bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravitreal aflibercept (IVT‐AFL) for macular edema secondary to CRVO: Results of COPERNICUS and GALILEO studies
Authors: CREUZOT C 
Published: November 2013

AbstractPurpose Evaluate efficacy and safety of IVT‐AFL for treatment of macular edema due to CRVO.Methods Patients randomized to IVT‐AFL 2‐mg (IVT‐AFL 2q4) or sham monthly for 24 weeks. COPERNICUS: all patients received IVT‐AFL PRN from week 24‐100 (IVT‐AFL 2q4PRN and shamIVT‐AFL PRN). GALILEO: IVT‐AFL PRN was administered to IVT‐AFL group from week 24‐76 and sham group from week 52‐76.Results Proportion of IVT‐AFL 2q4PRN and shamIVT‐AFL PRN patients gaining ≥15 letters was 56.1% vs 12.3% and 49.1% vs 23.3%, respectively, at week 24 and 100 (COPERNICUS) and 60.2% vs 22.1% and 57.3% vs 29.4%, respectively, at week 24 and 76 (GALILEO; all P<0.01). Mean change in BCVA was +17.3 vs ‐4.0 (P<0.0001) and +13.0 vs +1.5 ETDRS letters (P=0.007) at week 24 and 100 (COPERNICUS) and +18.0 vs +3.3 (P<0.001) and +13.7 vs +6.2 letters (P=0.007) at week 24 and 76 (GALILEO) in IVT‐AFL 2q4PRN and shamIVT‐AFL PRN groups, respectively. Mean reduction from baseline CRT was 457.2 vs 144.8 µm (P<0.001) and 390.0 vs 343.3 µm at week 24 and 100 in COPERNICUS and 448.6 vs 169.3 µm (P<0.0001) and 389.4 vs 306.4 µm at week 24 and 76 in GALILEO in IVT‐AFL 2q4PRN and shamIVT‐AFL PRN groups, respectively. Most frequent ocular SAEs in IVT‐AFL 2q4PRN group were cataract (COPERNICUS) and macular edema (GALILEO). APTC ATEs occurred only in COPERNICUS (2 (1.8%) IVT‐AFL, 2 (2.7%) sham).Conclusion IVT‐AFL treatment resulted in early, sustained VA gains. Maintenance of VA gains with an extended treatment interval after initial monthly dosing depended on monthly monitoring. Long‐term fixed dosing regimens may be a better treatment paradigm.
Commercial interest
Biomaterials in ophthalmic applications ‐ IOL´s and keratoprosthesis
Authors: STORSBERG J , SCHMIDT C , DUNCKER G , SCHRAGE N , SEL S 
Published: November 2013

AbstractBiomaterials can be regarded as synthetic or non‐living native materials used in therapeutic approaches. This direct contact with body tissue manifests itself in a wide spectrum of chemical, physical and biochemical interactions. In ophthalmology, biomaterials find their application in the development of intraocular lenses (IOL´s) and keratoprosthesis. The chemical nature of these materials encompasses the full spectrum of physico‐chemical properties of matter, e.g. hydrophilic and hydrophobic poly(meth)acrylates, silicones and fluorinated polymers. Concordantly, the intended use and functionality of the implant necessitates the strict selection of the desired chemical and physical characteristics of the materials to be used, if not the de‐novo creation of suitable substances. In addition, modification of surfaces or the creation of gradual changes in material properties by co‐polymerizations or alternative means of tailoring peculiar aspects of the device may be required to achieve reasonable or functional substitution of the diseased tissue, all the while maintaining ease of the device’s usage by the caring physician and, above all, uncompromised patient’s safety in the intended use of the device throughout its lifecycle.
Immunomodulatory effects of gene therapy in composite corneal grafts
Authors: PASTAK M , SINGER BB , SCHWARTZKOPFF J , SABAN D , CZUGALA M , DANA R , STEUHL KP , ERGüN S , FUCHSLUGER TA 
Published: November 2013

AbstractCorneal allografts overexpressing anti‐apoptotic protein p35 in BALB/c mice have shown significantly reduced delayed‐type hypersensitivity. However, the precise mechanisms responsible for altered immune response have been unclear. Based on previous data, we hypothesized that expression of p35 in corneal epithelium reduces the priming of T lymphocytes in draining lymph nodes after transplantation. In our results, mixed lymphocyte reaction with C57BL/6 splenocytes revealed statistically decreased frequency of CD4+ T cells in allograft group treated with p35 compared to other allogeneic groups. These findings provide new immunological insights on priming of T cells modified by genetically treated composite allograft to improve transplant survival.
Current available platforms for femtosecond laser cataract surgery
Authors: ALVAREZ DE TOLEDO J , BARRAQUER RI , NAGY Z 
Published: November 2013

AbstractDifferent femtosecond laser platforms are nowadays available. Main differences as the particular approaches in anterior segment imaging techniques to focus the laser pulses precisely, interface designs to efficiently and safely dock the patient´s eye and software options in each platform will be presented and discussed.
Proven advantages of femtosecond laser cataract surgery
Authors: NAGY Z 
Published: November 2013

AbstractResults with femtosecond laser cataract surgery especially with premium lenses (multifocal and accomodative lenses) will be presented. In peer‐reviewed articles was shown the superior results with better posterior chamber lens position, less PCO formation, more favorable results with postoperative higher order aberrations and vision quality will be discussed. The method also useful after ocular trauma, in eyes with loose zonules, in PEX syndrome, in white tumescent cataract and possibly in pediatric cataract. These result will be presented during the course.
Filamentary keratitis epidemiology
Authors: PRONKIN I , MAYCHUK D , VASILJEVA O 
Published: November 2013

AbstractPurpose To analyze concomitant pathology contributing to filamentary keratitis.Methods We examined 38 patients (76 eyes) with filamentary keratitis. All of them were consulted by co‐specialists (internist, endocrinologist, reumatologist) with the object to reveal concomitant diseases. The treatment regimen included keratoprotectors, artificial tears, 0,1% dexamethasone, 0,05% cyclosporine. Besides, in case of decompensated concomitant disease patients were treated by appropriate specialist. Among investigative methods were: biomicroscopy, Shirmer test – 1, TBUT‐test. Follow‐up period was 3‐5 months.Results Among concomitant pathology we revealed:  Thyroid gland disfunction (hypothireosis) – 34,2 %  Rheumatoid arthritis – 21,1 %  Sjögren's Syndrome – 2,6 %  Diabetes mellitus of 2nd type – 7,9 %  Combination of rheumatoid arthritis and thyroid gland dysfunction (nodes against a background of euthyreosis) – 10,5 %  Combination of diabetes mellitus of 2nd type and thyroid gland dysfunction – 13,2 %  Neither endocrine nor rheumatoid diseases revealed – 10,5 %. Among them 1 patient after previous PRK. Shirmer test – 1 results were variable and no appropriateness with treatment regimen was found. TBUT‐test data before treatment were low (6‐9 sec.) with an increase up to 9‐11 sec. after the treatment.Conclusion 89,5 % of patients had endocrine pathology or rheumatoid diseases or their combination. With this in view, we may consider filamentary keratitis not as a form of severe dry eye syndrome, but as a separate dystrophic corneal disorder with dry eye as its symptom.
Quercetin counteracts the cellular damage caused by HNE and inhibits inflammation in ARPE‐19 cells
Authors: HYTTI M , PIIPPO N , SALMINEN A , KAARNIRANTA K , KAUPPINEN A 
Published: November 2013

AbstractPurpose Age‐related macular degeneration(AMD) is the leading cause of blindness in the western world. And despite extensive research many questions about disease progression and formation still remain unanswered. One of the driving factors of AMD is a chronic inflammatory process, stimulated by life‐long exposure to light and oxidative stress. In the current study we try to evaluate the anti‐inflammatory properties of Quercetin, a plant derived polyphenol, and to determine the pathways by which it inhibits inflammation.Methods Cultured ARPE‐19 cells were treated with the lipid peroxidation endproduct 4‐Hydroxynonenal (HNE) to induce an inflammatory response. Quercetin was added 1 hour after stimulation with HNE to assess its power to suppress an already activated inflammatory response. The effects of the treatment on intracellular inflammation were measured with ELISA and quantitative Real‐Time PCR. Cell viability was assessed using the lactate dehydrogenase (LDH)‐assay.Results Our results show that Quercetin decreased the levels of the pro‐inflammatory cytokines MCP‐1 and IL‐8. It also protected the cells from HNE‐induced toxicity, as was evidenced by a decrease in LDH levels. Quercetin lowered the levels of mitogen‐activated protein kinase (MAP) p38 and of phospho‐CREB but did not affect the levels of NF‐κB or the DNA binding efficacy of its subunit p65.Conclusion Our results show that Quercetin can reduce the inflammatory response in retinal pigment epithelial cells by down regulating the MAPK pathway and decreasing the phosphorylation of CREB. Furthermore it is able to protect cells from death induced by oxidative stress. Quercetin may, therefore, be a valuable tool in the therapy of inflammation in AMD.
In vivo toxicity evaluation of mannitol included in freezed dry PEA‐III microparticles
Authors: ROJAS B , DE HOZ R , SALAZAR JJ , RAMíREZ AI , GALLEGO BI , TRIVIñO A , ANDRéS‐GUERRERO V , HERRERO‐VANRELL R , RAMíREZ JM 
Published: November 2013

AbstractPurpose To analyze short term toxicity of the mannitol included (3,375 µg; 0,225%) in an unilateral single intravitreal (ITV) injection (1.5µl) of freezed dry polyester amide (PEA) microparticles (“MPs”).Methods SD rats were divided into: G1: ITV Mannitol plus BSS; G2: ITV BSS; G3: Aged‐matched control. Clinical examination and animal sacrifice were performed 24 hours, 3 and 7 days post‐injection (PI). Tissue sections were processed for H&E and immunofluorescence with antibodies against GFAP, Iba‐1 and MHC class II.Results No clinical signs of inflammation were observed at any time point of the study. H&E: The conjunctiva in G1 and G2 had an inflammatory infiltrate that peaked at 24 hours and decreased by day 3. On day 7, tissues looked as aged‐matched control. In both groups, some inflammatory cells were found in the vitreous 24h and 3 days PI, the latter being more intense in G1. Immunostaining: the reactivity of astrocytes and Müller cells in G1 was higher than in G2 up to day 3. In day 7 PI, there was a mild and sectorial reaction of Müller cells in G1. Microglia in G1 and G2 showed morphological signs of activation 24h and 3 days PI, the reaction being stronger in G1. On day 7 PI: i) all microglia in G2 and the microglia in the outer retina in G1 looked like control; ii) the microglia in the inner retina showed signs of activation in G1. No MHC‐II upregulation was found in either group.Conclusion Intravitreal injection of 1.5µL of mannitol (3,375 µg; 0,225%) induces changes in the glial cells of SD rat retina that should be taken into account in biocompatibility assays after intravitreal injections of mannitol freezed dry microparticles.
Assessment of polyesteramide of PEA Microparticles for in vivo intraocular injections
Authors: DE HOZ R , ROJAS B , RAMíREZ AI , SALAZAR JJ , GALLEGO BI , TRIVIñO A , ANDRéS‐GUERRERO V , HERRERO‐VANRELL R , MIHOV G , DIAS A , ZONG M , RAMíREZ JM 
Published: November 2013

AbstractPurpose To analyze polyesteramide (PEA) microparticles (“MPs”) interaction with reagents used in histological analysis and their compatibility with the steps required for ocular injection.Methods Unloaded‐ and dye‐loaded (Chromoionophore II) PEA III MPs suspended in PBS/mannitol were: i) analyzed under light and fluorescence optic microscopy; ii) exposed to reagents, solutions and processes required to perform histological procedures; iii) released through different needle gauges and quantified in a Neubauer chamber. Rat eyes were divided into two groups: intravitreal injection (n= 20) and subtenon/subconjuntival injection (n=24). After sacrifice, tissues were processed as retinal whole‐mount and cryosections.Results i) PEA III MPs were stable when contacted with distilled water, PBS, 4% PF and 2% glutaraldehyde; ii) PEA III MPs lost shape or dissolved when in contact with Xylene, EtOH or acetone; iii) freezing at ‐20ºC and heating at 60ºC does not impact particles re‐dispersion, shape and polydispersity; iv) no significant differences in MPs number released through different needle gauges (25G, 27G, 30G, 32G) were found; v) in unstained tissues, MPs preserved their morphological characteristics and coalesced into depots.Conclusion MPs: i) are compatible with some of the steps required for routine histological processing. ii) can be released through needle gauges used in human clinical setting; iii) the injection should be done during the 30 minutes following suspension preparation.
Aquaporin expression in the human retinal pigmented epithelial cell line ARPE‐19
Authors: SALIK D , MOTULSKY E , PERRET J , CASPERS L , DELPORTE C , WILLERMAIN F 
Published: November 2013

AbstractPurpose Aquaporins (AQPs) are a family of transmembrane channel proteins permeable to water. They are likely to play an essential role in the outer blood retinal barrier allowing passive water transport through the retinal pigmented epithelium (RPE). The identification of AQPs expressed in the RPE could contribute to a better understanding of the development of macular edema in several eye diseases such as diabetic retinopathy. However, the type of AQPs expressed by the RPE is currently a subject of controversy.Methods We investigated the expression of AQPs in the human RPE cell line ARPE‐19, a model of human RPE. First, AQPs mRNA expression was determined by quantitative real‐time PCR (qRT‐PCR). Furthermore, protein expression was analyzed by both immunofluorescence (IF) and Western blot (WB).Results The mRNA of AQP1, AQP4, AQP6 and AQP11 were expressed in ARPE‐19 cells. However, the expression of AQP3, AQP4, AQP6, AQP7, AQP8, AQP9, AQP11 and AQP12 were found by IF. Finally, the expression of AQP4 and AQP6 was found by WB.Conclusion In conclusion, several AQPs were detected both at the mRNA and at the protein level in ARPE‐19 cells and may account for water movement in those cells.
Effect of systemic hyperoxia on retinal oxygen saturation
Authors: TOLD R , PALKOVITS S , BOLTZ A , NAPORA KJ , SCHMIDL D , GARHöFER G , SCHMETTERER L 
Published: November 2013

AbstractPurpose Several groups have reported that 100% oxygen breathing caused an increase in retinal venous oxygen saturation. In the present study we set out to study the effects of 100% oxygen breathing on retinal blood flow and retinal oxygen saturation to gain more insight into the regulation of retinal oxygenation.Methods 30 healthy volunteers were included into the present study. The effect of 100% oxygen breathing on retinal blood velocities was performed using laser Doppler velocimetry (LDV). Retinal vessel diameters were measured with the Dynamic Vessel Analyzer (DVA, Imedos, Germany). Retinal oxygen saturation was evaluated in retinal arteries and retinal veins using spectroscopy also employing the DVA. The effect of 100% oxygen breathing on systemic oxygen tension was evaluated based on arterialized blood samples drawn from the earlobe.Results Breathing 100% oxygen caused systemic hyperoxia as evidenced from a pronounced increase in systemic oxygen tension (p < 0.001). Oxygen saturation increased in both retinal arteries and retinal veins (p < 0.05 each) but the effect in veins was more pronounced. As expected we observed a decrease in retinal vessel diameters, retinal blood velocities as well as in retinal blood flow (p < 0.001 each).Conclusion The results are compatible with the idea that increased venous oxygen saturation during 100% oxygen breathing is due to a pronounced decrease in retinal blood flow. In addition, our data indicate unchanged retinal oxygen extraction during hyperoxia.
IL18 does not reduce choroidal neovascularization and causes retinal dysfunction in mice
Authors: YASUMA T , HIRANO Y , KIM Y , YASUMA R , FOWLER B , CARVALHO A , GELFAND B , AMBATI J 
Published: November 2013

AbstractPurpose It was reported that intravitreous administration anti‐mouse IL18 antibody increases the size of laser‐induced choroidal neovascularization (CNV) lesions in mice (Doyle et al. Nat Med 2012). IL‐18 administration was therefore proposed as a potential therapeutic for CNV, although this hypothesis was never directly tested. Here, we determined the effect of IL‐18 injection on laser CNV in mice, and also show for the first time that IL‐18 is toxic to retinal function.Methods Laser photocoagulations were performed to perforate Bruch’s membrane followed by intravitreous injections of recombinant IL‐18 (rIL‐18) or PBS, and the eyes were collected and analyzed on the day 7 after laser treatment. Laser‐induced CNV lesions stained with isolectin B4 were imaged by a confocal microscope system (Leica). Mice receiving rIL‐18 or PBS were subjected to electroretinography 7 days after sub‐retinal injection. RPE flat mounts of rIL‐18 or PBS treated wild type, Fas‐/‐, and FasL‐/‐ mice were stained for intercellular junctions.Results Average CNV volume was not different in eyes treated with recombinant IL‐18 compared to vehicle treated. Wild‐type mice receiving rIL‐18 had RPE degeneration, but the degeneration did not occur in Fas or FasL knockout mice. We also injected plasmids coding pro‐IL‐18 and mature IL‐18, and found mature IL‐18 didn't change CNV volume but caused degeneration. Wild type mice receiving rIL‐18 injections showed lower amplitude in electroretinography compared to vehicle injected eyes.Conclusion IL‐18 injections did not reduce CNV. Also, IL‐18 administration induced RPE degeneration via a Fas/Fas ligand‐dependent pathway.
Ocular and systemic distribution of MRZ‐99030 in pigmented mouse, rat, rabbit and non‐human primate by quantitative tissue analysis
Authors: STRUBLE C , PRESCOTT E , KLEIN KU , WEGENER N 
Published: November 2013

AbstractPurpose The ocular tissue distribution and systemic pharmacokinetics of MRZ‐99030 was determined after single or repeated topical ocular dose regimens of MRZ‐99030 to pigmented mice, rats, rabbits, and non‐human primates. MRZ‐99030, an amyloid‐β aggregation modulator, is currently under development for the treatment of glaucoma and AMD, which are the leading causes of blindness and represent diseases with high unmet medical need.Methods Dutch Belted rabbits, Cynomolgus monkeys, Dark Agouti rats, and C57/BL6 mice received single or repeated bilateral topical ocular doses of MRZ‐99030. Ocular tissues and plasma were collected up to 24h after dosing and analyzed for MRZ‐99030 by liquid chromatography‐mass spectrometry (LC‐MS).Results MRZ‐99030 was readily absorbed into ocular tissues for all species with highest concentrations observed in the cornea and conjunctiva. MRZ‐99030 was also found in the ocular tissues of the posterior segment (choroid with RPE and retina) at all time points. Pharmacokinetics show MRZ‐99030 in all tissues and systemically, with elimination half‐lives that indicate somewhat sustained concentrations in melanin containing tissues. Concentrations in ocular tissues, in particular for the retina, increase with an increase in dose level (mouse and rat) and dose frequency (all species).Conclusion The results show that MRZ‐99030 is absorbed into the ocular tissues in all species following topical administration and is readily distributed to the posterior segment of the eye, including the retina. Therefore, this finding strongly supports that MRZ‐99030 is able to modulate the Aß aggregation in the target tissue of glaucoma and AMD.
Late results of sclera reconstructive surgery aimed at preventing the progression of myopic macular dystrophies
Authors: MARKOSSIAN G , TARUTTA E , IOMDINA E , KRUZHKOVA G 
Published: November 2013

AbstractPurpose To assess the long‐term efficiency of scleroplasty performed using a simplified technique of buckling the posterior pole in patients with congenital myopia complicated by macular dystrophy and posterior staphyloma of the scleraMethods The surgery was performed according to Snyder–Thompson technique in which the buckle made of a biologically active synthetic graft was sutured using a simplified technique of its localization at the posterior pole. 42 surgeries were administered to 34 patients aged 13–43 with myopia of –11.5 to –31.0 D. The shape and stage of staphyloma was determined by ultrasound scanning or with an ophthalmoscope. The follow‐up period reached 3‐8 yrs (4.2±1.3 yrs).Results Next day after surgery, flattening of the staphyloma can be seen on B‐scan. The axial length becomes 1.0‐2.0 mm shorter, the acoustic density of the posterior pole of the sclera increases by 5.3 dB, visual acuity shows a 0.1‐0.3 growth, while the refraction is 1.5‐2.5 D lower. The late follow‐up results (6‐8 years) demonstrated myopia stabilization in 90.2% of cases. Myopia progression rate turned out to be half as slow as prior to the surgery, and B‐scan showed a sustainable flattening of the staphyloma. Over the whole observation period, no new pathological processes emerged in the macular area, while no existing pathological processes showed progressionConclusion Scleroplastic surgery combined with posterior pole bucking with a biologically active synthetic graft should be recommended for the treatment of high complicated myopia, the prevention of staphyloma progression, myopic macular dystrophies and vitreomacular traction syndrome.
Evaluation of choroidal thickness depending on the stage of diabetic retinopathy by SD‐OCT
Authors: CHAKER N , MGHAIETH F , DALLELI F , CHEBIL A , BOURAOUI R , MRABET A , EL MATRI L 
Published: November 2013

AbstractPurpose To evaluate the choroidal thickness in diabetes and study its variation with different stages of diabetic retinopathy (DR).Methods Retrospective study of 155 eyes of 83 diabetic patients treated between June 2011 and October 2012. All patients benefited from a complete ophthalmologic examination, laboratory tests conventional A‐scan ultrasonography,choroidal and retinal tomographyResults The mean age patients was 57,54 with. There was not diabetic retinopathy DR(‐) in 36,77% of cases. There was a minimal noproliferative diabetic retinopathy NPDR in 17,41%, moderate NPDR in 15%, moderate preproliferative PPDR in 5,8%, severe PPDR in 11,6%, moderate PDR in 6,45%, severe PDR 4,51% and 2,58% in complicated PDR. The tomographic study objectified a thinner choroid in diabetic patients, with mean choroidal thickness (MCT=263+30µm) and subfoveal thickness (SFVCT=261.4+33.8µm). In the group with RD (+), choroid thickness (p=0,04), significantly decreased compared to DR (‐) group, but not correlate with the severity of DR. There was, however, a statistically significant difference between the different stages of DR for the following variables: HBA1C, visual acuity and near VA (p<10‐3). The SD‐OCT has objectified a macular retinal thickening which increased significantly with the severity of DR (p<10‐3). Moreover, the choroidal thickness varied little between the various stages of DR. We found a statistically significant correlation between SFVCT: duration of hypertension, the rate group. While the MCT was significantly correlated with serConclusion SD‐OCT now possible to explore the choroid, measure its thickness and assess its variation with the DR stages