J. Clin. Transl. Ophthalmol., Volume 2, Issue 1 (March 2024) – 2 articles

The purpose of this study was to determine if worse visual acuity is associated with an increased risk of incident fall or mortality, independent of other relevant cofounders. This was a single-center retrospective cohort study of 428 new cases of anterior ischemic optic neuropathy (AION). Separate Cox proportional hazards models were constructed to evaluate the relationship between either logMAR visual acuity (VA) or legal blindness (20/200 or worse VA) and survival time to (1) encounter for fall, (2) mortality, and (3) a composite adverse outcome. Multivariable models were adjusted for a priori confounders. In adjusted models, a 1-unit increase in logMAR VA was associated with a significantly greater risk of an incident fall (adjusted HR 1.36, 95% CI (1.06–1.73), p = 0.014) and of mortality (adjusted HR 1.44, 95% CI (1.15–1.82), p = 0.002). Meeting criteria for legal blindness was also significantly associated with a higher risk of incident fall (HR 1.80, 95% CI (1.05–3.07), p = 0.032) and mortality (adjusted HR 2.16, 95% CI (1.29–3.63), p = 0.004). Among patients with AION, worse visual acuity or legal blindness conferred a significantly increased risk of falls and mortality, independent of coexistent comorbidities. Future studies should consider fall reduction interventions for patients with poor vision from severe eye disease such as AION. Full article

Glaucoma therapy aims at lowering intra-ocular pressure (IOP). Brinzolamide, a carbonic anhydrase inhibitor, is utilized as a second-line medication for treating ocular hypertension and primary open-angle glaucoma (POAG). The drug lowers the IOP making it a therapeutic agent against glaucoma, and due to its poor water solubility, is commercially available as Azopt^®, a 1% ophthalmic suspension. Adverse effects such as blurred vision, ocular irritation, discomfort, and bitter taste are associated with the use of the marketed brinzolamide formulation. This study aims to test the feasibility of formulating and in vitro testing of brinzolamide-PLGA nanoparticles for improved toxicity profile. The nanoparticles were prepared by the oil-in-water (O/W) emulsion-solvent evaporation method. Particle size and zeta potential were determined by dynamic light scattering (DLS). The morphology of the nanoparticles was determined by scanning electron microscopy (SEM). Encapsulation of the drug was verified by high-performance liquid chromatography (HPLC) and the compatibility of the polymer and drug was verified by Fourier transform infrared (FTIR) spectroscopy. The in vitro drug release profile was assessed employing the dialysis method. Intracellular localization of the nanoparticles was assessed by confocal microscopy utilizing Rhodamine 123-loaded nanoparticles. Cytotoxicity of the formulation was assessed on Statens Seruminstitut Rabbit Cornea (SIRC) and transfected Human Corneal Epithelial (SV40 HCEC) cell lines. The particle size of the nanoparticle formulations ranged from 202.3 ± 2.9 nm to 483.1 ± 27.9 nm for blank nanoparticles, and 129.6 ± 1.5 nm to 350.9 ± 8.5 nm for drug-loaded nanoparticles. The polydispersity of the formulations ranged from 0.071 ± 0.032 to 0.247 ± 0.043 for blank nanoparticles, and 0.089 ± 0.028 to 0.158 ± 0.004 for drug-loaded nanoparticles. Drug loading and encapsulation efficiencies ranged from 7.42–15.84% and 38.93–74.18%, respectively. The in vitro drug release profile for the optimized formulation was biphasic, with a ~54% burst release for the initial 3 h, followed by a cumulative 85% and 99% released at 24 and 65 h, respectively. Uptake study showed nanoparticles(NPs) localization in the cytoplasm and around the nuclei of the cells. Brinzolamide-PLGA nanoparticles were successfully developed, characterized, and tested in vitro. Preliminary data show intracellular localization of the nanoparticles in the cytoplasm of SIRC and SV40 HCEC cells. The formulations appeared to be relatively non-cytotoxic to the cells. The research data from the study provided preliminary data for successful development and promising in vitro absorption efficacy for brinzolamide-loaded PLGA nanoparticle formulation. Full article