Pulmonary functions deteriorate significantly for at least 3.5 months after cardiac surgery. Preoperative cardiac ischaemic and failure symptoms are inversely related to perioperative PFTs.
The purpose of this study was to evaluate the potential value of different epithelial cell culture systems as in vitro models for studying corneal permeability. Transformed human corneal epithelial (HCE-T) cells and Statens Serum Institut rabbit corneal (SIRC) cells were cultured on permeable filters. SkinEthic human corneal epithelium (S-HCE) and Clonetics human corneal epithelium (C-HCE) were received as ready-to-use systems. Excised rabbit corneas (ERCs) and human corneas (EHCs) were mounted in Ussing chambers, and used as references. Barrier properties were assessed by measuring transepithelial electrical resistance, and by determining the apparent permeability of markers with different physico–chemical properties, namely, fluorescein, sodium salt; propranolol hydrochloride; moxaverine hydrochloride; timolol hydrogenmaleate; and rhodamine 123. SIRC cells and the S-HCE failed to develop epithelial barrier properties, and hence were unable to distinguish between the permeation markers. Barrier function and the power to differentiate compound permeabilities were evident with HCE-T cells, and were even more pronounced in the case of C-HCE, corresponding very well with data from ERCs and EHCs. A net secretion of rhodamine 123 was not observed with any of the models, suggesting that P-glycoprotein or similar efflux systems have no significant effects on corneal permeability. Currently available corneal epithelial cell culture systems show differences in epithelial barrier function. Systems lacking functional cell–cell contacts are of limited value for assessing corneal permeability, and should be critically evaluated for other purposes.
BackgroundEye drops containing 0.1% hyaluronic acid (HA) and 0.5% carboxymethylcellulose (CMC) applied one drop three times a day per affected eye were compared in patients with moderate keratitis or keratoconjunctivitis related to dry eye disease (DED).Patients and methodsThis was a prospective, randomized, multicenter, Phase IIIB noninferiority study, with a single-masked phase in parallel mode with two groups over 84 days. The primary efficacy outcome was change in ocular surface (OS) staining between day 0 (D0) and day 35 (D35). The conjunctiva and cornea were stained with lissamine green and fluorescein. Secondary efficacy measures at day 84 (D84) were OS-staining score (SS), ocular comfort index, tear-film breakup time and how patients and investigators rated treatment efficacy and safety.ResultsAt D35, 0.1% HA achieved a 46.6% reduction in OS-SS (−2.03±1.35 points, n=39 patients) and 0.5% CMC treatment, followed by a 34.9% reduction (−1.61±1.69 points, n=38 patients) compared to D0. At D84, the SS difference to D0 improved by −2.58±1.45 points (−59.2%) for 0.1% HA and −2.59±2.27 points (−54.4%) for 0.5% CMC. Ocular comfort-index scores improved, with significantly lower (better) values for stinging and itching on D84 for 0.1% HA. Patients assessed treatment with 0.1% HA as significantly better than 0.5% CMC (Likert scale, 4.82 vs 3.97; P=0.018). Four adverse events (AEs) occurred in four of 41 patients (9.8%) treated with 0.1% HA, and three AEs in two of 39 patients (5.1%) treated with 0.5% CMC. No serious AEs were noted.ConclusionDED signs and symptoms of DED significantly improved with both eye drops. OS staining improved >54% at D84. Treatment was well tolerated, with only minor AEs <10%. 0.1% HA and 0.5% CMC were equally safe and effective. Significant and nonsignificant results were constantly in favor of 0.1% HA.
PurposeComparison of efficacy and safety of 0.2% and 0.18% hyaluronic acid (HA) eye drops three times a day (tid) in patients with moderate to severe dry eye disease, related to keratitis or keratoconjunctivitis.Patients and methodsProspective, multicenter, randomized, single-masked, phase IIIb, noninferiority study (0.2% HA vs 0.18% HA) in two parallel groups over a period of 84 days. N=70 patients were evaluated. Primary efficacy outcome was ocular surface (OS) staining change on day 35 (D35), compared to baseline. Fluorescein and lissamine green were used for staining of cornea and conjunctiva. Secondary efficacy outcome included tear film breakup time, OS staining score on day 84 (D84), ocular comfort index, as well as patients’ and doctors’ evaluation.ResultsCompared to day 0 (D0), 0.2% HA achieved a 47.7% reduction in staining score (−3.00±2.81 [standard deviation] points, n=38 patients) at D35; 0.18% HA showed a 41.2% reduction (−2.59±2.20 [standard deviation] points, n=32 patients). Statistical analysis showed noninferiority in efficacy of 0.2% HA compared to 0.18% HA on D35. At D84, the reduction in staining score had further increased to 64.5% for 0.2% HA and to 56.4% for 0.18% HA. Both eye drops improved tear film breakup time and ocular comfort index values. Investigators and patients assessed both treatments with 5 of 7 points (Likert Scale, medians). The rate of adverse events (AE) was 2.3% for 0.2% HA and 7.1% for 0.18% HA with no serious AE.Conclusion0.2% and 0.18% HA eye drops significantly improved signs and symptoms of dry eye disease and were well tolerated with few AEs. Noninferiority of 0.2% HA compared to 0.18% HA was demonstrated for reduction of OS lesions. In some parameters, there was a nonsignificant trend in favor of 0.2% HA concentration.
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