bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐invasive, needle‐free drug delivery for treatment of retinal degeneration on Bardet‐Biedl syndrome
Authors: Roberto Ajoy Moreno Daniel , Basetto Marco , Obringer Obringer Cathy , Messaddeq Nadia , Poulhès Florent , Zelphati Olivier , Dollfus Hélène , Marion Vincent 
Published: December 2019

AbstractPurposeTo develop a non‐invasive drug delivery system based on superparamagnetic nanoparticles (NP) for the treatment of retinal degeneration on Bardet‐Biedl syndrome (BBS). The delivery system will be used to deliver two small molecules, valproic acid (VPA) and Guanabenz (GBZ).MethodsA mixture of two NP (one loaded with VPA and other with GBZ) was applied as eyedrops on 14‐days old mice with the use of a magnetic field. The treatment was assessed in both wild type and a mice model for BBS (Bbs12−/−). The effects of the treatment were evaluated 2 weeks post treatment at 1‐month‐old. Retinal structure and function were analysed using electroretinogram recordings (ERG), histology and transmission electron microscopy (TEM).ResultsIn vitro studies showed no important toxic effects in cell cultures for retinal pigmented epithelium (RPE1) and 661W (murine photoreceptor precursor) after treatment with unloaded NP. Scotopic and photopic ERG recordings showed no toxic effect of the NP on photoreceptor (PR) function. TEM analysis indicated the presence of the NP in the PR layer of the retina after eyedrop application. TEM images showed a decrease in Endoplasmic Reticulum (ER) dilatation. The treated group with loaded NP showed an increase in the thickness of the inner nuclear layer, outer nuclear layer, inner PR segment and outer PR segment.ConclusionsThese results highlight the potential for these NP for non‐invasive drug delivery to the retina. Both the presence of the NP and biological effect were shown in our mouse model. The VPA and GBZ combination has already shown decrease of cell death mediated by ER stress in the Bbs12−/− model. This is an unmet clinical need with no curative treatment for retinal ciliopathies. The possibility of delaying PR death would increase the therapeutic window of gene therapy potentially increasing its effectivity.
Retinal oximetry as a biomarker in multiple sclerosis
Authors: Drobnjak Nes Dragana , de Rodez Benavent Sigrid A. , Berg‐Hansen Pål , Høgestøl Einar A. , Beyer Mona K. , Rinke Dan A. , Veiby Nina , Addorisio Vito , Petrovski Beata Eva , Celius Elisabeth G. , Harbo Hanne F. , Petrovski Goran 
Published: December 2019

AbstractPurposeStructural and physiological abnormalities have been reported in the retina in patients with multiple sclerosis (MS). Retinal oximetry has recently detected changes in retinal oxygen metabolism in Alzheimer’s disease, mild cognitive impairment and in a small cohort of MS patients with history of optic neuritis. Our goal was to determine whether oxygen saturation in retinal blood vessels of newly diagnosed MS patients is different from that of a healthy population.MethodsOxygen saturation of hemoglobin was measured in retinal blood vessels, using imaging with spectrophotometric non‐invasive retinal oximeter. Six newly diagnosed MS patients were measured and compared to six healthy individuals that were age‐ and gender‐matched with the MS patients.ResultsVenular oxygen saturation was increased in patients with MS compared to healthy individuals (mean: 61.9% versus 56.3%). Retinal venular diameter (138.2 µm versus 160.2 µm: mean) and retinal arteriolar diameter were smaller in MS patients (111.8 µm versus 131.3 µm: mean) when compared to healthy individuals. No big difference could be measured in the oxygen saturation in arterioles when patients with MS (mean: 91.2%) and healthy individuals (mean: 92.3%) were compared.ConclusionIncreased venular oxygen saturation and smaller retinal venular and arteriolar diameter in patients with MS may indicate reduced oxygen uptake in the retina. This may be due to less oxygen demand following axonal loss and may be a useful objective biomarker for MS. Further studies are needed to confirm and expand these findings.
Safety and effects of intravitreal or subretinal injections of human bone marrow‐derived mononuclear cells to P23H‐1 and RCS rats
Authors: Di Pierdomenico Johnny , González‐Herrero María Elena Rodríguez , Blanquer Miguel Blanquer , Ayuso Diego García , Barriuso Marta Agudo , Sanz Manuel Vidal , Pérez María Paz Villegas 
Published: December 2019

AbstractPurposeTo determine the safety and effects of intravitreal or subretinal injections of human bone marrow‐derived mononuclear cells (HBMNCs) in two different rat models of hereditary photoreceptor (FR) degeneration.Methods21‐days‐old Homozygous P23H‐1 albino rats, Royal College of Surgeons (RCS) pigmented rats or control SD and PVG rats received one intravitreal injection or one subretinal injection of HBMNCs (5µl; 50,000 cells/µl). As controls, intact animals of P23H‐1, RCS, SD and PVG strains were used. All animals were immunosuppressed with oral cyclosporine and intraperitoneal dexamethasone and were processed 7, 15, 30 or 60 days after transplantation. The eyes were cross‐sectioned in a cryostat and the sections immunodetected to visualize HBMNCs (□‐human CD45), photoreceptors (□‐Recoverin), astrocytes and Müller cells (□‐GFAP), or microglial cells (□‐Iba‐1). Sections were examined under fluorescence and confocal microscopy to investigate retinal structure and photoreceptor cell survivalResultsIn HBMNCs treated eyes no macro or microscopic anomalies, tumours, necrosis, inflammation or infective phenomena were observed. In the intravitreally injected eyes, HBMNCs‐CD45+ were found in the vitreous and attached to the inner limiting membrane. In the eyes with subretinal injections, HBMNCs‐CD45+ were found forming a layer in the subretinal space. When compared to control animals, the transplanted eyes of P23H‐1 and RCS rats showed decreased GFAP expression, indicating a reduction of gliosis. However, we did not observe increased photoreceptor survival in dystrophic animals after transplantation.ConclusionsHBMNCs injection to the vitreous or subretinal space in immunosupresed rats lack adverse effects and in P23H‐1 and RCS rats decrease the retinal gliosis but do not elicit photoreceptor neuroprotective effects.
Photo‐ablation of human vitreous opacities by light‐induced vapor nanobubbles
Authors: Sauvage Félix , Fraire Juan , Remaut Katrien , Sebag J. , Peynshaert Karen , de Velde Frans Van , Xiong Ranhua , Tassignon Marie‐José , Brans Toon , Braeckmans Kevin , De Smedt Stefaan 
Published: December 2019

AbstractPurposeFloaters are collagen aggregates that can form in the vitreous of the eye due to structural changes and which cast shadows on the retina. Current therapies are based on laser treatment with an yttrium garnet laser (YAG) or vitrectomy (i.e. the replacement of the vitreous by a saline solution) but most of the time, floaters are left untreated. Besides, the efficacy of YAG laser treatment is still controversial and vitrectomy can be associated with important side effects (cataract formation, endophthalmitis).MethodsIn this work we propose a nanotechnology‐based approach for the treatment of floaters using the plasmon properties of gold nanoparticles (AuNPs). When exposed to pulsed‐laser light (typically a nanosecond laser), AuNPs able to bind floaters, heat up and generate vapour nanobubbles (VNBs) due to the evaporation of the surrounding water. These VNBs will then burst providing sufficient mechanical energy to fragment floaters.ResultsTo maximize the probability of AuNPs to reach and bind floaters after intravitreal injection, we coated them with hyaluronic acid (HA‐AuNPs) and observed they had a better diffusion in vitreous and could bind and fragment collagen I fibers and human floaters obtained from patients. Since smaller AuNPs have a higher threshold to generate VNBs we hypothesized smaller HA‐AuNPs (10 nm), would be able to clusterize on the floaters to locally decrease the threshold to generate VNBs preserving the surrounding vitreous and ocular tissues from being damaged. With smaller particles we were able to destroy human vitreous opacities, in a fast and reproductive manner.ConclusionOur strategy can effectively and rapidly destroy floaters by using lower energy levels compared to current YAG therapy and paves the way for the use of pulsed‐lasers and nanotechnologies in the posterior segment of the eye.
Do macular OCT‐A measures correlate with functional outcomes in diabetic patients?
Authors: Bontzos Georgios , Garnavou‐Xirou Christina , Xirou Tina , Gkizis Ilias , Kabanarou Stamatina , Chatziralli Irini 
Published: December 2019

AbstractPurposeTo investigate the association between anatomic changes, as measured optical coherence tomography‐angiography (OCT‐A), and functional visual outcomes in diabetic patients.MethodsParticipants in this cross‐sectional study were 60 patients (60 eyes) with diabetes mellitus and 20 normal subjects (20 eyes). Patients underwent complete ophthalmologic examination, including staging of diabetic retinopathy (DR). Patients were divided in 3 groups: (i) diabetes without retinopathy (noDR); (ii) background retinopathy (NPDR) and (iii) proliferative retinopathy (PDR). Best‐corrected distance visual acuity (BCVA) was measured using ETDRS charts, while contrast sensitivity was evaluated with the Pelli‐Robson charts. Patients underwent OCT‐A to measure the area of FAZ (mm2) and the vessel density (%) at the macular and paramacular area.ResultsBCVA was 83.7 ± 5.3 for the healthy subjects and did not differ significantly compared to diabetic group (78.8 ± 10.6, p = 0.281). There was a statistically significant difference (p < 0.01) in contrast sensitivity between control(28.1 ± 3.4) and diabetic group (22.2 ± 6.7).In NPDR group, vessel density was reduced in the deep capillary plexus (mean = 21.4%). In the PDR group, vessel density was significantly reduced in the superficial (mean = 35.8%) and the deep (mean = 18.3%) capillary plexus. BCVA was significantly associated with FAZ area only in the PDR group (r = 0.61; p < 0.01), while contrast sensitivity was not associated with vessel dropout, nor with FAZ area in all groups.ConclusionsFunctional impairment related to contrast sensitivity may precede visual acuity decrease in diabetic patients. However, only BCVA and not CS recordings were significantly associated with OCT‐A measurements, such as FAZ area and vessel density in diabetic patients and mainly with proliferative disease. OCT‐A is a valuable tool for documenting early structural alterations in diabetic retina, which can be related to some functional visual parameters.
Using 3D simulation in reconstructive‐rehabilitation surgery in patients with defects in orbital walls
Authors: Petrenko Oksana , Prusak Olha 
Published: December 2019

AbstractIntroductionRestoration of the volume of the orbit and its integrity, elimination of aesthetic and functional complications in patients with defects in the walls of the orbit remains an urgent problem of ophthalmology and maxillofacial surgery.PurposeTo evaluate the results of surgical treatment of patients with defects in orbital walls using individually‐made implants using 3D modeling based on CT data.MethodsCT Toshiba Activion 16, CT Philips Diamond Select Brilliance CT 64, software environment Sim Plant 13.02 and Geomagic Freeform Plus, statistical data processing.ResultsAfter treatment of patients with orbital bone defects using individually‐made implants using computer 3D modeling based on CT data, the mean difference in orbital volume was 2.7 ± 0.9 cm3.ConclusionThe use of computer 3D modeling in the manufacture of individual implants for the treatment of patients with defects in the orbital walls increases the accuracy of the recovery of the orbital volume, and, accordingly, minimizes the number of postoperative complications.
Conjunctival melanoma is a molecular distinct mucosal melanoma with high expression of PD‐L1
Authors: Hjorth Mikkelsen Lauge , Maag Emil , Kruhøffer Mogens , Bjerre Toft Peter , Klarskov Andersen Mette , Wadt Karin , Larsen Ann‐Cathrine , Heegaard Steffen 
Published: December 2019

AbstractPurposeConjunctival melanoma is a unique mucosal melanoma due to its location in the sunexposed conjunctiva. The purpose of this study was to contextualize conjunctival melanoma as a mucosal melanoma based on molecular profiling. This is the first study of its kind.Material and Methods12 primary conjunctival melanomas and 28 primary mucosal melanomas from non‐sunexposed sites (nasal cavity, vagina, and rectum) were subjected to molecular profiling using targeted next‐generation sequencing (Oncomine Comprehensive Cancer Panel) and NanoString gene expression profiling (PanCancer Pathways Panel, 770 cancer genes). Normal conjunctiva and mucosa were used as internal controls.ResultsGenetically, conjunctival melanomas harboured BRAF‐V600E mutations and NF1 mutations, whereas other mucosal melanomas harboured more unspecific mutations, such as atypical BRAF mutations and mutations in KIT. Non‐sunexposed mucosal melanomas frequently presented amplification of MYC. When comparing the gene expression profile of conjunctival melanoma and non‐sunexposed mucosal melanoma, 41 genes were found to be significantly deregulated. 24 genes were upregulated, whereas 17 were downregulated in conjunctival melanoma. Many of the deregulated genes were involved in immunological pathways when performing an in silico pathway analysis. Most intriguingly, programmed death‐ligand 1 (PD‐L1) presented a significant 6‐fold upregulation in conjunctival melanoma. This finding could be validated with immunohistochemistry (p = 0.041, Fisher’s exact test). A network analysis revealed that PD‐L1 was co‐expressed with 8 other genes.ConclusionsComprehensive molecular profiling on the DNA and mRNA level revealed that conjunctival melanoma is a distinct molecular mucosal melanoma characterized by a higher frequency of BRAF‐V600E mutations, low expression of MYC and a high expression of PD‐L1 and other genes involved in immune response. This finding is important, as this suggests a higher response to checkpoint inhibition in conjunctival melanoma metastases when compared to other mucosal melanomas.
Significance of corneal rigidity at measuring of intraocular pressure
Authors: Shargorodska Iryna , Dziameshka Dziyana 
Published: December 2019

AbstractPurposeTo optimize tactics of determination of IOP for emmetropic and myopic eyes by application a correction to the coefficient on cornea rigidity (KER).MethodsThe 160 myopic and 80 emmetropic eyes were included in the study. All eyes were examined with the methods of the measuring of cornea rigidity in vivo (Sergienko N.M., Shargorodska I.V. 2013).ResultsThe results showed no dependence of cornea rigidity was educed from the cornea central thickness (r = 0.04) and sagital front‐back size of eyes for all inspected patients (r = 0.12). Cross‐correlation dependence between these indexes was statistically not reliable (p > 0.05). The results of analysis testified to high the degree of dependence of coefficient cornea rigidity from age and sex of patient (r = 0.53 and r = 0.59 accordingly, p < 0.05), refraction (r = 0.77, p < 0.05), spherical equivalent (r = 0.79, p < 0.05). The most strong cross‐correlation dependence was educed between KER and degree of curvature of cornea in a «steep» meridian (r = 0.78, p < 0.05), elevation of back cornea surface of (r= 0.93, p < 0.05) and exentrisite (r = 0.87).ConclusionThe cornea rigidity index are forward as an integral index that takes into account influence of different factors: age, sex, clinical refraction, spherical equivalent and others. Using of cornea rigidity index for measuring of level IOP will allow more exactly to estimate, removing influence of central cornea thickness on level IOP.ReferencesThe problem of study of biomechanics properties of cornea a long ago attracts attention researchers (Perkins E.S., 1981; Phillips J.R., 1990; Iomdina E.N., 2006; Svetlova O.V., 2010). The functional features of co‐operation of biomechanical properties of cornea with other eye regulator systems of eye can play substantial influence on exactness to measuring of ophthalmotonus (Young F.A., Leary G.A., 1991; Koshitz I.N., 2001).
Contact lens and eye glass wearers with and witouth ocular symptoms: differences in corneal sensitivity, blinking, tearing and corneal surface temperature
Authors: Pastor‐Zaplana José Ángel , Gallar Juana , Acosta M. Carmen 
Published: December 2019

AbstractPurposeTo analyze corneal sensitivity, blink frequency (BF), tearing rate (TR), TBUT, and corneal surface temperature (CST) in young contact lens (CLs) and eye glass (EGs) wearers with and without ocular discomfort symptoms.MethodsEGs (n = 18) and CLs (n = 23) young subjects (18–40 years old, both sexes) participated voluntarily. CLs were classified as asymptomatic (A) or symptomatic (S) depending on their OSDI score (< 13 or ≥ 13, respectively). Corneal sensitivity to mechanical and chemical air puffs (3s duration, applied with a gas esthesiometer) and cold (4°C) saline drops was explored. Sensations evoked by each stimulus was scored with 0 to 10 VAS. BR (1 min at rest or during a task), TR (mm of wet phenol red threads, 15 s), TBUT (s), and CST (IR video thermography) were also measured.ResultsVAS values of irritation sensation evoked by mechanical and chemical stimulation (p < 0.05) were higher in CLs than in EGs while VAS values of cold sensation evoked by saline drops were similar in both groups. Although CST and TR were similar in EGs and CLs, TBUT was significantly shorter (p < 0.001) and BR was higher in CLs both at rest (p < 0.001) and during a visual task (p < 0.01). Although VAS values scored to corneal mechanical, chemical and cold stimulation were lower in CL‐S than in CL‐A, no differences were found in BR at rest or during the task, TR, TBUT and CST. Corneal sensitivity and CST were also similar in EG‐A and EG‐S, although TR (p < 0.05) and BF at rest (p < 0.05), but not during the task, were higher in EG‐S.ConclusionsResults show a reduced corneal sensitivity in symptomatic CL wearers, which suggests that corneal sensory nerve activity must be altered in a different degree in asymptomatic and symptomatic individuals, thus leading to changes in tearing and blinking regulation.Support: AEI‐ERDF SAF‐2017‐83674‐C2‐1‐R and 2‐R
Environmental light intensity determines the temporal progression of retinal degeneration in rd10 mice
Authors: Kutsyr Oksana , Sánchez‐Sáez Xavier , Albertos‐Arranz Henar , Maneu Victoria , Lax Pedro , Cuenca Nicolás 
Published: December 2019

AbstractThe rd10 mouse is a model of autosomal recessive retinitis pigmentosa (RP). This animal model carries a mutation in the Pde6b gen that generates a progressive loss of photoreceptors which leads to complete blindness. The aim of this study was to evaluate the effect of environmental light intensity on the degenerative process of the rd10 model. Three rd10 mice groups have been exposed from birth to P30 to different environmental light intensities: low (5 lux), medium (50 lux) and high (300 lux) intensity. Age‐matching C57BL/6J mice were used as controls. At the end of the experimental procedure, retinal function was assessed by electroretinography (ERG) and optomotor test. In addition, OCT images, hematoxylin staining, and immunohistochemistry were performed to analyze the structural integrity of the retinas of the three experimental groups. The rd10 mice housed at 5 lux intensity showed better functional response that the rd10 mice maintained at 50 or 300 lux, exhibiting significantly higher amplitudes in a‐ and b‐waves, as well as higher visual acuity. In the same line, the rd10 mice at 50 lux presented higher responses than the mice at 300 lux. Furthermore, the thickness of the ONL showed differences between the three rd10 groups. As the light intensity is lower, the thickness of the measured ONL is greater. These findings correlated with the morphology of the cones where better‐preserved photoreceptor morphology was found in the dystrophic animals housed at 5 lux. No significant differences were found between normal C57BL/6J animals kept at different light intensities. Environmental light intensity accelerates or delays the degeneration in rd10 mice. These data indicate that light intensity is a key factor to consider in studies carried out in retinal degenerative animal models, determining the temporal progression of the disease.MINECO‐FEDER BFU2015‐67139‐R, RETICS‐FEDER RD16/0008/0016, Prometeo 2016/158, ACIF/2016/055, FPU16/04114.
Uveitis and immune checkpoint inhibition: when a blockage isn’t just a blockage
Authors: Potvin Arnaud , Rottey Sylvie , Geldhof Kurt , Demedts Ingel , De Zaeytijd Julie , De Schryver Ilse 
Published: December 2019

AbstractPurposeTo report uveitis triggered by immune checkpoint inhibition.MethodsRetrospective analysis of 5 charts of patients with metastatic cancer on immunotherapy.ResultsFive male patients, mean age 68.4 years, received immune checkpoint inhibition (pembrolizumab n =1, nivolumab n = 2, ipilimumab+nivolumab n = 2) with a mean duration of 2.05 months before onset of ocular symptoms. The primary malignancies were two cutaneous melanomas, a NSCLC, an oesophageal adenocarcinoma and an urothelial carcinoma of the bladder. Two patients presented with a bilateral acute anterior uveitis (AU) with fine keratic precipitates, anterior chamber (AC) cells grade 1+ (Standardization of the Uveitis Nomenclature), no posterior synechiae and no other abnormalities on dilated fundus examination and sd‐OCT. Two other patients presented with a bilateral panuveitis with AC cells 2+, vitreal cells and serous retinal detachments in the posterior pole. One patient showed serous retinal detachments in the posterior pole without AC or vitreal cells. The cases with AU responded to topical steroids with clinical remission within 4 weeks. Topical treatment failed to control the cases with panuveitis. Systemic steroids were successfully added. Nonetheless, checkpoint inhibition needed to be discontinued in all cases with serous retinal detachments.ConclusionsCheckpoint inhibition is a promising new treatment for metastatic cancer. Several adverse effects of immunotherapy have been reported, including uveitis. In the two cases with AU, immunotherapy was continued after therapeutic response to topical steroids. Checkpoint inhibition needed to be discontinued in the three cases with serous retinal detachment despite treatment with systemic steroids. Although AU is the most common ocular side effect, serous retinal detachment can be related to checkpoint inhibition in very rare cases.
EU COST Action ANIRIDIA‐NET: A new, inclusive pan‐European network for aniridia research
Authors: Lagali Neil 
Published: December 2019

AbstractCongenital aniridia is a rare but devastating pan‐ocular disease resulting from mutations in the PAX6 gene causing under‐ or mis‐developed ocular structures and serious vision impairment or blindness. Aniridia is often associated with early development of cataract, glaucoma, and a keratopathy originating from a progressive limbal stem cell insufficiency. Recently new diagnostic, genetic and molecular methods have become available and are for the first time being applied to better characterize aniridia with the hope of developing more effective treatments to improve vision in this underserved population. In parallel, more detailed phenotypic and genetic studies are being undertaken to examine individuals and cohorts with aniridia, with new information rapidly advancing our understanding. Patients and advocacy associations are becoming better informed and engaged in their medical care, while also supporting and promoting research. To bring together the various existing efforts to understand, manage, and treat aniridia, and to develop harmonized approaches for addressing some of the most difficult challenges, a new EU COST Action ANIRIDIA‐NET (2019‐2023) has just been established. This pan‐European network is open and inclusive, and to date participants from over 20 European countries have joined. Here, a brief description of the network, its planned goals and activities, and opportunities for interested researchers and practitioners to participate will be presented.