bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for association of HTRA1 promoter polymorphism in Polish patients with age‐related macular degeneration
Authors: OLDAK M , SZAFLIK JP , MAKSYM RB , FRANASZCZYK M , SZAFLIK J , PIOSKI R 
Published: September 2008

Abstract Purpose Age‐related macular degeneration (AMD) is a leading cause of visual impairment in developed countries, particularly in the Caucasian population above 65 years. It is a complex disorder with both genetic and environmental factors playing a role. Variants of HTRA serine peptidase 1 gene (HTRA1), particularly a single nucleotide polymorphism (SNP) in its 5’ regulatory region –512G>A (rs11200638), is among those most strongly associated with AMD susceptibility but so far its frequency has not been analyzed in the Polish population. The purpose of this study was to investigate the association of rs11200638 with AMD in Polish patients. Methods AMD patients (n=140) and age‐matched controls (n=162) were enrolled in the study. Total genomic DNA was isolated from blood and rs11200638 was genotyped in both groups by restriction fragment length polymorphism (PCR‐RFLP) analysis using MspI endonuclease and direct sequencing. PCR primers were designed based on the reference sequence of the gene (AF157623). Allele and genotype frequencies were compared between the groups by Chi square test and odds ratio (OR) with 95% confidence intervals (95% CI) were calculated to estimate risk. Results Frequencies of the GG, GA and AA genotypes were 52%, 33% and 15% in control subjects and 28%, 15% and 57% in AMD patients, respectively. The AA genotype was significantly more prevalent in patients with AMD than among control subjects (OR= 7.7, 95%CI: 4.4‐13.2, Chi square 53.6, P<10‐6). Conclusion In the present study, polymorphic variant of HTRA1 gene (rs11200638) showed strong association with AMD, verifying its significant role as a disease susceptibility gene also in Polish patients.
The in vitro effects of anti‐angiogenic AMD treatments on human choroidal endothelial cells
Authors: STEWART EA , AMOAKU WMK 
Published: September 2008

Abstract Purpose Age‐related macular degeneration (AMD) is the most common cause of irreversible visual loss in elderly populations in the western world. Neovascularisation by choroidal endothelial cells (hCEC) causes AMD; however, the mechanisms responsible are not fully understood. Vascular endothelial growth factor (VEGF) is thought to be the most significant growth factor in AMD and subsequently, molecular inhibitors including pegaptanib (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin) have been developed as treatments for AMD. Methods hCEC were isolated from cadaver eyes and cultured in EBM2‐MV medium as previously published. hCEC proliferation after exposure to VEGF isoforms 165 and 121 and anti‐angiogenic treatments was measured using the WST‐1 assay. The effect of the VEGF isoforms and anti‐angiogenic treatments on angiogenesis was assessed using a double layer Matrigel technique. Results hCEC proliferation in response to VEGF 121 and 165 was found to be equivalent. Individually and in combination both Ranibizumab (Lucentis) and bevacizumab (Avastin) were effective in decreasing proliferation of hCEC. Pegaptanib (Macugen) was moderately effective in controlling the proliferation of hCEC stimulated by VEGF 165, but was ineffective against the stimulatory effect of VEGF 121. Conclusion Although molecular inhibitors of angiogenesis have been shown to have a beneficial effect as treatments for AMD, direct comparison of the efficiency of the drugs is complicated, due to variations between trials and dosing regimes. In vitro testing of the drugs on the proliferation and angiogenesis of hCEC showed that the efficacy is in the order Lucentis>Avastin>Macugen, in line with the current clinical outcomes seen.
Intravitreal bevacizumab versus triamcinolone acetonide for exudative age‐related macular degeneration
Authors: LIBONDI T , JONAS JB , IHLOFF AK , HARDER B , KREISSIG I , SCHLICHTENBREDE F , SPANDAU UHM , VOSSMERBAEUMER U 
Published: September 2008

Abstract Purpose To compare an intravitreal high‐dose injection of triamcinolone acetonide versus an intravitreal injection of bevacizumab for treatment of progressive exudative age‐related macular degeneration (AMD). Methods The comparative non‐randomized retrospective clinical interventional study included 305 patients with progressive AMD, divided into a bevacizumab group of 36 patients (1.5 mg bevacizumab) and a triamcinolone group of 269 patients (about 20 mg triamcinolone). All patients were consecutively included, in the first phase of the study for triamcinolone, and in the second phase of the study for bevacizumab. Mean follow‐up was 8.5 ± 6.8 months (2‐35.7 months). Results In the bevacizumab group, best visual acuity increased significantly (P<0.001) by 3.2±3.4 Snellen lines, with 25 (69%) eyes and 21 (58%) eyes, improving by at least 2 Snellen lines and 3 lines, respectively. In the triamcinolone group, the visual acuity change was not statistically significant whenever within the first 3 months. Maximal increase in visual acuity, visual acuity change at 2 months after injection, and the percentage of patients with an improvement by at least 2 Snellen lines and 3 lines were significantly (P<0.001) higher in the bevacizumab group than in the triamcinolone group. Intraocular pressure increased significantly (p<0.001) in the triamcinolone group, and did not change significantly (P=0.47) in the bevacizumab group. Conclusion In exudative AMD, intravitreal bevacizumab (1.5mg) compared with intravitreal triamcinolone acetonide (about 20mg) results in a higher improvement of visual acuity and does not markedly influence intraocular pressure within 2 months after injection
Intravitreal bevacizumab (Avastin®) in wet AMD: the OCT‐assisted “wait and see” management
Authors: NERI P , HERBORT CP 
Published: September 2008

Abstract Purpose To retrospectively review the evolution of our patients managed with the OCT‐assisted “wait and see” approach after intravitreal bevacizumab (IB) injection. Methods Charts of 46 consecutive patients affected by wet AMD that had received IB (1.25 mg) for recent CNV and completed ≥ 9‐month follow‐up were reviewed. The patients were divided into 3 groups, on the basis of the number of injections: “1 injection” (group 1), “2 injections” (group 2) and “≥ 3 injections” (group 3). Visual gain and loss were defined as improvement or worsening of 2 or more lines of BCVA, respectively. Injections were repeated in case of OCT worsening and decreased BCVA, confirmed by FA. Main outcome measures were the stability/improvement of the BCVA, and both the FA and OCT stability/improvement. Results Sixteen patients needed only 1 injection (34.8%), 11 needed 2 injections (23.9%) and 16 (41.3%) patients ≥ 3 injections. In group 1, the median follow‐up time, was 14 months, while, in group 2 and 3, it was 12 months. In group 1, 14/16 patients (87.5%) had stable/improved BCVA (P<.05), while in group 2 and 3, 9/11 (81.8%, P<.05) and 17/19 (89.5%, P<.05) patients had stable/improved BCVA, respectively. All the patients that had stable/improved BCVA had both stable/improved FA and OCT. No differences were observed between the outcomes of the groups (P>.05). Conclusion In 1 patient out of 3 a single IB and in more than 50% of patients no more than 2 IB were sufficient to treat CNVs. Our data indicate that bevacizumab is effective even if administered on the basis of the CNV activity, and the scheme of 3 automatic initial injections proposed in trials using other anti‐VEGF agents should be revised at least for bevacizumab. Further trials are mandatory to validate our data.
Lessons learned in setting up a reading centre network for high volume grading in Europe
Authors: PATTON WP , MULDREW KA , HARDING SP , CHAKRAVARTHY U , PETO T 
Published: September 2008

Abstract Purpose In 2004, the Verteporfin Photodynamic Therapy (VPDT) study was commissioned in the UK to assess patients with CNV undergoing PDT. A Reading Centre network (NetwORC UK) was established to independently grade 5000+ angiograms per year. Previous to this, there were no independent RCs in Europe capable of grading this volume. Methods Three geographically distinct centres (Belfast, Liverpool and London) form NetwORC UK with a management facility (CARF) coordinating the administrative and technical aspects. A custom software platform was developed to manage the import, transmission and grading of images, collection of data between the three RCs, and ensure communication across separate IT networks. Quality assurance and concordance ensure grading is consistent across NetwORC UK. Results Between October 2005 and October 2007, 12612 angiograms were graded and 6833 were baseline angiograms. The grading of angiograms is ongoing in NetwORC UK and will continue until the study ceases. Conclusion A network structure has enabled grading of a large volume of images from the VPDT study. Regular training and concordance exercises have contributed to the success of this service. The authors recommend that the administration and management is separate from grading ensuring grading staff are dedicated to grading tasks. Therefore technical queries and software can be managed in one location, importing and exporting data can be centralised, vacation and sickness cover is easier to maintain, and unique training is offered by pooling staff from different locations. Regular monitoring of IT systems ensures data has integrity and dedicated IT personnel are essential. Future studies of this size will now be possible in Europe using NetwORC UK.
Investigation of the effect of the Alcon AcrySof Natural (ANIOL) blue‐filtering intraocular lens on macular pigment
Authors: O'REILLY P , LOANE E , LOUGHMAN J , BEATTY S , NOLAN J 
Published: September 2008

Abstract Purpose Photo‐oxidation is believed to play a role in age‐related macular degeneration (AMD). Macular pigment (MP), consisting of the carotenoids: lutein (L), zeaxanthin (Z) and meso‐Z, protects the retina from photo‐oxidative damage. This study was designed to test the effect of the Alcon AcrySof Natural (ANIOL) blue‐filtering intraocular lens on MP. Methods Forty four patients scheduled for cataract surgery were recruited into our study. These patients all had pre‐operative best corrected visual acuity (BCVA) of at least 6/18 in the study eye. Patients were randomised to have either the standard Alcon AcrySof three‐piece acrylic intraocular lens (AIOL) [controls] or the ANIOL. We measured the spatial profile of MP using customised heterochromatic flicker photometry (cHFP) pre‐operatively and post‐operatively, and at three, six and 12 months after surgery. BCVA was measured in the study eye at each visit and a blood sample was taken to control for changes in serum carotenoid levels. Results The mean age (± SD) of our study group was 69 (± 11) years. The last patient study will be completed by 27th of June 2008 and randomisation and final study data will be available for analysis and presentation after this date. Preliminary analysis shows that the mean (± SD) MP optical density at peak (0.25o eccentricity) was 0.301 (± 0.159) before and 0.296 (± 0.142) after cataract extraction (Paired‐sample t‐test, p = 0.616). Conclusion Customised HFP appears to be unaffected by lens opacity where BCVA is at least 6/18 and can be used to obtain reliable measurements of the spatial profile of MP in patients with cataracts. Further comment will be made following final study analysis in June.
Commercial interest
Effects of photodynamic therapy on subfoveal blood flow in neovascular age‐related macular degeneration patients
Authors: CHIQUET C , VINH MOREAU GAUDRY V , ROMANET JP , HERA R , MILLET JY , GEISER M 
Published: September 2008

Abstract Purpose To assess the short‐term changes in choroidal blood flow after photodynamic therapy (PDT) in patients with neovascular age‐related macular degeneration (AMD). Methods Fourteen patients with exudative AMD were included after complete ophthalmologic examination, fluorescein and indocyanine green angiography and optical coherence tomography. Subfoveal choroidal blood flow was assessed using laser Doppler flowmetry (LDF) in both treated (n=14) and nontreated controlateral (n=8) eyes, 1 h and 1 week after PDT. Ocular perfusion pressure was calculated. Results The detection sensitivity of the LDF measurements at 2‐min intervals before PDT in treated eyes was 7.4% for volume, 6.3% for velocity, and 10.4% for choroidal blood flow. Initial mean visual acuity was 0.68±0.3 logMar. Macular thickness at baseline as measured by OCT3 was at median [interquartile range], 326.5 mm[188–367]. One hour and 7 days after PDT, a significant increase in velocity (15.8% and 24.4%, respectively) and a significant decrease in volume (11% and 17.9%, respectively) were noted in treated eyes. Choroidal blood flow and ocular perfusion pressure remained similar during follow‐up. No significant change in flow parameters was reported in untreated eyes. Conclusion The LDF technique provides feasible and reliable measurements of blood flow parameters before and after PDT in a selective population of patients with exudative AMD. The prognostic value of these early blood flow parameter changes also needs to be assessed.
Aquaporins expression on blood retinal barrier cells during experimental autoimmune uveitis
Authors: MOTULSKY E , WILLERMAIN F , JANSSENS S , KOCH P , LIENART M , VANBELLINGHEN A , CASPERS L , MARTIN‐MARTINEZ M , DELPORTE C 
Published: September 2008

Abstract Purpose To study the expression of aquaporins 1 and 4 on blood retinal barrier cells during EAU. Methods Experimental Autoimmune Uveitis (EAU) was induced in C57Bl6 mice by immunization with interphotoreceptor retinoid‐binding peptide 1‐16. Four weeks later animal were sacrificed. The severity of the disease was graded and the expression of AQP1 and AQP4 were detected by immunofluorescence (IF). In vitro using ARPE‐19 cells, basal expression of AQP1 and 4 was analysed by RT‐PCR, Western blot(WB) and IF. The effects of IFN‐gamma and TNF‐alpha on AQP1 and AQP4 expression in ARPE‐19 cells were determined by WB. Results In controls animals, AQP1 expression was limited to the photoreceptor layer while AQP4 expression extended from the internal limiting membrane to the external limiting membrane. The patterns of AQP1 and AQP4 expressions were not changed during uveitis. Neither AQP1 nor AQP4 were found in RPE cells in controls or EAU animals. However AQP4 was expressed in ARPE‐19 cells and its expression somewhat upregulated by IFN‐gamma and TNF‐alpha. Conclusion The patterns of AQP1 and AQP4 expressions in the internal blood retinal barrier are not modulated during EAU. Besides, in vivo, the AQP1 or AQP4 expressions could not be detected on the external blood retinal barrier (RPE cells). In contrast, in vitro, AQP4 expression was detected in a human ARPE cell line and slightly increased by proinflammatory cytokines.
Lack of association of the Toll‐like receptor 4 gene polymorphisms Asp299Gly in Italian patients with Fuchs uveitis
Authors: CIMINO L , FARNETTI E , CASALI B , NICOLI D , BOIARDI L , CAPPUCCINI L , SALVARANI C 
Published: September 2008

Abstract Purpose Fuchs uveitis is a chronic low grade intraocular inflammation of unknown etiology that is usually painless and characterized by the presence of persistent infiltrating cells in the anterior chamber and vitreous. One commonly occurring Single Nucleotide Polymorphism (SNP) in the human TLR4 gene (Asp299Gly) has been shown to be associated with increased risk of Gram‐negative bacteremia in sepsis patients and with susceptibility to inflammatory bowel disease and autoimmune disease. Methods 75 Italian patients with Fuchs heterochromic cyclitis and 210 healthy age and sex matched blood donors were genotyped for the Toll‐like receptor 4 gene polymorphisms Asp299Gly gene by molecular methods. Results The distribution of allele and genotype frequencies of the Toll‐like receptor 4 gene polymorphisms Asp299Gly did not differ significantly between the patients with Fuchs heterochromic cyclitis and the healthy controls. Conclusion Our data suggest that the Toll‐like receptor 4 gene polymorphisms Asp299Gly in Italian patients with Fuchs uveitis is not associated with susceptibility of Fuchs uveitis Italian patients.
The narrowing choice of keratoprostheses
Authors: LIU C 
Published: September 2008

AbstractThere is a narrowing choice of keratoprostheses. The mainstream KPros include the age old osteo‐odonto‐keratoprosthesis (OOKP) which is capable of withstanding a hostile, dry ocular environment. Its derivatives (OOKP allograft, tibial bone KPro, Pintucci KPro, HAKPro) can be used when there is no suitable single rooted tooth available, but they do not match the longevity of the OOKP. For the wet blinking eye, it looks as though the Boston Type 1 KPro is favoured over the AlphaCor as the former gives much better vision and is no longer associated with corneal melts. Many “new” devices have failed the test of time. Yet others such as the Keralia are not yet established. The author surveys the changing scene in the world of KPros.
Boston KPro experience in Barcelona
Authors: DE LA PAZ M , ALVAREZ DE TOLEDO J , MICHAEL R , BARRAQUER R , BARRAQUER J 
Published: September 2008

Abstract Purpose To describe the indications, intraoperative complications, post‐operative complications and anatomical and functional results of Type I Boston keratoprosthesis at our eye center in Barcelona. Methods Retrospective interventional case series on 24 eyes of 22 patients who underwent Boston keratoprosthesis implant from May 2006 to May 2008. Results The main indication for Boston keratoprosthesis implantation was a repeated failed graft (mean = 2.33 previous grafts). The most common principal pathologies were: bullous keratopathy, herpetic keratitis, aniridic keratopathy, corneal ectasia, calcific band keratopathy. No major intraoperative complications were noted and average time of surgery was 47 minutes. The mean follow‐up time was 7.42 months. The major post‐operative complications encountered were retroprosthetic membrane in 2 eyes, endophthalmitis in 2 eyes and corneal graft melting in 1 eye. The mean best corrected visual acuity improved from 0.015 pre‐operatively to 0.1 post‐operatively. Only one case of extrusion due to melting was encountered which was resolved by a reimplantation of the keratoprosthesis. Conclusion Our short‐term experience with the type I Boston Keratoprosthesis is a good alternative for patients with repeated graft failures. Improvement in visual acuity is immediate and only minor complications were encountered.
Retinal vessel pulse amplitude in health and disease
Authors: PAQUES M , TICK S , GENEVOIS O , ADAM P , SAHEL JA 
Published: September 2008

Abstract Purpose End‐organ microvascular diseases is a major cause of morbidity and mortality in the general population. There is however a lack of objective, quantitative methods for evaluation of microcirculation. We hypothesized that the systolodiastolic variation in vessel diameters may be an indicator of microvascular stiffness. Methods The amplitude of systolodiastolic variations of the diameters of temporal arterioles and venules were recorded using the Retinal Vessel Analyzer (RVA®)in 37 normal eyes, 19 eyes of arterial hypertensive patients, 16 eyes that had recovered from CRVO and 9 fellow normal eyes. A minimum of 20 cardiac cycles were averaged. Results In control eyes, the mean (±SD) pulse amplitude over the cardiac cycle was 1.9% (± 0.5) for arterioles and 3.3% (± 1.1) for venules. Reproducibility (mean (±SD) intersession difference; n=14) was 3% (± 0.4) for arterioles ( ICCs: ) and 2.5% (± 0.5) for venules, with ICCs of 0.94 (± 0.2) and 0.94 (± 0.3), respectively. There was a significant positive correlation between arterial pressure and venular relative pulse (r: 0.49; p < 0.01) but not with arteriolar pulse (r: ‐0.004; p= 0.9). The venular pulse amplitude was significantly lower in post‐CRVO eyes (1.4% ± 0.9; p<0.002). Conclusion Pulse amplitude of retinal venules, but not of arterioles, is positively correlated with arterial pressure, and negatively correlated with CRVO history. Additional basic and epidemiological studies are needed in order to determine if the measure of retinal vessel pulse amplitude is of interest for management or follow‐up of cardiovascular and eye diseases.
Is pulse‐wave velocity in retinal arteries of healthy volunteers age dependent?
Authors: KOTLIAR KE , LANZL IM 
Published: September 2008

Abstract Purpose Pulse wave velocity in large vessels has been extensively used in clinical practice as an indirect measure of arterial stiffness and an indicator of cardiovascular risk factors. Arterial stiffness increases with age and in coronary arterial disease. An in‐vivo clinical method to characterise arterial stiffness of the central microcirculation was developed. Pulse wave velocity was measured in retinal arteries using the Dynamic Vessel Analyzer (DVA, Fa. IMEDOS, Jena). Methods Time dependent alterations of retinal vessel diameter were examined continuously by DVA in a randomly chosen eye of 10 young (26,0(23,5; 27,0) [median(1. quartile;3. quartile)] and 10 senior (67,0(61,3; 69,5) years old) healthy volunteers.Two segments of a retinal artery were measured simultaneously. The phase delay between the pulsations of the segments and the distance between the segments were assessed. The data was filtered and analysed by methods of signal analysis. Results There was a significant difference in pulse wave velocity between both groups (p<0,01, U‐Test). It amounted to 21,5(17,9; 34,6) mm/s in young volunteers and to 243,8(186,1; 347,7) mm/s in seniors. Retinal arterial elasticity calculated on the base of these data amounted to 5,5(3,8; 12,5) Pa in young volunteers and to 607,5(329,8; 1426,8) Pa in seniors (p<0,05). Conclusion An important clinical parameter, pulse‐wave velocity, can be measured in the central microcirculation in‐vivo using a commercially available medical device. Pulse wave velocity in retinal arteries increases significantly with age. This represents the age‐dependent increase in retinal arterial stiffness which is part of the general aging processes in the human vasculature and might be the basis of age related ocular vascular disorders.
To investigate the association between visual acuity and visual function questionnaire in patients having ranibizumab treatment
Authors: THIAGARAJAN M , TRIKHA S 
Published: September 2008

Abstract Purpose The investigation of the responsiveness of the National Eye Institute (NEI) 25‐item Visual Function Questionnaire (VFQ‐25) to changes in visual acuity (VA) in patients having Ranibizumab treatment for neovascular age‐related macular degeneration (ARMD). Methods A total of 60 consecutive cases awaiting intravitreal ranibizumab injection for neovascular ARMD were recruited. The main outcome measures were interviewer administered NEI VFQ‐25 composite score and Snellen VA represented as a logMAR equivalent, both before treatment and after their third Ranibizumab injection. VFQ‐25 composite scores and VA were compared between pre‐ and post‐treatment and also analysed for correlation between VA and NEI VFQ‐25. Results There was no statistically significant difference between pre‐ and post‐treament VA, with a mean difference of 0.04 (95% CI 0.06, 0.15). There was an improvement in the VFQ‐25 composite score with treatment of 7.5 that was statistically significant (95% CI 3.83, 11.67). The association between pre‐treatment VA and VFQ‐25 composite score was not statistically significant(Pearson correlation=0.14, p=0.37). The association between post treatment VA and composite VFQ‐25 score shows a weak but statistically significant correlation (Pearson correlation=0.36, p=0.013). The association between the change in VA and the change in VFQ‐25 composite score was not statistically significant (Pearson correlation=0.034, p=0.82). Conclusion The VFQ‐25 composite score does not show a close correlation with logMAR VA either pre‐ or post‐Ranibizumab injection. However, these composite scores show a significant improvement with Ranibizumab injection.