Thyroid Eye disease in the Biologic Era: a 40-year paradigm shift in nonsurgical therapeutic strategies

Over the last four decades, there has been a progressive increase in the number of publications and citations on research related to thyroid-associated ophthalmopathy (TAO) nonsurgical treatment across many countries/regions, institutions, and authors, with a special focus on biological immunotherapy. Examing 1600 publications collected from the Web of Science Core Collection database on TAO research from 1983 to 2023, our bibliometric analysis evaluated various bibliometric indicators, among which some important subtopics were identified and further discussed and reviewed. The study showed that novel insights into the pathogenesis of TAO and new immunological targets for nonsurgical treatments were the major research focus over the past 40 years. Especially, targeted biological immunotherapies were on the rise, promoting treatments efficacy and patients’ quality of life. Our study provided a thorough overview and visual presentation of the evolutionary landscape and emerging frontiers for nonsurgical treatment of TAO surrounding its immunological mechanism and therapeutic strategy. It also shed light on its global collaboration patterns, current trends and research hotspots, hopefully to facilitate collaborative initiatives and guiding future research. (A) An overall of the structure and content of bibliometric analysis. The bibliometric indicators that the study analyzed can be divided into four classes: publication volume, collaboration, articles, and keywords, whose specific parameters were further shown in the light purple boxes. By interpreting the four classes of bibliometric data, conclusions about the evolutional trends, current hotspots and research frontiers of thyroid-associated ophthalmopathy (TAO) nonsurgical treatments were reached, which were further discussed and reviewed in the following article. (B) Summary of the development timeline of TAO nonsurgical treatments including mechanism, targets and therapies. Based on our bibliometric results, the study revealed that TAO nonsurgical treatments have evolved from the earlies glucocorticoids therapy to the novel biological therapies and combination therapies nowadays. The labeled year of each treatment indicated the year of the medicine’s earlist documented successful randomized controlled trial (except teprotumumab, which indicates its year of FDA approval). (C) Pathology of TAO. The pathology of TAO including lymphocytes filtration, orbital fibroblast activation and downstream inflammation and other pathologic changes was shown here. The targets of the biologics discussed in the study were labeled in the pathogenesis pathway.