bluuebunny/crossref_metadata_2025 huggingface dataset:
Updated direct costs of medical care for HIV‐infected patients within a regional population from 2006 to 2017
Authors: Krentz HB , Vu Q , Gill MJ
Published: December 2019

Objectives

The aim of the study was to reappraise the precise costs of HIV care and cost drivers, to determine the optimal tools for modelling costs for HIV care, and to understand the implications of changing medical management of HIV‐infected patients for both subsequent outcomes and health care budgets.

Methods

We obtained all drug, laboratory, out‐patient and in‐patient care costs for all HIV‐infected patients followed between 1 January 2006 and 31 December 2017 (2017 Cdn$). Mean cost per patient per month (PPPM) was used as the standard comparator value. Patients were stratified based on CD4 count: (1) ≤ 75, (2) 76–200, (3) 201–500 and (4) > 500 cells/μL. We determined the cost for only HIV‐related expenses. We compared current costs with costs previously reported for the same population.

Results

The number of HIV‐infected patients in care doubled from 2006 to 2017; total costs increased from $12.4 to $30.1 million, with antiretroviral (ARV) drugs accounting for 78.8% of costs by 2017. Out‐patient/laboratory costs declined from 12% to 8.5%, while in‐patient costs exhibited more annual variation. Mean PPPM costs increased from $1316 in 2006 to $1712 in 2014, declining to $1446 in 2017. Higher PPPM costs were associated with CD4 counts < 200 cells/μL. Costs have shifted. While the cost of ARV drugs increased by 32%, the costs of out‐patient and in‐patient services decreased by 80% and 71%, respectively. Most of the decrease for in‐patient costs was attributable to a substantial decrease in HIV‐related hospitalizations.

Conclusions

Although antiretroviral therapy (ART) provides immense benefits, it is not inexpensive. ARV drugs remain the largest cost driver. Hospital costs have remained low. Substantial costs of lifelong ART necessitate innovative, locally applicable strategies for ARV selection and use.
Transglutaminase and tyrosinase as potential cross‐linking tools for the improvement of rheological properties of gluten‐free amadumbe dough
Authors: Manhivi Vimbainashe E. , Amonsou Eric O. , Kudanga Tukayi
Published: December 2019

Gluten‐free bread remains of poor quality despite efforts to amend gluten‐free flours with ingredients such as hydrocolloids and proteins. Enzymatic modification of the proteins in dough may result in polymers that mimic gluten. This research investigated the effects of transglutaminase and tyrosinase on the rheological properties of amadumbe dough. Tyrosinase oxidation resulted in a 7.7–39.4% decrease in dough‐free amine, and a 16.8–46.3% decrease in the dough thiol content as activity was increased from 0 to 80 U g−1 flour. Transglutaminase treatment decreased the dough‐free amino groups by 10–38.1% as activity was increased from 0 to 2 U g−1 flour. Evidence of tyrosinase and transglutaminase‐mediated cross‐linking was provided by relevant model reactions monitored by mass spectrometry. An increase in dough G′ and G″ showed that both transglutaminase and tyrosinase improved dough viscoelasticity. The increase in the viscoelasticity of the dough potentially improves carbon dioxide retention during proofing.
Psychometric properties of the Arabic version of the International Consultation on Incontinence Questionnaire on Long‐Term Catheter Quality of Life
Authors: Youssef Naglaa , Best Catherine , Mackay William Gordon , Hagen Suzanne , Shepherd Ashley
Published: December 2019

Aim

To translate the International Consultation on Incontinence Questionnaire (ICIQ) Long‐Term Catheter Quality of Life (LTCqol) questionnaire (ICIQ‐LTCqol) from English to Arabic and evaluate its psychometric properties.

Background

Currently, no tool for Arabic‐speaking patients is available to measure the quality of life in patients using long‐term urinary catheters.

Design

Translation and psychometric assessment of questionnaire.

Methods

The internal consistency and construct validity of the translated Arabic version of the ICIQ‐LTCqol were evaluated in a convenience sample of 141 participants recruited from a hospital in Egypt from April to September 2017. Test‐retest reliability was assessed for a sample of 15 participants who completed this version at two time points. Construct validity was assessed by factor analysis.

Results

The translated Arabic version of the ICIQ‐LTCqol showed satisfactory test‐retest reliability and internal consistency, with the Cronbach α = .75. Confirmatory factor analysis confirmed the same two factors (“catheter function” and “lifestyle”) structure as found in the English version of the tool supporting the construct validity of the translated questionnaire.

Conclusion

This original and significant study allows, for the first time, researchers and clinicians working with Arabic‐speaking patients, the opportunity to evaluate the quality of life in long‐term urinary catheter users.
Pricing and introductory scarcity strategies based on consumers' response
Authors: Chen Shaohua , Jia Junxiu
Published: December 2019

In industries such as electronics, automobiles, and luxury goods, we have observed numerous cases of intentional undersupply when a new product is introduced. Previous research has shown that introductory scarcity has a positive effect on consumers' willingness to pay, but this effect has yet to be quantified. This paper investigates how scarcity strategies affect product pricing and a firm's profits. We consider two types of scarcity strategies, a real and a fake scarcity strategy, and propose a two‐period model in both markdown and markup scenarios. We find that an introductory scarcity strategy is profitable in a markup scenario only if the discount factor is greater than a critical value and payoffs are compartmentalized. Moreover, an introductory scarcity strategy could result in profits in a markdown scenario if consumers are sensitive to scarcity. However, a scarcity strategy is always detrimental to a firm with low‐quality products in both scenarios. If there are uninformed consumers in the market, a fake scarcity strategy is beneficial for firms in the short term but not in the long term.
Ocular thermography in ocular inflammation and dry eye
Authors: Acosta M. Carmen
Published: December 2019

Measurement of the ocular surface temperature (OST) has been proposed as a diagnostic method for ocular surface pathologies as dry eye disease (DED), due to the involvement in its pathophysiology of tear evaporation rate.

During mild inflammation induced by UV radiation in guinea pigs, no changes in the initial OST measured immediately after eye opening and in the rate of OST decrease during the interblink interval (IBI) were observed. However, during allergic keratoconjunctivitis, where tearing and blinking were significantly increased and a prominent inflammation was induced, the initial OST was significantly increased.

In animals with experimentally‐induced tear deficiency, a variability in the initial OST values was found: some animals showed a “cold spot” (increasing in intensity and size during IBI) in the central cornea, while in other animals initial OST was warmer than control, suggesting a subclinical inflammation.

Eyes from Sjögren syndrome patients, besides a reduced tearing rate, showed higher initial OST and faster ocular surface cooling between blinks than eyes from age‐matched healthy subjects.

Although OST values per se do not provide relevant information on ocular surface disease, due to the differences in etiology and pathophysiology of DED, it may be a valid diagnostic method if combined with the clinical evaluation of inflammation, and tear volume, composition and stability.

Support: AEI‐ERDF SAF‐2017‐83674‐C2‐1‐R and 2‐R; Generalitat Valenciana PROMETEO/2018/114.
iSyTE: A web resource tool to expedite eye gene discovery
Authors: Lachke Salil
Published: December 2019

The identification of genes linked to eye development and its associated defects presents a formidable challenge. In the recent past however, genome‐level transcript profiling (transcriptomics) has become increasingly feasible due to technologies such as microarrays and RNA sequencing. Their application to interrogate specific eye tissues and cell types holds high promise to impact ocular gene discovery. However, global gene expression profiling has brought with it new challenges, such as parsing through the large amounts of data to prioritize select candidates for further analysis. Toward this goal, the development of strategies such as “in silico subtraction” has led to the construction of a systems‐based web‐resource tool called iSyTE (integrated Systems Tool for Eye gene discovery). In this presentation, I will discuss the impact of iSyTE and eye‐tissue transcriptomics on identification of new genes linked to lens biology and cataract, and outline the ongoing efforts for extending this approach to other ocular tissues such as the retina and the cornea.
History of the development of intraocular lenses
Authors: Eppig Timo
Published: December 2019

Couching as the first surgical method for cataract has been performed for about 4000 years. Until mid of the 20th century, attention was spent on removing the opaque lens from the line of sight – refractive correction was provided as spectacle lenses. During World War II – the British ophthalmologist Harold Ridley had to treat pilots suffering from penetrating eye injuries after being shot down. He found that splints from the cockpit cover – which were made from PMMA – did not induce inflammatory reactions. Inspired by his student Steve Parry he started to develop an intraocular implant made of PMMA – which was the birth of the modern intraocular lens. The invention of phacoemulsification by Charles Kelman and the capulorhexis by Neuhann and Gimbel led the way to the success of modern posterior chamber lenses. Until the late 1970’s, lenses were made of PMMA until the first flexible silicone lenses came up. Starting in the late 1980s the silicone lenses were successively replaced by acrylic lenses. Nowadays the majority of lenses are made from acrylic material.
Optical concepts – monofocal, aspheric, toric, multifocal, EDOF
Authors: Kaymak Hakan
Published: December 2019

We will present an overview of the various optical concepts used in intraocular lenses: while the conventional monofocal lens was designed to provide basic refractive correction, modern aspheric lenses aim to provide better contrast sensitivity by compensation of intrinsic or corneal spherical aberration. Toric lenses were developed to correct corneal astigmatism during cataract surgery. Multifocal lenses aim to provide functional visual acuity at various distance levels. There are basically two concepts of implementing multifocality: those based on refraction and those based on diffraction. Modern extended depth of focus lenses try to fill in the gap between monofocal and multifocal lenses by providing acceptable visual acuity from far distance to intermediate distance.
Matching analysis with your study design
Authors: Kivelä Tero
Published: December 2019

This talk will highlight some key issues in choosing statistical methods for ophthalmic research, based on personal experience of the speaker as a writer, reviewer and editorial board member. The items discussed, based on examples from recent literature, will include: (1) proper ways of summarising and comparing visual acuities; (2) proper ways of analysing data collected from both eyes of the same patients, (3) proper ways of analysing longitudinal follow‐data, and (4) proper ways of analysing contigency table data. Correct reporting and analysis of data related to the eye is not too difficult as long as one is aware of a few basic rules. Putting them into action helps to ensure that the conclusions you put forward and those that the readers draw from your study will be proper.
Comparison of conjunctival vascularity changes using optical coherence tomography angiography after trabeculectomy and phacotrabeculectomy
Authors: Hyun Seo Je
Published: December 2019

Purpose

To compare the bleb vascularity using optical coherence tomography angiography (OCT‐A) between mitomycin‐C (MMC) augmented trabeculectomy and phacotrabeculectomy and to investigate the relationship between bleb vascularity and surgical outcomes.

Methods

We retrospectively reviewed data for 72 eyes from 72 glaucoma patients who underwent MMC augmented trabeculectomy with/without cataract surgery. Bleb area scans were obtained using OCT‐A during the preoperative period and 1, 2, 4, and 6 weeks, and 2, 4, and 6 months postoperatively. For conjunctival vascularity analysis, a semi‐automated program was used to calculate the densities of color and brightness of the selected area.

Results

Color and brightness densities were decreased in the trabeculectomy group during all periods, whereas it did not decrease in the phacotrabeculectomy group at 4 and 6 weeks, 2, 4, and 6 months. The color and brightness densities were significantly higher in the phacotrabeculectomy group than in the trabeculectomy group after 6 weeks and 2, 4, and 6 months. A Kaplan‐Meier survival graph showed that the intraocular pressure was not different according to surgery type, but glaucoma type. Logistic regression analysis revealed that the brightness density 1 week postoperation was correlated with reoperation.

Conclusions

Following trabeculectomy with MMC, The brightness density one week postoperation may be a predictive index for surgical outcomes, suggesting that a more accurate prediction could be made if evaluation of bleb structural analysis and bleb vascularity are performed simultaneously.
Tips and tricks on how to write a good scientific paper
Authors: Oddone Francesco
Published: December 2019

Writing for peer‐reviewed publication is an important part of the careers of many clinicians and researchers. Writing a paper and getting it published is hard work, even after the hard work that led to the publishable results. The presentation will focus on tips and tricks about how to make this process easier through an organized step by step algorithm to guide the writer from the first paragraph to the last in a clear and effective way.
How to get your research known by your peers!
Authors: Barbosa Breda Joao
Published: December 2019

Nowadays it is almost as important to properly divulge your research as to actually make it. A paper’s real impact is certainly linked to the amount of people that read it, cite it and, in some cases, put it to use in the clinics/labs. The whole purpose of research is to lead to changes according to the new evidence, and that is only possible if the message is passed on to the audience/readers. This talk will focus on how to create a clean and concise message that can be used in the channels that allow your research results to be disseminated. An overview of the different platforms that can be used to get your research known will also be performed. The goal is to enable Young Ophthalmologists and/or Researchers with the tools to more effectively transport the message imbedded in the research work they have done to their peers.
Understanding organelle biogenesis during the autophagy process in the RPE
Authors: Sinha Debasish
Published: December 2019

The retinal pigmented epithelium (RPE) is critically important to retinal homeostasis, in part due to it's very active processes of phagocytosis and autophagy. Both of these processes depend upon the normal functioning of lysosomes, organelles which must fuse with (auto)phagosomes to deliver the hydrolases that effect degradation of cargo. It has become clear that signaling through mTOR complex 1 (mTORC1), is very important in the regulation of lysosomal function. Lysosomes are cellular organelles that modulate various processes such as autophagy and heterophagy, plasma membrane repair, cholesterol homeostasis, and cell death. The number, size, and content of lysosomes vary in different cell types. The distribution of lysosomes within the cell is determined by the nutrient sensing machinery at the lysosomal membrane, and is an important factor in lysosomal catabolic function. In this course, we will focus on the effector molecules present in RPE cells that impact the lysosomal‐autophagic pathway in retinal health and disease.
Efficacy of an ophthalmic fixed combination of tetracycline, chloramphenicol and colistin on planktonic growth and preformed biofilm
Authors: Rita Blanco Anna , Nostro Antonia , D’ Arrigo Manuela , Marino Andreana
Published: December 2019

Purpose

Bacteria colonization on the lid margin could play a crucial role in developing of biofilm causes of chronic infections such as blepharo‐conjunctivitis or lacrimal system disease. The aim of this study was to evaluate the efficacy of an ophthalmic fixed antibiotics/steroid combination (AC) containing tetracycline (TET), chloramphenicol (CAF) and colistin (CS), in the ratio 2:1:3, on bacterial planktonic growth and preformed biofilm.

Methods

The antimicrobial effect of AC against Staphylococcus aureus 815 and Pseudomonas aeruginosa 1 ocular strains was evaluated by time‐killing curves analysis at 30’, 2, 4, 6, 8 and 24 hr. The activity of AC (exposure of 2 and 6 hr) on preformed 24 hr‐biofilm was evaluated by cell viability and biomass measurements, expressed as logarithm of colony‐forming units/ml (Log10 CFU/ml) and optical density values, respectively.

Results

Time‐killing curves showed that AC was able to reduce the load of planktonic growth of both strains versus control. A significant reduction of 5 Log10 CFU/ml after 8h for S. aureus and after 4h for P. aeruginosa was reported. The AC was active against preformed biofilm, with a viability significant reduction (>2 Log10 CFU/ml versus control) of both strains at the exposure times. A biomass reduction of 40% and 60% for S. aureus and P. aeruginosa respectively, was detected at the exposure time of 2 hr and maintained at 6 hr.

Conclusions

The three antibiotics CAF, TET and CS present in AC showed a significant antimicrobial and antibiofilm effect. Antibiotics combination is a promising strategy for increasing treatment efficacy and for controlling resistance evolution. The results of this study, taken together, suggest the applications of this fixed combination in the treatment of chronic ocular infections where planktonic cells and biofilm are involved.

Keywords

antibiotics combination, biofilm, ocular infection, lacrimal system
Pattern‐stimulation in the complex management of patients with operated retinal detachment
Authors: Kazanskaya Tamara
Published: December 2019

Introduction

The problem of increasing visual function after surgical treatment of retinal detachment retains its relevance. Existing methods do not take into account the possibilities of the retinal‐cortex system stimulation.

Objective

Evaluation of the functional effect of pattern‐stimulation in the complex management of retinal detachment operated patients.

Patients and methods

Forty patients with an extrascleral retinal procedure. The median of age is 53.6 [23; 75] years. Patients in group 1a (10 eyes with macula‐on before surgery) and 1b group (with macula‐off before surgery) underwent a course of drug therapy (peptides, meldonium, antioxidants), patients of group 2a (10 eyes macula‐on before surgery) and 2b Groups (macula‐off before surgery) – a similar course of drug treatment combined with a pattern‐stimulation course. All groups are comparable in age, sex, visual acuity, data of electrophysiological studies – macular electroretinogram (ERG), visual evoked cortical potentials (VECP). According to the results of optical coherent tomography carried out before the start of treatment, there were no gross organic changes in the area of the macula in patients. Starting treatment 6 months after surgery. Evaluation of the treatment effectiveness after 3 months after its completion.

Results

Increased visual acuity after treatment in group Ia occurred at 0.05, in group Ib by 0.03, in group IIa by 0.17, in group IIb by 0.21. The amplitude of wave‐a of macular ERG increased by 4.07 mV in group Ia, by 5.4 mV in group Ib, by 2.9 mV in group IIa, by 8.17 mV in group IIb; changes in wave amplitude‐in different directions: in group Ia, an increase of 3.5 mV, in group Ib a decrease of 0.4 mV, in group IIa and IIb an increase of 5.19 mV and 10.86 mV, respectively. VECP N 75 latency decreased by group Ia by 1.46 ms, by group 19.2 ms by group IIa, by 14.94 ms by group IIb, and increased by 1.1 ms by group Ib; P100 decrease in groups: Ia by 0.93 ms, IIa by 14.39 ms, IIb by 14.94 ms, increase in group Ib by 1.2 ms; the amplitude of the N75‐P100 VECP wave increased in all groups: Ia by 1.3 mV, Ib by 1.55 mV, IIa by 3.48 mV, IIb by 10.58 mV. An increase in visual acuity on the background of drug treatment correlated with an improvement in the amplitude characteristics of the local ERG (r = 0.47), using pattern stimulation with an increase in the amplitude characteristics of the VECP (r = 0.46).

Conclusion

Using the stimulation pattern in complex management of the retinal detachment operated patients helps to improve the amplitude indices of local ERG and VECP by more than three times, reducing VECP latency values, increasing visual acuity 4 times in comparison with the routine drug therapy results in patients 1a and 1b groups. The results obtained indicate the feasibility of using the method of pattern‐stimulation in patients with operated retinal detachment to enhance the functional effect of surgical treatment.
Difference of corneal endothelial cells according to senescence
Authors: Joo Shin Young , Sun Hwang Jin , Kyung Jang Yoon
Published: December 2019

Purpose

Bullous keratopathy is a painful corneal endothelial disease and its treatment requires corneal transplantation because human corneal endothelial cells (HCECs) do not proliferate in vivo. In this study, we evaluated differences between HCECs depending on senescence.

Methods

HCECs were cultured and were classified into two groups: cells with small size and mosaic pattern (normal group), and cells with large size and no mosaic pattern (SA group). Cell shape, cell viability, and cell proliferation rate were evaluated. Cell cycle analysis, mitochondrial oxidative stress, and mitochondrial membrane potential were assessed. Western blotting was performed to evaluate expression of various proteins.

Results

Cell shape and size were different between normal and SA groups. Cell viability and cell proliferation rates were found to be lower in the SA group. Cell cycle analysis, mitochondrial oxidative stress, and mitochondrial membrane potential revealed differences between normal and SA groups. Protein expression was different between the normal group and the SA group.

Conclusions

Differences in phenotype between normal and SA groups might contribute to the pathogenesis of corneal endothelial diseases.

References

Siu GD, Young AL and Jhanji V. Alternatives to corneal transplantation for the management of bullous keratopathy. Curr Opin Ophthalmol. 2014; 25(4):347–352.

Choi SO, Jeon HS, Hyon JY, Oh YJ, Wee WR, Chung TY, Shin YJ and Kim JW. Recovery of Corneal Endothelial Cells from Periphery after Injury. PLoS One. 2015; 10(9):e0138076.

Eghrari AO, Riazuddin SA and Gottsch JD. Overview of the Cornea: Structure, Function, and Development. Prog Mol Biol Transl Sci. 2015; 134:7–23.
Development of a nomogram using fundus photography to predict glaucoma progression in patients showing disc hemorrhage
Authors: Kim Sangah , Won Bae Hyoung
Published: December 2019

Purpose

To develop a nomogram to predict the progression of glaucoma by fundus photography in patients with disc hemorrhage.

Material and methods

Retrospective review of the medical records of patients with disc hemorrhage, which was detected during follow up with open angle glaucoma, from January 2010 to January 2019. Patients were divided into glaucoma progression (n = 52) or non‐progression (n = 38) groups. We assessed proximal location and morphology of disc hemorrhage; relationship to retinal nerve fiber layer defects with disc hemorrhage; and angular extent of disc hemorrhage, between groups using fundus photography. Multiple logistic regression analysis was performed to select prognostic factors, and we constructed a nomogram to predict glaucoma progression.

Result

The incidences of disc hemorrhage at the border of retinal nerve fiber layer defects (p < 0.001) and peripapillary disc hemorrhage (p = 0.009) were significantly higher in the progression group. We used angular extent; location of disc hemorrhage with retinal nerve fiber layer defects; and proximal location of disc hemorrhage to construct the nomogram. The area under the receiver operating characteristic curve of the nomogram was 0.829.

Conclusion

We created the nomogram using fundus photography in patients showing disc hemorrhage as a novel and accurate screening method to predict glaucoma progression and aid clinicians to decide on the best treatment plan.
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

Purpose

To compare meibomian gland (MG) morphology and function, and blinking pattern in Korean pediatric subjects with or without overnight orthokeratology wear.

Methods

The 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).

Results

No 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).

Conclusions

Based 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

Purpose

To 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.

Setting

Department of ophthalmology, the Chinese PLA general hospital, Beijing, China.

Design

Prospective clinical trial.

Methods

In 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.

Results

Transient 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.

Conclusions

The 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

Purpose

To investigate the effect of non‐invasive tear stability assessment with forced eye opening on the upper and lower tear meniscus.

Methods

Ten 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.

Results

The 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).

Conclusions

Forced 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

Purpose

We 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.

Methods

We 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 urgency

Results

After 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.

Conclusions

The 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

Purpose

To 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).

Methods

Fifteen 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.

Results

The 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).

Conclusions

These 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

Purpose

Pathophysiological 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.

Methods

We 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.

Results

We 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.

Conclusions

Due 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.

Reference

H 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

Purpose

Preservatives 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.

Methods

This 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.

Results

The 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.

Conclusions

We 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

Purpose

Human 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.

Methods

Selected 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).

Results

Median 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).

Conclusion

CBS 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

Background

Transcorneal 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.

Methods

A 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®.

Results

Six 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).

Conclusion

These 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

Purpose

Dry 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.

Methods

A 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.

Results

Four 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.

Conclusions

The 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

Purposes

TGF‐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.

Methods

4th 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.

Results

Addition 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.

Conclusion

Fibroblast 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.