bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new era for age‐related macular degeneration: insights pertaining to a key role for the complement system
Authors: HAGEMAN G 
Published: September 2008

AbstractAge‐related macular degeneration (AMD) is characterized by a progressive loss of central vision attributable to degenerative and, in advanced cases, neovascular lesions in the macula. As the leading cause of irreversible vision loss in the developed world, AMD affects an estimated 25% of individuals over the age of 75. A host of new discoveries has begun to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Among the first was the discovery that a variety of complement components, complement activators, and complement regulatory proteins are molecular constituents of drusen, a hallmark risk factor for AMD. These observations formed the basis for the concept that drusen are a byproduct of chronic, local inflammatory processes characterized, in part, by robust activation of the complement cascade along the RPE‐choroid interface. Strong support for this new paradigm emerged from subsequent discoveries that revealed a highly significant association between AMD and variations in several complement‐associated genes: Factor H (CFH), Component 3 (C3), and Factor B (CFB). Haplotypes defined by polymorphisms in these genes confer an increased risk for, or protection from, developing AMD. Moreover, a large deletion encompassing two CFH‐related genes ‐‐ CFHR1 and CFHR3 ‐‐ defines one of the CFH protective haplotypes. Similar variations in CFH and CFH‐related genes are also associated with seemingly unrelated systemic diseases, perhaps offering an explanation for some or the previously established risk factors for AMD.
Commercial interest
Functional analysis of mutants of the optineurin gene, associated with some forms of glaucoma
Authors: BALASUBRAMANIAN D , CHALASANI M , SWARUP G , AGARWAL N 
Published: September 2008

Abstract Purpose Mutations in the gene OPTN are associated with normal tension and open angle glaucomas. We have studied the effects of some of these mutations on the cellular biology of retinal ganglion cells, and tried to infer the role of the protein optineurin. Methods We transfected plasmids expressing normal or wild‐type (WT) and E50K, R545Q, H26D, and H486R mutant optineurin into a variety of cells such as HeLa, COS‐1, retinal pigment epithelial (RPE), and the rat retinal ganglion cell (RGC) line RGC‐5, and followed their effects on cell survival by morphologic observation of cells. Expression of optineurin and its mutants was monitored by immunofluorescence staining of cells and by Western blotting. Results The E50K mutant of optineurin, which is associated with the severest phenotype, was seen to selectively induce the death of retinal ganglion cells but not of the other cell lines tested. Neither the wild type cDNA nor the other mutants have any such effect. This cell death induced by E50K OPTN was inhibited by the antioxidants N‐acetylcysteine and Trolox. E50K was seen to generate reactive oxygen species (ROS), which were reduced by antioxidants. Coexpression of manganese superoxide dismutase with the E50K mutant abolished ROS production and inhibited cell death. Conclusion E50K optineurin is a gain of function mutant, which has acquired the ability to induce cell death selectively in retinal ganglion cells. This cell death was mediated by oxidative stress. The present findings suggest the possibility of antioxidant use for delaying or controlling some forms of glaucoma.
OCT imaging in uveitis: advantages and limits
Authors: HERBORT CP , DE SMET MD 
Published: September 2008

AbstractOptical Coherence Tomography (OCT) has gradually invited itself into everyday practice. The imaging quality is steadily improving with new generations of instruments giving fascinating insight into the retina. Although OCT investigation gives stunning pictures of the retina it is basically imaging those structures for which imaging access was already possible. The novelty is, with the new machines especially, the degree of precision of the information we can gather: A corollary to this first point, is the fact that we can get this information instantly without invasive procedures. For conditions such as choroïdal neovessels, much closer follow‐up has allowed, in parallel with the availability of potent intravitreal anti‐VEGF therapy to improve drastically the management of AMD cases. In inflammatory diseases the availability has changed our attitude in the management of CME, increasingly based on OCT profile rather than strictly functional parameters. In diabetic maculopathy also OCT came along with the advent of new performing therapies the effect of which can so be optimally verified. One drawback of OCT is the fact that information is lost or OCT is impossible when turbid media are present. It has also to be acknowledged that information on the underlying choroid is limited. Many cases will be presented with discussion especially on inflammatory and AMD.
Neural networks compared with Cox regression
Authors: DAMATO B , TAKTAK A , ELEUTERI A 
Published: September 2008

Abstract Purpose Survival prediction is useful in patient care and research. Most studies rely on Cox analysis and Kaplan‐Meier curves whereas we have preferred neural networks. The aim of this presentation is to compare these methods and to discuss the advantages and limitations of each. Methods This presentation will be based on our experience with uveal melanoma. A neural network was trained with data from 1780 patients and evaluated with data from another 874 patients. Clinical, histopathological and cytogenetic data were included in the model. All cause mortality was reported, both for patients and for the matched general population. Results Cox analysis assumes linear correlations between variables and proportional hazards throughout the follow‐up period. Kaplan‐Meier analysis requires large patient categories, so that the precision of any prognostication is reduced. Neural networks overcome these limitations. Our model does censor non‐metastatic deaths so that melanoma‐related mortality is not exaggerated in groups of patients with significant competing risks. Conclusion Neural networks allow large numbers of variables to be included in predictive models with relatively small numbers of patients, thereby improving prognostication. Nevertheless, care must be taken when interpreting survival results to avoid serious misconceptions about the natural history of a disease and the impact of treatment.
History
Authors: GOLNIK K 
Published: September 2008

AbstractThe two most common causes of acute visual loss and unilateral optic disc swelling are acute optic neuritis (AON) and Nonarteritic anterior ischemic optic neuropathy (NAION). Important historical points include patient age, presence of pain, and predisposing medical conditions (diabetes, hypertension, hypercholesterolemia, sarcoidosis, recent viral infections/illnesses, other autoimmune conditions). In patients over 50 years of age, symptoms of giant cell arteritis (scalp tenderness, headache, jaw claudication, weight loss, fatigue, fever) must be discussed. Details of the onset of visual loss may be important because occasionally more chronic loss of vision is suddenly discovered when the good eye is occluded. Finally, one must be sure that this is a completely isolated, unilateral visual problem by ascertaining whether any other symptoms exist.
Examination of the patient with visual loss and unilateral disc swelling
Authors: KAWASAKI A 
Published: September 2008

AbstractThis presentation will show multiple examples of disc swelling and the clues one must use to decide its cause. Several congenital conditions (tilted disc, hypoplasia, disc hamartoma, drusen) have an elevated or even swollen‐looking appearance which may, at first glance, be mistaken for acquired disc edema. Acquired swelling of the optic disc represents axoplasmic stasis due to obstruction of orthograde axoplasmic transport. A variety of insults (compression, ischemia, inflammation, metabolic derangement, toxicity and malignancy) to the proximal portion of the optic nerve can disrupt axoplasmic flow , so disc swelling (edema) is a rather non‐specific finding. It is presence of other accompanying fundus abnormalities which is helpful for distinguishing the mechanism of disc swelling, and these can be divided into disc‐related signs and retinal signs and will be discussed. It is also helpful to examine the contralateral disc. For example, a small or absent cup suggests a structural risk for ischemic injury. Of note, papilledema due to increased intracranial pressure is rarely a cause of unilateral disc edema (less than 5% of cases).
Ancillary testing and differential diagnosis
Authors: BORRUAT FX 
Published: September 2008

AbstractThe most frequent mechanisms leading to acute visual loss in the setting of a unilateral swollen optic disc include : ischemia (anterior ischemic optic neuropathy, arteritic versus non‐arteritic) inflammation (demyelinative disorder or other inflammatory diseases), and infection (Lyme, syphilis, Bartonellosis). Less frequent causes include: infiltration (lymphoma, leukaemia, metastasis), paraneoplastic mechanisms, unilateral papilledema, pseudopapilledema (drusen), hereditary (Leber’s optic neuropathy). Ancillary testing will be directed according to the presumed mechanism. Apart from a complete visual function examination (visual acuity, color vision, visual field) and pupillary testing, various tests are available including : retinal angiography (fluorescein, indocyanine green), electrophysiology (VEP, mfERG), to name a few.
Examination of the patient with visual loss and normal fundus
Authors: KAWASAKI A 
Published: September 2008

AbstractThis presentation will discuss certain examination clues that help to distinguish visual loss from retinal disease from visual loss due to optic nerve disease when the fundus appears normal. Chief among these is the relative afferent pupillary defect. The standard clinical technique for detecting an RAPD is the alternating light test and neutral density filters can be used to quantify the amount of pupillomotor asymmetry. Another useful examination technique is measuring the time it takes to recover central visual function, e.g. acuity, following exposure to a bright light. This is the principle of the photostress test and it is very useful for distinguishing maculopathy. The recovery time is prolonged in a variety of macular disorders but are normal in optic neuropathies. Other specific findings such as a carotid bruit which hints to a specific etiology, e.g. retinal emboli from carotid artery plaque will be discussed.
Epidemiology of corneal viral infections
Authors: LABETOULLE M 
Published: September 2008

AbstractThe three main causes of viral keratitis are Herpes simplex virus (HSV), varicella‐zoster virus (VZV) and adenovirus (ADV). Corneal HSV infection is a frequent cause of severely impaired visual acuity. Despite the effectiveness of currently available antiviral drugs, the incidence of herpetic corneal events does not tend to decrease in the general population, as recently showed in a nationwide epidemiological study performed in France. On the other hand, corneal transplantations relative to herpes keratitis tend to become rarer thanks to the effectiveness of preventive oral treatment. Management of herpes keratitis could thus be improved by a better knowledge of epidemiological data. For example, children and atopic patients are now identified as groups of patients with increased risk of severe herpetic disease. The epidemiology of VZV‐related keratitis may drastically vary in the future, due to the generalization of the vaccination against chickenpox/herpes zoster, with a probable increase in the next decades, followed by a progressive and durable decrease. Finally, outbreaks of ADV‐related keratitis are now less frequent than fifty years ago, thanks to the more rigorous hygiene in the general population.
Commercial interest
Electroretinography
Authors: LEROY BP 
Published: September 2008

Abstract Purpose To illustrate the value of electroretinography in clinical practice. Methods A case presentation format will be used to illustrate how pattern electroretinography, full‐field flash electroretinography and multifocal electroretinography can be used in clinical practice. Results As will be shown by the cases to be discussed, each of the electroretinography techniques has a specific role to play in making a better diagnosis. Conclusion All electroretinography techniques have a specific role to play in the evaluation of retinal disease.
Pattern electroretinography and imaging of the macula
Authors: HAWLINA M 
Published: September 2008

Abstract Purpose Pattern electroretinogram (PERG) is retinal response to contrast stimulation that originates from inner retina, mostly from ganglion cells. PERG may help to answer frequent diagnostic ambiguities between macular and optic nerve diseases and can serve as a link between flash and multifocal ERG and VEP. Methods Current trends with emphasis on PERG recording in relation to mfERG, flash ERG and VEP, perimetry, microperimetry and scanning laser ophthalmoscope imaging including autofluorescence of the RPE and OCT will be reviewed in representative clinical cases. Results Global retinal function is well assessed by flash evoked ERGs, but these may be normal in macular disease. PERG and multifocal ERG in combination with autofluorescence imaging and OCT may delineate macular diseases in very early stages. OCT may reveal transversal loss of photoreceptors which correlates well with PERG amplitude. In differential diagnosis, optic nerve diseases usually do not affect multifocal ERG but can affect PERG, especially its N95 component. Combination of reduced N95 component and delay in VEP is strongly suggestive for optic nerve or ganglion cell disease in which autofluorescence imaging would usually be normal. Conclusion By judging the cause of visual loss, PERG in combination with mfERG and morphological features by RPE autofluorescence and OCT with psychophysical methods usually leads to correct diagnosis.
Diagnosis of intraocular and conjunctival tumours
Authors: KIVELÄ T 
Published: September 2008

Abstract Purpose To summarise clinical methods used to diagnose eye cancer. Methods Personal experience of the author and other members of the European Ophthalmic Oncology Group. Results Conjunctival tumours are generally excised based on provisional clinical diagnosis or cosmetic considerations or, if they are extensive, atypical or part of systemic disease such as lymphoma, biopsied to obtain a histopathologic diagnosis. Additional methods to diagnose and stage conjunctival tumours are high frequency ultrasonography (US) or ultrasound biomicroscopy (UBM) to noninvasively measure their thickness, in vivo confocal microscopy or impression cytology to chart their extent, and exfoliative cytology to get a provisional diagnosis. Ciliary body tumours are visualised by radical biomicroscopy, transillumination and indirect ophthalmoscopy with scleral indentation, supplemented with high frequency US or UBM. Binocular indirect ophthalmoscopy and US form the basis or diagnosing choroidal tumours. In addition to fluorescein and indocyanine green angiography, optical coherence tomography to detect minor subretinal fluid and autofluorescence to detect orange pigment are useful adjuncts in telling a small melanoma from a nevus. The mnemonic “To Find Small Ocular Melanomas” (from Thickness >2mm, subretinal Fluid, Symptoms, Orange pigment, Margin touching disc) is also useful in this respect. Clinical diagnosis of medium‐sized to large melanomas is 99% accurate, whereas fine needle aspiration or vitrectomy biopsy is used to diagnose atypical tumors and for prognostic purposes. Conclusion Conjunctival tumours are almost always diagnosed histopathologically, whereas diagnosis of uveal tumours is usually based on clinical examination. While clinical diagnosis is usually reliable, biopsy of uveal tumours is increasingly used for prognostic purposes.
Management of uveal tumors
Authors: DAMATO B , COUPLAND SE 
Published: September 2008

Abstract Purpose In this presentation, we will overview the management of uveal tumours, focussing on melanomas, metastases, lymphomas and haemangiomas. Methods As with other diseases, proper management relies on full systemic and ocular assessment. Accurate measurement of tumour dimensions is especially important. Trans‐retinal or trans‐scleral biopsy may be needed for diagnosis or to grade the degree of malignancy. Uveal melanomas can be treated by: radiotherapy, delivered with plaque, proton beam or stereotactic methods; local resection, performed trans‐retinally or trans‐sclerally; phototherapy using a diode laser, with or without a photodynamic agent; and enucleation. Metastases and lymphomas usually respond to external beam radiotherapy. Haemangiomas resolve after one or two sessions of photodynamic therapy. Prognostication is important, especially in the case of melanoma and this requires both histology and cytogenetics. It is essential to address psychological issues to improve well‐being as much as possible. Results Outcomes are measured in terms of vision, local tumour control, ocular conservation, survival and quality of life. Such results are more meaningful if analyzed according to clinical, histological and cytogenetic baseline variables, depending on the underlying condition. Pathological studies are especially important and require a a specialized pathologist, with good facilities and the support of a highly‐skilled team. Conclusion The management of patients with uveal tumour requires access to a wide range of therapeutic modalities, close collaboration with the pathologist, the support of a multidisciplinary team, and an infrastructure for performing continuous outcomes analyses and research.
Form‐deprivation myopia in the guinea pig: scleral myofibroblasts and biomechanics
Authors: PHILLIPS JR , BACKHOUSE S 
Published: September 2008

Abstract Purpose To investigate the effect of induced myopia on cell populations and biomechanical properties of the sclera. Methods Week‐old guinea pigs (n = 29) were monocularly deprived (MD) of form vision for 14 days. Total cells and myofibroblast (contractile) cells were visualized using DAPI and α‐smooth muscle actin (α‐SMA) antibodies respectively in 20 µm thick scleral sections. Ocular biomechanics were investigated by raising the IOP to 50 mmHg for one hour in anaesthetized animals. Ultrasound biometry measures were made before, during (every 10 min) and after raising the IOP. Results As expected, MD eyes developed significant axial myopia. Generally, MD had no effect on total cell number or myofibroblast number compared to control or normal eyes. However, in MD eyes a significant decrease in total cell number was observed between the optic nerve and 10° nasal (equivalent to human temporal myopic crescent). Overall, myofibroblasts accounted for 63.67 ± 1.65% of scleral cells (mean ± SEM: three groups combined; n = 30 eyes). On increasing IOP, there was significant elastic expansion of the vitreous chamber depth (VCD) in deprived and control eyes but not in normal eyes. The VCD creep response to increased IOP stabilized at equivalent lengths to MD and control eyes. Conclusion A high proportion of scleral cells are myofibroblasts, but cell number is unaffected by MD. The biomechanical response of MD eyes differs from normal eyes, suggesting that something other than myofibroblast cell number controls axial length.
Contribution of Müller cells to blue light injury
Authors: WIEDEMANN P , BRINGMANN A 
Published: September 2008

Abstract Purpose Excessive light causes both damage to the photoreceptors and pigment epithelium, and degenerative alterations in the inner retina, for example apoptotic death of ganglion cells and a decrease in the thickness of the inner plexiform layer. We investigated whether gliotic alterations of Müller cells may contribute to the light‐evoked degenerative alterations in the inner retina. Methods Retinas of adult rats were exposed to blue light for 30 minutes. At various time periods after treatment, retinal slices were immunostained against potassium and water channel proteins. Recordings of potassium currents were made in isolated Müller cells, and the swelling of Müller cell bodies was recorded in retinal slices. Results After blue light treatment, Müller cells displayed hypertrophy and an increase in glial fibrillary acidic protein. The immunostaining of the glial water channel aquaporin‐4 was increased in the outer retina while the immunostaining of the photoreceptor water channel aquaporin‐1 disappeared. Blue light treatment resulted in a decrease and mislocation of the glial Kir4.1 protein in the whole retinal tissue, and a decrease in the potassium conductance of Müller cells. Hypoosmotic stress evoked a swelling of Müller cell bodies in blue light‐treated retinas that was not observed in control tissues. Conclusion Gliosis of Müller cells associated with a loss of functional Kir4.1 channels will result in a disturbance of the retinal potassium and water homeostasis contributing to the degenerative alterations of the inner retina after exposure to blue light.
Localization of cathepsin x in the mouse retina
Authors: BERGER ST , STAHL A , GROSS NJ , SEVENICH L , MARTIN G , REINHECKEL T , AGOSTINI HT 
Published: September 2008

Abstract Purpose Cathepsin X is a recently identified member of the papain‐like cysteine protease family that is expressed by many cell types. The in vivo functions of Cathepsin X are unknown. Hence, the aims of this study are to localize cathepsin X expression in the mouse retina and to compare the retinal morphology and ERG function of cathepsin X knock‐out mice (Ctsx‐/‐) to congenic wild type C57Bl/6 mice (Ctsx+/+). Methods Left eyes of adult mice were prepared for paraffin‐ and right eyes for cryo‐sections. Histology was accomplished by Hämalaun‐Eosin and PAS staining after depigmentation. Expression of cathepsin X and the proliferation marker Ki67 were investigated by immunohistochemistry. Retinal function was tested by ERG. Results Cathepsin X expression in WT mice accumulates along the external limiting membrane. Additionally, a netlike pattern of cathepsin X was found around the neuronal cells in the inner nuclear and ganglion cell layer. There is no significant difference between cathepsin X knock‐out and WT mice in retinal morphology, cell proliferation or ERG readings. Conclusion We found prominent expression of cathepsin X in WT mice retina. Normal retinal morphology and ERG function in cathepsin X knock‐out mice, however, suggest that other cathepsins might compensate for the loss of retinal cathepsin X.