Phase 2 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 2 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 2 study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 μg/ml, 20 μg/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 μg/ml (+35.3%; 97.06% confidence interval [CI], 15.88–54.71; P < 0.001) and 58.0% receiving rhNGF 20 μg/ml (+38.4%; 97.06% CI, 18.96–57.83; 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 μg/ml (+31.4%; 97.06% CI, 11.25–51.49; P = 0.001) and 74.0% receiving rhNGF 20 μg/ml (+30.9%; 97.06% CI, 10.60–51.13; 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

IC3D Classification of Corneal Dystrophies-Edition 3

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature. METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)]. RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4. Lisch epithelial corneal dystrophy, previously reported as X-linked, has been discovered to be autosomal dominant ( MCOLN1 mutations, chromosome 19). Classic lattice corneal dystrophy (LCD) results from TGFBI R124C mutation. The LCD variant group has over 80 dystrophies with non-R124C TGFBI mutations, amyloid deposition, and often similar phenotypes to classic LCD. We propose a new nomenclature for specific LCD pathogenic variants by appending the mutation using 1-letter amino acid abbreviations to LCD. Pre-Descemet corneal dystrophies include category 1, autosomal dominant, punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) ( PRDX3 mutations, chromosome 10). Typically asymptomatic, it can be distinguished phenotypically from pre-Descemet corneal dystrophy, category 4. We include a corneal dystrophy management table. CONCLUSIONS: The IC3D third edition provides a current summary of corneal dystrophy information. The article is available online at https://corneasociety.org/publications/ic3d

New Strategy for Rapid Diagnosis and Characterization of Fungal Infections: The Example of Corneal Scrapings

PURPOSE: The prognosis of people infected with Fungi especially immunocompromised depends on rapid and accurate diagnosis to capitalize on time administration of specific treatments. However, cultures produce false negative results and nucleic-acid amplification techniques require complex post-amplification procedures to differentiate relevant fungal types. The objective of this work was to develop a new diagnostic strategy based on real-time polymerase-chain reaction high-resolution melting analysis (PCR-HRM) that a) detects yeasts and filamentous Fungi, b) differentiates yeasts from filamentous Fungi, and c) discriminates among relevant species of yeasts. METHODS: PCR-HRM detection limits and specificity were assessed with a) isolated strains; b) human blood samples experimentally infected with Fungi; c) blood experimentally infected with other infectious agents; d) corneal scrapings from patients with suspected fungal keratitis (culture positive and negative) and e) scrapings from patients with suspected bacterial, viral or Acanthamoeba infections. The DNAs were extracted and mixed with primers diluted in the MeltDoctor® HRM Master Mix in 2 tubes, the first for yeasts, containing the forward primer CandUn (5'CATGCCTGTTTGAGCGTC) and the reverse primer FungUn (5'TCCTCCGCTT ATTGATATGCT) and the second for filamentous Fungi, containing the forward primer FilamUn (5'TGCCTGTCCGAGCGTCAT) and FungUn. Molecular probes were not necessary. The yields of DNA extraction and the PCR inhibitors were systematically monitored. RESULTS: PCR-HRM detected 0.1 Colony Forming Units (CFU)/µl of yeasts and filamentous Fungi, differentiated filamentous Fungi from yeasts and discriminated among relevant species of yeasts. PCR-HRM performances were higher than haemoculture and sensitivity and specificity was 100% for culture positive samples, detecting and characterizing Fungi in 7 out 10 culture negative suspected fungal keratitis. CONCLUSIONS: PCR-HRM appears as a new, sensitive, specific and inexpensive test that detects Fungi and differentiates filamentous Fungi from yeasts. It allows direct fungal detection from clinical samples and experimentally infected blood in less than 2.30 h after DNA extraction

Emission time scale of light particles in the system Xe+Sn at 50 AMeV. A probe for dynamical emission ?

Proton and deuteron correlation functions have been investigated with both impact parameter and emission source selections. The correlations of the system (129Xe + natSn) at 50 AMeV have been measured with the 4 pi INDRA which provides a complete kinematical description of each event. The emission time scale analyzed with a quantum model reveals the time sequence of the light particles emitted by the projectile-like fragment. The short and constant emission time of the proton, independent of the impact parameter, can be attributed to a preequilibrium process.Comment: 20 pages, with 11 included figures; Accepted by European Physics Journal

Thérapie cellulaire dans le syndrome de déficience en cellules souches limbiques (nouvelles perspectives)

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Le Temps des passions: XIXe-XXIe siècles

International audienceLes passions sont dans le temps, et contribuent à son expérience. Ce constat fonde l’étude de la représentation de la vie affective selon un temps psychologique, social ou historique, du XIXe au XXIe siècle ; elle relève de la poétique, de l’histoire des représentations, des théories de la lecture

Facteurs pronostiques associés à une prise en charge chirurgicale des kératites amibiennes

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Morphométrie des cellules épithéliales de cornées saines et de cornées opérées de kératoplastie lamellaire profonde

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Analyses géométriques et optiques de la cornée

La toricité de la face antérieure de la cornée joue un rôle majeur dans l'astigmatisme réfractif. La toricité de la cornée est le principal facteur cornéen limitant l'acuité visuelle alors que les différents indices topographiques quantifiant l'irrégularité et l'asphéricité sont décevants pour prédire l'acuité visuelle corrigée. Les expressions "non polaires" de l'astigmatisme régulier utilisant 2 cylindres croisés de Jackson d'axes 0/90 (composante directe/inverse) et 45/135 (composante oblique) permettent de quantifier l'ortho-astigmatisme, l'énantiomorphisme et la défocalisation. La norme du sphérocylindre dans un espace dioptrique est fortement corrélée à l'acuité visuelle sans correction confirmant la pertinence du modèle sphérocylindrique. La géométrie de la cornée et les propriétés optiques sont assez bien décrites par le modèle géométrique sphéro-torique et sa traduction optique sphérocylindrique.Refractive astigmatism is mainly explained by the toricity of the cornea. Corneal toricity is the major factor limiting visual acuity, whereas the different topographic indices quantifying regularity and asphericity are poorly correlated with best spectacle-corrected visual acuity. The 'non-polar' expressions of regular astigmatism using two Jackson cross cylinders with 0/90 (direct/inverse component) and 45/135 (oblique component) permit the quantification of orthoastigmatism, enantiomorphism, and defocus. The norm of the spherocylinder in the three-dimensional dioptric space shows a strong correlation with unaided visual acuity, which confirms the pertinence of the spherocylindrical model. Finally, the geometry of the cornea and the optic properties are sufficiently described by the sphericotorical model and its optical spherocylindrical expression.COMPIEGNE-BU (601592101) / SudocSudocFranceF