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

Phase I trial of recombinant human nerve growth factor for neurotrophic keratitis

Neurotrophic keratitis/keratopathy (NK), a rare degenerative corneal disease, lacks effective pharmacologic therapies.1 Because NK pathology involves trigeminal nerve damage and loss of corneal innervation, nerve growth factor (NGF) is surmised to promote healing of NK.2 Preliminary studies with murine NGF demonstrated efficacy for treating corneal neurotrophic ulcers;3 however, the complex tertiary structure of NGF has complicated the production of recombinant human NGF (rhNGF) suitable for clinical development. To this end, we developed an Escherichia coli–derived rhNGF formulation that demonstrated to be well tolerated and safe for topical ophthalmic use in a phase I study in healthy volunteers.4 We report phase I results of topical rhNGF for patients with moderate-to-severe NK

New transgenic analysis of corneal sensory innervation

La cornée est le tissu le plus densément innervé du corps humain. Cette innervation joue un rôle dans la régulation de la sécrétion du film lacrymal et exerce un rôle trophique direct sur l'épithélium cornéen. Les axones cornéens expriment différents types de récepteurs et répondent à des fonctions de mécano-nocicepteurs, de récepteurs au froid ou de récepteurs polymodaux. Nous avons pu identifier de nouvelles lignées de souris transgéniques et les utiliser pour caractériser ces différentes populations axonales. L'innervation cornéenne débute à E12.5 chez la souris et est régulée par les molécules de Slits et de Sémaphorines et leurs récepteurs Robo et Plexines/Neuropilines respectivement. Nous avons pu étudier le rôle de ces deux familles dans le développement de l'innervation cornéenne. Les mutants Slits et Robos présentent une réduction du nombre et de la taille des terminaisons axonales épithéliales cornéennes. A l'âge adulte, les mutants Robos présentent une dégénérescence précoce des terminaisons épithéliales. Les mutants plexine-A4 et Neuropiline-1 présentent à l'inverse une augmentation du nombre de divisions des troncs stromaux cornéens. A l'âge adulte les mutants Plexine-A4 retrouvent une organisation classique de l'innervation alors que les mutants Neuropiline-1 conservent la désorganisation de l'innervation cornéenne. Nous avons également étudié la régénération de l'innervation après lésions de grattage de l'épithélium cornéen. Nos résultats préliminaires semblent en faveur d'une augmentation de la régénération de l'innervation cornéenne chez les mutants Neuropiline-1.The cornea is the most densely innervated tissue in the entire body. Corneal innervation plays a role in regulating the secretion of lacrimal film and exerts a direct trophic role on the corneal epithelium. Corneal axons express different types of sensory receptors ranging between mechano-, thermo-, and polymodal nociceptors. We identified transgenic mouse lines to characterize these different axonal populations. Corneal innervation begins at E12.5 in mice and is regulated by a range of axon guidance cues such as Slits and Semaphorins, which respond to their receptors Robo and Plexin/Neuropillin respectively. We studied the role of these two families in the development of corneal innervation. The Slits and Robos mutants show a reduction in the number and size of the corneal epithelial nerves endings. In adult, Robos mutants exhibit early degeneration of the epithelial nerves endings. Plexin-A4 and Neuropilin-1 mutants, on the other hand, show an increase in the number of divisions of the corneal stromal nerve trunks. In adult, Plexin-A4 mutants regain a classical organization of innervation whereas Neuropilin-1 mutants retain the disorganization of corneal innervation. Following a lesion, corneal innervation is able to regenerate, however the axons never regain their initial morphology or complexity. Due to the increased corneal innervation observed in the Neuropilin-1 mutants, we wondered whether the regeneration of innervation after scrapping lesions of the corneal epithelium could be enhanced in Neuropilin-1 loss of function. Our preliminary results support an increase in corneal innervation regeneration in Neuropilin-1 mutants

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

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Kératoplastie transfixiante combinée à une greffe de membrane amniotique au cours du syndrome d’insuffisance en cellules souches limbiques

International audiencePurpose: To describe the outcomes of simultaneous penetrating keratoplasty (PK) and amniotic membrane transplantation (AMT) performed both as a ring-shaped graft and as a temporary patch in eyes with a history of limbal stem cell deficiency (LSCD).Methods: Prospective observational case series including 48 simultaneous PK/AMT procedures (48 patients) in eyes with a history of partial or total LSCD. Patients with total LSCD were first treated with limbal stem cell transplantation. The preoperative indication was graft failure in 58.3% of cases. Most recipients (89.6%) were at high-risk for rejection.Results: The mean graft reepithelialization time was 29.2 ± 30.8 days. Graft reepithelialization was achieved in 30 days in 70.8% of cases. No AMT-related adverse events were observed. The mean time from keratoplasty-to-last visit was 84.5 ± 54.5 months. The 3-year graft survival rate was 62.5%. Recurrence of corneal epithelial defects after graft reepithelialization (47.9%) was associated with lower graft survival (P = 0.004). In eyes with successful grafts at the last visit, the mean LogMAR visual acuity was 1.90 (20/1575) ± 5 lines before keratoplasty and 0.89 (20/155) ± 10 lines at 5 years. A ring of amniotic membrane was visible between the graft stroma and the corneal epithelium on slit-lamp examination and optical coherence tomography in all successful cases.Conclusions: In this series of eyes with a history of LSCD and at high-risk of rejection, simultaneous PK and AMT were associated with satisfactory graft survival and no additional adverse events.Introduction: Notre but est de rapporter les résultats de la kératoplastie transfixiante (KT) combinée à une greffe de membrane amniotique (GMA) en anneau et en patch temporaire au cours du déficit en cellules souches limbiques (DCSL).Matériel et méthodes: Il s’agit d’une série prospective observationnelle incluant 48 chirurgies combinées KT/GMA (48 patients) réalisées dans des yeux ayant des antécédents de DCSL partiel ou total. Les patients ayant un DCSL total ont été traités préalablement par une greffe de cellules souches limbiques. L’indication de la greffe était un échec de greffe dans 58,3 % des cas. La plupart des receveurs (89,6 %) étaient à haut risque de rejet.Résultats: Le temps moyen de réépithélialisation du greffon était de 29,2 ± 30,8 jours. Le greffon était réépithélialisé au cours du premier mois dans 70,8 % des cas. Aucun effet indésirable lié à la GMA n’a été observé. Le délai moyen entre la greffe et la dernière visite était de 84,5 ± 54,5 mois. Le taux de survie du greffon à 3 ans était de 62,5 %. La récurrence de défects épithéliaux après réépithélialisation du greffon (47,9 %) était associée à une survie du greffon diminuée (p = 0,004). En cas de présence d’un greffon clair lors de la dernière visite, l’acuité visuelle LogMAR moyenne était de 1,90 (0,013) ± 5 lignes avant greffe et 0,89 (0,13) ± 10 lignes à 5 ans. Un anneau de membrane amniotique était visible à la lampe à fente et en tomographie à cohérence optique entre le stroma du greffon et l’épithélium cornéen dans tous les cas de succès de la greffe.Conclusions: Dans cette série de yeux à haut risque de rejet ayant un DCSL, la chirurgie combine KT/GMA a permis une survie du greffon satisfaisante sans créer d’effet indésirable supplémentaire

Anterior chamber fibrin reaction during Descemet membrane endothelial keratoplasty

International audiencePurpose: To report a series of five cases of intraoperative spontaneous anterior chamber fibrin reaction during Descemet Membrane Endothelial Keratoplasty (DMEK). Methods: We retrospectively collected demographic data and data for ocular disease history for each patient. Donor age, preoperative graft endothelial density, surgical complications on surgery and intraoperative OCT videos, intraoperative management and outcome were assessed. The same standardized DMEK technique was used for all patients. Results: We report intraoperative fibrin formation in five eyes subjected to DMEK. Three pseudophakic eyes underwent single DMEK, and the other two underwent combined DMEK and cataract surgery. In one case, a fibrin filament was observed before graft insertion, with multiplication during surgery, whereas, in the other four cases, strands of fibrin from the iris appeared after graft insertion. This complication resulted in graft failure in four cases (80%). No recipient- or donor-related risk factor was identified. Conclusions and importance: The anterior chamber fibrin reaction is a very uncommon complication of DMEK. The underlying pathophysiological mechanisms remain unknown, but analyses of surgical videos and intraoperative OCT suggest iris involvement. This phenomenon may be induced by chronic subclinical anterior chamber inflammation, due to a blood-aqueous barrier breakdown associated with acute iris trauma during surgery. Thus, intraoperative microtraumatism of the iris should be avoided

Multimodal Imaging Features of Schnyder Corneal Dystrophy

International audienceOBJECTIVE: To describe the multimodal imaging of Schnyder corneal dystrophy.METHODS: Seven eyes of seven patients (5 female and 2 male patients) aged 52 to 92 years were included in this prospective observational study. Diagnosis of SCD was confirmed by histology after keratoplasty. In vivo multimodal imaging consisted of spectral domain-optical coherence tomography with cross sections, en face scans, corneal pachymetry, and epithelial mapping, and in vivo confocal microscopy was recorded. Ex vivo full-field optical coherence tomography scans of two corneal buttons were analyzed. The seven corneal buttons obtained during penetrating or deep anterior lamellar keratoplasty were processed for light microscopy.RESULTS: Slit-lamp examination showed central stromal opacities, arcus lipoides, and midperipheral haze. Corneal crystals were found in 2 out of 7 eyes. SD-OCT cross sections and en face scans showed diffuse hyperreflectivity of the anterior, mid, and posterior stroma with a maximum in the anterior stroma, hyporeflective stromal striae, and epithelial hyperreflectivity. Central corneal thickness ranged from 507 to 635 μm. IVCM revealed hyperreflective deposits in the epithelium and throughout the stroma, thin subepithelial nerves, and needle-shaped and rectangular crystals. Keratocyte nuclei were rare or undetectable. FF-OCT scans confirmed the presence of small round and needle-shaped hyperreflective deposits in the epithelium and stroma. Histology revealed vacuolization of the basal epithelial cells and empty interlamellar stromal vacuoles.CONCLUSION: High-resolution multimodal imaging demonstrates the characteristic features of SCD which involve both the corneal epithelium and stroma, and it provides diagnosis confirmation even in eyes with no visible corneal crystals at slit-lamp examination

Genetic Analysis of the Organization, Development, and Plasticity of Corneal Innervation in Mice

International audienceThe cornea has the densest sensory innervation of the body, originating primarily from neurons in the trigeminal ganglion. The basic principles of cornea nerve patterning have been established many years ago using classic neuroanatomical methods, such as immunocytochemistry and electrophysiology. Our understanding of the morphology and distribution of the sensory nerves in the skin has considerably progressed over the past few years through the generation and analysis of a variety of genetically modified mouse lines. Surprisingly, these lines were not used to study corneal axons. Here, we have screened a collection of transgenic and knockin mice (of both sexes) to select lines allowing the visualization and genetic manipulation of corneal nerves. We identified multiple lines, including some in which different types of corneal axons can be simultaneously observed with fluorescent proteins expressed in a combinatorial manner. We also provide the first description of the morphology and arborization of single corneal axons and identify three main types of branching pattern. We applied this genetic strategy to the analysis of corneal nerve development and plasticity. We provide direct evidence for a progressive reduction of the density of corneal innervation during aging. We also show that the semaphorin receptor neuropilin-1 acts cell-autonomously to control the development of corneal axons and that early axon guidance defects have long-term consequences on corneal innervation

Programmation au laser excimer de l'astigmatisme réfractif ou de l'astigmatisme cornéen antérieur en cas d'astigmatisme oculaire résiduel (ORA)

International audiencePurpose: To determine whether manifest refractive astigmatism (RA) or anterior corneal astigmatism (CA) is the best value for excimer laser programming in cases of ocular residual astigmatism (ORA). Patients and methods: Patients who had undergone LASIK surgery with a disagreement between manifest refractive and corneal cylinder (ocular residual astigmatism ORA) > 0.75 D were included retrospectively in this study. We calculated target induced astigmatism vector (TIA), surgically induced astigmatism vector (SIA), difference vector between the astigmatism correction programmed in the excimer laser and refractive astigmatism (DVRA), difference vector between the astigmatism correction programmed in the excimer laser and corneal astigmatism (DVCA) and difference vector between TIA and SIA (DV), by the Alpins method. Vectorial differences between DV and DVRA, and between DV and DVCA, were then calculated to determine whether RA or CA was closest to the ideal cylinder for laser programming. Results: Of a total of 104 eyes undergoing LASIK, 22 eyes of 12 patients (21.1%) had an ORA > 0.75 D and were included. Mean ORA was 0.9 ± 0.2 D and mean postoperative subjective cylinder was 0.45 D. The DV-DVRA difference vector was 0.57 ± 0.2 D, and the DV-DVCA difference vector was 0.86 ± 0.4 D (P = 0.02). RA was closer than CA to the ideal astigmatism correction. Conclusion: In cases of discrepancy between manifest astigmatism and corneal astigmatism, correction of manifest refractive astigmatism seems to give a better refractive result