Aims: To examine the effi cacy of tacrolimus ophthalmic suspension 0.1% in treating severe allergic conjunctivitis. Methods: This was a multicenter, randomized, double-masked, placebo-controlled clinical trial. Fifty-six patients with severe allergic conjunctivitis in whom topical antiallergic agents and corticosteroids had been ineffective were randomized to tacrolimus or placebo treatment. Patients were treated either with tacrolimus or placebo twice-daily for 4 weeks. Severity of objective signs in palpebral and bulbar conjunctiva, limbus, and corneal involvement was assessed using 4 grades. Seven subjective symptoms were evaluated by visual analog scale (VAS) assessment. The primary effi cacy endpoint was change in the total score of objective signs at the end of treatment. The secondary effi cacy endpoints included change in the score for each objective sign and change in the VAS for each subjective symptom. Safety was assessed based on the severity and the incidence of adverse events. Results: Mean change from baseline in total score for objective signs was signifi cantly greater in the tacrolimus (−5.6 ± 5.1) than in the placebo group (−0.1 ± 4.5; P < 0.001). Tacrolimus signifi cantly improved giant papillae ( P = 0.001) and corneal involvement ( P = 0.005). Five subjective symptoms (itching, discharge, hyperemia, lacrimation, and foreign body sensation) were signifi cantly better in the tacrolimus than in the placebo group. The most frequent treatment-related adverse event in the tacrolimus group was mild ocular irritation upon topical instillation, which was well-tolerated. Conclusion: Tacrolimus ophthalmic suspension 0.1% is effective in treating severe allergic conjunctivitis.

Abstract:Poor drug delivery to lesions in patients' eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood-retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/ nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases.

The IL-6 classic- and trans-signaling pathways have an important role in corneal sterile inflammation and wound healing.

BackgroundThe objective of this study was to investigate the efficacy of topical 0.1% tacrolimus in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement.MethodsThis prospective observational study included 1436 patients with refractory allergic conjunctivitis whose condition had responded poorly to conventional antiallergic drugs and/or topical steroids and/or topical cyclosporine. All patients received tacrolimus eye drops twice daily during the study period. Ten clinical signs and six clinical symptoms were rated on a four-grade scale. The primary endpoint was the change from baseline in total clinical signs and symptoms score at the last observation or following 6 months of treatment.ResultsTotal signs and symptoms score significantly decreased after 1 month of treatment (p<0.001). Giant papillae and corneal lesions were also reduced by tacrolimus eye drop use (p<0.001). The drug proved effective in patients whose condition did not respond well to topical cyclosporine therapy. About 50% of all patients using topical steroids were weaned. The most common adverse reaction was a transient burning sensation (3.20%).ConclusionsTacrolimus eye drops are highly effective in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement, and may reduce or replace topical steroid use.Trial registration numberUMIN 000008640.

Purpose/Aim of the Study. Subthreshold micropulse diode laser photocoagulation is an effective treatment for macular edema. The molecular mechanisms underlying treatment success are poorly understood. Therefore, we investigated the effects of sublethal laser energy doses on a single layer of densely cultured ARPE-19 cells as a model of the human retinal pigment epithelium (RPE). Materials and Methods. A single layer of densely cultured human ARPE-19 cells was perpendicularly irradiated with a micropulse diode laser. Nonirradiated cells served as controls. Sublethal laser energy was applied to form a photocoagulation-like area in the cultured cell layers. Hsp70 expression was evaluated using quantitative polymerase chain reaction and immunocytochemistry. Results. Photocoagulation-like areas were successfully created in cultured ARPE-19 cell layers using sublethal laser energy with our laser irradiation system. Hsp70 mRNA expression in cell layers was induced within 30 min of laser irradiation, peaking at 3 h after irradiation. This increase was dependent on the number of laser pulses. Hsp70 upregulation was not observed in untreated cell layers. Immunostaining indicated that Hsp70 expression occurred concentrically around laser irradiation sites and persisted for 24 h following irradiation. Conclusion. Sublethal photothermal stimulation with a micropulse laser may facilitate Hsp70 expression in the RPE without inducing cellular damage.