bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterozygous B6;C3‐Opa1Q285STOP mouse model of dominant optic atrophy displays subtle neuromuscular features with age
Authors: VOTRUBA M , TAYLOR E , DAVIES J , POWELL K , DAVIES V
Published: November 2010

Purpose OPA1 autosomal dominant optic atrophy is a slowly progressive optic neuropathy. A neurological ‘plus’ phenotype has been reported with some OPA1 mutations, prompting further systemic evaluation of our mouse model. Heterozygous Opa1 mutant mice (B6;C3‐Opa1Q285STOP), with documented visual defects on optokinetic drum tracking and optic nerve defects on electron microscopy, were assessed. Here we explore neuromuscular aspects of the phenotype.

Methods Published husbandry and genotyping protocols were used. Body weight, SHIRPA test, accelerating rotarod and visual acuity testing using the optokinetic drum was carried out.

Results Mean weights of all Opa1 male and female mice over 6 months age showed a trend towards lighter weight in Opa1+/‐ mice (WT 32.74g, SD=6.0; Het 29.47g, SD=2.7 ; p> 0.05). By 20 months of age there was a statistically significant difference between WT and Hets (WT 40.6g, SD=3.1; Het 28.77g, SD=2.44; p< 0.05). SHIRPA neurological screen of 12 month old animals showed that Opa1+/‐ (Hets) were less active than wild type (WT) in an open arena (p<0.05), and less able to perform the wire hang test (p<0.05). 12 month Opa1+/‐ showed reduced mean performance on rotarod (WT 92s, SD=10; Het 70s, SD=20.9; p=0.05). Rotarod testing at 20 months was discontinued since grossly obese wild type mice were unable to perform the test and act as controls.

Conclusion Opa1+/‐ mice are lighter than WT age and sex matched controls. Rotarod testing confirms a subtle neuromuscular defect in Opa1+/‐ mice in line with neurological (SHIRPA) testing.
Age‐related modifications in RPE cells
Authors: MANNERMAA E
Published: November 2010

Age‐related macular degeneration (AMD) is a multi‐factorial polygenetic aging disease. It has been shown that RPE dysfunction predisposes neural retinal dysfunction and the development of choroidal neovascularization. The pathogenesis of age‐related macular degeneration (AMD) essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells and extracellular drusen formation, as well as the presence of chronic inflammation. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. This presence of lipofuscin decreases lysosomal enzyme activity and impairs autophagic clearance of damaged proteins which should be removed from cells. Proteasomes are another crucial proteolytic machine which degrades especially cellular proteins damaged by oxidative stress. The cross‐talk between lysosomes, autophagy and proteasomes in RPE cell protein aggregation, their role as a possible therapeutic target and their involvement in the pathogenesis of AMD is discussed. In addition, age related changes in Bruch’s membrane and choroidal blood flow may take part in the pathogenesis of AMD. This will be also discussed.
Why are retinal pigment epithelial cells so resistant to oxidative stress?
Authors: BRUNK U , KURZ T , KARLSSON M
Published: November 2010

Purpose The functional integrity of postmitotic retinal pigment epithelial (RPE) cells is crucial for photoreceptor survival, and RPE malfunction is considered an important factor behind age‐related macular degeneration (AMD). Although RPE cells daily phagocytose large amounts of fatty acid‐rich distal photoreceptor material, their lysosomal accumulation of lipofuscin (LF) is nevertheless slow. Only late in life do humans have LF‐loaded RPE cells, which then not only have a reduced capacity to endocytose photoreceptor material but also are less capable of keeping up with normal autophagy. The latter activity is important for normal turnover of the cell’s own components.

Methods ARPE‐19 cells in culture were evaluated with respect to lysosomal stability at oxidative stress. Redox‐active iron, autophagic activity (evaluation of LC3‐I and LC3‐II protein), and anti‐oxidative proteins were assayed using cytochemistry (Sulphide‐Silver Method), electron spin resonance (ESR) and western blotting for a variety of stress proteins.

Results The lysosomal compartment of the ARPE‐19 cells was found remarkably resistant to oxidative stress. The SSM and ESR methods suggested low lysosomal amounts of redox‐active iron and no enhanced autophagy following oxidative stress. The normal autophagy rate was higher than in other professional scavengers.

Conclusion The found low amount of lysosomal redox‐active iron explains the slow formation of lipofuscin over time and the remarkable stability that ARPE‐19 cells and their lysosomes show even under severe oxidative stress. The molecular mechanisms behind this phenomenon may be an unusual capacity to quickly export low mass iron from lysosomes to the cytosol and/or a high normal degree of autophagy of iron‐binding stress proteins.
Childhood onset retinal dystrophy in Northeastern Tunisia: phenotypic characteristics and RPE65 gene analyses
Authors: CHEBIL A , LARGUECHE L , TRIKI M , BAKLOUTI K , CHOUCHENE I , OUECHTATI F , ABDELHAK S , MUNIER F , EL MATRI L
Published: November 2010

Purpose To describe the phenotypic characteristics of seven families with childhood onset retinal dystrophy in Northeastern Tunisia and to determine the linkage with RPE65 gene mutation.

Methods Seventy subjects were concerned (18 affected patients and 52 unaffected). Ophthalmic examinations included visual function testing, fundus examination, full field ERG, spectral OCT and fluoroangiography. After patients consent, screening of RPE65 gene was performed by bi‐directional sequencing.

Results All affected members had a severe retinal dystrophy with history of low visual acuity since infancy. The age at first ophthalmic examination ranged from 5 to 55 years old. Visual acuity ranged from no light perception to 2/10. Two retinal patterns were identified: the first one presented midperipheral white dot deposits, whereas the second showed midperipheral pigmented clumps without any white deposits. Atrophic and /or pigmentary macular changes were present in most patients. Mutational screening of the RPE65 gene identified an homozygous R91W mutation co‐segregating with the disease in 11 affected individuals. Two siblings were compound heterozygous for this mutation.

Conclusion We identified and characterized an endemic form of early onset rod‐cone dystrophy in a consanguineous population from northeastern Tunisia, due to the prevalence of a single single homozygous missense R91W mutation in exon 4 of the RPE65 gene. This could have practical value for genetic screening strategy in young affected tunisian patients.
Principles of genetic counselling
Authors: HALL G
Published: November 2010

Purpose To present the genetic counselling needs of families with inherited eye disease.

Methods A presentation on the counselling challenges and ethical dilemmas in genetic services for inherited eye disease using case illustrations and review of research and current literature.

Results Genetic counselling for families with inherited eye disease is rapidly advancing with improvements in molecular testing leading to accurate diagnosis and information for families. With increasing patient demand and expectation, families request genetic counselling to understand the inheritance pattern and the risks to themselves and their children. However, the heterogeneity, variable penetrance and overlapping phenotypes make this particularly challenging in genetic eye disease. Genetic counselling is a communication process to provide information about the genetic condition, its inheritance and to facilitate decision‐making around genetic testing and reproduction. Genetic counsellors have experience in helping individuals decide and come to terms with results from genetic testing such as pre‐symptomatic testing, childhood testing and pre‐natal diagnosis. In addition, families are often coping with the psychological burden of progressive blindness and the impact of vision loss and risk to other family members. Recent publications highlight the disparity in specialist service provision for families with inherited eye disease and calls for research and improvements in evidenced‐based practice.

Conclusion Families with inherited eye disease have complex genetic counselling needs requiring multidisciplinary co‐ordination of services for accurate diagnosis, information provision, genetic testing and decision‐making, and support and follow‐up.
Update on ophthalmic molecular genetics
Authors: DE BAERE E
Published: November 2010

Purpose To provide an overview of the recent technological advances in human molecular genetics that can be applied in ophthalmic genetics.

Methods Since the finalization of the Human Genome Project many novel genomic technologies emerged that led to significant advances in gene identification and genetic testing of hereditary eye disorders: (1) genomewide copy number screening (array CGH); (2) genomewide SNP genotyping; (3) next‐generation sequencing.

Results (1) Microarray comparative genomic hybridisation or array CGH allows genomewide discovery of submicroscopic deletions and duplications in a single experiment. This technique is applied in routine molecular cytogenetic testing. Using array CGH a causal genomic defect can be found in at least 10% of all cases with mental retardation and/or multiple congenital anomalies. In ophthalmic genetics array CGH is mainly useful in the context of developmental eye disorders, with chorioretinal coloboma and anterior segment dysgenesis as an example. (2) Genomewide chip‐based SNP genotyping can be used for homozygosity mapping in inbred and outbred pedigrees. Recent successes in gene identification using this approach are illustrated. (3) Next‐generation sequencing or NGS. The application of this technology in gene identification and genetic testing of genetically heterogeneous conditions (with LCA as a paradigm) is discussed.

Conclusion The rapid progress of genomic technologies such as array CGH, SNP chip analysis and next‐generation sequencing lead to a boost in gene identification and genetic testing of both developmental and retinal eye disease.
Update on inherited ocular developmental disease
Authors: BLACK GCM
Published: November 2010

Purpose To provide an overview of progress in understanding of the genetics of developmental ocular disease.

Methods A systematic review, including case presentations, to illustrate insights into genes underlying developmental ocular disorders:

Results Studies suggest that, in developed countries, between a third and a half of the diagnoses underlying childhood blind or partial‐sighted registration are genetic while a number of other ‘non‐genetic’ conditions also have a substantial genetic contribution. Such a figure is likely to be an underestimate. Although most of these conditions are rare, many of the issues regarding diagnosis and counselling apply to the group as a whole and it is therefore possible to consider a common approach to many aspects of their clinical management. An important challenge, for example, is to improve genetic counselling for patients affected by, and at risk of, disorders that may be caused by a genetic change in one of many possible genes, which typifies many inherited conditions associated with blindness (developmental ocular disorders, early‐onset retinal dystrophies, congenital cataract). Most diagnostic genetic testing currently being undertaken focuses on single genes; this will be illustrated for ocular conditions such as retinoblastoma, Norrie disease and microphthalmia. However future prospects will focus upon use of new higher throughput technologies (e.g Microarray technologies).

Conclusion The recent identification of genes underlying, for example, anophthalmia/microphthalmia spectrum (e.g. VSX2, SOX2, BCOR), anterior segment dysgenesis (e.g. PITX2, FOXC1, FOXE3) and early–onset retinal disorders (e.g. ADVIRC, RPE65) has shed light on the pathways and processes underlying a range of the biological processes underlying ocular development.
Electrodiagnosis in inherited retinal disease
Authors: HOLDER GE
Published: November 2010

Purpose To describe the roles of electrophysiology in the diagnosis and counselling of patients with inherited retinal disease.

Methods Electrophysiological testing performed to incorporate and extend the recommendations of the International Society for Clinical Electrophysiology of Vision.

Results Using a case‐based presentation, it will be shown that electrophysiological testing can objectively assess the function of the different cell types and layers within the retina of the patient with inherited retinal dysfunction, which enables accurate diagnosis and counselling when placed in clinical context. The roles of pattern and multi‐focal ERG in the assessment of macular function will be discussed. The electrophysiological findings will be discussed in relation to imaging studies when appropriate. It will shown that distinctive electrophysiological findings can direct appropriate and therefore cost‐effective mutational screening in patients with atypical fundus changes.

Conclusion Electrophysiological testing is fundamental to the successful management of patients with inherited disorders of retinal function.
Canaliculitis: epidemiology and care in about 8 cases
Authors: DUPLA JB , LEGARREC J , ABADIE C , MOURIAUX F
Published: November 2010

Purpose Canaliculitis is a cause of recurrent conjunctivis and epiphora, commonly misdiagnoses. The medical treatment is usually inadequate and surgery is the mainstay of treatment.

Methods It is a retrospective study of surgical procedures associated with subsequent topical antibiotic therapy. We report the clinical features, microbiological profile and treatment outcome in a series of 8 patients with suppurative lacrimal canaliculitis over a period of 4 years in Caen teaching hospital.

Results Actinomyces israelli was identified in 7 cases. Canalicular curretage was performed in 5 cases with intubation in 3 cases. 3 patients were treated by anterior canaliculotomy. The canaliculitis resolved completely after surgery in 7 cases. All patients have patent canalicula. One case of early recurrence was treated by a second curretage successfully.

Conclusion Canaliculitis is often delayed diagnoses. The treatment must be a surgical removal of all possible concretions for cure. Canalicular curretage is efficient in most of cases and preserves the lacrimal puctum. Intubation can be discussed.
Anterior uveitis caused by Herpes viruses
Authors: MARKOMICHELAKIS N
Published: November 2010

Abstract not provided
Fuchs’ uveitis
Authors: BOUCHENAKI N
Published: November 2010

Abstract not provided
Chorioretinitis
Authors: HERBORT CP
Published: November 2010

Abstract not provided
Inflammatory neovascular membrane
Authors: NERI P
Published: November 2010

Purpose To describe the most common mistakes in the management of inflammatory choroidal neovascularization (CNV).

Methods The current literature is reviewed and the experience of a tertiary referral centre is reported.

Results CNV is a potentially sight‐threatening sequela of uveitis. Several mistakes can be done during patients examination: CNV might not be recognized both at biomicroscopy and at fluorescein angiography (FA), for instance. Moreover, since some doctors are not aware of the importance of Indocyanine Green Angiography (ICGA), the choroidal involvement during inflammatory CNV might not be appreciated. These are just some examples of possible errors which can be done during the daily practice. The outcome of subfoveal CNV is poor if untreated: several procedures have been considered, even though there is lack of guidelines. The most important mistake can be represented by the lack of criticism on the treatment techniques: several methods have been proposed, albeit some of them should not be used on the basis of the treatment rationale and on the better knowledge of CNV pathophysiology. The presentation shows the most typical cases where the above mentioned mistakes have been done, suggesting some methods in order to avoid them.

Conclusion CNV secondary to uveitis is a severe sequela, which can lead to significant visual impairment. Several mistakes can be done during both the diagnosis and the therapeutic procedures. Although no guideline is provided, the current medical literature can give the basis for a successful treatment strategy.
Retinal disease masquerading posterior pole inflammation
Authors: KHAIRALLAH M
Published: November 2010

Abstract not provided
C3 gene polymorphism R102G in a Greek population with age‐related macular degeneration
Authors: PHARMAKAKIS N , DELIS A , MARIOLIS D , HAVAS I , ZARKADIS I
Published: November 2010

Purpose To elucidate whether C3 R102G polymorphism is a major genetic determinant of AMD in a Greek population as well as to evaluate its prognostic importance for progression to advanced AMD

Methods A clinic‐based case‐control association study was conducted, comprising 98 Greek patients with early‐ and advanced‐stage AMD and 125 independent controls of Caucasian origin. All participants underwent a complete ophthalmic examination, fluorescein angiography and OCT. Information on cigarette smoking, hypertension and family history was obtained by interview at baseline. Moreover, they were genotyped for C3 R102G polymorphism, by using ARMS‐PCR.

Results The frequency of the C3 R102G allele was significantly higher in AMD patients in comparison with controls while the odds ratio (OR) for AMD was 1,46 (CI 95% = 0,82‐2,59). Statistical comparison between early and advanced AMD patients, on the basis of C3 genotypic frequencies, revealed that the C3 R102G allele was more prevalent in advanced AMD patients (P<0,05, OR=2,62). Moreover, both GG and CG genotypes were found to be more prevalent in patients with neovascular AMD (ORs = 3,95 and 2,51, respectively) when compared with non‐exudative AMD patients. Concerning family history, it is significantly higher among patients with GG genotype when compared to CG and CC genotypes. On the contrary, C allele was associated with hypertension and smoking in AMD patients when compared to G allele.

Conclusion The replication of the reported associations of C3 R102G polymorphism with AMD suggest that the 102G allele could serve as a genetic marker for the development of AMD and the progression of the disease to the advanced clinical stage in the Greek population.
Development and evaluation of PLGA nanoparticles with cyclosporine and the inclusion of HPβCD for ocular use
Authors: HERMANS K , WEYENBERG W , LUDWIG A
Published: November 2010

Ocular delivery of peptides requires new concepts in order to optimize the bioavailability and its therapeutic effect. The first peptide selected in present research project is Cyclosporine A (CyA) used in the treatment of the dry eye syndrome and against corneal graft rejection. The aim of the project is the development of nanoparticles with physicochemical properties for a suitable and prolonged release of CyA, using a factorial design. These drug delivery systems will be produced employing PLGA using the emulsification solvent evaporation method. Positively charged polymers as chitosan or Eudragit® will be incorporated to obtain nanoparticles with a positive particle charge. Electrostatic interactions with the negatively charged mucins lead to a prolonged residence time at the precorneal area. Nanoparticles will be evaluated on zeta potential, particle size and their in vitro drug release properties. CyA and CyA complexed with HPβCD will be compared. The most suitable preparations will be selected in a next phase of the project for an in vivo study using an animal model.
Analysis of the utility of QuantiFERON‐TB GoldTM in tube and measurement of IFNγ release by peripheral mononuclear cells in response to different mycobacterium antigen in the work‐up of patients with uveitis
Authors: MAKHOUL D
Published: November 2010

Purpose Tuberculosis remains an important cause of infectious uveitis and immune reaction against mycobacteria may contribute to the development of certain forms of autoimmune uveitis. Moreover, many non‐infectious uveitis patients are treated with immunomodulatory treatment. The evaluation of tuberculosis immunity is thus an important aspect in the work‐up of patients with uveitis. In this work, we would like to investigate the usefulness of different methods of tuberculosis immunity testing in a series of patients with intraocular inflammation.

Methods Patients with uveitis will undergo a standard diagnosis procedure, including a chest Xray. Quantiferon TB Gold in Tube (QFT) and tuberculin skin test (TST) will be performed. IFNγ production by mononuclear cells in response to PPD and to HBHA will be measured by ELISA.

Results Thirty‐two patients have already been recruited. Sixteen had a negative QFT and a negative TST. In two of them, mononuclear cells produce IFNγ in response to PPD (but not to HBHA) and in 1 in response to HBHA (but not to PPD). In 11 patients QFT and TST were positive. In this group, IFNγ response to PPD was observed in 82% but only in 50% in response to HBHA. Discordant results between QFT and TST were observed in 5 patients. One had a positive QFT and a negative TST and 4 had a positive TST and a negative QFT. In this group IFNγ response to PPD or HBHA was not observed.

Conclusion Discordant results between QuantiFERON‐TB Gold and TST were observed in 15 % of uveitis patients. Analysis of the IFNγ production in response to PPD and to HBHA seems to add important information in both concordant and discordant group.
Expression and role of aquaporins in diabetic retinopathy
Authors: MOTULSKY E
Published: November 2010

Purpose Aquaporins (AQP) are involved in water movements but also in cell proliferation. The aim of our study is to investigate their potential role in diabetic retinopathy

Methods In vitro, human and mouse RPE cell line will be grown under different conditions. Expression of AQPs will be investigated by RT‐PCR and Western blot. Immunofluorescence will be used to determine AQP expression on retinal section from normal and NOD diabetic mice, and on on vitreoretinal membranes removed from patients with proliferative retinopathy

Results Human ARPE‐19 cells expressed AQP4, while mouse B6‐RPE07 cells expressed AQP1. Hypertonic conditions strongly decrease AQP4 expression in ARPE‐19, but not AQP1 expression in B6‐RPE07 cells. In B6‐RPE07 cells, significantly decrease in AQP1 expression was obtained following TNFα treatment. In normal mice, AQP1 and AQP4 expression were restricted to the photoreceptor layer and to the Müller cells, respectively. Retinal endothelial cells did not express AQP1. No AQP4 expression was detected in RPE cells. AQP1 was strongly expressed by choroidal endothelial cells, rendering difficult the evaluation of AQP1 expression by RPE cells in vivo

Conclusion Our preliminary data confirms that blood retinal barrier cells express AQPs in vitro and in vivo. More studies are needed to precise the nature and regulation of this expression in normal and diabetic conditions. We hope that our combined in vitro and in vivo approaches might help to better understand this complex aspect of retinal biology
Three dimensional computed tomography application for ocular foreign bodies visualization
Authors: ASOKLIS R , PAJAUJIS M , BUTKIENE L , MAKSELIS A , RUTKAUSKAITE D
Published: November 2010

Purpose To present 3 cases reports of eye injuries and application of three dimensional computed tomography (3DCT) for the ocular foreign bodies (FB) localization.

Methods Case 1. 34 years old female was admitted to hospital because of the right eye injury during a car accident. Giant glass fragment in the right orbit was visible, extent of the lesion was obscure. Case 2. 49 years old male was admitted to hospital because of the right eye open globe injury. The fishing hook in the right eye cornea, laceration of the iris, and traumatic cataract were found. Case 3. 36 years old male was admitted to hospital because of the left eye open globe injury with a drill fragment. After the pupil dilatation the FB in the lens was detected. In all cases X‐ray examination, single slice computer tomography (SSCT) and 3DCT reconstruction images were performed.

Results Data of 3DCT allowed discovering extent of the injury and localization of the FB. Patients were operated, FB’s were removed. In case 1 periocular skin lacerations were sutured recovering anatomical and functional tissue integrity. In case 2 and 3 extraction of traumatic cataracts and intraocular lens implantation were performed.

Conclusion Conventional radiological methods such as X‐ray examination and SSCT can be insufficient suggesting complex eye trauma cases. 3DCT is informative tool and helps to determine the location of the FB and extent of the injury.
Ability of Fourier domain OCT to evaluate macula in retinitis pigmentosa patients
Authors: GARCIA MARTIN E , PINILLA I , IDOIPE M , FUERTES MI , CRUZ N , ABECIA E , GIL‐ARRIBAS L , GUERRI MONCLUS N , FERNANDEZ S
Published: November 2010

Purpose To evaluate the ability of Fourier domain optical coherence tomography (OCT) detecting changes in macular structure and thickness in patients diagnosed of Retinitis Pigmentosa (RP).

Methods Thirty‐two eyes of 16 patients with RP and 30 eyes of 30 healthy subjects underwent a complete ophthalmic examination with best corrected visual acuity, 512x128 macular volume cube protocol using Cirrus HD‐OCT (Carl Zeiss Meditec, Inc., USA) and Spectralis OCT (Heidelberg Engineering, Germany). Macular changes as retinal schisis, macular hole (MH), epiretinal membrane (EM), retinal pigment epithelial detachment (PED) or macular drusen, were registered. Comparisons between RP and healthy eyes were done for the nine macular areas defined by the Early Treatment Diabetic Retinopathy Study (ETDRS).

Results All macular thickness parameters showed a statistically significant decrease in the RP patients (p<0.05, t test). The greater difference with control eyes was observed in the nasal inner ETDRS area (247.54 vs 328.99 µm with Cirrus OCT and 259.65 vs 351.74 µm using Spectralis OCT). Retinal abnormalities found in RP eyes were: 16% retinal schisis, 3.3% MH, 6.6% EM and 3.3% PED.

Conclusion Retinal atrophy and structural alterations can be detected in RP patients using Fourier domain OCT.
Electrophysiological findings in a large sample of children with diagnosis of Joubert syndrome
Authors: SUZANI M , RUBERTO G , SIGNORINI S , BERTONE C , BARILLA D , MISEFARI W , ANTONINI M , TINELLI C , BIANCHI PE
Published: November 2010

Purpose To compare electrophysiological data in a group of patients with Joubert syndrome (JS).

Methods We enrolled 26 JS patients. They underwent to complete ophthalmological assessment and functional analysis by mean of electroretinogram (ERG) and patterned evoked potentials (pVEPs) recorded in awake conditions. Patients were divided into 2 groups, depending on the presence of retinal dystrophy at clinical evaluation. We compared data from electrophysiological assessment between three groups of eyes: 1) JS subjects with retinal dystrophy (RD‐JS): 15 patients 2) JS subjects without retinal dystrophy (NRD‐JS): 11 patients 3) Control (CTRL) eyes: 18 patients

Results Our three groups did not statistically differ in age. In the RD‐JS, traces were really poor, mostly the 30 Hz and "a“ component, or not measurable at all. Though, for the “b“ trace, it was possible to measure reliable signal in 7 of 15 patients. As a result of the statistical analysis (ANOVA Kwallis with adjust p values for two comparisons) mean ERG amplitudes and latencies were reduced and delayed respectively, not only in the analysis “RD‐JS vs CTRL” and “RD‐JS vs NRD‐JS”, but also, for some parameters, between NRD‐JS and the CTRL.

Conclusion The electrophysiological alterations in the ERG and pVEPs recordings might be an index of subclinical involvement or imply both a central retinal alteration and a central nervous system disease.
How to find the difficult balance between a busy clinical schedule and teaching possibilities ?
Authors: SPILEERS W
Published: November 2010

Abstract not provided
Protected time for education of young ophthalmologists; the Danish experience
Authors: PRAUSE JU
Published: November 2010

Abstract not provided
Time is money, but money is not necessarily time
Authors: SEREGARD S
Published: November 2010

Abstract not provided
Training contract vs time and motivation
Authors: ACLIMANDOS W
Published: November 2010

Abstract not provided
Influence of change in body position on choroidal blood flow in patients with obstructive sleep apnea syndrome
Authors: ALMANJOUMI A , TONINI M , KHAYI H , PEPIN JL , RENARD E , LEVY P , ROMANET JP , GEISER MH , CHIQUET C
Published: November 2010

Purpose Obstructive sleep apnea syndrome (OSA) has been reported to be associated with ischemic and glaucomatous optic neuropathy (especially normal tension glaucoma). OSA per se is able to generate hypertension, atherosclerosis and autonomic dysfunction, all conditions possibly interacting with ocular vascular regulation. The aim of our study was to characterize the choroidal vascular reactivity to change in body position in OSA patients, as compared with matched healthy control subjects.

Methods Eighteen newly diagnosed OSA patients were included in this prospective study. Control subjects were matched with OSA patients for body mass index (BMI), gender and age. At the screening visit, each subject underwent a general exam, cardiovascular, neurologic and ophthalmological examinations, and overnight polysomnography. The LDF instrument used in this study to measure subfoveal choroidal blood flow (ChBF), ChBVel , velocity (kHz); and volume, ChBVol (in arbitrary units, AU) Vascular choroidal reactivity was tested during the change in body position from the sitting to the supine position (10 min).

Results OSA patients exhibited a similar choroidal reactivity during change in body position than controls with increased ChBVel (+15%), decreased ChBVol (‐11.6%), and unchanged ChBF. IOP increased by 14.2% in the supine position whereas ocular perfusion pressure remained stable.

Conclusion This prospective comparative study showed for the first time unimpaired choroidal vascular reactivity in otherwise healthy OSA patients. This suggests OSA patients, without comorbidities, has long‐term adaptive mechanisms active in ocular microcirculation.
Preservative free tafluprost 0.0015% in the treatment of patients with ocular hypertension and glaucoma: results of a multi‐center open‐label observational study
Authors: LANZL I , ERB C , SEIDOVA S , KIMMICH F
Published: November 2010

Purpose Efficacy, tolerability and safety of the novel preservative‐free prostaglandin tafluprost 0.0015% were investigated.

Methods Data were collected in a non‐interventional prospective multi‐center observational open label study. IOP readings were recorded for each eye at baseline (prior therapy or untreated) and 12 weeks after changing or initiating treatment with preservative‐free tafluprost. Change in IOP was evaluated over the study period for all patients and for specific pre‐treatment subgroups. Local comfort was measured using a 5 step scale. All adverse events were recorded.

Results Data from 2123 patients with glaucoma or ocular hypertension were eligible for the final evaluation. In all patients preservative‐free tafluprost lowered IOP from 19.5+4.4 mmHg at baseline to 16.4+2.9 mmHg after 12 weeks. Preservative‐free tafluprost also lowered IOP significantly in all monotherapy‐subgroups: Naϊve patients (N=440): 22.6+3.9 mmHg to 16.7+2.7mmHg; betablockers (N=307): 20.3+3.5 mmHg (baseline) to 16.7+2.6 mmHg (week 12); CAI’s (N=158): 19.0+3.6 mmHg to 16.0+2.6 mmHg; PG’s (N=447): 16.8+2.9 mmHg to 15.8+2.6 mmHg. Local comfort was rated as 'very good' or 'good' by 85.6% of patients at the final visit. Only few adverse events occurred during the treatment period.

Conclusion Preservative‐free tafluprost was effective, well tolerated and safe in a broad patient population. Local comfort and patient satisfaction improved after change of medical treatment in the vast majority of patients.

Commercial interest
Pathological changes of anatomical structure and markers of limbal stem cell niche due to inflammation
Authors: CURCIO C , CALIENNO R , LANZINI M , PEDROTTI E , NUBILE M , MASTROPASQUA L
Published: November 2010

Purpose It’s known that severe inflammatory processes may cause limbal stem cell (SC) deficiency decreasing the number of SC niches and changing the microanatomy of these structures.

Methods The aim of this study was to evaluate the expression of different SC markers in normal human limbus and to study how an inflammatory conditions can modulate these antigens. To understand the pathological changes in limbal crypts structure due to severe inflammation, a case of corneal melting and perforation in advanced herpes simplex (HSV) disease, two cases of endophthalmitis and a case of fungal infection were analyzed.Samples were examined by immunohistochemistry or immunofluorescence for p63, vimentin, laminin5, integrin (Int) α6, int β1, int β4, ABCG2, desmoglein 3, connexin43, N‐cadherin and cytokeratin (K) 12 positivity. We evaluated the anatomical structure of limbal crypts in each case and the positivity for SC marker used to identify SC.

Results In normal limbus, the investigated SC markers were positive. In the HSV we didn’t observe presence of crypts, whereas in both cases of endophthalmitis crypts were still present but they had an atypical structure: the basal cells in the crypts were “stretched” and endowed by inflammatory cells. In the pathological cases, we observed positivity for K12 while, among SC markers, p63, ABCG2 and connexin43 were still present; the others antigens were variably expressed.

Conclusion Different pathologies involving the limbus may result in marked chenges of expression of SC markers within the crypts.
Cultivation of limbal stem cells‐derived corneal epithelium on different biologic materials for clinical transplantation
Authors: PETROVSKI G , ALBERT R , BERéNYI E , MOE MC , JOHNSEN EO , NICOLAISSEN B , MODIS LJR , BERTA A
Published: November 2010

Purpose To develop simple, reproducible, animal‐materials free method for cultivating limbal stem‐cells and differentiating them into corneal epithelium on different human biologic materials for clinical transplantation.

Methods The limbal tissues (2x2mm) were harvested from cadavers not more than 8 hours after death and proliferated in vitro on cell culture tissue plates, human amniotic membranes (HAM) or human lens capsules in medium containing human AB serum. Cell viability was tested using the MTT assay and annexin‐FITC/Propidium Iodide positivity methods. Molecular gene and immunofluorescent marker studies for stemness, proliferation and differentiation were used for the analysis.

Results Over a period of one year, 50 limbal tissue explants were cultivated. Emergence of cells at one edge of the explants occurred within 24 hours from culturing and formed monolayer within 14 days. Although the speed of cell growth varied among donors and types of media for growth, inadequate growth at two weeks was never recorded. The viability of the cells at 7 and 14 days of cultivation was higher than 96% except in case of HAM use where viability was below 80%. The growing cells were characterized for their positivity for stemness (P63, ABCG2), proliferation (ki67) and epithelial cell markers CK 3, 8, 12, 14, 18 and 19.

Conclusion We demonstrate a simple, animal‐materials free technique for generating corneal epithelium from cadavers or alternatively from autologous donors for viable cell growth on different biologic materials for transplantation. The growth of corneal epithelium on lens capsules proved to be superior compared to the other cultivation techiques.
First genetically characterized mouse model for age‐related cataracts is a mutation in the bA2‐crystallin encoding gene
Authors: PUK O , AHMAD N , WAGNER S , HRABé DE ANGELIS M , GRAW J
Published: November 2010

Purpose The purpose of this study was the morphological and genetic characterization of the novel eye‐size mutant Aca30 in the mouse.

Methods The eyes of the mutants were investigated by laser interference biometry and histology. Linkage analysis was performed using single nucleotide polymorphisms and micro‐satellite markers.

Results Aca30 is a new dominant eye size mutant, which was recovered in an ENU mutagenesis program at the HMGU. The pathologic phenotype is characterized by a clear, but significantly smaller lens. At the age of 11 weeks, the mean lens axis length is 2.1 mm (± 0.01 mm) for wild type mice and 1.9 mm (± 0.03 mm) for heterozygotes. The smaller size of the clear lens was more pronounced in the homozygous mutants (1.7 mm ± 0.03 mm), which were fully fertile and viable. The mutation was mapped to chromosome 1 between the markers D1Mit251 and D1Mit253. Using a positional candidate approach, the bA2‐crastallin encoding gene Cryba2 was sequenced; a T → C exchange at cDNA position 139 leads to an S47P amino acid exchange. Histologically, the eye of newborn homozygous mutants showed small vacuoles at the anterior pole of the lens. At the age of three weeks, some clefts appeared at the anterior cortical region. Later, at the age of 25 weeks, heterozygous lenses developed a subcapsular cortical cataract, while homozygous lenses were completely opaque.

Conclusion Our data demonstrate the first mutation in the Cryba2 gene in any organism so far. CRYBA2 should be considered as a candidate for human age‐related cataracts. Moreover, the slightly smaller size of the lens might be understood as an early biomarker for age‐related cataracts.
Dendritic pruning of retinal ganglion cells in a mouse model of dominant optic atrophy (ADOA)
Authors: VOTRUBA M , WILLIAMS P , MORGAN JE
Published: November 2010

Purpose The model of ADOA (B6;C3‐Opa1Q285STOP ), displays visual dysfunction and optic nerve changes after 12 months age. We explore dendritic morphology of ON‐Centre and OFF‐Centre retinal ganglion cells (RGCs) in the mutant mouse.

Methods Retinas of Opa1+/‐ mice (n=12) and age/sex matched Opa1+/+ (n=5), were flat‐mounted and RGCs labelled by Diolistics (DiI). Animals were assessed at <10 months of age (+/+ n=2, +/‐ n=2), 10‐15 months (+/+ n=1, +/‐ n=3) and 20> months (+/+ n=2, +/‐ n=7)). Retinas were fixed (4%PFA) and imaged (x20). Dendritic morphologies were analysed in image stacks of RGCs (ImageJ) and quantified by Sholl analyses (Matlab).

Results Dendritic trees show decreased average dendritic field area at 10‐15 months (‐35.1%; p < 0.05; number of cells=12) and 20> months (‐48.3%; p < 0.0001; n=45). There is a decrease in the average total dendritic length in 10‐15 month mice (‐44.9%; p < 0.05; n=12) and 20> month mice (‐62.9%; p < 0.0001, n=45). Sholl analysis showed a marked difference in the dendritic arborisation of the 10‐15 month and the 20> month group. (SE were all non‐overlapping). There was no change in <10 month mice compared to controls (p > 0.05). There was no marked difference in dendritic density, implying pruning of secondary and tertiary dendrites, rather than primary dendrites. There was no statistical difference in average dendritic field area and average total dendritic length between Opa1+/‐ and Opa1+/+ in OFF‐centre cells in mice (at<10 months and 20> months).

Conclusion The presence of dendritic pruning in the ON‐Centre RGCs of the OPA1+/‐ mouse model of ADOA offers a putative mechanism for the visual dysfunction observed. The changes precede onset of clinical visual loss, structural c
Ophthalmological findings in patients with mitochondrial diseases divided into infantile or juvenile onset
Authors: SEYEDI HONARVAR AK , DARIN N , TULINIUS M , ANDERSSON GRöNLUND M
Published: November 2010

Purpose The aim of this study was to describe ophthalmological findings in a large cohort of individuals diagnosed with mitochondrial disorders divided into typically infantile or juvenile onset of the disease.

Methods A retrospective study was performed on 117 patients diagnosed with a mitochondrial disease during 1984 to 2003 at the Queen Silvia Children’s Hospital, Gothenburg, Sweden. 113 patients (56 females) with a mean age of 8.6 years (0.1‐35.0 yrs) had undergone an ophthalmological examination including visual acuity (VA), eye motility, refraction, slit‐lamp examination, and ophthalmoscopy. Full‐field electroretinogram (ERG) and pachymetry were performed in 40 and 22 individuals, respectively.

Results 87/113 (77%) of the patients showed one or more ophthalmological findings; 40/56 (71%) in the infantile group and 47/57 (82%) in the juvenile group. Ptosis (n=15/56 vs 4/52; p=0.01) and reduced eye motility (n=21/54 vs 7/47; p=0.008) were more commonly seen in patients with a juvenile onset of the disorder, and nystagmus (n=15/52 vs 5/55; p=0.01) was more frequently found in the infantile group. No significant different was found between the two group regarding strabismus, subnormal VA, refractive errors, optic atrophy, pigmentation of the fundus, or ERG‐verified retinal dystrophy. 9/22 (41%) had increased central corneal thickness (>600), equally divided among different subgroup of patients.

Conclusion The results show that a vast majority of patients with mitochondrial diseases have ophthalmological abnormalities. We recommend an early contact with an ophthalmologist for an initial examination and follow‐up in all patients who have been diagnosed with a mitochondrial disorder.
Intravenous hypertonic saline reduces intraocular pressure
Authors: HARJU M , LINDBOHM N , KOIVUSALO R , PALOHEIMO M
Published: November 2010

Purpose To study the effect of intravenous hypertonic saline (HTS) solution on intraocular pressure (IOP).

Methods Nineteen patients (mean age ±SD, 66 ± 11 years) with glaucoma and IOP ≥30 mmHg were recruited. HTS solution with sodium chloride concentration of 7,5% (Natriumklorid Braun 234 mg/ml, B.Braun Medical Oy, ) was given intravenously in an antecubital vein. IOP was measured every minute for 10 minutes and less frequently for up to 2 hours after treatment. The dosage given was 0,5 mmol/kg in 11 patients (Group05) and 1,0 mmol/kg in eight patients (Group1).

Results The maximum mean (±SD) IOP reduction was achieved 5 minutes after treatment at which point mean IOP had reduced from 40 ± 11 mmHg before treatment to 33 ± 12 mmHg (P < 0.001). The mean percentage IOP reduction was 20 ± 10 % (range 8% – 40%) and the absolute IOP reductions ranged 4 to 16 mmHg. Two hours after treatment, mean IOP was still reduced to 33 ± 13 mmHg (P< 0.001). There was no difference between Group05 and Group1 in the amount of IOP reduction, but there was a trend that the IOP reduction sustained longer in Group1. Four patients reported mild to severe pain in the arm after injection. Especially patients in Group1 had a feeling of warmth in the head and neck region. These symptoms lasted for 1‐2 minutes.

Conclusion Intravenous HTS solution reduces IOP within minutes after injection.
The influence of central corneal thickness and corneal biomechanics in glaucoma
Authors: LAM FC , LI YIM J , MONTGOMERY D
Published: November 2010

Purpose To look at the impact that central corneal thickness and corneal biomechanics can have on intraocular pressure (IOP) measurements and their effect on visual fields.

Methods Written and informed consent from patients and guidance from the local research ethics committee was obtained. Ocular diagnoses and ocular medications were recorded. IOPs were recorded using Goldmann applanation tonometry (GAT)followed by dynamic contour tonometry with the Pascal tonometer. Central corneal thickness(CCT) was measured using ultrasound. Visual fields were recorded using Humphries perimetry. Bland‐Altman plots were used to compare the 2 methods.

Results 92 eyes of 46 patients were included. Median CCT 556µm(range:427µm‐634µm). Despite a good correlation of the IOP measurements usin the two different techniques(r=0.7; p< 0.01), there was a significant difference in limits of agreement(LOA) of DCT to GAT on the Bland‐Altman analysis. The LOA was 8.6mmHg to ‐4.8mmHg with a mean bias of 1.9mmHg. This persisted even after correction for CCT. Ocular hypertensives had a wider LOA than glaucoma patients.

Conclusion DCT IOP measurements can be significantly different from GAT IOPs even after taking into account central corneal thickness. Compared to CCT, corneal hysteresis appears to have a greater impact on IOP measurements. This could have important prognostic implications.
The range of waveform score of Ocular Response AnalyzerTM (ORA) in healthy subjects: interim analysis
Authors: VANTOMME M , MOUSTAKA L , POURJAVAN S
Published: November 2010

Purpose To assess the range of waveform score in IOP measurements with ocular response analyzer (ORA, Reichert) in healthy subjects.

Methods Prospective study including both eyes of healthy subjects with no ocular pathology or previous refractive surgery. The IOP measurements with ORA from both eyes were performed. The inclusion criteria of the measurements were solely based on good waveforms by an experienced clinician. The waveform score of three measurements were included for statistical analysis. Other parameters including age, central corneal thickness (CCT) and axis length were also analysed to evaluate possible correlations. Spearman correlation coefficient was used to assess the correlation.

Results To date, both eyes of 42 healthy subjects are included (Mean age: 46.6 ± 14.3 yrs, Axial length: 23.7 ± 1.1, CCT: 554 ± 34 µm). The mean waveform scores from the first IOP measurement were 4.2±2.3 and for the 2de and 3th respectively 4.2±1.9 and 4.2±2.1 (not significantly different). The mean waveform score of 252 signals (both eyes and 3 measurements) was 4.2±2.1 and ranged from 0.3 to 9.6. Considering the best signal value per patient, the mean of all best signal values was 5.5±2.0 and it ranged from 1.9 to 9.5. The lowest 10% of all the best signal value was<3.

Conclusion The waveform score is a new parameter indicating the reliability of each measurement signal. The best signal value indicates the best measurements of each session (Not the mean of the measurements). To date, our results show that the lower 10% percentile is <3. This could suggest that all the measurements with waveform score lower than 3 should be discarded.
Diurnal variation of ocular pulse amplitude in primary open angle glaucoma patients
Authors: PINTO LA , LEITãO P , FERREIRA J , DOMINGUES I , VANDEWALLE E , FERNANDES F
Published: November 2010

Purpose (1) to determine the diurnal behaviour of the ocular pulse amplitude (OPA) in primary open angle glaucoma (POAG) patients. (2) To identify any variables modulating OPA.

Methods In this prospective study we included 22 POAG patients under topical intraocular pressure (IOP)‐lowering treatment, who underwent contour dynamic tonometry measurements every three hours from 9am to 6pm for IOP and OPA readings. Heart rate (HR) and blood pressure (BP) were simultaneously recorded during the ocular measurements. Only the eye with greater glaucomatous damage was selected per patient.

Results Both IOP and OPA did not change during the day (OPA: 3.0±1.3, 3.2±1.4, 2.9±1.5, 3.0±1.3; IOP: 19.3±2.9, 20.0±3.0, 19.1±3.0, 19.8±2.6; multiple comparisons p=0.21, p=0.27 respectively). Systolic, diastolic and did not present significant diurnal variation (p<0.05 all measurements). OPA was significantly correlated at all time‐measurements with arterial pulse pressure, but not by IOP, median ocular pulse pressure(MOPP) nor median arterial pressure (p<0.05). Univariate analysis revealed HR to negatively correlate OPA at the 15h and 18h measurements (r= ‐0,42, p=0.049; r= ‐0,53, p=0.01; respectively). Multiple linear regression analysis identified blood pressure amplitude as an independent factor contributing to OPA (p<0.05 at all measurements). These observations were more pronounced in patients with high blood pressures.

Conclusion OPA readings seem to be influenced by blood pressure amplitude in POAG patients. High blood pressure amplitude values may overcome the eye self‐regulation mechanisms, resulting in the OPA becoming dependent on the blood pressure amplitude rather than of the IOP.