Review History
Occult zonulopathy detected during cataract surgery in patients with acute primary angle closure: a retrospective study

Dear authors.
congratulations! It was not easy but i think your manuscript is now ready for publication.

Dear authors,

Thank you for your resubmission and efforts. While you have demonstrated the study's validity with statistical content and explanations, i think one of the reviewers appears to want an actual an attempt to address the perceived limitations of the study. While the authors mentioned that the study is not aimed at determining causality, you could further clarify or highlight this in the manuscript. You can explicitly state that the primary goal is to explore associations and propose potential links between occult zonulopathy and APAC, leaving causality for future studies. Also, you could add a brief explanation that and how the study's design was meant to explore potential associations rather than establish definitive cause-and-effect relationships. A mention of why this approach is relevant for understanding the pathophysiology of APAC could help contextualize the study’s aims. You could provide more detailed information on how the sample size was calculated, including the effect size used, the alpha level (0.05), and why this specific sample size was deemed sufficient. This would help reviewers and readers understand the robustness of the analysis better. (I think it was in the rebuttal but not in the manuscript itself). If feasible, you can include a sensitivity analysis showing how changes in sample size or variations in certain parameters (like effect size or assumptions about prevalence) could impact the findings. This could demonstrate that their results remain stable even with variations in sample size or data assumptions.

Moreover, though the authors mention that they couldn’t reliably measure IOP and other factors, they could expand this discussion in the limitations section, explaining how their clinical setting or data collection challenges impacted their ability to measure those parameters. You should also mention any potential confounders considered (e.g., age, underlying conditions, prior treatments) and why these were or were not included in the analysis. This would add depth to their justification and make it clear that they have accounted for other possible variables.

The authors mentioned that occult zonulopathy might cause subtle changes in ocular structures that aren't statistically significant. To further address this concern, they could add more context, perhaps referencing other studies that highlight the challenges of detecting subtle changes in biometric measures or using statistical methods that are sensitive to small effects (e.g., regression models or non-parametric tests) (or better, to add in the supplementary data that show exactly this).

In addition to clarifying the study's aims, the authors could better discuss how even small, non-significant changes in biometric parameters could still be relevant clinically. They could explain how these findings might inform clinical practice, even if the results aren’t statistically significant, particularly for surgeons when assessing APAC patients.

The authors could consider conducting subgroup analyses, if appropriate, to see whether certain characteristics (e.g., severity of zonulopathy, age, or other clinical variables) might reveal patterns that weren't evident in the overall sample. (also, if not already considered, show that you considered different statistical approaches to address potential limitations in the data; if and where relevant).

In order to continue to highlight the attempted overcome of this barrier or limitation, the authors can further still expand their discussion by comparing their findings with similar studies in the literature, especially those that also used biometric measurements in APAC or zonulopathy.

The reviewer raised concerns that the biometric differences found (such as shallower anterior chamber depth and lens position closer to the anterior) might be related to APAC rather than occult zonulopathy. The authors could provide additional references to support why these biometric markers could still be associated with zonulopathy, even if APAC itself is a confounding factor. You can also suggest how future studies might focus on these variables to better distinguish the role of zonulopathy.

So, altogether, i believe that by refining the manuscript for clarity, especially the methods and results sections; clearer explanations of key concepts or aspect and the logic behind the study design could help to mitigate misunderstandings and overcome this standoff. (and showing, although non-significant data results in the supplementary is advisable, in this situation)

Reviewers 2 and 3 have both commented on the small sample size and limited number of clinical features, which together have implications on the ability to draw meaningful conclusions

Unless these issues can be resolved (for example by expanding the sample; or providing a more robust statistical justifications; or including additional parameters) it is unlikely that the article can move forward.

[# PeerJ Staff Note: It is PeerJ policy that additional references suggested during the peer-review process should *only* be included if the authors are in agreement that they are relevant and useful #]