bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical cases
Authors: CREUZOT‐GARCHER C
Published: August 2014

Clinical cases of diabetic retinopathy with or without diabetic macular edema will be discussed with the audience. These cases will define the role and the pros and cons of different therapeutic options. Cases with macula edema with proliferative diabetic retinopathy, without diabetic retinopathy in phakic or pseudophakic patients will be presented.
Neuroprotection in the real world
Authors: KURYSHEVA N
Published: August 2014

Glaucoma causes vision loss through the degeneration of retinal ganglion cells and their axons. Lowering IOP does not necessarily stop degeneration. Therefore neuroprotection is directed at neurons independently of its effects on IOP [1]. As the topical ocular hypotensive treatment is the main option in glaucoma nowadays, the direct neuroprotective effect of hypotensive eye drops is important. It has been postulated that PG analogues may have an IOP independent neuroprotective effect at clinically available intracameral concentration [2]. In vivo experiments demonstrated the neuroprotective properties of betaxolol [3]. The recent study of LoGTS demonstrates that the α2 agonist brimonidine may have a beneficial effect on visual function independent of IOP lowering [4]. Our recent research revealed the high antioxidant activity of fixed combinations of carboanhydrase inhibitors with timolol [5]. References 1. Cheung W, Guo L, Cordeiro MF. Optom Vis Sci. 2008;85:406‐416. 2. Yamagishi R., et al. Exp. Eye Res. 2011;93:265‐270. 3.Osborne NN, et al. Brain Res. 1997;751:113–123. 4.Krupin T, et al. 2011;151(4):671– 681. 5.Kurysheva N.I., et al. Rus. Ophthalm. J. 2013;6(2):41 – 45.
Wavefront Aberrometry: from basics to daily practice
Authors: GICQUEL J
Published: August 2014

Quality of vision is a new comprehensive set of measures that determines visual performance at near, far and in variable light conditions. Good vision is no longer defined by 20/20 vision. The necessity of evaluating vision beyond Snellen acuity has led clinicians and vision scientists to utilize contrast sensitivity, wavefront aberrometry and straylight measurement in most clinical trials related to vision. Recently,the advent of 3D movies and 3D TVs brought us new challenges regarding 3 3 Dimensional Quality of Vision. In this course, experts will share with you their experience on this new frontier of modern ophthalmology.
Cytokine gene expression and protein production in West Nile virus‐infected retinal pigment epithelium
Authors: MUNOZ‐ERAZO L , MADIGAN M , KING NJC
Published: August 2014

Purpose To investigate if West Nile virus (WNV) infection of human retinal pigment epithelium (RPE) cells induces differential expression of mRNA and proteins for cytokines important for leucocyte recruitment (e.g. CCL5) and integrity of the outer blood retinal barrier (BRB) (e.g. TNF).

Methods Primary human RPE cells (P3‐5) were cultured until a complete monolayer was observed, and then infected with 1, 5 or 10 plaque‐forming units (p.f.u.) of WNV (Sarafend) for 24, 48 and 72hrs. Supernatants were collected for Luminex‐based cytokine assay. RNA was prepared from cells and processed for real‐time (RT)‐PCR. Pro‐inflammatory, leucocyte recruitment and viral defense cytokines and chemokines were studied.

Results CCL5, IL8, IL6 (pro‐inflammatory) and IFNB1 (anti‐viral) showed increases in mRNA expression from 24 h post‐infection (p.i.) and protein levels from 48h p.i. However in WNV‐infected RPE, protein levels of VEGF and TNF were similar to mock‐infected cells, despite significant increases in mRNA (TNF 24 h p.i., p <0.05; VEGF 48 h, p<0.01). Interestingly, CCL2 mRNA and protein showed no change in expression post‐WNV infection at 24, 48 and 72h

Conclusion We previously observed that WNV induced transepithelial electrical resistance (TEER) changes in human RPE (outer BRB) after 48 hours, although the mechanisms(s) remain unclear. Studies in mice show that both TNF and CCL2 are important for blood‐brain barrier integrity and leucocyte recruitment following WNV infection. Surprisingly we find little or no effect on TNF or CCL2 expression in WNV‐infected RPE, suggesting alternate mechanisms operate in RPE post‐viral infection. Funding‐ NFMRI and NHMRC
Advanced glycation end‐products induced activation of NFkB and its suppression by different neurotrophic factors
Authors: BIKBOVA G , OSHITARI T , YAMAMOTO S
Published: August 2014

Purpose To determine the effect of high doses of AGEs on neurite regeneration in isolated rat retinas, and the regenerative effects of different neurotrophic factors.

Methods Retinal explants of 4 adult SD rats were three‐dimensionally cultured in collagen gel, and incubated in: 1) serum free control culture media; 2) 100 μg/ml glucose‐AGE‐BSA, glycolaldehyde‐AGE‐BSA, glyceraldehyde‐AGE‐BSA media; 3) glucose, glycol, glycer+100 ng/ml neurotrophin 4 (NT‐4)media; 4) glucose, glycol, glycer+100 ng/ml hepatocyte growth factor (HGF) media; 5)glucose, glycol, glycer+100 ng/ml glial cell line derived neurotrophic factor (GDNF) media; or 6) glucose, glycol, glycer+100 ng/ml tauroursodeoxycholic acid (TUDCA) media. After 7 days, the number of regenerating neurites were counted under a phase‐contrast microscope. The explants were immunostained for NFkB transcription factor. Statistical analyses were performed by one‐way ANOVA.

Results In retinas incubated with AGEs, the number of regenerating neurites were fewer than in control. Neurotrophic factors increased the number of neurites, but more significantly in the NT4 group. The number of NFkB immunopositive cells was higher in retinas exposed to AGEs than in control (53,2 ± 7,2% vs.31,6 ± 16,08%,P = 0,0146). Neurotrophic factors decreased the number of immunopositives cell, but more significantly in the NT4 group.

Conclusion High dose AGEs induce activation of NFkB and NT4 significantly suppresses this activation and enhances neurite regeneration in isolated retinas compared with other neurotrophic factors such as HGF,GDNF,and TUDCA.
Focal venous hypertension as a pathophysiologic mechanism for port‐wine stains and the Sturge‐Weber syndrome
Authors: PARSA C
Published: August 2014

Purpose To provide an in‐depth re‐examination of assumed causes of tissue hypertrophy, port‐wine stains and the Sturge‐Weber and related syndromes to support an alternative unifying pathophysiologic mechanism of venous dysplasia producing focal venous hypertension with attendant tissue responses and to propose a novel etiological hypothesis for the venous dysplasia in these syndromes with supportive evidence.

Methods Data from twenty patients with port‐wine stains was collected prospectively by the author in an institutional referral‐based practice. The literature was searched using Medline.

Results Newly obtained dermatologic, corneal pachymetry, fundus ophthalmoscopic, ocular and orbital venous Doppler ultrasonography, and magnetic resonance imaging findings in patients with the Sturge‐Weber syndrome or isolated port‐wine stains, along with published data, reveal diffusely thickened tissues and neural atrophy in all areas associated with venous congestion.

Conclusion Contrary to traditional understanding, signs and symptoms in the Sturge‐Weber and related syndromes, including both congenital and acquired port‐wine stains are shown to arise from effects of localized primary venous dysplasia or acquired venous obstruction rather than neural dysfunction, differentiating these syndromes from actual phacomatoses. Effects of focal venous hypertension are transmitted to nearby areas via compensatory collateral venous channels in the above conditions. Conclusion: A novel underlying etiology—prenatal venous thrombo‐occlusion—may be responsible for the absence of veins with persistence and enlargement of collateral circulatory pathways with data in the literature backing this offshoot hypothesis. The mechanism for isolated pathologic tissue
A new pediatric vision screener employing polarization‐modulated, retinal‐birefringence‐scanning‐based strabismus detection and bull's eye focus detection
Authors: IRSCH K , GAMATIKOV B , WU YK , GUYTON D
Published: August 2014

Purpose Commercially available pediatric vision screening devices that test for amblyopia’s primary causes (strabismus and defocus) can detect strabismus only indirectly and inaccurately via assessment of the positions of external light reflections from the cornea, but they cannot detect the anatomical feature of the eyes where fixation actually occurs (the fovea).

Methods Our laboratory has been developing technology to detect true foveal fixation, by exploiting the birefringence of the uniquely arranged Henle fibers delineating the fovea, using retinal birefringence scanning (RBS), and we recently described a new, polarization‐modulated approach to RBS that enables entirely direct and reliable detection of true foveal fixation, with greatly enhanced signal‐to‐noise ratio and essentially independent of corneal birefringence. Here we present a new pediatric vision screener (PVS) that employs polarization‐modulated RBS for strabismus detection, and double‐pass focus detection using a bull’s eye photodetector and improved target system with accommodative control.

Results Performance tests in adult volunteers and pediatric patients demonstrate that our new PVS 1) is capable of detecting even small angles of eye misalignment (at least 0.75° or 1.3 PD), 2) has the potential to detect spherical focus within ±1.00 D, and 3) has the potential to detect the misalignment in patients with accommodative esotropia who only develop a crossed eye when focusing intently on a near target.

Conclusion In conclusion, the new PVS shows real promise in supplying the demand for a reliable, automated strabismus/defocus screening tool for children at risk for amblyopia.
Normal pigment production
Authors: ARVEILER B
Published: August 2014

Melanin is synthesized in melanocytes and retinal pigment epithelial cells. Two main types of melanin are produced: eumelanin (brown, black) and phaeomelanin (yellow, orange). Pigmentation is a complex process involving various steps from normal development of melanocytes to the synthesis of melanin itself. In the skin and choroid, precursors of melanocytes are melanoblasts which are derived from the neural crest. Retinal pigment epithelium cells are generated directly from the optic neuroepithelium. Melanoblasts migrate and colonize the epidermis, hair follicles, and ocular, ear and nervous structures. The differentiation of melanoblasts into melanocytes is controlled by numerous transcription factors and signalling pathways, and is characterized by the acquisition of Tyrosinase activity, the presence of mature melanosomes, and the formation of dendrites. Melanin production results from catalytic activities by Tyrosinase, TRP‐1 and TRP‐2 and occurs in melanosomes which follow a maturation process involving four stages (I – IV). Melanosomes are transported from the perinuclear region to the end of melanocytic dentrites, where they are eventually transferred to keratinocytes.
The array of clinical albinism subtypes
Authors: LEROY BP
Published: August 2014

Purpose: To illustrate the different types of clinical subtypes of albinism. Methods: A systematic overview of the different clinical subtypes of albinism will be given. The relationship between the different phenotypes and their respective genotypes will be explained. Results: In general, a distinction is made between ocular albinism and oculocutaneous albinism. The latter can be isolated or syndromic. Examples of syndromic albinism include the Hermansky‐Pudlak and Chediak‐Higashi syndromes. Conclusions: Ocular and oculocutaneous types of albinism exist. The latter can isolated or can be part of syndromic oculocutaneous albinism.
Automatic application of warmth and expression – a breakthrough in physical therapy of dry eye
Authors: GREINER J
Published: August 2014

The most common form of dry eye disease is evaporative dry eye resulting from meibomian gland dysfunction (MGD) based on obstructed MG. A prospective, randomized, crossover, multicenter clinical study employed a single treatment with the automated computer controlled LipiFlow thermal pulsation system (LTPS). Improvement in signs & symptoms and its duration in patients with evaporative dry eye secondary to MGD was investigated over several time points. Initial results verified significant improvement of MG secretion at 2 & 4 weeks compared to conventional warm compress method. This was based on evaluation of tear film break up time (TF‐BUT), ocular surface staining, patient symptoms (OSDI & SPEED test). The secretion score improved significantly from baseline (4.4 ± 4.0) to 1‐month post‐treatment (11.3 ± 6.2; p < 0.0001) and this improvement was maintained with no significant regression at 9 months (11.7 ± 5.9) and even at 3‐years (18.4±6.2) after therapy. Treatment with the Lipiflow device is a technological advance that exceeds any known form of dry eye therapy in duration and efficacy, since it is efficacious even for extended durations (9‐mos, 1‐, 2‐ and 3‐years) following a single 12‐minute treatment.
Virtual glaucoma services in Finland
Authors: TUULONEN A
Published: August 2014

The number of patients using reimbursed glaucoma medications in Finland has increased 2.4‐fold since 1986 and increases by 2.5 % every year. In 2020, 100 000 patients are expected to be using glaucoma drops in a population of 5.4 million. Simultaneously the gap between diagnostic and therapeutic possibilities and available resources is broadening more rapidly. It is obvious that radical changes and new insights in attitudes and policies are mandatory to make the glaucoma processes more cost‐effective and to be able to guarantee access to high quality, high volume and low cost care. There is a continuous trade‐off ‘right’ level or services. Paradoxically, just adding more care may not always be better. What is too early vs. too late diagnosis? What represents under‐ vs. over treatment in glaucoma care? Is ‘good enough’ enough? With limited resources more resources are allocated for patients with greatest risk of visual disability. Physicians’ time is spent in developing the health care system to find and segment the aggressive and rapidly progressive glaucoma patients from ‘usual’ stable patients ‐ as well as organizing and supervising the work of other professionals and care processes. As it is very expensive – time and money wise – to receive simple care from highly trained professionals (e.g. tonometry‐based follow‐up of glaucoma), shared care is of utmost importance. Whatever we do, we start by asking whether the intervention (test, treatment, care protocol etc) is necessary, i.e. beneficial to the patient’s well being. If the answer is ‘yes’– and the society affords the intervention ‐ the next question asks who should do it and could technology substitute professionals (e.g. imaging, home‐tonometer etc). As it is especially the cumulative effect of small changes in clinical practices (e.g. adding new diagnostic tests or therapy) that has a massive impact on the healthcare budgets, clinician weighs not only their benefits and risks but should also consider the costs. Whenever we wish to add more care, we simultaneously consider removing unnecessary old interventions and preventing the adoption of useless new interventions. The principles of virtual glaucoma virtual glaucoma services in Finland can be summarized as the priorization and segmentation (most resources allocated to prevent permanent visual disability), standardization and efficient ways to produce services as well as shared care among different professionals and patients.
Enhanced access to glaucoma diagnosis and management via patient centered collaborative teleglaucoma (TG) approaches in Northern Alberta and in Ethiopia
Authors: DAMJI KF
Published: August 2014

We describe patient centered collaborative TG care models in Northern Alberta & Ethiopia (1‐3). Optometrists or technicians select high risk patients & those with possible early glaucoma, & upload structured history, exam, & diagnostic tests. Data is stored on a secure web platform (teleophthalmology.com) & graded by glaucoma specialists with recommendations for care. Validation included comparison of optic nerve features with digital 3D & 2D vs 3D slide film, and in person vs virtual exam. Stakeholder feedback improved front line & grading protocols. Some TG consults are ineffective due to patient cooperation, media opacities, & technology challenges (4). Opportunities exist for mobile phone photography of the anterior & posterior segment & leveraging ‘m health’ for e‐learning, research & patient education. Future research could focus on validation of TG models & optimal use of finite resources, including cost & comparative effectiveness. 1. J Telemed Telecare 2012;18(7):367‐73 2. MEAJO;2013:20(2):142‐9 3. Clin Exp Optom. 2013 Jun 13 4. MEAJO 2013;20(2):150‐7 Acknowledgements: Drs A Giorgis, A Mulugeta, F Kassam, S Arora, A Kurji, M Edwards, A Moalin & Secure Diagnostic Imaging
What do retinal telangiectasia tell us about the control of vasculature in the retina?
Authors: FRUTTIGER M
Published: August 2014

Neurodegenerative changes in the retina and retinal vasculature abnormalities are two closely linked processes. In addition, both of these processes have been linked to inflammation numerous times in humans and in model systems. We have studied Macular Telangiectasia type 2 (MacTel), which is an uncommon eye disease that is characterised by both neurodegenerative and vascular changes. However, histological analysis on post‐mortem tissue provided no evidence for inflammation in the retina of MacTel patients. This demonstrates that inflammation is not necessarily linked to neurodegeneration and vascular changes.

Commercial interest
Cases
Authors: HAMEL C
Published: August 2014

There will be presentation of clinical cases in the field of retinal genetics
The corneal epithelial basement membrane: Master regulator of the stromal myofibroblast response to injury
Authors: WILSON S , TORRICELLI A
Published: August 2014

The corneal epithelial basement membrane (EBM) is positioned between basal epithelial cells and the stroma. This highly specialized extracellular matrix functions not only to anchor epithelial cells to the stroma but also during migration, differentiation, and maintenance of the differentiated epithelial phenotype. Basement membranes are composed of a diverse assemblage of extracellular molecules, some of which are likely specific to the cornea. In general, they are composed of four primary components—collagens (types IV and VII), laminins, heparan sulfate proteoglycans, and nidogens. Our recent studies have demonstrated defective regeneration of the EBM in corneas that develop haze after high correction photorefractive keratectomy (PRK) in rabbits or irregular PTK in mice. Likely this is attributable to myofibroblast generation from bone marrow‐derived and keratocyte‐derived precursor cells that persist in the subepithelial stroma and block keratocyte/corneal fibroblast contribution of EBM components. In turn, persistent EBM defects facilitate the development and persistence of myofibroblasts via augmented TGF beta and PDGF penetration into the anterior stroma. Similar mechanisms underlie corneal scaring after most injuries.
The role of inflammation and extracellular matrix in the wound healing after glaucoma surgery
Authors: UUSITALO H
Published: August 2014

Wound healing is a complex process involved in ocular surgery, trauma and pathogenesis of several eye diseases. Due to the delicate and sensitive structures of the eye wound healing is playing a essential role in ophthalmology. In glaucoma surgery well controlled wound healing process is as important for the creation of a functioning passage to aqueous humor out of the eye. There are growing body of evidence that the preoperative state of the conjunctiva is of great importance for the success of glaucoma surgery. This has been demonstrated in trabeculectomy and in non‐penetrating glaucoma surgery like deep sclerectomy. The presence of inflammatory cells in the conjunctival specimens taken during the surgery and the success of the operation points out the role of inflammation in wound healing processes. The data obtained from the specimens taken from the eyes with good and poor ontrol of IOP after glaucoma implants demonstrating the accumulation of extracellular components and activated myofibroblasts further indicates the activation of the whole wound healing cascade. The role of matrix metalloproteinases and their endogenous inhibotors (TIMP's) is evident but seem to be rather specifically involving certain MMP's.

Commercial interest
Trehalose and hyaluronic acid association; added benefits
Authors: PINTO‐BONILLA I
Published: August 2014

Abstract not provided
Systemic safety of VEGF antagonists and their influence on vascular homeostasis
Authors: MACHALINSKA A
Published: August 2014

Intravitreal vascular endothelial growth factor (VEGF) inhibitors constitutes currently the first‐line treatment in neovascular age‐related macular degeneration (AMD) and diabetic oedema. By intravitreal application of the drug, the dosage can be kept low while maximizing its effect on retina and minimizing potential adverse systemic effects. However, the eye‐blood barrier is often disrupted in ophthalmic neovascular disorders and the drugs can be detected in circulating blood despite being administered as an intraocular injection. As patients with AMD or diabetes mellitus constitute a high‐risk population for cardiovascular events, the safety of anti‐VEGF therapies must be precisely and thoroughly assessed. Here, the recent reports documenting systemic safety of intravitreal VEGF inhibitors will be reviewed. Moreover, the novel methods to assess the potential systemic effect on vascular homeostasis as the consequence of such therapy will be also discussed.
Wet lab training of trabeculectomy and tube surgery
Authors: SHAH P
Published: August 2014

This lecture covers Professor Shah’s experience of developing a glaucoma surgery wet‐lab training facility in Birmingham, UK. Topics covered include: (a) Facility set‐up, (b) Safety issues, (c) Preparation of surgical material, (d) Instrumentation, (e) Mentor‐mentee ratios, (f) Faculty briefing, (g) Logistical difficulties and (h) Future developments. Preliminary data on the impact of trabeculectomy wet‐lab training will be presented.
Experimental retinal vein occlusion, a model of non‐neovascular microvascular remodeling
Authors: PAQUES M
Published: August 2014

The main cause of visual loss after retinal vein occlusion and diabetes is microvascular remodelling, a spectrum of functional and morphological changes affecting vessels. Some are beneficial, such as collateral vessel development. The other manifestations of microvascular remodelling are usually detrimental such as chronic rupture of the blood‐retinal barrier, capillary closure or macroaneurysms. The processes underlying microvascular remodelling are poorly understood, in part because of the absence of a clinically meaningful animal model. We have been investigating the effet of retinal vein occlusion in rodents using laser photocoagulation, which eanbled us to reproduce many of the features of human microvascular remodelling. Based on our experience, we will discuss issues related to interspecies variability and clinical relevance.
Using animal models for the study of uveitis
Authors: DICK A
Published: August 2014

Our understanding of inflammatory responses and mechanisms of immune‐mediated tissue damage in man has been greatly facilitated by our animal models systems. The talk will discuss the utility of animal model in uveitis from two aspects. Firstly, permitting fundamental elucidation of immune pathogenic mechanisms that are at play in uveitis and secondly, delivering a platform for preclinical assessment of drug or biologic intervention. We have been fortunate to be able to further manipulate animal models to create spontaneous models of uveitis and also humanised models of uveitis to assess antigen repertoires and responsiveness. Further we now have persistent models of disease activity, which have illuminated mechanisms of tissue repair and also mechanisms of immune mediated angiogenesis. To this end. the models permit us to look at and translate through to man interventions that have benefitted uveitic patients, and such successes will be highlighted throughout the talk
Pinosylvin protects retinal pigment epithelial cells from oxidative stress by activating Nrf2‐mediated antioxidant defence system
Authors: KOSKELA A , REINISALO M , HYTTINEN J , KAARNIRANTA K , KARJALAINEN R
Published: August 2014

Purpose The constant light exposure, high metabolic rate and high lipid concentration expose retinal pigment epithelial (RPE) cells to chronic oxidative stress, which may lead to RPE cell degeneration and evokes secondarily photoreceptor damage and visual loss. In this work, we assessed the protective role of wood derived polyphenol, pinosylvin (PS), in the prevention of oxidative stress and the molecular mechanisms behind these effects

Methods ARPE‐19 cells were exposed either to PS or hydroquinone (HQ) or both simultaneoulsy. Toxicity and protective effects of PS against HQ‐induced oxidative stress were determined by colorimetric cell viability test (MTT‐test). Signalling mechanism of PS was studied by analyzing mRNA levels of Nrf2 (nuclear factor‐erythroid 2‐related factor‐2) and its target genes heme oxygenase‐1 (HO‐1), glutathione S‐transferase pi 1 (GSTP1) and sequestosome 1 (p62) by PCR. Moreover, Nrf2 and p62 were silenced by using siRNA technology.

Results PS treatment protected ARPE‐19 cells from HQ, when analyzed by MTT assay. PS treatment significantly increased the expression of HO‐1 that was abolished by Nrf2 siRNA . PS did not protect p62 siRNA‐treated cells from HQ induced oxidative stress.

Conclusion Our results suggest that PS treatment conferred protection against HQ‐induced oxidative stress through the induction of HO‐1 in ARPE‐19 cells. Consequently, PS‐stilbene compounds may possess health‐promoting properties against oxidative stress‐related diseases such as AMD.
Autophagy stimulus promotes HuR protein phosphorylation and SQSTM1/p62 protein up‐regulation in ARPE‐19 cells
Authors: AMADIO M , MARCHESI N , GOVONI S , PASCALE A , KAARNIRANTA K
Published: August 2014

Purpose Age‐related macular degeneration (AMD) pathogenesis involves impaired protein degradation in retinal pigment epithelial (RPE) cells. Our recent observation reveals that the expression of autophagy receptor SQSTM1/p62 is positively regulated by HuR protein (mRNA‐stabilizing human Embryonic Lethal Abnormal Vision protein) (Viiri et al. 8(7):e69563, 2013, PLoS One). In this study, we investigated the effects of AICAR (autophagy inducer, 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside) with/without MG‐132 (proteasome inhibitor) on HuR post‐translational activation and p62 protein levels in ARPE‐19 cells.

Methods ARPE‐19 cells were treated with MG‐132 (1µM) and/or AICAR (2mM) for increasing times (from 15 min to 2 h) and subjected to cell fractionation. HuR and SQSTM1/p62 protein levels were measured by Western blotting. HuR phosphorylation in threonine residues was evaluated by Western blotting following immunoprecipitation.

Results AICAR+MG‐132 co‐treatment induces early translocation of HuR protein from the nucleus to the cytoplasm (already after 15 min). In this latter cellular fraction, after 2 h an increase of HuR protein phosphorylation (+94% vs control) and an up‐regulation of p62 protein levels are observed (+85% vs control).

Conclusion In the cytoplasm of ARPE‐19 cells AICAR+MG‐132 co‐treatment leads to HuR protein activation, which in turn may determine the increased p62 protein expression.
Gene therapy for bestrophinopathies
Authors: GUZIEWICZ K , BELTRAN W , CIDECIYAN A , KOMÁROMY A , IWABE S , DUTROW E , ZANGERL B , HAUSWIRTH W , JACOBSON S , AGUIRRE G
Published: August 2014

Human bestrophinopathies, a group of inherited retinal disorders caused by mutations in BEST1, are one of the most common early‐onset macular dystrophies still considered incurable. The disease is usually diagnosed in early childhood or adolescence, and primarily affects macular region leading to major declines in central vision later in life. Canine multifocal retinopathy, a spontaneous animal model of BEST1‐associated retinopathies in man, captures the full spectrum of clinical and molecular features observed in human disease, including the salient predilection of lesions to the canine fovea‐like region, and constitutes an important translational model for development and testing of therapeutic strategies. We have previously shown that rAAV2‐mediated BEST1 gene delivery controlled by human VMD2 promoter specifically targets RPE cells, and is well tolerated in the wt canine retina. Here, we demonstrate that rAAV2‐mediated BEST1 gene augmentation reverses the characteristic BEST1 lesions and pathology in cmr models up to 23 months post‐injection. The talk will highlight the natural history of the disease and elaborate on the potential of rAAV2‐mediated BEST1 gene replacement therapy for prevention as well as reversal of disease.
AIDS thirty years later, lessons from a pandemic
Authors: KESTELYN P
Published: August 2014

At the start of the AIDS epidemic in the early eighties panic, fear and disbelief prevailed. A new "Great Plague" had arrived! Now, thirty years later, we know the enemy, we have devised effective weapons that transform a deadly disease into a chronic condition, and very recently we made our first attempts at engineering cellular resistance to HIV. This lecture will explore the many new insights we gained during our fight against AIDS, with some emphasis on the ophthalmic aspects of the disease.
Fingolimod‐associated cystoid macular oedema
Authors: LIU L , CUTHBERTSON F
Published: August 2014

Fingolimod‐associated cystoid macular oedema has been reported in treatment of MS and following renal transplantation. This seems to be dose‐dependent with an incidence of approximately 0.5% with 0.5mg oral dose. Although most patients develop macular oedema between 3 to 4 months after initiation, we reported an incidence as early as 5 days. The mechanism underlying fingolimod‐associated macular oedema is not entirely clear. It has been shown that fingolimod, the S1P receptor, not only plays a role in recruiting T lymphocytes, but also in regulating vascular permeability. Patients on fingolimod should be advised of the possible adverse visual symptoms. It may be helpful for patient to self‐monitor with an Amsler chart, and urgent ophthalmology review is suggested for patients with painless reduced vision.
Angle closure glaucoma in Asians: comparison of biometric and anterior segment parameters between Japanese and Chinese subjects
Authors: HO H , OZAKI M , MIZOGUCHI T , NONGPIUR M , HOW A , HE M , WONG T , PERERA S , AUNG T
Published: August 2014

Purpose To compare anterior segment parameters in Chinese and Japanese subjects using anterior segment optical coherence tomography (ASOCT) and to determine if the associations between these parameters and angle closure vary between the two ethnic groups.

Methods We conducted a case‐control study among 117 Japanese and 102 Chinese patients with primary angle closure (PAC) or primary angle closure glaucoma (PACG); and 117 Japanese and 176 Chinese controls. All participants underwent A‐scan biometry and ASOCT imaging (Visante, Carl Zeiss Meditec, Dublin, Ca). ASOCT‐derived biometric parameters were compared between groups. Multivariate analysis was performed to determine predictors of angle opening distance at 750µm from the scleral spur (AOD750).

Results Japanese were older (p<0.001) and consisted of more females (p<0.001). Age and gender adjusted analysis of covariance showed that Japanese eyes with angle closure had a significantly shallower anterior chamber depth (p=0.015), shorter axial length (p<0.001), greater lens thickness (p<0.001), lens vault (LV) (p=0.001) and iris curvature (I‐Curv) (p<0.001), and a smaller anterior chamber area (p=0.044) and volume (p=0.028); but no significant difference was noted for anterior chamber width (ACW). In Japanese, the predictors of AOD750 were LV (p=0.004), ACW (p=0.049) and ICurv (p=0.017); in Chinese, only the LV (p<0.001) was a determinant factor.

Conclusion Japanese eyes with angle closure were smaller, with thicker lenses. LV is an important factor for angle closure in both races. These results suggest differing mechanisms of angle closure pathogenesis between the two ethnic groups.
Novel cell therapeutical approaches to treat the corneal endothelium
Authors: FUCHSLUGER T
Published: August 2014

The talk will give an overview of cell therapeutical treatments of corneal endothelial cells. The use of different vectors in nano‐scale will be presented. Functional data on transfering nucleic acids to the corneal endothelium will be discussed.
Long‐term follow‐up of the bag‐in‐the‐lens in children
Authors: TASSIGNON MJ
Published: August 2014

Over the years the visual prognosis of pediatric cataract has significantly improved. Final visual outcome depends upon many factors: age of onset, uni‐ or bilaterality, pre‐ and coexisting ocular abnormalities, timing of surgery, postoperative course and complications, and adherence to amblyopia treatment. We present a series of 46 eyes implanted with the bag‐in‐the‐lens intraocular lens (BIL IOL), of which 30 bilateral and 16 unilateral eyes. A significant improvement in best‐corrected visual acuity (BCVA) was obtained in all but one case (PFV case with glaucoma) though with a significant difference between uni‐ and bilateral cases. BCVA above 0.5 was achieved in 26, and of 1.0 in 17 of the bilateral cases. Of the unilateral cases only 5 achieved a BCVA above 0.5 while none achieved 1.0. The likely reasons for the poorer outcome in unilateral cases include a higher rate of ocular comorbidity (4 cases of PFV in this series) and the increased tendency towards amblyopia in unilateral cases despite early and intensive visual rehabilitation treatment. In conclusion, the BIL IOL can be considered a safe and well‐tolerated approach for pediatric cataract with favorable visual outcomes and a low rate of VAR and other complications.

Commercial interest
Update from the Swedish national pediatric cataract quality registry
Authors: TORNQVIST K
Published: August 2014

Purpose: To present recent data from the Swedish/Danish pediatric cataract register (PECARE), a register with the aim of improving pediatric cataract care. Methods: A web‐based register, the Pediatric cataract register, PECARE, with data on cataract operations in children <8 years old in Sweden and Denmark is used. The participating clinics have access to their own results together with the results of the total database on‐line at any time. Results: On Dec 31 2013 the register contained data on 562 registered operations in 403 children, 209 (52%) boys and 194 (48%) girls.In 199 cases (49%) the cataract was bilateral and in 204 (51%) unilateral. Altogether 159 individuals (39%) had undergone bilateral operation and 244 (61%) unilateral operation. In 67/159 cases (42%) operation had been performed in both eyes the same day. Totally 209 patients (300 eyes) have at least one registered follow‐up at 1, 2, 5 or 10 years of age. Data from these follow up registrations will be presented. Conclusion: The web based register “Pediatric cataract register, PECARE” gives the participating clinics up dated results on line. Aggregated data provide valuable information which can be used to improve the care of children with cataract.
Genetically determined disorders
Authors: LEROY B
Published: August 2014

Purpose: To describe genetically determined conditions which affect retinal and optic nerve function and can lead to seeing things which aren't there. Methods: A case presentation format will be used to illustrate different genetically determined conditions leading to visual hallucinations. Both clinical and electrophysiological phenotypes as well as genotypes will be discussed. Results: Phenotypes of genetically determined retinal diseases leading to visual hallucinations are very different. Often, the ophthalmologist can make a real difference by explaining the cause of the complaints. Conclusions: Very diverse conditions may give rise to seeing things which aren't there. Clinical examination and electrophysiology allow making a correct diagnosis.
The role of electrophysiological investigation
Authors: HOLDER GE
Published: August 2014

Purpose: To describe the diagnostic electrophysiological features associated with disorders that may present with positive phenomena. Methods: Standardised electrophysiological testing, performed to incorporate and exceed the Standards of the International Society for Clinical Electrophysiology of Vision. Results: Illustrative cases will be used to demonstrate diagnostic electrophysiological features in a variety of disorders. Conclusions: The objective functional data provided by electrophysiological testing are of considerable importance to the diagnosis and management of conditions associated with positive phenomena.
Visual outcomes following intravitreal aflibercept in patients with myopic choroidal neovascularisation
Authors: KOROBELNIK J , IKUNO Y , ASMUS F
Published: August 2014

Purpose To evaluate visual acuity outcomes in patients (pts) with myopic CNV receiving intravitreal aflibercept (IVT‐AFL) or sham injection in the international, 48 week, Phase 3 MYRROR trial (NCT01249664).

Methods Pts were randomised 3:1 to IVT AFL or sham/IVT‐AFL (sham to Week 20; IVT‐AFL from Week 24 to Week 48). We report on exploratory post hoc analyses evaluating proportions of pts achieving visual gains (ETDRS letters) and the associated time course.

Results 121 pts were analysed (IVT‐AFL, n=90/ sham/IVT‐AFL, n=31). At Week 24, 63.3% and 38.9% of IVT‐AFL pts had gained ≥10 or ≥15 letters from baseline. In the sham/IVT‐AFL group, 12.9% and 9.7% had gained ≥10 or ≥15 letters from baseline. By Week 48, the proportion of IVT‐AFL pts gaining ≥10 or ≥15 letters was 68.9% and 50.0%, respectively. At Week 48 in the sham/IVT‐AFL group (i.e., 24 weeks after IVT‐AFL initiation), 41.9% and 29.0% of pts had gained ≥10 or ≥15 letters from baseline, respectively. Ocular AEs were mainly mild and occurred at a similar rate with IVT‐AFL and sham/IVT‐AFL (37.4% vs 38.7%; most common, respectively: conjunctival haemorrhage [11.0%] and punctate keratitis [12.9%]). 7 (5.7%) pts had a serious AE (all IVT‐AFL; only one SAE in study eye [macular hole]). No deaths were reported.

Conclusion The proportion of IVT‐AFL pts who gained ≥10 or ≥15 letters by Week 24 was well maintained and even slightly increased at Week 48. Clinically meaningful benefits from IVT‐AFL were also observed at Week 48 in the sham/IVT‐AFL group. However, the proportion of gainers did not reach the extent seen in the initial IVT‐AFL group, suggesting that earlier IVT‐AFL treatment should be recommended.

Commercial interest
Science behind the disease
Authors: SCHLINGEMANN R
Published: August 2014

Abstract not provided
VIVID and VISTA: Clinical trial results and implications
Authors: KOROBELNIK J
Published: August 2014

Abstract not provided
LDF and assessment of autoregulation
Authors: SCHMETTERER L
Published: August 2014

The main advantage of laser Doppler flowmetry is its excellent time resolution. This allows for continuous measurement of tissue blood flow during changes in perfusion pressure. As such the technique is optimally suitable to assess autoregulation, referring to the ability of a vascular bed to maintain its blood flow in response to changes in perfusion pressure. In the eye the technique has been applied for both measuring optic nerve head blood flow and subfoveal choroidal blood flow. For both vascular beds data have been obtained using either an experimental increase or decrease in ocular perfusion pressure. In addition, data are available showing the complex regulation of ocular blood flow when both mean arterial pressure and intraocular pressure are modified.
How to get your research published?
Authors: KIVELÄ T
Published: August 2014

A primary criterion for publishing a paper is novelty of its data. This extends to the introduction and discussion of the paper. These can not consequently be cut and pasted from published literature, not even from the author's previously published papers. The journals typically require the authors to confirm that their submission is unique and that the data are new. Violations of these rules may today result in retraction of the paper after publishing, even years or decades after its publication, if plagiarism or self plagiarism is later detected. One must also be certain to submit only unaltered images and data. Many universities and some journals provide today on‐line tools that can be used to check whether the manuscript has borrowed verbatim from the literature. The advent of on‐line manuscript review and publishing may tempt to copy from previous papers without rephrasing or attribution, habits which should carefully be avoided. On the other hand, electronic publishing is low cost and easy to start, which recently has resulted in proliferation of so‐called "predatory" gold open access publishers. Guidelines are discussed which may help authors to identify such publishing forums and to avoid plagiarism.
Corneal dystrophies related to cholesterol metabolism (fish eye and Schnyder dystrophy)
Authors: KESTELYN P
Published: August 2014

Schnyder corneal dystrophy (SCD) is a rare corneal dystrophy characterized by abnormally increased deposition of cholesterol and phospholipids in the cornea. SCD is inherited as an autosomal dominant trait with high penetrance and has been mapped to the UBIAD1 gene on chromosome 1p36.3. Diseases of systemic lipid metabolism that cause corneal opacification, such as lecithin‐ cholesterol acyltransferase (LCAT) deficiency and fish eye disease (FED), should be considered in the differential diagnosis. LCAT deficiency and FED are both entities that result from deficiency of the LCAT enzyme. LCAT deficiency is defined by deficient LCAT activity towards HDL and LDL whereas FED is defined by decreased LCAT activity against HDL only. When comparing LCAT deficiency and FED to SCD, there are numerous differences to help distinguish all 3 entities. Both LCAT deficiency and FED are inherited in an autosomal recessive manner while SCD has autosomal dominant inheritance. Systemically, SCD has a normal level of LCAT enzyme activity and normal HDL levels. Both LCAT deficiency and FED show abnormally low levels of HDL. SCD is often associated with a true arcus lipoides, unlike FED and LCAT deficiency.
Characteristic features of choroidal tumors in Deep Range Imaging OCT (DRI‐OCT)
Authors: ROMANOWSKA DIXON B , JAKUBOWSKA B , MARKIEWICZ A
Published: August 2014

Purpose To find and analyze characteristic features of choroidal tumors and surrounding tissues, retina, choroid and vessels.

Methods Patients with choroidal tumors (choroidal nevus, choroidal melanoma, choroidal metastses, choroidal hemangioma, choroidal osteoma and others) diagnosed and treated in Department of Ophthalmology and Ocular Oncology of University Hospital were included. Swept Source OCT (DRI OCT‐1) developed by Topcon was used for imaging.

Results Deep range imaging DRI‐OCT‐1 displays detail structures of not only retina but choroid and even sclera. The characteristic features, of intraocular tumors can improve the differential diagnosis and estimation of progression or treatment effects.

Conclusion The new diagnostic modality may be useful for the evaluation of abnormalities observed intratumoral and in a border area and can improve diagnostic accuracy.
Secondary Intraocular lymphoma of the iris following a succussefully treated diffuse large B‐cell lymphoma of the orbit
Authors: MEYER P , GRAEFF E
Published: August 2014

Purpose To report clinical findings of a rare case of lymphoma with iris involvement and therapeutic approach with local application of rituximab

Methods Case report

Results A¬n 80‐year old patient reported blurred vision in the right eye for one week. After dacryodacryocystorhinostomy he suffured from decreased vision, chemosis and double vision on downgaze. MRI of the head revealed a right orbital tumor mass, arising from a distinct tumor mass of the right maxillary and ethmoid sinuses. Biopsy revealed CD5‐positive, diffuse large B‐cell lymphoma. The patient was managed with tumor debulking and systemic chemotherapy. At completion of therapy he remained in remission until presentation of a cutaneous relapse on the lower leg with simultaneous eye discomfort. On ocular examination the visual acuity was hand motion in the right eye with normal Intraocular pressure.The right eye showed diffuse keratic precipitates and moderate cells and flare in the anterior chamber.From 8 to 1 o‘clock the iris showed diffuse thickening of the stroma and irregular pupil.Examination with ultrasound biomicroscopy showed involvement of the anterior part of the cilliary body. Posterior segment examination was unremarkable. Aspiration of the anterior chamber showed CD20 positive, atypical lymphocytes, compatible with the previously diagnosed non‐Hodgkin’s lymphoma. After local application of rituximab three weeks later the thickening of the iris tissue had resolved.

Conclusion Lymphomatous involvement oft he iris should be considered in the differential diagnosis of a severe anterior uveitis in elderly patients with known aggressive systemic lymphoma. An additional local application of rituximab may be suggested in isolated iris lymphoma.
When the clinician has to rely on disease phenotype alone for diagnosis: the example of Behçet’s uveitis
Authors: TUGAL‐TUTKUN I
Published: August 2014

Behçet’s disease (BD) is a complex inflammatory disorder characterized by recurrent inflammatory attacks in multiple organ systems There is no specific diagnostic test. Clinical diagnostic criteria have been developed based on the presence of characteristic ocular and systemic inflammatory manifestations. However, ocular lesions defined in the current sets of diagnostic or classification criteria are nonspecific. It is important to recognize characteristic features of BD uveitis because there are BD patients with other forms of uveitis by coincidence, and patients with typical ocular involvement but without systemic manifestations of the disease. The course of the disease is characterized by recurrent nongranulomatous uveitis attacks of variable severity. Transient nature of the acute inflammatory signs is the most important diagnostic clue. Transient retinal infiltrates and inferior peripheral pearl‐like precipitates are the pathognomonic findings that help differentiating BD uveitis from other causes of panuveitis and retinal vasculitis.