bluuebunny/crossref_metadata_2025_split huggingface dataset:
External testing of an established glaucoma screening AI on a glaucoma clinic population from Finland
Authors: Hemelings Ruben , Schmetterer Leopold , Stalmans Ingeborg , Tuulonen Anja 
Published: January 2024

Purpose: To assess the external performance of an existing deep learning regression model for glaucoma detection (G‐RISK) in a glaucoma clinic population from Finland.Methods: Colour fundus images were retrospectively collected from the Tampere University Hospital (Tays), Finland. Eyes that had a visit in 2019 or 2020 were included based on the availability of ground truth labels. Ground truth labels for glaucoma were obtained through clinical evaluation of the optic nerve head (ONH) from colour fundus photos, clinical evaluation of retinal nerve fibre layer (RNFL) defects from fundus photos imaged with a cobalt filter, and clinical evaluation of the SITA Fast visual field (VF) test. Glaucoma diagnosis at Tays followed the ‘2 out of 3 rule’ recommended by the Finnish Evidence‐Based Guideline for Glaucoma, which requires at least 2 positive indications of glaucoma tests for referral [1]. Preprocessed colour fundus images were used as input to a previously trained deep learning model (G‐RISK) [2]. Performance was evaluated using the area under the receiver operating characteristic curve (AUC), accompanied by 95% confidence intervals. Patient aggregated results were obtained by comparing the maximum of both prediction and ground truth label.Results: Over 3000 patients had at least one ground truth available for a visit in 2019 or 2020. Clinical evaluation of structural features (ONH, RNFL) triggered more glaucomatous symptoms than the SITA Fast VF test. When thresholding the AI prediction against a single ground truth type, the best AUC was obtained on the ONH label (0.90 [0.89–0.91]), followed by RNFL (0.84 [0.83–0.86]) and VF (0.83 [0.81–0.84]). When implementing the 2 out of 3 rule, AUC reached 0.88 [0.82–0.90].Conclusion: The model performed best when using the ONH label and incorporating the ‘2 out of 3 rule’, reaching an AUC of 0.88. These findings suggest that the G‐RISK model could be a valuable tool for screening in clinical practice.References1. The Finnish Medical Society Duodecim. Update of Current Care Guideline for Glaucoma. March 28, 2023.2. Hemelings, R., Elen, B., Barbosa‐Breda, J. et al. Deep learning on fundus images detects glaucoma beyond the optic disc. Sci Rep 11, 20 313 (2021).
Effects of primed adipose mesenchymal stem cell‐derived exosomes on immunomodulation in Behcet uveitis
Authors: Gözel Merve , Aydemir Ayse Dilara , Kaleli Humeyra Nur , Canbulat Zehra , Güleser Ümit Yaşar , Kesim Cem , Kızılok Billur Sezgin , Sahin Afsun , Uçar Didar , Hatemi Gülen , Hasanreisoğlu Murat 
Published: January 2024

Aims/Purpose: Exosomes of interferon‐gamma (IFN‐ γ) primed (IFN + Exo) and non‐primed (IFN‐Exo) adipose‐derived mesenchymal stem cells (AdMSCs) were studied for their possible significance in the therapy of Behçet Disease (BD) uveitis (BU).Methods: Adipose tissue was used to isolate AdMSCs. Characterization as well as multipotency investigations were carried out. Exosomes of AdMSCs were also identified and characterized. Lymphocytes were isolated from the peripheral venous blood of patients with BD uveitis (n = 15) and healthy controls (n = 15). AdMSCs were preincubated for 48 h with or without IFN‐ γ. Peripheral Blood Mononuclear Cells (PBMC) of BD uveitis patients and healthy controls were cultivated with exosomes separately for 72 h. Flow cytometry was used to assess lymphocyte proliferation, viability, and apoptosis after the culture period. Real‐time polymerase chain reaction (RT‐PCR) was used to assess the expression of interleukin‐10 (IL‐10), interleukin‐17 (IL‐17), transforming growth factor‐ β (TGF‐ β), and interferon‐ γ (IFN‐ γ).Results: In patients with BD uveitis, IFN + Exo inhibited lymphocyte apoptosis. IFN + Exo reduced the viability of BD uveitis T lymphocytes. Both exosomes also raised IL‐10 level as an anti‐inflammatory cytokine and decreased IL‐17, TGF‐ β, IFN‐γ levels as a pro‐inflammatory cytokine in BD uveitis patients' lymphocytes. However, exosomes were ineffective in stimulating T lymphocyte proliferation.Conclusions: Exosomes of AdMSCs stimulated with and without IFN‐ γ decrease the abnormal inflammatory response caused by BD uveitis PBMC. This study's findings have the potential to pave the road for MSC/exosome therapy in BD uveitis.
Bloody tears: A new option for early diagnosis of endometriosis
Authors: Huseva Yuliya 
Published: January 2024

Aims/Purpose: To investigate the cytological composition of tears to determine the potential diagnostic criteria of endometriosis.Methods: Tear samples obtained from the lower fornix of the conjunctiva using a glass capillary tube were examined by microscopy in 100 people: 60 healthy women who made up the control group and 40 patients with endometriosis.Results: The proportion of women with endometriosis, in whose tear erythrocytes were determined was significantly higher, 32.5%, compared with the control group ‐ 25.0%. In 69.2% of women with endometriosis, latent haemolacria was detected in the follicular phase of the menstrual cycle, which significantly exceeded the 30.8% of people with erythrocytes in tears detected in the luteal phase. Epitheliocytes were found in tears in 97.5% of patients with endometriosis versus 75.0% of healthy women, at the same time, in 100.0% cases, − in the follicular phase of the menstrual cycle, compared with 74.3% of healthy women in the same phase of the cycle. The proportion of women with epitheliocytes in the tear in the amount of “++” was 56.4%, which was significantly more compared to 20.0% of people from the control group with epitheliocytes in the same amount; at the same time, group accumulations of epitheliocytes were found in 15.0% of patients with endometriosis, which was significantly higher than in healthy women ‐ 8.3%. In 90.0% of cases in the group with endometriosis, glandular cuboidal epithelial cells were found in the tear, morphologically resembling endometrial cells.Conclusions: The revealed features of the cytological composition of tears in patients with endometriosis, which differed from those in the control group, reflected certain links in its etiopathogenesis, so the study of tear parameters can be useful for predicting the prevalence of “endometrioid disease” and developing pathogenetically substantiated treatment.
Promising preclinical efficacy of intravitreally administered tafasitamab and anti‐Hu CD199 on immunocompetent murine model of primary intraocular lymphoma
Authors: Skrlova Eva , Uherkova Eva , Klimova Aneta , Malarikova Diana , Svozilkova Petra , Matous Petr , Herynek Vit , Kucera Tomas , Klener Pavel , Heissigerova Jarmila 
Published: January 2024

Aims/Purpose: This project aimed to evaluate the efficacy of anti‐CD19 monoclonal antibody tafasitamab and experimental chemokine receptor blocker anti‐Hu CD199 and to study the impact of the microbiome on immunotherapy in an experimental immunocompetent murine model of primary intraocular lymphoma (PIOL).Methods: PIOL was induced in immunocompetent mice BALB/CaNn by intravitreal injection of syngeneic lymphoma A20‐CD19 cell suspension. To eliminate intestinal microflora, 50% of the mice were pre‐treated with broad‐spectrum antibiotics (metronidazole and ciprofloxacin). On days 3 and 7, mice were treated intravitreally either with tafasitamab (20 μg) or anti‐Hu CD199 (1 μg). Following the injection mice were monitored clinically 2 times per week. The experiment was terminated at the first signs of exophthalmos or on day 30. Eyes were collected post‐mortem and histologically processed.Results: In both treated groups the signs of PIOL were delayed in comparison to the control group. The untreated group started to show signs of PIOL on day 7. In the group treated with tafasitamab first signs of PIOL started to appear on days 10–14. In the group which received experimental anti‐Hu CD199, signs of PIOL first appeared on day 17. Development of exophthalmos was delayed as well, most significantly in the group treated with anti‐Hu CD199. So far, we did not observe statistically significant differences in PIOL behaviour and the effect of the treatment between the group with the intact microbiome and the group treated with antibiotics.Conclusions: Results of in vivo experiments confirm the efficacy of both tafasitamab and experimental anti‐Hu CD199 administered intravitreally in immunocompetent mice with PIOL. However, experimental chemokine receptor blocker anti‐Hu CD199 shows greater potential in the intravitreal treatment of PIOL.Financial support of this project: AZV MZ CR NU20‐03‐00253, SVV UK 260631.
Developing gene‐independent approaches for retinal dystrophies
Authors: Sahel José‐Alain 
Published: January 2024

Inherited retinal dystrophies (IRDs) display remarkable genetic heterogeneity, with over 300 retinal disease genes mapped and/or identified. Profound vision loss and blindness, often from birth, is a common occurrence in these clinically heterogeneous disease conditions. The therapeutic options for IRDs are currently very limited but recent advancements in understanding mechanisms of retinal degeneration and technological progress paved the way towards development of novel therapies. Much progress has been made in moving from gene discovery to gene therapy. However, the genetic heterogeneity of IRDs represents a significant challenge for development of gene therapy.Many studies from our group have demonstrated that the survival of cones (responsible for diurnal and high‐resolution vision) depends on the presence of rods (responsible for vision at low light levels) that secrete a diffusible trophic factor identified as rod‐derived cone viability factor (RdCVF). The discovery of RdCVF, of its receptor and mechanism of action, and the demonstration of its mutation‐independent therapeutic potential in several animal models of IRDs paved the way to the development (with the start‐up company Sparing Vision) of RdCVF neuroprotective gene therapy that entered in clinical trial in 2023.IRDs destroy photoreceptors but leave intact and functional a significant number of inner retinal cells. Using viral vectors, light‐sensitive microbial opsins can be expressed in these remaining cells, making possible their conversion into ‘artificial photoreceptors’. Our group in Paris, together with Botond Roska (IOB, Basel) and the biotech company GenSight, demonstrated that this technology, named optogenetics, can restore vision in secondary retinal neurons which can survive years after the degeneration of photoreceptors. Our groups established the foundation for the first‐in‐man clinical trial (NCT03326336) with the photoactivatable optogene ChrimsonR (developed by Ed Boyen at MIT) delivered in the eye via adeno‐associated viral vectors and electronic goggles to intensify the light and provide adaptation. We demonstrated (Nat Med 2021) that optogenetics is a remarkably effective way to restore partial vision and provide useful vision restoration in blind people.Gene‐independent approaches such as neuroprotection and optogenetics would allow for the treatment of a broad spectrum of retinal dystrophies, even at advanced stages of disease, giving hope for vision rescue and vision restoration to approximately 2 million people with IRDs worldwide.
Corneal sensory nerve function: An overview
Authors: Gallar Juana 
Published: January 2024

Somatosensory innervation of the cornea is provided by the peripheral axons of a small number of primary sensory neurons located in the ophthalmic region of the trigeminal ganglion. Corneal sensory nerve fibres are heterogeneous and may express different neurotransmitters and ion channels involved in transduction and coding of the stimuli acting on the tissue. Based on their activation by one or several types of physical and chemical stimuli, corneal nerve fibres are classified as polymodal nociceptors, mechanonociceptors and cold thermoreceptors. Impulse activity originated at corneal sensory nerves reaches second‐order neurons located at the lower brainstem, from where sensory information travels to the contralateral posterior thalamus and, then, to the brain cortex.After processing, the activation of the different classes of corneal neurons results in different sensations that depend on the type of primary sensory neuron initially activated by the stimulus, although pain is the main sensation elicited by corneal stimulation. Sensations originated at the cornea are explored by esthesiometry, allowing to quantify the threshold, intensity and quality of the evoked sensations. Sensitivity of the ocular surface is reduced with age and altered by several pathological processes that affect sensory innervation, either ocular (such as allergic keratoconjunctivitis, infectious keratitis, eye surgery, hereditary corneal dystrophies, dry eye, etc.) or systemic diseases, such as diabetes and peripheral neuropathies.A prominent feature of ocular nociceptors is their sensitization by the inflammatory mediators released after noxious stimulation or tissue injury, while cold thermoreceptor activity is inhibited by inflammatory substances. Both the spontaneous and the stimulus‐evoked activity increases in sensitized nociceptors, which causes sustained pain and hyperalgesia. After corneal sensory nerves damage (produced as a consequence of an ocular or systemic disease, or by accidental or surgical injury), part of sensory nerves degenerates leading to reduced sensitivity to natural stimulation in the affected area. At the same time, axons start to regenerate and to recover the ability to transduce and encode the stimulus. During this regeneration process, cold thermoreceptor and nociceptor nerves may become hyperexcitable due to changes in their expression/activity of ion channels, which give rise to dryness sensation and ocular neuropathic pain.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)
Why Gonioscopy remains essential in the time of anterior segment OCT
Authors: Hommer Anton 
Published: January 2024

Beside the examination of optic nerve head and retinal nerve fibre bundles, gonioscopy is the most important examinations we have to perform when performing structure analysis.The differentiation of angle closure, angle closure suspect and open angle is essential not only for the correct diagnosis, but as well to draw the best therapeutic consequences out of these findings.In addition to grading systems that help us to classify the types of glaucoma, we can find pathological changes like abnormal vessels, inflammatory induced changes, pigmentations, clefts etc. that help us to make the right diagnosis and therapy.Nowadays As‐OCT is a big help and makes it a lot easier, but there are still essential deficits, that do not allow to replace gonioscopy by this new examination.In the presentation we will show, what we can see in normal and pathological eyes and which findings can be seen in AS‐OCT and which ones cannot been seen.
Neuro‐vascular coupling as a potential biomarker
Authors: Garhöfer Gerhard 
Published: January 2024

Neuro‐vascular coupling is a physiological key feature of neural tissues to adapt its blood flow to local metabolic demands. It has been shown that also in the human retina neurons, glia cells and blood vessels are closely coupled. As such, increased retinal neural activity, induced for example by visual stimulation, leads to an immediate increase in blood flow in the optic nerve head as well as in the retinal vasculature.Because of its optical properties and its easy accessibility, the eye offers a unique possibility to non‐invasively investigate neuro‐vascular coupling in humans. The current talk aims to summarize how the role of neuro‐vascular coupling and its potential applications in the diagnosis and follow up in systemic and ocular diseases.
Medical students' learning experience with the Eyesi slit lamp simulator
Authors: Deuchler Svenja , Dail Yaser Abu , Koch Frank , Büdel Claudia , Ackermann Hanns , Flockerzi Elias , Seitz Berthold 
Published: January 2024

Introduction: Simulation technology is constantly improving medical education in various fields. In ophthalmology, simulation is already successfully used to teach conservative and surgical skills. In 2022, the Eyesi slit lamp simulator was introduced for the first time, allowing students to learn various examination techniques and ocular pathologies. This study describes medical students' learning experience.Methods: In this exploratory study, 50 medical students without previous experience with slit lamp examination were selected. Each student then had two training sessions, one with the classic slit lamp and one with the Eyesi slit lamp simulator. At the end of the training, students compared their learning experiences in the two sessions using a questionnaire.Results: The simulator course was considered useful for learning slit lamp examinations (p = 0.05). Slit lamp simulator was particularly beneficial for learning ocular pathologies (p = 0.03), as these were constantly available and systemically presented without the need of direct contact with patients. On the other hand, examination of a healthy eye was judged to be better learned (p < 0.001) by reciprocal examination with the real slit lamp.Conclusion: The Eyesi slit lamp simulator provides a structured and promising learning experience. Thanks to the growing library of modelled clinical cases, ocular pathologies can be learned in situations similar to everyday life without the need for patients to be present, allowing students to learn at their own pace and ask questions without being shy in front of patients.
Vitreoretinal complications of uveitis: The role of vitrectomy
Authors: Vakalis Athanasios 
Published: January 2024

The scope of vitreoretinal intervention in patients with uveitis has recently expanded. Therapeutic vitrectomy is performed to address complications such as visual loss from vitreous opacities, retinal detachment, development of epiretinal membranes, hypotony and in certain cases to remove confined infective foci and assist in sustained drug delivery and diagnosis.While a plethora of studies report favourable outcomes of PPV in the management of uveitis, the quality of data remains poor, with a paucity of standardized reporting and limited prospective data.We will discuss our own experience and review the literature on each of the above surgical indications.
Retinal oximetry in vascular diseases
Authors: Šín Martin 
Published: January 2024

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of haemoglobin. The imaging technology is non‐invasive and reproducible with remarkably low variability on test–retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic disease. The aim of this presentation is review of state of the art knowledge of us of retinal oximetry in vascular diseases and its possible clinical application.In diabetic retinopathy, retinal venous oxygen saturation is elevated and arteriovenous difference progressively reduced in advanced stages of retinopathy compared with healthy persons. This correlates with pathophysiology of diabetic retinopathy where hypoxia stimulates VEGF production. Laser treatment and vitrectomy both improve retinal oximetry values, which correlate with clinical outcome. The oximetry biomarker may allow automatic measurement of severity of diabetic retinopathy and predict its response to treatment.Central retinal vein occlusion is characterized by retinal hypoxia, which is evident in retinal oximetry. The retinal hypoxia seen on oximetry correlates with the extent of peripheral ischemia, visual acuity and thickness of macular oedema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia.Retinal oxygen metabolism is altered in uveitis associated with VKH disease. Oxygen saturation profile is abnormal in acute uveitic phase of the disease and returns to normal in those who recover with normal fundus appearance, but not in eyes that suffer permanent anatomical damage with “sunset glow fundus” and chorioretinal atrophy. Retinal oximetry may be of value in evaluating vascular and metabolic aspects of posterior uveitis.
No dye, no glory: FFA and ICGA in uveitis
Authors: Gonzalez‐Lopez Julio J. 
Published: January 2024

Uveitis is a potentially sight‐threatening condition characterized by inflammation of the uvea. Accurate diagnosis of uveitis is crucial for appropriate management and preservation of vision. The diagnosis of uveitis can be challenging due to the overlapping clinical features with other ocular diseases. In this context, imaging techniques such as fluorescein angiography (FA) and indocyanine green angiography (ICGA) have become indispensable tools in the differential diagnosis of uveitis.FA is a widely used imaging modality in the diagnosis and management of uveitis. It involves the intravenous injection of fluorescein dye, which highlights the blood vessels of the retina and choroid. FA can reveal the presence of leakage, staining, and non‐perfusion areas in the retinal and choroidal vasculature, which are indicative of the inflammatory process in uveitis. Moreover, FA can detect complications such as occlusive vasculitis or choroidal neovascularization. FA can also be used to monitor the response to treatment and detect complications of uveitis such as cystoid macular oedema.ICGA is another imaging modality that complements FA in the diagnosis of uveitis. ICGA involves the intravenous injection of indocyanine green dye, which better highlights the choroidal vasculature. ICGA can identify areas of choroidal hypoperfusion, which are often seen in posterior uveitis such as Vogt‐Koyanagi‐Harada disease or Birdshot retinochoroiditis. ICGA can also delineate areas of choroidal neovascularization. Furthermore, ICGA can help differentiate between active and inactive uveitis, which is crucial in determining the appropriate course of treatment.In addition to their diagnostic value, FA and ICGA can provide valuable information on the pathogenesis of uveitis. FA and ICGA can reveal the presence of subclinical inflammation in asymptomatic patients, which can guide the early initiation of treatment and prevent irreversible damage to the retina and choroid. Additionally, FA and ICGA can identify the location and extent of inflammation in uveitis, which can help in the selection of appropriate treatment modalities such as corticosteroids, immunomodulators and biologic agents.In conclusion, FA and ICGA are invaluable tools in the differential diagnosis and management of uveitis. These imaging modalities can provide vital information on the presence, location and extent of inflammation in uveitis, which can guide the selection of appropriate treatment modalities and prevent irreversible visual loss.
Managing challenging paediatric vitreoretinal disease
Authors: Salvanos Panagiotis 
Published: January 2024

Purpose: Vitreoretinal diseases in the paediatric age group carry significant visual morbidity. We present current vitreoretinal techniques for restoring normal visual potential in these challenging cases.Materials and Methods: Selected challenging paediatric vitreoretinal cases operated upon from September 2020 to September 2023 were included. Operative techniques used were analysed based on disease pathophysiology, surgical indication and timing, anatomical and visual outcomes.Results: A total of 32 eyes from 23 patients were included. Diseases included ROP, FEVR, PFV, Coats disease, congenital cataract complications, retinal detachment from optic disc coloboma, morning glory anomaly, X‐linked retinoschisis and expulsive haemorrhage. A thorough understanding of embryological disease origins, surgical anatomy in this age group, as well as pathophysiology of the selected disease entities are essential. Surgical techniques that were found to offer advantages are presented.Conclusions: Children's age, surgical timing and operative methods are important for visual prognosis.