A narrative review of TriNetX in ophthalmology: applications, advantages, and pitfalls

Background and Objective: TriNetX is a global, federated, health research network that has become increasingly utilized in academic medicine. In the last 2 years, the field of ophthalmology has seen an uptick in the number of publications of TriNetX analyses. The objective of this review is to summarize the process of conducting a TriNetX study, the trends in TriNetX use, and the utility of TriNetX in ophthalmology research. Additionally, the strengths and limitations of TriNetX use in ophthalmology research will be discussed. Methods: A PubMed and Scopus literature search was performed using the search terms: “TriNetX” and “Ophthalmology” or “Eye”. Included articles were English language only from the years 1994 to June 1, 2024. The twenty-one included articles were analyzed for trends in study design, strengths, and weaknesses. Additionally, a mock study was performed to describe the process of completing a TriNetX study. Key Content and Findings: The literature search revealed a marked increase in TriNetX publications in ophthalmology journals in the years 2023 to 2024. Using a methodology similar to the studies identified in the literature search, a mock investigation of the relationship between cataract removal and hip fracture was detailed from start to finish, providing a framework for the use of TriNetX in ophthalmology research. The mock study provided results consistent with previously reported findings. Lastly, a thorough review of the strengths and limitations of TriNetX identified major considerations in study design, coding, data availability, propensity score matching, bias, and analytical challenges that researchers must be aware of when conducting research with TriNetX. However, many of the discussed limitations can be circumvented with careful and informed use of the platform. Conclusions: TriNetX is a powerful research tool that offers volumetric advantages and time efficiency, making it an attractive option for conducting observational studies. Despite its strengths, caution must be exercised when designing studies to ensure their validity and quality. With careful informed use, TriNetX is a valuable resource in ophthalmology research.