Segmentation of retinal vessels in adaptive optics images for assessment of vasculitis

International audience—In this paper we propose a new method for segmenting retinal vessels in adaptive optics images. This method is particularly dedicated for segmenting vessels with significant morphological alterations due to vasculitis, but it is also accurate for vessels with moderate or without alteration. It relies on a pre-segmentation step which is crucial for the robustness and accuracy of the results. This step is based on a specific morphological processing of isolines of the original image: they constitute of good basis for the segmentation because they are disposed along the wall borders of the vessels. Regularization is then performed using active contour model embedding a parallelism constraint. This novel model allows precise segmenting inner and outer walls of the vessel. In particular it is more accurate in the case of vasculitis than the existing methods. This is the only method that allows quantification. The results and the runtime make it suitable for clinical use

TREATMENT OF MACULAR FOLDS COMPLICATING RETINAL DETACHMENT SURGERY USING AIR FOR RETINAL UNFOLDING

We discuss a modified surgical procedure for the treatment of macular folds complicating retinal reattachment surgery

Perspectives for immunotherapy in noninfectious immune mediated uveitis

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Cytoprotective Effects of Natural Highly Bio-Available Vegetable Derivatives on Human-Derived Retinal Cells

International audienceRetinal pigment epithelial cells are crucial for retina maintenance, making their cytoprotection an excellent way to prevent or slow down retinal degeneration. In addition, oxidative stress, inflammation, apoptosis, neovascularization, and/or autophagy are key pathways involved in degenerative mechanisms. Therefore, here we studied the effects of curcumin, lutein, and/or resveratrol on human retinal pigment epithelial cells (ARPE-19). Cells were incubated with individual or combined agent(s) before induction of (a) H2O2-induced oxidative stress, (b) staurosporin-induced apoptosis, (c) CoCl2-induced hypoxia, or (d) a LED-autophagy perturbator. Metabolic activity, cellular survival, caspase 3/7 activity (casp3/7), cell morphology, VEGF levels, and autophagy process were assessed. H2O2 provoked a reduction in cell survival, whereas curcumin reduced metabolic activity which was not associated with cell death. Cell death induced by H2O2 was significantly reduced after pre-treatment with curcumin and lutein, but not resveratrol. Staurosporin increased caspase-3/7 activity (689%) and decreased cell survival by 32%. Curcumin or lutein protected cells from death induced by staurosporin. Curcumin, lutein, and resveratrol were ineffective on the increase of caspase 3/7 induced by staurosporin. Pre-treatment with curcumin or lutein prevented LED-induced blockage of autophagy flux. Basal-VEGF release was significantly reduced by lutein. Therefore, lutein and curcumin showed beneficial protective effects on human-derived retinal cells against several insults

Safety of Intravitreal Gene Therapy for Treatment of Subjects with Leber Hereditary Optic Neuropathy due to Mutations in the Mitochondrial ND4 Gene: The REVEAL Study

International audienceBackground: Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease whose primary clinical manifestation is bilateral visual loss. Only a single therapy, idebenone, is approved in Europe for use in exceptional circumstances and no therapy is currently approved in the USA. LHON remains a disease with a high unmet medical need.Objective: This is a report of an open-label, single-center, dose-escalation study that evaluated the safety and tolerability of lenadogene nolparvovec in 15 subjects with LHON for up to 5 years following a single intravitreal injection at four dose levels.Methods: Subjects were enrolled sequentially in four cohorts followed by an additional cohort at the dose selected, and safety was assessed by an independent data safety monitoring board (DSMB) prior to any dose escalation.Results: Overall, the treatment was well tolerated during the 5-year follow-up. No serious adverse events were considered related to treatment, no unexpected adverse events occurred, and no grade 3 or 4 Common Terminology Criteria for Adverse Events were reported. Anterior chamber inflammation and vitritis were mostly managed with topical steroids, and ocular inflammation was considered to be dose limiting by the DSMB based on the benefits/risks for the subjects. Analysis of the logarithm of the minimal angle of resolution (LogMAR) visual acuity in both treated and untreated eyes showed clinically relevant and durable improvements compared with baseline. Mean improvements of - 0.44 and - 0.49 LogMAR for treated and untreated eyes, respectively, were noted, with a mean (± standard deviation) final value of LogMAR + 1.96 ± 0.60 and + 1.65 ± 0.34, respectively, at 5 years post-treatment administration. For the six subjects treated with the optimal dose level (9 × 1010 viral genomes [vg]/eye), the mean visual acuity improvement from baseline reached - 0.68 LogMAR for treated eyes and - 0.64 LogMAR for untreated eyes, with a mean final value of LogMAR + 1.77 ± 0.52 and + 1.78 ± 0.34, respectively. While there was a meaningful improvement in visual acuity for REVEAL subjects, the final visual acuity was less favorable than that seen in the two subsequent pivotal phase III studies in which subjects were treated earlier during the course of their disease.Conclusion: Lenadogene nolparvovec was well tolerated with a good safety profile during 5 years of follow-up and may offer meaningful lasting improvements in vision for this LHON population

Cellular and molecular mechanisms of NiONPs toxicity on eel hepatocytes HEPA-E1: An illustration of the impact of Ni release from mining activity in New Caledonia

International audienceAnthropic activities such as open pit mining, amplify the natural erosion of metals contained in the soils, particularly in New Caledonia, leading to atmospheric emission of nickel oxide nanoparticles (NiONPs). These particles are produced during extraction end up in aquatic ecosystems through deposition or leaching in the rivers. Despite alarming freshwater Ni concentrations, only few studies have focused on the cellular and molecular mechanisms of NiONPs toxicity on aquatic organisms and particularly on eels. Those fish are known to be sensitive to metal contamination, especially their liver, which is a key organ for lipid metabolism, detoxification and reproduction. The objective of this study was to assess in vitro the cytotoxic effects of NiONPs on Anguilla japonica hepatocytes, HEPA-E1. HEPA-E1 were exposed to NiONPs (0.5-5 μg/cm2) for 4 or 24 h. Several endpoints were studied: (i) viability, (ii) ROS production, SOD activity and selected anti-oxidant genes expression, (iii) inflammation, (iv) calcium signalling, (v) mitochondrial function and (vi) apoptosis. The results evidenced that NiONPs induce a decrease of cell viability and an increase in oxidative stress with a significant superoxide anion production. An increase of mitochondrial calcium concentration and a decrease of mitochondrial membrane potential were observed, leading to apoptosis. These results underline the potential toxic impact of NiONPs on eels living in mining areas. Therefore, eel exposure to NiONPs can affect their migration and reproduction in New Caledonia

High-Resolution Imaging of Retinal Vasculitis by Flood Illumination Adaptive Optics Ophthalmoscopy: A Follow-up Study

International audiencePurpose: To monitor perivascular sheathing during the course of retinal vasculitis by flood illumination adaptive optics ophthalmoscopy (AOO). Methods: Perivenous sheathing and venous diameters were quantitatively analyzed by semi-automatic segmentation of AOO images in 12 eyes of treatment-naive patients with retinal vasculitis. Results: The width of venous sheathing ranged from 45 to 225 µm (mean 101.0 µm ± 54.3). In 10 cases, the underlying vein showed focal narrowing (mean ± SD 14% ± 10). Focal narrowing of arteries was also present in one eye. At presentation, width of sheathing and vessel diameters were not correlated with fluorescein leakage. During follow-up, 5 eyes showed an increase in vein diameter or resolution of narrowing and in 10 eyes a thinning of vascular sheathing was observed (p= .003). Conclusions: Perivenous sheathing may be quantitatively analyzed and monitored by AOO. AOO may therefore contribute to monitor vascular sheathing during posterior uveitis

OCT Angiography in Noninfectious Uveitis: A Description of Five Cases and Clinical Applications

Background: Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality used to analyze the retinochoroidal vasculature and detect vascular flow. The resulting images can be segmented to view each vascular plexus individually. While fluorescein angiography is still the gold standard for the diagnosis of posterior uveitis, it has limitations, and can be replaced by OCTA in some cases. Methods: This case series describes five patients with posterior noninfectious uveitis and their description by OCTA. Results: Cases included lupus retinopathy (n = 1) for which OCTA showed ischemic maculopathy as areas of flow deficit at the superficial and deep capillary plexus; choroidal granulomas (n = 1) with a non-detectable flow signal in the choroid; active punctate inner choroiditis and multifocal choroiditis (n = 1) with OCTA that showed active inflammatory chorioretinal lesions as non-detectable flow signals in choriocapillaris and choroid; dense type 2 inflammatory secondary neovascularization (n = 1) associated with active choroiditis; and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1) without flow abnormalities at the superficial and deep retinal plexuses but non-detectable flow at the levels of the choriocapillaris and choroid. Conclusions: Ophthalmologists can use OCTA to identify inflammatory changes in retinal and choroidal vasculature, aiding in the diagnosis, management, and monitoring of posterior uveitis