Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I/IIa Clinical Trial, Cohorts 1-5.

Purpose: To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4.

Design: Nonrandomized multicenter phase I/IIa clinical trial.

Methods: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment.

[Glaucomatous trabeculum: An inflammatory trabeculopathy? [French translation]].

Glaucoma is an optic neuropathy in which the primary risk factor is increased intraocular pressure (IOP), attributed to increased resistance to trabecular outflow of aqueous humor (AH). This resistance is believed to result from trabecular degeneration secondary to chronic oxidative stress and cellular senescence but may also involve inflammatory mechanisms whose roles are little known. In fact, inflammatory processes play a major role in the pathophysiology of glaucoma to varying degrees, affecting all structures of the eye, including the ocular surface, the anterior and posterior segments, and even the visual pathways of the brain.

Macular edema in Cogan-Reese syndrome.

Purpose: Iridocorneo-endothelial (ICE) syndrome is known as a rare spectrum causing glaucoma, corneal and iris damages. Retinal complications are uncommon.

Observations: We report the case of a middle-aged woman suffering from a Cogan-Reese Syndrome (CRS) with refractory ocular hypertension (OHT) who presented a cystoid macular edema (CME) during follow up.

Persistent epiphora after endonasal ENT surgery: CT dacryography findings.

Objectives: To analyze postoperative CT dacryography features in patients with persistent epiphora after endonasal surgery.

Methods: We conducted a retrospective study of 76 patients with a history of persistent epiphora after endonasal ENT surgery who underwent CT dacryography between January 2014 and February 2020. Volume acquisition of sub-millimeter sections allowed 2D and 3D reconstructions with virtual endoscopy of the nasosinusal cavities and the lacrimal canal.

[Dupilumab-related blepharoconjunctivitis: Recommendations of the CEDRE group. Atopic dermatitis, conjunctivitis and dupilumab: Which management approach?].

Dupilumab is a recombinant monoclonal IgG4 type antibody which inhibits IL4 and IL13 signaling. It is indicated in moderate to severe atopic dermatitis (AD) in adults and adolescents over 12 years of age. Its side effects include conjunctivitis and blepharoconjunctivitis, affecting between 4.

Proteomic Analysis of Tears and Conjunctival Cells Collected with Schirmer Strips Using timsTOF Pro: Preanalytical Considerations.

This study aimed to investigate the human proteome profile of samples collected from whole (W) Schirmer strips (ScS) and their two parts-the bulb (B) and the rest of the strip (R)-with a comprehensive proteomic approach using a trapped ion mobility mass spectrometer, the timsTOF Pro. Eight ScS were collected from two healthy subjects at four different visits to be separated into three batches, i.e.

Vision Restoration by Optogenetic Therapy and Developments Toward Sonogenetic Therapy.

After revolutionizing neuroscience, optogenetic therapy has entered successfully in clinical trials for restoring vision to blind people with degenerative eye diseases, such as retinitis pigmentosa. These clinical trials still have to evaluate the visual acuity achieved by patients and to determine if it reaches its theoretical limit extrapolated from ex vivo experiments. Different strategies are developed in parallel to reduce required light levels and improve information processing by targeting various cell types.

[Ocular syphilis, the rise of a forgotten disease: Retrospective study of 18 cases diagnosed at Amiens University Hospital].

Objectives: A disturbing resurgence of syphilis has been observed in the past few years. Ocular involvement of syphilis is infrequent. The goal of our study was to analyze the demographic data and clinical features and to analyze visual outcomes in cases of ocular syphilis at Amiens UH between January 1, 2015 and December 31, 2019.

The trabecular meshwork in glaucoma: An inflammatory trabeculopathy?

Glaucoma is an optic neuropathy in which the primary risk factor is increased intraocular pressure (IOP), attributed to increased resistance to trabecular outflow of aqueous humor (AH). This resistance is believed to result from trabecular degeneration secondary to chronic oxidative stress and cellular senescence but may also involve inflammatory mechanisms whose roles are little known. In fact, inflammatory processes play a major role in the pathophysiology of glaucoma to varying degrees, affecting all structures of the eye, including the ocular surface, the anterior and posterior segments, and even the visual pathways of the brain.

Corneal and Epithelial Thickness Mapping: Comparison of Swept-Source- and Spectral-Domain-Optical Coherence Tomography.

Objective: To compare the results and repeatability of the corneal thickness (CT) and epithelial thickness (ET) maps provided by Swept-Source-Optical Coherence Tomography with those of Spectral-Domain-OCT in normal eyes.

Methods: 30 normal eyes of 30 patients were assessed by 3 trained operators with SS-OCT and SD-OCT.

Results: The central and minimum ET obtained with both devices were correlated: central ET,  = 0.

An overview of current alternative models in the context of ocular surface toxicity.

The 21st century has seen a steadily increasing social awareness of animal suffering, with increased attention to ethical considerations. Developing new integrated approaches to testing and assessment (IATA) strategies is an Organisation for Economic Co-operation and Development (OECD) goal to reduce animal testing. Currently, there is a lack of alternative models to test for ocular surface toxicity (aside from irritation) in lieu of the Draize eye irritation test (OECD guideline No.

Comparison of Two Experimental Mouse Dry Eye Models through Inflammatory Gene Set Enrichment Analysis Based on a Multiplexed Transcriptomic Approach.

The goal of this study was to explore the specific signaling pathways related to inflammation in two experimental mouse dry eye (EDE) models. Female C57BL/6 mice housed for 10 days in a controlled desiccative environment were either treated with scopolamine (EDE-1; = 18) or subjected to extraorbital lacrimal gland excision bilaterally (EDE-2; = 10). Non-induced mice ( = 20) served as healthy controls.

Characteristics of Retinitis Pigmentosa Associated with and Comparison with in Patients from a Multicentric Usher Syndrome Study Treatrush.

In contrast to , variants in are a minor cause of Usher syndrome type 2, and the associated phenotype is less known. The purpose of the study was to characterize the retinal phenotype of 18 patients (9 male, 9 female; median age 52 years) and compare it with that of 204 patients (111 male, 93 female; median age 43 years) in terms of nyctalopia onset, best corrected visual acuity (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) features. There was no statistical difference in the median age at onset (30 and 18 years; Mann-Whitney U test, = 0.

Retinal blood flow reversal quantitatively monitored in out-of-plane vessels with laser Doppler holography.

Laser Doppler holography is a planar blood flow imaging technique recently introduced in ophthalmology to image human retinal and choroidal blood flow non-invasively. Here we present a digital method based on the Doppler spectrum asymmetry that reveals the local direction of blood flow with respect to the optical axis in out-of-plane vessels. This directional information is overlaid on standard grayscale blood flow images to depict flow moving towards the camera in red and flow moving away from the camera in blue, as in ultrasound color Doppler imaging.

Laser Doppler holography of the anterior segment for blood flow imaging, eye tracking, and transparency assessment.

Laser Doppler holography (LDH) is a full-field blood flow imaging technique able to reveal human retinal and choroidal blood flow with high temporal resolution. We here report on using LDH in the anterior segment of the eye without making changes to the instrument. Blood flow in the bulbar conjunctiva and episclera as well as in corneal neovascularization can be effectively imaged.

Cerebellar Transcranial Direct Current Stimulation Reconfigures Brain Networks Involved in Motor Execution and Mental Imagery.

Transcranial direct current stimulation (tDCS) is growingly applied to the cerebellum to modulate the activity of cerebellar circuitry, affecting both motor and cognitive performances in a polarity-specific manner. The remote effects of tDCS are mediated in particular via the dentato-thalamo-cortical pathway. We showed recently that tDCS of the cerebellum exerts dynamic effects on resting state networks.

Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study.

Background: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials.

Methods: In RESCUE and REVERSE, 76 subjects with LHON because of the m.

Substantial restoration of night vision in adult mice with congenital stationary night blindness.

Complete congenital stationary night blindness (cCSNB) due to mutations in , , , , or leucine-rich repeat immunoglobulin-like transmembrane domain 3 () is an incurable inherited retinal disorder characterized by an ON-bipolar cell (ON-BC) defect. Since the disease is non-degenerative and stable, treatment could theoretically be administrated at any time in life, making it a promising target for gene therapy. Until now, adeno-associated virus (AAV)-mediated therapies lead to significant functional improvements only in newborn cCSNB mice.

AOP and IATA applied to ocular surface toxicity.

Until now, the Draize test on rabbits has been the only test performed to anticipate ocular toxicity of pharmaceutical compounds, mainly irritation. The OECD is urging the scientific community to develop and validate alternative methods to reduce the need for animal testing. Since the models and tests used cannot reflect the entire biologic response, it is necessary to combine them into integrated approaches to testing and assessment (IATA) to obtain robust data.