bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline variants in the MBD4 gene are rare in patients with uveal melanoma
Authors: Repo Pauliina , Jäntti Johannes , Järvinen Reetta‐Stiina , Täll Martin , Raivio Virpi , Kivelä Tero , Turunen Joni 
Published: December 2019

AbstractPurposeThe mutation profile of uveal melanoma (UM) is unusual as these tumors generally have very few somatic events. Eight genes are recognized as drivers of UM tumorigenesis, typically consisting of one mutually exclusive mutation in GNAQ, GNA11, PLCB4 or CYSLTR2 combined with one mutually exclusive mutation in EIF1AX, SF3B1, SRSF2 or BAP1. Germline variants predisposing to UM have so far been described only in BAP1. Recently, four patients with UM were found with germline loss of function (LOF) variants in the methyl‐CpG binding domain 4 (MBD4) gene that was suggested to be a UM predisposition gene. Loss of functional MBD4 induces a hypermutated profile, making the tumor more susceptible to immune checkpoint inhibitors. We investigated MBD4 variants in patients with UM to identify pathogenic variants and to estimate their clinical relevance.MethodsSanger sequencing of MBD4 in 440 Finnish patients with uveal melanoma diagnosed from 2010 to 2017.ResultsEight rare (minor allele frequency in gnomAD Fin <0.5%) MBD4 missense variants were identified in 16 patients. One of them was likely pathogenic. The UM has not metastasized. The frequency of likely pathogenic MBD4 variants in Finnish patients with UM was 0.2% (95% CI, 0.01–1.3). No LOF variants were found. The frequency of LOF variants in the general population in Finland is 0.05%, according to the gnomAD database, suggesting one should occur by chance in every 2000 patients with UM.ConclusionsMBD4 variants do not seem to predispose to UM in Finland. Somatic loss of MBD4 function might still modify the tumor phenotype through accumulating mutations and changing the response of the tumor to immune checkpoint inhibitors. However, the utility of germline MBD4 sequencing is low.
Improvement and validation of high precision ocular oximetry using a convolutional neural network algorithm and a phantom eye
Authors: Desroches Joannie , DePaoli Damon , Lapointe Nicolas , Paulin Catherine , Tossou Prudencio , Sauvageau Patrick , Sauvageau Dominic , Côté Daniel 
Published: December 2019

AbstractRetinal oximetry is a non‐invasive imaging technology that enables the measurement of oxygen saturation (StO2) in the eye fundus. The goal of this research was to validate a convolutional neural network (CNN) algorithm designed to calculate and improve the precision of StO2 measurements from diffuse reflectance spectra (DRS) taken on the optic nerve head (ONH). Zilia’s multi‐wavelength retinal oximetry device was used to acquire experimental spectra from the ONH which allowed us to simulate reasonable digital spectra replicates with known absorber concentrations. These spectra were used to train a novel machine learning algorithm based on CNN. The device was then used to acquire diffuse reflectance spectra on several ONH‐mimicking liquid optical phantoms (phantom eye) with dynamic oxygenation cycles between 0% ‐ 100% in order to validate the improvements of this CNN on experimental data. Measurements were made simultaneously with gold standard devices for comparison. The procedure was then repeated with several cataract‐simulating contact lenses integrated in the optical path to show the robustness of oximetry measurements. We found good agreement in StO2 measurements between the results obtained with the Zilia device using the CNN algorithm and the gold standard references in all phantom cases. Applying the various algorithms to data acquired on the validation phantom show the marked improvements in using the CNN on experimental data, validating its high potential for clinical use. We specifically show strong robustness in precision, even when cataract‐simulating lenses were used. We present further validation that the oximetry device and CNN algorithm produces reliable, precise measurements even under conditions where blood volume fractions vary, optical scattering changes, and cataract‐simulating contact lenses are included.
Retinal thickness of the triple‐transgenic mice model of Alzheimer\’s disease at the age of one month
Authors: Bernardes Rui , Ferreira Hugo , Martins João , Moreira Paula I. , Castelo‐Branco Miguel , Ambrósio António F. , Serranho Pedro 
Published: December 2019

AbstractPurposeIn this work, we aimed to assess the difference in thickness of the retina of the triple‐transgenic mice model of Alzheimer’s disease (3xTg‐AD), compared to controls (wild‐type ‐ WT), at the age of one month.MethodsMice’s retinas were imaged by optical coherence tomography (OCT) using the Phoenix Micron IV OCT (Phoenix Research Labs, USA) to produce 512 B‐scans of 512 A‐scans each. All right eyes of 45 3xTg‐AD and 46 WT mice were imaged in vivo, and all scans were performed horizontally centred in the optic disc and vertically above it. All mice were weighted at the scan time. A software was developed to determine the inner limiting membrane and the photoreceptor‐retinal pigment epithelium interface, automatically, to produce a detailed thickness map of 512 × 512 values, later split into 3x3 regions. The average thickness of each region and the average of the entire imaged area were computed. All processing, software development and statistical analyses were performed using Matlab R2019a (The Mathworks Inc, USA).ResultsThe Kolmogorov‐Smirnov normality test was applied to all measures. Since the majority failed the normality assumption, the Mann‐Whitney test was used to determine differences between groups. No statistically significant differences were found between groups for the weight (p‐value=0.9536; m(sd): 14.84(2.71) grams for 3xTg‐AD and 14.88(2.58) grams for WT). A strong statistically significant difference (p‐value < 0.001) was found between the thickness of the retina of the two groups for all nine regions and the average retinal thickness, with the 3xTg‐AD mice presenting a thinner retina ‐ average values for the entire imaged area of 290.26(7.15) (m(sd)) microns compared to the WT (302.20(4.08)).ConclusionsThe 3xTg‐AD mice present a statistically thinner retina regarding the control group, at the age of one month, even though no statistically significant differences were found between groups for the weight.
Solo surgeon strabismus surgery technique
Authors: Feng Lo Phey , Lockwood Alastair , Evans Anthony , Thornton Richard , Townsend Dominic 
Published: December 2019

AbstractBackgroundStrabismus surgery is frequently undertaken solo without surgical assistants, requiring alternative methods for accurate muscle isolation and placement. We aim to describe a novel single surgeon technique during recti muscle surgery in the management of horizontal strabismus.MethodsAfter isolating the recti muscle on a hook, the muscle is secured with a double armed 6‐0 Vicryl (Ethicon) on a spatulated needle at the point of insertion. A partial thickness bite is taken at the muscle belly followed by two full thickness locking bites at the superior and inferior poles of the muscle. For recessions, the 6‐0 suture is placed behind the blades of the Cook speculum which acts to keep sutures away from the area and provides some traction opposite to that from the Moody forceps. This allows good visualisation and allows the surgeon to mark the suture placement site. Tucking the suture behind the Cook speculum also helps with resection but there is less of a traction element required here.ResultsThis technique has been proven to be effective in allowing the surgeon to operate without an assistant. There have been fewer lists cancellations due to absences and lack of an assistant. Furthermore postoperative results have been comparable to those operated with an assistant.ConclusionThe advantages of this technique are its ease of execution without having to rely on extra instrumentation. It allows the solo surgeon to operate without having to depend on an assistant thereby increasing efficiency and reducing waiting list times. It is also a very handy tip and easily taught to trainees.ReferenceWinter TW, Olson RJ et al. Resident and Fellow Participation in Strabismus Surgery: Effect of level of training and number of assistants on operative time and cost. (2014) Ophthalmology, 121(3), 797‐801.
Refractory atypical corneal lesions with or without extension onto the conjunctiva responding to Acanthamoeba treatment
Authors: Dubois Pauline , Weiss Azzam , Valyi Zsuzsanna , Le Aurelie , Bradly Kenza , Willermain François , Caspers Laure 
Published: December 2019

AbstractPurposeAcanthamoeba keratitis (AK) is a sight‐threatening infection classically linked to contact lens wear. Starting as a non‐specific unilateral epithelial irregularity like punctate or pseudo‐dendritic lesions, AK can evolve to a ring‐shaped stromal infiltrate with risk of corneal melting. Radial keratoneuritis may appear. Diagnosis relies on protozoan identification by culture with direct exam and PCR analysis. Acanthamoeba can also be demonstrated by in vivo confocal microscopy (IVCM). Early phase AK is treated with a combination of topical amoebicides. We report three atypical cases of suspected AK.MethodsRetrospective report of three women with unilateral atypical corneal lesions, two of them extending to the conjunctiva. Slit lamp photographs, corneal oct and confocal microscopy will be presented.ResultsThree patients, two women in their thirties and one in her sixties, consulted for chronic ocular discomfort unsuccessfully treated by topical antibiotics and corticosteroids for months to years. No history of contact lens wear or water exposure was reported. Two had visual acuity (VA) at 20/20 and one a variable VA for 4 years. Slit lamp examination showed an atypical superficial well delimitated linear lesion across cornea and conjunctiva. In all patients, successive examinations had revealed a moving and migrating character of the refractory lesions to topical antibiotics and corticosteroids. All had a rapid response to Polyhexamethylenebiguanide (PHMB) and propamidine (Brolene) and healed without stromal opacification in a few weeks. Although corneal scrapping cultures remained negative, two of them realized an IVCM with signs of AK and all responded rapidly and completely to amoebicide drops supporting the diagnosis of AK.ConclusionsThese cases show a particularly atypical involvement of corneal and conjunctival refractory lesions responding very well to PHMB and Brolene suggesting an AK origin.
Pupil irregularity after ultrasound ciliary plasty in glaucoma treatment
Authors: Bolek Bartlomiej , Wylegala Adam , Mazur Robert , Wylegala Edward 
Published: December 2019

AbstractPurposeThe aim of a study is to evaluate pupil irregularity eyes after transscleral Ultrasound Ciliary Plasty. How dimensions of the pupil are changing after UCP procedure.Setting/VenueClinical Department of Ophthalmology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland.MethodsTwenty two patients with primary and secondary refractory glaucoma were enrolled to ultrasound ciliary plasty procedure. The pupil size was measured at the widest dimension in which irregularity was observed. Measurements were performed before the procedure, 6 and 12 months after. Analyzed pupil parameter was obtained with SS OCT CASIA 2.ResultsPreliminary results reveal that there is no significant difference in pupil widest dimension after UCP procedure comparing size before (4.03 ± 0.56 mm), 6 months (4.15 ± 0.61 mm; p = 0.432) and 12 (4.02 ± 0.56 mm; p = 0.647 ) months after.ConclusionUCP seems to have influence on pupil size. However we are observing pupil irregularity few months after procedure, the results are not significant.
Histology of myopic posterior scleral staphylomas
Authors: Jonas Jost , Ohno‐Matsui Kyoko , Holbach Leonard , Panda‐Jonas Songhomitra 
Published: December 2019

AbstractPurposeSince histomorphometric descriptions of posterior scleral staphylomas, although forming a major part of myopic maculopathy, have been scarce so far, we histomorphometrically examined scleral staphylomas in enucleated human eyes.DesignHistomorphometric study.MethodsUsing light microscopy, we examined sagittal histological sections of human globes enucleated due to malignant choroidal melanomas or secondary angle‐closure glaucoma.ResultsOut of 246 globes included into the study, posterior scleral staphylomas were detected in 10 eyes (mean length: 31.4 ± 3.0 mm; range: 28.0–37.0 mm). In the staphylomatous region in the study group as compared with the corresponding region of a control group adjusted for age and axial length, scleral thickness was significantly lower (109 ± 25 µm versus 319 ± 161 µm; p = 0.001). The study group in the staphylomatous region as compared to the highly myopic control group in the corresponding region did not differ significantly in retinal pigment epithelium (RPE) cell density (19.6 ± 4.9 cells/300 µm versus 21.1 ± 5.7 cells/300 µm; p = 0.84) and RPE height (8.2 ± 3.0 µm versus 6.0 ± 2.5 µm; p = 0.11), Bruch´s membrane (BM) thickness (3.5 ± 1.1 µm versus 3.9 ± 2.1 µm; p = 0.63), and choriocapillaris thickness (5.0 ± 2.7 µm versus 4.1 ± 2.7 µm; p = 0.50) and density (164 ± 99 µm versus 226 ± 38 µm; p = 0.13). All staphylomatous regions showed a localized BM defect.ConclusionsMarked scleral thinning and spatially correlated BM defects histologically characterized myopic scleral staphylomas, while thickness and density of the choriocapillaris, RPE and BM did not differ significantly between staphylomatous versus non‐staphylomatous eyes in the respective regions. These findings support the notion that a locally reduced scleral resistance against a backward pushing BM led to a local scleral outpouching. The outpouching‐associated increase in curvature length may stretch BM with the sequel of a localized BM rupture
Choriocapillaris thickness and density in high myopia
Authors: Holbach Leonard , Jonas Jost , Panda‐Jonas Songhomitra 
Published: December 2019

AbstractPurposeMyopic axial elongation is associated with choroidal thinning in general. We examined whether the thickness of the choriocapillaris decreases in relationship to axial length.MethodsUsing light microscopy, we measured thickness and density of the choriocapillaris in various ocular regions on sagittal histological sections of human globes enucleated due to malignant choroidal melanomas or secondary angle‐closure glaucoma.ResultsThe study included 75 globes with a mean age of 62.6 ± 17.0 years (range: 24–88 years) and a mean axial length of 27.8 ± 3.8 mm (range: 22.0–37.0 mm). The choriocapillaris was significantly (p = 0.008) thicker at the posterior pole (6.8 ± 6.0 µm) than at the posterior pole‐equator midpoint (5.0 ± 3.8 µm), where it was thicker (p = 0.03) than at the equator (4.0 ± 3.4 µm), with no significant (p = 0.16) difference from there to the ora serrata (4.6 ± 3.8 µm). Choriocapillaris thickness was not significantly associated with axial length, neither at the posterior pole (p = 0.83), posterior pole‐equator midpoint (p = 0.79), equator (p = 0.99) or ora serrata (p = 0.18). Mean choriocapillaris density was 216 ± 56 µm/300 µm at the posterior pole, 193 ± 64 µm/300 µm at the posterior pole‐equator midpoint, 174 ± 73 µm/300 µm at the equator, and 196 ± 66 µm/300 µm close to the ora serrata. The difference in choriocapillaris density between the posterior pole and the equator was significant (p = 0.02). Choriocapillaris density was not significantly associated with axial length (posterior pole: p = 0.29; posterior pole‐equator midpoint: p = 0.68; equator: p = 0.76; ora serrata: p = 0.61). At the posterior pole, choriocapillaris density was associated with a higher RPE cell height (p = 0.02) and higher RPE cell density (p = 0.02).ConclusionsChoriocapillaris thickness and density, decreasing from the posterior pole to the fundus periphery, were not significantly associated with axial length. Higher choriocapillaris density was associated with higher RPE cell height and density. These findings may be of interest for the understanding of pathologic myopia.
Refraction in eyes filled with silicone oil
Authors: Kanclerz Piotr , Grzybowski Andrzej , Leisser Christoph , Lipowski Pawel 
Published: December 2019

AbstractPurposeCataract development is common in phakic eyes filled with silicone oil (SO), necessitating subsequent cataract removal. This study evaluated the refractive outcome in eyes filled with SO undergoing phacoemulsification cataract surgery (PCS).MethodologyThis retrospective study evaluated patients with SO tamponade who were scheduled for PCS.ResultsSubjects (n = 26) were followed‐up for 29.5 ± 13.9 months after cataract surgery. The median spherical equivalent refraction (SER) was +5.3 D (interquartile range [IQR] +2.9 to +6.7) before PCS, and +3.4 D (IQR +2.0 to +4.4) after PCS. Within the follow‐up period retinal reattachment after SO removal was achieved in 15 out of 26 eyes (57.7%). In 13 eyes assessment of refraction after SO‐removal was possible, and showed a myopic shift of −4.6 D (IQR −2.9 to −7.3) in the SER. After SO removal, five of 13 eyes (38.5%) were within ±1.0 D of the target refraction, while nine out of 13 eyes (69.2%) were within ±2.0 D.ConclusionThe refractive outcome after PCS for eyes filled with SO is less predictable than that for normal eyes. Optical biometry should be performed before vitrectomy with SO administration when possible. Some of the eyes undergoing silicone oil injection may require long‐term tamponade.
Transduction pattern of adeno‐associated viruses in the trabecular meshwork and anterior‐segment structures in a rat model of ocular hypertension
Authors: Lee Si Hyung , Woo Sang Earn , Park Tae Kwann 
Published: December 2019

AbstractPurposeTo investigate transduction patterns of self‐complimentary adeno‐associated virus (scAAV) serotype 2, 5, and 8 in trabecular meshwork (TM) and anterior segment structures of ocular hypertensive (OHT) rat models.MethodsWe assessed transduction efficiencies of scAAV 2, 5, and 8 in the anterior‐segment structures of the eyes of SD rats with OHT by circumlimbal suturing, followed by intracameral injection of scAAV2, 5, or 8 packaged with EGFP, and compared with the control. Expression level of receptors for scAAV2 (perlecan and syndecan), scAAV5 (2, 3‐linked sialic acid), and scAAV8 (67kDa laminin receptor) was analyzed by using immunohistochemistry and quantitative PCR.ResultsThe transduction of scAAV2 and 5 in the TM of OHT rats was markedly enhanced after 1 month, and transduction of scAAV5 was more efficient than that of scAAV2; transduction of scAAV8 into the TM did not occur. The transduction of scAAV2, 5, and 8 was enhanced in the ciliary body, iris, and corneal endothelium of the OHT eyes for 3 months. The expression levels of receptors for scAAV2 and scAAV5 were significantly increased in the OHT compared with control eyes.ConclusionsThe results showed that scAAV 2 and 5 effectively target the ciliary body and TM in OHT eyes, and OHT related changes in anterior segment structures enhance scAAV transduction.
The tear film cytokine profile is altered in congenital Aniridia
Authors: Sommer Landsend Erlend 
Published: December 2019

AbstractIncreased levels of inflammatory cytokines in the tear fluid have been found in patients with dry eye disease (DED). Dry eye disease is highly prevalent in congenital aniridia and correlates with severity of aniridia associated keratopathy (AAK). As inflammation can damage the corneal epithelium, DED may initiate and worsen AAK. Additionally, inflammation also characterizes AAK and might exacerbate DED, creating a vicious circle. We carried out an extensive analysis of inflammatory cytokines in the tear fluid of aniridia patients and control subjects. The results were correlated with several clinical parameters, including tests for DED and meibomian gland dysfunction (MGD). The concentration of a number of pro‐inflammatory cytokines was significantly elevated in tear fluid from aniridia patients. Increasing level of these cytokines was related to parameters for MGD, including atrophy of meibomian glands, and shorter break‐up time of the tear film. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients and explain the high prevalence of MGD and DED in these patients.
New insights in the genetic and pathophysiology of dominant optic atrophy
Authors: Lenaers Guy 
Published: December 2019

AbstractInherited Optic Neuropathies are blinding diseases related to mitochondrial dysfunctions in retinal ganglion cell (RGC). There are two main forms: the Leber Hereditary Optic Neuropathy (LHON) related to mutations in the mitochondrial genome, and the Kjer dominant optic atrophy (DOA) related to mutations in nuclear genes. Since the initial discovery of the OPA1 gene as the major gene causing DOA, the use of NGS disclosed many novel genes responsible for DOA. Beyond the genes recently identified involved in mitochondrial dynamics, we identified novel genes involved in other mitochondrial functions that are crucial for RGC physiology. We report here the pathophysiological analyses of their involvement in mitochondrial physiology and metabolism. These data are shedding novel lights on DOA pathophysiology, beyond mitochondrial dynamics, as novel culprit mechanisms responsible for RGC degeneration, which will condition the design of future therapeutic approaches.
Chromatin dynamics, DNA‐binding transcription factors and lens differentiation
Authors: Cvekl Ales 
Published: December 2019

AbstractPurposeLens differentiation is an advantageous model to study how chromatin structure and dynamics (“open” and “closed” chromatin) regulates gene expression of both regulatory factors and proteins needed for intricate lens fiber cell structure and function. Our purpose was to map and explain dynamic changes in local chromatin structure of genes during lens differentiation at genome‐wide level.MethodsATAC‐seq experiments were conducted using epithelia and fibers from E14.5 and newborn (P0.5) mouse lenses. RNA‐seq data from similar samples were included in the analysis.ResultsOpen chromatin changes were defined through identification of differentially accessible regions coupled with differential gene expression during lens differentiation. Lens‐specific regulatory regions are shown using ES cells, forebrain, and liver. Two pathways were identified: epiE14.5 → fibE14.5 → fibP0.5 (path1) and epiE14.5 → epiP0.5 (path2). Unbiased cis‐motif analysis of “open” regions corresponding to promoters and enhancers revealed the cis‐regulatory principles of lens differentiation via known (e.g. AP‐1, Ets, Hsf4, Maf, and Pax6) and novel (e.g. CTCF, Tead, and NF1) motifs.ConclusionsThe current data support a general model of dynamic changes in open chromatin associated with transcriptional activities of functionally related genes that required for lens fiber cell differentiation and epithelial maturation. Together, the data pave the road for detailed studies of lens‐specific enhancers, identification of gene regulatory networks underlying lens morphogenesis, and identification of cataract‐causing mutation in non‐coding regulatory sequences.