bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orbital pleomorphic sarcoma: A case report
Authors: Mesa Sara Mesa , Borrero Cristina Gonzalez , Hoyos Carolina Ceballos , Usuga Juan Cadavid 
Published: January 2024

Aims/Purpose: To report a case involving an undifferentiated pleomorphic sarcoma localized in the orbit.Methods: Case report and literature review.Results: Undifferentiated pleomorphic sarcomas (UPS) are one of the least common types within all malignant sarcomas, with their incidence reaching 5–10% of the cases. Within this group of UPS, tumours involving the head and neck have an even lower incidence (approximately 3 to 5%). We report the case of an 86 year old male with a history of cardiovascular disease, presenting with a painless lesion in his right eye. The orbit CT reported a soft tissue lesion in contact with the right ocular globe, lacrimal gland and extraconal fat. At examination the patient registered best corrected visual acuity right eye (OD) no light perception right eye and left eye (OS) 20/50. At slit lamp examination OD is not evaluable due to corneal compromise. OS anterior segment and posterior pole with no alterations. Immunohistochemistry was negative for P40, desmine, CD34, SOX‐10 and cytokeratin cocktail. S100 had weak and patchy staining. These results led to a giant cell pleomorphic sarcoma diagnosis, histological grade 3. The patient underwent urgent orbital exenteration, with an adequate postsurgical evolution and oncology follow up.Conclusions: The diagnosis of an UPS is based on exclusion, due to their heterogeneous nature, with histological characteristics that overlap with other malignant mesenchymal neoplasms, mainly with metastatic sarcomatoid carcinoma and melanoma. These tumours are characterized by their rapid growth and potential for metastasis, especially in the lungs. Treatment includes surgical resection, sometimes combined with adjuvant chemotherapy. Strict periodic checkups are essential, since local recurrence is frequent (between 19 to 31%), with most cases occurring within the first 24 months.
Intravitreal application of stem cells and their products does not ameliorate experimental autoimmune uveitis
Authors: Skrlova Eva , Uherkova Eva , Palacka Katerina , Hermankova Barbora , Holan Vladimir , Heissigerová Jarmila 
Published: January 2024

Aims/Purpose: Stem cell therapy has demonstrated potential therapeutic benefits in various medical disciplines. This study evaluated therapeutic effects of mesenchymal stem cells (MSCs) or their by‐products on intraocular inflammation in experimental autoimmune uveitis (EAU) model.Methods: EAU was induced in C57BL/6J mouse strain through administration of IRBP, Freund's adjuvant and pertussis toxin. Conditioned medium was procured through cultivation of MSCs in serum‐free medium, while MSC supernatant was obtained via MSC centrifugation and membrane removal. Either conditioned medium or MSC supernatant was intravitreally administered unilaterally, typically on day 14 post‐EAU induction. Ocular fundus of mice was documented regularly. Experiments were generally concluded on day 28, with eyes processed for FACS and PCR analysis. Infiltration of retina by inflammatory cells (F4/80, CD11c, CD45, CD80, CD86, CD206) and gene expression of pro‐inflammatory factors (Gfap, Iba‐1, IL‐1, iNOS) were quantified.Results: Across all experiments, clinical grading, FACS, and PCR analysis indicated exacerbation of intraocular inflammation. Post‐intravitreal administration of MSC by‐products into eyes with EAU, increased infiltration of retina by inflammatory cells and upregulation in gene expression of pro‐inflammatory factors were observed. These findings were corroborated in vitro, where co‐culturing of retina with EAU in presence of MSCs or their supernatant did not significantly reduce gene expression of pro‐inflammatory factors. Upsurge in pro‐inflammatory factors was also noted in control experiments on healthy eyes post‐intravitreal injection of no substance, serum‐free medium, PBS, or conditioned medium.Conclusions: No improvement in EAU was observed following application of MSC products, both in vivo and in vitro. Instead, inflammation was more severe. Trauma induced by intravitreal application itself significantly influenced outcome.Financial support: GA UK 309621, SVV UK 260631.
Role of corneal sensory nerves in tearing and blinking
Authors: Acosta M. Carmen 
Published: January 2024

The cornea is innervated trigeminal neurons classified in three different functional types: polymodal nociceptor, mechano‐nociceptor and cold thermoreceptor neurons. Corneal sensory nerves are responsible of the conscious sensations evoked by corneal stimulation, and are also involved in the trophic maintenance of the tissue. Besides, corneal nerve activity is also involved in the regulation of the protective functions of the ocular surface such as tearing and blinking.Regulation of reflex and basal tearing is integrated at the brainstem and, in both cases, under the influence of the sensory inflow provided by several types of corneal sensory nerves. While reflex tearing is induced selectively by the stimulation of corneal polymodal nociceptors, basal tearing rate depends on the spontaneous activity of cold thermoreceptors. Thus, when cold thermoreceptors are silenced by environmental warming, basal tearing is compromised.Voluntary, reflex and spontaneous (basal) blinking present differences in their characteristics and regulation mechanisms. Voluntary blinking depends on the direct instructions generated at the brain cortex, acting over the motor neurons located at the facial nucleus. Reflex blinking is integrated at the brainstem, being induced by the stimulation of the cornea and periocular skin, and even by loud sounds. Spontaneous blinking is claimed to be controlled by a CNS centre that established a blinking pattern. This pattern is modified under different conditions such as cognitive activity, being for example reduced during visual attentional tasks in order not to lose relevant visual information. When the activity of corneal cold thermoreceptors is abolished or reduced by ocular instillation of local anaesthetics, the frequency and characteristics of the spontaneous blinking is not modified. However, when the activity of cold thermoreceptors is increased for prolonged periods (for instance after topical instillation of F6H8 drops, which reduces the ocular surface temperature), blinking pattern become more regular and an increased number of blinks of larger the amplitude and shorter duration are induced. This increased blinking frequency produced when the activity of cold thermoreceptors is increased is sufficient to even counteract the reduction of blinking frequency induced during visual tasks performance. The increase in blink frequency driven by corneal cold thermoreceptors' activation may constitute a protective mechanism to prevent excessive desiccation of the ocular surface.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)
Glaucoma or not glaucoma? ‐ How to navigate problematic cases?
Authors: Smedowski Adrian 
Published: January 2024

Optic neuropathies refer to a group of eye conditions that involve acute or chronic damage to the optic nerve, which is responsible for transmitting visual information from the eye to the brain. The optic nerve is made up of millions of nerve fibres that can be affected by a variety of primary or secondary insults, leading to progressive neurodegeneration of optic nerve axons, being projections of retinal ganglion cells. The most common optic neuropathies that we should consider in differential diagnosis represent glaucoma, ischemic, inflammatory, toxic, hereditary, traumatic, and compressive optic neuropathies.Although the visual field test is one of the most basic and oldest diagnostic method in ophthalmology, it represents a sophisticated test that allows to differentiate ongoing pathology, based on features of observed scotomas. The specific features include localization, steepness, relativity and symmetry of visual field defects. By combining those features with clinical anamnesis, imaging techniques and electrophysiological data, properly used visual fields can be a powerful tool to provide patients and other medical specialists with further direction of diagnostic process and treatment. This course aims to provide a series of cases‐based analysis of different visual field results, to establish certain universal rules and to provide useful tips, how to diagnose difficult glaucoma cases using perimetry and how to rule out non‐glaucomatous neuropathies, allowing to speed up and to properly direct the diagnostic process.
Does the Eyesi direct ophthalmoscope increase interest in ophthalmology?
Authors: Flockerzi Elias , Deuchler Svenja , Abdin Alaa Din , Flockerzi Veronika , Löw Ursula , Flockerzi Fidelis , Koch Frank , Seitz Berthold 
Published: January 2024

Purpose: This study based on direct ophthalmoscopy (DO) teaching in medical curricula aimed to integrate both classic and simulator‐based DO techniques into the teaching of medical students.Methods: 110 medical students received a multiple‐choice questionnaire (four theory questions, six fundus photographs) prior to simulator‐based (EyeSi® Direct, Haag‐Streit Simulation, Germany) and classic DO training (Heine BETA®200, Heine Optotechnik GmbH, Germany). Simulator‐based DO training was performed in groups of up to eight students.Thereafter, they underwent an objective standardized clinical examination containing questions about (1) pupil dilation, (2) mydriasis contraindication, (3) ophthalmoscope adjustment and a practical test checking whether (1) optic nerve head, (2) macula, (3–6) upper/lower vessel arcade nasally versus temporally were identified correctly. Subsequently, classic DO was performed mutually and they reported the funduscopic structures they had recognized. Finally, the questionnaire was repeated 1 week later in combination with an evaluation of simulator‐based versus classic DO.Results: Students improved from an average of 4.0 ± 1.5/10 before to 8.8 ± 1.5/10 correctly answered questions after training (p < 0.0001, Wilcoxon matched‐pairs test). 87|34|61 students named pupil dilating time mydriasis contraindication and adjusted the ophthalmoscope correctly. They successfully identified the optic nerve head (n(simulator)|n(classic) DO: 110|68, p < 0.0001, Fisher's exact test), the macula (93|22, p < 0.0001), the upper (98|75, p = 0.0002) and lower temporal vessel arcade (101|91, p = 0.0672), the upper (84|56, p = 0.0001) and lower nasal vessel arcade (87|48, p < 0.0001). They wished for more simulator‐based training, indicated a higher interest in ophthalmology after training and stated an improvement of their ophthalmoscopy skills.Conclusion: A standardized simulator‐based approach improves medical students' skills in ophthalmoscopy and arouses professional interest in ophthalmology.
Simulator approaches in otorhinolaryngology ‐ Looking beyond the ophthalmological horizon
Authors: Flockerzi Veronika , Schick Bernhard , Flockerzi Elias , Berndt Sabrina 
Published: January 2024

Purpose: To improve medical students' learning of handheld otoscopy technique and findings based on a standardized simulator‐based procedure.Methods: A group of 120 medical students received a questionnaire containing 10 multiple choice questions (four theory questions, six pathological eardrum findings) prior to simulator‐based training (Earsi otoscope, Haag‐Streit Simulation, Germany) and classic otolaryngology internship without separate otoscopy training. Simulator‐based practical training was performed in groups of four students for 90 min with 40 students (“simulator group”) in addition to the classic otolaryngology internship (“control group”). After training, the students in the simulator‐group underwent an objective standardized clinical examination. Items assessed were (1) use of the correct hand, (2) correct handling of the otoscope, (3) stabilization of the otoscope with a finger, (4) pulling pinna upwards and backwards, (5) correct insertion depth, (6) atraumatic performance, (7) time required for task completion and (8) percentage of the assessed eardrum surface (cut‐off <85%). In addition, students were asked to draw the pathology shown during the examination (myringosclerosis, a whitish scar on the tympanic membrane) on a provided tympanic membrane sketch. The drawing was classified as “correct” or “incorrect” by a person uninvolved in the course. A maximum of eight points could be achieved. Students evaluated the simulator‐based otoscopy training afterwards. At the end of the otolaryngology internship, the questionnaire was repeated 4 weeks after the simulator‐based otoscopy training.Results: All participating students improved from an average of 4.5 ± 1.7/10 before otolaryngology internship to 6.4 ± 1.7/10 correctly answered questions after training. Looking at the two subgroups, it is noticeable that the students in the simulator group (7.1 ± 1.6/10) performed better than those without simulator‐based otoscopy training (6 ± 1.6/10). All students in the simulator group achieved good results in the objective standardized clinical examination (5.1 ± 1.4/8).The participating students rated the simulator‐based training mostly as “very good“. The students wished for more simulator‐based training and indicated higher interest in otolaryngology after training. Furthermore, they stated an improvement of their otoscopy skills and understanding of eardrum findings.Conclusion: A standardized simulator‐based approach improves medical students' skills in handheld otoscopy and arouses professional interest in otolaryngology.
The implantable miniature telescope (IMT) new developments: The US and UK experience
Authors: Levy Marc H. , Keegan David , Neffendorf James E. 
Published: January 2024

The Implantable Miniature Telescope (IMT) is a viable option for patients afflicted with decreased vision in both eyes (20/160 to 20/800) from the advanced form of dry age‐related macular degeneration. It has a 21‐year history of being both safe and effective. The IMT uses a Galilean telescope design that utilizes wide‐angle quartz micro‐optics when used in conjunction with the cornea to create a telephoto system that magnifies objects in view by 2.7X. This axial magnification allows central images to be projected onto healthy paramacular areas of the retina instead of the fovea alone, thereby reducing the central blind spot and allowing the patient to discern images that may have been previously unrecognizable or difficult to see. The IMT is both FDA approved and carries a CE mark. The FDA lowered the minimum age from 75 to 65 years of age, based on the 5‐year FDA data that showed slightly more visual improvement in younger patients than patients aged 75 years and older.Based on the UK experience, the FDA initiated an independent study on pseudophakic patients to monocularly exchange a posterior chamber intraocular lens for the 2.7X IMT, but unfortunately recruitment was inadequate to derive useful data. An injectable form of the IMT (SING) is currently being investigated in the US and UK which shortens the surgical time, incision length and capsulorhexis requirements. As the incidence of advanced age‐related macular degeneration increases due to the development of geographic atrophy, the IMT should be strongly considered in patients who are visually symptomatic in order to gain an increase of daily living.
Small extracellular vesicles derived from reactive microglia contribute to retinal neuroinflammation and neurodegeneration
Authors: Aires Inês Dinis , Boia Raquel , Ribeiro‐Rodrigues Teresa , Girão Henrique , Francisco Ambrósio António , Santiago Ana Raquel 
Published: January 2024

Glaucoma is a leading cause of blindness worldwide and is characterized by progressive degeneration of retinal ganglion cells and damage to the optic nerve. Elevated intraocular pressure is a main risk factor. Moreover, chronic neuroinflammation plays an important role in glaucoma. Microglia become reactive when challenged with elevated pressure, releasing cytotoxic factors that contribute to retinal ganglion cell death. We have been reporting that controlling microglia‐mediated neuroinflammation in experimental glaucoma is sufficient to protect retinal ganglion cells from damage.Small extracellular vesicles are constitutively released by most cells and are important vehicles of intercellular communication, conveying lipids, proteins and genetic material. Small extracellular vesicles derived from microglia exposed to elevated pressure trigger a pro‐inflammatory response in microglia, as determined by increased production of proinflammatory cytokines, microglia motility, phagocytosis, and proliferation. These small extracellular vesicles also increase cell death and impact the survival of retinal ganglion cells. The depletion of retinal microglia halt neuroinflammation induced by small extracellular vesicles isolated from microglia at elevated pressure, suggesting that microglial small extracellular vesicles preferentially interact with microglia. Small extracellular vesicles isolated from microglia challenged with elevated pressure are also enriched in proteins associated with inflammatory signalling and RNA processing and in miRNAs that modulate the NF‐kappaB pathway.This route of communication between microglia involving small extracellular vesicles helps to clarify the pathological mechanisms in glaucoma and may open new perspectives for the development of therapies targeting microglia neuroinflammation.Funding: FCT, Portugal (UID/NEU/04539/2019; UIDB/04539/2020; UIDP/04539/2020), COMPETE‐FEDER (FCOMP‐01‐0124‐FEDER‐028417; POCI‐01‐0145‐FEDER‐007440), Centro 2020 Regional Operational Programme (CENTRO‐01‐0145‐FEDER‐000008: BRAINHEALTH2020).
microRNAs as markers of congenital aniridia
Authors: Stachon Tanja , Nastaranpour Mahsa , Fries Fabian N. , Seitz Berthold , Amini Maryam , Suiwal Shweta , Ludwig Nicole , Szentmáry Nóra 
Published: January 2024

Subjects with congenital aniridia often develop aniridia‐associated keratopathy (AAK), which is related to limbal stem cell insufficiency. Loss of limbal epithelial stem cell function results in corneal inflammation and neovascularization, and several subjective symptoms. MicroRNAs (miRNAs) are approximately 22 nt long non‐coding RNA molecules capable of regulating gene expression at the post‐transcriptional level.It is of interest to investigate the expression of microRNAs and their possible effect on AAK development, as deeper understanding of their function in limbal epithelial cells could help in designing new therapeutic approaches of AAK.Previous studies verified deregulated miRNAs in conjunctival cells of aniridia subjects, among others miR‐204‐5p and miR‐7150, which are more deregulated in mild cases of AAK. In addition, numerous studies suggest that miRNAs regulate genes involved either directly or indirectly in inhibition or promotion of pathological angiogenesis of the cornea. Several pathways, including JAK–STAT, focal adhesion, Hippo, WNT and PI3K‐AKT signalling pathways, could potentially play a role. In limbal epithelial cells of aniridia subjects, deregulation of miR‐138‐5p may play a role, which is involved in the regulation of cell differentiation and migration and in Hippo, Wnt, Focal adhesion cAMP and p53 signalling pathways.
Retinal biomarkers in vascular occlusion
Authors: Makled Hebatalla 
Published: January 2024

Objective: To clarify the diagnostic and prognostic values of the biomarkers detected by multimodal imaging procedures as coloured fundus imaging, fluorescein angiography, near infra‐red imaging, fundus Autofluorescence, SD‐OCT, and OCT angiography to predict the prognosis and the response to therapy in retinal vascular occlusions (artery or vein).Recently, there has been an interest in determining the prognostic value of changes on optical coherence tomography (OCT) in retinal vein occlusion as it allows both quantitative and qualitative analysis of imaging biomarkers such as central retinal thickness, choroidal thickness, intraretinal hyper‐reflective foci (HRF), disorganization of the inner retinal layers (DRIL), external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption. Also classifying the intraretinal edema if sponge‐like or cystoid or serous retinal detachment (and detecting its height). Also signs of ischemia can be detected such as prominent middle limiting membrane (p‐MLM), paracentral acute middle maculopathy (PAMM), as well as hyperreflectivity of the inner retinal layers (HIRL) which is commonly seen in cases of acute retinal artery occlusion. Internal limiting membrane detachment (ILMD) which is a novel biomarker that can be detected in some cases of acute CRAO.OCT Angiography has added more information about the assessment of microvascular alterations, especially vessel density in the deep retinal vascular plexus, the foveal avascular zone and of areas with no capillary perfusion. Biomarkers of ultra‐widefield angiography, such as peripheral ischemia (ischemic index) and neovascularization are essential for retinal laser treatment decision.Finally, FAF has been a very useful tool in monitoring the disease progression and response to treatment.The speaker will present examples of multimodal imaging of different retinal biomarkers in retinal vascular occlusion that help in predicting the prognosis.
Improving transparency and corneal wound healing in rare diseases by promoting corneal nerve regeneration
Authors: Gallar Juana 
Published: January 2024

Corneal nerves play a crucial role in maintaining the integrity of corneal tissue, as well as the proper regulation of tearing and blinking. When activated, corneal nerves release locally several factors, including neuropeptides, that contribute to the trophic maintenance of corneal tissues. So that, the reduction or absence of corneal nerves led to impaired corneal wound healing in addition to a loss of sensory input, resulting in lack of sensitivity and alterations in tearing and blinking rate. Such consequences are seen clinically in several rare diseases where severe nerve deficit is a prominent factor such as in neurotrophic keratopathy, where the cornea spontaneously ulcerates due to its inability to renew the epithelium and to heal epithelial wounds, leading to loss of corneal transparency. An advanced molecular therapy to increase corneal nerve regeneration and support the corneal neurotrophic environment in such ocular rare diseases is proposed.(Supported by RESTORE VISION – 101 080 611, Horizon Europe Framework Programme, European Commission)
AI‐based studies using fundus images
Authors: Grzybowski Andrzej 
Published: January 2024

The artificial intelligence (AI)/deep learning (DL) algorithms were shown to detect diseases based on image analysis, including retinal diseases from fundus photos and optical coherence tomography (OCT) scans, lung diseases from chest radiographs, and skin disorders from skin photos. It was also shown that retinal photos can be used to identify risk factors related with cardiovascular disorders, including blood pressure, smoking and body mass index.The fundus picture was shown to source data for developing AI/DL algorithms detecting many ophthalmic diseases and pathologies, including diabetic retinopathy, diabetic macular edema, retinal artery and vein occlusion, macular hole, epiretinal membrane, AMD, glaucoma, retinopathy of prematurity, myopia, myopic macular degeneration, hyperopia, optic disc edema, optic nerve atrophy, central serous retinopathy, myelinated nerve fibres, and retinitis pigmentosa. Moreover, fundus pictures were also used to develop many AI/DL algorithms detecting non ophthalmic diseases and pathologies, including Alzheimer and Parkinson disease, risk of stroke, risk of cardiac infarction, systemic hypertension, chronic renal disease, peripheral arterial disease, and anaemia.