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The anatomy and vasculature of the optic nerve head are complex and subject to numerous variations. The main risk factor for glaucomatous optic neuropathy is elevated intraocular pressure, but many other factors have been identified. A vascular component seems to play an important role in the pathogenesis and/or progression of glaucomatous optic neuropathy, either under the influence of ocular hypertension or as an independent risk factor, particularly as in normal tension glaucoma (NTG). Reduced ocular blood flow has been identified as a risk factor for glaucoma. Numerous instruments have therefore been developed to explore the vasculature of the optic nerve head and to try to better understand the changes in blood flow in the optic nerve in glaucomatous optic neuropathy. In this review, we provide an update on the various means of imaging the vasculature of the optic nerve head, from angiography to the most modern techniques with angiographic OCT and laser Doppler holography. Using the results found in glaucomatous optic neuropathies, we will explore the close link between reduced ocular blood flow and the development or progression of glaucoma. A better understanding of this pathophysiology opens the door to improved management of our glaucoma patients., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Paracentral acute middle maculopathy is a lesion of the inner nuclear layer and outer plexiform layer of the macula associated with local or systemic vascular diseases that can induce retinal hypoxia. The etiologic mechanism may be related to the increase in intraocular pressure which creates conditions of hypoperfusion in the retinal vasculature. We present a case that shows a possible association between paracentral acute middle maculopathy and glaucoma with the trauma of elevated intraocular pressure as a triggering event., (Copyright © 2024. Published by Elsevier Masson SAS.)

Prcis: The lamina cribrosa (LC) pores of patients with high-tension glaucoma (HTG) appear to take a more tortuous pathway than the LC pores of patients with non-glaucomatous (NG)., Objective: To compare the LC pore microarchitecture in patients with HTG, normal tension glaucoma (NTG), and NG, by reconstructions of the LC made from tomographic images., Patients and Methods: Spectral domain-optical coherence tomography images of 52 eyes (18 NG, 18 HTG, and 16 NTG) of 29 patients were analyzed. Pores were traced using segmentation software. Pore length, tortuosity, and verticality were the 3 quantitative parameters compared among the 3 groups. Correlation analyses were performed to determine the effects of covariates on the 3 quantitative parameters., Results: Pore tortuosity in HTG (1.419 ± 0.093) was significantly higher ( P = 0.011) than in NG (1.347 ± 0,034) but did not differ from that of NTG eyes ( P = 0.251). In addition, NTG had significantly shorter pores ( P = 0.005) than NG. No difference in pore tortuosity or verticality was found between NG and NTG ( P = 0.587 and P = 0.120, respectively). Pore verticality and length in HTG eyes did not significantly differ from that of NG eyes ( P = 0.049 and P = 0.033, respectively) and NTG eyes ( P = 0.827 and P = 0.968, respectively). All of the quantitative parameters measured were not correlated with age but were associated with glaucoma severity (Visual Field Index, mean deviation, retinal nerve fiber layer, and ganglion cell complex), except for pore verticality, which was not correlated with retinal nerve fiber layer., Conclusion: The LC pores of patients with HTG appear to be more tortuous than the pores of patients with NG, and the pores of patients with NTG are shorter than those of patients with NG. Changes in pore parameters appear to be associated with the severity of glaucomatous optic neuropathy., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study examines the impact of dry eye on screen reading, with an emphasis on glare and visual comfort for patients., Population and Methods: We recruited ten patients with dry eye and nine healthy controls. Clinical signs of dry eye were quantified to determine the quality of the tear film and corneal aberrations. Questionnaires related to quality of life and light sensitivity were administered. All participants underwent a screen reading test under five different levels of brightness., Results: Patients with dry eye presented with more significant ocular inflammation (Oxford score) and reduced tear breakup time (BUT; DED: 4.1s, CO: 11.8s; W=90, P<0.001) compared to the control population. Patients also exhibited impaired quality of life (OSDI score: CO: 15.044±9.16, DED: 38.150±18.66, P=0.004) and increased light sensitivity (Glare test: CO: 96.56±65.5 arc.min, DED: 204.1±82.5 arc.min, W=15, P=0.013; VLSQ score: CO: 16.44±4.85, DED: 22.0±6.34, P=0.049). Reading tests did not show a significant difference between the groups (CO: 155±23.3 words/min and DED: 149±28.0, F=1.935, P=0.169). Brightness did not influence reading speed (F=1.308, P-value=0.275). A correlation was observed between reading speed and the OSDI quality of life questionnaire (R=-0.7, P=0.043)., Conclusion: Although screen brightness did not have a significant impact on reading speed, glare proved to be a major issue for patients with dry eye. The associations between clinical manifestations of dry eye and reading performance emphasize the importance of comprehensive management of this condition. The results suggest that dry eye can influence both quality of life and screen reading, highlighting the need for dedicated approaches to improve the visual comfort of patients., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The surgical treatment of glaucoma has been and is still based on filtering surgeries, commonly used for about half a century. The safety and efficacy of these techniques have been well described, as it has also been done for cyclophotocoagulation and valves or tubes, indicated in France mostly for refractory glaucoma. Minimally invasive glaucoma surgeries have emerged in recent decades, increasing the number of therapeutic options, and allowing treatment decisions to be as patient-centered as possible. Most of these techniques have now been studied for more than five years. Since glaucoma is a chronic, progressive optic neuropathy, the sustainability of each surgery's results is essential. The amount of available data concerning long-term efficacy and safety of glaucoma surgeries is increasing, so we have decided to describe it through this review of the literature., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Motor activity is organized by neuronal networks composed of motor neurons and a wide variety of pre-motor interneuron populations located in the brainstem and spinal cord. Differential expression and single-cell RNA sequencing studies recently unveiled that these populations subdivide into multiple subsets. However, some interneuron subsets have not been described yet, and the mechanisms contributing to this neuronal diversification have only been partly deciphered. In this study, we aimed to identify additional markers to further describe the diversity of spinal V2 interneuron populations. Here, we compared the transcriptome of V2 interneurons with that of the other cells of the embryonic spinal cord and extracted a list of genes enriched in V2 interneurons, including Arid3c . Arid3c identifies an uncharacterized subset of V2 that partially overlaps with V2c interneurons. These two populations are characterized by the production of Onecut factors and Sox2, suggesting that they could represent a single functional V2 unit. Furthermore, we show that the overexpression or inactivation of Arid3c does not alter V2 production, but its absence results in minor defects in locomotor execution, suggesting a possible function in subtle aspects of spinal locomotor circuit formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Renaux, Baudouin, Schakman, Gay, Martin, Marchese, Achouri, Rezsohazy, Gofflot and Clotman.)

PAX6-related congenital aniridia is a genetic pan-ocular disease characterized by a partial or total absence of the iris and foveal hypoplasia. The mechanisms involved in the development of ocular hypertension and glaucoma in patients with congenital aniridia are still unknown. Many hypotheses have been proposed and the advent of new anterior segment imaging techniques has allowed the identification of various potential mechanisms: congenital trabecular dysfunction, progressive closure of the iridocorneal angle, postoperative ocular hypertension. The diagnosis must take into account the various obstacles to clinical examination (corneal opacity, obturating cataract, foveolar aplasia, significant nystagmus) and is often considered only upon detection of ocular hypertension. Glaucoma remains, along with limbal insufficiency, one of the major causes of blindness in congenital aniridia. The treatment of glaucoma in congenital aniridia is primarily medical. The benefit/risk ratio of a surgical intervention should always be thoroughly evaluated in order to not underestimate the postoperative complications associated with congenital aniridia., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Aims: To analyse the correlation between the physician categories defined by the 3C classification (crystal-complication-compliance) and the ocular manifestations of nephropathic cystinosis., Methods: The last visit data of 64 patients aged between 2 and 64 attending the centre for management of cystinosis were reviewed. Each patient had been placed into one of four categories by the clinician based on disease severity. The correlation between these categories and markers of the disease was assessed using Pearson's correlation., Results: Photophobia (0.647, p<0.001), visual acuity (-0.695, p<0.001), Gahl's score (0.603, p<0.001), optical coherence tomography (OCT)% (0.713, p<0.001) and in vivo confocal microscopy (IVCM)% (0.845, p<0.001), showed a strong, highly significant correlation between key signs and symptoms and the 3C classification. Corneal complications were strongly correlated with the 3C classification with scores of 0.802 (p<0.001), 0.634 (p<0.001), 0.726 (p<0.001) and 0.677 (p<0.001) for band keratopathy, keratitis, neovascularisation and corneal ulceration, respectively. 75% of those classified as most severe had all four complications. The use of artificial tears and ciclosporin strongly correlated with the categorisation, 0.574 (p<0.001) and 0.631 (p<0.001), respectively. With all cystinosis markers, the 3C classification showed a stronger correlation than age and crystal scores by Gahl's and OCT. Category and age were strongly correlated (0.656, p<0.001). There was a moderate negative correlation with therapeutic compliance with cysteamine eye-drops and categorisation (-0.422, p<0.001). The compliance pattern observed may help to explain why the disease progresses in some patients., Conclusion: 3C classification is a reliable tool to categorise ocular cystinosis and can support clinical management decisions allowing more reliable comparison of datasets., Competing Interests: Competing interests: VG is an employee of Recordati Rare Diseases, HL and CB have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss, is closely linked to increased intraocular pressure (IOP), with the trabecular meshwork (TM) playing a critical role in its regulation. The TM, located at the iridocorneal angle, acts as a sieve, filtering the aqueous humor from the eye into the collecting ducts, thus maintaining proper IOP levels. The transforming growth factor-beta 2 (TGF-β2) signaling pathway has been implicated in the pathophysiology of primary open-angle glaucoma POAG particularly, in the dysfunction of the TM. This study utilizes human TM explants to closely mimic in vivo conditions, thereby minimizing transcriptional changes that could arise from cell culture enabling an exploration of the transcriptomic impacts of TGF-β2. Through bulk RNA sequencing and immunohistological analysis, we identified distinct gene expression patterns and morphological changes induced by TGF-β2 exposure (5 ng/ml for 48 h). Bulk RNA sequencing identified significant upregulation in genes linked to extracellular matrix (ECM) regulation and fibrotic signaling. Immunohistological analysis further elucidated the morphological alterations, including cytoskeletal rearrangements and ECM deposition, providing a visual confirmation of the transcriptomic data. Notably, the enrichment analysis unveils TGF-β2's influence on both bone morphogenic protein (BMP) and Wnt signaling pathways, suggesting a complex interplay of molecular mechanisms contributing to TM dysfunction in glaucoma. This characterization of the transcriptomic modifications on an explant model of TM obtained under the effect of this profibrotic cytokine involved in glaucoma is crucial in order to develop and test new molecules that can block their signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The goal of this study was to assess the efficacy and safety of inferior implantation of the Xen Gel 45® Stent in a cohort of refractory glaucoma patients who had undergone multiple failed procedures and lacked healthy superior conjunctiva., Patients and Methods: We retrospectively included individuals with refractory glaucoma who underwent implantation of a Xen 45® in the inferior quadrants of the conjunctiva. At the 12-month mark, two success criteria were assessed: "Complete" success, defined as an intraocular pressure (IOP)≤21mmHg with a≥20% reduction in IOP without additional IOP-lowering medications, the absence of a requirement for additional filtering surgery, and the absence of chronic hypotony; and "Qualified" success, which consisted of patients meeting the same criteria but requiring glaucoma medications postoperatively. Safety was also monitored throughout the 12-month follow-up., Results: A total of 35 patients who underwent inferior Xen implantation were assessed. After 12months, 20 patients (57.1%) achieved qualified success, with twelve patients (34.3%) attaining complete success. Excluding five patients who underwent additional filtering surgery during follow-up, the mean IOP decreased significantly from 30.73±9.7mmHg to 16.49±7.9mmHg, representing a mean decrease of 14.24±12.13mmHg (46.5%; P<0.0001). The mean number of medications at 12months decreased from 3.43±1.6 to 1.53±1.52 (-55.4%; P<0.0001). The mean number of needlings was 1.29±1.2. Implant exposure was observed in two patients during the first postoperative month., Conclusions: Inferior placement of Xen appears to be a viable treatment option for patients with refractory glaucoma and a history of multiple failed glaucoma procedures. It demonstrates both significant efficacy and acceptable safety., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Prcis: We have developed through a consensus process 24 clinical recommendations for the comprehensive management of ocular surface inflammation in glaucoma patients, including diagnostic criteria, prevention measures, and treatment strategies according to ocular surface disease severity., Purpose: To obtain expert consensus on the diagnosis, prevention, and management of ocular surface inflammation (OSI) in patients with glaucoma., Methods: An international steering committee of glaucoma and/or ocular surface disease (OSD) experts and a wider faculty of members from the Educational Club of Ocular Surface and Glaucoma (ECOS-G) collaborated to develop clinical recommendations on best practice in the management of OSI in glaucoma patients using a nonanonymous interactive quasi-Delphi process. Clinical recommendations were formulated by the steering committee based on an analysis of the recent literature to determine unmet needs, together with a web-based interactive survey of faculty members' opinion in seven identified areas of OSI management in glaucoma. Topics included (1) diagnosis of OSD, (2) diagnosis of OSI, (3) causes of OSI, (4) impact of OSD/OSI, (5) prevention of OSI, (6) treatment of OSI, and (7) inflammation and the deep structures of the eye. Faculty members were invited to vote on the clinical recommendations, and the steering committee then determined whether consensus had been achieved., Results: Consensus was obtained on 24 clinical recommendations by 80%-100% of faculty members. There was consensus that OSI should be investigated in all glaucoma patients. The main prevention measure in glaucoma patients with pre-existing OSD was the elimination/minimisation of preserved medications, especially BAK-preserved eye drops. A subtractive treatment strategy rather than an additive strategy is recommended according to OSI/OSD severity to improve the ocular health and/or before glaucoma surgery., Conclusion: These recommendations for the management of OSI in glaucoma should be useful to guide decision-making in clinical practice., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Ocular surface disease (OSD) is a complex condition that can cause a range of symptoms (e.g, dryness, irritation, and pain) and can significantly impact the quality of life of affected individuals. Iatrogenic OSD, a common finding in patients with glaucoma who receive chronic therapy with topical ocular antihypertensive drugs containing preservatives such as benzalkonium chloride (BAK), has been linked to damage to the ocular surface barrier, corneal epithelial cells, nerves, conjunctival goblet cells, and trabecular meshwork. Chronic BAK exposure activates inflammatory pathways and worsens symptoms, compromising the success of subsequent filtration surgery in an exposure-dependent manner. In eyes being treated for glaucoma, symptomatic treatment of OSD may provide some relief, but addressing the root cause of the OSD often necessitates reducing or, ideally, eliminating BAK toxicity. Strategies to decrease BAK exposure in patients with glaucoma encompass the use of preservative-free formulations or drugs with alternative and less toxic preservatives such as SofZia®, Polyquad, potassium sorbate, or Purite®. Though the benefits of these alternative preservatives are largely unproven, they might be considered when financial constraints prevent the use of preservative-free versions. For patients receiving multiple topical preserved drugs, the best practice is to switch to nonpreserved equivalents wherever feasible, regardless of OSD severity. Furthermore, nonpharmacological approaches, including laser or incisional procedures, should be considered. This review explores the effects of BAK on the ocular surface and reviews strategies for minimizing or eliminating BAK exposure in patients with glaucoma in order to significantly improve their quality of life and prevent complications associated with chronic exposure to BAK., Competing Interests: Declaration of competing interest MYK: Patent royalties: Alcon, SpyGlass Pharma, and New World Medical. Ownership Interest: New World Medical, SpyGlass Pharma, Aurea Medical Consultant: New World Medical, SpyGlass Pharma. CJR: Avellino, Baxis, Bio-Tissue, Celularity, Dompé, Emmecell, Glaukos, Kala, Oyster Point, Sight Sciences, Tarsus, TearLab/Trukera. EM: Alcon, AbbVie, Bausch + Lomb, DMG, Dompé, GlaxoSmithKline, Kala, Novartis, Sanofi, Santen, Shire, Sifi, Sun Pharmaceuticals, Théa, TRB-Chemedica, Ursapharm Arzneimittel, Visufarma. NMR: Consultant for Alderya, Aerie Pharmaceuticals; Alcon Vision, Alimera Sciences, AbbVie, Bausch + Lomb, Belkin, Dompé, Eyepoint Pharmaceuticals, Glaukos, Imprimis, Iridex, Kala Pharmaceuticals, Lumenis, Novartis, Ocular Science, Ocular Therapeutix, Omeros, Rayner, Reichert, Santen, SpyGlass, Tarsus, TearClear, Théa. AG: Consultant for Novartis, Oyster Point, Dompé, AstraZeneca, Oculis, EyeCool Therapeutics. Grant funding: B&L. CB: Alcon, Horus Pharma, Oculis, Santen, Théa., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Glaucoma is a leading cause of blindness, affecting retinal ganglion cells (RGCs) and their axons. By 2040, it is likely to affect 110 million people. Neuroinflammation, specifically through the release of proinflammatory cytokines by M1 microglial cells, plays a crucial role in glaucoma progression. Indeed, in post-mortem human studies, pre-clinical models, and ex-vivo models, RGC degeneration has been consistently shown to be linked to inflammation in response to cell death and tissue damage. Recently, Rho kinase inhibitors (ROCKis) have emerged as potential therapies for neuroinflammatory and neurodegenerative diseases. This study aimed to investigate the potential effects of three ROCKis (Y-27632, Y-33075, and H-1152) on retinal ganglion cell (RGC) loss and retinal neuroinflammation using an ex-vivo retinal explant model., Methods: Rat retinal explants underwent optic nerve axotomy and were treated with Y-27632, Y-33075, or H-1152. The neuroprotective effects on RGCs were evaluated using immunofluorescence and Brn3a-specific markers. Reactive glia and microglial activation were studied by GFAP, CD68, and Iba1 staining. Flow cytometry was used to quantify day ex-vivo 4 (DEV 4) microglial proliferation and M1 activation by measuring the number of CD11b + , CD68 + , and CD11b + /CD68 + cells after treatment with control solvent or Y-33075. The modulation of gene expression was measured by RNA-seq analysis on control and Y-33075-treated explants and glial and pro-inflammatory cytokine gene expression was validated by RT-qPCR., Results: Y-27632 and H-1152 did not significantly protect RGCs. By contrast, at DEV 4, 50 µM Y-33075 significantly increased RGC survival. Immunohistology showed a reduced number of Iba1 + /CD68 + cells and limited astrogliosis with Y-33075 treatment. Flow cytometry confirmed lower CD11b + , CD68 + , and CD11b + /CD68 + cell numbers in the Y-33075 group. RNA-seq showed Y-33075 inhibited the expression of M1 microglial markers (Tnfα, Il-1β, Nos2) and glial markers (Gfap, Itgam, Cd68) and to reduce apoptosis, ferroptosis, inflammasome formation, complement activation, TLR pathway activation, and P2rx7 and Gpr84 gene expression. Conversely, Y-33075 upregulated RGC-specific markers, neurofilament formation, and neurotransmitter regulator expression, consistent with its neuroprotective effects., Conclusion: Y-33075 demonstrates marked neuroprotective and anti-inflammatory effects, surpassing the other tested ROCKis (Y-27632 and H-1152) in preventing RGC death and reducing microglial inflammatory responses. These findings highlight its potential as a therapeutic option for glaucoma., (© 2024. The Author(s).)

Objectives: To evaluate the validity and reliability of the new Fast Assessment of the Ocular Surface Trouble (FAST®) questionnaire for identifying glaucoma or ocular hypertension (OHT) patients at risk of ocular surface disease (OSD)., Methods: A multicenter, international, cross-sectional, epidemiological survey evaluated the most accurate interview items and ocular signs on the initial 14-item version of FAST® to develop a shorter version for routine, quick clinical use. Rasch analysis and least absolute shrinkage and selection operator (LASSO) method was used to reduce the number of items on the questionnaire. Sensitivity and specificity of FAST® were assessed with receiver operating characteristic (ROC) curves for the detection of OSD with the questionnaire and ophthalmic assessment., Results: A total of 2308 eyes (1154 patients) were analyzed in this study by 92 ophthalmologists. The initial version of the FAST® indicated 60% of the subjects had OSD. Rasch analysis allowed removal of some clinical signs. The LASSO method allowed elimination of some items from the original questionnaire for a 9-item and a 6-item version of FAST®. For the 6-item questionnaire, the sensitivity and specificity were 71.9% and 74.3% respectively and the area under the curve was 0.815., Conclusions: The FAST® questionnaire is a valid and reliable tool for use in routine clinical practice and in clinical trials. The short versions of the questionnaire allow quick detection of the majority of patients with OHT or glaucoma at risk of dry eye., Competing Interests: Declaration of conflicting interestsChristophe Baudouin is a consultant for Alcon, Horus Pharma, Oculis, Santen and Thea. Ingeborg Stalmans reported the following commercial relations: Grant/research support: Théa and Santen; Clinical trial participation: Aerie, Bausch&Lomb, Omikron, Théa, Santen; Consultant for: Alcon, Allergan/AbbVie, Bausch&Lomb, Elios Vision, EyeD, Horus, Mona, Omikron, Santen, Théa; and Investments: Mona. John Thygesen is a consultant for Santen and Théa and have given lectures for both companies for which he has received an honorarium. Joanna Wierzbowska and Marta Misiuk Hojło have given lectures for Thea. Jose M. Benitez-del-Castillo is a consultant for Thea, Santen, Brill, and Horus. Alfonso Anton is a consultant for Horus Pharma and Thea. Grant/research support: BrudiLab and Thea Clinical trial participation: Aerie, Omikron, Théa, Santen; Honoraria/Consulting fees: Alcon, Horus, Omikron, Santen, Théa. Jonathan Clarke has consulted for Thea, Glaukos and Santen.

Purpose: The purpose of this study was to determine the association between corneal images provided by in vivo confocal microscopy (IVCM) with clinical parameters and conjunctival expression of HLA-DR antigen in patients with dry eye disease (DED)., Methods: Two hundred fourteen eyes of 214 patients with DED were analyzed, consisting of 2 groups of patients - 63 with autoimmune dry eye disease (AIDED) and 151 with non-autoimmune dry eye disease (NAIDED). Patients underwent a full clinical examination, including symptom screening, using the Ocular Surface Disease Index (OSDI) questionnaire, and objective analysis of DED signs by Schirmer's testing, tear break-up time (TBUT), Oxford's test, and IVCM corneal imaging. The IVCM scoring criteria were based on corneal sub-basal nerve density (ND), nerve morphology (NM), and inflammatory cell (IC) density. Quantification of conjunctival HLA-DR antigen was performed by flow cytometry., Results: The total IVCM score (T-IVCM) as well as the IVCM-IC subscore (sc) were positively correlated with HLA-DR levels with r = 0.3, P < 0.001 and r = 0.3, P < 0.01, respectively in the total population of patients with DED. The IVCM-NDsc was negatively correlated with TBUT in patients with AIDED (r = -0.2, P < 0.05) and with the Schirmer's test in patients with NAIDED (r = -0.24, P < 0.05). However, the IVCM-NMsc was positively correlated with the Oxford score only in patients with AIDED (r = 0.3, P < 0.05)., Conclusions: The proposed IVCM scoring system showed significant correlations with clinical parameters along with conjunctival HLA-DR quantification in patients with DED., Translational Relevance: The IVCM grading score represents an interesting point of commonality among clinical parameters, imaging, and molecular investigation of the ocular surface.

Introduction: Damage to the corneal nerves can result in discomfort and chronic pain, profoundly impacting the quality of life of patients. Development of novel in vitro method is crucial to better understand corneal nerve regeneration and to find new treatments for the patients. Existing in vitro models often overlook the physiology of primary sensory neurons, for which the soma is separated from the nerve endings., Methods: To overcome this limitation, our novel model combines a compartmentalized microfluidic culture of trigeminal ganglion neurons from adult mice with live-imaging and automated 3D image analysis offering robust way to assess axonal regrowth after axotomy., Results: Physical axotomy performed by a two-second aspiration led to a reproducible 70% axonal loss and altered the phenotype of the neurons, increasing the number of substance P-positive neurons 72 h post-axotomy. To validate our new model, we investigated axonal regeneration after exposure to pharmacological compounds. We selected various targets known to enhance or inhibit axonal regrowth and analyzed their basal expression in trigeminal ganglion cells by scRNAseq. NGF/GDNF, insulin, and Dooku-1 (Piezo1 antagonist) enhanced regrowth by 81, 74 and 157%, respectively, while Yoda-1 (Piezo1 agonist) had no effect. Furthermore, SARM1-IN-2 (Sarm1 inhibitor) inhibited axonal regrowth, leading to only 6% regrowth after 72 h of exposure (versus 34% regrowth without any compound)., Discussion: Combining compartmentalized trigeminal neuronal culture with advanced imaging and analysis allowed a thorough evaluation of the extent of the axotomy and subsequent axonal regrowth. This innovative approach holds great promise for advancing our understanding of corneal nerve injuries and regeneration and ultimately improving the quality of life for patients suffering from sensory abnormalities, and related conditions., Competing Interests: CB is a consultant for Oculis, Alcon, Allergan, Horus Pharma, Santen and Théa. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bonneau, Potey, Blond, Guerin, Baudouin, Peyrin, Brignole-Baudouin and Réaux-Le Goazigo.)

Paralog factors are considered to ensure the robustness of biological processes by providing redundant activity in cells where they are co-expressed. However, the specific contribution of each factor is frequently underestimated. In the developing spinal cord, multiple families of transcription factors successively contribute to differentiate an initially homogenous population of neural progenitors into a myriad of neuronal subsets with distinct molecular, morphological, and functional characteristics. The LIM-homeodomain transcription factors Lhx3, Lhx4, Isl1 and Isl2 promote the segregation and differentiation of spinal motor neurons and V2 interneurons. Based on their high sequence identity and their similar distribution, the Lhx3 and Lhx4 paralogs are considered to contribute similarly to these processes. However, the specific contribution of Lhx4 has never been studied. Here, we provide evidence that Lhx3 and Lhx4 are present in the same cell populations during spinal cord development. Similarly to Lhx3, Lhx4 can form multiproteic complexes with Isl1 or Isl2 and the nuclear LIM interactor NLI. Lhx4 can stimulate a V2-specific enhancer more efficiently than Lhx3 and surpasses Lhx3 in promoting the differentiation of V2a interneurons in chicken embryo electroporation experiments. Finally, Lhx4 inactivation in mice results in alterations of differentiation of the V2a subpopulation, but not of motor neuron production, suggesting that Lhx4 plays unique roles in V2a differentiation that are not compensated by the presence of Lhx3. Thus, Lhx4 could be the major LIM-HD factor involved in V2a interneuron differentiation during spinal cord development and should be considered for in vitro differentiation of spinal neuronal populations., (© 2024. The Author(s).)

First-line options for the treatment of dry eye disease (DED) rely on artificial tears (ATs), among which cationic emulsion (CE)-based ATs have been developed in order to mimic the healthy tear film for an improved restoration of the ocular surface homeostasis. In this review, we describe the outcomes reported in several studies, assessing the mode of action, ocular tolerance and clinical performance of a CE-based AT. Pilot studies have revealed that CE-based ATs can increase the volume and stability of the tear film while limiting its evaporation rate. Larger studies have demonstrated that CE-based ATs play a significant role in the improvement of both objective and subjective DED parameters, including superior efficacy on DED symptoms compared to several other available AT formulation types. Concomitantly, CE-based ATs have been shown to help patients to prevent or recover from corneal defects associated with refractive surgery. These positive outcomes on ocular surface epithelia are likely due to the combination of unique rheological behaviour and intrinsic anti-inflammatory properties. Based on all clinical findings, CE-based ATs represent a valuable treatment option for patients with various etiologies of DED including evaporative forms and would deserve evaluation of benefits in other surgical intervention types triggering DED., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Introduction: Even though the local tolerance of prostaglandin (PG) analogues has improved drastically since the introduction of preservative-free (PF) eye drops, prescription patterns still vary widely among practitioners and between countries and could have an impact on the ocular surface of treated patients and, in consequence, their adherence. The aim of this study is to explore the prescribing patterns of PG analogues monotherapy in France and to evaluate their impact on ocular surface status., Methods: This was a national multicenter cross-sectional observational study that was conducted by 18 glaucoma experts in France. Patients over 18 years of age and receiving monotherapy with topical PG analogues for the treatment of ocular hypertension and/or glaucoma, with no history of prior glaucoma surgery, were consecutively selected from the glaucoma outpatient clinics of participating physicians and underwent an ocular surface examination., Results: A total of 344 eyes of 344 patients were enrolled between November 2022 and November 2023. Prescribed PG monotherapy was PF in 271 (78.7%) patients. Clinical history and ocular surface evaluation indicated that 79.4% of the study population (n = 273) presented with at least one symptom or clinical sign of dry eye and that three patients out of four had an unstable tear film. Subgroup analysis comparing preserved and PF PG analogues showed a higher prevalence of conjunctival hyperemia and corneal staining in the preserved group. Multivariate analysis identified conjunctival hyperemia as consistently associated with preservative use (odds ratio = 7.654; p = 0.003 for moderate conjunctival hyperemia)., Conclusions: This study highlights the growing trend toward PF PG analogue prescriptions by specialists in France. However, ocular surface issues remain prevalent, impacting patient adherence and treatment efficacy. Comprehensive ocular surface examinations are crucial in glaucoma management to enhance long-term tolerance, compliance, and overall treatment success., (© 2024. The Author(s).)

In the interfollicular epidermis, keratinocyte stem cells (KSC) generate a short-lived population of transit amplifying (TA) cells that undergo terminal differentiation after several cell divisions. Recently, we isolated and characterized a highly proliferative keratinocyte cell population, named "early" TA (ETA) cell, representing the first KSC progenitor with exclusive features. This work aims to evaluate epidermis, with a focus on KSC and ETA cells, during transition from infancy to childhood. Reconstructed human epidermis (RHE) generated from infant keratinocytes is more damaged by UV irradiation, as compared to RHE from young children. Moreover, the expression of several differentiation and barrier genes increases with age, while the expression of genes related to stemness is reduced from infancy to childhood. The proliferation rate of KSC and ETA cells is higher in cells derived from infants' skin samples than of those derived from young children, as well as the capacity of forming colonies is more pronounced in KSC derived from infants than from young children's skin samples. Finally, infants-KSC show the greatest regenerative capacity in skin equivalents, while young children ETA cells express higher levels of differentiation markers, as compared to infants-ETA. KSC and ETA cells undergo substantial changes during transition from infancy to childhood. The study presents a novel insight into pediatric skin, and sheds light on the correlation between age and structural maturation of the skin.

Changes in the bacterial flora in the gut, also described as gut microbiota, are readily acknowledged to be associated with several systemic diseases, especially those with an inflammatory, neuronal, psychological or hormonal factor involved in the pathogenesis and/or the perception of the disease. Maintaining ocular surface homeostasis is also based on all these four factors, and there is accumulating evidence in the literature on the relationship between gut microbiota and ocular surface diseases. The mechanisms involved are mostly interconnected due to the interaction of central and peripheral neuronal networks, inflammatory effectors and the hormonal system. A better understanding of the influence of the gut microbiota on the maintenance of ocular surface homeostasis, and on the onset or persistence of ocular surface disorders could bring new insights and help elucidate the epidemiology and pathology of ocular surface dynamics in health and disease. Revealing the exact nature of these associations could be of paramount importance for developing a holistic approach using highly promising new therapeutic strategies targeting ocular surface diseases., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hyperbaric oxygen therapy consists of breathing 100% oxygen continuously or intermittently in a chamber at a pressure equal to or greater than 1.4 absolute atmospheres. Indicated for the emergency treatment of carbon monoxide poisoning and other medical-surgical pathologies such as gas embolism or necrotizing soft-tissue infections, various studies have shown a beneficial effect of hyperbaric oxygen therapy in certain ocular pathologies, notably of microcirculatory origin, such as central retinal artery occlusion or macular edema linked to retinal vein occlusions. In addition, hyperbaric oxygen might represent an alternative treatment for ocular quinine toxicity and might also be useful as an adjuvant to surgery and antibiotics in cases of periorbital necrotizing fasciitis. On the other hand, oxygen in high concentrations has toxic ocular effects due to the production of reactive oxygen derivatives., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The relationship between glaucoma and Obstructive Sleep Apnea Syndrome (OSAS) has long been discussed, with conflicting study findings. OSAS appears in the most recent studies to be more of an aggravating factor than an independent risk factor for glaucoma. Patients with OSAS may develop a more rapid progression of primary open-angle glaucoma (POAG). OSAS may damage the optic nerve not only by increasing the intraocular pressure (IOP) but also by altering the blood supply to the optic nerve as shown by more recent work with OCT-Angiography. Although the systemic benefits of Continuous Positive Airway Pressure (CPAP) have been demonstrated, few studies have evaluated its effect on the optic nerve. CPAP might act on glaucomatous neuropathy by improving the blood supply to the optic nerve. The study of this mechanism of action might provide new insights into the relationship between OSAS and glaucoma., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The surgical management of glaucoma has been enriched in recent years by the arrival of new surgical techniques as a group known as MIGS (minimally invasive glaucoma surgery). The objective of these new techniques is to reduce intraocular pressure (IOP) while limiting the risk of complications of conventional filtering surgery and allowing faster visual recovery. MIGS can be classified into three main categories depending on the route used to promote the outflow of aqueous humor: the trabecular route, the suprachoroidal route and the subconjunctival route. MIGS using the subconjunctival route are also called minimally invasive bleb surgery (MIBS). These new techniques do not replace conventional filtering surgery, which remains the gold standard technique, but now offer new alternatives for the surgical management of glaucoma patients in combination with cataract surgery or as stand-alone procedures., (Copyright © 2023. Published by Elsevier Masson SAS.)

The tear film forms a protective barrier between the ocular surface and the external environment. Despite its small volume, recent advancements in preanalytical and analytical procedures have enabled its in-depth analysis using multiple approaches. However, the diversity of tear film collection methods and the lack of standardization in pre-analytical methods represent the main obstacles to reproducible results and comparison among different studies. In this study, we first improved the pre-analytical procedures for the extraction of various molecular entities from Schirmer strips (ScS). Subsequently, our investigation focused on analyzing the molecular variances that might occur between two primary tear collection methods: capillary tube (CT) and ScS. Additionally, we examined different parts of the ScS to underscore these variations, which could serve as crucial factors for developing a standardized, optimized protocol for sample processing. Our results show that the inclusion of surfactants in the extraction process enhanced both the yield of protein extraction and the number of proteins identified in ScS, by effectively lysing the cells and improving the solubility of several intracellular proteins. In addition to proteins, nucleic acids could also be recovered for gene expression analyses, particularly from the bulb region of the ScS which is placed in the cul-de-sac. Despite their diluted nature, extracts from ScS remain a suitable material for retrieving tear proteins such as IL-17A at levels as low as the fg/mL range, thanks to highly sensitive immunoassays. Collection methods can affect measured tear protein levels. Lactoferrin is found in higher percentages in capillary electrophoresis analysis of tears collected using ScS compared to tears collected by CT (39.6 ± 4.8% versus 31 ± 4.4%)., Competing Interests: Declaration of competing interest C.B. is a consultant for Aerie, Alcon, Allergan, Horus Pharma, Santen, and Théa; C.B. and F.B.-B. have received research grants from Horus Pharma, Santen, and Théa., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Prcis: The iStent inject W implanted during phacoemulsification effectively reduces IOP., Purpose: The purpose of this study was to evaluate the efficacy and safety of iStent inject W combined with phacoemulsification in patients with controlled open angle glaucoma undergoing cataract surgery., Patients and Methods: We conducted a retrospective, bicentric study of patients with controlled chronic open angle glaucoma who underwent phacoemulsification combined with the injection of 2 iStent inject Ws. Patient characteristics, including intraocular pressure (IOP) and the number of glaucoma medications, were evaluated preoperatively and 1 week, 1 month, and 6 months postoperatively. The primary end point was IOP reduction, and the secondary end point was the reduction in the number of glaucoma medications., Results: In this study, 85 eyes were included. The majority of patients had primary open angle glaucoma (85% of eyes). Preoperative mean IOP was 16.1±2.0 mm Hg with a mean of 2.3±0.5 glaucoma medications. At 1 week postoperatively, the mean IOP was 16.7±3.1 mm Hg with a mean of 2.0±0.7 hypotensive medications. At 1 and 6 months, the mean IOP was 14.2±2.1 and 13.0±1.5 mm Hg, with a mean of 2.0±0.6 and 1.8±0.5 glaucoma medications, respectively. The percentage IOP reduction at 1 and 6 months was 11.6% ( P =0.001) and 19.3% ( P <0.0001), respectively. Regarding glaucoma medications, at 1 and 6 months, the reduction in the number of medications was 12.9% ( P =0.025) and 22.4% ( P =0.003), respectively. The most frequent significant postoperative adverse events were corneal edema in 7%, IOP spikes in 6%, and hyphema in 6% of eyes, which resolved spontaneously., Conclusions: The iStent inject W implanted during phacoemulsification effectively reduces IOP and the number of glaucoma medications needed at 6 months of follow-up, with a favorable safety profile in patients with controlled open angle glaucoma., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To provide an overview of the existing alternative models for studying trabecular meshwork (TM)., Methods: Literature review., Results: The TM is a complex tissue that regulates aqueous humor outflow from the eye. Dysfunction of the TM is a major contributor to the pathogenesis of open-angle glaucoma, a leading cause of irreversible blindness worldwide. The TM is a porous structure composed of trabecular meshwork cells (TMC) within a multi-layered extracellular matrix (ECM). Although dysregulation of the outflow throughout the TM represents the first step in the disease process, the underlying mechanisms of TM degeneration associate cell loss and accumulation of ECM, but remain incompletely understood, and drugs targeting the TM are limited. Therefore, experimental models of glaucomatous trabeculopathy are necessary for preclinical screening, to advance research on this disease's pathophysiology, and to develop new therapeutic strategies targeting the TM. Traditional animal models have been used extensively, albeit with inherent limitations, including ethical concerns and limited translatability to humans. Consequently, there has been an increasing focus on developing alternative in vitro models to study the TM. Recent advancements in three-dimensional cell culture and tissue engineering are still in their early stages and do not yet fully reflect the complexity of the outflow pathway. However, they have shown promise in reducing reliance on animal experimentation in certain aspects of glaucoma research., Conclusion: This review provides an overview of the existing alternative models for studying TM and their potential for advancing research on the pathophysiology of open-angle glaucoma and developing new therapeutic strategies.

Glaucoma is a chronic optic neuropathy characterized by progressive sclero-laminar remodeling. The main factor at the origin of these deformations is the intraocular pressure (IOP), the effect of which varies according to the biomechanical properties of the individual lamina cribrosa (LC). In this environment, the LC represents a malleable zone of weakness within a rigid corneoscleral shell. It is a dynamic structure whose movements play a key role in the pathogenesis of glaucoma: displacing it posteriorly, in addition to contributing to the characteristic appearance of glaucomatous cupping, would increase constriction on the nerve fibers and the laminar capillaries. Often incorrectly considered permanent in adults, these deformations have a certain degree of reversibility, which is currently better characterized thanks to progress in imaging techniques. The occurrence of anterior displacement and laminar thickening following a reduction in IOP could thus constitute a good prognostic factor by reducing mechanical stress on this region. These changes would tend to reduce laminar pore tortuosity and shear forces, which are probably key mechanisms of axonal loss in glaucoma., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Dry eye disease (DED) is a chronic inflammatory disease of the ocular surface requiring long-term therapy. Severe forms of DED generally do not respond to tear substitutes alone or combined, and often require treatment with topical anti-inflammatory agents to break the vicious circle of inflammation. This review summarises data from randomised controlled trials and real-world evidence on the efficacy and safety of ciclosporin A 0.1% cationic emulsion (Ikervis®) for the management of DED. Improvements in clinical signs and symptoms were reported from as early as 4 weeks after treatment initiation, although it can take a few months to reach the full benefits. Treatment periods of up to 12 months provide sustained benefit to patients. In the most responsive patients, treatment discontinuation is possible with no further substantial relapse over 12 months in over 65% of patients. Transient local ocular effects are the most commonly reported adverse events.

Part of the lacrimal functional unit, the cornea protects the ocular surface from numerous environmental aggressions and xenobiotics. Toxicological evaluation of compounds remains a challenge due to complex interactions between corneal nerve endings and epithelial cells. To this day, models do not integrate the physiological specificity of corneal nerve endings and are insufficient for the detection of low toxic effects essential to anticipate Toxicity-Induced Dry Eye (TIDE). Using high-content imaging tool, we here characterize toxicity-induced cellular alterations using primary cultures of mouse trigeminal sensory neurons and corneal epithelial cells in a compartmentalized microfluidic chip. We validate this model through the analysis of benzalkonium chloride (BAC) toxicity, a well-known preservative in eyedrops, after a single (6h) or repeated (twice a day for 15 min over 5 days) topical 5.10 -4 % BAC applications on the corneal epithelial cells and nerve terminals. In combination with high-content image analysis, this advanced microfluidic protocol reveal specific and tiny changes in the epithelial cells and axonal network as well as in trigeminal cells, not directly exposed to BAC, with ATF3/6 stress markers and phospho-p44/42 cell activation marker. Altogether, this corneal neuroepithelial chip enables the evaluation of toxic effects of ocular xenobiotics, distinguishing the impact on corneal sensory innervation and epithelial cells. The combination of compartmentalized co-culture/high-content imaging/multiparameter analysis opens the way for the systematic analysis of toxicants but also neuroprotective compounds., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The ocular surface (OS) enzymes are of great interest due to their potential for novel ocular drug development. We aimed first to profile and classify the enzymes of the OS to describe major biological processes and pathways that are involved in the maintenance of homeostasis. Second, we aimed to compare the enzymatic profiles between the two most common tear collection methods, capillary tubes (CT) and Schirmer strips (ScS). A comprehensive tear proteomic dataset was generated by pooling all enzymes identified from nine tear proteomic analyses of healthy subjects using mass spectrometry. In these studies, tear fluid was collected using CT (n = 4), ScS (n = 4) or both collection methods (n = 1). Classification and functional analysis of the enzymes was performed using a combination of bioinformatic tools. The dataset generated identified 1010 enzymes. The most representative classes were hydrolases (EC 3) and transferases (EC 2). Phosphotransferases, esterases and peptidases were the most represented subclasses. A large portion of the identified enzymes was common to both collection methods (n = 499). More enzymes were specifically detected in the ScS-extracted proteome. The major pathways in which the identified enzymes participate are related to the immune system and protein, carbohydrate and lipid metabolism. Metabolic processes for nucleosides, cellular amides, sugars and sulfur compounds constituted the most enriched biological processes. Knowledge of these molecules highly susceptible to pharmacological manipulation might help to predict the metabolism of ophthalmic medications and develop novel prodrug strategies as well as new drug delivery systems. Combining such extensive knowledge of the OS enzymes with new analytical approaches and techniques might create new prospects for understanding, predicting and manipulating the metabolism of ocular pharmaceuticals. Our study reports new, essential data on OS enzymes while also comparing the enzyme profiles obtained via the two most popular methods of tear collection, capillary tubes and Schirmer strips., (© 2023. Springer Nature Limited.)

There is growing interest nowadays for artificial intelligence (AI) in all medical fields. Beyond the direct medical application of AI to medical data, generative AI such as "pre-trained transformer" (GPT) could significantly change the ophthalmology landscape, opening up new avenues for enhancing precision, productivity, and patient outcomes. At present, ChatGPT-4 has been investigated in various ways in ophthalmology for research, medical education, and support for clinical decisions purposes. This article intends to demonstrate the application of ChatGPT-4 within the field of ophthalmology by employing a 'mise en abime' approach. While we explore its potential to enhance the future of ophthalmology care, we will also carefully outline its current limitations and potential risks., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Vision plays an important role in an athletes' success. In sports, nearly 80% of perceptual input is visual, and eye health and sports medicine are closely intertwined fields of utmost importance to athletes. The physical nature of sports activities renders individuals more prone to various eye injuries than the general population. Ocular trauma can lead to lifelong sequelae, and impaired vision requires careful follow-up and management. Apart from injuries, athletes may also experience vision problems that can hamper their performance, including blurred vision, double vision, and light sensitivity. The interdisciplinary nature of sports medicine necessitates collaboration between sports medicine professionals and ophthalmologists. Through such collaborations, athletes can receive appropriate eye care, education on proper eye protection and guidance on adopting good eye health practices. If any inconspicuous symptoms are not detected and treated promptly, athletes may acquire systemic injuries because of defective vision, preventing them from achieving high level athletic performance in competitions. The protection of the elite athlete is the responsibility of all of us in sports medicine. To advance a more unified, evidence-informed approach to ophthalmic health assessment and management in athletes and as relevant for sports medicine physicians, the International Olympic Committee Consensus Group aims for a critical evaluation of the current state of the science and practice of ophthalmologic issues and illness in high-level sports, and present recommendations for a unified approach to this important issue., Competing Interests: Competing interests: RB is the IOC Medical and Scientific Director. LE is the IOC Head of Science Activities and an Editor of BJSM IPHP. UE is an IOC member and the Chair of the IOC Medical and Scientific Commission. KS is coeditor of the British Journal of Sports Medicine—Injury Prevention & Health Protection. BT is a member of the IOC Medical and Scientific Commission, and Vice President of the Singapore National Olympic Council. YPP is a member of the IOC Medical and Scientific Commission, a member of the Executive Committee and Chair of the Scientific Commission of the International Sports Medicine Federation (FIMS), a member of the Scientific and Education Commission of the European Federation of Sports Medicine Associations (EFSMA), a member of WADA’s Health Medical Research Committee (HMRC)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Declaration of competing interest Financial disclosures are listed above.

The word "elective" refers to medications and procedures undertaken by choice or with a lower grade of prioritization. Patients usually use elective medications or undergo elective procedures to treat pathologic conditions or for cosmetic enhancement, impacting their lifestyle positively and, thus, improving their quality of life. However, those interventions can affect the homeostasis of the tear film and ocular surface. Consequently, they generate signs and symptoms that could impair the patient's quality of life. This report describes the impact of elective topical and systemic medications and procedures on the ocular surface and the underlying mechanisms. Moreover, elective procedures performed for ocular diseases, cosmetic enhancement, and non-ophthalmic interventions, such as radiotherapy and bariatric surgery, are discussed. The report also evaluates significant anatomical and biological consequences of non-urgent interventions to the ocular surface, such as neuropathic and neurotrophic keratopathies. Besides that, it provides an overview of the prophylaxis and management of pathological conditions resulting from the studied interventions and suggests areas for future research. The report also contains a systematic review investigating the quality of life among people who have undergone small incision lenticule extraction (SMILE). Overall, SMILE refractive surgery seems to cause more vision disturbances than LASIK in the first month post-surgery, but less dry eye symptoms in long-term follow up., Competing Interests: Declaration of competing interest José Alvaro P. Gomes: Alcon (F,C), Allergan (F,C), Johnson & Johnson (F,C), Latinofarma/Cristália (F,C), Ofta Vision Health/EMS (F,C), Bausch-Lomb (F), Novartis (C), Ophthalmos (C). Dimitri T. Azar: Twenty/Twenty Therapeutics (F,I,P,E). Christophe Baudouin: Horus Pharma (F,C), Pharma (F), Santen (F,C), Théa (F,C), Opia (P), Alcon (C), Allergan (C), Oculis (C), Aerie Pharmaceuticals (C). Etty Bitton: Johnson & Johnson Vision (F), I-Med Pharma (F), Shire (F,C), Valeant (F), Alcon (C), Aequus Pharmaceuticals (C), Brio (C), Labtician-Théa (C), Novartis (C), Snell Communications (C). Wei Chen: Santen (C). Farhad Hafezi: Light for Sight Foundation (F), Schwind Eye Tech Solutions (F), VELUX Foundation (F), Gelbert Foundation (F), SOOFT Italia (F), EMAGine AG (I), ELZA Institute (E), GmbH-Switzerland (C). Pedram Hamrah: Novartis (F,C), CooperVision (F), Dompé (F), Oyster Point Pharma (F,C), OKYO (F,C), Noveome (I,F,C), Eyegate Pharma (I,C), Clementia (C), Novaliq (C), Santen (C) Sanofi (C), Astra Zeneca (C), Ocunova (C), Neuroptika (C). Ruth E. Hogg: Okko Healthcare (F), Roche (C). Jutta Horwath-Winter: Bausch + Lomb (C), Allergan (C), CromaPharma (C), MC2 Therapeutics (C), Omnivision (C) Santen (C), Théa (C), TRB Chemedica (C), Ursapharma (C), Shire (C). Georgios A. Kontadakis: None. Jodhbir S. Mehta: UK Network Medical (P,R), Cordlife (P,R), Asia Genomics (P,R), Carl Zeiss Meditec (C), Ziemer (C), Moria (C), Santen (C). Elisabeth M. Messmer: Alcon/Novartis (C), Chiesi (F,C), DMg (C), Dompé (C), Kala (C), Novartis (C), Allergan (C), Santen(C), Shire (C), Sun (C), Sifi (C), Théa (C), TRB Chemedica (C), Ursapharma (C), Visufarma (C). Victor L. Perez: Alcon (F), Heat Biologics (F), Alcon (C), Aldyra (C), Dompé (C), Kala (C), Mallinkrodt (C), Novartis (C), Oculis (C). David Zadok: DiagnosTear Ltd (C), Precise-Bio (C). Mark D.P. Willcox: Alcon (F), Allergan (F), CooperVision (F), Johnson and Johnson Vision (F), Ophtecs (C,F)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prostaglandin analogue topical medications are one of the most effective therapeutic approaches for the chronic management of glaucoma and ocular hypertension, through the reduction of elevated intra ocular pressure (IOP). While many of the first generations of anti-glaucoma eye drops were preserved with benzalkonium chloride, their repeated use may induce chronic ocular surface toxicity that leads to ocular surface disease (OSD) signs and symptoms. As a result, soft-preservatives and preservative-free formulations have been developed with the goal to avoid the long-term iatrogenic toxicity of the preservative agents. In addition, it has been suggested that OSD and its associated inflammation may negatively impact the efficacy of the IOP-lowering medications, including treatment adherence and compliance. Hence, it may be particularly interesting that glaucoma medications can concomitantly protect and "heal" the ocular surface and its environment while lowering elevated IOP, for the greater benefit of glaucoma patients. The objective of the present review is to briefly present the preclinical data of the cationic oil-in-water emulsion of latanoprost (latanoprost-CE) to shed some light on its mechanisms of action. It overall supports the following hypothesis: the restoration of a healthy ocular surface environment and treatment of the OSD signs and symptoms will allow for an improved elevated IOP reduction and glaucoma management. This would be achieved with a once daily dosing regimen to preserve glaucoma patients' vision, ocular surface, and quality-of-life and wellness.

Introduction: Early initiation of anti-inflammatory therapies is recommended for dry eye disease (DED) to break the vicious cycle of pathophysiology. However, there is limited guidance on how to implement topical ciclosporin (CsA) and corticosteroid treatment into clinical practice. This expert-led consensus provides practical guidance on the management of DED, including when and how to use topical CsA., Methods: A steering committee (SC) of seven European DED experts developed a questionnaire to gain information on the unmet needs and management of DED in clinical practice. Consensus statements on four key areas (disease severity and progression; patient management; efficacy, safety and tolerability of CsA; and patient education) were generated based on the responses. The SC and an expanded expert panel of 22 members used a nine-point scale (1  =  strongly disagree; 9  =  strongly agree) to rate statements; a consensus was reached if ≥75% of experts scored a statement ≥7., Results: A stepwise approach to DED management is required in patients presenting with moderate corneal staining. Early topical CsA initiation, alone or with corticosteroids, should be considered in patients with clinical risk factors for severe DED. Patient education is required before and during treatment to manage expectations regarding efficacy and tolerability in order to optimise adherence. Follow-up visits are required, ideally at Month 1 and every 3 months thereafter. Topical CsA may be continued indefinitely, especially when surgery is required., Conclusion: This consensus fills some of the knowledge gaps in previous recommendations regarding the use of topical corticosteroids and CsA in patients with DED.

The corneal epithelium is one of the first tissue barriers of the eye against the environment. In recent years, many studies provided better knowledge of its healing, its behavior and its essential role in the optical system of the eye. At the crossroads of basic science and clinical medicine, the study of the mechanical stresses applied to the cornea makes it possible to learn the behavior of epithelial cells and better understand ocular surface disease. We describe herein the current knowledge about the adhesion systems of the corneal epithelium and their resistance to mechanical stress. We will also describe the involvement of these mechanisms in corneal healing and their role in epithelial dynamics. Adhesion molecules of the epithelial cells, especially hemidesmosomes, allow the tissue cohesion required to maintain the integrity of the corneal epithelium against the shearing forces of the eyelids as well as external forces. Their regeneration after a corneal injury is mandatory for the restoration of a healthy epithelium. Mechanotransduction plays a significant role in regulating epithelial cell behavior, and the study of the epithelium's response to mechanical forces helps to better understand the evolution of epithelial profiles after refractive surgery. A better understanding of corneal epithelial biomechanics could also help improve future therapies, particularly in the field of tissue engineering., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose : Describe the cognitive and behavioral symptomatology of patients with chronic ocular rubbing in keratoconus (KC) and Ocular Surface Disease (OSD) using a self-questionnaire. Methods : A prospective study was conducted in a tertiary ophthalmology center between May and July 2021. We consecutively included all patients presenting with one of the following conditions: KC and OSD. A questionnaire including the evaluation of Goodman and CAGE-modified criteria for eye rubbing was given to patients in consultation to evaluate their ocular symptoms and medical background. Results : We included 153 patients in the study. Of these, 125 (81.7%) patients reported eye rubbing. The average Goodman score was 5.8 ± 3.1 and was ≥ 5 in 63.2% of cases. The CAGE score was ≥ 2 in 74.4% of patients. Addiction ( p = 0.045) and psychiatric family history ( p = 0.03) were more frequent in patients with higher scores. Ocular symptoms and eye rubbing were significantly more frequent and intense in patients with higher scores; Conclusion : Eye rubbing presents addictive-like cognitive and behavioral characteristics in patients with KC or OSD. The eye rubbing cycle could play an essential role in the onset and progression of keratoconus and could be a factor in the maintenance of dry eye.

Background: The goal of this study was to assess the efficacy and safety of phacoemulsification combined with iStent Inject® implantation for the treatment of chronic open-angle glaucoma controlled on topical anti-glaucoma medications and associated with cataract., Methods: This study was a retrospective analysis of patients who underwent phacoemulsification and implantation of an iStent Inject® for chronic open-angle glaucoma associated with cataract. For all patients, pre- and postoperative characteristics, including number of glaucoma medications and intraocular pressure (IOP), were compared using Paired-sample t-tests and Wilcoxon signed-rank tests, respectively. Postoperative visits were scheduled at 7 days and 1, 3, 6, and 12 months after surgery., Results: Forty-nine eyes of 39 patients were included in the study. Mean preoperative IOP at baseline was 16.3±4.3mmHg (range, 10-29mmHg) with a mean of 2.2±1.0mmHg antiglaucoma medications. At 1 month, the mean IOP reduction was 16% (P<0.05) along with an 18.7% reduction in the mean number of medications. At 6 months, the mean IOP was 12.8±2.6, with a mean of 1.1±0.9 antiglaucoma medications. The mean IOP reduction at 6 months was 22% (P<0.05) along with a 49% reduction in the mean number of medications. At 12 months, the mean IOP was 13.8±2.5 with a mean of 1.1±1.2 medications. The mean IOP reduction at 12 months was 15% (P<0.05) along with a 47% reduction in the mean number of medications. No severe device-related side effects were observed., Conclusions: iStent Inject® implantation combined with phacoemulsification resulted in effective IOP reduction and medication burden in patients with mild to advanced chronic open-angle glaucoma and preoperative IOP well controlled with topical hypotensive medications., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Ocular itching and eye rubbing are frequent complaints in an ophthalmology practice. Numerous studies address the consequences of eye rubbing, such as keratoconus. However, there are few studies concerning the pathophysiology of itching, its transmission pathways, or its interactions with eye rubbing. Through this literature review, we will address the various clinical, physiological and therapeutic aspects of this pair of symptoms with a variety of ocular consequences. We will then describe the state of the art in itching and scratching in dermatology, in order to draw a parallel between these two vicious cycles. A better understanding of the pathophysiology of ocular itching and eye rubbing, as well as new studies based on dermatological data, might allow more appropriate clinical management of our patients and their symptoms., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)