and IL-6 levels in the REB group relative to BL group levels (P < 0.01). Hematoxylin and eosin staining showed preservation of corneal epithelial thickness. Conclusions: Rebamipide alleviated BL-induced oxidative damage to ocular surfaces by reducing ROS levels, inhibiting apoptosis, and suppressing inflammatory cytokine expression.

Purpose: Diabetic patients have been proven to have higher incidence of subcapsular cataract, and the subcapsular cataract formation has a closed link with epithelial-to-mesenchymal transition (EMT). EMT in numerous tissues can be regulated by the endoplasmic reticulum stress response (ER stress). In this study, we aim to explore the role of ER stress high glucose (HG)-induced EMT of human lens epithelial cells (HLECs). Methods: The human lens epithelial cell line SRA01/04 was treated under HG conditions, and 4-phenylbutyrate (PBA) or tauroursodeoxycholic acid (TUDCA) was used for 24 h to restore endoplasmic reticulum (ER) homeostasis under HG condition. The long axis and the aspect ratio of the cells were analyzed with ImageJ software to evaluate the morphology of the cells. Western blot analysis and immunofluorescence staining were applied to measure ER stress makers: glucose-regulated protein 78 (GRP78), phosphorylation of eukaryotic initiation factor-2α (P-eIf2α), activating transcription factor 6 (ATF6), phospho-inositol-requiring enzyme1 (P-IRE1α), and the EMT makers: fibronectin, vimentin, alpha-smooth muscle actin (α-SMA), and N-cadherin. Additionally, wound-healing assays were performed to evaluate the cell migration ability. Results: Under HG, the morphology of HLECs became elongated, accompanied by a significantly increased cellular aspect ratio. Both the expression of ER stress markers (GRP78, P-eIF2α, ATF6, and P-IRE1α) and the EMT markers (fibronectin, vimentin, αSMA, and N-cadherin) increased. Conversely, the expression of E-cadherin, a marker of epithelial cells, decreased, and wound-healing assays indicated enhanced cell migration ability. All of these alterations were inhibited by PBA or TUDCA treatment. Conclusions: ER stress regulates HG-induced EMT in lens epithelial cells.

Purpose: To characterize the safety profile of cenegermin through an analysis of postmarket adverse events (AEs). Methods: The U.S. Food and Drug Administration adverse event reporting system was queried for AEs associated with cenegermin use between 2019 and 2023. Demographic information was collected. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to determine adverse reactions that were significantly more likely to be caused by cenegermin use compared with other ophthalmical topicals. Results: Most AEs occurred in females (65.16%). The most common AEs were eye pain (46.94%), irritation (14.46%), and ocular hyperemia (9.8%). Of 34 eye disorders that were found to be associated with cenegermin use, the ones with the highest odds ratios were periorbital pain [ROR: 25.34, confidence interval (CI): 20.70-31.01, PRR: 16.45], eyelid pain (ROR: 22.96, CI: 19.39-27.19, PRR: 15.50), and eye pain (ROR: 20.02, CI: 18.77-21.35, PRR: 16.08). Patients taking cenegermin were significantly more likely to develop eye disorders (ROR: 2.21, CI: 2.12-2.31, PRR: 1.46), but were not more likely to develop disorders of other system organ classes. In terms of patient outcomes, patients taking cenegermin were at higher risk for hospitalization (ROR: 16.39, CI: 12.84-20.94, PRR: 12.17) and surgery (ROR: 9.57, CI: 6.14-14.93, PRR: 8.01). Conclusion: Postmarket surveillance of cenegermin demonstrates that eye pain and irritation are the most common AEs. Involvement of other organ systems is highly unlikely. Patients using topical cengermin should be counseled accordingly.

Purpose: The aim of this study was to identify and quantify the occurrence of corneal deposits caused by medications, utilizing data from the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We conducted a retrospective analysis of the national FAERS database, focusing on instances of drug-induced corneal deposits reported between 2004 and the third quarter of 2023. Our methodology included applying the proportional reporting ratio, reporting odds ratio, empirical Bayes geometric mean, and information component in our disproportionality analysis. A signal was considered present if all four of these disproportionality metrics showed positive results. Results: Over the span of 20 years, our research identified 383 adverse event reports linked to corneal deposits associated with 349 different medications. The most common age-group of these reports involved patients over 65 years of age (32.4%), with equal distribution between male (40.0%) and female (42.8%) patients. Thirty-one medications showed a positive signal. Notably, drugs such as amiodarone (68 reports), prednisolone (60 reports), and timolol (54 reports) were most frequently mentioned. Cyclopentolate and chloramphenicol demonstrated robust statistical relevance in association with corneal deposits. Conclusions: Positive signals for drug-induced corneal deposits included both well-known medications such as amiodarone and lesser-studied medications such as prednisolone and timolol. Clinician awareness of these findings alongside further investigation is needed.

Purpose: Steroid-induced ocular hypertension is poorly understood in children, despite its frequent occurrence. Significant knowledge voids exist in steroid responsiveness, especially in the pediatric population. Therefore, highlighting the most critical risk factors in pediatric patients can help ophthalmologists identify who is at increased risk of developing a high steroid response. Methods: A manual search was conducted in PubMed and Google Scholar in search of relevant articles on the steroid-induced glaucoma subtopic. Results: Key risk factors for high steroid response include glaucoma family history, previous glaucoma diagnosis, young age, steroid type, administration route, and diseases such as vernal keratoconjunctivitis (VKC) and uveitis. Clinically, it presents similarly to primary glaucoma, except for steroid usage history. Steroid cessation or reduction can normalize intraocular pressure (IOP) levels; however, in some cases, pressure-lowering drugs are necessary for treatment. Conclusion: Topical ocular steroids are frequently used by pediatricians and ophthalmologists alike. Understanding the importance of risk factors allows for a timely diagnosis of steroid response and adequate treatment before glaucomatous vision loss can occur.

Losartan is an angiotensin II receptor blocker (ARB) that also inhibits transforming growth factor (TGF)-beta signaling by blocking the activation of extracellular signal-regulated kinase (ERK) in the noncanonical TGF-beta signaling pathway. Rabbit studies demonstrated the efficacy of topical losartan in reducing fibrotic scarring following a variety of corneal injuries, such as descemetorhexis, alkali burns, and photorefractive keratectomy (PRK). Several human case reports have subsequently shown the efficacy of topical losartan in treating scarring fibrosis resulting from surgical complications and infections. Since rabbit studies have also found concentration-dependent corneal epithelial toxicity associated with topical losartan, a lower concentration of 0.2 mg/mL administered 6 times daily is recommended in corneas with epithelial defects until epithelial closure is achieved before using standard 0.8 mg/mL losartan 6 times a day for the duration of treatment. For eyes with intact epithelium, a dose of 0.8 mg/mL 6 times daily is recommended throughout the treatment period. Doses of topical losartan above 0.8 mg/mL should be avoided due to dosage-related increases in persistent epithelial defects. Clinical studies are needed to further assess questions such as which corneal fibrotic disorders are most likely to respond to topical losartan treatment and whether a lower frequency of application leads to greater treatment failure.