Corneal Penetration Research Articles

Poly(l-Histidine)-Mediated On-Demand Therapeutic Delivery of Roughened Ceria Nanocages for Treatment of Chemical Eye Injury.

Development of topical bioactive formulations capable of overcoming the low bioavailability of conventional eye drops is critically important for efficient management of ocular chemical burns. Herein, a nanomedicine strategy is presented to harness the surface roughness-controlled ceria nanocages (SRCNs) and poly(l-histidine) surface coatings for triggering multiple bioactive roles of intrinsically therapeutic nanocarriers and promoting transport across corneal epithelial barriers as well as achieving on-demand release of dual drugs [acetylcholine chloride (ACh) and SB431542] at the lesion site. Specifically, the high surface roughness helps improve cellular uptake and therapeutic activity of SRCNs while exerting a negligible impact on good ocular biocompatibility of the nanomaterials. Moreover, the high poly(l-histidine) coating amount can endow the SRCNs with an ≈24-fold enhancement in corneal penetration and an effective smart release of ACh and SB431542 in response to endogenous pH changes caused by tissue injury/inflammation. In a rat model of alkali burn, topical single-dose nanoformulation can efficaciously reduce corneal wound areas (19-fold improvement as compared to a marketed eye drops), attenuate ≈93% abnormal blood vessels, and restore corneal transparency to almost normal at 4 days post-administration, suggesting great promise for designing multifunctional metallic nanotherapeutics for ocular pharmacology and tissue regenerative medicine.

Novel Photodynamic/Photothermal Treatment of Fungal Keratitis Using Rose Bengal-Loaded Polypyrrole-Gold Nanoparticles in Wistar Albino Rats.

Purpose: Fungal keratitis is a potential corneal contagious disease mainly caused by yeast such as Candida albicans and filamentous fungi such as Aspergillus niger. The response of fungal keratitis to standard antifungals is limited by the poor bioavailability, the limited ocular penetration of antifungal drugs, and the development of microbial resistance. Photodynamic therapy using rose bengal (RB) as a photosensitizer was found to be effective in fungal keratitis management; however, the hydrophilicity of RB limits its corneal penetration. Polypyrrole-coated gold nanoparticles (AuPpy NP) were introduced as a nano-delivery system of RB with high loading capacity. It was proved that (RB-AuPpy NP) exhibited a combined photodynamic/photothermal effect. This study aims to use the combined photodynamic/photothermal effect of RB-AuPpy NP as a novel protocol for treating Fungal Keratitis in albino Wistar rats. Methods: The rats were infected by C. albicans and A. niger. Each infected group of rats was subdivided into groups treated by RB followed by radiation (photodynamic only), AuPpy NP followed by radiation (photothermal only), and RB-AuPpy NP followed by radiation (combined photodynamic/photothermal). Histopathological examination and slit lamp imaging were done to investigate the results. Results: The results revealed that 3 weeks post-treatment, the corneas treated by RB-AuPpy NP (combined photodynamic/photothermal effect) exhibited the best improvement compared to other groups. Conclusion: This protocol can be considered a promising one for Fungal Keratitis management that overcomes microbial resistance problems.

Topical ocular protein delivery based on protein powder suspensions in semifluorinated alkanes

The field of ocular diseases, specifically retinal diseases is a successful target area for protein drugs with various marketed products. Besides the intraocular treatment of the retina, the topical treatment of corneal or conjunctival diseases is a promising approach. Topical ocular protein formulations face the challenges of poor penetration and potentially low stability. In this study we tested suspensions based on the semifluorinated alkane F6H8 to improve the topical ocular protein delivery. Such suspensions are well known for the increased protein stability compared to aqueous solutions. Furthermore, F6H8 is well known as vehicle for ocular delivery due to its easy spreading on the cornea.Penetration of a model mAb and its Fab fragment was tested in an ex vivo corneal penetration test. The amount of penetrated protein was increased when the protein powder suspensions were used compared to the respective aqueous solutions. Sodium caprate as penetration enhancer at 5 mg/ml substantially increased the Fab fragment (7-fold) and the mAB (3-fold) concentration in the corneal tissue when applied as an aqueous solution. The effect was surprisingly more pronounced, when Fab fragment (31-fold) or mAb (13-fold) and the penetration enhancer were formulated as F6H8 suspensions. The same penetration enhancement from suspensions could be achieved with 2.5 mg/ml, but the penetration was reduced compared to 2.5 mg/ml in the aqueous solution. A test based on stratified human keratinocytes did not indicate eye irritation by the tested formulations.Furthermore, stability studies for bevacizumab suspensions in semifluorinated alkanes were investigated and showed superior long-term stability compared to the marketed aqueous solution. Overall results demonstrate the high potential of topical ocular protein delivery using powder suspensions in non-aqueous vehicles based on semifluorinated alkanes.

The effect of charges on the corneal penetration of solid lipid nanoparticles loaded Econazole after topical administration in rabbits

Fungal keratitis is an infectious disease caused by pathogenic fungi with a high blindness rate. Econazole (ECZ) is an imidazole antifungal drug with insoluble ability. Econazole-loaded solid lipid nanoparticles (E-SLNs) were prepared by microemulsion method, then modified with positive and negative charge. The mean diameter of cationic E-SLNs, nearly neutral E-SLNs and anionic E-SLNs were 18.73±0.14, 19.05±0.28, 18.54±0.10 nm respectively. The Zeta potential of these different charged SLNs formulations were 19.13±0.89, -2.20±0.10, -27.40±0.67 mV respectively. The Polydispersity Index (PDI) of these three kinds of nanoparticles were all about 0.2. The Transmission Electron Microscopy (TEM) and Differential Scanning Calorimetry (DSC) analysis showed that the nanoparticles were a homogeneous system. Compared with Econazole suspension (E-Susp), SLNs exhibited sustained release capability, stronger corneal penetration and enhanced inhibition of pathogenic fungi without irritation. The antifungal ability was further improved after cationic charge modification compared with E-SLNs. Studies on pharmacokinetics showed that the order of the AUC and t1/2 of different preparations was cationic E-SLNs > nearly neutral E-SLNs > anionic E-SLNs > E-Susp in cornea and aqueous humor. It was shown that SLNs could increase corneal penetrability and ocular bioavailability while these capabilities were further enhanced with positive charge modification compared with negative charge ones.

Recent advances in nanotechnology for the treatment of fungal keratitis.

Fungal keratitis (FK) is a serious pathogenic disease usually associated with serious ocular complications. The current mainstay of treatment for FK is topical eye drops; however, poor corneal penetration, low bioavailability of the drug and the need to administer high and frequent doses due to the presence of an effective clearance mechanism in the eye result in poor patient compliance. Nanocarriers can extend the duration of drug action through sustained and controlled release of the drug, protect the drug from ocular enzymes and help overcome ocular barriers. In this review, we discussed the mechanisms of action of antifungal drugs, the theoretical basis for the treatment of FK, and recent advances in the clinical treatment of FK. We have summarized the results of research into the most promising nanocarriers for ocular drug delivery and highlight their efficacy and safety in the therapy.

Design, Development and Optimization of Solid Lipid Nanoparticles for Ocular Delivery of an Antifungal Agent

Oral and intravenous dosing of the second-generation antifungal drug voriconazole (VCZ), with its wide range of antifungal action, is commercially accessible. Visual and hepatic problems might occur when VCZ is used in large doses. Voriconazole SLNs were prepared in this study with the goal of increasing corneal penetration and drug release. The thin fi lm hydration approach was used to make VCZ SLNs. The central composite experimental design was used to maximize the impacts of independent processing factors on vesicle size (R1), drug entrapment effi ciency (%EE) and zeta potential (ZP; R3) responses on lipid concentration (X1), surfactant concentration (X2), and sonication duration (X3). An evaluation of the drug release profi le, corneal penetration, antifungal susceptibility, and cytotoxicity of the improved formula was conducted. The improved recipe achieved the best results with a ZP of -39.6 ± 0.28 mV, an average particle size of 156 ± 3.84 nm, and an EE% of 89.2 ± 2.01. When compared to the unformulated drug solution, the VCZ-SLNs had a prolonged 10 hours drug release profi le with improved corneal penetration, with Papp and Jss measuring 14.35×10-2 cm h-1 and 4.61 mol h-1, respectively, instead of 7.28×10-2 cm h-1 and 2.48 mol h-1. Non-irritating VCZ-SLNs were determined to be corneal tissue, according to the study. Improved corneal penetration and higher antifungal activity without harmful eff ects on ocular tissues were achieved by VCZ-SLNs

Chitosan-poly(lactide-co-glycolide)/poloxamer mixed micelles as a mucoadhesive thermo-responsive moxifloxacin eye drop to improve treatment efficacy in bacterial keratitis

A mucoadhesive self-assembling polymeric system was developed to carry moxifloxacin (M) for treating bacterial keratitis (BK). Chitosan-PLGA (C) conjugate was synthesized, and poloxamers (F68/127) were mixed in different proportions (1: 5/10) to prepare moxifloxacin (M)-encapsulated mixed micelles (M@CF68/127(5/10)Ms), including M@CF68(5)Ms, M@CF68(10)Ms, M@CF127(5)Ms, and M@CF127(10)Ms. The corneal penetration and mucoadhesiveness were determined biochemically, in vitro using human corneal epithelial (HCE) cells in monolayers and spheroids, ex vivo using goat cornea, and in vivo via live-animal imaging. The antibacterial efficacy was studied on planktonic biofilms of P. aeruginosa and S. aureus (in vitro) and Bk-induced mice (in vivo). Both M@CF68(10)Ms and M@CF127(10)Ms demonstrated high cellular uptake, corneal retention, muco-adhesiveness, and antibacterial effect, with M@CF127(10)Ms exhibiting superior therapeutic effects in P. aeruginosa and S. aureus-infected BK mouse model by reducing the corneal bacterial load and preventing corneal damage. Therefore, the newly developed nanomedicine is promising for clinical translation in treating BK.

Celastrol Alleviates Corneal Stromal Fibrosis by Inhibiting TGF-β1/Smad2/3-YAP/TAZ Signaling After Descemet Stripping Endothelial Keratoplasty.

The purpose of this study was to investigate the effect of celastrol (CEL) on corneal stromal fibrosis after Descemet stripping endothelial keratoplasty (DSEK) and its associated mechanism. Rabbit corneal fibroblasts (RCFs) were isolated, cultured, and identified. A CEL-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration. CCK-8 and scratch assays were performed to evaluate cytotoxicity and the effects of CEL on the migration of RCFs. The RCFs were activated by TGF-β1 with or without CEL treatment, and then the protein expression levels of TGFβRII, Smad2/3, YAP, TAZ, TEAD1, α-SMA, TGF-β1, FN, and COLI were assessed by immunofluorescence or Western blotting (WB). An in vivo DSEK model was established in New Zealand White rabbits. The corneas were stained using H&E, YAP, TAZ, TGF-β1, Smad2/3, TGFβRII, Masson, and COLI. H&E staining of the eyeball was performed to assess the tissue toxicity of CEL at 8 weeks after DSEK. In vitro CEL treatment inhibited the proliferation and migration of RCFs induced by TGF-β1. Immunofluorescence and WB showed that CEL significantly inhibited the protein expression of TGF-β1, Smad2/3, YAP, TAZ, TEAD1, α-SMA, TGF-βRII, FN, and COL1 induced by TGF-β1 in RCFs. In the rabbit DSEK model, CEL significantly reduced the levels of YAP, TAZ, TGF-β1, Smad2/3, TGFβRII, and collagen. No obvious tissue toxicity was observed in the CPNM group. CEL effectively inhibited corneal stromal fibrosis after DSEK. The TGF-β1/Smad2/3-YAP/TAZ pathway may be involved in the mechanism by which CEL alleviates corneal fibrosis. The CPNM is a safe and effective treatment strategy for corneal stromal fibrosis after DSEK.

Phacoemulsification in patients after previous implantation of a complete intrastromal ring into a corneal transplant

BACKGROUND: The MyoRing implantation into a corneal transplant can significantly compensate for irregular post-keratoplastic astigmatism. However, the cataract that occurs in this category of patients and the lack of information in the literature on its phacoemulsification and the calculation of a toric intraocular lens (tIOL) power in them determines the relevance of our study.
 AIM: The aim of the study is to conduct a clinical and functional analysis of phacoemulsification in patients after previously performed implantation of a MyoRing into a corneal transplant.
 MATERIALS AND METHODS: We operated on 21 patients (21 eyes) who had previously undergone the MyoRing implantation into a corneal transplant. According to keratotopography, all patients were diagnosed with a regular form of corneal astigmatism. All patients underwent phacoemulsification with tIOL implantation. When calculating the tIOL power, its diopter value was corrected depending on the average value of the corneal transplant keratometry according to the keratotopogram data. The observation period duration was 6 months.
 RESULTS: One month after the procedure, there was an increase in uncorrected visual acuity by 0.2 0.9 LogMAR, best corrected visual acuity by 0.3 1.0 LogMAR, the spherical component of refraction up to 0.4 0.44 D, the cylindrical component of refraction up to 0.62 0.18 D, all of which did not change later on.
 CONCLUSIONS: Phacoemulsification with tIOL implantation, with its power calculated taking into account an additional correction for its diopter value, is an effective, predictable and safe method of treating patients after previously performed MyoRing implantation into a penetrating corneal transplant.

Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking.

Previously, we found norepinephrine (NE) could affect the corneal epithelial integrity, herein we investigated the feasibility and safety of NE serving as a chemical enhancer to promote corneal penetration of riboflavin during transepithelial corneal crosslinking (CXL). The dosage of NE that could promote riboflavin diffusion through the healthy epithelial barrier without inducing epithelial damage in C57BL/6 mice was determined. The safety of NE treatment was confirmed by morphological and histological examinations of the whole cornea. The efficacy of NE in promoting riboflavin penetration was verified by slit lamp and scanning electron microscope (SEM), and corneal biomechanical measurement after CXL. To better fit the clinical scenario, increased NE dosage and shortened riboflavin infiltration time were further evaluated. The lowest dosage of NE (1 mg/mL) that facilitated transepithelial riboflavin permeation was 2 µL. No visible corneal structure alteration was observed after NE treatment. SEM indicated dissociation of intercellular junctions among corneal epithelial cells. Homogenous distribution of riboflavin throughout corneal stroma was observed. NE-treated corneas reached comparable biomechanical properties after CXL, including stress-relaxation curve and elastic modulus, with corneas treated with the commercially available transepithelial drug Peschke TE. To better fit the clinical scenario, increasing NE up to 5.5 µL helped riboflavin infiltrate the corneal stroma within 30 minutes. After CXL with 9 mW/cm2 ultraviolet-A (UVA) for 2.5 minutes, the cornea showed significantly enhanced corneal biomechanical properties with undisturbed corneal endothelium. NE serves as an effective enhancer in increasing riboflavin diffusion with limited impairment on corneal epithelium and has great potential for clinical application. NE serves as an effective enhancer for riboflavin penetration and clinical transepithelial CXL.

TPGS-chitosan conjugated mucoadhesive micelles of brinzolamide for glaucoma therapy: In vitro and in vivo evaluation

Micelle is a promising avenue for ophthalmic drug development technology and an especially suitable choice for hydrophobic drugs. The aim of this investigation was to synthesize Brinzolamide (BRZ) loaded d-alpha-tocopherol polyethylene glycol succinate (TPGS) - Chitosan conjugated micelles (BTCM) prepared by solvent evaporation method and to investigate their intraocular pressure (IOP) reducing efficacy for the management of glaucoma. The formulated BTCM was evaluated with various parameters such as size, zeta potential, morphology, percentage drug entrapment efficiency, drug loading capacity, and mucoadhesion strength, in-vitro and ex-vivo release. In-vivo anti-glaucoma efficacy study was conducted by glucocorticoid-induced glaucoma rabbit eye model and evaluated with the Marketed formulation (MF). The optimized formula showed a micelle size of 74.32±1.46 nm, and suitable physicochemical properties and in-vitro release mechanism were observed in that biphasic erosion-diffusion pattern of BRZ releases up to 8 h. The Ex-vivo corneal penetration of BRZ from BTCM showed a higher permeability rate than MF. Additionally, BTCM showed sustained release of BRZ, better corneal tissue compatibility, and improved anti-glaucoma potential, as compared to MF. The results concluded that BTCM is the suitable option for anti-glaucoma therapy because of its capability to improve ocular mucoadhesion of loaded BRZ via the interaction with the mucous membrane of the corneal surface.

Influence of the Size and Charge of Carbon Quantum Dots on Their Corneal Penetration and Permeation Enhancing Properties.

Reaching the corneal endothelium through the topical administration of therapeutic drugs remains a challenge in ophthalmology. Besides, endothelial cells are not able to regenerate, and diseases at this site can lead to corneal blindness. Targeting the corneal endothelium implies efficient penetration through the three corneal layers, which still remains difficult for small molecules. Carbon quantum dots (CQDs) have demonstrated great potential for ocular nanomedicine. This study focuses on the corneal penetration abilities of differently charged CQDs and their use as permeation enhancers for drugs. Excised whole bovine eyes were used as an ex vivo model to investigate corneal penetration of CQDs derived from glucosamine using β-alanine, ethylenediamine, or spermidine as a passivation agent. It was found that negatively charged CQDs have limited corneal penetration ability, while positively charged CQDs derived from glucosamine hydrochloride and spermidine (CQD-S) penetrate the entire corneal epithelium all the way down to the endothelium. CQD-S were shown to enhance the penetration of FITC-dextran 150 kDa, suggesting that they could be used as efficient penetration enhancers for therapeutic delivery to the corneal endothelium.

Congenital limbal dermoid in a 10-year-old male

The most typical choristomas, sometimes referred to as congenital benign tumors, are limbal dermoids. Limbal dermoids are typically seen in the inferotemporal quadrant, but they can sometimes exclusively be found in the conjunctiva and sclera or present fully within the perilimbal cornea. Despite being benign, progressive limbal dermoids may result in anisometropic amblyopia because of the development of corneal astigmatism, encroachment on the visual axis, and corneal penetration of fatty components. Anatomically, there are three different classes of limbal dermoids. Grade I limbal dermoids are small, superficial tumor lesions that are currently being treated with conservative medicine. Large Grade II limbal dermoids penetrate both Descemet´s membrane and the corneal stroma. Grade III limbal dermoids impact all histological structures between the eyeball´s anterior surface and the iris´s pigmented epithelium, penetrate the anterior chamber and completely cover the cornea. The histologically abnormal tissues that can be found in limbal dermoids include epidermal appendages, connective tissues, skin, fat, sweat glands, lacrimal glands, neurological tissues, and hyperplasia. Here we represent a 10-year-old male with progressive limbal dermoid in the inferior quadrant in the left eye at 6 o´clock with hair follicles over it associated with the preauricular tag. A dermoid cyst was also present at 5 o´clock. It was progressive in nature and was associated with diminution of vision. Keeping that in mind surgical excision of the limbal dermoid was planned. The best timing and methods for surgical procedures in newborns and young children depend on the tumor size, tumor growth rate, and the affected locations.

Low-intensity low-frequency ultrasound mediates riboflavin delivery during corneal crosslinking.

We employed the mechanical effect from 40 kHz ultrasound (US) to improve the delivery of riboflavin into corneal stroma for collagen crosslinking, which can benefit the treatment of keratoconus and other corneal ectasias. Experiments were conducted, first with porcine corneas ex vivo and then with New Zealand white rabbits in vivo, at varying mechanical index (MI) and sonication time. Results showed that 15 min of US applied on the cornea at MI=0.8 in the presence of 0.5% of riboflavin solution enabled its delivery to deeper corneal stroma. Excessive heat was removed by a cooling setup to negate the thermal effect. The corneal absorption amount and penetration of riboflavin through cornea as detected by fluorotron, as well as the enhancement of corneal stiffness as measured by Young's modulus, were comparable to the conventional approach that requires complete corneal epithelium debridement. Histological analysis revealed minor exfoliation of superficial cell layers of corneal epithelium and loss of ZO-1 tight junctions immediately after US. Full recovery of the corneal epithelium and restoration of tight junctions occurred in 3-4 days. The study shows that low-intensity low-frequency ultrasound (LILF US) is a less invasive alternative to the conventional epithelium-off method for delivering riboflavin into the corneal stroma.

Penetrating corneal fish hook injury: A case report

Fishing is a popular recreational activity. Ocular penetrating fish hook injury is an unusual cause of ocular trauma and is often challenging in management. We are presenting a case report of a 29 year old male who came to our casualty with penetrating corneal injury due to a barbed fish hook while trying to catch fish. Fish hook was seen penetrating through the cornea and iris and the tip was not seen. We enlarged the wound and used foreign body forceps to separate the ocular tissues from the barb of the hook. Knowing the structure of fish hook and its relation to ocular tissues is important for successful removal of fish hook and for a good outcome. 1: The technique for removal of fish hook from eye depends on the relation of the hook to the ocular tissues; 2: Appropriate surgical intervention is necessary for a good outcome

Nanogel Development and its Importance in Ophthalmic Drug Delivery System

Background: The current review focuses on ophthalmic nanogels, their applications, their benefits over traditional gels, and the challenges and opportunities of nanogels. The major goal is to investigate ophthalmic nanogels from preparation through characterization and how nanogels are the future of the ophthalmic drug delivery system compared to traditional gels, eye drops, and ointments. Objective: Because of the ophthalmic bioavailability, delivery to the eye is crucial. The lacrimal flu-id in the eye clears the eye surface, and the ocular sight is washed away as a result of this medicine. The limited ocular bioavailability was also due to the different obstacles present. Drug nano-gelling systems are effective in improving ocular bioavailability and corneal permeation time. Nanoparti-cles abound in these nanogels. Various natural polymers, such as Chitosan and Alginate, and syn-thetic polymers, such as PLA and PLGA, can be used to make nanogels. The use of nanotechnology improves medicine bioavailability and penetration in the eye. However, nanotechnology has some limits, such as large-scale manufacturing, restricting medicine doses, and so forth. Conclusion: Nanotechnology offers much clinical potential when it comes to treating eye issues. Although ophthalmic nanogels are suited for effective drug delivery, they must meet several re-quirements. First, the drug component must be encapsulated adequately in a stable polymer com-plex. In ocular drug delivery, nanogels are a preferable option since they can improve patient com-pliance and therapeutic impact. In addition, the nanogel has a faster corneal penetration time and higher bioavailability.

Pronounced capping effect of olaminosomes as nanostructured platforms in ocular candidiasis management

The aim of this study was to formulate and boost ocular targeting of Fenticonazole Nitrate (FTN)-loaded olaminosomes in order to improve drug corneal permeation and candidiasis treatment. Olaminosomes were formulated by ethanol injection technique applying a central composite design. The independent variables were: span 80 amount (mg) (A), oleylamine concentration (mg%) (B) and oleic acid: drug ratio (C). The dependent responses were: percent entrapment efficiency (EE %), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and in vitro drug release after 10 hours (Q10h). Numerical optimization by Design-Expert® software was adopted to select the optimum formula. This formula was chosen based on highest EE %, ZP (as absolute value) and Q10h and lowest PS and PDI. The optimum formula was subjected to further in vitro characterization via Differential scanning calorimetry, Transmission electron microscopy, Fourier transform infrared spectroscopy, pH determination, effect of storage, influence of terminal sterilization, detection of Minimal Inhibitory Concentration and ex vivo corneal penetration analysis. Safety and antifungal activity of the optimum formula were tested through various in vivo studies like ocular irritancy, corneal tolerance, corneal uptake and susceptibility test. The optimum formula with the maximum desirability value (0.972) revealed EE% (84.24%), PS (117.55 nm), ZP (−74.85 mV) and Q10h (91.26%) respectively. The optimum formula demonstrated ocular tolerance with enhanced corneal penetration behavior (428.66 µg/cm2) and boosted antifungal activity (56.13%) compared to FTN suspension (174.66 µg/cm2 and 30.83%). The previous results ensured the ability of olaminosomes to enhance the corneal penetration and antifungal efficacy of Fenticonazole Nitrate.

Corneal targeted fenticonazole nitrate-loaded novasomes for the management of ocular candidiasis: Preparation, in vitro characterization, ex vivo and in vivo assessments

The purpose of this manuscript was to develop and optimize Fenticonazole Nitrate (FTN)-loaded novasomes aiming to enhance drug corneal penetration and to improve its antifungal activity. Ethanol injection was used to formulate FTN-loaded novasomes adopting a central composite design. The researched factors were: stearic acid concentration (g%) (A), span 80: drug ratio (B) and cholesterol amount (mg) (C), and their effects on percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), and in vitro drug release after 8 hours (Q8h) were studied. Numerical optimization by Design-Expert® software was employed to select the optimum formula in respect to highest EE%, ZP (as absolute value), and Q8h >80% and lowest PS and PDI. Additional evaluation of the optimum formula was accomplished by short term stability study, effect of gamma sterilization, determination of Minimal Inhibitory Concentration and ex vivo corneal permeation study. The in vivo evaluation of the optimum formula was done to ensure its safety via in vivo ocular irritancy and in vivo corneal tolerance studies. Also, the efficacy was confirmed through in vivo corneal uptake study and susceptibility test. The optimum formula with the highest desirability value (0.738) showed EE% (94.31%), PS (197.05 nm), ZP (-66.95 mV) and Q8h (85.33%). It revealed to be safe, with augmented corneal permeation (527.98 µg/cm2) that leads to higher antifungal activity. The above results confirmed the validity of novasomes to improve the corneal permeation and antifungal activity of Fenticonazole Nitrate.

Anatomical and functional outcomes of Boston type I keratoprosthesis as primary penetrating corneal procedure in high-risk and non-high-risk cases.

To analyze the anatomical and functional results of Boston type I keratoprosthesis (B1-KPro) as a primary corneal procedure in high-risk (HR) cases and non-high-risk (NHR) cases. In this retrospective interventional case series, all patients who underwent B1-KPro at a single center between January 2006 and March 2021 were reviewed and identified. Cases were classified according to the primary diagnosis. Anatomical failure was considered in the case of prosthesis extrusion or phthisis bulbi. Functional failure was a postoperative corrected distance visual acuity (CDVA) ≥ 1.3 LogMAR (≤ 0.05 decimal) at the end of the follow-up period. Twenty-three eyes were included for analysis. Thirteen eyes were classified as HR and 10 as NHR. The mean age was 46.5 ± 26.5years (5-84years) in the HR group and 49.5 ± 26.9years (2-78years) in the NHR group. The mean follow-up was 42.0 ± 35.9months (1.5-118months) in HR and 44.8 ± 38.8months (1-107months) in NHR. Three eyes in the HR and none in the NHR group showed anatomical failure. Functional failure was reported in 5/13 eyes in the HR and 8/10 in the NHR group. Functional cumulative survival probability was 92% and 82% for the HR group at 1 and 2years, respectively. In the NHR group, it was 27% at both times. No significant differences were found between groups, except for functional survival in the HR group due to better visual potential of the eyes. B1-KPro as a primary corneal procedure is a valid option for visual rehabilitation in high-risk cases.

Clinical Study and Profile of Ocular Trauma: Findings From a Rural Hospital in Central India.

ObjectiveIn this study, we aimed to examine the presence of visual damage due to ocular trauma and assess visual outcomes, and document the clinical spectrum and outcomes following ocular injuries among patients presenting to a tertiary care hospital in rural central India.MethodsThis was a hospital-based prospective interventional study conducted over a period of two years from August 2019 to August 2021. Patients with ocular injuries attending the casualty and the Ophthalmology department were included in the study after applying the inclusion and exclusion criteria. A detailed and comprehensive ophthalmic examination was performed and visual acuity was noted at the presentation and follow-ups. The patients were followed up at regular intervals, initially at one week and subsequently at three and six weeks.ResultsThe incidence of ocular trauma was highest in the age group of 31-40 years. There were only three patients aged more than 60 years; 15 were in the pediatric age group (1-20 years). The ocular trauma was highest in males (88.33%) than in females (11.67%). The majority of the patients were from rural areas (70%) and 30% were from urban areas. In this study, both eyes were equally involved. The right eye was involved in 45% of patients and the left eye was involved in 55%. Of note, 80% of the patients presented with closed globe injury, and 20% presented with open globe injury. On classifying the open and closed globe injuries into their subtypes, it was observed that the majority of the patients had lid laceration (n=43, 71.67%), followed by corneal penetration in 12 patients (20%), corneal abrasion in three patients (5%), and lid abrasion in two patients (3.33%). While 34 patients presented to the hospital with a history of road traffic accidents (56.67%), accidental trauma (by a wooden stick, hook of a blouse, bangle, etc.) was noted in 17 patients (28.33%), trauma by soil particle and hand pump in five patients (8.33%), and electrical trauma caused by the blast of capacitor in one patient (1.67%). One patient (1.67%) had sustained trauma from a piece of wood while working on the farm and two patients (3.33%) had a trauma because of assault. Thirty-four patients (66.67%) had a history of falls from bikes, and the next most common object causing trauma was a wooden piece/stick (four patients, 6.67%), followed by trauma caused by an iron particle in four patients (6.67%), trauma by stone in three patients (5%), and trauma by hand pump in two patients (3.33%).ConclusionRoad traffic accidents were the most common cause of ocular trauma in patients attending this rural hospital in central India. The ocular structures involved and types of ocular trauma play a significant role in determining the visual outcomes in these patients.