bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nrf2‐ and PGC‐1α‐deficient mice: A novel animal model for impaired autophagy in AMD?
Authors: Paterno J.J. , Smedowski A. , Hytti M. , Bjørkøy G. , Amadio M. , Levonen A.L. , Tavi P. , Kauppinen A. , Kaarniranta K. 
Published: September 2015

PurposeTo clarify the complex role of impaired autophagy in RPE damage, we analysed mice deficient in both Nrf2 and PGC‐1α. Increasing evidence of impaired autophagy as a contributor to AMD has raised the importance of animal models that fundamentally mimic autophagy decline in RPE.MethodsWe analysed morphological and immunohistochemical changes in the retina of aged Nrf2 and PGC‐1α double knock‐out (dKO) mice and wild‐type controls. The Keap1‐Nrf2 pathway, an essential system involved in oxidative stress response, is regulated by proteasomes and autophagy. PGC‐1α is a master regulator of ROS‐scavenging enzymes, and it has a role in inducing autophagy/mitophagy. We performed immunostaining of proteins related to oxidative stress and autophagy (4‐HNE, Beclin‐1, HuR, LC3, p62, and ubiquitin).ResultsRPE degeneration was prominent in dKO mice and it was associated with changes in autophagy and oxidative stress.ConclusionsOur findings suggest Nrf2 and PGC‐1α deficiency increases oxidative stress and affects autophagy. This coincides with the retinal degeneration observed in the promising new AMD mouse model.
Differential molecular signature of ectatic and non‐ectatic areas from Keratoconus patient corneas
Authors: Pahuja N. , Rajiv Kumar N. , Shetty R. , Shroff R. , Ghosh A. 
Published: September 2015

PurposeTo evaluate if the gene expression profile of corneal epithelium from the cone area in Keratoconus (KC) differs from the peripheral non‐ectatic areas.HypothesisThe ectasia in Keratoconic cornea is localized to the cone while the peripheral areas are apparently normal. Hence we hypothesized that within the cone of a KC patient cornea, the structural weakness may be a function of localized gene expression differences.MethodsStudy group contained 54 KC patients undergoing epithelium off corneal collagen crosslinking (CXL) and 9 non‐ectatic subjects undergoing photo refractive keratectomy (PRK) as controls. The cone vs periphery distinction is based on keratometry and location of the cone based on elevation map. Using a 4.5 mm trephine centered on the cone, epithelium was scraped separately for cone and rest as periphery. In non‐ectatic controls, the central 4.5 mm area was taken as cone. Gene expression profiling was performed for each pair of cone and periphery samples by quantitative PCR.ResultsLysyl oxidase levels were significantly reduced in the cone of KC patients (p = 0.002). Structure related genes COL1 (p = 0.01) and COL4 (p = 0.008) were also reduced significantly in KC patient cones. The cytokines IL6, TGFβ and TNFα did show an increased trend; regulatory cytokine IL10 did not show significant trend. Matrix remodeler MMP9 showed an increasing trend at the cone while its inhibitor TIMP1 showed a reducing trend that was not significant(p = .09).ConclusionsEctasia in KC may be driven by local molecular factors at the cone that possibly spreads to other parts of cornea as disease progresses.
Self‐complementary vectors for optimization of AAV2‐mediated gene‐therapy of corneal endothelial cells
Authors: Gruenert A. , Buening H. , Schnoedt M. , Schmeer M. , Schleef M. , Kruse F.E. , Fuchsluger T. 
Published: September 2015

PurposeRecombinant adeno‐associated viruses 2 (rAAV2) represent a nonpathogenic and safe alternative to other viral delivery systems. However, their transduction efficiency in corneal endothelial cells (CEC) is limited. As the level of transgene expression is dependent on the conversion of single‐stranded (ss)‐ into double‐stranded (ds)‐DNA, self‐complementary (sc)‐AAV vectors have been developed to circumvent this problem. The aim of this study was to evaluate the use of scAAV2 in terms of transduction efficiency in CEC. Additionally, the impact of transduction on cell viability was investigated.MethodsA human corneal endothelial cell line (HCEC‐12) as well as organ‐cultured human donor corneas were transduced with different titers of ss‐ or sc‐AAV2. Transduction efficiencies were compared by means of GFP‐transgene expression. GFP‐expression in HCEC‐12 cells was evaluated by flow cytometry over a period of 28 days. GFP‐expression in human donor corneas was analyzed by confocal microscopy on day 6. 7‐AAD staining and flow cytometry as well as MTT‐assay were performed to determine cell viability after transduction.ResultsGFP‐expression was significantly higher in cells transduced with scAAV2 than in cells transduced with ssAAV2. The difference in transduction efficiency decreased with increasing vector titer. The highest transgene expression rate using scAAV2 was 86.9% compared to 80.5 % using ssAAV2. In human donor corneas GFP‐expression was observed in 72.2% (scAAV) and 44.1% (ssAAV) of CEC respectively. There was no significant difference between viability of transduced and untreated cells.ConclusionsScAAV2 vectors are an effective tool to enhance transduction efficiency in CEC. Allowing higher transduction rates with lower vector titers, this could improve AAV2‐mediated gene therapy to protect CEC in corneal allografts.
Uveal melanoma in Finnish patients with congenital ocular melanocytosis
Authors: Mamunur R. , Kivelä T. 
Published: September 2015

PurposeTo described the characteristics of uveal melanoma in congenital ocular melanocytosis in Finland.MethodsFor this retrospective observational case series, we identified all 15 of 867 (1.7%; 95% CI 1.0–2.8) uveal melanoma patients (5 male, 10 females) with congenital ocular melanocytosis during January 2000‐May 2015 at the Ocular Oncology Service, Helsinki University Hospital. The patient was followed up at 3 and 6 months, every 6 months for 3 years, and thereafter annually. The diagnosis of uveal melanoma was based on clinical and ultrasonographic features, and metastases were screened with annual abdominal ultrasonography and liver function tests.ResultsThe mean age at diagnosis was 55 years as compared with 64 years for all 867 patients. The mean thickness and basal diameter of the tumours were 6.5 (SD 3.6) and 13.1 (SD 4.4) mm, respectively, as compared to 5.1 (SD 3.9) and 12.5 (SD 4.5) among all patients, respectively. The melanoma involved the ciliary body in 6 patients (40%). The tumours represented TNM stages I in 4 (27%) patients, II in 5 (33%), III in 5 (33%) and IV (metastases at the time of diagnosis) in 1 patient. Enucleation was done in 2 cases, I‐125‐brachytherapy in 7 cases, and 5 patients were treated with Ru‐106. Recurrent tumour growth was observed in 2 patients. Overall 5‐ and 10‐year survival was 68% (95% CI 35–87) and 13% (95% CI 1–43). Survival was associated with TNM stage: 100%, 80%, 33% and 0% at 5 eyars for stages I‐IV, respectively. One patient survived for 10 years without metastasis.ConclusionsIn our data set, uveal melanoma patients with congenital ocular melanocytosis are on average 9 years younger than uveal melanoma patients in general, and have a tendency to die of metastases.
Glaucoma patient satisfaction regarding tolerance to their prostaglandin treatment: results from the GOAL (Glaucoma patients treated with prOstaglandins; sAtisfaction evaLuation) survey in Europe
Authors: Clarke J. , Stalmans I. , Lemij H. , Baudouin C. 
Published: September 2015

PurposeThe high prevalence of ocular surface diseases (OSD) in patients treated for OHT/glaucoma is expected to displease them. To evaluate this, a survey was conducted in three European countries: the Netherlands, Belgium and United Kingdom.MethodsIn this multicentre epidemiological survey, the following data were recorded during a visit to the ophthalmologist: glaucoma history, previous treatments and reasons for any change, tolerance, patient satisfaction, ocular signs and the presence of OSD.ResultsThe data of 793 patients treated with prostaglandins were analysed (168 from the Netherlands, 253 from Belgium and 372 from England). Only 9% of the treatments were preservative‐free.A very large number (93.7%) of patients declared to be satisfied or very satisfied with their current glaucoma treatment. The mean score of tolerance evaluated on a Visual Analog Scale (VAS) was 82.7 ± 16.1 mm (range from 0 mm: very bad tolerance to 100 mm: very good tolerance).At the same time, the survey revealed (displayed in percentage of all patients):

OSD was diagnosed in 42.5%

symptoms upon instillation in 31.4%

symptoms between instillations in 57.3%

a conjunctival hyperaemia in 32%

frequent use of artificial tears in 25.1%

The presence of hyperaemia, ocular signs, and symptoms upon or between instillations, positive conjunctival staining and frequent use of tear substitutes was statistically significantly linked to patient satisfaction (p ≤ 0.006).ConclusionsA high percentage of satisfied patients (94%) was found in this survey, despite OSD signs and symptoms. Tear film substitutes are commonly prescribed to treat these side effects. Alternative treatment regimes such as preservative free treatments may reduce local side effects and encourage ophthalmologists to convince their patients that local intolerance is no longer inevitable.
Clinical characteristics and surgical outcomes of mesectodermal leiomyoma of the ciliary body and choroid
Authors: Park H.J. , Lee J.H. , Lee S.C. 
Published: September 2015

PurposeMesectodermal leiomyoma is a rare tumor that can arise from smooth muscle tissue in the iris or ciliary body or from heterotopic smooth muscle in the choroid. The purpose of this study was to describe the clinical characteristics and surgical outcomes of mesectodermal leiomyoma of the ciliary body and choroid.MethodsRetrospective observation case series of 8 patients who were diagnosed with mesectodermal leiomyoma with histopathologic and immunohistochemical confirmation.ResultsThe median age at presentation was 37.5 years. The median follow‐up period was 27 months. Ultrasonography showed dome‐shaped smooth surface with low to medium internal reflectivity and regular internal structure in all tumors. The tumor had a median largest base diameter of 10.4 mm and a median thickness of 7.7 mm. They revealed pinkish colored surface and vessels that more developed than other intraocular tumors. The tumors located on ciliary body only in 4 eyes, on choroid only in 2 eyes, and on ciliochoroid in 2 eyes. 6 patients who had tumors on ciliary body only or ciliochoroid underwent lamellar sclerouvectomy. 2 patients who had choroidal tumor received enucleation or partial excision for biopsy each. On immunohistochemistry, all the tumors were stained positively for smooth muscle actin and desmin. After lamellar sclerouvectomy, the tumor did not show recurrence in follow up period. But the patient that underwent partial removal of tumor on choroid showed irregularly changing surface with increasing size.ConclusionsMesectodermal leiomyoma did not show the recurrence after lamellar sclerouvectomy and malignant change of tumor. However these tumors are difficult to differentiate from other intraocular tumor and to conclude definitely that they do not develop malignant change because they have heterogeneity from benign leiomyoma of other body organs.
Changes in choroidal thickness after intraocular pressure reduction following trabeculectomy
Authors: Kadziauskiene A. , Kuoliene K. , Galgauskas S. , Asoklis R. 
Published: September 2015

PurposeTo evaluate changes of choroidal thickness (CT) after an acute reduction in intraocular pressure (IOP) following trabeculectomy.MethodsSubfoveal and peripapillary CT and IOP were measured in 40 glaucomatous eyes (40 patients) 1 day before, 1 week and 1 month after the trabeculectomy. The choroid was evaluated using spectral domain optical coherence tomography enhanced depth imaging at the fovea and 1.7 mm superior, temporal, inferior and nasal to a optic nerve head centre. Biometry was performed preoperatively.ResultsThe mean IOP was significantly reduced after trabeculectomy at both follow‐up visits (P < 0.001). The mean subfoveal CT (±SD) increased from 216.1 (±86.1) µm at baseline to 260.3 (±86.9) µm after one week and 243.1 (±87.1) µm after one month postoperatively (P < 0.001). The mean CT significantly increased one week after trabeculectomy at all peripapillary locations (P < 0.01), however, the thickening of choroid was significant only temporally after one month. There was positive correlation between the magnitude of change in subfoveal CT and the IOP reduction (r = 0.518, P < 0.001 for the 1‐week follow‐up; r = 0.290, P = 0.034 for the 1‐ month follow‐up). The preoperative axial length correlated positively with the magnitude of thickening of subfoveal CT after one week (r = 0.451, P = 0.002).ConclusionsThe subfoveal and peripapillary CT increased with the IOP reduction following trabeculectomy, however, choroidal thickening around the optic nerve disc appeared to be short‐term. The thickening of subfoveal CT was found to be related to the greater IOP reduction and longer axial length.
Lack of collagen XVIII in mice evokes age‐dependent deficiency in retinal pigment epithelium proteostasis
Authors: Kivinen N. , Felszeghy S. , Aikio M. , Pihjalaniemi T. , Kaarniranta K. 
Published: September 2015

PurposeCollagen XVIII is a unique component of basement membranes (BMs) with the structural properties of both a collagen and a proteoglycan. It has been found at the basement membrane/stromal interface and is thought to mediate their attachment. Proteolytic cleavage within its C‐terminal domain releases a fragment, endostatin, which has been reported to have anti‐angiogenesis effects. Age‐dependent loss of vision in the collagen XVIII mutant mice is associated with pathological accumulation of deposits under the retinal pigment epithelium. We have recently shown that impaired proteasomal and autophagy clearance associate with the pathogenesis of age‐related macular degeneration (AMD). In this study, staining levels of proteasomal and autophagy markers were studied in different ages of the Col18a1−/− mice.MethodsEnucleated eyes from 3, 12 and 18 months old mice were embedded in paraffin according to a routine protocol. Serial 5 μm‐thick parasagittal samples were immunostained for proteasomal ubiquitin (Ub) and autophagy markers SQSTM1/p62 and Beclin. The extent of immunopositivity in the retinal pigment epithelial cells was evaluated during confocal microscopic analysis.ResultsLack of collagen XVIII in mice evoked age‐dependent retinal pigment epithelium (RPE) degeneration and drusen‐like deposit accumulation. Proteasomal Ub protein conjugate staining was prominent in both RPE cytoplasm and extracellular space. Autophagy markers SQSTM1/p62 and beclin stainings were prominent in the basal part of RPE cell cytoplasm in the Col18a1−/− mice.ConclusionsDisturbed proteostasis regulated by collagen XVIII may induce RPE degeneration, increase protein aggregation and finally predispose to the choroidal neovascularization.
Pore size assessment during corneal endothelial cell permeabilization by femtosecond laser‐activated carbon nanoparticles
Authors: Jumelle C. , Mauclair C. , Houzet J. , Bernard A. , He Z. , Piselli S. , Perrache C. , Gain P. , Thuret G. 
Published: September 2015

PurposeTherapeutic molecules delivery represents a promising solution to maintain human corneal endothelial cells (HCECs) viability, but transport across cell membrane must be facilitated. A new delivery method consists in ephemerally permeabilizing cell membranes using a photo‐acoustic reaction produced by carbon nanoparticles (CNPs) and femtosecond laser (FsL). The aim of this work is to investigate the size of pores formed at cell membrane by this technique.MethodsTo induce cell permeabilization, HCECs (B4G12 cell line) were put in contact with CNPs and irradiated with a 500 µm diameter Ti:Sa FsL focalized spot. Four sizes of fluorescent reporter molecules were delivered into HCECs to investigate pore sizes: calcein (1.2 nm), FITC‐Dextran 4 kDa (2.8 nm) and FITC‐Dextran 70 kDa (12 nm) and FITC‐Dextran 2MDa (50 nm). Uptake of each molecule was assessed by flow cytometry immediately after irradiation.ResultsThe delivery rate was dependent of their size. Calcein was delivered in 56 ± 8% of HCECs, FITC‐Dextran 4 kDa in 42 ± 4%, FITC‐Dextran 70 kDa in 22 ± 3% and finally FITC‐Dextran 2MDa in 13 ± 2%, suggesting that a large number of pores in the size ranging from 1.2 to 2.8 nm were formed. However, 12 nm and larger pores were almost half more infrequent.ConclusionsPore sizes formed at cell membrane by the technique of cell permeabilization by FsL activated CNPs were investigated for the first time. This innovative non‐viral method is characterized by pore sizes large enough for the efficient delivery of small, medium and big therapeutic molecules on HCECs. GRANT: Fondation des Aveugles de France, Fondation de l'Avenir, Fondation Visaudio (ET1‐638).
Transfer of molecules into the endothelial cells of whole human corneas using carbon nanoparticles activated by femtosecond laser
Authors: Jumelle C. , Mauclair C. , Houzet J. , Barnard A. , He Z. , Piselli S. , Perrache C. , Gain P. , Thuret G. 
Published: September 2015

PurposeThe targeted delivery of drugs and genes represents a promising solution to modify human corneal endothelial cells (HCECs), however, it remains limited by the difficulty to efficiently cross cell membranes without altering their integrity. Aim: to adapt an innovative technique of macromolecules delivery in corneal endothelium using carbon nanoparticles (CNPs) activated by femtosecond laser (FsL).MethodsHCECs of 35 whole human corneas stored in organ culture were permeabilized by photo‐acoustic reaction induced by irradiation of CNPs by FsL beam. The uptake of dextran AlexaFluor 488, a 3000‐Da fluorescent macromolecule, was assessed using fluorescent microscopy. Three fluences (20, 30 and 40 mJ/cm2) and protective additives (ROCK inh and Poloxamer 407) were tested in order to increase uptake efficiency while limiting cell mortality (ethidium +). Dextan uptake and cell mortality rates were quantified using the CorneaJ plugin for ImageJ.ResultsDextran delivery significantly increased with fluence, reaching a mean of 13% of HCECs for 40 mJ/cm2. Induced mortality varied from 0 to 53% and was more dependent of the cornea itself than on fluence. Treatment by either protective additive did significantly enhance the delivery rate, nor HCECs viability.ConclusionsFor the first time, ex vivo HCECs of whole corneas were permeabilized by mediated‐nanoparticles laser perforation. Even if the delivery rate was lower than for viral vectors, it remained high for a non‐viral technique. Mortality was variable according to corneas tested even with the use of protective additives. GRANT: Fondation des Aveugles de France, Fondation de l'Avenir, Fondation Visaudio (ET1‐638).
Retinal vein occlusion in a patient with jugular vein compression by metastasis of carcinoma of the oral tongue
Authors: Navarro Perez , Ascaso F.J. , Sánchez J.I. , Esteban O. , Martinez M. , Del Buey M.Á. , Núñez E. 
Published: September 2015

PurposeRetinal Vein Occlusion (RVO) is the second retinal vascular disease after the diabetic retinopathy. It has been associated with multiple factors both systemic (arterial hypertension, diabetes mellitus, hemoglobinopathy, …) and local (glaucoma, hyperopia, …). We report the very uncommon case of a central RVO that appeared after the patient suffered an internal jugular vein compression syndrome secondary to metastases of squamous cell carcinoma of the oral tongue (SCCOT).MethodsSpectral‐domain optical coherence tomography (SD‐OCT) and fluorescein angiography (FA) were used in the diagnosis and follow‐up of the visual disorder and PET‐CT and cervical ultrosonography were used in the diagnosis of jugular compression.ResultsA 48‐year‐old male complained with decreased visual acuity on his right eye. Best‐corrected visual acuity (BCVA) was 0.2 in the RE and 0.63 in the LE. Fundus examination revealed image of impending CRVO. FA showed severe bilateral venous stasis especially on the RE. He had been diagnosed with a SCCOT. PET‐ CT revealed a tongue neoplasia with right anterior jugular adenopathy. A cervical ultrosonography showed a compression on both uptown jugular veins and more constricted in high area on the right one. The tumor was considered unresectable. The patient underwent palliative chemotherapy and the ophthalmological symptoms and signs significantly improved. VA improved to 0.5 in the right eye and 0.8 in the left eye after chemotherapy.ConclusionsOphthalmologists should be aware of internal jugular vein compression as a possible cause of CRVO in patients suffering from metastases of cervicofacial neoplasies.
Efficacy and safety of ranibizumab in diabetic macular edema: real life study
Authors: Hrarat L. , Fajnkuchen F. , Sarda V. , Grenet T. , Buffet S. , Chaine G. , Giocanti‐auregan A. 
Published: September 2015

PurposeTo evaluate the efficacy and safety of ranibizumabin patients with vision loss secondary to diabetic macular edema (DME).MethodsRetrospective analysis of a cohort of patients withvision loss (VA) due to DME and treated by ranibizumab. Patients were examined before treatment and during treatment every 4–6 weeks. Ophthalmologic examination included:measure of the best corrected visual acuity (BCVA) on the ETDRS scale, examination at the slit lamp, fundus, and SD‐OCT (Cirrus 5000, Carl Zeiss Meditec). All patients receiveda loading dose of 3 monthly injections followedby re‐treatments on an as‐needed basis (PRN regimen) The primary endpoint was the change in visual acuity at 12 months. The other criteria assessed were central retinal thickness (CRT) after loading dose, and at 12 months, and the number ofintravitreal injections (IVT) during the first year of follow‐up.Results109 eyes of 79 consecutive patients treateded since November 2012 have been included. At baseline the mean BCVA was 48.77 letters, the CRT was 517 microns. At 12 months the average BCVA was of 60.80 letters (p < 0.05), with an average VA gain of +14.67 letters and 25% of patients had a BCVA> 70 letters. The mean CRT after 3 injections was 344.32 microns (p < 0.05) and 332 microns (p < 0.05) at 12 months, with 57.23% of patients with CRT ≤ 300 microns. At 12 months the average VA in patients with CRT ≤ 300 microns was 63.51 letters (p < 0.05) and the average AV in patients with ERC> 300 .microns was 57.39 letters (p < 0.05). The average number of IVT performed during the first year of follow up was 5.59. No serious adverse event was noted.ConclusionsPivotal studies have clearly shown the benefit of ranibizumab treatment of vision loss due to DME. This study in a “real life” setting confirms the results obtained in randomized trials.