bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic characterization of Meibomian gland morphology
Authors: Novo‐Diez Andrea , Blanco‐Vázquez Marta , Arlanzón‐Lope Pablo , Valencia‐Sandonís Cristina , González‐García María J. , Fernández Itziar
Published: January 2024

Aims/Purpose: To characterize the Meibomian gland (MG) morphology in healthy subjects with an automatic software.

Methods: An automatic software was developed for image analysis in R code, consisting of 4 stages: (1) selection of the region of interest, (2) image preprocessing to obtain a binary and a skeleton image, (3) modelling of each MG to fit each MG to a piecewise linear model, and (4) quantification of the following MG features: tortuosity, MG shortening, number of MGs, deviation from a vertical line, and MG area. Meibography images of the upper eyelid were acquired using the Easy Tear View+®. A group of 156 healthy subjects were included, with a mean age and confidence interval (CI) of 43.88 (95% CI: 41.38–46.37) years, range 16–76 years. Reference intervals (RI) were calculated for each MG feature to be used as a diagnostic tool to classify a specific value as normal or non‐normal. Generalized Additive Models for Location, Scale and Shape were used to estimate the percentile curve for each morphologic feature of MG, considering the influence of age and sex.

Results: Age had an influence on tortuosity, mean = 0.3 (95% CI: 0.3–0.31), RI: 0.19–0.4 <20 years, and 0.24–0.39 at 50–60 years. Age and sex had an influence in the MG shortening, mean = 63% (95% CI: 62–64%), mean RI: 58–74% <20 years; 59–84% >75 years; women RI: 56–71% <20 years; 57–82% >75 years. The rest of the variables were not affected by age or sex: number of MGs = 16.05 (95% CI: 15.28–16.82), RI: 8–27; vertical deviation = 0.37 (95% CI: 0.36–0.38), RI: 0.29–0.45, and MG area = 14% (95% CI: 14–15%), RI: 8.17–19.81%.

Conclusions: Tortuosity variability decreases between 45 and 60 years of age. The MG shortening increases with age and is higher in men. These values could be useful to classify a meibography image as normal or non‐normal, helping to diagnose MG alterations in an objective way.
Morphogeometric characterization in keratoconus according to the RETICS grading system
Authors: Jaimes Claudia Patricia Tarazona , Megiddo Elinor , Gomez Carmelo , Moya Alejandro , Martinez Francisco Cavas , Alio Jorge
Published: January 2024

Aims/Purpose: Keratoconus progression characterizes by corneal thinning resulting in irregular astigmatism and visual impairment. In the present work a computerized 3D modelling method is used to describe different morphogeometric variables in healthy corneas and keratoconus. RETICS grading system was used to characterize keratoconus with best corrected visual acuity (BCVA) as the major grading parameter. Analyzing morphogeometric variables and its correlation with visual acuity (VA) may help understand structural changes associated with visual decline in keratoconus.

Methods: 124 healthy corneas and 257 eyes with keratoconus were included and classified according to the RETICS grading system as grade 1 (n = 94) when VA > 0.9; grade 2 (n = 65) when 0.6 < VA ≤ 0.9; grade 3 (n = 50) when 0.4 < VA ≤ 0.6; grade 4 (n = 31) when 0.2 < VA ≤ 0.4 and grade 5 (n = 17) when VA ≤ 0.2. Computerized 3D modelling was done and morphogeometric variables analysed: anterior surface area (ASA), posterior surface area (PSA), total area (TA), total volume (TV), anterior apex deviation (AAD), posterior apex deviation (PAD), anterior minimum thickness point deviation (AMTPD) and posterior minimum thickness point deviation (PMTPD).

Results: All morphogeometric variables showed differences between normal and keratconic eyes (p < 0.001). ASA and PSA present higher values in keratoconus (p < 0.001), while TV shows lower values in the same subjects (p < 0.001). Correlation between BCVA and all variables was calculated showing a positive correlation for the ASA (p = 0.0036) and PSA (p = 0.0172), and a negative correlation for TV (p = 0.1612) and PAD (p = 0.0821).

Conclusions: As keratoconus progresses and VA worsens, corneal structural changes include an increase in the PAD, in addition to an increase of both anterior and posterior corneal areas while TV tends to decrease. Morphogeometric variables represent a new parameter to characterize keratoconus and some demonstrate a statistically significant correlation with visual loss.
miRNA profiling in the aqueous humour in patients with Fuch's endothelial corneal dystrophy
Authors: Wróbel‐Dudzińska Dominika , Kosior‐Jarecka Ewa , Ćwikińska‐Haszcz Agnieszka , Czop Marcin , Kocki Janusz , Żarnowski Tomasz
Published: January 2024

Aims: The aim of the study was to determine and compare the expression profiles of miRNA molecules in the aqueous humour (AH) of patients with Fuch's endothelial corneal dystrophy (FECD) and patients with normal corneal endothelium undergoing cataract surgery.

Methods: The study consisted of 20 Caucasian patients (10 FECD and 10 control patients) who underwent comprehensive ophthalmology examination, thus routine corneal transplant or cataract surgery. 100 μL of AH were obtained from the anterior chamber at the beginning of the surgery with special care to avoid contamination with blood tears. The total RNA was isolated from the AH samples using an miRNeasy Serum/Plasma kit according to the manufacturer's instructions. The RNA concentration was determined by using NanoDrop2000c spectrophotometer. In addition, RNA analysis was performed using Agilent Bioanalyzer2100 and PicoRNA Kit according to the manufacturer's protocol. A microarray system (GeneChip miRNA 4.0 Array chip, Affymetrix) was used to determine the miRNA expression profiles. The RNA preparation and hybridization were performed according to the manufacturer's protocol, with one modification to extend the hybridization time to 42 h. The gene chips were scanned with an Affymetrix GeneChip Scanner 3000.

Results: We found significant overexpression of hsa‐miR‐4532, hsa‐miR‐6800‐5p, hsa‐miR‐3621, hsa‐miR‐4270, hsa‐miR‐548ac, hsa‐miR‐328‐5p, hsa‐miR‐6771 ‐5p, hsa‐miR‐6858‐5p, hsa‐miR‐548a‐3p, hsa‐miR‐6069, hsa‐miR‐6716‐5p, hsa‐miR‐7151‐3p, hsa‐miR‐5189‐5p, hsa ‐miR‐4279, hsa‐miR‐1233‐5p, hsa‐miR‐455‐3p in patients with FECD compared to those patients with normal corneal endothelium. Reduced expression of hsa‐miR‐3613‐3p, hsa‐miR‐1298‐3p, hsa‐miR‐16‐2‐3p, hsa‐miR‐4668‐5p was observed in patients with FECD in addition to the control group.

Conclusions: The analysis of miRNA expression profiles and their application as potential biomarkers will facilitate and accelerate the diagnosis of FECD, as well as enable the development of individualized molecularly targeted therapy.
The second rapid assessment of avoidable blindness survey in Palestine: A national cross‐sectional study
Authors: Mikki Nahed , Mactaggart Islay
Published: January 2024

Aim: To assess prevalence and main causes of blindness, vision impairment and cataract surgical coverage in Palestinians aged 50 years and older.

Methods: The survey was part of a larger population‐based survey using the rapid assessment of avoidable blindness (RAAB) methodology to estimate prevalence of vision impairment, blindness and disability in individuals aged 50 years and older in Palestine. It was a nationally representative, cross‐sectional, population‐based survey in Gaza Strip and West Bank. A sample size of 4224 participants aged 50 years and older was determined in 69 clusters in the West Bank and 52 clusters in the Gaza Strip. Within each cluster, 35 people aged 50 years or older were examined in their homes.

Results: The total examined was 3848. Adjusted prevalence of blindness was 2.6%. This is a non‐significant decrease from 3.4% in 2008. The prevalence of blindness in Gaza (4.0%) was higher than the prevalence of blindness in the West Bank (1.8%). The prevalence was higher among females than males.

Adjusted prevalence of severe vision impairment, moderate vision impairment and mild vision impairment was 1.4%, 10.2% and 11.6%, respectively. Principal cause of blindness, severe and moderate vision impairment was untreated cataract followed by diabetic retinopathy. Refractive error was the principal cause of mild vision impairment. More than 80% of vision impairment was avoidable.

Unmet need for cataract surgery varied from 0.9% among blind participants to 6.5% among participants with mild vision impairment. Effective cataract surgical coverage was low in general and varied from 42.4% among blind operated participants to 25.9% among participants with mild vision impairment.

Conclusions: Around 80% of vision impairment was avoidable. Untreated cataract and diabetic retinopathy were the main causes of blindness, severe and moderate vision impairment. Refractive error was the principal cause of mild vision impairment. Effective cataract surgical coverage was low.
Diplopia as the presenting symptom of a post‐transplant lymphoproliferative disorder in a bilateral inferior lim transplanted young adult
Authors: Fustel Paula Boned , García Laura Fernández , Martí M. Ángeles Ruth Bort , Gregori Enrique España
Published: January 2024

Aims/Purpose: To present a unique case of post‐transplant lymphoproliferative disorder (PTLD) after bilateral inferior limb transplantation, which is still controversial due to the absence of precedents in the literature and the unclear risk–benefit ratio.

Methods: Case report.

Results: A 22‐year‐old male presented to the emergency room complaining of double vision. He had a history of bilateral inferior limb amputation 8 years ago and received a bilateral lower limb transplantation 2 years later. He had normal graft function and was receiving cytomegalovirus prophylaxis. During neurological examinations left abducens nerve (CN VI) palsy was noted. Other cranial nerves affected produced facial hypoesthesia (CN V) and mild paresis (CN VII), hearing loss and tinnitus in left side (CN VIII) and soft palate asymmetry (CN X). He was otherwise neurologically intact, alert and orientated. MRI revealed a lesion located at the facial colliculus at the floor of 4th ventricle. In the context of immunosuppression, the differential diagnosis included abscess versus PTLD. Biopsy of the lesion was performed. Morphologically atypical lymphocytic cells suggestive of B lymphoma were identified. Monoclonal rearrangement for heavy chain Igen and immunoglobulins were identified with molecular biology techniques. The histology features were consistent with a diagnosis of CNS B lineage primary lymphoma. Two days later, bilateral supracondylar amputation was performed. Following the explant, immunosuppression was withdrawn. His underlying condition was finally diagnosed as PTLD, for which he started a chemotherapeutic regimen with radical intention (methotrexate and cytosine arabinoside). The patient recovered fully and up to date, 10 years later, is doing well.

Conclusions: Due to its diverse aetiologias, a proper workup must be done of the patients presenting with diplopia to the emergency room. PLTD must be a condition to always be considered in patients with history of solid organ transplant; since the early diagnosis is crucial for a successful management of this often‐fatal condition.
When atypical becomes urgent: Unleashing the ophthalmologist's role in managing unconventional macroadenomas
Authors: Martí M. Ángeles Ruth Bort , Fustel Paula Boned , Pelaez Blanca Casado , García Laura Fernández , Gregori Enrique España
Published: January 2024

Aims/Purpose: To present an atypical macroadenoma case and its management, in which the visual monitoring was key to indicate surgical intervention.

Methods: Case report.

Results: A 55‐year‐old male who was admitted to our emergency department with a main complaint of bilateral central and painless visual loss of 2 days' duration. He had DM type II. BCVA OU was 0.2, with no RAPD, but bilateral dyschromatopsia (OD: 4/16 OS: 10/16). Computerized visual field testing revealed a central scotoma (OD) and temporal hemifield loss (OS). An urgent CT scan revealed the presence of a 24 × 15 × 3 mm sellar‐suprasellar mass, with a locoregional mass effect and possible extension to cavernous sinuses and optic chiasm compression. 12 h after admission, deterioration of BCVA was observed (OD: 0.05 and OS: 0.1), along with worsening of dyschromatopsia (OD: 2/16 and OS: 7/16) and campimetric deficit progression (left homonymous hemianopic pattern). The MRI revealed the presence of a 21 × 21 × 36 mm sellar mass, without signs of recent intratumoral bleeding, with solid suprasellar extension, posterior cystic degeneration, compressing optic nerve, right optic tract, optic chiasm, and invading right cavernous sinus. Due to the worsening visual function, a consensus decision was made to proceed with same‐day endoscopic transsphenoidal resection. 24 h post‐surgery, the patient showed improvement in BCVA (1.0 OU) and dyschromatopsia (OD: 10/16 and OS: 12/16).

Conclusions: In our case, despite unclear compressive effect on neuroimaging, careful monitoring of visual function allowed to timely indicate surgery, as the positive outcomes reflect. Managing this pathology in tertiary hospitals goes beyond the required experience of the neurosurgical team. The time for surgery indication is a big challenge due to the lack of clear definitions to indicate surgical intervention: “impending vision loss” or “clinically significant increase in size near the visual pathway.”
Nrf2 and HuR/ELAV1 as determinant factors for VEGF expression and secretion in ARPE‐19 cells under stress stimuli
Authors: Bresciani Giorgia , Manai Federico , Govoni Stefano , Amadio Marialaura
Published: January 2024

Aims/Purpose: The transcription nuclear factor E2‐related factor 2 (Nrf2) pathway is a key antioxidant system in the RPE, protecting it from oxidative stress and inflammation. Its dysfunction is a renowned aspect of Age‐related Macular Degeneration (AMD). As previously documented, RNA‐binding protein HuR/ELAVL1 interacts with Nrf2 mRNA, as well as many of its targets at the post‐transcriptional level. Among them, vascular endothelial growth factor (VEGF) is a crucial one, being involved in both physiological maintenance of vasculature and pathological angiogenesis. Purposes of our study were disclosing the crosstalk between Nrf2 and HuR in RPE cells subjected to stressful stimuli and understanding their regulatory effect on VEGF.

Methods: Wild type, Nrf2‐ or HuR‐deficient ARPE‐19 cells were used. As stressful stimuli, MG132 (5 μM) and Bafilomycin (50 nM) for 24 h, or 4‐Hydroxynonenal (4‐HNE; 50 or 100 μM) for 6 h, were used. Cell viability was assayed by enzymatic fluorescence analysis; VEGF expression and extracellular secretion were evaluated by RT‐qPCR and ELISA, respectively.

Results: When subjected to intense toxic stimuli, HuR‐deficient cells display impaired viability, although to a lesser extent compared to Nrf2‐deficient cells. In these silenced cell models, 4‐HNE seems to be more harmful than the autophagy inhibitors. Nrf2 or HuR deficiency markedly affects VEGF levels and secretion, even more than stressful conditions. Furthermore, distinctive effects of silencing either Nrf2 or HuR on the level of the other factor have been disclosed.

Conclusions: Both HuR and Nrf2 are involved in the constitutive regulation of VEGF levels; contexts characterized by oxidative stress or impaired clearance induce more significant changes in RPE featured by an impairment of Nrf2 than of HuR levels. Further elucidations in how the crosstalk between these two factors regulate common targets (e.g., VEGF) may improve our understanding of RPE homeostasis and alteration, and consequently AMD pathophysiology.
Influence of dark adaptation on the perceptual threshold of electrically evoked phosphenes
Authors: Link Dietmar , Noether Eva , Freitag Stefanie , Graichen Uwe , Klee Sascha
Published: January 2024

Aims/Purpose: Phosphenes are light phenomena in the eye that have been studied since the 18th century. They can be evoked mechanically or by electrostimulation, for example. The perception of phosphenes and their threshold, the limit of phosphene perception, has been the subject of numerous studies. In this work, the dynamics of the threshold shift of electrically evoked phosphenes during dark adaptation is recorded. Statistically it was tested whether the phosphene thresholds differ before and after dark adaptation.

Methods: A study was conducted on 16 healthy subjects (7 w, 9 m, 28.5 ± 6.8 yr). Each subject sat approximately 30 cm in front of a black cloth‐covered semi‐circular screen placed on a table. On the table was a signal generator (33250A, Agilent Technologies Inc, Santa Clara, CA, USA) with a rotary control for the subject's own setting of the current intensity for the current stimulation (sinusoidal, 20 Hz) using a transcranial electrical stimulator (DC‐Stimulator PLUS, neuroConn GmbH, Ilmenau, Germany). The electrodes were a ring electrode at one eye and a rectangular electrode at the back of the head. After the subject had been instructed, and the electrodes had been attached, the subject had to set the phosphene threshold in room light conditions (125 cd/sqm) 10 times in succession (baseline B1, bright adapted). Lightproof glasses were then worn. For 40 min, each subject adjusted the threshold at intervals of 2 min. After 40 min, 10 more threshold values were recorded (baseline B2, dark adapted). Means were calculated for each subject for both baselines B1 and B2 and tested for discrimination using the Wilcoxon signed‐rank test.

Results: All subjects were able to successfully complete the test. The global thresholds before and after dark adaptation were 132.3 ± 13.8 μA and 329.5 ± 38.0 μA respectively. The difference between the conditions B1 and B2 is significant (p = 0.0002). All measurement curves of the threshold progression show an increasing behaviour with a pronounced plateau after approximately 15 min.

Conclusions: We successfully performed a study on the generation of phosphenes during current stimulation. The dynamics of the threshold progression from light to dark adaptation could be recorded. A significant threshold shift is shown for all subjects.
Distinct metabolic profiles in ocular hypertensive individuals responding
Authors: Langbøl Mia , Andreasen Jens Rovelt , Bocca Cinzia , Saruhanian Sarkis , Tiedemann Daniel , Vohra Rupali , Lenaers Guy , Kolko Miriam
Published: January 2024

Aims/Purpose: To determine the effect of hypoxia on the plasma metabolic signature of patients with normal‐tension glaucoma (NTG) and ocular hypertension (OHT), compared to healthy controls.

Methods: Metabolomic profiles of plasma from patients with NTG (n = 10) and OHT (n = 10) were compared to age‐matched controls (n = 10) to investigate the signature of hypoxia. Participants underwent two hours of exposure to normobaric hypoxia, followed by a 30‐min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and recovery. Plasma samples were analysed using a non‐targeted metabolomics approach based on liquid chromatography coupled with high‐resolution mass spectrometry (LC‐HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares‐discriminant analysis (OPLS‐DA), as well as univariate analysis with Wilcoxon signed‐rank test and false discovery rate (FDR) correction.

Results: Overall, controls, OHT, and NTG patients had similar regulatory patterns. Only few metabolites involved in fatty acid biosynthesis, ketone body metabolism and kynurenine pathway were affected in OHT patients exposed to hypoxia, whereas metabolites related to energy production were not modified in NTG and OHT patients. No differences were found when comparing them pairwise at baseline, or during hypoxia and recovery.

Conclusions: OHT patients have altered regulation of ketogenesis and kynurenine pathway, that may explain why they do not suffer from degeneration of the optic nerve. The metabolomes of NTG and OHT patients are regulated differently from controls, and omit to regulate metabolites that are important for energy production. This can potentially contribute to neurodegeneration and ultimately cell death in retinal ganglion cells.
Ocular manifestations of juvenile lupus erythematosus: An 2023 update
Authors: Nikolaidou Anna , Frantzidis Christos
Published: January 2024

Aims/Purpose: Juvenile Systemic Lupus Erythematosus (jSLE) is a chronic multisystem inflammatory disease that manifests before the age of 16 years, following a remitting ‐ relapsing course. The range of clinical presentations of juvenile Systemic Lupus Erythematosus (jSLE) in children is multifaceted. Ocular manifestations are uncommon for children with jSLE but can have a significant effect on their vision if not diagnosed early. Any part of the visual pathway can be affected by jSLE. The aim of this report is to systematically review the ocular manifestations of jSLE.

Methods: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 Guidelines was conducted searching MEDLINE and Scopus, including reference lists with appropriate terms for jSLE ocular manifestations. Epidemiological studies, preferably cross‐sectional studies, that describe the prevalence of ocular manifestations in children with a diagnosis or upon diagnosis of jSLE were assessed.

Results: Our search yielded 131 results, screened by two independent reviewers. 33 studies were finally included in the review after preliminary assessment. Keratoconjunctivitis sicca, dry eye syndrome, retinopathy and optic neuritis are among the conditions that have been reported. Ocular manifestations in jSLE may be the result of three different mechanisms: the disease itself, infections related to immunosuppression and side effects of drug therapy. Retinal involvement is one of the most important manifestations, implying high possibility of visual loss. It is usually caused by immune complexes and autoantibodies deposition to the retinal vessels or hypertension resulting from kidney disease.

Conclusions: Ocular manifestations can occur early in the course of jSLE, sometimes even before other systemic symptoms and can serve as markers of disease activity. Diagnosing ocular manifestations in children with jSLE is important for early intervention, monitoring disease activity, preventing vision loss and providing comprehensive care. By addressing ocular manifestations alongside systemic lupus management, healthcare providers can optimize outcomes and improve the overall well‐being of children with jSLE.
Brain‐derived neurotrophic factor alleviates clinical symptoms of experimental autoimmune uveoretinitis and supports retinal regeneration
Authors: Zloh Miloslav , Štofková Andrea
Published: January 2024

Purpose: Brain‐derived neurotrophic factor (BDNF) is one of the most important neurotrophins that has a fundamental role in the regulation of neuronal growth, proliferation, and regeneration, as well as an important modulatory effect on the immune cells. In addition, BDNF potentiates the neurodifferentiation of Müller cells (MCs), thus supporting retinal regeneration. Therefore, we aimed to investigate the anti‐inflammatory effect of BDNF in experimental autoimmune uveoretinitis (EAU), a severe neuroinflammatory condition, and whether BDNF could facilitate the regenerative capacity of MCs in EAU.

Methods: EAU in mice was induced by s.c. administration of retinal antigen IRBP1‐20 emulsified in a complete Freud's adjuvant, followed by i.v. administration of Pertussis toxin. BDNF was administered daily in the form of eye drops from day 8 to day 14 after immunization. On day 14, fundoscopy was performed to assess clinical signs of EAU. Mice were then euthanized, and their eyes and retinas were isolated for further Western blot, RT‐qPCR, flow cytometry, and immunohistochemistry analyses.

Results: The treatment with BDNF significantly improved the clinical manifestations of EAU, including optic disc oedema, vasculitis, and inflammatory infiltrates in the retina. BDNF significantly decreased the infiltration of CD4+ T cells, CD8+ T cells, and CD11b+ myeloid cells into the retina and also suppressed the expression of several pro‐inflammatory cytokines and chemokines. In addition, BDNF administration significantly increased the expression of markers of neurogenesis in retinal MCs.

Conclusions: Together, our results demonstrate that BDNF has important anti‐inflammatory and neurogenic properties and that it may serve as a promising target for developing novel therapeutic strategies for neurodegenerative and neuroinflammatory diseases of the retina.

Support.

This study was supported by the following grant projects: GAUK 378421, 260 648/SVV/2023, and COOPERATIO Neurosciences.
Combined treatment of a giant palpebral keratoacanthoma
Authors: Sanchez Manuel Morales , Revuelta Alvaro Diaz‐Rato , Hernandez Eduardo Conesa , Artola Ines , Pernas Sergio
Published: January 2024

Aims/Purpose: To highlight the relevance of a therapeutic approach adapted to the clinical characteristics of the eyelid lesion found at the time of surgery to ensure an optimal functional and aesthetic result.

Methods: Clinical case assessed, intervened and followed up at our centre.

Results: A 76‐year‐old woman consulted for a nodular umbilicated lesion of recent appearance on the outer third of the upper eyelid of the left eye (UELE) measuring 0.5 cm in greatest diameter and 0.5 cm in elevation. The patient was placed on the waiting list for surgical excision and subsequent pathological examination (PE) of the lesion to confirm the initial clinical suspicion of keratoacanthoma (KA). One month later, the patient went to the operating room for surgery. During this time the lesion increased its initial size by more than 4 times, had a large necrotic centre, active borders and generated an evident left mechanical ptosis. As an alternative to the complete excisional surgery initially proposed, we offered the injection of neoadjuvant intralesional chemotherapy (CT) with the aim of reducing the size of the lesion to obtain a better functional and aesthetic result. The patient accepted this therapeutic alternative. KA was treated with weekly intralesional injections of 1 mL of methotrexate (MTX) 12.5 mg/mL. In our case, 3 injections were necessary to achieve a 78% reduction in the diameter of the lesion to allow reconstruction of the UELE with grafting of the contralateral upper eyelid. One week after the third injection of MTX, reconstruction of the UELE was performed after excisional surgery with wide margins for PE. One week later, the PE result ruled out malignancy and the graft had a pink appearance with complete vascular permeability, so the sutures were removed. Two weeks after reconstruction, the functional and aesthetic results were satisfactory.

Conclusions: Therefore, in our experience, we recommend the above combined treatment for giant palpebral KA and stress the relevance of a therapeutic approach adapted to the clinical characteristics of the palpebral lesion at the time of surgery to ensure an optimal functional and aesthetic outcome.

References

1. Patel NP, Cervino AL. Treatment of keratoacanthoma: is intralesional methotrexate an option? Can J Plast Surg 2011; 19: e15‐8.
Optical coherence tomography ‐ Basic optical principles
Authors: Irsch Kristina
Published: January 2024

Optical Coherence Tomography (OCT) is an optical analogue to ultrasound imaging. The much higher speed of light compared with sound allows for finer cross‐sectional views of the retina and anterior segment. Since it is extremely difficult to directly detect the shorter “echo” times it takes light to travel from different structures at axial distances within the eye, interferometry is used. Incident light is thus split into two beams, and the beam backscattered from the ocular tissue is then compared (“interfered”) with the beam that has travelled a known time from the reference mirror. Broadband (i.e. low “coherence”) light sources are used, because they produce a wider band of wavelengths, and thereby enable greater sensitivity in comparing the travel time differences of the two beams. In time‐domain OCT, the reference mirror position is altered, so that interference patterns are generated whenever the two beams have travelled almost the same amount of time. In spectral‐domain OCT, the reference mirror position is fixed and the mixed interference patterns are separated via spectral wavelength analysis. This lecture will explain underlying concepts of OCT and its technological variations.
Adaptive optics ‐ Basic optical principles
Authors: Irsch Kristina
Published: January 2024

Adaptive Optics (AO) refers to a technique to compensate for distortions caused by optical aberrations in the media between the camera and the object being imaged. It was originally developed for use in astronomical telescopes to compensate for optical distortions induced by the inhomogeneous earth atmosphere. It has since evolved to become a powerful clinical tool in ophthalmology. In the eye, a “wavefront sensor” (aberrometer) measures the distortion of incoming light induced by inhomogeneities within the cornea and crystalline lens, which is then “undistorted” via reflection by a deformable mirror. AO thus enables imaging of the human retina with unprecedented resolution in vivo, such as revealing individual photoreceptors or the walls of blood vessels. One should note that AO by itself does not provide an image; rather an AO subsystem is incorporated into an existing imaging device. AO subsystems have thus far been successfully integrated into three ophthalmic imaging devices: fundus cameras, scanning laser ophthalmoscopes, and the OCT device. This lecture will introduce the basic principles of AO, illustrate its value with state‐of‐the‐art clinical examples, and discuss potential future applications in ophthalmology.
Genetic findings of inherited retinal diseases in France
Authors: Zeitz Christina , Audo Isabelle
Published: January 2024

Inherited retinal diseases (IRDs) are a major cause of retinal degeneration leading to progressive blindness with limited therapeutic options. The last decades have seen promising therapeutic development urging for a better characterization and understanding of IRDs. The genetics of IRDs is heterogeneous but the advent of high throughput sequencing including whole genome sequencing have greatly accelerated our capacity to identify their genetic cause, which is a prerequisite for adequate genetic counselling and developing innovative treatments. The success rate in detecting the genetic cause is however far from being complete with about 30% of cases that remains unresolved. Since the establishment of our group in 2007, we are working on a large cohort of patients (more than 8000 cases) with annual growth of 800 cases clinically investigated at the rare disease center REFERET of the Quinze‐Vingts hospital, Paris, France. By analysing >1000 cases with IRDs we delivered prevalence data and genotype–phenotype correlations of known gene defects. Furthermore, our group was successful in identifying 8 novel gene defects and novel phenotype–genotype associations in non‐syndromic and syndromic IRDs. Using Sanger sequencing, targeted next generation sequencing and whole exome sequencing we detect in ~70% of the cases with IRDs the underlying gene defect. Subsequently, the remaining cases are analysed by whole genome sequencing (WGS) and either identify missed structural and deep intronic variants in known genes or novel candidate genes. One challenge with current genomic‐based technologies is the capacity to unravel numerous genetic variants that are difficult to interpret in the context of the disease. Therefore, there is a need to conduct systematic studies associated with relevant functional validation to better decipher underlying gene defects that will lead to an enhanced understanding of the disease and improve patients' care. To validate the pathogenic role of a novel candidate gene and to further investigate the pathogenic mechanism, we developed a pipeline combining WGS, functional assays and disease modelling using induced pluripotent stem cells and more recently using zebrafish modelling. This revealed selected genetically unresolved families on which WGS analysis was performed and functional assays were initiated.
Microglial involvement in ocular hypertension
Authors: Salobrar‐Garcia Elena
Published: January 2024

Glaucoma, a chronic and multifactorial neurodegenerative disease, is the leading cause of irreversible blindness. It is characterized by the degeneration of retinal ganglion cells (RGCs), loss of their axons, and damage to the lamina cribrosa. To study glaucomatous optic neuropathy, experimental rodent models are commonly used due to their low cost, ease of handling, and similarities to the human retina. The ideal model must reproduce tissue changes observed in human glaucoma, such as alterations of the optic nerve head, thinning of the retinal nerve fibre layer, activation of glial cells, and progressive degeneration of RGCs.

The DBA/2J transgenic mouse model is the most commonly used genetic model, characterized by a gradual increase in intraocular pressure (IOP) with age, leading to rapid and progressive loss of RGCs and optic nerve degeneration. However, limitations such as iris atrophy and peripheral anterior synechiae can alter the anterior segment and influence IOP measurement. Induced models of ocular hypertension (OHT) have a predictable IOP increase following experimental procedures, but this increase is usually rapid and sustained for a relatively short time, which may not represent the slow and sustained IOP elevation observed in primary open‐angle glaucoma. Nonetheless, induced models produce similar pathophysiological mechanisms to genetic models. Other models include the injection of hypertonic saline into episcleral veins to cause scarring of the trabecular meshwork and elevate IOP, and the intracameral injection of polystyrene or magnetic microbeads to obstruct normal drainage flow of aqueous humour, resulting in an IOP increase. A new model employs an intracameral injection of a cross‐linking polymer that produces a viscosity increase, impeding normal drainage of the aqueous humour and resulting in an IOP increase and loss of RGCs.

In this SIS, we review the different glaucoma models, their methods, and the retinal tissue changes, with a focus on microglial cell changes.
Retinal glial cell response in a neurodevelopmental disease such as the Dravet syndrome
Authors: Fernández‐Albarral José A.
Published: January 2024

Dravet syndrome (DS) is an epileptic encephalopathy caused by mutations in the Scn1a gene encoding the α1 subunit of the Nav1.1 sodium channel, which is associated with recurrent and generalized seizures, highly resistant to antiepileptic drugs, which is related to cognitive impairment, developmental delays, hyperactivity, dysautonomia, attention deficit, language impairment, autistic features, even leading to death. GABAergic interneurons are particularly affected, where the Nav1.1 channel is mainly located and the consequent imbalance between excitation and inhibition triggers brain hyperexcitability and seizures, altering the correct functioning of neural networks involved in cognitive processes.

Glial reactivity and neuroinflammatory processes have been shown to be present in childhood epileptic processes and therefore cytokines may exert a neuromodulatory role directly impacting neuronal excitability. Indeed, astrocytes have been documented to be involved in the pathogenesis of epilepsy, regulating neurotransmitter and ion concentrations.

In our experimental model of DS (Syn‐Cre/Scn1aWT/A1783V), inflammatory events in the prefrontal cortex and dentate gyrus of the hippocampus expressed as an increase in GFAP (astrocyte marker) and Iba‐1 (microglia marker) immunoreactivity have been observed, in addition to morphological changes compatible with activated astrocytes and microglia.

The retina is a projection of the brain, and in several pathologies affecting the central nervous system, such as neurodegenerative diseases, correlation between changes occurring in the brain and those occurring in the retina has been shown. Therefore, the analyse of the changes that may occur in retinal glial cells (astrocytes and microglia) in an experimental model of DS, and the correlation with the alterations observed in some specific cerebral areas of these animals could be good predictive and prognostic biomarkers for future treatment.

This study analyzes the retinal histological changes in glial cells (microglia and astrocytes), retinal ganglion cells (RGCs) and GABAergic amacrine cells in an experimental model of DS (Syn‐Cre/Scn1aWT/A1783V) compared to a control group at postnatal day (PND) 25. Retinal whole‐mounts were labelled with anti‐GFAP, anti‐Iba‐1, anti‐Brn3a and anti‐GAD65/67. Signs of microglial and astroglial activation and the number of Brn3a+ and GAD65+ 67+ cells were quantified. We found retinal activation of astroglial and microglial cells but not death of RGCs and GABAergic amacrine cells. These changes are similar to those found at the level of the hippocampus in the same experimental model in PND25, indicating a relationship between brain and retinal changes in DS. This suggests that the retina could serve as a possible biomarker in DS.
What about generic glaucoma medications and the ocular surface?
Authors: Kolko Miriam
Published: January 2024

There is an ongoing debate among healthcare providers about the safety and effectiveness of generic eye drops compared to branded eye drops. Although one would expect generic eye drops to be a true copy of the original eye drop, there are surprisingly few requirements for the introduction of a generic eye drop on the market. Thus, only the concentration of the active ingredients must be identical to that of the original product. As many other factors such as bottle material, bottle shape and size and cap colour, drop size, pH, viscosity and buffer capacity can influence the efficacy, there are doubts whether generic products are truly identical to their original variants. This presentation will provide an overview of current original/generic eye drops and the challenges that patients may face when using generic variants.
Biomarkers in macular hole surgery
Authors: Motta Lorenzo
Published: January 2024

A macular hole is a condition that affects the central part of the retina, the macula. It is characterized by the formation of a hole or tear in the tissue, which can lead to blurred or distorted vision. Early detection and treatment of macular holes are critical to prevent permanent vision loss. Biomarkers are measurable indicators of biological processes that can aid in the diagnosis and management of macular holes.

One of the most commonly used biomarkers for macular holes is optical coherence tomography (OCT). OCT uses light waves to create high‐resolution images of the retina, allowing for the detection and monitoring of macular holes. OCT can also be used to measure the size and depth of the hole, which can help guide treatment decisions.

Another biomarker for macular holes is the presence of cytokines and growth factors in the vitreous, the gel‐like substance that fills the eye. Cytokines and growth factors are signalling molecules that play a role in the inflammatory response and tissue repair. In patients with macular holes, the levels of certain cytokines and growth factors are altered, indicating the presence of inflammation and tissue damage.

Recent studies have also identified genetic biomarkers associated with the development and progression of macular holes. For example, mutations in the FZD4 gene have been linked to an increased risk of macular holes, while variations in the CX3CR1 gene have been associated with a more severe form of the condition.

Biomarkers can also be used to monitor the response to treatment in patients with macular holes. For example, changes in cytokine and growth factor levels following treatment can indicate whether the treatment is effective in reducing inflammation and promoting tissue repair. Similarly, changes in OCT measurements can indicate whether the hole is closing and vision is improving.

Overall, biomarkers play an important role in the diagnosis, management, and monitoring of macular holes. By providing objective measures of disease progression and response to treatment, biomarkers can improve outcomes for patients with this condition. However, more research is needed to fully understand the role of biomarkers in macular holes and to identify new biomarkers that may aid in the diagnosis and treatment of this condition.
Biomarkers in diabetic retinopathy
Authors: Zaman Anwar
Published: January 2024

Diabetic retinopathy (DR) is a leading cause of blindness in working‐age adults worldwide, affecting up to 80% of patients who have had diabetes for more than 10 years. Biomarkers are measurable indicators that can be used to diagnose diseases or monitor their progression. In DR, biomarkers can be found in various structures of the eye, including the retina, vitreous, and aqueous humour.

One of the most commonly used biomarkers in DR is glycated haemoglobin (HbA1c), which reflects long‐term blood glucose control. Elevated HbA1c levels are associated with an increased risk of developing DR, and strict glycemic control can help to prevent or delay its onset.

Other biomarkers in DR include imaging techniques such as optical coherence tomography (OCT) and fundus photography, which can provide detailed images of the retina and allow for the detection of microaneurysms, haemorrhages, and exudates. OCT angiography (OCTA) can also visualize changes in retinal blood flow, which may be indicative of early DR.

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 DR and assess the efficacy of treatment.

Recent advances in biomarker research have led to the discovery of new markers for DR, including genetic markers, inflammatory markers, and metabolic markers. Genetic markers, such as single nucleotide polymorphisms (SNPs), have been associated with an increased risk of developing DR. Inflammatory markers, such as cytokines and chemokines, are elevated in the aqueous humour and vitreous of patients with DR and may contribute to the development and progression of the disease. Metabolic markers, such as advanced glycation end‐products (AGEs), are elevated in patients with DR and may play a role in the pathogenesis of the disease.

Overall, biomarkers are an important tool in the diagnosis, monitoring, and management of DR. They may also help to improve our understanding of the disease and facilitate the development of new therapies. By identifying patients at high risk of developing DR, biomarkers may enable earlier interventions to prevent or delay the onset of vision loss.
Biomarkers in epiretinal membrane surgery
Authors: Vakalis Athanasios
Published: January 2024

Vitreoretinal Surgery for the removal of Epiretinal membranes is a well‐established surgical indication. Despite refinement of surgical techniques and the revolution in imaging brought by the advent of Optical Coherence Tomography, a significant proportion of patients fails to gain vision postoperatively.

In this talk we will discuss OCT biomarkers that help as distinguish those who can improve most following surgery from those unlikely to respond.
The importance of precisely phenotyping patients with high myopia
Authors: Audo Isabelle , Zeitz Christina
Published: January 2024

High myopia can be isolated or a phenotypic feature of a Mendelian gene defect. These should be recognized as they may require a specific patient’ management and counselling. They should also be precisely individualized while conducting research on deciphering the risk haplotypes for the development of idiopathic myopia as they would represent confounding factors. The presentation will review the differential diagnosis for syndromic myopia and suggest a set of minimal ophthalmic testing to establish an appropriate diagnosis.
The limbal stem cell niche in development, insights from mouse models and children with aniridia
Authors: Lagali Neil
Published: January 2024

Congenital aniridia, a rare eye disease of underdevelopment of the eye, leads to multiple eye abnormalities and pathologies, including a progressive limbal stem cell deficiency leading to the emergence and progression of an aniridia‐associated keratopathy. A deeper understanding of the characteristics of this deficiency could help to explain the observed pattern of progression and may provide insights into future treatments of this, and other types of limbal stem cell deficiency. From imaging studies in infants and young children with aniridia but with clear corneas, early phenotypic changes are apparent at the limbal border, with vascular tissue and inflammation apparent. In the central cornea, elevated inflammation and a nerve deficit are present early in life. In a novel mouse model of aniridia with slow development of keratopathy, limbal stem cell markers are perturbed after birth in clear corneas, and exhibit a characteristic time‐dependent pattern as the onset of clinically visible keratopathy emerges and starts to progress. Changes in the stromal and subbasal corneal nerves are also visible in the model and can provide insights into the neural deficit seen in the human disease. The model is moreover ideal for the evaluation of novel compounds aiming to slow the progression of keratopathy and preserve corneal transparency.
IOL's material and PCO
Authors: Grzybowski Andrzej
Published: January 2024

Posterior capsular opacification (PCO) is the most common of late post‐surgery complications and can lead to reduced visual acuity, diplopia, or glare. The different types of material used in intraocular lenses (IOLs) plays a significant role in possible post‐surgery complications, such as anterior capsule opacification (ACO) and phimosis, posterior capsule opacification (PCO), and the formation of IOL opacification. PCO incidence increases with time and varies from 10% to 50%. The incidence of PCO will rise in the nearest future since IOLs will stay longer in the eye, as people's lifespans are increasing. It was shown that hydrophilic IOLs had significantly more and denser PCO than hydrophobic or silicone IOLs. The higher incidence of PCO formation in hydrophilic than in hydrophobic IOLs should be considered as an important medical and health economic issue when choosing the IOL for implantation.
Effect of antiglaucomatous eye drops on corneal endothelium
Authors: Gugleta Konstantin
Published: January 2024

First choice therapy for reducing the intraocular pressure in context of glaucoma remains the applications of eye drops. Longterm exposure to topical therapy can clearly have an impact on the ocular surface, but as the medications penetrate through the cornea and are present in humour aqueous, also on all other layers of cornea, including corneal endothelium. In general, none of the medications from the standard pharmacological groups influences significantly an otherwise healthy corneal endothelium in an eye with glaucoma or ocular hypertension – be it in terms of central corneal thickness, be it in terms of endothelial cell density and morphology, be it for beta blockers, carbonic anhydrase inhibitors, pilocarpine, alpha2 agonists or prostaglandin analogues. The situation changes in diseased corneas, such as in Fuchs endothelial dystrophy, where topically applied carbonic anhydrase inhibitors can lead to increase in corneal thickness. Benzalkonium chloride has been proven toxic for corneal endothelial cells in vitro. However, in the daily practice and under real life circumstances, it is from the specific point of view on the corneal endothelium still not clear whether using non‐preserved topical glaucoma medications is an absolute imperative. One separate topic here is also a group of Rho‐kinase inhibiting topical medications. Apart from new mechanisms of action for reducing the intraocular pressure, this group of medications has also a direct influence on the corneal structures – from cornea verticillata on the epithelium corneal level, to mobilizing peripheral endothelial corneal cells as a possible therapeutic path for Fuchs endothelial dystrophy. One part of the lecture will address also these issues.