Journal of Ocular Pharmacology and Therapeutics最新文献

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.

Corticosteroid use as an anti-inflammatory agent in infective conjunctivitis has been met with concerns about prolonged infection. This systematic review aims to evaluate the safety and efficacy of corticosteroids as a treatment for infective conjunctivitis. A comprehensive search was conducted on PubMed, Cochrane, Scopus, ScienceDirect, Embase, and ProQuest for clinical trials of topical corticosteroids with or without combination with other medications in bacterial or viral conjunctivitis up to November 2023. The studies were screened, and data on safety and efficacy were extracted. The quality of studies was assessed using the Jadad Scale. Meta-analysis was performed using the random-effects model, with heterogeneity assessed with the I² statistic. We found ten clinical trials that met the inclusion criteria. Overall meta-analysis revealed significant clinical resolution in dexamethasone-containing therapy compared to non-corticosteroid treatment (OR 1.51; 95% CI 1.19-1.92), with several studies reporting significantly reduced clinical symptoms severity. Two of the six studies assessing viral and bacterial eradication reported significantly improved viral clearance rates. Meta-analysis indicated no difference in ocular adverse effects compared to nonsteroid therapy (OR 1.33; 95% CI 0.82-2.16). In conclusion, corticosteroid use in infective conjunctivitis is relatively safe and may help improve clinical resolution and reduce symptom severity, especially when combined with antibiotics and antiseptics.

Purpose: To identify and quantify adverse events (AEs) associated with alpha-2 adrenergic agonists prescribed for the treatment of glaucoma in infants. Methods: We queried the Federal Adverse Event Reporting System (FAERS) from 2004-2023Q1 for AE reports related to brimonidine use in patients aged 12 months or younger. We then conducted a disproportionality analysis using data mining algorithms, including the reporting odds ratio, proportional reporting ratio, empirical bayes geometric mean, and information component to identify significant symptoms. Results: We identified 35 unique AE reports associated with brimonidine. Of these, 27 cases involved hospitalization, 13 cases involved life-threatening complications, 18 cases reported other complications, and 1 case involved a congenital anomaly. The most commonly reported AE was hypotonia, occurring in 20 cases. This was followed by other systemic symptoms, including hypothermia, depressed level of consciousness, lethargy, general toxicity, and pallor, among others. All symptoms were found to be significant in the disproportionality analysis. Notably, most cases were not known to involve an ophthalmic route of exposure. Conclusions: The use of alpha-2 adrenergic agonists in infants aged 1 year or younger has been associated with various systemic AEs, including hypotension, respiratory depression, and central nervous system depression. Ophthalmologists should be aware of these potential risks. Further, more rigorous warnings should be in place to prevent unintentional exposure of infants to brimonidine.

Background/Aims: To investigate the effectiveness of re-esterified triglyceride form of omega 3 (rTG-omega 3) on patients with meibomian gland dysfunction (MGD) after cataract surgery. Methods: This multicenter, randomized, investigator-blinded, clinical study was conducted between June 2021 and March 2023 and enrolled 107 patients with MGD who had undergone cataract surgery within 3 months at seven sites across South Korea. Patients were randomly assigned to rTG-omega 3 group or a control group. We compared (1) tear film break-up time (TBUT) (s), (2) corneal fluorescein staining score [National Eye Institute/Industry (NEI) scale], (3) conjunctival fluorescein staining score (NEI scale), (4) strip meniscometry (SM) tube score (mm), (5) MGD stage, (6) MG quality, (7) MG expressibility, (8) Standard Patient Evaluation of Eye Dryness (SPEED) score, and (9) Ocular Surface Disease Index (OSDI) scores at baseline and 6 and 12 weeks. Results: TBUT, corneal fluorescein staining score, and SM tube score were significantly improved in the rTG-omega 3 group compared with control group (P = 0.005, P = 0.003, and P = 0.0049, respectively). Subjective questionnaire responses were also improved significantly (SPEED score, P = 0.022; OSDI score, P = 0.0011). MGD parameters were not significantly different. However, during subanalysis, significant improvements in MG quality and expressibility were observed in the MGD stage 4 group with rTG-omega 3 supplementation (P = 0.0177 and P = 0.0205, respectively). Discussion: rTG-omega 3 supplementation facilitated improvements in both objective and subjective parameters. In particular, MG quality and expressibility were significantly improved in the severe MGD group.

Purpose: Renin-angiotensin system (RAS) is expressed in neuronal tissue and plays a role in neurodegenerative diseases involving excitotoxicity as a pathophysiological mechanism. In retina, excessive excitatory neurotransmission via N-methyl-d-aspartate (NMDA) receptors underlies neuronal apoptosis in conditions like glaucoma. However, it is not known if NMDA-mediated excitotoxicity alters retinal RAS expression. Hence, this study investigated the effect of NMDA exposure on the expression of RAS in rat retinas. Methods: Two groups of Sprague-Dawley rats received either phosphate buffer saline or NMDA (160 nmol). On day 7 posttreatment, retinal expression of RAS components including renin, angiotensinogen, angiotensin-converting enzyme (ACE), angiotensin II (Ang II), Ang 1-7, Ang 1-9, MAS receptor, angiotensin II type 1 receptor (AT1R), ACE2, and aldosterone was measured using enzyme-linked immunosorbent assay and polymerase chain reaction. Morphometric studies were done to assess morphological alterations. Results: Following the exposure to NMDA, an upregulation of ACE expression was noted at both the protein (2.03-folds; P < 0.001) and mRNA (1.86-folds; P < 0.01) levels in rat retinas. AT1R protein and mRNA expression were greater by 1.73 (P < 0.0001) and 2.28-folds (P < 0.0001), respectively. However, mRNA expression for ACE2, Ang 1-7, and Ang 1-9, showed a 1.51-(P < 0.05), 2.41-(P < 0.001), and 2.37-(P < 0.0001) fold decrease. Ganglion cell layer (GCL) thickness and linear cell density in GCL were significantly lower in the NMDA-treated group (P < 0.05). Conclusions: NMDA exposure increases expression of the classical RAS and suppresses that of alternate RAS in rat retinas. These alterations are associated with retinal morphological changes indicating significant loss of neuronal cells in the GCL of rat retinas.

Uveitis remains one of the leading causes of blindness worldwide, with different etiologies requiring separate approaches to treatment. For over a decade, oral, topical, and local injection of corticosteroids as well as systemic conventional disease-modifying antirheumatic drugs (DMARDs) have remained the most effective treatment for noninfectious uveitis (NIU). Systemic administration of antitumor necrosis factor-α and other biological DMARDs have been used for treating cases that responded inadequately to conventional treatments. Unfortunately, some refractory patients still suffer from frequent attacks despite the combination of multiple treatments. Recently, there has been promising evidence for Janus kinase (JAK) inhibitors as the next-generation therapy for NIU. The JAK/signal transducers and activators of the transcription (STAT) signaling pathway mediate the downstream events involved in immune fitness, tissue repair, inflammation, apoptosis, and adipogenesis by binding various ligands, such as cytokines, growth hormones, and growth factors. The mutation or loss of JAK/STAT components is implicated in autoimmune diseases, thus inhibition of such pathways has been an important area of research in therapeutic development.¹ In this review, we provide a comprehensive overview of the efficacy and safety of JAK inhibitors for the management of NIU, with evidence from current trials and case reports.

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.