bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resilience and neuroprotection: The efficacy of saffron Repron® in counteracting the progression of inherited retinal degeneration
Authors: Piano Ilaria , Corsi Francesca , Galante Alessia , Bisti Silvia , Gargini Claudia 
Published: January 2024

E‐mail: ilaria.piano@unipi.it.Retinal diseases can be induced by several factors, including genetic mutations, environmental stresses, and dysmetabolic processes. The result is a progressive loss of visual function, that can leading to total blindness. Among the diseases still orphaned of an effective therapy for slowing retinal degeneration is Retinitis Pigmentosa (RP). RP is one of the inherited retinal degenerative diseases (IRDs) whose cause is attributed to genetic mutations mainly at the level of rod‐specific genes. To date, about 150 mutations out of 60 different genes have been identified.Several therapeutic strategies are being investigated, although the results are still mostly unsatisfactory and limited to specific diseases, particularly in the case of gene therapy, which is applicable only to specific mutations and therefore not applicable on a large scale. Most of the proposed treatments have been tested in animal models, but few have progressed to human clinical trials. An important approach is to identify targets at the level of those mechanisms that are in common in all forms of RP and that drive disease progression, such as stress‐oxidative and inflammation that all together are known as oxinflammation. Here we provide data showing that in RP natural compounds are effective in slowing down the progression of the disease mainly counteracting oxinflammation. Specifically, saffron “Repron” was proved to be effective in AMD and Stargardt patients as well as in pre‐clinical models both “in vitro” and “in vivo.” We tested this treatment in a IRD model. Preliminary obtained in an animal model of RP (rd10 mice) where saffron treatment was able to slow down even the degeneration of rod due to a genetic mutation. In this study, the treatment began in rd10 pregnant females and continued throughout the weaning phase and then in pups that had become autonomous. Functional, immunohistochemical, molecular biology and biochemical analyses were performed at multiple time points from P20 to P120. The results obtained show a protective effect of saffron on both retinal function and morphology, opening a prospect of preventive treatment for those inherited diseases whose progression is known.
Pellino‐2 and NLRP3 inflammasome activation in corneal disease
Authors: Cristea Ileana 
Published: January 2024

Inflammation is a common factor in disease development of several corneal diseases. While a successful inflammatory response can clear an infection, eliminate a trigger, and repair tissue damage, it has also been shown that persistent antigenic stimulus, autoimmunity, long term exposure to irritants or a faulty inflammatory response can lead to chronic inflammation. The consequences of such chronic inflammation can be tissue damage, misdirected and incomplete wound repair, and can be accompanied by ingrowth of new blood vessels.Well‐regulated NLRP3 inflammasome activation has been shown to have protective effects against keratitis and corneal neovascularization. In contrast, abnormal activation of the NLRP3 inflammasome has been seen in acute glaucoma, age‐related macular degeneration, uveitis and Behcet's syndrome, as well as in hereditary, monogenic diseases, such as keratitis fugax hereditaria.A common trigger for NLRP3 inflammasome activation, upon treatment with various NLRP3 stimuli, is the efflux of cytosolic potassium (K+). We have recently shown that the E3 ubiquitin ligase Pellino‐2 changes intracellular localization following K+ efflux from immune cells and colocalizes with NLRP3 in activated macrophages, suggesting that Pellino‐2 is essential for mediating the effect of K+ efflux on NLRP3 inflammasome activation. Hyperactivation of the inflammasome has been linked to the formation of keloids as well as the development of corneal neovascularization.Here the implications of the NLRP3 inflammasome activation in innate immune cells will be discussed, and how an overactivated inflammasome contributes to corneal disease development.
Retinal biomarkers in diabetic macular edema
Authors: Elsanabary Zeinab 
Published: January 2024

Objective: To clarify the prognostic value 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 response to therapy in different retinal diseases as diabetic macular edema.Recently, there has been an interest in determining the prognostic value of changes on optical coherence tomography (OCT) such as foveal intraretinal cysts and edema, including size and location, presence of subretinal fluid (SRF), sub‐RPE fluid, subretinal hyper‐reflective material, intraretinal hyper‐reflective foci, photo‐receptor integrity and vitreo‐retinal interface.OCT Angiography has added more information about the precise areas of capillary non‐perfusion, presence of collaterals or retinal/optic nerve head neovascularization, and abnormalities of the FAZ. It can also differentiate between IRMA and neovessels.Finally, FAF has been studied recently in Diabetic Macular Edema, which may help to monitor the disease progression and response to treatment.The speaker will present examples of multimodal imaging of different retinal biomarkers in diabetic macular edema that help in predicting the prognosis.
Corneal degenerations
Authors: Modis László 
Published: January 2024

The concept of degeneration means that previously intact tissues are slowly and gradually deteriorating, often to the point where they cannot perform their function properly. As their aetiology is not uniform, their clinical manifestations are also very diverse. The same is true for corneal degenerative conditions. Corneal degeneration may involve deposition of certain substances, thinning of the tissue, vascularization, or a combination of these. What distinguishes them from corneal dystrophies is that they are not hereditary, are often unilateral, and their morphology and localization are much less regular.Corneal degeneration may be peripheral and/or central, superficial and/or deep. It may be primary or secondary according to its origin. They can be grouped in several ways. In origin, they may be (a) age‐related, (b) may develop at the base of other corneal or eye diseases (c) may be the consequence of systemic diseases. (d) may also be caused by drugs and toxins. In many cases the aetiology is obscured. Environmental factors, ultraviolet radiation and oxidative stress are also thought to play a role.Proper diagnosis is essential in choosing effective treatment strategy and thus achieving positive clinical results. When corneal degenerations significantly affect visual acuity, the treatment should aim relieving the primary disease before inducing further changes in the cornea.
The newest IC3D classification of corneal dystrophies
Authors: Seitz Berthold , Lisch Walter 
Published: January 2024

In the year 2015, the International Committee for the Classification of Corneal Dystrophies (IC3D) incorporated new clinical, histopathologic, and genetic information into the former 2008 classification. To this end, the IC3D sighted and evaluated worldwide peer‐reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this information, corneal dystrophy templates including categories 1 to 4 and anatomic classification were updated. New clinical, histopathologic, and confocal photographs were added.On the basis of revisiting the cellular origin of corneal dystrophies, a modified anatomic classification was proposed consisting of (1) epithelial and subepithelial dystrophies, (2) epithelial‐stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial dystrophies. The entity “Epithelial recurrent erosion dystrophies ERED” actually includes a number of potentially distinct epithelial dystrophies (Franceschetti corneal dystrophy, Dystrophia Smolandiensis, and Dystrophia Helsinglandica) but must be differentiated from dystrophies such as TGFBI‐induced dystrophies, which are also often associated with recurrent epithelial erosions. The chromosome locus of Thiel‐Behnke corneal dystrophy is only located on 5q31. The entity previously designated as a variant of Thiel‐Behnke corneal dystrophy on chromosome 10q24 may represent a novel corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is most likely only an autosomal recessive disorder. The so‐called autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to continue to be considered a unique corneal dystrophy. On review of almost all of the published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1). Anterior segment OCT has emerged as a helpful tool to reveal in vivo features of several corneal dystrophies that previously required histopathologic examination in order to definitively diagnose them.This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophies that more accurately classifies TGFBI dystrophies affecting multiple layers rather than being confined to one corneal layer. At this time, a 3rd edition of the IC3D classification of corneal dystrophies is under way.
Management of glaucoma in patients with ocular surface disease
Authors: Cvenkel Barbara 
Published: January 2024

Glaucoma and ocular surface disease (OSD) are common diseases in the elderly population. As the prevalence of both conditions increases with age, they often occur together and can present in a spectrum of disease ranging from mild to severe.The management of glaucoma in patients with OSD is challenging, especially when the treatment of glaucoma, for which topical medications are usually the first choice, can further compromise the ocular surface and exacerbate the signs and symptoms of dry eye disease. In patients with glaucoma and co‐existing ocular surface disease, both need to be treated, depending on the severity of each disease and the likelihood of loss of visual function. Frequent visual field testing is required to monitor and assess the progression of glaucoma. In patients with OSD, the visual field is often unreliable and makes it difficult to diagnose and detect the progression of glaucoma.In early to moderate open‐angle glaucoma or ocular hypertension, selective laser trabeculoplasty is a good option for initial treatment as it delays the need for topical treatment. In advanced disease, the lowest number of preservative‐free eye drops should be prescribed, or glaucoma surgery should be performed.
7‐methylxanthine for myopia control in Denmark – Clinical results 2003–2023
Authors: Trier Klaus 
Published: January 2024

In 2009, the Danish Medicines Agency authorized the use of pharmacy‐compounded 7‐methylxanthine (7‐MX) tablets for treatment of progressive myopia in children. 7‐MX has since been prescribed to more than 1200 individuals with no reports of adverse effects. A high compliance rate has demonstrated that the concept of using an oral pharmaceutical to control myopia progression is feasible.
Analysis with the use of linear mixed models of longitudinal data from 711 children aged 7–14 years and with less than 10 diopters (D) of myopia at baseline has shown that myopia progression and axial eye growth is linearly associated with the average daily dose of 7‐MX taken during the observation period.
Linear regression of data from 350 children aged 7–10 years at baseline who completed 3 years of follow‐up suggest that the absolute reduction of myopia progression and axial growth over 3 years associated with taking 400 mg three times daily is approximately 1.2 D and 0.35 mm, regardless of baseline myopia.
Linear regression of data from 157 children aged 7–10 years at baseline who completed 5 years of follow‐up suggest that the absolute reduction of myopia progression and axial growth over 5 years associated with taking 400 mg three times daily is approximately 1.8 D and 0.62 mm.Thus, the efficacy of 7‐MX does not seem to decrease with duration of treatment.
Negative eye growth (eye shortening) of 0.05 mm or more in children taking an average daily dose of 640 mg or more occurs in 1% of children aged 6–9, 3% of children aged 10–13, and 8% of children aged 14–15 at baseline. The largest eye shortening found was in a 6‐year‐old child with an initial myopia of −7.125/−7.75 diopters (D) and axial length of 26.07/26.29 mm who took an average dose of 1152 mg 7‐MX per day. After 1 year, the myopia was reduced to −5.5/−5.75 D and the axial length reduced to 25.77/25.94 mm.
7‐MX does not seem to induce thickening of the choroid and may therefore work by another mechanism than other myopia control interventions. Preliminary data suggest that the effects of 7‐MX and other myopia control methods are additive.
In conclusion, based on 20 years of clinical experience in Denmark, 7‐MX shows promise as a non‐toxic, side‐effect free, oral myopia control pharmaceutical, suitable for use as a supplement when myopia progression cannot be completely arrested by monotherapy with low‐dose atropine or an optical device.
Overview of biomarkers in vitreoretinal conditions
Authors: Panos Georgios 
Published: January 2024

Biomarkers are measurable indicators that can be used to diagnose diseases or monitor their progression. In vitreoretinal conditions, biomarkers can be found in various structures of the eye, including the retina, vitreous, and choroid.One of the most commonly used biomarkers in vitreoretinal conditions is visual acuity, which is a measure of how well a person can see. Other biomarkers include imaging techniques, such as optical coherence tomography (OCT) and fundus photography, which can provide detailed images of the retina and vitreous.In addition to structural biomarkers, there are also functional biomarkers that can be used to evaluate visual function, such as contrast sensitivity and visual field testing. These measures are often used to monitor the progression of diseases such as macular degeneration and diabetic retinopathy.Recent advances in biomarker research have led to the discovery of new markers for vitreoretinal conditions, including genetic markers, inflammatory markers, and metabolic markers. These markers may provide new insights into the underlying mechanisms of disease and may help to identify new therapeutic targets.Overall, biomarkers are an important tool in vitreoretinal conditions for the diagnosis, monitoring, and management of a wide range of ocular diseases. They may also help to improve our understanding of these conditions and facilitate the development of new therapies.
Modulation of steroid pathway to preserve corneal transparency
Authors: Behar‐Cohen Francine , Rodrigues‐Braz Daniela , Gélizé Emmanuelle , Bourges Jean‐Louis , Zhao Min 
Published: January 2024

Purpose: Corneal neovascularization (CN) is a major cause of blindness worldwide. We previously showed that endothelial mineralocorticoid receptor (MR) contributed to CN in mice. In this study, we investigated the mechanisms of action of MRA in a rat model of limbal deficiency.Methods: CN was induced in Lewis rats by total corneal de‐epithelialization and limbal scratching. Spironolactone (SPL, 25 mg/kg) or eplerenone was administered daily. Control eyes received vehicle. Rats were euthanized at day 3 and 7, and corneas were dissected for transcriptomic analysis. Proteins extracted from corneas at day 7 were used for western blot. Corneal innervation was evaluated by immunostaining of TUBB3 on corneal flat mounts at day 16. Corneal morphology and CN were assessed in vivo by Micron III optical coherence tomography and fluorescein angiography at day 14.Results: MR antagonists (MRA) favoured epithelial regeneration and nerve growth, reduced corneal angiogenesis, edema and inflammation in a rat model of CN. Transcriptomic analysis showed 75 differentially expressed genes in SPL groups. Gene set enrichment analysis highlighted pathways including wound healing and differentiation, inflammatory and immune responses, hypoxia, angiogenesis and neuroprotection. SPL upregulated Dcn, Col1a1, Timp2 and downregulated Lrg1 at day 3, and induced Pedf at day 7. Increase in DCN protein by SPL was confirmed by western blot.Conclusions: MRA regulates genes/proteins involved in anti‐inflammatory and anti‐angiogenic processes, and improves corneal re‐innervation in CN model. Dcn is one of the downstream regulated targets.
Ophthalmic evaluation of a population simulated with AI: Epidemiology and future disease trends
Authors: Poschkamp Broder , Stahl A. 
Published: January 2024

The development of AI models for the diagnosis of diseases in Ophthalmology is accelerating rapidly. These models, however, mostly refer to a single or only a few diseases. In addition, only a few examination techniques are considered in a given model. For example, many current AI models only consider fundus images for their diagnosis. Thus, general clinical information that is also available about a patient is often neglected. This information includes, for example, age, sex and secondary diagnoses.In most cases, diseases have different frequencies depending on age and sex. This leads to a different a priori probability for a disease diagnosis depending on the patient's age. When considering several diseases in one model, this class imbalance must be considered in the model. Large longitudinal data sets of disease histories of individual persons are rare or under high data privacy requirements.With the aim of more holistic AI models that include multiple diagnoses, a novel AI model was developed that is able to simulate longitudinal disease histories of individual (synthetic) patients. This was made possible based on data from the German Federal Statistical Office and a newly developed AI algorithm. In this present study, the model is used to simulate different diagnoses of the German population that lead to inpatient hospital admissions. The data were generated as completely synthetic data and have no data privacy requirements. Information on epidemiology and disease incidence can be derived from this model. Furthermore, it is possible to generate forecasts about future hospital admissions and their underlying diagnoses by extrapolating the model into the future.
Evaluating the neuroprotective potential of MSC secretome for retinal neurodegenerative diseases
Authors: Fernandez‐Bueno Ivan 
Published: January 2024

Retinal neurodegenerative diseases (RND), including age‐related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and others, are the most common cause of irreversible low vision and blindness. Although the aetiology and clinical characteristics of retinal RND can differ phenotypically, the neurodegenerative mechanisms of these diseases share common cellular and molecular signalization pathways. No cures are available for most RND, and cell‐based therapy may be a potential treatment through the paracrine properties of mesenchymal stromal cells (MSC). Furthermore, developing cell‐free compositions based on the production of “MSC secretome cocktails” is a promising therapeutic strategy and has significant advantages over using living cells in clinical practice.Ex vivo neuroretina models are adequate tools for evaluating retinal physiology and pathobiology. Neuroretina explant cultures closely resemble in vivo conditions, thus, preserving complex in vivo neuronal connections and retaining the functionality of non‐neuronal cells of the retina. Furthermore, cellular and molecular biology techniques can be applied to retinal explant cultures.In the ex vivo spontaneous neuroretinal degeneration model, the MSC secretome preserves retinal morphology and limits pro‐apoptotic‐ and pro‐necroptotic‐related genes and protein expression. Furthermore, the MSC secretome modulates autophagy‐related genes and proteins and stimulates the activation of antioxidant‐associated genes. Therefore, the neuroprotective ability of the MSC secretome is associated with the inhibition of apoptosis and necroptosis, modulation of autophagy, and activation of the antioxidant machinery during retinal degeneration.MSC secretome shows neuroprotective properties and the potential to modulate retinal responses to neurodegeneration, thus reinforcing the idea that MSC secretome may be a therapeutic strategy for treating RND.
Induced pluripotent stem cells as tool for cornea study in regenerative medicine
Authors: Balmer Pierre 
Published: January 2024

Induced Pluripotent Stem Cells technology as tool for cornea study in regenerative medicine.The ocular surface consists of an epithelial surface with specialized regions, including cornea lacrimal gland and conjunctiva. Altogether, these regions play a role in vision maintenance by transmitting light and, as first eye layer, ensure protection for the whole eye.These major roles are subject to defective developments or imbalanced maintenance, due to genetic variants or cellular degeneration, respectively, causing vision‐related problems. Intensive research is performed world‐wide to develop new therapies for such vision defects by using in vitro models, but lack of eye donations or low viability is an obstacle for such assays. At the same time, variability among donors on their genetic or epigenetic background is the main barrier for reproducibility, in addition to advanced age of donor, which is a factor limiting cell expansion or present a high number of senescent cells.A promising approach is to use stem cells to generate ocular surface cells or tissue, by mimicking the embryo development. It exists multiple sources of stem cells able to in vitro models, adult corneal cells isolated from biopsies have the advantage to resemble the organ source, but the collection has the disadvantage to be invasive. An alternative and highly valuable approach to generate organoid is from pluripotent stem cells, carrying the potential to differentiate into most cell types of the body and are subdivided into embryonic stem cells, derived from the inner cell mass of preimplantation embryos, and induced pluripotent stem cells (IPSCs) reprogrammed from adult cells.As IPSCs are one of the most promising approaches to counteract this lack of donations, several assays were performed to select the best conditions to generate cornea cells. The main goal is to characterize the developmental procedure by growth factors modulation and assess the maturation degree for the final product. The most important aspect to generate such final product is the heterogeneity of cell population during differentiation or maturation, as epithelial cornea layer has a different cell origin in comparison to stroma or endothelial cornea.Once differentiation and maturation are achieved, this in vitro model can be used for multiple downstream applications. As therapeutic approaches, organoids can be used as a living biobank or to model corneal diseases, either by using cells from affected patients or by base editing, introducing a causative mutation into the genome. Either patient‐derived or control organoids have the high potential to develop gene therapy, optogenetics, be a source of transplantable cells to replace generating tissue or screen small molecules treatments.For this topic, we will focus on the IPSC technology to derive cornea tissue and its perspective for eye development studies, clinical or preclinical study by comparing the methodology depending of the potential applications.