bluuebunny/crossref_metadata_2025 huggingface dataset:
Useful indices of thrombogenesis in the exclusion of intra‐cardiac thrombus
Authors: Ibebuogu Uzoma N. , Schafer Joseph H. , Schwade Mark J. , Waller Jennifer L. , Sharma Gyanendra K. , Robinson Vincent J. B.
Published: December 2019

Background

Cardioversion in patients with atrial fibrillation (AF) can cause cardioembolic stroke, and effective clinical management is necessary to reduce morbidity and mortality. Currently, transesophageal echocardiography (TEE) is the accepted standard to diagnose cardiogenic thromboemboli; however, a negative TEE does not eliminate the possibility of left atrial thrombus. The objective of this study was to evaluate the diagnostic value of supplementing the TEE with additional noninvasive markers to ensure thrombus absence.

Methods

A prospective study was conducted on 59 patients who underwent TEE for suspected intra‐cardiac thrombi. The TEE indications included acute ischemic stroke (45.7%) and AF or flutter (59.3%). D‐dimer level and white blood cell counts were assessed.

Results

A negative D‐dimer level (<200 ng/mL) excluded the presence of intra‐cardiac thrombi. Groups with either negative (n = 14) or positive (n = 45) D‐dimer levels had comparable clinical characteristics. Comparing positive D‐dimer–level patients with thrombus (n = 7) and without thrombus (n = 33), patients with thrombus had reduced left atrial appendage (LAA) velocity (P = .0024), reduced left ventricular ejection fraction (LVEF) (P = .0263), increased neutrophil percent (P = .0261), decreased lymphocyte percent (P = .0216), and increased monocyte counts (P = .0220). The area under the receiver operating characteristic (ROC) curve for thrombus diagnostics was larger for combinations of clinical and biochemical data than for each parameter individually.

Conclusions

Supplementing the gold standard TEE with the analysis of LAA velocity, noninvasive LVEF, D‐dimer, and hemostatic markers provided additional useful diagnostic information. Larger studies are needed to further validate the efficacy of supplementing the TEE to better assess patients for intra‐cardiac thrombi.
Understanding muscle regenerative decline with aging: new approaches to bring back youthfulness to aged stem cells
Authors: Muñoz‐Cánoves Pura , Neves Joana , Sousa‐Victor Pedro
Published: December 2019

Aging is characterized by the progressive dysfunction of most tissues and organs, which has been linked to the regenerative decline of their resident stem cells over time. Skeletal muscle provides a stark example of this decline. Its stem cells, also called satellite cells, sustain muscle regeneration throughout life, but at advanced age they fail for largely undefined reasons. Here, we discuss current understanding of the molecular processes regulating satellite cell maintenance throughout life and how age‐related failure of these processes contributes to muscle aging. We also highlight the emerging field of rejuvenating biology to restore features of youthfulness in satellite cells, with the ultimate goal of slowing down or reversing the age‐related decline in muscle regeneration.
Microbial carbon limitation: The need for integrating microorganisms into our understanding of ecosystem carbon cycling
Authors: Soong Jennifer L. , Fuchslueger Lucia , Marañon‐Jimenez Sara , Torn Margaret S. , Janssens Ivan A. , Penuelas Josep , Richter Andreas
Published: December 2019

Numerous studies have demonstrated that fertilization with nutrients such as nitrogen, phosphorus, and potassium increases plant productivity in both natural and managed ecosystems, demonstrating that primary productivity is nutrient limited in most terrestrial ecosystems. In contrast, it has been demonstrated that heterotrophic microbial communities in soil are primarily limited by organic carbon or energy. While this concept of contrasting limitations, that is, microbial carbon and plant nutrient limitation, is based on strong evidence that we review in this paper, it is often ignored in discussions of ecosystem response to global environment changes. The plant‐centric perspective has equated plant nutrient limitations with those of whole ecosystems, thereby ignoring the important role of the heterotrophs responsible for soil decomposition in driving ecosystem carbon storage. To truly integrate carbon and nutrient cycles in ecosystem science, we must account for the fact that while plant productivity may be nutrient limited, the secondary productivity by heterotrophic communities is inherently carbon limited. Ecosystem carbon cycling integrates the independent physiological responses of its individual components, as well as tightly coupled exchanges between autotrophs and heterotrophs. To the extent that the interacting autotrophic and heterotrophic processes are controlled by organisms that are limited by nutrient versus carbon accessibility, respectively, we propose that ecosystems by definition cannot be ‘limited’ by nutrients or carbon alone. Here, we outline how models aimed at predicting non‐steady state ecosystem responses over time can benefit from dissecting ecosystems into the organismal components and their inherent limitations to better represent plant–microbe interactions in coupled carbon and nutrient models.
Prevalence of dental caries in preschool children born preterm and/or with low birth weight: A systematic review with meta‐analysis of prevalence data
Authors: Occhi‐Alexandre Ingrid Gomes Perez , Cruz Poliana Valdelice , Bendo Cristiane Baccin , Paiva Saul Martins , Pordeus Isabela Almeida , Martins Carolina Castro
Published: December 2019

The aim of the present systematic review and meta‐analysis was to evaluate the prevalence of dental caries among preschool children who had been born preterm and/or with low birth weight (LBW) compared with those who had been born full term and/or with normal birth weight (NBW). Eight electronic databases were searched from interception up to November 2018 with no restrictions imposed regarding the date of publication or language. Two independent reviewers screened studies, extracted data, and assessed the risk of bias. A random‐effects meta‐analysis was run to pool the crude prevalence of dental caries according to gestational age and birth weight. We performed a narrative synthesis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Fifty‐nine observational studies were included (55 in the meta‐analysis). The prevalence of dental caries was 39% among preterm children, 30% among full‐term children, 40% among LBW children, and 33% among NBW children (I2:97%‐99%). The majority of studies reported that dental caries was not associated with gestational age or birth weight, with very low certainty of evidence. Preschool children born preterm or with LBW have similar dental caries experience as those born full term or with NBW, with very low certainty of evidence (PROSPERO #CDR42018118086).
Lipids and the eye, beyond fat
Authors: Bron Alain
Published: December 2019

Even though great lipids experts have already brought their knowledge on the EVER stages, lipids as a whole are not really considered as they should, taking in consideration their important role in eye physiology and eye diseases. The aim of this simple and humble journey through lipids is to stimulate the interest of young investigators for the fascinating world of lipids, from the tear film to the brain.
Immunology and the elder eye
Authors: Jager Martine J.
Published: December 2019

Several eye diseases occur more frequently in the elderly, such as age‐related macular degeneration (AMD), primary open angle glaucoma and intraocular melanoma. Inflammation has become an important player, and while in the past AMD was considered purely a vessel disease, it has become clear that macrophages and complement play an important role in the development of the leaky vessels. The function of macrophages changes when we age. As Makitie and Kivela had shown that macrophages have a prognostic value in uveal melanoma, we started to investigate the role of aging in the development of ocular tumors in a mouse model. Ly observed that depletion of macrophages had no effect in young mice, but prevented intraocular tumor growth in old mice. Maat, Bronkhorst and Brouwer showed that specific chromosomal abnormalities in a uveal melanoma are associated with prognosis, influx of macrophages and a high vessel density.

While working on this, I learned about a patient with glaucoma who had the impression that her visual field had decreased when she had the flu. Around the same time, Dr Dong Feng Chen of the Schepens Eye Research Institute in Boston developed a murine glaucoma model. A Dutch PhD student, Dr Khanh Vu, set out to determine whether inflammation plays a role in glaucoma, and indeed, glaucomatous damage following high eye pressure increased through the induction of immune responses. High eye pressure led to influx of macrophages and T cells into the retina, and the induction of specific antibodies and T cell responses. The T cells are directed against heat shock proteins, which become expressed after trauma. Blocking T cell immune response limited the loss of retinal ganglion cells and axons in the mouse after glaucoma induction. The anti‐heat shock immune response did not develop when the mouse lacked a microbiome. Patients with glaucoma also showed anti‐heat shock protein antibodies and T cell responses.These data show that inflammation plays a role in several age‐related eye disease, including age‐related macular degeneration, uveal melanoma and glaucoma.

Makitie T. et al. Tumor‐infiltrating macrophages (CD68+ cells) and prognosis in malignant uveal melanoma. Invest Ophthalmol Vis Sci 2001; 42: 1414‐1421. Bronkhorst I.H. et al. Detection of M2 macrophages in uveal melanoma and relation with survival. Invest Ophtalmol Vis Sci 2011; 52: 643‐650. Doi: 10.1167/iovs.10‐5979. Ly L.V. et al. In aged mice, outgrowth of intraocular melanoma depends on proangiogenic.

M2 type macrophages. J Immunol. 2010; 185: 3481‐3488. Chen H. et al. Commensal microflora‐induced T cell responses mediate progressive neurodegeneration in glaucoma. Nat Commun 2018; Aug 10;9(1): 3209. Doi: 10.1038/s41467‐018‐05681‐9
Recent advances in nanoscopic drug delivery systems for the treatment of glaucoma
Authors: Sánchez López Elena
Published: December 2019

Neuroprotection for glaucoma is still an unmet medical need and a proper drug delivery to the posterior segment of the eye is crucial. During the last decade, researchers have focussed their attention in the development of new drug delivery systems such as nanostructured lipid carriers, liposomes and polymeric nanoparticles. These nanoscopic systems overcome ocular barriers and provide a prolonged drug delivery on the target tissue avoiding adverse effects of the encapsulated drugs. During this course, recent advances and future perspectives in nanoscopic drug delivery systems for the treatment of glaucoma would be reviewed. Moreover, among several drug delivery systems, biodegradable polymeric nanoparticles have been proven to constitute a safe and suitable vehicle to encapsulate a wide range of drugs and be administrated as eye‐drops. Therefore, poly‐lactic‐co glycolic acid (PLGA) in addition to be biodegradable, biocompatible and non‐toxic, have demonstrated to be an effective drug carrier for ocular drug delivery. In this sense, Memantine loaded PLGA nanoparticles functionalized with polyethylene glycol (MEM‐NP) constitute a suitable neuroprotective strategy to increase MEM availability. MEM‐NP adminstered as eye‐drops confirmed to be safe, well‐tolerated and neuroprotective in an experimental glaucoma model. Nanoscopic systems could be the key for the efficient topical administration of neuroprotective compounds glaucoma treatment.
Basics for ultrastructures in transmission electron microscopy
Authors: Kaarniranta Kai
Published: December 2019

Age‐related macular degeneration (AMD) is a complex eye disease. Retinal pigment epithelium (RPE) degeneration is one of the primary sign in AMD pathology. RPE cells are constantly exposed to oxidative stress that contributes to protein misfolding, aggregation and functional abnormalities during pathological aging. The protein aggregates formed at the cell periphery are delivered along the microtubulus network to a juxtanuclear location. RPE damage secondarily affects on survive of photoreceptors. Main cellular waste in AMD are extracellular drusen and lysosomal lipofuscin. Theirs accumulation is related to decreased ubiquitin‐proteasome system (UPS) and lysosomal autophagy clearance. Endoplasmic reticulum stress, damaged mitochondria, and pigmentation alterations are also associated with the degeneration of RPE cells and photoreceptors. Ultrastructures observed in AMD pathology are showed in transmission electron micrographs.
Tips and tricks on how to plan a good study
Authors: Lains Ines
Published: December 2019

In this session, we will address crucial steps for appropriate planning of a research project. Specific examples will be used and tips and tricks will be shared regarding: (1) the relevance of formulating a good research question and strategies to achieve it; (2) the relevance of knowing the literature and the gaps in current knowledge; (3) different types of study designs and how to choose the most appropriate to address a certain research question; (4) execution planning and stepwise approaches to ensure the feasibility of the proposed study within the available timeframe. The relevance of ethical considerations and the eventual needs for a multidisciplinary team will also be covered. At the end of this session, participants are expected to feel more comfortable with planning of their research studies.
Changes in the ABCD keratoconus grade after corneal cross linking
Authors: Ali Yekta Abbas , Reza Sedaghat Mohammad , Momeni‐Moghaddam Hamed , Danesh Zienab , Khabazkhoob Mehdi , Heravian Shandiz Javad , Azimi Khorasani Abbas , Ostadimoghaddm Hadi , Ehsaei Asieh , Yekta Reihaneh
Published: December 2019

Purpose

To assess the changes in the ABCD keratoconus staging system after 3 and 6 months and Material corneal cross linking.

Methods

Thirty one eyes of 31 pationts with keratocnus who were corneal cross linking with the rebofelavin A and ultraviolet ray laser were assessed preoperative and postoperative assessments included determination of distance corrected visual acuity (DCVA), refraction. and Scheimpflug tomography with the Pentacam HR. In the ABCD keratoconus staging system, the elements A, B, C, and D stand for anterior and posterior radii of curvature in a 3.0‐mm zone centered on the thinnest point (TP), corneal thickness at the TP, and DCVA, respectively.

Results

Corneal cross linking produced no significant changes (preoperatively vs. postoperatively) in the anterior (6.91 ± 0.39 vs. 6.92 ± 0.41 vs. 6.94 ± 0.40 mm, p = 0.397) and posterior (5.29 ± 0.42 vs. 5.23 ± 0.44 vs. 5.26 ± 0.44 mm, p = 0.003) radii of curvature of the 3‐mm zone centered on the corneal TP associated with a statistically significant invariant in the DCVA (0.82 ± 0.16 vs. 0.76 ± 0.18 vs. 0.79 ± 0.20 in the decimal notation, p = 0.066) with a little improvement in the corneal thickness at the TP (446.77 ± 89.01 vs. 453.96 ± 38.16 vs. 457.64 ± 37.93 µm, p < 0.001). The most changes occurred in element B of the ABCD keratoconus classification. and elements A, C and D did not show changes in their postoperative stages after corneal cross linking. ABCD keratoconus staging before corneal cross linking was A1B2C1D1 and changed to A1B2C1D1 3and 6 months after surgery.

Conclusion

The ABCD staging system provides a more comprehensive guide that better illustrates the structural changes and visual acuity as one aspect of visual function after the corneal cross linking.
Estimation of the variance components in TP53 mRNA expression in the rat lens after in vivo exposure to UVR‐B
Authors: Galichanin Konstantin
Published: December 2019

Purposes

The aim of this study is to investigate the variance components in TP53 mRNA expression after in vivo exposure to double threshold dose of UVR‐B.

Methods

Twelve six‐week‐old female albino Sprague‐Dawley rats were exposed to double threshold dose (8 kJ/m2) of UVR‐B unilaterally and sacrificed at 1, 3, 8 and 24 hr after exposure. Lenses were enucleated and TP53 mRNA expression was detected by qRT‐PCR. Variance components for groups, animals and measurements were estimated with analysis of variance.

Results

The variance for groups is 0.15 rel.2. The variance for animals is 0.29 rel.2. The variance for measurements is 0.32 rel.2.

Conclusions

The variance for animals is on the same order as the variance for measurements. The reduction of the variance for measurements is needed in order to obtain the acceptable level of detection the difference in TP53 mRNA expression and the reduction in sample size.
Benchmarking posterior capsule rupture rate in glaucoma patients before and after patient‐surgeon risk match
Authors: Susanna Fernanda , Puertas Renata
Published: December 2019

Purpose

To investigate posterior capsule rupture (PCR) rate in glaucoma patients before and after the implementation of patient risk and surgeon match system.

Methods

The study included patients from the Glaucoma service between 2010 and 2017 that had phacoemulsification. Rates of PCR are analysed annually for internal reporting use and were compared before and after implementation of patient risk and surgeon match system.

Results

The rate of PCR was 1.75% in 2010–2011, 1.04% in 2012–2013, 1.30% in 2014, 0.91% in 2015, 1.01% in 2016 and 1.03% in 2017. The mean rate before matching system was 1.36%; after intervention the PCR rate dropped to 0.98%, showing a reduction of 27.9% in the unadjusted PCR rate.

Conclusion

The PCR rate was within national standards by the Royal College of Ophthalmologists (1.95%) at all time. It also concurred with the 30% reduction in National Ophthalmic Database between first reporting in 2010 and subsequent one in 2016–2017. This shows how a robust reporting system with feedback can aid to patient safety, boosting performance with benchmarking.
Prevalence of Endophthalmitis after Aqueous Shunt Implants and related procedures in an eye service
Authors: Puertas Renata , Susanna Fernanda , Turner Suzanne , Grant‐McKenzie Nadine , Wagland Catherine , Papadopoulos Maria
Published: December 2019

Purpose

To investigate the rate of endophthalmitis, its microorganisms, risk factors and visual outcomes, related to aqueous shunt implant (tube) surgery in the Glaucoma service in 5 years of laboratory electronic database.

Methods

This study was approved by the Clinical Audit Office. All eyes with tube implant or related surgery were reviewed from 2009 to 2013. Development of endophthalmitis was identified from the electronic database and notes reviewed.

Results

A total of 1827 tubes, 893 revisions and 2391 removal of stent suture (RoS) were performed in that period. In total six eyes developed endophthalmitis related to tube surgery, all were following revision/RoS, none were after tube implant only. Time till onset was 8 ± 6.7 days. The rate of endophthalmitis was 0.67% after tube revision and 0.25% after RoS. No microorganisms were identified in any samples.

Conclusion

Endophthalmitis is a rare complication of tube surgery, its rate in this study was less than reported in literature and was only observed after revision/RoS surgeries.
Keratoconus recognition using a parameter set determined from IOP‐matched scenario
Authors: Tian Lei
Published: December 2019

Purpose

Among the current practices for keratoconus recognition using biomechanical parameters from corneal visualization Scheimpflug technology (Corvis ST), matching intra‐ocular pressure (IOP) is often required to eliminate the biasing influence; as a result, the combined biomechanical parameters determined from IOP‐unmatched scenario possibly bring in confounding influence. This paper was therefore designed to introduce a novel compatible parameter set (CPS) determined from IOP‐matched scenario, hopefully could show its compatibility and superiority for recognizing keratoconus in both IOP‐matched and not scenarios.

Methods

A total of 335 eyes were included. Among them, 70 eyes (35 keratoconus and 35 normal eyes; pairwise matching for IOP) were used to determined CPS by forward logistics regression, 62 eyes (31 keratoconus and 31 normal eyes; pairwise matching for IOP) were used to validate CPS in IOP‐matched scenario, and resting 203 eyes (112 keratoconus and 91 normal eyes; not pair matching for IOP) were used to validate CPS in IOP‐unmatched scenario. To analyze its superiority, CPS was also compared with other two reported Biomechanical Indexes (aCBI 6,7 and DCR 8) in both scenarios. Receiver operating characteristic curves (ROC), accuracy, FI, sensitivity and specificity were used to access and compare the performance of these three parameter sets in both scenarios.

Results

The resulting CPS was comprised of only 3 biomechanical parameters: DA Ratio Max 1mm (DRM1), the first applanation time (AT1) and an energy loading parameter (Eload). In the IOP‐matched validation, the area under ROC (AUC) reached 95.73%, with an accuracy of 95.2%, sensitivity of 93.5% and specificity of 96.8% (leave one out cross‐validation). All these indicators reached 96.54%, 95.1%, 95.6% and 94.6% respectively, in the IOP‐unmatched validation (leave one out cross‐validation). Surprisingly, CPS performed better than other two parameter sets on a whole.

Conclusions

The parameter set determined from IOP‐matched scenario indeed exhibit its superiority for differentiation of keratoconus and normal corneas, regardless of IOP‐matched or not.
Is central corneal thickness a constant during air puff indentation with Corvis ST?
Authors: Tian Lei
Published: December 2019

Purpose

Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) is the only commercial device that can capture corneal dynamic deformation in real time and provide a number of dynamic parameters, which include central corneal thickness (CCT). This study aimed to quantitatively analyse the change in CCT during air puff indentation using Corvis ST.

Methods

Sixty‐seven keratoconic eyes and 84 normal eyes were enrolled in this study. Dynamic videos were obtained from Corvis ST. An adaptive bilateral filtering method and a frame correlation method were used to remove noises. An adaptive threshold segmentation method was used to extract corneal boundary. The change in central corneal thickness, described as relative change rate of central corneal thickness (RCRCCT) and change speed of central corneal thickness (CSCCT) were compared between keratoconus group and normal cornea group.

Results

It is shown that CCT would change and these two parameters were statistically significantly different between the keratoconus group and the normal cornea group RCRCCT, p = 0.014; CSCCT, p = 0.001.

Conclusions

The result of this study approved that CCT would change during air puff indentation. Further study is needed to develop more clinical applications based on these new findings, such as distinguishing keratoconus from normal cornea.

image

Fig. 1 Curves of changes in cornea and force over time. (A) Curve of corneal apex displacement and curve of air puff force; (B) A typical curve of the CCT changingover time. The red lineis the central corneal thickness‐time curve, the blue line is the force ‐time curve, and the green line is the fitting curveof force curve.
Effects of vitamin D deficiency on intraocular pressure values obtained by ocular response analyzer
Authors: Kocaturk Tolga , Bekmez Sinan , Unubol Mustafa
Published: December 2019

Abstarct

To compare corneal biomechanical properties measured with ocular response analyzer (ORA) and intraocular pressure (IOP) measurements in patients with vitamin D deficiency and in healthy cases.

One hundred twenty eyes of 120 subjects (between the ages of 19–78) who applied to university outpatient clinic between June 2015 and August 2018 were included in this study, 41 lack of vitamin D (Group 1), 39 insufficient vitamin D (Group 2) and 40 controls (Group 3). The eyes included in the study were randomly chosen. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular pressure (IOPg) and corneal compensated intraocular pressure (IOPcc) of patients were measured by ORA. The study protocol had the approval of the university’s ethics committee and complied with the guidelines set forth in the Declaration of Helsinki.

The mean ages were 48.9 ± 12.1, 52.8 ± 13.6 and 52.1 ± 13.9 in Group 1, 2 and 3, respectively (p = 0.370). 22 (53.7%) were female, 19 (46.3%) were male in Group 1, 20 (51.3%) were female, 19 (48.7%) were male in Group 2 and 20 (50.0%) were female, 20 (50.0%) were male in Group 3 (p = 0.946). Mean IOPcc values were 16.5 ± 3.6 (8.1–27.3), 16.7 ± 2.7 (12.0–22.7) and 16.3 ± 3.3 (10.8–27.4) mmHg (p = 0.889); mean IOPg values were 16.8 ± 5.0 (6.5–39.5), 16.3 ± 2.9 (10.3–23.0) and 15.9 ± 3.2 (10.0–26.0) mmHg (p = 0.539); mean CH values were 10.8 ± 1.9 (8.3–19.0), 11.4 ± 1.6 (6.9–14.0) and 11.2 ± 1.5 (7.5–13.2; p = 0.257); mean CRF values were 10.5 ± 2.7 (7.4–25.0), 11.1 ± 1.5 (6.8–13.5) and 10.5 ± 1.2 (7.7–12.8; p = 0.282) in Groups 1, 2 and 3, respectively. There was no statistical difference between the groups in terms of IOPcc, IOPg CH and CRF. However, mean CH values were found less in the lack of vitamin D group.

In our study, we found that the CH values were lower and the IOPg values were higher in cases of vitamin D deficiency. Corneal biomechanical differences in patients with lack of vitamin D were not statistically significant.
In vitro evaluation of antibacterial activity of fluorescein 0.5% eye drops
Authors: Bouche Thibaud , Claude Quintyn Jean , Join Lambert Olivier , Guerin Francois , Auzou Michel
Published: December 2019

Purpose

Fluorescein is commonly used in ophthalmology to confirm a diagnostic of corneal ulceration. In case of infectious keratitis, microbiological investigations are necessary involving anesthetic eye drops administration and corneal sampling. An antibacterial activity has already been described associated with anesthetic eye drops yielding therefore a risk of false negative result. However fluorescein influence has never been studied. This study was aimed at evaluating antibacterial in vitro activity for fluorescein and for most common anesthetic eye drops.

Methods

The most frequently isolated germs in case of infectious keratitis (S. epidermidis, S. aureus, P. aeruginosa, S. pneumoniae, M. lacunata, M. catarrhalis and C. macginleyi) have been tested. The determination of the minimum inhibitory concentrations (MICs) for the different eye drops (0.5% fluorescein, 0.4% oxybuprocaine and 1% tetracaine) was achieved by microdilution in liquid medium.

Results

Fluorescein did not exhibit antibacterial activity for most germs (MICs > 2500 mg/L) except for Moraxella (M. catarrhalis and M. lacunata), for which the MICs observed were 1250 mg/L and 625 mg/L respectively and corresponding to a dilution of 1/4 and 1/8 of the commercial solution.

Conclusion

At the usual concentration of 0.5% (5 g/L), fluorescein does exhibit antibacterial activity for Moraxella bacteria. Therefore, it is essential to properly wash the eye with sterile physiological serum before sampling in order to eliminate fluorescein and local anesthetic.
A preclinical study of the intraocular pressure lowering efficacy of bimatoprost sustained release in eyes pretreated with selective laser trabeculoplasty
Authors: Ghosn Corine , Engles Michael , Rajagopalan Lakshmi , Ugarte Sveti , Mistry Shruti , Orilla Werhner , Goodkin Margot , Robinson Michael , Rivas Marcos , Dibas Mohammed
Published: December 2019

Purpose

Selective Laser Trabeculoplasty (SLT) is a treatment for lowering intraocular pressure (IOP) in patients with glaucoma, however IOP‐lowering is not sustained after SLT over long term in a substantial proportion of patients. Recent human studies found less reduction in IOP when SLT and topical prostaglandin analogues (PGA) were used in combination. Bimatoprost Sustained Release (BimSR) implant is currently in development as an IOP‐lowering agent delivered intracamerally (IC). The purpose of this study was to assess the efficacy of BimSR in both eyes of a cohort of dogs following unilateral SLT treatment.

Methods

Unilateral SLT was performed in 11 female, normotensive, drug‐naïve beagle dogs. IOP was monitored up to 10 weeks following SLT. Six to ten weeks post SLT, nine of 11 eyes returned to their baseline IOP. Dogs were administered BimSR (15 μg) IC in both eyes. Percent change in IOP from baseline was calculated in SLT‐treated and naïve eyes. Data expressed as mean ± SE. A linear mixed effects model was used to evaluate the treatment effect of BimSR in SLT‐treated and contralateral SLT‐naïve eyes.

Results

BimSR was equally efficacious in lowering IOP in both SLT‐treated and SLT‐naïve eyes. Mean percent decrease in IOP following BimSR administration to SLT‐treated eyes was 34.2% ± 2.8 and 34.7% ± 1.7 in contralateral, SLT‐naïve eyes. BimSR lowered IOP equally in eyes that responded to SLT (sustained decrease in IOP of ≥3 mmHg in the laser treated eye, n = 6, mean percent IOP decrease, 34.3% ± 4.2) and eyes that did not respond to SLT treatment (decrease in IOP of <3 mmHg in the laser treated eye, n = 5, mean percent IOP decrease, 34.1% ± 2.7).

Conclusions

Intracameral BimSR had substantial IOP‐lowering effects in eyes previously treated with SLT, suggesting that eyes that have been treated with SLT can still benefit from IC drug delivery of the BimSR implant. Importantly, BimSR was effective in lowering IOP in eyes that were previously non‐responders to SLT.
Prevalence of Risk Variants for Glaucoma in the MYOC gene in the General Population
Authors: Liuska Perttu , Kivelä Tero , Turunen Joni
Published: December 2019

Purpose

To assess the clinical relevance of myocilin (MYOC) gene variants reported in association with glaucoma in the literature, and to estimate the prevalence of these variants in different populations.

Methods

We reviewed the literature for published MYOC variants in glaucoma patients and estimated their prevalence in the general population using the gnomAD and BRAVO databases. We used several bioinformatics tools and the criteria of the American College of Medical Genetics and Genomics (ACMG) to assess the pathogenicity of the variants. We evaluated the carrier frequency of likely pathogenic and risk variants in gnomAD, including its subpopulations.

Results

We found 13 reported missense and 5 loss‐of‐function (LOF) variants in MYOC that were both likely pathogenic or risk variants and listed in the gnomAD database. Six likely pathogenic missense variants were p.Gly399Val (c.1196G>T), p.Thr377Met (c.1130C>T), p.Thr353Ile (c.1058C>T), p.Gly326Ser (c.976G>A), p.Gln48His (c.144G>T), and p.Cys25Arg (c.73T>C). They were most prevalent in East and South Asia (frequency, 0.0092 and 0.0081, respectively). The most common missense variants were p.Thr353Ile (0.0091 in East Asia) and p.Gln48His (0.0079 in South Asia). Five LOF variants were p.Gln368Ter (c.1102C>T), p.Arg272Ter (c.814C>T), p.Arg91Ter (c.271C>T), p.Arg46Ter (c.136C>T) and p.Tyr453MetfsTer11 (c.1357delT). We considered these glaucoma risk variants. They were most prevalent in the East Asian and the Finnish population (0.0093 and 0.0033, respectively).

Conclusions

Pathogenic MYOC variants appear to be population‐associated. Likely pathogenic missense variants seem to be most prevalent in Asia. The glaucoma risk variant p.Gln368Ter is most common in the European population with the highest prevalence in the Finnish population. Our results highlight allelic heterogeneity of MYOC variants in open‐angle glaucoma.
Dose‐dependent density change of lens epithelial cells after in vivo UVR exposure
Authors: Yu Zhaohua , Talebizadeh Nooshin , Söderberg Per
Published: December 2019

Introduction

Our research group focuses on the mechanism of ultraviolet radiation (UVR) induced lens damage. Posterior capsule opacification (PCO) is the most common complication for cataract surgery. PCO results from the growth and abnormal proliferation of lens epithelial cells (LECs) on the posterior capsule. Lens epithelium is the first target for toxic factors such as ultraviolet radiation. UVR‐300 nm (UVR‐B) is especially an important risk factor for cataract development. Our previous findings show that exposure to UVR‐B can damage the lens epithelium, affect the expression of proteins, induce apoptosis and lead to cataract formation. Therefore, it is possible to prevent PCO by sufficient dose exposure of ultraviolet radiation to residual lens epithelial cells after cataract surgery.

Purpose

To determine the effect of different doses of UVR on the distribution of lens epithelial cells (LECs).

Methods

Altogether, 40 Sprague Dawley rats were unilaterally exposed in vivo to 1, 3, 6 and 8 kJ/m2 UVR‐300 nm for 15 min. One week after UVR exposure, exposed and contralateral non‐exposed lenses were removed. One midsagittal section from each lens was stained with DAPI for fluorescence microscopy in order to determine the spatial distribution of LECs.

Results

The LECs density difference between exposed and contralateral non‐exposed eyes at exposure dose of 1, 3, 6 and 8 kJ/m2 was estimated as a CI (95%), −0.1 ± 2.1, 0.1 ± 3.0, −4.1 ± 1.4 and −2.9 ± 2.7 Cell μm−1 10−2, respectively. Data was fit to a linear model considering the initial density difference at 0. The inclination coefficient was estimated as CI (95%), −0.4 ± 0.1 Cell μm kJ−1 1010.

Conclusion

UVR‐300 nm induces significant LECs density decrease at exposure dose ≥6 kJ/m2. With fitting to a linear model the evolution of dose‐cell density dependence can be determined.
Migraine headache and high tension glaucoma among adult population living in Armenia: a case‐control study
Authors: Giloyan Aida , Harutyunyan Tsovinar , Hakobyan Varsik , Kirakosyan Lilit , Petrosyan Varduhi
Published: December 2019

Purpose

Glaucoma is the leading cause of global irreversible blindness and the second leading cause of blindness globally. This study assessed the association between migraine headaches and high tension glaucoma among adult population living in Armenia.

Methods

This case‐control study recruited 145 cases and 250 controls from Optomed Canada Eye Diagnostic Center (OCEDC) in Armenia. Cases were patients with glaucoma, while controls were patients with no glaucoma and no other ocular disorders except refractive errors. A structured interviewer‐administered questionnaire contained socio‐demographic questions, family history of glaucoma and stroke, smoking status, migraine and obstructive sleep apnea. The details on ocular health were retrieved from patients’ medical records. This study used Migraine Screening Questionnaire for assessment of possible migraine and Berlin Questionnaire to assess obstructive sleep apnea.

Results

Mean age of cases and controls was 62.8 (SD = 12.6) and 39.5 (SD = 13.5), respectively. Women comprised 64.1% of cases and 69.1% of controls in the sample. About 17.5% of cases and 19.0% of controls were identified having possible migraine. In the adjusted analysis age (OR = 1.15; 95% CI: 1.10; 1.19), having average and lower than average socio‐economic status (OR = 3.45; 95% CI: 1.04; 11.4) and family history of glaucoma (OR = 3.96; 95% CI: 1.56; 10.1) were significantly associated with glaucoma.

Conclusion

This study found no statistically significant association between migraine headache and high tension glaucoma. Due to the limited number of cases with normal tension glaucoma in the sample, the study could not assess its associations with migraine. Timely screenings for eye pathologies among those with average/low socio‐economic status could facilitate early detection of eye diseases and help to prevent visual loss.
Comparison of vessel density and retinal nerve fiber layer thickness in patients between both eyes of subjects with clinically unilateral pseudoexfoliation syndrome using optical coherence tomography angiography
Authors: Yang Heon , Young Ryu Jin , Heon Lee Tae
Published: December 2019

Purpose

The purpose of the study was to compare vessel density (VD) and retinal nerve fiber layer thickness (RNFLT) between eyes with pseudoexfoliation material (PE+) and fellow unaffected (PE−) eyes of patients using optical coherence tomography angiography (OCTA).

Methods

A retrospective analysis of 36 eyes from 18 patients with clinically unilateral pseudoexfoliation syndrome was performed. The circumpapillary (cp) VD and RNFLT were obtained using OCTA and perifoveal, parafoveal VD and RNFLT were also calculated using OCTA. Circumpapillary parameters were obtained from octametric sections: superonasal (SN), nasalsuperior (NS), nasalinferior (NI), inferonasal (IN), inferotemporal (IT), temporalinferior (TI), temporalsuperior (TS), and superotemporal (ST) and perifoveal, parafoveal parameters were obtained in 4 different quadrants: temporal, nasal, inferior, superior.

Results

In PE+ eyes, the cpVD was significantly lower in all eight sectors (p < 0.05), while the cpRNFLT showed significant reduction in six sectors (p < 0.05): NS, NI, IN, IT, ST and SN). Perifoveal VD was significantly decreased in temporal, inferior quadrant (p < 0.05) and parafoveal VD was significantly lower in only temporal quadrant (p < 0.05) in the PE+ group. While, significant difference was not detected in RNFLT between PE+ and PE− eyes.

Conclusions

Eyes with clinically unilateral pseudoexfoliation syndrome have low VD and thin RNFLT as compared to fellow unaffected eyes, but not with the all sectors. These changes appear to be associated with pseudoexfoliation material. The roles and mechanisms in pseudoexfoliative material need clarification.
Evolution of AMD drusenoid deposits Protein‐Cellular Type," P": density, structure, volume, complications study
Authors: Gonzalez Corinne , Gonzalez Corinne
Published: December 2019

Purpose

To study evolution of AMD drusenoid deposits “P”: density, structure, volume parameters with Morphology‐structural software, complications with OCT, Multimodal exam. Six years follow‐up.

Methods

234 eyes of 194 patients with AMD drusenoid deposits “P”, Protein‐Cellular Type: Cuticular drusen, Pseudovitellifom AMD, Subretinal drusenoid deposits (SDD), Drusenoid PED "P". Deposits were evaluated by Multimodal exam, OCT (Spectralis spectral domain HRA‐OCT) and Morphology‐Structural software (M‐S software). Multimodal exam, OCT let analyze deposit evolution, itself and its environment. M‐S software let drusenoid deposit contents analyze, discrimination, differentiation, let grading (volume, contours analyze), let measurements: volume (in µm3), density (grey levels of deposits), structure (structural measures, texture parameters), so evaluation, characterization of those “P” deposits evolution. Evaluation, comparison for each eye, each patient, between all studied patients was done every 6 months, during 6 years.

Results

AMD Drusenoid Deposit “P” density, structure evolution was with no much less density, more structure, 2 years cycle evolution with bell‐shaped curve, smooth for density, more prominent for structure; for volume evolution: rather increase volume, 1 year ½ cycle with irregular bell‐shaped curve. Evolution: 45% No complication, rather unchanged, 44% to Neovascular Complication(choriocapillaris change‐pigment epithelium involution: more dense, irregular, inhomogeneous, crumbled‐inflammation‐neovascular signs), 11% to Atrophy (Pigment Epithelium layer granular, irregular, less thick, thinner and thinner to disappear). M‐S Software reliable, relevant for characterization, evolution study of deposit; Density: good criteria to characterize drusenoid deposit and evolution, too for Structure to study contents, modifications, evolution; Volume: interesting criteria for lesion, eye, patient study but no or less according whole studied patients

Conclusion

Evolution of AMD Drusenoid deposits Protein‐Cellular Type, “P”, contribute to and improve AMD knowledge, its complication understanding and get AMD biomarker feature.
PLGA microspheres loaded with a ROCK inhibitor as an intravitreally injectable drug delivery system for the management of glaucoma
Authors: Mietzner Raphael , Kade Christian , Froemel Franziska , Fuchshofer Rudolf , Wegener Joachim , Breunig Miriam
Published: December 2019

Purpose

Primary open‐angle glaucoma (POAG) is a chronic, progressive neuropathy of the optic nerve and one of the major causes of blindness worldwide [1]. ROCK inhibitors such as fasudil are a promising class of drugs on the market allowing a causative therapy of POAG. Unfortunately, a major drawback of topically applied fasudil is its high hydrophilicity and consequently low intraocular bioavailability [1]. In addition, short half‐life severely limits its time of action. Therefore, we propose intravitreal injectable fasudil loaded poly(lactide‐co‐glycolide) microspheres (fasudil‐MS) as promising depot formulation increasing the effect, stability and bioavailability of fasudil to a maximum. In different cell‐based assays the biological activity of fasudil‐MS was tested.

Methods

Fasudil‐MS were prepared by the water‐in‐oil‐in‐water solvent evaporation technique. Manufactured fasudil‐MS were characterized regarding size by laser diffraction, encapsulation efficiency by HPLC and in vitro release. Measurement of biologic activity of released drug was performed in different cell‐based assays. Therefore, preliminary cell studies were established with free fasudil and the glaucomatous factors connective tissue growth factor (CTGF) and transforming growth factor‐β2 (TGF‐β2) to analyze cell contractility and expression of a‐smooth muscle actin (a‐SMA) by qPCR.

Results

Fasudil‐MS had a size of 20‐25µm and spherical shape. Fasudil was released in a controlled biphasic releasing profile. In preliminary experiments, fasudil demonstrated its ability to diffuse through the vitreous body and was able to reduce the cell contractility as well as the gene expression of a‐SMA induced by CTGF and TGF‐β2.

Conclusion

The proposed formulation could be a promising strategy increasing therapy effectiveness.

Reference

Mietzner R, Breunig M. Causative glaucoma treatment: promising targets and delivery systems. Drug Discov Today. 2019.
Influence of strabismus on the motor skills in children
Authors: Hemptinne Coralie , Pellissier Thomas , Ruiz Clément Ramirez , Vanderveken Catherine , Yuksel Demet
Published: December 2019

Purpose

Together with anisometropia and organic causes of visual deprivation, strabismus, if not treated before the age of 7 or earlier, depending on studies, leads to amblyopia and loss of binocularity. In this study, we first examined which parameters of strabismus influenced the motor development in children. Second, we assessed to what extent different motor skills were impacted by strabismus.

Methods

To this end, we evaluated the motor skills of 40 children between 3 and 12 years old suffering from strabismus using the Movement Assessment Battery for Children – Second Edition (MABC‐2).

Results

According to MABC‐2, 19 children had no motor disability, and 21 had risk of or significant motor disabilities. As for the first question, results at MABC‐2 were significantly lower for children without compared to those with binocularity (p‐value = 0.002), and significantly lower for participants with binocularity but without stereoscopy in comparison with those with stereoscopy (p‐value = 0.099). However, results did not differ significantly according to the type of strabismus, that is infantile, secondary or acquired strabismus. Differences were not significant either according to the angle of deviation. Regarding our second question, binocularity significantly impacted static balance (p‐value = 0.003) and to a smaller extent dynamic balance (p‐value = 0.05). Performance for catching, but not for shooting, was significantly affected by binocularity (p‐value = 0.042).

Conclusions

Our study shows that the development of motor skills in children is significantly affected when binocularity and stereoscopy are absent, independently from the type of strabismus. Among the motor skills, static balance and catching are significantly impacted by that absence of binocularity. These results should be confirmed with a larger sample, including older patients, to assess the compensation mechanisms put in place and the actual impact of strabismus on overall motor performance.
Resvega alleviates oxidative stress and inflammasome activation in retinal pigment epithelial cells
Authors: Bhattarai Niina , Korhonen Eveliina , Toppila Maija , Kaarniranta Kai , Kauppinen Anu
Published: December 2019

Purpose

Oxidative stress and inflammation have been shown to associate with the pathogenesis of age‐related macular degeneration. Oxidative stress is known to induce inflammasome activation. The aim of the study was to investigate the effects of the resveratrol‐containing Resvega on the inflammasome activation in retinal pigment epithelial (RPE) cells exposed to oxidative stress.

Methods

For the investigation of intracellular reactive oxygen species (ROS) production and inflammasome activation, ARPE‐19 cells were exposed to hydroquinone or MG‐132 and bafilomycin A1 primed with IL‐1α. Experiments were performed with and without pre‐treatment with Resvega (Laboratoires Théa, France). ROS production was measured using the 2′,7′‐dichlorofluorescin diacetate (DCFDA) probe. Caspase‐1 activity was determined using a specific fluorochrome inhibitor of caspases (FLICA). The amount of secreted IL‐1β and NLRP3 were measured using the enzyme‐linked immunosorbent assay (ELISA) method. Cell viability and cytotoxicity were determined using the thiazolyl blue tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays.

Results

Hydroquinone induced intracellular ROS production, which was reduced by pre‐treatment with Resvega. However, reduction did not result from increased cytotoxicity or declined cell viability. Inflammasome activation by MG‐132+bafilomycin A1 in IL‐1α ‐primed cells was detected by the activation of caspase‐1 and increased secretion of IL‐1β and NLRP3. All those were reduced by the pre‐treatment with Resvega, which had no impact on the cell viability.

Conclusions

Our results suggest that Resvega has potential to alleviate oxidative stress and inflammation in human retinal pigment epithelial cells.
Ahmed glaucoma valve versus Ex‐PRESS glaucoma shunt in the surgical treatment of glaucoma: 2‐year follow up
Authors: Lee Jiyoung , Choi Jin A
Published: December 2019

Purpose

To compare the surgical outcomes of Ex‐press glaucoma shunt with Ahmed glaucoma valve in glaucoma patients.

Methods

This study retrospectively reviewed the records of patients who underwent Ahmed valve implantation or EX‐PRESS shunt surgery. Neovascular glaucoma patients were excluded. Primary outcome measure was surgical success, defined as an intraocular pressure between 5 and 21 mmHg and a 20 % intraocular pressure reduction from baseline (with or without glaucoma medications) without glaucoma reoperation. Preoperative and postoperative endothelial cell count was also compared.

Results

In total, 52 patients (56 eyes) were included (27 Ahmed valve, 29 Ex‐PRESS shunt). 2 years complete success rate (without glaucoma medication) was 84.9% for Ahmed valve, 81.3% for Ex‐PRESS shunt (p = 0.452), and qualified success rate (with/without glaucoma medication) was 95.8% for Ahmed valve, 96.6% for Ex‐PRESS shunt. (p = 0.877) The Ex‐PRESS group had significantly greater reduction of intraocular pressure than Ahmed valve group at post‐op 3, 6 months. (18.3±5.3 mmHg versus 14.2±6.2 mmHg, 15.4±3.9 mmHg versus 13.3±4.4 mmHg, p = 0.001, p = 0.033). The number of glaucoma medication was significantly lower in Ex‐PRESS group than Ahmed valve group throughout the follow up period. At post‐op 2 years, corneal endothelial cell counts were significantly higher in Ex‐PRESS group than Ahmed valve group at post‐op 2 years. (1794.5±403.5 /mm2 versus 2212.2±399.0/mm2, p = 0.010).

Conclusions

Compared with Ahmed valve, Ex‐PRESS shunt showed similar success rate and greater intraocular lowering effect until post op 6 months. Ex‐Press shunt also seems to be a safer surgery regarding the risk of endothelial cell loss.