Distinctive Mechanisms and Patterns of Exudative Versus Tractional Intraretinal Cystoid Spaces as Seen With Multimodal Imaging.

PurposeTo determine clear-cut distinctions between tractional and exudative intraretinal cystoid spaces subtypes.DesignRetrospective, multicenter, observational case series.MethodsA cohort of patients diagnosed with intraretinal cystoid spaces and imaged with optical coherence tomography (OCT), fluorescein angiography (FA), blue fundus autofluorescence (BFAF), en face OCT, and OCT angiography (OCT-A) was included in the study. All images were qualitatively and quantitatively evaluated.ResultsIn this study were included 72 eyes of 69 patients. Exudative intraretinal cystoid spaces (36/72 eyes, 50%) displayed a "petaloid" morphology as seen with en face OCT, FA, and BFAF. Tractional intraretinal cystoid spaces (24/72 eyes, 33.3%), displayed a radial "spoke-wheel" en face OCT pattern. There was no leakage with FA and BFAF did not reveal specific patterns. Eyes with full-thickness macular hole (FTMH, 12/72 eyes, 16.7%) displayed a "sunflower" en face OCT appearance. FTMH showed OCT, OCT-A, and BFAF features of both exudative and tractional cystoid spaces, but without any FA leakage. Inner nuclear layer (INL) thickness was significantly lower in tractional cystoid spaces (P < .001). There were a greater number of INL cystoid spaces in both the exudative and FTMH subgroups (P = .001). The surface area of INL cystoid spaces was significantly lower in the tractional subgroup (P < .001). There was a significant reduction of the microvascular density in eyes with exudative vs tractional (P = .002) and FTMH (P < .001) subgroups.ConclusionsExudative and tractional intraretinal cystoid spaces displayed characteristic multimodal imaging features and they may represent 2 different pathologic conditions with equally different clinical implications

Causative Pathogens of Endophthalmitis after Intravitreal Anti-VEGF Injection: An International Multicenter Study

Purpose: The main objective of this study was to investigate the microbiological spectrum of endophthalmitis after anti- VEGF injections and to compare streptococcal with nonstreptococcus- associated cases with regard to baseline characteristics and injection procedure. Methods: Retrospective,international multicenter study of patients with culture-positive endophthalmitis after intravitreal anti-VEGF injection at 17 different retina referral centers. Results: Eighty-three cases with 87 identified pathogens were included. Coagulasenegative staphylococci (59%) and viridans streptococci (15%) were the most frequent pathogens found. The use of postoperative antibiotics and performance of injections in an operating room setting significantly reduced the rate of streptococcus-induced endophthalmitis cases (p = 0.01 for both). Conclusion: We found a statistically significant lower rate of postinjectional local antibiotic therapy and operating room-based procedures among the streptococcus-induced cases compared to cases caused by other organisms

Effet de l’exposition aux lipides sur l’activation des cellules gliales rétiniennes

Diabetic retinopathy (DR) remains the first cause of visual loss in the age-working population in industrialized countries, and current treatments of the disease are not fully satisfying. Growing evidences indicate that Müller glia cells (MGCs) activation is involved in DR formation and may occur early, even before any vascular changes. Glucose may not be the only factor leading to inflammatory and vascular changes in DR, and recent studies demonstrated the role of dyslipidemia and fatty acids in this disease. We aimed to investigate MGCs inflammatory and angiogenic response to high glucose and high lipid exposure. In this work, we described for the first time the production of Müller cells from reprogrammed induced pluripotent stem iPS (hiMGCs) from different origins, and assayed their response to DR-relevant stress to evaluate their potential use in disease modeling approaches. Using a transcriptomic approach, we showed that unstimulated hiMGCs express 18 key MGCs proteins at similar levels to post-mortem human retina. Similar to primary MGCs, hiMGCs poorly respond to glucose but respond to high lipid exposure by up-regulating their inflammatory and angiogenesis reactions. Finally, we showed that PA stimulated hiMGCs secrete angiogenic factors related to DR such as VEGF, IL-8, IL-1ß and ANGPTL4 and have a pro-angiogenic activity ex-vivo. Taken together, these hiMGCs represent an extremely valuable tool to better understand mechanisms of complex diseases and for the development of new therapeutics. In particular, hiMGCs can be generated from donors and easily expanded to be used in high-throughput drug screens.La rétinopathie diabétique (RD) reste la première cause de cécité dans la population active dans les pays industrialisés et les traitements actuels ne sont pas totalement satisfaisants. De nombreuses études ont démontré l’implication précoce de l’activation des cellules gliales de Müller (CGMs) dans la survenue de la RD, même avant l’apparition des lésions vasculaires. Par ailleurs, le glucose ne serait pas le seul facteur impliqué dans ces modifications vasculaires et inflammatoires, et des études récentes ont montré le rôle de la dyslipidémie et des acides gras dans la RD. L’objectif de ce travail était d’évaluer la réaction inflammatoire et angiogénique des CGMs en réponse à l’hyperglycémie et l’hyperlipidémie. Dans ce travail, nous avons tout d’abord décrit la première production de CGMs à partir de cellules souches pluripotentes de différentes origines (hiMGCs), puis évaluer leur réponse aux différents stimuli de la RD. L’étude de la transcriptomique a montré que les hiMGCs exprimaient 18 protéines clé des CGMs. Tout comme les CGMs primaires, les hiMGCs répondent peu à l’hyperglycémie mais sont très activées par l’exposition aux acides gras, notamment le palmitate. Enfin, nous avons montré que le palmitate stimulait la sécrétion par les hiMGCs de facteurs pro-angiogéniques, tels que le VEGF, l’IL-8, l’IL1 ß et ANGPTL4 et que les hiMGCs exposées au palmitate exerçaient une activité pro-angiogénique ex-vivo. Ainsi, ces hiMGCs, qui peuvent être générées à partir de donneurs sains et facilement multipliées représentent un outil fiable pour mieux comprendre les mécanismes complexes impliqués dans la RD et pour le développement de nouvelles thérapeutiques

Hémophilie B (des thérapeutiques actuelles aux thérapeutiques de demain)

PARIS-BIUP (751062107) / SudocSudocFranceF

Résultats de la vitrectomie dans la rétinopathie diabétique floride après traitement anti-VEGF (Vascular Endothelial Growth Factor)

La rétinopathie diabétique floride (RDF) est une cause majeure de cécité chez le jeune diabétique de type 1. A ce jour, aucune série n'a étudié spécifiquement le bénéfice des anti- VEGF dans la chirurgie de la RDF. L'objectif principal de cette étude est de rapporter les résultats à long terme de la vitrectomie dans un groupe de patients diabétiques de type 1 atteints de RDF et traités par une injection d'anti-VEGF en pré-opératoire (Groupe A). L'objectif secondaire est de comparer ces résultats à ceux d'une série antérieure de RDF opérés sans anti-VEGF (Groupe O). Notre étude est une étude rétrospective de données ophtalmologiques et systémiques de patients opérés de RDF au Centre Hospitalier Universitaire de Lariboisière entre 1991 et 2002 (groupe O) et entre 2006 et 2011 (Groupe A). Les indications chirurgicales retenues étaient: le décollement de rétine tractionnel atteignant ou menaçant la macula, la prolifération fibrovasculaire d'extension rapide malgré la pan-photocoagulation au laser et l'hémorragie intra- vitréenne persistante. Les patients du groupe A ont tous reçu une injection intra-vitréenne de Bevacizumab en pré- opératoire, une semaine avant la vitrectomie (dans 68% des cas) ou en per-opératoire (32% des cas). Les résultats de notre étude montrent qu'une amélioration significative de l'acuité visuelle est obtenue en post-opératoire: 67% des yeux ont un gain d'acuité visuelle de plus de 10 lettres dans le groupe A. Un succès anatomique, défini par une rétine à plat sans silicone, est obtenu chez 82% des patients (groupe A) avec un nombre moyen de 1,82 chirurgies par œil. La comparaison de ces résultats (groupe A) à une série antérieure opérée sans anti-VEGF (Groupe O) et présentant les mêmes caractéristiques démographiques et oculaires, soulignent les bénéfices des anti-VEGF comme traitement adjuvant à la vitrectomie dans la RDF. Pour une même acnité visuelle pré-opératoire moyenne, le gain d'acuité visuelle est plus élevé dans le groupe A : +1,1 LogMAR (Snellen: 20/250) et +0,8 logMAR (Snellen : 20/125) pour les groupes O et A respectivement (P = 0.03). Le nombre moyen d'interventions chirurgicales est également abaissé dans le groupe A par rapport au groupe 0 (p = 0.06). De plus, la procédure chirurgicale paraît facilitée par l'injection pré-opératoire d'anti-VEGF. Le nombre de déchirures iatrogènes est en effet réduit de façon significative dans le groupe A (p<0.01) et le recours à la rétinectomie a été moins fréquent dans le groupe A par rapport au groupe O (p = 0.03). Enfin, le taux de succès anatomique était significativement plus élevé dans le groupe A (p = 0.054) et le risque de récurrence de décollement de rétine abaissé par rapport au groupe O. En conclusion, cette étude rapporte les effets bénéfiques du traitement par anti-VEGF lors de la vitrectomie, avec une amélioration des résultats anatomiques et fonctionnels, dans cette forme sévère de rétinopathie diabétique dont le pronostic reste sombre. Des études prospectives randomisées sont nécessaires pour confirmer la place de ce traitement adjuvant dans la chirurgie de la RDF.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Nitrogen autumnal remobilization in poplar : roles of arginine and cationic amino acid transporters

International audienc

Comparing microscope light-associated glare and comfort between heads-up 3D digital and conventional microscopes in cataract surgery: a randomised, multicentre, single-blind, controlled trial

Objective To compare subjective levels of comfort and visual experiences related to microscope light in patients undergoing their first cataract surgery with topical anaesthesia using a digital microscope (the NGENUITY three-dimensional (3D) visualisation system) or a conventional microscope.Methods and analysis A prospective, randomised, single-blinded, parallel-group, multicentre, interventional study. Patients (n=128) were randomly assigned to one of two treatment groups: the experimental group (n=63) had surgery using the digital microscope and the control group (n=65) had surgery with a conventional microscope. The primary outcome was patients’ subjective experience of glare from the microscope light during surgery on a numerical scale from 0 to 10. Key secondary outcomes were patients’ subjective levels of comfort and visual experiences related to the microscope light.Results The experimental group reported significantly lower levels of glare; median levels were 1.0 (0.0–4.0) for the experimental group vs 3.0 (0.0–6.0) for the control group (p=0.027). They also reported higher levels of comfort; median ratings were 8.0 (6.5–10.0) in the experimental group and 7.0 (5.0–9.0) in controls (p=0.026). There were no group differences in ratings of subjective pain or visual disturbances. Median microscope light intensity was lower in the experimental group than controls; 3425.0 (2296.0–4300.0) Lux vs 24 279.0 (16 000.0–26 500.0) Lux (p&lt;0.0001), respectively.Conclusion Compared with conventional microscopes, the NGENUITY 3D visualisation system allows surgeons to operate with lower levels of light exposure, resulting in significantly less glare and improved comfort in patients undergoing cataract surgery.Trial registration number NCT05085314

Reduced vessel density in the superficial and deep plexuses in diabetic retinopathy is associated with structural changes in corresponding retinal layers.

PurposeTo explore the relationships between vessel density (VD) in the retinal vascular plexuses with the thickness and structural changes of their corresponding retinal layers in patients with diabetic retinopathy (DR).MethodsRetrospective analysis of 17 eyes of 17 Type 1 diabetes (T1D) patients with severe non-proliferative or proliferative DR and no current or past macular edema. Seventeen age- and sex-matched healthy subjects were included as controls. Using optical coherence tomography (OCT) and OCT-angiography (OCTA), VD was measured in the superficial vascular plexus (SVP) and deep vascular complex (DVC) that includes the intermediate (ICP) and deep capillary plexuses (DCP), and compared to the retinal thickness (RT) of the inner (from the inner limiting membrane to the inner plexiform layer) and intermediate (inner nuclear and outer plexiform layer) retinal layers. The correlation between the inner and intermediate RT and the VD of the corresponding vascular networks (SVP and DVC, respectively) was assessed. All OCT and OCTA examinations were performed using the RTVue XR Avanti (Optovue, Fremont, CA).ResultsThe inner RT and VD in all plexuses were significantly reduced in T1D patients compared to healthy subjects. The capillary drop-out patterns were polygonal and well-defined in the SVP while the ICP and DCP showed a more diffuse capillary rarefaction and a VD that varied in the same proportion. The inner RT significantly correlated with VD in the SVP (r = 0.71 in healthy subjects and r = 0.62 in T1D patients, p ConclusionsIn T1D subjects, OCTA allowed observing different capillary drop-out patterns in the SVP and in the ICP-DCP, with different structural changes in the corresponding retinal layers, suggesting that they should be considered as distinct anatomical and functional entities

Topographic Variations of Choroidal Thickness in Healthy Eyes on Swept-Source Optical Coherence Tomography

International audiencePURPOSE: To assess topographic variations of choroidal thickness (CT) in the fovea and beyond in healthy eyes.METHODS: This cross-sectional study included healthy subjects ≤ 55 years of age with axial lengths (22-26 mm) and refractive error margins (-4D, +4D) in normal ranges. Images were acquired using swept-source optical coherence tomography angiography (OCT-A). Corneal thickness (CT) maps from 12 × 12-mm radial scans and 9 × 9-mm OCT-A B-scans were analyzed.RESULTS: The study included 64 eyes of 33 subjects (mean age, 37 years). Mean CT was >300 µm in all locations except the nasal outer macula. The subfoveal CT was >395 µm in 30% of cases; in 38.7% of cases, >50% of the CT map was thicker than 395 µm. The mean thickest choroidal point was 395.2 µm (range, 164-548 µm), located superior and temporal to the macula in 72.2% of cases and subfoveally in 1.8% of cases. The CT pattern was symmetrical (58%) or asymmetrical (42%) along a horizontal axis correlating with choroidal vein distribution. Half of the asymmetrical patterns were thicker in the inferior quadrants, with an oblique temporal watershed of venous drainage, and the other half were thicker superiorly. The mean vascularity index was ∼75% regardless of the mean CT.CONCLUSIONS: One-third of healthy eyes of patients younger than age 55 had a thick choroid (>395 µm). In these normal eyes, the thickest choroidal point was not subfoveal, CT symmetry above and below the fovea depended on choroidal vein distribution, and choroidal vascularity index was independent from CT. No patients demonstrated fundus autofluorescence abnormalities, and the choriocapillaris remained visible even in thick choroids. These features could be interesting when differentiating normal versus pathological states