bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ghrelin and obestatin decreases the IOP in a acute glaucoma model
Authors: ROCHA DE SOUSA AA , TAVARES‐SILVA M , PEREIRA‐SILVA P , AZEVEDO‐ PINTO S , RODRIGUES‐ARAUJO J , LEITE‐MOREIRA AF 
Published: December 2011

AbstractPurpose The aim of this study is to evaluate the effect of the pro‐ghrelin derived peptides in the intra‐ocular pressure in animal models of acute glaucoma.Methods The first part of the experimental protocol was the calibration of the Tonovet® used to measure the IOP. In the second part of the protocol we studied, in a rabbit model of acute glaucoma, the effects of ghrelin (10‐4M, n=6), des‐acyl‐ghrelin (10‐4M, n=7) and obestatin (10‐4M, n=7), as well as the subcellular pathways involved. This model was achieved with an intra‐vitreal injection of 20% NaCl. Then, one of the three peptides was sub‐conjunctivally injected. Concerning the subcellular pathways, keterolac (a COX inhibitor; 30mg/ml; 500microl; n=7) and L‐NAME (a NO synthase inhibitor; 150mg/Kg; 500 microl; n=11) were sub‐conjunctivally injected previously to both NaCl and ghrelin injection. All the results were compared to a control group which did not receive ghrelin, des‐acyl‐ghrelin or obestatin.Results There is a linear correlation between the IOP measured by the Tonovet (Y) and its real value (X), being that underestimated (Y= ‐0,331 + 0,750X). Our results show that the NaCl injection increases the IOP from 9.9 ± 1.9 to 44.9 ± 4.1. After that ghrelin promotes a decrease of 20,8 ± 5,0 mmHg (decrease of 47,9 ± 11,6%); obestatin promotes a maximal decrease of 15,8 ± 3,9 mmHg (decrease of 37,5 ± 9,4%), while des‐acyl‐ghrelin does not significantly change IOP. When keterolac or L‐NAME are added, ghrelin’s effect is completely blunted.Conclusion Ghrelin showed to promote a decrease of the intra‐ocular pressure, independently from GHSR‐1a and dependently on NO and prostaglandins. Obestatin also promotes a decrease in the IOP.
Management of mild and moderate Graves' Orbitopathy
Authors: BOSCHI A 
Published: December 2011

AbstractPurpose Management of Graves orbitopathy (GO) varies according to the level of its activity and its severity. For the activity evaluation, although no method is both specific and completely reliable, a simple office‐based tool is the Clinical Activity Score, which reflects the presence or absence of symptoms and signs that indicate inflammation. In addition, the severity of disease should be assessed by measuring exophthalmos, lid width, evaluating soft‐tissue involvement and extra‐ocular muscle function, and assessing corneal involvement and optic‐nerve involvement. Features of mild and moderate to severe GO will be presented.Results Specific treatments for GO vary depending on the severity of the disease. Mild GO usually does not require any treatment except for local measures ( ex lubrificants, ointments, dark lenses, and prisms to to reduce diplopia).However, in some patient quality of life is so impaired that treatment such as that for more severe GO might be suggested. Regular follow‐up every 3‐6 months is recommended, since progression of GO is observed in about 25% of the pats. Patients with moderate to severe with active disease (CAS>/=3) should be treated with immunosuppressive treatment modalities, while those with inactive GO may benefit from rehabilitative surgery.Conclusion The treatment of choice for moderate to severe GO is IV glucocorticoids +/‐ orbital radiation therapy, if GO is inactive, surgery as orbital decompression and /or squint surgery and/or eyelid surgery
Abnormal retinal vascular function and cognitive loss in Alzheimer's Disease patients
Authors: GHERGHEL DOINA , BENAVENTE‐PEREZ A , MROCZKOWSKA S 
Published: December 2011

AbstractPurpose To identify signs of abnormal retinal vascular function and their relationship to cognition deficits in newly diagnosed mild AD patientsMethods Retinal arterial and venous reaction times to flickering light were assessed in 10 AD patients and 28 age‐matched healthy individuals by means of Dynamic Vessels Analysis (DVA). Minimental state examination (MMSE) and Addenbrooke's Cognitive Examination‐Revised (ACE‐R), as well as blood pressure measurements and blood analyses for lipid metabolism markers were also performed in patients and controls.Results AD patients demonstrated differences in their vascular reaction times to repeated cycles of flicker exposure at the retinal arterial level compared with healthy controls, which correlated with the degree of the patients’ cognitive impairment at the time of the testConclusion It proposed that a simple screening of the retinal vascular function could offer valuable information about risk for future vascular complications as well as progressive cognitive decline in newly diagnosed patients suffering from mild AD.
Impairment of 4th neuron‐ axons correlates with retinal nerve fiber loss in glaucoma
Authors: MICHELSON G , WAERNTGES S , ENGELHORN T , EL‐RAFEI A , HORNEGGER J , DOERFLER A 
Published: December 2011

AbstractPurpose In glaucoma damage of retinal ganglion cells may continue to the linked optic radiations (OR). This damage may concern the axonal integrity as well as demyelination or glia cell impairment. This study investigated measures of axonal demyelination, i.e. radial diffusivity (RD), in the optic radiation of glaucoma patients. The results were correlated with the homonymous retinal nerve fiber layer thickness (RNFL).Methods Fourteen control subjects (mean age, 52.0±11.7 years) were age‐adjusted to 12 patients with normal tension glaucoma (NTG, mean age, 58.3±9.5 years; p=0.157) and 18 patients with primary open angle glaucoma (POAG, mean age, 55.7±7.3 years; p=0.296). The control subjects had eye diseases without neuronal participation. All subjects underwent magnetic resonance (MR) tomography‐based diffusion tensor imaging (DTI) of the optic radiation and eye examination by the Spectralis optical coherence tomography. MR images did not show cerebral space occupying lesions along the visual pathway. The optic radiations in the DTI were outlined semi‐automatically and the mean values of FA and RD of both OR’s were measured. The homonymous RNFL thickness corresponding to the respective OR was calculated.Results If corrected for age, gender, and diagnosis groups (control, NTG, POAG) partial correlation analysis disclosed a correlation between RD and the RNFL thickness (right OR: r=‐0.350, p=0.025; left OR: r=‐0.478, p=0.002).Conclusion In glaucoma DTI‐derived parameters of axonal integrity and demyelination of the optic radiation (4th neuron) are suggested to change with decreasing retinal nerve fiber layer thickness (3rd neuron), i.e. with increasing glaucoma severity.
C‐Met signaling and preclinical analysis of Crizotinib in uveal melanoma
Authors: VAN DER VELDEN PA , DE LANGE M , DA SILVA CG , VERSLUIS M , LUYTEN GPM , JAGER MJ 
Published: December 2011

AbstractPurpose Uveal melanoma (UM) is the most common intra‐ocular tumor in adults that often leads to metastases for which no effective treatment is available. The aim of this study was to analyze molecular mechanisms in UM in order to reveal treatment targets.Methods Efficacy of kinase inhibitors and molecular mechanisms are analyzed in preclinical models of UM. Focus in this study was on the kinases and pathways that are associated with metastasis.Results Based on c‐Met expression in UM with a bad prognosis (monosomy 3) and activation of c‐Met in all metastasis cell lines c‐Met was chosen as treatment target and Crizotinib was chosen as candidate drug. Crizotinib is a dual kinase inhibitor that inhibits both ALK and c‐Met. Molecular analysis revealed that Crizotinib was able to inhibit c‐Met in UM effectively at nano‐molar range. Proliferation was however not affected by Crizotinib treatment when cells were grown attached to culture dishes. To achieve growth inhibition with Crizotinib cells had to be grown non‐attached. Moreover, only tumor cells that contained activated c‐Met were affected by Crizotinib while c‐Met negative cells continued to grow in the presence of the drug. Molecular analysis furthermore revealed that focal adhesion kinase (FAK) is a downstream target that was also inactivated in response to Crizotinib treatment. FAK is involved in tumor cell motility and tumor cell extravasation that are both crucial processes in metastasis.Conclusion We propose Crizotinib as a possible treatment option for metastasizing UM. As c‐Met expression is highly correlated with monosomy 3, both c‐Met and monosomy 3 may be evaluated as biomarker for Crizotinib treatment.
Immunosuppressive inflammation is an inherent characteristic of prognostically‐bad uveal melanoma.
Authors: BRONKHORST IHG , VU THK , JORDANOVA ES , ONKEN MD , VERSLUIS M , VAN DER VELDEN PA , LUYTEN GPM , HARBOUR JW , VAN DER BURG SH , JAGER MJ 
Published: December 2011

AbstractPurpose The presence of infiltrating immune cells in uveal melanoma is associated with poor prognosis. An analysis of the different functional phenotypes of the tumor‐infiltrating leukocytes (TIL) may help to gain insight in the role of these infiltrating immune cells.Methods The density of CD8+ (CD3+CD8+ T cells) and CD4+ (CD3+CD8− T cells) T lymphocytes, CD4+ regulatory T cells (Tregs; CD3+CD8‐Foxp3+ cells), CD68+ and CD68+CD163+ macrophages was evaluated by immunofluorescence histochemistry in 43 cases of uveal melanoma. The correlations between different parameters were analyzed and their presence compared to known morphologic, immunologic, cytogenetic and molecular prognostic variables.Results The presence of increased numbers of all T cell subsets was associated with an epithelioid cell type, monosomy 3, and the class 2 gene expression profile (GEP). The presence of TIL was very variable, but strong correlations were observed between the different types of TIL. The presence of Tregs was correlated with the presence of M2 macrophages.Conclusion Uveal melanoma with more malignant characteristics such as monosomy 3 and the class 2 GEP contained more TILs, which included Tregs. These data suggest that tumor‐intrinsic factors distinguishing bad from good melanoma probably control the initiation of inflammation, which involves infiltration of tumors by different lymphocytic and myeloid immune cell subtypes, and support the notion that immunosuppressive inflammation contributes to increased malignancy in high risk uveal melanoma cases.
Inflammation in primarily and secondarily‐enucleated eyes with uveal melanoma
Authors: VU THK , BRONKHORST IHG , VERSLUIS M , MARINKOVIC M , VAN DUINEN SG , VROLIJK J , LUYTEN GPM , JAGER MJ 
Published: December 2011

AbstractPurpose Uveal melanoma with a bad prognosis contain high numbers of infiltrating macrophages, especially of the M2 phenotype, and different subsets of lymphocytes. The aim of this study is to determine the presence of inflammatory cells in uveal melanoma‐containing eyes enucleated after different types of irradiation, i.e. ruthenium‐106 brachytherapy, sandwich therapy, or proton beam irradiation.Methods We analyzed 46 eyes enucleated due to tumor recurrence, non‐responsiveness, or complications after irradiation. Immunofluorescence staining was performed to determine the presence of CD68+ and CD68+CD163+macrophages, CD3+, CD8+ and Foxp3+ regulatory T lymphocytes. Outcomes were compared with known clinical and histological prognostic parameters.Results Numbers of CD68+ and CD68+CD163+ macrophages in secondarily‐enucleated eyes varied widely, but was not related to the reason for enucleation. The median of CD3, CD8, FoxP3+ lymphocyte counts was 55, 99 and 9 cells/mm2, respectively. When compared to primarily‐enucleated eyes, the lymphocytic infiltration was significantly (p<.02) higher in irradiated eyes.Conclusion Numbers of T‐lymphocytes and macrophages varied widely. Irradiation has no clear effect on the number and type of macrophages in uveal melanoma. However, there were higher numbers of lymphocytes in previously irradiated uveal melanoma.
Preclinical study of a glycoengineered anti‐human CD20 antibody in murine models of primary cerebral and intraocular B‐cell lymphomas
Authors: BAGGA RYM 
Published: December 2011

AbstractPurpose Primary cerebral lymphomas (PCL) and primary intraocular lymphomas (PIOL), related to the systemic diffuse large B‐cell lymphoma family, are highly aggressive tumors, with poor prognosis and any specific therapy. Despite good results obtained with chemotherapy, many patients relapse and new therapeutic strategies are needed. PCL and PIOL are characterized by the presence of CD20+ lymphomatous B‐cells and as such are eligible for therapy with anti human CD20 antibodies.Methods In this study, we evaluated the efficiency of LFB‐R603, a promising glycoengineered anti‐hCD20 monoclonal antibody that displays a high affinity for FcgRIIIa (CD16) receptors, when injected intumoraly. We used a murine lymphomatous B cell line transfected with the human CD20 gene to generate two syngeneic murine models of PCL and PIOLResults After a single therapeutic injection of LFB‐R603 mAb, a strong anti‐tumor response was noted against the PCL and a less pronounced response in the PIOL model. This was linked to an inhibition of tumor growth and infiltration with CD8+ T‐cells in both models. Interestingly, therapeutic effects were much better than those obtained with the Rituximab used as a reference.Conclusion These in vivo results confirm the potential of the LFB‐R603 mAb as an innovative therapeutic approach for the treatment of PCNSL tumors.
Intravitreal bevacizumab (Avastin) in treating macular oedema associated with central retinal vein occlusion
Authors: ADEPEGBA O , GEORGE S 
Published: December 2011

AbstractPurpose To report the response following intravitreal bevacizumab(IVB) therapy in macula oedema associated with central retinal vein occlusion(CRVO).Methods Clinic charts of consecutive patients with macula oedema secondary to CRVO were retrospectively reviewed. Data from ophthalmological examination, Visual acuity, OCT (optical coherence tomography) fundus fluorescein angiography were recorded. All patient received one intravitreal bevacizumab 1.25mg/0.05ml at baseline and retreatment was on prn (pro re nata ) basis.Results Twenty‐five eyes of 25 eyes of 25 patients with a mean age of 73.1±12.1 were reviewed. Average time between diagnosis and initiation of IVB was 9.3±8.2weeks(range=0‐52weeks). Follow up was 12 months. All patients were treatment naïve. Mean baseline visual acuity and central retinal thickness(CRT) was 32.5±7.2ETDRS letters and 625±240µ respectively. The mean change in in vision at month 1, 3, 6 and 12 was + 4.5(p=0.10), +9.6(0.051), +11(p=0.062) and 13.6(p=0.049) ETDRS letters respectively. The mean change in CRT from baseline at month one was ‐209µ(p=0.056) and ‐335µ(p=0.009), ‐263µ(p=0.03) and ‐258µ(p=0.022) at month 3, 6 and 12 respectively. Mean number of injection was 3.4 at month 6 and 5.2 at month 12. There were no complications recorded.Conclusion Treatment of macula oedema secondary to CRVO with IVB resulted in improvement of visual acuity and significant decrease in macula oedema over 12 follow up.
Corneal Stromal Mesenchymal Stem Cells for Corneal Stroma Reconstruction
Authors: GRIFFITH M , RAFAT M 
Published: December 2011

AbstractPurpose To date, corneal epithelial reconstruction has been very successful. However, in a number of cases of injury or disease, the stromal layer is affected. Our goal is to develop biomaterials that will enable the regeneration of the corneal stroma. In this study, we compare endogenous vs exogenous stem cell courses for corneal stromal regeneration.Methods We have previously developed collagen‐based corneal stromal extracellular matrix substitutes based on EDC crosslinked collagen, and have shown that they promote ingrowth of stromal cells from the host cornea (Merrett et al. 2009; Fagerholm et al. 2010). For cases where stromal progenitors are depleted, we developed a non‐toxic collagen‐based hydrogel system where a macromolecular photoinitiator (Dex‐BBA)was used to form the hydrogel around cells. The feasibility of Dex‐BBA as a photoinitiator to initiate the gelation of aminoethylmethacylate‐modified collagen (Coll‐AEMA) was examined with or without the presence of stroma cells.Results The Dex‐BBA crosslinked hydrogels were weaker than the EDC crosslinked constructs. However, they were fairly robust and no apparent toxicity of the hydrogel system to mesenchymal stroma (or stem) cells (MSCs)were observed during the culture of 7 days, which indicated that Dex‐BBA based macrophotoinitiator and our collagen‐based hydrogel system may have potential in corneal stromal regeneration applications.Conclusion We show that corneal stromal regeneration can be achieved by endogenous stimulation of existing corneal progenitor cells. Where the host cells may be depleted, our results show that hydrogel encapsulated stem cells may be used in the future.
Commercial interest
The dexamethasone drug delivery system for the treatment of retinal venous occlusion with cystoid macular edema
Authors: EGEA ESTOPINAN C , IDOIPE M , PRIETO CALVO E , FERNANDEZ LARRIPA S , FERRERAS A , PABLO L , ABECIA MARTINEZ E 
Published: December 2011

AbstractPurpose To report our case report with sustained‐release dexamethasone 0.7 mg intravitreal implant (Ozurdex®; Allergan, Inc., Irvine, CA) in retinal vein occlusion with macular edema.Methods A 67‐years old female patient with recent retinal vein occlusion with macular edema treated with sustained‐release dexamethasone 0.7 mg intravitreal implant was performed. On initial examination, the right best‐corrected visual acuity (BCVA) was 0,3. Right fundoscopy revealed dilatation and tortuosity of the retinal veins and retinal hemorrhage in the superior quadrant of the retina. The fluorescein retinal angiography showed a delay of filling time and spectral domain optical coherence tomography (Spectralis SD‐OCT; Heidelberg Engineering, Heidelberg, Germany) showed macular edema.Results The patient was treated with two intravitreal ranibizumab injections but two moths later the visual acuity was 0,2 and then we treated with sustained‐release dexamethasone 0.7 mg intravitreal implant and six moths later the right BCVA was improved to 0.7. Funduscopy and optical coherence tomography confirmed reduction of edema and tolerability of the implant was assessed.Conclusion The dexamethasone drug delivery system is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. In patients with macular edema in retinal vein occlusion, sustained‐release dexamethasone 0.7 mg intravitreal implant may be an effective treatment option to control macular edema
Retinal Vein Occlusion : Treatment by series of 3 Ranibizumab IVT
Authors: GONZALEZ C 
Published: December 2011

AbstractPurpose To evaluate the functional, anatomical, vascular flow, anti‐ exudative effects of intravitreal injections(IVT) for Retinal Vein Occlusion ,by a protocol with 3 Ranibizumab IVT series, and the recurrences frequency at 3 years evolution.Methods 17 eyes of 17 patients with Retinal Vein Occlusion received intravitreous Ranibizumab, 3 times, every 4 weeks in an inductive treatment. The next injections depended on the follow‐up results and were done by series of 3. First and 2 months’ interval follow‐up exams included ETDRS visual acuity (VA), complete ophthalmic examination, optical coherence tomography (OCT), and fluorescein angiography (FA).VA and OCT were done before each IVT. We want to evaluate the incidence of this protocol on the exudation and frequency of recurrence and so on the number of IVT needed.Results VA improved in 16 eyes, stabilized in 1. Diffuse edema was 53% normalised ,total thickness was 60% less in the average follow‐up, cysts 100% disappeared in 75% cases, in 60% were diminished in size , volume and number, by OCT. At Angiography, no leakage in 65% cases, cystoids macular edema disappeared, vascular abnormalities diminished. Most of patients had good functional, anatomical results, with few IVT needed, no scars in the retina. Inductive treatment was sufficient in 5 cases, needed 2 IVT Series in 27% cases, failed in no cases. This protocol was compared ,discussed .Conclusion The results with improved visual acuity, reduction of exudation at OCT, vessel’s leakage and structure normalized at FA, suggest this protocol, with series of 3 Ranibizumab IVT, seems effective, more retinal protective. This protocol seems attractive, specific indication criteria and its indication must be optimized.
Design and rationale of COMO, a 12‐month study that compares the safety and efficacy of dexamethasone intravitreal implant versus ranibizumab in branch retinal vein occlusion
Authors: LOEWENSTEIN A , BANDELLO F , KAMPIK A , SOUIED E , FIGUEROA M , TUFAIL A , HEYWOOD A , FULFORD‐SMITH A 
Published: December 2011

AbstractPurpose The DEX implant 0.7 mg and ranibizumab have not been directly compared in a randomized trial in branch retinal vein occlusion (BRVO). Inclusion of different patient populations in the GENEVA[1] and BRAVO[2] trials also prevents an indirect comparison. Duration of disease and visual acuity at baseline have been shown to impact outcomes following treatment. BRAVO recruited patients with a shorter duration of macular oedema (ME) and lower best corrected visual acuity (BCVA) at baseline than GENEVA. Sub‐analysis of GENEVA showed a greater BCVA improvement which peaked at day 60 (17.8 letters, p=0.002) and was sustained out to day 180 (14.4 letters, p=0.138).[3]Methods This Phase IV, multinational, randomized, 12 month study directly compares DEX implant 0.7 mg with ranibizumab in BRVO with ME for <90 days. Recruitment will begin in 2011 and circa 400 patients will be enrolled and randomized (1:1). Stratification will be according to BCVA.Results The primary endpoint is the mean change in BCVA from baseline to month 12 in the intention‐to‐treat population using a non‐inferiority analysis. Secondary endpoints include other measures of visual acuity and quality of life.Conclusion The results of this first head‐to‐head comparison of DEX implant 0.7 mg with ranibizumab will have implications for future practice. References 1.Haller JA, et al. Ophthalmol 2010;117(6):1134‐46. 2.Campochiaro PA, et al. Ophthalmol 2010;117(6):1102‐1112. 3.Allergan data on file. GENEVA sub‐analysis.
The effect of intravitreal ranibizumab on retinal oxygenation in central retinal vein occlusion
Authors: TRAUSTASON S , LA COUR M , LARSEN M 
Published: December 2011

AbstractPurpose To investigate the effect of intravitreal anti‐VEGF on retinal oxygenation in patients with central retinal vein occlusion. Intravitreal anti‐VEGF injections have recently become an approved method of treatment for retinal vein occlusions, as several studies have shown a beneficial effect on visual acuity and retinal thickness. However, there are indications that intravitreal anti‐VEGF may cause constrictions of the retinal vessels, leading to a reduction in retinal blood flow.Methods Retinal oxygen saturation in patients with CRVO was analysed, using the Oxymap Retinal Oximeter P3, before and during 6 months of treatment with intravitreal injections of ranibizumab.Results Our preliminary results indicate that retinal oxygen saturation is not decreased by intravitreal anti‐VEGF injections.
Commercial interest