bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential retinal causes: when and how to investigate
Authors: Leroy B.P. 
Published: September 2015

SummaryPurposeTo describe the retinal conditions that need to be excluded when non‐organic visual loss is suspected, and the investigations required to either confirm or exclude them.MethodsA case presentation format will be used to illustrate those conditions which can be discovered using psychophysical and electrophysiological tests as well as special imaging including blue and near‐infrared autofluorescence and reflectance imaging and spectral‐domain optical coherence tomography, in patients in whom a non‐organic origin for visual loss is initially suspected.ResultsInherited retinal diseases such as Stargardt macular dystrophy, X‐linked retinoschisis and cone dystrophy as well as Batten disease in their early stages all need to be excluded when visual loss is thought to be non‐organic. In addition, several acquired retinal conditions such as acute acular neuroretinopathy need to be taken into account. Visual field testing, ISCEV‐standard full‐field flash electroretinography, pattern electroretinography and visual evoked potentials and specialised imaging techniques contribute significantly to making the correct diagnosis.ConclusionsVisual loss in a list of organic conditions may mimic non‐organic visual loss. Functional testing as well as specialised imaging techniques are essential in differentiating true organic from non‐organic visual loss.
A novel method for measuring outcome of orbital decompression in Graves’ orbitopathy
Authors: Baldeschi L. 
Published: September 2015

SummaryTo evaluate the outcome of a graded bone removal rehabilitative infero‐medial orbital decompression in Graves’ orbitopathy (GO) by means of a novel stratified appraisal (NSA) versus the traditional group analysis (TGA). This retrospective follow‐up study included all the orbits decompressed (06/1999–12/2005), at the Department of Ophthalmology University of Amsterdam by one surgeon (L.B.), using the technique under evaluation. NSA assessed or quantified: (i) the invasiveness of surgery, allowing to calculate a mean index of invasiveness per orbit (MIIO) and per patient (MIIP) (25% ≤ values ≤ 100%); (ii) at ≥ 6 months postoperatively surgical targets (desired exophthalmos reduction, improvement of retroocular tension, reduction of peri‐orbital puffiness, resolution of lagophthalmos) were scored as achieved or not allowing to calculate a mean index of targets achieved per orbit (MITAO) and per patient (MITAP) (0 ≤ values ≤ 1); (iii) an index of diplopia (ID) (decompression‐induced / decompressio‐cured diplopia); (iv) demographics and preoperative characteristics were compared after stratification of the included orbits for surgical target; surgical outcomes were assessed after stratification for amount of desired exophthalmos reduction and invasiveness of surgery. TGA examined the entire series as a single homogeneous cohort independently of the different targets and invasiveness of surgery. NSA and TGA were compared and complications noted. 151 orbits of 84 patients (78% female, mean age 45.5 ± 9.7 years) were included. The NSA detected differences among groups within the studied cohort, the overall achievement of surgical targets was high, indices precisely quantified the extent of applied surgery and surgical results, at variance with results obtained with TGA. A negligible complication rate was recorded. The NSA may represent a step forward towards a more comprehensive and accurate evaluation of decompression surgery outcomes.
Orbital implantation of biocompatible magnets for the treatment of intractable nystagmus
Authors: Verity D.H. , Kennard C. , Pankhurst Q. , Geoffrey E.R. 
Published: September 2015

SummaryIntractable acquired nystagmus causes debilitating symptoms and medical and surgical treatment is typically unsatisfactory. We describe a pilot study in which pairs of custom‐designed titanium‐encased magnets were sequentially implanted in an adult male patient with recalcitrant vertical nystagmus to achieve a reversible dampening of the nystagmus in the primary position. Under general anaesthesia, one magnet was sutured within the inferior retractor sheath, and, with the globe in the primary position, the fellow magnet was secured to the orbital floor with histoacryl glue, thereby dampening the nystagmus. The procedure was repeated on the fellow orbit several weeks later. This pilot study on a single patient was completed without complication, and has achieved a dramatic improvement in objective and subjective visual functions, including the spatial distribution of eye position during fixation in the primary position, together with a marked subjective improvement in quality of life. NIHR funding has been secured to extend this study to a larger cohort of patients to determine the extent and duration of this dampening effect in a larger cohort of patients.
Consecutive esotropia in contralateral recess‐resect for recurrent intermittent exotropia after unilateral recess‐resect
Authors: Cho S.Y. , Lee S.Y. 
Published: September 2015

PurposeTo report consecutive esotropia in contralateral recess‐resect for recurrent intermittent exotropia after unilateral recess‐resect. To evaluate the surgical outcome of ‘modified contralateral recess‐resect’ for intermittent exotropia after unilateral recess‐resect.Methods36 subjects were included in this retrospective study. All underwent, as a primary surgery for intermittent exotropia, unilateral recess‐resect on the non‐dominant eye. They were assigned to the subsequent contralateral recess‐resect(CRR, n = 19, surgical dosages based on Wright's surgical table) or modified contralateral recess‐resect (MRR, n = 17, surgical dosages 5Δ reduced on Wright's surgical table) for recurrent exotropia. Surgical success rate was evaluated. Re‐operation rate or prism glasses prescription rate due to consecutive esotropia was evaluated.ResultsThe mean follow‐up duration after the reoperation was 25.8 months in CRR group and 24.0 months in MRR group. Surgical success rate was 47.4% in CRR group and 76.5% in MRR group (p = 0.078). Recurrence rate was 0% in CRR group and 17.6% in MRR group (p = 0.059). Re‐operation rate or prism glasses prescription rate due to consecutive esotropia was 52.6% in CRR group and 5.9% in MRR group (p = 0.003).ConclusionsFinal outcomes were better in MRR group than in CRR group. Consecutive esotropia was significantly more frequent in CRR group than in MRR group. To reduce consecutive esotropia in surgery for recurrent exotropia, MRR is recommended.
MicroRNA‐124 regulates transforming growth factor β1‐induced epithelial‐mesenchymal transition in the retinal pigment epithelium by Down‐regulating expression of the RhoG
Authors: Jun J.H. , Joo C.K. 
Published: September 2015

PurposeMicroRNA‐124 (miR‐124) is thought to be involved in the epithelial‐mesenchymal transition (EMT) of retinal pigment epithelium (RPE). In the present study, we investigated the regulation of miR‐124 on EMT induced by transforming growth factor β1 (TGF‐β1) in human RPE cells (APRE‐19).MethodsThe expression of miR‐124 was evaluated after treatment of TGF‐β1 by quantitative RT‐PCR. Phenotypic alterations were analyzed by western blot analysis and immunocytochemical staining. Target validation was performed to identify the putative target of miR‐124 by luciferase reporter assay.ResultsThe expression level of microRNA‐124 (miR‐124) was down‐regulated during the progression of EMT. Overexpression of miR‐124 upregulated the levels of zonular occludens 1 and RPE65, and down‐regulated fibronectin, α‐smooth muscle actin, and vimentin. Furthermore, inhibition of endogenous miR‐124 increased and decreased the levels of mesenchymal and epithelial factors, respectively. TargetScan predicted two well‐conserved and two vertebrate‐only conserved miR‐124 target sequences in the 3′ untranslated region (UTR) of the RHOG mRNA. Direct targeting of this 3′ UTR by miR‐124 was demonstrated using a luciferase assay. Silencing of RHOG using a specific siRNA had identical effects on EMT regulation. Overexpression of miR‐124 repressed TGF‐β1‐induced RPE cell‐collagen gel lattice contraction by altering cell spreading/cell‐to‐cell adhesion.ConclusionsThis study describes the regulation of EMT in RPE cells by TGF‐β1/miR‐124/RHOG signaling and suggests that the supplement of miR‐124 expression would be a crucial therapeutic target for the prevention or treatment of proliferative vitreoretinopathy.
Myofibroblasts in proliferative diabetic retinopathy can originate from infiltrating fibrocytes and through endothelial‐to‐mesenchymal transition (EndoMT)
Authors: Abu El Asrar A. , De Hertogh G. , van den Eynde K. , Alam K. , Van Raemdonck K. , Opdenakker G. , Van Damme J. , Geboes K. , Struyf S. 
Published: September 2015

PurposeThe fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endothelial cells via endothelial‐to‐mesenchymal transition (EndoMT) and/or bone marrow‐derived circulating fibrocytes contribute to the myofibroblast population present in PDR membranes.MethodsEpiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. In addition, we investigated the phenotypic changes that take place in human retinal microvascular endothelial cells following exposure to transforming growth factor‐β1 (TGF‐ β1), connective tissue growth factor (CTGF) and the proinflammatory cytokines interleukin‐1β (IL‐1β) and tumor necrosis factor‐a (TNF‐a).ResultsAll membranes contained neovessels expressing the endothelial cell marker CD31. CD31+ endothelial cells co‐expressed the fibroblast/myofibroblast markers fibroblast‐specific protein‐1 (FSP‐1) and a‐SMA, indicative for the occurrence of endoMT. In the stroma, cells expressing FSP‐1, a‐SMA, the leukocyte common antigen CD45, and the myelomonocytic marker CD11b were detected. Double labeling showed co‐localization of CD45 with FSP‐1 and a‐SMA and co‐localization of CD11b with a‐SMA and matrix metalloproteinase‐9, demonstrating the presence of infiltrating fibrocytes. Retinal microvascular endothelial cells changed morphology upon cytokine exposure, lost the expression of endothelial cell markers (endothelial nitric oxide synthase and vascular endothelial‐cadherin) and started to express mesenchymal markers (calponin, snail, transgelin and FSP‐1).ConclusionsThese results suggest that endothelial cells as well as circulating fibrocytes may differentiate into myofibroblasts in the diabetic eye and contribute to pathologic fibrosis in PDR.
Target region sequencing in sporadic congenital cataracts reveals a new genotype‐phenotype relation for the GALK1 gene
Authors: Li D. , Yang J. , Ye H. , Tang Y. , Luo Y. , Lu Y. 
Published: September 2015

PurposeThe purpose of this study was to investigate the genetic effects underlying sporadic congenital cataracts (SCC).MethodsWe collected DNA samples from 74 SCC patients and 20 traumatic cataract (TC) patients in the same age group as normal controls and performed genomic sequencing of 61 cataract‐related genes (including introns, exons and 10 bases from the 3′ and 5′ ends) by target region capture and next generation sequencing. We chose previously reported cataract‐related genes and also included other lens disease‐related genes, including microphthalmia (SOX2, PAX6, OTX2, RAX, FOXE3 and CRYBA4); aniridia (FOXC1, PITX2 and PITX3); Marfan syndrome (FBN1); ectopia lentis (ADAMTSL4 and ADAMTS17) and Alport syndrome (COL4A5).ResultsBy filtering the SNPs that were previously deposited in the NCBI SNP database (dbSNP) or were associated with TC cases, we identified 72 novel variants in 40 genes from 49 patients. The mutation frequency of the GALK1 gene was much higher than the other tested genes, with mutations detected 10 times in 7 patients; followed by CRYBB3 and FBN1 the mutation of which were detected 4 times. Moreover, we observed a posterior polar‐cataract phenotype in 86% (6 out of 7) of SCC patients with mutations in GALK1.ConclusionsWe conclude that genetic mutations could be important contributing factors to non‐hereditary congenital cataract; for example, GALK1, the most frequently mutated gene in this group of patients, was related to the posterior polar subtype of cataract.
Comparison of Optical Coherence Tomography Measurement Reproducibility between Children and Adults
Authors: Kim S.H. , Chung H.K. , Han Y.G. , Oh S. 
Published: September 2015

PurposeTo compare the reproducibility of SD‐OCT (spectral‐domain optical coherence tomography) measurements of RNFL (retinal nerve fiber layer) and macular thickness between children and adults.MethodsSeventy‐one eyes of 71 healthy myopic children and 71 eyes of 71 normal adults were enrolled. RNFL and macular thicknesses were measured by one operator, with a brief rest between measurements. The two measurements were obtained using the eye tracking and retest function of Spectralis SD‐OCT. Reproducibility was evaluated with reference to COVs (coefficients of variation) and ICCs (intraclass correlation coefficients). The ICC values of the RNFL and macular thicknesses were compared, respectively between the two groups, by Fisher's z‐test.ResultsThe RNFL and macular thicknesses did not differ between the two groups. The COVs of the RNFL measurements ranged from 0.945 to 4.531% in the children group and from 0.496 to 1.391% in the adults group. In most of the RNFL sectors, the ICCs of the children group (range: 0.784–0.987) were significantly lower than those of the adults group (range: 0.986–0.993). The COVs of the macular measurements ranged from 0.496 to 1.157% in the children group and from 0.275 to 0.656% in the adults group. The ICCs (range: 0.859–0.973) in the children group, significantly lower than for the adults (range: 0.989–0.995), in all of the macular sectors.ConclusionsThe reproducibility of SD‐OCT RNFL and macular measurements for healthy myopic children was excellent, albeit statistically lower than that for adults.
Impact of disease modifying anti‐rheumatic drugs (DMARDs) on the uveitis risk in juvenile idiopathic arthritis
Authors: Tappeiner C. , Klotsche J. , Schenck S. , Niewerth M. , Minden K. , Heiligenhaus A. 
Published: September 2015

PurposeTo analyze the influence of methotrexate (MTX), Tumour necrosis factor (TNF) inhibitors, and their combination on uveitis occurrence in juvenile idiopathic arthritis.MethodsData of a nation‐wide prospective rheumatological and ophthalmological database in Germany were evaluated for the years 2002 to 2013. Patient with JIA disease duration of less than 12 months at initial documentation and with a follow‐up of ≥ 2 years were included in this analysis. Discrete‐time survival analysis was performed to evaluate the impact of disease modifying anti‐rheumatic drugs (DMARDs) on the occurrence of uveitis.ResultsA total of 3,512 JIA patients fulfilled the inclusion criteria (mean age 8.3 ± 4.8 years, female 65.7%, ANA‐positive 53.2%, mean age at arthritis onset 7.8 ± 4.8 years, mean follow‐up time 3.6 ± 2.4 years). Uveitis manifested in 180 patients (5.1%) within one year after JIA onset, and in further 251 patients (7.1%) after the first year. MTX (HR 0.63, p = 0.022), TNF inhibitors (HR 0.56, p < 0.001) and a combination of the two (HR 0.10, p < 0.001) in the year before uveitis onset significantly reduced the risk for uveitis. MTX treatment within the first year after JIA diagnosis revealed the lowest uveitis risk (HR 0.29, p < 0.001).ConclusionsDMARDs in JIA patients significantly reduce the risk for uveitis onset. A relevant protective effect was found especially for early MTX use within the first year of arthritis onset and for the combination of MTX with a TNF inhibitor.
Intraocular Pharmacokinetics of Povidone‐iodine and the Effect of Repeat Injection with low concentration on the Experimental S. epidermidis Endophthalmitis
Authors: Byon I. , Kim K. , Yu J. , Yoon I. , Lee J. 
Published: September 2015

PurposeTo investigate the safety and a half‐life of intravitreal povidone‐iodine (PVI) and the efficacy of single and repeat PVI injection in experimental S. epidermidis endophthalmitis.MethodsIn Phase I study, the pharmacokinetics and the safety of PVI were investigated. Forty New Zealand White rabbits receiving intravitreal 0.1% and 0.3% PVI were divided into Group I and II. The pharmacokinetics of PVI was analyzed using high performance liquid chromatography (HPLC). To confirm the safety of intravitreal PVI, electroretinography (ERG) and histologic examination were conducted at baseline, 6 and 12 hours. In Phase II study, the efficacy of PVI for the treatment of S. epidermidis endophthalmitis was evaluated in 4 groups (n = 10 in each group). After the induction of S. epidermidis endophthalmitis, 0.1% and 0.3% PVI were injected once in Group A and B, and three times every second day in Group C and D respectively. The fellow eyes receiving sham injection were the control. ERG, histologic examination and vitreous culture for S. epidermidis were conducted at day 14.ResultsIn Phase I, 0.1% and 0.3% PVI groups did not show notable retinal damage in ERG and histologic findings and half‐life in vitro was 3.27 and 3.58 hours, respectively. In Phase II, all Groups showed a significant improvement of endophthalmitis, compared to the controls. However, four eyes in Group A and 3 eyes in Group B demonstrated a bacterial growth in vitreous at day 14, but none in Group C and D. In the histologic findings, retinal damage was detected as lymphocyte infiltration in the inner retinal layers of eyes with bacterial growth.Conclusions0.1% and 0.3% PVI can be tolerated in rabbit eyes. Half‐life of the PVI was about 3 hours in vitreous. Repeat PVI injection with low concentration is likely to be effective and safe for the treatment of S. epidermidis endophthalmitis.
αB‐Crystallin Phosphorylation as a Precursor to Cataractogenesis
Authors: Thornell E. , Ecroyd H. , Aquilina A. 
Published: September 2015

PurposeThe molecular mechanism behind age‐related cataract formation is yet to be elucidated, although phosphorylation induced hyperactivity of αB‐crystallin (αB) and its subsequent association with fibre cell membranes has been implicated. This study evaluates the effect phosphorylation of αB at three well characterised sites (S19, S45 and S59) has on its chaperone activity and aims to characterise αB's membrane association with a focus on its role in cataractogenesis.MethodsThe chaperone activity of αB phosphomimics (S→D) were measured via aggregation assays using creatine phosphokinase (CPK) as a substrate. In vivo association of αB phosphoisotypes with two abundant membrane proteins, connexin 46 (cx46) and aquaporin 0 (AQP0) in aged human lenses was visualised using Duolink proximity assays and confocal microscopy.ResultsThe chaperone activity of αB increased with an increase in modification sites. Modification at the S19 and S59 residues activated αB to a greater extent than at S45. In the lens, phosphorylated αB was found to interact with Cx46 and AQP0 at cell membranes.ConclusionsThis study confirms that multiple phosphorylation events of αB cause a cumulative increase in activity, and that membrane association, at least in part, is mediated by interactions with membrane pore proteins. The proposed mechanism of cataractogenesis is that phosphorylation induced increases in substrate affinity of αB may lead to increased association with membrane pore proteins, leading to the obstruction of the diffusion of small molecules into inner regions of the lens, contributing to cataract formation.
Expression of histamine receptors in the gerbil retinal neurons
Authors: Miyachi E. , Imada H. , Ohkuma M. , Sakai K. 
Published: September 2015

PurposeThe presence of histamine receptors (HRs) in mammalian retinae has been reported by several laboratories. In order to confirm the presence of histaminergic pathway in the retina, we made experiments using physiological and immunohistochemical analyses.MethodsAll experiments were performed using the gerbil (Meriones unguiculatus). The activity of the HR was measured by fura‐2 based calcium‐imaging technique and by whole‐cell patch‐clamp technique from slice preparation of the retina. Localizations of the subtypes of HRs, H1 receptor (H1R), H2 receptor (H2R) and H3 receptor (H3R), were examined by avidin‐biotin‐peroxidase complex immunocytochemical staining or immunofluorescence in retinae from 1 to 350 postnatal days. All animal experiments are approved by the ethics committee of Fujita Health University.ResultsPhysiology: A bath application of 100 µM histamine increased the intracellular calcium concentration in some retinal ganglion cells (RGCs). Under voltage‐clamp condition, histamine increased the amplitude of the outward or inward current in some RGCs.Immunohistochemistry: We found that H1R, H2R and H3R expressed on RGCs. H1R expresses through the retinal maturation. On the other hand, the expressions of H2R and H3R became maximum from 14 to 21 postnatal days. Since the gerbil opens the eyes at 3 weeks old, it is considered that the H2R and H3R play some specific roles at the formation of the early visual system. Histidine decarboxylase, which produces histamine from histidine, also expressed in RGCs, and moreover, each of HRs and histidine decarboxylase were co‐localized at the same RGCs.ConclusionsOur findings suggest that RGCs interact with each other via histamine, and that histamine is one of the important neurotransmitters and/or neuromodulators in the visual information processings of the mammalian retina.
Association between drusen and blood test results in a colony of 1,174 monkeys
Authors: Nishiguchi K. , Yokoyama Y. , Fujii Y. , Furukawa T. , Ono F. , Shimozawa N. , Togo M. , Suzuki M. , Nakazawa T. 
Published: September 2015

PurposeTo ascertain the association between fundus drusens and biological parameters in a colony of 1174 monkeys.MethodsPresence or absence of drusens was determined through the assessment of fundus photos taken during 2011 – 2013 from 1,174 Macaca fascicularis at Tsukuba Primate Research Center. Biological data from these monkeys including blood test result, age, sex, and body weight were tested for an association between the presence of drusens by applying t‐test and logistic regression analysis.ResultsWe identified 387 and 787 monkeys with and without drusens, respectively. Among them, 317 and 628 monkeys with and without drusens that had a complete biological data set were further studied. After comparing each parameter in monkeys with and without drusens, 13 factors with a significance of P < 0.1 (t‐test) were selected for logistic regression analysis. Regression analysis showed association of age (odds ratio: 1.092, 95% confidence interval: 1.061–1.125) and platelet count (odds ratio: 1.022, 95% confidence interval: 1.005–1.038) with drusens. In addition, an association was implicated between drusens and white blood cell count (odds ratio: 1.005, 95% confidence interval: 1.000–1.011).ConclusionsAge, platelet count, and white blood cell count may be associated with the development of drusens in Macaca fascicularis.