Small extracellular vesicles derived from microRNA-22-3p-overexpressing mesenchymal stem cells protect retinal ganglion cells by regulating MAPK pathway.

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.

Economic cost of management of glaucoma in public and private health facilities in the Tema metropolis in Ghana.

Objectives: This study sought to determine the economic cost of the management of glaucoma among patients seeking care in health facilities in Ghana. Design: A cross-sectional cost-of-illness (COI) study from the perspective of the patients was employed. Setting: The study was conducted in public and private eye care facilities in the Tema Metropolis of Ghana. Participants: About 180 randomly selected glaucoma patients seeking healthcare at two facilities participated in the study. Main outcome measure: Direct cost, including medical and non-medical costs, indirect cost, and intangible burden of management of glaucoma. Results: the cost per patient treated for glaucoma in both facilities was US$60.78 (95% CI: 18.66-107.80), with the cost in the public facilities being slightly higher (US$62.50) than the private facility (US$ 59.3). The largest cost burden in both facilities was from direct cost, which constituted about 94% of the overall cost. Medicines (42%) and laboratory and diagnostics (26%) were the major drivers of the direct cost. The overall cost within the study population was US$10,252.06. Patients paid out of pocket for the frequently used drug- Timolol, although expected to be covered under the National Health Insurance Scheme (NHIS). Patients, however, expressed moderate intangible burdens due to glaucoma. Conclusion: The cost of the management of glaucoma is high from the perspective of patients. The direct costs were high, with the main cost drivers being medicines, laboratory and diagnostics. It is recommended that the National Health Insurance Authority (NHIA) should consider payment for commonly used medications to minimize the burden on patients. Funding: None declared.

[Research progress in the diagnosis and treatment of childhood glaucoma].

Childhood glaucoma is a disease that seriously endangers children's visual health. It will accompany the patients throughout their lives and bring a heavy burden to families and society. Most childhood blindness caused by glaucoma is preventable or treatable. Relevant research has made progress in recent years. Based on the new consensus reached by the World Glaucoma Association and the latest medical evidence at home and abroad, this article summarizes the definition, classification, diagnosis, molecular genetics, pathogenesis and comprehensive treatments including drugs and surgery of childhood glaucoma, with a focus on the application of various surgical methods, so as to provide reference for clinical and scientific research and improve the clinical diagnosis and treatment of childhood glaucoma.

[INTERVENTIONAL GLAUCOMA - A SHIFT IN THE TREATMENT PARADIGM].

INTRODUCTION: Glaucoma is a progressive optic neuropathy and is the leading cause of preventable irreversible blindness worldwide. Glaucoma causes progressive visual field loss and can have significant implications on the patient's quality of life. Lowering intraocular pressure (IOP) is the only treatment proven to prevent vision loss from glaucoma. It is achieved using medication, laser treatment and surgery. The treatment paradigm of glaucoma has been one whereby surgical intervention has been left for advanced cases due to a variety of reasons, mainly concerning safety and long term success. The past two decades have seen a paradigm shift towards earlier IOP lowering interventions using a wide array of different technologies in the laser and surgical spaces. This review aims to understand the background to this paradigm shift, its necessity, and its potential impact on the vision and life of glaucoma patients.

[OPHTHALMOLOGY - ON THE TIP OF THE SPEAR].

INTRODUCTION: Ophthalmology is a broad branch of medicine, which includes an extensive range of sub-specialties on one hand, and interfaces with other fields of medicine on the other. This issue contains papers from different sub-specialties of ophthalmology, that together cover several of the most important issues in this field. These papers present the topics in a manner compatible with the wide readership of the journal, and touch upon the most current updates and innovations. The original articles in this issue deal with treatments for the prevention of myopia progression in children, treatment of complicated cases of retinal detachment in children, ocular manifestations of vascular abnormalities in patients with coronavirus, and a series of patients with corneal damage due to ultraviolet-C (UVC) lamps intended to clear the air of this virus. The review papers describe glaucoma and the current change in its treatment paradigm, which focuses on earlier intervention, ocular manifestations of systemic autoimmune diseases, and the possibilities for artificial corneal implantation. We hope that this special issue will be of interest and clinical value to its readers.

[Glaucoma Patient with Suspected Flammer Syndrome: Diagnostic Procedures and Therapeutic Implications]. / Glaukompatient mit Verdacht auf Flammer-Syndrom: diagnostische Schritte und therapeutische Konsequenzen.

If glaucoma damage develops despite normal intraocular pressure or if the damage progresses despite well-controlled intraocular pressure, we usually find other risk factors. One important group are the vascular factors. We should focus not only on the classical risk factors of atherosclerosis, such as arterial hypertension or dyslipidaemia, but also on dysregulation of blood flow, especially on primary vascular dysregulation (PVD). Low blood pressure, either current or in adolescence, low body mass index or frequently cold hands and feet may provide important hints. Very often PVD is coupled with a number of other symptoms and signs, and we then speak of a Flammer Syndrome (FS). If there is any indication of FS, we take a targeted patient history, undertake 24 h blood pressure monitoring, measure retinal venous pressure, and perform a dynamic retinal vessel analysis or nail fold capillary microscopy. This is especially recommended if the patient is relatively young or the damage is progressing rapidly. If the suspicion is confirmed, we then try to reduce the drops in blood pressure, lower the retinal venous pressure, improve the regulation of blood flow and reduce the oxidative stress in the mitochondria.

AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?

Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.

The Effect of Yoga on Intraocular Pressure Using the "iCare HOME2" Tonometer.

BACKGROUND: Various yoga positions may have an unfavorable impact on intraocular pressure (IOP) and may therefore be seen as a potential risk factor for the progression of glaucoma. The new "iCare HOME2" is a handheld self-tonometer for IOP measurements outside clinical settings. This is the first study to evaluate the immediate effect of common yoga postures on the IOP of healthy and glaucomatous eyes using the "iCare HOME2" self-tonometer and to compare the time of IOP recovery in both groups. METHODS: This is a single-center, prospective, observational study including 25 healthy and 25 glaucoma patients performing the following yoga positions: "legs up" (Viparita Karani), "bend over" (Uttanasana), "plough pose" (Halasana), and the "down face dog" (Adho Mukha Svanasana) for 90 s each, with a 2-min break in between. IOP was measured with the "iCare HOME2" before, during, and after each position. RESULTS: IOP significantly increased in all eyes in all positions (p < 0.05), showing no statistically significant difference between healthy or glaucomatous eyes (p > 0.05). The mean rise in IOP in healthy subjects was 1.6 mmHg (SD 1.42; p = 0.037), 14.4 mmHg (SD 4.48; p < 0.001), 7.5 mmHg (SD 4.21; p < 0.001), and 16.5 mmHg (SD 3.71; p < 0.001), whereas in glaucoma patients, IOP rose by 2.8 mmHg (SD 2.8; p = 0.017), 11.6 mmHg (SD 3.86; p < 0.001), 6.0 mmHg (SD 2.24; p < 0.001), and 15.1 mmHg (SD 4.44; p < 0.001) during the above listed yoga positions, repsectively. The highest increase in IOP was seen in the down face position, reaching mean IOP values above 31 mmHg in both study groups. IOP elevation was observed immediately after assuming the yoga position, with no significant change during the following 90 s of holding each pose (p > 0.05). All IOP values returned to baseline level in all individuals, with no significant difference between healthy and glaucoma participants. CONCLUSION: Our data show that common yoga positions can lead to an acute IOP elevation of up to 31 mmHg in healthy as well as glaucoma eyes, with higher IOP values during head-down positions. Given that IOP peaks are a major risk factor for glaucomatous optic neuropathy, we generally advise glaucoma patients to carefully choose their yoga exercises. If and to what extent practicing yoga leads to glaucoma progression, however, remains unclear and warrants further research.

[Hegemony in medical pluralism: articulations and relationships in care, a case study]. / Hegemonía en el pluralismo médico: articulaciones y relaciones en la atención, un estudio de caso.

This study aims to describe and analyze the medical pluralism and the type of hegemony-subordination relation between forms of care or knowledge in the treatment of a patient with glaucoma to show the articulatory and transactional process between several therapeutic resources and understand which structural elements shaped the treatment itinerary and option. This is a qualitative research that used a narrative case study. To reconstruct the narrative, a semi-structured interview was conducted based on a thematic script previously established by a set of a priori categories to later transcribe the data and perform hermeneutic triangulation. Results showed that the hegemony in medical pluralism was based on equivalence relations, so that the patient replaced the use of pharmacological drugs with alternative medicine treatments. However, the relational process of equivalence developed itself in a context of biomedical significance, in which the treatment or control of intraocular pressure configured the substitution premise. Thus, the processes that triggered the hegemonic relations were constituted by various social, cultural, and economic factors such as unemployment, social security, and gender, which played a fundamental role during the search for care.

Este estudio tiene como objetivo describir y analizar el pluralismo médico y el tipo de relaciones de hegemonía-subalternidad entre diversas formas o saberes de atención, que se desarrollaron en el itinerario terapéutico de una padeciente de glaucoma, para mostrar el proceso articulatorio y transaccional entre distintos recursos terapéuticos, así como comprender qué elementos estructurales configuraron el itinerario y la elección terapéutica. La investigación es cualitativa, un estudio de caso en el cual se utilizó el enfoque narrativo. Para la reconstrucción de la narrativa se realizó una entrevista semiestructurada, dirigida por una guía temática previamente determinada por un conjunto de categorías apriorísticas, para posteriormente transcribir la entrevista y realizar un proceso de triangulación hermenéutica. Los resultados mostraron, en este caso, que la hegemonía en el pluralismo médico se constituyó mediante relaciones de equivalencia, así, la padeciente sustituyó el uso de medicamentos farmacológicos por terapias de medicina alternativa, no obstante, el proceso relacional de equivalencia se desarrolló en un contexto de significación biomédica, en el cual tratar o controlar la presión intraocular fue la premisa del remplazo. Asimismo, los procesos que desencadenaron la presencia de relaciones hegemónicas se constituyeron por diversos factores sociales, culturales y económicos como el desempleo, la seguridad social y el género, que desempeñaron un papel fundamental durante la búsqueda de la atención y del cuidado.

Este estudo visa descrever e analisar o pluralismo médico e o tipo de relação de hegemonia-subalternidade entre diversas formas de atendimento ou conhecimentos, que ocorreram no tratamento de um paciente com glaucoma, com a finalidade de mostrar o processo articulatório e transacional entre diferentes recursos terapêuticos, bem como entender quais elementos estruturais moldaram o itinerário e a opção de tratamento. Trata-se de uma pesquisa qualitativa, que utilizou um estudo de caso com abordagem narrativa. Para a reconstrução da narrativa, foi realizada uma entrevista semiestruturada, com base em um roteiro temático previamente estabelecido por um conjunto de categorias a priori, para posteriormente transcrever os dados e realizar a triangulação hermenêutica. Os resultados mostraram que a hegemonia no pluralismo médico esteve baseada em relações de equivalência, de modo que o paciente substituiu o uso de medicamentos farmacológicos por tratamentos da medicina alternativa; no entanto, o processo relacional de equivalência desenvolveu-se em um contexto de significância biomédica, na qual o tratamento ou controle da pressão intraocular foi a premissa para a substituição. Desse modo, os processos que desencadearam a presença de relações hegemônicas foram constituídos por fatores sociais, culturais e econômicos diversos como desemprego, previdência social e gênero, os quais tiveram papel fundamental durante a busca por atendimento e cuidado.

Telemedicine for Screening and Follow-Up of Glaucoma: A Descriptive Study.

Introduction: Glaucoma is a leading cause of irreversible blindness. It is a prevalent disease worldwide, affecting ∼70 million people and expected to reach up to 112 million by 2040. Purpose: The aim of this study is to describe the implementation and initial experience of a telemedicine program to monitor glaucoma and glaucoma suspect patients in a large, integrated health care system during the COVID-19 pandemic. Methods: A retrospective chart review of established glaucoma or glaucoma suspect patients who participated in a telemedicine evaluation at the ophthalmic center of a large, Colombian health care system between June 2020 and April 2023 was conducted. Clinical and sociodemographic variables were analyzed. Generated clinical orders for additional testing, surgical procedures, follow-ups, and referrals, as well as changes in medical treatment, were evaluated. Results: A total of 11,034 telemedicine consults were included. The mean ± standard deviation age of this group was 63 ± 17.2 years and 67% were female. Of the patients who attended teleconsults, 49% were glaucoma suspects and 38.5% were followed with a diagnosis of open-angle glaucoma. After the consult, 25% of patients were referred to a glaucoma specialist, 40% had additional testing ordered, and 8% had a surgical procedure ordered, mainly laser iridotomy (409 cases). Almost a third of patients returned for subsequent telemedicine visits after the initial encounter. Despite some technical difficulties, 99.8% of patients attended and completed their scheduled telemedicine appointments. Conclusions: A telemedicine program aimed to monitor established glaucoma patients can be successfully implemented. Established patients within an integrated health care system have high adherence to the virtual model. Further research by health care institutions and government agencies will be key to expand coverage to additional populations. Clinical Trial Registration Number: CEIFUS 1026-24.

Effect of digital ocular massage on intraocular pressure and Schlemm's canal dimensions.

Digital ocular massage has been reported to temporarily lower intraocular pressure (IOP). This could be related to an enhanced aqueous humor outflow; however, the mechanism is not clearly understood. Using anterior segment optical coherence tomography, the Schlemm's canal (SC) and trabecular meshwork (TM) can be imaged and measured. Here, 66 healthy adults underwent digital ocular massage for 10 min in their right eyes. The IOP and dimensions of the SC and TM were measured before and after ocular massage. All subjects demonstrated IOP reduction from 15.7 ± 2.5 mmHg at baseline to 9.6 ± 2.2 mmHg immediately after, and median of 11.6 mmHg 5-min after ocular massage (Friedman's test, p < 0.001). There was significant change in SC area (median 10,063.5 µm2 at baseline to median 10,151.0 µm2 after ocular massage, Wilcoxon test, p = 0.02), and TM thickness (median 149.8 µm at baseline to 144.6 ± 25.3 µm after ocular massage, Wilcoxon test, p = 0.036). One-third of the subjects demonstrated collapse of the SC area (-2 to -52%), while two-thirds showed expansion of the SC area (2 to 168%). There were no significant changes in SC diameter (270.4 ± 84.1 µm vs. 276.5 ± 68.7 µm, paired t-test, p = 0.499), and TM width (733.3 ± 110.1 µm vs. 733.5 ± 111.6 µm, paired t-test, p = 0.988). Eyes with a higher baseline IOP demonstrated a greater IOP reduction (Pearson correlation coefficient r = -0.521, p < 0.001). Eyes with smaller SC area at baseline showed greater SC area expansion (Pearson correlation coefficient = -0.389, p < 0.001). Greater IOP reduction appeared in eyes with greater SC area expansion (Pearson correlation coefficient r = -0.306, p = 0.01). Association between change in IOP and change in TM thickness was not significant (Spearman's ρ = 0.015, p = 0.902). Simple digital ocular massage is an effective method to lower IOP values, and change in the SC area was significantly associated with IOP changes.

Addressing neurodegeneration in glaucoma: Mechanisms, challenges, and treatments.

Glaucoma is the leading cause of irreversible blindness globally. The disease causes vision loss due to neurodegeneration of the retinal ganglion cell (RGC) projection to the brain through the optic nerve. Glaucoma is associated with sensitivity to intraocular pressure (IOP). Thus, mainstay treatments seek to manage IOP, though many patients continue to lose vision. To address neurodegeneration directly, numerous preclinical studies seek to develop protective or reparative therapies that act independently of IOP. These include growth factors, compounds targeting metabolism, anti-inflammatory and antioxidant agents, and neuromodulators. Despite success in experimental models, many of these approaches fail to translate into clinical benefits. Several factors contribute to this challenge. Firstly, the anatomic structure of the optic nerve head differs between rodents, nonhuman primates, and humans. Additionally, animal models do not replicate the complex glaucoma pathophysiology in humans. Therefore, to enhance the success of translating these findings, we propose two approaches. First, thorough evaluation of experimental targets in multiple animal models, including nonhuman primates, should precede clinical trials. Second, we advocate for combination therapy, which involves using multiple agents simultaneously, especially in the early and potentially reversible stages of the disease. These strategies aim to increase the chances of successful neuroprotective treatment for glaucoma.

Aqueous misdirection syndrome: clinical outcomes and risk factors for treatment failure.

PURPOSE: To evaluate the outcomes of postoperative aqueous misdirection and factors predicting failure of interventions. METHODS: This retrospective study included 49 eyes from 47 patients with aqueous misdirection following glaucoma or cataract surgery. Resolution of aqueous misdirection (AM) was deepening of the central anterior chamber (AC) and intraocular pressure (IOP) ≤ 21 mmHg. The Cox proportional hazards regression model was used to evaluate risk factors for failure of various treatments. RESULTS: 10/49 eyes (20%) resolved with conservative management, and 39/49 eyes (80%) needed multiple intervention, of which 95% (37/39) eyes achieved resolution of aqueous misdirection. Pseudophakia predicted the need for multiple interventions with a hazard ratio of 2.391 (1.158-4.935), p = 0.02). Among the risk factors assessed for resolution of AM, longer axial length (HR: 0.61 (0.414-0.891), p < 0.01) and eyes with prior glaucoma surgery predicted resolution (HR: 0.142 (0.027-0.741), p < 0.01) and delayed presentation predicted failure (HR: 1.002 (1.0002-1.0031), p < 0.02). CONCLUSION: Pseudophakic eyes were more refractory and predicted the need for multiple interventions. Eyes with prior glaucoma surgery and those with longer axial length had achieved resolution faster, and delayed presentation was a risk factor for failure to resolve.

iPSC-derived cells stimulate ABCG2+/NES+ endogenous trabecular meshwork cell proliferation and tissue regeneration.

A major risk factor for glaucoma, the first leading cause of irreversible blindness worldwide, is the decellularisation of the trabecular meshwork (TM) in the conventional outflow pathway. Stem cell-based therapy, particularly the utilisation of induced pluripotent stem cells (iPSCs), presents an enticing potential for tissue regeneration and intraocular pressure (IOP) maintenance in glaucoma. We have previously observed that differentiated iPSCs can stimulate endogenous cell proliferation in the TM, a pivotal factor in TM regeneration and aqueous humour outflow restoration. In this study, we investigated the response of TM cells in vivo after interacting with iPSC-derived cells and identified two subpopulations responsible for this relatively long-term tissue regeneration: ATP Binding Cassette Subfamily G Member 2 (ABCG2)-positive cells and Nestin (NES)-positive cells. We further uncovered that alterations of these responsive cells are linked to ageing and different glaucoma etiologies, suggesting that ABCG2+ subpopulation decellularization could serve as a potential risk factor for TM decellularization in glaucoma. Taken together, our findings illustrated the proliferative subpopulations in the conventional outflow pathway when stimulated with iPSC-derived cells and defined them as TM precursors, which may be applied to develop novel therapeutic approaches for glaucoma.

Glaucoma Agreement in New Zealand (GAINZ).

CLINICAL RELEVANCE: With an ageing population, ophthalmologists are becoming burdened with glaucoma management, and patient care can be delayed. Therefore, the use of optometrists in glaucoma management can help alleviate the burden. BACKGROUND: The ageing population and subsequent rise of glaucoma prevalence are putting a strain on the public health system in New Zealand. Glaucoma collaborative care between optometrists and ophthalmologists has been gaining support with the aim to reduce this burden on ophthalmologists. There has been little investigation of the agreement in care and management of mild-to-moderate severity glaucoma patients by optometrists and ophthalmologists. METHODS: One hundred and three glaucomatous eyes were used in a survey where clinical history and examination, intraocular pressures (IOPs), visual field testing and optical coherence tomography (OCT) imaging were evaluated for glaucoma progression and decision-making regarding subsequent management by four participants. Two participants were glaucoma-credentialled optometrists (Group 1), and the other two were glaucoma specialists (Group 2). RESULTS: With respect to glaucoma progression, Spearman coefficients identified strong agreement between the two groups for IOP, visual fields and overall status and moderate agreement for OCT imaging. A confusion matrix was used to analyse management and found 80% ± 10% agreement between the two groups. Review periods gave an agreement of 55% ± 20% between the two groups. CONCLUSION: There was strong agreement in the assessment of glaucoma progression between the two groups. The 80% level of agreement for subsequent management between the two groups is comparable to other published reports. These results provide some reassurance that a collaborative care system can perform safely and as intended.

Nationwide consensus on quality indicators to assess glaucoma care: A modified Delphi approach.

PURPOSE: Performance assessments are essential to tracking and improving quality in health care systems. Key aspects of the care process that act as indicators must be measured in order to gain an in-depth understanding of a care unit's operation. Without standardized quality indicators (QIs), it is difficult to characterize and compare the abilities of institutions to achieve excellence. The aim of this study is to reach a consensus among glaucoma specialists concerning the development of a set of QIs to assess the performance of glaucoma care units. METHODS: A two-round Delphi technique was performed among glaucoma specialists in Portugal, using a 7-point Likert scale. Fifty-three initial statements (comprising process, structure, and outcome indicators) were evaluated and participants had to agree on which ones would be part of the final set of QIs. RESULTS: By the end of both rounds, 28 glaucoma specialists reached consensus on 30/53 (57%) statements, including 19 (63%) process indicators (mainly relating to the proper implementation of complementary exams and the setting of follow-up intervals), 6 (20%) structure indicators, and 5 (17%) outcome indicators. Of the indicators that were part of the final list, functional and structural aspects of glaucoma progression and the availability of surgical/laser procedures were the most prevalent. CONCLUSIONS: A set of 30 QIs for measuring the performance of glaucoma units was developed using a consensus methodology involving experts in the field. Their use as measurement standards would provide important information about unit operations and allow further implementation of quality improvements.