Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives.

Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases represent scientific and therapeutic challenges because different cellular and molecular actors involved in the pathophysiology are still being identified. Visual system components, particularly retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune responses activated by local insults contribute to biological events, culminating in vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and some of them, such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and diabetic retinopathy, are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cell degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiological and molecular features and biochemical hallmarks, and possible research directions for novel treatments to assist as a guide for innovative research. The knowledge expansion upon the mechanistic bases of the pathobiology of eye diseases, including information on complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors, will prompt the identification of new therapeutic strategies.

The Association between Vascular Abnormalities and Glaucoma-What Comes First?

Glaucoma is a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) presents a major risk factor, the underlying pathophysiology still remains largely unclear. The correlation between vascular abnormalities and glaucoma has been deliberated for decades. Evidence for a role played by vascular factors in the pathogenesis of glaucomatous neurodegeneration has already been postulated. In addition, the fact that glaucoma causes both structural and functional changes to retinal blood vessels has been described. This review aims to investigate the published evidence concerning the relationship between vascular abnormalities and glaucoma, and to provide an overview of the "chicken or egg" dilemma in glaucoma. In this study, several biomarkers of glaucoma progression from a vascular perspective, including endothelin-1 (ET-1), nitric oxide, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), were identified and subsequently assessed for their potential as pharmacological intervention targets.

Establishing Functional Retina in a Dish: Progress and Promises of Induced Pluripotent Stem Cell-Based Retinal Neuron Differentiation.

The human eye plays a critical role in vision perception, but various retinal degenerative diseases such as retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD) can lead to vision loss or blindness. Although progress has been made in understanding retinal development and in clinical research, current treatments remain inadequate for curing or reversing these degenerative conditions. Animal models have limited relevance to humans, and obtaining human eye tissue samples is challenging due to ethical and legal considerations. Consequently, researchers have turned to stem cell-based approaches, specifically induced pluripotent stem cells (iPSCs), to generate distinct retinal cell populations and develop cell replacement therapies. iPSCs offer a novel platform for studying the key stages of human retinogenesis and disease-specific mechanisms. Stem cell technology has facilitated the production of diverse retinal cell types, including retinal ganglion cells (RGCs) and photoreceptors, and the development of retinal organoids has emerged as a valuable in vitro tool for investigating retinal neuron differentiation and modeling retinal diseases. This review focuses on the protocols, culture conditions, and techniques employed in differentiating retinal neurons from iPSCs. Furthermore, it emphasizes the significance of molecular and functional validation of the differentiated cells.

Characterization of Vascular Morphology of Neovascular Age-Related Macular Degeneration by Indocyanine Green Angiography.

Age-related macular degeneration (AMD) is a leading cause of blindness among older individuals, and its prevalence is rapidly increasing due to the aging population. Choroidal neovascularization (CNV) or wet AMD, which accounts for 10%-20% of all AMD cases, is responsible for an alarming 80%-90% of AMD-related blindness. Current anti-VEGF therapies show suboptimal responses in approximately 50% of patients. Resistance to anti-VEGF treatment in CNV patients is often associated with arteriolar CNV, while responders tend to have capillary CNV. While fluorescein angiography (FA) is commonly used to assess leakage patterns in wet AMD patients and animal models, it does not provide information about CNV vascular morphology (arteriolar CNV vs. capillary CNV). This protocol introduces the use of indocyanine green angiography (ICGA) to characterize lesion types in laser-induced CNV mouse models. This method is crucial for investigating the mechanisms and treatment strategies for anti-VEGF resistance in wet AMD. It is recommended to incorporate ICGA alongside FA for comprehensive assessment of both leakage and vascular features of CNV in mechanistic and therapeutic studies.

Central retinal artery occlusion in a young child affected by COVID-19: a first case report.

BACKGROUND: Central retinal artery occlusion (CRAO) is an ophthalmic emergency, and its etiology is generally ascribed to vessel occlusion by a thrombus or embolus, eventually due to a hypercoagulable state. CRAO occurrence is described even in the pediatric population, but its incidence is very rare. SARS-CoV-2 infection has a multitude of presentations, and almost any organ may be involved including the ocular district. Cases of CRAO in patients affected by COVID-19 are reported in the literature in the adult population, but not in the pediatric one. CASE PRESENTATION: We describe the case of a six-year-old otherwise healthy girl, who presented a sudden and complete bilateral vision loss after a one-day fever. All the clinical, ophthalmological, laboratory and instrumental investigations led to the diagnosis of a right CRAO and the suspicion of a contralateral posterior optic nerve affection. These manifestations could not be ascribed to any etiological condition apart from the documented ongoing mild SARS-CoV-2 infection. Treatment with anticoagulants and steroids was tried but the visual outcome was poor during the one-month hospitalization and at the last follow-up. CONCLUSIONS: To the best of our knowledge, this is the first report of CRAO in the course of SARS-CoV-2 infection in the pediatric age. In our review of the literature, we found few cases of CRAO in adults with COVID-19; we highlighted differences in anamnestic, clinical, and interventional aspects and therefore we tried to summarize the state of the art on this topic to facilitate further studies. Even if rare, the prognosis of CRAO is poor and the thrombolytic treatment could be effective only if rapidly administered, so the disease suspicion should be high in a patient with sudden vision loss, also in pediatric age.

Neurogenic thoracic outlet syndrome: When to consider the diagnosis and current management options.

BACKGROUND: Thoracic outlet syndrome (TOS) refers to a group of compressive disorders that occur in the thoracic outlet and can affect the brachial plexus, subclavian artery and vein. Neurogenic TOS (nTOS) is the most common form of TOS, accounting for approximately 97% of cases. nTOS and its resulting compressive brachial plexopathy can lead to potentially disabling symptoms and reduced quality of life. OBJECTIVE: This article reviews the current literature on nTOS and summarises the pathophysiology, diagnostic pathways and the management options for nTOS. DISCUSSION: nTOS is an uncommon but disabling disorder with no single 'rule-in' test, often resulting in diagnostic delays and late referral. Initial management is non-operative with targeted physiotherapy. If this is unsuccessful, symptoms can be relieved with scalene botulinum toxin injections and surgical intervention.

Deploying efficient net batch normalizations (BNs) for grading diabetic retinopathy severity levels from fundus images.

Diabetic retinopathy (DR) is one of the main causes of blindness in people around the world. Early diagnosis and treatment of DR can be accomplished by organizing large regular screening programs. Still, it is difficult to spot diabetic retinopathy timely because the situation might not indicate signs in the primary stages of the disease. Due to a drastic increase in diabetic patients, there is an urgent need for efficient diabetic retinopathy detecting systems. Auto-encoders, sparse coding, and limited Boltzmann machines were used as a few past deep learning (DL) techniques and features for the classification of DR. Convolutional Neural Networks (CNN) have been identified as a promising solution for detecting and classifying DR. We employ the deep learning capabilities of efficient net batch normalization (BNs) pre-trained models to automatically acquire discriminative features from fundus images. However, we successfully achieved F1 scores above 80% on all efficient net BNs in the EYE-PACS dataset (calculated F1 score for DeepDRiD another dataset) and the results are better than previous studies. In this paper, we improved the accuracy and F1 score of the efficient net BNs pre-trained models on the EYE-PACS dataset by applying a Gaussian Smooth filter and data augmentation transforms. Using our proposed technique, we have achieved F1 scores of 84% and 87% for EYE-PACS and DeepDRiD.

The Fibro-Inflammatory Response in the Glaucomatous Optic Nerve Head.

Glaucoma is a progressive disease and the leading cause of irreversible blindness. The limited therapeutics available are only able to manage the common risk factor of glaucoma, elevated intraocular pressure (IOP), indicating a great need for understanding the cellular mechanisms behind optic nerve head (ONH) damage during disease progression. Here we review the known inflammatory and fibrotic changes occurring in the ONH. In addition, we describe a novel mechanism of toll-like receptor 4 (TLR4) and transforming growth factor beta-2 (TGFß2) signaling crosstalk in the cells of the ONH that contribute to glaucomatous damage. Understanding molecular signaling within and between the cells of the ONH can help identify new drug targets and therapeutics.

Belgian Endothelial Surgical Transplant of the Cornea (BEST cornea) protocol: clinical and patient-reported outcomes of Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) versus Descemet Membrane Endothelial Keratoplasty (DMEK) - a multicentric, randomised, parallel group pragmatic trial in corneal endothelial decompensation.

OBJECTIVES: Corneal blindness is the third most frequent cause of blindness globally. Damage to the corneal endothelium is a leading indication for corneal transplantation, which is typically performed by lamellar endothelial keratoplasty. There are two conventional surgical techniques: Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK). The purpose of this study is to compare both techniques. METHODS AND ANALYSIS: The trial compares UT-DSAEK and DMEK in terms of clinical and patient reported outcomes using a pragmatic, parallel, multicentric, randomised controlled trial with 1:1 allocation with a sample size of 220 participants across 11 surgical centres. The primary outcome is the change in best-corrected visual acuity at 12 months. Secondary outcomes include corrected and uncorrected vision, refraction, proportion of high vision, quality of life (EQ-5D-5L and VFQ25), endothelial cell counts and corneal thickness at 3, 6 and 12 months follow-up appointments. Adverse events will also be compared 12 months postoperatively. ETHICS AND DISSEMINATION: The protocol was reviewed by ethical committees of 11 participating centres with the sponsor centre issuing the final definitive approval. The results will be disseminated at clinical conferences, by patient partner groups and open access in peer-reviewed journals. GOVERNANCE OF THE TRIAL: Both, trial management group and trial steering committee, are installed with representatives of all stakeholders involved including surgeons, corneal bankers, patients and external experts. TRIAL REGISTRATION NUMBER: NCT05436665.

Polio outbreaks in Cameroon following the COVID-19 pandemic.

Polio is an infectious and disabling life-threatening disease caused by the poliovirus. This disease is prevented through vaccination. Though this viral infection has been eliminated in most parts of the world, a few countries are still endemic to wild poliovirus. In 2020, the World Health Organization (WHO) African Region, including Cameroon, was certified free of wild poliovirus. Some countries recurrently report circulating vaccine-derived poliovirus cases (cVDPV) despite recorded achievements. Also, the risk of importing poliovirus from endemic settings remains, particularly in the context of coronavirus disease (COVID-19). This study aimed to assess the state of polio in Cameroon and identify the situation during COVID-19. A data review was conducted from February to March 2023. Data on polio cases and vaccination coverage per region of Cameroon were reviewed from 2014 to 2022. Data were analyzed with Microsoft Excel, and the results were presented as proportions. The last wild poliovirus was reported in Cameroon in 2014, and the country benefitted from a response. No case of poliovirus was detected in the country from 2015 to 2018. After that, an increasing number of type two cVDPV were reported across 50% of the country's regions from 2019 to 2022. The outbreaks benefitted from responses with various oral polio vaccines, including the type two novel oral polio vaccine (nOPV-2). Though wild polioviruses have been eliminated in most countries, including Cameroon, cVDPV remains a significant problem. There is an urgent need to strengthen disease surveillance and vaccination to prevent cVDPV-2 in this country, particularly in the COVID-19 context.

Steroid-induced glaucoma: an avoidable cause of irreversible blindness.

A man in his 70s on regular follow-up with an ophthalmologist for 10 years presented with blurry vision in his right eye for 4 days. He was diagnosed with elevated intraocular pressure (IOP) bilaterally 18 months earlier and treated with antiglaucoma eye-drops. On direct questioning, he admitted to using fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops frequently to relieve ocular redness and discomfort in both eyes for 3.5 years without his ophthalmologist's knowledge. Examination disclosed markedly elevated IOP, advanced optic disc cupping and tunnel vision due to steroid-induced glaucoma bilaterally. After cessation of the eye-drops and 2 weeks of antiglaucoma therapy, his IOP returned to normal and his visual field remained stable for 4 years.Our case highlights the danger of habitual self-treatment of prescription medications containing corticosteroids and the importance of taking a detailed medication history in the diagnosis and management of steroid-induced glaucoma.

Evidence-Based Taiwan Consensus Recommendations for the treatment of Parkinson's disease.

Parkinson's disease (PD) is a common and disabling neurodegenerative disorder with a prevalence set to double by 2030. People with PD present both motor symptoms (such as tremor, rigidity, slowness of movements, and postural instability) and non-motor symptoms (such as dementia, psychiatric symptoms, and sleep disturbances). The treatment of PD is challenging and is highly individualized. The Taiwan Movement Disorder Society (TMDS) has published its treatment recommendations for PD in 2017. Since then, because the advent of medical and device-aided therapy has developed rapidly, the TMDS has recognized the need to disseminate the updated knowledge about the management of PD. The TMDS acknowledges the importance of evidence-based medicine (EBM) in clinical practice. Therefore, we strive to align our treatment recommendations with EBM principles. Nevertheless, it still needs to be emphasized that therapeutic recommendations should always be tailored to the individual patient, based not only on an accurate understanding of the efficacy and side effect profile of available treatments (the primary focus of guidelines), but also the physician's judgment, patient's preference, and the regulations of national health insurance. To ensure that the updated Taiwan treatment suggestions are appropriate and feasible, the treatment guideline subcommittee of TMDS referred to the guidelines from the International Movement Disorder Society and other treatment suggestions from United States and Europe concerning the level of evidence, recommendation levels, clinical efficacy, and potential adverse reactions of therapeutics for the treatment of motor and non-motor symptoms of PD. By incorporating the latest research, international guidelines, and treatment suggestions, the TMDS aims to provide comprehensive and up-to-date recommendations for the management of PD in Taiwan. These recommendations serve as a valuable resource for healthcare professionals to enhance their understanding of PD treatment options and optimize patient care. Key Words: Parkinson's disease; treatment; guidelines; evidence-based medicine.

Corneal blindness and eye banking: Current strategies and best practices.

Corneal blindness (CB) is one of the leading causes of blindness in India and globally, affecting around 8 million population worldwide. Many of these corneal blind patients may be visually rehabilitated by corneal transplantation (CT). Eye banking plays a crucial role in facilitating CT and ocular research. Many countries have adopted regulatory frameworks, quality assurance programs, and technological advancements to enhance the efficacy and safety of CT. Various infrastructural and organizational frameworks of eye banks (EBs) in India, according to the Eye Bank Association of India (EBAI), aid in establishing guidelines and standards for EB practices. Initiatives such as the National Programme for Control of Blindness (NPCB) have significantly contributed to eye donation rates and improved access to donor corneas. This review article discusses the established eye banking networks in countries such as India, the United States (USA), and Europe, where dedicated EB organizations work collaboratively to ensure efficient procurement, processing, and distribution of corneal tissue. It also highlights specific strategies employed in India and global countries to address EBs' challenges. These challenges include the shortage of donor corneas, improving donor screening and tissue processing techniques, ensuring timely distribution of corneal tissue, and maintaining high-quality standards. Interestingly, the comparative analysis between India and other developed countries highlights the similarities and differences in eye banking strategies. By understanding the strategies employed by different regions, EBs can learn from each other's experiences and work toward achieving optimal outcomes in CT and ocular research worldwide. It underscores the importance of knowledge sharing and collaborative efforts in addressing common challenges and implementing best practices in eye banking.

Evolution of eye banking in India - A review.

Corneal blindness ranks third among the causes of blindness worldwide, after cataract and glaucoma. Corneal transplantation offers us a means to address this, and is currently the most commonly performed transplantation procedure worldwide - restoring the gift of sight to many an eye. Eye banks play a very important role in these procedures. India was quick to develop its own eye bank in 1945 soon after the launch of world's first eye bank in 1944. The evolution over the past six decades has been tremendous, placing India on the top, with one of the largest eye-banking system in the world. As of 2023, around 740 members are registered under the Eye Bank Association of India. The highest-ever collection of 71,700 donor eyes was achieved in 2017-2018. The overall tissue utilisation rate ranged between 22 - 28 % for voluntary donations and 50% for hospital-based corneal retrieval programs. Though India has an excellent infrastructure and readiness for corneal transplantation surgery, the need of the hour is to create a strong and independent nodal system. It shall take care of the logistics and factor in technological advances - surgical and otherwise. Public awareness, a national corneal grid, and reducing the red-tape barriers, shall improve availability of grafts nationwide. This review aims to detail the evolution of eye banking in India, to provide a comprehensive understanding, and help the stakeholders focus on the road ahead to attain our targets faster.

Methods for a population-based Comprehensive Eye care Workload Assessment (CEWA) study in Southern India.

Eye care programs, in developing countries, are often planned using the prevalence of blindness and visual impairment, often estimated from Rapid Assessment of Avoidable Blindness (RAAB) surveys. A limitation of this planning approach is that it ignores the annual overall eye care requirements for a given population. Moreover, targets set are arbitrary, often influenced by capacity rather than need. To address this lacunae, we implemented a novel study design to estimate the annual need for comprehensive eye care in a 1.2 million populations. We conducted a population-based longitudinal study in Theni district, Tamil Nadu, India. All permanent residents of all ages were included. We conducted the study in three phases, (i) household-level enumeration and enrollment, (ii) basic eye examination (BEE) at household one-year post-enrollment, and (iii) assessment of eye care utilization and full eye examination (FEE) at central locations. All people aged 40 years and above were invited to the FEE. Those aged <40 years were invited to the FEE if indicated. In the main study, we enrolled 24,327 subjects (58% aged below 40 years and 42% aged 40 years and above). Of those less than 40 years, 72% completed the BEE, of whom 20% were referred for FEE at central location. Of the people aged ≥40 years, 70% underwent FEE. Our study design provides insights for appropriate long-term public health intervention planning, resource allocation, effective service delivery, and designing of eye care services for resource-limited settings.

Effects of Blindness on Sleep/Wakefulness States in Mice.

To examine the effects of blindness on sleep/wakefulness states, we compared locomotor activity and delayed recovery from isoflurane anesthesia induced by hypnotics during light and dark periods in sighted CBA/N and blind CBA/J mice. Locomotor activity around the switch from the dark to light period significantly differed in both mice. Delayed recovery induced by brotizolam was attenuated in both periods in CBA/J mice. In addition, the period specificity of delayed recovery caused by suvorexant or diphenhydramine in CBA/N mice was abolished in CBA/J mice. These results suggest that blindness impairs sleep quality.

Enhanced maternal behaviors in a mouse model of congenital blindness.

In mammals, mothering is one of the most important prosocial female behavior to promote survival, proper sensorimotor, and emotional development of the offspring. Different intrinsic and extrinsic factors can initiate and maintain these behaviors, such as hormonal, cerebral, and sensory changes. Infant cues also stimulate multisensory systems and orchestrate complex maternal responsiveness. To understand the maternal behavior driven by complex sensory interactions, it is necessary to comprehend the individual sensory systems by taking out other senses. An excellent model for investigating sensory regulation of maternal behavior is a murine model of congenital blindness, the ZRDBA mice, where both an anophthalmic and sighted mice are generated from the same litter. Therefore, this study aims to assess whether visual inputs are essential to driving maternal behaviors in mice. Maternal behaviors were assessed using three behavioral tests, including the pup retrieval test, the home cage maternal behavior test, and the maternal aggression test. Our results show that blind mothers (1) took less time to retrieve their offspring inside the nest, (2) spent more time nursing and licking their offspring in the second- and third-week postpartum, and (3) exhibited faster aggressive behaviors when exposed to an intruder male, compared to the sighted counterparts. This study provides evidence that congenitally blind mothers show more motivation to retrieve the pups, care, and protection towards their pups than sighted ones, likely due to a phenomenon of sensory compensation.

A Call for Regular Ophthalmologist Cover for Rehabilitation Centers for the Blind.

A call to the governments of developing countries that parents of visually impaired, all eyecare workers especially ophthalmologists including all schools where visually impaired people are being educated, to see the advantage of proper screening and continuous eyecare of individuals who present to these schools/rehabilitation centers by qualified eyecare personnel as well as have proper knowledge of where such rehabilitative services are available by those who should knowthe eyecare workers. The specific role of the ophthalmologist is highlighted.

Un appel aux gouvernements des pays en voie de développement, aux parents de malvoyants, à tous les professionnels de la vue, en particulier les ophtalmologistes, et à toutes les écoles où les malvoyants sont éduqués, pour qu'ils voient l'avantage d'un dépistage approprié et de soins oculaires continus des individus qui se présentent dans ces écoles/ centres de rééducation par un personnel ophtalmologiste qualifié, et pour que ceux qui devraient savoir - les professionnels de la vue - sachent où ces services de rééducation sont disponibles. Le rôle spécifique de l'ophtalmologiste est souligné. Mots clés: Cécité, Réadaptation, Ophtalmologue.

Understanding the behavioral determinants that predict barriers and enablers of screening and treatment behaviors for diabetic retinopathy among Bangladeshi women: findings from a barrier analysis.

BACKGROUND AND AIM: While early detection and timely treatments can prevent diabetic retinopathy (DR) related blindness, barriers to receiving these DR services may cause permanent sight loss. Despite having similar prevalence to diabetes and DR, women are less likely than men to perform these behaviors due to multi-faced barriers in screening and receiving follow-up treatments for DR. This study, therefore, aimed at identifying the barriers to - and enablers of - screening and follow-up treatments behaviors for DR among women aged more than 40 years with diabetes from the behavioral perspectives in Bangladesh. METHODS: This Barrier Analysis study interviewed 360 women (180 "Doers" and 180 "Non-doers") to explore twelve behavioral determinants of four DR behaviors including screening, injection of anti-vascular endothelial growth factor (anti-VEGF medication), laser therapy and vitro-retinal surgery. The data analysis was performed to calculate estimated relative risk to identify the degree of association between the determinants and behaviors, and to find statistically significant differences (at p < 0.05) in the responses between the Doers and Non-doers. RESULTS: Access to healthcare facilities was the major barrier impeding women from performing DR behaviors. Difficulty in locating DR service centers, the need to travel long distances, the inability to travel alone and during illness, challenges of paying for transportation and managing workload significantly affected women's ability to perform the behaviors. Other determinants included women's perceived self-efficacy, perceived negative consequences (e.g. fear and discomfort associated with injections or laser treatment), and cues for action. Significant perceived enablers included low cost of DR treatments, supportive attitudes by healthcare providers, government policy, and perceived social norms. CONCLUSION: The study found a host of determinants related to the barriers to and enablers of DR screening and treatment behaviors. These determinants included perceived self-efficacy (and agency), positive and negative consequences, perceived access, perceived social norms, culture, and perceived risk. Further investments are required to enhance the availability of DR services within primary and secondary health institutions along with health behavior promotion to dispel misconceptions and fears related to DR treatments.