bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic potential of targeting BMP/ALK pathway in pathological retinal neovascularization
Authors: AL‐Shabrawey Mohamed , Ghishan Maria , Koneru Nandini , Sharma Sonali , Moustafa Mohamed
Published: January 2025

Aims/Purpose: Pathological retinal neovascularization (PRNV) in ischemic retinopathies presents a significant clinical challenge. This study investigates the role of bone morphogenetic protein (BMP) signaling via ALK receptors in PRNV, with a focus on epigenetic modifications.

Methods: The oxygen‐induced retinopathy (OIR) mouse model was utilized to investigate BMP signaling. Experimental groups included OIR mice treated with Noggin (a BMP inhibitor) or vehicle via ip from postnatal day 12‐16. Additional groups included a combined ALK2 and ALK3 endothelial conditional knockout mice (ALK2/3eKO), subjected to OIR. Capillary degeneration and neovascularization were assessed at postnatal day 17 in flat‐mount retinas using isolectin‐B4 staining. Immunostaining of retinal sections evaluated BMP2, BMP4, and ALK3 localization. In vitro experiments involved human retinal endothelial cells (HRECs) treated with BMP2 (50 ng/ml) or exposed to hypoxia (1% O2) for 48 hours. The impact of BMP2 on vascular endothelial growth factor (VEGF) was assessed through ELISA. MicroRNA (miRNA) expression was analyzed using the GeneChip miRNA 3.0 array. DNA methylation of HRECs was quantified using a colorimetric kit.

Results: Immunostaining revealed an upregulation of BMP2, BMP4, and ALK3 expression in retinal vessels. Noggin‐treated and ALK2/3eKO OIR mice exhibited a significant reduction in capillary dropout and neovascularization (p < 0.01). BMP2 treatment of HRECs elevated VEGF production. MiRNA array analysis indicated significant alterations by BMP2 (4%) and hypoxia (5%), including miRNAs linked to VEGF signaling and angiogenesis. Specifically, BMP2 downregulated miR‐4521, miR‐769‐3p, miR‐23b‐5p, miR‐3195, and miR‐6781‐5p, while upregulating miR‐126‐3p, miR‐921, miR‐7515, miR‐29c, and miR‐20b‐5p. Interestingly, BMP2 and hypoxia induced similar effects on certain miRNAs, such as miR‐769‐3p, miR‐23b, and miR‐20b. The DNA methylation assay demonstrated a statistically significant reduction induced by BMP2.

Conclusions: BMP/ALK signaling plays a potential role in the pathogenesis of PRNV, possibly mediated through epigenetic modifications. Thereby, targeting BMP/ALK signaling holds a promise to mitigate PRNV in ischemic retinopathies
Orbital abscesses in children: An update on microbiology trends and antibiotic selection
Authors: Kawar Luai , Kubba Haytham
Published: January 2025

Aims/Purpose: Orbital abscesses are a common cause of morbidity in children. This study aims to provide an update on the microbiology, sensitivity rates and antibiotic prescribing patterns for orbital abscesses at Scotland's largest paediatric tertiary centre. This is essential for empirical antibiotic choices given the rapidly growing rates of resistance among commonly encountered isolates.

Methods: A retrospective case note review of all patients admitted to the Royal Hospital for Children (RHC) in Glasgow between April 2019 and 2022 with an orbital abscess that underwent incision and drainage. Exclusion criteria included patients with underlying anatomic eye abnormalities and/or immunodeficiency.

Results: Seventeen orbital abscesses were identified. Streptococcus pyogenes was the commonest micro‐organism (47 per cent), followed by Streptococcus intermedius (24 per cent). One abscess grew Fusobacterium necrophorum complicated by a subdural empyema and Lemierre's syndrome. Most organisms were widely sensitive; there was a single episode of penicillin resistance in an abscess caused by S. aureus. The most common initial antibiotic regimen was a combination of flucloxacillin and cefotaxime. In approximately half of the identified cases, the antibiotics were changed to a regimen containing clindamycin.

Conclusions: Gram positive cocci remain the most common organisms isolated in orbital abscesses, with a relative increase in the Streptococcus anginosus group. Resistance among orbital abscesses remains low. Empirical use IV cefotaxime and flucloxacillin is recommended. Additional anaerobic cover (eg, metronidazole, clindamycin) should only be added if there is no clinical improvement after 24‐36 hours.
Modeling senescence in ARPE19 cells to investigate the role of small extracellular vesicles in age‐related macular degeneration
Authors: Fernandes Rosa , Correia Diana , Martins Beatriz , Malva João , Girão Henrique
Published: January 2025

Aims/Purpose: Age‐related macular degeneration (AMD) is a degenerative disease causing significant vision loss in the elderly. The molecular mechanisms of AMD onset and progression are not fully understood. Senescent cells are known to secrete increased amounts of small extracellular vesicles (sEV). However, the impact of sEVs on RPE dysfunction and AMD through senescence spreading remains unclear. Our study aimed to develop an in vitro model of RPE cell senescence.

Methods: We used the retinal pigment epithelial cell line, ARPE‐19. Senescence induction in RPE cells was achieved through two different approaches: repeated passaging (replicative senescence) and ionizing radiation (DNA damage‐induced senescence). Characterization of sEVs released by RPE cells was performed and markers of senescence were assessed.

Results: RPE cells subjected to replicative exhaustion or ionizing radiation showed higher H2AX foci accumulation compared to p9 cells. Ionizing radiation significantly increased nucleus area and deformation, with a similar trend at p21 and p31. Levels of p21, critical for establishing senescence, increased at p31 and showed a tendency to rise in ionizing radiation‐exposed cells. Levels of p16, maintaining the senescence phenotype, also increased in ionizing radiation‐exposed cells and tended to rise at p21 and p31. Activities of active MMP‐2 and ‐9 increased in the conditioned medium of senescent cells, with MMP‐2 activity correlating with higher protein levels. sEVs from senescent cell‐conditioned medium showed significant increases in concentration and mean size compared to p9 cells.

Conclusions: We successfully induced senescence in ARPE19 cells, creating a valuable model to investigate the role of sEVs in spreading senescence to neighboring cells, especially in the context of AMD onset.

Support: FCT, Portugal: 2020.04811.BD; PEst UIDB/04539/Base/2020 and UIDP/04539/Programatico/2020.

European Union's Horizon 2020 Teaming project MIA‐Portugal (no 857524) and CHAngeing – Connected Hubs in Ageing: Healthy Living to Protect Cerebrovascular Function (no 101087071), funded by Excellence Hubs Call – Horizon‐ WIDERA‐2022‐ACCESS‐04‐01.
To what extend cataract surgery changes perceptual functions?
Authors: Garobbio Simona , Hall Ursula , Zuche Hanna , Herzog Michael
Published: January 2025

Aims/Purpose: Cataract, i.e., an opacification of the natural intraocular lens, is one of the leading causes of visual impairments worldwide. Cataract surgery, which involves the removal of the opaque lens and implantation of an artificial intraocular lens, is one of the most cost‐efficient interventions in all of health care to improve visual impairments. However, it remains unclear how exactly visual performance changes after surgery, which we aim to investigate in our study.

Methods: We tested 30 older adults undergoing cataract surgery longitudinally with a battery of visual tests. Participants were tested a total of four times: before surgery, after surgery on one eye, after surgery on the second eye, and a few weeks after surgery when vision was fully stabilized. The battery tested various visual abilities and included the following tests: visual acuity, contrast sensitivity, coherent motion, orientation discrimination, reaction time, and visual search. All tests were performed binocularly, and a subset of tests was repeated monocularly.

Results: Results suggest that visual acuity and orientation discrimination performance increase after each surgery. Performance in contrast sensitivity and coherent motion significantly increases after the surgery on the first eye but not between the second and third tests. Thus, monocular surgery is sufficient to improve performance in these tests. On the other side, visual search and reaction time performance do not seem to benefit from cataract surgery. For all tests, the level of performance after surgery is maintained in the last testing.

Conclusions: Our study shows that cataract surgery leads to improved perceptual functions in most, but not all, tests. Future analysis will determine whether the level of performance change depends on baseline performance, and whether predictions about surgery success can be made based on performance in the tests.
Visual acuity outcomes by age at symptom onset in the natural history of leber hereditary optic neuropathy: Analysis of historical data from Case Record Survey‐2 (CRS‐2)
Authors: Llòria Xavier , Yu‐Wai‐Man Patrick , van Everdingen Judith , Leroy Bart , Krawczynski Maciej , Lamperti Costanza , Carelli Valerio , Klopstock Thomas
Published: January 2025

Aims/Purpose: The clinical progression of Leber hereditary optic neuropathy (LHON) is thought to be influenced by the age at symptom onset. The Case Record Survey‐2 (CRS‐2; NCT02796274) aimed to establish the natural history of LHON in idebenone‐naïve patients. Here, we report 12‐month clinical outcomes by age at symptom onset.

Methods: Data were extracted from case records (20 sites, 7 European countries) meeting the following criteria: aged ≥12 years, m.11778G > A, m.3460G > A or m.14484T > C mitochondrial DNA mutation, onset of symptoms (OoS) after 1999 and ≥2 visual acuity assessments (VAA) within 5 years of OoS. Baseline (BL) was defined as the first VAA after OoS. Spontaneous clinically relevant benefit, recovery, stabilisation and worsening (sCRB, sCRR, sCRS and sCRW, respectively) were calculated as previously described.1 Eyes eligible for analysis had a VAA 12±3 months from BL and were stratified according to age at OoS ( < 15, 15–35 and > 35 years).

Results: A total of 21, 42 and 44 eyes were eligible for the 12‐month analysis in those aged < 15, 15–35 and > 35 years at OoS, respectively.

Greater sCRB rates were observed in eyes aged < 15 years at OoS (42.9%, 9/21) compared to eyes aged 15–35 years (19.0%, 8/42), and > 35 years (15.9%, 7/44). This was largely driven by higher sCRS rates ( < 15 years: 54.5%, 6/11; 15–35 years: 28.6%, 4/14; > 35 years: 15.8%, 3/19). Higher sCRR rates ( < 15 years: 19.0%, 4/21; 15–35 years: 11.9%, 5/42; > 35 years: 11.4%, 5/44) and lower sCRW rates ( < 15 years: 47.4%, 9/19; 15–35 years: 85.7%, 24/28; > 35 years: 60.0%, 21/35) were also observed in eyes aged < 15 years.

Conclusions: Better clinical outcomes were observed in eyes aged < 15 years at OoS in CRS‐2, consistent with previous reports. Outcomes did not markedly differ between eyes with OoS between 15–35 years and > 35 years. The CRS‐2 study offers important insights into the impact of age on the natural history of LHON.

References

1. Yu‐Wai‐Man P, et al. Cell Rep Med. 2024;5:101437.
Vision‐related quality of life of myopic children using combination treatment: Atropine and defocus‐incorporated multiple segment spectacle lenses
Authors: Villahoz Noemi Guemes , Hernandez‐Garcia Elena , Gomez‐de‐Liano C. Nunila , Porras‐Angel Paloma , Bella‐Gala Rafael , Talavero‐Gonzalez Paula , Ruiz‐Pomeda Alicia , Martin‐Garcia Beatriz , Shah Rakhee , Feijoo Julian Garcia , Gomez‐de‐Liano Rosario
Published: January 2025

Purpose: To assess vision‐related quality of life (VR‐QoL) in children undergoing myopia control treatment with atropine compared to children treated with combination treatment of atropine and Defocus incorporated multiple segments (DIMS) spectacle lenses.

Methods: Longitudinal study that included myopic children aged 4 to 16 years undergoing myopia control treatment. Group A included children on 0.025% atropine eyedrops and single‐vision lenses, and group B included children on combined treatment of 0.025% atropine and DIMS lenses. Demographic and clinical data, including cycloplegic spherical equivalent refraction (SER) and axial length (AL), were noted. VR‐QoL was assessed using the Children's Visual Function questionnaire (CVFQ) and the Pediatric Eye Questionnaire (PedEyeQ) before initiating and after 6 months of treatment. Statistical analyses (Mann‐Whitney U‐test or t‐test) were performed.

Results: 95 patients were included: 50 children in group A, mean age 8.94 ±2.50 years and 45 children in group B, mean age 9.51 ±2.46 years (p = 0.266). No significant differences were found in the overall VR‐QoL between both groups with PedEyeQ. Functional Vision and Social item scores (PedEyeQ) significantly improved at the 6M follow‐up in group A (p = 0.03 and p = 0.016, respectively) and group B (all p = 0.01). Scores on the Eye Condition item (PedEyeQ) at baseline and at 6M follow‐up were reversed; a decrease in group A, 89.73 [69.86‐89.73] and 64.98 [50.02‐74.99] (p < 0.01), and an increase in group B, 69.96 [69.96‐89.72] and 74.97 [43.62‐85] (p = 0.039). For the CVFQ, only Group B showed an improvement in General Vision (p = 0.049) and Competence (p = 0.031) scores.

Conclusions: Myopic children treated with atropine and those using combination treatment (atropine and DIMS) do not seem to have significant differences in overall VR‐QoL following 6 months of treatment. General Vision (CVFQ), Competence (CVFQ) and Eye Condition (PedEyeQ) scores improve significantly for children on combination treatment.
Retinal oxygen extraction during systemic hypoxia assessed with laser‐speckle flowgraphy and retinal oximetry
Authors: Pai Viktoria , Lindner Theresa , Janku Patrick , Schmetterer Leopold , Schmidl Doreen , Garhöfer Gerhard
Published: January 2025

Aims/Purpose: Retinal oxygen extraction has been found to be altered in several ocular and systemic diseases, such as diabetic retinopathy, glaucoma or neurodegenerative diseases. However, measurement techniques for the assessment of retinal oxygen extraction are limited because most of them are based on time‐consuming and custom‐built devices. In the present pilot study, we assessed retinal oxygen extraction during systemic hypoxia with a combination of two commercially available devices: Laser‐Speckle Flowgraphy (LSFG) and retinal oximetry.

Methods: Retinal blood flow and retinal oxygen saturation were measured in each vessel around the optic nerve head at the same position. Arterial and venous oxygen content was estimated from the measured retinal oxygen saturation parameters and the difference between these two parameters was calculated (cO2,DIFF). By using mean vessel flow rate (MV) for retinal blood flow and cO2,DIFF, retinal oxygen extraction was determined. For each healthy study participant, baseline measurement and measurement during inhalation of 88% nitrogen in 12% oxygen were performed.

Results: Ten (10) healthy subjects (4 females, 6 males) with a mean age of 27 ± 3 years were included in this study. During systemic hypoxia, a significant decrease in arterial oxygen content occurred (p = 0.046) while venous oxygen content did not change, leading to a decrease in cO2,DIFF. As expected, this was accompanied by a significant increase in MV (p = 0.014). No change in retinal oxygen extraction was observed (46 ± 8 a.u. at baseline vs. 46 ± 5 a.u. during hypoxia, p = 0.997).

Conclusions: Breathing of 88% nitrogen in 12% oxygen caused a significant decrease in retinal arterial oxygen content. This was compensated by an increase in retinal blood flow in order to keep retinal oxygen extraction constant. This was physiologically expected, and these findings are consistent with the literature. Therefore, the presented approach for measurement of retinal oxygen extraction appears to be feasible.
Early detection of biochemical changes in tear fluid induced by contact lens wear using Raman spectroscopy
Authors: Tavazzi Silvia , Pezzoli Fabio , Ponzini Erika , Duse Alessandro
Published: January 2025

Aims/Purpose: The aim of this study is to evaluate different approaches to investigate early alterations in tear biomolecular profiles induced by contact lens (CL) wear. This includes assessing the impact of CL wear on tear volume, osmolarity, and biomolecular composition using Raman spectroscopy.

Methods: Two participants of the same sex (male), age (23 years), and with a similar lifestyle wore different CLs for two hours. Ocular analysis was performed at three time points: before CL insertion, immediately after CL removal, and two hours post‐removal. The analyses included tear meniscus height and osmolarity measurements. Tear samples were collected at each time point and analyzed using Raman spectroscopy.

Results: Tear volume and osmolarity remained unchanged throughout the study. Raman spectroscopy highlighted notable changes in the biomolecular profile of tears after CL wear, particularly in the 2700‐3200 cm‐¹ spectral window.

Conclusions: Among the analyses performed, only Raman spectroscopy revealed significant changes. It highlighted alterations in the biomolecular profile of tears post‐CL wear, particularly in the 2700‐3200 cm‐¹ spectral window associated with C‐H stretching. The ability of Raman spectroscopy to detect these subtle, subclinical changes underscores its value as a non‐invasive tool for analyzing individual responses to CLs. Notably, Raman spectroscopy captures molecular‐level alterations, which form the basis of changes in the physical and functional properties of the tear film, including those measured by tear meniscus height and osmolarity. These changes become detectable by traditional techniques only in a late stage, while molecular‐level alterations can be detected earlier, providing an opportunity for proactive intervention and management.
Metabolomics reveals pathophysiological mechanisms of proliferative diabetic retinopathy progression
Authors: Mansikkaviita Jannika , Korhonen Ani , Finell Johan , Loukovaara Sirpa , Nieminen Anni
Published: January 2025

Aims/Purpose: Diabetic retinopathy (DR) is a common, sight‐threatening microvascular complication of diabetes. The end‐stage form of the disease, proliferative DR (PDR), is characterized by ischemia and inflammation‐induced pathological neovascularization at the vitreoretinal interface, often accompanied by vitreous hemorrhage and tractional retinal detachment (TRD). The mechanisms behind the progression of PDR, and the effect of different treatments on these processes, are not fully understood. As the number of diabetics is on the rise, and current treatment options are invasive and limited in their efficacy, the search for novel targets for treatment and prevention of PDR progression is crucial.

The aim of our study is to reveal differences between vitreous metabolite profiles of non‐PDR and PDR disease states, and the effect of treatment on those profiles. We aim to better understand the progression of the disease and to identify potential target metabolites and pathways.

Methods: We analyzed metabolites in vitreous samples from type II diabetic patients with different stages of DR (non‐PDR patients, PDR patients, and PDR patients with TRD) via targeted LC‐MS metabolomics. Pathway enrichment analyses were performed using MetaboAnalyst 5.0.

Results: We identified various significantly altered metabolites such as deoxycarnitine, indole‐3‐acetic acid and glycine between non‐PDR and PDR patients. Metabolite enrichment analyses revealed strong associations with, for example, tryptophan and glycine metabolism.

Conclusions: We identified metabolites, processes and metabolic pathways of interest in PDR progression in type II diabetic patients, some of which could be potentially useful for development of novel treatment options. Furthermore, this metabolic information provides new insight into pathogenetic mechanisms behind PDR progression.
The cumulative impact of air pollution on dry eye disease: Evidence from the Korea National Health and Nutrition Examination Survey (2017–2020)
Authors: Shin Dong Weon , Cho Yunnie , Rim Tyler , Seo Kyung Yul
Published: January 2025

Aims/Purpose: This study investigated the relationship between environmental pollution and dry eye disease (DED), focusing on the cumulative impact of air pollutants.

Methods: Cross‐sectional data from the 7th and 8th Korea National Health and Nutrition Examination Survey (KNHANES) (2017‐2020) were analyzed alongside air pollution data from the National Ambient Air Quality Management Information System (NAMIS). Non‐smokers aged between 40 and 80 were selected (n = 8,840). The daily cumulative index (CI) of air quality was calculated for each region of residence based on key pollutants, including SO₂, NO₂, PM2.5, and PM10. Using Gaussian mixture models, each day was categorized as usual, poor, or bad based on CI values. Multiple logistic regression analysis assessed the impact of air pollutants on DED while accounting for clinical, demographic, and meteorological factors. Additionally, the Aggregated Air Quality Index (AAQI) was calculated and evaluated for the same dataset.

Results: Multiple logistic regression analysis indicated that the proportion of high pollution days within a year significantly increased the odds of DED (OR: 4.19, 95% CI: 1.23–14.25, p = 0.02), after adjusting for factors associated with DED as covariates. Although the AAQI did not show statistical significance, the Cumulative Index effectively demonstrated the aggregated effect of multiple air pollutants on DED.

Conclusions: This research highlights the utility of a model using regularly measured air quality indicators, providing a comprehensive assessment of the aggregated effect of air pollutants. Implementing these measures can help identify at‐risk populations and consider environmental factors in managing and preventing DED.

References: Saxena, A., & Shekhawat, S. (2017). Ambient Air Quality Classification by Grey Wolf Optimizer Based Support Vector Machine. Journal of environmental and public health, 2017, 3131083. Kyrkilis, G., Chaloulakou, A., & Kassomenos, P. A. (2007). Development of an aggregate Air Quality Index for an urban Mediterranean agglomeration: relation to potential health effects. Environment international, 33(5), 670–676.
Studies in the electroretinogram I‐wave: Evidence for off pathway origin and association with a myopia risk locus
Authors: Vetrivel Krishnika , Tan Jit Kai , Xu Zihe , Jiang Xiaofan , Leo Shaun , Bhatti Taha , Tariq Ambreen , Hammond Christopher , Hysi Pirro , Mahroo Omar
Published: January 2025

Aims/Purpose: A myopia‐risk locus near the GJD2 gene has been associated with cone‐driven electroretinograms (ERGs), specifically cone‐driven OFF pathway signals. In light‐adapted ERGs to a standard flash, conventionally measured components are the a‐wave and b‐wave. A later component, the “i‐wave”, is thought to originate in retinal OFF pathways, as evidenced by pharmacological experiments in primates. We investigated this component in human ERGs, testing the hypothesis that an association would be found with the myopia risk locus.

Methods: ERGs were examined from patients with rare monogenic post‐phototransduction deficits affecting only ON pathways, or both ON and OFF pathways, to explore which gave rise to the i‐wave. ERGs were then analysed from genotyped healthy adults from the TwinsUK cohort. The i‐wave amplitude was measured in the standard flash ERG by two investigators independently. We investigated association with allelic identity, adjusting for age, sex and inter‐individual relatedness. Separately, we adjusted for refractive error where this was available.

Results: Patient recordings showed i‐waves persisted in absence of ON pathway signals, but were abolished when both ON and OFF pathways were impaired. Recordings and genotypes were available in 184 TwinsUK individuals (95% female). Mean (SD) age was 64.1 (9.7) years. Allelic dosage at the risk locus was significantly associated with i‐wave amplitude Refractive error was available for 175 participants. The association in these individuals remained significant both before and after adjusting for refractive error (p = 0.035 and p = 0.043 respectively).

Conclusions: ERGs in patients are consistent with the human i‐wave arising from cone‐driven OFF pathways. i‐wave amplitudes associated significantly with allelic dosage at the myopia risk locus. This supports importance of cone‐driven signalling in myopia development and adds evidence that this locus affects cone‐driven OFF pathway signals.
Patient demographics and surgical outcomes of dropped nucleus in cataract surgery
Authors: Martins Pedro , Cabanas João , Cardoso Daniel , Sousa‐Neves Filipe
Published: January 2025

Aims/Purpose: To analyse the baseline demographic/clinical characteristics and visual outcomes of patients who experienced nucleus drop during cataract surgery with subsequent need for pars plana vitrectomy (PPV).

Methods: Retrospective case series of patients who underwent phacoemulsification for non‐traumatic cataract and experienced nucleus drop during surgery, with subsequent need for PPV to extract the dropped fragments. Demographic data, ocular comorbidities (such as ocular hypertension – OHT/glaucoma, pseudoexfoliation – PEX, presence of advanced white or brunescent cataract, shallow anterior chamber or previous intravitreal injections – IVI), timing of nucleus drop, intraoperative complications and post PPV visual outcomes and complications, for the study period (2018 to 2023), were collected.

Results: Over the study period 33 eyes of 33 patients experienced nucleus drop. 17 (52%) were male with a mean age of 74.4±9.4 (45‐92) years. Pre‐operative visual acuity ranged from light perception to 0.22 logmar. Three patients (9.1%) had previously undergone IVI and 7 (21.2%) had glaucoma or OHT; 9 (27.3%) had PEX ‐ all but one had poor pupillary dilation ( < 5 mm). A significant proportion of patients (13, 40.4%) presented with advanced brunescent/white cataracts. Most nucleus drops occurred following a posterior capsular rupture during quadrant removal (18 cases – 54.5%) or hydro‐dissection (8 cases – 24.3%); remaining cases occurred following a radialized capsulorhexis with posterior extension or due capsular bag‐nucleus luxation to the vitreous. PPV was uneventful in most cases – one patient developed an epiretinal membrane 2 years after PPV. Visual acuity improved by an average of ‐0.96 logmar in the post‐operative period.

Conclusions: PPV is the preferred management for nucleus drop after complicated cataract surgery. Current devices and surgeon expertise allow for a low risk of complications and good visual/anatomical outcomes.
Adipose‐derived mesenchymal stem cells (ADMSCS) and retinal pigment epithelial cells (RPE‐1) interactions in stress environments via tunneling nanotubes
Authors: Gozel Merve , Senkoylu Karya , Kesim Cem , Hasanreisoğlu Murat
Published: January 2025

Aims/Purpose: The study aims to elucidate the potential role of TNT‐mediated intercellular communication between the AdMSCs and RPE‐1 cells in reducing stress‐induced damage.

Methods: Oxidative stress and serum starvation were used as stress to create TNTs between the AdMSC and RPE‐1 cells. Immunofluorescence and scanning electron microscopy were used to show that TNT formation. Following stress conditions, the cells' viability was examined by CTG assay, and the levels of reactive oxygen species (ROS) were measured by H2DCFH‐DA probes. Microscopy showed that JC‐1 labelled mitochondrial exchange occurs between cells via TNTs. To prevent TNTs, a transmembrane culture system was used and evaluated how to effect on cell viability and changes of ROS levels.

Results: We examined how TNTs support mitochondrial transport and intercellular communication between AdMSCs and RPE‐1 during stress. We discovered that TNT‐mediated mitochondrial translocation from AdMSCs to RPE‐1 contributes to both increased cell survival and a decrease in ROS levels. We showed that AdMSCs and RPE‐1 had a direct connection that was essential for stress recovery. After stress‐induced damage, co‐culture improved vitality and maintained retinal function. Because mechanical restriction of TNT synthesis reduced cell viability and raised ROS levels, it is clear that TNTs are essential for cellular defence.

Conclusions: Overall, our study provides valuable insights into the cellular mechanisms underlying stress response and underscores the therapeutic promise of AdMSC derived TNTs in preserving retinal health.
Clinical and morphological parallels in the assessment of the lamina cribrosa of sclera as a risk factor and potential target in promotion for survival of optic nerve axons
Authors: Huseva Yuliya
Published: January 2025

Purpose: To study the lamina cribrosa (LC) of sclera in people of different age.

Methods: Longitudinal sections of trepanned fragments of 31 enucleated eyeballs of deceased donors aged from 27 to 81 years stained by Masson trichrome were studied histologically and immunohistochemically with an antibody to glial fibrillary acidic protein (GFAP). The results were compared with optical coherence tomography (OCT) of the optic disc (OD) of 32 eyes of patients aged 34 – 74 years. Four age groups were identified. The optic nerve (ON) prelaminar and retrolaminar parts and LC of sclera were assessed. The data was statistically approved, the Pearson, Spearman correlation coefficients, the Kruskal‐Wallis and Mann‐Whitney tests were calculated.

Results: Three patterns of LC were identified based on connective and glial tissue ratio: mixed predominated in all age groups; elastic was more common until 44 years (45.5%); collagenous was typical for group III over the age of 60 (40%) and after 75 years (50%). The perivascular proliferation of collagen fibres was mostly after 75 years (group IV), correlated with deformation of LC anterior surface resulting in a decrease in LC elasticity in groups III and IV, increased frequency of axonal deviation in group III (40%) and IV (50%) and a ‘slowing down’ myelination of ON axons (35.5%). The age‐related tendency to LC superficial location, disorganisation of its structure and deformation of its anterior surface in all groups was revealed. The prelaminar zone showed a decreased number of fibroblast processes in groups II and III compared to group I. All ON zones demonstrated immunoreactivity to GFAP, predominantly in the prelaminar determining its susceptibility to ischaemia. Distribution and morphology of GFAP‐positive cells demonstrated that the structure of astrocytes decreased with age.

Conclusions: Age‐related morphological features of the LC beyond 60 years are considered to be risk factors for ischaemia and blockade of axonal transport. The effect of age on LC should be taken into account when predicting the results of treatment of optic neuropathies. The variability of cells in LC opens up new prospects for developing protection and regeneration of ON, in particular, influencing the process of LC remodelling.
Efficacy and safety of non‐penetrating surgery versus trabeculectomy in open‐angle glaucoma: A systematic review and meta‐analysis
Authors: Song Tianyu , Anantharaj Rishi Miriyala , Normando Eduardo Maria
Published: January 2025

Aims/Purpose: Whilst trabeculectomies (TE) remain the gold‐standard treatment for open‐angle glaucoma (OAG), non‐penetrating surgery (NPS) are rising in popularity as an alternative. This systematic review and meta‐analysis compared the efficacy and safety of trabeculectomy and NPS for OAG.

Methods: The following databases of PubMed, Embase, Medline, Scopus and Cochrane Library were searched for original studies comparing TE to NPS (from inception to 23/01/2024). The primary outcome was IOP reduction, with secondary outcomes including success rate, medication score, visual acuity (BCVA) and complications. A random‐effects model on ReviewManager (RevMan) was used for the meta‐analysis. Sub‐group analyses for concomitant mitomycin C and hyaluronate were performed, unlike current existing reviews.

Results: Initially 529 papers were identified. Of these, 20 studies containing 1422 participants (1565 eyes) were included. 16 studies reported higher complete success rates with TE. Meta‐analysis showed that although the IOP reduction was larger in TE, this was not statistically significant (mean difference = ‐1.31, 95% CI: ‐3.12 to 0.50). There was no significant difference in reduction of medications but there was significant improvement in BCVA at 12 months with NPS (unweighted average: TE = 0.078, NPS = ‐0.015, p < 0.00652). The relative risk of complications (hypotony, choroidal detachment, cataract, shallow anterior chamber and hyphaema) were higher in TE than all NPS (RR: 2.80, 95% CI: 2.13 to 3.68, p < 0.0001). However, hyphaema was less likely to occur in TE compared to canaloplasty (NPS) (RR: 0.14, 95% CI: 0.03 to 0.62, p < 0.0090).

Conclusions: Findings show trabeculectomy and NPS appear to reduce IOP comparably, a finding not found in previous reviews. However, complication risks increased in trabeculectomy, potentially favouring the use of NPS. However, the training requirement for NPS may limit its universal uptake.
Comparative analysis of methods in detecting glaucomatous progression
Authors: Fernandez‐Velasco Diego , Mallen Victor , Bermudez Javier , Biescas Andrés , Rius Nuria , Ila Carmen , Monleón Claudia Hernández‐Barahona , Navarro Damián García , Santana Carlos , Munuera Inés
Published: January 2025

Aims/Purpose: Glaucoma is an optic neuropathy that, if left untreated, leads to irreversible blindness, making reliable methods for detecting progression essential. Functional damage is assessed by the reduction of the visual field (VF), and structural damage is evaluated by the thinning of retinal parameters. Since 50% of ganglion cells are located in the macular area, their study could be a good indicator of progression. The objective of this work is to evaluate the utility of ganglion cell layer (GCL) analysis using optical coherence tomography (OCT) in diagnosing glaucoma progression.

Methods: This is a retrospective cross‐sectional study including 205 eyes with glaucoma followed for at least three years. The progression analysis values obtained from OCT of the GCL and the optic nerve fiber layer (NFL) are compared, taking the VF as a reference and stratifying by severity into mild and moderate‐advanced glaucoma.

Results: In mild glaucoma, VF has limitations because functional damage does not occur until there is a 20‐40% loss of ganglion cells. Structural tests classify more cases as progression, and the concordance between them is higher than with VF. OCT of the GCL is the test that classifies progression the most. In moderate‐advanced glaucoma, VF classifies more cases than in mild glaucoma. However, VF is a variable test, influenced by the learning effect, and when damage is very advanced, results can be erroneous because the retina loses sensitivity. OCT of the NFL classifies fewer cases than in mild glaucoma because debris creates a floor effect that artifacts the measurement. OCT of the GCL is the test that classifies progression the most. The concordance is greater between OCT of the GCL and VF.

Conclusions: In conclusion, OCT of the GCL may be a better indicator of progression than NFL in both mild and moderate‐advanced glaucoma. It could be a useful strategy in clinical practice for diagnosing glaucomatous progression.

References

Munuera I, Gándara‐Rodriguez de Campoamor E, Moreno‐Montañes J. Study of the ganglion cell complex of the macula by optical coherence tomography in the diagnosis of glaucoma progression. Arch Soc Esp Oftalmol (Engl Ed). 2024 Apr;99(4):145‐151.
Adherence to the mind diet, genetic susceptibility, and glaucoma prevalence
Authors: Vergroesen Joëlle , Klaver Caroline , Ramdas Wishal
Published: January 2025

Purpose: The Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet may be associated with glaucoma. We aimed to confirm this association and to identify who could benefit most from this diet.

Methods: This study consisted of 316 (clinically confirmed) glaucoma patients and 107 healthy controls from the Erasmus Glaucoma Cohort. Dietary data was collected using validated food frequency questionnaires. The association between MIND diet adherence and glaucoma prevalence was analyzed using multivariable logistic regression analyses. We further stratified on family history of glaucoma. The association between family history of glaucoma and MIND diet adherence was analyzed using multivariable linear regression analyses. All analyses were adjusted for age, gender, BMI, and energy intake.

Results: Adherence to the MIND diet was significantly associated with glaucoma prevalence, but only in participants without a positive family history (Odds ratio [OR] with [95% confidence interval (CI)]: 0.84 [0.71‐1.00]). The more unfavorable the diet, the higher the prevalence of glaucoma (~2 times in both the group with and without positive family history). In the group with a positive family history, the OR increased from 5.8 to 10.9 in individuals with an unfavorable diet. Having affected relatives may therefore be an incentive to adhere to a healthy diet. Indeed, a positive family history appeared associated with greater MIND diet adherence (Beta [95%CI]: 0.32 [‐0.01‐0.64]). This was observed particularly in glaucoma patients (Beta [95%CI]: 0.46 [0.09‐0.84]), and more distinct when it affected a first degree relative (Beta [95%CI]: 0.58 [0.16‐1.00]).

Conclusions: The MIND diet may be associated with glaucoma. These dietary recommendations may particularly be interesting for glaucoma patients without a positive family history of glaucoma. Nevertheless, the effectiveness of this diet in slowing down glaucoma progression is yet to be determined by longitudinal studies.
A service evaluation of patient satisfaction with the current standard of glaucoma care provision at Derriford Hospital
Authors: Teo Ryan , Tsakiris Kleonikos
Published: January 2025

Aims/Purpose: The social and economic burden of glaucoma are likely to increase in the future because of longer life expectancies and an ageing population.

Healthcare providers must continually monitor and improve their management of glaucoma patients.

The project's purpose was to identify areas of improvement in the Royal Eye Infirmary at Derriford Hospital's provision of glaucoma care and thereby, advance the European Glaucoma Society's mission statement to maintain or improve the quality of life in affected patients.

Methods: The methodology included the following:

Designing the Glaucoma Service Evaluation (12 questions)

Administering the Service Evaluation

Statistical Analysis of the Results

Responses were based on a five‐point Likert Scale, with 1 being the most negative patient satisfaction score and 5 being the most positive.

Results: 50 patients, comprising 28 males and 22 females, undertook the questionnaire.

The mean age was 73 years.

Patient response rate to all 12 questions was 100%.

The average five‐point Likert Scale Score across all 12 questions was 4.35.

Conclusions: The results suggest that overall patient satisfaction with the standard of glaucoma care at Derriford Hospital is positive to a large extent.

Patients are happy with evolutions in glaucoma care such as Virtual Clinics, and the role of allied health professionals.

However, it identified significant areas of improvement ‐ enhancing patient education through the use of leaflets.

This service evaluation demonstrated that patients are largely satisfied with the current level of glaucoma care at Derriford Hospital. Most patients are open to novel initiatives, which would minimise patient waiting time at clinics.

More measures, such as patient counselling of medication side‐effects and distribution of informative leaflets, should be implemented to improve the standard of glaucoma care and hence, raise patient satisfaction at Derriford Hospital.

References

Batra R, Sharma H, Elaraoud I, Mohamed S. Resource Planning in Glaucoma: A Tool to Evaluate Glaucoma Service Capacity. Seminars in Ophthalmology. 2017;:1‐6.

Holdsworth E, Datta J, Marks D, Kuper H, Lee H, Leamon S et al. A Mixed‐Methods Evaluation of a Community‐Based Glaucoma Check Service in Hackney, London, UK. Ophthalmic Epidemiology. 2017;24(4):248‐256.
Differential profile of mirnas in aqueous humour: A new potential epigenetic mechanism for pseudoexfoliation glaucoma
Authors: Villanueva Carolina Garcia , Andrés‐Blasco Irene , Martucci A. , Lopez J. F. Ramos , Moreno Vicente Zanon , Montero M. Gonzalez , Nucci C. , Durán Maria Dolores Pinazo , Feijoo Julian Garcia
Published: January 2025

Aims/Purpose: Pseudoexfoliation glaucoma (PEG), is the most prevalent of the secondary glaucomas, characterized by the accumulation of fibrillar extracellular material in the anterior eye chamber. The miRNAs are regulators of gene expression, as epigenetic effectors. Our aim is to identify candidate miRNAs that may be involved in PEG physiopathology.

Methods: A collaborative, longitudinal, prospective, case‐control study was set up in 120 participants, of both sexes, that were classified as: PEG patients (n = 60) and healthy individuals (CG n = 60). Sociodemographic and opththalmologic data were recorded. Aqueous humor was collected at the onset of glaucoma surgery, labelled and stored at. ‐80° until processing. Total ARN was obtained, and expression and quantitation of the miRNAs ‐122‐5p, ‐146a‐5p and ‐320a‐3p, were assayed by real time quantitative polimerase chain reaction (RT qPCR) in both study groups. Databases DIANA TOOLS, miRDB, TargetScanHuman 7.2 were used to connect the target genes with its biological functions. Data were processed by IBM SPSS 28.0 statistical program.

Results: Mean age was 73±11 years. Gender distribution was 32 % men/68 % women. Mean intraocular pressure was 17 mmHg in the right eye (RE) and 19 mmHg in the left eye (LE). Mean retinal nerve fiber layer thickness was 73 μm in RE and 71 μm in LE. MiRNAs ‐122‐5p (p = 0,02),146a‐5p (p = 0,02) and ‐320a‐3p (p = 0,04) showed a significantly higher expression in the aqueous humor of PEG versus CG.

Conclusions: miRNAs ‐122‐5p, ‐146a‐5p and ‐320a‐3p are involved in PEG pathogenesis, epigenetically affecting the expression of target genes and protein translation, by means of their biological functions, in relation to extracellular matrix, metalloproteinases, glutamate, and the signaling pathways MAPK and RhoA/ROCK. We may suggest to investigate new biological therapies on the basis of the above miRNAs in PEG patients.
Study of the variation of intraocular pressure after blood collection in patiens over 60 years old
Authors: Ramón‐Campillo Aida , Bueno‐Gimeno Inmaculada , Gené‐Morales Javier , Gené‐Sampedro Andrés
Published: January 2025

Aims/Purpose: This study aims to assess whether changes in intraocular pressure (IOP) occur after a blood draw and quantify these changes’ magnitude in a group of patients over 60 years old.

Methods: We analysed data from the right eye of 54 subjects, with a mean ( SD) age of 68 4 years. The measurements were conducted in the morning while fasting. First of all, subjects rested in a seated position for 5 minutes to equalise baseline conditions. IOP was then measured using the iCare rebound tonometer (IC100, iCare Oy, Finland) and the mean value obtained from 6 measurements was recorded. After 10 minutes, subjects underwent the blood draw. Five minutes after the blood draw, the subject sat back in the chair for the second IOP measurement, conducting the same procedures for both measurements. Pre‐ and post‐drawing IOP values were compared with Wilcoxon signed rang test, for related samples.

Results: The analysis showed that IOP decreased after extraction, with a mean ( SD) of 14.09 3.18 mmHg pre‐extraction and a mean ( SD) of 13.33 2.90 mmHg post‐extraction. Grouping the sample into age groups, no statistically significant differences were found in the 60‐64 age group (n = 11; p = 0.35) and the 75‐79 age group (n = 5; p = 0.68). A trend towards significance was found in the 70‐74 age group (n = 18; p = 0.06) and statistically significant differences in the 65‐69 age group (n = 20; p = 0.04). Grouping the sample according to their IOP values (using to the sample IOP median) no statistical differences were found when IOP values were between 8 and 15 mmHg (n = 38; p = 0.57) and statistically significant differences were found in the group with IOP between 16 and 28 mmHg (n = 16; p = 0.001).

Conclusions: It was found that IOP decrease after a blood draw, tending to decrease more in subjects aged 65 to 74 years and remains unchanged in the other age groups. Additionally, higher baseline IOP levels lead to greater changes post‐extraction. These results may be related to reflex effects of the autonomic nervous system, activating a vagal reflex, which may induce a decrease in IOP. Future studies are required to analyse the various influencing factors.
Assessment of fixation stability and ocular torsion in a patient with ciancia syndrome: Case report
Authors: Ramón‐Campillo Aida , Gimeno Inmaculada Bueno , Sampedro Andrés Gené
Published: January 2025

Aims/Purpose: This study, performed as a clinical case, was carried out with the aim of evaluating fixation stability by means of the MAIA microperimeter and the presence of ocular torsion by retinography in a patient with Ciancia syndrome.

Methods: Two subjects both 24 years old were selected, one without visual system alterations, and the other with Ciancia syndrome, operated three times in childhood for strabismus, leaving 30 DP of residual Endotropia (ET). Fixation stability was assessed using the MAIA microperimeter by performing two tests, an expert examination and a fixation stability test for 30 seconds. Torsion was evaluated by performing retinography with the Topcon MAESTRO‐2 device and measuring the disc‐fovea angle (DFA).

Results: The patient with Ciancia syndrome had fixation stability within normal limits but a greater number and amplitude of microsaccadic fixations, as well as a greater number of refixations, compared to the normal subject. Additionally, the strabismic subject presented physiological torsion in the right eye (RE) (2°) and exciclotorsion in the left eye (LE) (11°), while the normal subject presented physiological torsion within the norm in both eyes RE (8°) and LE (2°).

Conclusions: Early treatment of Ciancia Syndrome in children improves visual and motor development, providing the patient achieves normal fixation stability. However, patients exhibit many microsaccadic movements and refixations to maintain a fixed gaze. Early treatment also reduces ocular torsion caused by muscular alterations.

References

Milla‐Barrios M, Piñero DP, Molina‐Martín A. Fixation Pattern Analysis With Microperimetry In Strabismic Subjects: A Pilot Study. Seminars in Ophthalmology 2022 ‐06‐06;37(6):699.

Khanna RK, Pasco J, Santallier M, Pisella PJ, Arsene S. Objective ocular torsion outcomes after unilateral horizontal rectus surgery in infantile esotropia. Graefe's Archive for Clinical and Experimental Ophthalmology. 2018 Sep 1;256(9):1783–8.