Glaucoma and the Human Microbiome.

PURPOSE OF REVIEW: To explore a view of the human microbiome as an interconnected, functional, dynamic system that may be linked to the pathogenesis and progression of glaucoma. METHOD: A literature review was undertaken that included publications from 1966 to 2023. RESULTS: Bacterial lipopolysaccharides (LPS) activate toll-like receptors (TLR) and mediate the human immune response. The LPS-TLR4 pathway is a potential avenue for the ocular, gut, and oral microbiomes to interface and/or influence ocular disease. Studies of gut dysbiosis have shown that alterations on the healthy microbiota can predispose the host to immune-mediated inflammatory and neurodegenerative conditions, while oral and ocular surface dysbiosis have been correlated with glaucoma. While developmental exposure to commensal microflora has shown to be necessary for the autoimmune and neurodegenerative responses to elevated intraocular pressure to take place, commensal bacterial products like short chain fatty acids have regulatory effects protective against glaucoma. SUMMARY: Alterations to human microbiotas have been associated with changes in intestinal permeability, gene regulation, immune cell differentiation, and neural functioning, which may predispose the host to glaucoma. Select microbes have been highlighted for their potential contributions to glaucoma disease progression or protection, raising the potential for microbiota-based treatment modalities. Current topical glaucoma treatments may disrupt the ocular surface microbiota, potentially having ramifications on host health. Further study of the relationships between human microbiome and glaucoma is needed.

Topical Glaucoma Therapy Is Associated With Alterations of the Ocular Surface Microbiome.

Purpose: To investigate the ocular surface microbiome of patients with unilateral or asymmetric glaucoma being treated with topical ophthalmic medications in one eye and to determine whether microbial community changes were related to measures of ocular surface disease. Methods: V3-V4 16S rRNA sequencing was conducted on ocular surface swabs collected from both eyes of 17 subjects: 10 patients with asymmetric/unilateral glaucoma using topical glaucoma therapy on only one eye and seven age-matched, healthy controls with no history of ocular disease or eyedrop use. Samples were categorized into three groups: patients' glaucomatous eye treated with eyedrops, patients' contralateral eye without eyedrops, and healthy control eyes. Comparisons were made for microbial diversity and composition, with differences in composition tested for association with ocular surface disease measures including tear meniscus height, tear break-up time, and Dry Eye Questionnaire. Results: Samples obtained from the patients' treated and untreated eyes both had significantly greater alpha-diversity and relative abundance of gram-negative organisms compared to healthy controls. The microbial composition of patient eyes was associated with decreased tear meniscus height and tear break-up time, whereas metagenomic predictions, based on 16S rRNA data, suggested increased synthesis of lipopolysaccharide. Conclusions: The ocular surface microbiome of patients taking unilateral preserved glaucoma drops is characterized by a highly diverse array of gram-negative bacteria that is significantly different from the predominantly gram-positive microbes detected on healthy control eyes. These compositional differences were associated with decreased tear film measures and distinct inferred protein synthesis pathways, suggesting a potential link between microbial alterations and ocular surface inflammation.

Exploring Potential Schedule-Related and Gender Biases in Ophthalmology Residency Interview Scores.

Purpose Prior studies have revealed grading discrepancies in evaluation of personal statements and letters of recommendation based on candidate's race and gender. Fatigue and the end-of-day phenomenon can negatively impact task performance but have not been studied in the residency selection process. Our primary objective is to determine whether factors related to interview time and day as well as candidate's and interviewer's gender have a significant effect on residency interview scores. Methods Seven years of ophthalmology residency candidate evaluation scores from 2013 to 2019 were collected at a single academic institution, standardized by interviewer into relative percentiles (0-100 point grading scale), and grouped into the following categories for comparisons: different interview days (Day 1 vs. Day 2), morning versus afternoon (AM vs. PM), interview session (Day 1 AM/PM vs. Day 2 AM/PM), before and after breaks (morning break, lunch break, and afternoon break), residency candidate's gender, and interviewer's gender. Results Candidates in the morning sessions were found to have higher scores than afternoon sessions (52.75 vs. 49.28, p < 0.001). Interview scores in the early morning, late morning, and early afternoon were higher than late afternoon scores (54.47, 53.01, 52.15 vs. 46.74, p < 0.001). Across all interview years, there were no differences in scores received before and after morning breaks (51.71 vs. 52.83, p = 0.49), lunch breaks (53.01 vs. 52.15, p = 0.58), and afternoon breaks (50.35 vs. 48.30, p = 0.21). No differences were found in scores received by female versus male candidates (51.55 vs. 50.49, p = 0.21) or scores given by female versus male interviewers (51.31 vs. 50.84, p = 0.58). Conclusion Afternoon residency candidate interview scores, especially late afternoon, were significantly lower than morning scores, suggesting the need to further study the effects of interviewer's fatigue in the residency interview process. The interview day, presence of break times, candidate's gender, and interviewer's gender had no significant effects on interview score.