bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Benefits and limitations of low dose atropine
Authors: Grzybowski Andrzej
Published: January 2024

Atropine is an anti‐muscarinic agent and can be used as a monotherapy or as a combination to slow the progression of myopia. It has been advocated as the first line of treatment in children with lower cost compared with other therapies, and it is a good option for children intolerant to contact lenses and when other treatment options are rejected by parents. The major limitations of topical atropine therapy include the adverse effects with higher concentrations (0.1% and higher), such as reduced amplitude of accommodation and photophobia, and the need for daily dosing. Efficacy of low‐dose atropine treatment has been confirmed by several meta‐analysis showing reduced SE progression and decreased axial elongation. The results from the Low‐Concentration Atropine for Myopia Progression (LAMP) study (3‐year RCT results) in Chinese children showed that 0.05% atropine conferred the best efficacy compared with 0.025% and 0.01%. However, it was postulated that the use of 0.05% topical atropine in Caucasian children may lead to more side effects compared to 0.01%, which can compromise parent's acceptance or children's compliance. The efficacy and safety of 8 atropine concentrations for myopia control in children was reported in a recent network meta‐analysis, in which the 0.05% was found the most beneficial for control of overall myopia progression. It is generally believed that the atropine dose should be adjusted based on the risk factors and progression.
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.
Modulating neuroinflammation to restore vision
Authors: Ferrari Giulio
Published: January 2024

Corneal inflammation is a common feature in most diseases of the eye, including rare eye diseases. Specifically, it has a key role in dry eye, infectious keratitis and after surgery. While the immune system was originally considered the master generator of the inflammatory response, the role of the nervous system (both central and peripheral) in regulating immune activation has finally emerged. Specifically, the role of neurotransmitters and neruopeptides in exacerbating, or modulating, the inflammatory response has been described. These recents findings have shed light on novel mechanisms which can be exploited therapeutically for the treatment of blinding ocular diseases, such as aniridia, graft versus host disease, or corneal burns.
Do differentially expressed genes explain high myopia in congenital stationary night blindness?
Authors: Zeitz Christina , Roger Jerome E. , Michiels Christelle , Sánchez‐Farías Nuria , Varin Juliette , Frederiksen Helen , Wilmet Baptiste , Gimenez Marie‐Laure , Bouzidi Nassima , Blond Frederic , Guilllonneau Xavier , Léveillard Thierry , Sahel José‐Alain , Picaud Serge , Audo Isabelle
Published: January 2024

Myopia is the most common eye disorder, caused by heterogeneous genetic and environmental factors. Rare inherited retinal disorders are often associated with high myopia. Genes implicated in myopia encode proteins involved in eye morphogenesis, extracellular matrix organization, visual perception, circadian rhythms, and retinal signalling. Differentially expressed genes (DEGs) identified in animal models mimicking myopia are helpful in suggesting candidate genes implicated in human myopia. Complete congenital stationary night blindness (cCSNB) in humans and animal models represents an ON‐bipolar cell signal transmission defect and is also associated with high myopia. The purpose of this work was to identify the molecular cause of myopia present in cCSNB. A whole transcriptome sequencing (RNA‐seq) approach was performed using retina from three mouse lines with cCSNB, Gpr179−/−, Lrit3−/− and Grm6−/− and the expression data compared to data of age‐matched wild‐type littermates (n = 5). DEGs with fold changes of at least 1.2, P‐values of ≤0.01, an expression value of at least 5 transcripts per million reads and appearing in at least two cCSNB mouse lines were investigated in detail. A meta‐analysis was performed by a) comparing our data with published transcriptome data from purified retinal cells and single cell RNA‐Seq data, b) pathway analyses, c) myopia databases and publications concerning their role in normal vision. Several of the DEGs were validated by RT‐qPCR experiments and analysed by western blot and immunolocalization studies. More than 50 DEGs were found in at least two cCSNB mouse lines. Expression of those was found in different retinal cell types. The difference in expression was independent of the number of nuclei present in wild‐type and mutant inner retina. Pathway analysis revealed that mitogen‐activated protein kinase pathways, synaptic signalling, G protein‐coupled receptor ligand binding pathways, and proteins implicated in eye, endoderm and connective tissue development were affected in cCSNB. More than half of the genes were already associated with myopia. Our study reveals DEGs in all retinal cell types of cCSNB models, previously associated with myopia and novel candidates. These studies combined with pathway analyses provide the basis for the development of pharmacological and optical myopia therapies.
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.
Human pluripotent stem cells as a scalable source for limbal stem cells ‐ From basic biology towards clinical applications
Authors: Skottman Heli
Published: January 2024

There is an unmet clinical need to treat especially bilateral limbal stem cell deficiency (LSCD). For this allogeneic source of limbal stem cells (LSCs) differentiated from human pluripotent stem cells (hPSC) could provide a solution. In our studies, we have developed efficient methods to produce an enriched population of ABCG2‐positive as well as later arising p63/ABCB5‐postive hiPSC‐LSCs and our current research hypothesis is that these cells including both quiescent and proliferative sub‐populations could represent high regenerative potential in future clinical applications. Towards that end, we have been conducting molecular and functional analyses of these different sub‐populations to increase the understanding of their identity and heterogeneity as comparison to native human corneal limbus. With this approach we wish to gather data‐driven strategy towards clinical applications.
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.
Aniridia cohort data from the Schwiete center
Authors: Szentmáry Nóra , Fries Fabian N. , Náray Annamária , Munteanu Cristian , Stachon Tanja , Lagali Neil , Seitz Berthold , Käsmann‐Kellner Barbara
Published: January 2024

In congenital aniridia, there is malformation of almost all eye segments. In addition, endocrinologic, metabolic and central nervous systems diseases may be present. The most common ophthalmic signs in congenital aniridia are AAK, iris malformation, cataract and macular hypoplasia. Between 556 eyes of 286 subjects (20.1 ± 20.1 years; 45.5% males), there was nystagmus in 518 (93.7%) eyes, strabismus in 327 (58.8%) eyes. There was iris malformation with atypical coloboma in 34 eyes (6.1%), more than 6 clock hours of iris remnants in 61 eyes (10.9%), less than 6 clock hours of iris remnants in 96 eyes (17.2%), and complete aniridia in 320 (57.5%) eyes. The patients were graded according to the following aniridia‐associated keratopathy (AAK) stages: Stage 0 (96 eyes (17.2%), no keratopathy), Stage 1 (178 eyes (32.0%)), Stage 2 (107 eyes (19.2%)), Stage 3 (67 eyes (12.0%)), Stage 4 (62 eyes (11.1%)), Stage 5 (45 eyes (8.0%)). There was clear lens in 127 (22.8%), cataract in 224 (40.2%), subluxated lens in 9 (1.6%), pseudophakia in 129 (23.2%), aphakia in 32 (5.7%) eyes. There was secondary glaucoma in 307 (55.5%), macular hypoplasia in 395 (71.4%) and congenital optic nerve head pathology in 223 (40.3%) eyes. The iris malformation type may indicate future expression of AAK, cataract and glaucoma development and it is correlated with congenital optic nerve head and macular pathology. Our registry will support further detailed longitudinal analysis of ophthalmic and systemic diseases of aniridia subjects during long‐term follow‐up.
Basic concepts of exercise physiology for the vision and eye research community
Authors: Aracil‐Marco Adolfo
Published: January 2024

The epidemiology of the second half of the 20th century has been marked by a transition from infectious to non‐communicable diseases. Instead of having a unique etiological cause, the non‐communicable diseases are believed to develop by the temporal confluence of several risk factors on a given individual. Risk factors of genetic origin are considered non‐modifiable nowadays. In contrast, behavioural risk factors, including lifestyle, are considered modifiable, and, therefore the preventive and adjuvant interventions aimed to reduce the risk or modify the natural course of non‐communicable diseases are based in lifestyle changes.

Since the seminal work of Jeremy Morris in the 50's (the so‐called “London Bus Study”) epidemiological evidences have been accumulating over time on the potential role of a reduced physical activity in every domain of daily life as a risk factor for several non‐modifiable diseases. This is aggravated by the progressive trend of a reduced physical activity performed by the worldwide population during the last decades. The relationship of physical inactivity and/or sedentarism with several systemic diseases is clearly proven nowadays, and the underlying pathophysiological explanations are starting to be understood.

In contrast what it happens in other organs or systems the potential effects of physical activity on ocular physiology and/or pathophysiology are still almost unknown. The design and development of future studies focused on these topics would need that the eye and vision research community is familiarized with: a) the current terminology on the field of physical activity and exercise; b) the hormetic properties of exercise, and consequently, the differences among acute responses and chronic adaptations to it; and, c) the potential physiological mechanisms ‐ranging from classical neuroendocrine responses to the recent concept of exerquines‐ that may explain them. All of them will be presented and discussed at this talk.
Can physical exercise influence the ocular surface homeostasis?
Authors: Serramito‐Blanco María
Published: January 2024

Over the last two decades, physical exercise has experienced a great increase in its practice in developed populations, thanks to which the quality of life of people has improved and the risk of suffering from certain diseases has been reduced. The scientific literature has described what happens in some organs of the human organism concerning exercise, however, one of the little‐known organs in relation to physical exercise is the human eye.

Recently, understanding what happens in the human eye with physical activity has gained interest among scientists. Specifically, in the last 5 years, studies have begun to be carried out on physical activity in relation to the changes it can cause on the ocular surface. The scientific literature currently available is diverse in terms of the population evaluated, the study design, and the analysis methodology. Published studies have described some effects on the ocular surface after acute exercise and others with chronic exercise. Some of them have followed an experimental design such as clinical trials or tear analysis and others an observational design utilizing subjective questionnaires on dry eye symptoms, obtaining promising results. A summarized vision of the most representative works on the field will be presented and discussed.
Known genes, new genes and new phenotypes in mitochondrial eye diseases
Authors: Jurkute Neringa
Published: January 2024

Primary mitochondrial diseases together represent a major cause of inherited neurological disorders that, due to dysfunction of the mitochondrial respiratory chain, can affect many parts of body, especially high energy demand organs, such as liver, heart, kidney, muscle and the eye. As the eye is particularly vulnerable to mitochondrial dysfunction, approximately half of all the patients with confirmed mitochondrial disease will develop significant ocular involvement and the complication that patients are most afraid of is visual loss. This can arise either from a primary optic neuropathy (the most common ocular involvement), from outer retinal degeneration, or in some cases from retrochiasmal visual pathway involvement resulting in varying patterns of visual field defects. To date, inherited optic neuropathies have been linked with pathogenic variants in over 40 genes across both the mitochondrial (mtDNA) and nuclear (nDNA) genomes with maternal (mtDNA) inheritance, autosomal dominant, recessive and x‐linked inheritance observed. Inherited optic neuropathies are a significant cause of blindness in both the paediatric and adult population with an estimated prevalence of 1 in 10 000 in the UK. The prevalence is estimated low because of the difficulty in making a confirmed molecular diagnosis due to multiple factors: mutations have been identified in both genomes, a limited number of genes are included in next generation sequencing (NGS) panels, phenocopies etc. Current genetic testing strategies for inherited eye diseases fail to identify pathogenic variants in a significant proportion of cases suggesting that previously unidentified genes harbouring pathogenic variants remain to be identified. However, whole exome sequencing (WES) and particularly whole genome sequencing (WGS), and unbiased interrogation of genomic variants offers an unparalleled opportunity to detect variants in both uncharacterised genes and non‐coding regions of the genome leading to previously unknown gene‐disease associations. This presentation highlights the power of unbiased WGS to elucidate the missing heritability in mitochondrial eye diseases and reports novel gene‐disease associations and novel phenotypes associated with known genes defects.
Natural history of mitochondrial optic neuropathies
Authors: Klopstock Thomas
Published: January 2024

Mitochondrial optic neuropathies (MON) may occur as a single organ disease (non‐syndromic MON) or in the context of a multisystem mitochondrial disorder (syndromic MON). By far the most frequent MON are Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA). LHON is in most cases caused by mitochondrial DNA (mtDNA) mutations m.11778G>A, m.3460G>A or m.14484T>C, while ADOA is most frequently due to mutations in the OPA1 gene. As therapy trials have been performed, are ongoing or are planned for LHON and ADOA, it is important to know about the natural history of these disorders which may help to design trials or may serve as an external comparator.

In LHON, an international observational retrospective registry (REALITY) analysed the visual course and outcome in 44 LHON patients, and found (after an average follow‐up time of 32.5 months) the mean best‐corrected visual acuity (BCVA) to be 1.46 LogMAR in m.11778G>A, 1.52 LogMAR in m.3460G>A, and 0.97 LogMAR in m.14484T>C mutations carriers. In line with previous findings, children below age 12 years at onset had the best visual prognosis. Since 25 of the 44 patients had taken idebenone at some point, this work does not qualify as a natural history study, though.

A meta‐analysis of 12 retrospective and 3 prospective studies included data from 695 LHON patients with the m.11778G>A mutation. This meta‐analysis was hampered by the poor and variable definition of recovery among studies, and by the fact that idebenone use could not always be excluded. Main findings were some degree of recovery in 14.4% of patients, and 11.3% in those above age 15 years. Final BCVA of better than 1.0 logMAR was rare.

In an own study of 83 LHON patients (73.5% with m.11778G>A mutation), BCVA at last observation was better than 1.0 logMAR in 18.1%, between 1.0 and 1.68 logMAR in 33.7% and worse than 1,68 logMAR (off‐chart) in 48.2%. Spontaneous recovery by at least 0.2 logMAR occurred in 16.3% of patients.

In OPA1‐ADOA, a retrospective analysis of data from 64 affected patients showed a mean age at visual failure onset of 7.0 years (range 1.0–16.0 years), and a mean BCVA at last observation of 1.02 LogMAR. Longitudinal data in 43 OPA1 patients with a mean follow‐up duration of 18.0 years showed on average a slow visual decline of 0.032 LogMAR/year, but some patients deteriorated much faster (range 0–0.171 LogMAR/year).

In conclusion, currently available data on the natural history of MON are hampered by retrospective analysis, low sample sizes, unsystematic phenotyping, variable definitions of key outcomes (eg, recovery) and often incomplete information on the administration of idebenone or other drugs. Large multicenter studies on natural history are needed but are more and more difficult to perform with the advent and sometimes even approval of disease‐modifying treatments.
Differences in Müller's glia between the central and peripheral retina and its effect in glaucoma
Authors: Vecino Elena , Pereiro Xandra , Ruzafa Noelia
Published: January 2024

Glaucoma is a neurodegenerative disease and the leading cause of irreversible blindness in the world, whose main risk factor is increased intraocular pressure. When visual problems are first detected in patients with glaucoma, already half of the retinal ganglion cells (RGCs), the neurons that send visual information from the eye to the brain, have died principally in the peripheral retina. The timeframe of cell death is prolonged, lasting even decades after an initial diagnosis. Müller glia (MG) are the main macroglial cell in the retina, play prominent roles regulating normal and pathological physiology and react to neuronal injury in glaucoma. The change to a reactive phenotype of MG initiates signalling cascades that may serve a neuroprotective role, but may also proceed to promote damaging effects on RGCs. However, the underlying mechanisms and signalling pathways that specifically promote protective versus destructive roles of reactive glial cells are mostly unclear.

Using cell cultures of Müller cells, retinal ganglion cells or cocultures subjected to hydrostatic pressure, we have been able to prove that Müller cells in the periphery react to pressure by secreting harmful proteins that induce ganglion cell death. Proteomic analysis has provided us with information on the different behaviour of Müller cells in the periphery versus those in the center.

Elevated hydrostatic pressure on MG induces the expression of proteins associated to apoptosis, oxidative stress and inflammation in the peripheral MG. This study confirms that MG could have a role in RGCs death in glaucoma opening new avenues for research. Preventing MG response to elevated pressure, MG can neuroprotect RGCs in early stages of glaucoma.

Supported by ELKARTEK (KK‐2019/00086), MINECO‐Retos (PID2019‐111139RB‐I00), PIBA (2020_1_0026), Grupos Consolidados Gobierno Vasco, UPV/EHU:
Clinical and histological characteristics of axial myopia
Authors: Jonas Jost
Published: January 2024

Myopic axial elongation is associated with various non‐pathological changes. These include a decrease in photoreceptor cell and retinal pigment epithelium (RPE) cell density and retinal layer thickness, mainly in the retro‐equatorial to equatorial regions; choroidal and scleral thinning pronounced at the posterior pole and least marked at the ora serrata; and a shift in Bruch's membrane opening (BMO) occurring in moderately myopic eyes and typically in the temporal/inferior direction. The BMO shift leads to an overhang of Bruch's membrane (BM) into the nasal intrapapillary compartment and BM absence in the temporal region (i.e., parapapillary gamma zone), optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter, fovea–optic disc distance elongation, reduction in angle kappa, and straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibres. Highly myopic eyes additionally show an enlargement of all layers of the optic nerve canal, elongation and thinning of the lamina cribrosa, peripapillary scleral flange (i.e., parapapillary delta zone) and peripapillary choroidal border tissue, and development of circular parapapillary beta, gamma, and delta zone. Pathological features of high myopia include development of macular linear RPE defects (lacquer cracks), which widen to round RPE defects (patchy atrophies) with central BM defects, macular neovascularization, myopic macular retinoschisis, and glaucomatous/glaucoma‐like and non‐glaucomatous optic neuropathy. BM thickness is unrelated to axial length. Including the change in eye shape from a sphere in emmetropia to a prolate (rotational) ellipsoid in myopia, the features may be explained by a primary BM enlargement in the retro‐equatorial/equatorial region leading to axial elongation.
Inhibiting myopia development by the digital chromatic filters
Authors: Swiatczak Barbara
Published: January 2024

We had previously found that simulated chromatic defocus, imposed by spatially filtering the RGB channels of the computer screen, induces significant changes in choroidal thickness already after 45 min (Swiatczak and Schaeffel, 2022). In emmetropes, the “red in focus” filter, which blurs the image in the blue channel and simulates myopic chromatic defocus, induced thickening of the choroid and eye shortening, while the “blue in focus” filter, which blurs the image in the red channel and simulates hyperopic chromatic defocus, induced thinning of the choroid and eye elongation. Strikingly, eyes that were already myopic were not responsive to these filters, suggesting that (1) they may no longer detect longitudinal chromatic aberration (LCA), (2) the imposed signal was too weak to induce significant changes in choroidal thickness, or (3) the signal was detected by the retina, but it was not transmitted to the choroidal tissue. To gain a better understanding of the underlying mechanisms and their roles in emmetropization, we measured in emmetropic and myopic subjects (1) the long‐term effect of repetitive exposure to the “red in focus” filter over 12 days of treatment, followed by 2 days of recovery, (2) the accommodation responses to visual targets with simulated myopic and hyperopic LCA, and (3) visual acuity and contrast sensitivity in red and blue light.

Our results showed that as previously found for choroidal changes, simulated hyperopic or myopic LCA also affected accommodation. The “blue in focus” filter induced more accommodation than the “red in focus” filter (difference in emmetropes: 0.13D, p < 0.05). Strikingly, accommodation in myopic eyes was not responsive to simulated LCA. Moreover, visual acuity was severely reduced when subjects were looking through a short‐pass blue filter (cut‐off at 490 nm) compared to visual acuity in red light (long‐pass red filter, cut‐off at 610 nm) which was observed in both emmetropic and myopic subjects. Furthermore, emmetropes displayed higher contrast sensitivity in red than in blue light, but this difference was not found in myopes.

Our findings confirm that there is a difference in retinal processing between emmetropes and myopes which includes lower sensitivity to LCA in myopes. Furthermore, we showed that these differences show up in both, changes in choroidal thickness as well as accommodation.
Soemmerring's rings developed in‐vivo can present internal transparent areas
Authors: D'Antin Justin Christopher , Tresserra Francesc , Barraquer Rafael I. , Michael Ralph
Published: January 2024

Purpose: To test whether any part of Soemmerring's rings developed, in‐vivo, in adults could be transparent and how this transparency relates to morphological factors.

Methods: Sixteen Soemmerring's rings were extracted from donor eye globes. After frontal imaging, they were thickly sectioned sagittally in order to analyse the degrees of transparency of the cross‐section both at the periphery and center. All samples were also histologically analysed using alpha smooth muscle actin, Vimentin, wheat germ agglutinin and DAPI in order to correlate transparency to certain morphological factors.

Results: When viewed frontally within the dark field, all Soemmerring's ring samples were apparently opaque. However, after sectioning, 20 of the 30 samples were more transparent in the center than at the periphery. Of the morphological factors that we analysed, only lens fibre organization at the bow region and an increased area of mature lens fibre cells had a significant relation to the degree of transparency at the center of cross‐sections.

Conclusions: Soemmerring's rings can maintain the ability to produce organized and transparent areas of lens cells.
The human capsular bag model as a pre‐clinical evaluation tool for IOLs
Authors: Wormstone Michael
Published: January 2024

Cataract affects the vision and well‐being of millions. At present the only means of treating cataract is through surgical intervention. Modern cataract surgery typically retains a ring of anterior lens capsule and the entire posterior capsule. This is known as a capsular bag, which can house an intraocular lens (IOL) implant. Initial surgical outcomes are excellent, but with time lens cells that remain following surgery undergo a wound‐healing response. In essence the trauma of surgery provokes cells to proliferate and migrate across the acellular capsular surfaces and in some case the IOL surface. Most importantly, cells ultimately grow within the visual axis, on the central posterior capsule, and undergo fibrotic events that are associated with transdifferentiation to myofibroblasts, matrix deposition and matrix contraction that can lead to a secondary loss of vision termed posterior capsule opacification (PCO). PCO affects a large proportion of patients and is one of the most common fibrotic conditions in the world. It is therefore of great importance to better understand this condition and thus strong experimental systems are required for this purpose. To this end cataract surgery can be performed on human donor eyes within a laboratory setting to provide a biological product that is configured in the same manner as in the patient. This is known as the human capsular bag model. Using this clinically relevant model it has been possible to tease our key regulatory molecules driving human lens growth and fibrosis. While the human capsular bag model has been a useful tool to identify therapeutic targets or test putative therapeutics no pharmacological treatment is currently in clinical use. As a result, the intraocular lens is currently the major tool employed to manage PCO progression. Characteristics required for an IOL include strong optical performance, stability within the lens capsular bag and anti‐PCO properties. To meet international standards for IOL manufacture a number of tests are performed to predict IOL behaviour when implanted. However, ISO guided tests take place in a non‐biological setting and are limited to assessing purely physical characteristics. Therefore, understanding how the IOL interacts with the capsular bag and how wound‐healing responses could influence IOL position and stability is an area of great importance. The human capsular bag model can address this shortfall in the IOL development pipeline to relate design features to IOL stability and anti‐PCO performance in a clinically relevant setting. The presentation will highlight the evolution of the model as a tool for IOL testing and development.
Indomethacin and bromfenac may be effective in the prevention of posterior capsule opacification
Authors: Yao Ke
Published: January 2024

Posterior capsule opacification (PCO) is the most common long‐term postoperative complication of cataract surgery, leading to secondary vision loss. Optimized intraocular lens (IOL) structure and appropriate pharmacological intervention can provide physical barriers and biological inhibition, respectively, to block the migration, proliferation, and epithelial‐mesenchymal transition (EMT) of lens epithelial cells (LECs) for PCO prophylaxis. We demonstrated that non‐steroidal anti‐inflammatory drugs (NSAIDs) are effective in preventing posterior capsule opacification. Indomethacin (INDOM) not only suppresses cell migration and down‐regulates the expression of cyclooxygenase‐2 (COX‐2) and EMT markers, including alpha‐smooth muscle actin (α‐SMA) and cyclin D1, but also promotes autophagy activation in LECs. Autophagy was also verified as a potential therapeutic target for down‐regulating EMT in LECs. Bromfenac effectively inhibits cell migration, overexpression of EMT markers such as fibronectin (FN), matrix metalloproteinase 2 (MMP2), α‐smooth muscle actin (α‐SMA), and transcription factor Snail, and extracellular signal‐regulated kinase (ERK)/glycogen synthase kinase‐3β (GSK‐3β) signalling induced by transforming growth factor‐β2 (TGF‐β2) in vitro. Based on ultrasonic spray technology, we developed a drug‐eluting intraocular lens (IOL) using poly (lactic‐co‐glycolic acid) (PLGA) with sustained release ability of indomethacin/bromfenac for PCO prevention. The novel IOL, serving as a drug delivery platform, can carry an adjustable dose of drugs with sustained release ability for more than 28 days. In the rabbit PCO model, the novel IOL showed excellent anti‐inflammatory and anti‐PCO effects. In summary, indomethacin and bromfenac are effective pharmacological interventions for PCO prophylaxis, and the novel IOL we developed prevented PCO in vivo, providing a promising approach for PCO prophylaxis in clinical applications.
Immunonutrition in glaucoma patients: A new microbiota‐based treatment
Authors: Zanon‐Moreno V.
Published: January 2024

Glaucoma is one of the main causes of irreversible blindness, producing 12.3% of blindness worldwide. There are about 4.5 million people with glaucoma in the world. However, the real number should be much higher if we consider all people with undiagnosed glaucoma.

Glaucoma is an age‐related multifactorial disease determined by both genetic and environmental factors. The cause remains unknown. So, efforts are focused on preventing blindness through early diagnosis and hypotensive treatment, which is not always effective. Currently, neuroprotective treatment is also considered.

Among the most studied processes in relation to optic nerve degeneration in glaucoma are inflammation and apoptosis. Several studies show that genes associated with inflammation are upregulated in the trabecular meshwork, which could be related to the onset or progression of glaucoma. However, the most visible manifestations of inflammation in glaucoma occur on the ocular surface. This produces, for example, an infiltration of inflammatory cells and a reduction in corneal sensitivity. Like inflammatory processes, apoptosis has been associated with glaucomatous disease. In fact, vision loss is caused by the death of retinal ganglion cells (RGCs), whose axons form the fibres of the optic nerve. The survival of RGCs is key to the prevention of glaucomatous blindness.

The ocular microbiota has recently been studied, analysing the possible association between the inflammatory molecules produced by the ocular microbiome and the etiopathogenic mechanisms of this optic neuropathy.

The aim of these studies is the development of probiotics as a therapy for glaucoma. Probiotic strains allow a rapid and stable recovery of the normal ocular microbiota, providing faster anti‐inflammatory and antihistamine effects. In addition, they are antagonists of the pathogens without the risk of the appearance of resistance, which avoids the use of antibiotics. In this way, probiotics represent an alternative to the abusive use of antibiotics, thus avoiding the problem of resistance development. In this sense, polyphenols are very interesting since they are capable of exerting neuroprotective and immunomodulatory effects and also can remodel the microbiota.
Glaucoma pharmacogenetics. Role in neuroprotection
Authors: Milla Elena
Published: January 2024

Glaucoma is a blinding disease that can occur at all ages, with Mendelian inheritance typical for the rare early onset disease (before age 40) and complex inheritance evident in common adult‐onset forms of disease. Genetic and genomic studies, including genome‐wide association studies (GWAS) have identified new genetic variants contributing to glaucoma in the last years. Genes correlating with glaucoma risk may involve: ocular development, intraocular pressure, trabecular meshwork function or some of them are directly related to optic nerve susceptibility such as retinal ganglion cell membranes, mitochondrial function, reactive oxygen species production and management, and mechanisms controlling apoptosis. These findings are providing new insights into the underlying molecular mechanisms responsible for glaucoma that could eventually lead to novel gene‐based therapies, including strategies for neuroprotection.

We present our study about the genetic analysis of a cohort of Spanish patients with primary open‐angle glaucoma to determine the contribution of rare variants associated with this disease through next generation sequencing (NGS) glaucoma gene panel, as a future method of diagnosis and early treatment. We found some rare variants associated with optic disk parameters and function in some families with high and normal tension glaucoma with allelic frequencies significantly higher than the frequency in the general population by NGS. Those rare variants are located in SIX6, CARD10, MFN1, OPTN, and WDR36 glaucoma‐related genes.

These risk variants have been associated to the alteration of retinal ganglion cells through different mechanisms, thereby increasing the risk of glaucoma‐associated vision loss.

The discovery of new genetic variants associated with augmented susceptibility of the optic nerve may in the future open the door to designing new neuroprotection gene therapies aimed at repairing damaged genes or providing them through different vectors.