Corneal Ulcers in Critically Ill Foals in Intensive Care: Case Series of Standard Treatment and Corneal Cross-Linking.

Riboflavin/UV-A corneal cross-linking (CXL) has been applied to treat corneal ulcers in adult horses, but its use in critically ill neonatal foals has not been described. Five cases of hospitalized, critically ill neonatal foals that were in intensive care with corneal ulcers, the ophthalmic treatment, and their outcome up to 1 year are described. A single treatment of CXL phototherapy was performed in three of five foals (five eyes). The application of a riboflavin ophthalmic solution for 20 minutes was followed by the UV-A light irradiation at 30 mW/cm2 for 3 minutes. Topical antibiotic administration was withdrawn after CXL. Two other foals received standard treatment. Descriptions of ocular lesions, fluorescein staining, and photographic documentation were recorded. The visual outcome, corneal transparency, and aesthetics, as well as healing time were evaluated in the follow-up. The frequency of topical medication considerably decreased in cases treated with CXL. Corneal opacity and pain decreased within 3 days following CXL. In the foals treated with CXL, the ulcers healed (fluorescein stain negative) in 24, 28, and 35 days after the onset of clinical signs and 10, 15, and 21, after CXL. No fibrosis or corneal scars were found in the cases treated with CXL. The two standard treatment cases healed after 26 and 36 days respectively. Corneal cross-linking may be an additional or alternative treatment of corneal ulcers in critically ill neonatal foals and may reduce the use of antibiotics.

Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study.

BACKGROUND: We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. METHODS: Twenty-nine patients (15 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4ß7 therapy. Biopsies were taken for fluorescein isothiocyanate-labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. RESULTS: In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn's disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). CONCLUSIONS: Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF-responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders.

Photoinactivation of herpes simplex virus by rose bengal and fluorescein. In vitro and in vivo studies.

Rose bengal and fluorescein are photosensitive dyes in widespread use in the evaluation of ocular surface diseases, including herpes simplex virus (HSV) keratitis. These dyes have recently been shown to penetrate living cells, and rose bengal was previously reported to possess antiviral activity. Several experiments reported herein suggest that these dyes do possess the potential for potent antiviral activity against extracellular virus, but only in the presence of light. Rose bengal is substantially more effective in vitro than fluorescein, and the effect is greater with increasing concentration of dye and duration of light exposure. Electron microscopic evaluation of treated virus showed no structural difference from untreated virus, in spite of 4- to 5-log decreases in virus titer. Intracellular virus was found to be markedly resistant to photoinactivation. In a rabbit model of acute primary HSV keratitis, daily application of topical rose bengal followed by light exposure had no therapeutic effect, although an adverse effect on culture sensitivity testing was seen.

The antiviral effects of rose bengal and fluorescein.

We evaluated the antiviral effects of rose bengal and fluorescein sodium. The direct antiviral activity was determined by an in vitro direct neutralization assay. The 50% inhibitory dose was 16 micrograms/mL for rose bengal and 460 micrograms/mL for fluorescein. The in vivo antiviral effects of these drugs were determined in the mouse herpetic keratitis model. Following topical application, rose bengal reduced surface virus titers (swabs) 1 million-fold, and residual ocular virus (eye homogenates) 32-fold, compared with controls. No infectious virus was recovered by swabbing after topical application of rose bengal. Fluorescein had no significant effect on virus replication. Thus, rose bengal, unlike fluorescein, has significant antiviral activity, and the diagnostic use of rose bengal prior to viral culture may preclude a positive result. Also, the use of rose bengal to grade keratitis in the study of new antiviral agents should be discouraged.

[Drug therapy of angiolopathies]. / Thérapeutiques médicamenteuses des angiolopathies.

The treatment of angiolopathies is rather difficult, at this time, at least concerning functional angiopathies. It is a fact that protection against cold represents, in all angilopathies, one of the main elements of the treatment besides medications which are essentially vasoactive drugs, myorelaxants or alpha-blockers, and possibly venous tonics. Fluorescein or Sodium fluoresceinate at 5%, administered in slow intra-venous injections, represents one of the best treatment of acrocyanosis, in combination with vitamins A and D, given at the beginning of fall. Other angiolopathies, especially those of organic nature, are represented by allergic vascularitis and will be treated accordingly. In infectious and toxic forms, antibiotics should be prescribed in addition to steroids, preferred in allergic forms, especially granulomatous forms. In conclusion, the treatment of angiolopathies is extremely difficult, and must be particularly adapted to the clinical forms.

Studies on the therapeutic use of Mercurascar. Part III. Influence of Mercurascan on some metabolic changes in experimental myocardial ischaemia in dogs. Section I: Energetic and ionic metabolism.

In experimental studies on dogs, the authors investigated the effect of small does of mercurascan (MSC) on metabolism of the heart muscle damaged by ischaemia. MSC is selectively accumulated and fixed in tissue damaged by ischaemia. MSC was demostrated to inhibit severe disturbances of metabolism in the ischaemic focus. It improves energy metabolism in the damaged tissue by maintaining the concentrations of nucleotides, creatinephosphate and total creatine at a higher level, thereby increasing the energy potential level of the adenylate system. Further, MSC decreases lactate concentration in tissue and reestablishes the disturbed ionic balance. By an hitherto unknown mechanism MSC regulates concentrations of potassium and sodium ions in the ischaemic focus and prevents increased hydration of tissue. Improved metabolic relations in the ischaemic tissue contribute towards normalisation of the heart action.