Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis

Purpose: To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Design: Phase II multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. Methods: The REPARO phase II study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 \u3bcg/ml, 20 \u3bcg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Main Outcome Measures: Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed post hoc by masked central readers using a more conservative measure (0-mm staining in the lesion area and no other persistent staining). Results: At week 4 (primary end point), 19.6% of vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining) versus 54.9% receiving rhNGF 10 \u3bcg/ml (+35.3%; 97.06% confidence interval [CI], 15.88\u201354.71; P < 0.001) and 58.0% receiving rhNGF 20 \u3bcg/ml (+38.4%; 97.06% CI, 18.96\u201357.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 \u3bcg/ml (+31.4%; 97.06% CI, 11.25\u201351.49; P = 0.001) and 74.0% receiving rhNGF 20 \u3bcg/ml (+30.9%; 97.06% CI, 10.60\u201351.13; P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up. Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient. Conclusions: Topical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe NK

Integrase-Mediated Recombination of the bel-1 Gene Cassette Encoding the Extended-Spectrum β-Lactamase BEL-1.

Integrons are genetic elements that can acquire and rearrange gene cassettes. The bla <sub>BEL-1</sub> gene encodes an extended-spectrum β-lactamase, BEL-1, that is present at the second position of the variable region of class 1 integrons identified in Pseudomonas aeruginosa The mobility of the bel-1 gene cassette was analyzed under physiological conditions and with the integrase gene being overexpressed. Cassette mobility in Escherichia coli was detected by excision/integration into the recipient integron In3 on the conjugative plasmid R388 with the overproduced integrase. Despite several antibiotic pressures, the bel-1 cassette remained at the second position in the integron, highlighting its stability in P. aeruginosa Overexpression of the integrase gene in E. coli induced bel-1 cassette recombination. However, cassettes containing two genes (bla <sub>BEL-1</sub> and smr2 or bla <sub>BEL-1</sub> and aacA4) were excised, suggesting that the bel-1 cassette attC site was defective. We show that bel-1 is a stable gene cassette under physiological growth conditions, irrespective of the selective antibiotic pressure, that may be mobilized upon overexpression of the integrase gene

Characterization and Control of Supercapacitors Bank for Stand-Alone Photovoltaic Energy

AbstractIn this paper, a simple scheme of the supercapacitor based on (RC) circuit is modeled and characterized using experimental methods. Then, computer simulations and experimental results showed very good agreement which demonstrates the accuracy of the adopted model. An example of hybrid photovoltaic/supercapacitor stand-alone system is considered in this paper. Dynamic model of photovoltaic system component is developed and validated with experimental results. In addition, the maximum power point tracking (MPPT) control for photovoltaic and the supercapacitor state of charge (SOC) control are also addressed in this work. Based on the dynamic component models, a simulation model for the considered hybrid energy system has been developed using MATLAB/Simulink. The simulation results show the primary role of the supercapacitor when the load changes rapidly

Corneal crosslinking in keratoconus management

International audienc

Orbital in Juries in Wartime: Historical Study from Paul Tessier's Work in Iran.

International audienceINTRODUCTION: Paul Tessier was a leading French oculoplastic surgeon who took part in several surgical missions in Iran to manage victims of the Iraq-Iran conflict in the late 1980's and early 1990's. METHODS: We collected the records of 322 patients who underwent surgical procedures for the management of wartime injuries by Paul Tessier's team in Iran from 1990 to 1993. We also report one of the most representative cases of orbital reconstruction performed by Tessier. RESULTS: Mean age at the time of trauma was 20.65±7.04 years (range: 2−62). Craniofacial CT-scans were available for 54 patients. The bones of the upper third of the face and the orbital contents were affected in 124/322 patients (38.50%). Soft-tissue lesions of the upper third included 13 frontal lacerations (4.04%), 60 orbital injuries (18.63%) and 95 uni- or bilateral enucleations (29.50%). Thirty-nine uni- or bilateral lid injuries (12.11%) and 8 tear duct injuries (2.48%) were reported. A specific case of orbital reconstruction using antero-internal and posterior iliac bone grafts was reported as a representative example of Tessier's techniques. CONCLUSION: This study highlights the challenges of orbital reconstruction in wartime injuries and provides insights on the work of one of the most renowned surgeons in this field