bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is macular pigment spatial profile a clinical biomarker in children of AMD parents?
Authors: Richer S. , Huntjens B. , Pratt S. , Rutledge G. , Perry B. , Novil S. , Pratt G. 
Published: September 2017

SummaryA central dip in macular pigment (MP) has shown to be more prevalent with age, in AMD patients, and in smokers. We investigated clinical and genetic biomarkers in non‐smoking children of AMD parents (n = 131) over 40 years of age without AMD pathology in relation to their MP spatial profile. MP peak and volume were obtained with ARIS (Visual Pathways, Inc, Prescott, AZ USA) while spatial profiles for both eyes were classified visually and objectively. We explored risk factors including serum carotenoids and in‐vivo skin carotenoids, and cardiovascular biomarkers including omega‐3 fatty acids EPA and DHA, methylenetetrahydrofolate reductase C677T and A1298C in this well‐nourished Caucasian study group. Objectively, a central dip appeared more prevalent in children of AMD patients (41%) when compared to a healthy population. Those with central dip showed increased mean MP peak and volume, decreased serum L, Z, EPA and DHA, and decreased skin carotenoids in comparison to no dip. Identifying biomarkers in children genetically susceptible to AMD and introducing lifestyle changes such as nutrient repletion could provide invaluable advice to those associated with increased risk of AMD.
The importance of the polarity proteins CRB in the differentiation process of the RPE cells
Authors: Lillo C. , Paniagua A.E. , Segurado A. , Fernandez‐Dolón J. , Valle V. , Albertos H. , Velasco A. 
Published: September 2017

SummaryApicobasal polarity is essential for epithelial cell function, and it is determined by the expression of three polarity protein complexes: Scribble, Par and Crumbs. Both the Par and the Crumbs complex, promote apical membrane identity. Crumbs complex is composed by PALS1, PATJ and the Crumbs homologs (CRB) proteins. We have recently described the expression of one of the Crumbs proteins, CRB2, in the retinal pigment epithelial (RPE) cells. To better understand this process, we have studied the role of CRB2 in human RPE cells during differentiation in vitro and in the mouse retina in vivo. To achieve this goal, we analyzed the temporal sequence of the establishment of the polarity proteins during human fetal RPE cells polarization and knocking‐down CRB2, we analyzed the establishment of junctional complexes and features involved in the acquisition of polarization compared to the control RPE cultures. We demonstrate that, in differentiating RPE cells, CRB2 functions, as the sole CRB protein, in the formation of the junctional complex and apicobasal polarity. Additionally, the absence of the CRB2 protein from these cells results in a delay in the formation of cell‐cell junctions and in an increase in cell proliferation in RPE cells.
Interventions to increase attendance for diabetic retinopathy screening: a systematic review and meta‐analysis
Authors: Lawrenson J.G. , Graham‐Rowe E. , Lorencatto F. , Bunce C. , Burr J.M. , Francis J.J. , Rice S. , Aluko P. , Vale L. , Peto T. , Presseau J. , Ivers N.M. , Grimshaw J. 
Published: September 2017

PurposeStudy objectives were to: 1) determine the effectiveness of interventions to improve diabetic retinopathy screening (DRS) attendance; 2) specify intervention content in terms of behaviour change techniques (BCTs); 3) determine whether interventions that included particular BCTs were more effective in increasing attendance.MethodsWe searched the Cochrane Library, MEDLINE, EMBASE and clinical trials registers to February 2017 for randomised controlled trials (RCTs) that were designed to improve attendance for DRS or were evaluating general quality improvement (QI) strategies for diabetes care and reported the effect of the intervention on DRS attendance. We did not use any date or language restrictions in the searches. We identified and categorised component BCTs using an established BCT Taxonomy (BCTTv1).ResultsWe included 66 RCTs. QI interventions were multifaceted and targeted patients, healthcare professionals (HCPs) or healthcare systems. Overall, DRS attendance increased by 12% (risk difference (RD) 0.12 [95% CI 0.10‐0.14]) compared with usual care, with substantial heterogeneity in effect size. Both DRS‐targeted and general QI interventions were effective, particularly where baseline DRS attendance was low. All frequently identified BCTs were associated with significant improvements in attendance. Higher effect estimates were observed in sub‐group analyses for the BCTs ‘goal setting (outcome)’ (0.26 [0.16‐0.36]) and ‘feedback on outcomes of behaviour’ (RD 0.22 [0.15‐0.29]) in interventions targeting patients, and ‘restructuring the social environment’ (RD 0.19 [0.12‐0.26]) and ‘credible source’ (RD 0.16 [0.08‐0.24]) in interventions targeting HCPs.ConclusionsRCT evidence indicates that QI interventions incorporating specific BCT components are associated with meaningful improvements in DRS attendance compared to usual care.
Cost‐effectiveness of intravitreal therapy with both anti‐VEGF and Dexamethasone implant in patients with Diabetic Macular Edema
Authors: D'amico Ricci G. , Bouzios D. , Boscia F. , Lupino M. , Pinna A. 
Published: September 2017

PurposeThe aim of this study was to evaluate the cost‐effectiveness of intravitreal therapy (IVT) with both anti‐VEGF and Dexamethasone implant in patients with Diabetic Macular Edema (DME) during two years’ follow‐up.MethodsA retrospective review of 191 patients (382 eyes) with type I and II diabetes and DME was performed. Pre‐IVT and final best correct visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), number and type of IVT,number of examinations, and fluorescein angiography were assessed. Based on surgery procedure other than IVT, patients were divided into 5 groups. To avoid bias, we analysed only patients who had undergone cataract surgery before (group 1) or during enrolment (group 2).Results41 eyes from Group 1 and 48 eyes from group 2 were evaluated. Median BCVA ranged between 20/80 and 20/63 Snellen (P = 0.008) in Group 1 and from 20/63 to 20/40 Snellen (P = 0.0035) in Group 2, while improvement up to 1 Snellen line was observed in 58.5 and 68.75% of eyes in Group 1 and 2, respectively.In terms of median CMT, a statistically reduction (P = 0.0007) was found in Group 2 (‐85 μm), whereas no statistical differences were found in Group 1. The two groups showed no statistically significant difference in median IOP. The estimated cost per eye was €7803 in Group 1 and €8988 Group 2, whereas the mean cost per patient was €15190 and €16580 in Group 1 and 2, respectively. Analysis between groups did not show any statistical difference in the considered parameters.ConclusionsIn this study, despite the high treatment cost, vision improvement in DME patients undergoing IVT was disappointing. Our results emphasise the need for a better understanding of the cost‐effectiveness of DME treatment
Fluorescence lifetime imaging ophthalmoscopy
Authors: Dysli C. , Wolf S. , Zinkernagel M.S. 
Published: September 2017

SummaryFluorescence Lifetime Imaging Ophthalmoscopy (FLIO) allows in vivo measurement of autofluorescence lifetimes of natural retinal fluorophores upon laser excitation. Beyond fluorescence intensity, lifetimes provide further information about the metabolic state of the retina as they are dependent on micro environmental factors.Fluorescence lifetimes were investigated in healthy retinae and compared with retinal diseases such as retinal artery occlusion, geographic atrophy due to age related macular degeneration, central serous chorioretinopathy, Stargardt disease, and choroideremia.Retinal autofluorescence lifetimes feature disease specific patterns. They allow identifying differences within retinal deposits and changes of local or systemic metabolic conditions over time. Thereby, FLIO provides a promising tool for investigation of retinal metabolic changes. Especially neurodegenerative diseases associated with intracellular deposits shall be further investigated. As FLIO is a non invasive imaging technique which is easy to apply it might qualify as a screening technique for early detection of retinal changes also in neurodegenerative diseases.
What makes ocular surface anatomy attractive for a scleral lens?
Authors: Knop E. 
Published: September 2017

SummaryThe ocular surface consists of the moist mucosal organs at the anterior eye surface. They are a continuous anatomical unit from the lacrimal gland over conjunctiva & cornea into the lacrimal drainage system. Joined by the flow of tears and governed by regulatory systems, e.g. nerves, hormones & immune system ‐ thus they also form a functional unit as a constant moist chamber (for details please see: WWW.OSCB‐BERLIN.ORG). The main function is to provide the environment for vision by the entrance of light and its refraction.“MOISTURE is KEY” because it keeps the cornea transparent and establishes the pre‐ocular tear film as main refraction unit. At the same time the moist chamber is highly endangered in our humid environment.SCLERAL CONTACT LENSES are large contact lenses that rest on the sclera and vault over the cornea by providing a pool underneath, with the patient′s own tears including all factors for nutrition & regulation. Sclerals are thus a unique medical tool to restore both essential functions when the ocular surface and particularly the cornea is altered: constant moisture and a homogeneous refraction interface. In addition they shield the cornea against the chronic mechanical forces in eye movements and blinking.
Two photon microscopic findings of sonoporation‐assisted enhancement of corneal penetration of fluoroquinolone antibiotics
Authors: Lee J.A. , Jeong H. , Kim J.Y. , Tchah H. , Kim K.H. , Kim M.J. 
Published: September 2017

PurposeTo investigate the sonoporation‐assisted enhancement of corneal penetration of fluoroquinolone antibiotics.MethodsEnucleated mouse corneas were imaged by two‐photon microscopy to observe normal corneal structure ex vivo. For estimation of the threshold of corneal epithelial damage, sonoporation was applied with different intensities (1.5, 2.0 and 3.0 W/cm2) for 5 minutes on each cornea. Gatifloxacin and besifloxacin were applied on each cornea and the depth of drug penetration was observed with two‐photon microscopy. After sonoporation (1.5 and 1.7 W/cm2, respectively) was applied with fluoroquinolone eyedrops, we compared the aspects of drug penetration in sonoporated cornea with those in normal cornea. In vivo two photon microscopy imaging was conducted with gatifloxacin application.ResultsNormal cornea observed with two‐photon microscopy showed regular arrangement of epithelial cells without any damaged cells. Threshold intensity of sonoporation that can damage some epithelial cells without significant structural destruction was determined as 1.5~2.0 W/cm2. When gatifloxacin was applied on normal cornea, gatifloxacin fluorescence was observed only on surface of corneal epithelium. After sonoporation, whole epithelium showed increased gatifloxacin and besifloxacin fluorescence. But the penetration depth and the extent of Besifloxacin were less than those of gatifloxacin, due to its own molecular structure. The threshold intensity was revealed as 1.3 W/cm2 in vivo. In vivo corneal penetration of gatifloxacin enhanced after sonoporation, and this result was comparable with that of ex vivo.ConclusionsWe observed the enhancement of corneal penetration of fluoroquinolone antibiotics after sonoporation was done on mouse cornea ex vivo as well as in vivo. Besifloxacin showed poor penetration compared with gatifloxacin even after sonoporation.
Nevus, melanocytoma and melanoma: differential diagnosis
Authors: Shields C. 
Published: September 2017

SummaryA major analysis on 3680 cases of iris tumors revealed two main types of tumors including solid (79%) and cystic (21%). The most common solid mass was the melanocytic tumor, which included nevus (60%), melanocytoma (3%), and melanoma (26%).Iris nevus is benign. This tumor tends to occur in the inferior portion of the iris. In an analysis of 1611 consecutive eyes with iris nevus, growth into melanoma was documented in 4% at 10 year followup. Statistical analysis for nevus at greatest risk for growth can be remembered by the lettering ABCDEF representing Age (< 40 years), Blood (hyphema), Clock hour inferior, Diffuse configuration, Ectropion, Feathery margins.Iris melanocytoma is benign and appears as a dark brown mass, occasionally with iris and angle seeding. This tumor carries 1% risk for transformation into melanoma.Iris melanoma is malignant and represents 4% of all uveal melanomas. This tumor exhibits slow growth. An analysis of 317 eyes with iris melanoma documented risk for metastasis at 10 years in 9%. Factors predictive of metastasis included extraocular extension and secondary glaucoma.Differentiation and understanding the behavior of these three similar‐appearing tumors is important in their management.
Circumscribed irido‐ciliary melanoma: surgery versus irradiation
Authors: Desjardins L. , Cassoux N. , LumbrosoLeRouic L. , Dendale R. 
Published: September 2017

SummaryIris tumors include congenital benign cyst, naevi, melanocytomas malignant melanomas, benign adenoma,leiomyomas, metastatic tumors, iris location of leukemia or lymphomas and histiocytic proliferations like iris xanthogranuloma.Patients with metastatic disease rarely develop a bilateral diffuse melanocytic uveal proliferation (BDUMP) which can cause retinal detachment and blindness.The diagnosis of an iris tumor is made by careful medical history, slit lamp examination, UBM ultrasonography and OCT of the iris.In rare instances fine needle aspiration biopsy can be useful but follow up is often the more important test to differentiate stable naevus versus malignant melanoma of the iris.Treatment can be a simple observation for naevi or melanocytoma..Surgery is still the best option for adenomas and leiomyomas. Metastatic disease can be treated by chemotherapy and external beam radiation. Xanthogranulomas of the iris usually respond well to steroids. For melanoma of the iris a lot of centers do not use surgery and prefer radiotherapy most often proton beam radiotherapy. Results of proton beam therapy of iris melanoma will be presented.
In vitro modeling of aniridia‐related PAX6 haploinsufficiency by the use of CRISPR/Cas9 on limbal epithelial cells
Authors: Roux L. , Concordet J.P. , Ferrigno O. , Aberdam D. 
Published: September 2017

PurposeHaploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by iris hypoplasia and reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia‐related keratopathy (ARK), caused by a combination of factors including limbal stem‐cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub‐epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation.MethodsWe used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation into one allele of the PAX6 gene in TERT‐immortalized limbal cells, which remain identical to primary limbal cells able to differentiate into corneal cells upon calcium raise at confluency.ResultsA resulting mutated clone, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency, was further characterized. Sequencing analysis showed that no off‐target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of recombinant PAX6 protein was able to activate endogenous PAX6 gene and, as a consequence, rescue partially the phenotype.ConclusionsOur in vitro model will be powerful to identify drugs that could rescue the corneal defect.
Association between the retinal vascular network, cardiovascular history and risk factors in the elderly
Authors: Arnould L. , Binquet C. , Guenancia C. , Kawasaki R. , Daien V. , Bron A. , Creuzot‐Garcher C. 
Published: September 2017

PurposeTo identify patterns summarizing the retinal vascular network in the elderly and to investigate the relationship of these vascular patterns with cardiovascular history.MethodsWe conducted a population‐based study, the Montrachet study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases), in participants older than 75 years. History of cardiovascular disease and a score‐based estimation of their 10‐year risk of cardiovascular mortality (Heart SCORE) were collected. Retinal vascular network analysis was performed by means of Singapore “I” Vessel Assessment (SIVA) software. Principal component analysis was used to condense the information contained in the high number of variables provided and to identify independent retinal vascular patterns.ResultsOverall, 1069 photographs (1069 participants) were reviewed with SIVA software. The mean age was 80.0 ± 3.8 years. We extracted three vascular patterns summarizing 41.3% of the vascular information. The most clinically relevant pattern, Sparse vascular network, accounted for 17.4% of the total variance. It corresponded to a lower density in the vascular network and higher variability in vessel width. Diabetic participants with hypoglycemic treatment had a sparser vascular network pattern than subjects without such treatment (Odds ratio, [OR], 1.68; 95% CI, 1.04–2.72; P = 0.04). Participants without history of cardiovascular disease who had a sparser vascular network were associated with a higher Heart SCORE (OR, 1.76; 95% CI, 1.08–2.25; P = 0.02).ConclusionsThree vascular patterns were identified. The Sparse vascular network pattern was associated with being a higher risk profile for cardiovascular mortality risk at 10 years.
X‐linked juvenile retinoschisis: different mutations – same phenotype
Authors: Strupaite R. , Ambrozaitytė L. , Cimbalistienė L. , Ašoklis R. , Utkus A. 
Published: September 2017

PurposeTo describe the phenotype‐genotype correlation of three X‐linked retinoschisis (XLRS) cases in juveniles with different novel mutations from Lithuanian population.MethodsBased on clinical symptoms and family history, a preliminary diagnosis of XLRS was established in three adolescent male patients. Comprehensive ophthalmological examinations, including best‐corrected visual acuity (BCVA), slit‐lamp, fundus examination, spectral domain optical coherent tomography (SD‐OCT) and full‐field electroretinography, were performed. RS1 (NM_000330.3) gene coding exons Sanger sequencing was performed.ResultsAt the time of ophtalmic and genetic counselling the patients were 9, 12 and 17 years old. The patients demonstrated macular retinoschisis and typical cyst‐like cavities on SD‐OCT images with logMAR BCVA ranging from 0.5 to 0.2. The mean central foveal thickness was 569.7 μm. Two of the three patients presented with peripheral retinoschisis. Flash‐ERG demonstrated a reduced b/a ratio (<1.0) in all patients. RS1 c.599G>T (p.R200L) mutation was detected in one case, in silico analysis showing to be pathogenic. HGMD involves three other different mutations at the same position supporting the pathogenicity of the identified variant. c.(92_97)insC (p.W33 fs) mutation was identified for another proband, in silico analysis indicating the variant is possibly damaging. The third case was identified with a pathogenic mutation c.422C>G (p.R141H), HGMD CM981753.ConclusionsThese are the first cases of XLRS in the Lithuanian population confirmed by molecular genotyping. Although clinical expression of XLRS is highly variable presented patients had a different genotype but similar phenotypic traits. Functional analysis would be of benefit to characterise the identified variants on the effect of retinoschisin expression.
Non‐surgical treatment of idiopathic macular hole (IMH)
Authors: Xirou T. 
Published: September 2017

SummaryOcriplasmin and Pneumatic vitreolysis are the two non surgical treatment options for the management of IMHs. While closure of IMH after vitrectomy has a success rate very high, it is challenging the option of managing IMHs without the necessity of a surgical procedure. Cost‐effectiveness and safety profile are the main parameters to be considered in these relative new non surgical treatment options, mainly proposed for IMHs less than 400 μm in diameter with vitreomacular traction.
Why the eye? Current understanding on the pathogenesis of ocular toxicities
Authors: Neri P. , Nicolai M. , Bisceglia P. 
Published: September 2017

SummaryThe increased use of several different pharmaceutical agents has provided a positive impact to patients benefits. On the other hand, the ophthalmologist is seeing more patients with ocular side effects secondary to such agents. In particular, ocular toxicity induced by cancer chemotherapy, biologic agents and immunesuppressive drugs includes a broad spectrum of disorders, which reflect the peculiar physiological, anatomical and biochemical characteristics of the eye. The progresses achieved by the science in understanding ocular biostructure has allowed a better knowledge on ocular side effects. This achievement assists the ophthalmologist and other specialists to recognize them early and intervene before severe visual impairment occurs. A prompt intervention for the treatment‐related toxicities may also provide the opportunity for a minimization or resolution of an expected side effect. Therefore, ophthalmologist should examine patients for any therapy that can present potential ocular side effects, according to the type of used drug. The biostructure and pathophysiology of potential toxicity of different drugs will be reviewed.
MEKi‐related retinopathy
Authors: Jager M.J. , van Dijk E.H.C. , van Herpen C.M.L. , Marinkovic M. , Luyten G.P. , Kapiteijn E.H. , Boon C.J. 
Published: September 2017

SummaryPatients that are being treated for different types of malignancies may develop eye problems, which may be due to their treatment. We studied patients that received treatment with the MEK inhibitor binimetinib prospectively: 23% of 30 patients with metastatic cutaneous melanoma and 5 patients with metastatic uveal melanoma reported visual complaints during treatment. These complaints were time‐dependent, mild, and reversible. OCT revealed serous subretinal fluid in 74% of patients. Moreover, a persistent profoundly abnormal electro‐oculogram was found, indicating a panretinal dysfunction of the retinal pigment epithelium. Since no other abnormalities could be detected on multimodal imaging, this clinical entity is referred to as MEK‐associated serous retinopathy.Ophthalmological monitoring is warranted in patients using MEK inhibitors; however, discontinuation of administration generally does not seem necessary because of the relatively low visual impact and transient nature of the associated serous retinopathy. Possible pathogenetic mechanisms of this retinopathy include anti‐RPE and anti‐retinal autoantibodies and/or direct RPE toxicity of MEK inhibitors.Ophthalmology. 2015 Sep;122(9):1907‐16. https://doi.org/10.1016/j.ophtha.2015.05.027