Intraocular foreign body in the anterior chamber angle of the eye—a 30-year-old ‘emergency’

ABSTRACT We report an unusual case of a missed intraocular foreign body, which was incidentally discovered in the anterior chamber drainage angle of the left eye of a retired masonry worker, some 30 years after the inciting injury. The ocular penetration and intraocular foreign body were missed during initial emergency management, despite the high-velocity mechanism of chiselling granite, which was reported. This case effectively highlights the need for a careful history and examination in high-velocity injuries to the eye (such as those caused by hammering and grinding), a high index of suspicion for intraocular foreign bodies, and considers best practice in managing such presentations.

Polymeric Micelles for the Enhanced Deposition of Hydrophobic Drugs into Ocular Tissues, without Plasma Exposure

Commercial topical ocular formulations for hydrophobic actives rely on the use of suspensions or oil in water emulsions and neither of these formulation modalities adequately promote drug penetration into ocular tissues. Using the ocular relevant hydrophobic drug, cyclosporine A (CsA), a non-irritant ocular penetration enhancer is showcased, which may be used for the formulation of hydrophobic actives. The activity of this penetration enhancer is demonstrated in a healthy rabbit model. The Molecular Envelope Technology (MET) polymer (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan), a self-assembling, micelle-forming polymer, was used to formulate CsA into sterile filtered nanoparticulate eye drop formulations and the stability of the formulation tested. Healthy rabbits were dosed with a single dose of a MET–CsA (NM133) 0.05% formulation and ocular tissues analyzed. Optically clear NM133 formulations were prepared containing between 0.01–0.1% w/v CsA and 0.375–0.75% w/v MET polymer. NM133 0.01%, NM133 0.02% and NM133 0.05% were stable for 28 days when stored at refrigeration temperature (5–6 °C) and room temperature (16–23 °C), but there was evidence of evaporation of the formulation at 40 °C. There was no change in drug content when NM133 0.05% was stored for 387 days at 4 °C. On topical dosing to rabbits, corneal, conjunctival and scleral AUC0–24 levels were 25,780 ng.h g−1, 12,046 ng.h g−1 and 5879 ng.h g−1, respectively, with NM133 0.05%. Meanwhile, a similar dose of Restasis 0.05% yielded lower values of 4726 ng.h/g, 4813 ng.h/g and 1729 ng.h/g for the drug corneal, conjunctival and scleral levels, respectively. NM133 thus delivered up to five times more CsA to the ocular surface tissues when compared to Restasis. The MET polymer was non-irritant up to a concentration of 4% w/v. The MET polymer is a non-irritant ocular penetration enhancer that may be used to deliver hydrophobic drugs in optically clear topical ocular formulations.

Penetration Enhancers for Topical Drug Delivery to the Ocular Posterior Segment—A Systematic Review

There is an unmet clinical need for eye drop formulations to efficiently treat the diseases of the posterior ocular segment by non-invasive topical administration. Here, we systematically reviewed the literature on ocular penetration enhancers and their ability to transfer drugs to the posterior segment of the eye in experimental studies. Our aim was to assess which penetration enhancer is the most efficient at delivering drugs to the posterior segment of the eye, when topically applied. We conducted a comprehensive search in three electronic databases (Ovid Embase, Ovid MEDLINE, and PubMed) to identify all the relevant manuscripts reported on ocular penetration enhancers based on the PRISMA guidelines. We identified 6540 records from our primary database search and filtered them per our inclusion/exclusion criteria to select a final list of 14 articles for qualitative synthesis. Of these, 11 studies used cell penetrating peptides (CPPs), 2 used chitosan, and 1 used benzalkonium chloride (BAC) as the penetration enhancer. Cationic and amphipathic CPPs, transactivator of transcription (TAT), and penetratin can be inferred to be the best among all the identified penetration enhancers for drug delivery to the fundus oculi via topical eye drop instillation. Further high-quality experimental studies are required to ascertain their quantitative efficacy.

Distribution of polymeric nanoparticles in the eye: implications in ocular disease therapy

Advantages of polymeric nanoparticles as drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, and surface ligands, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. This review seeks to discuss the available literature on the biodistribution of polymeric nanoparticles and discuss the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications.

1166. Evaluating the Impact of the 2016 Candidemia Guidelines on the Incidence of Ocular Complications of Candidemia

Background The incidence of Candida bloodstream infections has risen over the last several decades. Complications of candidemia include endogenous fungal endophthalmitis which can result in devastating outcomes including vision loss. In 2015, the IDSA guidelines were updated to recommend echinocandins as initial therapy for candidemia. Given the poor ocular penetration of echinocandins there has been some concern this change may portend an increased incidence of ocular complications in candidemic patients. We sought to examine whether patients who received empiric echinocandin therapy developed higher rates of ophthalmic complications of candidemia. Methods We identified patients in our healthcare system who had blood cultures positive for Candida species and a completed ophthalmology consult between January 1, 2014 and April 30, 2019. Chi-squared analysis was used to compare antifungal prescribing patterns before and after release of the updated IDSA guidelines. We assessed whether the switch to empiric echinocandin therapy as directed by the guidelines was associated with higher rates of abnormal eye exams. Results 47 patients treated before the guideline change were compared to 57 patients treated after the guideline change. There was no significant difference in age, gender, or comorbid diabetes and hypertension between the groups. Before the guideline change, 24/47 (51%) of patients received eye-penetrating antifungals. This decreased to 21/57 after the updated guideline (37%, p=0.21). The percentage of patients with positive eye exams was nearly equal before and after the updated guidelines, 10/47 (21%) before vs 13/57 (22%) after (p=1). After the guideline change, 7/21 (33%) of the patients treated with penetrating antifungals had positive eye exams vs 6/36 (16%) who received echinocandins (p=0.19). Conclusion Echinocandins are known to have poor ocular penetration yet our data demonstrate no change in the incidence of ophthalmic complications of candidemia after the 2016 guideline endorsed echinocandins as empiric therapy. The prevalence of positive eye exams throughout our study period was 22%, suggesting ongoing utility for these exams. Ongoing investigation is necessary to confirm and further study these findings. Disclosures All Authors: No reported disclosures