We would like to thank tang et al for their thoughtful note regarding our article,1 raising important discussion points about the study design and conclusions. We appreciate their insights and the opportunity to clarify key aspects of our research.
First, Tang et al suggested incorporating propensity score matching, and we would like to clarify that propensity score matching in different subgroups was indeed conducted as part of our sensitivity analyses (as mentioned in the “Methods” section of our published article). We chose not to include these analyses in the main article due to the robustness of the primary results and space constraints. The sensitivity analyses assessed the stability of our findings within specific subgroups, such as patients using semaglutide, and patients with more extensive intraocular pressure (IOP) measurements (eg, at least 3 pre- and 3 postexposure IOP records), both compared with 1:3 propensity score-matched controls. The results of these analyses reinforced the conclusions of our primary findings.
Regarding the coadministration of metformin, in our manuscript, we did not report that 93% of the subjects were on metformin as suggested by Tang et al. This may have originated from a separate source. However, we did account for metformin as a confounding variable by incorporating the number of oral antidiabetic medications in both the de-mographics table and the regression analyses. The median number of active oral antidiabetic medications was similar between the two groups, and it was not significantly associated with Δ OP in the univariable regression analysis. 1 This ensured that the potential effects of metformin and other oral antidiabetic medications were properly adjusted for in our study.
Tang et al also raised the issue of corticosteroid use and its impact on IOP. We appreciate this point and agree that corticosteroids, which are known to elevate IOP to varying extents in a subgroup of the population, should be accounted for in future research to ensure that the effects of GLP-1 receptor agonists are not confounded by these risk factors. Finally, we appreciate the suggestion to monitor glaucoma progression during follow-up, as it is indeed a critical endpoint. Future studies would benefit from tracking not only IOP but also clinical markers of glaucoma severity to provide a more comprehensive assessment of the long-term effects of GLP-1 receptor agonists. However, glaucoma progression was not among our primary or secondary outcomes, as it was outside the scope of this particular study. We are currently pursuing progression analyses as a follow-up to our initial findings reported here. Further, Tang et al suggested that the effects of hypotensive medications and glaucoma surgeries were not accounted for in our study. However, as noted in the “Methods” section, we accounted for the initiation of hypotensive medications, glaucoma surgeries, and laser therapy by censoring the data at first exposure to these therapies, thereby minimizing the confounding effects of glaucoma treatments.
Once again, we thank Tang et al for their feedback and look forward to incorporating these important considerations and suggestions into our future studies.
Financial Disclosures:
Dr Baxter reports consulting fees from Topcon and equipment support from Topcon and Optomed outside the submitted work. Dr Cui reports a provisional patent application related to the topic of this study (publication number: US20220193201A1). SH, WH, and BGC: None. Dr Weinreb reports consulting fees from Abbvie, Alcon, Balance, Editas, Eyenovia, iSTAR Medical, Nicox, and Topcon outside the submitted work. He also has stock options from Balance, Eyenovia, Iantrek, Implandata, and Toku outside the submitted work and intellectual property licensed from UCSD to Toromedes outside the submitted work. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.
Footnotes
CREDIT AUTHORSHIP CONTRIBUTION STATEMENT
Shahin Hallaj: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. William Halfpenny: Data curation, Formal analysis, Investigation, Methodology, Writing – review & editing. Benton G. Chuter: Data curation, Formal analysis, Validation, Writing – review & editing. Robert N. Weinreb: Conceptualization, Funding acquisition, Resources, Supervision, Writing – review & editing. Sally L. Baxter: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. Qi N. Cui: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing.
Contributor Information
SHAHIN HALLAJ, Division of Ophthalmology Informatics and Data Science, Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, California, USA; Department of Medicine, Division of Biomedical Informatics, University of California San Diego, San Diego, California, USA.
WILLIAM HALFPENNY, Division of Ophthalmology Informatics and Data Science, Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, California, USA; Department of Medicine, Division of Biomedical Informatics, University of California San Diego, San Diego, California, USA.
BENTON G. CHUTER, Division of Ophthalmology Informatics and Data Science, Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, California, USA Department of Medicine, Division of Biomedical Informatics, University of California San Diego, San Diego, California, USA.
ROBERT N. WEINREB, Division of Ophthalmology Informatics and Data Science, Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, California, USA
SALLY L. BAXTER, Division of Ophthalmology Informatics and Data Science, Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, California, USA Department of Medicine, Division of Biomedical Informatics, University of California San Diego, San Diego, California, USA.
QI N. CUI, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
REFERENCE
- 1.Hallaj S, Halfpenny W, Chuter BG, Weinreb RN, Baxter SL, Cui QN. Association between glucagon-like peptide-1 receptor agonists exposure and intraocular pressure change: GLP-1 receptor agonists and intraocular pressure change. Am J Ophthalmol. 2025;269:255–265. [DOI] [PMC free article] [PubMed] [Google Scholar]