bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normal, age‐related differences in cone‐ and rod‐enhanced rapid flicker thresholds
Authors: Hafeez Aiman , Binns Alison , Ctori Irene , Barbur John 
Published: January 2025

Aims/Purpose: To establish the differences in normal, age‐related, monocular thresholds and the inter subject variability in cone and rod‐mediated flicker thresholds at the point of fixation and in each quadrant at 5o eccentricity.Methods: We examined 108 normal participants aged 10 to 86 years. None had any history or signs of ocular disease. Monocular flicker thresholds were measured under stimulus conditions that favoured either rods or cones to establish the limits of flicker sensitivity and changes in inter subject variability with increasing age. Mean luminance, spectral composition, stimulus size and temporal flicker frequency were selected appropriately so as to isolate either rods or cones. The measurements were carried out at the fovea (0o) and at an eccentricity of 5o in each quadrant.Results: Below 45 years of age both cone and rod mediated flicker thresholds remain relatively stable, both centrally and in the periphery. Above 45 years, cone and rod thresholds increase exponentially with increasing age. The rate of increase in threshold with increasing age is ~ 1.4 times greater for rods than for cones. Peripheral thresholds exhibit much reduced inter subject variability for both rods and cones. Rod thresholds increased more rapidly in central vision above 45 years of age and exhibited progressively larger inter subject variability.Conclusions: Although both rod and cone‐mediated thresholds increase systematically with increasing age, two major differences have emerged. The inter subject variability remains relatively constant in the periphery for both rods and cones. In central vision, the measured thresholds reveal much greater variability which increases monotonically with age. Differences in retinal illuminance caused by variations in macular pigment optical density in central vision and selective, lens absorption of short wavelength light with increasing age account well for the large variability in rod‐mediated thresholds in central vision.
Closed‐perfusion transretinal erg (tERG) on mouse and human retinas
Authors: Saeid Sama , Pitkänen Marja , Ilonen Emma , L'Ecuyer Zia , Niskanen Jukka , Tenhu Heikki , Vinberg Frans , Koskelainen Ari 
Published: January 2025

Aims: The isolated mouse and postmortem human retina can serve as a sensitive biosensor for preclinical drug testing. To facilitate testing with minimal amounts of potential drug molecules or nanostructures, we developed a closed‐perfusion tERG setup. The major challenge with small perfusate volumes was the healthiness and stability of the retina in prolonged experiments.Methods: We conducted ex vivo tERG experiments using WT C57BL/6J and Gnat1‐/‐ mouse, and human donor retinas (Lion's Eye Bank, Utah). The isolated mouse or punches of human retinas were embedded in a specimen holder and the retina was perfused with a constant flow (5–6 ml/min) from photoreceptor side, circulated with a peristaltic pump. Added Penicillin‐Streptomycin to prevent bacterial growth. 50 μM BaCl2 inhibited the K+ currents in Müller glial cells, and 20 μΜ D, L‐2‐amino‐4‐phosphonobutyric acid was added to isolate the rod component. Stimulated the dark‐adapted retina with 530 nm full‐field flashes. The electrical connection through the perfusate from the peristaltic pump to the specimen holder was cut off with burettes that also attenuated the pulsation from the pump. The stimulus and recording devices were remotely controlled by an automatic setup implemented with LabVIEW software.Results: The minimum perfusate needed in our closed perfusate circulation was 50 ml. Pen‐Strep was indispensable for long recordings. With mice, rod responses were stable for more than 24 hours and rod and cone bipolar cell responses for up to 12 hours. Rod responses from human donor tissue were stable up to 12 hours. We used our setup to test the zwitterionic polymer poly (sulfobetaine methacrylate), serving as a promising material for thermoresponsive nanostructures, for possible harmful effects on mouse rod and bipolar cell functioning. No effects on rod and bipolar cell responses were observed.Conclusions: Our method enables long, stable tERG recordings with closed perfusion on mouse and human retinas, allowing fast preclinical drug efficacy and biocompatibility testing with tiny amounts of drug molecules, materials, or nanostructures. Sulfobetaine as monomer or linear polymer did not harm rod, ON‐bipolar, or synapse functioning, suggesting the material can safely be used for constructing thermoresponsive nanostructures for drug delivery.
Evaluation and evolution of an algorithm‐based subjective refraction in children
Authors: Francois Daniel , Ong Wee Sing , Lam Andrew Kwok‐cheung , Liu Kenneth Ka‐king , Longo Adele 
Published: January 2025

Aims/Purpose: Assessing a method for refracting children using the Vision‐R™ 800, evaluating usability, followed by examining consistency and clinical relevance of an improved refraction protocol, time savings and children's experience.Methods: Two studies involved Chinese children aged 6 to 13. Study 1 (N = 159) assessed subjective refraction using Vision‐R™ 800 algorithm‐based software (SR1), followed by manual subjective refraction (SSR) and a second algorithm‐based refraction post‐cycloplegia (SR2). Study 2 (N = 66) evaluated SR1 using a modified algorithm and a manual subjective refraction (SSR2) following standard practice post‐cycloplegia.The primary outcomes were the differences and 95% Limits of Agreement (LoA) between the refraction methods, being secondary outcomes method‐duration and children's feedback. Results of right eyes are presented.Results: Study 1 average spherical equivalent (M) of ‐1.50 ± 1.50 D for SR1, ‐1.33 ± 1.57 D for SSR, and ‐1.35 ± 1.58 D for SR2. SR1 was ‐0.17 D more negative than SSR, and LoA was ± 0.75 D (p < 0.01) with no significant differences between SSR and SR2. Astigmatism differences were clinically insignificant. Timewise, SR1 took 7.64 ± 2.41 mins, SSR 4.94 ± 1.36 mins, and SR2 6.92 ± 2.51 mins. Ratings: SR1: “Okay” 60.4%, “Really Good” 32.1%, “Fantastic” 6.3%.The initial algorithm protocol was usable and well‐received, with 95% of children completing the examination. Study 2 found M values of ‐1.14 ± 1.49 D for SR1 and ‐0.93 ± 1.52 D for SSR2, with SR1 being ‐0.22 D more negative than SSR2 (p < 0.01). The LoA were ± 0.50 D for sphere, ± 0.35 D for J0, and ± 0.30 D for J45. These values showed greater consistency and smaller standard deviations in M (0.26D vs.0.38D) compared to Study 1. The modified algorithm reduced refraction time to 5.70 mins for SR1 vs. 4.77 mins for SSR2 (p < 0.05), with SR1 ratings: “Okay” 17%, “Really good” 44.7%, “fantastic” 38.3%, outperforming the earlier program.Conclusions: While cycloplegic subjective refraction remains the standard for children, the proposed algorithm‐based, non‐cycloplegic refraction with the Vision‐R™ 800 showed reasonable agreement with the cycloplegic standard. This advancement is crucial for exploring alternatives to cycloplegic refraction in future pediatric clinical practices.
Use of biologics other than adalimumab in non‐infectious pediatric uveitis
Authors: Whitfield Rafael , Mano Sofia , Ramos Filipa , Marques Raquel Campanilho , Leal Inês 
Published: January 2025

Aims/Purpose: Non‐infectious uveitis (NIU) is a leading cause of blindness in children, treated with steroids, conventional disease‐modifying antirheumatic drugs (csDMARDs), and biologics (bDMARDs). bDMARDs, particularly tumor necrosis factor inhibitors (TNFi) like adalimumab (ADA), have improved NIU management. However, increasing cases of non‐response or adverse events with ADA necessitate off‐label use of other bDMARDs. This study describes children with NIU treated with bDMARDs other than ADA at our tertiary center over the past five years.Methods: A retrospective study using the Uveite.pt database extracted data on pediatric patients treated with bDMARDs between 2018 and 2023, including demographic details, ophthalmological variables, and rheumatology data.Results: The study identified 34 pediatric patients receiving biologics (bDMARDs) for non‐infectious uveitis (NIU) (21 received 1 biologic, 10 received 2 biologics, 2 received 3 biologics, and 1 received 4 biologics), with 23 females and a mean age of 14 years. The main two conditions were juvenile idiopathic arthritis (JIA) and idiopathic NIU. Among these patients, at the end of this observational period, 23 were on ADA, while the rest were on other biologics: 3 on etanercept, 3 on infliximab, 2 on tocilizumab, 2 on golimumab, and 1 on abatacept. Reasons for using biologics other than ADA included ineffective control of ocular inflammation (7 patients) and initiation of treatment by the rheumatology team with a bDMARD other than ADA initially (4 patients). Thirteen patients required treatment with more than one biologic. Reasons for switching among bDMARDs included infusion reactions, anaphylaxis, and poor joint and ocular inflammatory control.Conclusions: Thirteen patients required treatment with more than one biologic during the course of the disease. Seven pediatric NIU patients used bDMARDs other than ADA to achieve better control of ocular inflammation. This finding aligns with existing literature that supports ADA as an effective first‐line treatment, yet it also highlights that ADA may not be suitable for all paediatric NIU patients.
Probiotic bacteria reduce damages of pretreated corneal epithelial cells due to pathogen infections
Authors: Marino Andreana , Scuderi Sarah , Cambria Lucia , Nostro Antonia , Esposito Emanuela , Paterniti Irene 
Published: January 2025

Aims: the aim of this study was to evaluate the protective effect of probiotic strains on pretreated human corneal epithelial cells (HCE) infected by Staphylococcus aureus and Pseudomonas aeruginosa.Methods: the bacterial strains used were probiotics Lactobacillus reuteri DSM20016 and Bifidobacterium longum subsp. infantis DSM20088, and pathogens S. aureus ATCC 6538 and P. aeruginosa ATCC 9027. Pretreatment of HCE with each probiotic strain at 24 h prior to S. aureus or P. aeruginosa inoculation followed by 24 h of growth in combination was performed. Cytotoxicity, anti‐inflammatory and anti‐nitrosative activities of each probiotic strain in combination with each pathogen were compared to those of pathogen alone.Results: the pretreatment with probiotic strains significantly protected HCE cells against infection. L. reuteri and B. longum showed ability to adhere to HCE cells, increase viability and demonstrated to reduce anti‐inflammatory and anti‐nitrosative biomarkers associated to infection.Conclusion: the topical administration of probiotic strains could prevent the severity of the recurrent keratitis caused by S. aureus and P. aeruginosa and to avoid corneal ulceration.
Prognostic impact and correlation with disease activity of three‐dimensional oct biomarkers in vogt‐koyanagi‐harada patients
Authors: Lima‐Cabrita Afonso , Vieira Diogo Fróis , Fernandes João Lourenço , Salbany João , Sousa David , Sanches João , Marques‐Neves Carlos , Leal Ines 
Published: January 2025

Aims/Purpose: Vogt‐Koyanagi‐Harada syndrome (VKH) is an autoimmune disease characterized by a chronic bilateral granulomatous panuveitis accompanied by extraocular manifestations, namely of the nervous, auditory, and integumentary systems. Retinal changes documented by optical coherence tomography (OCT) were found to have prognostic value, including detachments between retinal layers with fluid accumulation. The aim of this study was to estimate the total detachment volume (TDV) between retinal layers with fluid accumulation that characterizes the Vogt‐Koyanagi‐Harada syndrome.Methods: An OCT analysis framework was developed in Python which, after a parameter tuning process, automatically segments the 3D detachments between retinal layers and calculates the TDV. The pipeline processes each slice individually following a chain of image processing steps: image enhancement; binarization; size filter; and contour detection. To validate this strategy, this method was applied to one 3D OCT image of a patient with VKH, and the resulting masks were compared with the ground truth obtained after manual segmentation by an expert.Results: Our pipeline has revealed an Intersection of Union (IoU) score of 84%, demonstrating its ability to efficiently segment retinal detachments after a parameter tuning process. As a consequence of such capability, the relative deviation between the experimental and ground truth TDV was 8.3%.Conclusions: This semi‐automated approach offers a promising tool for clinicians to detect retinal changes in VKH patients. By enabling early and precise detection of fluid accumulation and retinal detachments, this method can enhance prognostic evaluations and potentially improve patient management and treatment outcomes. Future work should focus on validating this framework across a larger dataset and refining the processing pipeline to further improve segmentation accuracy and robustness.
Efficacy and safety of intralesional bleomycin as a treatment in eyelid hydrocystomas
Authors: Arzola Martin , Cárdenas‐Belaunzarán Jorge , Garcia Ariel Ceriotto 
Published: January 2025

Aims/Purpose: To evaluate the efficacy and safety of intralesional bleomycin as a treatment for eyelid hydrocystomas.Methods: A prospective, longitudinal, experimental, descriptive study was carried out; 33 patients with a clinical diagnosis of eyelid hydrocystoma were evaluated. Measurements were made in length, width and depth to obtain the volume of the lesion, clinical photographs were taken and intralesional bleomycin diluted at 1 unit – 1 milliliter was applied. Afterwards, a safety questionnaire was given. Clinical photographs, volume measurement and safety questionnaire were carried out at 3, 6 and 9 weeks post‐treatment. Persistent cysts received an additional injection. A repeated measures ANOVA was performed to analyze volumetric changeResults: 33 patients were evaluated, presenting with 102 hydrocystomas. Cyst mean volume was 21.16 mm3, 62.74% showed involution after 3 weeks of intralesional bleomycin injection.After the first application of bleomycin, a decrease in the average millimeter volume of hydrocystomas of 92.2% was achieved.At this point, remaining lesions had a mean volume of 1.66 mm3. At 6 weeks 90.19% showed involution with a mean volume of 0.98 mm3 and at 9 weeks 100% showed involution. This difference was clinically and statistically significant (F = 16.75, p < 0.05).Conclusions: This study is a milestone to continue the evaluation of the effectiveness and safety of sclerosing treatments for hydrocystomas, the results obtained through intralesional injection of bleomycin are promising.We can conclude that the use of bleomycin is safe and effective as a treatment modality for hydrocystomas.References
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Contribution of lymphatic‐like vessels to severe neovascularization following stent‐assisted coiling of an unruptured carotid artery aneurysm
Authors: Korhonen Ani , Brown Erika Hagan , Parkkinen Tommi , Loukovaara Sirpa 
Published: January 2025

Aims/Purpose: Intracranial aneurysms (IAs) are a leading cause of hemorrhagic stroke. One method of treatment for unruptured IAs is stent‐assisted coil embolization, which can result in complications affecting the eye. These complications can involve severe ischemia of the eyeball, accompanied by neovascularization in both the anterior and posterior segments of the eye, conditions with poorly characterized underlying pathological processes.We aim to characterize a case where severe neovascular glaucoma (NVG) developed as a complication of a neurosurgical stent‐assisted coiling of an internal carotid artery aneurysm. In particular, we investigate potential lymphatic and immune involvement in the vasculature in NVG resulting from complications following neurosurgical coiling of unruptured brain aneurysm.Methods: Case study of 59‐year‐old Caucasian female who underwent evisceration of the right eye after complications of elective neurosurgery for coiling of an unruptured anterior communicating artery aneurysm left the eye painful and blind. Patient had developed end‐stage neovascular glaucoma, fibrotic retinal detachment, and optic disc neovessel formation in the eye.We subjected tissues from both the anterior segment (cornea, iris, limbus, lens) and posterior segment (optic nerve head, retinal/detached pathological tissue) of the eviscerated eye to immunohistochemistry.Results: We identified various cell types and structures in both anterior and posterior segment samples, including immune cells and vascular structures with positivity for lymphatic markers.Conclusions: There is potential lymphatic and immune involvement in the neovasculature resulting from complications following neurosurgical coiling of unruptured brain aneurysm. The mechanisms governing lymphatic‐like differentiation in severe vitreoretinal ischemic eye disorders remain a potential area for further in‐depth research.
Employing deep learning for prediction of the refractive error after cataract surgery
Authors: Hartmann Lennart , Tim Freisenich , Armin Wolf , Christian Wertheimer 
Published: January 2025

Aims/Purpose: In addition to good visual acuity, the refractive outcome after cataract surgery is an important indicator of the success of the operation. Many preoperative factors can increase the risk of a high refractive error after cataract surgery. Neural networks are predestined to extract meaningful information from such complex data sets. This study therefore aimed to establish a neural network to evaluate the risk of high refractive error individually before cataract surgery based on various factors.Methods: This is a retrospective, monocentric study that was approved by the responsible ethics committee. Following strict quality control, a total of 1357 eyes with cataract surgery were included. Preoperative biometry was performed on all eyes using the IOL Master 700 (ZEISS). The following factors were considered for the study: K1, age, K1 of the fellow eye, lens thickness, axial length, corneal thickness and corneal thickness of the fellow eye, anterior chamber depth, chord alpha and main diagnosis (e.g. cataract, epiretinal membrane, amotio retinae). The eyes were then annotated; a postoperative refractive error of more than 0.75 diopters deviation was classified as a high refractive error. After annotation, the dataset was divided into a training dataset, a validation dataset and a test dataset.Results: The neural network was trained using the training and validation data sets. The accuracy of the correct classification was then evaluated using the unknown test data set. Using the neural network, an accuracy of 83% was achieved for the classification into a high or low postoperative refractive error.Conclusions: Using the developed neural network, we were able to show that a prediction of a high postoperative refractive error after cataract surgery was only possible with the help of values from biometry in more than 8 out of 10 patients, which could improve preoperative counseling.
Curcumin nanoparticles: Neuroprotection in Alzheimer's disease assessed through the eye
Authors: Shamsher Ehtesham , Davis Benjamin , Guo Li , Luong Vy , Ravindran Nivedita , Somavarapu Satyanarayana , Cordeiro Maria Francesca 
Published: January 2025

Aims/Purpose: Alzheimer's disease (AD) is the most prevalent form of dementia and remains a pressing concern in our society with an ageing population. Increasing evidences suggest a link between brain damage and retinal ganglion cell (RGC) loss opening new paradigm to diagnose this condition using the eye as a window to the brain. Curcumin is a natural polyphenol with neuroprotective properties but a low bioavailability preventing its use as a potential treatment in AD. The goal of this research was to assess a novel formulation of curcumin in a triple transgenic Alzheimer's disease (3xTg‐AD) mouse model and to demonstrate a correlation between Aβ/pTau brain deposition and RGC loss.Methods: 10‐month‐old 3xTg‐AD mice were treated for 3 months with either 0.38 mg/kg intranasal curcumin nanoparticles (CNs) (n = 7) or the equivalent vehicle (n = 6). After 3 months of treatment, animals were imaged using Detection of Apoptosing Retinal Cells (DARC). DARC count was defined as the number of fluorescent spots counted by a masked investigator. After sacrifice, their brains were harvested and immunostained for amyloid‐beta (Aβ) and phosphorylated tau (pTau). Retinas were immunostained with Brn3a, a retinal ganglion cell (RGC) marker. Then, RGC regularity index (RI) was calculated because it is more sensitive than RGC density and declining values of RI are observed during RGC loss and correlate with disease severity.Results: In the brain, CNs were able to reduce Aβ deposition (2.9 ± 0.3 vs 4.4 ± 0.4 Aβ score, p < 0.05) and pTau deposition (1.9 ± 0.7 vs 6.3 ± 1.5 pTau deposition, p < 0.05) compared to the equivalent vehicle. DARC count was reduced with CN treatment compared to vehicle (17.4 ± 3.3 vs 49.1 ± 13.3 DARC spots, p < 0.05). More importantly, CN treatment increased significantly RGC RI compared to vehicle (1.73 ± 0.04 vs 1.58 ± 0.04, p < 0.05) suggesting a neuroprotective effect by reducing RGC loss. Interestingly, DARC count correlated with RGC RI (correlation coefficient ‐0.452, p < 0.05) and Aβ deposition in the brain (correlation coefficient 0.509, p < 0.05).Conclusions: CNs are neuroprotective by reducing Aβ and pTau deposition in the brain and RGC loss. More importantly, DARC can be used to monitor disease activity as it correlates with RGC loss and Aβ deposition in the brain. Further studies are needed to confirm these results.