Ocular Infectious Research Articles

Association of weather variables with pathogens contributing to conjunctivitis worldwide.

To identify weather variables associated with pathogens contributing to infectious conjunctivitis globally. Sample collection and pathogen identification from patients with acute infectious conjunctivitis was performed from 2017 to 2023. We linked pathogens identified from 13 sites across 8 countries with publicly available weather data by geographic coordinates. Mixed effects logistic regression analysis was performed to estimate the associations between temperature, precipitation, and relative humidity exposures, and the prevalence of infection types (RNA virus, DNA virus, bacteria, and fungus). 498 cases from the United States, India, Nepal, Thailand, Burkina Faso, Niger, Vietnam, and Israel were included in the analysis. 8-day average precipitation (mm) was associated with increased odds of RNA virus infection (odds ratio (OR)=1.47, 95% confidence interval (CI): 1.12 to 1.93, P=0.01) and decreased odds of DNA infection (OR=0.62, 95% CI: 0.46 to 0.82, P<0.001). Relative humidity (%) was associated with increased odds of RNA virus infections (OR=2.64, 95% CI: 1.51 to 4.61, P<0.001), and fungal infections (OR=2.35, 95% CI: 1.19 to 4.66, P=0.01), but decreased odds of DNA virus (OR=0.58, 95%CI: 0.37 to 0.90, P=0.02) and bacterial infections (OR=0.42, 95% CI: 0.25 to 0.71, P<0.001). Temperature (°C) was not associated with ocular infections for any pathogen type. This study suggests that weather factors affect pathogens differently. Particularly, humidity and precipitation were predictors for pathogens contributing to conjunctivitis worldwide. Additional work is needed to clarify the effects of shifts in weather and environmental factors on ocular infectious diseases.

Role of gene sequencing for the diagnosis, tracking and prevention of ocular infections

Next-generation sequencing (NGS) is a robust platform which can be employed for pathogen detection. It has the potential to identify pathogens in an unbiased nature including bacteria, fungus, parasites, DNA/RNA viruses and even newer novel pathogens which have been previously reported. The high sensitivity of this technology makes it suitable for ophthalmology applications that rely on very small clinical specimen volumes. Currently, the diagnosis of ocular pathogens relies mainly on conventional procedures such as culturing and microscopy. Traditional methods lack sensitivity, which can be compensated by the application of molecular tools, such as polymerase chain reaction and NGS. In this review, we will look at how NGS can be used to treat ocular infectious diseases such as keratitis, conjunctivitis, trachoma, dacryocystitis, lacrimal sac infection, endophthalmitis and uveitis, with added information on the limitations, advantages and disadvantages on the ocular implication of this NGS technology. NGS-based approaches increase the sensitivity of pathogen detection as well as have the potential to improve healthcare services. NGS still requires advancement in the data analysis tools, establishing standards and reducing turnaround time. We are now closer to realising the full potential of this high-throughput technology. Importantly, NGS also delivers additional data which gives a unique opportunity to explore potential biomarkers of disease pathogenicity or underlying genetic predisposition.

The Epithelial Cell Glycocalyx in Ocular Surface Infection.

The glycocalyx is the main component of the transcellular barrier located at the interface between the ocular surface epithelia and the external environment. This barrier extends up to 500 nm from the plasma membrane and projects into the tear fluid bathing the surface of the eye. Under homeostatic conditions, defense molecules in the glycocalyx, such as transmembrane mucins, resist infection. However, many pathogenic microorganisms have evolved to exploit components of the glycocalyx in order to gain access to epithelial cells and consequently exert deleterious effects. This manuscript reviews the implications of the ocular surface epithelial glycocalyx to bacterial, viral, fungal and parasitic infection. Moreover, it presents some ongoing controversies surrounding the functional relevance of the epithelial glycocalyx to ocular infectious disease.

Practical use of multiplex and broad-range PCR in ophthalmology.

Polymerase chain reaction (PCR) can be used to confirm or deny infectious ocular inflammation such as uveitis. The purpose of this article is to review the current practical use of PCR examination in ophthalmology, especially multiplex and broad-range PCR, and a novel PCR, termed Strip PCR. At first, in the Introduction, we show the development of the PCR examination in ophthalmology. We next show the clinical applications of multiplex PCR and broad-range PCR. These advances in PCR continue to contribute greatly to the ophthalmology field. We also show how the sample for PCR is collected. Recently, we established a novel examination, a multiplex real-time PCR (Strip PCR) prototype for detecting 24 pathogens responsible for ocular infectious diseases. Moreover, we developed the Direct Strip PCR method, which skips the DNA extraction step in the procedure. This PCR is anticipated to ease etiologic evaluation, increasing pathogen detection in the intraocular fluids of uveitis patients even by general ophthalmologists. We also describe the following: (1) representative cases in which PCR is useful, (2) representative cases in which PCR can exclude a diagnosis, (3) the current status of PCR in the diagnosis of infectious uveitis and advanced medical service, and (4) the prospects for clinical PCR in ophthalmology. We have established and developed the multiplex PCR, broad-range PCR, Strip PCR, and Direct Strip PCR methods and have reported the efficacy of such tests in multicenter studies. Our goal is "rapid and simple comprehensive PCR diagnosis anywhere and by anyone" for ocular infections.

Research advances regarding fungal biofilms and related ocular diseases

Clinical studies on refractory fungal infections have revealed that fungal pathogens in infected lesions often existed in the form of biofilms.A biofilm is a complex of microbial communities enclosed in an extracellular matrix.Biofilm formation helps the fungus evade host cellular immune system clearance and the attacks of drugs, causing persistent infections and then threatening human health.In recent years, research has shown that biofilms can form on the surfaces of intraocular lenses, corneal contact lenses, scleral buckles and other intraocular implants.Moreover, growing evidence shows that fungal biofilms play an important role in ocular infectious diseases, such as endophthalmits and keratitis.Therefore, the study of fungal biofilms and their correlations with ocular diseases is of considerable clinical significance.In this study, we focused on the formation and structure of fungal biofilms, the factors influencing biofilms formation, resistance mechanism, treatment strategies and the association of biofilms in ocular disease. Key words: Biofilm; Fungi; Ocular infections; Keratits; Implant-related ocular infections

Monitoring the antimicrobial activity of antiseptic eye drops

Introduction. Antiseptic drugs currently occupy an important place in the treatment and prevention of ocular infectious and inflammatory diseases. Often microorganisms are characterized not only by resistance to a single antibiotic, but also by the presence of multiple resistances, which limits the choice of an effective drug. This problem requires a detailed study and monitoring of the sensitivity of the main pathogens of ocular infections, not only to antibiotics but also to antiseptics.&#x0D; The aim was to study the species composition of conjunctival microflora in patients with ocular surface infection and to evaluate the antimicrobial activity of antiseptic eye drops.&#x0D; Materials and methods. Investigation was carried out in 20122018 in 4237 bacterial conjunctivitis patients. The sensitivity to antiseptic preparations of pathogens isolated from patients with conjunctivitis was detected.&#x0D; Results. 1068 strains of microorganisms isolated from the conjunctival cavity of patients were tested. Gram-positive cocci dominated among clinically significant pathogens 47.4%. Antimicrobial activity of Vitabact eye drops against gram-positive cocci was higher than that of antiseptic Okomistin.&#x0D; Summary. Antimicrobial activity of the studied antiseptics against gram-positive and gram-negative pathogens was different. It is necessary to conduct further research on the antimicrobial activity of antiseptic eye drops.

MicroRNAs in Ocular Infection.

MicroRNAs (miRNAs) are small, non-coding, regulatory RNA molecules and constitute a newly recognized, important layer of gene-expression regulation at post-transcriptional levels. miRNAs quantitatively fine tune the expression of their downstream genes in a cell type- and developmental stage-specific fashion. miRNAs have been proven to play important roles in the normal development and function as well as in the pathogenesis of diseases in all tissues and organ systems. miRNAs have emerged as new therapeutic targets and biomarkers for treatment and diagnosis of various diseases. Although miRNA research in ocular infection remains in its early stages, a handful of pioneering studies have provided insight into the roles of miRNAs in the pathogenesis of parasitic, fungal, bacterial, and viral ocular infections. Here, we review the current status of research in miRNAs in several major ocular infectious diseases. We predict that the field of miRNAs in ocular infection will greatly expand with the discovery of novel miRNA-involved molecular mechanisms that will inform development of new therapies and identify novel diagnostic biomarkers.

The Role of Pneumococcal Virulence Factors in Ocular Infectious Diseases.

Streptococcus pneumoniae is a gram-positive, facultatively anaerobic pathogen that can cause severe infections such as pneumonia, meningitis, septicemia, and middle ear infections. It is also one of the top pathogens contributing to bacterial keratitis and conjunctivitis. Though two pneumococcal vaccines exist for the prevention of nonocular diseases, they do little to fully prevent ocular infections. This pathogen has several virulence factors that wreak havoc on the conjunctiva, cornea, and intraocular system. Polysaccharide capsule aids in the evasion of host complement system. Pneumolysin (PLY) is a cholesterol-dependent cytolysin that acts as pore-forming toxin. Neuraminidases assist in adherence and colonization by exposing cell surface receptors to the pneumococcus. Zinc metalloproteinases contribute to evasion of the immune system and disease severity. The main purpose of this review is to consolidate the multiple studies that have been conducted on several pneumococcal virulence factors and the role each plays in conjunctivitis, keratitis, and endophthalmitis.

Current and future molecular diagnostics for ocular infectious diseases.

Confirmation of ocular infections can pose great challenges to the clinician. A fundamental limitation is the small amounts of specimen that can be obtained from the eye. Molecular diagnostics can circumvent this limitation and have been shown to be more sensitive than conventional culture. The purpose of this review is to describe new molecular methods and to discuss the applications of next-generation sequencing-based approaches in the diagnosis of ocular infections. Efforts have focused on improving the sensitivity of pathogen detection using molecular methods. This review describes a new molecular target for Toxoplasma gondii-directed polymerase chain reaction assays. Molecular diagnostics for Chlamydia trachomatis and Acanthamoeba species are also discussed. Finally, we describe a hypothesis-free approach, metagenomic deep sequencing, which can detect DNA and RNA pathogens from a single specimen in one test. In some cases, this method can provide the geographic location and timing of the infection. Pathogen-directed PCRs have been powerful tools in the diagnosis of ocular infections for over 20 years. The use of next-generation sequencing-based approaches, when available, will further improve sensitivity of detection with the potential to improve patient care.

Role of molecular diagnostics in ocular microbiology.

Although microbial culture remains the gold standard for diagnosis of many ocular infections, the technique is limited by low yield, inability to detect certain organisms, and potentially long delays to results. DNA-based molecular diagnostic techniques use detection of specific nucleic acid sequences as evidence for presence of suspected pathogens. The polymerase chain reaction (PCR) is a powerful molecular biology technique that allows for detection of fewer than 10 copies of pathogen genome. Recent technical advances in PCR have permitted quantitation of pathogen load using quantitative PCR (qPCR), and have permitted multiplexing of primer sets. Use of pan-bacterial and pan-fungal primers for ribosomal DNA sequences has allowed diagnosis of bacterial and fungal infections using molecular techniques. In this review, we highlight recent advances in the application of PCR to the diagnosis of anterior segment and posterior segment ocular infectious diseases.

PHARMACOECONOMICS OF OCULAR ANTI-INFECTIVE TREATMENTS

Efforts to improve the overall quality and efficiency of medical care within limited budgets are ongoing across all medical specialties, including ocular infectious disease. As part of this movement, decision makers are requesting data regarding the value of medical treatments increasingly, in addition to traditional measures of efficacy and safety. The demand for value data within medical care has spurred the growth of outcomes research that is focused on the final end points of treatments, as opposed to intermediate end points, surrogate markers, or the structure and process of providing medical care. Value is a multidimensional concept that requires simultaneous assessment and balancing of many factors affecting the costs and benefits of a treatment. A model illustrating a decision-making structure for conducting multidimensional value assessments for medical interventions has been proposed by Kozma and colleagues. 6 The model includes three types of outcomes of medical care: economic, clinical, and humanistic outcomes (ECHO). Examples of variables within each outcome category are presented below.* *Adapted from Kozma CM, Reeder CE, Schulz RM: Economic, clinical, and humanistic outcomes: A planning model for pharmacoeconomic research. Clin Ther 15:1121–1132, 1993; with permission. Economic Outcomes Direct medical costs Cost of drug Cost of drug administration Cost of treating adverse events Direct nonmedical costs Transporation to clinic Indirect Costs Lost work days Decreased productivity Lost earnings Intangible costs Pain Suffering Clinical Outcomes Efficacy Onset of action Percentage of patients who become pain free Recurrence of symptoms Adverse events Humanistic Outcomes Health-related quality of life Return to normal functioning Satisfaction with therapy Some category examples may be relevant to a significant other or caregiver as well as the patient. The relevance of each type of outcome is dependent chiefly on the clinical characteristics of a disease. For example, the indirect cost of lost work days may be relevant in the treatment of a disease with debilitating symptoms, such as migraine, but have less relevance in a silent, less symptomatic disease, such as hypertension or glaucoma. Chronic diseases with high prevalence and expenditure rates have been first priority for identifying which treatments offer the most value by maintaining or improving quality of care in a cost-efficient manner. Many of these first-priority areas have been addressed to date, and the outcomes movement is now expanding to assess the value of treatments for acute or less prevalent diseases that have several alternative medical treatments available. Given the recent advances in therapies for many diseases of the eye, ophthalmologic treatments should be expected to come under increasing value scrutiny. Glaucoma is an obvious choice, given the number of recently introduced alternative treatments for this chronic disease that effects a growing segment of our population. Perhaps less obvious is the need to assess the comparative value of treatments for ocular infections that are less prevalent and generally of a more acute nature. Over the past few years, however, an increasing array of new, broader spectrum, higher cost treatments (antibacterials, antifungals, and antivirals) have become available, making relative value decisions more important. The purpose of this article is to describe the basic principles of pharmacoeconomic analyses that can be used to enhance the treatment selection process for ocular infections by including a value component.

A new perspective in ocular infection and the role of antibiotics.

A new concept of ocular infectious diseases includes two modes of pathogenesis, one being an acute inflammation caused by the attachment of free-floating bacteria, and another being intractable biofilm-related ocular infections. 15-20% of Staphylococcus epidermidis strains isolated from human conjunctiva exhibit slime formation and can be pathogens causing inflammation. Topical application, in the form of, for example, eye drops, of a combination of two antimicrobial agents is usually applied to treat such infections. Any antimicrobial agent having a post-antibiotic effect is generally administered in a twice-a-day regimen.