Therapeutic Possibilities of Ceftazidime Nanoparticles in Devastating Pseudomonas Ophthalmic Infections; Keratitis and Endophthalmitis

As the number of contact‐lens wearers rises worldwide, Pseudomonas aeruginosa (PA) keratitis is attracting more attention as a major public health issue. Corneal lesions of PA, being the most intimidating complication of contact‐lens wearer, can progress rapidly in spite of local antibiotic treatment, and may result in perforation and the permanent loss of vision. One of the explanations proposed for the evasion of the pathogen from immune responses of the host as well as antibacterial treatment is the fact that invasive clinical isolates of PA have the unusual ability to invade and replicate within surface corneal epithelial cells. In this manner, PA is left with an intracellular sanctuary. Endophthalmitis, albeit rare, is another ophthalmic infection faced by the challenge of drug delivery that can be potentially catastrophic. The present hypothesis is that nanoparticles can carry anti‐pseudomonas antibiotics (e.g. ceftazidime) through the membranes, into the “hidden zone” of the pathogen, hence being an effective and potent therapeutic approach against pseudomonas keratitis and endophthalmitis

Effects of adjuvant omega-3 fatty acid supplementation on dry eye syndrome following cataract surgery: A randomized clinical trial

AbstractPurposeTo investigate the effect of omega-3 polyunsaturated fatty acid supplement on qualitative and quantitative subjective (ocular surface disease index: OSDI) and objective (Schirmer's test, tear break up time [TBUT], and tear osmolarity) dry eye indices after cataract surgery.MethodsIn this randomized clinical study, 61 eyes of 48 patients complaining of new onset dry eye symptoms after phacoemulsification were enrolled. Subjects were randomly allocated into two groups using urn randomization. Controls received conventional treatment. The treatment group received omega-3 dietary supplement in addition to conventional therapy.ResultsThere was no significant difference between the control and treatment groups in pre-treatment indices of Schirmer (3.50 ± 3.13and 2.96 ± 3.39, respectively, P = 0.582), TBUT (6.67 ± 1.36 and 4.87 ± 2.22, respectively, P = 0.687), osmolarity (316.66 ± 8.50 and 315.4 ± 17.06, respectively, P = 0.906), and OSDI (32.99 ± 19.03 and 35.32 ± 18.99, respectively, P = 0.635).Mean pre-treatment OSDI in the control group was 32.99 ± 19.03, which improved significantly after treatment to 25.43 ± 14.49 (P = 0.003). The mean pre-treatment OSDI in the treatment group was 35.32 ± 18.99 (range: 7.5–77.77), which improved significantly after treatment to 16.31 ± 13.72 (range: 2.77–47.22) (P < 0.001). OSDI improvement was significantly higher in the treatment group than the control group (P = 0.026).TBUT improved in both the control and treatment groups after treatment (P < 0.001). However, TBUT was affected significantly more in the treatment group compared with the control group (P = 0.038).Mean tear film osmolarity in the control group was 316.67 ± 8.50 (range: 308–325), which improved insignificantly after treatment to 311.33 ± 6.35 (range: 304–315) (P = 0.157). Mean pre-treatment tear film osmolarity in the treatment group was 315.40 ± 17.06 (range: 279–340), which improved significantly after treatment to 296.90 ± 14.39 (range: 260–310) (P < 0.001). Also, post-treatment Schirmer results between the two groups were not statistically significant (P = 0.155).ConclusionOmega-3 dietary supplements have an additive effect on tear film indices of patients with dry eye syndrome after phacoemulsification

Therapeutic Possibilities of Ceftazidime Nanoparticles in Devastating Pseudomonas Ophthalmic Infections; Keratitis and Endophthalmitis

As the number of contactâ€lens wearers rises worldwide, Pseudomonas aeruginosa (PA) keratitis is attracting more attention as a major public health issue. Corneal lesions of PA, being the most intimidating complication of contactâ€lens wearer, can progress rapidly in spite of local antibiotic treatment, and may result in perforation and the permanent loss of vision. One of the explanations proposed for the evasion of the pathogen from immune responses of the host as well as antibacterial treatment is the fact that invasive clinical isolates of PA have the unusual ability to invade and replicate within surface corneal epithelial cells. In this manner, PA is left with an intracellular sanctuary. Endophthalmitis, albeit rare, is another ophthalmic infection faced by the challenge of drug delivery that can be potentially catastrophic. The present hypothesis is that nanoparticles can carry antiâ€pseudomonas antibiotics (e.g. ceftazidime) through the membranes, into the “hidden zone†of the pathogen, hence being an effective and potent therapeutic approach against pseudomonas keratitis and endophthalmitis

Comparative modeling of CCRL1, a key protein in masked immune diseases and virtual screening for finding inhibitor of this protein

Human CCRL1 belongs to the family of silent chemokine receptors. This transmembrane protein plays a role in blunting function of chemokines through binding to them. This will attenuate immune responses. Interaction between CCRL1 and CCL21 determines this immune extinction. Thus inhibiting the action of this atypical chemokine seems to stimulate immune responses especially in the case of suppressed and immune deficient conditions. In this study we predicted 3D structure of CCRL1 using comparative modeling and Hiddebn Markov Model algorithm. Final predicted model optimized by Modeller v9.8 and minimized regarding energy level using UCSF chimera candidate version1.5.3. ClasPro webserver was used to find interacting residues between CCRL1 and CCL21. Interacting residues were used as target for chemical inhibitors by simulated docking study. For finding potential inhibitors, library of KEGG compounds screened and 97 obtained chemicals docked against interacting residues between CCRL1- CCL21 and MolDock was used as docking scoring function. Results indicated that Hexadecanal is a potential inhibitor of CCRL1- CCL21 interaction. Inhibition of this interaction will increase intercellular level of CCl21 and interaction between CCL21 and CCR7 causes immune potentiaiton

Tacrolimus phospholipid based nanomicelles as a potential local delivery system for corneal neovascularization therapy

Introduction: Tacrolimus, an immunosuppressive agent, has been shown to be an effective treatment against corneal neovascularization (CNV). However, the poor solubility of this compound restricts its clinical application. The goal of this study was to incorporate tacrolimus into phospholipid-bile salt mixed micelles. Methods and Results: Tacrolimus loaded phospholipid-bile salt mixed micelles were prepared, employing three different methods of direct dispersion, thin film hydration, and remote film loading, and the effects of various formulation parameters (type of dispersion medium, phospholipid to bile salt molar ratio, lipid-to-drug (L/D) molar ratio, time of probe sonication, and type of bile salt) on the physicochemical characteristics of the mixed micelles were assessed. Remote film loading method indicated higher efficacy for drug entrapment in comparison to the other methods. Encapsulation of tacrolimus within the micelles increased remarkably by the use of sodium taurocholate (NaTC) as bile salt, higher phospholipid percentage, and increasing the total lipid level. Atomic force microscopy (AFM) studies confirmed the size and size distribution of the mixed micelles and their spherical morphology. It was observed that release of tacrolimus from the micelles was in a controlled manner, without an initial burst. Conclusions: By adjusting process and formulation factors, phospholipid-bile salt mixed micelles with high entrapment efficiency of (99.5 %) and controlled release behavior were achieved, which possess great potential to be valuable carriers for ocular delivery of tacrolimus for the treatment of CNV.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp

MyoRing Implantation with and without Corneal Collagen Crosslinking for the Management of Keratoconus

Purpose: To evaluate the safety and efficacy of femtosecond laser-assisted MyoRing implantation with concurrent corneal collagen crosslinking (CXL) compared to MyoRing alone for the treatment of progressive keratoconus. Methods: A total of 60 patients were enrolled in this randomized controlled trial. The patients were randomly allocated into two groups. In the first group, MyoRing was implanted, while in the second, it was inserted in the corneal stroma using the same technique, along with simultaneous CXL. Visual, refractive, topographic, and abberometric outcomes were measured preoperatively and at every postoperative visit. Results: Data of 47 patients were available at the end of the study; 28 in the MyoRing group and 19 in the MyoRing + CXL group. The mean uncorrected distance visual acuity (UDVA) improved from 0.79 ± 0.39 logMAR to 0.52 ± 0.31 logMAR (P &lt; 0.05) in the MyoRing + CXL group and from 0.65 ± 0.38 logMAR to 0.62 ± 0.23 logMAR (P = 0.70) in the MyoRing group. CDVA changed from 0.33 ± 0.19 logMAR to 0.25 ± 0.16 logMAR (P = 0.10) in the MyoRing + CXL group and 0.32 ± 0.22 logMAR to 0.33 ± 0.17 logMAR (P &gt; 0.5) in the MyoRing group. The mean keratometry (Km) decreased from 47.5 ± 2.7 D to 43.8 ± 3.2 D (P &lt; 0.001) in the MyoRing group and 49.3 ± 3.4 D to 45.1 ± 3.0 D (P &lt; 0.001) in the MyoRing + CXL group. Besides, horizontal coma was significantly lower in the MyoRing + CXL group (P = 0.022). Conclusion: MyoRing insertion combined with CXL is a safe and effective method for the treatment of keratoconus. The visual and topographic outcomes were comparable to that for MyoRing insertion after 10 months; however, horizontal coma was significantly lower in the MyoRing + CXL group

Concomitant optic nerve transection and chorioretinitis sclopetaria

BACKGROUND: Optic nerve transection and chorioretinitis sclopetaria may occur following blunt ocular trauma. However, simultaneous occurrence has not yet been reported. We report the first case of concomitant optic nerve transection and chorioretinitis sclopetaria. CASE PRESENTATION: A 12- year- old boy with history of BB gun injury to his right eye was referred for loss of vision. His visual acuity was counting fingers at one meter in the right eye and with 3+ relative afferent pupillary defect (RAPD). On slit lamp examination, the right eye appeared normal except for 1+ vitreous reaction. Fundus examination of the right eye revealed a pale disc with superior retinal scar and diffuse submacular fibrosis compatible with chorioretinitis sclopetaria. Orbital CT- scans showed transection of the optic nerve by the BB gun pellet, which was lodged at the orbital apex. CONCLUSION: BB gun injury may cause concomitant optic nerve transection and chorioretinitissclopetaria

Comparison of silicon oil removal with various viscosities after complex retinal detachment surgery

BACKGROUND: Despite the progress in vitreoretinal surgery and the importance of silicone oil as an adjunct for the treatment of complex forms of retinal detachment, controversy still surrounds the issue of selecting the proper oil viscosity for clinical use. Herein, we evaluate the outcomes of retinal detachment (RD) surgery after removing silicone oils of different viscosities. METHODS: In this retropsective cohort study, eighty-two eyes with surgically re-attached retinas, of which 53 were filled with 5000cs silicone oil and 29 with 1000cs silicone oil were enrolled. We evaluated the outcomes and complications following silicone oil removal. Final anatomic success (stable re-attachment), final visual acuity (VA) and intraocular pressure (IOP)were recorded and analysed. RESULTS: Of 82 eyes, 41 had proliferative vitreoretinopathy (PVR), 24 were associated with intraocular foreign bodies, 10 had endophthalmitis and 7 had proliferative diabetic retinopathy with tractional retinal detachment. Prior to silicone oil removal, the retina was attached in all eyes, 29% had VA ≥ 6/120 and 52% had IOP ≥ 21 mmHg. After silicone oil removal, the retina remained attached in 59(72%) of the eyes, 34% had VA ≥ 6/120 and 9% had IOP ≥ 21 mmHg. Comparing 1000cs and 5000cs silicone oil filled eyes, redetachment occurred more frequently in the latter group especially in cases with associated PVR. Final VA worse than 6/120 was associated with initial VA < 6/120 (OR = 32.2 95%CI 7.4–140.2) and use of 5000cs silicone oil (OR = 7.9 95%CI 1.9–32.2). No factor was significantly associated with final IOP ≥ 21 mmHg. CONCLUSION: In complicated retinal detachment surgery, use of 5000cs silicone oil may be associated with a poorer anatomic and visual outcome compared with 1000cs silicone oil. However there was no difference between the two viscosities in IOP elevation. A randomized controlled study is necessary to further evaluate such a possibility

Recent developments in nanotechnology to overcome the challenges in topical drug delivery to the anterior and posterior segments of the eye: review article

Eyes and the vision system allow the human being to receive information from the environment to the extent that 90% of the man’s information is acquired through observation, thus health and correct function of this organ have always been important. Diseases threatening vision such as Acute Macular Degeneration and Diabetic Retinopathy deprive millions of people of seeing every year while access to proper cures can prevent many ocular damages. Despite scientific progress in the medical fields over the recent decades there still exist many challenges in the field of ophthalmology and ocular diseases. As for ocular treatments, major challenges stem from pharmaceutical weaknesses, in other words in spite of access to the suitable drugs for ocular complications we have not yet succeeded to achieve an appropriate method to apply these drugs. By appropriate application of drugs we may deliver the active pharmaceutical ingredient to the target organ with the least side-effect, the most benefit and the highest level of patient compliance. Incapability of effective delivery of drug to the eye arises from the special physiology and anatomy of this organ. The static barriers such as Blood-Aqueous and Blood-Retinal and dynamic barriers such as conjunctival blood circulation and lymphatic clearance will reduce the bioavailability of ocular drugs. Overcoming the above-mentioned weaknesses requires a complete knowledge of the eye characteristics as well as acquaintance with novel drug delivery system. When speaking of drug delivery system (DDS) it means employing a two-part structure consist of active pharmaceutical ingredient (API) and carrier that in fact characteristics of formulated DDS will determine by the carrier. We may hope that by applying and designing modern pharmaceutical systems that mainly take advantage of nanoparticles we would be able to overcome many challenges of ocular drug delivery. The present study is aimed at reviewing the eye structure, challenges faced by ocular drug delivery, familiarity with nanotechnology and approaches of this science in the area of ophthalmology as well as mechanisms of designing a local system for effective drug delivery to the eye tissue