bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly elastic epoxy cross‐linked collagen hydrogels for corneal tissue engineering
Authors: RAFAT M , KOH LB , ISLAM MM , LIEDBERG BO , GRIFFITH M 
Published: August 2012

AbstractPurpose Our objective is to develop novel materials that support the regeneration of diseased or damaged corneas. Despite the promising clinical results that we previously reported on biosynthetic corneas, more robust and elastic materials are required to withstand the adverse host conditions faced for high risk transplantation in severely damaged or diseased corneas. This presentation will provide details on an epoxy cross‐linked collagen‐based scaffold with enhanced mechanical properties.Methods We have developed a range of collagen‐based materials as mimics of the cell‐free corneal stromal extracellular matrix. In this study, cross‐linked polymer networks of collagen hydrogels were prepared using a hybrid of 1,4‐butanediol diglycidyl ether (BDDGE) and carbodiimides (e.g. EDC‐NHS) as cross‐linkers. Briefly, 10w/w% porcine collagen type I was mixed in a T‐piece system at various compositions and pH, e.g. pH 5, pH 11, and incorporated with laminin adhesive peptides (YIGSR, and IKVAV). Promising material formulations were tested for their physiochemical properties (e.g. mechanical, optical, water uptake, FTIR, and thermal degradation) and physiological properties (e.g. interactions with corneal cells, and biodegradation).Results The hybrid BDDGE hydrogels demonstrated improved mechanical properties and degree of cross‐linking while maintaining their optical clarity and biocompatibility compared to controls (e.g. EDC/NHS‐crosslinked hydrogels). Incorporation of laminin‐derived cell‐adhesive peptide (IKVAV) demonstrated significant increase in corneal cells (HCECs) proliferation compared to controls.Conclusion The hybrid BDDGE‐crosslinked collagen‐based hydrogels have the potential for use as tissue‐engineered corneal substitutes.
Intraocular administration of biodegradable microspheres to increase drug bioavailability and extend therapeutic effect
Authors: HERRERO‐VANRELL R 
Published: August 2012

AbstractPurpose Treatment of posterior segment diseases often requires repeated intravitreal injections to achieve and maintain steady state concentrations of the active substance in the target site. However, intraocular injections are associated to adverse effects and the risk of complications increases with the number of administrations. Biodegradable microspheres (MPs) are considered an alternative to multiple injections as they are able to release the encapsulated drug over weeks or months. Copolymers of lactic and glycolic acids (PLGA) are FDA approved biodegradable biomaterials commonly used to prepare MPs. They are biocompatible and degrade to metabolic products that are easily eliminated from the body. The main advantages of these systems is that they can be injected as a conventional suspension without surgical procedures. After intravitreal administration, PLGA microspheres suffer aggregation disappearing from the site of injection after delivering the drug. Microspheres can be loaded with different active substances (small molecules and biotechnological products) useful to treat vitreoretinal diseases. Administration of microparticles can be performed by periocular, intravitreal, sub‐ retinal, or other intraocular routes to treat posterior segment disorders.Conclusion PLGA microspheres are emerging therapeutic tools for the treatment of posterior segment diseases in which steady state concentrations of the active substance is needed over an extended period of time. Acknowledgements: PANOPTES‐Peptide‐based Nanoparticles as Ocular Drug Delivery Vehicles‐ collaborative project (FP7‐NMP‐2009); Spanish Ministry of Economy MAT 2010‐18242, UCM Research Group 920415 and RETICs (RD07/0062/2002)
Use of bevacizumab (anti‐VEGF treatment) in high‐risk corneal grafts
Authors: DEKARIS I , DRACA N , RATKOVIC M , PAUK M 
Published: August 2012

AbstractPurpose We evaluated the effect of bevacizumab treatment in a prospective 2 year follow‐up study of 50 [bdquo]high risk“ eyes undergoing penetrating keratoplasty (PKP).Methods Hihg‐risk diseases were: 2 Stevens Johnson syndrome (SJS), 6 chemical burns, 9 post‐herpetic, 16 other vascularized scars, 13 rejected grafts and 4 ulcers. PKP was performed in all 50 patients; combined with other procedures as follows: 12 “triple” procedures (PKP + cataract),11 PKP+ amniotic membrane transplantation (AMT),4 triple+AMT+ transplantation of limbal cells (LCAT). Subconjunctival injection of 25 mg/ml of bevacizumab was given to all patients at the end of surgery. Recipient corneal buttons were dissected into 3 corneal layers, stored in media for 24 hours at 37oC, and frozen till detection of VEGF quantity by immunoassay (ELISA). Corneal buttons from patients with non‐inflammatory diseases served as controls.Results Decrease of corneal neovascularization was observed in 88% of patients who received bevacizumab, and 86% of grafts remained clear. Mean best corrected visual acuity had statistically significant increase in all groups from 0.03 to 0.5, with the poorest visual outcome in SJS patients. Average postoperative astigmatism was ‐4,83 Dcyl. Average endothelial cell loss was 22.83% after one, and 31.97% after two years (similar in all groups). Secreted VEGF was significantly higher in high risk cases (2436.7 pg/ml) as compared to non‐inflamed corneas (504.7 pg/ml).Conclusion Combined “anti‐inflammatory“approach of AMT, LCAT and bevacizumab may significantly improve corneal graft survival rate in [bdquo]high‐risk“ eyes.
Stem cell culture for limbal deficiency
Authors: BORDERIE V 
Published: August 2012

AbstractPurpose Cultured stem cell transplantation is a new promising technology for eye diseases associated with destruction, dysfunction, or genetic abnormalities of ocular stem cells. The first group of ocular diseases targeted is limbal stem cell deficiency. Various ocular disorders, including ocular burns, Stevens‐Johnson syndrome, cicatricial ocular pemphigoid, severe infectious keratitis, contact lens‐induced keratopathy, multiple surgical procedures involving the limbal region, aniridia, congenital erythrokerato‐dermia, and keratitis associated with multiple endocrine deficiencies, may induce limbal deficiency.Methods Various culture techniques have been developed that can be classified according to the type of stem cells (limbal epithelium or oral mucosal epithelium), the source of stem cells (autologous or allogeneic), the type of culture (explants or dissociated cells, feeders or no feeders), the carrier used to grow cells (amniotic membrane, fibrin, temperature‐responsive plastic), and culture media. Eye banks are often involved in the preparation of these cell therapy products.Results Prospective clinical trials have shown that transplantation of cultured epithelial stem cells improves the ocular surface condition of patients with limbal deficiency with a high success rate, especially when autologous limbal stem cells can be used as the source of cultured cells.Conclusion However, many issues are still to be investigated. Among them, selection and screening of donor tissue, microbiological safety of stem cell production process, safety of transplantation of cells cultured with products or feeder cells from animal origin, choice of the best technology to be used for growing stem cells, evaluation of the cell therapy product before transplantation, definition of success after transplantation.
Pan‐endothelial viability assessment with the triple HEC staining of organ cultured precut DSAEK vs full thickness corneas
Authors: CAMPOLMI N , HE Z , GAIN P , MURAINE M , TOUBEAU D , PIPPARELLI A , ACQUART S , GARRAUD O , PISELLI S , DUMOLLARD JM , PEOC'H M , THURET G 
Published: August 2012

AbstractPurpose To assess the viable endothelial cell density (vECD) of posterior lamellar grafts, stored in organ culture, precut by eye bank technicians, and sent to a distant center.Methods Paired corneas with an ECD >2200 cells/mm2 at the standard assessment with the SambaCornea analyser (TribVn, France), were stored in CorneaMax (Eurobio, France) and deswelled in CorneaJet (5% Dextran T500) for 6 to 24 hours prior to pre‐cutting. They were randomly assigned as full‐thickness grafts or as precut posterior transplants for DSAEK using a microkeratome with a 350μm head (Moria, France). Corneas were sent to a distant center where the vECD was assessed by using the triple Hoechst/Ethidium/Calcein (HEC) staining and ﬂuorescent image analysis of the entire posterior surface: calculation of the area covered by living cells (H+/C+/E‐) coupled with counting of nuclei in large areas allowed to determine the vECD, i.e. the useful cell pool (Pipparelli. IOVS 2011.52:6018). DSAEK and controls data were compared with non‐parametric tests.Results In both groups, the vECD was lower than the standard ECD determined by the eye bank (for 20±7% for full thickness grafts, 34±16% for DSAEK), because living cells never completely covered the entire posterior surface. vECD were respectively of 2006+/‐349 vs 1661+/‐464 (P=0.075).Conclusion The HEC triple staining combined with image analysis provides a unique accurate assessment of the endothelial quality by giving the vECD. This laboratory technique allows a reliable assessment of the endothelial quality of tissues supplied to surgeons, precut or not. It can also be used to assess any methods liable to modify EC.
Worldwide Eye Banking (WEB) project: international survey of demand and supply
Authors: JULIENNE R , ALDOSSARY M , NEFZAOUI C , HE Z , HA THI BM , CAMPOLMI N , THURET G , GAIN P 
Published: August 2012

AbstractPurpose The whole eye banking (EB) process, from corneal retrieval to surgery, is improving. Paradoxically, corneal blindness worldwide is still increasing. Supply seems lagging far behind global demand but only partial data of the worldwide situation is available. We therefore launched an international survey on the balance of demand and supply, called the “Worldwide Eye Banking” (WEB)‐project. Our goal is to identify suitable solutions in countries willing to improve their corneal supplyMethods Descriptive epidemiological worldwide transversal study. A questionnaire was designed and e‐mailed to EB staff and ophthalmologists involved in corneal grafts using mailing lists from local and international ophthalmological societies or by face to face interview during international ophthalmology, eye research or EB congressesResults Significant disparities were highlighted. Developed countries tended to satisfy corneal demand. EBs in the United‐States use short term storage and are exporters, while Europeans use long‐term organoculture and nearly satisfy local demand. Keratoplasty indications have 2 profiles: infections, mainly trachoma, for developing countries and keratoconus, endothelial dystrophy or iatrogenic edema in developed countriesConclusion This demand/supply disparity, at this stage of the study (ongoing), is severe in most developing countries. Decreasing demand requires: 1) Trachoma fight in endemic zones, 2) Iatrogenic edema prevention. Increasing supply requires: 1) Corneal donation politic dynamism, 2) Local eye banking implantation in each country, 3) Optimizing storage technique for better efficiency (retrieved/delivered graft ratio), 4) Bioengineering of endothelial graft
Light microscopy of the corneal pathologies that we meet in our daily practice as an eye banker
Authors: JIRSOVA K 
Published: August 2012

AbstractPurpose Organ culture is the method of choice for the preservation of a human donor cornea for transplantation throughout Europe. This method is often closely connected with the assessment of the cornea using light microscopy. The corneal endothelium, its polymeghatism, pleomorphism, cornea guttata and other endothelial abnormalities as well as epithelial and stromal pathologies will be presented to show the usefulness of light microscopy in the evaluation of corneal pathologies.Methods Photographs from light microscopy (both phase contrast and bright field) taken before and after corneal storage in organ culture will be compared and discussed in relation to changes in endothelial morphology and the swelling of the intercellular spaces. The individual corneal layers (the corneal epithelium, the stroma and the endothelium) of pathological corneas will be compared to those of control corneas.Results Among corneal pathologies, cornea guttata, corneal dystrophies (Fuchs endothelial corneal dystrophy, posterior polymorphous corneal dystrophy) and crystalline keratopathy will be shown using pathological explants. Moreover, the corneal pathologies will be correlated with histological findings. Finally, bacterial and fungal contamination of the cornea during organ culture will be shown.Conclusion Light microscopy is an essential part of qualitative and quantitative corneal assessment, which allows corneas with a variety of pathologies, mostly endothelial in origin, to be excluded from grafting. This work was supported by the project PRVOUK‐P24LF13 of Charles University in Prague.
Appraisal of choroiditis in birdshot retinochoroiditis is essential and only possible using indocyanine green angiography
Authors: HERBORT CP , PAPADIA M 
Published: August 2012

AbstractPurpose Birdshot retinochoroiditis (BRC) belongs to the group of stromal choroiditis entities including also VKH disease. In contrast to VKH where the origin of inflammation is limited to tha choroid, inflammation starts both in the choroid and the retina in BRC.Without indocyanine green angiography (ICGA), global appraisal of BRC is not possible as choroidal inflammation cannot be detected nor followed. The aim here was to analyze the practical contribution of ICGA to the management of BRC.Methods Charts of patients with the diagnosis of BRC seen in the Centre for Ophthalmic Specialised Care (COS), Lausanne, Switzerland from 1995‐2011 were reviewed. Standard fluorescein‐ICGA work‐up was performed at presentation and during follow‐up. Diagnostic and monitoring contribution of ICGA was analyzed.Results In a collective of 1268 patients seen from 1995‐2011 at the COS, 25 patients (2.0%) were diagnosed as BRC. 19 had sufficient data to be included in the study. Mean age was 49 years, HLA‐A29 positivity was 100% and follow‐up was 112 months. IGA contribution was twofold; (1) Early diagnosis could not have been without ICGA in 3/19 patients a proportion that increased to 3/7 (43%) if only considering patients with early stage disease at entry. (2) ICGA further showed that choroidal disease responded well to therapy and stayed under control as long as therapy was continued.Conclusion ICGA was found to be essential for early diagnosis of BRC, an element that is crucial as early therapy is crucial in the control of disease. ICGA further allowed to monitor choroidal disease showing a good response in contrast to retinal disease. Hence global appraisal is needed for BRC and is not possible without ICGA.
Voclosporin: newer analyses of a randomized, controlled trial for noninfectious uveitis
Authors: BODAGHI B , LUMINATE INVESTIGATOR GROUP  
Published: August 2012

AbstractPurpose To provide an overview of the voclosporin clinical development program for noninfectious uveitis involving the posterior segment.Methods Two trials, LX211‐01 (active uveitis) and LX211‐02 (clinically controlled, quiescent uveitis), were conducted for noninfectious uveitis involving the posterior segment. All trials were dose‐ranging and double‐masked. Study LX211‐01 enrolled 218 patients with active, posterior segment uveitis. The co‐primary efficacy endpoints were mean change from baseline in vitreous haze (VH) score after 16 and 24 weeks of therapy or at time of rescue, if earlier. Study LX211‐02 enrolled 232 patients with clinically quiescent posterior segment uveitis. The primary endpoint for this study was the proportion of patients who experienced an inflammatory exacerbation.Results In Study LX211‐01, the voclosporin 0.4 mg/kg group BID demonstrated statistically significant differences from placebo in the co‐primary endpoints, Week 16 and Week 24 (p=0.008 at 16 weeks, p=0.027 at 24 weeks). Analyses of important subpopulations, support the effect of voclosporin on severe uveitis. In Study LX211‐02, voclosporin 0.4 mg/kg BID reduced the rate of recurrence of inflammatory exacerbation in patients with quiescent disease by up to 50% over a 26‐week period.Conclusion In Study LX211‐01, clinically meaningful reduction in vitreous haze with strong statistical significance was observed. The response to treatment with voclosporin was early and sustained. In Study LX211‐02, there was an up to 50% reduction vs. control in inflammatory exacerbation recurrence rate. Voclosporin safety is consistent with the class and is manageable with routine monitoring.
Commercial interest
Genotype‐phenotype correlations in Stargardt disease/ABCA4‐related retinopathy
Authors: HOLDER GE , FUJINAMI K , ROBSON AG , WEBSTER AR , MICHAELIDES M 
Published: August 2012

AbstractPurpose To investigate genotype‐phenotype correlations in patients with Stargardt Disease (STGD) / ABCA4‐related retinopathyMethods 195 patients diagnosed with STGD and harbouring ABCA4 variants were recruited. A detailed clinical history and examination were undertaken. Pattern and full‐field ERGs (PERG; ERG) were used to classify 175 patients into three groups (Lois et al. 1999); dysfunction confined to the macula; macular and cone ERG abnormality; and macular and both cone and rod abnormality. Patients were also grouped by genotype: G1 ‐ two null variants (N=9); G2 ‐ at least one null variant with or without missense variants (67); G 3 ‐ at least two missense variants (50); G 4 ‐ one missense variant (69).Results All G1 patients had a group 3 ERG. 26/58 G2 were in ERG group 1; 26/58 in Group 3. 24/47 G3 patients were ERG group 1; 7/47 group 2; and 16/47 in ERG group 3. 31/61 G4 patients were in ERG group 1; 5 in group 2; and 25/61 in group 3. Significant clinical differences were also observed between the genotypes.Conclusion Patients with two null ABCA4 variants had the most severe phenotype. In comparison, patients with two or more missense variants had a more variable phenotype and included many with normal full‐field ERGs. This large survey confirms previous suggestions based on smaller cohorts and individual families.
Recovery of the ERG from very low SNR recordings using a robust frequency domain approach: an Internet open source implementation
Authors: FISHER A , ELEUTERI A , TEYMOURI R , HAGAN RP 
Published: August 2012

AbstractPurpose To present a statistically robust method of estimating the transient electroretinogram (ERG) in extremely poor recordings (very low SNR) contaminated by continuous noise (electrode noise, EMG, exogenous electrical interference) and discontinuous noise (eye‐movements and blinks). The transient ERG (ERG) is estimated by ensemble averaging with standard errors and p value, derived by either Magnitude Square Coherence or Bootstrap Resampling. However, both techniques are susceptible to noise. A robust estimator noise is required.Methods A series of ERG’s was recorded in normal subjects, containing numbers of prescribed eye movements and blinks. AR models were derived using the Burg algorithm over a range of explicit SNR’s. The ERG record was recovered as its Fourier Series representation over 9 harmonics. p values were derived for all estimates. An Excel implementation is presented which accesses remote Internet resources using MatSOAP©.Results The robust estimator was validated in Monte Carlo realisations of the AR model with expected high levels of performance for amplitudes and p values. In estimations in the raw data sets, high levels of statistical agreement were achieved for each subject across no‐noise:noise series. The recovery by ensemble averaging performed poorly.Conclusion The robust estimation in the ERG as presented here is novel and offers an important advance in clinical ERG measurement. The complexity is hidden from the User by providing a familiar Excel© spreadsheet interface.
Mechanisms & recovery of vitamin A deficiency
Authors: LEROY BP , DE ZAEYTIJD J , DE LOOZE D , DELANGHE J , KESTELYN P 
Published: August 2012

AbstractPurpose To illustrate different mechanisms which lead to vitamin A deficiency and result in retinal dysfunction. To show how a diagnosis can be made, and how, and to which degree, in such cases, retinal function can be recovered.Methods A case presentation format will be used to illustrate different mechanisms of retinal dysfunctions due to vitamin A deficiency. Patient history taking, clinical and electrophysiological phenotypes and therapeutic approaches will be addressed.Results Mechanisms of vitamin A deficiency are very different, but all have fat malabsorption in common. Often, other concomitant vitamin deficiencies exist. With vitamin A repletion therapy, either partial or complete restoration of retinal function can be attained.Conclusion Causes of vitamin A deficiency are very diverse. Thorough history taking, in combination with an extensive clinical examination and psychophysical and electrophysiological tests, most often allows making a more specific diagnosis of an underlying malabsorption. Vitamin A repletion therapy is effective in such cases.
Spherical aberration and binocularity
Authors: VANDERMEER G , NOCHEZ Y , GICQUEL JJ , LEGRAS R , PISELLA PJ 
Published: August 2012

AbstractPurpose To evaluate the effect of different combinations of spherical (SA4) and secondary spherical (SA6) aberration on each eye on binocular subjective quality of vision.Methods A numerical eye model was used to generate images (ie three 0.4 logMAR high contrast letters) viewed through a 4.7mm pupil diameter and degraded by various spherical aberrations (SA4‐0.4μm, SA4+0.4μm, SA4‐0.4μm and SA6+0.2μm, SA4+0.4μm and SA6‐0.2μm). Binocular vision was simulated using a 3D‐NVIDIA video system projecting different image on each eye. Through‐focus quality of vision was evaluated using a grading scale (ITU‐R 500 recommendation) by three subjects under monocular and binocular condition for each tested conditions (ie various combination of the five aberration profiles).Results Binocular through‐focus curve followed the best monocular curve. Binocular inhibition was obtained if subjective image quality was too different between the two eyes. We rarely measured binocular summation in term of subjective quality of vision. Ocular dominance seemed to affect the level of inhibition: binocular inhibition was limited when the dominant eye saw the best image. Area under the binocular curve (ie a way to evaluate subjective depth‐of‐focus) measured for a fair or higher image quality was increased with all combinations compared to naked eye because of the summation of the two best monocular curves. The greatest increase was obtained with reverse profile of SA4 and SA6 between each eye (ie SA4‐0.4μm and SA6+0.2μm on one eye and SA4+0.4μm and SA6‐0.2μm on the other eye).Conclusion The use of different spherical aberration on each eye leads to a better binocular through‐focus curve especially with combination of opposite sign of SA4 and SA6. However there is no binocular summation of vision quality.