bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifocal electroretinogram in the diagnosis of Stargardt disease
Authors: Sopeña‐Pinilla Maria , Álvarez Marta Arias , Fernández‐Espinosa Guisela , Alonso Sofia Bielsa , Tomas‐Grasa Cristina , Boned‐Murillo Ana , Díaz‐Barreda Mª. Dolores , Hospital Elvira Orduna , Pinilla Isabel 
Published: January 2024

Aims/Purpose: Electrophysiological vision tests have been a key method in the diagnosis and monitoring of inherited retinal dystrophies (IRD). With the development of mfERG, the clinical applications of these tests have expanded to cone dystrophies such as Stargardt disease, which is the most common cone‐IRD. This disease is typically associated with an autosomal recessive inheritance pattern, primarily, although not exclusively, due to mutations in the ABCA4 gene. The introduction of different diagnostic techniques such as Optical Coherence Tomography (OCT), OCT Angiography (OCTA), autofluorescence (FAF) and microperimetry has diminished the importance of fluorescein angiography (FA). These techniques have been joined by the diagnostic role of mfERG.The aim of this study is to evaluate functional changes in patients with Stargardt disease using mfERG.Methods: Eighteen eyes of patients with Stargardt disease were included. The disease was previously confirmed by genotyping with homozygous ABCA4 mutations or heterozygous PROM1 mutations. The patients were evaluated using mfERG, using the standardized international ISCEV guidelines. Electrical density and implicit time of each first‐order response (K1) in the five concentric rings centered on the fovea were measured and analysed.Results: Mean best‐corrected visual acuity (BCVA) was 0.5 (0.12–1.0). First‐order responses (K1) showed a decreased electrical density, predominantly in central rings, along with minimally prolonged latencies of the P1. FAF showed central atrophy in 6 patients, atrophy with flecks within or beyond the vascular branches in 8 and 4 patients respectively.Conclusions: Stargardt disease involves cones and is characterized by a significant decrease in foveal and central response in mfERG, even in early stages when BCVA remains relatively preserved and fundus findings are minimal. Flash ERG may show normal results or minimal abnormalities.
The use of colour and rapid flicker sensitivity tests for early detection and monitoring of vision changes in diabetes
Authors: Vaughan Megan , Bohra Sajni , Patterson Emily , Rodriguez‐Carmona Marisa , Barbur John 
Published: January 2024

Aims/Purpose: There is increasing evidence of impaired visual function prior to the presence of diabetic retinopathy (DR), yet current diagnostic criteria and treatment onset rely mostly on retinal vascular changes. In this study we measured changes in chromatic and rapid flicker sensitivity in subjects with prediabetes and diabetes to establish the value of such tests as a potential biomarker in the detecting early diabetes.Methods: Three groups of subjects were recruited: 1) normal controls, 2) subjects with prediabetes (HbA1c between 42‐47 mmol/mol), and 3) diabetics (with or without DR). Monocular cone‐ and rod‐enhanced flicker modulation thresholds (FMTs) were measured at the point of regard and in four parafoveal (5°) locations using the Flicker‐Plus test. Monocular red/green (RG) and yellow/blue (YB) colour thresholds were also measured at the fovea using the Colour Assessment and Diagnosis (CAD) test.Results: Both the RG and YB thresholds, as well as rod‐ and cone‐mediated flicker thresholds were significantly higher in both diabetic and prediabetic groups (when compared with healthy controls). When examined individually, ~50% and ~ 63% of the prediabetics and ~ 58% and ~ 70% of the diabetics revealed abnormal RG and YB thresholds, respectively (when compared with the upper normal limits for the corresponding age). HBA1c levels also revealed a positive trend with increasing RG and YB thresholds in the prediabetic group.Conclusions: In agreement with previous findings, both colour and FMTs are affected in patients diagnosed with diabetes. Unexpectedly, those deemed prediabetic that do not meet the clinical criteria for diabetes exhibit considerable loss of both colour and flicker sensitivity. The results suggest that colour and rapid flicker tests can provide useful information when screening for diabetes.
Postoperative glaucoma following cataract surgery in children
Authors: Hammoumi Zineb , Ghizlane Daghouj , Sarah Houti , Mathilde Otsasso , Loubna El Maaloum , Bouchra Allali , Asmaa El Kettani 
Published: January 2024

Aims/Purpose: The aim of this work is to investigate the prevalence of secondary glaucoma and its associated risk factors in children undergoing congenital cataract surgery.Methods: A retrospective study was performed, spread over 8 years, from January 2014 to October 2021, in the paediatric ophthalmology department at the August 20 Hospital in Casablanca. It includes 516 eyes of children operated on for congenital cataract and aged under 16.Results: Development of glaucoma was defined as IOP > 22 mmHg, increased corneal diameter, increased cup to disc ratio, and reduced anterior chamber depth. We mainly evaluated the following risk factors: age at the time of surgery, unilateral or bilateral cataract, presence of microcornea, performance of posterior capsulotomy with anterior vitrectomy and primary implantation.Conclusions: Congenital cataract surgery at an early age increases the risk of developing glaucoma, whether the eye is aphakic or pseudophakic. The management of secondary glaucoma is heavy, the visual prognosis is compromised, hence the interest of long‐term follow‐up.
Kinetics of infection and local immune response in a model of chlamydia trachomatis conjunctival infection
Authors: Paulet Elodie , Galhaut Mathilde , Contreras Vanessa , Le Grand Roger , Labetoulle Marc , Rousseau Antoine 
Published: January 2024

Aims/Purpose: Trachoma is caused by Chlamydia trachomatis conjunctival infections and evolves in two phases: i) active or acute trachoma caused by repeated infections and ii) scarring or chronic trachoma leading to conjunctival scarring, eyelid malposition, and corneal opacification. It remains the first cause of infectious blindness in developing countries. The purpose of this study was to precisely describe the kinetics of infection and local immune response in a non‐human primate model of acute trachoma.Methods: Cynomolgus Macaques received a single conjunctival inoculation of B/Tunis‐864 strain (104 IFU) and were assessed at weeks 2, 4, 6, 9, and 11. Clinical evaluation was performed by 3 independent masked observers on standardized ocular surface photographs graded using specific scores for both inflammation and follicles. Local immune response was assessed using multiparameter flow cytometry of conjunctival cells eluted from conjunctival prints. Tears cytokines were quantified using bead‐based Luminex multiplex assay. Bacterial quantification in conjunctival fluids was performed with quantitative PCR.Results: All animals (n = 12) developed typical follicular conjunctivitis (n = 12). The first 4 weeks post‐exposure were characterized by a conjunctival T cell influx (63% of CD45+ cells at week 3), with elevated interleukins 4, 8, and 5. In the later phase, after 9 weeks, we observed an influx of monocytes (53,2% of CD45+ cells at week 11) with reduced immune cells and a return to the initial cytokines level.Conclusion: This model faithfully mimics trachoma's acute phase. Local immunologic assays showed an early lymphocyte response with long‐term persistence of innate immune effectors. It offers an opportunity to assess potential preventive therapeutic strategies. Further studies, including implementing repeated bacterial conjunctival inoculations, are warranted to investigate the later stages of the diseases.
Identification of the characteristic visual field loss patterns in optic neuropathies
Authors: Barboni Piero 
Published: January 2024

Visual fields support physicians in the diagnosis and progression tracking of optic neuropathies, enabling the visualization of the site of the optic nerve or optic pathways damage. Furthermore, the identification of the underlying patterns of different optic neuropathies can strengthen the diagnosis or help the clinicians for the patient's prognosis. Different abnormalities have been described and associated to neuroophthalmological diseases, such as central and ceco‐central scotomas related to hereditary optic neuropathies as Leber and dominant optic atrophy diseases which are mostly affected in the macular retinal ganglion cells and the papillomacular bundle. Altitudinal defects are usually associated with ischemic optic neuropathies, and in the big field of glaucoma the most commonly abnormalities are the arcuate and the nasal step.Related to this topic, artificial Intelligence is gaining traction, implementing, and testing different approaches to the automatic detection of visual field loss patterns in distinct diseases. For example, application of archetype analysis for the detection of glaucoma progression or for the assessment of efficacy in idiopathic intracranial hypertension treatment trial.
The future of visual fields
Authors: Tatham Andrew 
Published: January 2024

Perimetry forms an essential component of the assessment of visual function, particularly for glaucoma and neurological conditions affecting vision. Conventional automated perimetry though has limitations, including that it is disliked by patients, takes considerable time, particularly in those with poor vision, and is subject to visit‐to‐visit variability meaning a large number of tests are often needed to confidently detect change over time. Regrettably visual field testing is often performed less frequently than it should. Though imaging techniques such as optical coherence tomography (OCT) provide objective information about the structure of the retina and optic nerve head, imaging is not a substitute for assessment of visual field, and perimetry remains a measure more directly relevant to vision‐related quality of life.Several new perimetry devices are under development and evaluation including devices for home perimetry using virtual reality headsets or tablet computers, and devices which detect response to stimuli using eye tracking rather than relying on the patient pressing a button. Such technologies may allow a greater number of visual field assessments, potentially improving ability to detect change. Progress is also being made to optimize visual field test strategies and to combine information from tests of structure and function.
How imaging can make challenging cases in uveitis easy
Authors: Koutsiouki Chrysoula 
Published: January 2024

Uveitis cases can be challenging in diagnosis, management, monitoring the treatment response and prognosis.The Multimodal imaging can provide us with key features findings in diagnostic dilemma cases, treatment response and prognosis response in severe refractive posterior uveitis cases.Fluorescein and Indocyanine Angiography have been the Gold Standard for many years along with the OCT expanding role in Uveitis in recent years (ex‐Bacillary Detachment, Acute Macular Neuropathy, White Dot Syndromes etc.).Fundus Autofluorescence (FAF), Enhanced Deep Imaging of the Choroid (EDI), OCT –Angiography inclusive Wide Field imaging play also a crucial role in the management of challenging Uveitis cases .Challenging Uveitis cases combined with complex Uveitic treatment highlight the importance of Multimodal imaging key role for all Uveitis specialist.
The two extremes of retinal fold management
Authors: Stappler Theodor 
Published: January 2024

Aims/Purpose: Retinal folds represent a debilitating complication following retinal detachment surgery. While some patients may experience partial retinal flattening with minimal or moderate improvement of visual function, many will go on to suffer severe permanent vision loss. The indication and timing of possible reintervention is still debated, particularly for how long after initial retinal fold formation there can still be a reasonable expectation of anatomical and functional improvement.Methods: We present the cases of two patients suffering debilitating postoperative macular folds at opposite ends of the intervention window, who were referred to the Jules Gonin Hospital at different postoperative timepoints following retinal detachment surgery. Patient Nr 1 was re‐operated within 20 days of the initial surgery, patient Nr 2 10 months later. Retinal folds were confirmed by preoperative OCT and pre‐ and post‐op cyclotorsion was measured on fundus photography.Results: Patient Nr 1 recovered vision from CF to 0.2 logMar within 3 months, improving to 0.0 logMar after 1 year. Patient No 2 recovered from HM to 0.6 after 3 months and further to 0.5 logMar after 1 year. Most importantly, while patient Nr 1 had no more cyclotorsion, undisturbed binocular vision already on day one postoperatively, even to the absence of metamorphopsia during follow‐up, patient Nr 2 recovered slowly, also regaining binocularity without cyclotorsion, but with lasting metamorphopsia. During the video presentation the different retinal elasticity at these differing timepoints can be demonstrated intraoperatively as well as different strategies to induce retinal separation so that the central retina can be reattached in a new, more physiological position.Conclusions: Our cases illustrate that early intervention can lead to a virtually symptom‐free result while even delayed intervention may still be able to achieve some improvement in visual function and the avoidance of monocularity.References:Heimann H, Bopp S. Retinal folds following retinal detachment surgery. Ophthalmologica. 2011;226 Suppl 1:18–26.Wong R. Longitudinal study of macular folds by spectral‐domain optical coherence tomography. Am J Ophthalmol. 2012 Jan;153(1):88‐92.e1.
Genetic background of congenital aniridia
Authors: Damian Alejandra , Blanco‐Kelly Fiona , Tamayo Alejandra , Swafiri Saoud T. , Villaverde Cristina , Ruiz‐Sánchez Carolina , Tory Kálmán , Szentmáry Nóra , Ayuso Carmen , Corton Marta 
Published: January 2024

Congenital aniridia is a complex disease, characterized mainly by iris and foveal hypoplasia, but patients show great clinical variability with overlapping of different anterior and posterior segment anomalies. More than 90% of patients carry heterozygous variants in the PAX6 gene, a highly conserved transcriptional regulator that plays a key role in normal ocular development. Loss‐of‐function variants causing premature stop codons are the most frequent within the broad mutational spectrum of PAX6, with more than 750 different mutations identified to date. 11p13 microdeletions altering PAX6 or its downstream regulatory region have been found in ~25% of patients. Iris abnormalities are also present in various aniridia‐mimicking conditions, such as FOXC1 and PITX2‐related anterior segment dysgenesis, among other minor genes. Therefore, this is now recognized that genetic and clinical diagnosis of patients with suspected aniridia is challenging. Genetic testing has proven to be crucial for differential diagnosis. Here, we update best practices to improve genetic testing and clinical management of aniridia using more cost‐effective next‐generation sequencing analysis.Recent advances in genomic sequencing contributed to increasing diagnostic yield in congenital aniridia and allied conditions, from 70 to 95% as we demonstrated in a cohort of Spanish patients, and also in a “naïve” cohort of Hungarian patients without previous genetic testing. NGS allowed us to identify pathogenic PAX6 variants in patients with an atypical or incomplete presentation of aniridia, such as isolated foveal or optic nerve hypoplasia. In addition, genomic approaches contributed to elucidating new molecular mechanisms underlying the etiopathogenesis of congenital aniridia involving non‐coding PAX6 variants and revealed an unexpected role of mosaic variants in the intrafamilial variable expressivity of aniridia.Emerging long‐read sequencing techniques may provide insight into hidden sources of variation at PAX6 locus in some patients with unexplained genetic causes of aniridia. Nanopore‐based long‐read whole genome sequencing unveiled cryptic balanced chromosomal structural variants that directly disrupt PAX6 or its regulatory elements.In conclusion, NGS‐based genetic testing is crucial to ensure a correct and timely clinical diagnosis, and provide better prognosis and management of patients with aniridia or aniridia‐like, besides the further benefits to families by allowing prenatal and preimplantation genetic testing. Genetic findings would also be critical in defining eligible patients for future clinical trials.
Identification of duloxetine to treat aniridia‐related keratopathy: Link to inflammation?
Authors: Evnouchidou Irini , Aberdam Daniel 
Published: January 2024

Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by iris hypoplasia and reduced visual acuity. Patients have also progressive disorders including aniridia‐related keratopathy (ARK), caused by a combination of factors including limbal stem‐cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub‐epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. There is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9) to introduce a nonsense mutation into one allele of the PAX6 gene in limbal stem cells.The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also altered. Of interest, recombinant PAX6 protein was sufficient to rescue the phenotype. By High Throughput Screening of a FDA‐approved library, we identified Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor antidepressant, that rescued both PAX6 endogenous protein level and altered cell migration of the mutant limbal stem cells, through specific inhibition of the ERK/MEK pathway. Furthermore, we found that Duloxetine modulates inflammation through activation of Pax6, strongly suggesting that Pax6 could be a modulator of neuroinflammation. Since Duloxetine is already used as anti‐psychotropic drugs, its repurposed use to treat topically aniridia eye and other ocular inflammatory diseases could become realistic.
Detection of the sign of defocus by the retina and its implication for myopia
Authors: Goethals Sarah 
Published: January 2024

To reduce myopia progression and mitigate its impact, it is necessary to slow down eye growth. Previous studies have shown that the retina is able to detect if the visual image, transformed by the eye optics, is focused in front or behind the retina, and subsequently modulates eye growth. However, it is not clear how it can achieve such a feat. We do not know what feature the retina extracts from the visual scene to detect if there is a positive (hyperopic) or negative (myopic) defocus. In this work, we aimed at understanding how the mouse retina can compute the sign of defocus from the visual input it receives.To investigate that question, we separated the respective contributions of the eye optics and of retinal processing by performing in vitro recordings of the isolated mouse retinas with multi‐electrode arrays while presenting natural images transformed by the simulated optics of the mouse eye for different values of defocus, simulating images focused in front of behind the retina.Our preliminary results show that this approach can be a promising method to understand how the retina detects whether the image is focused in front or behind the retina and can provide a mechanistic explanation for several results about myopia control solutions.
The role of optical coherence tomography biomarkers in predicting the outcome of epiretinal membrane removal surgery
Authors: Georgiadis Odysseas 
Published: January 2024

Epiretinal membrane (ERM) is a common condition that can cause visual impairment. ERM removal surgery is an effective treatment option, but predicting postoperative visual outcomes is challenging. Imaging modalities, particularly optical coherence tomography (OCT), have emerged as valuable tools for preoperative evaluation and predicting surgical outcomes. This presentation focuses on the role of preoperative OCT biomarkers in estimating postoperative vision improvement after ERM removal surgery. Such biomarkers include the disorganization of retinal inner layers (DRIL), the presence of ectopic inner foveal layer (EIFL), the cotton ball sign, the cone outer segment tips (COST) line, the photoreceptor outer segment (PROS) length, the inner retina irregularity index, and the presence of posterior vitreous detachment (PVD).DRIL refers to the abnormal appearance of the inner retinal layers on OCT, and has been found to be associated with poorer postoperative visual outcomes in ERM removal surgery. Significant EIFL has also been associated with poorer visual outcomes after surgery. The cotton ball sign, which appears as a hyper‐reflective area in the inner nuclear layer, has been found to be associated with increased difficulty in ERM removal and poorer visual outcomes. These biomarkers suggest that a greater degree of retinal disorganization and irregularity may lead to more challenging surgeries and poorer visual outcomes.In contrast, the presence of intact COST line and normal PROS length have been associated with better visual function. PVD, which represents separation of the vitreous from the retina, has been shown to be associated with less surgical trauma and better postoperative outcomes. The inner retina irregularity index, which measures the extent of disorganization of the inner retinal layers, has also been found to correlate with the changes in metamorphopsia and quality of vision after surgery.These biomarkers have the potential to improve the accuracy of preoperative evaluation and prediction of surgical outcomes in ERM removal surgery. By identifying patients with a greater degree of retinal disorganization and irregularity, we can anticipate more challenging surgeries and poorer visual outcomes. Conversely, patients with minimal COST line defects, normal PROS length and full PVD may have better postoperative visual outcomes.In summary, preoperative OCT findings can help predict postoperative visual outcomes in ERM removal surgery. The use of imaging modalities and specific biomarkers can provide useful insight in management decisions, case selection, and timing of surgery.