Background: The poor bioavailability of ophthalmic drops is mainly due to the rapid nasolacrimal drainage of the drug and very low permeability of corneal epithelium. Hence, there is an interest to find an effective system to improve drug permeability and bioavailability. Objectives: The aim of the present study was to design and characterize a novel microemulsion system as an ocular delivery system for Azithromycin and evaluate its physicochemical characteristics and rabbit corneal permeability in order to enhance the penetration of the drug. Methods: The prepared microemulsions (MEs) were assessed for their viscosity, pH, particle size, surface tension, DSC, stability, in vitro drug release, and corneal rabbit permeability. In this study, a full factorial design was employed with 3 variables at 2 levels for preparing 8 formulations and data analysis. Results:The results showed that the average droplet size of ME formulations was in the range of 6.78 to 26.65 nm while pH values were 5.1 to 5.7 and viscosity range was 115 -361 cps. Drug release profile revealed that 79.066% of the drug released in 24 hours of the experiment. The maximum and minimum percentages of drug permeated through rabbit cornea were observed in MEA-7 (12.87%) and MEA-2 (0.909%), respectively. All ME formulations with different compositions and properties significantly increased partitioning, flux, and permeability coefficient from rabbit cornea. Dapp and Papp parameters in MEA-1 and MEA-7 formulations were 0.00882 cm 2 h -1 and 2.391 cmh -1 , which were 17.65, 35.17 times higher than those of control (AZ suspension, 1%), respectively. The
Background/aimsSLC4A11 is the only known causative gene of congenital hereditary endothelial dystrophy (CHED). Mutation screenings have shown that most but not all patients with CHED harbour mutations in SLC4A11, suggesting that other CHED-causing genes may exist. We aimed to screen SLC4A11 in Iranian patients to learn the mutation spectrum of this gene among Iranians and to gain further knowledge on potential contribution of other genes to CHED aetiology.MethodsSLC4A11 was screened in 21 Iranian patients with CHED by sequencing. Previously unreported variations were checked in at least 200 controls, and segregation analysis within families and bioinformatics predictions on effects of variations were performed. Exome sequencing was done for the single patient without an SLC4A11 mutation and for her parents.ResultsNine previously reported and 10 unreported SLC4A11 mutations were observed among 20 patients; a mutation was not found in one patient. A mutation in MPDZ was identified as the only candidate cause of CHED in this patient. Her mother who carried the same mutation was diagnosed with Fuchs endothelial corneal dystrophy (FECD).ConclusionSLC4A11 mutations are the usual cause of CHED in Iranians. The 10 novel mutations observed contribute significantly to the approximately 85 mutations reported since discovery of the role of the gene in CHED pathogenesis more than 10 years ago. MPDZ mutations may be a cause of CHED and even FECD in a minority of patients. Proposed functions of MPDZ with respect to tight junctions and maintenance of the corneal endothelial barrier are in accordance with a role in corneal endothelial pathobiology.
A cataract is an ocular complication of diabetes mellitus, and the risk of developing diabetic macular oedema (DME) increases in cataract surgery. This randomized, single-blind clinical trial study was conducted on 45 eyes (39 patients) with stable diabetic retinopathy with cataract to compare the efficacy of three therapeutic procedures in the prevention of DME after phacoemulsification through intraocular lens implantation. After cataract surgery by phacoemulsification, the patients were randomly assigned into three groups. The group A received 1.25 mg of intravitreal bevacizumab, and group B received a sub-tenon injection of 40 mg triamcinolone at the end of the surgery. The group C received topical diclofenac drops every 8h for four weeks after the surgery. Results showed there was no significant difference in the demographics and clinical features, central macular thickness, and systemic condition of the three groups at the beginning of the study. There was a significant difference between the preoperative and postoperative periods (i.e., three months after surgery) in the three groups regarding mean macular thickness; however, the difference among the three groups was not significant in the post-operative periods. The DME after cataract surgery occurred in 4 eyes (26.67%) in the diclofenac group and three eyes (20.00%) in the intravitreal bevacizumab and three eyes (20.00%) in sub-tenon triamcinolone groups. According to results, the administration of these three therapeutic procedures can be beneficial in the prevention of DME in patients with cataract and diabetic retinopathy.
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