Hybrid thermosensitive-mucoadhesive in situ forming gels for enhanced corneal wound healing effect of L-carnosine.

PURPOSE: Thermosensitive in situ gels have been around for decades but only a few have been translated into ophthalmic pharmaceuticals. The aim of this study was to combine the thermo-gelling polymer poloxamer 407 and mucoadhesive polymers chitosan (CS) and methyl cellulose (MC) for developing effective and long-acting ophthalmic delivery systems for L-carnosine (a natural dipeptide drug) for corneal wound healing. METHODS: The effect of different polymer combinations on parameters like gelation time and temperature, rheological properties, texture, spreading coefficients, mucoadhesion, conjunctival irritation potential, in vitro release, and ex vivo permeation were studied. Healing of corneal epithelium ulcers was investigated in a rabbit's eye model. RESULTS: Both gelation time and temperature were significantly dependent on the concentrations of poloxamer 407 and additive polymers (chitosan and methyl cellulose), where it ranged from <10 s to several minutes. Mechanical properties investigated through texture analysis (hardness, adhesiveness, and cohesiveness) were dependent on composition. Promising spreading-ability, mucoadhesion, transcorneal permeation of L-carnosine, high ocular tolerability, and enhanced corneal epithelium wound healing were recorded for poloxamer 407/chitosan systems. CONCLUSION: In situ gelling systems comprising combinations of poloxamer-chitosan exhibited superior gelation time and temperature, mucoadhesion, and rheological characteristics suitable for effective long-acting drug delivery systems for corneal wounds.

Solulan C24- and Bile Salts-Modified Niosomes for New Ciprofloxacin Mannich Base for Combatting Pseudomonas-Infected Corneal Ulcer in Rabbits.

Keratitis is a global health issue that claims the eye sight of millions of people every year. Dry eye, contact lens wearing and refractive surgeries are among the most common causes. The resistance rate among fluoroquinolone antibiotics is >30%. This study aims at formulating a newly synthesized ciprofloxacin derivative (2b) niosomes and Solulan C24-, sodium cholate- and deoxycholate-modified niosomes. The prepared niosomal dispersions were characterized macroscopically and microscopically (SEM) and by percentage entrapment efficiency, in vitro release and drug release kinetics. While the inclusion of Solulan C24 produced something discoidal-shaped with a larger diameter, both cholate and deoxycholate were unsuccessful in forming niosomes dispersions. Conventional niosomes and discomes (Solulan C24-modified niosomes) were selected for further investigation. A corneal ulcer model inoculated with colonies of Pseudomonas aeruginosa in rabbits was developed to evaluate the effectiveness of keratitis treatment of the 2b-loaded niosomes and 2b-loaded discomes compared with Ciprocin® (ciprofloxacin) eye drops and control 2b suspension. The histological documentation and assessment of gene expression of the inflammatory markers (IL-6, IL1B, TNFα and NF-κB) indicated that both 2b niosomes and discomes were superior treatments and can be formulated at physiological pH 7.4 compatible with the ocular surface, compared to both 2b suspension and Ciprocin® eye drops.

Preparation and Evaluation of Cubosomes/Cubosomal Gels for Ocular Delivery of Beclomethasone Dipropionate for Management of Uveitis.

PURPOSE: Topical corticosteroids administration is commonly used for management of various ocular conditions especially those affecting the anterior segment of the eye. Poor solubility and limited pre-corneal residence time result in insufficient drug penetration to the outer (cornea and conjunctival-scleral) coats of the eye. This study aimed to prepare and evaluate cubosomes for prolonging residence time and enhancing ocular bioavailability of BDP. METHODS: GMO-cubosomes were prepared using the top-down technique. Two stabilizers were investigated: poloxamer 407 and solulan C24. Particle size, EE %, polarized-light microscopy, TEM, in vitro release, transcorneal permeation, BCOP, histopathology and in vivo evaluation for treatment of uveitis in a rabbits' model were studied. RESULTS: The prepared cubosomes were of nano-sizes (100 nm - 278 nm); EE% was around 94%. The cubosomes were confirmed by visualizing the "Maltese crosses" textures. Transcorneal permeation was significantly (p < 0.05) improved, compared to BDP-suspension (the control formulation). The optimized cubosomes F1P was incorporated in CMC gel (Cubo-gel). The prepared Cubo-gel formulations showed better rheological characteristics and high ocular tolerability. Superior anti-inflammatory properties were recorded for the Cubo-gel for treatment of endotoxin-induced uveitis in the rabbit model when compared to the control BDP-suspension. CONCLUSIONS: Transcorneal permeation parameters Papp and flux and AUC0-10h markedly enhanced by up to 4-, 5.8-and 5.5-fold respectively, compared to the control BDP-suspension formulation. This study suggested that cubosomes/Cubo-gel could be an auspicious ocular delivery system for BDP that was able to effectively treat uveitis (a disease of the posterior segment of the eye).

Triple Procedure for Dense Cataractous Neovascular Glaucoma Patients.

PURPOSE: One of the most difficult refractory glaucomas is the neovascular type (NVG), and its association with dense cataract adds to this difficulty. This study aimed to provide results of the triple surgical procedure for such conditions. METHODS: 12 eyes of 12 patients with NVG and dense cataract were included in this case series study. The mean age of patients was 57.25 ± 5.9 years. The mean preoperative intraocular pressure (IOP) was 47.25 ± 4.04 mmHg with maximum antiglaucoma therapy. The mean best corrected distant visual acuity (BCDVA) in LogMAR was 2.13 ± 0.38. All patients received intravitreal injection of 1.25 mg (0.05 ml) bevacizumab followed by phacoemulsification, pars plana vitrectomy (PPV) including panretinal photocoagulation (PRP), and trabeculectomy with mitomycin C (MMC). Mean IOP and BCDVA changes were the main outcome results of this study. RESULTS: The follow-up period was 2 years. The mean BCDVA was improved to 1.22 ± 0.35, 1.13 ± 0.34, 1.12 ± 0.37, 1.06 ± 0.38, and 1.01 ± 0.37 at 1, 3, 6, 12, and 24 months, respectively, after this procedure. This improvement was statistically significant when compared with preoperative BCDVA (P < 0.0001). The mean postoperative IOP was dropped to 20.08 ± 4.1, 17.08 ± 2.1, 17.17 ± 5, 15.75 ± 4.7, and 16.17 ± 6.1 mmHg, respectively. At the last follow-up, the mean IOP was statistically significantly lower than preoperative IOP (P < 0.0001) at the previously mentioned time points. The success rate was complete in 90.9% of eyes and qualified in 100% of eyes. Iris and angle neovascularization had regressed significantly in all patients, and no serious complications occurred during the follow-up period. CONCLUSIONS: This triple surgery can safely improve patients with NVG and dense cataract regarding BCDVA and IOP control. This trial is registered with NCT04143620.

Evaluation of primary internal limiting membrane peeling in cases with rhegmatogenous retinal detachment.

BACKGROUND: Epiretinal membranes (ERMs) have been reported after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Peeling of the internal limiting membrane (ILM) can prevent post-PPV ERM formation but has a potential negative impact on macular structure and function. PURPOSE: To investigate the anatomical and functional outcomes of ILM peeling during PPV for primary RRD. METHODS: This was a prospective nonrandomized study that included 60 eyes of 60 patients with a primary macula-off RRD and less than grade C proliferative vitreoretinopathy (PVR). Eyes were allocated into 2 groups; Group A underwent PPV without ILM peeling and Group B had ILM peeling. At postoperative month 6, all patients underwent retinal imaging using spectral domain optical coherence tomography (OCT) and OCT angiography and macular function was assessed using multifocal electroretinogram (mfERG). Baseline characteristics and postoperative anatomical and visual outcomes were recorded and statistically analyzed. RESULTS: We enrolled 30 eyes of 30 patients in each group. In Group A, mean age was 44.6 years, while the mean age of Group B patients was 49.9 years. Postoperative LogMAR visual acuity was significantly better in Group A than in Group B (p < 0.001). ERMs were demonstrated on OCT in 13.3% of Group A and none of Group B patients (p = 0.04). Retinal dimples were found in 53.3% of Group B and none of Group A eyes (p < 0.001). OCTA showed a greater vessel density of the superficial capillary plexus (SCP) in Group A compared to Group B eyes (p = 0.046), while no difference was found regarding deep capillary vessel density (p = 0.7). Mean amplitude of mfERG P1 wave was significantly higher in Group A eyes than in Group B (p = 0.002). Both the SCP vessel density and P1 amplitude were positively correlated with visual acuity (p < 0.001). CONCLUSION: This study suggests that ILM peeling prevents ERM development in eyes undergoing PPV for uncomplicated macula-off RRD, but potential damage to macular structure and function were found.Trial registration Retrospectively registered on 09/24/2019 on ClinicalTrials.gov with an ID of NCT04139811.

Comparison Between Silicone Oil and Gas in Tamponading Giant Retinal Breaks.

PURPOSE: The purpose of this study is to compare anatomical and visual outcomes after using silicone oil (SO) or C3F8 gas as tamponades after pars plana vitrectomy (PPV) for retinal detachment (RD) associated with giant retinal tears (GRTs). METHODS: A retrospective chart review was conducted for cases that underwent PPV for GRT-associated RD. We excluded eyes that had prior vitreoretinal surgery, a history of ocular trauma or worse than grade B proliferative vitreoretinopathy (PVR). Baseline demographic and ocular characteristics, surgical details and postoperative anatomical and visual outcomes were recorded and statistically analyzed. RESULTS: We included 88 eyes; 48 eyes had C3F8 gas and 40 eyes had SO as a tamponading agent. Mean age was 39 years. All eyes underwent 23G PPV with no adjuvant scleral buckling and phacovitrectomy was performed for all phakic eyes. Final retinal reattachment was achieved in 86 eyes (97.7%). One eye from each group had recurrent RD. Postoperative vision was significantly better in the gas group (p= 0.008). Prolonged increase of IOP developed in 6 eyes in the SO group and 5 eyes in the gas group. Prolonged uveitis developed in 4 eyes in the gas group and 6 eyes in the oil group (P= 0.04). Epiretinal membranes (ERM) developed in 10 eyes in the gas group and 9 eyes in the oil group. We found no significant difference between both groups regarding postoperative glaucoma or ERM formation. CONCLUSION: Both agents achieved similar favorable anatomical outcomes in a series of eyes with fresh GRT-associated RD and low-grade PVR, with better visual outcome and less frequent uveitis associated with the use of gas tamponade.

Use of Epimacular Amniotic Membrane Graft in Cases of Recurrent Retinal Detachment Due to Failure of Myopic Macular Hole Closure.

BACKGROUND AND OBJECTIVE: To study the anatomical and functional outcomes of using epimacular amniotic membrane graft (AMG) to close myopic macular holes (MMHs) in patients with recurrent retinal detachment (RD). PATIENTS AND METHODS: Fourteen patients with recurrent MMH-RD were enrolled in a single-arm, prospective study. Pars plana vitrectomy with peeling of any residual internal limiting membrane, preserved AMG was placed over the macular hole (MH) after air-fluid exchange, all patient left on 16% of C2F6. RESULTS: Fourteen patients (11 females and three males) with an average age of 58.7 years were included; follow-up was 6 months. Thirteen patients (93%) showed retinal reattachment and closure of the hole confirmed by optical coherent tomography. The mean logMAR of best-corrected visual acuity improved to 1.38 compared to 2.2 preoperatively (P < .002, paired t-test), with no serious intraoperative or postoperative complications. CONCLUSION: Epimacular AMG for MMH-RD is a safe and effective treatment for closure of myopic MHs. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:101-108.].

Novel Technique of Pneumatic Posterior Capsulorhexis for Treatment and Prevention of Posterior Capsular Opacification.

PURPOSE: To evaluate a new technique of posterior capsulorhexis using air support to treat primary posterior capsular opacification (PCO) during cataract extraction surgery or to prevent postoperative PCO. SETTING: (1) Ophthalmology department, Faculty of Medicine, Minia University, 61519, El-Minia, Egypt. (2) Security Forces Hospital, Ophthalmology Department, Riyadh, Kingdom of Saudi Arabia. DESIGN: Prospective, randomized, consecutive case comparative non controlled study. METHODS: One hundred eyes of 100 patients with a mean age of 63.3 years with dense cataract were enrolled in the study. Fifty of them (group (1)) were with primary PCO (discovered during the operations) and fifty (group (2)) with clear posterior capsule. All of the patients underwent phacoemulsification and posterior capsulorhexis using the air to support the posterior capsule. Then, IOL implantations were done between the anterior and posterior capsular rims. Postoperatively, each patient was evaluated for the following: visual acuity (UCVA and BCVA), manifest refractive spherical equivalent (MRSE), intraocular pressure, intraocular lens (IOL) stability, visual axis opacification, and posterior segment complications as retinal breaks, retinal detachment, or cystoid macular edema (CME). RESULTS: There were no significant differences in UCVA, BCVA, and MRSE. All cases had a clear visual axis, with stable IOL and normal IOP during the follow-up period without posterior segment complications. The VA improved significantly throughout the follow-up periods in both groups without significant clinical difference. CONCLUSION: Pneumatic posterior capsulorhexis is a new effective technique for the treatment of primary PCO in dense cataract and for prevention of postoperative PCO with the good visual outcomes and minimal complications. This trial is registered with NCT04007965.

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac.

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, ß-, γ-, and HP-ß-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, ß-, γ-, and HP-ß-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with ß-, γ-, and HP-ß-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-ß-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-ß-CD demonstrated fast healing without scar formation.

In Vivo Positional Analysis of Implantable Collamer Lens Using Ultrasound Biomicroscopy.

Purpose. To evaluate the anterior segment, the anatomical position of the implantable collamer lenses (ICL), and its relationship to adjacent ocular structures using Ultrasound Biomicroscopy (UBM). Methods. In a prospective study, 142 myopic eyes of 93 patients implanted with Visian ICL were subjected to UBM examination between March 2010 and January 2015. The relative position of ICL to the adjacent structure and the overall iris configuration were evaluated. The machine calibers were used to measure the minimum central distance between the ICL and anterior lens capsule (vault) and the vertical central distance between the corneal endothelium and the ICL (E-ICL). Results. The mean ICL vault was 376 ± 105 µm. The mean E-ICL was 2826 ± 331 µm. Contact between ICL and the posterior epithelium of the iris was present in all eyes. The overall iris configuration was flat in 89 eyes. Central anterior convexity was present in 41 eyes and mild peripheral iris bombe in 12 eyes. The haptics could be imaged in the ciliary sulcus in 112 eyes and at least one haptic resting on the lens periphery and zonules in 30 eyes. Conclusion. UBM can provide valuable anatomical information that allows detailed postoperative in vivo assessment of ICL.