bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravitreal mobility of nanoparticles: how to make a move toward successful ocular gene delivery?
Authors: Remaut K. , Devoldere J. , Peynshaert K. , Martens T. , Engbersen J. , Braeckmans K. , De Smedt S. 
Published: September 2016

SummaryIntravitreal injection is an interesting delivery route for the administration of nanoparticles for treatment of a variety of retinopathies. To reach the retina, nanoparticles need to diffuse through the vitreous and travel across the vitreoretinal interface. We have recently optimized an ex vivo assay that allows to measure the mobility of fluorescent nanoparticles in intact vitreous humour on a single‐particle level. With this model, we optimize surface coating strategies of nanoparticles to assure good vitreal mobility, while maintaining the normal transfection efficiency. Also, we developed a novel ex vivo retinal model that is bovine‐derived and, in contrast to existing models, keeps the vitreous and the vitreoretinal interface intact. This model is used to identify the potential of nanoparticles to reach retinal cell types after intravitreal injection. As Müller cells are the only cell type connecting the vitreal and retinal side of this interface, we specially focus on the role of Müller cells as our gateway to shuttle intravitreally injected particles across the vitreoretinal interface. As nanoparticles, we focus on polymer‐ or lipid based nanoparticles carrying messenger RNA or plasmid DNA as therapeutic molecules.
Looking for a sensitive biomarker for genetically determined neurodegenerative diseases through the window of the eye
Authors: Martinuzzi A. , Vavla M. , Capello G. , Papayannis A. , Petacchi E. , Paparella G. , Privato F. , Prosdocimo G. 
Published: September 2016

SummaryBiomarkers are valuable tools offering quantifiable objective measures for biological processes. In neurodegenerative diseases mitochondria are frequently either primarily or secondarily involved, but the difficulty in directly assessing the target tissue and the frequently slow progression makes the search for reliable, convenient, sensible, specific and objective biomarkers a particularly relevant issue. The visual system is the primary target where mitochondria dysfunction frequently manifests itself. The definition of a typical, objective, quantifiable pattern of neuro‐ophtamological alteration that shows correlation with clinical measures and is sensible to progression may be very important. We had previously identified by advanced neuroimaging and OCT specific changes discriminating patients from controls in f hereditary spastic paraplegia (HSP) and Friedreich's ataxia (FRDA) patients. We now tested these approaches for their ability to provide timely information on disease progression by evaluating longitudinally 21 HSP and 12 FRDA patients.
Current gene therapy trials for inherited retinal disorders
Authors: Leroy B.P. , Maguire A.M. , Russell S.R. , Wellman J. , Yu Z.F. , Chung D.C. , High K.A. , Bennett J. 
Published: September 2016

SummaryPurposeTo discuss the current status of gene therapy for inherited retinal disease.MethodsData from the literature on gene therapy trials for several inherited retinopathies will be combined with those of the Phase 1, Phase 1 follow‐on and Phase 3 trials for RPE65‐related inherited retinal disease at The Children's Hospital of Philadelphia, Philadelphia, PA, USA.ResultsGene therapy is capable of improving or stabilizing visual function. According to some recent reports, there is progression of disease in RPE65‐related IRD trial participants despite successful subretinal delivery of RPE65 using an AAV2 vector. Other data suggest that there may at least be a decrease in the speed of retinal degeneration, if not stabilization.ConclusionsGene therapy for inherited retinal disease using viral vectors has demonstrated safety and improvement or stabilization of visual function in some diseases. Whereas disease progression is noted in some RPE65‐related IRD trial participants, despite successful application of subretinal gene therapy, others may even have either a stable or slower disease course after treatment.
OCT imaging in glaucoma and PEX
Authors: Sapeta S. 
Published: September 2016

SummaryGlaucoma, as one of the leading causes of blindness worldwide, can be characterized by abnormalities in the aqueous outflow system (AOS) structures, including Schlemm's canal, that regulate the IOP in a healthy eye. Furthermore, the accumulation of pseudoexfoliation (PEX) deposits in the anterior chamber can increase the risk of the disease. The imaging of the anterior eye segment and here in particular the limbal area and anterior lens capsule could have a special clinical significance, since there is an evidence that symptomatic PEX is preceded by subclinical ultrastructural changes in the anterior segment including the lens surface.In this course, ultrahigh‐resolution optical coherence tomography for imaging of the anterior eye segment in glaucoma and PEX patients will be introduced. The advantage of the superior resolution as compared to commercially available OCT technology for visualization of AOS structures and PEX deposits on the lens capsule as well as its potential for evaluation of Schlemm's canal diameter will be shown and possible applications of the technology in clinical practice will be discussed.
Effects of a thiol antioxidant in various cataract models
Authors: Ercal N. , Maddirala Y. , Carey J. , Tobwala S. 
Published: September 2016

SummaryCataracts are the most common cause of treatable blindness worldwide, and result from loss of transparency of the lens. It has been demonstrated that oxidative stress plays an important role in cataract etiopathogenesis. Oxidative damage reduces solubility of crystallins, the main structural proteins of the lens, resulting in opacification. Cells have evolved to combat this damage with antioxidant enzymes and low molecular weight antioxidants such as glutathione (GSH). Our primary objective was to evaluate a GSH prodrug for cataract treatment because current surgical options are neither economical nor safe. Recent literature indicates that thiol compounds like N‐acetylcysteine (NAC) may ameliorate the risk for cataracts. Our data indicates that the analog of NAC, N‐acetylcysteine amide (NACA), is more effective than NAC due to its higher bioavailability. Therefore, the present study was performed to determine whether NACA is also effective in sodium selenite and L‐buthionine‐(S,R)‐sulfoxamine (BSO)‐induced cataracts. In both models, NACA significantly decreased lens opacity and improved redox balance. The data suggest that NACA has the potential to significantly improve both patient health and the clinical treatment of cataracts.
Presence of proteinase inhibitor‐9 and granzyme B in healthy and pathological human corneas
Authors: Jirsova K. , Reinstein Merjava S. , Chudickova M. , Holan V. 
Published: September 2016

SummaryAim: To determine whether proteinase inhibitor‐9 (PI‐9) and granzyme B (GrB) are expressed in normal and pathological corneas.Methods: Cryosections and endothelial, epithelial and conjunctival imprints of 12 human cadaverous corneo‐scleral discs and 13 pathological corneas (corneal melting and herpes virus keratitis) were used. Protein localization was examined using fluorescent and enzymatic immunohistochemistry, and mRNA expression was determined by qRT‐PCR.Results: PI‐9 is predominantly expressed in the superficial and suprabasal epithelial layers of the cornea and conjunctiva. The corneal endothelium showed positivity in about 50% of cells. GrB was weakly present in healthy corneal epithelium and endothelium. The expression of both proteins was confirmed using qRT‐PCR. Besides altered expression in pathological corneas, strong positivity for PI‐9 and GrB was present in stromal infiltrates and some stromal cells that were positive for HLA‐DR and CD45. A marker typical of keratocytes, CD34, was decreased or totally absent in pathological infiltrates.Conclusions: The changes of PI‐9 and GrB expression in pathological tissue indicate that these proteins participate in the corneal immune response during the inflammatory process.
Controversies between lymphoma and uveitis – the point of view of the ophthalmologist
Authors: Touitou V. 
Published: September 2016

SummaryDiagnosis of primary vitreoretinal lymphoma (PVRL) is often challenging. One of the reasons of this challenge relies on the absence of specificity of the clinical signs (masquerade syndrome mimicking uveitis), the low number of cells in the vitreous, and its fragility leading to rapid degradation of the cells during or after vitrectomy. Anterior chamber cytokine dosage provides important informations regarding the screening of patients suspect of PVRL. It also proved to be a valuable tool to detect early relapses of patients during the follow‐up. New molecular diagnostic tools or new biological scores based on intraocular cytokine dosage have been developed to increase the yield of cytokine level measurement and help in the decision to propose diagnostic vitrectomy. It may also be helpful to evaluate the ocular response to treatment in order to tailor the therapeutic strategy for each patient.
Nrf2‐ and PGC‐1α‐deficient mice: A novel animal model for disturbed proteostasis and RPE degeneration
Authors: Kaarniranta K. 
Published: September 2016

SummaryImpaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age‐related macular degeneration (AMD). Both of them participate in the regulation of proteostasis in the retina. Nrf2 and PGC‐1 transcription factors mediate cellular defence against oxidative stress. We describe a novel Nrf2 and PGC‐1 knock‐out mouse model that induces RPE degeneration. Aged Nrf2/PGC1 knock‐out mice developed RPE degeneration, associated with upregulation of lipid peroxidation marker 4‐HNE, ubiquitin protein aggregates, selective autophagy markers Beclin‐1, SQSTM1/p62 and LC3. These changes were accompanied by impaired visual function as assessed by ERG. Our findings suggest that combined Nrf2 and PGC‐1 deficiency increases oxidative stress and protein aggregation, and affects autophagy in RPE. Nrf2 and PGC‐1 knock‐out mouse model provides a novel tool to study role of proteostasis in the degeneration of RPE and autophagy as therapy target in the prevention of age‐related cellular damages.
Problems in the diagnosis of intraocular lymphoma
Authors: Cassoux N. 
Published: September 2016

SummaryIntraocular lymphoma means different entities. Primary vitreoretinal lymphoma can mascarade a chronic uveitis. This lymphoma is a subset of primary cerebral lymphoma. The disease is a B cell non hodgking lymphoma, aggressive, with a survival rate of less than 2 years after the occurrence of cerebral localization. Clinical examination, fluorescein angiography, OCT can be highly suggestive combined with resistance to corticosteroids. Diagnosis is based on cytokines levels (IL10/IL6) in aqueous humor or vitreous and diagnostic vitrectomy. Uveal localization of MALT lymphoma is rare and much more difficult to diagnose. This affection can mimic choroidal metastasis or a posterior scleritis or achromic uveal melanoma. The diagnosis can be suspected clinically (unpainfull choroidal thickening), hypoechogenic choroidal infiltration, typical aspect on ocular MRI. The diagnosis is based on episcleral, or choroidal biopsy.
Inflammation the good and the bad
Authors: Calonge M. , Herreras J.M. , Stern M.E. 
Published: September 2016

SummaryInflammation at the ocular surface is the most commonly encountered pathology in Ophthalmology, irrespective of age, gender, race or geographical area. Inflammation in the form of primary keratitis of any origin represents a real threat for visual loss. The commonest way though to eventually have a vision‐threatening corneal problem is as a consequence of an inflammatory process initiated in the eyelid margin (i.e. meibomitis), in the conjunctiva (i.e. conjunctivitis that eventually develop into kerato‐conjunctivitis) or Dry Eye Disease (DED).DED serves as an example which explains the role of the lacrimal functional unit (LFU). The LFU, initially defined in 1988 and later expanded, comprises the ocular surface (cornea, conjunctiva, limbus, and tear film), all tear‐producing glands and cells (lacrimal glands, mucus producing system and Meibomian glands) and all the neuro‐hormonal controlling interactions. Thus, the LFU is a crucial concept to understand how inflammation in a tissue not belonging to the optic system (i.e. eyelids or conjunctiva) may end up causing visual disability by involving the visual axis in the cornea. Examples of inflammation in the LFU as well as their deleterious consequences will be presented.
The firsts in ophthalmic echography
Authors: Kivelä T. 
Published: September 2016

SummaryClinical ophthalmic ultrasound began with the A‐scan. The most recognized early pioneer in this field was a Finnish ophthalmologist Dr. Arvo Oksala (1920–1993), later Professor and Chair of the Turku University Eye Clinic. He began to explore ultrasound with the physicist Antti Lehtinen in 1957, a year after the first paper on this topic written by Mundt and Hughes. Oksala and Lehtinen used an industrial ultrasound from a large metal company. The same year they published their first results: detection of non‐metallic foreign bodies, retinal detachments and tumors in the eye. Further work allowed differentiation between a subretinal haemorrhage and a choroidal tumor. Together these two investigators published 23 papers on ophthalmic ultrasound within the first 5 years. From 1968 to 1971, prof. Oksala was the President of the Societas Internationalis pro Diagnostica Ultrasonica in Ophthalmologia (SIDUO) that had been founded in 1964, and in 1971 he became its Honorary Member and in 1984 he received its Pioneer Award. The second recipient of the Pioneer Award in 1984 was Dr. Gilbert Baum (1922–2002) from the Albert Einstein College of Medicine, New York. He was the primary developer of the B‐scan technique to examine the human eye.
When and why proteomic approach is needed?
Authors: Uusitalo H. 
Published: September 2016

SummaryOcular surfaces are delicate structures of the anterior segment of the eye protected, nourished and lubricated by tear fluid. The system has it's own regulatory mechanisms. Ocular surfaces are exposed environmental factors, topical ophthalmic drugs and affected by various ocular and systemic diseases. Inflammation and wound healing are vital processes involved in the defense mechanisms of the human body and pathogenesis of many eye diseases. It is also one of the most important factors in many ocular surgeries e.g. corneal, refractive and glaucoma surgery. It consists of many overlapping processes like inflammation, fibroblast activation, ECM production and remodeling of the ECM and there are many mechanisms and mediators involved in it. Tear proteomics is a powerful tool to diagnose and detect mechanisms and drugable targets of the ophthalmic and systemic diseases. This course is focusing in the proteomics and biomarkers of the tears and anterior surface of the eye in relation these diseases. The idea is to give practical instructions and advice when and how proteomic analysis is relevant to perform in research.
Adaptive optics – basic optical principles
Authors: Irsch K. 
Published: September 2016

SummaryAdaptive Optics (AO) refers to a technique to compensate for distortions caused by optical aberrations in the media between the camera and the object being imaged. It was originally developed for use in astronomical telescopes to compensate for optical distortions induced by the inhomogeneous earth atmosphere. It has since evolved to become a powerful clinical tool in ophthalmology. In the eye, a ‘wavefront sensor’ (aberrometer) measures the distortion of incoming light induced by inhomogeneities within the cornea and crystalline lens, which is then ‘undistorted’ via reflection by a deformable mirror. AO thus enables imaging of the human retina with unprecedented resolution in vivo, such as revealing individual photoreceptors or the walls of blood vessels. One should note that AO by itself does not provide an image; rather an AO subsystem is incorporated into an existing imaging device. AO subsystems have thus far been successfully integrated into three ophthalmic imaging devices: fundus cameras, scanning laser ophthalmoscopes, and the OCT device. This lecture will introduce the basic principles of AO, illustrate its value with state‐of‐the‐art clinical examples, and discuss potential future applications in ophthalmology.
Treatment of hard exudates in CSME in PDR using Micropulse mode
Authors: Saksonov S. , Teslenko A. , Vitovska O. 
Published: September 2016

SummaryHard exudates are common in Diabetic Maculopathy. Quite often, it overlies the central part of the fovea causing severe visual loss. Some of the exudates may resorb while anti‐VEGF treating is performed or while normalizing diabetic control. Some of exudates remain in the fovea preventing visual function increase. Focal conventional laser coagulation as a DME treatment can speed up the proses of lipid resorption but it is associated with potential iatrogenic visual loss, especially in fovea region. Micropulse mode suggested to be safe and macular‐friendly treatment. This mode of laser energy delivery, if accurately titrated, do not left any signs of laser burns seen no on FA no on OCT. Micropulse 577 nm laser influence on lipids and surrounding RPE can stimulate hard exudates resorption and macular clearance. This potentially can be useful in case of visual loss due to hard exudates persisting in macular and especially foveal region.
Sclear embedded iol
Authors: Pappas G. 
Published: September 2016

SummaryAimTo evaluate if the embedding of an Intraocular lens in the sclera is an easy, safe and beneficial for the patients with aphakia surgical procedure.MethodsWe examined the notes of 42 patients who underwent surgery for aphakia and they had an scleral embedded IOL. All procedures performed by the same surgeon under the same settings at Venizeleio Hospital of Heraklion.ResultsFinal visual acuity, stability, difficulty of the procedure, astigmatism produced, complications and patients satisfaction were recorded. We will also present videos with different techniques to stabilize an IOL in the sclera.ConclusionWe will produce evidence that scleral embedded IOLs is a safe and easy procedure which produces very good results.
OCT angiography: evaluation of the macular perfusion
Authors: Pournaras C. 
Published: September 2016

SummaryOCT angiography (OCT‐A) as a new non‐invasive imaging technology that enables the monitoring of the macular circulation. OCT‐A has a better rate of detection either of the macular capillaries plexus or the distribution of the macular cystoid spaces, than using fluoserseine angiography (FA), allowing the evaluation, of either superficial or deep perifoveal capillary layers.During the evolution of the ischemic micro‐angiopathies, the appearance of the capillaries ischemic areas, the micro‐aneurysms, the capillaries segments dilations as well as the distributions and the evolution of the capillaries collaterals, can be monitored. The evaluation of the deep capillary plexus, appears to be more severely affected than the superficial capillary plexus, resulting to deep non perfused capillaries areas. The perifoveal capillary arcade disruption, observed on OCT‐A in eyes with retinal vein occlusions, was correlated with the presence of retinal peripheral ischemia.OCT‐A progressively became a useful imaging modality in the evaluation and management of macular hemodynamic changes observed during the evolution of the retinal ischemic micro‐angiopathies allowing to evaluate the treatment effects on the capillary circulation.
Retinal toxicity following intra‐vitreal injections of melphalan
Authors: Munier F. , Gaillard M.C. , Stathopoulos C. , Beck‐Popovic M. 
Published: September 2016

SummaryWe report a retinal toxicity grading system as observed in a cohort of 110 retinoblastoma eyes treated by intra‐vitreal injections of melphalan to control vitreous seeding.By definition grade 1 and 2 correspond to a salt and pepper retinopathy anterior to the equator of 2 quadrants and 2 quadrants respectively; grade 3 any extension behind the equator, grade 4 extension involving the macula and grade 5 diffuse retinopathy with optic nerve atrophy. In our series grade 4 and 5 toxicity could be avoided in 100% of the cases. We conclude that our injection technique is safe enough to prevent severe sight‐threatening toxicity.
Optimisation of RPE65 gene delivery for treatment of Leber congenital amaurosis patients
Authors: Georgiadis T. 
Published: September 2016

SummaryVirally‐mediated gene therapy to treat inherited retinal disorders has proven to be safe and well tolerated through a number of phase I/II clinical trials. RPE65 deficiency is the cause of Leber congenital amaurosis type 2 and clinical trials, including our own, using recombinant AAV serotype 2 to deliver the human RPE65 gene into the patients’ RPE cells have shown moderate levels of efficacy. We aim to increase the potency and persistence of treatment effect by employing a range of optimisations to the recombinant AAV gene therapy vector. We assessed the preclinical efficacy of a novel gene therapy vector for RPE65 gene replacement in vitro and in vivo following optimisation of the viral serotype, transgene promoter and transgene sequence. We observed a 300‐fold increase in efficacy in a mouse model lacking Rpe65 when compared to the original AAV2 gene therapy vector. We aim to bring this vector forward for a new phase I/II clinical trial in patients with LCA2.
Light‐Adjustable Lens: A non‐invasive approach to adjust remaining refractive errors after cataract surgery
Authors: Hengerer F. , Conrad‐Hengerer I. 
Published: September 2016

SummaryYet, in spite of improvements in preoperative lens power calculation, many patients are in need of spectacle correction to achieve emmetropia and/or an optimal distance vision after cataract surgery.One possibility to reduce this is to have the ability to adjust residual spherical and astigmatic errors postoperatively in a predictable and non‐invasive way.Calhoun Vision's LAL is based upon the inclusion of a proprietary photoreactive silicone macromer within a silicone polymer matrix. Selective irradiation of the implanted LAL by targeted dosages of UV light (365 nm) produces modifications in the lens curvature resulting in a predictable spherical and/or cylindrical power change postoperatively. After achieving the desired refractive outcome, the LAL is irradiated to polymerize remaining photosensitive macromers and prevent additional change in lens power.The purpose of this presentation will explain the LAL technology, as well as treatment options and expected future applications.