bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uveal melanoma and other cancers
Authors: Desjardins L. , Villaret J. , Cassoux N. , LumbrosoLeRouic L. , Levy C. , Plancher C. , Savignoni A. 
Published: September 2015

PurposeWe evaluated in a retrospective study the frequency and nature of other cancers in uveal melanoma patients.MethodsPatients and methodA prospective registry of uveal melanoma patients is pêrformed in our center including usual datas on patients and tumor characteristics and since 2000 cancer past history. Each patient is followed during ten years after initial treatment and occurence of second cancer after uveal melanoma is registered.Resultsthere are 6262 patients in the database with uveal melanoma and for 3934 history of previous cancer was registered. We had 548 cases of associated cancer: 423 had a past history of cancer before uveal melanoma was diagnosed and 102 patients développed a second cancer after the diagnosis of uveal melanoma. Cutaneous melanoma and renal carcinoma were found to be more frequent than expected.ConclusionsRecent genetic improvments led to new discovery of germinal mutations responsible for cancer. As known for BRCA mutations and breast cancer or Rb1 gene and retinoblastoma, BAP 1 mutations has been found to predispose to mesothelioma, clear cells renal cancer and cutaneous and uveal melanoma. For young patients or patients with multiple cancers or family high frequency of cancer genetic counseling has became essential.
Selecting uveal melanoma for PRAME‐TCR T cell immunotherapy
Authors: Jager M.J. , Krijgsman D. , Luyten G.P.M. , Luk S.J. , der Velden P. Van , Heemskerk M.H.M. 
Published: September 2015

PurposeTo determine which uveal melanoma may be candidates for PRAME‐directed immunotherapy using TCR‐modified autologous T cells.MethodsExpression of PRAME was determined in uveal melanoma by an Illumina array. HLA polymorphisms were determined on peripheral blood leukocytes. Clinical and histological characteristics of UM were derived from clinical charts and pathology reports.ResultsPRAME expression was highly variable; tumor size, thickness, and the presence of an inflammatory phenotype were associated with PRAME expression. 20/37 monosomy 3 cases expressed PRAME, and 8/20 disomy 3 tumors. 10‐year survival data on 60 UM showed worse survival of UM with high PRAME compared to those with a low PRAME. However, six of the eight PRAME‐positive disomy 3 cases died from metastases. With this information, all cases with PRAME‐positive primary tumors who carry the HLA‐A2 antigen should be followed closely for the development of metastases, as they can be candidates for PRAME‐TCR autologous T cell therapy.ConclusionsUveal melanoma may be good candidates for treatment with autologous T cells that have been modified so that they carry PRAME‐specific T cell receptors. Large uveal melanoma with a high PRAME expression (independent of chromosome 3 status) in HLA‐A2 positive patients are potential candidates for PRAME‐TCR autologous T cell therapy. A high PRAME expression, also in disomy 3 tumors, was associated with an inflammatory phenotype and with death due to metastases.
Selective laser trabeculoplasty: Results on intraocular pressure and number of topical antiglaucoma medications
Authors: Bonnel S. , Fenolland J.R. , Marill A.F. , Gaillard R. , Rosenberg R. , Theillac V. , Mazharian A. , Mouinga A. , Giraud J.M. , Renard J.P. 
Published: September 2015

PurposeTo evaluate results at one year of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) and assess if differences are related to number of topical treatments in ocular hypertension (OHT) and open angle glaucoma (OAG) patients.MethodsWe performed a retrospective chart review of 106 eyes treated by SLT. Indications for SLT treatment were insufficient IOP control, allergy, discomfort or non‐compliance to antiglaucoma treatment. Only patients with at least 1 year of follow‐up after SLT were included. IOP was measured before and at 1, 6 and 12 months after SLT. All IOP measurements were performed with Goldmann applanation tonometry.Results106 eyes of 68 patients untreated (n = 13), or treated with one (n = 25), two (n = 39) or three (n = 28) topical antiglaucoma medications were included. Mean preoperative IOP was 19.4 ± 3.6 mmHg (respectively 21.1 ± 2.7, 19.8 ± 3.1, 19.1 ± 4.2 and 18.9 ± 3.4 mmHg corresponding to the group without, one, two or three treatments) and 15.7 ± 3.1 mmHg at 12 months (respectively 16.2 ± 3.5, 15.6 ± 2.6, 15.6 ± 3.4 and 15.5 ± 2.8 mmHg for each groups) which corresponds to an average decrease of 18.3% (respectively 23.7%, 19.7%, 17.2% and 16.1% for each groups). At 1 year, 62.2% (n = 66) were responders (≥3 mmHg reduction from baseline IOP = 15.5% of IOP baseline): 92.3% without treatment (n = 12), 68% with one (n = 17), 59% with two (n = 23) and 50% with three treatments (n = 14). The average IOP of responders decreased from 20.7 ± 3.4 to 15.2 ± 2.9 mmHg (26.6%), respectively from 20.8 ± 2.6 to 15.8 ± 3.2 (25%) without treatment, from 20.6 ± 3.2 to 14.9 ± 3.7 (27.3%) with one, from 20.8 ± 4.1 to 15.5 ± 3.3 (25.1%) with two and from 20.7 ± 3.2 to 14.4 ± 2.4 mmHg (29.7%) with three treatments.ConclusionsLowering of IOP and number of responders after SLT appears to be more important un OHT and OAG patients with less topical antiglaucoma treatment.
Impact of Storage Temperature on Gene Expression of Cultured ARPE‐19 Cells
Authors: Pasovic L. , Eidet J.R. , Olstad O.K. , Chen D.F. , Lyberg T. , Utheim T.P. 
Published: September 2015

PurposeThe development of a suitable storage method for retinal pigment epithelium (RPE) is necessary in the establishment of future RPE replacement therapy, and storage temperature has proven to be pivotal for cell survival. We analyzed the gene expression profile of cultured human RPE cells after storage at 4°C, 16°C, and 37°C.MethodsARPE‐19 cells were cultured until confluence and stored in Minimum Essential Medium at 4°C, 16°C, and 37°C for seven days. DNA microarrays validated by qRT‐PCR were used to determine the gene expression profile.ResultsThe gene expression profile of cultures stored at 4°C cluster closest to the control cultures that were not stored and display the least change in gene expression after storage (157 differentially expressed genes compared to controls), while cultures stored at 16°C and 37°C display much larger changes compared to controls (1787 and 1357 differentially expressed genes, respectively). Expression levels of key genes involved in phagocytosis, pigment synthesis, the visual cycle, cell junctions, and cellular transport were maintained close to control levels in cultures stored at both 4°C and 16°C in contrast to 37 °C.ConclusionsRPE cell cultures stored at 16°C appear to modulate their gene expression profile in a manner that supports cell survival during storage, while maintaining the expression levels of genes important for key RPE functions.
Occult non‐metallic intraocular foreign body causing recurrent anterior uveitis
Authors: Morreale Bubella R. 
Published: September 2015

PurposeTo describe the case of textile worker with recurrent anterior uveitis following the traumatic penetration of nylon thread into the anterior segment of the eye.MethodsExamination by slit‐lamp of the affected eye B‐scan ultrasonography during the inflammatory episode and after the resolution of the uveitis. Visual Acuity Measurement during the inflammatory episode and after the resolution of the uveitis.ResultsThe use of topical therapy together with antibiotic systemic therapy led to the regression of the inflammatory symptoms (intense epibulbar and tarsal hyperemia with perikeratic reaction, corneal sub‐oedema with some folds in the Descemet's membrane, Tyndall 2+ and a layer of lower hypopyon associated with a filamentous foreign body with a spiral shape at the base of the lower chamber. In miosis the pupil did not react to a light stimulus) and pain. Removal of the foreign body allowed the rapid resolution of the recurrent uveitis.ConclusionsThis case underlines the need for an accurate search for possible foreign bodies in cases of ocular traumas, even apparently slight ones, once penetration into the posterior chamber has been excluded.
Sarcoidosis of orbita and central nervous system presenting as a non‐arteritic ischemic optic neuropathy
Authors: De Bruyn D. , Ninclaus V. , Leroy B.P. , De Schryver I. , De Zaeytijd J. 
Published: September 2015

PurposeTo describe a patient who presented with non‐arteritic ischemic optic neuropathy (NA‐AION) as an initial manifestation of neurosarcoidosis.MethodsA case of a 70‐year‐old woman who presented with loss of vision in the left eye and normal neuroimaging, was initially diagnosed as a NA‐AION. An extensive workup included MRI orbita and PET/CT scan.ResultsAt the initial presentation, the left eye showed loss of vision and papilloedema. Further ophthalmological examination was normal, as was a CT scan of the brain. A diagnosis of NA‐AION was entertained. After 4 months, she had no light perception vision. Fundoscopy of the LE showed papilloedema with retinal infiltrates and severe ischaemia. MRI of the brain showed mass infiltration of the intraorbital and the intracranial optic nerve up to the optic chiasm. A complete systemic workup revealed a monoclonal gammopathy with cervical and hilar lymph nodes noted on PET/CT scan. Mediastinoscopy with biopsy of the hilar lymph nodes demonstrated a non‐caseating granulomatous lesion and a diagnosis of sarcoidosis was confirmed.ConclusionsSarcoidosis is a multisystemic disease characterized by granulomatous inflammation. Ocular involvement is seen in approximately 25% of patients with sarcoidosis. Uveitis is the most common ocular manifestation. Orbital and CNS manifestations of sarcoidosis are uncommon. Involvement of the optic nerve, chiasm and visual tract only represent 1–5% of neurosarcoidosis cases. In the latter, sarcoidosis can be initially misdiagnosed as NA‐AION, before involvement of the orbit and the CNS. Systemic involvement should be ruled out in any case of AION with an atypical evolution.
Repeatability of wide‐field autofluorescence lifetime imaging at the human retina in healthy volunteers
Authors: Klemm M. , Dietzel A. , Nagel E. , Schweitzer D. 
Published: September 2015

PurposeThe detection of metabolic changes in the retina is the goal of fluorescence lifetime ophthalmoscopy (FLIO). We performed an observational clinical study in young healthy volunteers to examine the usability of 55° wide‐field fluorescence lifetime images.MethodsThe time‐resolved retina autofluorescence was measured (scanning laser ophthalmoscope: 55° of fundus, 62 µm resolution; excitation: diode laser with pico‐second pulses, 473 nm, 80 MHz repetition rate; detection: spectral channels 500–560 nm (ch1) and 560–720 nm (ch2), time‐correlated single photon counting method) in the right eye of 11 healthy volunteers (28.7 ± 3.6 years). Three repetitive measurements (m1–m3) on different days within one week at a similar time have been performed. All subjects had a crystalline lens and an undilated pupil. A modified 3‐exponential approach was applied to determine the fluorescence lifetimes τ. τ were computed on the ETDRS grid and in a 15 × 15 pixel region 25° superior to the fovea.Results49% of the measurements had shadowing effects in the inferior image region caused by eye lashes. τ (mean ± std) over all volunteers are: outer ring ETDRS gridsuperior regionch1ch2ch1ch2m1: 350 ± 25 ps255 ± 11 ps 348 ± 20 ps260 ± 7 psm2: 357 ± 27 ps257 ± 12 ps 357 ± 20 ps261 ± 7 psm3: 350 ± 26 ps257 ± 12 ps 327 ± 17 ps254 ± 5 psResults for the inner ring of the ETDRS grid are similar to the outer ring. The coefficient of variation in the superior region is 5.5% in ch1 and 2.5% in ch2. τ of repetitive measurements as well as of ETDRS grid's outer ring and the superior region are within the standard deviation.ConclusionsFLIO measurements in young healthy volunteers using a 55° lens are repeatable. Spectral channel 2 is preferable because of its lower variability.
Choroidal Thickness and Systemic Examination in Diabetic Patients without Diabetic Retinopathy
Authors: Cardigos J. , Vicente A. , Costa L. , Crisóstomo S. , Marques N. , Cunha J.P. , Pinto L.A. , Ferreira J. 
Published: September 2015

PurposeThe choroidal circulation receives nearly 95% of ocular blood flow and it is essential for a normal retinal structure and function. Recently, several clinical studies showed a variation in choroidal thickness (CT) even before the presence of diabetic retinopathy (DR), which the meaning remains uncertain and questionable. Our objective was to analyze and correlate the CT with the disease duration, systemic blood pressure (SBP) and analytic evaluation.MethodsProspective, observational case‐control study. A complete ophthalmological examination was performed, including dynamic contour tonometry and axial length. CT was assessed by a non‐invasive procedure using an OCT (Spectralis Heidelberg Engineering) with an enhanced depth mode (EDI) at 13 different locations (subfoveal and 3 measurements 500 μm apart in all 4 directions – nasal, temporal, superior and inferior). The SBP was measured and an analytical evaluation was performed, including glycemia, glycosylated hemoglobin – HbA1c, lipid parameters, renal function, ionogram and microalbuminuria. Correlation between variables was explored using Spearman correlations.ResultsThe study included 65 diabetic patients without DR (36 females; mean age 67.23 ± 9.08 years), with an average disease duration of 90.42 ± 81.82 months. The CT didn't showed a correlation with disease duration, SBP, glycemia, HbA1c, renal function, lipid parameters, homocysteinemia, natremia or microalbuminuria. However, the CT was positively correlated with potassium and chlorine serum levels in 5 points, with statistic significance (r between 0.26 and 0.31, p < 0.05).ConclusionsCT may be positively influenced by serum levels of potassium‐chlorine in diabetic patients but not in healthy controls. These abnormal CT relationships can be detected even with no visible DR. Further studies are needed to explore these differences.
Analysis of Mp‐1 audio‐biofeedback impact on fixation in low vision patient with maculopathy
Authors: Sato G. , Rizzo R. , Villani G.M. , Camerucci C. 
Published: September 2015

PurposeTo study the impact of a low vision rehabilitation strategy based on Nidek MP‐1 auditory biofeedback (BFB).MethodsRetrospective study of 39 eyes/26 consecutive patients referred for low vision rehabilitation. Patients received 8 monocular training sessions of BFB, each of 10 minutes duration, 7–14 days apart. Microperimetry, ETDRS VA and Pelli‐Robson was performed at the beginning and at the end of the sequence. BFB employs a sound to train the patient to keep a specific gaze position.ResultsAge median was 70. Pre‐BFB logMAR VA was 1, logCS 0.60. Post‐BFB logMAR VA was 1, logCS 0.75. Dense central scotomas and eccentric fixation locations were detected in 35 eyes/24 patients, and relative scotomas with central fixations in 4 eyes/2 patients. Mean sensitivity was 7.60 dB pre‐BFB, and 8 db post‐BFB. Pre‐BFB fixation stability was 24% within 2°, and 67% within 4°; post‐BFB, it was 25% within 2°, and 64% within 4°. BCEA analysis showed pre‐BFB values for 68.2% BCEA to be 3.6, and 4.46 post‐BFB. After BFB, no significant difference was found for any of the above‐mentioned parameters in the sample as a whole. Nevertheless, grouping cases by change in pre‐vs post‐BFB BCEA (group A: decrease in BCEA, n = 21; group B: increase in BCEA, n = 18) showed a significant difference in terms of BCEA itself, and in the related fixation stability (p < 0.05).ConclusionsAlthough no significant difference in VA, CS, mean sensitivity, fixation stability at 2° and 4°, and BCEA was found after BFB in the sample as a whole, still there was an improvement in 21 eyes (53.8%) in terms of BCEA and fixation stability. Grouping analysis demonstrated that, while other tested outcome measures were not affected, some cases did respond significantly to BFB improving their fixation stability.
The effect of macular edema on the measurement of retinal nerve fiber layer thickness and the thickness of peripapillary retina
Authors: Kim S. , Lee S. , Lee J. 
Published: September 2015

PurposeWith advanced in accuracy and reproducibility of spectral domain optical coherent tomography, It issuggested that the serial changes of retinal nerve fiber layer (RNFL) thickness could reflect the progression of glaucoma. But, patient may have accompany disease that affect retinal structure such as diabetes, venular occlusive diasese and macular degenerative diasese. So, we investigated the factors that influence the measurement of RNFL and peripapillaryretina.MethodsIn this retrospective controlled case series, we reviewed the eyes with macular edema. Analyzed factorsassociated RNFL thickness and peripapillary retina ranging from 3 mm and 5 mm of optic disc included age, IOP, visualacuity, central macular thickness (CMT), central macular thickness changes and kinds comorbid diasese. All themeasured values were obtained at initial presentation and the presentation when macular edema was relieved. The RNFL thickness and peripapillary retinal thickness were measured by SD‐OCT (Spectralis OCT).ResultsThe measured value RNFL thickness and peripapillary retina were significantly fluctuate with the macularedema. The initial CMT, CMT changes were quantitively correlated with RNFL thickness alteration (p < 0.01). The initialCMT, CMT changes also significantly correlated with peripapillary retina ranging from 3 and 5 mm of optic disc, butthere was distinction associated with geographic difference. In the subgroup analysis, there were difference associations according to kinds comorbid diasese.ConclusionsThe macular edema effected the RNFL and the peripapillary retina. The measurements of RNFL andperipaillary retina were quantitively correlated in some kinds of comorbid diasese. The central macular thickness shouldbe considered in clinical application of detection about decreased RNFL thickness in patients who have macular edema.
Topical treatment with a new matrix therapy agent (RGTA, CACICOL) improves epithelial wound healing after penetrating keratoplasty in a rabbit model
Authors: Crouzet E. , He Z. , Olmiere C. , Perrache C. , Piselli S. , Jullienne R. , Gain P. , Thuret G. 
Published: September 2015

PurposeEpithelial wound healing is a milestone in the early post‐operative care after penetrating keratoplasty (PKP). It reduces the infectious risk, allows safe instillation of steroids, and conditions discharge from hospitalization. The present study assessed a new matrix therapy agent, for the management of post PKP epithelial defects in a preclinical rabbit model of PKP.MethodsNew Zealand white rabbits received a 7.1/7 mm PKP with a desepithelialized rabbit cornea from the same sibling. Immunosuppression was obtained thanks to subconjonctival corticosteroid. Rabbits were randomized to receive either CACICOL (n = 3) or a placebo (n = 3). Investigators were masked. Eyedrops were instilled immediately after graft and repeated on alternate day until complete reepithelilalization. The epithelial wound healing was monitored fluorescein staining. Corneal thickness was monitored using AS‐OCT. Rabbits were euthanatized and corneas were analyzed using histological cross sections, confocal microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM).ResultsCorneas receiving CACICOL healed in 6, 6 and 8 days versus 8, 8 and 10 days with the placebo (P = 0.099). Epithelial thicknesses were 45, 32 et 23 μm with CACICOL and 25, 29 et 19 μm with the placebo. In SEM superficial cells of the CACICOL group were similar to normal corneas and had more numerous microvilli with the placebo. MET showed normal epithelial ultrastructure in the CACICOL group with more hemidesmosomes than with the placebo.ConclusionsRGTA seems a potentially useful, noninvasive therapeutic approach in PKP management.
Cell penetrating peptide constructs: A novel drug delivery to the eye
Authors: Scott R. , Hill L. , de Cogan F. , O'Neill J. , Logan A. 
Published: September 2015

PurposeIn neovascular age‐related macular degeneration (AMD) blood vessels grow from the choroid under the retina causing macular damage and scarring. Anti‐VEGF drugs such as, ranibizumab or aflibercept are administered by intravitreal injection to treat AMD related neovascularisation, We present a novel cell‐penetrating peptide construct (CPPC) topical delivery system to deliver Ranibizumab to the retina using drops.MethodsPeptides were produced using standard solid‐phase peptide synthesis. They were analysed using mass spectrometry and purified using high‐pressure liquid chromatography and used at a purity of >95%. CPPC were built around the drugs by vortexing for 10 seconds and incubating at room temperature. Drug delivery experiments were carried out ex‐vivo in freshly enucleated porcine eyes. In vivo experiments were carried out in C57 mice. Mice had a three 100 μm laser burns to the choroid to model neo‐vascularisation in AMD. They then received a single intravitreal injection of an anti‐VEGF agent or CPPC/Ranibizumab applied topically to the conjunctival sac twice daily for the duration of the experiment. Choroidal neovascularisation was measured by immunohistochemistry.ResultsEx vivo delivery to enucleated porcine eyes demonstrated that a single 60 μL drop could deliver 1.7 ± 0.4 μg/mL of ranibizumab to the vitreous cavity. Confocal images of immunohistochemistry on retinal wholemounts showed ranibizumab within the retina. In vivo experiments demonstrated both intravitreal injection and CPPC bound Ranibizumab reduced neovascularisation equally, compared to controlsConclusionsCPPC can be used topically to deliver therapeutic levels of Ranibizumab to the posterior segment.
BAP1 correlates with metastasis in polyploid uveal melanoma
Authors: Kilic E. , Yavuzyigitoglu S. , Mensink H. , Vaarwater J. , Naus N. , Paridaens D. , de Klein A. 
Published: September 2015

PurposeMost of the Uvea melanoma (UM) display a near‐diploid karyotype with only a few chromosomal changes. In contrast to these simple aberrations 10% of the UM samples show a polyploid character (> 58 chromosomes) and were associated with unfavorable prognosis. This study attempts to gain insight in polyploidy in UM and supplement the old data with the current knowledge on mutations in UM specific genes.MethodsFluorescence‐In‐Situ‐Hybridization (FISH) and/or Single‐Nucleotide‐Polymorphism (SNP) array was used to determine the ploidy status. Tumors showing signs of polyploidy (range tri‐ tetraploidy) were further investigated. Immune‐histochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) or the hotspots for the GNAQ, GNA11, SF3B1 and EIF1AX genes was carried out using Sanger Sequencing .ResultsPolyploidy was seen in 23 tumor samples. Fourteen of the UM patients developed metastases with a median follow‐up of 35 months. Thirteen tumors showed loss of BAP1 expression and all genetically tested polyploid tumors harbored a GNAQ or GNA11 mutation. SF3B1 mutations were found in three UM specimens and one of the tumors harbored an EIF1AX mutation. Univariate analyses showed a significant association with decreased survival for chromosome 1, 3 and 8 aberrations, SF3B1 wild type and a loss of BAP1 expression. In the multivariate analyses, BAP1 expression was the only independent prognostic marker within the polyploid tumors (HR 10.1; p = 0.008).ConclusionsAlso for the tumors displaying polyploidy loss of BAP1 expression is associated with an increased risk of metastatic disease.