bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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

There 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.
Orbital floor triamcinolone acetonide in the treatment of pseudophakic cystoid macular oedema
Authors: SULEMAN H , MATHEW M , LAKSHMANAN A , ABEDIN A , ORR GM
Published: September 2008

Purpose To report the outcome of orbital floor triamcinolone acetonide (OFTA) in refractory pseudophakic cystoid macular oedema(PCMO) and to determine the visual outcome in these patients

Methods Six eyes of 6 patients with PCMO inadequately responsive to treatment combinations of topical steroidal and non‐steroidal agents were retrospectively studied. All received 40mg (1ml) OFTA injection. Post‐operative Visual acuity (VA), intraocular pressure (IOP) and OCT findings were assessed. Other potential complications were looked for retrospectively.

Results The average age was 72 years(+/‐12 years). OFTA was given, on average, 4 weeks after a diagnosis of PCMO was made (range 0‐6 weeks) and treated with topical anti‐inflammatory agent combinations. The mean follow‐up was 11.0 months (range, 5‐18), and the mean improvement of VA after OFTA was Snellen, (6/18‐6/12). This was noticed at a mean of 12 weeks (range 4‐72). At last follow‐up, five eyes showed an improvement of two lines or more, while in one eye vision was maintained at 6/24 which developed diabetic maculopathy and required grid laser. None of the patients developed post‐treatment raised IOP or lost vision. There was a significant reduction of retinal thickness and cystoid space height (P = 0.003). The dosage of topical steroids was reduced or stopped altogether in all 6 eyes. There were no cases of injection‐related retrobulbar haemorrhage, cellulitis, or globe perforation

Conclusion In cases of psuedophakic CMO, initial response to OFTA treatment was encouraging. Further larger long term studies are required to ascertain whether re‐treatment is effective with subsequent orbital floor steroid injections. This is with a view to maintain the initial improvement.
The relationship between macular pigment optical density and ApoE genotype
Authors: LOANE E , NOLAN JM , MCKAY G , STACK J , BEATTY S
Published: September 2008

Purpose To investigate the relationship between macular pigment optical density (MPOD) and ApoE genotype in healthy subjects with and without a family history of age‐related maculopathy (ARM).

Methods We recruited 336 subjects for this study. Demographic and health details were recorded. MPOD was measured by customised heterochromatic flicker photometry using the Macular Densitometer. Genotype data was downloaded from HapMap for the CEU population. Genotyping was performed using SNaPshot assays on an ABI 3100 genetic analyser.

Results 4 subjects did not meet our analysis criteria and were excluded. Genotype data were available on 94.3% of our sample. 62.6% of subjects had the ε3ε3 genotype (non‐risk); 25.2% had at least 1 ε4 (protective) allele; 12.7% had at least 1 ε2 (risk) allele. Only 1 subject had the ε2ε2 genotype; this subject had a family history of ARM. Of the 8 subjects with the ε4ε4 genotype, only 2 had a family history of ARM. There was no significant difference in the remaining genotype distribution between subjects with and without a family history of ARM. We divided our sample into 3 genotype groups: Group 1: ε2ε2 or ε2ε3 (n=38); Group 2: ε3ε3 (n=194); Group 3: ε2ε4, ε3ε4 or ε4ε4 (n=78). There was a statistically significant difference in peak MPOD between these groups: Group 3 had the highest mean MPOD; Group 1 had the lowest (p=0.002). This significant association remained after controlling for age, sex, BMI, family history of ARM, smoking, alcohol intake, dietary and serum lutein and zeaxanthin.

Conclusion The presence of the Apo ε4 allele appears to be associated with higher MPOD values in healthy subjects. The importance of this finding rests on the fact that the Apo ε4 allele is protective against ARM.

Commercial interest
Efficacy and tolerance of early high‐dose corticosteroid therapy in Vogt‐Koyanagi‐Harada disease
Authors: BOUCHENAKI N , HERBORT CP
Published: September 2008

Purpose Early high dose corticosteroid therapy with "adequate" duration has become the mainstay therapy in Vogt‐Koyanagi‐Harada (VKH) disease. This work report the tolerance and side‐effects in a small series of VKH patients having received “maximal” Inflammation Suppressive Therapy (IST).

Methods Medical records of VKH patients seen in the the COS uveitis clinic in Lausanne were analyzed. Standard care consisted in prolonged high IST including high dose oral prednisone (60‐200 mg/day), slowly tapered, with or without initial 3‐day megadose (500‐1000 mg of methylprednisolone) intravenous pulse therapy with adjunction of immunosuppressive therapy if necessary. Follow‐up time, total prednisone dose, duration of therapy, adjunctive immunosuppressive treatments, major side‐effects, clinical outcomes were recorded.

Results Nine patients were included. Initial oral daily corticosteroid dose was above 60 mg of prednisone in all patients. Immunosuppressive therapy was used in 6 patients either to reinforce IST or to obtain a corticosteroid‐sparing effect. Major side effects were recorded in one patient who developed a bilateral aseptic hip necrosis needing bilateral hip replacement. Clinical outcomes were favorable in 8/9 patients with no sunset‐glow fundus at the one year follow‐up visit and with 7/9 patients beeing treatment free after a slow, mostly indocyanine green angiographically controlled tapering over more than 2 years.

Conclusion High dose IST was relatively well tolerated and associated with favorable clinical outcome. Side‐effects of maximal IST are not to be minimized, but seem however acceptable in view of the favorable outcome induced. Treatment duration was found to be much longer than usually recommended in textbooks.
Interest of an interferon‐gamma release assay for diagnosing tuberulosis‐related ocular inflammation
Authors: GINEYS R , TRAD S , TERRADA C , LE THI HUONG DU , FARDEAU C , CASSOUX N , LE HOANG P , BODAGHI B
Published: September 2008

Purpose Tuberculosis‐related ocular inflammation has many clinical presentations. Most of the time, bacteriological proof is not available and the diagnosis remains presumptive. Workup for another site of infection is seldom rewarding and tuberculin skin test (TST) results can be misleading. QuantiFERON‐TB Gold test is an interferon‐gamma release assay now currently available for tuberculosis screening.

Methods We made a review of the charts of the patients who had had a QuantiFERON‐TB Gold test in the ophthalmology department in Pitié‐Salpêtrière, Paris, France between January and October 2007.We included patients with intraocular inflammation who had the QuantiFERON test done before the TST was performed. We decided to conduct a full anti‐tuberculosis therapeutic test in those patients who had a positive QuantiFERON‐TB Gold test result.

Results We found 96 QuantiFERON‐TB Gold test results. The mean age at presentation was 51 years (22‐88, SD=17)and the F/M ratio was 60%. Patients exhibited all types of uveitis (anterior, intermediate, posterior, panuveitis) and some of them had scleritis. QuantiFERON‐TB Gold turned out positive in 41 cases, among whom 33 had positive TST, 9 had negative TST and 9 had undetermined TST. Twenty‐six patients received the treatment. At six months of follow‐up, 16 of them had no intraocular inflammation.

Conclusion QuantiFERON‐TB Gold test is a convenient ancillary test compared to TST (no control visit, no stimulation of the patient's immune system). It appears useful to help identify patients with tuberculosis‐related ocular inflammation. Further studies are needed to determine whether we should use it instead of TST in this setting.