bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Patient specific differences in retinitis pigmentosa in vitro model
Authors: Lukovic Dunja , Garcia‐Bohórquez Belén , Garcia Gema Garcia , Gallardo Maria Esther , Ayuso Carmen , Millán José Maria 
Published: January 2025

Aims/Purpose: Mutations in USH2A are the most common cause of autosomal recessive retinitis pigmentosa (RP) and syndromic RP in combined deaf‐blindness, Usher syndrome type 2 (USH2). In both cases, the effective treatment is lacking. The failure of retinal phenotype in available animal models warrants the generation of human tissue mimics in which to explore the underlying molecular mechanism and test available therapeutic modalities. To model this disease in vitro, we generated iPSC‐derived retinal organoids from patients bearing the two most common mutations in USH2A and explored disease specific events. We aimed to depict the mutation specific distinctive in vitro phenotype.Methods: Patient and isogenic control fibroblasts were reprogrammed into iPSCs using Sendai virus. The iPSCs were subjected toward retinal organoid differentiation according to Zhong et al., 2014 and analysed by fluorescence microscopy throughout the protocol, stage specific retinal cell markers were followed, and ultrastructural changes observed by TEM.Results: Two retinitis pigmentosa patients affected by USH2A mutation and an isogenic control were induced successfully toward retinal organoids with all mayor retinal cell types. We observe reduced efficiency in neural retina formation and paucity in cellular laminar arrangement of patients’ cells. The isogenic control was able to revert disease related cellular phenotypes and subcellular features. The frequency of cones and rods was examined in organoids of different stages by immunocytochemistry and by gene expression. The notable difference between two USH2A genetic backgrounds is proposed to lie in the abundance of cone photoreceptors. Cell death was more pronounced in the patient with missense mutation.Conclusions: Our study corroborates the feasibility of generating retinal organoid disease model of USH2A and CRISPR/Cas9 editing of genetic lesion in disease bearing hiPSCs further supporting the applicability of CRISPR/Cas9 machinery in in vivo settings. We have identified mutation specific differences in in vitro disease phenotype.
Assessment of silica as an intravitreal drug delivery vehicle in a preclinical in vivo tolerability study
Authors: Winter Sophie , Dargelas Frederic , Leino Lasse , Pollari Ville , Reay Marcus , Assmuth Tatu , Wirman Linda , Toropainen Elisa , Kaarniranta Kai 
Published: January 2025

Aims/Purpose: Many severe ocular diseases leading to blindness are currently treated by frequent intravitreal (IVT) injections that not only cause tolerability issues, but also results in decreased patient treatment‐compliance and ultimately loss of vision. Attempts to reduce IVT administration frequency by sustained release of active ingredients through drug delivery systems have failed due to poor tolerability. Our aim in this study was to evaluate the intraocular tolerability of biodegradable non‐porous silicon dioxide (silica) based test items in a preclinical New Zealand White (NZW) rabbit study.Methods: Silica microparticles (MPs) were manufactured by sol‐gel chemistry and spray drying and γ‐sterilized. Silica MPs were combined under aseptic conditions with sterile silica hydrogel (HG) or endotoxin free water to form injectable silica MP‐silica HG (depot) or MP suspensions (MPsusp). 24 NZW rabbits received IVT injections of depot ranging between 10‐50μl via 27G UTW needles and 8 rabbits received MPsusp at 50μl. The test items were evaluated up to 3 months via clinical observations, intra ocular pressure (IOP), slit lamp exam with ocular safety and tolerability criteria, fundus imaging, histopathology analysis of ocular tissues and aqueous‐ and vitreous‐humor proteomics.Results: Clinical observations by veterinarians showed no adverse events. IOP increased immediately after injection but returned to baseline values within 30 minutes. Slit lamp examination revealed no abnormalities in the lid margin, conjunctiva, cornea, lens or retina. Fundus imaging conducted prior to dosing, right after dosing and at days 7 and at 1‐, 2‐, 3‐months showed no deviations. Histopathology confirmed the absence of tissue damage or inflammation. Screening of proteins associated with inflammation revealed no significant changes in the protein profiles of the aqueous and vitreous humor.Conclusions: The results suggest that both silica depots and silica MP suspensions are well tolerated in rabbit eyes for periods up to 3 months at doses ranging from 10‐50μl in IVT administration.