RNA-seq transcriptomic profiling of TGF-ß2-exposed human trabecular meshwork explants: Advancing insights beyond conventional cell culture models.

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-ß2) 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-ß2. Through bulk RNA sequencing and immunohistological analysis, we identified distinct gene expression patterns and morphological changes induced by TGF-ß2 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-ß2'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.

[Glaucoma surgeries: Long-term results - A review]. / Les principales chirurgies du glaucome : résultats à long terme ­ une revue de la littérature.

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.

One year efficacy and safety of inferior implantation of Xen 45® Gel Stent in refractory glaucoma.

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.

[Hyperbaric oxygen therapy and eye disease: Review of the literature]. / Oxygénothérapie hyperbare et maladies oculaires : une revue de la littérature.

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.

[Primary open angle glaucoma and sleep apnea syndrome: A review of the literature]. / Glaucome primitif à angle ouvert et syndrome d'apnée du sommeil : une revue de la littérature.

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.

[Review by the French Glaucoma Society on the roles of new surgical techniques in glaucoma]. / Mise au point de la Société française du glaucome sur la place des nouvelles techniques chirurgicales dans le glaucome.

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.

[Biomechanics of the lamina cribrosa: A determining factor in glaucomatous neuropathy. A review of the literature]. / Biomécanique de la lame criblée : un facteur déterminant de la neuropathie glaucomateuse. Une revue de la littérature.

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.

Evaluating the potential of ChatGPT-4 in ophthalmology: The good, the bad and the ugly.

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.

[Corneal epithelial biomechanics: Resistance to stress and role in healing and remodeling]. / Biomécanique de l'épithélium cornéen : résistance au stress et implications dans la cicatrisation et le remodelage.

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.

Safety and efficacy of iStent Inject trabecular micro-bypass stents in combination with phacoemulsification for chronic open angle glaucoma associated with cataract.

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.

[From ocular itching to eye rubbing: a review of the literature]. / Du prurit aux frottements oculaires : une revue de la littérature.

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.

[Role of the lamina cribrosa in the pathogenesis of glaucoma. A review of the literature]. / Rôle de la lame criblée dans la pathogenèse du glaucome. Une revue de la littérature.

Located within the scleral canal, the lamina cribrosa is a sieve-like structure separating the intraocular and retrobulbar portions of the optic nerve. Identified as the main site of axonal damage in glaucomatous optic neuropathy, the study of the lamina cribrosa has been of great interest for many years. Numerous studies have explored the histological and morphological characteristics of the laminar region in healthy subjects as well as glaucoma patients. More recently, the development of adaptive optics systems and new generations of OCT has allowed great progress in the understanding of the pathogenesis of glaucoma and has opened new perspectives for the improvement of diagnostic procedures.