Ruthenium-induced corneal collagen crosslinking under visible light.

Corneal collagen crosslinking (CXL) is a commonly used minimally invasive surgical technique to prevent the progression of corneal ectasias, such as keratoconus. Unfortunately, riboflavin/UV-A light-based CXL procedures have not been successfully applied to all patients, and result in frequent complications, such as corneal haze and endothelial damage. We propose a new method for corneal crosslinking by using a Ruthenium (Ru) based water-soluble photoinitiator and visible light (430 nm). Tris(bipyridine)ruthenium(II) ([Ru(bpy)3]2+) and sodium persulfate (SPS) mixture covalently crosslinks free tyrosine, histidine, and lysine groups under visible light (400-450 nm), which prevents UV-A light-induced cytotoxicity in an efficient and time saving collagen crosslinking procedure. In this study, we investigated the effects of the Ru/visible blue light procedure on the viability and toxicity of human corneal epithelium, limbal, and stromal cells. Then bovine corneas crosslinked with ruthenium mixture and visible light were characterized, and their biomechanical properties were compared with the customized riboflavin/UV-A crosslinking approach in the clinics. Crosslinked corneas with a ruthenium-based CXL approach showed significantly higher young's modulus compared to riboflavin/UV-A light-based method applied to corneas. In addition, crosslinked corneas with both methods were characterized to evaluate the hydrodynamic behavior, optical transparency, and enzymatic resistance. In all biomechanical, biochemical, and optical tests used here, corneas that were crosslinked with ruthenium-based approach demonstrated better results than that of corneas crosslinked with riboflavin/ UV-A. This study is promising to be translated into a non-surgical therapy for all ectatic corneal pathologies as a result of mild conditions introduced here with visible light exposure and a nontoxic ruthenium-based photoinitiator to the cornea. STATEMENT OF SIGNIFICANCE: Keratoconus, one of the most frequent corneal diseases, could be treated with riboflavin and ultraviolet light-based photo-crosslinking application to the cornea of the patients. Unfortunately, this method has irreversible side effects and cannot be applied to all keratoconus patients. In this study, we exploited the photoactivation behavior of an organoruthenium compound to achieve corneal crosslinking. Ruthenium-based organic complex under visible light demonstrated significantly better biocompatibility and superior biomechanical results than riboflavin and ultraviolet light application. This study promises to translate into a new fast, efficient non-surgical therapy option for all ectatic corneal pathologies.

Noninvasive optical coherence tomography imaging correlates with anatomic and physiologic end-organ changes in healthy normotensives with systemic blood pressure variability.

OBJECTIVE: Blood pressure variability (BPV) is considered as a novel risk factor for cardiovascular disease including left ventricular hypertrophy, vascular stiffness, and renal dysfunction. In this study, we aimed to determine the relationship between ambulatory BPV with subclinical organ damage and vascular stiffness parameters in normotensive healthy subjects. METHODS: A total of 100 healthy subjects over 18 years of age were included in this cross-sectional study. We divided the participants into two groups according to the median value of the SD of mean 24-h blood pressure (BP) (Group 1: SD of mean 24-h BP <10.15 and Group 2: SD of mean 24-h BP >10.15). BPs of these subjects were recorded over a 24-h period using ambulatory BP monitoring. Mobil-O-Graph device was used to estimate the augmentation index (AIx), pulse wave velocity (PWV), and ambulatory BP measurement. The choroidal thickness was measured by using optical coherence tomography device. RESULTS: The mean age of the patients was 25.4 ± 5.0 years. Choroidal thickness was correlated with PWV, AIx, protein excretion, and SD of systolic and diastolic BP (P < 0.05). Additionally, participants with higher BP variability have lower choroidal thickness and higher AIx. CONCLUSION: We showed that even in normotensive subjects, BPV correlates with choroid thickness. Thus, BPV can be an early prognostic parameter for pathologic vascular changes.

Capecitabine-Induced Bilateral Ectropion: A Rare Ocular Manifestation Requiring Surgical Intervention.

It has been established that many chemotherapeutic agents are associated with a variety of ocular side effects. As an antineoplastic agent, 5-fluorouracil (5-FU) is the chemotherapeutic agent that is frequently linked with cicatricial ectropion. Capecitabine is a prodrug of 5-FU and has a more favorable side effect profile than 5-FU. Frequent side effects of capecitabine include gastrointestinal events and hand-foot-mouth syndrome; cicatricial ectropion is rather uncommon. Enzyme deficiencies affecting the capecitabine metabolism have been reported to be associated with exaggerated generalized systemic and cutaneous side effects; however, there are no cases in the literature reporting capecitabine-induced isolated bilateral-progressive ectropion. Although cessation of the agent is frequently sufficient for the treatment of ectropion, close follow-up is indicated in such patients as permanent damage may occur if the problem is left untreated. We report a case of capecitabine-induced bilateral cicatricial ectropion refractory to treatment cessation, ultimately requiring surgical treatment.