bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous choroidal thickness pattern in diabetic patients without diabetic retinopathy
Authors: Vicente A. , Costa L. , Cardigos J. , Santos A. , Amado D. , Cunha J.P. , Abegao Pinto L. , Ferreira J. 
Published: September 2015

PurposeThe authors intend to present an analysis and comparison of the choroidal thickness in more distant superior regions. Choroidal thickness is increased in a heterogeneous pattern superiorly to the fovea in diabetic patients without diabetic retinopathy.MethodsObservational case‐control study of 60 eyes of 60 patients with diabetes mellitus type 2 without diabetic retinopathy. A control group of 31 eyes of 31 patients without diabetes with similar demographic features was also created. All the patients were recruited from the same outpatient clinic. Enhanced depth imaging spectral‐domain optical coherence tomography (EDI SD‐OCT SPECTRALIS®) was performed and high‐resolution macular scans were obtained. Choroidal thickness was evaluated 2000 μm superiorly to the fovea by manual layer segmentation. Previous studies have validated the validity of using a manual layer segmentation procedure in OCT. Statistical analysis was done with SPSS Statistics. A p value <0.05 was considered statistically significant.ResultsDiabetic patients were in average 67.0 ± 9.6 years old and 56.7% were male. Average choroidal thickness 2000 μm superiorly to the fovea was 287.77 ± 74.32 μm in diabetic patients and 249.81 ± 53.96 μm in non‐diabetic patients. There was a significant increase in choroidal thickness in diabetic patients when compared to non‐diabetic patients (T‐student, p = 0.014).ConclusionsChoroidal thickness can be accurately measured using high‐definition macular OCT scans. This study documented structural differences in the choroid associated with diabetes mellitus type 2 that are not only present in the central foveal area as reported in previous studies. Diabetes Mellitus is associated with multiple microvascular dysfunctions that are probably coupled with choroidal vascular modifications that induce changes in thickness.
Macular diseases in myopia
Authors: Creuzot C. 
Published: September 2015

SummaryPathologic myopia is a leading cause of blindness wordlwide with macular degeneration often related to a posterior ectasia named staphyloma. This degeneration leads to a progressive thinning of the retinal pigment epithelium and choroid. The main signs of macular diseases due to myopia can vary from yellow‐white breaks in Bruch's membrane called lacquer cracks, subretinal hemorrhages and secondary neovascularisation that can be associated. The diagnosis can be made with visual acuity measurement, fundus exam, OCT, autofluorescence and angiography to differentiate isolated hemorhhages and choroidal neovascularisation. The prognosis of myopic choroidal neovascularisation has been greatly improved with antiangiogneic agents.
Outcomes of using intravitreal ranibizumab to treat patients with ischaemic diabetic maculopathy
Authors: Begum S. , Lockwood A. , Mourtzouko S. 
Published: September 2015

PurposeTo report the functional and anatomical outcomes of using intravitreal ranibizumab (IR) for patients with ischaemic diabetic maculopathy (IDM).MethodsRetrospective analysis of 11 consecutive patients treated with IR for IDM from Nov 2008 to May 2015. The number of injections, fluorescein fundus angiography (FFA) results, visual acuity (VA) and central retinal thickness (CRT) prior to commencing IR were recorded. VA was assessed with logMAR.ResultsThree eyes were excluded as one had a history of vein occlusion, one was amblyopic and the other patient had multiple vitreous haemorrhages and vitrectomy.There were equal numbers of females and males, the average age was 67 (34–82 years) and patients had on average 5 (range 3–11) injections of IR. Average length of follow up was 13 months (5–18 months). On FFA 4 patients had enlargement of foveal avascular zone (FAZ), 1 patient had fragmentation of FAZ, 1 patient had deregulation of FAZ and 1 patient had an increase in FAZ. The average initial VA was +0.9 (+0.3 to +1.78) and the average final VA was +1.05 (+0.6 to +1.78). The average change between initial and final VA was +0.15. Initial average CRT was 558 (306–785) reducing to an average of 447 (197–892) at the final follow up. The average CRT reduction was 111 between initial and final CRT.ConclusionsAnatomical thickness appears to be reduced with IR injections, but without improvement in visual acuity. No adverse complications were noted with this regimen.
Clinical Experience with the Ruthenium‐ plaque Brachytherapy in Case of Choroidal Melanoma
Authors: Grajewski L. , Kneifel C. , Ciernik I. , Ebrahimi F. , Krause L. 
Published: September 2015

PurposeThe brachytherapy with β‐ emitting ruthenium‐ plaques is a well‐established treatment for patients with choroidal melanoma. This treatment modality has been used in our department since January 2011.MethodsA retrospective study of 104 eyes with choroidal melanoma that were treated with ruthenium‐ brachytherapy between January 2011 and December 2014. Patients were followed for regression and associated side‐ effects. The study included patients that had a follow‐ up time of at least 3 months.ResultsOf the 104 melanomas nine also showed an infiltration of the ciliary body, 32 manifested at a central location and 59 eyes showed an exudative retinal detachment prior to brachytherapy. The mean sclera contact dose was 519 Gy, the mean apical dose applied was 105 Gy. The mean apical depth of the melanoma prior to therapy was 4.3 mm and after 12 months 2.2 mm. In three cases a movement of the plaques was necessary since the plaque did not cover the tumour margins in total because of the diameter of the melanomas. In eight cases the tumour showed regrowth after an initial regression was noticed. All together four eyes had to be removed. In eight cases distant metastasis were detected and two eyes showed a radiation retinopathy.ConclusionsFor the treatment of choroidal melanoma the β‐ emitting ruthenium‐ plaques represent a therapy with a local tumour control rate of 92.3% and eye salvaging rate of 96.2%.
Neurotrophic keratitis (NK) in carotid cavernous fistulae (CCF)
Authors: Stephan S. , Rouger H. , Doan S. , Lamirel C. , Cochereau I. , Gabison E. 
Published: September 2015

PurposeCarotid cavernous fistulae (CCF) are rare, with a poor visual outcome. In addition, lesions of trigeminal nerve induced by an elevated venous pressure in the cavernous sinus may induce a neurotrophic keratitis (NK). Embolization is the standard care.The objective of this study was to assess NK in a group of patients treated by embolization of their CCF using in vivo confocal microscopy.MethodsPatients treated for an indirect CCF from January 2004 to May 2013 were prospectively included. The diagnostic of NK was assessed by Oxford's test, Cochet‐Bonnet's esthesiometry and a study of corneal nerves by in vivo confocal microscopy. Results were compared using Student t‐test.Results13 patients, 5 men and 8 women, with a median age of 67 years old were included with a median follow‐up of 51 months: 38% (5/13) had a NK, of which 40% (2/5) bilateral. 60% (3/5) were clinically cured, with a minimal to moderate NK; and 40% (2/5) had persisting CCF symptoms with a moderate to severe NK.ConclusionsTo our knowledge, NK resulting of a compression of the trigeminal nerve by CCF has never been studied. On the other hand, NK is a challenging diagnosis because of a poor clinical presentation. Recently, in vivo confocal microscopy has been developed for corneal nerves analysis and should therefore be considered as an interesting tool to assess NK in patients treated for a CCF.NK are frequent (38%) in patients treated for CCF. NK are minime to moderate and sometimes bilateral. Early diagnosis using in vivo confocal microscopy should avoid corneal complication.
Proteomic analysis of the uveal melanoma (UM) secretome reveals novel insights and potential biomarkers
Authors: Angi M. , Kalirai H. , Coupland S. 
Published: September 2015

PurposeUM is the most common primary intraocular tumour in adults. Despite successful ocular treatment, 50% of patients develop fatal metastatic spread, usually involving the liver. UM patients are stratified into high risk (HR) or low risk (LR) metastatic groups, according to clinical, histopathological and genetic features of their tumours. Blood biomarkers are urgently needed to detect the early development of metastatic disease. The aims of this work were to increase our understanding of UM metastasis processes, and to identify secreted biomarkers of UM metastatic disease.MethodsComparative analysis of the secretome from short‐term cultures of HR and LR UM patient samples was performed by nanoLC‐MS/MS‐based label‐free quantitative proteomics. Normal (N) controls included the secretome of cultured normal choroidal melanocytes. Secreted proteins were predicted based on their sequences. Bioinformatic analyses were performed using Partek and Ingenuity Pathway Analysis software.ResultsEighteen UM (4LR; 14HR) and 5N cultures were established and their secretomes analysed. 1917 proteins were identified, and 1857 quantified in all subgroups. 627/1857 (34%) were classically and non‐classically secreted, and 554/1857 (30%) represented exosomal proteins. 947 proteins were differentially expressed between UM and N; pathway analysis demonstrated upregulation of proteins involved in mTOR signalling amongst others. An 18‐protein signature that discriminated between HR and LR UMs was identified.ConclusionsOur comparative study of the secretome of N versus UM has identified cancer‐associated proteins linked to cell proliferation and cancer progression. Moreover, a UM secretome signature of metastatic risk was identified. Further studies on the exosomal fraction are also being performed.
Novel SRPK1 inhibitors specifically target alternative splicing in human primary retinal epithelial cells
Authors: Rowlinson J. , Batson J. , Toop H. , Allen C. , Gibbons B. , Babaei‐Jadidi R. , Zhang J. , Wearmouth S. , Knapp S. , Morris J. , Bates D. 
Published: September 2015

PurposeSpecifically altering the splicing of VEGF‐A from pro‐angiogenic VEGF‐A165a to anti‐angiogenic VEGF‐A165b could prove effective in the treatment of wet AMD. VEGF‐A alternative splicing is controlled through RNA binding protein SRSF1 which when phosphorylated by the serine kinase SRPK1 induces pro‐angiogenic VEGF‐A165a expression. We aimed to use novel SRPK1 inhibitors that specifically alter splicing in retinal pigment epithelial (RPE) cells.MethodsRPE cells were treated with novel compounds, synthesized based on the structure of SRPK1, followed by extraction of RNA and protein. RT‐PCR and digital PCR was used to examine splicing of genes expressed in the eye or known targets of SRPK1, and ELISA and immunoblotting were used to detect VEGF‐A isoform expression.ResultsNovel SRPK1 inhibitors dose‐dependently increased the expression of the anti‐angiogenic VEGF‐A165b isoform. RT‐PCR showed that SRPK1 inhibition altered alternative splicing of MKNK2, a known splicing target of SRSF1, resulting in a 2 fold change to isoform a in RPE cells. No change in splicing was observed for BCL2L1, ARR1, CAMK2D, RAC1, FN1 or hnRNPB1/A2. Other SRSF1 targets such as TEAD1, BIM and MST1R were not expressed in RPE cells.ConclusionsWe have developed novel SRPK1 inhibitors that specifically target splicing within the retina and offer an alternative more specific therapeutics for patients with exudative AMD.
Stimulation of TLR4 Increases Angiogenic and Anti‐Angiogenic Gene Expression in Choroidal Endothelial Cells
Authors: Stewart E. , Wei R. , Uribe M. , May S. , Amoaku W. 
Published: September 2015

PurposeThe Toll‐like receptor (TLR) family initiate the innate immune response in reaction to invading microbes. Studies confirm the expression of TLRs in a variety of ocular tissues and cells, and it has also been suggested that selected TLRs may be associated with geographic atrophy and neovascularisation in age‐related macular degeneration, diabetic retinopathy and other vascular and inflammatory diseases of the ocular posterior segment. However, the exact mechanisms of TLR stimulation and the mechanism of endothelial inflammatory and angiogenic effects have not been defined.MethodsMicroarray analysis was performed on primary human choroidal endothelial cells stimulated with LPS, a specific TLR ligand. Microarray results were validated using qPCR and the functional significance of increased factors were investigated using proliferation and migration assays.ResultsMicroarray indicated a large increase in expression of angiogenic (e.g. CCL2, IL‐8) and anti‐angiogenic (e.g. CXCL10, CXCL11) molecules. The fold change in expression of these molecules was validated using qPCR and the secretion using ELISA. Reported angiogenic molecules were confirmed to have a pro‐angiogenic effect in vitro.ConclusionsThis profiling of factors increased during TLR4 stimulation will help inform our understanding of inflammation in choroidal vascular diseases, as well as the development of future treatments for intraocular vascular diseases.
Two Sisters with Congenital Blindness caused by Osteoporosis‐pseudoglioma Syndrome due to new Mutations in the LPR5 Gene
Authors: Welinder L. , Robitaille J.M. , Boerkoel C.F. , Rupps R. , Lyons C. 
Published: September 2015

PurposeTo discover the reason behind two sisters being born blind with retinal detachment and microphthalmia with later findings of severe osteoporosis with low impact fractures.MethodsMolecular testing identified biallelic lipoprotein receptor‐related protein 5 (LRP5) mutations (NM_002335.3:c. [889dupA]; [2827 + 1G4A]) confirming a diagnosis of osteoporosis–pseudoglioma (OPPG) syndrome.ResultsTwo new mutations in the LPR5 gene were each found in the unrelated parents of the girls and were found heterozygote in the girls. Both parents were then discovered to have osteopenia, as did several relatives, who all started preventive treatment.ConclusionsOPPG is a autosomal recessive disease almost uniformly causing blindness from very early age with severe osteoporosis and low impact fractures, which was also the case of our two sisters. The diagnosis of OPPG was confirmed by sequencing the LPR5 gene, where two new mutations were found.
Significance of Camouflage, Chromatic Acuity and Contour in the Design of Pseudoisochromatic Plates
Authors: Krastel H. , Schultze‐Lutter S. , Mothes N. , Udodov E. , Kahlert C. , Jonas J.B. 
Published: September 2015

PurposePseudoisochromatic plates use a pseudo‐chaotic pattern of image dots to conceal the contour of colour optotypes. By our study we wantto improve the understanding of functional principles of pseudoisochromatic plates.MethodsThe circular elements of red/green pseudoisochromatic plates were varied in size and degree of pseudo‐chaotic arrangement. Illuminated by standard white D 65, colour optotypes were presented to daltonians and to normal observers, and the rates of failure and success in recognition were recorded.ResultsRecognition of pseudoisochromatic optotypes is related to the size of elements in a non‐ linear way. Towards small visual angles, colour optotype recognition may improve due to fusion of the perceived colour of adjacent small elements. Towards large visual angles, colour optotype recognition may again improve due to detection of the individual colours of elements. Weakening of contours by defocus may improve the recognition of colour optotypes due to loss of camouflage. Loss of camouflage also occurs with a more regular, less pseudo‐chaotic arrangement of image dots, thus facilitating the recognition of colour optotypes.ConclusionsBesides the colours themselves, arrangement and size of coloured elements need careful consideration in designing pseudoisochromatic plates. In application of the plates defocusing has to be avoided.
The “complete vitrectomy performed early” treatment philosophy
Authors: Rocha De Sousa A. , Gouveia P. , Correia‐Pinto J. , Alves P. , Falcao‐Reis F. 
Published: September 2015

PurposeTo compare the impact of early versus late complete vitrectomy in the management of acute postoperative endophthalmitis (PE).MethodsRetrospective study.Results57 eyes from 57 patients were included in this study. 49.1% of patients were males. Baseline characteristics were similar in all groups (VIT, NVIT, VIT_early and VIT_late). Mean visual acuity at presentation was hand movements (2.3 logMAR) in all groups. After treatment mean visual acuity was 1.2 ± 1.1 logMAR in the NVIT group and 1.9 ± 1.2 logMAR in the VIT group (p = 0.075). The differences between visual outcomes in VIT_early and VIT_late groups, however, achieved statistical significance (p = 0.012): 0.8 ± 1.1 logMAR in the VIT_early group whereas in the VIT_late group it was 2.2 ± 1.0 logMAR. Significant differences between visual outcomes were also encountered when comparing NVIT and VIT_late groups (p = 0.008). The difference in final visual acuity between VIT_early and NVIT didn't not attain statistical difference (p = 0.459).ConclusionsThis study highlights the impact of a complete early vitrectomy in the management of PE. A complete vitrectomy didn't surpass the visual results of intravitreal antibiotics alone (p = 0.075). Howeverm a complete vitrectomy performed within the first 24 hours after presentation was clearly beneficial when compared to vitrectomy performed later (p = 0.012). Furthermore, our series suggests that a late vitrectomy is detrimental to visual results when compared to intravitreal antibiotics (p = 0.008).
Intra and inter‐rater agreement of anterior lamina cribrosa depth measurements using enhanced‐depth imaging optical coherence tomography
Authors: Leal I. , Cordeiro Sousa D. , Couceiro R. , Barata A. , Abegao Pinto L. , Pinto F. , Marques‐Neves C. 
Published: September 2015

PurposeTo determine intra and inter‐rater agreement of anterior lamina cribrosa depth (ALCD) manual measurements using enhanced depth imaging spectral‐domain optical coherence tomography (EDI‐OCT).MethodsDouble blind prospective observational study between December 14 and May 15. EDI‐OCT of optic nerve head was performed in subjects with an irrelevant ophthalmologic history (2 cross scans: vertical and horizontal). ALCD was defined as the perpendicular distance between the line connecting both edges of Bruch's membrane and the anterior border of the lamina cribrosa, at the maximum depth point. Two double‐blinded experienced operators manually measured ALCD twice, with a one‐month interval. Intra and inter‐rater agreement was evaluated using intraclass correlation coefficients (ICC), concordance correlation coefficients (CCC) and Bland‐Altman (BA) plots for the right eye vertical (RV) and horizontal (RH) scans and left eye vertical (LV) and horizontal (LH) scans. Statistical analyses were performed using STATA 13.0.ResultsStudied population included 44 subjects (26 women), with a mean age of 62.9 ± 14.3 years. Mean vertical and horizontal maximum ALCD was 453.3 ± 88 μm and 436.1 ± 78.7 μm, respectively. Intra‐rater ICC for ALCD in RV, RH, LV and LH were 0.98, 0.94, 0.97 and 0.96, respectively. Inter‐rater ICC for ALCD in RV, RH, LV and LH were all 0.99. Intra‐rater CCC for ALCD in RV, RH, LV and LH were 0.98, 0.93, 0.97 and 0.96. Inter‐rater CCC for ALCD in RV, RH, LV and LH were all 0.99. Bland–Altman plots suggested that almost all observations were within the 95% limits of agreement.ConclusionsALCD manual measurements with EDI‐OCT showed high agreement among intra and inter‐rater measurements in healthy eyes. EDI‐OCT is a reliable tool for ALCD measurement, which can provide potentially useful information for integrated glaucoma management.
Testing of an automated tablet‐based method for the determination of low contrast near visual acuity in ophthalmic patients
Authors: Mirza N. , Tahir H.J. , Wang Y. , Parry N.R.A. , Murray I.J. , Aslam T.M. 
Published: September 2015

PurposeTo test an automated, tablet‐based self‐testing method for the determination of low contrast near visual acuity in ophthalmic patients.MethodsThe Mobile Assessment of Vision by intERactIve Computer (MAVERIC) system consists of a calibrated tablet computer (Samsung Galaxy Tab S 8.4) running purpose‐built software housed in a bespoke physical booth. Near low contrast (25%) visual acuity was measured in one eye using the MAVERIC system and a near ETDRS chart at a distance of 40 cm on a population of ophthalmic patients with various retinal conditions. Patients independently completed testing using the MAVERIC system once an explanation of its use had been given. Repeat measures of near acuity were also conducted using the MAVERIC system.ResultsThe MAVERIC system displayed excellent repeatability. Bland Altman analysis of data showed reasonable agreement between measurements obtained using MAVERIC and the near ETDRS chart. The degree of difference between data sets was consistent.ConclusionsThis study demonstrates the potential viability of the MAVERIC self‐testing system as a means to test low contrast near visual acuity in ophthalmic patients with a high degree of reliability and thus a potential method of both initial assessment and monitoring of near visual acuity in such patients.
Assessing the microstructures of the human cornea using Gabor‐Domain optical coherence microscopy with large field of view and high resolution
Authors: Thuret G. , Tankam P. , He Z. , Lanis M. , Canavesi C. , Lepinet T. , Hindman H. , Topham D. , Gain P. , Rolland J.P. 
Published: September 2015

PurposeTo investigate the performances of a new large field of view and high volumetric‐resolution Gabor‐Domain Optical Coherence Microscope (GD‐OCM) in imaging human corneal microstructuresMethodsThe GD‐OCM combined the high sectioning capability of optical coherence tomography with the high lateral resolution of confocal microscopy. We developed a system that achieved high‐contrast imaging with a field of view of 1 ± 1 mm2 and volumetric cellular resolution of 2 μm across a thickness of up to 2 mm in tissue. The system fitted on a movable cart and the handheld scanning probe was attached to an articulated arm that may be adjusted to image different locations of the cornea without contact. For real time visualization, we implemented a parallelized Multi‐Graphic Processing Units architecture to speed up the processing of data. In this investigation, we focused on imaging the microanatomy of the corneal stroma keratocytes as well as corneal endothelial cells of ex vivo human corneas maintained in an innovative bioreactorResultsThe overall time to 3D visualization, including acquisition that is 1.5 minutes, processing and rendering of a 1000 × 1000 × 400 voxels, was <2 minutes compared to 2 hours on a conventional CPU. The system produced 3D high‐resolution images of the distribution of epithelial cells, stromal keratocytes and endothelial cells, comparable to standard in vivo confocal microscopyConclusionsThis innovative GD‐OCM allows pseudo histology of the cornea in an unprecedented wide field and a short acquisition time compatible with analysis of ex vivo living corneas