bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic alterations in uveal melanoma
Authors: ZESCHNIGK M , SCHOLZ M , LOHMANN DR , THOMAS S , BORNFELD N 
Published: September 2008

Abstract Purpose Epigenetic alterations are frequently observed in many tumors. Aberrant hypermethylation of CpG rich regions can silence gene expression and, therefore, can result in loss of function equivalent to a null mutation. Recently, regional hypomethylation of CpG rich regions that can result in activation of affected genes has gained increasing attention. Like somatic mutations epigenetic alterations may be used as molecular markers indicating the presence of cancer and minimal residual disease Methods To study the epigenetic alterations in uveal melanoma we determined DNA methylation by direct sequencing and sequence‐based quantitative methylation analysis (SeQMA) of PCR products from bisulfite treated genomic DNA from primary uveal melanomas, uveal melanoma cell lines, mononuclear blood cells and sperm samples of healthy donors. Results We have found a frequent epigenetic mutation in the OXTR gene located within a minimal deleted region on chromosome 3p25‐26 in uveal melanoma. Real‐time RT‐PCR showed that OXTR hypermethylation does not affect OXTR expression thus suggesting that this epimutation may affect expression of distant genes. We also identified a CT gene that is hypomethylated and consequently activated in about half of uveal melanomas. Interestingly, hypomethylation of this gene was biallelic. Conclusion Therefore this alteration is unlikely to be the result of stochastic demethylation processes. We suggest that this region is actively demethylated or selectively protected from maintenance methylation during cell proliferation, or that hypomethylation of CT genes reflects the origin of the malignant cells from an unmethylated progenitor.
Genomic profiling and identification of high‐risk tumours in uveal melanoma by array‐CGH analysis of primary tumours and liver metastases
Authors: COUTURIER J , TROLET J , HUPE P , MARIANI P , SASTRE X , ASSELAIN BERNARD , BARILLOT E , SAULE S , PIPERNO‐NEUMANN S , DESJARDINS L 
Published: September 2008

Abstract Purpose Current therapeutic efforts in Uveal Melanoma are directed toward detection of liver metastases at an earlier stage and adjuvant systemic therapy in high risk patients. Beside clinical and histological features, specific cytogenetic alterations, particularly monosomy 3 and gain of 8q, are strongly associated with metastasis. Methods A series of of 78 ocular tumours (OT) (median follow‐up 54 mo.)and of 66 liver metastases (LM), was analysed by CGH on a genome‐wide BAC/DNA microarray (CIT, INSERM U830), with a 1 Mbase average resolution. Correlations were looked for between genomic profiles of OT and the metastatic status of patients, and a prognostic classifier was built, in order to identify tumour profiles of high risk patients. Results Hierarchical clustering shows that status of chromosome 3 defines two groups of genomic profiles in OT and LM: group 1, with disomy 3, and group 2, with monosomy 3. Seven OT show a partial loss of chr 3, with a minimal deletion of 8.9 Mbase, distal to 3p25.3. Groups 1 and 2 can be subdivided in subgroups according to the presence of additional imbalances. Same genomic groups are found in OT and LM, but with different frequencies. The disomy 3 group represents 20% of metastases. A prognostic classifier including the status of chromosomes 3, 6p, 8p, 8q, 16q, and the position of breakpoint in 8q gains, leads to the best prediction performance in this sample (82%). Conclusion Genomic profiling by array‐CGH, combined with the allelic status of chromosome 3, should be a robust and reliable approach for identifying high‐risk patients eligible for LM screening and adjuvant systemic therapy.
Use of PLGA microparticles for vitreous staining during anterior vitrectomy
Authors: TINT NL , CHAU DYS , DUA HS , SHAKESHEFF KM , GRIFFIN M , ROSE FRAJ 
Published: September 2008

Abstract Purpose To demonstrate in vitro the potential use of FDA‐approved PLGA poly(lactic‐co‐glycolic acid) microparticles to aid visualisation of vitreous during anterior vitrectomy following posterior capsule rupture and to compare with the use of triamcinolone suspension. Methods 10‐60um sized PLGA microparticles were fabricated using the single and/or double emulsion technique(s) and used i) untreated (ii) pre‐treatment with sodium hydroxide (iii) surface adsorption of a protein/synthetic peptide. Particle size, shape, morphology and surface topography were also assessed using scanning electron microscopy (SEM). The efficacy of these microparticles to enhance visualisation of vitreous against triamcinolone suspension was assessed using a simple in vitro set‐up exploiting human cadaveric vitreous. Results Unmodified PLGA displayed a degree of hydrophobicity and also a high rate of dispersion following repeated wash cycles. Interestingly, surface modified PLGA microparticles demonstrated a significant improvement in its 'vitreophilic' properties and were comparable to a triamcinolone suspension. Conclusion The use of modified biodegradable PLGA microparticles may represent a novel method of visualising vitreous and aiding anterior vitrectomy. This method may provide a distinct alternative for the visualisation of vitreous without the pharmacological effects of triamcinolone. Furthermore, such a technique allows the incorporation of drugs, growth factors and/or antibiotics within the microparticles which may be desirable in complicated cataract extraction. Animal models are required to assess in vivo biocompatibility of this method.
PASCAL Photocoagulator, is it better ?
Authors: ISSA M 
Published: September 2008

Abstract Purpose To demonstrate the advantages of the new PASCAL system over conventional laser Methods Review of new laser modality Results PAttern SCan Laser is a new retinal (amongst other things) photocoagulator which has many advantages over conventioal laser.It is a fully integradted laser system using frequency‐doubled Nd‐YAG diode pumped solid state laser with short 5532 nm pulses and can deliver anything from a sigle spot or a predetermined patternarray of up to 56 spots at the press of a pedal. Conclusion PASCAL system delivers a comprehensive range of laser treatments in a considerably shorter time and more comfort and precision in comparison with conventional laser.
An assessive model for corneal endothelium morphometry by diffraction
Authors: BUCHT C , SÖDERBERG PG , MANNEBERG G 
Published: September 2008

Abstract Purpose Most in vivo measurements on the corneal endothelium morphology are done by specular microscopy. This is a time consuming process, due to the need of operator involvement. To assess alternative methods, an experimental optical setup for corneal endothelium morphometry by diffraction has been created. Methods A phantom Polymethyl methacrylate (PMMA) cornea was created, having dimensions of a real cornea. The posterior surface of the phantom cornea was grated to allow for identification of a reflected far field (Fraunhofer) diffraction. The grating was manually etched under a microscope and consisted of a quadratic mesh with a periodicity of approximately 80 µm. The phantom cornea was fitted to a phantom anterior chamber. Because of differences in refractive indices, the phantom anterior chamber was filled with a water/sugar solution (61%) to fully emulate the relative reflection of the cornea‐aqueous humor interface. Light from a He‐Ne laser at 632.8 nm was modulated with achromatic lenses towards the phantom cornea at an incident angle of 45 degrees. The light reflected from the phantom cornea‐aqueous humour interface was collected at the opposite 45 degree angle. The Fraunhofer diffraction pattern was recorded with a CCD chip. Results Experiments showed that a diffraction pattern of the periodicities of the emulated corneal endothelium could be recorded. Conclusion A simple optical setup was created and a grated emulated cornea was used to assess the possibilities of corneal endothelium morphometry using diffraction. Even with the low reflective power of the emulated cornea‐aqueous humor interface, clear diffraction patterns could be recorded. The result is encouraging for further development of an optical system for in vivo morphometry on the corneal endothelium.
Optimisation of amniotic membrane (AM) denuding for tissue engineering
Authors: HOPKINSON A , SHANMUGANATHAN VA , YEUNG AM , GRAY T , LOWE J , DUA HS 
Published: September 2008

Abstract Purpose Amniotic Membrane (AM) has gained increasing popularity as a useful carrier for ex‐vivo expanded cells for tissue engineering, particularly in ocular surface reconstruction. However, current methods employed for denuding AM are highly variable and the consequent effects on the structural and molecular composition of the AM basement membrane (BM) are ambiguous. We compare the effects of the main denuding procedures, and propose a highly effective standardised alternative. Methods AMs preserved for transplantation were denuded using published EDTA and Dispase‐based methodologies and our novel thermolysin‐based procedure. Scanning and Transmission electron microscopy and immunohistochemistry, for BM components (Collgens IV, and VII, laminin 5, and inegrins α6 and ‐β4) were used to assess effectiveness of denuding epithelium, whilst maintaining the integrity of the BM. Results EDTA and Dispase‐based denuding techniques resulted in the disaggregation and even destruction of the BM structure and molecular composition. Employing thermolysin effectively denuded epithelium whilst maintaining BM structural and molecular integrity. Conclusion Current procedures for preparing AM are variable and often ineffective, resulting in non standard membranes. Our novel thermolysin‐based technique effectively denudes the AM whilst preserving an essentially intact and consistent BM. Therefore, we propose this novel thermolysin procedure may potentially improve overall generation of tissue engineered constructs using AM.
Morphological link between accommodation, presbyopia and cortical cataract
Authors: MICHAEL R , BARRAQUER RI , VRENSEN G 
Published: September 2008

Abstract Purpose Evaluation of the gross morphology, the cortical location and the fiber cell architecture of cortical opacities in the aging human lens. Methods 39 human donor lenses were photographed in toto in frontal view using dark‐field stereomicroscopy. 15 lenses were fixed, cut in axial slices and photographed the same way. Details of fiber cell architecture were investigated by fluorescent staining for membranes and by scanning electron microscopy. Results Small focal and cuneiform cortical cataracts are discrete opacities located at a specific depth below the capsule, and extending from the equatorial region in anterior and posterior direction. A sharp border is observed, between the opacities with their disorganized fiber architecture and the deeper nuclear layers, which show a regular fiber pattern. This border is at a mean depth of 700 µm below the capsular surface. Close examination of the opacities revealed fiber folds, fiber undulations, fiber‐to‐fiber separations, fiber breaks, water lakes and fiber displacement. Because the lens cortex and nucleus have different viscoelastic properties in young and old lenses, we hypothesize that external forces during accommodation cause shear stress predominantly in this border zone. Conclusion The location of the described changes suggests that mechanical forces may cause fiber disorganization, small cortical opacities, and, ultimately, cuneiform cataracts. Our hypothesis would be in line with recent findings by Truscott and co‐workers about a two‐compartmental organization of the human lens. They found biochemical arguments for a transport barrier developing at a middle age at the cortical/nuclear interface.
The time of onset of inherited cataract
Authors: BRON AJ , HANNAN F , MUSHTAQ B , KORETZ JF 
Published: September 2008

Abstract Purpose The lens grows by addition of fibres to its surface, with the newest fibres just under the epithelium anteriorly and the capsule posteriorly. In slit‐section the cortex shows 4 optical zones of dysjunction (C1 to C4) with differing light‐scattering properties. We explore the clock‐like implications of this arrangement and how the spatiotemporal distribution of opacities implies the timing of mutated gene expression and/ or the influence of modifying factors. Methods Methods: A case report, literature review and proposal of a hypothesis Results We have observed dot cataract in a mother (42 years) and 2 sons (16 and 11 years) expressing a dominantly inherited, activating mutation of the calcium sensing receptor (CaSR). In each patient, lens opacities were present in the deep and superficial cortex (C2, 3 and 4) but absent from C1 and lens nucleus. Conclusion In our family, absence of opacities in the lens nucleus implies either that the mutated gene is not expressed pre‐natally or that there is protection from the effects of the mutation in utero, which is lost post‐natally. Absence of opacities in C1 implies the same for these young fibres and suggests that expression of disease (lens opacity) does not occur immediately after birth. We hypothesise that in our family, the expression of lens opacities once these fibres have entered C2, may be related to the switch from aerobic to anaerobic metabolism in the transitions from C1 to C2, to denucleation and loss of organelles and to other structural and functional changes which occur in this region. We suggest that the location and timing of appearance of inherited cataracts is related to the onset of gene expression and the presence of modulating factors which influence the effects of the mutated protein.
In vivo high power infrared radiation exposure time dependence of lens light scattering
Authors: AL‐SAQRY R , GALICHANIN K , LI Y , SÖDERBERG PG , SCHULMEISTER K , HUSINSKI J , BUCHT C 
Published: September 2008

Abstract Purpose To determine the exposure time dependence of lens light scattering after high power in vivo infrared radiation exposure of the eye. Methods The experimental animal was 6 weeks old albino SD rat. Altogether, 12 animals were divided into four exposure time groups (5, 8, 13, 20 s). The animals were anesthetized with ketamine‐xylazine, 95/14 mg/kg bodyweight, 20 min prior to exposure and both eyes were dilated with tropicamide 10 mg/ml. The infrared radiation source was a single mode CW fiber laser emitting at 1090 nm (Model SP‐120C, SPI Lasers, UK) with the output power set to 6.2 W. The primary laser beam was focused just in front of the anterior focal point of the eye with an F# close to that of the rat eye so that a divergent beam entered the eye with a spot size of 3 mm in diameter inside the dilated pupil. This allowed for a homogenous intensity distribution within the lens and a large spot size on the retina. One week after exposure, the animal was sacrificed and the lenses were extracted for darkfield macroscopic imaging and measurement of intensity of forward light scattering. Results The intensity of forward light scattering increased with increasing exposure time. The increase was well described by a 2nd order polynomial, omitting the 0:th and the first order term. The threshold exposure time, estimated as Maximum Tolerable exposure Time (MTT:2.3:16) was 4.8 s. Considering the power used, this corresponds to 30 J, thus delivered over 3 mm diameter which implies a radiant exposure of 4.2 MJ/m2. Conclusion At 1 week after exposure to 6.2 W of 1090 nm, the intensity of forward light scattering in the lens increases with increasing exposure time and the threshold exposure time is 4.8 s.
Genetic testing in retinal dystrophies
Authors: DOWNES SM 
Published: September 2008

Abstract Purpose To describe genetic testing in autosomal recessively inherited retinal dystrophies. Methods Retinal dystrophies (RD) are a heterogeneous group of diseases characterised by progressive retinal degeneration leading to severe visual disability. The prevalence of RD is ~ 1/3500; of these up to 40% are presumed autosomal recessive (AR). AR inheritance is frequently seen in juvenile onset cases, but also presents in young adults. The heterogeneity of inherited eye disease can make differential diagnosis difficult. For a sporadic case in a young male the differential diagnosis may include autosomal recessive, X‐linked or autosomal dominant RD. Although there are no treatments yet available for inherited RD, knowledge of the underlying genetic variation can be helpful for: clinical diagnosis in patients with signs and symptoms of disease; pre‐symptomatic testing for individuals who do not have the disease, but given their family history, are at risk for the disease; carrier testing for individuals who may carry a gene mutation that can be passed on to their children; and may be useful if genetic therapy becomes a viable option. Methods: Testing strategies using novel technologies are now being adopted to increase identification of disease causing mutations. One major advance includes the use of high throughput sequencing platforms. The introduction of this technology is likely to overcome many of the problems associated with testing multiple patient samples and multiple genes, as well as providing the accuracy required in a diagnostic setting. Even these technologies will not identify all types of mutations, for example large deletions so other technologies will be required.
Diagnostic difficulties in orbital pathology
Authors: BONSHEK RE 
Published: September 2008

Abstract Purpose To describe and discuss sources of difficulty in histopathological diagnosis in orbital pathology and the approach to problematic diagnostic cases. Methods Review of case material in Manchester Royal Eye Hospital and Manchester National Specialist Ophthalmic Pathology Service Laboratory archives and review of the literature. Results Problems may be due to inadequacies of the process of specimen submission/handling, eg inadequate clinical information, inadequate sampling or crush/cautery artefact in small biopsies. They may be due to insufficient or uncertain histopathological criteria, eg isolated or rare orbital presentation of systemic pathology (such as isolated orbital Wegener’s granulomatosis), isolated presentation of metastatic malignancy with unknown primary site, anaplastic malignancy and other lesions of uncertain histogenesis, inflammatory lesion vs lymphoreticular neoplasm (such as lymphoid hyperplasia vs low grade B‐cell non‐Hodgkin’s lymphoma and necrotizing inflammation vs T/NK cell lymphoma). Conclusion Good communication between clinicians and pathologists is essential at all stages during the diagnostic process. Sound morphological assessment remains crucial. Immunohistochemistry plays a valuable part in assisting diagnosis of lesions of uncertain histogenesis and in lymphoreticular pathology. There is an expanding use of molecular genetic analysis. Electron microscopy has largely been supplanted by immunohistochemistry but still has a role to play. Despite the vastly increased technological armamentarium there remain lesions which are very difficult to diagnose or classify. The multidisciplinary team approach fosters interplay among the differing areas of clinical and diagnostic expertise and allows a rational approach to diagnosis and management of problematic cases.
The effect of corneal hydration on corneal ablation rate at 193nm and 213nm
Authors: PENTARI A , GINIS H , TSATSARONIS D , TSIKLIS N , PALLIKARIS I 
Published: September 2008

Abstract Purpose The ablation rate of corneal tissue depends primarily on the fluence of the laser and corneal hydration. It was the purpose of the study to compare the dependence of the ablation rate on corneal hydration for two different laser wavelengths (193 and 213‐nm). Methods ArF Excimer laser (Allegretto, Wavelight) with a wavelength of 193nm and Nd:YAG CustomVis laser with a wavelength of 213nm were used for the study. Corneal discs were harvested from porcine eye within 24 hours post‐mortem. Corneal epithelium was removed with a blunt spatula. The disks received ablation equivalent to the ablation of 100 microns at a circular zone having a diameter of 7mm. Before and after ablation, each disk was weighted and subsequently dried in order to calculate its dry mass and therefore hydration during ablation. In order to test the ablation rate at different hydrations, the disks were ablated at different time intervals fooling their preparation. The hydration ranged from 66 to 80% w/w. Results The ablated mass showed a positive linear correlation with hydration for both lasers. The corresponding normalised dry mass, which is more critical for the accuracy of refractive corrections, exhibited a negative linear correlation with hydration with similar slopes for the two lasers tested (‐0,0651 for the 193nm and ‐0,0568[hydration‐1] for the 213nm). Conclusion Results of this study reveal the similar behaviour in the dependence of ablation rate from the hydration of cornea at the 193‐ and 213‐nm laser wavelengths.
Comparison of real intraocular pressure (IOP) during LASIK versus Epi‐LASIK
Authors: CANADAS SUAREZ P , HERNANDEZ ‐ VERDEJO J , DE BENITO L , TEUS M 
Published: September 2008

Abstract Purpose To compare real‐time intraocular pressure (IOP) in LASIK versus Epi‐LASIK in porcine eyes during flap creation using the Moria 2 microkeratome and the Moria Epi‐KTM epikeratome. Methods Interventional, prospective study of two keratomes: Moria Group (M2) and epipolis laser in situ keratomileusis Group (MEpi‐K). These devices were used to create a lamellar corneal or epithelial flap respectively in freshly enucleated porcine eyes. The IOP changes induced by the procedures were recorded using manometry by direct cannulation with a reusable blood pressure transducer connected to the anterior chamber. Results 7 eyes were included for M2 Group and 10 for the MEpi‐K Group. In the M2 Group the IOP increased during suction phase to a mean value of 122.53±30.40 mm Hg and to 160.52±22.73 mm Hg during cutting phase (mean time: 21.42±7.48 and 15.71±1.88 secs respectively). In the MEpi‐K Group, mean IOP increase was 100.66±18.60 mm Hg during suction phase, 91.38±17.79 mm Hg during cutting phase and 74,37±12.70 during low‐back phase (mean time: 25.79±3.44, 33.68±2.81 and 29.74± 3.11 secs respectively). IOP values in both groups showed statistical significant difference in all comparison (p<0.01). Conclusion Real‐time IOP can be measured during flap creation process using direct manometry in the anterior chamber. Our results show a significant increase in IOP during the surgical procedure in both groups although the IOP increase reached with MEpi‐K epikeratome seems to be lower than M2 microkeratome.