bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional and structural evaluation of the meibomian gland using a LipiView interferometer in Orthokeratology wearers
Authors: Ha Minji , Na Kyungsun , Lee Jiyoung 
Published: December 2019

AbstractPurposeTo compare meibomian gland (MG) morphology and function, and blinking pattern in Korean pediatric subjects with or without overnight orthokeratology wear.MethodsThe retrospective study was conducted. Twenty‐eight participants were divided two groups: control (n = 11) and overnight orthokeratology group (n = 16). Control group was examined before OOK lens fitting and OOK group was examined during OOK lens wear. Meiboscore(0‐3), lipid layer thickness (um), blinking quality (%) were measured using LipiView ® II Ocular Surface Interferometer (TearScience, Morrisville, NC).ResultsNo significant differences in average lipid layer thickness and blinking quality between groups were found (all p’s > 0.05). However, meiboscore was statistically higher in OOK group than control group (OD p = 0.003, OS p = 0.03, respectively). The correlation analysis between OOK wearing period and Lipiview ® variables (lipid layer thickness, blinking quality, meiboscore) showed no statistical significance (all p’s > 0.05). No differences were found in Lipivew ® variables (lipid layer thickness, blinking quality, meioscore) compared long OOK wearing period with short OOK wearing period (all p’s > 0.05).ConclusionsBased on the findings, the lipid layer thickness and blinking pattern were relatively stable in OOK group. However, the area of meibomian gland loss was significantly larger than the control group.
Epithelium‐off and trans‐epithelial pulsed accelerated corneal cross‐linking for treatment of progressive keratoconus: Twelve‐month results
Authors: Tian Lei 
Published: December 2019

AbstractPurposeTo compare the outcomes of epithelium‐off pulsed accelerated corneal cross‐linking (ACXL) and trans‐epithelial pulsed accelerated corneal cross‐linking (Trans‐ACXL) in progressive keratoconus.SettingDepartment of ophthalmology, the Chinese PLA general hospital, Beijing, China.DesignProspective clinical trial.MethodsIn total, 69 eyes (54 patients) with progressive keratoconus were subjected to ACXL (36 eyes; ACXL group), and Trans‐ACXL (33 eyes; Trans‐ACXL group). Patients were evaluated through visual acuity, keratometry, corneal biomechanics, corneal tomography, endothelial cell count, anterior segment optical coherence tomography and in vivo confocal microscopy. The follow‐up period was 12 months.ResultsTransient haze was observed in 21% of keratoconic corneas in the ACXL group and none in the Trans‐ACXL group. There were no significant postoperative differences in astigmatism, corneal biomechanical parameters or endothelial cell counts; while visual acuity, keratometry and manifest refraction spherical equivalent showed significant improvement at 12th months postoperatively in both groups. The demarcation line depth was 220.27 ± 41.34 µm in ACXL group, deeper than in Trans‐ACXL group, whose depth was 197.54 ± 32.37 µm (P = 0.014), at 1 month postoperation. In vivo confocal microscopy showed keratocytes apoptosis and stromal edema 1 month postoperation; but the changes gradually recovered similar to normal status after 12 month postoperation in both groups. There were no apparent changes to the posterior stroma and endothelium in either group.ConclusionsThe results of this study revealed that both ACXL and Trans‐ACXL were safe and effective at stabilizing the progression of keratoconus. The ACXL technique offers more effective visual and topographic outcomes than Trans‐ACXL, but Trans‐ACXL with less micro‐structural damage.
Effect of non‐invasive tear stability assessment on the upper and lower tear meniscus height
Authors: Tian Lei 
Published: December 2019

AbstractPurposeTo investigate the effect of non‐invasive tear stability assessment with forced eye opening on the upper and lower tear meniscus.MethodsTen eyes with evaporative dry eye disease and 10 normal eyes were enrolled. All subjects underwent imaging with a Keratograph 5M equipped with a modified tear film scanning function. The upper and lower tear meniscus height (U‐TMH and L‐TMH) at the central point relative to the pupil center was measured with an integrated ruler before and after non‐invasive Keratograph break‐up time (NIKBUT) measurements in each subject. Subjects were instructed to keep their eyes open as long as possible during NIKBUT measurements, and the recording was discontinued at the next blink.ResultsThe U‐TMH values of the normal and dry eye groups were 0.21 ± 0.06 mm and 0.14 ± 0.09 mm; while the L‐TMH values were 0.27 ± 0.12 mm and 0.22 ± 0.07 mm, respectively, at baseline. The TMH values of dry eyes were significantly smaller than those of normal eyes (p < 0.001). Significant increases in L‐TMH values were observed in both normal (0.19 ± 0.13 mm) and dry eyes (0.14 ± 0.11 mm) with the NIKBUT measurement (p < 0.001, p = 0.027); while there were no significantly increases of U‐TMH in both group (normal, 0.08 ± 0.09 mm, p = 0.067; dry eyes, 0.06 ± 0.08 mm, p = 0.054). The changes of L‐TMH were more significantly than the U‐TMH in both groups (both P<0.001).ConclusionsForced eye opening required for the non‐invasive tear stability assessment influences the TMHs measurement possibly due to reflex tear secretion. The L‐TMH values were more severely affected by than the U‐TMH.TMHs should be assessed before tests that require forced eye opening.
A pilot autonomous AI‐based DR screening in Poland
Authors: Grzybowski Andrzej , Brona Piotr 
Published: December 2019

AbstractPurposeWe would like to share our experience and results in instigating a pilot diabetic retinopathy (DR) screening programme based on artificial intelligence (AI) in Poland. Diabetes prevalence is increasing and as a result so is DR. Only a few developed countries could so far afford to establish national screening programmes. Those were so far based on work done by ophthalmologists or specialty trained human graders.MethodsWe have set‐up our screening programme in a diabetic clinic. Patients who visited the clinic were offered DR screening based on non‐mydriatic retinal images (TRC‐NW400, Topcon). These images were analysed by IDx‐DR, a deep‐learning network based autonomous DR screening system. Based on the IDx‐DR output patients were recommended another screening after 1 year, or an ophthalmology referral with appropriate urgencyResultsAfter an initial period with a number issues related to image quality, staff training, locale etc. we have managed to get the pilot screening programme on working. The AI systems tolerance for image quality was similar to that of a human grader. Compared to an ophthalmologist’s grading the IDx‐DR system achived over 90% sensitivity and specificity for referable DR.ConclusionsThe cost of a human specialty grader based DR screening programme is prohibitively high for a developing country such as Poland in terms of both human and financial resources. The advent of AI DR screening technology brings a cheaper, easier to roll out alternative that can be successfully employed on a local level. Additionally patients receive a near‐instant result with a satisfactory accuracy. Effectiveness of such system on a larger scale remains to be seen.
Correlation between disease duration and retinal sensitivity and structure in patients with neuromyelitis optica spectrum disorder with no history of optic neuritis
Authors: Yokouchi Hirotaka 
Published: December 2019

AbstractPurposeTo determine whether there is a significant correlation between the disease duration and the sensitivity and structure of the retina in patients with neuromyelitis optica spectrum disorder (NMOSD) with no history of optic neuritis (ON).MethodsFifteen eyes of 15 patients with NMOSD (2 men, 13 women; mean age 50.2 ± 11.2 years) who had no history of ON were studied. The retinal sensitivity of the central 10º was determined by macular integrity assessment (MAIA), a microperimetric method, and the retinal structure by spectral‐domain optical coherence tomography (SD‐OCT). For MAIA, the retina was stimulated with a scanning laser ophthalmoscope at 37 loci covering 10° of the central retina. For the retinal structures, the mean thickness of the ganglion cell complex (GCC) thickness and outer nuclear layer (ONL) thickness were measured in the SD‐OCT images. The correlations between the disease duration and the sensitivity and the GCC thickness or the ONL thickness were determined by the Spearman’s rank‐correlation coefficients.ResultsThe mean best‐corrected visual acuity(BCVA) was 0.05 ± 0.03 logMAR units. The mean disease duration was 42.4 ± 37.4 months with a range of 1 to 103 months. The mean retinal sensitivity of the central 10º was 27.6 ± 1.78 dB. The mean GCC thickness was 95.0 ± 8.99 μm, and the mean ONL thickness was 53.8 ± 5.43 μm. There was a significant correlation between the disease duration and the sensitivity of the central 10º (r = 0.48, p = 0.034; Spearman’s rank‐correlation coefficients) and the ONL thickness (r = 0.60, p = 0.016; Spearman’s rank‐correlation coefficients). However, there was not a significant correlation between disease duration and GCC thickness (p > 0.05; Spearman’s rank‐correlation coefficients).ConclusionsThese results indicate that the visual function is impaired even before the development of the ON in patients with NMOSD. We recommend that microperimetry and OCT be used in eyes with NMOSD because subclinical optic neuritis may be present.
The role of hypoxia‐inducible factors in age‐related macular degeneration
Authors: André Helder 
Published: December 2019

AbstractPurposePathophysiological mechanisms of age‐related macular degeneration (AMD) have been attributed mainly to local tissue ischemia or the presence of low‐grade inflammatory reaction. A fundamental difference between both types of AMD is the increased vascular endothelial growth factor (VEGF) level in neovascular AMD (nAMD), a result of underlying tissue hypoxia and upregulation of hypoxia‐inducible factor (HIF) in the retinal pigment epithelium (RPE), leading to choroidal neovascularization (CNV). Here, we will present a summary of our studies in the benefits of mitigating HIF responses in models of nAMD.MethodsWe have addressed the hypoxia response in RPE cells in vitro (retinal cells cultures) and in vivo (laser‐induced CNV model), using tissue ischemia molecular modulators (UPARANT), HIF‐specific inhibitors (Echinomycin) and HIF molecular negative regulators (prolyl hydroxylase domain 2) as a negative‐modulators of HIF.ResultsWe have demonstrated that expression of HIF is upregulated in RPE cells in vivo during progression of CNV, and was associated with increased VEGF levels. Collectively, our data has demonstrated a role for HIF in nAMD, and that negative‐regulation of the hypoxia pathway in RPE cells abnegates the increase in VEGF, together with other HIF‐mediated factors, significantly reducing CNV associated with nAMD.ConclusionsDue to the protracted nature of AMD, the multifactorial mechanisms involved, and current therapeutic limitations there is a great need for long‐term therapies that can mitigate multiple angiogenic and inflammatory factors known to be associated with nAMD, allowing for sustainable treatments. We have established a molecular role for HIFs in nAMD progression, and have identified molecules capable of regulating hypoxia processes that have pronounced translational therapeutic potential.ReferenceH André et. al. IOVS 2015; M Cammalleri et al. IOVS 2016; A Takei et al. Sci Rep 2017; F. Plastino et al. EVER2019 abstract.
Association of preservative‐free versus glaucoma eye drops with preservatives and further glaucoma surgery. A retrospective study based on the French national health insurance information system, 2008‐2016
Authors: Chamard Chloé , Larrieu Sophie , Baudouin Christophe , Bron Alain , Villain Max , Daien Vincent 
Published: December 2019

AbstractPurposePreservatives contained in glaucoma eye drops have been shown to have a deleterious impact on the ocular surface. This study aimed to assess the impact of preservatives on further glaucoma surgery among patients with glaucoma or ocular hypertension in France between 2008 and 2016.MethodsThis was a retrospective analysis of prospectively collected data from a French medical‐administrative database. Three groups were created according to the level of preservative consumption during the whole follow‐up: ‘0% preservatives’, ‘mixed’ and ‘100% preservatives’. The risk of glaucoma surgery was estimated according to preservative exposure indicators in Cox multivariate models. The adjustment variables were age, sex, number of glaucoma drops classes, use of systemic anti‐hypertensive treatment, and duration of exposure to intraocular pressure (IOP)‐lowering agents.ResultsThe sample consisted of 12 454 patients firstly treated for glaucoma or ocular hypertension between January, 1st, 2008 and December, 31st, 2015. The median (interquartile range) follow‐up was 4.1 (1.7–6.1) years. A total of 231 (1.9%) patients underwent glaucoma surgery during follow‐up. On multivariable analysis, the risk of glaucoma surgery was increased for the ‘mixed’ group [hazard ratio (HR) = 3.94 (95% CI, 1.54–10.05)] and for the ‘100% preservative’ group [HR = 7.97 (95% CI, 3.07–20.67)] when compared with the 0% preservatives group.ConclusionsWe found a strong association between exposure to glaucoma eye drops preservatives and the prevalence of further glaucoma surgery. In real life, in a large sample of patients, these results bring new and novel arguments to privilege preservative‐free IOP‐lowering eyedrops for the medical treatment of glaucoma.
Cord blood serum (CBS) reduces the expression of GFAP and inflammatory cytokines in retinal Muller cells under stress damage
Authors: Ciavarella Carmen , Buzzi Marina , Bergantin Elisa , Coslovi Chiara , Di Marco Stefano , Bisti Silvia , Campos Emilio , Versura Piera 
Published: December 2019

AbstractPurposeHuman cord blood serum (CBS) is enriched with neurotrophins endowed of neuroprotective functions. Muller cells orchestrate retinal functioning, but their hyper‐activation can exacerbate retinal damage under oxidative stress, which typically occurs during neurodegenerative diseases. In this study we tested whether CBS could regulate human Muller cell activation under H2O2‐ and IL‐1□‐ induced damage.MethodsSelected neurotrohpins (BDNF, TGF‐□, NGF, GDNF, EGF) were analysed in CBS (Human Magnetic Luminex Screening Assay). The human Muller cell line Moorfields/Institute of Ophtalmology‐Muller 1 (MIO‐M1) was obtained from the UCL Institute of Ophtalmology, London, UK1. MIO‐M1 were seeded in growth media enriched with standard FBS or CBS, both at 5%. After 24 h, MIO‐M1 were exposed to H2O2 and IL‐1□ for 24 h. CBS effects were compared to FBS control cells in terms of cell survival (MTT assay), activation (GFAP mRNA) and inflammation (TNF‐□ and IL‐6 mRNA).ResultsMedian levels of neurotrophins in CBS were: BDNF 1.5 ng/ml, NGF 3.0 pg/ml, GDNF 1.5 pg/ml, TGF‐□ 36.3 pg/ml, EGF 820 pg/ml. MIO‐M1 pre‐cultured with CBS and exposed to H2O2, underwent a 50% decrease of GFAP mRNA in comparison to FBS control cells. CBS also mitigated the inflammatory activation, as shown by a significant 50% reduction of IL‐6 and TNF‐□ mRNA levels. The CBS ability to modulate the inflammatory pathway was confirmed by the significant decrease of IL‐6 and TNF‐□ genes (6‐ and 4‐ fold lower than FBS, respectively) in MIO‐M1 exposed to IL‐1□ (50 ng/ml).ConclusionCBS protects retinal Muller cells from damage under in vitro stress conditions. The main targets of this neuroprotecting stretegy are GFAP, marker of Muller cell activation, and the inflammatory cytokines, closely related to the neurodegenerative diseases. Therefore, CBS represents a promising therapeutic agent for the neurodegenerative diseases and further studies are necessary to validate this issue.Reference

Limb GA et al. 2002, IOVS, 43; 864–869.
Retinal vessel oximetry as a sensitive metabolic monitoring method for transcorneal electrical stimulation in retinitis pigmentosa
Authors: Waizel Maria della Volpe , Zuche Hanna , Müller Ursula , Scholl Hendrik P. N. , Todorova Margarita G. 
Published: December 2019

AbstractBackgroundTranscorneal electrical stimulation (TES; OkuStim®) is a novel therapy method for patients with retinitis pigmentosa (RP). With progression of RP, loss of photoreceptors leads to less oxygen consumption and lower demand in the inner retina. Retinal oximetry (RO) as a non‐invasive method to analyze oxygen saturation in retinal vessels promises to be a useful therapy monitoring tool. The aim of our study was to compare the RO parameters at baseline and following TES.MethodsA total of 43 eyes of 22 subjects (11♀ 11♂) suffering from RP were examined. Stimulation was performed for 30 minutes weekly at 200% of the individual phosphene threshold on both eyes. The oxygen saturation was examined at baseline (BL), 1 week and 6 months after TES stimulation with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Germany). The global oxygen saturations, within 1.0–1.5 optic disc diameters from the disc margin, in retinal arterioles (A‐SO2; %) and venules (V‐SO2; %) were estimated and their difference (A‐V SO2; %) was calculated. In addition, we evaluated the diameters in the corresponding arterioles (D‐A; μm) and venules (D‐V; μm). ANOVA‐based linear mixed‐effects models were calculated with SPSS®.ResultsSix months after TES the A‐SO2 showed a tendency to increase (from 96.48 ± 12.27% to 100.15 ± 5.56%, p = 0.09), while the V‐SO2 showed a slight decrease (from 61.61 ± 12.78% to 59.79 ± 11.15%, p = 0.48). The A‐V SO2, which represents the oxygen consumption of the retina, showed a significant increase from 34.87 ± 9.38% at BL to 41.36 ± 9.18% after 6 months (p = 0.02). TES had no influence on the D‐A and D‐V (p > 0.6).ConclusionThese data indicate that TES therapy in RP leads to an increased oxygen consumption of the retina. Thus, RO proves to serve as a sensitive monitoring method for TES therapy in RP patients.
The effect of preservative free hydrocortisone 0.335% eye drops on tear film thickness in patients with moderate to severe dry eye disease
Authors: Schmidl Doreen , Kallab Martin , Hommer Nikolaus , Szegedi Stephan , Stegmann Hannes , Werkmeister René , Schmetterer Leopold , Garhofer Gerhard 
Published: December 2019

AbstractPurposeDry Eye Disease (DED) has been found to be associated with reduced pre‐corneal tear film thickness (TFT). Previous studies have shown that topical lubricants have the potential to increase TFT in patients with DED. In the present study, we investigated whether anti‐inflammatory therapy with topical low dose preservative free (PF) soft steroid, hydrocortisone 0.335% eye drops also has an effect on TFT in patients with moderate to severe DED.MethodsA total of 60 patients with moderate to severe DED were included. Patients were randomized to receive either hydrocortisone 0.335% for 12 days 4 times daily followed by 2 days twice daily instillation (intense treatment group) or 8 days 3 times daily followed by 3 days twice daily treatment (recommended treatment group). TFT was assessed using a custom‐built ultra‐high resolution optical coherence tomography system at baseline, at day 14 and day 28. Measurement of intraocular pressure (IOP) and standard clinical tests to assess signs and symptoms of DED, such as the Ocular Surface Disease Index (OSDI), were performed.ResultsFour weeks after treatment start, a significant increase in TFT was observed in both groups (5.3 ± 8.9%, p = 0.03 vs. baseline in the intense and 5.6 ± 13.1%, p = 0.04 vs. baseline in the recommended treatment group) with no difference between the two groups (p = 0.94). IOP did not change at the end of the treatment period in neither of the two treatment groups (p = 0.38, from 14.1 ± 1.8 to 13.9 ± 2.0 mmHg in the intense and from 12.8 ± 1.9 to 13.3 ± 2.1 mmHg in the standard treatment group). OSDI significantly decreased from baseline during the study period in both study groups (p < 0.001, by 19.5 ± 39.1% and 24.1 ± 33.9%, respectively) after PF hydrocortisone treatment.ConclusionsThe present data show that low dose hydrocortisone PF eye drops have the potential to restore TFT in patients with moderate to severe DED. This indicates that this anti‐inflammatory therapy option acts directly in the disease process.
The role of ROS levels on the activation of SMAD2 by TGFβ1 in corneal fibroblasts
Authors: Wang Zheng , Bernstein Audrey , Mario Wolosin J. 
Published: December 2019

AbstractPurposesTGF‐1/TGFβR‐induced corneal myofibroblast genesis is mediated by the positive feedback loop (TGFβR ‐>> p‐SMAD2↑ ‐>> ROS↑‐>>TRPV1↑ ‐>> Ca↑‐>> p‐p38↑‐>> p‐SMAD2↑‐>ROS..‐> p‐SMAD2↑). Inhibition of pp38, ROS, TRPV1, Ca influx or N‐acetyl cysteine (NAC; 1 µM), a ROS scavenger, reduces SMAD2 phosphorylation (PLOS1, 2013: e77300). Our studies seek to identify signal transduction components of the loop.Methods4th generation cultures of fibroblasts derived from donor cadaver corneas (HCF) seeded in a FBS‐free fibroblast medium for 24h were incubated with inhibitors (15 min at 10‐50 x of inhibitor Kd) and the changes in p‐SMAD2 and p‐p38 upon addition of TGFβ1 (2 ng/ml for 5‐60 min) were determined by Western blot. Untreated HFCs showed nil p‐SMAD2 and a low p‐p38 level.ResultsAddition of TGFβ1 to uninhibited cells caused a 4.7‐fold p‐p38 increase (n=3) and the de novo accumulation of p‐SMAD2. Inhibition of maternal embryonic leucine zipper kinase (MELK) by 100 nM OTSSP168, phospholipase D by 1 µM FIPI, PI3Kα by 50 nM PI3K Inhibitor #2, or the superoxide conversion to H2O2 in the mitochondria by 500 µM Mito‐Tempo resulted in > 5‐fold increase in p‐p38 and pronounced or full inhibition of the de novo SMAD2 activation by TGFβ1. The increase in p‐p38 and inhibition of SMAD2 activation was also elicited by incubation with the cellular oxidant p‐Nitrophenyldisulfide (NPDS; 10 nM). Next, we treated the cells with NAC, 0‐500 nM NPDS and TGFβ. As the [NPDS] was increased, the inhibitory effect of NAC on both [p‐p38] and [p‐SMAD2] was decreased and canceled at [NPDS] = 15 nM. Further increases in [NPDS] thought, elevated [p‐p38] but inhibited SMAD2 activation by TGFβ1.ConclusionFibroblast activation by TGFβ1/TGFβR requires a very precise ROS level. The inhibitory effect of some signal transduction pathways may occur indirectly through their effect of the redox cellular status. Inflammations or infections that increases ROS may delay the wound healing response.