bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible association with obesity‐related loci and outcome of wet AMD
Authors: Kaarniranta K. , Helisalmi S. , Birling A. , Saavalainen L. , Tolppola O. , Vajanto V. , Uusitupa M. , Paterno J.J. 
Published: September 2016

PurposeTo investigate whether obesity‐related genes affect a visual outcome of anti‐VEGF‐treatment in wet AMD.MethodsThirty‐seven patients with wet AMD (mean age: 77.0 years) in Kuopio University Hospital, Finland, solely treated with anti‐VEGF as needed, were genotyped for 40 recently associated obesity‐related loci using the Sequenom iPlex platform. Diabetes and other causes of macular oedema diagnosed by ophthalmologist were exclusion criteria. Obesity‐loci were examined with respect to retrospective clinical monitoring data, including also visual acuity (VA) measured by Snellen decimals.ResultsVisual outcome was associated with rs10938397 (GNPDA2), rs1555543 (PTBP2), and rs7359397 (SH2B1). Mean differences in VA between the two homotsygotes were 0.25 (p = 0.03), 0.25 (p = 0.002), and 0.26 (p = 0.003), respectively. Genotypes did not differ by age, baseline VA, body mass index (BMI), gender, the number of anti‐VEGF injections, smoking, or the use of dyslipidemia medication, expect for rs10938397 (mean BMI difference 3.2 kg/m2, p = 0.38) and rs7359397 (mean age difference 8.5 years, p = 0.14).ConclusionsOur data suggest, that at least rs1555543 (PTBP2) might have some effect on the visual outcome of anti‐VEGF‐treatment in wet AMD. The present study may be affected by the small sample, and it need to be replicated in a larger prospective setup. Diseases associated with PTBP2 include cancer‐associated retinopathy. Nevertheless, the potential role of the abundant genetic variation in modifiying drug responses in wet AMD should be further investigated.
The ON/OFF system pathway of the retina
Authors: Castelo‐Branco M. 
Published: September 2016

SummaryThe ON/OFF pathways in the retina represent parallel systems with asymmetric properties. Here we discuss the basic anatomy and function of these pathways in health and disease, from the point of view of luminance, contrast and motion perception. We will also highlight how receptive field properties are shaped within each of these pathways and how they cross‐talk within other parallel streams in the retina. Finally, we will address experimental and disease models that dissect the function of each of these pathways.
Grading iris color of post‐mortem human eyes
Authors: Madigan M. , Cionaca V. , Sitiwin E. , Ton H.T. 
Published: September 2016

PurposeIris colour encompasses a continuum from pale blue to very dark brown and is usually classified via a descriptive three colour scale: blue, green‐hazel or brown. Digital imaging technologies provide an opportunity to quantify iris colour, and are increasingly used for studies of genetic variations in iris colour. We explored the use of digital imaging and colour space information for grading of iris colour in post‐mortem eyes, including eyes with choroidal naevi.MethodsPost‐mortem adult human irises (n = 25) were examined and photographed using a Jenoptik digital camera and ProgResCaptureProv2.8.9 software. Standard lighting (colour temperature) and parameters for imaging were established and used for all specimens. Iris colour was graded (n = 5) (using a nine‐category system; Mackey et al. Clin Exp Ophthalmol, 2011). We also developed a method in Photoshop to express iris colour as Hue in the Hue, Saturation, Brightness (HSB) colour space, for comparison with the category grading.ResultsUsing the nine‐category grading end‐point grades (light blue and dark brown) were consistently graded. Intermediate grades were categorised differently for some observers, usually with adjacent categories. Green irises were not observed in this small series. Digital imaging using standard iris images and an averaging filter, provided colour information (Hue) for each iris. This allowed discrimination of iris colour compared to category grading.ConclusionsAs expected category‐grading was not always consistent between observers. We developed a digital imaging approach using HSB color space to give a H value for each iris. We are exploring the utility of processing functions such as gaussian blur. This approach provides a standard iris colour for post‐mortem tissue and will be used for comparison with fundus colour.
Regression of corneal neovascularization associated with corneal epithelial defect after treatment with regenerating agents (Cacicol®)
Authors: Del Buey M.A. , Esteban O. , Lanchares E. , Martinez M. , Casas P. , Ascaso F.J. , Cristobal J.A. 
Published: September 2016

PurposeCorneal neovascularization is formed in response to inflammation and hypoxia. It is secondary to different conditions such as herpes simplex stromal keratitis, persistent corneal epithelial defects, contact lens use, keratoplasty of infections. The use of Regenerating Agents (RGTA) is a new treatment that mimics the function of extracellular matrix components. It makes extracellular matrix resistant to inflammatory molecules, restoring the properties and the micro‐‐environment needed for the normal corneal tissue regeneration. We report number of cases showing the role of Cacicol® in the regression of severe corneal neovascularization in patients with neurotrophic keratitis.MethodsInterventional number of cases (N = 5) treated with RGTA (Cacicol®) for two months. The patients presented central corneal epithelial defect caused by neurotrophic keratopathy. These defects showed superficial and deep stromal neovascularization. The patients was treated with conventional therapy. We decided to combine this conventional treatment with RGTA (Cacicol®) one every two days for one month. After that period, we spread the dose to once a week for one month more.ResultsAfter first month, we observed that the dimensions of the epithelial defect decreased in two cases and it had disappeared in three cases. After second month, all patients had complete corneal healing and we also observed a regression of superficial and deep stromal vascularization. In three cases, neovascularization had decreased considerably and it had disappeared in two cases.ConclusionsRGTA (Cacicol®) improves corneal melting and epithelial defects associated to corneal neurotrophic pathology. Moreover, in cases with corneal neovascularization associated, we find an important decrease of superficial and deep neovessels.
SD‐OCT for study of retinal layers segmentation in patients under Hydroxychloroquine treatment
Authors: Costa L. , Basílio A.L. , Proença R. , Cunha J.P. , Vieira L. , Flores R. , Santos A. 
Published: September 2016

PurposeHydroxychloroquine has been used for decades in treatment of rheumatic disorders. Macular toxicity is an adverse effect dependent to duration of treatment and daily dosage. Although, the exactly retinal structure under this toxic effect is not yet totally understandable.To study the sectorial effect of Hydroxychloroquine in all retinal layers in 1st, 2nd, 3th and 6th mm centered on fovea by automatic segmentation using Spectral‐Domain Optical Coherence Tomography.MethodsRetrospective, non‐randomized study involving 44 eyes of 44 patients under treatment with Hydroxychloroquine. The authors have created two age‐matched groups. A group 1 of patients in treatment duration under 10 years (n = 30) and a group 2 above 10 years of treatment (n = 14).ResultsThe inner retinal layers thickness of 1st and 2nd mm is impaired in group 2 but the results did not showed significant difference between groups. The automatically segmentation of layer by layer did not prove a sectorial defect in inner retina. The thickness of Outer Nuclear Layer (ONL) was impaired in group 2, in opposition to Outer Plexiform Layer (OPL). This analysis has demonstrated a tendency for inversion of ONL and OPL thickness values in both groups.ConclusionsThe toxicity of Hydroxychloroquine apparently was not responsible for significant alterations in inner retinal thickness. That is a tendency for reduction in ONL thickness. The higher thickness of OPL in group 2 is a surprising aspect that needs additional analysis. The outcomes were very dependent to the limited number of patients in our sample. Further longitudinal studies about this topic will be necessary.
Mid‐term clinical outcomes of collagen‐phosphorylcholine cornea substitutes for therapeutic anterior lamellar keratoplasty
Authors: Buznyk O. , Islam M.M. , Iakymenko S. , Pasyechnikova N. , Griffith M. 
Published: September 2016

PurposeTo assess safety and efficacy of biosynthetic collagen‐phosphorylcholine implants as corneal substitutes in patients with severe pathologies for whom human donor cornea transplantation carries a high risk of rejection.MethodsRecombinant human collagen type III and 2‐methacryloyloxyethyl‐phosphorylcholine were fabricated into collagen‐MPC corneal substitutes (CMCS). CMCS were implanted into the corneas of 8 patients (3 Phase 0, 5 Phase 1 patients) by anterior lamellar keratoplasty (ALK). The pathologic areas were excised and replaced with CMCS grafts. Benchmark patients were grafted by conventional ALK and human amniotic membrane (HAM). Follow‐up ranged from 12 to 36 months.ResultsPre‐operatively, CMCS patients had persistent ulcers or recurrent erosions from chemical or thermal burns, keratitis or failed penetrating grafts. All patients were relieved of pain and photophobia post‐operation. 7/8 CMCS grafted corneas epithelialized within 4–50 weeks leading to improved visual acuity in 4/8 patients. Neovascularisation developed in 2/8 patents. Ten patients with similar conditions grafted by conventional ALK took 2–12 weeks to epithelialize. Neovascularisation developed in 9/10 patients, and visual acuity improved in 3/10 patients. In HAM patients, corneas epithelialized within 2–3 weeks, neovascularization developed in 7/10 patients, vision improved in 4/10 patients.ConclusionsThese results suggest that CMCS are safe in patients. In addition, they appeared to withstand the adverse microenvironment within corneas with severe pathology, and restored corneal integrity in high risk keratoplasty patients. Further clinical testing is needed to verify these early results.
Proton beam radiotherapy (PBR) for the treatment of retinal capillary haemangioblastoma
Authors: Hussain R. , Hassan S. , Ho V. , Kacperek A. , Errington D. , Heimann H. 
Published: September 2016

PurposeWe describe the treatment of retinal haemangioblastomas with proton beam radiotherapy as a primary treatment for juxtapapillary lesions, and as a secondary treatment in refractory cases.MethodsRetrospective analysis of patients from Jan 1997–Dec 2011 with retinal haemangioblastomas treated in the Clatterbridge Cancer Centre Douglas Cyclotron. Patients were treated with reduced dose 18 Gy.ResultsSeven patients were treated, 4 with Von Hippel Lindau syndrome. Five cases had juxtapapillary lesions; 5 had previous failed therapy; argon laser photocoagulation‐3, photodynamic therapy‐3, intravitreal anti‐VEGF (bevacizumab/abflibercept)‐4, ruthenium‐106 plaque brachytherapy‐2, vitrectomy with endolaser‐1. Tumour diameter was 4.0–7.2 mm (mean 4.8 mm) and thickness 1.2–4.2 mm (mean 2.2 mm) with visual acuity logMAR 0.0‐hand movements (mean 0.9). Mean follow up was 24 months (12–48 m). Within three months, all lesions regressed which continued over 18 months; tumour diameter decreased by 2.7 mm (1.5 mm depth). All cases demonstrated resolution of subretinal fluid within 3–6 months; however 3 developed radiation maculopathy at 12–22 months and were treated with intravitreal bevacizumab with good effect. Five patients had visual stabilisation; one case had visual improvement and another lost vision (HM to PL) (mean 0.8) due to radiation maculopathy.ConclusionsPBR is an effective treatment for retinal haemangioblastomas with good regression of tumours; side effects are fewer and less severe than that reported with external beam radiotherapy, however our rates of radiation maculopathy were >40% despite a dose of 18 Gy. Although the expense and difficulty with access may limit its use, PBR ought to be considered in refractory cases unresponsive to alternative therapies, and in juxtapapillary lesions where alternative treatments cause rapid and severe visual loss.
Relationship between immune response and ocular inflammation after intravitreal injection of rAAV2/2–ND4 (GS010) in Leber hereditary optic neuropathy (LHON) patients
Authors: Vignal Clermont C. , Bouquet C. , Uretsky S. , Galy A. , Thomasson N. , Fitoussi S. , Combal J.P. , Sahel J. 
Published: September 2016

PurposerAAV2/2‐ND4 vector (GS010), under development by GenSight‐Biologics as a treatment for vision loss in LHON patients bearing ND4 mutation, is administered via intravitreal injection (IVI). Immune response to intraocular AAV administration may impact safety and efficacy of AAV‐delivered ocular gene therapy. We investigated the relationship between systemic anti‐AAV2 antibody levels pre‐ and post‐IVI and ocular inflammatory reactions after GS010 injection.MethodsFifteen LHON‐ND4 patients (Phase I/IIa; ClinicalTrials.gov NCT02064569) underwent IVI of GS010 with four escalating dose levels (9E9; 3E10; 9E10; 1.8E11 vg/eye). Ocular examinations were performed up to 48 weeks. Serum anti‐AAV2 IgG were quantified by ELISA and Neutralizing antibodies (Nab) were quantified using a seroneutralization luciferase cell‐based assay. The complete data at 48 weeks will be presentedResultsAt baseline, NAb levels in serum were undetectable in 7 patients and above 1:1,000 titer for 2. After 2 weeks, IgG titers increased up to 19 times baseline levels in 7 patients and NAbs up to 39 times in 10. At week 8, NAb titers remained above 1:1,000 titer for 6 patients; then titers tended to decrease progressively overtime. 13 patients experienced mild to moderate ocular inflammation (anterior chamber and/or vitritis), that resolved with standard therapy, without apparent correlation with the humoral serum response.ConclusionsA humoral serum response against AAV2 was observed from 2 weeks post‐injection of GS010 in LHON patients. Ocular inflammation was reported, with no consistent correlation with anti‐AAV2 antibody levels and non‐detectable impact on pharmacodynamics trends. Additional follow‐up of humoral and cellular immunogenicity in Phase III trials will confirm these observations and delineate the potential predictable impact for contralateral eye injection.
A descriptive subgroup analysis of within hospital glaucoma referral in a tertiary center in Portugal
Authors: Leal I. , Cordeiro Sousa D. , Marques‐Neves C. , Abegao Pinto L. 
Published: September 2016

PurposeGlaucoma is a progressive and irreversible optic neuropathy carrying tremendous burden in healthcare systems. The aim of our study was to characterize the population referred to a glaucoma subspecialty department (GSD) in a university hospital.MethodsWe analyzed retrospectively the within‐hospital referral to the GSD. Electronic medical records and referral letters between Jan and Dec 2014 were screened. Data was screened for ancillary exams, type of tonometry, number of IOP‐lowering medications and extent of the disease (HODAPP classification). Statistics were performed with STATA v13.0.ResultsA total of 151 patients (78 males) were referred. Mean age was 68.2 (range 18–91). Thirty‐six patients (23.8%) were referred with visual field, pachimetry and OCT. Of those with a visual field, 38 (55.1%) had a mean defect >6 db (of which 17 had >12 dB), with 34 patients having at least two exams. In contrast, 16 (10.6%) were referred with no ancillary exam performed and 67 (50%) had all IOP measurements performed with pneumotonometry. Sixteen patients (10.6%) had a description of a gonioscopy. All patients were under IOP‐lowering treatment, of which 83 (55%) were under 2 or more IOP‐lowering medications. The number of patients referred with more than 80 years old was 29 (19.2%), 5 (18.52)% of which had a complete documentation of the disease. In this subset of patients, 6 (42.8%) had an advanced form of the disease.ConclusionsBetter understanding of our population characteristics will lead to a more accurate referral system. In a significant part of GDS referrals there was insufficient or poor quality clinical data. Our study raises awareness on the importance of an efficient within hospital subspecialist referral, leading to economic and health gain in Ophthalmology departments.
Difference between manifest and cycloplegic refraction in healthy non‐presbyopic patients
Authors: Del Buey M.A. , Lanchares E. , Pinilla I. , Almenara C. , Perez I. , Minguez E. , Cristobal J.A. 
Published: September 2016

PurposeTo study the variation of objective refraction between manifest and cycloplegic conditions in healthy myopic patients younger than 40 years.MethodsSixty‐six myopic eyes of healthy patients under the age of forty years were included in this study. Manifest refraction, mean corneal power, white‐to‐white measurement, pupil diameter, central corneal thickness and anterior chamber depth weremeasured. Following the evaluation, 1% cyclopentolate was applied to induce cycloplegia and autorefractometer refraction was determined again. A statistical analysis was accomplished to investigate the relation ofthe mentioned parameters with the variation between manifest and cycloplegic refraction.ResultsTwenty‐eight eyes showed no difference between non‐cycloplegic and cycloplegic refraction. Thirty‐eight eyes presented a relevant difference (over 0.5D) between both measurements. The statistical analysis showed no differences between these two groups in age, non‐cycloplegic refraction, keratometry, white‐to‐white, central corneal thickness or anterior chamber depth. The only significant difference found between groups was the pupil diameter. Those patients with smaller pupil diameters presented greater changes in refraction. On the contrary, patients with wider pupils had negligible changes of refraction.ConclusionsAccording to our outcomes, not only hyperopic patients and children, but also myopic patients may require refraction assessment under cycloplegic conditions when autorefraction is used, since many of them show a significant modification with respect to manifest refraction. Our results show a relation between this change in autorefractometer refraction with and without cycloplegia and the pupil diameter.
Semi‐fluorinated alkanes for topical delivery of Cyclosporine
Authors: Agarwal P. , Scherer D. , Günther B. , Rupenthal I. 
Published: September 2016

PurposeCyclosporine A (CsA) is an anti‐inflammatory agent that has been frequently used to treat ocular inflammatory conditions, such as dry eye syndrome. However, the poor water solubility of CsA makes it difficult to formulate into an acceptable ocular dosage form. Semi‐fluorinated alkanes (SFAs) are a novel class of inert, non‐toxic and amphiphilic liquids that form clear solutions with CsA and have been suggested as efficient carriers for topical administration of CsA. The aim of this study was to assess the corneal bioavailability of CsA from SFAs compared to currently marketed formulations.MethodsAn ex vivo porcine eye model was used to study the penetration of a) Restasis® (0.05% CsA ophthalmic emulsion), b) Ikervis® (0.1% CsA ophthalmic emulsion), and c) 0.05% or 0.1% CsA in SFAs. The amount of drug penetrated per gram of cornea between 0.5 and 4 h after application was assayed by HPLC and statistically compared using a two‐way ANOVA. Drug distribution in different layers of the cornea was also visualized by substituting CsA with a lipophilic fluorescent dye and viewing corneal sections under a fluorescent microscope.ResultsSignificant improvement in corneal penetration of CsA could be observed for 0.05% CsA in SFAs (C1 h = 5.844 ± 2.408 ng/g) over Restasis (C1 h = 761 ± 221 ng/g), with the area under curve (AUC) being more than 8‐folds greater. The AUC of 0.1% CsA in SFAs (C1 h = 12.556 ± 4.017 ng/g) was 3.6 folds greater than Ikervis (C1 h = 2.900 ± 341 ng/g). Microscopic examinations revealed that the dye incorporated into SFAs tended to accumulate mainly in the corneal epithelium.ConclusionsOverall, this study showed that SFAs can significantly improve the corneal absorption of lipophilic drugs, such as CsA, and could therefore be a promising platform for drug delivery to the eye.
A curry a day keeps glaucoma away? – A curcumin study
Authors: Balendra S.I. , Davis B.M. , Guo L. , Cordeiro M.F. 
Published: September 2016

PurposeCurcumin's neuroprotective potential is challenged by its low solubility and stability at physiological pH. We aimed to solubilise curcumin into a formulation with high encapsulation efficiency (EE) and stability in phosphate buffer solution and to demonstrate its neuroprotective efficacy in vitro and in vivo upon topical administration in the well‐established ocular hypertensive (OHT) rat model of glaucoma.MethodsA thin‐film hydration technique was employed to manufacture curcumin‐loaded micelles which were characterised for size and dispersity using dynamic light scattering and transmission electron microscopy. EE was assessed spectroscopically. Stability of the formulation was assessed by measuring changes in particle physical properties and EE over time. Assessment of curcumin mediated neuroprotection in vitro was achieved using an alamarBlue cell‐viability assay in paraquat‐treated primary retinal ganglion cells (RGCs). In vivo assessment of topical curcumin micelle mediated neuroprotection was assessed in the OHT model with primary endpoint of whole retinal Brn3a histology.ResultsA solubilised micellar formulation was developed containing 4.5 mg/ml of curcumin with >90% EE. This was found to be stable at room temperature for >45 days, increasing to >6 months with lyophilisation in presence of a cryoprotectant. Curcumin versus vehicle‐only pre‐treated RGCs had a significantly higher IC50 in vitro (p < 0.05). Curcumin‐treated versus untreated OHT eyes had a significantly higher RGC density on Brn3a histology (p < 0.001).ConclusionsA novel curcumin formulation is described which increases its solubility 100‐fold to 4.5 mg/ml and is stable for >60 days at room temperature and >6 months on lyophilisation. This formulation elicited significant neuroprotection in vitro and on 3 weeks of topical ocular instillation in vivo, with no toxicity findings.
En‐face imaging of epiretinal membrane using swept source optical coherence tomography
Authors: Kim J.T. , Chung H. 
Published: September 2016

PurposeTo define morphologic features of epiretinal membrane (ERM) using en face images from swept‐source optical coherence tomography (SS OCT).MethodsConsequtive patients with idiopathic ERM were analyzed for en face imaging analysis within a 6‐month period. All patients had undergone 3D volume scan of swept source OCT (Triton OCT, Topcon, Japan). The patients were devided into 3 groups, retinal thickening without retinal hole (Group 1); retinal thickening with lamellar macular hole (Group 2); retinal thickening with macular pseudohole (Group 3). Secondary ERM were excluded from analysis. En face imaging was analyzed on and under the level of ILM.ResultsMean patient age was 63.6 ± 10.8 years (n = 77). Mean central retinal thickness (CRT) in group 1, 2, and 3 was 422.3 ± 73.3 μm (n = 51), 334.1 ± 39.6 μm (n = 34) and 277.7 ± 58.6 μm (n = 12). En face imaging under ILM level well visualized central tractional membrane (CTM), and imaging on the ILM level showed well radiating folds (RF) over the posterior pole. Group 1 had CTM over the fovea (100%), however Group 2 had CTM outside the fovea (94.1%). Group 3 had better BCVA and lesser CRT than the other groups (ANOVA p < 0.05).ConclusionsEn face SS OCT provides an useful tool to visualize the pathologic features in epiretinal membrane. Lamellar macular hole might be associated with perifoveal or extrafoveal epiretinal membrane and it's tractional force. Macular pseudohole might be associated with ERM or prior macular traction. En face SS OCT provides an useful tool to visualize the pathologic features in epiretinal membrane.