Application of eye organoids in the study of eye diseases.

The eyes are one of the most important sensory organs in the human body. Currently, diseases such as limbal stem cell deficiency, cataract, retinitis pigmentosa and dry eye seriously threaten the quality of people's lives, and the treatment of advanced blinding eye disease and dry eye is ineffective and costly. Thus, new treatment modalities are urgently needed to improve patients' symptoms and suffering. In recent years, stem cell-derived three-dimensional structural organoids have been shown to mimic specific structures and functions similar to those of organs in the human body. Currently, 3D culture systems are used to construct organoids for different ocular growth and development models and ocular disease models to explore their physiological and pathological mechanisms. Eye organoids can also be used as a platform for drug screening. This paper reviews the latest research progress in regard to eye organoids (the cornea, lens, retina, lacrimal gland, and conjunctiva).

Running the enrollment numbers on ophthalmic clinical trials in the United States.

SIGNIFICANCE: This is one of the first reports to summarize the enrollment metrics for ophthalmology trials completed in the United States (US). PURPOSE: This study aimed to describe US ophthalmology clinical trial enrollment metrics to facilitate planning and budgeting of US Food and Drug Administration-regulated ophthalmological drugs trials. METHODS: A GlobalData PLC search was conducted on or before February 27, 2024, to evaluate the clinical trial landscape for completed ophthalmology clinical trials conducted in the US. The primary search contained only the term "ophthalmology," which was restricted to trials that were completed and were conducted within the US. Trials were classified as multicenter when trials included three sites or more, and when the enrollment search resulted in ≥30 multicenter trials for an individual indication, enrollment data were further broken down by Food and Drug Administration trial phase. RESULT: The search yielded 2229 trials, which analyzed 980 different drugs produced by 854 different sponsors. The most common indications evaluated in US trials were macular degeneration, glaucoma, macular edema, allergies, and keratoconjunctivitis. Multicenter trials by indication had an overall median enrollment period range of 4.8 to 35.1 months; number of subjects enrollment, range of 36 to 518 subjects; number of sites utilized, range of 4 to 74 sites; and enrollment rate, range of 0.11 to 4.04 subjects/sites per month. There were 17 indications with ≥30 multicenter trials, which allowed for enrollment metric calculation by trial phase. CONCLUSIONS: This study provides sponsors with an understanding of the number of subjects and sites needed to complete a trial while also setting realistic enrollment timelines. Although this work represents the US market, more work is needed to better understand other countries given that country-specific guidelines and subject beliefs may impact enrollment metrics.

Bibliometric analysis of ophthalmic OCT and OCT angiography research trends over the past 20 years.

PURPOSE: Optical coherence tomography (OCT) and OCT angiography (OCTA) are widely used in the diagnosis of ophthalmic diseases. This study aims to provide a comprehensive bibliometric analysis of ophthalmologic OCT and OCT angiography. METHODS: We retrieved publications on ophthalmic OCT and OCTA from 2003 to 2022 from the Web of Science Core Collection and used bibliometric tools to analyze and visualize the distribution, trend, and hotspots. RESULTS: In total, 20,817 articles written by 48,160 authors from 106 countries were selected. The number of publications has significantly increased. In the last two decades, the USA was the most productive country and received the highest citations. The most productive journal was Investigative Ophthalmology and Visual Science and received the highest number of citations. Moorfields Eye Hospital was the most productive institution. Bandello F published the most papers, while Spaide RF was the highest cited author. SPAIDE RF, 2011, AM J Ophthalmology was the most cited document. "OCT", "glaucoma" and "OCTA" were three hotspots in the last two decades. "Vessel density" and "deep learning" would be research hotspots in the future. CONCLUSION: The bibliometric analysis of ophthalmic OCT and OCTA research over the past two decades on keywords, authors, citations, hotspots and trends will provide global researchers with valuable information for future research and cooperation.

[Ocular manifestations of rheumatic diseases]. / Glaznye proyavleniya revmaticheskikh zabolevanii.

Rheumatic diseases are a large group of conditions of various origins, predominantly systemic in nature, with persistent or transient joint syndrome and involvement of other organs and systems, including the eyes. Many rheumatic diseases are characterized by specific types of ocular inflammation, which manifests through its localization, symmetry, and clinical features.

Impact of COVID-19 pandemic on ocular disease: KNHANES 2015-2021.

The aim of this study was to evaluate the impact of COVID-19 on ocular diseases and changes in risk factors before and after the COVID-19 pandemic. This study was conducted using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015-2021, a national cross-sectional health examination and survey. Associations between ocular diseases and risk factors were determined using the chi-squared test and logistic regression analysis. Bivariable adjusted logistic regression analysis was performed to examine the odds ratio (OR) and 95% confidence interval (CI) to evaluate of the impact of COVID-19 on ocular diseases. Individuals were divided into two age groups (< 60 and ≥ 60 years). A total of 50,158 people were diagnosed, of whom 7270 were diagnosed with cataract, 921 with glaucoma, and 439 with age-related macular degeneration (AMD). Risk factors for cataract were COVID-19 pandemic (OR 1.161), hypertension (OR 1.608), diabetes (OR 1.573), dyslipidemia (OR 1.167), stroke (OR 1.272), and depression (OR 1.567). Risk factors for AMD were COVID-19 pandemic (OR 1.600), dyslipidemia (OR 1.610), and depression (OR 1.466). Risk factors for glaucoma were hypertension (OR 1.234), dyslipidemia (OR 1.529), diabetes (OR 1.323), and depression (OR 1.830). The COVID-19 pandemic was a risk factor for cataracts and AMD, but not for glaucoma. Cataracts and AMD may be more influenced by the acquired health conditions or the environment.

Ocular manifestations and treatment progress of Crouzon syndrome.

PURPOSE: Crouzon syndrome is a congenital genetic disease caused by mutations of the FGFR2 gene on chromosome 10. It is usually inherited in an autosomal dominant pattern and is one of the most common types of craniosynostosis syndromes. This article focuses on the ophthalmology-related aspects of Crouzon syndrome in order to help diagnose and develop personalized treatment plans. METHODS: A combined systematic search of PubMed electronic database by using Boolean operators AND and OR was conducted, choosing the following keywords: "Crouzon", "craniosynostosis", " eye ", " oculus ", " ocular ", " ophthalmic ", " ophthalmologic ", " ophthalmology ", " globe ", " orbit ", " exophthalmos ", " exorbitism ", " keratopathy ", " visual " etc. After the initial screening of these articles, repetitive literatures were excluded. RESULTS: 47 articles were selected. This article introduces the ocular manifestations, possible pathogenesis and treatment progress in Crouzon syndrome. CONCLUSIONS: The incidence of ocular abnormalities in Crouzon syndrome is very high, such as shallow orbits, exophthalmos, hypertelorism, exposure keratopathy, strabismus, optic neuropathy, ametropia, glaucoma, etc. The pathogenesis of these ocular abnormalities is related to orbital deformities. Most of the treatments are aimed at compensating the abnormal anatomic structure at present.

[Effectiveness of the Eye Care Protocol in the Intensive Care Unit Patients: A Randomized Controlled Trial].

PURPOSE: This study investigated the effects of an eye care protocol (ECP) on patients in the intensive care unit (ICU). METHODS: This study utilized a randomized controlled design. Participants were patients who met the inclusion criteria and were admitted to the ICU (36 in the experimental group and 38 in the control group). The experimental group received an ECP, while the control group received standard eye care, starting the day after admission, for a duration of 10 days. The ECP classifies the degree of eyelid obstruction into three stages based on the degree of exposure to the lower eyelid conjunctiva and cornea. The protocol included cleansing with normal saline gauze, administering eye drops, applying silicone and polyurethane films, and recommending consultation with an ophthalmologist if necessary. The effectiveness of ECP was assessed by analyzing tear volume, hyperemia, chemosis, and eye discharge. Data analysis was conducted using SPSS 27.0, employing the Mann-Whitney U-test and generalized estimating equations. RESULTS: On day 5, the experimental group demonstrated a significant increase in tear volume in both eyes compared with the control group. However, no statistically significant differences were observed in the incidence of hyperemia, chemosis, and eye discharge on days 5 and 10 of the intervention. CONCLUSION: The application of the ECP in this study increased tear volume in ICU patients, thereby reducing discomfort caused by dry eyes. It has the potential to prevent complications such as damage to the surface of the eyeball resulting from decreased tear volume.

Towards Standardizing Ophthalmic Data for Seamless Interoperability in Eye Care.

INTRODUCTION: Seamless interoperability of ophthalmic clinical data is beneficial for improving patient care and advancing research through the integration of data from various sources. Such consolidation increases the amount of data available, leading to more robust statistical analyses, and improving the accuracy and reliability of artificial intelligence models. However, the lack of consistent, harmonized data formats and meanings (syntactic and semantic interoperability) poses a significant challenge in sharing ophthalmic data. METHODS: The Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR), a standard for the exchange of healthcare data, emerges as a promising solution. To facilitate cross-site data exchange in research, the German Medical Informatics Initiative (MII) has developed a core data set (CDS) based on FHIR. RESULTS: This work investigates the suitability of the MII CDS specifications for exchanging ophthalmic clinical data necessary to train and validate a specific machine learning model designed for predicting visual acuity. In interdisciplinary collaborations, we identified and categorized the required ophthalmic clinical data and explored the possibility of its mapping to FHIR using the MII CDS specifications. DISCUSSION: We found that the current FHIR MII CDS specifications do not completely accommodate the ophthalmic clinical data we investigated, indicating that the creation of an extension module is essential.

The Economic Burden of Childhood Ocular Morbidity in Bangladesh.

INTRODUCTION: Childhood eye morbidity is a great public health problem, especially in low-income countries. This study aimed to determine the economic burden of childhood ocular morbidity on attending tertiary hospitals in Bangladesh. This study also assessed the catastrophic health expenditure (CHE) for childhood ocular morbidity in Bangladesh. METHODS: A cross-sectional mixed method was used for this study from April to October 2023 at two tertiary hospitals in Bangladesh, one government-funded and one private. Face-to-face interviews using a semi-structured quantitative questionnaire with the caregivers/parents and in-depth interviews (IDIs) were conducted among the same respondents of these two hospitals, and a workshop was conducted with the stakeholders during the study period. RESULTS: This was the first study in Bangladesh to determine the cost of pediatric ocular morbidity. Among 335 patients, the total median direct cost at a single time was 3740 ± 18,285 BDT (34 ± 166.2 USD) at the government hospital and 7300 ± 40,630 BDT (66.36 ± 369.36 USD) at the private hospital. The disease-specific median overall cost from diagnosis of the disease was 65,000 BDT (591 USD) for squint, 50,000 BDT (454.54 USD) for cataract, and 30,000 BDT (272.72 USD) for eye injury. Almost 90% of the caregivers/parents faced CHE due to different pediatric ocular morbidity. CONCLUSIONS: These cost estimates can be used as an initial basis for financial decisions that aim to enhance access to care, management, and follow-up of children with ocular morbidity. These cost estimates also offer helpful information for organizational and financial sustainability initiatives. Policymakers can consider serious immediate interventions for securing ocular health services in Bangladesh and prevent families from CHE.

Genetic therapies and potential therapeutic applications of CRISPR activators in the eye.

Conventional gene therapy involving supplementation only treats loss-of-function diseases and is limited by viral packaging sizes, precluding therapy of large genes. The discovery of CRISPR/Cas has led to a paradigm shift in the field of genetic therapy, with the promise of precise gene editing, thus broadening the range of diseases that can be treated. The initial uses of CRISPR/Cas have focused mainly on gene editing or silencing of abnormal variants via utilising Cas endonuclease to trigger the target cell endogenous non-homologous end joining. Subsequently, the technology has evolved to modify the Cas enzyme and even its guide RNA, leading to more efficient editing tools in the form of base and prime editing. Further advancements of this CRISPR/Cas technology itself have expanded its functional repertoire from targeted editing to programmable transactivation, shifting the therapeutic focus to precise endogenous gene activation or upregulation with the potential for epigenetic modifications. In vivo experiments using this platform have demonstrated the potential of CRISPR-activators (CRISPRa) to treat various loss-of-function diseases, as well as in regenerative medicine, highlighting their versatility to overcome limitations associated with conventional strategies. This review summarises the molecular mechanisms of CRISPRa platforms, the current applications of this technology in vivo, and discusses potential solutions to translational hurdles for this therapy, with a focus on ophthalmic diseases.

The profile of patients attending to the general emergency department with ocular complaints within the last year: is it a true ocular emergency?

PURPOSE: Ocular emergencies require immediate intervention to prevent rapid vision loss or functional impairment. The aim of this study was to determine the proportion of true ocular emergencies among patients who presented to the general emergency department with ocular complaints and were referred to the Eye Clinic. METHODS: In a retrospective cross-sectional study in a tertiary hospital in Istanbul, patients aged 0-100 years who presented to the general emergency department with ocular complaints between January and December 2022 were included. Inconclusive diagnoses and incomplete records were excluded. Patients were divided into three groups: top eye emergencies (TE), relative eye emergencies (REE), and non-emergency eyes (NEE). RESULTS: Among the 652,224 individuals seeking care, 9,982 (1.5%) were referred to the Eye Emergency Clinic. Of these, 2,788 (27.9%) were female, and 7,194 (72.1%) were male, with ages ranging from 0 to 98 years. TopEye Emergencies (TEE), Relative Eye Emergencies (REE), and Non-Eye Emergencies (NEE) accounted for 13%, 60%, and 27% of the cases, respectively. Common top-eye emergencies (TEE) include chemical injuries, orbital-preseptal cellulitis, and orbital fractures. Relative eye emergencies (REEs) commonly feature corneal foreign bodies, corneal erosion, and conjunctivitis. Nonemulsion eye (NEE) methods involve simple eye redness, trauma without eye involvement, and subconjunctival haemorrhage. CONCLUSIONS: Consistent with the literature, 1.5% of patients presenting to the general emergency department had eye complaints.However, 27% of those referred to the ophthalmological clinic did not have an urgent eye condition. This is partly due to the high proportion of patients presenting to the emergency department with ocular complaints and the lack of knowledge of ophthalmological diseases by emergency physicians, leading to unnecessary referrals to the ophthalmology clinic, resulting in a loss of the workforce and reduced time allocated to patients with true ocular emergencies.

Carbon quantum dots for the diagnosis and treatment of ophthalmic diseases.

Carbon quantum dots (CQDs), an emerging nanomaterial, are gaining attention in ophthalmological applications due to their distinctive physical, chemical, and biological characteristics. For example, their inherent fluorescent capabilities offer a novel and promising alternative to conventional fluorescent dyes for ocular disease diagnostics. Furthermore, because of the excellent biocompatibility and minimal cytotoxicity, CQDs are well-suited for therapeutic applications. In addition, functionalized CQDs can effectively deliver drugs to the posterior part of the eyeball to inhibit neovascularization. This review details the use of CQDs in the management of ophthalmic diseases, including various retinal diseases, and ocular infections. While still in its initial phases within ophthalmology, the significant potential of CQDs for diagnosing and treating eye conditions is evident.

Barriers to the uptake of eye care services: A cross-sectional survey from rural and urban communities.

PURPOSE: To explore the barriers to the uptake of eye care services in urban and rural communities in Papua New Guinea. METHODS: This was a population-based cross-sectional descriptive study and involved multi-stage sampling. Communities were randomly selected from each of the three clusters of Madang District for free eye care outreaches from June to September 2022. A structured questionnaire was used to collect data from the outreach patients. The study excluded attendees who refused to consent. Responses were rated from 1 (not a barrier) to 10 (a very strong barrier). The p-value significance was set at ≤ 0.05. RESULTS: The majority of the 972 participants (60.2%) were from rural communities. The mean age of participants was 40.82 ± 13.14 years. Almost two-thirds of the participants (61.4%) never had an eye examination before this study was conducted. All the participants reported that time constraint, insufficient income, good vision in the fellow eye, not considering their eye conditions as serious issues and cultural beliefs were personal barriers to accessing eye care services. Provider-related challenges included long waiting periods at eye clinics and fear of procedure complications. There were differences in barriers with respect to the participants' demographic clusters. CONCLUSION: There are major personal- and service-related barriers to eye care services in Madang. These barriers could be overcome through strategic human resource development, health education, school screening programs, and establishing eye care centres in the communities to improve the uptake of eye care services in Madang and more widely across the country.

Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.

BACKGROUND: Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups. METHODS: The BeyeOMARKER study is a prospective, observational, longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being ≥ 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial inflammation, and conditions in surrounding structures of the eye that are not engaged in vision. The BeyeOMARKER cohort (n = 700) will undergo blood collection to assess plasma p-tau217 levels and a brief cognitive screening at the eye clinic. All participants will subsequently be invited for annual longitudinal follow-up including remotely administered cognitive screening and questionnaires. The BeyeOMARKER + cohort (n = 150), consisting of 100 plasma p-tau217 positive participants and 50 matched negative controls selected from the BeyeOMARKER cohort, will additionally undergo Aß-PET and tau-PET, MRI, retinal imaging including hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments. RESULTS: We aim to implement the current protocol between April 2024 until March 2027. Primary outcomes include the performance of plasma p-tau217 and hyperspectral retinal imaging to detect AD pathology (using Aß- and tau-PET visual read as reference standard) and to detect cognitive decline. Initial follow-up is ~ 2 years but may be extended with additional funding. CONCLUSIONS: We envision that the BeyeOMARKER study will demonstrate the feasibility of early AD detection based on blood- and eye-based biomarkers in alternative screening settings, and will improve our understanding of the eye-brain connection. TRIAL REGISTRATION: The BeyeOMARKER study (Eudamed CIV ID: CIV-NL-23-09-044086; registration date: 19th of March 2024) is approved by the ethical review board of the Amsterdam UMC.