bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and incidence of epimacular membranes in patients with wet AMD
Authors: Ricouard F. , Foveau P. , Zimmermann A. , Conart J.B. , Gaucher D. , Saleh M. 
Published: September 2016

PurposeThe purpose of this study was to report the prevalence of epimacular membranes (ERM) in a population followed for age‐related macular degeneration (AMD) and to assess their incidence of onset over time.MethodsMulticentric study of the EAST group (Eastern French Studies and Trial Group) (3 sites: Besancon, Nancy, Strasbourg) from the Vitreo‐macular interface in the Age‐related macular degeneration study (EVA study). All patients had consecutive control visits with Spectral‐Domain OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The OCT protocol consisted of the acquisition of horizontal cross‐sectional scans passing through the fovea and 3 and 6 mm of either side. The vitreomacular interface has been described according with the IVTS nomenclature.Results312 patients with one or both eyes treated for wet AMD (410 eyes) were studied. The average age was 80 years (55–96 year). The mean follow‐up was 30 months (2.9–110). 17.3% of eyes treated displayed an ERM at baseline and 18.8% at the end of follow‐up. During follow‐up, 13 eyes treated (3.2%) have developed ERM. 18% of eyes in the wet AMD group displayed an ERM against 10% of the eyes in the control group (190 fellow controled eyes), (OR = 2.08 CI95% = 1.22–3.49). Final visual acuity (VA) was significantly lower in patients with ERM (p < 0.01) with an average of 44.3 ETDRS letters against 52.6 in patients without ERM. The average number of IVI in patients with ERM was not significantly higher (p > 0.05). 17 patients (4.1%) with ERM underwent vitreoretinal surgery, with an average gain of 8.3 ± 18.4 letters.ConclusionsEpiretinal membranes are frequent in patients treated for wet AMD and are associated with a lower VA. Nevertheless, they do not imply a higher need of injections. A study to assess the benefit of ERM surgery in patients with AMD is currently conducted.
Hemodynamic changes in eyes with early primary open‐angle glaucoma measured by transpalpebral rheoophthalmography
Authors: Kleyman A. , Kiseleva O. , Iomdina E. , Bessmertny A. , Luzhnov P. , Shamaev D. 
Published: September 2016

PurposeTo evaluate the hemodynamic parameters in eyes with primary open‐angle glaucoma (POAG) and early glaucomatous visual field defects (early nasal step) using transpalpebral rheoophthalmography (TR).MethodsTwo groups of subjects were examined. Group 1 consisted of 56 eyes of 39 patients aged 57–79 (ave. age M ± σ = 67.33 ± 6.78) with POAG and early nasal step. Of these, 17 patients had POAG in both eyes. Group 2 consisted of 54 eyes of 27 patients aged 56–73 (ave. age 63.96 ± 5.54) without any eye pathology except initial cataract. Patients with any other optic disc or macular pathology, previous intraocular surgery, ocular trauma, or severe somatic pathology, were excluded from the study. All subjects underwent complete ocular and visual field examination, Goldmann intraocular pressure (IOP) measurement and TR. TR signals were registered using a specially designed tetrapolar lead system. Signal processing of TR with special software allowing automated analysis included three basic parameters: the rheographic index (RI), the period of maximum filling (PMF), and the indicator of the elastic modulus (IEM).ResultsThe measured IOP was 16.9 mmHg (±1.7) in group 1 and 14.6 mmHg (±2.1) in group 2. A statistically significant difference was observed between the average RI (mΩ): for group 1 (M ± σ = 14.76 ± 3.18) vs. group 2 (26.44 ± 3.31), p < 0.05. A slight increase in the values of other parameters in group 1 (PMF = 21 ± 3 cs, IEM = 26 ± 4 cs) as compared to group 2 (PMF = 19 ± 3 cs, IEM = 24 ± 4 cs) was observed. This may be associated with a decrease in elasticity of intraocular blood vessel walls and their sclerotic changes.ConclusionsThe proposed new TR method is easy to use, highly informative and sufficiently accurate, allowing to objectively assess the changes of ocular hemodynamics, and facilitating the diagnosis of glaucoma at an early stage.
Evaluation of progressive visual dysfunction and degeneration of the retinal nerve fiber layer and macular thickness in patients with Parkinson disease
Authors: Satue M. , Rodrigo M.J. , Obis J. , Cipres Alastuey M. , Vilades E. , Garcia‐Martin E. 
Published: September 2016

PurposeTo quantify changes in visual function parameters, in the retinal nerve fiber layer (RNFL) and macular thickness of patients with Parkinson disease (PD) over 5 years.MethodsThirty patients (60 eyes) with EP and 30 healthy subjects (60 eyes) underwent a complete ophthalmic evaluation, including assessment of visual acuity (VA) with ETDRS chart, contrast sensitivity vision (CSV) with Pelli Robson and CSV 1000E tests, color vision with Farnsworth and Lanthony D15 tests and retinal evaluation using Spectral domain Optical coherence tomography (SD‐OCT). All subjects were reevaluated after 5 years to quantify changes in visual function parameters, the RNFL and macular thickness.ResultsChanges were detected in visual function parameters (VA, CSV and Lanthony color indexes; p < 0.05) and RNFL thickness (inferotemporal, superotemporal and temporal sectors; p < 0.001) in PD patients compared to controls. Greater changes in VA, CSV and color vision (p < 0.05) were detected during the follow‐up in the PD group compared to healthy subjects. Greater loss of the RNFL (superotemporal and temporal sectors; p < 0.001) and macular thickness (all sectors except inner superior and inner inferior sectors, p < 0.001) was observed in the patients group after the 5‐year follow‐up.ConclusionsProgressive visual dysfunction, macular thinning and axonal loss can be detected in PD patients. Analysis of the macular thickness and the RNFL by SD‐OCT can be useful for evaluating PD progression.
Measuring scleral thickness with optical coherence tomography in osteogenesis imperfecta: a case report
Authors: Brehon A. , Jullienne R. , Kaspi M. , Perrot J.L. , Grivet D. , Peoc'h M. , Gain P. , Thuret G. 
Published: September 2016

PurposeThe blue sclera appearance is a distinctive but non‐specific clinical sign for osteogenesis imperfecta (OI), a connective tissue disorder caused by an abnormality of type I collagen. It is a challenging diagnosis because multiple bone fractures, occurring in early childhood, can be the only sign of the non‐lethal forms of OI. In these situations, differential diagnosis with child abuse is a major concern for Pediatricians. Aim: to investigate the scleral optical coherence tomography (OCT) and thickness measurement as a diagnostic test for OI.MethodsThe sclera of a 28‐year‐old man affected by a mild form of OI and presenting a blue scleral hue was examined with the sclera mode coupled with the enhanced depth imaging of the spectral domain OCT equipped with the anterior segment module device (SD‐ASOCT) (Heidelberg Engineering GmbH, Heidelberg, Germany). The scleral thickness was measured at a distance of 2000 μm from the scleral spur in eight meridians. Three measurements in each meridians were averaged and the mean and the standard deviation of the eight meridians were calculated. The examination of an age matched healthy volunteer served as a control.ResultsThe mean scleral thickness of the OI patient was lower than that of the healthy patient, 277 μm ± 43 μm vs. 470 μm ± 50 μm. The superotemporal meridian was the thinnest in both patients.ConclusionsThese findings are consistent with the pathologic features previously described. The blue color results from the visualization of the underlying choroid through the translucent and thinner sclera. The in vivo scleral thickness measurement is a rapid and non‐invasive diagnostic tool that may be useful for challenging cases, especially in children with multiple fractures.
Ca2+ activity during ATP‐induced tone changes in porcine retinal arterioles in vitro spreads along the processes of perivascular cells
Authors: Kudryavtseva O. , Bek T. 
Published: September 2016

PurposeRecently, a novel population of perivascular cells (PVC) located immediately external to the vascular smooth muscle cells of retinal arterioles has been identified. These cells display Ca2+ activity simultaneously with tone changes of retinal arterioles and have processes extending into the retina. This data suggests that PVCs could play a role in the neurovascular coupling in the retina. The aim of the study was to investigate Ca2+ signals in PVCs and their processes during successive contraction and relaxation of retinal arterioles induced by ATP.MethodsFirst order porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a confocal myograph and loaded with the Ca2+‐sensitive fluorophore Oregon Green. The arterioles were preconstricted with 5*10‐8 – 10‐6 M U46619 and after the addition of ATP (10‐4 M) intracellular fluorescence from the PVC layer was recorded by a confocal microscope simultaneously with the vascular tone.ResultsATP induced a biphasic tone response in 19% (5 out of 26) of the studies arterioles. The tone response consisted of 15 ± 4% initial contraction followed by 30 ± 20% relaxation. ATP induced Ca2+ waves in 49 ± 16% PVCs and 46 ± 14% processes during the contraction and in 46 ± 16% PVCs and 46 ± 14% processes during the relaxation. There was no significant difference between the frequency of Ca2+ waves in PVCs and their processes during contraction and relaxation (p > 0.05), but the amplitude of Ca2+ waves was significantly higher (p < 0.01) during contraction than during relaxation in the two structures.ConclusionsPVC Ca2+ waves associated with contraction and relaxation of porcine retinal arterioles spread along cellular processes. The amplitude of Ca2+ waves in PVCs and their processes can be used to differentiate contracting and relaxing responses of retinal arterioles.
Application of laser radiation exposed Chlorpromazine for the treatment of pseudotumours induced in rabbit eyes
Authors: Popa Cherecheanu A. , Tozar T. , Geamanu A. , Iancu R. , Duta S. , Pirvulescu R. 
Published: September 2016

PurposeMultiple drug resistance (MDR) is a challenge that requires a flexible approach to find medicines able to overcome it. Among the methods used to overcome it, there is the exposure of existing medicines to UV laser beams to generate active photoproducts against bacteria and/or malignant tumors.MethodsWe studied the interaction of UV activate Chlorpromazine (CPZ) (irradiated with 266 nm pulsed laser beams), at concentrations of 10 and 20 mg/ml in ultrapure water, with rabbit eyes pseudotumors.ResultsThe use of CPZ water solution exposed to 266 nm in the treatment of pseudotumor tissues produced on rabbit eyes shows that treatment results depend on initial (before irradiation) CPZ concentration and exposure time. At this stage, one may not specify which out of the generated photoproducts, individual or as a group, is/are efficient in pseudotumor cure but overall effects are observable. Application of CPZ irradiated solutions on rabbit eyes pseudotumors seems to produce a faster recovery of tissues with respect to control, untreated eyes.ConclusionsHistologic findings in the treated tissues show a good antiinflamatory response. The results obtained open perspectives to fight MDR and/or development of pseudotumoral processes with substances that were not initially made for this purpose (non‐antibiotics, for instance).
Retinal α‐synucleinopathy: taking a new look at Parkinson's disease
Authors: De Groef L. , Normando E.M. , Andries L. , Davis B. , Lefevere E. , Van den Haute C. , Baekelandt V. , Cordeiro M.F. , Moons L. 
Published: September 2016

PurposeAlthough it is well‐documented that many patients with Parkinson's disease (PD) present with visual disabilities, scientific research has largely neglected the relation between PD and retinal dysfunction. A profound understanding of the retinal manifestations of PD, however, would not only help to gain new insights into its pathogenesis, it would also open up new avenues to improved disease management. Therefore, we have set out a comprehensive study to map retinal changes in several rodent models of PD/α‐synucleinopathy.MethodsTwo established models of PD/α‐synucleinopathy were used, i.e. the rotenone‐induced PD model in rats and a Thy1‐aSYN transgenic mouse line. In addition, a novel mouse model for the study of α‐synucleinopathy in the retina, based on local, viral vector‐mediated overexpression of α‐synuclein, was developed. Retinal neurodegeneration was studied via (i) in vivo imaging with optical coherence tomography and DARC (detection of apoptotic retinal cells); (ii) vision‐guided behavior tests; and (iii) (immuno) histological stainings for dopaminergic neurons (tyrosine hydroxylase), Lewy bodies (α‐synuclein, thioflavin) and apoptosis (cleaved caspase‐3), combined with specific retinal cell markers.ResultsOur results suggest that retinal changes related to PD/α‐synucleinopathy can be identified non‐invasively in these animal models and monitored over time. Moreover, histological analysis points out that specific retinal cell populations are affected, and that retinal changes precede PD manifestations in the brain.ConclusionsThis study brings together the first comprehensive data set on retinal manifestations in rodent models of PD/α‐synucleinopathy, and provides novel conceptual insights to support the idea that changes in retinal function/morphology can be used as early biomarkers for diagnosis and evaluation of treatment.
Therapeutic potential of non‐viral MRNA delivery to Müller cells for neuroprotection
Authors: Devoldere J. , Peynshaert K. , De Smedt S. , Remaut K. 
Published: September 2016

PurposeRetinal cell degeneration is a leading cause of vision loss in many ocular diseases. The progressive loss of retinal cells is often hereditary, but rarely monogenic. This enormous diversity in disease‐inducing mutations has hampered the development of gene replacement strategies to prevent or reverse retinal degeneration. Therefore interest has augmented for a treatment strategy that halts the degeneration process, rather than correcting the initial causative mutation. This work aims to evaluate the potential of chemically modified mRNA as a therapeutic strategy to stimulate neuronal survival and save vision, regardless of the initial genetic defect.MethodsEvaluation of mRNA delivery to Müller cells was conducted in MIO‐M1 cells, using modified and unmodified reporter mRNA encoding the Green Fluorescent Protein (GFP). Lipid‐based vectors carrying the mRNA were delivered to Müller cells via serum‐containing medium or injected into fresh bovine vitreous, applied on top of the cells. In both setups uptake, level and duration of eGFP expression and toxicity of the lipoplex formulations were evaluated. In addition, the suitability of these complexes for intravitreal injection was assessed by measuring their mobility in bovine vitreous on a single‐particle level.ResultsOverall transfection levels are decreased in presence of vitreous, indicating that the vitreous is an important barrier for non‐viral mRNA delivery to the retina. Chemical modification of the mRNA substantially increased eGFP expression in >80% of cultured Müller cells.ConclusionsOur data demonstrate that non‐viral lipid based carriers show good potential to transfect Müller cells in vitro. However, to make these mRNA therapeutics suitable for ocular targets, development of strategies to overcome the vitreal barrier will be crucial to implement ocular mRNA therapy in the future.
Pseudodominance in a Czech family with Usher syndrome type II
Authors: Kousal B. , Dudakova L. , Skalicka P. , Bujakowska K. , Liskova P. 
Published: September 2016

PurposeUsher syndrome is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa developing in late childhood and adolescense. We have identified a Czech family not aware of consanguinity with four members in two subsequent generations clinically diagnosed with Usher syndrome type II. The major aim of our study was to determine the disease‐causing mutation(s) in this family.MethodsAs an initial approach Sanger sequencing of USH2A exons 6, 7, 11, 13, 20, 61 was performed in the proband, followed by next‐generation sequencing of a panel testing 286 genes known to cause various inherited ocular disorders. Available relatives were screened by Sanger sequencing for the detected mutations. 1,161 population specific controls were used to check for allele frequencies of the identified sequence variants.ResultsThe proband was found to harbour compound heterozygous mutations c.11864G>A; p.(Trp3955*) and c.13342_13347del; p.(Asp4448_Ser4449del) in USH2A while her affected daughter and son were homozygous for the c.11864G>A mutation. Segregation analysis confirmed that father of the affected children was a heterozygous carrier of the USH2A c.11864G>A. Affected brother of the proband was not available for our investigation. Mutation c.11864G>A has been previously observed in patients with Usher syndrome type II. Geographical origin in a particular region in Moravia was noted for parents of both the affected proband and her spouse. None of the two mutations were detected in Czech controls.ConclusionsPseudodominance may occur in outbred families. The estimation of the chance that a person will be a heterozygote carrier of a recessive disorder needs to be implemented into counselling. Geographic distribution of pathogenic alleles may display regional differences.
Phenotype of maculopathy in primary hyperoxaluria type 1
Authors: Derveaux T. , Delbeke P. , Walraedt S. , Raes A. , Van Laecke S. , Leroy B.P. , De Zaeytijd J. 
Published: September 2016

PurposeTo describe the structural and functional characteristics of oxalate retinopathy, an entity described in only 40 cases until now.MethodsFive patients with molecularly confirmed primary hyperoxaluria type 1 were subjected to multimodal retinal imaging (spectral‐domain optical coherence tomography, white light, and HRA multispectral imaging) and functional testing, including color vision testing, Goldmann perimetry, and ISCEV standard electrophysiological testing.ResultsOne patient with a c.[33dupC]; c.[731T > C] mutation showed bilateral perifoveal retinal pigment epithelium hyperplasia. The fundus in the four other patients, all of whom share an identical homozygous c.[33dupC] mutation, ranged from normal to bilateral widespread distribution of retinal crystals and confluent macular retinal pigment epithelium hyperplasia with subfoveal fibrosis. All patients who had developed end‐stage renal disease showed some sign of retinopathy, more severe with earlier onset.ConclusionsRetinopathy in primary hyperoxaluria type 1 shows considerable interindividual variation. No correlation between genotype and retinal phenotype was detected. A proposed clinical grading system of oxalate maculopathy derived from a literature review may help clinicians in estimating not only current visual function but also prognosis in this patient population that largely consists of preverbal infants.
Maculopapillary analysis in the posterior pole in patients with mild Alzheimer's disease
Authors: Salobrar‐Garcia E. , Garcia Y. , Lostao C. , Jañez L. , de Hoz R. , Rojas B. , Salazar J.J. , Ramirez A.I. , Gil P. , Yubero R. , Triviño A. , Ramirez J.M. 
Published: September 2016

PurposeTo correlate the thickness of focal regions of the macula with those of the peripapillary nerve fiber layer using optical coherence tomography (OCT) in mild Alzheimer's disease (AD) patients and to compare them with age‐matched controls.MethodsOCT of the macula and of the optic nerve from 19 mild AD patients and 25 control patients were included in the study. The thickness of 36 macular voxels of the 6 × 6 grid considered for analysis was correlated with the thickness of the 7 temporal papillary wedges across subjects. Each macular voxel was labeled with the peripapillary wedge with the highest correlation using a color‐coded map.ResultsIn comparison with the controls, mild AD patients presented a significant: (i) thinning in the macular voxels 5, 6, 12, 15, 16, 18, 21, and 22 (p < 0.05) and; (ii) correlation between several macular voxels and some of the peripapillary wedges between groups (p < 0.05).ConclusionsThere were significant differences in the maculopapillary correlation map pattern between mild AD patients and control group. The OCT changes detected could be ascribed to the inflammation and neurodegeneration that occur in the early stages of AD and could serve as a basis for future research aimed to develop a quick, easy, and non‐invasive biomarker of AD.
Toward rational design of gene carriers: a novel ex vivo model to study the vitreoretinal interface as a barrier
Authors: Peynshaert K. , Fradot V. , Picaud S. , De Smedt S. , Remaut K. 
Published: September 2016

PurposeThe vitreoretinal interface poses a serious hurdle for the retinal delivery of viral and non‐viral gene vectors after intravitreal injection. We have therefore developed a retinal model especially designed to study to which extent the ILM is a barrier for the penetration of vectors into the retina. In contrast to all existing explant models, ours is bovine‐derived and more importantly, the vitreous remains attached to the retina at all times to guarantee an intact vitreoretinal interface.MethodsTo investigate the influence of nanoparticle physicochemistry on their ability to penetrate the ILM we have injected various carboxylated polystyrene particles with a size range between 20 and 200 nm intravitreally in our model. After diffusion overnight the Müller cells are stained with Mitotracker Deep red and the nuclei with Hoechst. Finally, a z‐stack of confocal images of the retina is recorded using a water dipping objective that is brought into contact with the vitreous layer on top of the retina.ResultsOur data clearly illustrated that the ILM significantly hinders particle penetration into the retina. We also found that this penetration is greatly size‐dependent: the cut‐off for nanoparticles to cross the ILM lies between 40 and 100 nm. Intriguingly, the particles that did cross the ILM co‐localized solely with Müller cells, indicating these cells actively capture the nanoparticles out of the ILM and shuttle them into the retina.ConclusionsIn conclusion, we developed a model set‐up greatly mimicking human physiology to investigate the influence of particle physicochemistry on their ability to cross the ILM after intravitreal injection. This data collection will signify a leap forward in the rational design of gene vectors with the retina as their target, since this way their design can be tuned to actual in vivo requirements.