bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the efficacy of the tissue regenerating agent (RGTA) 0.01% poly‐carboxymethylglucose sulfate in the treatment of neurotrophic corneal ulcers and persistent epithelial defects
Authors: Del Buey M.A. , Casas P. , Caramello C.M. , Esteban O. , Martinez M. , Sánchez N. , Pinilla I. , Lanchares E. 
Published: September 2015

PurposeTo report the results obtained in a series of 58 eyes with chronic corneal ulcers and persistent epithelial defects resistant to conventional therapy and treated with 0.01% poly‐carboxymethylglucose sulfate based on tissue regenerating agent technology (RGTA, Cacicol®).MethodsA prospective study was made of 58 eyes. The ulcers were essentially chronic and slow‐evolving, with mean vertical and horizontal diameters of 2.4 and 2.7 mm, respectively (range 1‐5.5 mm). The patients received an initial dose of one drop every 48 hours during 10 days. After evaluation of the effects of treatment, new dosing schemes were prescribed for those patients who had improved their clinical condition though without complete resolution of the disease.ResultsImportant variation was observed in the time to recovery of corneal integrity, ranging from a few days to some weeks, depending on the severity and etiology of the case. Full healing was recorded in 50 patients. The patients with large neurotrophic ulcers showed improvement of the lesions, with a decrease in lesion size after 15 days of treatment. All patients reported subjective improvement. The drug showed immediate efficacy in 11 eyes with epithelialisation disorders following PRK or trauma, with recovery of tissue integrity after the first treatment period.ConclusionsThe tissue regenerating agent (RGTA Cacicol®) is an interesting and effective topical adjuvant product for the treatment of severe and chronic corneal ulcers resistant to conventional treatment. Its efficacy remains to be confirmed in the context of double‐blind, randomised clinical trials.
Immediate Effect of Ultraviolet‐A Collagen CXL Therapy on Biomechanics and Histology of Human Cornea
Authors: Del Buey M.A. , Lanchares E. , Calvo B. , Lavilla L. , Almenara C. , Pérez I. , Idoate A. , Pinilla I. , Ascaso J. , Cristobal J. 
Published: September 2015

PurposeTo evaluate the immediate effect of the CXL treatment on the biomechanical properties and histological microstructure of healthy human corneal tissue. With this purpose, in vitro mechanical tests and histological observation of cross‐linked and untreated human corneal tissue were performed.MethodsMechanical tensile test and histological analysis were performed in de‐epithelialized healthy human corneal tissue treated with riboflavin solution (0.01% riboflavin‐5‐phosphate and 20% dextranT‐500) – 30 min UVA irradiation (treated sample TS). A similar study was performed to untreated de‐epithelialized healthy human corneal tissue (control sample, CS). Both histological and mechanical analyses were performed immediately after treatment.ResultsThe analysis of the stress‐strain curves showed a different corneal response between treated (TS) and untreated (CS) samples. TS showed a stiffer behaviour than CS. The treated corneal tissue (TS) resulted 1.8, 1.6, 1.7 and 1.5 fold stiffer than the untreated sample (CS) at 6, 8, 10 and 12% stretch, respectively. The histological analysis of TS showed an increased fibrillar density with decrease of interlamellar space in comparison with CS. Keratocyte apoptosis was observed in TS even at deep stromal level.ConclusionsThe UVA‐induced CXL has an immediate biomechanical and histological effect over the treated healthy human corneal tissue. Stiffening of the tissue, keratocyte apoptosis and stromal compacting were observed.
Generic Drugs‐ are they as good as brand‐names?
Authors: Kolko M. , Ali N. , Jensen P.K. 
Published: September 2015

PurposeThe aim of the present study was to investigate different characteristics of six Latanoprost generics.MethodsPrize, drop size and volume in each generic were determined. The hardness of each bottle was further evaluated using a fish weight and a hook. Finally, pH was measured and the buffer capacity evaluated by addition of NaOH.ResultsPrice, drop size and volume varied significantly between the brand version (xalatan) and the generic latanoprost products. Hence, drops sized were in the range 40–47 µl and the number of drops in each generic bottle varied between 95 and 111 drops. The embalages of each latanoprost product were different in both size and hardness. The control value of pH in the brand version (Xalatan) was 5.99 ± 0.01 (mean ± SD), whereas the generic latanoprost products had significantly higher values within the range 6.70–6.82. Hence, titration of 2.5 µl Xalatan to neutrality required 70.4 ± 0.4 nmol NaOH compared to the generic latanoprost products which required within the range 28.1–33.7 nmol NaOH.ConclusionsThe present study identifies differences among latanoprost generics such as different pH values and different buffer capacities. Moreover, the emballages varies significantly, thereby leading to critical variations in the handling of the generics. Finally, the number and size of drops in each generic were different, not to mention the prize variations between the brand version and the generics. Over all, generic eye drops should not be considered identical. Therefore, re‐evaluation of the requirements for introducing generic drugs seems reasonable.
Study of XAILIN HA Physical Properties versus Marketed Hyaluronate Based Ocular Lubricants
Authors: Pilotaz F. ,  Saldo J. ,  Boix M. 
Published: September 2015

PurposeXailin HA is a multi‐dose lubricating eye drop for alleviating symptoms of moderate to severe dry eye sensations. It contains sodium hyaluronate (HA) 0.2% w/w and sodium perborate in aqueous buffered vehicle. Perborate is a disappearing preservative that turns into water and oxygen upon contact with the ocular surface.Comparative studies were performed with Xailin HA against other EU marketed HA products in order to assess its key physical properties.MethodsThe parameters studied were the following: Macroscopic appearance, pH, osmolality, viscosity at 25°C, drop size and surface tension. The marketed products assessed in this study were: Xailin HA, Vismed multi, Hyabak, Hyalistil, Optive Fusion, Hylo‐Comod, Hylo‐vision HD, Artelac Splash MDO, Hylo‐Gel.ResultsAll products are clear and colourless and their pH range is between 6.8 and 7.4. The tested products remain in the common range of osmolality for topical ophthalmic forms except Vismed multi (hypotonic, 150 mOsm/kg). Xailin HA presents the next lower osmolality (260 mOsm/kg). Four categories from less to more viscous products are observed: (i) Hyabak and Hylo‐Vision (ii) Artelac Splash MDO, Hyalistil, Optive Fusion, Hylo‐Comod and Vismed Multi (iii) Xailin HA (iv) Hylo‐Gel Xailin HA is significantly different from all others products with the lowest surface tension recorded.ConclusionsXailin HA is a new hyaluronan‐based ocular lubricant. Its low surface tension property should reflect a better distribution and spreading capacity on corneal surface than the other marketed products tested.
Optical Coherence Tomography and Fundus Autofluorescence evaluation in an animal model of Retinal Degeneration
Authors: Segura F. , Fernandez‐Sanchez L. , Sánchez‐Cano A. , Tamarit J.M. , Fuentes‐Broto L. , Del Buey M. , Cuenca N. , Pinilla I. 
Published: September 2015

PurposeTo evaluate fundus autofluorescence (FAF) and OCT changes comparing with immunohistochemical (ICC) analysis in long term degeneration of P23H rat and to investigate retinal and choroidal vascularization using fluorescein and indocianin green angiography.MethodsTwenty‐albino homozygous P23H line 1 rats aging from 18 postnatal days (P18) to 27 months and wild‐type albino Sprague‐Dawley (SD rats) (2 and 15 months old) were used for this study. Normal pigmented Long Evans (LE) 2 months old rats were used to compare FAF findings. ICC was performed to correlate with the findings of OCT and AF changes.ResultsFAF pattern varied from not findings at P18 to a mosaic of hyperfluorescent dots in the rats of 6 months or older. Retinal thicknesses diminished during the time: 205.2–183.18 μm in SD rats and 189.88–58.15 μm in P23H rats. In long term degeneration, OCT showed severe changes at the retinal layers; ICC helped to identify the cell loss and remodeling changes.ConclusionsAutofluorescent ophthalmoscopy is a non‐invasive method that can detect changes in metabolic activity at the RPE in animal models of retinal degeneration in vivo. Retinal vascular plexus changed with aging. OCT showed a diminution of retinal thickness and retinal layer changes with the degeneration. ICC shows a good correlation.
Assessment of corneal layers thickness with spectral‐domain optical coherence tomography
Authors: Segura F. , López de la Fuente C. , Sáchez‐Cano A. , Orduna E. , Del Buey M. , Pinilla I. 
Published: September 2015

PurposeTo assess the corneal layers thickness in healthy young adults using spectral‐domain anterior segment optical coherence tomography (AS‐OCT).MethodsThere were 86 eyes of 86 healthy volunteers, 55 females and 31 males, which were included in the study. The mean age ± standard deviation (SD) was 22.87 ± 3.90 years (range, 20–43). Spectral‐domain AS‐OCT was performed using Spectralis OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). Measurements of central corneal thickness, and central thickness of epithelium, Bowman's layer, stroma and the complex Descemet‐endothelium were performed.ResultsMean central corneal thickness, epithelium, Bowman, stroma and Descemet‐endothelium were 555.50 ± 29.64 µm (range 510–624), 54.60 ± 4.25 µm (range 45–63), 16.70 ± 1.73 µm (range 14–20), 467.51 ± 28.91 µm (range 420–533) and 16.74 ± 1.66 µm (range 14–20), respectively.ConclusionsSpectralis OCT can be easily used to non‐invasive measurements of the anterior segment parameters and this study establishes a normal database for corneal thickness and all its layers in healthy young adults.
Intravitreal Aflibercept (IVT‐AFL) for Diabetic Macular Edema (DME): 3 Year Data from VIVID‐DME and VISTA‐DME
Authors: Staurenghi G. , Metzig C. 
Published: September 2015

PurposeTo evaluate long‐term outcomes with IVT‐AFL injection in the treatment of DME.Methods406 patients (VIVID‐DME) and 466 patients (VISTA‐DME) were randomized to IVT‐AFL 2 mg every 4 weeks + sham laser (2q4), IVT‐AFL 2 mg every 8 weeks (after 5 initial monthly doses) + sham laser (2q8), or laser + sham injections. From week (W)100 to W148, laser patients could receive IVT‐AFL if retreatment criteria were met. Primary efficacy endpoint was the mean change from baseline (BL) in best corrected visual acuity (BCVA) at W52. Outcomes at W100 and W148 are described.ResultsAt W100, mean BCVA gains from BL in the IVT‐AFL 2q4, 2q8 and laser groups were +11.4, +9.4 and +0.7 letters (VIVID‐DME; P < 0.0001), and +11.5, +11.1 and +0.9 letters (VISTA‐DME; P < 0.0001). In VISTA‐DME, improvements in BCVA were maintained to W148 in the IVT‐AFL 2q4 (+10.4 letters) and 2q8 (+10.5 letters) groups. Cataract was the most frequent ocular serious AE in both studies through 100 weeks (VIVID‐DME: 2.2%; VISTA‐DME: 1.3%); incidence of Antiplatelet Trialists’ Collaboration‐defined arterial thromboembolic events with IVT‐AFL was similar across the studies (VIVID‐DME: 4.8%; VISTA‐DME: 7.8%). Safety outcomes at W148 in VISTA‐DME were consistent with W100 data with no new safety signals observed. The third year of VIVID‐DME is ongoing.ConclusionsIn both studies, IVT‐AFL demonstrated superior outcomes compared with laser through W100, with similar efficacy in the 2q4 and 2q8 groups. In VISTA‐DME, BCVA gains from BL with both IVT‐AFL regimens were sustained through W148. Through 100 weeks the incidence of AEs was consistent with the known safety profile of IVT‐AFL.
Lactate transport and receptor actions: Potential roles in inner retinal function and disease
Authors: Vohra R. , Vosborg F. , Henriksen U. , Gurubaran I.S. , Hasan‐Olive M. , Holm E. , Skytt D. , Gjedde A. , Storm‐Mathisen J. , Kolko M. , Bergersen L.H. 
Published: September 2015

PurposeIn the brain and in adipose tissue activation of the lactate receptor GPR81 is known to promote downregulation of cAMP. Lactate is hereby involved in excitability, metabolism and inflammation. Neurodegenerative diseases in retina may in a similar manner be linked to disturbed lactate homeostasis.MethodsqPCR was performed on retina and brain extracts to investigate whether the lactate receptor GPR81 is expressed in the retina. Immunocytochemistry was performed on primary cell cultures of Müller cells (MC) and retinal ganglion cells (RGC) from mice to evaluate the presence of lactate receptors in neuronal and glial cells in the retina. Lactate assays were made to show the changes in lactate concentrations during different conditions of stress.ResultsGPR81 mRNA was twice as high in retina as in hippocampus or cerebral cortex. Immunocytochemistry indicated lactate receptors in both RGC and MC. Lactate assays showed a decreased release of lactate from MC upon energy restriction. Interestingly, the combination of inhibited mitochondrial function and energy restriction significantly increased the amount of released lactate.ConclusionsThe presence of lactate receptors in the retina as well as the changed levels of lactate in response to stress support the suggestion that lactate could be of great importance in retinal homeostasis and as such in the pathogenesis of inner retinal diseases.
Anatomical digital image analysis of the angle and optic nerve – a novel method for glaucoma imaging
Authors: Russell G. , Szabó Á. , Sziklai P. , Facskó A. , Kolko M. , Petrovski G. 
Published: September 2015

PurposeTo devise a simple, fast and low‐cost method for glaucoma imaging using anatomical digital image analysis of the angle and optic nerve in human subjects.MethodsA pilot study included 10 open‐angle glaucoma patients attending the glaucoma services at the Department of Ophthalmology, University of Szeged, Hungary; colour photographs of the fundus, standard optic nerve images with OCT and additional digital slit lamp images of the angle where collected. Digital image conversion and analysis of the angle using Image J (NIH, USA) and adaptive histogram equalization Contrast Limited AHE (CLAHE) to prevent noise amplification. Angle and optic nerve images, were analyzed separately in the Red, Green and Blue (RGB) channels, then 3D volumetric analysis of the degrees of angle, cup volume of the optic nerve took place. Horizontal tomogram reconstitution and nerve fiber detection methods were developed and compared to a standard Topcon 3D OCT.ResultsAngle measurements from digital angle images by gonioscopy all fitted within one standard deviation of Anterior OCT measurements. Comparative analysis of RGB channels produced volumetric cup and Horizontal tomogram results closely resembling those of OCT 3D appearance and B‐scan of the cup, respectively. Similar RGB channel splitting and image subtraction produced a map closely resembling that of the thickness RNFL map on OCT.ConclusionsWhile spectral domain OCT is rapidly progressing in the area of optic disc and chamber angle assessment, rising health care costs and lack of availability of the technology, opens demand for alternative forms of image analysis of glaucoma. Volumetric, geometric and segmentational data obtained through digital image analysis correspond well to those obtained by high definition OCT imaging. A larger number of subjects is needed to further validate the method.
Eyelid disorders evaluation in the Ophthalmic current practice in Belgium, Denmark, France, Netherland, Portugal and Turkey: The Meibum Study
Authors: Diaz Valle D. , Doan S. , Yagmur M. , Benitez del Castillo J.M. 
Published: September 2015

PurposeTo determine the incidence and characteristics of eyelid inflammatory disorders during general ophthalmological consultations and to demonstrate the association between palpebral pathologies and ocular surface pathologies in 6 of the 9 European countries involved in the MEIBUM survey.MethodsMulti‐center, international, transversal and epidemiological survey. The primary objective was to assess the percentage of eyelid disorders in patients attending a current ophthalmologic consultation. The secondary objectives were to assess the association between palpebral pathologies and ocular surface pathologies, the impact of eyelid disorders on patient's daily life (on vision, on daily life activities/work, on leisure, on contact lens wearing, on emotions and on sleep).ResultsA total of 1398 were included by ophthalmologists from Belgium, Denmark, France, Netherland, in Portugal and Turkey.The mean age was 56.2 (±17.5). At least an ocular history was found in 78.4% of the patients. The main antecedents were “Dry eye” (25%), “Glaucoma” (15.7%) and “Cataract” (19.8%). The percentage of eyelid disorders was 73.4%. The diagnostic of Meibomian Gland Dysfunction (MGD) was established in 45.4% of the total patients and dry eye in 63.4%. The impact of MGD on daily life was mainly on vision for 60.2% of the patients, on daily activities/work (49.7%), on leisure (40.8%), but also on emotions (22.1%) and sleep (15.8%). MGD were treated by eyelid hygiene recommendations: warming (68.5%), massaging (67.7%) cleansing (78.9%), and eye drops for dry eye (79.5%).ConclusionsMGD was diagnosed in nearly half of the patients with a strong link to dry eye. The impact on daily life is notable. Only dry eye symptoms seem to be taken in charge more often than MGD.
Combination of Resveratrol with omega‐3 fatty acids synergize to counteract VEGF‐R pathway in sick retinal pigment epithelium cells mimicking AMD
Authors: Chalons P. , Scagliarini A. , Courtaut F. , Olmière C. , Delmas D. 
Published: September 2015

PurposeThe aim of this work is to assess whether RSV (Resveratrol) can act synergistically with omega‐3 fatty acids to modulate VEGF (Vascular Endothelial Growth Factor) signaling pathway in order to identify a new and more effective therapy for the treatment of AMD (Age‐Related Macular Degeneration).MethodsIn this study, undifferentiated and differentiated human retinal pigment epithelial cells (ARPE‐19) were used. The cells were treated with an omega‐3/RSV preparation (Resvega®), or a RSV‐free formulation or RSV alone for 24 h. The expression of key proteins in VEGF signaling pathway was evaluated by Western Blotting.ResultsWe observed that the combination omega‐3/RSV preparation (Resvega®) induces a stronger inhibition of the VEGF‐R pathway activation than the RSV‐free formulation or RSV alone in sick retinal cells. Surprisingly, Resvega® maintains and increases the functional VEGF‐R pathway in normal retinal cells.ConclusionsThis work brings a new insight into the mechanism by which omega‐3/RSV could counteract AMD and could protect the other eye when AMD is already present.Financial Support: This work is supported by Théa laboratory.
Effects of recurring intraocular pressure elevations on the retina and the autoimmune component
Authors: Teister J. , Gramlich O. , Neumann M. , Tao X. , Pfeiffer N. , Grus F. 
Published: September 2015

PurposeIn glaucoma, complex changes of IgG serum autoantibody (Aab) repertoire highlight the possible contribution of an autoimmune component in the pathogenesis of this neurodegenerative disease. An elevated intraocular pressure (IOP) and its fluctuations are considered as major risk factors. The aim of the study was to identify the systemic influence of fluctuations using recurring pressure peaks and drops in a glaucoma animal model.MethodsSedated male Long Evans rats experienced a unilateral, intermittent IOP manipulation using a silicone loop adjusted around the eye globe for 1 hour during 27 treatments. The pressure profile included pressure peaks to 35 and 45 mmHg and drops to a physiologic value of 8 mmHg. Contralateral (n = 12) and untreated eyes (n = 14) served as controls. Neurodegeneration was determined after paraphenylenediamine staining and Brn3a staining. Microglia activation was identified after Iba1 staining in retinal cross‐sections. Changes of serum immunoreactivities were identified using a microarray approach with a glaucoma‐specific antigen Setup.ResultsA loss of axon density (as axons/0.05 mm2) of treated eyes (19624 ± 1709) compared to contralateral (21943 ± 1510; p < 0.01) and untreated eyes (22267 ± 1408; p < 0.01) occured, which was confirmed by retinal ganglion cell count. Next to an activation of microglia, upregulated Aab reactivities for GST, transferrin, and NSE were identified in serum of treated animals in comparison to control serum.ConclusionsThis animal model including pressure peaks and drops allows the establishment of individual IOP profiles. The retina and the optic nerve sustained a significant damage and an altered autoimmune repertoire could be induced. A significant influence of recurring pressure fluctuations could be demonstrated using this sophisticated glaucoma animal model.
Corneal nerve activity during ocular inflammatory processes
Authors: Luna C. , Quirce S. , Belmonte C. , Gallar J. , Acosta M.C. 
Published: September 2015

PurposeTo study the changes in sensory nerve activity of the eye associated with ocular inflammation in two different experimental models developed in the guinea‐pig.MethodsAllergic keratoconjunctivitis (AK): Ovalbumin sensitization was induced and blinking and tearing rate was measured before and after the allergic challenge. UV photokeratitis: One eye of the anesthetized guinea‐pig was exposed to 254 nm radiation during different times. Blinking rate and tear secretion were measured before and 48 h after UV. In both models, nerve activity was recorded in vitro in the whole eye or the excised cornea superfused with physiological saline at a controlled temperature. Spontaneous (SA) and stimulus‐evoked electrical activity were recorded. Mechanical, thermal and chemical sensitivity were tested in control and inflamed eyes.ResultsIn AK model tearing and blinking rate increased significantly. In nociceptors, mechanical threshold decreased, the percentage of units with SA increased and the impulse response to chemical stimulation increased significantly in inflamed eyes compared with controls. On the contrary, SA and response to cold of cold thermoreceptors decreased during inflammation.ConclusionsIn ocular pathological processes primarily characterized by local inflammation, nociceptors became sensitized while cold thermoreceptors became desensitized, due to changes in the expression and/or activity of ion channels present in sensory nerve terminals. Disbalance in the sensory input from the different functional types of sensory nerve fibers innervating the ocular surface in inflammatory conditions may be in the bases of the unpleasant sensations evoked by inflammatory pathological processes affecting the ocular surface in humans.