bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological tissue as a active substances drug prolonged diffusion support
Authors: Grossetete Florine , Barnouin Laurence 
Published: December 2019

AbstractObjectiveUse of ground proceed umbilical cord lining (Wharton Jelly) for an prolonged diffusion of active substance with a progressive disintegration of the tissue within few days.MethodsGround proceed umbilical cord lining is a tissue that contains proteoglycans, TGFß, elastin, and collagen. By calibrating the grinding and associating a freeze‐drying with a second desiccation at 35°C‐ 50 microBar, fibers are sticking together and enable having a compact and shaped final product. The addition of solution of gentamycin sulfate in the ground gelatinous tissue is performed before the step of freeze‐drying.Titrations of gentamycin in the solution of ground tissues before and after freeze‐drying are performed according to the method A from European Pharmacopeia.ResultsTitration of gentamycin mixed with ground tissues is from an average of 3024 UI/sample (SD 94) before freeze‐drying. After freeze‐drying: 2997 UI/sample (SD:189). This titration is the one expected regarding the solution preparation, so there is no loss of active principle activity. Titration in time submitted to mechanical and hydration stress are in progress.DiscussionTissues extracted from Wharton Jelly are products used for different pathologies of ocular surface. The use of a solid form, shaped at convenience can enable diffusion of active substance drug to treat more complex infections of the ocular surface and also in eye chambers.
Corneal refractive surgery and the risk of retinal detachment
Authors: Kanclerz Piotr , Grzybowski Andrzej 
Published: December 2019

AbstractPurposeCorneal refractive surgery (CRS) is an elective procedure presenting a low risk of complications. Nevertheless, as commonly eyes with perfect best corrected visual acuity are treated, sight‐threatening complications are a major concern. The aim of this study was to evaluate the association between corneal refractive surgery and the risk for developing retinal detachment (RD).MethodologyPubMed and Web of Science were the main resources used to search the medical literature search.ResultsPresumed mechanisms by which CRS would induce RD include biomechanical changes caused by the suction ring, excimer laser shock wave or the use of femtosecond laser. However, the reported RD rates after CRS were similar to those of an unoperated myopic cohort. We found no differences between RD rates in laser in situ keratomileusis and superficial CRSs. The pooled analysis found an overall risk of developing RD after laser in situ keratomileusis of 0.08% (95% CI: 0.69%–0.82%). Higher preoperative refractive error, older patients age and male sex were associated with an increased risk of developing RD after CRS.ConclusionsThe current analysis presents no convincing evidence supporting the association between CRS and increased risk for developing RD. Patients at risk of developing RD should be treated with caution and informed that CRS reduces the refractive error, but does not eliminate the risks related to myopia.
Afro‐Caribbean patients have a lower disc vascular density than European patients: a cross‐sectional study
Authors: Liseth Salazar Quiñones Maria , Sheng Lim K. , Yu‐Wai‐Man Cynthia , De Antonio Ramirez Alba , García Feijoo Julián , Dora Méndez Hernánez Carmen , Peña Urbina Pilar 
Published: December 2019

AbstractPurposeTo determine if there are racial differences in disc vascular density between Afro‐Caribbean and European patients, and the relationship with disease severity in glaucoma.DesignCross‐sectional study.Participants50 eyes from 32 Afro‐Caribbean glaucoma patients, 35 eyes from 22 European glaucoma patients, 23 eyes from 14 Afro‐Caribbean normal controls, 24 eyes from 12 European normal controls.MethodsAll patients underwent a complete ophthalmic examination. Disc vascular density was measured using OCT angiography. We compared the disc vascular density of Optic head nerve and peripapillary between Afro‐Caribbean and European patients in normal controls and glaucoma patients. We evaluate superficial vascular complex and matched the severity of glaucoma between the two groups using mean deviation from Humphrey visual field 24‐2 test. We also performed Spearman correlation between the disc vascular density and mean deviation, visual acuity, intraocular pressures, central corneal thickness and cup‐disc ratio.Main Outcome MeasuresDisc vascular density.ResultsAfro‐Caribbean normal controls had a lower mean disc vascular density (42.4 ± 0.8 [SEM]) than European normal controls (46.2 ± 0.2; p < 0.0001). We matched the severity of visual field loss in 32 eyes from Afro‐Caribbean glaucoma patients (MD = 5.97 ± 0.75) and 32 eyes from European glaucoma patients (MD = 4.17 ± 0.73; p = 0.090). Afro‐Caribbean glaucoma patients also had a lower mean disc vascular density (33.26 ± 6.60 [SEM]) than European glaucoma patients (36.68 ± 5.28; p = 0.022). There was a moderate correlation between disc vascular density and mean deviation (r = −0.70, p < 0.0001) in the Afro‐Caribbean glaucoma patients. We found no correlation between disc vascular density and mean deviation (r = −0.31, p = 0.070) in the European glaucoma patients.ConclusionsAfro‐Caribbean patients have lower disc vascular density than European patients in normal controls but not subgroup mild, moderate or advanced glaucoma.
TelCaps in retinal vascular diseases: an overview
Authors: Paques Michel 
Published: December 2019

AbstractTelangiectatic capillaries (TelCaps), also termed capillary macroaneurysms, are commonly observed in retinal vascular diseases and may cause chronic macular edema even if distally located. Their recognition is important since their targeted photocoagulation may be clinically beneficial. Diagnosis of TelCaps is facilitated by the use of indocyanine green angiography, particularly in its late frames, since they appear to be a correlation between ICG staining and the intensity of blood –retinal barrier breakdown. This is a crucial point, since TelCaps often escape fundus and OCT examination. As such, the identification of TelCaps may contribute to a reevaluation of chronic macular edema management. Here we will discuss this emerging concept, and its integration into management schemes of chronic macular edema, especially for diabetic macular edema. A randomized study is currently ongoing in France, aiming at investigating the potential of targeted photocoagulation to reduce the amount of intravitreal injections.
Optical coherence tomography biomarkers for idiopathic epiretinal membrane after pars plana vitrectomy
Authors: Chatziralli Irini 
Published: December 2019

AbstractIdiopathic epiretinal membrane (iERM) refers to fibroglial cellular proliferation at the vitreoretinal interface, above the internal limiting membrane (ILM) mainly at the macular area. The gold standard for the treatment of iERM is pars plana vitrectomy (PPV), which provides good anatomical and functional results. However, some patients did not exhibit visual acuity improvement after PPV for iERM. Advances in optical coherence tomography (OCT) have led to the introduction of new anatomic measures, such as precise evaluation of individual layers, qualitative and quantitative assessment of fluid distribution, inner retinal irregularity, ellipsoid zone integrity and disorganization of inner retinal layers (DRIL), which may predict more accurately the treatment success or failure after treatment. The purpose of this lecture is to investigate if characteristics identified on OCT may serve as biomarkers to predict postoperative visual outcomes in patients with iERM treated with PPV.
De novo missense variants in WDR37 cause a severe ocular syndrome
Authors: Semina Elena 
Published: December 2019

AbstractUsing exome sequencing we have discovered de novo missense variants in WDR37 in unrelated patients with a complex phenotype, which we named WDR37 syndrome. Patients with this syndrome demonstrated corneal opacity, coloboma and microcornea, dysmorphic facial features, significant neurological impairment with structural brain defects and seizure onset shortly after birth, poor feeding, and variable skeletal, cardiac, genitourinary defects and early lethality in one. WDR37 encodes a protein of unknown function with seven predicted WD40 domains. We undertook further functional characterization of the gene and variants in human cell lines and zebrafish. Immunocytochemistry and Western blot studies revealed that wild‐type WDR37 is predominantly localized in the cytoplasm and mutant proteins showed similar expression levels and localization. CRISPR‐Cas9 mediated genome editing generated zebrafish mutants with missense and frameshift variants, including one that replicated a human variant. Zebrafish carrying heterozygous missense mutations demonstrated larval lethality, while embryos with frameshift alleles survived to adulthood, suggesting a dominant negative mechanism for the human missense variants. Analysis of RNAseq data from mutant zebrafish embryos revealed significant upregulation of cholesterol biosynthesis pathways. Additional studies into possible function of this important factor and disease mechanisms are ongoing. In summary, we report a novel human disease gene with an essential role in vertebrate development and provide the first insight into its possible role.
The fish scale based Biocornea: an off‐the shelf device for managing acute corneal perforations
Authors: Schuitmaker Hans 
Published: December 2019

AbstractThe fish scale based ologen™ Biocornea is developed as an alternative to the temporary cadaveric corneas that do not meet all the criteria of transplantation grade tissue. Such temporary corneas (so‐called “0‐cornea”) can be used to patch a perforated, lacerated or ulcerated cornea for hours up to a few days, until a suitable donor cornea is procured for transplantation. The temporary cornea ensures integrity of the eye globe, maintaining inner eye structures and intraocular pressure so that other eye structures are not damaged while the patient waits for donor tissue. However, a 0‐cornea is not always available and for these circumstances the fish scale based Biocornea offers an alternative way to close the eye for a limited period of time to preserve the globe, until a human donor cornea is available. The Biocornea implant is composed of decellularized fish scales that have been acquired from a certified fish processing plant operating according to the EU Food Safety Management System. Initially, these ologen™ Biocorneas were tested for the intended purpose in a pig transplantation model. The favorable outcome of these experiments forms the basis for a “first in man” clinical trial which now runs in Cologne and Bochum in Germany as part of the ARREST BLINDNESS project. The experience obtained from the clinical trial will be the basis for further development of new prototype Biocorneas.
Pain and sensation in dry eye disease
Authors: Gallar Juana 
Published: December 2019

AbstractThe recent definition of dry eye disease (DED) proposed by DEWS II includes, for the first time, neurosensory abnormalities in etiology of the disease. In DED, reduced tear secretion leads to inflammation and corneal nerve damage, which induce sensitization of corneal polymodal and mechano‐nociceptors, and an abnormal activity of cold thermoreceptors thus evoking pain and eye dryness sensations. Moreover, long‐term nerve damage and inflammation, modify the expression of ion channels involved in the stimulus detection (transduction) and excitability of ocular sensory neurons, changing their impulse firing and their connectivity at the CNS, which is the basis of neuropathic pain and dysesthesia referred to the eye surface in DED patients. These altered transducing and encoding ion channels are potential molecular targets to modulate neuropathic nerve activity in DED, currently under study. Although many subjective (surveys and questionnaires, corneal sensitivity measurement) and objective metrics (morphology and density of subbasal corneal nerves and immune cells, blink parameters, biomarkers in tears) are currently used to evaluate pain in DED patients, new instruments and procedures designed to obtain more reliable information on eye sensations and pain in DED need to be developed (SAF‐2017‐83674‐C2‐1‐R and 2‐R, Agencia Estatal de Investigación‐ERDF, Spain‐EU, and PROMETEO/2018/114, Generalitat Valenciana, Spain).
Biomechanical profile of refractive surgery procedures
Authors: Balidis Miltos 
Published: December 2019

AbstractThe impact of corneal biomechanics continues to be increasingly recognized as an integral part of refractive surgery outcomes. Corneal biomechanical properties are of major importance in laser refractive surgery and must be taken into consideration to reduce the risk for iatrogenic ectasia. Some in vivo corneal biomechanical alterations are possible to quantify with ORA and Corvist ST but are difficult to interpret and use in clinical practice due to their dependence of IOP, CCT, refractive status, time from surgery and age. Development and refinement are needed if ORA and Corvis ST should be implemented in a screening procedure of the biomechanical strength before refractive surgery.Flap‐creation technique plays a major role in changing the biomechanical stability of the cornea. Nevertheless several studies suggest that the type of procedure is not as important as the native charac‐teristics of the patient’s cornea in determining the risk for ectasia. Although we may have reached a plateau of technological improvement in excimer laser tissue ablation, the introduction of small incision lenticule extraction (ReLEx SMILE), has changed the face of corneal refractive surgery in particular in its effect on corneal biomechanics. Mathematical analysis and finite‐element models suggest that SMILE may preserve corneal biomechanical properties better than LASIK. Furthermore, the current in vivo studies performed with ORA and Corvis ST indicate that SMILE is equal or superior to LASIK in terms of preservation of the postoperative biomechanical strength.However CH and CRF were reduced after refractive surgery but no differ‐ences were found between SMILE and flap‐based (FLEx and FS‐LASIK) refractive surgeries in the RCTs. Studies have demonstrated that in LASIK and PRK, the amount of refractive error corrected is related to the changes in corneal biomechanical properties. Considerable reduction in the corneal biomechanical properties observed even in ‘flap‐less’ procedures like PRK and SMILE,Brillouin microscopy provides safe and non contact method for measuring longitudinal elastic modulus of ocular tissues. It provides three‐dimensional resolution of the imaged tissue revealing spatial variations in mechanical properties. Its clinical usefulness has already been demonstrated in corneal diagnostic and treatment monitoring and may eventually be a valuable tool for surgical planning of refractive and therapeutic procedures.question both in vivo and ex vivo, and by mathematical or finite‐element models of the cornea
Accommodative intraocular lens concepts
Authors: Eppig Timo 
Published: December 2019

AbstractThe restoration of accommodation still remains the biggest challenge of cataract surgery. The desire for real pseudophakic accommodation remains unchanged although modern multifocal lenses provide acceptable presbyopic correction and visual quality. Numerous concepts for accommodative intraocular lenses have been presented during the last decades but none of these were as successful as multifocal lenses are today. These concepts can be divided into three principles: Optic shift moves a single lens or a set of lenses along the optical axis such as the, for example, the 1CU (HumanOptics), the Crystalens (Bausch & Lomb) and the Synchrony (Visiogen/AMO). Varying radius of curvature changes refraction oft he lens such as, for example, the Juvene (LensGen). Replacement of the or refilling of the capular bag remains an interesting option but refilling has not reached the stage of human clinical trials. We will present an overview on the various concepts for the restoration of accommodation in the pseudophakic eye and the current clinical status.
Significance of ocular signs of monoclonal gammopathy
Authors: Szentmary Nora 
Published: December 2019

AbstractMonoclonal gammopathy of undetermined significance (MGUS), solitary bone plasmocytoma, Waldenström’s disease (macroglobulinaema) and asymptomatic or symptomatic multiple myeloma are all different stages of the same disease, all with monoclonal gammopathy. Up‐to date there are no data on ocular signs of monoclonal gammopathy , especially concerning corneal signs, in the literature.Our aim was to examine the ophthalmic signs of monoclonal gammopathy.Patients of the South‐Pest Hospital Center – National Institute for Infectology and Haematology, Department of Hematology and Stem Cell Transplantation, with monoclonal gammopathy, were enrolled in our study. Beside detailed ophthalmic and slit‐lamp examination, haematological history and blood counts were recorded and analysed.Fifty‐five patients were examined (17 male, 38 female, age 68±9.6 years). We observed corneal immunoglobulin deposition in 4 (7.28%), dry eye disease in 18 (32.75%), cataract in 28 (50.9%), epiretinal membrane in 4 (7.27%), glaucoma in 3 (5.45%), and a stage following central retinal artery occlusion in 1 patient (1.81%). 10 patients (20%) underwent cataract surgery prior enrollment, 7 of them (12,72%) had surgery on both eyes. Monoclonal gammopathy was related to IgG heavy chains in 41 (74.5%), IgA in 13 (23.5%) and IgM in 1 patient (1.81%) and concerning light chains, kappa‐chain was dominant in 35 (63.6%) and lambda in 20 patients (36.3%).Due to the relative high prevalence of dry eye disease and cataract in patients with monoclonal gammopathy, we recommend regular ophthalmological checkup of these patients. The occurrence of corneal deposits is relative uncommon (7,28%) in monoclonal gammopathy.
Pathogenesis of idiopathic epiretinal membrane
Authors: Kontou Evgenia 
Published: December 2019

AbstractTo describe the pathophysiological events involved in the formation and progression of epiretinal membranes (ERMs).Epidemiologic studies have found a clear relationship between ERM formation, ageing, and posterior vitreous detachment. Increased prevalence of ERM is noted in the population older than 60 years, with peak prevalence between 70 and 79 years. Histologic studies of surgically obtained ERM specimens identified cellular and extracellular matrix components. A key element in ERM formation and its progression toward a contractile membrane is the transdifferentiation of those cellular components toward myofibroblasts. ERMs stiffness is a result of the proportion between its collagenous and non‐collagenous elements. Additionally, modifications of membrane macromolecules, such as accumulation of advanced glycation end products, which constitutes an age‐related phenomenon, may increase stiffness of the membrane and contribute to the fibrotic process.Retinal membranes have been described for more than 150 years and comprise the most common type of fibrocellular proliferation found at the vitreoretinal interface. Although patients with ERM can be asymptomatic when the membrane is thin and translucent, its progression to a thick, and contractile membrane may result in macular distortion, inducing metamorphopsia and loss of visual function. Understanding disease pathogenesis is essential in order to develop appropriate therapeutic approaches.
OCT Angiography ‐ A new tool to assess vascular autoregulation in the retina
Authors: Garhöfer Gerhard 
Published: December 2019

AbstractVascular autoregulation is defined as the ability of a vascular bed to keep blood flow constant despite changes in ocular perfusion pressure. In the eye, the retinal circulation and also to a certain degree the choroidal circulation exhibit autoregulatory properties in response to changes in blood or intraocular pressure. Interestingly, it has been shown that these autoregulatory properties are compromised in ocular diseases such as glaucoma or diabetic retinopathy. New tools such as OCT angiography allow now for the investigation of vascular changes up to the microvascular level. The current talk will summaries how these new technologies can be used to get more insight in the complex regulation of blood flow in the eye.
Definition and diagnosis of Dry Eye Disease (DED)
Authors: Messmer Elisabeth M. 
Published: December 2019

AbstractAccording to the Dry Eye Workshop (DEWS) II report, Dry eye is defined as ‘a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles’. Diagnosing DED includes triaging questions, an analysis of risk factors, symptom evaluation using questionnaires, and diagnostic testing for homeostasis markers. These include non‐invasive tear film break up time for tear film stability, tear film osmolarity and ocular surface staining. For specific treatment recommendations, hyperevaporative DED and aqueous deficient DED must be differentiated by meibomian gland and tear lipid evaluation as well as tear volume assessment.
Novel therapies for Bestrophinopathies
Authors: Carr Amanda‐Jayne 
Published: December 2019

AbstractBestrophinopathies are a group of clinically distinct diseases caused by mutations in Bestrophin1 (BEST1). BEST1 is expressed exclusively in the retinal pigment epithelial (RPE) cells of the eye, where it functions as an ion channel. Mutations in the BEST1 gene affect the function of the RPE leading to the death of overlying retinal cells and subsequent vision loss.The dominant and recessive nature of Bestrophinopathies may necessitate different approaches to prevent or ameliorate these diseases. Potential therapeutic options for Bestrophinopathies focus on restoring correct gene expression, though viral gene therapy and gene editing, or by targeting nonsense mutations through translational readthrough‐inducing drugs. We are using induced pluripotent stem‐derived RPE created from patients with Bestrophinopathies to investigate these potential therapies in vitro.
Mutation in the mouse histone gene Hist2h3c1 leads to degeneration of the lens vesicle and severe microphthalmia
Authors: Graw Jochen 
Published: December 2019

AbstractDuring an ENU (N‐ethyl‐N‐nitrosourea) mutagenesis screen, we observed a dominant small‐eye mutant mouse with viable homozygotes (gene symbol Aey69). We determined linkage to mouse chromosome 3 between the markers D3Mit188 and D3Mit11; sequencing demonstrated a 358A‐>C mutation (Ile120Leu) in the Hist2h3c1 gene and a 71T‐>C (Val24Ala) mutation in the Gja8 gene. Analysis of eye development in the homozygous mutants documented an altered lens development starting from the lens vesicle stage including decreasing expression of crystallins and of lens‐specific transcription factors PITX3 and FOXE3. In contrast, we observed an early expression of retinal progenitor cells characterized by BRN3 and OTX2. These changes in the retina happen in parallel with apoptotic processes in the lens vesicle. The excessive retinal hyperproliferation is characterized by an increased level of Ki67. At postnatal stages, all principal retinal cell types are present, when the overgrowing retina fills the entire bulbus. Morpholino‐mediated knock‐down of the hist2h3ca1 gene in zebrafish leads to a specific perturbation of lens development. When injected into zebrafish zygotes, only the mutant mouse mRNA leads to severe malformations (cyclopia to microphthalmia). The wild‐type Hist2h3c1 mRNA can rescue the morpholino‐induced defects corroborating its specific function in lens development. The data highlight the importance of Hist2h3c1 (encoding a canonical H3.2 variant) in the formation of lens and retina.