bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of deviations from soybean product crushing estimates on return and risk
Authors: Abdoh Hussein , Chitavi Michael
Published: January 2024

This study explores how differences in market yields of soymeal and soyoil, as derived from market prices compared to those obtained through the physical process of crushing soybeans, impact the returns and volatilities of these commodities. Positive (negative) deviations are associated with negative (positive) changes in return. Additionally, these deviations positively correlate with return volatility, suggesting that variations from the expected yields lead to price shifts and heightened return volatility. In summary, deviations from the crushing estimates significantly shape the modeling of soybean commodity returns and volatilities, with implications for understanding returns, hedging ratios, and portfolio return variance.
The mechanisms of tumor necrosis factor α in regulating Krüpple‐like factor 4 expression in SK‐BR‐3 breast cancer cells
Authors: Liu Caiyun , Feng Chengbao , Li Haifei , Zhang Erying , Liu Bo , Wang Ying , Wang Peng
Published: January 2024

Objective

To explore the expression and functional role of Krüpple‐like factor 4 (KLF4) protein stimulated by tumor necrosis factor α (TNF‐α) in SK‐BR‐3 breast cancer cells.

Methods

SK‐BR‐3 cells were stimulated with various concentrations of TNF‐α at 0, 1, 5, 10, and 20 ng/mL. Expression levels of KLF4 protein were detected by Western blotting. In the detection of apoptosis, flow cytometry, and DAPI staining were used for detecting the level of apoptosis.

Results

KLF4 expression was markedly elevated following stimulation of SK‐BR‐3 with TNF‐α. At the same time, the expression of KLF4 protein increased gradually with the increase of TNF‐α stimulation concentration. TNF‐α stimulation of SK‐BR‐3 cells increased apoptosis as measured by apoptosis levels. By overexpressing KLF4 protein in SK‐BR‐3 cells, it similarly increased apoptosis and promoted cell death of SK‐BR‐3 cells.

Conclusion

TNF‐α promotes KLF4 expression, while TNF‐α promotes apoptosis in SK‐BR‐3 cells, a process that may be due to elevated KLF4 protein expression.
Cost‐effectiveness of testosterone treatment utilising individual patient data from randomised controlled trials in men with low testosterone levels
Authors: Hernández Rodolfo , de Silva Nipun Lakshitha , Hudson Jemma , Cruickshank Moira , Quinton Richard , Manson Paul , Dhillo Waljit S. , Bhattacharya Siladitya , Brazzelli Miriam , Jayasena Channa N.
Published: January 2024

Background

Testosterone is safe and highly effective in men with organic hypogonadism, but worldwide testosterone prescribing has recently shifted towards middle‐aged and older men, mostly with low testosterone related to age, diabetes and obesity, for whom there is less established evidence of clinical safety and benefit. The value of testosterone treatment in middle‐aged and older men with low testosterone is yet to be determined. We therefore evaluated the cost‐effectiveness of testosterone treatment in such men with low testosterone compared with no treatment.

Methods

A cost‐utility analysis comparing testosterone with no treatment was conducted following best practices in decision modelling. A cohort Markov model incorporating relevant care pathways for individuals with hypogonadism was developed for a 10‐year‐time horizon. Clinical outcomes were obtained from an individual patient meta‐analysis of placebo‐controlled, double‐blind randomised studies. Three starting age categories were defined: 40, 60 and 75 years. Cost utility (quality‐adjusted life years) accrued and costs of testosterone treatment, monitoring and cardiovascular complications were compared to estimate incremental cost‐effectiveness ratios and cost‐effectiveness acceptability curves for selected scenarios.

Results

Ten‐year excess treatment costs for testosterone compared with non‐treatment ranged between £2306 and £3269 per patient. Quality‐adjusted life years results depended on the instruments used to measure health utilities. Using Beck depression index‐derived quality‐adjusted life years data, testosterone was cost‐effective (incremental cost‐effectiveness ratio <£20,000) for men aged <75 years, regardless of morbidity and mortality sensitivity analyses. Testosterone was not cost‐effective in men aged >75 years in models assuming increased morbidity and/or mortality.

Conclusions and future research

Our data suggest that testosterone is cost‐effective in men <75 years when Beck depression index‐derived quality‐adjusted life years data are considered; cost‐effectiveness in men >75 years is dependent on cardiovascular safety. However, more robust and longer‐term cost‐utility data are needed to verify our conclusion.
Identifying changes in the distribution of income from higher‐order moments with an application to Australia
Authors: Martin Vance L. , Shi Jialu , Song Yang , Yao Wenying
Published: January 2024

Changes in the distribution of income over time are identified based on an adjusted two‐sample version of the Neyman smooth test by using subsampling methods to approximate the sampling distribution of the test statistic when samples are not independent of each other. A range of Monte Carlo experiments show that the approach corrects for size distortions arising from dependent samples as well as generating monotonic power functions. Applying the approach to studying the distribution of income in Australia over the business cycle and the Global Financial Crisis, the empirical results highlight the importance of higher‐order moments and demonstrate that business cycles are not all alike as the relative strengths of higher‐order moments vary over phases of the cycle.
The impact of acute kidney injury stages on the outcomes of veno‐arterial extracorporeal membrane oxygenation
Authors: Kallur Akhil S. , Armijo‐Alba Julian , Russell Jacqueline L. , Sallam Tariq , Bien‐Aime Fred , Sanghavi Kavya K. , Garg Mohil , Khan Naveera , Bakri Mouaz Haj , Zaghlol Louay , Khan Imran , El‐Akawi Shadi , Llama Adrian , Sawalha Yazan , Trivedi Suraj , Alassar Aiman , Zaaqoq Akram M.
Published: January 2024

Background

Although acute kidney injury (AKI) has been established as an independent risk factor for in‐hospital mortality for patients on veno‐arterial (V‐A) extracorporeal membranous oxygenation (ECMO), the impact of Kidney Disease Improving Global Outcomes (KDIGO) stages of AKI has yet to be elucidated as a risk factor.

Methods

We conducted a retrospective analysis of patient outcomes based on KDIGO stages of AKI at a single institution. The analysis was a cohort of 179 patients; 66 without AKI, 19 with stage 1 AKI, 18 with stage 2 AKI, and 76 with stage 3 AKI.

Results

Every 1‐year increase in age was associated with 4% increased odds of mortality at 30 days (95% confidence interval [CI] 1.01, 1.07; p = 0.004). The presence of AKI at any stage was associated with 59% increased odds of 30‐day mortality (95% CI 0.81, 3.10; p = 0.176). The presence of stage 1 AKI was associated with a 5% decreased odds of 30‐day mortality (95% CI 0.32, 2.89). The presence of stage 2 AKI (odds ratio [OR] 2.29, 95% CI 0.69, 7.55; p = 0.173) and stage 3 AKI (OR 1.68, 95% CI 0.81, 3.46; p = 0.164) was associated with increased odds of 30‐day mortality.

Conclusion

Based on our single‐center study, higher KDIGO stages of AKI likely have increased odds of mortality at 30 days. Larger studies are needed to confirm these findings.
Multi‐omic study of a cellular model of the retinal pigment epithelium producing extracellular deposits
Authors: Alvarez‐Barrios Ana , Álvarez Jorge García , García Rosario Pereiro , Gonzalez‐Iglesias Hector , Álvarez Lydia
Published: January 2024

Aims/Purpose: To study transcriptomic and metabolomic changes during a 6‐month follow‐up of an in vitro model of the retinal pigment epithelium (RPE) producing extracellular deposits.

Methods: Primary cultures of human fetal RPE cells were established in P12 transwell inserts for 6 months and harvested at 4, 12, 17 and 25 weeks. Progressive accumulation of extracellular material was determined by apolipoprotein E (APOE) and hydroxyapatite (HAP) localization. Transcriptome was analysed by RNA sequencing (RNAseq) and differential expression analysis was conducted using the platform Dr. Tom. Untargeted metabolomics was carried out by high‐resolution mass spectrometry (LC‐IM‐QTOF) and bioinformatic analysis was performed using Mass Professional Profiler software.

Results: RPE cells formed a fully differentiated monolayer at 4 weeks in culture, but tight junctions and electrical resistance decreased from 12 weeks onwards, coinciding with the formation of extracellular deposits containing APOE and HAP. RNAseq showed alterations of cell migration, adhesion and differentiation, and oxidation–reduction, lipid metabolic and apoptotic processes during RPE ageing (4 vs 25 weeks, Q‐value < 0.001). Untargeted metabolomics provided 350 non‐redundant compounds, and principal component analysis showed a clear separation between time points and good reliability within each group (55% of cumulative variance). Moderated t‐test (Benjamin‐Hochberg correction) provided 103 compounds differentially altered during RPE follow‐up (p‐value < 0.001, fold‐change > 2), belonging to trans‐sulfuration, one carbon metabolism, glutathione metabolism, Kennedy pathway for sphingolipids and cysteine and methionine catabolism.

Conclusions: Time‐dependent changes were observed in the cell culture model, including progressive sub‐RPE accumulation of APOE and HAP, and alterations in cell adhesion and migration, lipid metabolism and sphingolipids pathway contributing to photoreceptor protection and calcium mobilization.
TNF‐a/IL‐1B cytokine licensing enhances immunomodulatory potential of allogeneic mesenchymal stromal cells
Authors: Canning Aoife , Donohoe Ellen , Wang Jiemin , Moosavizadeh Seyedmohammad , Treacy Oliver , Ryan Aideen , Ritter Thomas
Published: January 2024

Aims/Purpose: Mesenchymal stromal cells (MSCs) have shown great potential for therapeutic treatment of inflammatory diseases; however, their immunomodulatory potential can be further enhanced by cytokine licensing. The aim of this work was to assess changes in MSC surface characterization profile and immunomodulatory function following licensing with TNF‐α/IL‐1β pro‐inflammatory cytokines.

Methods: MSCs were isolated from the bone marrow of FVB mice (H2kq) and licensed with a combination of 50 ng/mL TNF‐α and 50 ng/mL IL‐1β or cultured in growth medium alone. MSCs were harvested following 72‐h cytokine stimulation and added to immune cell potency assays. Characterization of MSC surface marker expression was assessed by flow cytometry. The immunology potential of FVB MSCs as an allogeneic cell therapy was assessed in vitro through co‐culture with Balb/c (H2kd) αCD3/CD28 activated T lymphocytes or Balb/c IFN‐γ/LPS‐stimulated macrophages.

Results: TNF‐α/IL‐1β licensing was found to induce surface marker phenotype alterations compared with unlicenced MSCs, with increased expression of CD73, CD44, Sca‐1, CD29 and PD‐L1 observed. TNF‐α/IL‐1β licensed MSCs also secreted significantly higher quantities of nitric oxide compared with their untreated counterparts at two separate timepoints, 24‐h and 42‐h post‐stimulation. TNF‐α/IL‐1β MSCs significantly suppressed both CD4+ and CD8+ T cell proliferation at three different rations (1:5, 1:10, 1:50 MSCs: T cells) and significantly increased expansion of CD4+CD25++FoxP3+ regulatory T cells following co‐culture. TNF‐α/IL‐1β MSCs were found to significantly decrease levels of IFN‐γ from proliferating T cells. TNF‐α/IL‐1β MSCs were positive for CD80 expression had significantly reduced MHC I expression and could increase expansion of CD206 on M1‐like macrophages. Both T cell and macrophage co‐cultures with TNF‐α/IL‐1β MSCs showed a significant increase in IL‐6.

Conclusions: Our results show the potential to enhance the therapeutic effects of MSC through cytokine licensing. Currently, TNF‐α/IL‐1β MSCs are being tested in ocular surface injury models for therapeutic efficacy.

Keywords: Mesenchymal Stromal Cells, Cytokine Licensing, Immunomodulation, TNF‐α/IL‐1β.
Analysis of fixation patterns among glaucoma patients using a superfast eye tracking system
Authors: Gorczyca Aleksandra , Tamborski Szymon , Meina Michał , Zabel Przemysław , Gębska‐Tołoczko Martyna , Zabel Katarzyna , Suwała Karolina , Szkulmowski Maciej , Kaluzny Jakub
Published: January 2024

Aims/Purpose: The effect of glaucoma on eye movements is not well understood, so it is extremely important to be able to quantitatively characterize eye movement data which could accelerate glaucoma diagnosis. The aim of the study was to determine differences in eye movements among glaucoma patients and healthy subjects, using a superfast eye tracking system, FreezEye Tracker (FET).

Methods: To study eye movements during a 30‐second fixation task, we used a prototype device FET, which was designed and assembled in our laboratory (Bartuzel et al., 2020). The unique capability of this device is to provide precise information (with an accuracy of about 1 μm on the retina) on eye movements during the fixation task (and other visual tasks) collected at high frequency (more than 1240 eye position measurements per second). We conducted a study on 13 glaucoma patients and 13 healthy subjects of similar age (69 ± 67). The participants' task was to look at the fixation point displayed in the centre of the screen for the period of 30 s.

Results: During the fixation task, we reconstructed the trajectory of the eye movements (in the horizontal and vertical axis) and calculated area of the fixation points, called bivariate contour area (BVRCA) as a measure of fixation stability. Results show that in glaucoma patients the horizontal axis trajectory length (H) and BVRCA were smaller compared to healthy subjects. In glaucoma patients the avg. horizontal axis trajectory length was 60.91° [deg] and BVRCA parameter was 0.19°2. In a healthy group, the average horizontal axis trajectory length was 71.80° and BVRCA parameter was 0.36°2.

Conclusions: The results of the study indicate that the glaucoma patients had greater fixation stability during the task, and their microsaccades showed smaller deviation from the centre of fixation, compared to healthy subjects. The results of the study show that the device has the potential to differentiate basic eye movement parameters in glaucoma patients and healthy subjects.

Reference

Bartuzel MM, Wróbel K, Tamborski S et al. High‐resolution, ultrafast, wide‐field retinal eye‐tracking for enhanced quantification of fixational and saccadic motion. Biomedical Optics Express, 2020, 11(6), 3164–3180.
Development and validation of a new colour vision screener: A multi‐centre study
Authors: Evans Benjamin , Rodríguez‐Carmona Marisa , Llapashtica Emsal , Barbur John
Published: January 2024

Aims/Purpose: The detection of acquired and congenital colour vision deficiency is of importance in the clinic for the early detection of ocular disease and determination of occupational suitability. Conventional methods of colour vision screening often fail to pass all normals and/or correctly identify those with acquired and congenital colour vision deficiency. The Colour Vision Screener (CVS) test [1] was developed to utilize an improved understanding of colour vision mechanisms to overcome the limitations present in conventional colour screening methods. This study aimed to use a robust multi‐centre methodology to fully validate the CVS test.

Methods: Over 400 participants, including 124 normal trichromats, 166 deutans and 62 protans, were recruited from 10 international Colour Assessment and Diagnosis (CAD) testing centres. Each participant completed the CVS and the CAD test with calibrated visual displays. The red/green (RG) and yellow/blue (YB) CVS test sensitivity and specificity were established. The RG statistics were compared to the ‘gold standard’ reference for screening for RG congenital colour vision deficiency—the Ishihara pseudoisochromatic plate test.

Results: The CVS test correctly identified ~99.1% of normal trichromats. All subjects with congenital RG loss and acquired loss on top of congenital RG deficiency were identified as having abnormal colour vision by the CVS. The Ishihara test, based upon 0 errors on the first 25 plates of the 38‐plate edition, correctly identifies ~80.6% of normal trichromats and 99.5% of subjects with congenital RG loss.

Conclusions: Data collected across 10 international CAD centres demonstrate that the CVS can achieve a high sensitivity without sacrificing specificity. This multi‐centre study demonstrates that the CVS is quick, efficient, and easy to use and allows for the rapid and reliable screening of congenital and acquired colour vision deficiencies in large populations.

Reference

1. Barbur JL, Rodriguez‐Carmona M, Evans BEW. Colour vision assessment‐3. An efficient, two‐step, colour assessment protocol. Colour Research & Application 2021; 46: 33–45. https://doi.org/10.1002/col.22599
Are red/green colour vision deficient individuals at altered risk of myopia?
Authors: Lingham Gareth , Biba Matilda , Harrington Siofra , Mackey David , Loughman James
Published: January 2024

Aims/Purpose: To investigate the association between red/green colour vision deficiency (CVD) and myopia in Irish and Australian participants.

Methods: Data from the Ireland Eye Study (IES; age 12–13 years), Raine Study Gen2 cohort (Australia; age 18–22 years) and Kidskin Study (Australia; age 25–30 years) were used. Colour vision was assessed with the Hardy‐Rand‐Ritler (IES) or Ishihara colour vision test (Raine, Kidskin). Right eye spherical equivalent refractive error (SER; myopia defined as SER ≤ −0.50 dioptres [D]) was measured with cycloplegic autorefraction and right eye axial length (AXL) with interferometry. Participants who were female, or with incomplete colour vision or refraction data, tritanomaly, monochromacy, previous surgery or condition‐altering refraction were excluded. Linear and logistic regression were used for analysing binary and continuous outcomes, respectively, with an interaction between study country and CVD.

Results: After exclusions (n = 56), there were 2488 participants of whom 1286 (51.7%) were male (IES: n = 503, Raine: n = 676 and Kidskin: n = 107). The prevalence of CVD across the IES, Raine and Kidskin studies, respectively, was 5.8% (16 deutan, 9 protan, 5 unclassified), 5.5% (18 deutan, 3 protan, 16 unclassified) and 6.5% (6 deutan, 1 unclassified). After adjusting for age, any red/green CVD was not associated with myopia risk (odds ratio [OR] = 1.31, 95% confidence interval [95%CI]: 0.86–2.32, p = 0.36), SER or AXL. However, when analysed by CVD type, deutan CVD was associated with higher odds of myopia (OR = 2.31, 95% CI 1.19 to 4.44, p = 0.01) and a more myopic SER (difference = −0.61D, 95% CI: −1.09 to −0.12, p = 0.02; AXL: difference = 0.09 mm, 95%CI: −0.19 to 0.37, p = 0.51), compared to non‐CVD participants, while other CVD types were not associated with myopia (protan: OR = 0.94, 95% CI 0.20–4.41, p = 0.94; unclassified: OR = 0.36, 95% CI 0.08–1.56, p = 0.17), SER or AXL.

Conclusions: In contrast to previous findings in Chinese school students, participants with a deutan CVD in this study had a higher risk of myopia.
Comparison of short‐term clinical outcomes between sutured scleral fixation and modified Yamane sutureless scleral fixation
Authors: Kim TaeHwan , Noh Seungyoon , Kwon Yoon Hyung
Published: January 2024

Aims/Purpose: To compare and investigate the short‐term clinical outcomes between 10‐0 polypropylene sutured intraocular lens (IOL) scleral fixation and modified Yamane sutureless IOL scleral fixation in patients with IOL or crystalline les dislocation and aphakic state.

Methods: From August 2012 to May 2022, medical records were retrospectively analysed for 43 patients with sutured scleral fixation and 40 patients with sutureless scleral fixation. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), total astigmatism, IOL astigmatism, refractive error, corneal endothelial cell density, surgical time and complications were compared before surgery, 1 week, 1 month and 3 months after surgery.

Results: In the two groups, after 3 months of surgery, UCVA and BCVA improved compared to before surgery, but there was no significant difference between two groups. The absolute refractive error and total astigmatism for 1 week after surgery and IOL astigmatism for 1 week and 1 month after surgery were significantly lower in sutureless fixation group. There was no significant difference in post‐operative corneal endothelial cell density changes between two groups, and total surgical time and IOL fixation time were measured significantly lower in sutureless fixation group.

Conclusions: Although modified Yamane sutureless IOL scleral fixation did not show significant improvement in visual acuity compared with conventional sutured IOL scleral fixation, sutureless fixation provided better stability of IOL in the early stages after surgery and short in the surgical time. So it can be an effective alternative to conventional sutured scleral fixation in patients with IOL or crystalline lens dislocation and aphakic state.
Thickness of the crystalline lens does not depend on cataract formation
Authors: la Rosa Alberto Lopez‐de , Diez‐Montero Cecilia , Martínez‐Plaza Elena , López‐Miguel Alberto , Maldonado Miguel J.
Published: January 2024

Aims/Purpose: To assess the influence of cataract formation on the lens thickness (LT), anterior (ACS) and posterior (PCS) cortex space and nuclear thickness (NT).

Methods: A prospective cross‐sectional study including patients seeking for cataract surgery was performed. The standardized Lens Opacification Classification System (LOCS)‐III was used to classify lens opacities. A control group composed of non‐cataractous patients was also created. In addition, cataract patients were also classified according to the cataract location (presence or absence of cortical, nuclear or posterior subcapsular cataract). Optical biometry was performed to measure LT, ACS, NT and PCS. Propensity score was used to match cataract and non‐cataract patients one‐to‐one for sex, age and axial length. Groups were compared using the Student's t‐test or Yuen's test.

Results: A sample of 603 volunteers (403 females, 200 males) aged 59.1 ± 18.8 years was recruited. Before matching, the lens cataract and the non‐cataract group was composed of 361 cataractous and 242 non‐cataractous volunteers. Also, all participants were classified into cortical and non‐cortical cataract groups (226 vs. 377), nuclear and non‐nuclear cataract groups (313 vs. 209) and into subcapsular and non‐subcapsular cataract groups (242 vs. 361). Before matching, cataract groups showed significant (p ≤ 0.003) higher LT (4.52 ± 0.39 vs. 3.94 ± 0.46 mm), ACS (0.75 ± 0.20 vs. 0.58 ± 0.23 mm), NT (3.34 ± 0.23 vs. 3.18 ± 0.25 mm) and PCS (0.42 ± 0.19 vs. 0.37 ± 0.19 mm). After matching, the lens, cortical, nuclear and subcapsular cataract samples were composed of 146, 258, 182 and 226 participants, respectively. Then, no significant (p ≥ 0.08) differences were found for LT, ACS, NT and PCS.

Conclusions: Thickness of the lens and/or its main components is not changed due to cataract formation. The progressive lens growth associated to aging might be the main confounding factor misleading the outcomes of previous studies that reported differences in LT between cataractous and non‐cataractous patients.
Interchangeability of bilateral anterior chamber depth in intraocular lens power calculation and its application in unilateral lens subluxation
Authors: Lou Wei , Chen Ziang , Huang Yang , Jin Haiying
Published: January 2024

Aims/Purpose: To assess the interchangeability of bilateral anterior chamber depth (ACD) in intraocular lens (IOL) power calculation, and to evaluate whether using the unaffected fellow eye's ACD can enhance refractive results in unilateral lens subluxation.

Methods: Axial length (AL), keratometry (K) and ACD were obtained by IOLMaster 700. In cataract surgery candidates (Group 1), the virtual implantation of the same IOL model was used. The predictive results closest to the Plano of the Kane formula, using the right eye's biometry (AL, K and ACD), served as a benchmark. The results of the corresponding IOL power were further calculated by substituting the left eye's ACD for the right eye's one and compared with the benchmark. Eyes with unilateral lens subluxation (Group 2) underwent in‐the‐bag IOL placement after the capsular hook(s) implantation, with refraction conducted at least 1 month post‐operatively. Prediction errors (PE) of the Kane formula with or without the unaffected fellow eye's ACD were compared.

Results: 392 eyes of 196 patients were analysed, including 173 candidates and 23 patients with unilateral subluxated lenses. In Group 1, there was no significant difference in bilateral ACD (p = 0.30). The predictive refraction using the right eye's ACD was −0.16 ± 0.10 diopter (D), and that obtained by the left eye's one was −0.16 ± 0.11 D (p = 0.64), with an absolute difference of 0.03 ± 0.03 D. In Group 2, the ACD was 2.89 ± 0.86 mm of the affected eye and 3.14 ± 0.37 mm of the fellow eye (p = 0.17). The median absolute PE, mean absolute PE and the percentage of PEs within ±0.50 D using the affected eye's ACD were 0.50 D, 0.59 D and 52.17%. Using the unaffected eye's ACD improved the outcomes to 0.45D, 0.52 D and 60.87%.

Conclusions: Bilateral ACD values are interchangeable in routine IOL power calculation, and using the unaffected fellow eye's ACD can improve its accuracy in cases of unilateral lens subluxation undergoing in‐the‐bag IOL implantation.
Difficulty of biometric images and calculation of intraocular lens in a patient with Sjogren's syndrome
Authors: Mesa Sara Mesa , Usuga Juan Cadavid , Zapata Luis
Published: January 2024

Aims/Purpose: To report a patient with a history of Sjogren's Syndrome and several ocular surface compromise with mature cataracts and difficult intraocular lens calculation.

Methods: Case report and literature review.

Results: A 75‐year‐old woman with a history of primary Sjogren's syndrome for almost 10 years with a long‐standing picture of foreign body sensation in both eyes, ocular burning, red eye and marked photophobia that was not improving despite several topical managements, currently with punctal plugs and using 0.5% carboxymethylcellulose, 0.4% sodium hyaluronate preservative free and ciclosporin emulsion 0.05%. Different topical treatments were used with any recovery on her ocular surface and the patient started developing dense cataracts in both eyes with important visual loss. The biometries performed were unreliable despite taking different images because of the great difficulty to get reproducibility on the keratometry measurements and for this reason it was not possible to predict the power of the lens to be implanted, we decided to try an aphakic refraction and multiply it by a conversion factor to get the power of the lens that was described long time ago in the literature. One month post‐op, the patient had a refraction of −1.50 −1.50 × 168° (0.3 LogMAR, J1) in the left eye and −0.50 −0.25 × 145° (0.3 LogMAR, J2) in the right eye.

Conclusions: We have a great limitation of information to calculate intraocular lenses in those patients who, for different reasons and despite very complete treatments, cannot reach an optimal ocular surface. There is currently no consensus on IOL calculations in severe ocular surface diseases.
Femtosecond laser iridorexis during cataract surgery
Authors: Cervantes Dayan Flores , Ramírez Emilio Dorronzoro , Haddi Inas Baoud Ould , Arias Cristina Bonnin , Sánchez Vanesa Blázquez
Published: January 2024

Introduction: Femtosecond laser‐assisted cataract surgery (FLACS) is currently the most widely used by surgeons, which is an evolution in technology compared to the phacoemulsification technique. However, the femtosecond laser may present complications such as increased intraocular pressure, incomplete fragmentation of the lens, incomplete capsulotomy, capsular tear, subconjunctival haemorrhage, among others. Its main advantages are less loss of endothelial cells, shorter phacoemulsification time, better visual and refractive prognosis, although its cost is higher. The femtosecond laser is the most commonly used technique for cataract surgery. However, it requires previous experience on the part of the surgeon, and in cases with miotic pupils, another approach is recommended.

Report of Case: An 82‐year‐old woman underwent cataract surgery. Pre‐operatively, she underwent visual acuity (VA) tests with and without correction, topography, biometry, endothelial count, optical coherence tomography (OCT), intraocular pressure (IOP) measurement and fundus examination. The surgery is performed with femtosecond laser with the laser platform Femtosegundovictus® (Bausch+Lomb., Messerschmittstr, Munich, Germany). By chance, iridorexis is produced to subsequently perform the extraction of the crystalline lens with the respective IOL implantation.

Discussion: Cataract surgery can present complications, one of which is iris rexis. This condition is rare and usually occurs because the pupils are too small or do not dilate well during cataract surgery, which leads to poorer management and control over the flap.

Conclusions: The use of femtosecond laser during cataract surgery is a high‐precision, personalized, safe and effective treatment, although it requires previous training and experience on the part of the surgeon for the success rate to be good.
Identification of new antioxidant drugs in a human in vitro model of ageing‐associated cataract
Authors: Infantes Estefania Caballano , Moshtaghion Mehdi , Peñalver Pablo , Morales Juan Carlos , Diaz‐Corrales Francisco
Published: January 2024

Aims/Purpose: Cataracts are a significant cause of global blindness, impacting millions (10.8 million patients), and their prevalence is expected to increase over the coming decades as our populations age. Oxidative stress disrupts ROS (reactive oxygen species) balance in lens fibre cells, leading to lens protein degradation and accumulation, developing age‐related cataracts. The lens has protective mechanisms, including high GSH levels and antioxidant enzymes like catalase, safeguarding lens health. While surgery is currently the only effective treatment, non‐invasive drug‐based approaches show potential by reducing risks and complications. With its potent antioxidant activity, resveratrol may protect lens cells and slow cataract development. However, the limited ability of resveratrol to penetrate lens tissue restricts its direct effects. Therefore, designing new molecules to improve ADME (absorption, distribution, metabolism and excretion) properties is required.

Methods: In this study, we used an in vitro model of cataracts by inducing oxidative stress and cell death by adding hydrogen peroxide (H2O2) and luperox to lens epithelial cells to evaluate the protective effects of new molecules against oxidative stress and compared them with resveratrol. Our study assessed the cell viability, intracellular ROS level, mitochondrial function, catalase activity and GSH/GSSH level.

Results: These compounds preserved cell viability, reduced ROS levels, maintained mitochondrial function and enhanced catalase activity and GSH levels in lens epithelial cells exposed to H2O2. The novel drugs, CAB‐C1 and CAB‐C2, demonstrated beneficial effects on cellular health.

Conclusions: Developing drugs for cataract treatment enables early intervention, particularly for individuals with mild or moderate cataracts who may not require surgery yet. Such advancements might improve patients' quality of life and have implications for ocular science and age‐related eye diseases.
Epidemiological and clinical profile of lens ectopias in children: About 126 eyes
Authors: Chahir Roukaya , Ghizlane Daghouj , Elmaaloum Loubna , Allali Bouchra , Elkettani Asmaa
Published: January 2024

Aims/Purpose: The aim of our work is to describe the clinical, epidemiological, therapeutic and evolutionary profile of this pathology.

Methods: Retrospective descriptive study of 63 children operated in the department of paediatric ophthalmology of Casablanca from January 2010 to September 2022. We studied the epidemiological, clinical, etiological, therapeutic and evolutionary elements of operated children. Lens subluxations of traumatic origin were excluded from our study.

Results: The average age of the operated children was 7.5 years with a male predominance of 70%. The decrease in visual acuity observed at school was the most frequent reason for consultation, associated with family cases in 16% of cases. The bilaterality of the disease was present in all patients with a corrected visual acuity varying between hand movement and 3/10. High myopia was present in 33% of the patients. 65% of the lens was subluxated, with 2 cases of lens dislocation in the anterior chamber. The associated ocular abnormalities were aniridia (5%), cataract (14%), ocular hypertonia (2.5%) and degenerative lesions of the retinal periphery (20%). Phacophagia with anterior vitrectomy was performed in all patients, and visual rehabilitation was based on the use of aphakic glasses or contact lenses and the treatment of amblyopia has been associated. One case of implantation by implant craftsman in a 17 year old girl. The final visual acuity was superior to 5/10 in 30% of the eyes. Post‐operative complications were rare, 2 cases of retinal detachment and 2 cases of glaucoma.

Conclusions: Crystalline ectopia is a progressive and serious disease requiring an urgent management. Conservative treatment is reserved for minor uncomplicated forms with a close monitoring. The discovery of a case requires an etiological investigation and family screening with regular follow‐up even after surgical treatment.
Unbalanced redox status network as an early pathological even in congenital cataracts
Authors: Bejarano Eloy , Whitcomb Elizabeth A. , Pfeiffer Rebecca L. , Rose Kristie L. , Rodríguez‐Navarro José Antonio , Ponce‐Mora Alejandro , Cantó Antolin , Almansa Inmaculada , Schey Kevin L. , Jones Bryan W. , Taylor Allen , Rowan Sheldon
Published: January 2024

Aims/Purpose: The lens proteome undergoes dramatic composition changes during development and maturation. Defective developmental processes lead to congenital cataracts that account for about 30% of cases of childhood blindness. Gene mutations are associated with approximately 50% of early‐onset forms of lens opacity, with the remainder being of unknown aetiology. To gain a better understanding of congenital cataractogenesis, we utilized a transgenic mouse model expressing a mutant ubiquitin protein in the lens (K6W‐Ub) that recapitulates many of the early pathological changes seen in human congenital cataracts.

Methods: We performed MS‐based tandem‐mass‐tag quantitative proteomics (TMT), computational molecular phenotyping (CMP), high‐performance liquid chromatography (HPLC), western blotting and immunohistochemical analysis in E15, P1 and P30 control or K6W‐Ub lenses.

Results: TMT identified proteins that were altered during normal lens differentiation, some of which were also altered in cataractous lenses. These included proteins in glutathione and amino acid metabolic pathways. CMP revealed that glutathione and taurine were reduced spatially altered in the K6W‐Ub cataractous lens. HPLC revealed that both the ratio GSH/GSSG and taurine, two indicators of redox status, were differentially compromised in K6W‐Ub cataractous lenses.

Conclusions: Our findings shed light on the molecular mechanisms associated with congenital cataracts and point out that unbalanced redox status due to reduced levels of taurine and glutathione, metabolites already linked to age‐related cataract, could be a major underlying mechanism behind lens opacities that appear early in life.

Funding: Funding was provided by grants RYC 2018‐024434‐I, MINECO PID 2020‐119466RB‐I00, FUSP‐PPC‐19‐B53C4C64, NIH RO1EY026979 (to AT), USDA 8050‐51000‐089‐01S (to AT).
Preliminary study on developing ocular formulations for natural antioxidants to prevent long‐term complications associated with high myopia
Authors: Ta Phuong Linh , Just Lucia Bernat , Alarma Vicente Rodilla , Castellano Alicia López , Morell Francisco Bosch
Published: January 2024

Aims/Purpose: The progression of retinal damage in high myopia (HM) has been associated with a reduction in its antioxidant capacity. α‐Lipoic acid (ALA), among other natural antioxidants, has gained important attention due to its impact on visual health1. The objective of this study is to develop ocular inserts containing ALA and to evaluate the potential ocular irritancy of ALA using the HET‐ CAM (hen's egg test‐chorioallantoic membrane) test.

Methods: In the HET‐CAM test, five eggs were used under the following conditions: negative control (NaCl 0.9%), positive control (NaOH 0.1%), low concentration (0.01 M ALA), medium concentration (0.1 M) and high concentration (0.2 M). Bleeding, vascular lysis and coagulation were assessed for 300 s to calculate the Irritation Index (IS)2. For each ocular formulation, 5 mg of ALA was dissolved in phosphate‐buffered saline solution (PBS) with a pH 7.4. Different proportions of selected polymers (HPMC, PVP, HA and PG as an adjuvant) were homogenized and placed into a Petri dish, dried overnight and cut into 1 cm2 inserts.

Results: The HET‐CAM measurement demonstrated the absence of haemorrhage, coagulation and lysis in the three tested concentrations of ALA. The IS score falls within the range of 0–0.9, classifying it as non‐irritant. In parallel, four ocular formulations containing 5 mg of ALA were prepared as follows: F1‐ PVP 10%; F2‐ PVP 2.5% and HPMC 1%; F3‐ PVP 2.5% and HA 1%; F4‐ PVP 1%, HA 1% and HPMC 1%. It was shown that F2 and F3 had preferred organoleptic characteristics.

Conclusions: ALA was a non‐irritant and probably suitable for ocular administration as an antioxidant. Further research will be conducted to assess the efficacy of the ophthalmic inserts. However, preliminary findings suggest that these inserts hold promise as a potential formulation to delay the long‐term progression of high myopia.

References

1. Salehi B. et al. Insights on the use of α‐lipoic acid for therapeutic purposes. Biomolecules. 2019;9(8):1–25.

2. de Araujo Lowndes Viera, L. M., et al. Comparison of the different protocols of the Hen's Egg Test‐Chorioallantoic Membrane (HET‐CAM) by evaluating the eye irritation potential of surfactants. Toxicol In Vitro. 2022; 78, 105255.
Extracellular vesicles mirror the beneficial effect of wild olive (acebuche) oil in hypertensive‐like retinal pigment epithelial cells
Authors: Santana‐Garrido Álvaro , Goya Claudia Reyes , Espinosa‐Martín Pablo , Andre Helder , Vázquez Carmen María , Mate Alfonso
Published: January 2024

Aims/Purpose: Arterial hypertension (AH) leads to oxidative and inflammatory imbalance triggering hypertensive organ damage via different pathways. Oil extracted from the wild olive tree (acebuche, ACE) has previously shown antioxidant and anti‐inflammatory properties against hypertensive ocular damage when regularly consumed in the diet1,2. We therefore speculate that circulating extracellular vesicles (EVs) isolated from ACE oil‐fed animals might play a role in modulating pathological mechanisms surrounding AH‐related ocular diseases, including oxidative stress, migration and angiogenesis processes.

Methods: Retinal pigment epithelium (ARPE‐19) cells mimicking a hypertensive phenotype induced by incubation with angiotensin II (AngII) were treated with EVs obtained from mice fed ACE oil or a reference extra virgin olive oil (EVOO). The 2′,7′dichlorodihydrofluorescein diacetate (DCFHDA) assay was used to estimate intracellular levels of reactive oxygen species (ROS). Furthermore, kinetic parameters for L‐arginine (L‐Arg) transport and the expression of L‐Arg transporter (CAT‐1) were also analysed. The wound‐healing assay was used to determine the anti‐migratory properties of ACE oil‐derived EVs, and the ability of EVs to modulate angiogenesis was assessed in aortic rings.

Results: Both ACE oil‐ and EVOO‐related EVs were able to reduce ROS production in ARPE‐19 cells. The normalization of intracellular redox status by EVs might be exerted through modulation of L‐Arg uptake and CAT‐1 expression. Anti‐migratory and anti‐angiogenesis properties were also displayed by oil‐derived EVs, suggesting their potential benefit in the setting of neovascular ocular diseases.

Conclusions: This is the first report to highlight the retinoprotective effects of EVs isolated from the plasma of animals subjected to ACE oil‐ and EVOO‐enriched diets against pathological events related to ocular diseases.

References

1. Santana‐Garrido Á et al. Antioxidants. 2020. DOI: https://doi.org/10.3390/antiox9090885

2. Santana‐Garrido Á et al. Foods. 2021. DOI: https://doi.org/10.3390/foods10091993
Retinal neurotoxicity induced by inhalation of isopropyl nitrite
Authors: Rivera Víctor David Ayala
Published: January 2024

Purpose: Popper is a slang term given broadly to drugs of the chemical class called alkyl nitrites that are inhaled. Most widely sold products include the original isopropyl nitrite (IPN) a mix of isopropyl alcohol with nitrous acid and sulphuric acid. Multiple cases of retinopathy have been reported since 2001 that have been associated with the inhalation of poppers, predominantly in Europe. However, no clear information about the effect of these inhalant agents on retinal cells have been shown to date. Our work tries to address the neurotoxic effect of IPN on outer retinal cells evidenced by immunocytochemical technique on murine model.

Methods: 8 Opn4‐KO mice were used, n:4 were treated with IPN using a aero chamber inhalator for 20 days (1 mL/5 s) and n:4 with oxygen (ctrl group). CARR antibody was used, encoded by the Arr3 gene in murine species. All the animals were supplied by the Animal Experimentation Center of the UAH. The euthanasia of the animals was carried out in accordance with RD 53/2013 Spanish regulations.

Results: The sagittal sections of the Opn4 mouse retina taken with confocal microscopy at 40×, the expression of arrestin‐C can be observed, predominantly in the internal and external segments of the cones without disruption, the presence of CARR confirms the presence of cells of retinal cone in our CARR cuts (Cy5, red), The exposure parameters of the samples and image capture in the confocal microscope were taken based on the immunoreactivity in the Opn4 animal model, remaining stable for the rest of the photos. Labelling at the level of the outer plexiform layer is equally intense in Opn4 Ctrl and Opn4 to animals.

Conclusions: The results failed to demonstrate morphological changes of clinical importance that could determine a neurotoxic role in the retina of IPN inhalation; however, we propose the existence of other factors and/or pharmacological interactions with the use of poppers in the aetiopathogenesis of this new ophthalmological disease.
Retinal oxygen extraction and hyperemic response in patients with Type II diabetes at different stages of non‐proliferative diabetic retinopathy
Authors: Lindner Theresa , Hommer Nikolaus , Schmidl Doreen , Kallab Martin , Schlatter Andreas , Howorka Kinga , Werkmeister René M. , Schmetterer Leopold , Garhöfer Gerhard
Published: January 2024

Purpose: Diabetic retinopathy (DR) is a worldwide cause of irreversible vision loss. Vascular factors such as reduced oxygen supply and impaired neurovascular coupling play a major role in the development of DR. We therefore investigated retinal oxygen metabolism and functional hyperemia in patients with Type II diabetes at different stages of non‐proliferative DR and healthy controls.

Methods: To study retinal oxygen metabolism, a total of 67 patients with Type II diabetes (34 patients with no, 15 with mild and 18 with moderate‐to‐severe DR) and 20 healthy controls were recruited. We used the oxygen module of a Retinal Vessel Analyzer to measure retinal oxygen saturation in arteries and veins, and a custom‐built Doppler optical coherence tomography (DOCT) system to assess total retinal blood flow (TRBF). Values of retinal oxygen saturation and TRBF were then used to calculate retinal oxygen extraction. To measure the hyperaemic response, 29 patients with no, 12 with mild, 15 with moderate‐to‐severe DR and 20 healthy controls were included. Retinal blood flow was assessed before and during visual stimulation by combined measurement of retinal vessel calibres and blood velocity using the Dynamic Vessel Analyzer (Imedos, Germany) and DOCT.

Results: Retinal oxygen extraction was lowest in patients with moderate‐to‐severe DR (1.78 ± 0.57 μL O2/min, p = 0.040 vs. healthy controls), followed by mild DR (1.90 ± 0.77 μL O2/min), no DR (2.14 ± 0.6 μL O2/min) and healthy controls (2.24 ± 0.57 μL O2/min). Compared to healthy controls (40.4 ± 27.2%), flicker responses were significantly decreased in patients with DR depending on the stage of DR (no DR 37.7 ± 26.0%, mild DR 26.2 ± 28.2%, moderate‐to‐severe DR 22.3 ± 13.9%; p = 0.035, ANOVA).

Conclusions: Our results indicate that retinal oxygen extraction as well as hyperaemic response decreases with increasing severity of DR. Further studies are needed to assess whether these retinal functional changes can be used to identify high‐risk patients.
Anti‐inflammatory and anti‐apoptotic activity of a TSPO ligand in slowing retina neurodegeneration in a model of retinitis pigmentosa
Authors: Corsi Francesca , Baglini Emma , Barresi Elisabetta , Galante Alessia , Passetti Federico Da Settimo , Taliani Sabrina , Gargini Claudia , Piano Ilaria
Published: January 2024

Aims/Purpose: An evolutionary well‐conserved protein called translocator protein (TSPO, 18 kDa) is found on the outer mitochondrial membrane. Under typical physiological conditions, TSPO expression in the central nervous system is rather low. Changes in TSPO expression, however, can result from several clinical conditions, including neurodegenerative diseases, and neuroinflammation. In a previous study (1) we test the efficacy of a new class of TSPO ligands (PIGAs) (1), in an in vitro model (661W, photoreceptor‐like cell line) of Lipopolysaccharide (LPS)‐induced neuroinflammation. We demonstrate the TSPO expression in retinal photoreceptor and the activity of this ligands in an in vitro neurodegeneration. Here, we examined the anti‐inflammatory effects of the highest active TSPO ligand (PIGA‐1138) on heterozygous (±) Tvrm4 mice (RhoTvrm4/Rho+) an animal model of autosomal dominant retinitis pigmentosa (RP) highly sensitive to light‐induced photoreceptor degeneration. The inflammatory component plays a predominant role in RP progression towards cone death and complete blindness.

Methods: Mice have been treated with 3 or 10 mg/kg/die for seven days, starting from the day of onset of retinal degeneration induced by exposure for 1 min to a white light of 12000lux intensity. At the end of the protocol retinal functionality was tested by recording Electroretinogram (ERG) flash response in both scotopic and photopic conditions. Retinal tissue was collected from recorded mice and the tissue was used for further analyses including biochemical and molecular biology assays.

Results: PIGA‐treated animal group shows improved response to flash ERG, reduced damaged area measured by cone‐arrestin staining, and modulation of pro‐ and anti‐inflammatory markers.

Conclusions: As conclusion, we were able to establish that the TSPO ligand can slow down photoreceptor degeneration and confirm the results of the in vitro study.

References

1. Corsi, F.; Baglini, E.; Barresi, E.; Salerno, S.; Cerri, C.; Martini, C.; Da Settimo Passetti, F.; Taliani, S.; Gargini, C.; Piano, I. Targeting TSPO Reduces Inflammation and Apoptosis in an In Vitro Photoreceptor‐Like Model of Retinal Degeneration. ACS Chem. Neurosci. 2022, 13 (22), 3188–3197. https://doi.org/10.1021/acschemneuro.2c00582.