bluuebunny/crossref_metadata_2025 huggingface dataset:
Soft matter 3D printed drug‐loaded subconjunctival inserts for post‐surgical anti‐inflammatory drug delivery
Authors: Alambiaga‐Caravaca Adrián , Bernat‐Just Lucia , Luembe Esther Nginyu , Hibbitts Alan
Published: January 2025

Aims/Purpose: The aim of this study is to develop 3D printed drug‐loaded subconjunctival inserts to reduce

inflammation post‐trabeculectomy by delivering antifibrotic therapies in a controlled and targeted

manner.

Methods: Different gelatin derivatives were functionalized with methacrylate anhydride to create printable hydrogels. Methacrylation was confirmed by FT‐IR and quantified by 1H NMR, identifying optimal functionalization methods. Various water‐soluble co‐polymers, were incorporated to enhance the mechanical properties, stability, and biocompatibility of the hydrogels as well as a photo‐initiator. The stability of the formulations was assessed by immersing them in PBS at 37°C for up to three months. Extrusion and printability tests were conducted to select the best‐performing blends, which were then used to print different models under UV light exposure to cross‐link the blends and control drug release based on surface contact.

Results: The incorporation of polymers improved the stability of the gelatin hydrogels, with controlled degradation possible between 2 and 12 weeks depending on polymer blend. Extrusion and printability tests identified lead candidates. Optimal candidates exhibited controlled drug release over a three‐month period, meeting the therapeutic goal for post‐surgical inflammation management.

Conclusions: The development of 3D printed drug‐loaded subconjunctival inserts shows promise in providing targeted antifibrotic therapy post‐trabeculectomy. The optimized hydrogels exhibit improved stability and controlled drug release, potentially enhancing post‐operative outcomes and reducing intraocular pressure effectively. Further studies are warranted to evaluate the ex vivo biodistribution, the in vitro performance in cell culture and long‐term benefits of these customized drug delivery systems.

References

Barroso IA, Man K, Robison TE, Cox SC, Ghag AK. Photocurable GelMA Adhesives for Corneal Perforations. Bioengieering. 2022, 9, 53.
Towards visual field reliability with machine learning
Authors: Wong Damon , Chua Jacqueline , Jonas Jost , Schmetterer Leopold
Published: January 2025

Aims/Purpose: To evaluate the reliability of visual field mean deviation slope with explainable artificial intelligence

Methods: 6,869 visual field reports (Humphrey Visual Field, Carl Zeiss) from a study of 645 participants with glaucoma were acquired using a 24‐2 SITA FAST protocol. An additional 704 visual field reports from 54 glaucoma patients with the same visual field protocol was also retrospectively acquired from the clinic. The visual field data was organized into 5‐visit segments and visual field mean deviation (MD) slope was calculated for each segment. 3‐visit MD slopes from corresponding segments aligned with the first visit of each 5‐visit segment were also obtained. A gradient‐boosted machine learning model was developed to predict if the difference between the 3‐visit and 5‐visit slopes was within 1 dB/year. 2,883 segments from the study cohort were used for model development. Area under the receiver operating curve was used to evaluate the model prediction performance, which was compared with a logistic regression baseline operating on the slope values. Model explainability was evaluated using Shapley additive explanations (SHAP).

Results: The models were evaluated on 815 segments from the study cohort and 449 from the clinical cohort. Of these, 221 from the study cohort (27%) and 204 (45%) from the clinical cohort were found to have MD slope differences within 1 dB/yr between the 3‐visit and 5‐visit segments. The machine learning model achieved AUCs of 0.89 and 0.88 on the study and clinical cohorts, compared to 0.87 and 0.85 respectively with logistic regression. SHAP analysis found that the key determinants of the model were the magnitudes of the slope values, followed by inter‐visit intervals.

Conclusions: The machine learning model better predicted visual field slope reliability compared to logistic regression. MD slope values and inter‐visit intervals were found to be important factors in VF reliability analysis.
Correlation between dyslipidaemia and glaucoma risk: insights from a population‐based glaucoma screening (NCT 05875090)
Authors: Whitfield Rafael , Lima‐Cabrita Afonso , Lobo Vasco , Monteiro Bernardo , Marques Rodrigo , Ourique Matilde , Leal Inês , Barão Rafael , Pazos Marta , Stalmans Ingeborg Stalmans , Abegão‐Pinto Luís
Published: January 2025

Aims/Purpose: Glaucoma, a leading cause of irreversible blindness globally, is often associated with elevated intraocular pressure (IOP). However, other risk factors may play a role, particular vascular related parameters. This investigation aimed to explore the association between glaucoma and dyslipidaemia (DL) in participants in a primary care screening pilot. NCT 05875090

Methods: analysis at screening visit comparing the odds of a positive referral between participants with and without DL. Secondary outcomes were medication with statins. Positive referral was defined by IOP≥24mmHg or AI≥0.73. Descriptive and bivariate analyses were used to compare the glaucoma proportions and IOP/AI means between groups. Significance was set at p < 0.05 with 95% confidence intervals (CI).

Results: Data from 839 participants (54% male, 62 ± 4 years) across 11 functional units were analysed. Many had low educational attainment (69%), diabetes (81,1%), hypertension (63,4%), and DL (66,2%). Among participants with DL, 7,38% had glaucoma positive outcome at screening. No difference in glaucoma odds was found between DL and non‐DL patients (OR 0.782; CI 0.400‐1.528), nor between DL patients medicated with statins compared to those non‐medicated (OR 2.083; CI 0.597‐7.276). Interestingly, DL may be associated with a positive referral due to high IOP (but not disc damage) when compared to non‐DL subjects (OR 0.404; CI 0.155‐1.055; p = 0.09), but further analyses with larger samples are needed.

Conclusions: Analysing the association between dyslipidaemia and glaucoma revealed a significant prevalence of DL, with 7,38% meeting positive referral criteria. While the study suggests a potential difference in glaucoma based on IOP between individuals with and without DL, this finding lacks statistical significance. Further analyses, including consideration of confounders and biases, are necessary for confirmation. Continued research and clinical observation are vital for a deeper understanding of this association.
Efficacy of orthokeratology on peripheral refraction in youth: A comprehensive meta‐analysis
Authors: Queirós António , Silva‐Pinheiro Inês , Fernandes Paulo
Published: January 2025

Aims/Purpose: This study aims to determine the impact of orthokeratology lenses on relative peripheral defocus (RPD) in children and adolescents through a systematic review and meta‐analysis.

Methods: A thorough literature search was conducted using PubMed and Web‐of‐Science databases, focusing on randomized controlled trials (RCTs) and cohort studies investigating the effects of orthokeratology on peripheral refraction. The search employed the keywords "peripheral refraction" AND "orthokeratology." The inclusion criteria required studies to report spherical equivalent (M) peripheral refraction at 25° and/or 30°, including standard deviation or standard error of the mean, and present data graphically or in tables for horizontal meridian measurements before and after orthokeratology treatment. Relative peripheral refraction (RPR) was computed. From an initial pool of 133 studies, 124 were excluded for various reasons, resulting in a final sample of 9 studies. Four studies included data up to 12 months, while five provided data for less than three months, allowing separate analyses before pooling for an overall effect.

Results: The 9 studies included 3 RCTs and 6 cohort studies with 239 participants aged 6 to 30 years. The pre‐treatment refractive error was M=‐2.48 ± 0.29D, with follow‐up periods ranging from 14 days to 1 year. All studies indicated a myopic shift at 30° Nasal (‐2.13 ± 1.05 D) and 30° Temporal (‐2.40 ± 0.47 D), averaging ‐2.27 ± 0.83D. The meta‐analysis yielded an overall myopic defocus effect size of M=‐2.29 (95% CI ‐1.94 to ‐2.64, Z=12.84, p < 0.001) using a random effects model due to observed heterogeneity (I2=63%; p < 0.001). Myopic blur induction was greater at 1 year (M=‐2.64, 95% CI ‐2.42 to ‐2.85, Z=24.52, p < 0.001; I2=0%; p = 0.84) compared to treatments under 3 months (M=‐1.98, 95% CI ‐1.94 to ‐2.64, Z=7.37, p < 0.001; I2=63%; p < 0.001).

Conclusions: The results suggest a more consistent effect with longer treatment durations, highlighting the necessity for extended follow‐up periods to achieve a reliable effect size estimate. Orthokeratology effectively induces myopic defocus at 30° eccentricity in children and adolescents over both short and long‐term treatments.
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 change

Results: 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

Koumaki, D. et al (2021). Apocrine and eccrine hidrocystomas: a clinicopathological study. Acta Dermatovenerologica Alpina, Panonica, et Adriatica, 30(2), 53–56.

Trischman, T., & Scott, J. F. (2020). Comparative efficacy of hidrocystoma treatments: A systematic review. Journal of Cutaneous Medicine and Surgery, 24(5), 474–480.

Froudarakis, M., et al (2013). Revisiting bleomycin from pathophysiology to safe clinical use. Critical Reviews in Oncology/Hematology, 87(1), 90–100

Dailey, R. A., et al. (2005). Treatment of multiple apocrine hidrocystomas with trichloroacetic acid. Ophthalmic Plastic and Reconstructive Surgery, 21(2), 148–150.
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.
Morpho‐functional alterations and mirnome dysregulation in the retina of a mouse model of Alzheimer's disease: Paving the way for new strategies of gene therapy
Authors: Guidotti Lorenzo , Amato Rosario , Lucchesi Martina , Borello Ugo , Cammalleri Maurizio , Monte Massimo Dal
Published: January 2025

Aims/Purpose: To investigate if the retina might be considered a reliable tool to monitor Alzheimer's disease (AD) progression and a benchmark for testing novel gene therapy strategies.

Methods: The morpho‐functional and molecular features of 5xFAD and wild‐type (WT) mice have been evaluated at different time points: 3, 6, and 9 months of age. To assess retinal function we used scotopic, photopic, and pattern electroretinogram. Retinal structure was evaluated through optical coherence tomography. Retinal sections were immunostained with rhodopsin, cone‐arrestin, and RNA binding protein mRNA processing factor in order to identify rods, cones, and retinal ganglion cells, respectively. Further retinal sections were immunostained with amyloid beta (Aβ) to visualize the presence of plaques. Western blot experiments were conducted to evaluate retinal levels of Aβ and Tau. Markers of neuroinflammation (NFκB and IL‐6) and oxidative stress (NRF2, HO‐1, and NQO1) were also assessed by Western blot. The retinal miRNome was analyzed to highlight the potentially dysregulated miRNAs between 5xFAD and WT.

Results: We observed a progressive loss of visual function followed by retinal thinning starting at 6 months of age. Moreover, photoreceptor and ganglion cell degeneration were reported from 6 months of age. Concurrently, molecular analyses demonstrated retinal Aβ and phospho‐Tau accumulation, which correlated with the progressive increment in oxidative and inflammatory markers. The miRNome analyses revealed several dysregulated miRNAs at 6 months of age in 5xFAD mice, which return to control levels at 9 months of age.

Conclusions: These data might pave the way for a possible novel gene therapy strategy based on reinstating miRNA homeostasis, to be preliminary tested in the easily accessible retina and then, if successful, in the brain.
Upregulation of rod ribbon synapse components implies homeostatic presynaptic scaling in early‐stage retinitis pigmentosa
Authors: Roihuvuo Elias , Tabaka Marcin , Montaser Ahmed , Choi Elliot , Palczewski Krzysztof , Vinberg Frans , Leinonen Henri
Published: January 2025

Aims/Purpose: Photoreceptor death triggers retinal rewiring and remodeling that are generally thought to be detrimental for vision. Some recent research results challenge this dogma. It was recently shown that in early‐stage retinitis pigmentosa (RP), the retina compensates for the reduced rod population activity by upscaling synaptic transmission between the remaining rods and rod bipolar cells. The purpose of the current project is to study the molecular mechanism behind this phenomenon.

Methods: To model the primary pathology, P23H mouse model of autosomal dominant RP was used. Notably, wild‐type mice were not used as controls, instead, cone‐transducin (GNAT2) knockout mice that lack cone photoreceptor functionality were used. To produce “rod‐function‐only” RP mice, P23H and Gnat2‐/‐ mice were cross‐bred. Single cell RNA‐sequencing (scRNA‐seq; Gnat2‐/‐, n = 4; P23H/Gnat2‐/‐, n = 4) and retinal global proteomics (Gnat2‐/‐, n = 5; P23H/Gnat2‐/‐, n = 10) analyses were performed at P30. Statistical significance was set at q < 0.05. Additional protein expression analyses for synaptic proteins were performed using immunohistochemistry and immunoblotting.

Results: ScRNA‐seq analysis revealed upregulation of several major ribbon synapse genes exclusively in P23H/Gnat2‐/‐ mouse rods. These included genes that are crucial in presynaptic structure and neurotransmitter release, such as the Ca2+ sensor Syt1, snare protein complex component Snap25, ribbon protein Ctbp2, and the synaptic vesicle protein Sv2b. In addition, upregulation of the glutamate transporter Slc1a2 was found. Based on proteomics data, STX1B and SYT7 were overexpressed in whole P23H/Gnat2‐/‐ mouse retinas as compared to controls.

Conclusions: Early‐stage RP in mice associates with increased expression of several rod ribbon synapse components that play a role in glutamate release. These results imply that regulation of presynaptic glutamate release may play a role in improving retinal synaptic transmission during RP.
Evaluation of macular ganglion cell layer‐inner plexiform layer (GCL‐IPL) thickness in patients treated with ozurdex: A retrospective study from a Swiss cohort of patients
Authors: Rizzato Angelica , Kochkorov Asan , Katamay Robert , Katja Hatz
Published: January 2025

Aims/Purpose: To investigate the effect of Dexamethasone intravitreal implants (Ozurdex®) on macular GCL‐IPL thickness in patients treated for diabetic macular edema (DME), retinal vein occlusion (RVO), and non‐infectious uveitic macular edema (UME).

Methods: All eyes receiving Ozurdex® between 2013 and 2021 were included and assigned to group 1 (≤5 implants) or group 2 ( > 5 implants). Clinical records were reviewed, and SD‐OCT images manually segmented. Data were evaluated at baseline and at 3 years ± 4 months. Exclusion criteria were poor imaging quality, lack of adequate follow‐up, and absence of dry SD‐OCT at the timepoints. Primary outcome is change in macular GCL‐IPL thickness between baseline and 3‐year follow‐up, compared using paired t‐test. Secondary outcome: incidence of ocular hypertension (IOP > 25mmHg) at three years, compared using Fisher's exact test.

Results: 82 eyes of 73 patients were included (mean age 67.5 years). 30 eyes with DME, 26 with RVO, and 26 with UME. Group 1 (40 eyes) received a mean of 3.0 injections (SD = 1.5; range = 1‐5), while group 2 (42 eyes) received a mean of 7.9 injections (SD = 1.7; range = 6‐14). Macular GCL‐IPL thickness in group 1 was not significantly reduced after 3 years (mean difference: ‐1.8μm, 95% CI: ‐4.4; 0.8, p = 0.18), while group 2 showed significant reduction (mean difference: ‐5.9μm, 95% CI: ‐10.5; ‐1.3, p < 0.05). However, no significant difference in new ocular hypertension cases between group 1 (42.5%) and group 2 (38.0%), p = 0.82 was found.

Conclusions: The study shows that repeated Ozurdex® injections are associated with significant reduction in macular GCL‐IPL thickness over 3 years, however, despite increased ocular hypertension in both groups, no significant differences between groups were found. These findings highlight the need for long‐term monitoring of macular GCL‐IPL thickness and intraocular pressure in patients receiving multiple Ozurdex® injections for DME, RVO, and UME.
Is intravitreal faricimab an effective treatment for diabetic macular oedema not‐responsive to aflibercept? An audit of treated patients at the Princess Alexandra eye pavilion
Authors: Lowe Cameron , Das Meghomala
Published: January 2025

Aims/Purpose: We aim to evaluate both functional and anatomical outcomes of patients switched from aflibercept to faricimab for management of treatment‐resistant diabetic macular oedema (DMO) in a real‐world environment, and the proportion of patients who achieved improvement, stability or deterioration.

Methods: Casenotes of 20 eyes not responding to aflibercept, then switched to faricimab were reviewed. Patient demographics, best‐corrected visual acuity (BCVA) and presence of macular oedema on OCT pre‐switch and at post‐treatment clinic review, and injection intervals were recorded. We then categorised whether there was an improvement, stability or deterioration in both BCVA and presence of macular oedema on OCT.

Results: Of 16 eyes where analysis was complete for BCVA, there was improvement in 31% (n = 5), stability in 19% (n = 3) and deterioration in 50% (n = 8). Of the eyes where there was deterioration, 4 had other co‐morbidity which affected BCVA. Of 17 eyes with pre‐ and post‐switch macular OCT, there was improvement in macular oedema in 71% (n = 12), stability in 24% (n = 4) and deterioration in 6% (n = 1). The mean injection interval where prescribed 4x 1 monthly (n = 13) was 61 days, with a range from 35 ‐ 138 days.

Conclusions: In this real‐world setting with challenges providing patients with regular monthly treatment, faricimab demonstrates the ability to improve DMO in chronic disease with sub‐optimal dosing regimens. A majority of patients demonstrated anatomical improvements, and functional stability or improvement was seen in half of treated eyes. Though the anatomical outcomes were more positive than the functional outcomes on BCVA, this likely reflects the chronicity of DMO in affected eyes, and notably in half of the eyes treated where BCVA deteriorated, there was an alternative cause for this. Given the poorer prognosis of treatment non‐responsive DMO, faricimab is promising as a further option for these harder to treat patients. Overall, there would appear to be a role for faricimab to be a treatment option in chronic‐DMO, and its increased durability is beneficial in busy centres where it is challenging to provide patients with 1‐monthly dosing. This could be further supported by investigating outcomes in patients with treatment‐naive disease.
Comparative retinal study by OCT in Alzheimer's disease: Insights from the app NL‐F/NL‐F model
Authors: Sanchez‐Puebla Lidia , López‐Cuenca Inés , Vázquez Alberto Arias , Salobrar‐Garcia Elena , Matamoros José A. , Lozano María Pilar Rojas , Fernández‐Albarral José A. , Elvira‐Hurtado Lorena , Ramirez Ana Isabel , Salazar Juan Jose , Saido Takaomi , Saito Takashi , Nieto‐Vaquero Carmen , Cuartero María Isabel , Moro María Ángeles , de Hoz Rosa , Ramirez Jose Manuel
Published: January 2025

Aims/Purpose: Transgenic mouse models of Alzheimer's disease (AD) have shown a correlation between retinal abnormalities and brain pathology. The APPNL‐F/NL‐F murine humanized AD model accurately replicates many pathological features seen in AD patients. This study aims to analyze, using manual retinal segmentation by optical coherence tomography (OCT), the changes occurring in several retinal layers in the APPNL‐F/NL‐F AD model at 6, 9, 12, 15, 17, and 20 months of age, in comparison to C57BL/6J mice (WT).

Methods: A diachronic study was conducted using OCT for manual retinal segmentation to evaluate changes in retinal layers. The analysis focused on retinal thickness in the retinal nerve fiber layer (RNFL)‐ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL) based on Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. The study included both the APPNL‐F/NL‐F AD model and age‐matched WT controls, with measurements taken at 6, 9, 12, 15, 17, and 20 months.

Results: Both the APPNL‐F/NL‐F model and WT animals exhibited changes in retinal thickness at various study time points. WT mice showed significant changes in the INL, OPL, and ONL. In contrast, the AD model exhibited significant changes in all analyzed retinal layers except for the IPL. The APPNL‐F/NL‐F model displayed significant thickness variations in the retinal layers analyzed, which closely resemble those found in humans during pre‐clinical, as well as mild and moderate stages of AD.

Conclusions: The study identifies early retinal vascular and structural changes in the APPNL‐F/NL‐F model that precede cognitive changes observed at later stages. These findings suggest that the retinal changes in this model more closely resemble those in human AD compared to other transgenic models, highlighting the potential of retinal assessments in early AD diagnosis.
Association between atherosclerotic cardiovascular disease risk and diabetic retinopathy in patients with type 2 diabetes mellitus
Authors: Agapitou Chrysa , Lampsas Stamatios , Risi‐Koziona Alexia , Kyratzidis Fotis , Pappelis Konstantinos , Theodossiadis Panagiotis , Chatziralli Irini
Published: January 2025

Aims/Purpose: The purpose of this study is to examine the association between diabetic retinopathy (DR) and the atherosclerotic cardiovascular disease (ASCVD) risk in patients with type 2 diabetes mellitus (DM) and to assess risk factors potentially associated with DR.

Methods: Participants in the study were 215 patients with type 2 DM, who underwent a thorough ophthalmic examination, including best‐corrected visual acuity (BCVA) measurement, dilated fundoscopy, fundus photography, optical coherence tomography (OCT) and OCT angiography (OCTA). DR was graded as no apparent retinopathy (NDR), mild non‐proliferative (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR). In addition, a detailed medical history of patients was recorded, while the ASCVD risk estimator plus by the American College of Cardiology was used to calculate the ASCVD risk.

Results: Multivariate logistic regression analysis showed that factors associated with DR independently were: DM duration (multivariate OR = 3.16, 95%CI: 1.55‐6.44, p = 0.002), HbA1c levels (multivariate OR = 2.94, 95%CI: 1.37‐6.32, p = 0.006) and presence of neuropathy (multivariate OR = 3.59, 95%CI:1.43‐9.05, p = 0.007). At the multivariate multinomial logistic regression analysis, NPDR development was associated with duration of DM (multivariate RR = 3.31, 95%CI: 1.57‐6.97, p = 0.002), HbA1c levels (multivariate RR = 2.24, 95%CI: 1.00‐5.02, p = 0.050) and neuropathy (multivariate RR: 3.94, 95%CI: 1.54‐10.11, p = 0.004), while PDR development was only associated with HbA1c levels (multivariate RR = 6.88, 95%CI: 2.19‐21.63, p = 0.001). The ASCVD score was not found to be significantly correlated with DR (p = 0.191).

Conclusions: Factors associated with DR were DM duration, HbA1c levels and presence of neuropathy, while the ASCVD score was not found to be significantly associated with DR.
Pilot outcomes of algorithmic decision support software for intravitreal treatment intervals
Authors: Zakri Rosina , Davies Nigel
Published: January 2025

Aims/Purpose: Timely intravitreal therapy to ensure best outcomes can be difficult to achieve owing to large numbers of patients needing treatment. A protocol‐driven approach to assessment would help train non‐medical staff make accurate decisions regarding treatment and treatment intervals. We develop algorithmic decision support software and present initial analysis comparing software decision with ophthalmologist for treatment interval in wAMD, DMO and RVO patients.

Methods: Ethical approval was obtained. Wet AMD, DMO and RVO patients with more than one year of treatment were recruited, seen as usual by an ophthalmologist. Visual acuity and OCT values were used to calculate two parameters: treatment response and comparison with normality. The algorithm outputs the number of weeks recommended before next treatment. This was compared with ophthalmologist decision.

Results: There was excellent agreement of algorithm recommendation in comparison with ophthalmologist decision. Overall there was exact agreement in 118/225 (52%) of cases and 201/225 (89%) were within 2 weeks of each other. When assessed prospectively in cross sectional single visit, 15/26 wAMD showed exact agreement, 23/26 within 2 weeks. For DMO 14/26 were in exact agreement, 25/26 within 2 weeks and RVO 18/26 exact agreement, 25/26 within 2 weeks. Longitudinal visits over 3 appointments 27/30 wAMD, 25/30 DMO, and 28/30 RVOs are within 2 weeks of each other. Algorithm decision recommendations outside 2 weeks were shorter treatment intervals than ophthalmologist decision.

Conclusions: The decision support algorithm shows excellent agreement with ophthalmologist treatment decisions for wAMD, DMO and RVO. The tool may be a useful aid for trained non‐medical staff working in injection clinics. We are working on further improvement in agreement by programming trend‐based outcomes.