bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of treatments for retinopathy of the premature in Africa
Authors: Queiros António , Hauela Gisela , Fernandes Paulo , Diaz‐Rey José
Published: January 2024

Aims/Purpose: Retinopathy of premature is currently one of the biggest causes of childhood blindness in the world. Its prevention and control has been widespread, although many underdeveloped countries face numerous difficulties in controlling it. To summarize the treatments types and methods of screening in Africa.

Methods: A systematic review of studies carried out in Africa using the statistical program R was performed, for data collection the Boolean operators (and, or) and mesh words (treatment, retinopathy of the premature and Africa) were used on the platforms of pubmed and google academic. 27 studies were found, 6 were clinical trials, with only 4 studies included in the meta‐analysis.

Results: the risks for developing retinopathy of premature are the premature birth of the baby and the lack of adequate monitoring during the incubation period. In African countries with published studies, the most used treatment methods are non‐invasive ventilation and the injection method of bevacizumab.

Conclusions: Low birth weight and lower gestational age are directly related to the risk of developing retinopathy in the baby, bevacizumab is the most effective method reported so far and the best screening method for this pathology is based on the algorithm of birth weight.
Color fundus photography versus fundoscopy in diabetic retinopathy patients: A pilot study
Authors: Kabanarou Stamatina , Bitzanakis Nikolaos , Bontzos Georgios , Smoustopoulos Georgios , Sgourou Chrysoula , Garnavou‐Xirou Christina , Xirou Tina
Published: January 2024

Aims/Purpose: To compare fundoscopy with Color fundus photography (CFP) in identifying diabetic retinopathy (DR) abnormalities.

Methods: This is a pilot cross‐sectional study of diabetic patients attending the medical retina clinic for routine examination. All patients underwent dilated indirect ophthalmoscopy and CFP, both performed by the same doctor. The following retinal features were identified in 5 segments during both procedures (CA‐central area, UT‐upper temporal, LT‐lower temporal, UN‐upper nasal, LN‐lower nasal): pre‐retinal/retinal (RH)/vitreous haemorrhages, exudates (EX), intraretinal microvascular abnormalities (IRMA), venous beading (VB), vein loops (VL), cotton wool spots (CWS), retinal neovascularization (NVD/NVE) and ghost vessels (GV).

Results: Thirty‐six eyes of 18 patients were included in the study. Overall, CFP recorded more retinal features in comparison with fundoscopy in most segments. In particular, in CFP: RH and VB were identified in 1 extra case but CWS was missed in 2 cases in CA. Imaging in UT segment revealed RH and CWS in 3 and 1 additional cases, respectively. RH, VB, CWS were recorded in 3, 1 and 1 extra cases in LT. RH and EX were documented in 4 and 1 additional cases respectively while CWS and GV were missed in 1 case in UN. In LN, RH and GV were identified in 2 extra cases, but NVD/NVE was missed in 1 case. The main differences were observed in the documentation of RH in all but one segment (apart from CA) as in >3 cases in each segment, RH was missed in fundoscopy. Moreover, in CA, retinal features were similarly identified in both examination techniques.

Conclusions: Fundoscopy is part of routine ophthalmic assessment but requires experience and adequate patient cooperation. CFP is a reliable imaging tool that can objectively document diabetic retinopathy lesions. New advances in retina imaging make CFP a promising device for DR assessment patients.
Evaluating the macular vascular complexes' density by OCTA for dyslexia
Authors: de los Reyes Retamero Sánchez María , Gómez‐Molina Celia , Miquel‐López Carmen , Navarro‐Abellán Maria Victoria , De‐Paco‐Matallana Maravillas , Espín‐López Laura , del Pino Sánchez María , del‐Río‐Vellosillo Mónica , García‐Medina Jose Javier
Published: January 2024

Aims/Purpose: To compare the vascular density of macular superficial and deep vascular complexes between dyslexic subjects and normoreaders at the fovea and parafovea.

Methods: We performed a pilot study examining 60 eyes—36 of subjects with dyslexia and 24 of normoreaders as controls. Al the participants underwent an ophthalmological examination complemented with an optical coherence tomography angiography (OCTA) (Spectralis, Heidelberg Engineering, Germany), in which we measured the vascular density of the deep and superficial vascular complexes of the macula using an ETDRS123 pattern.

Results: The deep vascular complex of the fovea was found to have a significant increase in the density of the different subfields of the inner and outer parafovea in the dyslexic group, as compared to the normoreaders. In contrast, no differences were found for the superficial vascular complex at any subfield.

Conclusions: The increase in the deep vascular complex density of the macula could be associated with dyslexia.
Choriocapillaris, photoreceptor and inner retinal layers in spatial relationship to parapapillary alpha, beta, gamma and delta zone
Authors: Jonas Jost , Jonas Rahul , Jonas Shefali , Panda‐Jonas Songhomitra
Published: January 2024

Aims/Purpose: To examine the spatial relationships between the choriocapillaris, retinal layers and retinal pigment epithelium (RPE) in the parapapillary region.

Methods: Human eyes enucleated due to uveal melanomas or secondary angle‐closure glaucoma were histomorphometrically examined.

Results: The investigation consisted of 100 globes. In non‐highly myopic non‐glaucomatous eyes, the photoreceptor layer, choriocapillaris and retinal inner nuclear layer (INL) ended approximately at the end of the RPE layer, with no significant (all p ≥ 0.10) difference between the layers. In the non‐highly myopic, glaucomatous eyes and the highly myopic eyes, the photoreceptor layer, choriocapillaris and inner nuclear layer ended in the majority of eyes beyond the RPE‐end in direction to the optic disc border, with the INL extending beyond the RPE‐end significantly more than the photoreceptor layer (non‐highly myopic non‐glaucomatous group: 133 ± 183 μm versus 66.5 ± 96.8 μm; p = 0.001; highly myopic glaucomatous eyes: (266 ± 395 μm vs. 211 ± 286 μm; p = 0.03). A larger extension of the photoreceptor layer, choriocapillaris and INL beyond the RPE‐end correlated with longer axial length (beta: 0.50; B: 32.2; 95% CI: 21.6, 42.8) and wider beta zone (beta: 0.28; B: 0.10; 95% CI: 0.04, 0.16), with longer axial length (beta: 0.24; B: 23.0; 95% CI: 1.6, 44.5) and longer beta zone (beta: 0.59; B: 0.32; 95% CI: 0.22, 0.41; p < 0.001), and with longer axial length (beta: 0.34; B: 43.7; 95% CI: 11.6, 75.7), longer gamma zone (beta: 0.52; B: 0.28; 5% CI: 0.15, 0.41) and diagnosis of non‐highly myopic glaucoma (beta: 0.28; B: 267; 95% CI: 80.8, 454), respectively.

Conclusions: Non‐glaucomatous non‐highly myopic eyes differ from highly myopic eyes and glaucomatous eyes in the spatial relationship of the parapapillary tissue layers. The findings support the notion of an axial elongation‐associated shifting of the parapapillary RPE and Bruch's membrane for development of myopic beta zone, and an RPE‐cell loss for development of glaucomatous beta zone.
The use of artificial tears among the danish population: Epidemiological observations
Authors: Ahrensberg Simone , Andreasen Jens Rovelt , Kolko Miriam
Published: January 2024

Aims/Purpose: To investigate the use of artificial tears (AT), identify which eye diseases are most prevalent among the users, determine which products are preferred by the population, and analyse their preservative content.

Methods: Data originate from the FOREVER questionnaire. Respondents are customers from Synoptik A/S aged from 18 years and of both genders, and have given written consent for the use of their data. All 48 AT in the questionnaire appear in The Nordic Guidelines Dry Eye Disease 2022. T‐test and chi2 were performed to examine significant differences in the data.

Results: 41.723 participants had answered the questionnaire, 15.613 men and 26.110 women, with a mean age of 55.4 (15.0) years. 10.1% reported having an eye disease diagnosed by a doctor, the most prevalent being cataract, then glaucoma, vitreous detachment and age‐related macular degeneration (AMD). 5129 (12.3%) used AT. This subpopulation consisted of 1268 men and 3861 women with a mean age of 61.2 (14.8) years. 21.8% had an eye disease diagnosed by a doctor. The most prevalent eye disease remained cataract, then glaucoma, vitreous detachment and AMD. Thealoz Duo (preservative free (PF)) was the most used brand, then Systane Ultra (PF or PolyQuad 0.001%) and Viscous Eye Drops (benzalkonium chloride (BAK) 0.011%). It was possible to identify 2560 respondents using a PF product and 874 using a product with a preservative. The mean age was significantly higher among those using AT, compared with those who did not use AT (54.6 ± 14.8 years) with p < 2.2·10−16. Also, a significant distribution between eye disease and the use of AT was found (p < 2.2·10−16).

Conclusions: Around 12% of the population used AT. Their mean age was significantly higher than those not using AT (61.2 years compared to 54.6 with p < 2.2·10−16) and the prevalence of eye disease was also significantly higher (21.8% compared to 10.1%, p < 2.2·10−16), but the four most common eye diseases was similar in both groups.
In‐vivo corneal collagen crosslinking using ruthenium and visible light
Authors: Gulzar Ayesha , Kaleli Humeyra Nur , Hasanreisoğlu Murat , Tas Ayse Yildiz , Sahin Afsun , Kizilel Seda
Published: January 2024

Aims/Purpose: Corneal collagen cross‐linking (CXL) treatment is widely applied to halt the progression of ectatic diseases such as keratoconus. Unfortunately, the standard CXL procedure based on riboflavin and UV‐A light can only be applied to cornea thicker than 400 μm and results in frequent complications, such as corneal haze and endothelial damage [1]. This study investigates a new CXL procedure based on ruthenium, which is a water‐soluble photoinitiator and visible light (430 nm) in vivo.

Methods: For the CXL procedure, tris(bipyridine)ruthenium(II) ([Ru(bpy)3]2+), an SPS solution was applied to the rat's cornea and exposed to blue light. After the crosslinking procedure, observations were made for corneal opacity, corneal neovascularization, limbal neovascularization and corneal epithelial damage. Furthermore, the corneas were isolated for histopathological examination, cell viability and SEM analysis, and the results were compared with the conventional riboflavin/UV‐A crosslinking approach.

Results: Crosslinked corneas with ruthenium‐based CXL approach showed significantly improved scoring in corneal opacity, corneal neovascularization, limbal neovascularization and corneal wound healing as compared to the standard riboflavin and UVA‐based CXL procedure. Histopathological analysis and cell viability revealed ruthenium to be nontoxic and create more bonds between collagen fibrils when observed under scanning electron microscopy.

Conclusions: In this in vivo study, the ruthenium and visible light‐based crosslinking approach proved to be non‐toxic and a faster alternative to the conventional riboflavin and UVA‐based CXL method. We foresee that ruthenium visible light‐based crosslinking treatment could potentially change the treatment modality in keratoconus patients in a clinical setting.

Funding Information: This work is supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK) under GrantARDEB‐219S349.

References:

1. Gulzar, A., et al., Ruthenium‐induced corneal collagen crosslinking under visible light. Acta Biomater, 2022. 147: p. 198–208.
In vitro compatibility study of a new preservative‐free multidose 0.6% bilastine eye drop formulation containing sodium hyaluronate with soft and gas rigid permeable contact lenses
Authors: Rey Eider Arana , Cortes Tatiana Suarez , Gonzalo Ana , Victoriano Noelia Andollo , Prat Inés Torrens , Zazpe Arturo , Hernández Gonzalo
Published: January 2024

Aims/Purpose: Despite many patients with allergic conjunctivitis are contact lens wearers, research on the physical compatibility of antihistamine eye drops and contact lenses is lacking. The aim of this work was to evaluate the in vitro compatibility of a new preservative‐free bilastine eye drops with the main types of contact lenses.

Methods: The physical compatibility of a new preservative‐free bilastine eye drops in comparison with an isotonic saline solution, was evaluated in three types of contact lenses: hydrogel, silicone hydrogel and gas rigid permeable. Physical properties evaluated: diameter of the lens, posterior vertex power, radius of curvature, physical appearance, and spectral transmittance were characterized. For initial characterization, the lenses (n = 60) were equilibrated in a saline solution at 20–25°C for 24 h. After, 10 lenses of each type were separately immersed in either the saline solution or the bilastine formulation, both at 20–25°C, for 1 h, and then subjected to 30 wash cycles. The physical characterization was carried out after 1, 15 and 30 wash cycles, measurements performed in triplicate. Measurement methods and tolerance limits of the physical properties and general procedure and performance criteria for assessing the physical compatibility of contact lens were conducted in accordance with the guidelines (UNE‐EN ISO 18369‐3:2007; UNE‐EN ISO 18369‐2:2007; UNE‐EN ISO 11981:2013).

Results: The incubation of contact lenses with the new preservative‐free bilastine eye drop formulation did not affect any of the physical properties of the lenses and the results were comparable to those exposed to the control saline solution. The physical properties of all the contact lenses tested in both conditions complied with the manufacturer's specifications and tolerance limits stablished.

Conclusion: These results indicate that the new preservative‐free bilastine eye drop is physically compatible with soft and rigid gas permeable contact lens.
Anterior chamber phakic lens implantation after deep anterior lamellar keratoplasty. Retrospective cohort with 24‐month follow‐up
Authors: Usuga Juan Cadavid , Velez Mauricio , Gomez Jorge Donado , Gomez Camilo , Izquierdo Luis
Published: January 2024

Aims/Purpose: To report the outcome of correction of high myopia with anterior chamber phakic intraocular lenses (IOLs) implantation after deep anterior lamellar keratoplasty (DALK).

Methods: Retrospective study with 7 eyes of patients who underwent DALK. The main variables measured were corrected visual acuity (CVA) and uncorrected visual acuity (UCVA), spherical equivalent, and endothelial cell density (ECD). Follow‐up was performed up to 24 months after the lens implant.

Results: The spherical equivalent (SE) recorded a mean of −14.16 (± 3.50) before the lens implant and −0.30 (±0.93) after the implant, with a mean difference of 13.85 (10.25 to 13.85) and a p‐value of <0.001. The mean of uncorrected visual acuity (UCVA) before the lens was 1.82 (±0.63), 6 months after lens implant was 0.22 (±0.07), and after 24 months, 0.30 (±0.14) with a p‐value of 0.001. Among patients, 85.71% had a UCVA equal to or better than 0.3 logMAR and 42.85% had a UCVA of 0.2 logMAR vs. 0% preoperatively. 71.42% of the patients had residual ametropia within ±1.00 D. The mean corrected visual acuity (CVA) was 0.31 (±0.06) before lens implantation, 0.12 (±0.04) 6 months post‐ implantation and 0.14 (±0.05) 24 months post‐implantation. All patients had improvement of UCVA of at least 10 lines of vision (range 10 to 14); at 6 months, 71.42% of patients had a gain of at least 2 lines of vision in CVA and at 24 months only one patient had a decrease in UCVA. The mean difference in ECD was 68.71 (95% CI 11.97 to 125.44), corresponding to a loss of 1.26% of cells per year.

Conclusions: Phakic IOLs are an effective and stable procedure for management of high myopia after DALK, demonstrating stable safety and efficacy rates up to 24 months. The known risk of endothelial loss should be closely monitored, as such loss is higher compared to eyes with phakic IOL implants without DALK.
Gene expression in calcium triggered healthy primary limabal epithelial cells, in vitro
Authors: Suiwal Shweta , Stachon Tanja , Fries Fabian Norbert , Li Zhen , Chai Ning , Seitz Berthold , Amini Maryam , Szentmáry Nóra
Published: January 2024

Aims/Purpose: Calcium supplementation can induce differentiation of several cell types. The tear film has an important role in maintenance of the ocular surface homeostasis with an ionic calcium concentration of 0.4 mM‐1.0 mM. The effect of calcium concentration on healthy primary limbal epithelial cells (LECs) has not been analysed, yet. Our purpose was to investigate the effect of calcium supplementation on gene expression of primary limbal epithelial cells (LECs) of healthy donor corneas, in vitro.

Methods: Primary LECs were isolated from corneoscleral rims of healthy donors (n = 6) and were cultured in serum free low calcium (0.06 mM Ca+2) Keratocyte growth medium 3 (KGM3). The primary LECs were then supplemented by 0.3 mM‐2.0 mM Ca+2 concentrations for 72 h. Control LEC cultures were supplemented by low calcium (0.06 mM Ca+2) KGM3 medium. After cell harvesting, RNA and protein were extracted from treated and control LECs to perform qPCR and western blot analysis.

Results: The calcium supplementation had no significant effect on PAX6 mRNA expression after 72 h. The differentiation marker and adhesion protein DSG1 and the cornea specific keratin K3 expression did not change significantly through Ca+2 supplementation (p ≥ 0.5). The retinoic acid signalling component fatty acid binding protein FABP5 expression (p ≥ 0.5) the wound healing and vascularization marker CAV1 gene expression (p ≥ 0.5) did not change significantly through Ca+2 supplementation, after 72 h.

Conclusions: Calcium supplementation for 72 h did not change PAX6 expression and did not trigger differentiation of healthy primary limbal epithelial cells. We plan to analyse the effect of longer incubation time in the future in order to trigger a full differentiated status of limbal epithelial cells, using calcium supplementation.
Simvastatin and amfenac act as immunomodulators during induced epithelial‐mesenchymal transition in ARPE‐19 cells
Authors: Harju (ex‐Bhattarai) Niina , Loukovaara Sirpa , Kauppinen Anu
Published: January 2024

Purpose: Rhegmatogenous retinal detachment can develop into proliferative vitreoretinopathy (PVR) after surgery. Inflammation contributes to epithelial‐mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells, which takes place in PVR. The aim here was to explore the effects of simvastatin and amfenac on inflammation during the EMT.

Methods: EMT in ARPE‐19 cells was stimulated by the commercial Stem X Vivo EMT supplement (R&D Systems) either in non‐inflammatory or inflammatory conditions induced by 2.5 pg/mL IL‐1β (Gibco) or 10 pg/mL IL‐1α (R&D Systems). Cells were treated concurrently with 5 μM simvastatin (Sigma Aldrich), 0.1 μM amfenac (Cayman Chemical) or both. The release of interleukin (IL)‐6 and IL‐8 (BD Biosciences), as well as monocytic chemoattractant protein‐1 (MCP‐1; Thermo Fisher Scientific) were measured using commercial enzyme‐linked immunosorbent assays. Lactate dehydrogenase (LDH) release and intracellular ATP levels were determined using commercial kits (Promega). Cells were photographed under an Axio Vert A1 Zeiss microscope.

Results: Simvastatin alone or with amfenac reduced the release of IL‐6 in inflammatory and non‐inflammatory conditions upon experimental EMT, increased the IL‐8 release upon IL‐1α exposure and MCP‐1 in non‐inflammatory conditions and upon IL‐1β exposure. During EMT process, LDH release was increased by simvastatin alone and together with amfenac. They also increased ATP levels without inflammation and with IL‐1α. Amfenac had no effects on the cytokine levels (IL‐6, IL‐8, MCP‐1), LDH release, or ATP upon EMT process without inflammation. However, amfenac increased IL‐6 and MCP‐1 release and reduced LDH levels upon IL‐1β, and reduced IL‐6 upon the IL‐1a exposure. Under microscope, cells appeared alive and bigger but partly detached upon simvastatin.

Conclusions: Simvastatin and amfenac showed immunomodulatory effects on ARPE‐19 cells during EMT. Further studies are needed concerning the effects of drugs on the EMT.
Mitophagy as a potential mediator for the anti‐inflammatory effects of metformin in human retinal pigment epithelium cells
Authors: Toppila Maija , Hytti Maria , Ranta‐aho Sofia , Kaarniranta Kai , Kauppinen Anu
Published: January 2024

Aims/Purpose: Mitochondrial malfunction and subsequent excessive production of reactive oxygen species (ROS), deficient autophagy and chronic inflammation are associated with many age‐related diseases, including age‐related macular degeneration. In this study, we investigated metformin and its ability to activate mitophagy and alleviate inflammation in retinal pigment epithelium (RPE) cells upon induced mitochondrial damage.

Methods: Experiments were conducted using the ARPE‐19 cell line. The cells were treated with 15 mM metformin (Met) for 1 h before adding 10 μM mitochondrial complex 3 inhibitor Antimycin A (Aa) for additional 2–24 h. The levels of proinflammatory cytokines IL‐6 and IL‐8 were measured using the enzyme‐linked immunosorbent assay (ELISA). The levels of the autophagy substrate SQSTM1/p62 and the autophagy marker LC3 were studied using the Western blot method. To further analyse mitophagy, LC3 and TOM20 colocalization was detected using immunofluorescence. Mitochondrial ROS production was assessed using MitoSOX CMXRos staining.

Results: The production of proinflammatory cytokines IL‐6 and IL‐8 were increased by Aa exposure. Conversely, Met treatment significantly reduced the levels of IL‐6 and IL‐8. The autophagy substrate SQSTM1/p62 was accumulated in the cells after Aa treatment implying a blockage in the autophagic flux. Met treatment induced the clearance of SQSTM1/p62 and LC3 I and II at 6‐h time point. At 24‐h time point, Met treatment increased the amount of LC3 puncta/cell and colocalization of LC3 and TOM20 suggesting enhanced mitophagy in cells suffering mitochondrial damage induced by Aa. Aa treatment led to increased production of mitochondrial ROS which was decreased by Met treatment.

Conclusions: Metformin has anti‐inflammatory and antioxidant properties in human RPE cells upon antimycin A exposure. Studies on autophagy markers suggest enhanced activation of autophagy, and mitophagy, upon metformin exposure, which could explain the detected positive effects on inflammation and oxidative stress.
The size of the ciliary body in human enucleated chronic angle‐closure glaucoma
Authors: Jonas Rahul , Jonas Jost , Panda‐Jonas Songhomitra , Jonas Shefali
Published: January 2024

Aims/Purpose:: The size of the body of the ciliary stroma in relation to the morphology of the angle of the anterior chamber in human enucleated eyes.

Methods: A histomorphometric analysis of enucleated human eyes using a light microscope.

Results: 107 enucleated human eyes (mean axial length 25.1 ± 2.8 mm; range 21.0–36.0 mm) were included for analysis using light microscope. 68 of those eyes had an open anterior chamber angle and 39 had an endothelialized and closed angle. The body of the ciliary stroma measured was broadest with 541 ± 210 μm vs 59 ± 179 μm (p < 0.001) and narrowest with 214 ± 107 μm vs 17 ± 55 μm (p < 0.001) and the highest ciliary muscle height was 593 ± 557 μm vs 293 ± 111 μm (p < 0.001). In the angle‐closure group these parameters were significantly smaller, than in the open‐angle group. The width of the broadest section of the stroma of the ciliary body increased with the presence of an open‐angle anterior chamber (beta:0.82; B:517; 95%CI:435599; p < 0.001) and a longer axial length (beta:0.17; B:18.2; 95%CI:4.2,32.2; p = 0.01). The width of the narrowest section of the stroma of the ciliary body correlated with an open anterior chamber angle (beta:0.65; B:177; 95%CI:140213; p < 0.001) and an increase in the height of the ciliary body muscle (beta:0.23; B:0.06; 95%CI:0.03,0.10; p = 0.001). The height of the ciliary body muscle increased with increasing maximal height of the stroma (beta:0.43; B:1.54; 95%CI:0.92,2.17; p < 0.001).

Conclusions: The size of the stroma of the ciliary body in eyes with an angle of the anterior chamber closed by endothelial cells is smaller than in open‐angle eyes. Due to the tightening of the anterior angle the access of aqueous humour to the trabecular meshwork and to the ciliary body stroma may cause a reduction of the uveoscleral or uveovortex outflow.
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.
Update on AMD imaging ‐ Initial diagnosis, follow‐up
Authors: Gawęcki Maciej
Published: January 2024

AMD is a clinical entity in which diagnostic and therapeutic recommendations are the subject of constant change and up‐date. During this course a basic knowledge on AMD diagnosis will be presented along with the employment of modern diagnostic techniques such as OCT‐angiography. Disease characteristics obtained from OCT, OCTA and fluorescein angiography imaging will be depicted in the context of modern recommendations for its treatment, especially anti‐VEGF treatment schedules. Management algorithms will be outlined along with most frequent therapeutic dilemmas occurring in that clinical entity.
Analysing OCT and OCT‐A
Authors: Salas Ester Carreño
Published: January 2024

Conventional imaging tests such as OCT and OCTA can give us a very complete and useful information for diagnosing and managing uveitis. The aim of this talks is to provide useful tricks for pattern recognition of the different uveitis entities.
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.
Myopia risk factors. Update 2023
Authors: Lanca Carla
Published: January 2024

The aetiology of myopia has been extensively studied in the past decades. It is estimated that almost 30% of uncorrectable vision impairment could be attributable to myopic related disease. The latest research confirms that several environmental risks factors are important myopia determinants. More evidence was published on the effect of COVID‐19 lockdown on myopia. Increased near work and digital screen time and decreased outdoor time remained after the lockdowns and changes in myopia prevalence and progression were reported. Behaviours that contribute to a higher risk of myopia persisted post lockdowns leading to children with higher myopic risk profiles. Outdoor programmes remain as an important strategy to reduce myopia incidence. Recent evidence does not support the role of near work breaks such as 20‐20‐20 rule as a treatment option to reduce digital eye strain. Nevertheless, there is insufficient evidence to determine if this can be an effective treatment to reduce myopia incidence or myopia progression. Research into the influence of diet on myopia development has been mixed. New factors have emerged from genetic studies showing that increased adiponectin levels are protective against myopia. High haemoglobin A1c (HbA1c) levels may be associated with increased risk of myopia. Thus, the role of regular exercise and healthy diet should be further explored as potential strategies to prevent myopia onset or delay the age of myopia onset in future research studies. There is a growing body of evidence on the role of sleep and body mass index as risks factors for myopia, although further research is still necessary to confirm those factors and its association with myopia. Ongoing research should continue to identify risk factors for myopia development. Better‐designed studies are necessary to identify more efficient ways to prevent myopia and decrease myopia progression.
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.