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Summary Purpose Descemet membrane endothelial keratoplasty (DMEK) combined with cataract extraction and intraocular lens insertion (new triple procedure) limits postoperative refractive errors. The objective of this study was to assess refractive accuracy after DMEK combined with cataract extraction and intraocular lens implantation. Setting Four university hospitals (Rouen, Paris, Reims, Grenoble). Design This retrospective multicenter study included patients with symptomatic corneal endothelial decompensation and cataract. Methods The primary outcome was the difference between the target spherical equivalent and postoperative refraction at months 2 and 6. Secondary outcomes were visual acuity, keratometry, pachymetry and endothelial cell density. Results A total of 130 eyes of 111 patients (mean age 66.2 years) were included (94% with Fuchs’ endothelial dystrophy). For a mean refractive target set at −0.50 (±0.57) D, the mean (95% CI) refractive error was hyperopia of +0.49 (0.314; 0.664) D at 2 months and +0.46 (0.299; 0.619) D at 6 months. Best corrected distance visual acuity was improved in all patients: from 0.49 (±0.3) logMAR to 0.14 (±0.14) logMAR at 2 months and 0.05 (±0.1) logMAR at 6 months. Mean corneal thickness decreased from 621.6 (±37.6) μm to 515.2 (±42.6) μm at 2 months and 539.0 (±39.0) μm at 6 months. Conclusions Good refractive accuracy was obtained after the new triple procedure with DMEK. Hyperopic shift is common after triple procedures, and its persistence should be evaluated in future studies in order to anticipate a change in its value to optimize intraocular lens power calculation.

Resume Introduction Entre 2010 et 2018, le numerus clausus des internes d’ophtalmologie a augmente de pres de 50 % (106 en 2010 vs 150 en 2018). Pour faire face a ce volume croissant d’etudiants en 3e cycle, le service d’ophtalmologie du CHU de Reims a mis en place des mai 2015 des agrements avec l’ARS permettant a certains ophtalmologistes liberaux d’accueillir un interne au sein de leur structure le temps d’un semestre. Nous vous presentons ici le bilan de ces 3 ans et demi d’experience. Materiel et methode Deux questionnaires retrospectifs ont ete realises et completes, l’un adresse a l’encadrant, l’autre a l’interne. Ils permettaient d’evaluer et de standardiser l’appreciation de l’experience de stage des deux points de vue. Les volets suivants ont ete explores : accueil, pratique et progression medicale de l’interne, pratique et progression chirurgicale de l’interne, emploi du temps, relations internes/patients et conclusions respectives. Nous avons egalement demande le nombre d’internes accueilli pour chaque etablissement liberal, ainsi que les points positifs et negatifs du stage pour le maitre de stage comme pour l’interne. Resultats Entre mai 2015 et octobre 2018, 12 internes du CHU de Reims ont realise un stage chez un des six ophtalmologistes liberaux accredites en region Champagne-Ardenne. Les internes accueillis se repartissaient entre leur deuxieme et huitieme semestre d’internat. Sept internes ont realise leur premier ou deuxieme stage d’ophtalmologie chez le praticien liberal. Les questionnaires permettaient de conclure a une experience positive pour le maitre de stage et pour l’interne, en particulier concernant la formation medicale et technique, le temps passe au bloc operatoire ainsi que les procedures chirurgicales realisees. Conclusion Devant l’augmentation du nombre d’internes en ophtalmologie et la limite des capacites de formation des stages hospitaliers, les stages chez les praticiens liberaux impliques dans la pedagogie augmentent les capacites d’accueil mais apportent surtout une formation complementaire au cursus hospitalier conventionnel des internes.

International audience; Today the noxiousness of blue light from natural and particularly artificial (fluorescent tubes, LED panels, visual displays) sources is actively discussed in the context of various ocular diseases. Many of them have an important neurologic component and are associated with ocular pain. This neuropathic signal is provided by nociceptive neurons from trigeminal ganglia. However, the phototoxicity of blue light on trigeminal neurons has not been explored so far. The aim of the present in vitro study was to investigate the cytotoxic impact of various wavebands of visible light (410-630 nm) on primary cell culture of mouse trigeminal neural and glial cells. Three-hour exposure to narrow wavebands of blue light centered at 410, 440 and 480 nm of average 1.1 mW/cm2 irradiance provoked cell death, altered cell morphology and induced oxidative stress and inflammation. These effects were not observed for other tested visible wavebands. We observed that neurons and glial cells processed the light signal in different manner, in terms of resulting superoxide and hydrogen peroxide generation, inflammatory biomarkers expression and phototoxic mitochondrial damage. We analyzed the pathways of photic signal reception, and we proposed that, in trigeminal cells, in addition to widely known mitochondria-mediated light absorption, light could be received by means of non-visual opsins, melanopsin (opn4) and neuropsin (opn5). We also investigated the mechanisms underlying the observed phototoxicity, further suggesting an important role of the endoplasmic reticulum in neuronal transmission of blue-light-toxic message. Taken together, our results give some insight into circuit of tangled pain and photosensitivity frequently observed in patients consulting for these ocular symptoms.

Resume La chirurgie refractive est une discipline en evolution constante. Depuis quelques annees une nouvelle technique est apparue sous la denomination SMILE (Small Incision Lenticule Extraction). Cette technique, realisee exclusivement a l’aide d’un laser femtoseconde permettrait de mieux respecter l’innervation et la biomecanique corneennes. Apres avoir detaille la technique, nous nous interesserons dans un premier temps aux preuves scientifiques de l’efficacite et de la surete de cette procedure ainsi qu’a ses indications actuelles. Dans une seconde partie, seront discutes les avantages du SMILE comparativement aux inconvenients potentiels des techniques conventionnelles, comme les risques de secheresse oculaire ou d’ectasie corneenne inherents au LASIK. Enfin, les limites actuelles du SMILE (indications, retraitement) seront envisagees puis discutees au regard des perspectives de developpement de cette procedure d’avenir.

Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g. diabetes). We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial cells and human diploid fibroblasts] in vitro. Elevated copper in senescent MEFs was accompanied by elevated levels of high-affinity copper uptake protein 1 (Ctr1), diminished levels of copper-transporting ATPase 1 (Atp7a) (copper export) and enhanced antioxidant defence reflected by elevated levels of glutathione (GSH), superoxide dismutase 1 (SOD1) and glutaredoxin 1 (Grx1). The levels of intracellular copper were further increased in senescent MEFs cultured in copper supplemented medium and in senescent Mottled Brindled (Mobr) MEFs lacking functional Atp7a. Finally, we demonstrated that the restoration/preservation of autophagic-lysosomal degradation in senescent MEFs following rapamycin treatment correlated with attenuation of copper accumulation in these cells despite a further decrease in Atp7a levels. This study for the first time establishes a link between Atp7a and the autophagic-lysosomal pathway, and a requirement for both to effect efficient copper export. Such a connection between cellular autophagy and copper homeostasis is significant, as both have emerged as important facets of age-associated degenerative disease., Graphical abstract fx1, Highlights • Copper accumulation is a feature of cellular senescence. • Elevated copper in senescent cells is associated with impaired autophagic-lysosomal function. • Restoration/preservation of lysosomal function attenuates copper accumulation. • Both Atp7a and autophagic-lysosomal function are required for copper export.

Refractive surgery is a field in constant evolution. In recent years, a new procedure has appeared under the name SMILE (SMall Incision Lenticule Extraction). This technique, carried out solely with a femtosecond laser, should make it possible to better preserve corneal innervation and biomechanics. After a detailed review of the technique itself, we then focus on the scientific evidence for the safety and efficacy of SMILE and its current indications. Advantages of SMILE will be discussed in comparison to the conventional techniques, particularly concerning dry eye and the risk of corneal ectasia related to LASIK. Lastly, the current limitations of SMILE (indications, retreatment) are discussed, and future applications are considered regarding new improvements in the technique.

Cellular senescence is characterised by the irreversible arrest of proliferation, a pro-inflammatory secretory phenotype and evasion of programmed cell death mechanisms. We report that senescence alters cellular iron acquisition and storage and also impedes iron-mediated cell death pathways. Senescent cells, regardless of stimuli (irradiation, replicative or oncogenic), accumulate vast amounts of intracellular iron (up to 30-fold) with concomitant changes in the levels of iron homeostasis proteins. For instance, ferritin (iron storage) levels provided a robust biomarker of cellular senescence, for associated iron accumulation and for resistance to iron-induced toxicity. Cellular senescence preceded iron accumulation and was not perturbed by sustained iron chelation (deferiprone). Iron accumulation in senescent cells was driven by impaired ferritinophagy, a lysosomal process that promotes ferritin degradation and ferroptosis. Lysosomal dysfunction in senescent cells was confirmed through several markers, including the build-up of microtubule-associated protein light chain 3 (LC3-II) in autophagosomes. Impaired ferritin degradation explains the iron accumulation phenotype of senescent cells, whereby iron is effectively trapped in ferritin creating a perceived cellular deficiency. Accordingly, senescent cells were highly resistant to ferroptosis. Promoting ferritin degradation by using the autophagy activator rapamycin averted the iron accumulation phenotype of senescent cells, preventing the increase of TfR1, ferritin and intracellular iron, but failed to re-sensitize these cells to ferroptosis. Finally, the enrichment of senescent cells in mouse ageing hepatic tissue was found to accompany iron accumulation, an elevation in ferritin and mirrored our observations using cultured senescent cells., Graphical abstract fx1, Highlights • Altered iron homeostasis in senescent cells is driven by impaired ferritinophagy. • Impaired ferritinophagy causes functional cellular iron deficiency. • senescent cells are resistant to iron mediated cell death including ferroptosis.

Resume Objectif Evaluer l’interet de la formule Holladay 2 par rapport aux formules de 3e generation dans le calcul de la puissance d’implant intraoculaire (IOL) avec une longueur axiale (LA) ou une keratometrie moyenne (Km) extremes avant chirurgie de cataracte. Patients et methodes Il s’agit d’etude retrospective realisee de janvier a decembre 2015. Les criteres d’inclusion etaient une LA 26 mm et une Km 46 D, repartissant ainsi les patients en 4 groupes. Les 7 parametres necessaires au calcul selon la formule Holladay 2 ont ete recueillis. Le resultat refractif post-operatoire a ete retranscrit en equivalent spherique pour calculer a posteriori la puissance ideale. L’ecart refractif entre les resultats obtenus avec les differentes formules et cette puissance ideale a ete calculee. Resultats Cent vingt-six yeux operes par deux chirurgiens ont ete inclus. La precision de calcul des differentes formules variait selon les groupes : (i) pour les grandes LA (n = 32), la formule SRK/T etait la plus precise ; (ii) pour les petites LA(n = 34) les formules Hoffer Q et Holladay 2 etaient meilleures ; (iii) pour les cornees cambrees (n = 27) les formules Hoffer Q, Haigis, Holladay 1 et 2 etaient toutes comparables en termes de resultat refractif ; et (iv) pour les cornees plates (n = 33), Holladay 1 et 2 etaient plus precises. Conclusion La formule Holladay 2 ne semble pas superieure aux autres dans cette etude quel que soit le groupe etudie.

Archaeologists have previously proposed several different measures of flaked stone raw material “quality”, but this variable has proven difficult to quantify, and the precise characteristics that improve performance remain unclear. This paper presents the results of controlled experiments that were designed to test projectile points made from stones with varying impact strength. By comparing an independent measure of strength with projectile point experimental data, our research suggests that this variable can be objectively measured, and it is a good predictor of some aspects of projectile tip function. Our results show that highly homogenous fine-grained materials with low impact strength (e.g., obsidian) perform well when penetrating elastic materials such as skin and muscle. These same materials, however, function poorly when penetrating more inelastic materials like rawhide, and they are substantially less durable.

The development of a novel two-step data analysis methodology to uncover signatures of potential cancer biomarkers in matrix assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectra of large serum peptidomes is described. First, raw spectral data are processed using QceAlign, which exploits Bayesian and maximum entropy methods for peak identification and calibration. The raw spectral data are baseline corrected and normalized. Peak identification is based on a Bayesian second derivative of the baseline-corrected and normalized raw data, with peak S/N statistics provided by a maximum entropy smoothing function. A reference MALDI-TOF reference spectrum is created from the data and each spectrum is slid by n data points to the right or left along the x axis of the reference file. At each relative position n, the Shannon entropy of the sum of the two files is computed. Optimal alignment is associated with the shift that produces the minimum Shannon entropy. Second, a genetic algorithm (GA) for pattern recognition analysis is applied to the peak matched data. The pattern recognition GA selects features that optimize the separation of the sample classes in a plot of the two or three largest principal components of the data. Because the largest principal components capture the bulk of the variance in the data, the spectral features chosen by the pattern recognition GA convey information primarily about the differences between classes in the data. In addition, the algorithm focuses on those classes and or samples that are difficult to classify as it trains by boosting the sample and class weights. Samples that consistently classify correctly are not as heavily weighted as those samples that are difficult to classify. The pattern recognition GA integrates aspects of artificial intelligence and evolutionary computations to yield a “smart” one -pass procedure for features selection, classification, and prediction in a single step.

Resume Introduction Le dysfonctionnement des glandes de Meibomius (DGM) est une pathologie frequente en consultation, souvent responsable d’un syndrome sec oculaire. L’examen a la lampe a fente avec expression digitale des glandes de Meibomius au niveau du tarse permet l’examen du contenu meibomien distal et du meat. En revanche, l’epithelium de la glande de Meibomius, l’espace interglandulaire et le contenu en amont ne sont pas examinables. La microscopie confocale in vivo (IVCM) est un examen rapide, non invasif, permettant d’obtenir des images de resolution quasi-cellulaire de la surface oculaire et des paupieres. L’objectif principal de cette etude etait d’etablir une classification des DGM en IVCM. Les objectifs secondaires etaient d’evaluer l’interet de l’analyse en IVCM des glandes de Meibomius et de rechercher une eventuelle association avec le score Ocular Surface Disease Index (OSDI), le score de meibographie infrarouge (IR) et la presence de Demodex. Patients et methodes Quarante-six patients souffrant de secheresse oculaire (OSDI superieur a 13) associee a un DGM ont ete recrutes. Dix sujets sains, sans secheresse oculaire ni blepharite, representaient les cas temoins. Un questionnaire OSDI, un examen clinique, une analyse en IVCM et une meibographie IR de la paupiere inferieure ont ete realises par le meme operateur. Resultats Les examens d’imagerie ont permis de definir un score constitue de trois stades de severite croissante : le stade obstructif sans atteinte du contenant, le stade inflammatoire, comprenant une obstruction et une inflammation de l’espace interglandulaire, et le stade de fibrose des glandes de Meibomius. L’evolution des stades en IVCM etait significativement correlee a l’augmentation du meiboscore en meibographie IR (coefficient de Spearman 0,47, IC95 % [0,22–0,66]). Conclusion L’examen des glandes de Meibomius par IVCM complete l’examen clinique en precisant le stade de la dysfonction et pourrait ainsi ameliorer l’evaluation et la prise en charge des DGM.

Mesenchymal stem cells (MSC) are adult stem cells, first identified in skeletal tissues and then found in the entire body. MSC are able to not only differentiate into specialized cells within skeletal tissue - chondrocytes, osteocytes, adipocytes and fibroblasts - but also secrete a large range of soluble mediators defining their secretome and allowing their interaction with a number of cell protagonists. Thus, in a general sense, MSC are involved in tissue homeostasis through their secretome and are specifically responsible for cell turn-over in skeletal tissues. For a decade and a half, safety and efficiency of MSC has led to the development of many clinical trials in various fields. However, results were often disappointing, probably because of difficulties in methods and evaluation. At a time when the first clinical trials using MSC are emerging in ophthalmology, the goal of this literature review is to gather and put into perspective preclinical and clinical results in order to better predict the future of this innovative therapeutic pathway.

Resume La chirurgie de la cataracte assistee au laser femtoseconde est une innovation technologique majeure. Le laser femtoseconde, lors d’une phase de pretraitement, permet de preparer l’œil du patient a la chirurgie proprement dite en realisant les incisions corneennes, la capsulotomie anterieure et la fragmentation cristallinienne de maniere automatisee. Ainsi, ces etapes sont realisees de facons precise et reproductible, et la prefragmentation cristallinienne diminue la quantite d’ultrasons necessaires en aval. Les inconvenients de cette technologie sont un temps operatoire plus long et un surcout significatif, tant pour la structure de soins que pour le patient. Le schema organisationnel du bloc operatoire, le circuit du patient et le mode de financement de l’acte devront etre repenses pour adapter notre offre de soins a cette procedure. Les benefices apportes en feront certainement un outil d’avenir incontournable, necessitant de repenser la chirurgie de la cataracte, en termes logistiques et economiques.

Purpose To compare small incision lenticule extraction (SMILE) versus LASIK for post-refractive dry eye disease. Design Prospective, comparative, nonrandomized clinical study. Participants Thirty patients scheduled for bilateral myopic SMILE and 30 age-, sex-, and refraction-matched patients scheduled for bilateral myopic LASIK were enrolled and followed for 6 months after the surgery. Methods Complete evaluation of dry eye disease was performed at 1 and 6 months postoperatively, which included vision-related quality of life (Ocular Surface Disease Index [OSDI]), clinical examinations (tear film breakup time [TBUT], Schirmer I test, corneal staining), and tear osmolarity measurements, together with an overall severity score. Function and morphology of the corneal innervation were evaluated by corneal esthesiometry and subbasal nerve imaging using in vivo confocal microscopy (IVCM). Main Outcome Measures Overall analysis of dry eye disease and corneal innervation. Results High incidence of mild to moderate dry eye disease was observed in both groups 1 month postoperatively, which remained significantly higher in the LASIK group than in the SMILE group 6 months after surgery (overall severity score [0–4]: 1.2±1.1 vs. 0.2±0.4, respectively, P P R ² = 0.48, P R ² = 0.50, P R ² = 0.21, P Conclusions The SMILE procedure has a less pronounced impact on the ocular surface and corneal innervation compared with LASIK, further reducing the incidence of dry eye disease and subsequent degradation in quality of life after refractive surgery.

Academic and industrial research has brought new insights into the pathogenesis of glaucoma, aiming at identifying and targeting specific mechanisms to improve our current therapeutic strategy. Retinal neurodegeneration is still the main focus, whether in terms of extrinsic factors such as neurotrophin deprivation, glutamate toxicity, vascular deficiency and neuro-inflammation from glial cells, or in terms of retinal ganglion cell intrinsic sensibility to proapoptotic signals. However, glaucoma is not solely a retinal disease but also involves retinal and trabecular meshwork degeneration, extending into and/or even originating from the brain. The present review summarizes our current knowledge of key mechanisms involved in glaucoma degeneration, focusing on the direction of current research towards the future of glaucoma therapy.

Summary Purpose To describe a new technique of endothelial keratoplasty (EK) that improves the quality of lamellar dissection of donor cornea. Methods We compared four techniques of donor cornea preparation for lamellar dissection on 8 donor corneas: mechanical dissection with a microkeratome, a single femtosecond laser lamellar cut, a double femtosecond laser lamellar cut and combined femtosecond laser lamellar dissection with excimer laser surface photoablation. The quality of the donor cornea interface was assessed and compared using scanning electron microscopy (SEM), and the most satisfactory technique was employed for EK on three patients. The postoperative anatomic results were analyzed with anterior segment spectral-domain optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM). Results The smoothest stromal interface was observed on SEM with the combined use of femtosecond laser dissection and excimer photoablation. The surgical procedures performed with donor cornea prepared by a combination of femtosecond and excimer lasers resulted in clear corneas after 1 month. SD-OCT showed good attachment of the endothelial graft and a hyperreflective interface. On IVCM, subepithelial haze, honeycomb-like activated keratocytes and needle-shaped particles were visible in the recipient corneal stroma as well as numerous hyperreflective particles on the donor–recipient interface. Conclusion A new technique, femtosecond and excimer laser-assisted endothelial keratoplasty (FELEK), which refines the current limitations observed in Descemet-stripping automated endothelial keratoplasty (DSAEK), is described. Femtosecond laser dissection provides a thin and reproducible endothelial graft cut with a high level of safety and accuracy, while excimer photoablation yields a smooth, high-quality interface.