bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peter's anomaly in twins: a rare incidence with novel associations
Authors: Khayat H. , Tayyib A. , Alsulami R. , alkahtani A. , alzahrani S. , Almarzoki H. 
Published: September 2016

PurposePeter's anomaly is a rare developmental malformation involving the anterior segment of the eye culminating in congenital blindness, with or without systemic associations. herein, we report an incidence of this anomaly in twins with novel associations.MethodsChart review, clinical and radiological assessment.ResultsThe probands are 2 year old Saudi boys (twin I and twin II) born to consanguineous mates at 36 weeks following uneventful pregnancy. On examination: both twins were not blinking in response to light and were not able to fixate and follow a moving object with prominent horizontal nystagmus. Slit lamp examination demonstrated varying degrees of central leukoma (corneal opacity) associated with iridocorneal adhesion characteristic of type I peter anomaly in both twins. No catarctous changes were observed. A normal intraocular pressure with intact retinas were seen in both twins. Striking pupillary abnormalities include bilaterally underdeveloped pupil (twin I) and bilateral absence of the pupil (twin II). Ocular ultrasound: revealed bilateral vitreous hemorrhage mostly linked to deranged coagulation. Ocular MRI: showed bilateral microophtalmia and optic nerves hypoplasia with small optic chiasm in both twins. Systemic associations: both twins have coarse facial features and a thrombophilia state secondary to homozygous protein C deficiency; a rare thrombotic condition seen in 1\4,000,000 live birth. Twin II developed bilateral inguinal hernia and cryptorchidismConclusionsThe novel concordance of peter's anomaly in these twins is probably an emerging evidence supporting the genetic basis of this defect. Optic nerve and optic chiasm hypoplasia along with the severe protein C deficiency and bilateral absence of the pupil are all important associations which have never been reported previously with this anomaly.
Modern aspects of demodex blepharitis treatment
Authors: Rykov S. , Petrenko O. , Shargorodskaya I. 
Published: September 2016

PurposeThe aim of conducted study was to evaluate the modern eyelid hygiene procedures effectiveness in treatment of demodex blepharitis.MethodsSixty patients with blepharitis and proved presence of Demodex mites were randomized into two groups: Group 1 (n = 30) received the standard treatment of blepharitis (antimicrobial, anti‐allergic, non‐steroidal therapy, artificial tears as required); Group 2 received the standard treatment in complex with eyelid hygiene procedures twice a day during at least one month: applying sterile wipes (Blephaclean®, Thea), warm compresses and eyelid massage. Effectiveness of treatment for each patient in both groups was assessed by means of subjective daily 3‐grade scale of patient's comfort, and objective 3‐grade scales: level of eyelids edge inflammation daily, condition of tarsal glands by meibomiography weekly, presence of Demodex mites, eggs, larvas in acarogramm every 2 weeks.ResultsThere was no significant difference in the average general grade of the clinical complaint between the groups at baseline. Both groups improved clinically with treatment but the subjective level of comfort was greater and appeared sooner in Group 2. By day 3, the grade of clinical complaints was significantly lower in Group 2 compared to Group 1 (1.3 vs. 2.6, p < 0.05). Similar average level (1.3) was gained in Group 2 only to 7th day. Redness and eyelid swelling reduced for at least 80% of subjects after 14 days in Group 1, but after only 10 days in Group 2. After 3 months Demodex specimens were still found in 28 (46.7%) patients in Group 1, but only in 10 (16.7%) in Group 2. There were no significant visual functions changes in both groups of patients during all follow‐up period.ConclusionsThe study demonstrated the important advantages of comprehensive eyelid hygiene procedures in addition to standard therapy of demodex blepharitis.
Classification and heritability of macular pigment spatial profile phenotypes using two‐wavelength fundus autofluorescence
Authors: Huntjens B. , Ctori I. , Mahroo O. , Williams K. , Hammond C. 
Published: September 2016

PurposeWe investigated the frequency and heritability of macular pigment (MP) spatial profile phenotypes determined by objective and subjective profile classification based on fundus autofluorescence (FAF).MethodsBetween scans Coefficient of Repeatability (CoR) of MP optical density (MPOD) was calculated from two FAF scans (Spectralis, Heidelberg, Germany) of 40 participants (39 ± 8.6 years) acquired in a single session. We then analyzed two FAF scans acquired in a single session from 314 twins (157 pairs; 39 ± 8.8 years) and classified each MP profile as exponential, ring‐like or central dip by subjective visual assessment. Profiles were also classified objectively based on deviations larger than the CoR away from the exponential fit. We calculated kappa agreement of the profiling methods, case‐wise concordance of non‐exponential profiles for the 88 mono‐ (MZ) and 69 dizygotic (DZ) twin pairs, and profile heritability.ResultsFollowing visual subjective profiling, 64% showed an exponential profile, 27% presented ring‐like and 9% central dip profiles; case‐wise concordance was 0.80 for MZ and 0.41 for DZ twins. Following objective classification, 71% showed an exponential profile, 29% ring‐like profile and no central dip profiles were identified; case‐wise concordance was 0.74 for MZ and 0.36 for DZ twins. Heritability was calculated as 81.5% (95% CI 61.1–93.1). Between scan repeatability of profile classification showed good agreement objectively (κ = 0.85, 95% CI 0.69–1.00; p < 0.0005) and moderate agreement visually (κ = 0.48, 95% CI 0.23–0.73; p < 0.0005). Agreement of subjective versus objective profiling was low (κ = 0.23, 95% CI 0.04–0.42; p = 0.02).ConclusionsMP profiles showed high heritability. Compared to visual assessment, objective profile classification is a more reliable method for future experimental studies using two‐wavelength FAF.
Metallothionein polymorphisms in a Northern Spanish population with Age‐Related Macular Degeneration (AMD)
Authors: Garcia M. , Álvarez L. , Fernandez Á. , Gonzalez‐Iglesias H. , Escribano J. , Fernandez‐Vega B. , Fernandez‐Vega Á. , Villota E. , Fernandez‐Vega L. , Coca‐Prados M. 
Published: September 2016

PurposeTo elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with aged‐related macular degeneration (AMD).MethodsA case‐control study of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls matched by age and ethnicity were enrolled. DNA was isolated from peripheral blood and genotyped for fourteen MT SNPs (MT1A: rs11076161, rs 11640851, rs8052394 and rs7196890; MT1B: rs8052334, rs964372 and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636 and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software.ResultsThe allelic frequency analysis revealed that rs28366003 in MT2A gene, showed the unique significant association with AMD (dry form; p = 4.40 × 10−4), increased disease susceptibility ranged from approximately 9.80 for the allele G (OR = 9.80, 95% CI: 1.11–86.25). The frequency of genotype AA at SNP rs28366003 was significantly lower in dry AMD cases than in control under a recessive association model (p = 2.65 × 10−4; AA vs. AG+GG) conferring protection from the disease (OR = 0.82, 95% CI: 0.71–0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the thirteen SNPs analyzed.ConclusionsThe present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 in the MT2A gene with susceptibility to the dry form of AMD in the Northern Spanish population.
4 Gy radiotherapy in 6 patients with orbit marginal zone lymphoma: A small case series
Authors: Graeff E. 
Published: September 2016

PurposeTo demonstrate therapeutic approach with low dose radiotherapy of 4 Gy in 6 cases of marginal zone lymphoma (2 lacrimal gland cases, 1 conjunctival case and 3 orbital cases itself)MethodsSmall case series of 6 patients with ocular marginal zone lymphoma, including diagnostic and therapeutic optionsResultsIn 6 patients (58–86 years) a marginal zone lymphoma of the orbit was diagnosed. A proptosis of the eye could be observed in one patient with lacrimal gland tumour as well as in three patients with orbital lesions itself. Two patients showed additional eye movement retraction accompanied by diplopia. In addition to a thorough ophthalmological examination, the staging of patient included ultrasound of the orbit, MRI of the head, gastroscopic examination and a PET‐CT of the whole body was performed. In all cases the diagnosis was made by ocular pathology. A focal radiotherapy with 4 Gy in two fractions was the only treatment in 5 cases. In one case a combination with additional systemical rituximab was necessary. A regression of all lesions could be observed and no tumour relapses occured until 7–29 months later.ConclusionsIn cases of orbit MALT lymphoma a gold standard radiotherapy of 30 Gy in 15 fractions was established. However in our small case series of 6 patients a complete regression of tumour mass was shown using 4 Gy in two fractions. Depending on the general state of the patient a reduced radiation therapy remains a usefull alternative.
Age related changes in axon guidance cues in the optic chiasm
Authors: Gomes Alves Da Conceicao R. , Barber A.C. , Martin K.R. 
Published: September 2016

PurposeAdult mammalian retinal ganglion cells (RGC) usually fail to regenerate axons post injury. Axon regeneration can be facilitated by several approaches but misguidance of regenerating axons at the optic chiasm is often observed and has been attributed to intrinsic proprieties of RGCs and/or a lack of extrinsic guidance cues in the adult visual system. This study characterizes the guidance cues present in the adult optic chiasm compared to the embryonic visual system.MethodsKnown guidance cues were examined in embryonic and adult optic chiasms of C57 mice by IHC. Radial glial markers (RC2/BLBP/Slit1) and developmental markers (Shh/Pax2) were assessed. RC2, BLBP, Slit1 and Shh are known as inhibitory guidance cues while Pax2 is a permissive guidance cue.ResultsStaining for glial markers RC2 & BLBP was detected immediately superior to the optic chiasm in coronal E15.5 samples. In coronal adult brain samples, RC2 & BLBP staining was observed in the optic chiasm midline; a very different distribution to E15.5 samples. No staining was observed in E15.5 or adult horizontal samples. Slit1 showed expression in the optic chiasm midline and optic tract at E15.5, but no staining was detected in the adult. Shh showed the same pattern as Slit 1 in the optic nerve at E15.5. Pax2 was present in optic nerves of both embryonic and adult samples.ConclusionsHere the profile of guidance cues in the embryonic and adult visual system was characterized. In the developing embryo all markers, known to be crucial for establishing axonal pathways along the optic stalk and optic tract, were present. In the adult visual system Slit1 and Shh were absent, RC2 and BLBP were ectopically expressed, and Pax2 expression was low. These results may explain misguidance of regenerating RGC axons in the adult optic chiasm, highlighting the importance of understanding this environment.
Quantitative assessment of retinal permeability in the diabetic Akimba mouse: validation of a promising animal model for diabetic retinopathy
Authors: Hu T.T. , Vanheukelom V. , De Vriese A. , Feyen J.H.M. 
Published: September 2016

PurposeUnravelling the pathogenesis of diabetic retinopathy (DR) remains largely elusive, mainly due to lack of reliable diabetic animal models. The Akimba mouse (Ins2AkitaVEGF+/−) was generated by crossing Akita (T1D) with hVEGF‐overexpressing Kimba mice. The aim of this study was to validate this innovative diabetic model as a quantitative in vivo screening tool for anti‐leakage therapeutics in the context of DR.MethodsFluorescein angiography (FA) and OCT were implemented to assess retinal permeability and edema in Akimba compared to WT. FITC‐BSA perfusion and immunohistochemistry (IHC) were performed as well. Metamorph software (Leica) was used for quantitative analysis. The efficacy of anti‐VEGF therapy was investigated in Akimba mice via intravitreal injection of anti‐VEGF or vehicle.ResultsWe report for the first time that quantitative analysis of FA images and FITC‐BSA perfused flatmounts revealed a significant increase of vascular leakage in the Akimba eye compared to WT. Analogous to the clinical DR situation, edema can be discerned in OCT scans of Akimba eyes. The effect of anti‐VEGF was monitored via longitudinal FA follow‐up before and 2–4 weeks after treatment. Anti‐VEGF treatment induced a significant decrease in vascular leakage (approx. 35%). IHC stainings confirmed that Akimba also exhibits other DR hallmarks such as inflammation, angiogenesis and fibrosis.ConclusionsCurrent study demonstrated that the Akimba mouse is a powerful model for screening therapeutics against sight‐threatening retinal edema. This diabetic model also exhibits other main DR‐related processes, signifying the relevance of the Akimba model for DR research. Further validation will be crucial to strengthen the toolbox of in vivo DR models and ultimately to address the unmet need for effective next generation therapies for DR.
Coats' syndrome is associated with reduced pressure autoregulation in retinal arterioles
Authors: Herborg A. , Bek T. , Petersen L. 
Published: September 2016

PurposeCoats’ disease is a rare condition characterised by dilatation and hyperpermeability of retinal vessels typically affecting one eye, which may lead to severe visual loss. The disease is treated by retinal photocoagulation, but there is a need for a treatment more targeted at the pathogenic mechanisms of the disease, which are presently unknown.Therefore, the purpose of the present study was to study the contribution of disturbed pressure and metabolic autoregulation to the pathogenesis of Coats’ disease.MethodsSeven patients, three males and four females aged 34.1, 11–69 years (mean, range) affected by Coats’ disease in one eye were studied in both eyes using the Dynamic Vessel Analyzer (DVA). Video recordings were used to measure the diameter of larger retinal arterioles during rest, during an increase in the arterial blood pressure by lifting a hand weight and during stimulation of retinal metabolism by flickering light.ResultsThe resting diameter of retinal arterioles was non‐significantly larger (mean ± SEM) in the affected eye (133.9 ± 8.3 μm) than in the unaffected eye (118.2 ± 8.6). The contraction of retinal arterioles during increased blood pressure secondary to isometric exercise was not significantly different from zero in arterioles, neither from the affected (0.1 ± 0.3%) nor from the unaffected (0.2 ± 0.6%) eye (p = 0.93).ConclusionsCoats’ disease is accompanied with impaired pressure autoregulation in retinal arterioles, but there is no significant difference between the response in the affected and the non‐affected eye. The pathogenesis of Coats’ disease is due to other factors than diameter autoregulation in the larger retinal arterioles.
DNA methylation patterns in uveal melanoma derived FFPE samples correlate with survival
Authors: Ness C. , Grüner C.C. , Meza Zepeda L. , Moe M.C. , Noer A. 
Published: September 2016

PurposeTo examine correlation of DNA methylation patterns of human uveal melanoma with survival.MethodsFFPE samples from 24 UM patients undergoing enucleation of the eye in the period 1976–1989 were included. Inclusion was based on histopathological data, data from the Norwegian Cancer Registry and the Norwegian Cause of Death Registry. DNA was isolated from the FFPE samples and further bisulphite converted and restored according to Illuminas recommendations. Bisulphite converted DNA was then run on The Infinium HumanMethylation450 BeadChip assay (HM‐450K). Bioinformatics analyses were conducted in R statistical software, including analysis of copy number variation.ResultsOur data shows subclustering correlated with survival and mortality, additionally our data informs on epigenetically deregulated genes with the potential of increasing our knowledge about the underlying mechanisms of UM.ConclusionsThe methylation profile of a given cancer can elucidate therapeutic targets, reveal biomarkers for early detection or identify high risk tumours. The present study is the first to report methylation changes in FFPE samples derived from UMs.
The change of Ganglion cell layer and Inner plexiform layer thickness in Type 2 DM with non‐proliferative diabetic retinopathy
Authors: Choi C. , Mun S.J. 
Published: September 2016

PurposeTo evaluate each retinal layer's thickness change in Type2 DM patients with non‐proliferative diabetic retinopathy by using Optical Coherence Tomography (OCT)MethodsWe compared the thickness of each retinal layers by using OCT in 102 eyes, composed of normal control 60 eyes and NPDR 42 eyes. The thickness of these 7 layers were measured; retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE). We excluded the patient who had refraction rate <−6D or greater than +3D, patients who had retinal disease other than diabetic retinopathy, and patient who had preretinal membrane, macular edema,. The each layer's thickness was measured in 4 different regions, 3 mm away from central fovea; superior, inferior, nasal, and temporal direction.ResultsThe thickness of each layer at all 4 different regions of GCL was thicker in normal control group than in NPDR. The average difference was 4.92㎛ and the result showed statistical significance in all four regions. Also, normal control group have thicker thickness in all four regions of IPL and the average difference was 2.67 μm. The nasal, temporal, superior regions showed statistically significant correlation, but the inferior region did not. However, normal control group and NPDR group had no significant difference in layer's thickness at RNFL, INL, OPL, ONL, RPE layers.ConclusionsWhen we compared and measured each retinal layer's thickness by OCT, the normal group showed thicker layer's thickness in GCL, IPL layers than NPDR group but had no significant difference in RNFL, INL, OPL, ONL, RPE layers. In conclusion, the thinning of Inner retinal layers such as GCL, IPL might be used as a useful tool to diagnose and follow‐up in early diabetic retinopathy.
Systematic assessment of clinical methods to diagnose and monitor diabetic retinal neuropathy
Authors: Jenkins K.S. , Rowan A. , Layton C. 
Published: September 2016

PurposeBackground and Purpose: Diabetic retinal neuropathy refers to retinal neural tissue damage occurring before diabetic retinopathy and fulfils many of the criteria for causality for the subsequent vasculopathy. Developing reliable means of measuring neuronal damage in diabetes may be important in efforts to prevent retinopathy. This study aimed to systematically assess current clinical measurements of diabetic retinal neuropathy.MethodsA systematic search of the medical literature since 1984 was performed on PUBMED and EMBASE and the evidence supporting each identified method as an indicator for clinically important diabetic retinal neuropathy was graded relatively as strong, medium or weak according to criteria assessing its relationship to subsequent diabetic retinopathy, quality of supporting studies and published reproducibility.ResultsThe systematic search yielded 6,421 results. Subsequent assessment by two independent investigators identified 601 multiple subject studies in humans assessing clinical aspects of retinal structure, function or psychophysics in the pre‐diabetic retina. Clinical methods assessed as being supported by relatively ‘strong’ evidence included FM‐100 hue colour vision changes, flash ERG b‐wave latency, flash multifocal b‐wave latency, scotopic flash ERG oscillatory potential amplitude and contrast sensitivity.ConclusionsConclusions/Discussions: The results showed moderately poor quality of extant evidence and indicate the best clinical methods for assessing diabetic retinal neuropathy remain to be confirmed. This is the first systematic assessment of the medical literature aiming to assess the breadth and validity of these methods and represents an early step in identifying and developing endpoints for use in trials designed to identify at risk patients or prevent diabetic retinopathy.
HuR/ELAVL1 expression in the human cataractous lens
Authors: Amadio M. , Marchesi N. , Govoni S. , Pascale A. , Petrovski G. 
Published: September 2016

PurposeCataract is a common age‐related ocular disease having as major determinants oxidative stress, accumulation of protein aggregates and inflammation. It has been previously reported that the expression of the RNA‐binding HuR/ELAVL1 (Embryonic Lethal Abnormal Vision‐Like 1) protein, a master regulator of many cellular functions including cell stress response, is altered in various ocular disorders. Here we develop a method to assess, by means of several techniques, the expression of HuR/ELAVL1 in human lens.MethodsHuman anterior lens capsules (aLCs) were collected from patients undergoing uneventful cataract surgery for mixed nuclear and cortical cataracts after informed consent was obtained. Control aLCs were obtained from non‐cataractous lenses derived from human cadaver eyes removed within 24 h of death. The samples collected were snap frozen for further processing. Quantitative real‐time PCR, Western blotting and ELISA assay were used to determine the expression and distribution of HuR/ELAVL1 in the lenses.ResultsHuR/ELAVL1 is expressed at both mRNA and protein level in the epithelial cells and aLC from age‐related cataract patients and healthy subjects.ConclusionsThis is the first study documenting the expression of HuR/ELAVL1 in human lens. Considering the importance of oxidative stress in the development of cataract, further experiments will allow to determine whether HuR/ELAVL1, which exerts in other ocular pathologies a post‐transcriptional control of stress response genes, may play a role in cataract pathogenesis.