Advances in Extracellular-Vesicles-Based Diagnostic and Therapeutic Approaches for Ocular Diseases.

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

Understanding Health Care Disparities Based on Medicare Use for Inflammatory and Infectious Eye Diseases.

Purpose: Inflammatory and infectious eye diseases are an important cause of visual impairment in patients older than 65 years of age. Health care disparities for eye care are present for general eye care. However, there is lack of national data on health disparities regarding eye care use for inflammatory and infectious eye diseases. Our study examines the effect of gender and race on eye care in patients with inflammatory and infectious eye diseases who are equal or greater than 65 years of age. Methods: We have used Medicare data to examine the effect gender and race on use of eye care services in patients with inflammatory and infectious eye diseases for 2014 to 2018. Medicare is a national insurance program administered by the government of United States to insure people age 65 years or older. Owing to its high enrollment, those in Medicare are representative of the U.S. population aged 65 and older. Results: We found that females have higher use for Medicare for inflammatory and infectious eye diseases across all races from 2014 to 2018. On examining the effect of race, African Americans have lower use as compared with Whites. People of Asian descent have the highest use, followed by Hispanic people. Conclusions: Health care disparities exist for eye care use for inflammatory and infectious eye diseases for patients 65 years of age and older. Future studies are required to address these disparities to provide equitable eye care. Translational Relevance: Identification of eye care disparities is the first step to addressing these disparities.

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.

Immunopeptides: immunomodulatory strategies and prospects for ocular immunity applications.

Immunopeptides have low toxicity, low immunogenicity and targeting, and broad application prospects in drug delivery and assembly, which are diverse in application strategies and drug combinations. Immunopeptides are particularly important for regulating ocular immune homeostasis, as the eye is an immune-privileged organ. Immunopeptides have advantages in adaptive immunity and innate immunity, treating eye immune-related diseases by regulating T cells, B cells, immune checkpoints, and cytokines. This article summarizes the application strategies of immunopeptides in innate immunity and adaptive immunity, including autoimmunity, infection, vaccine strategies, and tumors. Furthermore, it focuses on the mechanisms of immunopeptides in mediating ocular immunity (autoimmune diseases, inflammatory storms, and tumors). Moreover, it reviews immunopeptides' application strategies and the therapeutic potential of immunopeptides in the eye. We expect the immune peptide to get attention in treating eye diseases and to provide a direction for eye disease immune peptide research.

Gauging Public Interest in Pediatric Ophthalmology Conditions Using Google Trends.

Google Trends data were analyzed to assess search trends for pediatric ophthalmology and strabismus terms from 2010 to 2022. The highest average search volumes were "lazy eye," "strabismus," and "vision therapy." "Amblyopia" had the lowest search volume. These data highlight the importance of understanding the utilization of online resources in health care and patient education. [J Pediatr Ophthalmol Strabismus. 2024;61(4):e39-e42.].

Accessibility of and barriers to the use of eye health services in Kumasi Metropolis, Ghana.

BACKGROUND:  There is a high prevalence of vision impairment and blindness in Africa. The poor access to eye health services, among other barriers, has been found to have a considerable effect on the burden of avoidable vision loss and blindness, particularly in low- and middle-income countries. AIM:  To determine the accessibility of and barriers to the utilisation of eye health services in the Kumasi Metropolis of Ghana. SETTING:  A descriptive cross-sectional survey was conducted in the Kumasi Metropolis of the Ashanti Region in Ghana to identify barriers affecting the utilisation of eye health services. METHODS:  Convenience sampling was used to recruit participants visiting the eye clinics at five selected District Municipal Hospitals for the first time. Data were collected by means of questionnaires and analysed using Statistical Package for Social Sciences (SPSS). RESULTS:  Barriers faced by participants when accessing eye health services included distance to the clinic, cost of services, time spent away from work and/or school, self-medication and long waiting periods. CONCLUSION:  The study found that eye care services in the Kumasi Metropolis, Ghana are largely accessible, but underutilised. Improvement of public health education initiatives through engagement with community groups will also enhance uptake at health care facilities.Contribution: Underutilisation of health services in the Metropolis has been identified in the study and must be addressed by health managers in various sectors. Accessibility is relatively good but can further be improved especially for the elderly to be able to utilise health care services with ease.

Factors associated with pediatric ophthalmology follow-up adherence before and during the COVID-19 pandemic.

BACKGROUND: Studies describe poor follow-up among children in ophthalmology prior to the COVID-19 pandemic. Although the pandemic led to worse adherence for routine medical care in children, little information exists on pediatric ophthalmology follow-up adherence during COVID-19. The purpose of this study was to evaluate the effect of the COVID-19 pandemic on follow-up adherence for children with eye disease, and identified characteristics associated with follow-up adherence. METHODS: In this single-center study, the medical records of 519 new pediatric (≤18 years of age) patients seen during January, April, August, and December 2019 and 2021 were reviewed retrospectively. Patients were classified into two groups: adherent (patients who followed up within 30 days of recommended appointment time) or less-adherent (patients who followed up >30 days after recommended follow-up or never). Main outcome measure was patient adherence status. RESULTS: Follow-up adherence was similar before and during the COVID-19 pandemic (50.4% for 2019 and 49.6% for 2021 [P = 0.40]). Patients that were less likely to be adherent in both univariate and multivariable analyses included those with public insurance (adjusted OR = 0.63 [95% CI, 0.40-1.00]; P = 0.05), and those recommended to follow-up ≥3 months (adjusted OR ≤ 0.10; P < 0.001). In addition, in univariate analysis, those who declined to self-report race (OR = 0.53 [95% CI, 0.29-0.95]; P = 0.04) and those seen by optometrists (OR = 0.42 [95% CI, 0.29-0.60]; P < 0.001) were less likely to be adherent, while patients who traveled ≥177 miles to their provider were more likely to be adherent (OR = 2.88 [95% CI, 1.17-7.55]; P = 0.02). CONCLUSIONS: Follow-up adherence for childhood eye care was low but remained relatively stable before and during the COVID-19 pandemic; >50% of children were less-adherent.

Neutrophils in Ocular Diseases.

Neutrophils, traditionally viewed as first responders to infection or tissue damage, exhibit dynamic and diverse roles in ocular health and disease. This review elaborates on previous findings that showed how neutrophils contribute to ocular diseases. In ocular infections, neutrophils play a pivotal role in host defense by orchestrating inflammatory responses to combat pathogens. Furthermore, in optic nerve neuropathies and retinal degenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR), neutrophils are implicated in neuroinflammation and tissue damage owing to their ability to undergo neutrophil extracellular trap formation (NETosis) and secretion of inflammatory molecules. Targeting neutrophil-dependent processes holds promise as a therapeutic strategy, offering potential avenues for intervention in ocular infections, cancers, and retinal degenerative diseases. Understanding the multifaceted roles of neutrophils in ocular diseases is crucial for developing targeted therapies to improve patient outcomes.

Recent advancements and applications of ophthalmic gene therapy strategies: A breakthrough in ocular therapeutics.

Over the past twenty years, ocular gene therapy has primarily focused on addressing diseases linked to various genetic factors. The eye is an ideal candidate for gene therapy due to its unique characteristics, such as easy accessibility and the ability to target both corneal and retinal conditions, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), age-related macular degeneration (AMD), and Stargardt disease. Currently, literature documents 33 clinical trials in this field, with the most promising results emerging from trials focused on LCA. These successes have catalyzed further research into other ocular conditions such as glaucoma, AMD, RP, and choroideremia. The effectiveness of gene therapy relies on the efficient delivery of genetic material to specific cells, ensuring sustained and optimal gene expression over time. Viral vectors have been widely used for this purpose, although concerns about potential risks such as immune reactions and genetic mutations have led to the development of non-viral vector systems. Preliminary laboratory research and clinical investigations have shown a connection between vector dosage and the intensity of immune response and inflammation in the eye. The method of administration significantly influences these reactions, with subretinal delivery resulting in a milder humoral response compared to the intravitreal route. This review discusses various ophthalmic diseases, including both corneal and retinal conditions, and their underlying mechanisms, highlighting recent advances and applications in ocular gene therapies.

Tissue Engineering and Ophthalmology.

Tissue engineering (TE) is a field of science that combines biological, engineering, and medical sciences and allows the development of disease models, drug development and gene therapy studies, and even cellular or tissue-based treatments developed by engineering methods. The eye is an organ that is easily accessible and amenable to engineering applications, paving the way for TE in ophthalmology. TE studies are being conducted on a wide range of topics, including the tear film, eyelids, cornea, optic nerve, glaucoma, and retinal diseases. With the rapid scientific advances in the field, it seems that TE is radically modifying the management of ocular disorders.

Big data study using health insurance claims to predict multidisciplinary low vision service uptake.

SIGNIFICANCE: There is a lack of research from high-income countries with various health care and funding systems regarding barriers and facilitators in low vision services (LVS) access. Furthermore, very few studies on LVS provision have used claims data. PURPOSE: This study aimed to investigate which patient characteristics predict receiving multidisciplinary LVS (MLVS) in the Netherlands, a high-income country, based on health care claims data. METHODS: Data from a Dutch national health insurance claims database (2015 to 2018) of patients with eye diseases causing potentially severe visual impairment were retrieved. Patients received MLVS (n = 8766) and/or ophthalmic treatment in 2018 (reference, n = 565,496). MLVS is provided by professionals from various clinical backgrounds, including nonprofit low vision optometry. Patient characteristics (sociodemographic, clinical, contextual, general health care utilization) were assessed as potential predictors using a multivariable logistic regression model, which was internally validated with bootstrapping. RESULTS: Predictors for receiving MLVS included prescription of low vision aids (odds ratio [OR], 8.76; 95% confidence interval [CI], 7.99 to 9.61), having multiple ophthalmic diagnoses (OR, 3.49; 95% CI, 3.30 to 3.70), receiving occupational therapy (OR, 2.32; 95% CI, 2.15 to 2.51), mental comorbidity (OR, 1.17; 95% CI, 1.10 to 1.23), comorbid hearing disorder (OR, 1.98; 95% CI, 1.86 to 2.11), and receiving treatment in both a general hospital and a specialized ophthalmic center (OR, 1.23; 95% CI, 1.10 to 1.37), or by a general practitioner (OR, 1.23; 95% CI, 1.18 to 1.29). Characteristics associated with lower odds included older age (OR, 0.30; 95% CI, 0.28 to 0.32), having a low social economic status (OR, 0.91; 95% CI, 0.86 to 0.97), physical comorbidity (OR, 0.87; 95% CI, 0.82 to 0.92), and greater distance to an MLVS (OR, 0.95; 95% CI, 0.92 to 0.98). The area under the curve of the model was 0.75 (95% CI, 0.75 to 0.76; optimism = 0.0008). CONCLUSIONS: Various sociodemographic, clinical, and contextual patient characteristics, as well as factors related to patients' general health care utilization, were found to influence MLVS receipt as barriers or facilitators. Eye care practitioners should have attention for socioeconomically disadvantaged older patients when considering MLVS referral.

Changing trends in barriers to accessing eye care services in rural South India: results from the longitudinal Andhra Pradesh Eye Disease Study III (APEDS III) cohort.

PURPOSE: To assess the changing trends in barriers towards accessing eye care in a rural population cohort from Southern India. METHODS: This is a population-based longitudinal cohort of participants (the Andhra Pradesh Eye Disease study [APEDS]) from three rural regions of Telangana and Andhra Pradesh who were evaluated at baseline (APEDS I; 1996-2000), along with follow-ups at 10 years (APEDS II; 2009-10) and 15 years (APEDS III; 2012-2016). At follow-up, all participants 30 years and above were administered a structured questionnaire on barriers to uptake of eye care services. RESULTS: Of 3810 participants, 1449 had visual impairment (VI). Among them, 1302 noticed a reduction in vision over last five years and 722 sought treatment, a significant improvement from baseline (P < 0.001). Participants were more likely to seek treatment if they were educated (OR = 1.43, 95%CI: 1.07-1.89), had hypertension (OR = 1.36, 95%CI: 1.04-1.77), had VI from causes other than cataract and refractive error (OR = 2.49, 95%CI: 1.56-3.99) and were residents of Adilabad (OR = 2.21; 95%CI: 1.58-3.08) and Mahbubnagar (OR = 3.55; 95%CI: 2.48-5.08) districts. Those with moderate or worse VI were less likely to seek treatment (moderate VI: OR = 0.56; 95%CI: 0.42-0.75, severe VI: OR = 0.34; 95%CI: 0.19-0.57, blindness: OR = 0.38; 95%CI: 0.2-0.73). The most important barriers to uptake of services were, not perceiving loss of vision as a serious problem (25.9%), accepting it an aging process (21.4%) or due to economic reasons (16.0%). CONCLUSION: Personal and economic elements accounted for considerable amounts of barriers for utilization of eye care services. The uptake of services could be improved by addressing these specific barriers and risk factors for non-compliance.

Development and Validation of Eyes Care Bundle for Mechanically Ventilated Patients.

Lack of proper eye care (EC) for mechanically ventilated patients can lead to serious ocular complications. Objective of this study is to develop and validate eyes care bundle for mechanically ventilated patients. A Delphi design study was conducted between March and May 2021. The Content Validity Index (CVI) was used to calculate the degree of agreement among the experts to analyze the bundle. Content validity was determined by 5 experts using a 4-point Likert scale. They evaluated the items in terms of the following: 1 = "irrelevant," 2 = "somewhat relevant if the phrasing is profoundly adjusted," 3 = "relevant with some adjustment," and 4 = "very relevant." The CVI was applied, and the accepted value was ≥0.50. The validation of EC bundle was conducted through 3 rounds after developed it based on the evaluated research evidence. The items were reviewed for content and face validity. The bundle was validated with 5 items with a total CVI of 0.96, a face validity of 1, and a Scale-Level Content Validity Index/Universal Agreement calculation method value of 0.8. This bundle can help critical care nurses, doctors, academics, and students assess and provide standard EC for mechanically ventilated patients.

Approach to Immune-mediated Ocular Diseases.

Immune-mediated ocular inflammation is a common clinical diagnosis reached for horses with keratitis and uveitis. This diagnosis is made as a diagnosis of exclusion following a thorough effort to rule out an underlying cause for the inflammation, most importantly infectious and neoplastic disease. Practically, response to ophthalmic and systemic anti-inflammatory or immunomodulatory medications is used to support a diagnosis of immune-mediated ocular inflammation; however, such medications are often contraindicated in the face of infection or neoplasia. This article will summarize our current understanding and approach to the diagnosis and management of immune-mediated keratitis and recurrent or insidious uveitis in horses.

Implementation of anterior segment ophthalmic telemedicine.

PURPOSE OF REVIEW: The growing push to integrate telemedicine into ophthalmic practices requires physicians to have a thorough understanding of ophthalmic telemedicine's applications, limitations, and recent advances in order to provide well tolerated and appropriate clinical care. This review aims to provide an overview of recent advancements in the use of ophthalmic telemedicine for anterior segment eye examinations. RECENT FINDINGS: Virtual care for anterior segment evaluation relies on appropriate technology, novel workflows, and appropriate clinical case selection. Recent advances, particularly in the wake of the COVID-19 pandemic, have highlighted the utility of home-based assessments for visual acuity, external evaluation, tonometry, and refraction. Additionally, innovative workflows incorporating office-based testing into virtual care, termed 'hybrid telemedicine', enable high-quality ophthalmic testing to inform clinical decision-making. SUMMARY: Novel digital tools and workflows enable high-quality anterior segment evaluation and management for select ophthalmic concerns. This review highlights the clinical tools and workflows necessary to enable anterior segment telehealth.