Thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment.

Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects and many require more than one medication for IOP control. Recent studies have suggested that oxidative stress in the trabecular meshwork (TM) play an important role in the pathogenesis of impaired trabecular outflow facility. Curcumin, a natural phenolic compound, possesses anti-oxidant and anti-inflammation properties. In this study, we developed a thermosensitive hydrogel containing latanoprost and curcumin-loaded nanoparticles (CUR-NPs), and evaluated its possible therapeutic effects with cultured human TM cells under oxidative stress. The results demonstrated that 20 µM of CUR-NPs might be the optimal concentration to treat TM cells without causing cytotoxicity. Using the newly developed system, both latanoprost and CUR-NPs displayed a sustained-release profile. Treatment with this hydrogel containing CUR-NPs effectively decreased the oxidative stress-mediated damage in TM cells via decreasing inflammation-related gene expression, mitochondrial reactive oxygen stress (ROS) production and apoptosis level. The in vivo biocompatibility revealed no signs of inflammation or damage after topical application of developed hydrogel in rabbits. These results suggest that this dual-drug delivery system might enhance both trabecular and uveoscleral outflow and is promising to develop into a novel treatment for glaucoma.

Change of Serum IgG4 in Patients with Ocular Adnexal Marginal Zone B Cell Lymphoma Associated with IgG4-Related Ophthalmic Disease After Treatment.

PURPOSE: To investigate the change of serum IgG4 concentrations correlated with clinical evolution in patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-related ophthalmic disease (IgG4-ROD). METHODS: Three consecutive patients with histopathologically confirmed ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD were evaluated. Two patients received radiotherapy and 1 patient received steroid therapy. Treatment outcome was evaluated by clinical symptoms, radiologic examination, and change of serum IgG4 level in these patients. RESULTS: All patients had elevated serum IgG4 before treatment (462, 338, and 780 mg/dL respectively.) The 2 patients who received radiotherapy achieved complete remission and the serum IgG4 decreased to 345 and 92 mg/dL, respectively. The patient who underwent systemic steroid achieved partial remission and the serum IgG4 decrease to 161 mg/dL. CONCLUSION: Our study showed elevated serum IgG4 in all patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD. In addition, the elevated serum IgG4 may decrease or keep stable after treatment, accompanied by improvement in clinical symptoms and reduction of lesions.

Persistence of topical glaucoma medication: a nationwide population-based cohort study in Taiwan.

IMPORTANCE: Medication persistence is an important factor for treatment effect in patients with glaucoma. Evaluating risk factors for refill discontinuation might be helpful for improving persistence and preventing blindness in patients with glaucoma. OBJECTIVES: To estimate the persistence rate with topical glaucoma medication 2 years after diagnosis and evaluate risk factors for nonpersistence among patients in Taiwan with open-angle glaucoma and ocular hypertension. DESIGN, SETTING, AND PARTICIPANTS: A retrospective population-based study using claims data from the National Health Insurance Research Database. One million patients were randomly selected from the registered beneficiaries of the National Health Insurance Research Database in 2000. All patients with newly diagnosed open-angle glaucoma and ocular hypertension were included and followed up until December 31, 2008. Patients were included in the analysis only if they had follow-up data for more than 2 years after diagnosis. MAIN OUTCOMES AND MEASURES: Nonpersistence was defined as the patient not refilling any topical glaucoma medication for more than 90 days. Patient characteristics, prescription-related clinical factors, and physician and hospital characteristics were identified and considered in the analysis. The rate of persistence was estimated and risk factors for nonpersistence were investigated using Cox proportional regression models. RESULTS: A total of 3134 patients were identified and observed in the study. After a 2-year follow-up, 759 patients (24.2%) persisted with their glaucoma medications. Multivariate analysis showed that patients' living or working areas (P < .001), number of glaucoma medications (P < .001), prescription of pilocarpine hydrochloride (adjusted ratio of persistence = 0.72; 95% CI, 0.59-0.88) or prostaglandin analogs (adjusted ratio of persistence = 2.04; 95% CI, 1.82-2.33), the year in which glaucoma diagnosis was made (adjusted ratios of persistence for patients whose condition was diagnosed after 2004 = 1.18; 95% CI, 1.09-1.27), sex of the main physicians (adjusted ratios of persistence for male ophthalmologists = 0.82; 95% CI, 0.74-0.90), treatment in hospitals (P < .001), and continuity of care index (P < .001) were associated with patients' persistence with glaucoma medications. CONCLUSIONS AND RELEVANCE: The rate of persistence for glaucoma medications is low in Taiwan, although health care costs, including the cost of medication, are mostly covered by the nationwide health insurance system. This study suggests that factors other than cost, such as physician-patient relationship and patient education, may play an important role in the persistence of topical glaucoma medication.

Sustained delivery of latanoprost by thermosensitive chitosan-gelatin-based hydrogel for controlling ocular hypertension.

Glaucoma is an irreversible ocular disease that may lead to progressive visual field loss and eventually to blindness with inadequately controlled intraocular pressure (IOP). Latanoprost is one of the most potent ocular hypotensive compounds, the current first-line therapy in glaucoma. However, the daily instillation required for efficacy and undesirable side-effects are major causes of treatment adherence failure and persistence in glaucoma therapy. In the present study, we developed an injectable thermosensitive chitosan/gelatin/glycerol phosphate (C/G/GP) hydrogel as a sustained-release system of latanoprost for glaucoma treatment. The latanoprost-loaded C/G/GP hydrogel can gel within 1min at 37°C. The results show a sustained release of latanoprost from C/G/GP hydrogel in vitro and in vivo. The latanoprost-loaded C/G/GP hydrogel showed a good in vitro and in vivo biocompatibility. A rabbit model of glaucoma was established by intravitreal injection of triamcinolone acetonide. After a single subconjunctival injection of latanoprost-loaded C/G/GP hydrogel, IOP was significantly decreased within 8days and then remained at a normal level. The results of the study suggest that latanoprost-loaded C/G/GP hydrogel may have a potential application in glaucoma therapy.