Comment on: Changes in Aqueous Humor Cytokines and Metabolomics in Contralateral Eye After Unilateral Cataract...

We extend Li et al.'s investigation of aqueous humor (AH) metabolomics in sequential cataract surgery by referencing our prior study on interocular symmetry/asymmetry in AH metabolomic profiles from simultaneous bilateral cataract surgery in emmetropic patients, which demonstrated similar AH compositions in fellow eyes. We also illustrate variability with 2 sequential-surgery cases and highlight the most and least variable metabolites across 6 biochemical classes. Taken together with Li et al., these observations support careful attribution of second-eye changes to surgery versus biology.

To extend the findings of Li et al. on AH metabolomics in sequential cataract surgery by incorporating reference data on interocular symmetry/asymmetry in AH metabolomic profiles and illustrating variability in sequential cases.

We drew on our prior study of simultaneous bilateral cataract surgery in emmetropic patients, which demonstrated high interocular similarity, and examined AH metabolomic variability in 2 patients undergoing sequential cataract surgery.

Baseline interocular comparisons highlight metabolic symmetry in the AH among patients undergoing simultaneous cataract surgery. In 2 additional cases, we identified the most and least variable metabolites across 6 biochemical classes among patients undergoing sequential cataract surgery, complementing the observations of Li et al.Conclusion:Our reference data help contextualize Li et al.'s results. Although based on limited cases, our findings emphasize the need for caution when interpreting AH metabolomics in sequential surgery to distinguish true intra- and inter-individual biological variability from potential surgical effects on the second eye. Multimodal approaches integrating metabolomic and vascular metrics may improve biomarker selection and inform surgical timing.