bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corneal surface temperature and tear secretion in young and adult aqueous tear deficient guinea pigs
Authors: Gallar J. , Luna C. , Alonso E. , Revert R. , Quirce S. , Aracil A. , Belmonte C. , Acosta M.C. 
Published: September 2015

PurposeTo evaluate changes in ocular surface temperature and tear secretion in young and adult control and tear‐deficient (DE) guinea‐pigs.MethodsTearing rate (TR) was measured using phenol red threads (30s). Tear break‐up time (TBUT) was measured after fluorescein instillation. Corneal surface temperature (CST) was recorded continuously in the full open eye during 30s after the eye opening using an infrared thermal camera (InfRec R300SR, Nippon Avionics). Images were analyzed using dedicated software.ResultsTearing rate was significantly higher and TBUT was significantly lower (p < 0.05) in adult (12‐18 months) compared with young (2‐4 months) animals (p < 0.001). CST immediately after the eye opening had a value around 36.5°C in control eyes in young and adult animals. Most tear deficient eyes had initial CST over 37°C. The slope of temperature decrease during the interblink period was similar for all ages. As expected, DE animals had significantly lower TR (p < 0.001) and TBUT (p < 0.01) than intact animals, although their initial CST and the slope of interblink temperature decrease were similar to age‐matched control eyes.ConclusionsTear‐deficient eyes show higher CST values immediately after blink suggesting the presence of inflammation. Temperature reduction during the interblink period was not modified in DE, despite the reduced stability of tear film.
Insulin‐induced dilatation of porcine retinal vessels in vitro is most pronounced in precapillary arterioles
Authors: Jensen P.S. , Bek T. 
Published: September 2015

PurposeImpaired retinal blood flow is involved in the pathophysiology of diabetic retinopathy, and it has been shown that the smaller and larger retinal vessels may contribute differently to these flow changes. Diabetes mellitus is accompanied with changes in a number of metabolic parameters including a reduced effect of insulin. However, the vasoactive effects of insulin on retinal vessels with different calibers have not been studied in detail.MethodsPorcine hemiretinas were mounted in a newly established experimental model specifically developed for studying diameter changes of retinal vessels with different caliber. Changes in the diameter of larger arterioles (25 μm or larger), pre‐capillary arterioles (10‐25 μm) and capillaries (smaller than 10 μm) were studied after intravascular and extravascular addition of insulin in retinal vessels preconstricted with the prostaglandin analogue U46619 from altogether 6 hemiretinas from different animals.ResultsInsulin dilated preconstricted arterioles and pre‐capillary arterioles significantly after both intravascular and extravascular application (p < 0.01 for all comparisons), but had no significant effect on the diameter of capillaries after intravascular (p > 0.07) and extravascular (p > 0.31) application. The dilating effect of insulin was significantly more pronounced for pre‐capillary arterioles than for the two other vessel types after extravascular application (p < 0.01).ConclusionsInsulin dilates preconstricted retinal vessels, but the effect is most pronounced in pre‐capillary arterioles. This may have importance for understanding disturbances in retinal blood flow in diabetic retinopathy.
The Effect of Ikervis® (1 mg/mL Ciclosporin cationic emulsion) on severe keratitis in patients with dry eye disease participating in a phase III study
Authors: Leonardi A. , Labetoulle M. , Ismail D. , Garrigue J.S. , Rancho L. , Brignole‐Baudouin F. , Amrane M. , Baudouin C. 
Published: September 2015

PurposeThe treatment of severe keratitis in Dry eye disease (DED) represents a real therapeutic challenge. The effect of Ikervis®, an unpreserved 1 mg/mL ciclosporin A cationic emulsion, in this condition was evaluated.MethodsSansika study was a 12 month phase III, multicenter, double‐masked, vehicle controlled, in which 246 DED patients with severe keratitis (corneal fluorescein staining, CFS, grade 4 on modified Oxford scale), were randomised to one drop of Ikervis® or vehicle daily at bedtime for 6 months. Vehicle patients switched to Ikervis® after 6 months.ResultsThe proportion of patients achieving by M6 at least a two‐grade improvement in CFS and a 30% improvement in symptoms [Ocular Surface Disease Index (OSDI)] was 28.6% with Ikervis® vs 23.1% with vehicle, p = 0.326. There was a greater improvement in Ikervis® treated patients over vehicle in mean CFS change from baseline (CFB) at M6 (−1.81 vs −1.48, p = 0.037). The mean OSDI CFB was −13.6 with Ikervis® and −14.1 with vehicle at M6, p = 0.858. There was a reduction in the ocular surface inflammation assessed with Human Leukocyte Antigen‐DR (HLA‐DR) expression in favour of Ikervis® at M6 (p = 0.021). Post hoc analysis showed a greatest proportion of patients achieving a 3‐grade improvement in CFS with Ikervis® over vehicle (28.8% vs 9.6%) at M6.ConclusionsThis study confirmed the positive benefit/risk ratio of Ikervis® for the treatment of severe keratitis in DED. The availability in Europe of Ikervis® represents a significant progress in the management of this disease.
Treatment of peripheral exudative hemorrhagic chorioretinopathy by intravitreal injections of Aflibercept: report of 4 cases
Authors: Malcles A. , Russo A. , Agard E. , El‐Chehab H. , Dot C. 
Published: September 2015

PurposePeripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare disorder characterized by subretinal or sub‐pigment epithelial hemorrhage and exudation localized outside the macular region.Some authors consider PEHCR as the peripheral version of age‐related macular degeneration while others believe PEHCR is a specific variant of polypoidal choroidal vasculopathy (PCV).MethodsWe report 4 cases of PEHCR (3 women and 1 man) treated by intravitreal injections of Aflibercept. The mean age was 78 years (range 62–83 years). In all cases the presence of PCV was confirmed with indocyannine green angiography. Examination revealed peripheral subretinal or sub‐pigment epithelial hemorrhage with exudation extented into the macula in all patients. After 2 or 3 intravitreal injections of Aflibercept, PEHCR lesions and submacular exudation significantly regressed.ResultsGenerally PEHCR has a favorable prognosis, hovewer vision can be threated because of subretinal hemorrhage and fluid extension into the macula. In cases in which the macula appears threatened, intravitreal antivascular endothelial growth factor therapy and/or laser‐based therapies may be indicated. Peripheral lesion can be difficult to reach with photodynamic therapy. Intravitreal Aflibercept, with its mechanism of action, may be an effective treatment option to reduce subretinal fluid.ConclusionsPEHCR is not well‐recognized by the ophthalmologist and is often misinterpreted as a choroidal melanoma. To our knowledge this is the first report of Aflibercept use and efficacy in this indication.
3D Sphere cultures of uveal melanoma reveal a molecular signature with a potential target for cancer therapy
Authors: Ness C. , Garred Ø. , Eide N. , Bærland T. , Nicolaissen B. , Moe M. , Noer A. 
Published: September 2015

PurposeUveal melanoma (UM) is the most common intraocular malignancy and is fatal in approximately 50% of the cases. Cancer relapse can be seen years after treatment. Diverse mechanisms have been proposed to explain the late relapse of UM e.g cancer dormancy and the presence of cancers stem cells (CSCs). UM has the disadvantage of being difficult to culture, thus a limited number of cell lines are available. 3D sphere cultures of early passages offer a lower degree of clonal selection and perhaps a more accurate reflection of the primary tumours. The propagation of cells as spheres is believed to enrich for a CSC‐like population.Methods2D cultures were expanded in RPMI 1640 with 10% FBS, while 3D sphere cultures were expanded in hESC + MEF for 7–10 days.We compared UM primary tumours fresh frozen vs. 2D culture and 3D sphere culture of the same donors by microarray, qRT‐PCR, transmission electron microscopy (TEM), immunohistochemistry (IHC) and chromatin immunoprecipitation (ChIP).Results3D sphere cultures induce signalling pathways that enhance survival and increase oncogenic activity. They show ultrastructural resemblance to in vivo UMs. The metabolic shift seen in 3D cultures could reflect the survival patterns of pre‐metastatic cancer cells.ConclusionsThe molecular signature of the 3D cultures reveals the presence of attractive targets for future epigenetic modulation or cancer cell vaccines.
Clinical guidelines for acute exposure to laser pointer radiation
Authors: Löfgren S. , Hengstler J. , Jans E. 
Published: September 2015

PurposeTo describe clinical decision guidelines for eye health care professionals meeting patients exposed to laser pointers.MethodsThe Eye Emergency Department at St. Erik Eye Hospital in Stockholm primarily serves the Stockholm Metro region with its 2.2 million people. Every week, on average one patient seeks help at the Eye Emergency after exposure to laser pointer light. The bulk of the patients are subway and bus drivers and police and security officers. Since no objective retinal damage so far has been documented and there is no proven treatment against laser pointer retinal damage we have instigated an information campaign in order to reduce the number of patients seeking emergency care. The information is spread to all public transportation services in Stockholm, police and security officers, aviation authorities, and to the general population.ResultsThe information to all non‐medical staff is general, while the clinical guidelines details which procedures might be relevant and which may be inessential. The guidelines emphasize the importance of documenting a dynamic evolution of retinal damage before causality can be concluded. Within 2 months after the information campaign, there seems to be a decrease of patients seeking emergency eye care after laser pointer light exposure.ConclusionsThe clinical guidelines streamline the care of this patient group, and the information to the public should alleviate some of the worries that are associated to laser pointer light exposure.
Dry Eye Disease Therapy: who are the non‐responders?
Authors: Eidet J.R. , Ræder S. , Chen X. , Badian R. , Utheim Ø. , Utheim T.P. 
Published: September 2015

PurposeTo investigate the parameters that characterize the patients that responds or do not respond to dry eye disease (DED) therapy as recommended by the International Dry Eye WorkShop 2007.Methods217 DED patients were consecutively included at the Norwegian Dry Eye Disease Clinic in Oslo, Norway. All patients underwent a comprehensive ophthalmological examination. The patients’ symptoms were reported by means of three self‐questionnaires (Ocular Surface Disease Index [OSDI], McMonnies Dry Eye Inventory [MDEIS] and the Sjögren's syndrome [SS] questionnaire [SSQ]). Patients were defined as treatment‐responders if their dry eye severity level (DESL) score had improved following 6 months of treatment, and non‐responders if their DESL score was unchanged or worse.ResultsNon‐responders were older (P = 0.019), had lower baseline DESL score (P < 0.001), had less pathological tear meniscus height (P = 0.007) and used fewer systemic prescription drugs (P = 0.046). Linear regression analysis showed that age, DESL and number of systemic prescription drugs used were independently associated with treatment response (P < 0.05). Furthermore, patients were more likely to respond to therapy if it was initiated during winter, which suggests a seasonal effect. Females and males, as well as meibomian gland dysfunction (MGD) patients and non‐MGD patients, were equally likely to respond to treatment.ConclusionsAs the recommended therapy for DED is based on the DESL score of the patient our results may either indicate that the therapy recommended for the higher levels of DESL are more effective than that recommended for the lower levels of DESL or that effect is easier to detect in patients with more pronounced DED. Future studies should investigate whether patients with mild DED should be treated more aggressively.
APMPPE as a window on systemic granulomatous inflammation
Authors: Labalette P. , Bouabane I. , Maurage C.A. 
Published: September 2015

PurposeAcute posterior multifocal placoid pigment epitheliopathy (APMPPE) an unfrequent posterior uveitis presumed to be caused by a general hypersensitivity vasculitis.MethodsEight patients aged from 12 to 33 years presented with AMPPE were studied. For each patient a systemic work‐up for systemic granulomatous disease was performed, including pathologic analysis of accessory salivary glands biopsies.ResultsA granulomatous infiltration of the accessory salivary glands biopsies was found in six cases, a feature consistent with a systemic involvement rather than an isolated eye disease. In addition two patients were diagnosed for systemic sarcoidosis.ConclusionsIn numerous cases, AMPPE seems to be the eye expression of a systemic granulomatous reaction.
Advancing age does not strongly correlate with symptoms and signs of Dry Eye Disease in a large Norwegian cohort
Authors: Badian R.A. , Eidet J.R. , Ræder S. , Utheim Ø. , Chen X. , Stojanovic A. , Utheim T.P. 
Published: September 2015

PurposeTo evaluate the relationship between age and signs and symptoms of dry eye disease (DED) in a Norwegian cohort of patients with DEDMethodsClinical signs and symptoms were evaluated for 957 subjects at the Norwegian Dry Eye Clinic. All patients received an extensive ophthalmological work‐up, including tear meniscus height, blink rate, corneal sensibility, tear film break‐up time, Ocular Protection Index, vital staining, Schirmer I, meibum quality and meibum expressibility [CJ1], and in many cases osmolarity measurements. Pearson correlations between signs and symptoms were performed. P values below 0.05 were considered significant. [CJ1] This is not a real word, but may be in ophthalmology it is commonResultsNo correlations above r2 = 0.28 were found between age and signs or symptoms. Increasing age was only correlated with lower protection index (0.13), lower Schirmer I values (0.22), lower corneal sensibility (0.15) and higher Meibum expressibility (0.28)ConclusionsAdvancing age did not correlate strongly with any parameters of dry eye disease. This is particularly interesting as advancing age is regarded as a considerable risk factor for the development of dry eye disease.
Spectral‐domain EDI‐OCT in small uveal melanoma and “pseudomelanomas”
Authors: Saakyan S. , Neroev V. , Myakoshina E. , Zaitseva O. 
Published: September 2015

PurposeTo reveal diagnostic symptoms of small uveal melanoma and “pseudomelanomas” by spectral‐domain EDI‐OCT.MethodsThe results of complex research (ophthalmoscopy, ultrasonography, spectral‐domain EDI‐OCT) of 230 patients (230 eyes) aged from 13 to 75 (mean 49 ± 1.1) years with diagnosis “small uveal melanoma” were analyzed.ResultsIn 142 (61.7%) from 230 cases small uveal melanoma was diagnosed. The tomographycal symptoms were retinal thickness caused by neuroepithelium detachment, cystoid retinal edema; bow‐shaped choroidal profile; retinal thickness in contiguous zone caused by neuroepithelium detachment. In 88 cases (38.3%) “pseudomelanomas” were diagnosed. In age‐related macular degeneration (38) retinal pigment epithelium detachment, hyperreflective focus (subretinal membrane), equal choroidal profile; in subretinal hemorrhage (25) equal elevation of choroidal profile without retinal fluid; in peripheral retinal degeneration (12) retinal thinning, insignificant elevation of choroidal profile, hyperreflective foci on RPE level; in congenital hypertrophy of retinal pigment epithelium (13) equal choroidal profile, retinal thinning, thickness of retinal pigment epithelium were diagnosed.ConclusionsThus, spectral‐domain EDI‐OCT allow to reveal small uveal melanoma and “pseudomelanomas” symptoms for adequate treatment.
Treatment of Leber's hereditary optic neuropathy with EPI‐743: the Brazilian experience
Authors: Karanjia R. , Ganti A. , Chu E. , Wagschal T. , Belfort R. , Moraes‐Filho M. , Salomao S. , Chicani F. , Guy M. , Sadun A. 
Published: September 2015

PurposeTo determine the degree of visual improvement in a homogeneous Brazilian cohort of Leber's Hereditary Optic Neuropathy (LHON) 11778 receiving 18–24 months of therapy with the quinone EPI‐743MethodsSix patients with severe vision loss from LHON were enrolled in an open label clinical trial. Each patient received 400 mg TID of EPI‐743. Two patients were treated at the time of conversion, while 4 patients had chronic disease (>5 years). Outcome measures included best corrected visual acuity (BCVA), retinal nerve fiber layer (RNFL) thickness as measured by Optical Coherence Tomography and Humphrey Visual Fields (HVF) mean deviations. Mean deviations were calculated using the HVF algorithm (Stim III) or University of Iowa Visual Field Reading Center Algorithm (Stim V)ResultsVA declined or stabilized in the first 6 months, then improved gradually for all 6 patients and remained stable for 18–24 months with EPI‐743. VF increased marginally in one chronic and both acute patients, while 3 chronic patients remained at baseline. The acute patients showed continued bilateral progression for the first 6 months, consistent with the natural history of LHON. As expected, all eyes showed a decline in RNFL that stabilized after treatmentConclusionsVA improvements continued beyond the initial 1 year period to 18–24 months of treatment, including 4 patients who had lost vision over 5 years prior to start of EPI‐743. This data is consistent with data from the United States where an EPI‐743.
Fisetin and Luteolin decrease inflammation and oxidative stress‐induced cytotoxicity in ARPE‐19 cells
Authors: Hytti M. , Piippo N. , Korhonen E. , Kaarniranta K. , Kauppinen A. 
Published: September 2015

PurposeAge‐related macular degeneration (AMD) is the leading cause of blindness among the elderly in the western world. It represents not only a dramatic reduction in patients’ quality of life but also a significant burden to the general healthcare system. Yet, despite the severity of the disease much questions regarding the pathways of disease formation and progression are still unanswered and viable treatment options still undiscovered. Here, we evaluate the cytoprotective and anti‐inflammatory potential of fisetin and luteolin in human retinal pigment epithelial cells exposed to increased oxidative stress.MethodsARPE‐19 cells were treated with 4‐Hydroxynonenal (HNE) to simulate high levels of oxidative stress. Thereafter, fisetin or luteolin were added to the culture medium. The MTT and the lactate dehydrogenase assays were used to assess cellular toxicity. Inflammatory cytokines, as well as activation of transcription factors were measured using the ELISA method and a DNA‐binding transcription factor assay. To analyze the importance of SIRT1 and related pathways, the experiments were repeated after specific SIRT1 knock‐out using siRNA. Levels of intracellular SIRT1 were measured using Western Blot.ResultsFisetin and luteolin protected retinal pigment epithelial cells from oxidative stress‐induced cell death and exhibited potent anti‐inflammatory properties even after the initial insult. These effects seemed to be independent of NF‐κB or SIRT1.ConclusionsBioactive polyphenols, fisetin and luteolin are powerful anti‐inflammatory and anti‐oxidant agents and show potential for the development of drugs aimed at specific intracellular pathways that affect inflammation in AMD.
cis‐Urocanic acid prevents inflammation and cell death in UVB‐treated ARPE‐19 cells
Authors: Korhonen E. , Piippo N. , Hytti M. , Kaarniranta K. , Kauppinen A. 
Published: September 2015

Purposecis‐Urocanic acid (cis‐UCA) is an endogenous ultraviolet (UV) absorbing chromophore that is mainly produced in the upper layers of epidermis. The aim of our study was to investigate the cytoprotective capacity of cis‐UCA in UVB‐irradiated ARPE‐19 cells.MethodsARPE‐19 cells were pretreated with IL‐1α and cis‐UCA and then exposed to UVB radiation. Secretion of IL‐1β and ‐18 was measured using the ELISA method. Moreover, the cells were observed under an inverted microscope and cell viability was measured by lactate dehydrogenase (LDH) release assay. The proper cis‐UCA concentration was evaluated comprehensively beforehand using MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide), neutral red, and LDH tests.ResultsOur results show that UVB after IL‐1α priming activates IL‐1β and ‐18 secretion in ARPE‐19 cells and cis‐UCA clearly alleviates that. cis‐UCA also improves cellular viability.Conclusionscis‐UCA shows anti‐inflammatory and cytoprotective properties in ARPE‐19 cells.
Ophthalmic insert for pupillary mydriasis in neonates
Authors: Bremond‐Gignac D. , Jacqz‐Aigrain E. , Abdoul H. , Beresniak A. , Baud O. , Alberti C. 
Published: September 2015

PurposeTo study efficacy and tolerance of ophthalmic insert Mydriasert® versus standard treatment phenylephrine and tropicamide eye drops for fundus examination in neonates.MethodsProspective, randomised, single‐blinded non‐inferiority study of 80 premature and full‐term babies and infants treated for fundus examination. Mydriasis was obtained with two groups randomly assigned. The eye drop group received three instillations of 2.5% phenylephrine and 0.5% tropicamide and the insert group received Mydriasert® containing phenylephrine and tropicamide. The mydriasis was evaluated 75 minutes after the introduction of the mydriatic agents.ResultsThe mydriasis was successfully achieved in both eyes in 97.5% of infants in the insert group and 90% in the eye drop group at 75 minutes after dispensation. The efficacy of the insert was non‐inferior compared to the eye drops. To reach effective mydriasis, the insert group required fewer nursing interventions for one patient comparing to the eye drop group. Good general and local tolerance was observed in the two groups. However two patients reported an adverse event as bradycardia and gastro‐oesophageal reflux that could be related to neonate pathology.ConclusionsMydriasis obtained with the ophthalmic insert Mydriasert® was not inferior compared to standard eye drop treatment. Insert reduced the number of nursing interventions to obtain mydriasis for a fundus examination.