bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrops: Not that bad!
Authors: Mekki M.B. , Said Y. , Okba T. , Taibi A. 
Published: September 2017

PurposeTo demonstrate that hydrops is not a disaster and often evolves favorably especially under surgical treatment.MethodsProspective study of 30 eyes of 30 patients with corneal hydrops who underwent clinical examination with anterior segment photography, corneal topography, ultrasound corneal pachymetry and corneal OCT. All of them underwent in an outpatient setting and under topical anesthesia, anterior chamber air injection, peripheral iridotomy and deep corneal sutures perpendicular to Descemet membrane tear then kept under observation for 1 hour. Patients were asked to stay laying on their backs for 3 days. All patients were able to wear scleral lens after 1 week post surgery.ResultsCorneal edema decreased dramatically since the first day concomitantly with corneal thickness and average SimK reading. Mean LogMAR with scleral lens was 0.4.ConclusionsProper surgical approach of hydrops can provide a spectacular quick healing with visual improvement avoiding corneal graft.
The first consultation
Authors: De Zaeytijd J. 
Published: September 2017

SummaryPhotophobia is a common yet debilitating symptom. Patients experience an abnormal intolerance or even pain in the eye from a light source that should not be painful. The anatomy and pathophysiology of this phenomenon will be discussed. The clinical characteristics and disorders associated with photophobia will be reviewed. And finally, a practical approach will be presented to allow you to differentiate patients with common treatable causes such as dry eye disease from patients who need an in‐depth ophthalmic or neurologic evaluation to find the underlying disease.
Photophobia in retinal disease
Authors: Leroy B.P. 
Published: September 2017

PurposeTo describe the phenotypes and genotypes of photophobia due to inherited retinal disease.MethodsA case presentation format will be used to illustrate different genetically determined conditions leading to photophobia. Both clinical and electrophysiological phenotypes as well as genotypes will be discussed.ResultsPhenotypes and genotypes of genetically determined diseases leading to photophobia are very different. An important distinction to be made is the one between stationary and progressive diseases. Indeed, such distinction is important as the visual outcome may differ considerably between different conditions.ConclusionsGenetically determined retinal diseases leading to photophobia are very diverse. Visual electrophysiology allows an important distinction between progressive and stationary conditions.
Tumors and pseudo‐tumors of the iris: classification and imaging techniques
Authors: Zografos L. 
Published: September 2017

SummaryTumors and pseudo‐tumors of the iris are classified as:

Iris cysts

Pigmented tumors

Vascular tumors

Myogenic tumors

Tu. of the non pigm. cil. epithelium

Neurogenic tumors

Juvenile xanthogranuloma

Metastatic tumors

Pseudotumors

Split lamp examination, split lamp photography, gonioscopy and photography of anterior chamber angle as well as high frequency ultrasound are the main examination techniques.
Update in genetics of corneal dystrophies
Authors: Bourges J.L. , Burin des Roziers C. , Beugnet C. , Nedelec B. , Hoffart L. , Delbosc B. , Muraine M. , Hamel C. , Lacombe D. , Moriniere V. , Fourrage C. , Robert M. , Bremond‐Gignac D. , Valleix S. 
Published: September 2017

SummaryHereditary corneal dystrophies are a group of diverse bilateral disorders usually classified anatomically according to the layer of the cornea affected. They include many types, which differ by their clinical manifestations, their histological characteristics, and their pathophysiology. The molecular basis of these corneal inherited disorders have expanded greatly, and mutations in several genes have been identified. We develop a genotype‐based approach by using a targeted Next‐Generation Sequencing panel including 15 known genes, and a cohort of 90 French index patients were recruited after detailed ophthalmic examination. All exons of the 15 genes were amplified using the kit TrueSeq Custom Amplicon (TSCA, Illumina). The subsequent amplified libraries were sequenced using a MiSeq (Illumina, Inc, San Diego, CA, USA) sequencer. All pathogenic variants were confirmed by Sanger sequencing, and familial analyses were performed. A large spectrum of molecular defects were identified with numerous novel variants. This NGS approach is an efficient tool to improve molecular diagnosis, and provides insight into the genotype‐phenotype correlation of all these corneal disorders in a cost‐effective way.
Peters anomaly new insights
Authors: Atilla H. 
Published: September 2017

SummaryDevelopmental anomalies are one of the the main pathologies seen in infancy and childhood. Embryological development of the anterior segment structures are closely related to each other and the clinical manifestations can be complex with associated glaucoma and lens opacities. Also in infancy and childhood amblyopia is needed to addressed in order to support visual system development. The spectrum of developmental anomalies known as anterior segment dysgenesis can be mild as posterior embryotoxon or can affect iris, cornea and even crystalline lens in severe cases of Peters anomaly. Peters anomaly can be seen as a genetic syndrome (Axenfeld‐Rieger syndrome) or after congenital rubella. As the clinical manifestation vary, the treatment modalities vary accordingly.
Optical coherence tomography in the differential diagnosis of true edema versus pseudoedema of the optic disc
Authors: Gozzi F. , Aldigeri R. , Mora P. , Bianchi‐Marzoli S. , Barboni P. , Gandolfi S. , Farci R. , Fossarello M. , Incerti M. , Carta A. 
Published: September 2017

PurposeTo assess the predictive value of Spectral Domain OCT (SD‐OCT) to discriminate between pathological true optic disc edema (ODE) and mimickers responsible for pseudoedema (PODE).MethodsWe carried out an observational cross‐sectional study of subjects consecutively referred from 2011 to 2017 to the Neuro‐Ophthalmology service of 4 different hospitals for presumed acute ODE. Among a total of 155 eyes, 95 were identified as ODE and 60 as PODE. Patients underwent the optic nerve OCT evaluation using Zeiss Cirrus Optic Disc Cube 200x200 analysis. Average and four principal quadrants RNFL values were compared between ODE and PODE groups and then with age‐matched controls. ROC curve and AUC were calculated to determine optimal cut‐off values. Mann‐Whitney and chi‐square tests were used to compare groups. Statistical correlation was tested by Spearman's rho test. All tests were two sided with p<.05 being considered statistically significant. Statistical analysis was performed with IBM SPSS Statistics 24.ResultsAverage and RNFL thickness of each optic nerve quadrants resulted significantly higher in ODE compared to control and PODE; among quadrants, the highest correlation was reported for the inferior one. Combining the appropriate cut‐off value for average and inferior quadrant, we found a negative predictive value of 91% for ODE when compared to PODE. No statistically significant differences were seen between control and PODE.ConclusionsOur data show the usefulness of SD‐OCT in the management of acute optic disc elevation of uncertain causes. In particular, the results herein reported provide high negative predictive value in differentiating benign mimickers from true edema of the optic disc, thus avoiding misdiagnosis and invasive procedures not necessary for such patients.
Gene therapy targeting of choroidal disease and AAV transcytosis through the outer blood retina barrier epithelium
Authors: Layton C. , Dhungel B. , Andrzejewski S. , Jayachandran A. , Murali A. , Ramlogan‐Steel C. , Steel J. 
Published: September 2017

PurposeThe retinal pigment epithelium (RPE) forms the relatively impermeable outer blood‐retinal barrier, which, when intact, prevents intraocular gene therapy vectors from effectively targeting choroidal diseases such as choroidal melanoma or choroiditis. This study hypotheses that AAV vector optimisation may effectively penetrate this ocular barrier.MethodsMonolayers of aRPE‐19 and primary human RPE were established on 24 well plate transwell inserts and integrity confirmed with stable transepithelial resistance (TEER) of 35±5 Ω/cm2 and resistance to passage of FITC‐Dextran (400 kDa) at 4 weeks. 10^8±1 vgs of AAV serotypes 1, 2, 3, 4, 5, 6, and 8 were added to the apical surface and media collected from the basal surface at various time points. Viral concentrations were measured by qPCR.ResultsAAV serotype 6 moved through the intact monolayer of both aRPE‐19 and primary human RPE. 41.5%. 47.4% and 60.4% of AAV‐6 viral particles moved through the monolayer at 30 minutes, 3 hours and 5 hours respectively. Blocking RPE exocytosis with tannic acid prevented movement of AAV6 through the monolayer. All other serotypes were unable to penetrate the RPE monolayer, with less than 10% penetrance at 24 hours.ConclusionsThese results indicate that AAV6 passes through a model of the outer blood retina barrier by active intracellular transport. Additionally, this is the first report of AAV‐6 transcytosis across any barrier epithelium. AAV6 may be a promising tool to deliver therapeutic genes for ocular diseases which lay beneath the retinal epithelium.
Characteristics, socioeconomic status and ethnic variations of primary idiopathic macular hole repair in vitreoretinal centers in the United Kingdom
Authors: Velissaris S. , Papavasileiou E. , Garnavou‐Xirou C. , Theodorou O. , Zakir R. , Duguid G. , Sandinha T. , Steel D. , Jackson T.L. 
Published: September 2017

PurposeThe purpose of this multicentre retrospective study was to investigate the characteristics and role of ethnicity and socioeconomic status amongst patients with idiopathic macular holes (IMH) and the surgical outcome.MethodsConsecutive patients undergoing primary IMH surgery at three vitreoretinal units in the UK (King's College Hospital, London, UK, Western Eye Hospital, London, UK, Sunderland Eye Infirmary, Sunderland, UK) between January 2007 and May 2017 were included. The main outcome measure was anatomical closure of IMH.ResultsTwo hundred and thirty three primary IMH surgeries were included. All patients underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. 69.10% of patients were European Caucasian, 6.44% were Asian, and 24.46% were Afro‐Caribbean. The mean base macular hole diameter (BD) was 475.5 mcm. Mean BD was 432.2 mcm in European Caucasian patients, 481.3 mcm in Asians (P=0.005), and 505.61 mcm in Afro‐Caribbeans (P=0.006). Regression analysis demonstrated that BD and Afro‐Caribbean ethnicity were independent significant risk factors for surgical failure. Those who have longer duration of symptoms (Afro‐Caribbeans) and leave in more deprived places (Afro‐Caribbeans) in England where found to have lower success rate on macular hole closure.ConclusionsAsian and Afro‐Caribbean patients present with larger IMH than European Caucasians. In addition to IMH base diameter, black origin and lower socioeconomic status are independent risk factors for surgical failure. This study presents a large population‐based data analysis on ethnic variation in macular holes and may assist in the management and predicting the surgical outcome.
Partial thickness Macular holes and pharmaceutical treatment of FTMH
Authors: Pournaras J.A. 
Published: September 2017

SummaryThe pathophysiology of full thickness macular hole and lamellar macular hole aredifferent and will be discussed. Oct characteristics will be repeated according to newclassification. Taking in account the natural history, indication of treatment will bedetailled according to each stage of those diseases. Recently, ocriplasmin has beenintroduced as an alternative treatment to vitrectomy. Favorable Prognostic factorshave been recognized as age inferior to 65 years old, full thickness macular hole < 400microns, the absence of epiretinal membrane, vitreous adhesion < 1500 microns andphakic status. While management of full thickness macular hole shows good visualprognosis for the patients, the visual result of lamelar macular hole is not so obvious.
What to do? Management recommendations
Authors: Damato E. M. 
Published: September 2017

SummaryPatients on targeted oncology treatments, such as MEK inhibitors, may develop visual symptoms and can present to either their oncologist, general ophthalmologist or retinal specialist. This talk aims to describe the ophthalmic findings and main differential diagnoses, and to provide an approach to the general investigation of such patients. The significance of ocular findings is highlighted and a stepwise management strategy suggested. Close collaboration between the oncologist and ophthalmologist is recommended in these cases, which are likely to become more common in the face of ongoing advancements in the field of oncology.
Proteomics as a tool for stem cell research in the anterior segment of eye
Authors: Mikhailova A. 
Published: September 2017

SummaryLimbal epithelial stem cells (LESCs) are essential for corneal transparency and normal vision, as they are responsible for renewing the corneal epithelium. Damage or loss of LESCs may cause the ocular surface to become opaque and vascularized. Patients suffering from such severe ocular surface disorders do not benefit from corneal transplantation alone, because it does not replace the damaged stem cells.LESCs derived from human pluripotent stem cells (hPSCs) offer a novel cell‐based approach for ocular surface reconstruction. However, critical evaluation of these cells is crucial before considering clinical applications. Proteomics can help verify the authenticity of hPSC‐derived cells on a large scale.This talk will discuss proteomics as a tool for stem cell research, focusing on the ocular surface. As an example, a study using proteomics to compare native corneal cells at different maturity levels and LESCs derived from hPSCs in feeder‐free and serum‐free conditions will be presented.
Mutation in the Crybb1 gene encoding beta‐B1‐crystallin leads to recessive cataracts in the mouse
Authors: Graw J. , Amarie O. , Kumar D. , Scheideler A. , Hrabé de Angelis M. , Przemeck G. , Sabrautzki S. 
Published: September 2017

PurposeCongenital cataracts are caused by mutations in various genes, and CRYBB1 is one of them. Aim of the study was to create a corresponding mouse model for a cataract‐causing mutation in Crybb1.MethodsThe ENU‐sperm archive of F1 mouse mutants (https://www.helmholtz-muenchen.de/ieg/services/scientific-resources/index.html) was searched for mutations in Crybb1. After selection of an appropriate mutation the corresponding mouse mutant was recovered after in‐vitro fertilization.ResultsWe recently identified a mutation in exon 6 of CRYBB1 (c.613delC; p.Q205Sfs4*) as causative for congenital dominant cataracts in an Indian family. Correspondingly, we established a mouse mutant line, which affects the exon 5 of the Crybb1 gene (c.500A–>T; p.D167V). The mouse mutation affects the 3rd Greek Key motif; correspondingly, the size of the alpha‐helical region and the size of several beta‐sheets might be modified in the mutant protein. PolyPhen‐2 predicted this mutation as “possibly damaging” with a score of 0.731. This mutation leads to a recessive form of cataracts with clear lenses in heterozygotes, although Crybb1 is expressed in mouse lenses from E12.5 onwards. Similar to other beta‐crystallins, Crybb1 is also expressed in the brain, which might lead to additional neuronal changes and might explain the involvement of Crybb1 in association with schizophrenia and stress (Spadaro PA et al., Biol. Psychiatr. 2015;78: 848‐859).ConclusionsIn humans, several cataract‐causing mutations have been identified ‐ most of them leading to dominant cataracts, and only a few of these mutations have been shown to cause a recessive way of inheritance. Here we present the first Crybb1 mouse mutant line suffering from a recessive congenital cataract.
Genetic evidence for the role of ultraviolet radiation in the pathogenesis of uveal melanoma
Authors: Goh A. , Ramlogan‐Steel C. , Jayachandran A. , Steel J. , Layton C. 
Published: September 2017

PurposeRecent advances in the understanding and treatments of metastatic cutaneous melanoma (CM) have not led to parallel improvements in the care of metastatic uveal melanoma (UM), and consequently, the two conditions are now often viewed as separate entities. One possible difference is the aetiological role of ultraviolet (UV) radiation, which although well‐established in CM, remains uncertain in UM. This study hypothesised that UV radiation is a pathogenic factor in UM development, evidenced by genetic changes consistent with UV‐related damage in UM.MethodsWe analysed data from 993 UM patient samples and 11803 CM patient samples available from the Catalogue of Somatic Mutations in Cancer (COSMIC) as well as 80 UM patient samples and 343 CM patient samples from the Broad Institute GDAC FireBrowse. UM samples were probed to identify the most frequently mutated genes, mutation types and specific nucleotide substitutions. Somatic mutation data was then cross‐correlated with CM samples from COSMIC and Broad Institute GDAC FireBrowse.ResultsThe most common overlapping mutated genes were BRAF, PTEN, CDKN2A, TERT, NRAS, TP53 and ARID2, with four shared point mutations in BRAF (V600E (1799T>A)), NRAS (Q61R (182A>G)) and TP53 (R273C (817C>T)), R248Q (743G>A)). These gene mutations were found to be strongly associated with UV‐related damage in previous scientific reports. The proportion of samples with C>T substitutions (a marker of UV‐related damage) were similar between UM and CM on both DNA strands (20.35% vs 20.05%) and coding strand (11.3% vs 15.7%).ConclusionsThese findings support the hypothesis that the pathogenesis of UM is more dependent on UV radiation than previously thought.
Retinectomy and silicone oil in PVR surgery‐pearls and tricks
Authors: Acar N. 
Published: September 2017

SummaryAppropriate surgical technique is the most important factor for the anatomical success in the management of retinal detachment (RD) with PVR. Retinectomies are frequently required in detached eyes complicated by severe PVR. Knowing when and how to perform a retinectomy is necessary for a vitreoretinal surgeon and this talk will cover important steps in this surgical maneuver.Silicone oil endotamponade is also frequently preferred in PVR surgery. How to handle silicone oil during injection and its removal is important to avoid its major complications. Pearls related to these steps as well as some important properties of silicone oils will be discussed in this talk.
Mosaicking the subbasal nerve plexus
Authors: Allgeier S. , Reichert K.M. , Stachs O. , Köhler B. 
Published: September 2017

SummaryCorneal confocal microscopy (CCM) has been established as a noninvasive, in vivo imaging technology that provides high‐resolution images of the corneal tissue layers at a cellular level. In particular, several research groups focus on the nerve fiber bundles constituting the subbasal nerve plexus (SNP). The ability to visualize ‐ and quantify ‐ morphological alterations of the SNP provides a new and potentially sensitive diagnostic approach for peripheral neuropathies, e.g. associated with diabetes. However, because of the small field of view of current CCM systems (approx. 0.16 mm²) and the locally inhomogeneous distribution of the subbasal nerve structures, a single image does not reliably reflect the condition of the SNP. To address this issue, we present a highly automated and integrated system that facilitates the imaging of an extended contiguous SNP area in a short recording time by guiding the gaze direction of the patient with a computer‐controlled moving fixation target. The system achieves growth rates of the scanned area of approximately 0.16 mm² per second. Following the image acquisition process, a high‐quality mosaic image of the scanned area is computed using specialized image processing software.
Cracking the nuclear‐mitochondrial code in Leber hereditary optic neuropathy
Authors: Carelli V. 
Published: September 2017

SummaryLeber hereditary optic neuropathy (LHON) is primarily determined by mtDNA pathogenic mutations affecting complex I that are necessary but not sufficient to express the disease. In fact, there remain incomplete penetrance and male prevalence for which it is assumed that further complex genetic, anatomical and environmental interactions are necessary to trigger the neurodegenerative process. On the genetic ground, besides the primary mtDNA mutations there are further determinants, like the mtDNA copy number and the mtDNA background variability (haplotype) that are certainly relevant. However, variability of the nuclear genome is also assumed to play a relevant modifying role. Currently, multi‐layered strategies are employed to crack this nuclear‐mitochondrial code to finally reach a complete understanding of the genetic basis of LHON. The combination of next generation sequencing approaches, expression and metabolic profiles, and functional studies of neuronal tissue generated from patient‐derived reprogrammed stem cells casts hope to shed light on the genetic basis and pathogenic mechanisms in LHON, ultimately leading to the development of targeted therapeutic strategies.
Antisense oligonucleotide therapy for splicing defects in OPA1‐related dominant optic atrophy
Authors: Wissinger B. , Synofzik M. , Schöls L. , Bonifert T. 
Published: September 2017

SummaryMutations in OPA1 are the main cause of dominant optic atrophy (DOA) and have also been implicated in a variety of syndromic neuropathies such as DOAplus or Behr‐like syndrome. We have recently discovered a disease‐causing deep intronic mutation (DIM) in OPA1 that induces a constitutive inclusion of a cryptic exon into OPA1 transcripts. As a potential therapeutic strategy we sought to correct mis‐splicing of the mutant pre‐mRNA by using antisense oligonucleotides targeting the cryptic acceptor splice site and the novel branch point created by the DIM, respectively. Transfection of patient‐derived primary dermal fibroblasts with AONs resulted in splice correction of the mutant pre‐mRNA in a time and concentration dependent manner. Maximal rescue efficacy of up ~55% was obtained with the cryptic acceptor splice site targeting AON. Peak efficacy of splice correction was observed at 4 days after treatment. However, significant effects were still seen 14 days post‐transfection in the proliferating cell culture. Western blot analysis revealed increased amounts of OPA1 protein with maximum amounts at ~3 days post‐treatment. In summary, we provide the first mutation‐specific rescue strategy for OPA1 deficiency using synthetic AONs.