bluuebunny/crossref_metadata_2025_split huggingface dataset:
BAP1 germline mutations in uveal melanoma patients without family history of eye cancer
Authors: Turunen J. , Markkinen S. , Wilska R. , Raivio V. , Täll M. , Lehesjoki A.E. , Kivelä T. 
Published: September 2016

PurposeGermline pathogenic variants of the BRCA‐1 associated protein‐1 (BAP1) gene predispose to uveal melanoma and several other cancers. Testing for germline BAP1 mutations should be performed if typical BAP1 cancer predisposition syndrome tumors have been diagnosed in the family. We report the frequency of germline pathogenic variants of BAP1 in consecutive Finnish uveal melanoma patients without known history of eye cancer.MethodsIn Finland, uveal melanomas are treated centrally in the Ocular Oncology Service, Helsinki University Hospital. We collected clinical data and genomic DNA from 239 of 389 consecutive patients diagnosed from January 2010 to December 2015. Patients with verified family history of eye cancer were excluded. Fifteen patients had died before the study started and could not be sampled. The exons and exon‐intron junctions of BAP1 were sequenced.ResultsWe found only one probable pathogenic germline variant, a donor splice site mutation in a highly conserved region immediately after exon 2 in a 57‐year‐old male patient. Three of his family members had been diagnosed with typical BAP1‐related cancers (cutaneous melanoma, mesothelioma, and renal cell carcinoma). The mutation was not found in 61,486 controls from the ExAC (http://exac.broadinstitute.org). The frequency of germline BAP1 mutation in patients without any family history of eye cancer was 0.4% (1/239, 95% CI 0.01 to 2.2).ConclusionsThe frequency of BAP1 germline pathogenic variants in the Finnish patients with uveal melanoma without family history of ocular cancer is low. The family history of typical BAP1‐related cancers was informative, and should routinely be obtained to guide the BAP1 genetic testing.
Diagnosis and management of cytomegalovirus anterior uveitis/endothelitis in immunocompetent patients in 2 European referral centers
Authors: Antoun J. , Caspers L. , Groot‐Mijnes J. , Motulsky E. , Dam‐van Loon N.H.T. , Makhoul D. , Willermain F. , Judice Relvas L. 
Published: September 2016

PurposeTo evaluate the methods leading to the diagnosis of CMV anterior uveitis (AU) and/or endotheliitis from 2 uveitis tertiary referrals centers and to assess the outcome after topical ganciclovir treatment.MethodsRetrospective study of patients with a clinical and biological diagnosis of CMV AU/endothelitis demonstrated by a positive polymerase chain reaction (PCR) and/or Goldmann‐Witmer coefficient (GWc). The Belgian patients were treated with topical ganciclovir once the biological diagnosis was confirmed. The number of recurrences was evaluated in the pre‐ and post‐treatment period.ResultsWe report a series of 21 patients (15 from Brussels and 6 from Utrecht) presenting clinical characteristics of CMV AU and/or endothelitis with a positive PCR and/or GWc for CMV. PCR was positive in 15/21 (71.4%) patients, while GWc was positive in 8/9 (88.9%), including 6 patients initially tested for PCR and GWc and 3 secondary tested for GWc when the PCR was negative. 2/9 patients (22.2%) were GWc+/PCR+, 6/9 patients (66.7%) GWc+/PCR‐ and 1/9 patient was GWc‐/PCR+ (11.1%). Aqueous tap was repeated in 9 of the 15 Belgian patients (60%) (2 times in 6 cases, 3 times in 3 cases) to get the biological confirmation of CMV AU/endothelitis. Mean follow up duration was respectively 19.2 ± 23.8 and 46.7 ± 29.7 months in the pre‐ and post‐treatment period. Patients had a significantly lower number of recurrences/year post‐treatment (0.76 ± 0.57) than in the pre‐treatment period (3.76 ± 2.44) (p = 0.001).ConclusionsRepeated aqueous taps in order to perform PCR and GWc were found to be helpful to confirm biologically the clinical diagnosis of CMV AU/ endothelitis. Our results also suggest that patients with topical ganciclovir have a decreased frequency of CMV‐AU/endotheliitis recurrence and keep a relatively good vision over time.
The αA‐crystallin gene expression in differentiating lens fiber cells, FGF signaling, and transcriptional factories
Authors: Cvekl A. , Limi S. , Zhao Y. , McGreal R. , Xie Q. , Zheng D. 
Published: September 2016

PurposeEmbryonic lens development requires intricate temporal and spatial control of gene expression that is executed through specific gene regulatory networks regulated by FGF signaling. The αA‐crystallin is the most abundant mammalian lens protein; transcriptional studies of this gene provide detailed insights into the molecular mechanisms governing lens fiber cell differentiation.MethodsDynamic changes in chromatin structure and gene expression during lens developments were evaluated by a combination of RNA‐seq and ATAC‐seq. Expression of αA‐crystallin (ch1) and other crystallins (Cryga, Crybb1, and Crybb3, localized on chromosomes 1 and 5, respectively) in individual nuclei of the developing mouse lens were analyzed by RNA‐FISH. Transgenic mice with c‐Maf promoter were generated and expression of EGFP was evaluated in mouse embryos. Localization of c‐Jun, c‐Maf, Etv5/ERM, and Pax6 was determined by ChIP using the c‐Maf and Cryaa loci and mouse lens chromatin. Co‐transfection experiments with c‐Jun and Etv5 were conducted using c‐Maf and αA‐crystallin reporters.ResultsTranscriptional factories, a subset of topologically associating domains (TADs), are formed between different crystallin loci in lens cell nuclei. These specific TADs are enriched by RNA polymerase II and other proteins. Novel FGF2‐responsive region in the c‐Maf promoter was found. Both c‐Maf and Cryaa regulatory regions contain arrays of AP‐1 and Ets‐binding sites determined by ChIP assays.ConclusionsCollectively, these studies show that the lens fiber cell nuclei spatially organize crystallin loci into TADs, and that FGF signaling up‐regulates expression of αA‐crystallin both directly and indirectly via up‐regulation of c‐Maf. These molecular mechanisms are applicable for other crystallins and genes highly expressed in terminally differentiating lens fibers.
Clinical and radiological evidence of meningioma growth due to gestational or exogenous hormones: 2 cases
Authors: Marcelis W. , Sys C. , Acou M. , Leroy B.P. , Kestelyn P. , De Schryver I. 
Published: September 2016

PurposeWe report 2 cases with documented hormonal growth of meningiomas, one probably caused by exogenous hormonal therapy, one by pregnancy‐related hormonal changes.MethodsObservational report about 2 cases with either reproductive or exogenous hormonal growth of meningioma. Both patients underwent a full ophthalmological work up, including MRI‐volumetry.ResultsA 42 year‐old man presented with unilateral blindness. Examination showed no light perception in the left eye. MRI of the brain revealed 11 meningiomas, with a large one compressing the optic nerve of the left eye. He had been treated for 23 years with cyproterone acetate (CPA) 100 mg/day to reduce his undesirable sexual behavior. CPA treatment was stopped immediately, resulting in a decrease of volume of the large meningioma of 250 cc.A 33 year‐old woman was referred because of blurred vision, migraine with hemiparesis and aphasia following a twin pregnancy. The left eye showed papillary oedema. The right eye was blind due to an unknown cause at the age of 7. MRI at that time was negative. She had just delivered twins after a 3rd pregnancy over only 2 years. MRI showed large meningiomas in the left optic canal. Since they were inoperable, a shunt to release intracranial pressure was placed. The papillary edema resolved and the volume of the meningiomas decreased.ConclusionsTwo unrelated cases of hormone‐induced growth of meningiomas are described. Hormone withdrawal results in a decrease of meningioma volumes. These findings illustrate the role of female sex hormones in the development and growth of meningiomas.
Normal values for fundus perimetry with the MAIA microperimeter and short‐term repeatability evaluation
Authors: Baudin F. , Assad G. , Meillon C. , Koehrer P. , Bron A. , Creuzot C. 
Published: September 2016

PurposeTo assess retinal sensitivity by means of microperimetry and to evaluate the intersession fluctuation using the MAIA microperimeter in healthy volunteers.MethodsProspective, monocentre study. Fifty‐six healthy volunteers (age range, 20–80 years), underwent an automatic, full‐threshold microperimetry of the central field (custom grid, area of 10° in diameter, 37 stimulated points), with the MAIA microperimeter (CenterVue, Padova, Italy). A subgroup of 24 subjects was retested after 1 h (test 2) and 1 week (test 3) to determine the repeatability of the technique. A subgroup of 22 subjects was also tested on the OPKO microperimeter (Optos, Dunfermline, Scotland) (area of 10° in diameter, 28 stimulated points).ResultsMedian age was 30 years [25.3–47.8]. The overall mean sensitivity for test 1 was 29.4 ± 1.4 dB, 29.8 ± 1.0 dB for test 2 and 29.9 ± 1.1 dB for test 3, respectively. Linear regression analysis showed a significant 0.5 dB sensitivity loss for each decade of life (r² = 0.27). In a subset of 24 subjects, the repeatability of the test performed at 3 separate visits showed a statistically significant difference between test 1 and 3 (p < 0.004). Test 2 and 3 showed consistent values over time (p = 0.160). Furthermore, the MAIA showed higher threshold values than the OPKO for all test locations. Linear regression of the perimetric results showed significant correlation between the 2 machines (r = 0.44; p < 0.001).ConclusionsThis study found an age‐related macular sensitivity loss. These findings are in agreement with previous data obtained with the MP1 and the OPKO microperimeters. The increase in sensitivity between test 1 and test 2 and 3 should be taken into account in clinical practice. Automatic fundus perimetry with the MAIA microperimeter allows for accurate, repeatable examination, if a training session is performed.
Licence to save – a UK survey of anti‐VEGF use for the eye in 2015
Authors: Shalaby A. , Lockwood A. , Bush A. , Lewis K. , Di Simplicio S. , Meredith P. 
Published: September 2016

PurposeThe difference in cost of Anti‐vascular endothelial growth factor (anti‐VEGF) injections is significant. Prices, according to the British National Formulary (BNF), are: ranibizumab; £742 per single injection vial, aflibercept; £816 per single injection vial, and bevacizumab £242.66, but in standard practice each vial is divided into 20 injections, giving a price of £12.13 per injection. Because patients require repeated injections these costs are multiplied many times over.We hypothesised the majority of injections would be with the less expensive drug, bevacizumab. We therefore performed a survey of all United Kingdom (UK) NHS ophthalmological units.MethodsA freedom of information (FOI) request was submitted to all UK NHS Trusts and Health Boards requesting the number and cost of intravitreal injections of ranibizumab, aflibercept, and bevacizumab prescribed during the month of January 2015. Non‐NHS units were excluded.Costs per month were determined by multiplying injection numbers with BNF (British National Formulary) prices and then by 12 for yearly costs.ResultsA total of 189 FOI requests were sent. The overall response rate was 95.8%.Ranibizumab was used 30,634 times (61%), Aflibercept 18,095 (36%) and Avastin was only 1410 (3%).Costs per month were: £27,276,514 for Ranibizumab, £17,683,373 for Aflibercept, £20,530 for Bevacizumab.Total monthly costs were: £44,980,416.00. Estimated annual costs were: £539,764,992.00.ConclusionsThese results show the anti‐VEGF injection cost to the NHS. Contrary to hypothesis the vast majority (97%) were still with the more expensive drugs ranibizumab and aflibercept. If all injections used divided bevacizumab, the estimated drug cost would be £607,749 (£729,500 incl. VAT) saving the NHS £449,196,354 (£539,035,492 incl. VAT) per year. With 5% remaining unaccounted for the savings may be greater.
Visual dysfunction and its correlation with retinal changes in patients with Parkinson disease
Authors: Vilades E. , Garcia‐Martin E. , Satue M. , Rodrigo M.J. , Obis J. , Cipres Alastuey M. 
Published: September 2016

PurposeTo evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Parkinson disease (PD).MethodsPatients with PD (n = 37) and controls (n = 37) underwent visual acuity (VA), color vision (using the Farnsworth and L'Anthony desaturated D15 color tests), and contrast sensitivity vision (CSV; using the Pelli Robson chart and CSV 1000E test) evaluation to measure visual dysfunction. Structural measurements of the retinal nerve fiber layer (RNFL), and macular and ganglion cell layer (GCL) thicknesses were obtained using spectral domain optical coherence tomography (SD‐OCT). Comparison of obtained data and correlation analysis between functional and structural results were performed.ResultsVA (in all different contrast levels) and all CSV spatial frequencies were significantly worse in PD patients than in controls (p < 0.05). Color vision was significantly affected (p < 0.05) based on the L'Anthony color test. Macular thinning was detected in the central, outer (inferior and temporal), and superior (inner and outer) sectors (p < 0.05), and the RNFL had significant thinning in the temporal quadrant (p < 0.05). Significant GCL loss was observed in the superior and superonasal sectors and the minimum GCL + inner plexiform layer (p < 0.05). CSV was the functional parameter most strongly correlated with structural measurements in PD. Color vision was associated with most GCL measurements. Macular thickness was strongly correlated with macular volume and functional parameters (r > 0.70, p < 0.05).ConclusionsPatients with PD had visual dysfunction that correlated with structural changes evaluated by SD‐OCT. Macular and GCL measurements may be reliable indicators of visual impairment in PD patients.
Changes in choroidal thickness after ranibizumab and aflibercept Therapy for treatment‐naïve wet age‐related macular degeneration
Authors: Kang H.G. , Kim J.S. , Lee J.H. , Kim Y.I. , Lee S.H. 
Published: September 2016

PurposeTo compare the changes in subfoveal choroidal thickness between ranibizumab and aflibercept therapy for treatment‐naive wet age‐ related macular degeneration.MethodsThis retrospective, observational study included 47 eyes of treatment‐naive wet age‐related macular degeneration patients who were followed up for at least 6 months after initial injection. All eyes were treated with 3 consecutive monthly injection of ranibizumab or aflibercpt, and treated with PRN injection of anti‐vascular endothelial growth factor after 3 consecutive monthly injection. Subfoval choroidal thickness was measured using enhanced depth imaging optical chorence tomography.ResultsIn the ranibizumab injected group (25 eyes), mean changes in choroidal thickness was −9.80, −16.86, −25.08, −10.40 μm at 1, 2, 3, 6 months after initial injection respectively. In the aflibercept injection group (22 eyes), mean changes in choroidal thickness was −24.30, −32.73, −37. 52, −15.77 μm at 1, 2, 3, 6 months after initial injection respectively. The mean changes in subfoveal choroidal thickness was significantly greater in the aflibercept injected group (p < 0.05) at 1 month, but there was no significant difference between two group at 2, 3, and 6 months after initial injection (p > 0.05).ConclusionsSubfoveal choroidal thickness was decreased after ranibizumab and aflibercept therapy. The mean changes in subfoveal choroidal thickenss was greater in aflibercept injected group at 1 month, but there was no significant difference between two therapy at 2, 3, and 6 months after initial injection.
Clinical features of cataract extraction with negative power intraocular lens implantation in high myopia patients
Authors: Choi J.B. , Shin W.B. , Kim M.K. 
Published: September 2016

PurposeTo evaluate the clinical features of high myopic eyes with cataracts implanted with negative power intraocular lenses (IOLs) at the time of cataract surgery.MethodsA retrospective chart review was conducted of 18 eyes of 14 patients who underwent cataract surgery with negative power IOLs and 10 eyes in 9 patients with low power IOLs. We investigated axial length, IOL power, preoperative and postoperative best‐corrected visual acuity (BCVA) and preoperative and postoperative spherical equivalent (SE) refractive errors.ResultsMean BCVA showed significant improvement in both groups. We measured postoperative SE refraction and the difference between the mean intended and the mean achieved SE refractive errors in the negative power group (17 eyes) was +1.59 ± 1.34 D and +0.31 ± 0.50 D in the low power group.ConclusionsBCVA was significantly improved in the majority of eyes, although they had myopic macular degeneration or posterior staphyloma. However, the mean achieved postoperative SE refraction was more hyperopic than the predicted postoperative SE error. Additionally, hyperopic refractive error was greater in the negative power group than the low power group. Therefore, we recommend that postoperative hyperopic refractive error should be considered when performing cataract surgery in high myopic patients.
Validation of the STARS risk assessment tool for age‐related macular degeneration in an Algerian population
Authors: Delcourt C. , Lazreg S. , Sanchez A. , Bandello F. , Nouri M.T. 
Published: September 2016

PurposeA risk assessment tool for age‐related macular degeneration (AMD) has been previously developed and validated in two European countries (Italy, France). The objective of the present study was to validate its use in an Algerian population.MethodsThe STARS (Simplified Théa AMD Risk‐assessment Scale) questionnaire is a simple 13‐item, self‐administered questionnaire, including questions on socio‐demographic characteristics, family history of AMD, systemic and ocular risk factors. We included 1,183 patients over 55 years of age from 23 Algerian ophthalmologists. Patients completed the questionnaire, and ophthalmologists performed a fundus examination for AMD diagnosis (early AMD if soft drusen and/or pigmentary abnormalities; late AMD if atrophic and/or neovascular AMD). The validity of the final score was determined using ROC curves and Hosmer and Lemeshow testing. Patients were classified as low (score 0–9), moderate (10–19) or high risk (scores of 20+).ResultsComplete data was obtained for 942 (79.6%) patients, among whom 53 (5.6%) had late AMD and 288 (24.1%) had early AMD. The area under the ROC curve was 0.80, indicating good discrimination. The Hosmer and Lemeshow test was not statistically significant (p = 0.60), showing a good adaptation of the model to the data. Only 26 of the 662 (3.9%) patients without AMD were categorized as high risk and only 8 of the 53 patients (15%) with late AMD were categorized as low risk.ConclusionsThis study confirmed the validity of this short risk assessment tool, which shows good discrimination and high feasibility also in a North‐African country. Early diagnosis of AMD is key to improve disease outcomes in patients. STARS is a promising questionnaire that allows early, simple and fast identification of patients at risk of AMD.
UM Cure 2020 – A consortium of European experts in uveal melanoma to identify new therapies for patients with metastatic disease
Authors: Coupland S. , Kalirai H. , Jager M. , Jochemsen A.G. , van der Velden P.A. , Snaar‐Jagalska B.E. , Dhomen N. , Marais R. , Romanowska Dixon B. , Elas M. , Mione M.C. , Valente A. , Ryll B. , Ruijtenbeek R. , Prestat A. , Hafsi H. , Barnhill R. , Cassoux N. , Decaudin D. , Lantz O. , Piperno‐Neumann S. , Stern M.H. , Roman‐Roman S. 
Published: September 2016

PurposeUveal melanoma (UM) is a rare intraocular tumour with an incidence of 5 cases per million individuals per year. Up to 30% of UM patients develop metastases, most often in the liver, and there is no therapy to either prevent or treat these metastases. Despite new discoveries in the genetic and molecular background of the primary tumour, little is known about the metastatic disease.In UM Cure 2020, funded by European Union's Horizon 2020 programme, we will identify and validate at the preclinical level novel therapeutic approaches for the treatment of UM metastases (www.umcure2020.org). The Consortium brings together major EU experts in clinical, translational and basic research on UM, as well as patient representatives and innovative biotech companies.MethodsAn ambitious multidisciplinary approach is proposed to move from patient tissue characterisation to preclinical evaluation of single or combinations of drugs. We will characterise the genetic landscape of metastatic UM and its microenvironment, perform proteomic studies to address signalling pathway deregulation and establish novel relevant in vitro and in vivo UM models. Underpinning this will be our virtual sample registry, linking existing biobanks into a harmonised network, which will prospectively collect primary and metastatic UM samples.ResultsIn parallel, we are already evaluating in the first phase of the project the efficacy of a series of active compounds using partners’ available models. In addition to the initiation of UM‐dedicated clinical trials, dissemination of results includes initiatives to increase patient information and disease awareness, in particular by supporting the formation of a European UM patient network.ConclusionsThe UM Cure 2020 Consortium holds great potential to make significant advances in the treatment of metastatic UM, at present an incurable disease.
Spectral domain optical coherence tomography for detecting retinal arterial macroaneurysm
Authors: Ascaso F.J. , Berniolles J. , Bartolomé I. , Martínez M. , Esteban O. , Sánchez I. , Almenara C. , Del Buey M.A. 
Published: September 2016

PurposeRetinal arterial macroaneurysm (RAM) is an acquired sacular dilatation of a retinal arterial vessel. It is commonly associated with systemic arterial hypertension, vascular disease and women. It often appears in the sixth decade of life or older. RAMs are usually classified into three forms: quiescent, hemorrhagic and exudative. The first of them are asymptomatic, the exudative form courses with loss of visual acuity and the hemorrhagic form is responsible of hemathomas (either subretinal, intraretinal, retrohyaloid or intravitreal). The aim of this study was to describe retinal structural changes and tomographic features associated with RAM.MethodsA case report of an otherwise healthy middle aged man who was diagnosed with a RAM in his right eye and who underwent Heidelberg spectral‐domain optical coherence tomography (SD‐OCT).ResultsSD‐OCT was able to demonstrate and measure the RAM and the upstream/downstream vessel. Likewise, it showed other related OCT changes in the adjacent retina such as the presence of subretinal fluid and macular edema.ConclusionsSD‐OCT is an effective tool for detecting retinal macroaneurysms. It also provides important supplementary clinical information that may be helpful in planning the management of macroaneurysm, without the need for ancillary tests.