bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are we over prescribing in Glaucoma?
Authors: Tuulonen A. 
Published: September 2015

SummaryThe current cultural and legal environments exert tremendous pressure to do more. To choose to do nothing seems to be more open to criticism, rather than to take action, despite the risk that action might later prove to be harmful. It is well‐known for decades that high resource allocation does not necessarily lead to measurable benefits to the patients.Prescribing diagnostic tests and treatments are indicated when they provide benefits and outcomes that are important to patients, i.e. when interventions improve patients’ well‐being in every‐day life. More frequent testing leads to more diagnoses with newly detected cases being in general milder and non‐optimal specificities of diagnostic tests falsely classifying non‐glaucoma cases having glaucoma. Thus, outcomes will seem to improve, which stimulates to do even more.When we have evidence of treatment effectiveness, does it automatically imply that treatment should be administered to every patient? When e.g. the total costs of glaucoma medications increase five‐fold in 5 years, and one country treats 30% more patients with glaucoma compared to its neighbor, which patients are under‐ or over‐treated? Very different conclusions may result from the same evidence.
OCT in animal models
Authors: Normando E.M. 
Published: September 2015

SummaryDue to their accessibility, animal models are playing a major role in understanding some of the underlying causes of glaucoma. Optical Coherence Tomography (OCT) has been used extensively in these animal models giving us the advantage of longitudinal in‐vivo assessments of the natural history of this disease. Outer retina involvement has recently been demonstrated in‐vivo in experimental glaucoma. OCT segmentation software are now available as an aid for understanding the involvement of retinal layers other than the RNFL. Retinal blood flow is also currently under investigation in experimental glaucoma using ultra high resolution OCT. Furthermore, investigations of the irido‐corneal angle configuration and its structural modifications in response to anti glaucoma drugs have also been conducted in experimental models using anterior segment OCT. The talk will discuss the utility of OCT in animal models in Glaucoma.
Bioinformatics in tear proteome
Authors: Nykter M. 
Published: September 2015

SummaryTear is a complex fluid containing rich mixture of biomolecules. Current mass spectrometry based proteomic techniques are able to capture the expression of thousands of proteins from small tear volumes, opening possibility for data driven identification of predictive biomarkers. We have developed a bioinformatic approach for biomarker discovery that effectively finds associations between time course proteomic data and clinical phenotypic data. We first construct a feature matrix that contains the data and clinical information as well as various computationally derived features, for example pathway enrichments scores across thousands of pathways and various biologically motivated activity scores for master regulators. These feature matrices that can contain categorical, discrete or continuous data are then computationally analyzed to identify the strongest statistical associations with the phenotypes of interest. Cross validation strategy is utilized to make sure the identified associations are robust. Our approach has been applied to data from clinical patient samples to identify new candidate biomarkers.
The history of the description of retinopathy in onchocerciasis
Authors: Kestelyn P. 
Published: September 2015

SummaryUp until 1930 the scientific community considered African onchocerciasis to be a pure skin disease and not the blinding disease encountered in America. Jean Hissette, a belgian general practitioner with a special interest in eye pathology, was the first to document onchocerciasis in Africa as a blinding disease. Between 1931 and 1938, he published a series of articles on the subject, based on the experience he gained from several expeditions in the endemic Babindi country (Belgian Congo). His discussions with J Bryant in 1932 stimulated the latter to publish an article in 1935 on the posible relationship between Onchocerca volvulus and endemic choroiditis in Sudan. As the result of his collaboration with R Strong, an expert from Harvard on the Central American form of the disease, Hissette wrote a paper that appeared in 1938 as a supplement to the American Journal of Tropical Medicine. In this landmark paper he describes with great precision the chorioretinitis of the posterior pole typical of onchocerciasis, later to be known as the Hissette‐Ridley fundus. Although the names of the two men are linked, Hissette's work preceded Harold Ridley's publication in the BJO on ocular onchocerciasis in Ghana by more than a decade.
Peptide versus gene therapy: Cathelicidin LL‐37 and HSV‐1 corneal infection
Authors: Griffith M. , Lee C.J. , Buznyk O. 
Published: September 2015

SummaryWe compared the performance of biosynthetic corneal implants based on collagen‐phosphorylcholine (Coll‐MPC) with anti–Herpes Simplex Virus (HSV)‐1 activity achieved by sustained release of the cathelicidin LL‐37 from incorporated nanoparticles, to cell‐based delivery of the peptide from human corneal epithelial cells (HCECs) transfected to produce endogenous LL‐37. LL‐37 released from the implants blocked HSV‐1 infection of HCECs by interfering with viral binding. However, in pre‐infected HCECs, LL‐37 delayed but could not prevent viral spreading nor clear viruses from the infected cells. HCECs transfected with the LL‐37 to confer viral resistance expressed and secreted the peptide. Secreted LL‐37 inhibited viral binding in vitro but was insufficient to protect cells completely from HSV‐1 infection. Nevertheless, secreted LL‐37 reduced both the incidence of plaque formation and plaque size. LL‐37 released from composite nanoparticle‐hydrogel corneal implants and HCEC‐produced peptide, both showed anti–HSV‐1 activity by blocking binding. While both slowed down virus spread, neither was able on its own to completely inhibit the viruses.
The evolving role of nurses and allied health professionals in the management of age‐related macula degeneration
Authors: Hamilton R. , Mapani A. , DaCosta J. , Pavesio C. , Flanagan D. 
Published: September 2015

SummaryOne of the major developments within the medical retinal (MR) over the last five years has been the introduction of an intravitreal injection of anti‐vascular endothelial growth factor medications (Anti‐VEGFs) for patients with AMD and other macular disease. As a consequence of this development, outpatient attendances within the MR Service have increased significantly.The Royal College of Ophthalmologists acknowledges challenges related to staffing levels. A document produced by the Royal College of Ophthalmologists in 2009 stated that training nurses or technicians to perform intravitreal injections may offer a potential solution to increased pressure in the retinal therapies clinics despite the label recommending that intravitreal injections be given by trained ophthalmologists.Nursing staff at Moorfields Eye Hospital have given over 15,000 injections now and are currently giving over 60% of all injections. Enabling nurses to be trained to perform intravitreal injections has improved the efficient delivery and capacity of the injection service and enabled national guidelines and service delivery targets to be met, whilst maintaining high standards of care with an excellent safety record.
Cystoid macular oedema in endstage glaucoma
Authors: Bifrare D. 
Published: September 2015

SummaryMicrocystic macular changes associated with optic neuropathy.Microcystic macular edema has been first described in association with multiple sclerosis in 2012. Since then many papers have emerged, describing microcystic macular changes mainly in connection with inflammatory or non‐inflammatory optical neuropathy, suggesting the neuropathy to be the origin of these microcystic macular changes.The different neuropathies and the pathomechanism possibilities will be discussed according to recent litterature.
Doppler Optical Coherence Tomography ‐ A New Method For The Assessment Of Neurovascular Coupling In The Retina
Authors: Werkmeister R. , Aschinger G. , Schmetterer L. 
Published: September 2015

SummaryIn recent years, we have shown that a dual‐beam bidirectional Doppler OCT system allows to measure total blood flow in the ocular fundus and can also be used to detect changes in this flow values due to various stimuli.Neurovascular coupling (NC) refers to a phenomenon where local blood flow is elevated with increased neuronal activity. NC may be essential to deliver increased amounts of oxygen, glucose and other nutrients to neurons when they are active. As such a breakdown in NC may contribute to cell death in neurodegenerative diseases.OCT ‐ due to its high resolution ‐ is superior to other methods used to measure physiological parameters in the human body. In a recent study, we measured total retinal blood flow in the human eye and assessed flow changes due to a stimulus with diffuse luminance flicker. We measured an increase of about 40%, which is assumed to occur as a consequence of an increased firing rate of retinal ganglion cells.Our results show that dual‐beam bidirectional DOCT may serve as a powerful tool to study changes in ocular blood flow due to changes in neuronal activity and, thus may contribute to the investigation of neurodegenerative diseases and the development of neuroprotective strategies.
Relationship of ocular disease activities before and after starting infliximab using Behçet's disease ocular attack score 24
Authors: Kaburaki T. , Okinaga K.T.R. , Takamoto M. , Ohtomo K. , Yoshida A. , Kawashima H. , Komae K. , Fujino Y. 
Published: September 2015

SummaryPurposeTo investigate the relationship of ocular disease activities before and after starting infliximab using Behçet's disease ocular attack score 24 (BOS24).Patients and MethodsWe studied 69 eyes of 35 patients with ocular Behçet's disease (BD) who had started infliximab therapy. Total BOS24 scores during 1‐year period (BOS24‐1Y) before and after starting infliximab therapy were calculated and its correlation was examined. Patients were divided into three group according to the BOS24‐1Y before starting infliximab; H group (BOS24‐1Y of 40 points or more, n = 14), M group (20 to 39 points, n = 12) and L group (19 points or less, n = 9). Ocular disease activities after starting infliximab were compared among three groups.ResultsSignificant correlation was observed between BOS24‐1Y scores before and after starting infliximab (P < 0.0001). BOS24‐1Y after starting infliximab in H, M and L group were 20.9 ± 28.3, 7.3 ± 15.2, 0.6±1.9 points, respectively (P < 0.05). After starting infliximab, ocular attacks were disappeared in 8 cases (89%) in L group, whereas severe ocular attacks still occurred in 7 cases (50%) in H group.ConclusionsBOS24‐1Y before starting infliximab could be a predictor for disease activity after starting infliximab.
Subretinal implantation of human stem cell‐derived RPE on ultrathin carriers in rabbits
Authors: Stanzel B.V. 
Published: September 2015

SummaryTransplantation of retinal pigment epithelium (RPE) is being developed as a cell replacement therapy for age‐related macular degeneration (AMD). Human embryonic and adult human RPE stem cells (hESC and hRPESC, resp.) are known potential sources that are currently being pursued towards the clinic. Polarized monolayers of SC‐derived RPE were shown to grow on biostable polyester (PET) membranes. They were found to be similar to fetal hRPE monolayers and to have near‐native characteristics. Stamped pieces of RPE monolayers on the carrier were loaded into a custom‐designed surgical instrument and transplanted subretinally in the rabbit, a large‐eyed animal model. Compared to fetal and hRPESC derived RPE, hESC‐RPE xenografts showed better preservation of the neural retina overlying the implant. Histology obtained 4 weeks after implantation confirmed a continuous polarized human RPE monolayer on PET. We demonstrate that the xeno‐RPE monolayer implant survived well and retained its polarization. Moreover, our initial data suggest a distinctly advantageous tolerance of hESC derived RPE xenografts in rabbit subretinal space.
Antibiotic resistance and new types of antimicrobials
Authors: Beuerman R. 
Published: September 2015

SummaryThe World Health Organization has pointed out that all current antibiotics exhibit some level of resistance. Moreover, designing new antibiotics to avert resistance is difficult due to the ability of bacteria to mutate targets of current antibiotics. Conceptually, it was realized that to overcome resistance it was necessary to kill bacteria quickly and to avoid mutable targets. New molecules were designed using the fundamentals chemical interactions that would disrupt membrane organization. These small molecules were for both Gram positive and Gram negative bacteria, as well as mouse models of corneal infection. Specific chemical groups were attached to a series of small molecules that resulted in rapid kill time (<60 mins), had no effect on healing of an epithelial wound in rabbits, and in a mouse model of MRSA infection of the cornea were effective at 3 mg/ml compared to vancomycin at 50 mg/ml. Simulation of resistance showed that these new classes of antibiotics did not develop resistance although in the same protocol, MICs for gatifloxicin, gentamycin and norfloxicin increased by 10–140 times. Conclusion: New drug designs based on more predictive behavior could bring a series of new drugs to the clinic to lessen the impact of resistance on healthcare.
To the clinic and back
Authors: Gandolfi S. 
Published: September 2015

SummaryFor a clinician, neuroprotection in glaucoma means “decreasing vision loss without affecting intra ocular pressure”. In recent years, translational research on neuroprotection has offered several molecules for clinical testing. Unfortunately, after evaluation via randomized clinical trials, their efficacy is still a matter of debate. We are presently left with excessive patients’ attrition, poorly defined outcomes, borderline significances, clinically unrelevant results etc. A re‐thinking of the general approach to the issue of neuroprotection in glaucoma is then necessary. The molecules, before being chosen for evaluation in humans, should offer a more striking and unquestionable pre‐clinical efficacy profile. New outcomes, on top of the traditional standard automatic perimetry, are needed in order to shorten the duration of the trials and to reduce the “noise” of the system. New study designs, properly tailored on neurodegenrations, together with new strategies for data analysis are needed: futility trials, Bayesian approach and adaptive study designs will extensively be discussed as potential tools to return from the bench to the bedsite.
Choroidal thickness in acute and convalescent VKH disease
Authors: Takase H. 
Published: September 2015

SummaryVogt‐Koyanagi‐Harada (VKH) disease is a systemic autoimmune disorder against melanocytes, and is one of the leading causes of uveitis in many countries including Japan. The distribution of the melanocytes in the systemic organ such as eyes, internal ears, meninges, or skin, leads to the various symptoms or signs of VKH disease. Because melanocytes are abundantly present in the choroid, the primary site of the intraocular inflammation of VKH disease is the choroid. Therefore, to monitor the disease activity of VKH disease, indocyanine green angiography (ICGA) had long been the most useful tool. Recently, advances in optical coherence tomography (OCT) made it possible to visualize the cross section of the choroid in addition to the retina, and the findings in choroidal OCT are found to complement those in ICGA. In this presentation, the features of the choroidal changes by ICGA and OCT in VKH disease are discussed.
Vascular supply in mitochondrial optic neuropathy and glaucoma
Authors: Barboni P. 
Published: September 2015

SummaryTo quantitatively evaluate the vascular supply in patients at different stages of Leber's hereditary optic neuropathy (LHON). Twenty‐six LHON patients were recruited for the study. LHON patients were sub‐grouped in: acute (aLHON), chronic phase (chLHON) and asymptomatic carriers (LHON carriers). All subjects had an extensive ophthalmological examination, including Enhanced depth imaging‐optical coherence tomography (EDI‐OCT). Macular choroid thickness was significantly increased in aLHON patients and this was most evident nasally and superiorly. On the contrary, choroidal thickness was significantly reduced in chLHON patients in all measurement but the 1500 nasal. In comparison, LHON carrier subjects showed a significant increase of choroidal thickness in the 1500 inferior measurement. In the present study we show that choroidal thickness follows a pattern similar to that observed in RNFL, increasing in the pre‐symptomatic and acute stages and decreasing in the chronic stage. This feature might be explained by different hypotheses including: (1) a peripapillar microangiopathy, typical of the acute stage, involving the choroidal vessels; (2) increased blood flow through a thickened choroid in response to inefficient metabolism of the retina requiring more oxygenation or a greater heat state.
The role of Anti‐VEGFs in the management of DME in vitrectomized eyes
Authors: Kourentis C. 
Published: September 2015

SummaryThe role of Anti‐VEGFs in the management of diabetic macula edema (DME) is well established in large, randomized, controlled studies in eyes with naïve vitreous. The effect of Anti‐VEGFs may be altered in vitrectomized eyes and the question arises whether there is a difference in the efficacy of Anti‐VEGFs after vitrectomy. The replacement of the vitreous gel facilitates oxygen transport to the retina, as well as clearance of VEGF, thus VEGF and Anti‐VEGF pharmacokinetics can be altered. Pharmacokinetic data are largely based on experimental animal models but there is also a clinical impression that vitrectomized eyes have augmented pharmacokinetics with a faster clearance of Anti‐VEGFs and therefore their treatment could be less effective and requiring shorter treatment intervals, compared to non‐vitrectomized eyes. According to a study presented January 2015, vitrectomized eyes fared as well as non.vitrectomized eyes after treatment with ranibizumab for diabetic macular edema.
The impact of genetics on the clinical management of patients with monogenic corneal diseases
Authors: Tuft S.J. , Evans C. , Davidson A. , Hardcastle A. 
Published: September 2015

SummaryOver the last decade there has been a major reassessment of the classification of inherited corneal disease. In this presentation I discuss our program to genotype all patients attending our tertiary referral center who have suspected monogenic corneal disease. This has enabled us to distinguish the phenotypes of several closely related dystrophies as well as identify a small number of patients who have previously been misclassified. Some patients with important systemic associations have been identified and referred for further investigation and management. Finally, patients without changes in the genes commonly associated with corneal dystrophy have been selected for further evaluation. The impact of this for clinical care will be discussed.
Beta II tubulin as molecular marker of intraocular pressure in endothelial cells
Authors: Prokosch‐Willing V. 
Published: September 2015

SummaryThe human CNS ‐ like the adult mammalian CNS in general‐ lacks the capability to regenerate axons and restore neuronal tissue. After injury or in degenerative diseases like e.g. in glaucoma, neurons fail to regrow and reconnect with their target cells, frequently underlay apoptosis and are abnormally replaced. This regenerative failure in CNS remains an enormous scientific and clinical challenge. However under certain conditions neurons may regain the ability to regenerate in vivo and in vitro. One interesting group which shows enormous regenerative potential on retinal ganglion cells are the crystallins. We present our data on the regenerative potential of crystallins in experimental models.
Suspicious choroidal naevi: when to observe when to treat
Authors: Kivelä T. 
Published: September 2015

SummaryRecognition and characterization of choroidal naevi is based on fundus examination with the slit lamp and indirect ophthalmoscope, which ideally is supplemented with optical coherence tomography (presence of subretinal fluid, thickness and internal structure of lesions less than 1 mm in thickness), fundus autofluorescence (presence if recent or prior subretinal fluid, orange pigment) and ultrasonography (thickness and acoustic profile of lesions thicker than 1 mm). In spite of the advent of imaging, the challenge lies in telling small melanomas from naevi. The mnemonic ‘To Find Small Ocular Melanomas’ reminds us to look for tumour Thickness more than 2 mm, subretinal Fluid, visual Symptoms, Orange pigment and tumour Margin touching the optic disc. Each of these indicators approximately doubles the likelihood of growth and malignancy, although none of them alone is specific – up to ten percent of non‐growing naevi have orange pigment and subretinal fluid, for example, whereas some small melanomas initially show none of the five features. Surveillance for growth, a biopsy, or both, may thus be needed to make the treatment decision. This talk will introduce these principles using clinical examples.
Heterogeneity of retina Müller glia and their possible role neuroprotecting retinal ganglion cells
Authors: Vecino E. 
Published: September 2015

SummaryThe retinal Müller glia, provide structural and trophic support to retinal ganglion cells (RGCs) in the healthy retina and may also have a function in promoting cell survival after injury. Defining and understanding glial heterogeneity is an important goal since it would enable to better understand the fundamental role of these cells during retinal pathologies and could even open novel therapeutic avenues, such as targeted manipulations of sub‐populations in order to quench pro‐inflammatory destructive processes and/or stimulate regeneration of neurons in retinal degenerative diseases. Muller glia primary cell cultures in combination with RGCs have been studied. The heterogeneity of the glial cultures was characterized and their effect on RGC survival and neurite elongation. We found that cultured adult RGCs in close contact with adult Müller cells exhibit improved cell viability and significant neurite elongation. Not all Müller cells express their molecular markers with the same intensity. These results suggest that Müller glia support RGC regeneration not only by direct interaction, but also releasing soluble trophic factors. Further understanding of the relationship between retinal glia and RGCs is important in order to identify potential therapeutic targets to encourage retinal neuroregeneration.