Reproductibilité des injections intravitréennes d'acétonide de triamcinolone dans le traitement de l'oedème maculaire chronique du patient diabétique

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Efficacy of three intravitreal injections of bevacizumab in the treatment of exudative age-related macular degeneration

Publication originale : Etude préliminaire sur l’efficacité de 3 injections intravitréennes de bévacizumab dans le traitement de la dégénérescence maculaire liée à l’âge exsudativeabsen

Outcome of exudative aged-related macular degeneration (ARMD) after 3 intravitreal injections of bevacizumab

Purpose: To evaluate the efficacy of intravitreal injections of bevacizumab in exudative ARMD. Methods: Retrospective study including naive patients suffering from exudative ARMD whatever the type of neovascularisation. All the participants were treated with three monthly 1.25 mg intravitreal injections of bevacizumab.The primary objective was far and near visual acuity (VA) 1, 3 and 6 months after the third injection. The secondary objective was the residual activity of neovascularisation assessed with fluorescein and ICG angiography and retinal thickness evaluated with OCT3. Results 71 eyes of 66 patients were included. Neovascularisation was occult, visible or combined in 65%, 20% and 15% of the cases, respectively. A statistically significant improvement between pre and post‐injection VA (LogMAR) was observed one month after the third injection, 0.88±0.57 and 0.77±0.60, respectively, p=0.001). An active neovascularisation was still present at that time in 57.7% of the eyes and 34% at 6 months needing further bevacizumab injections (3.85±0.96 per eye). VA was similar at 1, 3 and 6 months (F71,2=1,54 ; p=0,46). A complication occurred in 3 eyes. Conclusion: Three bevacizumab intravitreal injections led to a significant VA improvement. However, more than half of the eyes had an active neovascularisation after these 3 injections

Activation of a caspase-3-independent mode of cell death associated with lysosomal destabilization in cultured human retinal pigment epithelial cells (ARPE-19) exposed to 7beta-hydroxycholesterol

International audiencePurpose: To characterize the possible cytotoxic effects of oxysterols (7-hydroxycholesterol (7-OH), 25-hydroxycholesterol (25-OH)) in human retinal pigment epithelial cells (ARPE-19) and to detail the relationships between some of these effects. Methods: ARPE-19 cells were treated with 7-OH and 25-OH. Cell viability was measured with the MTT assay. Membrane permeability, mitochondrial potential, and lysosomal integrity were measured by flow cytometry with propidium iodide, DiOC6(3), and acridine orange, respectively. Cell death was characterized by staining with Hoechst 33342, transmission electron microscopy, and analysis of the DNA fragmentation pattern. Caspase activity was examined with fluorochrome-labeled inhibitors of caspases (FLICA) and Western blotting. Immunofluorescence staining was used to visualize the cellular distribution of cytochrome c (Cyt-c) and apoptosis-inducing factor (AIF). The effect of the cathepsin inhibitor (z-FA-fmk) on oxysterol-induced cell death was evaluated. Results: Cell viability of ARPE-19 cells was decreased with 7-OH, whereas 25-OH had no cytotoxic effects. Loss of mitochondrial potential and lysosomal destabilization was associated with 7-OH-induced cell death, few morphologically apoptotic cells were identified, and no internucleosomal DNA fragmentation was found. Slight caspase activation was detected with FLICA, and no caspase-3 activation was revealed. A pronounced relocalization of Cyt-c and AIF was observed. Noteworthy, z-FA-fmk was able to prevent cell death. Conclusion: 7-OH induced a caspase-3-independent mode of cell death associated with lysosomal destabilization, which could play a key role in the signaling pathways leading to cell death, as shown by the ability of z-FA-fmk to counteract the cytotoxic effects of 7-OH

Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs

International audienceAim To investigate the ocular surface inflammatory response to chronic topical treatments in patients with glaucoma by measuring the cytokine level in tears using multiplex bead analysis. Methods Tear samples were collected from 21 patients with glaucoma and 12 healthy volunteers. Tears were analysed for the presence of 17 cytokines: interleukin (IL)1β, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, granulocyte‐colony stimulating factor, granulocyte‐macrophage stimulating factor, interferon (INF)γ, monocyte chemotactic protein (MCP)1, macrophage inflammatory protein 1β and tumour necrosis factor (TNF)α. The cytokines in each sample of tears were measured using multiplex bead analysis with microspheres as solid support for immunoassays. Results In the tears of treated patients, proinflammatory cytokines (IL1β, IL6, IL12, TNFα) were significantly increased compared with controls. T helper (Th)1 (INFγ, IL2) and Th2 (IL5, IL10, IL4) type cytokines were also significantly higher (p<0.05); however, the most marked increase was observed with Th1 cytokines. The expression of chemokine IL8 and MCP1 was also increased in the treated group. Conclusion This study shows that pro‐inflammatory cytokine secretion by conjunctival cells is increased in response to topical treatments for glaucoma. The characterisation of cytokines in tears was previously limited by the small volume attainable, a limitation that has been overcome by multiplex analysis

Assessment of the toxicity of cholesterol oxides on retinal pigment epithelial cultured cells

International audiencePurpose: Among the retinal lipid deposits found in AMD (age related macular degeneration), esterified and unesterified cholesterol have been identified. Cholesterol that accumulates in Bruch's membrane could be oxidized and lead to cholesterol oxides known as oxysterols. These compounds have cytotoxic activities on many vascular cell types, and we conducted this study to evaluate the cytotoxics effects of oxysterols on retinal pigment epithelial (RPE) cells. Methods: Human RPE cells (ARPE–19) were cultured and treated by 7–ketocholesterol (7–keto), 7–betahydroxycholesterol (7–beta) and 25–hydroxycholesterol (25–OH). ARPE–19 cells viability was determined with MTT analysis after incubation with the different oxysterols. To specify the mechanisms toxicity, flow cytometry analysis was performed with propidium iodide that measure membrane permeability, acridine orange was used to evaluate lysosomal degradation and DiOC6(3) to assess mitochondrial transmembrane potential. Apoptosis cellular death characteristics were harvested with Hoechst 33342 nuclear staining, DNA gel electrophoresis and measurement of caspases activity by Fluorochrome–Labeled Inhibitors of Caspases (FLICA). Results : 7–beta and 7–keto had cytotoxics effects on ARPE–19 cells. MTT analysis showed a decrease of cellular viability and propidium iodide analysis revealed an increase in membrane permeability. 25–hydroxy had no toxics effects on ARPE–19 cells. Nuclear morphology of cells treated with oxysterols was not typical of an apoptosis nuclear morphology, there was no DNA internucleosomal fragmentation and no activation of caspases was identified by FLICA analysis. Conclusions: 7–keto and 7–beta induce cellular death without typical characteristics of apoptosis. However it seems that mitochondria and lysosoma play a role in the ARPE–19 death after exposure to 7–keto and 7–beta. The ARPE–19 death is probably mediated by an alternative independent caspases pathway

Analogies entre le processus athéromateux et dégénérescence maculaire liée à l'âge : roles présumés des oxystérols

National audienceThe pathogenesis of age-related macular degeneration (ARMD) is not clearly understood. Like other age-related diseases, it is associated with abnormal deposits called drusen. These drusens are localized in Bruch's membrane. Recent investigations have shown a link between drusen formation and inflammatory and immunologic reactions. The involvement of oxidative stress is supported by available data as an important contributing factor in the developement of ARMD. The data regarding the nature and the source of the deposits suggest that ARMD may share similar pathways with atherosclerosis. The role of oxydized products of cholesterol, the oxysterols, in the pathogenesis of atherosclerosis is well known. As cholesterol is a constituent of drusens, oxysterols could be involved in retinal pigment epithelium and photoreceptor lesions occurring in ARMD owing to their cytotoxic, pro-inflammatory, and pro-oxydant properties.Les mécanismes physiopathologiques de la dégénérescence maculaire liée à l’âge (DMLA) sont encore peu connus. Comme d’autres pathologies du vieillissement telles que la maladie d’Alzheimer ou l’athérosclérose, la DMLA est associée à l’apparition de dépôts macromoléculaires anormaux appelés drusen. Ces derniers sont localisés au niveau de la membrane de Bruch. De récentes investigations sur la nature de ces dépôts, leurs relations avec les réactions inflammatoires et immunitaires ainsi que sur le rôle important du stress oxydatif ont permis d’élargir les hypothèses sur les mécanismes physiopathologiques conduisant aux lésions de DMLA. De nombreuses analogies avec les mécanismes impliqués dans la genèse des lésions d’athérosclérose suggèrent des similitudes physiopathologiques entre ces deux maladies. Le rôle pro-athérogène du cholestérol et de ses dérivés oxydés, les oxystérols, a été largement démontré dans les processus athéromateux. Il semblerait que ces composés interviennent également dans la genèse de la DMLA entraînant des activités cytotoxiques, pro-oxydantes et proinflammatoires

Incidence of retinal detachment after macular surgery: a retrospective study of 634 cases

Aims To evaluate the rate of retinal detachment after macular surgery. Methods A retrospective non‐randomised study of 634 macular surgery procedures was undertaken in two academic centres. Idiopathic macular hole (IMH) surgery (n = 272) and epiretinal membrane (ERM) surgery (n = 362) were performed between 2000 and 2003. We noted the anatomical and functional results of these procedures and we studied serious complications excluding cataract. Results Minimum follow up was 1 year. No retinal detachment (RD) occurred in patients presenting with an intraoperative or preoperative successfully treated retinal break (RB). The rate of RD occurring after IMH surgery was higher than after the ERM surgical procedure (6.6% vs 2.5%, p = 0.02). The rate of RD was higher in patients presenting with stage 2 and 3 IMH than with stage 4 IMH. However, lens status as well as preoperatively treated RD did not influence the rate of RD after macular surgery. Conclusion Retinal detachment remains the most common serious complication of macular surgery. Surgical detachment of the posterior vitreous face and associated peripheral retina anomaly seem to increase the rate of this complication. Careful examination of the peripheral retina is a key issue in preventing retinal detachment occurring after macular surgery

research on adaptive sketch user interface for virtual education application

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042 Effets de colorants intravitréens sur l’électrorétinogramme chez le rat

Communication orale lors du 113e congrès de la Société Française d'Ophtalmologie.International audienc