bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical evaluation on the biocompatibility and biosafety of a new foldable brown‐diaphragm intraocular lens: An in vitro and in vivo study
Authors: Zhang Keke , Zhang Shaohua , He Wenwen , Lu Yi , Zhu Xiangjia
Published: January 2025

Aims/Purpose: A new foldable brown‐diaphragm intraocular lens (IOL) was preclinically evaluated in vitro and in vivo by comparing its biocompatibility and biosafety with those of a commercially available IOL.

Methods: The new brown‐diaphragm IOL is made of hydrophobic acrylic material, with incorporating a transparent optical zone and surrounding brown diaphragm. Cellular experiments evaluating lens epithelial cell morphology, adhesion, and migration were conducted to exclude cytotoxic effects. Twelve New Zealand rabbits had the new brown‐diaphragm IOL implanted in one eye and another 12 had a commercially available foldable IOL implanted, followed by slit‐lamp evaluations, corneal endothelial cells density measurement and aqueous humor analysis to identify any dye leakage from the brown‐diaphragm IOL. Haematoxylin and eosin staining of ocular tissue and scanning electron microscopy (SEM) of the IOL surface were performed after 12‐week observation.

Results: In vivo experiments showed there were no statistically significant differences between the two groups in terms of postoperative inflammation and capsular biocompatibility. There were no significant changes in corneal endothelial cell density between before and after surgery in either group. LC‐MS/MS analysis showed that the target dye was not detected in aqueous humor samples. Histopathology of ocular sections and SEM imaging of IOL surfaces showed similar changes in both groups.

Conclusions: The newly‐invented brown‐diaphragm IOL showed good biocompatibility and biosafety. Combined with its foldability and peripheral shading, it could be a new choice for patients with iris defects.
Ocular post‐mortem analyses with histopathological and molecular assessments in leber hereditary optic neuropathy following AAV2 gene therapy
Authors: Carelli Valerio , Newman Nancy , Caporali Leonardo , Ross‐Cisneros Fred , Boschetti Elisa , Biousse Valérie , DuBois Lindreth , Liu Henry , Ancian Philippe , Taiel Magali , Sadun Alfredo
Published: January 2025

Aims/Purpose: To perform post‐mortem ocular analyses in two patients with Leber hereditary optic neuropathy (LHON) caused by the m.11778G > A MT‐ND4 mutation who received lenadogene nolparvovec (AAV2‐ND4) gene therapy.

Methods: Two patients with MT‐ND4 LHON received an intravitreal injection of lenadogene nolparvovec in one eye and a sham injection in the other during the RESCUE study. Post‐mortem histopathological and molecular (ddPCR) analyses were performed on laser‐captured retinal and optic nerve samples.

Results: Within 2 months of gene therapy, both participants developed intraocular inflammation in the treated eye; both events resolved within months. Patient 1 died of acute alcohol toxicity and patient 2 of cardiac arrest. Patient 1 had severe optic atrophy and loss of retinal ganglion cells (RGCs), while patient 2 was a much milder case of LHON, with consistent preservation of RGCs and optic nerve axons, being only the temporal fibers lost. In patient 1, an angiocentric lymphocytic chronic inflammation was noted in the optic nerve head and temporal retina. No persistent inflammation was seen in patient 2. AAV2‐ND4 distribution in the treated eye was asymmetric in both patients, more prevalent in temporal RGCs. A much lower level of AAV2‐ND4 was detected in the retina of the untreated eye in both cases. Finally, mtDNA copy number was upregulated in both eyes of patient 2, possibly reflecting better preservation of RGCs and axons.

Conclusions: This is the first postmortem study of human eyes injected unilaterally with AAV2‐based gene therapy. Gene transfection of RGCs was successful in both eyes despite unilateral administration. AAV2‐ND4 transfer seems to be facilitated by axonal preservation and may be confirmed, and further characterized by analysis of the eyes, nerves, optic chiasm and optic tracts from patient 2.
Exploratory and comprehensive description of an italian cohort of patients affected by leber hereditary optic neuropathy carrying the pathogenic variants m.11778G > A/MT‐ND4 and m.3460G > A/MT‐ND1
Authors: Romagnoli Martina , Carbonelli Michele , Amore Giulia , Fiorini Claudio , Zenesini Corrado , D'Agati Pietro , Tropeano Concetta Valentina , Cascavilla Maria Lucia , Barboni Piero , Caporali Leonardo , Carelli Valerio , La Morgia Chiara
Published: January 2025

Aims/Purpose: This is an observational study to track the disease course of patients affected by Leber Hereditary Optic Neuropathy (LHON), regularly attending the neurophthalmological clinic of the IRCCS ISNB (Bologna).

Methods: To satisfy inclusion criteria, subjects needed a confirmed genetic diagnosis for 2 of the 3 primary LHON mutations (m.11778G > A/MT‐ND4; m.3460G > A/MT‐ND1). There was no restriction on age, and patients could have received idebenone or any other treatment.

Results: 397 subjects from 137 families were enrolled, 196 symptomatic (49%; male: 79%), 201 asymptomatic (51%; male: 40%). Of these, 66 (17%; symptomatic: 55%) carried the m.3460G > A/MT‐ND1 variant, 331 (83%; symptomatic: 48%) the m.11778G > A/MT‐ND4, with a ratio of affected male: female of 2: 1 for the first, and 4: 1 for the m.11778G > A/MT‐ND4 carriers.

Of the 196 symptomatic patients, 37 had LHON childhood onset and 3 had unilateral LHON.

106 patients (54%) were treated with idebenone and/or lenadogene nolparvovec.

For both mutations the distribution of age at onset is multimodal, and different between males and females. LHON females showed later age at onset (post‐menopausal peak) in the m.11778G > A/MT‐ND4 subgroup, while the m.3460G > A/MT‐ND1 density plot showed a peak in the fertile young age.

Then, visual acuities of both eyes were collected from 1252 outpatient visits. The resulted best‐fitted LOWESS curve depicting the evolution of BCVA over time did not show a difference between m.11778G > A/MT‐ND4 and m.3460G > A/MT‐ND1 symptomatic patients.

Conclusions: We highlight the highest penetrance in females of the m.3460G > A/MT‐ND1 variant, for which females had an age of onset more similar to males at difference with the m.11778G > A/MT‐ND4 for which females had a delayed peak of onset, after menopause. Clinically, the two variants seem to behave similarly. This “real world” study is a precious tool to define genotype/phenotype relationships and highlight the most appropriate subpopulations for clinical trials.
Gut microbial dysbiosis in age‐related macular degeneration
Authors: Vergroesen Joëlle , Vermeulen Jeroen , Thee Eric , Liefers Bart , Klaver Caroline
Published: January 2025

Purpose: The gut microbiome is highly influential in diseases with inflammatory components. Multiple studies showed a link between the gut microbiome and age‐related macular degeneration (AMD). However, no consistent taxa have been reported.

Methods: We included 1372 participants from the Rotterdam Study (RS). AMD features (e.g. [reticular pseudo‐]drusen, retinal pigment epithelium degeneration, and hyperpigmentation) were graded by human graders on color fundus photographs. Next, areas of these features were automatically quantified by a deep learning segmentation model. Stages were determined according to the RS classification (preliminary = 239, early‐intermediate = 75, late = 6). Propensity score matching was performed on age, sex and BMI. Multivariable associations with taxonomic and functional profiles were assessed using zero‐adjusted models (MaAsLin2; Compound Poisson). p‐values were false discovery rate‐adjusted (q‐values). Taxa associated (q < 0.25) with at least two out of seven AMD(‐related) outcomes are reported.

Results: We observed no associations with alpha‐ or beta‐diversity. Nineteen taxa were associated with AMD, of which 7 persisted after additional adjustment for dietary data. Eubacterium xylanophilum group, Lachnoclostridium, Faecalibacterium, Odoribacter splanchnicus and Parabacteroides distasonis were associated with an AMD phenotype. Parabacteroides and Akkermansia were inversely associated with an AMD phenotype. Moreover, 46 MetaCyc pathways were associated with AMD, of which 15 persisted after additional adjustment for dietary data. GLUCARDEG.PWY, PWY.5028, PWY.5347, PWY.5415, PWY.5532, PWY.5971, PWY.6969 and TCA were associated with an AMD phenotype. FOLSYN.PWY, LEU.DEG2.PWY, PANTO.PWY, PANTOSYN.PWY, PWY.6612, PWY0.1586 and PYRIDNUCSYN.PWY were inversely associated with an AMD phenotype.

Conclusions: Several gut microbiota were associated with an AMD phenotype. AMD pathophysiology might be linked to changes in gut‐related metabolic pathways.
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.
Survey of B‐blockers against retinal degeneration
Authors: Makiou Anthi‐Styliani , Kalatanova Anna , del Amo Eva Maria , Leinonen Henri
Published: January 2025

Aims/Purpose: This project aims at finding the best clinically approved β‐blocker drug for RD prevention. The project is a part of a larger drug repurposing program that utilizes a combination of clinically approved G protein‐coupled receptor drugs as a therapeutic strategy.

Methods: Comprehensive literature review of β1‐blockers (including dual blockers of α‐ and β‐adrenoreceptors) focusing on the ability to accumulate in melanin‐rich eye tissues was performed. Physicochemical descriptors of the obtained 17 β‐blockers were generated and principal component analysis (PCA) was used for a concise overview of a dataset in the chemical space for further selection. The efficacy of selected drugs was tested in the acute bright light‐induced RD (LIRD) mouse model using standard ophthalmology imaging methods: electroretinography (ERG) and optical coherence tomography (OCT). LIRD was induced to dark‐adapted Balb/c mice between 4‐ and 5‐weeks of age, and the drug efficacy was examined one week after.

Results: Based on the PCA score plot, eight drugs were selected for testing so that the drugs would maximally represent the diversity of this drug class. ERG and OCT experiments revealed that non‐selective‐blockers propranolol, timolol and metipranolol were more efficacious against LIRD than selective β1‐blockers metoprolol, bisoprolol, and levobetaxolol, and more effective than dual α‐/β‐receptor blockers labetalol and carvedilol. Additionally, an experimental β2‐antagonist (ICI‐118551) was tested but its administration did not significantly protect from LIRD.

Conclusions: Non‐selective β‐blockers showed better retinal protection than β1‐selective blockers in this context. Future experiments will include testing dual administration of selective β1‐ and β2‐ antagonists. Additionally, the drug efficacy against stressors relevant for RD, such as H2O2 and all‐trans‐retinal, will be assessed using organotypic retina explants and oxidative stress and cell death markers.
Biodistribution of alpha‐lipoic acid in beta‐cyclodextrins: Analyzing ex vivo delivery to the posterior segment of the eye
Authors: Ta Phuong Linh , Just Lucia Bernat , Alambiaga‐Caravaca Adrián , Alarma Vicente Rodilla , Castellano Alicia López , Morell Francisco Bosch
Published: January 2025

Aims/Purpose: α‐lipoic acid (ALA), a natural antioxidant, has shown significant value in delaying retinal damage progression. The purpose of this study was to quantify the amount of α‐lipoic acid in β‐ cyclodextrins (ALA‐βCD) complexation in various ocular tissues, especially in the posterior segment of the eye and the neuroretina, after administration from solution and ocular inserts containing the drug.

Methods: ALA‐βCD was dissolved in phosphate saline solution (PBS) to obtain a 1 mg/mL solution. Inserts containing 1 mg/mL ALA‐βCD were prepared using eye‐compatible polymers: polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and hyaluronic acid (HA).

Porcine eyes were obtained from an abattoir shortly after sacrifice and they were cleaned and placed on a Franz diffusion cell. The solution (250 μl) was administered every 2h and washed after 5 min with PBS. The inserts were placed in contact with either the cornea or the sclera. Both experiments were carried out for 8h at 37°C with humidity control. The eyes were then washed with PBS and stored at ‐80°C for 12 h wrapped in parafilm to maintain their morphology. The frozen eyes were surgically dissected to separate the different eye structures. The ALA from various structures/tissues was extracted by soaking them in acetonitrile: water solution (80: 20, v/v) for 12h under constant stirring. The samples were then filtered, and the concentration of ALA determined by a validated HPLC method.

Results: ALA was detected in all ocular tissues. The higher content of ALA found in the inserts was due to its longer contact time than the solution, and it increased bioadhesibility allowed greater biodistribution of ALA in the ocular tissues. Up to 1.5 % of ALA in the inserts reached the neuroretina, the target tissue for the treatment of retinopathies.

Conclusions: The data show that in ex vivo, ALA can diffuse from the cornea and the sclera, reaching the posterior segment of the eye, and particularly the neuroretina. This data proves the way to carry out in vivo studies to assess the potential of topically administered ALA in protecting the eye from retinopathies.

References

Alambiaga‐Caravaca AM, et al. Biodistribution of progesterone in the eye after topical ocular administration via drops or inserts. Int Jour of Pharma. 2023 Jan; 630: 122453.
Comparative neuroprotective effects of xenogeneic and allogeneic bone marrow‐derived mesenchymal stromal cells in a murine model of sepsis
Authors: Campoverde Jhoana Abigail Guarnizo , Ramírez Kristy Tatiana Rodríguez , Bernal David García , Lucas‐Ruiz Fernando , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta
Published: January 2025

Aims/Purpose: Sepsis causes systemic inflammation (SI) and induces acute and long‐term neurological dysfunctions. In the retina, SI causes the loss of retinal ganglion cells (RGCs). Advanced cell therapy with bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) is a promising avenue for RGCs neuroprotection in SI due to their immunomodulatory properties. Here we analyze the neuroprotective properties of BM‐MSCs in two transplantation settings: xenogeneic and allogeneic in a murine model of SI induced by lipopolysaccharide (LPS).

Methods: 2‐month‐old C57BL/6J male mice were used in all groups. LPS was intraperitoneally injected (5mg/kg) at day 0. At day 1, BM‐MSCs isolated from BALB/C mice (allogenic) or human donors (xenogenic) were intravitreally administered in the left eye. As controls we used intact and LPS‐treated C57BL/6J animals. RGCs survival (Brn3a+) and microglial activation (Iba1+) were studied at 7 days in both retinas, the treated and the contralateral to the injection.

Results: BM‐MSCs were found forming an epiretinal membrane in both transplant modalities. RGCs death in LPS controls reached 20% of the original population. The allogeneic transplant rescued all RGCs in both eyes. In contrast, xenogeneic transplant only protected to the contralateral eyes and microglia were more activated and reactive.

Conclusions: These preclinical data show that allogeneic BM‐MSCs elicits a greater neuroprotection for sepsis induced RGCs degeneration in both eyes, the treated and contralateral. While the xenogeneic transplant does not neuroprotect RGCs in the treated eye, it does in the contralateral one, a neuroprotection that could be due to paracrine effects. These findings may be the basis to treat sepsis induced neurodegeneration.
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.
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.
Bilateral levator palpebrae superioris involvement by malt lymphoma
Authors: Ortega Aranzazu Caro , Ferrando Sergio Obiol , Fernando Diego Serrano , Rovira Elena Gracia , García Amparo Lanuza
Published: January 2025

Aims: Lymphoma is the most common malignant tumour in the ocular region. Among its histopathological subtypes, mucosa‐associated lymphoid tissue (MALT) is the most frequent. Extraocular muscles’ affectation by MALT lymphoma of the eye is uncommon (5%), more if possible, infiltration of levator palpebrae superioris (EPS), have not been described affectation of EPS isolated and none bilateral so far: We report one case of bilateral EPS involvement by MALT lymphoma.

Methods: A 67‐year‐old lady noticed of gradually solitary mass increment on the right upper eyelid. Examination revealed a fibrous, nonpitting, hard and non‐tender, subciliary mass measuring 2‐3 cm on this eyelid. The rest of the ophthalmological examination was normal. Orbital magnetic resonance imaging showed infiltration of right EPS. The histological and immunohistochemical result of the biopsy was MALT lymphoma. The serology resulted negative for Chlamydophila psittaci. Three weeks later a similar mass appears in the left upper eyelid.

Results: Ann Arbor's stage IV‐A was established. Haematology Committee decided treatment with six cycles of immunochemotherapy with: R‐CVP (Rituximab‐Cyclophosphamide‐Vincristine‐Prednisone). The tumor disappearance after the 4th cycle.

Conclusions: MALT lymphoma is the most frequent ocular adnexal lymphoma, although extraocular muscles involvement is rarity entity itself. The most common affected muscle is superior rectus. Eligible treatment for limited type is locoregional radiotherapy. In case of advanced disease chemotherapy is preferred. Hence MALT lymphoma is a rare disease, which frequently recurs locally and has potential for systematic spread and transformation to a high‐grade B cell lymphoma, so warrant alertness to this neoplasm is required to reach an early diagnosis.

References

Abalo‐Lojo, J. M., Baleato‐Gonzalez, S., Abdulkader, I., & Gonzalez, F. (2011). Extraocular muscle involvement in MALT lymphomas. Orbit (Amsterdam, Netherlands), 30(4), 186–188.
Hedgehog pathway inhibitors in eyelid tumors
Authors: Funes Elisa , Merino Jacobo Yañez , Sopeña‐Pinilla Maria , Ciobotaru Olga , Bestué Ana Pueyo , Pueyo‐Bestué Ignacio , Fernandez‐Velasco Diego , Mallen Victor , Bermudez Javier , Biescas Andrés
Published: January 2025

Aims/Purpose: Basal cell carcinoma (BCC) is the most common type of tumor worldwide. Although it has a low capacity for systemic spread, it exhibits a high rate of local invasion. The most frequently affected areas are the face and neck. So far, the most widely used treatment has been surgery in its various forms: excision‐electrodesiccation‐curettage, cryotherapy, or the increasingly common Mohs micrographic surgery. In recent years, various researchers have identified molecules that can reduce or even eliminate these lesions. Among them, we highlight Vismodegib due to the good results obtained. This molecule is the first selective Hedgehog pathway inhibitor approved for the treatment of local and metastatic BCC.

Methods: A 57‐year‐old female patient came to our clinic, referred by the dermatology department of our hospital, due to a basal cell carcinoma on the left lower eyelid affecting the free margin.

Results: An incisional biopsy of the lesion was performed, diagnosing nodular BCC. After explaining the characteristics of the tumor and the therapeutic options to the patient, it was decided to start treatment with Vismodegib, include her in the surgical waiting list, and perform monthly follow‐up. In subsequent check‐ups, the patient reported good tolerance and adherence to the treatment, without adverse side effects. During the consultations, a clear reduction of the lesion was observed. However, due to the incomplete disappearance of the lesion, it was decided to perform a wedge resection of the tumor.

Conclusions: Currently, the patient shows a good alignment of the free margin, with good tension and no signs of tumor activity.
Retrospective review of the annual endophthalmitis rates following intravitreal injections at Royal Bournemouth Hospital over an eight‐year period from 01/02/2016 until 31/01/2024
Authors: Tsokolas Georgios , Tossounis Charalambos , Anderson Owen , Matthews Non
Published: January 2025

Aims/Purpose: To present the annual rates of post‐intravitreal injection endophthalmitis at Royal Bournemouth Hospital (RBH) over an eight‐year period from 01/02/2016 until 31/01/2024.

Methods: The total number of intravitreal injections performed was identified retrospectively from our electronic records. The cases of post‐injection endophthalmitis were identified from the department's written logbook record.

Results: Over the above 8‐year‐period, a total number of 13 cases of endophthalmitis were identified. The total number of injections performed over this 8‐year‐period was 54,134. The annual endophthalmitis rates fluctuated from a minimum 0% (year 01/02/2016 until 31/01/20217) to a maximum of 0.05% (year 01/02/2019 until 31/01/2020). Mean annual endophthalmitis rate over this 8‐year‐period was 0.025%. 1 case occurred after an intravitreal Ozurdex injection and 12 following anti‐VEGF injections.

Conclusions: Despite the increasing number of injections every year, we noted that our endophthalmitis rates were consistently much lower than the estimated rate of 1 in 1000 (0.1%) in the literature. We postulate that our current standard local protocols and practices which include the use of sterile gloves, sterile drapes, face masks and pre‐injection instillation of povidone iodine in the fornix have played a pivotal role in keeping the annual endophthalmitis rates very low. Furthermore, the introduction of novel agents of biosimilars to Ranibizumab (Ongavia) and Faricimab (Vabysmo) which are withdrawn from vials and are not available in pre‐filled syringes did not have any adverse impact on our endophthalmitis rates. In 2014, the administration of chloramphenicol 0.5% antibiotic eye drops post‐intravitreal injections were stopped permanently. In 2016, specialist nurse injectors were introduced in our clinical practice. Based on our endophthalmitis rates over this 8‐year‐period, these two important changes in the clinical practice do not seem to have had a negative impact in our annual endophthalmitis rates. Our aim is to continue auditing our rates annually in order to ensure that we are a safe to practice macular unit and to maintain high quality patient care.
Clinical presentation and response to idebenone treatment in a 60‐year old female carrier of leber hereditary optic neuropathy
Authors: Kabanarou Stamatina , Bitzanakis Nikolaos , Sgourou Chrysoula , Garnavou‐Xirou Christina , Fragkiskos Petros , Xirou Tina
Published: January 2025

Aims/Purpose: To present a female carrier with Leber Hereditary Optic Neuropathy–(LHON) treated with idebenone.

Methods: A 60‐year‐old Caucasian female patient with a 5‐year history of gradual painless visual loss was tested positive for LHON (mitochondrial point mutations m.3460 G > A at MT‐ND1 gene) one year ago. Both her sons had been diagnosed with LHON and suffered severe bilateral visual/field loss. One of them showed major improvement at his visual fields (VF) after idebenone treatment, while her other son was reluctant to receive any treatment. Her flash visual evoked potentials (VEP) were delayed with normal amplitude. Full field ERG and pattern ERG were normal bilaterally. She was prescribed a course of 300mg idebenone per os 3 times/day for 6 months and referred to us for further follow‐up.

Results: At presentation to our clinic her ETDRS best corrected visual acuity (BCVA) was 1/10 in her right eye‐RE and 9/10 in her left eye‐LE (BCVA improved only in the left eye by 3 lines; the right one was amblyopic). Fundoscopy revealed pale optic discs bilaterally. During OCT imaging RNFL and GCC thickness were reduced bilaterally. VFs were affected bilaterally but showed improvement, especially in the LE, compared to the pre‐treatment ones. She was prescribed another 6‐month course of idebenone. Six months later, fundoscopic findings, RNFL and GCC thickness were unchanged. However, BCVA and VF were further improved.

Conclusions: We present a female carrier with typical manifestation of LHON who responded positively to a 12‐month course of idebenone treatment. LHON has been reported to affect males more often than females despite being a maternally inherited disease. Ηowever, in younger and older patients ( > 45 years old) the male‐to‐female ratio is approximately 1: 1. Female carriers with disease manifestation should not be overlooked, especially in these age groups, as prompt treatment may preserve their visual function/delay visual loss.
Retinal vein occlusion in young adults: The crucial role of underlying cause investigation
Authors: Simón Cristina Calvo , Remacha Carla Sánchez , Borghi Luca Manuel Bueno , Fernández Miguel Castillo , Clavería Julia Aramburu , Martínez Marta Suñer , Moscarda Eva Josefina Nuñez , de Rivas Marta Orejudo , Arias Pablo Cisneros , Pascual Ana María Abad , Duarte Javier Ramos , de la Cámara Sahuquillo Edurne , Sánchez Inmaculada Herrero , González Pablo Tejada , Puyuelo Francisco Javier Ascaso
Published: January 2025

Aims/Purpose: To present a case of a young patient with retinal vein occlusion (RVO) who was subsequently diagnosed with acute leukemia, highlighting the importance of early hematological evaluation in such cases.

Methods: A 40‐year‐old woman presented to the emergency department with a one‐week history of decreased visual acuity in her right eye. The visual acuity was 4/10 in the right eye and 10/10 in the left eye. Fundus examination of the right eye revealed papilledema, flame‐shaped hemorrhages, cotton‐wool spots, and vascular tortuosity. The left eye showed punctate hemorrhages in the superior retina, a choroidal nevus, and vascular tortuosity. OCT confirmed macular edema in the right eye. A full blood count was performed due to the patient's young age and lack of known cardiovascular risk factors.

Results: The patient was diagnosed with central retinal vein occlusion (CRVO) in the right eye and superior branch retinal vein occlusion (BRVO) in the left eye. As for the ocular management, an intravitreal injection of Ozurdex® was scheduled for the right eye to address the macular edema.

As for the systemic assessment, a complete blood count was performed. It included an antiphospholipid profile, antithrombin III and factor V Leiden, among others.

Although initial considerations focused on a potential thrombophilia, the blood tests revealed acute leukemia with 135,000 leukocytes, hemoglobin of 5.3 g/dL, and platelets of 104,000. This critical finding led to immediate specialized treatment for the underlying hematological condition.

Conclusions: This case underscores the significance of a thorough hematological evaluation in young patients presenting with retinal vein occlusion. Acute leukemia, although rare, can initially present with ophthalmological manifestations. Early diagnosis and treatment of systemic conditions can significantly improve patient outcomes. Interdisciplinary collaboration is essential in managing such complex cases.
Human iPSC‐derived RPE cells implantation into minipig eye – Six weeks follow‐up study
Authors: Ardan Taras , Erceg Slaven , Brýmová Anna , Studenovska Hana , Mueller Brigitte , Stieger Knut , Petrovski Goran , Lytvynchuk Lyubomyr , Straňák Zbyněk , Veith Miroslav , Juhás Štefan , Juhasová Jana , Nemesh Yaroslav , Ellederová Zdeňka , Motlik Jan
Published: January 2025

Aims/Purpose: The study of long‐term survival of transplanted retinal pigment epithelium (RPE) in animal models is very important for the development of promising cell‐based therapy of retinal degenerative diseases such as age‐related macular degeneration (AMD) or retinitis pigmentosa. We hereby present xenogeneic implantation of human iPSC‐RPEs into minipig eyes with a 6‐week follow‐up period.

Methods: The subretinal implantations of hiPSC‐RPEs‐scaffolds into the minipig eyes were performed using 3‐port pars plana vitrectomy. The xenogeneic character of RPE transplantation determined the use of pre‐ and post‐operative tacrolimus immunosuppressive therapy. At 6‐weeks following transplantation, non‐invasive OCT and fundus camera examinations of the implanted eyes were performed. The implanted retinas of enucleated eyes were then investigated immunohistochemically using specific markers for recognition of human cells including hRPEs, intercellular connections such as tight junctions, macro‐ and micro‐gliosis.

Results: The fundus imaging showed successful subretinal implantation of the implanted patch in the nasal part of the retina, while OCT scans demonstrated the good implant adherence to the circumjacent retinal structures, with preserved retinal layers and very small decrease of retinal thickness at the place of the implant. Immunohistochemical examination showed survival of hiPSC‐RPE with positivity of cell markers specific for human cells such as HNAA and STEM 121, preserved pigmentation and tight junctions, very mild gliosis, and less bloated and stressed Müller cell processes.

Conclusions: The 6 weeks post‐implantation study demonstrated the good survival of implanted human iPSC‐RPEs in the subretinal space as well as the ability to physiologically interact with adjacent photoreceptors.
Atypical response to hydroxychloroquine: Beyond bull's eye maculopathy
Authors: Álvarez María Carla Balmaseda , Claramonte Carmen Cabedo
Published: January 2025

Aims/Purpose: Hydroxychloroquine retinopathy is the most potentially dangerous ocular side effect, as it can lead to irreversible vision loss if not diagnosed early. There is currently no specific treatment for this condition and withdrawal of the drug is the only therapeutic measure. This is why early detection of hydroxychloroquine retinopathy is considered crucial, since in early stages retinal changes may be reversible. This challenge represents a priority in medicine today.

Methods and Results: We report the case of a 47‐year‐old woman with systemic lupus erythematosus, on treatment with hydroxychloroquine 200 mg/day for more than 20 years. Previous annual check‐ups showed no abnormalities until the last visit, when spectral‐domain optical coherence tomography (SD‐OCT) showed an alteration of the retinal pigment epithelium and bilateral drusen. In addition, the multifocal electroretinogram (mfERG) of the left eye showed a decrease in macular wave amplitude. Microperimetry was also performed and showed abnormal macular integrity in both eyes. It was decided to discontinue hydroxychloroquine treatment and switch to azathioprine 25 mg/day, in consensus with rheumatology. This resulted in a normalisation of the mfERG at 3 months, as well as almost complete regression of the retinal pigment epithelium alterations identified on SD‐OCT.

Conclusions: There are different types of presentation of HXQ retinopathy, beyond the typical bull's eye maculopathy. Atypical responses to hydroxychloroquine pose a diagnostic challenge, and in case of doubt regarding ocular toxicity, it is essential to assess the risk‐benefit of changing treatment. If retinopathy is confirmed, medication should be interrupted, always in agreement with the prescribing professional. Given the atypical retinal involvement and the reversibility of toxicity with discontinuation of treatment in this case, it is considered worthy of interest.
Retinal capillary density in metabolic syndrome and its association with main risk factors of cardiovascular disease
Authors: Simkiene Ieva , Gasiunas Kornelijus , Tarutyte Gabriele , Asoklis Rimvydas , Badariene Jolita , Schmetterer Leopold
Published: January 2025

Aims/Purpose: To describe retinal capillary density of normal eyes from patients with metabolic syndrome and to investigate possible associations with main risk factors of cardiovascular disease (smoking, arterial hypertension, dyslipidemia).

Methods: This was a prospective cross‐sectional study. We included 214 eyes (clear media, no ocular diseases, no prior surgery or ocular trauma) of 114 patients with metabolic syndrome (median age 54 (49.25, 59.0), male 51 (44.74%), female 63 (55.26%)). Data on ambulatory blood pressure (BP), triglycerides (TG), lipid profile and smoking status were collected. Retinal capillary density at the superficial vascular plexus (SVP) at 6 × 6 mm square of central macular area was measured with a commercial optical coherence tomography angiography OCT‐A (AngioVue®, OptoVue, Framont, CA, USA) system. Linear regression was used to investigate the association of risk factors with capillary density.

Results: In the multivariable analysis, older age was associated with sparser retinal vascular density in whole image (β = ‐0.198, p < 0.001), foveal (β = ‐0.264, p = 0.021), perifoveal (β = ‐0.226, p < 0.001) and parafoveal (β = ‐0.153, p = 0.007) areas. Lower capillary density in whole image (β = ‐0.149, p = 0.025) and perifoveal area (β = ‐0.162, p = 0.018) was also associated with higher body mass index in the multivariable analysis. Higher HDL and TG levels were associated with denser retinal capillaries in SVP in whole image (β = 2.064, p = 0.028 and β = 0.847, p = 0.001), perifoveal (β = 2.246, p = 0.023 and β = 0.899, p < 0.001) and parafoveal (β = 2.346, p = 0.047 and β = 0.865, p = 0.024) areas. Systolic and diastolic BP and smoking were not associated with capillary density (p > 0.05).

Conclusions: In adults with metabolic syndrome retinal capillary density in SVP was found to be reduced with older age and higher body mass index. Higher HDL and TG concentrations were associated with denser SVP capillaries. The latter results may be the consequence of vasodilatation due to sub‐clinical inflammation.
LCHAD chorioretinopathy case series long‐time follow up
Authors: Hubert Magdalena , Gawęcki Maciej
Published: January 2025

Aims/Purpose: The aim of this study is the present a long‐time follow up of patients with LCHAD deficiency – ocular findings and it's evolution.

Methods: The study included a group of 8 patients diagnosed with LCHAD deficiency, confirmed by genotyping as a mutation in HADHA gene c.1528 G > C. Patients were evaluated yearly, since 2013 to 2024. Examination included slit‐lamp examination, best corrected vision acuity, sOCT, fundus imaging and visual field – if possible to obtain. Patients were questioned about events of metabolic decompensation that required hospital treatment in the period of time since previous ophthalmological evaluation.

Results: Progressive deterioration of BCVA along with progressive myopia were observed. The loss of vision usually progressed rapidly and was unsymmetrical, thus usually unnoticed by the patient if the fellow eye maintained good vision acuity. The deterioration of the vision acuity was accompanied by presence of central scotoma, progression of myopia, chorioretinal thinning and in some cases forming of staphyloma. Pigment accumulation in the foveal area and in the central area was not associated with the vision deterioration or visual field loss. In 2 cases MNV occurred, followed by macular scarring in one patient. MNV if treated by anti‐VEGF injections without a delay responded very well, 2‐3 injections were needed to maintain the deasease inactive. Positive scotomas were associated with macular hemorhage. Bad metabolic status recognized by repeated necessity of in ward treatment due to metabolic decompensations was associated with progressive chorioretinopathy and it's complications.

Conclusions: Presence of the metabolic decompensations requires ophthalmological vigilance as it is a main factor for visual deterioration. The chorioretinal thinning is followed by staphyloma and progressive myopia. MNV can be successfully treated in those patients but evaluation should be done monthly afterwards.
Vogt‐Koyanagi‐Harada (VKH) like syndrome in a patient treated with pembrolizumab for metastatic colorectal cancer
Authors: Kontou Evgenia , Smoustopoulos George , Karamatzianni Georgia , Bontzos George , Konstantopoulou Kallirroi , Kabanarou Stamatina , Xirou Tina
Published: January 2025

Purpose: VKH is a systemic granulomatous autoimmune disease that affects melanocyte‐rich organs. While the aetiology remains unclear, there have been documented instances of VKH seemingly induced by specific medications. Our study describes a rare case of VKH‐like syndrome arising during immunotherapy with pembrolizumab in a patient with metastatic colorectal cancer.

Methods: A case report and a detailed evaluation of the relevant literature. Clinical course, comprehensive ophthalmic examination findings, and wide‐field retinal photography and fluorescein angiography (FA) were utilized to establish the diagnosis and guide treatment.

Results: A 39‐year‐old female presented with 1‐week history of decreased visual acuity in her left eye and recurring episodes of headache. She revealed a medical history of an operated colorectal cancer, treated with adjuvant pembrolizumab therapy (anti PD‐1 immunotherapy) over the past 5 months. The patient underwent a complete ophthalmic examination, multimodal imaging and neurological assessment. Best corrected visual acuity was 10/10 in her right eye and 4/10 in her left eye and slit lamp examination revealed 1‐2+ cells in the left eye confirming anterior uveitis. Fundus examination revealed bilateral serous retinal detachments (SRD) in the posterior pole and optic nerve oedema. Optical coherence tomography also revealed SRD and diffuse choroidal thickening. The following days the patient was scheduled and underwent FA, showing pinpoint areas of leakage and hot disc, so oral steroid therapy was initiated. During the course of the patient's follow‐up, the clinical symptoms gradually improved, following the steroid tapering and discontinuation of the immunotherapy.

Conclusions: New immunotherapy drugs raise concerns about uveitis as an adverse effect. Pembrolizumab's association with panuveitis & SRD emphasizes the importance of careful monitoring and development of a comprehensive steroid management strategy, in patients receiving this treatment.

Reference

Kurono Y, Takeda T, Kunimatsu Y, Tani N, Hashimoto I, Hirose K. Vogt‐Koyanagi‐Harada disease during chemoimmunotherapy for non‐small cell lung cancer. Respirol Case Rep. 2020 Feb 28; 8(3): e00545.
Correlations between oct‐angiography and maia microperimetry in patients who have suffered a rhegmatogenous retinal detachment
Authors: Díaz‐Barreda Mª. Dolores , Bartolome Isabel , Hospital Elvira Orduna , Boned‐Murillo Ana , Fernández‐Espinosa Guisela , Sopeña‐Pinilla Maria , Pinilla Isabel
Published: January 2025

Purpose: Describe the existing correlations between the OCT‐Angiography (OCTA) and the MAIA microperimetry in patients who have suffered a rhegmatogenous retinal detachment (RRD).

Methods: We conducted a cross‐sectional study comparing 65 eyes that suffered primary RRD that was successfully repaired by PPV and SF6 with a control group consisting of 136 eyes. All underwent a comprehensive ophthalmologic examination, including OCTA and MAIA microperimetry.

Results: There were no differences between the groups in terms of age, sex, laterality of the studied eye, or IOP.

The correlations between OCTA and MAIA in the RRD group were as follows:

The SCP: the S sector showed a positive correlation with the C (r = 0.314) and central‐superior (CS) (r = 0.339) sectors of the MAIA. The inferior (I) sector reached a negative correlation with the inferior‐outer (IO) (r = ‐0.298) and inferior‐inner (II) (r = ‐0.376) sectors of the MAIA. The N sector reached a positive correlation with the BCEA 63 angle (r = 0.306) while this correlation was negative with the C sector (r = ‐0.293) of the OCTA.

The DCP: the C sector of the OCTA correlated with the temporal‐inner (TI) sector (r = 0.297) of the MAIA. The area of the FAZ correlates with sector II (r = ‐0.298) of the MAIA. C sector reached correlation with BCEA 63 angle (r = ‐0.464) and 95 angle (r = ‐0.482), the area of the FAZ correlated with the BCEA 95 angle (r = 0.290) and the vertical diameter of the FAZ with both BCEA 63 angle (r = 0.345) and 95 angle (r = 0.341).

The CC: the S sector presented a positive correlation with the C (r = 0.409) and CS sectors (r = 0.333) of the MAIA. The BCEA area 63% (r = 0.290) and 95% (r = 0.292) of the MAIA correlated with the OCTA's. The BCEA angle 63% (r = 0.325) and 95% (r = 301) of the MAIA correlated with the OCTA T sector.

Conclusions: While OCTA vertical sectors achieve correlations with macular sensitivity in vertical sectors quantified by MAIA microperimetry, horizontal sectors correlate with fixation parameters.