Customized Corneal Cross-Linking with Microneedle-Mediated Riboflavin Delivery for Keratoconus Treatment.

In this study, a novel customized corneal cross-linking (CXL) treatment is explored that utilizes microneedles (MNs) for targeted riboflavin (RF) administration prior to the CXL procedure. Unlike the conventional "one-size-fits-all" approach, this protocol offers an option for more precise and efficacious treatment. To simulate a customized corneal crosslinking technique, four distinct microneedle (MN) molds designs, including circular, semi-circular, annular and butterfly shaped, are crafted for loading an optimized RF-hyaluronic acid solution and for the subsequent fabrication of MN arrays with varying morphologies. These MNs can gently puncture the corneal epithelium while preserving the integrity of the underlying stromal layer. Following the application of these microneedles, RF solution is replenished to enhance the RF content within the stroma through the punctures created by the MNs, resulting in exceptional customized corneal cross-linking effects that are comparable to the conventional epi-off CXL protocol. Additionally, it flattened the corneal curvature within the treated zone and facilitated rapid postoperative recovery of corneal tissue. These findings suggest that the integration of customized microneedle RF delivery with corneal crosslinking technology represents a potential novel treatment modality, holding promise for the tailored treatment of corneal pathologies, and offering a more precise and efficient alternative to traditional methods.

Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Evaluation of a New All-in-One Optical Biometer and Comparison With a Validated Swept-source OCT Biometer.

PURPOSE: To assess agreement between a new all-in-one non-contact optical biometer based on optical low coherence reflectometry (SW-9000 µm Plus; Suoer) and a swept-source optical coherence tomography biometer (OA-2000; Tomey). METHODS: Each eye was scanned three times in a row by each device at random. The measured ocular parameters included central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), axial length (AL), flat keratometry (Kf), steep keratometry (Ks), mean keratometry (Km), astigmatism, corneal diameter (CD), and pupil diameter (PD). The paired t test was used to show the differences between the SW-9000 and OA-2000. Bland-Altman plots and the 95% limits of agreement (LoA) were applied to assess the consistency of the measurements. RESULTS: Sixty eyes from 60 healthy participants were examined, with a mean spherical equivalent refraction of -5.58 ± 2.31 diopters and a mean age of 30.40 ± 6.07 years. The Bland-Altman plots showed high agreement for AL, ACD, LT, Kf, Ks, Km, astigmatism, and CD measurements (95% LoA: -0.06 to 0.04 mm, -0.10 to 0.06 mm, -0.12 to 0.11 mm, -0.30 to 0.29 D, -0.35 to 0.38 D, -0.29 to 0.30 D, -0.30 to 0.34 D, and -0.50 to 0.06 mm, respectively), whereas the agreement for CCT and PD were moderate (95% LoA: 7.12 to 20.43 µm, -0.75 to 1.19 mm, respectively). CONCLUSIONS: The new all-in-one non-contact biometer had high agreement with the OA-2000 biometer on the AL, ACD, LT, Kf, Ks, Km, astigmatism, and CD measurements. For most of the ocular parameters assessed, they were clinically interchangeable. [J Refract Surg. 2023;39(12):825-830.].

Urolithin B, a gut microbiota metabolite, protects against myocardial ischemia/reperfusion injury via p62/Keap1/Nrf2 signaling pathway.

Ischemia/reperfusion (IR) induces additional damage during the restoration of blood flow to ischemic myocardium. Urolithin B (UB) is one of the gut metabolites of ellagitannins, a class of antioxidant polyphenols, which was found to be protective against oxidative stress in multiple organs. However, the role of UB in cardiovascular disease remains elusive. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation for 30 min followed by 120 min of reperfusion, with or without UB treatment. In vitro, the H9c2 cardiomyocytes were subjected to hypoxia (94 %N2/5 %CO2/1 %O2) for 3 h, followed by reoxygenation (74 %N2/5 %CO2/21 %O2) for 3 h (HR). UB was found to decrease myocardial infarct size and attenuate the cardiac dysfunction in the rats after IR, and protect against HR injury in H9c2 cardiomyocytes. Mechanistically, UB inhibited autophagy by activating Akt/mTOR/ULK1 pathway and protected against oxidative stress and caspase 3-dependent cell apoptosis. In particular, UB induced accumulation of p62 and its interaction with Keap1, which promoted Nrf2 nuclear translocation during HR insult. Of note, the protection of UB against superoxide production and apoptotic cell death was compromised with Nrf2 gene silencing. Taken together, our findings suggested that UB protected against myocardial IR injury at least partially via the p62/Keap1/Nrf2 signaling pathway, which highlights the potential of UB as a novel therapy for ischemic heart disease.