bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lubricin: translating an idea into a cure
Authors: SULLIVAN DA , SCHMIDT T , KNOP E , KNOP N , SULLIVAN BD 
Published: August 2012

AbstractPurpose We hypothesize that lubricin, a boundary lubricant, is transcribed, translated and expressed by the ocular surface and serves to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink. We also hypothesize that lubricin deficiency increases shear stress and promotes corneal damage. Our objective was to test these hypotheses.Methods Human tissues and cells were processed for molecular, immunochemical and/or biomechanical procedures. Techniques included the use of real‐time PCR, microarrays, sequencing, immunohistochemistry and friction analyses. Methods also involved the corneal evaluation of wildtype and lubricin knockout (KO) mice.Results Our results show that lubricin is produced by human corneal and conjunctival epithelial cells. Lubricin absence in KO mice is associated with a significant increase in corneal fluorescein staining. Our findings also demonstrate that lubricin functions as a very effective friction‐lowering boundary lubricant at the human cornea‐eyelid interface.Conclusion Our data indicate that lubricin acts as a natural boundary lubricant to reduce shear stress at the ocular surface. We thank S Richards, S Liu, A Sahin, R Rahimi Darabad and W Kam (Boston) and S Morrison (Calgary) for their help with these studies. This research was supported by NIH grant R01EY05612, the Margaret S. Sinon Scholar in Ocular Surface Research fund, the Canadian Natural Sciences and Engineering Research Council & the Centre for Bioengineering Research and Education at the University of Calgary.
Commercial interest
A new matrix therapy agent in the treatment of corneal ulcers resistant to conventional treatments
Authors: COCHENER B , MURAINE M 
Published: August 2012

AbstractPurpose To report the cases of a series of patients suffering from corneal ulcers resistant to conventional therapies and treated with a new ophthalmologic solution based on ReGeneraTing Agent technology (RGTA, Cacicol®).Methods Twenty four patients with corneal ulcer, most often chronic, were included in this opened series. Eleven patients had a neurotrophic ulcer (5 post‐infectious keratitis, 3 chemical burns, 1 Lyell syndrome, 2 others) with corneal anesthesia and persisting despite a 15‐day treatment with only unpreserved artificial tears. Other patients (n=12) had a chronic corneal ulcer of various etiologies (including 2 chemical burns, one associated with neurotrophic keratitis, one Moreen ulcer), and one patient had a severe confluent keratitis. These 13 patients were previously treated with classical lachrymal substitutes, some of them also with topical cyclosporine, corticoids, and/or A vitamin ocular ointment. A total of 11 patients had already received one or several amniotic membrane grafts, without success. All Patients were treated with Cacicol® at a dose regimen of one drop daily every 2 or 3 days for one to 3 months depending on healing.Results Complete healing was observed for 16 patients, including 7 out of the 11 patients with neurotrophic ulcer, i.e. a cure rate of 67%. However, a large variation has been noted in the time period recovery of corneal surface integrity going from few days to few weeks. An analysis of potential factors that could influence the healing process will be provided. For other patients, 5 failures and 3 improvements without complete healing were reported.Conclusion Cacicol® appears as a new interesting healing eye drops in the context of severe corneal ulcers resistant to conventional therapies. Its efficacy remains to be proven in randomized double‐blind studies.
Optical coherence tomography: signal signature on neuronal ageing and blood‐retinal barrier status
Authors: BERNARDES R , SANTOS T 
Published: August 2012

AbstractPurpose We aim to identify the features that allow the discrimination between healthy controls and diabetic patients with optical coherence tomography (OCT) data from the human retina.Methods Prior studies from our research group showed the association between the status of the blood‐retinal barrier and the consequent changes on the optical characteristics of the retina. Following the same rationale, we have demonstrated the possibility to discriminate healthy controls and diabetic patients by age group and healthy controls from diabetic subjects even though no visible changes could be identified, using a spectral domain OCT, Cirrus HD‐OCT (Carl Zeiss Meditec, Dublin, CA, USA), to gather the refractive index data in between the inner limiting membrane and the retinal pigment epithelium, and the support vector machine (SVM) for the automatic classification. In the work herewith presented, we applied a backward elimination process aiming to reduce the number of features used while simultaneously increase the classification performance.Results In this work we were able to reduce the number of features used in the SVM algorithm from the initial 46 features down to 10, while simultaneously increase the accuracy up to 97%. Moreover, the different feature set used for the different classifications suggest the presence of specific signatures within OCT data distribution.Conclusion These findings also suggest the possibility to use this noninvasive imaging modality to assess the neuronal condition and blood‐retinal barrier status.
High‐resolution spectral domain optical coherence tomography findings in reticular pattern dystrohy
Authors: ZERBIB J , MASSAMBA N , QUERQUES G , BLANCO‐GARAVITO R , SROUR M , BONNET C , SOUIED EH 
Published: August 2012

AbstractPurpose To analyze specific outer retinal and retinal pigment epithelium (RPE) features in reticular pattern dystrophy using spectral‐domain optical coherence tomography (SD‐OCT).Methods Consecutive patients with reticular pattern dystrophy underwent a complete ophthalmologic examination, including assessment of best‐corrected visual acuity (BCVA), fundus biomicroscopy, and SD‐OCT (Spectralis SD‐OCT, Heidelberg Engineering). Outer retinal and RPE macular features, as evaluated by SD‐OCT (scan passing through the fovea) were analyzed by 3 authors (JZ, NM and GQ).Results 24 eyes of 13 patients (5 males, 8 women, mean age 71.4) were included. Mean visual acuity was measured at 0.30 (logMAR). The RPE layer in the foveal area appeared normal in 41.7% of scans, while small RPE elevations and RPE bumps were detected in 33.3% and 20.8% of scans, respectively. Inner segment/outer segment (IS/OS) junction appeared disrupted in 50% of scans, and absent in 58.3% of scans. SD‐OCT showed a slight IS/OS elevation in 54.2% of scans. The external limiting membrane (ELM), appeared disrupted in 50% of scans, absent in 37.5% of scans, and elevated in 66.7% of scans. Hypereflective subretinal material accumulation or hyporeflective subretinal lesions, were detected in 33.3% and in 12.5% of scans, respectively. SD‐OCT showed hyporeflective retinal pseudocysts in 16.7% of scans.Conclusion In this series of reticular pattern dystrophy, SD‐OCT showed disruption of RPE layer and RPE bumps. Outer retinal changes included absence and disruption of both IS/OS junction and ELM. Hypereflective subretinal material accumulation or hyporeflective subretinal lesions, and hyporeflective retinal pseudocysts were also noticed.
Assessment of the spectralis spectral domain oct segmentation software in a retrospective cohort study of exudative amd patients
Authors: TILLEUL J , QUERQUES G , CANOUI‐POITRINE F , LEVEZIEL N , SOUIED EH 
Published: August 2012

AbstractPurpose To assess the ability of the Spectralis optical coherence tomography (OCT) segmentation software to identify the inner limiting membrane and the Bruch’s membrane in exudative AMD patients.Methods Thirty‐eight eyes of 38 naive exudative AMD patients were retrospectively included. They all had a complete ophthalmologic examination including Spectralis OCT at baseline, at month‐1 and at month‐2. Reliability of the segmentation software was was defined as good if both inner limiting membrane and Bruch’s membrane were correctly drawn.Results A total of 38 patients charts were reviewed (114 scans). The inner limiting membrane was correctly drawn in 114/114 SD‐OCT scans (100 %). Conversely, the Bruch’s membrane was correctly drawn in 59/114 scans (51.8 %). The software was less reliable in locating the Bruch’s membrane in case of pigment epithelium detachment (PED) than without PED (42.5% vs 73.5 % respectively, p =0.049).Conclusion Segmentation of inner limiting membrane was constantly trustworthy but Bruch’s membrane segmentation was poorly reliable using the automatic SD‐OCT Spectralis segmentation software. Based on this software, evaluation of retinal thickness may be incorrect, particularly in case of PED.
Meganuclease targeting HSV‐1 limits viral endothelitis in vivo
Authors: CHAPELLIER B , LABETOULLE M , GAILLEDRAT M , GABISON E 
Published: August 2012

AbstractPurpose The aim of this study is to assess the antiviral property of a meganuclease targeting HSV‐1 in the prevention of HSV endothelitis in a newly develloped rabbit in vivo model.Methods NZW received intracamerular injection of recombinant adeno‐associated virus equipped with a constitutive expression cassette containing either the meganuclease gene or a non‐coding sequence. After treatment with intravitreal triamcinolone acetonide, HSV‐1 F(1) virus recombinant for LacZ reporter was injected in the inner chamber of the eye,for an analysis 2 days later. Corneal edema, keratic precipitates and the number of contamination plaques were evaluated.Results In 4 tests with 24 experimental or control corneas, the meganuclease‐treated groups systematically showed a decrease in their average number of contamination plaques while compared to controls (from 15 to 71%). Presence of protein and inflammatory cells in the aqueous humor or at the endothelium surface, as well as the extension of focal edema, was also limited by the endonuclease.Conclusion Meganuclease gene therapy targeting HSV‐1 DNA restricts degradation of the endothelium initiated by HSV‐1 injection.
The effects of autologous serum eye drops in the treatment of ocular surface diseases : a retrospective study
Authors: BASLI E , LAROCHE L , LAURENT M , DESPIAU MC , BORDERIE V 
Published: August 2012

AbstractPurpose To evaluate the efficiency of autologous serum eyedrops in the treatment of severe dry eye (DE) and persistent epithelial defects (PED).Methods Ninety‐seven patients with PED or DE, unresponsive to conventional treatment, were studied. Functional symptoms and slit‐lamp findings were recorded.Results The mean LogMAR visual acuity significantly improved from 1.81 (20/1291) +/‐ 9 lines before to 1.69 (20/980) +/‐ 6 lines after treatment (p = 0.01). Visual acuity increased by 2 lines or more in 29 out of 97 eyes (30%) and it decreased by 2 lines or more in 15 eyes (15%). Resolution of 3 subjective symptoms was noticed in 14 out of 97 eyes (14%), resolution of 2 in 22 (23%), resolution of 1 in 29 (30%), and no subjective improvement was found in 32 eyes (33%). Among 75 eyes with PED, ulcer healing was observed in 31 (41%) at 1 month and 61 (81%) at 3 months. In multivariate analysis only presence of limbal deficiency significantly influenced the healing time. The average time from treatment onset to ulcer healing was 213 days in eyes with limbal deficiency and 59 days in eyes with no limbal deficiency (p<0.0001). Among 22 eyes with DE, improvement of subjective symptoms was observed in 8 (36%) at 1 month and 12 (55%) at 3 months. At the end of follow‐up improvement of subjective symptoms was observed in 20 (91%) eyes.Conclusion Cicatrisation of PED and improvement of DE symptoms were observed in most eyes under autologous serum.
Severe corticoresistant Mooren Ulcers: management with Rituximab and peripheral lamellar graft
Authors: BEN MHAMED M , PEREIRA D , DOAN S , COCHEREAU I , GABISON E 
Published: August 2012

AbstractPurpose Mooren's ulcer is a rapidly progressive, painful, ulcerative keratitis which affects the peripheral cornea. We report 6 severe cases of Mooren Ulcers (4 patients) with corticoresistance favourably responding to Rituximab infusions.Methods Retrospective Case seriesResults Despite systemic intensive steroid (4/4 patients), and Cyclophosphamide (2/4 patients) therapy, the 6 cases of Mooren’s ulcers progressively spread circumferentially and centrally. Perforation occurred in 4/6 affected eyes, treatment included conjunctival resection and peripheral corneal graft. Rituximab biotherapy was associated with the stabilisation and the healing of the corneal lesions. Systemic steroid therapy was tapered then stopped in all patients within 2‐4 months following rituximab therapy.Conclusion Rituximab, an anti‐CD20 monoclonal antibody, has been successfully used off‐label for treatment of Severe corticoresistant Mooren’s Ulcer.
16S RNA PCR in the diagnosis of bacterial keratitis and endophthalmitis
Authors: ROBERT PY , SABATIER A , GARNIER F , PLOY MC 
Published: August 2012

AbstractPurpose Classical bacterial culture often fails to detect the infecting agent in bacterial keratitis and endophthalmitis. Our study was designed to evaluate the contribution of 16S RNA amplification using polymerase chain reaction (PCR) and nested PCR, when compared to culture, in the diagnosis of bacterial keratitis and endophthalmitis.Methods In this prospective study, we included 63 patients (24 bacterial keratitis and 39 endophthalmitis). For every patient, two samples were taken: one for bacterial culture, the other for PCR. PCR and nested PCR 16S rRNA were performed using universal primers (8/27‐1510 for PCR and 91E‐13BS for nested PCR) and the amplicons were thereafter sequenced.Results Culture offers a sensibility of 25%; associated to first PCR (8/27‐1510), this rate increase to 31,7%, and with nested PCR (91E‐13BS), we had 34,9% of identifications. We have to note that the rate of positive PCR were much better, but the sequencing rate was 59,5% only. For bacterial keratitis, culture was positive in 25% and PCR in 8%. For aqueous humor samples, culture was positive in 32%, PCR in 25% and nested PCR in 20,6%. Sequencing was possible in 76,5% for humor aqueous samples.. For vitreous samples, the culture alone was positive in 9%, PCR in 36,3%, and nested PCR in 36,3%.Conclusion 16S rRNA PCR is a rapid alternative to culture, sensitive and reproductible.. PCR associated to culture increases the number of positive samples. PCR was found necessary for the microbiological diagnosis in 10% of all cases (PCR+, cultures‐).
SPARCS: a new method of evaluating contrast sensitivity in patients with glaucoma
Authors: SPAETH G , RICHMAN J 
Published: August 2012

AbstractPurpose To evaluate a new contrast sensitivity instrument as a diagnostic test for glaucoma.Methods Glaucoma patients, glaucoma suspects, and controls were prospectively evaluated using the Spaeth‐Richman Contrast Sensitivity (SPARCS) method. Testing was performed monocularly in a standardized testing environment. Contrast thresholds for the central, superonasal, superotemporal, inferonasal, and inferotemporal areas of vision were determined. The contrast sensitivity scores for each area of vision and the cumulative scores were then compared to subjects’ visual field and the amount of optic nerve damage, measured by the Disc Damage Likelihood Scale (DDLS) and the vertical cup to disc ratio. The results were analyzed with Spearman coefficients for continuous variables and the Kruskal‐Wallis test for categorical variables.Results One hundred and eighteen patients with glaucoma, 18 glaucoma suspects, and 125 controls completed the study. The mean SPARCS scores were 63.0 for patients with glaucoma, 71.9 for glaucoma suspects, and 77.1 for controls (p < 0.01). SPARCS had strong correlations with patients’ visual field (r = 0.76, p < 0.01), DDLS (r = ‐0.73, p < 0.01), and vertical cup to disc (r = ‐0.64, p < 0.01).Conclusion SPARCS was able to discriminate well between patients with glaucoma, glaucoma suspects, and controls. SPARCS had strong relationships with the degree of visual field and optic nerve damage. SPARCS may become a standard technique to assess visual ability in glaucoma patients.
Commercial interest
Evaluation of the flicker defined form test versus matrix, in normal and glaucoma eyes
Authors: MAY F , GIRAUD JM , FENOLLAND J , EL CHEHAB H , SENDON D , FRANCOZ M , RENARD JP 
Published: August 2012

AbstractPurpose To evaluate a new perimetric test, the Flicker Defined Form (FDF), and to analyze its capacity to detect visual field defect, comparatively to Matrix, in normal subjects and patients treated for primary angle glaucoma (POAG).Methods Clinical comparative trial including 65 eyes of 35 subjects who performed: clinical examination, measurement of the retinal nerve fiber layer thickness by scanning laser polarimetry GDx‐Pro, standard automated perimetry (SAP) Humphrey SITA 24.2 test, and Matrix 24.2 test; each subject performed SAP, Matrix and FDF two times, and only the second test was used in the study. Subjects were classified in 2 groups. Control group:35 normal eyes, mean age 40,5 years, without any abnormality in GDx‐Pro or SAP. POAG group: 30 eyes, mean age 69,1 years, treated for POAG, and presenting glaucomatous abnormalities in GDx and SAP: 23 early POAG, 4 moderate and 3 advanced.Results Control group: 37% (13/35 eyes) present defects revealed by FDF, and 6% (2/35) by Matrix. FDF defects are significantly more frequent than Matrix defects (Pearson Chi 2 test: p < 0,01); in 8 cases of these 13, defects are extended more than 1 quadrant. POAG group: 87% (26/30 eyes) present defects revealed by FDF, and 90% (27/30) by Matrix; there is no significant difference between the 2 tests (Pearson Chi 2 test: p > 0,9). All moderate and advanced POAG eyes present defects in the both tests. Eyes without defect (FDF or Matrix) are 7 early POAG with mild SAP defects.Conclusion In POAG patients, FDF test and Matrix seem to present high sensibilities: 87% and 90%. Inversely, FDF test specificity is very low, 63%, comparatively to Matrix, 94%, probably in relation with a learning effect.
Delivering it: retinitis pigmentosa
Authors: BLACK GCM 
Published: August 2012

AbstractPurpose Current technologies for delivering gene testing through conventioinal Sanger sequencing are labour‐intensive and expensive. Over recent years, high‐throughput DNA sequencing techniques (next generation sequencing; NGS) have been successfully implemented in a research context. This presentation discusses the use of using in a clinical service context.Methods We have applied NGS of 105 genes to patients known to be affected by inherited forms of blindness. This is delivered in the setting of a UK National Health Service accredited diagnostic molecular genetics laboratory. The presentation will discuss the ability of an NGS protocol to identify likely disease‐causing genetic variants.Results Conventional testing is applicable to the minority of patients with inherited retinal disease and identifies mutations in fewer than one in four of those patients tested. The current NGS assay is directed at all patients with such disorders and identifies disease‐causing mutations in 50‐55% a dramatic increase.Conclusion An NGS approach delivers a step change in the diagnosis of inherited retnial disease and provides precise diagnostic information and extends the possibility of targeted treatments including gene therapy. Importantly it is likely that this approach will develop rapidly in the near future.
Delivering it: Stargardt disease
Authors: NEMETH AH , DOWNES S 
Published: August 2012

AbstractPurpose To investigate the use of Sanger and Next Generation Sequencing (NGS) in patients with Stargardt Disease and other ABCA4 retinopathiesMethods Comparison of NGS with traditional Sanger sequencing in patients with possible ABCA4 retinopathies and the development of a clinical diagnostics service for inherited retinal degeneration using NGS.Results When ABCA4 was tested using Sanger sequencing, the mutation detection rate in patients with a clinical diagnosis of STGD disease was ~80%. In patients with other phenotypes compatible with ABCA4 mutations (eg. end‐stage chorioretinal atrophy, Bulls eye maculopathy or Pattern dystrophy) the detection rate was lower but still significant. Evaluation of NGS using ABCA4 as a test system showed that this technology, particularly the Illumina platform, was highly reliable in detecting the mutations found using Sanger sequencing. When NGS was used in a group of patients with Retinitis Pigmentosa or Cone‐Rod Dystrophy, ~ 6% were found to have ABCA4 mutations, illustrating the heterogeneous phenotype of ABCA4 retinopathies and the difficulties in making a clinical diagnosis.Conclusion Sequencing is the most efficient method of detecting mutations in STGD and will replace screening technologies. Genetic testing in STGD allows clinicians to improve their clinical pattern recognition, facilitate genetic counselling and identify patients for clinical trials. NGS compared to Sanger sequencing has the added advantage that numerous other genes can be sequenced at the same time and is reliable and cost effective, thereby providing an invaluable diagnostic tool. Genetic testing using NGS for genes involved in retinal degeneration is now available as a service through the Oxford laboratory (www.ouh.nhs.uk/geneticslab).
Using it: NGS in the inherited retinal degeneration clinic
Authors: DOWNES S , NEMETH AH 
Published: August 2012

AbstractPurpose To describe the clinical application of Next Generation Sequencing (NGS) in a retinal dystrophy clinicMethods The use of NGS in a clinic setting is discussed using case histories from our research using NGS in IRD to illustrate the potential and complexities of NGS testing for the clinician.Results Inherited retinal degeneration (IRD) is a common cause of visual impairment (prevalence ~1/3500). There is considerable phenotype and genotype heterogeneity, making a specific diagnosis very difficult without molecular testing. With the introduction of NGS huge amounts of genetic information are generated which highlight the importance of careful clinical phenotyping in the proband and family members with follow up segregation studies and functional analysis in many cases.Conclusion From our experience in the clinical setting it is evident that NGS has a useful role in diagnosis. In our NGS study our mutation detection rate suggests that many patients are likely to have mutations in novel genes and it is clear that resources are needed to carry out careful family studies and appropriate functional analysis.