bluuebunny/crossref_metadata_2025_split huggingface dataset:
The novel Col8a2G257D mutant mouse line Aca23 – a model for endothelial corneal dystrophies
Authors: PUK O , AHMAD N , GRAW J 
Published: September 2008

Abstract Purpose The purpose of this study was the morphological and genetic characterization of the novel eye‐size mutant Aca23 in the mouse. Methods The eyes of the mutants were described by histology and in situ hybridization. Visual properties were examined in the optokinetic drum. Linkage analysis was performed using single nucleotide polymorphisms and micro‐satellite markers. The Aca23 mutation was identified by sequence analysis of positional candidate genes. Results Aca23 (ACMaster abnormality) is a new dominant eye size mutant, which was recovered in an ENU mutagenesis program at the HMGU. The pathologic phenotype includes increased anterior chamber depths, longer axes, and reduced corneal thicknesses. Visual properties are not affected by these irregular eye size parameters. In genome wide mapping studies, Aca23 was linked to the distal part of chromosome 4 between the markers D4Mit249 and D4Mit73. A G→A point mutation was identified at cDNA position 770 of the candidate gene Col8a2, which belongs to the collagen superfamily. The transition results in a G257D amino acid exchange within the collagen triple helix repeat. Col8a2 is expressed in the posterior part of the cornea. These data suggest that effects on structure and elasticity of the corneal Descemet’s membrane might cause the corneal thinning and anterior expansion in Aca23 eyes. Comparable pathologic abnormalities can be observed in human Fuchs’ endothelial dystrophy of the cornea (FECD) and posterior polymorphous corneal dystrophy (PPCD). Conclusion The mouse mutant described here offers a novel mutated allele of the collagen type VIII gene Col8a2 and represents a new model for endothelial corneal dystrophies.
Hereditary opacification of the anterior and posterior cornea: a new corneal dystrophy?
Authors: LAGALI NS , FAGERHOLM P 
Published: September 2008

Abstract Purpose To describe an inherited, progressive corneal disorder observed in a small Swedish family. Methods A mother and her son were initially examined for atypically‐distributed bilateral corneal opacities. Three years later, re‐examination of the mother and son and two additional family members was conducted using slit‐lamp biomicroscopy and in‐vivo confocal microscopy. Results Flat, rounded opacities were initially observed in the peripheral cornea at the level of Descemet’s membrane, in both the mother and son, while the mother exhibited additional round opacities in the central anterior cornea. Three years later the mother’s corneas were unchanged while in the son the condition had progressed, with numerous opacities appearing in the central anterior cornea as in the mother. Opacities were examined with in‐vivo confocal microscopy, which confirmed in both mother and son, that the corneal opacities were limited to the most anterior and posterior stroma with the central stroma remaining transparent. The size and morphologic features of the opacities in mother and son were remarkably similar at the microscopic level. The central anterior opacities occupied Bowman’s layer and the anterior stroma and appeared to affect the subbasal nerves. No abnormalities were noted in the two additional family members who were younger siblings of the son. In all cases vision was unaffected and subjects remained asymptomatic. Conclusion An atypical type of progressive corneal opacification with a dystrophy‐like presentation has been examined. The location and progression of the corneal changes do not correspond to any known corneal dystrophies and may represent a new dystrophy.
Genetics of high myopia in Polish families
Authors: GAJECKA M , SWAPAN N , PODFIGURNA‐MUSIELAK M , MRUGACZ M , FRAJDENBERG A , UPPALA R , BEJJANI BA , RYDZANICZ M 
Published: September 2008

Abstract Purpose Myopia is the most common of all ocular conditions. In high myopia, genetic factors appear to play a predominant role. The purpose of this study is to verify the available data and to identify a new high myopia susceptibility locus (loci). Methods Fifty two families with multiple members were diagnosed with high myopia (<‐6 diopters) without other ocular or systemic features. Prior to the targeting genotyping, linkage to markers for the myopic genetic syndromes were tested and genotyping of high myopia associated loci was performed. Next, we performed genome wide screen with 1) fluorescent markers with an average spacing of 8 cM spanning all chromosomes and 2) Affymetrix Genome‐Wide Human SNP Array 6.0 which contains 906,600 SNPs and 946,000 copy number probes. Results All previously reported high myopia loci were excluded in Polish families. The genome‐wide screen for a high myopia identified three novel loci. These loci are currently being verified using SNP array in the largest multigenerational family. Conclusion We have identified, collected and characterized a large cohort of polish families with high myopia and excluded the principal genetic cause of this phenotype. These families will be instrumental in identifying one or more loci for genetic high myopia.
Distribution and clinical peculiarities of monogenic retinal dystrophies at the Center for Ophthalmology, University of Tuebingen
Authors: PROKOFYEVA E , WILKE R , LOTZ G , TRÖGER E , STRASSER T , ZRENNER E 
Published: September 2008

Abstract Purpose To investigate distribution and clinical peculiarities of monogenic retinal dystrophies (MRD). Methods Patients, seen in Tuebingen Department of Ophthalmology in 1994‐1999 and diagnosed with Macular dystrophy (MD), Stargardt disease (ST), Bardet‐Biedl syndrome (BBS), Usher syndrome (USH) I and II, Central Areolar Choroidal Dystrophy (CACD) and Choroideremia (CHD) were selected from the database, containing 3787 records. Age, sex, diagnosis, age at first visual acuity (VA) decrease, at night blindness (NB), photophobia onset, types of visual field (VF) defects and mean age of onset (MAO), best corrected VA (BCVA) were analyzed. For VF assessment patients were divided into 2 groups: group 1: ST, MD, CACD; group 2: BBD, USH I, II, CHD. Results Records of 259 patients were reviewed. Male/female ratio was 2:1. Mean age (MA) of the patients was 47 (SD=15,6). Prevalence of diagnoses were ST‐34%, USH II‐22%, MD‐18%, CHD‐14%, USH I‐7%, BBS‐5%. In 29% of all patients were first diagnosed at age between 21‐30 years, when 29% of these patients noticed VF defects (MAO=26, SD=14.5) and 24% ‐ VA decrease (MAO=25, SD=14). MAO of NB‐23 years (SD=14.8), MAO of photophobia‐26 (SD=15). Group 1 presented concentric constriction in 82%, central scotoma in 14 % and ring scotoma in 4%, group 2 ‐ 29%, 57% and 14% respectively. 50% of all patients preserved BCVA at better eye at the level of 20/40 or higher, 31% had 20/40>VA>20/200, 12% had VA less or equal to 20/200. 7% were legally blind according to the German law, having VA<1/50 or VF<5°. Conclusion The most prevalent diagnoses were ST, USH II, MD. Concentric constriction and central scotoma were decreasing the quality of life of MRD patients.
Clinical features of serous pigment epithelial detachment using optical coherence tomography
Authors: CHOI M , YOU Y , LEE D , LEE J , CHO S 
Published: September 2008

Abstract Purpose To analyse clinical features of serous pigment epithelial detachment (PED) using optical coherence tomography (OCT). Methods Retrospective analysis was performed for 38 eyes of 34 patients with serous PED one‐fifth disc diameter or greater in size. Each patient was studied clinical examination with color photography, FAG and OCT. Cross‐sectional retinal images(the height, location and sectional area )through the center of the fovea were obtained from all eyes by OCT. They were statistically analyzed and correlated with best corrected visual acuity. To avoid cases associated with AMD, upper age limit was not 55 year. Patients with evidence of any other retinal or choroidal disease, including extensive drusen, were also eliminated. Results At initial examination, visual acuity was 20/25 or better in 23 eye, the Amsler grid was positive in 18 eyes, there were no drusen in 34 eyes and only minimal drusen in 4 eyes. The final visual acuity was 20/25 or better in 24 eyes, In 22 eyes of them, visual acuity was 20/50 or better. There was statistically correlation between final visual acuity and amount of subretinal fluid. The size, location of PED was not important factors affection visual acuity. Idiopathic CNV and subretinal hemorrhage can occur with this disease. This patient was treated with photocoagulation treatment. Conclusion The prognosis in Serous PED of eyes is excellent, because development of vascular complication was in only one case. Also OCT is potentially useful as a new, noninvasive diagnostic technique for quantitative examination by objectively monitoring the degree of serous PED.
A relevant panel of human uveal melanoma xenografts directly established from primary and/or metastatic patient’s tumor for pharmacological preclinical assays
Authors: DESJARDINS L , NEMATI F , SASTRE X , COUTURIER J , PIPERNO‐NEUMANN S , LANTZ O , DAHIANI A , ARRUFAT S , POUPON MF , DECAUDIN D 
Published: September 2008

Abstract Purpose Human cancer xenografts transplanted into immunodeficient mice constitute a useful preclinical tool for testing new agents and protocols and for further exploration of the biological basis of drug responses. The aim of this study was then to develop, establish, and characterize an in vivo panel of xenografts directly obtained from uveal melanoma patients. Methods Samples obtained from primary tumors after enucleation or from liver metastases, were subcutaneously xenografted into immunocompromised mice. A characterization of the xenografts growing into mice was then performed and compared to originated tumors, including histopathological, genetic (karyotype or FISH, and CGH‐array), and molecular assays. Results Thirty‐seven xenografts have been obtained among 95 patient’s tumor sample transplantations in which 10 have still grown after at least three transplantations in mice and have been characterized. Pathological analyses of these ten xenografts confirmed the diagnosis of uveal melanoma and showed, for the five models derived from primary tumors, similar chromosome 3 status. Bcl‐2 protein was overexpressed in all but 2 xenografts. NA17 and Melan‐A antigen expressions were positive in all tested samples, tyrosinase antigen expression was positive in all but 2 xenografts, and MAGE‐ (1/2/3/4/6/10), LAGE‐1, and MAGE‐C2 antigens expression were negative in all studied cases. Conclusion Our in vivo human uveal melanoma xenografts present the same histopathological and genomic characteristics of the patient’s originated tumors. This observation supports the use of our panel for pharmacological preclinical evaluations that could serve as a bridge linking pre‐clinical and clinical research, and drug development.
Effect of paclitaxel labeled cationic liposomes (EndoTAG1) and succinyl‐paclitaxel labeled cationic liposomes (EndoTAG SPA) in laser‐induced choroidal neovascularisation (L‐CNV) of mice
Authors: GROSS NJ 
Published: September 2008

Abstract Purpose Cationic liposomes bind specifically to activated endothelial cells. In this study we used paclitaxel (Taxol) and succinyl‐paclitaxel labeled cationic liposomes to reduce CNV in laser‐induced choroidal neovascularization (L‐CNV) of C57BL/6J mice. Methods Mice underwent ARGON‐Laser coagulations on day 0. Injection of different liposome formulations tagged with paclitaxel or succinyl‐paclitaxel via tail vein was performed on day 1,3,5,7 and 9. As control paclitaxel, succinyl‐paclitaxel, cationic liposomes or trehalosebuffer alone were injected at the same time points. Animals were perfused with fluorescein dextrane and enucleated at day10. Choroido‐sclera flat mounts were prepared for quantification of the CNV. Quantification of CNV was carried out by measuring the area of fluorescein dextrane positive vessels. Results There is a significant reduction of CNV area by EndoTAG1 and EndoTAG SPA compared to trehalose control group. The reduction of CNV area caused by paclitaxel, succinyl‐paclitaxel and cationic liposomes is not significantly different either to EndoTAG1, EndoTAG SPA or trehalose buffer group. However, there was a trend of EndoTAG1 and EndoTAG SPA being superior either to paclitaxel, succinyl‐paclitaxel or cationic liposome alone. Conclusion Cationic liposomes can be used to carry paclitaxel or succinyl‐paclitaxel to activated endothelial cells and reduce the groth of CNV membranes. In general, cationic liposomes could be used as a universal vector to transport different kinds of drugs specifically to activated endothelial cells.
Subcutaneous nadroparin calcium in the treatment of retinal vein occlusion
Authors: PINNA A , SIMULA P , SALVO M , DEVILLA L , ZINELLU A , CARTA A 
Published: September 2008

Abstract Purpose To date, no systemic intervention has been demonstrated to favorably affect the natural history of retinal vein occlusion (RVO). The purpose of this study was to evaluate the efficacy of nadroparin calcium in the treatment of RVO. Methods 13 patients with acute RVO (i.d. within a week of onset) were treated with subcutaneous injections of nadroparin calcium for 2 months. The same dose used for the treatment of deep venous thrombosis (200UI/kg/die) was given. Best corrected visual acuity (BCVA) in the affected eye was measured at baseline and after 3 months. In addition, macular thickness was measured by Stratus OCT (Carl Zeiss Meditec, USA) at baseline and after 3 months. Results Mean visual acuity was 0.39±0.33 at baseline and 0.70±0.32 after 3 months; differences were statistically significant (P=0.024). Macular thickness was measured in 8 patients; mean thickness was 510±239 μm at baseline and 331±190 μm after 3 months; differences were not statistically significant (P=0.12). After 3 months, fluorescein angiography disclosed no signs of retinal ischemia in all cases. Conclusion This preliminary study suggest that subcutaneous nadroparin calcium may be effective in the treatment of RVO. Larger long‐term studies are warranted to confirm this results.
Case of ischemic retinopathy induced by chemotherapy with paclitaxel and carboplatin
Authors: MATSUYAMA K , ANDO A , WADA M , OGATA N , NISHIMURA T 
Published: September 2008

Abstract Purpose To report a case of ischemic retinopathy induced by chemotherapy for non‐small cell lung cancer (NSCLC). Methods Case report. A 59‐year‐old man was diagnosed with NSCLC, and began treatment with both paclitaxel and carboplatin on June 1, 2007. Thereafter, he consulted our department for a fundus examination due to diabetes mellitus. Results Corrected visual acuity was 3/20 in both eyes. In spite of good control of blood glucose, shown by an HbA1c level of 5.8%, large numbers of soft exudates and retinal hemorrhages were observed in both eyes. Although no microaneurysm was found, non‐perfusion areas were revealed in the nasal retina by fluorescein angiography. We performed laser photocoagulation for the non‐perfusion areas in the retina of the left eye, however, retinopathy gradually progressed. We suspected a side effect from the chemotherapy and consulted with the attending physician. After changing the anticancer drugs, the soft exudates and retinal hemorrhages decreased and promptly disappeared. In January 2008, a vitreous hemorrhage was found in the left eye. Fluorescein angiography showed no neovascularization in the retinas of both eyes, however, the non‐perfusion areas were increased in the left. Following additional laser photocoagulation, the vitreous hemorrhage disappeared. Conclusion It is important to remember that anticancer drugs can induce severe retinopathy. Patients should be followed even after retinopathy is improved for possible recurrence.
Treatment of patients with central retinal vein occlusion by anticoagulation
Authors: REHAK M , LANGOVA K , FRIC E , REHAK J 
Published: September 2008

Abstract Purpose For patients with central retinal vein occlusion (CRVO) no effective causal therapy has been described to date. The aim of our study was to assess the safety and efficacy of anticoagulation with warfarin in patients with CRVO. Methods Retrospective interventional study evaluated 93 patients with CRVO treated with warfarin for one year between 2002 and 2007. Patients were divided into two subgroups according to the initial best corrected visual acuity (BCVA) measured by Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Group A included patients with BCVA 20/200 or worse (logMAR ≥ 1,0), group B with 20/40 or better (logMAR ≤ 0,3). Main outcome was BCVA, the frequency of unfavourable final BCVA (20/200 or worse) was evaluated and the results were compared with published results of the natural course of CRVO (Quinlann et al, Am J Ophthalmol. 1990). Results The part of patients with unfavourable final BCVA (20/200 and worse) was significantly smaller in patients treated with warfarin compared to untreated patients (21,6 %; versus 49,5 %). The significant effect of anticoagulation to final BCVA was found in patients with non‐ischemic CRVO and initial VA 20/200 or worse (37,5 % versus 88,2 %). In patients with initial VA 20/40 and better as well as in patients with ischemic CRVO no significant effect of anticoagulation was found. Relevant is the reduction of neovascular glaucoma in patients with ischemic CRVO. No adverse events (severe bleeding)were observed. Conclusion Anticoagulation seems to be an effective method affecting the causality of CRVO and reduces the frequency of unfavourable final BCVA in patients with initial BCVA 20/200 or worse. Further randomized and controlled studies are required to confirm the observed effect.
Fast accurate measurement of macular pigment with a novel technique for setting flicker thresholds
Authors: BERENDSCHOT TJM , VAN DER VEEN LP , CARDEN D , MAKRIDAKI M , MURRAY IJ 
Published: September 2008

Abstract Purpose To evaluate a new clinical method for estimating Macular Pigment Optical Density (MPOD) in large populations. Methods The principle of heterochromatic flicker photometry is used. For a series of green‐blue ratios, the modulation is slowly reduced from 60Hz (at 6 Hz/sec). Observers press a button when they detect flicker of a green‐blue (530‐465nm) temporally modulated target. Repeatability was tested on 11 subjects. Measurements (n=5) were repeated after an interval of at least three days. Healthy subjects (n=22, 22‐64 years) were tested with the new method and compared with an established spectral fundus reflectance technique. MPOD spatial profiles (n = 7) were obtained with the new method. MPOD data were collected from 5581 subjects (2435 females and 3146 males) measured in 48 optometric practices in the US. Results The new method has good repeatability (r =0.96, ~12%). The data compare well with retinal reflectometry (r =0.85, p<0.001). The spatial profiles are described by a decaying exponential function (r = 0.99), consistent with previous reports. The mean MPOD of the large data set was 0.33 ± 0.187 which is similar to previous studies. Conclusion The task is relatively easy for naïve and elderly observers. The instrument can be readily operated by non‐professional staff under clinical conditions. A further advantage is that there is a real‐time graphical output indicating satisfactory progress. The instrument provides fast, reliable, accurate MPOD data. It is ideal for large‐scale epidemiological study of the macular pigment and also for every‐day use in ophthalmic clinics and offices.
Commercial interest
Assessment of fixation locus with microperimetry and OCT in patients with Stargardt disease
Authors: LENASSI E , JARC‐VIDMAR M , HAWLINA M 
Published: September 2008

Abstract Purpose Patients with maculopathies adapt to foveal vision loss by choosing an eccentric retinal area for fixation (preferred retinal locus; PRL). The aim here was to evaluate fixation patterns by microperimetry (MP) and to correlate the results with retinal morphology seen by optical coherence tomography (OCT) in patients with genetically confirmed Stargardt disease (mutations on both alleles). Methods Fourteen patients with Stargardt disease were examined. In all patients, full ophthalmological examination, MP (Nidek Technologies MP1 Microperimeter), OCT (Topcon 3D OCT‐1000) and autofluorescence imaging (Heidelberg Engineering HRA) were performed. The results of MP testing were superimposed on the fundus image with a rectangular grid of retinal thickness as measured by OCT. Results In three eyes, fixation was central and stable. In 25 eyes, fixation was eccentric, with a superior shift in 20, a temporal shift in two, and a nasal shift in three eyes. The eccentric fixation was stable in nine, relatively unstable in 11, and unstable in five. The mean visual acuity (VA) in central fixation was 0.7 ±0.2, and in eccentric fixation 0.15 ±0.1. The mean macular thickness in central fixation was 212 ±11 μm, and in eccentric fixation 181 ±32 μm. A correlation between VA and macular thickness was seen (r = 0.43, p = 0.02). Conclusion In early stages of Stargardt disease a stable central fixation with a VA range of 0.5‐0.9, and a macular thickness range of 201‐222 μm was seen. In eyes with loss of central function, a shift of fixation to PRL was seen, with a VA range of 0.01‐0.4 and a macular thickness range of 118‐228 μm.
Macular retinal thickness in amblyopic and normal eyes of children evaluated with spectral domain OCT
Authors: KOK PHB , BESSELINK YC , DE KINKELDER R , VAN DIJK HW , VAN VELTHOVEN MEJ , VERBRAAK FD 
Published: September 2008

Abstract Purpose The purpose of this study was to investigate the macular retinal thickness, in relation to the axial length in amblyopic and normal eyes, using spectral domain OCT. Methods Included amblyopic and healthy children underwent a standard orthoptic examination and were scanned with spectral domain OCT (3D OCT‐1000, Topcon). The mean, nasal, temporal and foveal retinal thicknesses (RT) were used for analysis. We recorded the axial length using the IOL master (Zeiss). Nonparametric testing for paired data and correlations were performed using SPSS 14.0.2. Results Fifteen amblyopic patients (7 male and 8 females, mean age 8.2 ± 2) and 13 healthy children (7 males and 6 females, mean age 8.3 ± 1.5) were enrolled in this study. Compared to their fellow eyes the amblyopic eyes were 0.3 (0.6 – 0.1) mm shorter (p<.02) and had a 2.6 (0.6 – 4.5) micron thicker mean RT (p<.02) and a 4.2 (1.0 – 7.4) micron thicker temporal (p<.02) RT. No significant differences were found in the nasal and foveal minimal RT. In the normal controls none of the parameters differed significantly between both eyes (p>.05). The longer eyes were significantly correlated (r = 0.4, p<.04) with a thinner RT in this control group. However, after correcting for the axial length, the amblyopic eyes still had a significantly thicker mean and temporal RT (differences 3.4 (0.7 – 6.1) and 3.1 (0.6 – 5.5) micron, p<0.02). Conclusion Based on this study in 28 children, amblyopic eyes are slightly but significantly shorter and have thicker mean and temporal RT compared to their fellow eyes. The thicker RT in amblyopic eyes seems not to be explained by their shorter axial length.