Clinical Predictors of Surgical Management in Patients with Chronic Epiphora: A CT-DCG–Supported Analysis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Major Concerns

1. Retrospective Ethics Approval: The text states the study ran from December 2022 to May 2024, yet the Ethics Committee approval is dated July 1, 2024. Securing ethics approval after completing a study violates the Declaration of Helsinki. The authors need to clarify this timeline immediately.
2. Conflicting Inclusion/Exclusion Criteria: Patients were required to have epiphora for over six months, and acute dacryocystitis was an exclusion criterion. However, Table 1 shows that 46 of the 127 patients (36.2%) had an “acute disease course". Including an acute subgroup in a chronic epiphora study breaks the core logic of the paper.
3. Multicollinearity in the Statistics: In the univariate analysis, ENT comorbidity appears in 32.3% of the surgical group and 58.1% of the non-surgical group (p=0.004), meaning it correlates with a lower chance of surgery. In the multivariable logistic regression model (Table 4), this same variable suddenly increases the odds of surgery by almost five times (OR 4.98, p=0.002). The authors shrug this off by stating the “direction changed". This actually points to a massive interaction effect or Simpson's Paradox. They need to calculate Variance Inflation Factors (VIF) and fix their model. Also in Table 4, the odds ratio for purulent discharge is 22.8, but the 95% confidence interval is massive (7.18–89.05). This points to an inadequate sample size within the cells or severe model overfitting.
4. Outdated Measurements: The authors rely entirely on subjective, highly variable functional tests like Schirmer and dye disappearance. Modern ophthalmic research defaults to anterior segment OCT (AS-OCT) for objective measurements of the tear meniscus. The decision to skip AS-OCT introduces bias and needs to be addressed as a limitation.
5. Lack of Clinical Utility: The authors boast a model AUC of 0.89. However, the model relies on obvious clinical signs, like symptom duration and purulent discharge, to predict surgery. Any ophthalmologist knows these signs point straight to the OR without needing a CT-DCG. Exposing patients to radiation to confirm what a standard clinical exam already tells us is not a clinical breakthrough. The discussion needs a realistic defence of how this imaging actually changes standard surgical triage.

Minor Concerns

• Incomplete Reference: Reference 4 (“Li R, Li Y, McArdle B") is missing publication details and needs proper formatting.
• Low-Resolution Images: Figure 2 is blurry. The authors should provide high-resolution versions and add arrows pointing directly to the stenoses or obstructions.
• Selection Bias: Figure 1 shows that only patients already suspected of having nasolacrimal duct involvement were sent for a CT-DCG. This introduces a selection bias right from the start. They mention it briefly in the limitations, but they need to explore how it inflates their specificity.
• Final Note: The revisions I have outlined above, particularly crucial matters like methodological contradictions and ethics committee inconsistencies, must be meticulously corrected. The study's ability to serve scientific merit and patient safety depends on the resolution of these fundamental issues.

Author Response

Reviewer 1

Major Concerns

Comment 1: Retrospective Ethics Approval: The text states the study ran from December 2022 to May 2024, yet the Ethics Committee approval is dated July 1, 2024. Securing ethics approval after completing a study violates the Declaration of Helsinki. The authors need to clarify this timeline immediately.

Response 1: We thank the reviewer for this important comment and apologize for the lack of clarity. The study was a retrospective observational analysis of clinical and imaging data obtained during routine ophthalmologic care between December 2022 and May 2024. CT-DCG examinations were performed as part of standard diagnostic evaluation and not specifically for research purposes. Ethical approval obtained on July 1, 2024 covered the retrospective analysis and publication of anonymized patient data. The manuscript has been revised throughout to clarify the retrospective design and timeline.

 

Comment 2: Conflicting Inclusion/Exclusion Criteria: Patients were required to have epiphora for over six months, and acute dacryocystitis was an exclusion criterion. However, Table 1 shows that 46 of the 127 patients (36.2%) had an “acute disease course". Including an acute subgroup in a chronic epiphora study breaks the core logic of the paper.

Response 2: We appreciate the reviewer for pointing out this ambiguity. All included patients had chronic epiphora lasting longer than six months. The term “acute disease course” was not intended to indicate acute dacryocystitis or acute onset disease, but rather intermittent exacerbations of symptoms occurring in the setting of chronic epiphora. Patients with active acute dacryocystitis were excluded from the study. To avoid misunderstanding, the terminology has been revised throughout the manuscript and tables.

 

Comment 3: Multicollinearity in the Statistics: In the univariate analysis, ENT comorbidity appears in 32.3% of the surgical group and 58.1% of the non-surgical group (p=0.004), meaning it correlates with a lower chance of surgery. In the multivariable logistic regression model (Table 4), this same variable suddenly increases the odds of surgery by almost five times (OR 4.98, p=0.002). The authors shrug this off by stating the “direction changed". This actually points to a massive interaction effect or Simpson's Paradox. They need to calculate Variance Inflation Factors (VIF) and fix their model. Also in Table 4, the odds ratio for purulent discharge is 22.8, but the 95% confidence interval is massive (7.18–89.05). This points to an inadequate sample size within the cells or severe model overfitting.

Response 3: We appreciate the reviewer’s thoughtful statistical comments. In response, we assessed multicollinearity among predictors included in the logistic regression model using variance inflation factors (VIFs). No severe multicollinearity was identified (all VIF values < 5), suggesting that the observed change in the association of ENT comorbidity between univariate and multivariable analyses was more likely related to confounding or interaction among clinical variables rather than substantial collinearity. To reflect this more accurately, we revised the Discussion section and interpreted this finding more cautiously. We also agree that the wide confidence interval for purulent discharge indicates limited precision of the estimate, likely related to the relatively small subgroup size and event distribution. Accordingly, we softened the interpretation of the regression model results and added an additional limitation acknowledging potential model instability and the need for external validation.

 

Comment 4: Outdated Measurements: The authors rely entirely on subjective, highly variable functional tests like Schirmer and dye disappearance. Modern ophthalmic research defaults to anterior segment OCT (AS-OCT) for objective measurements of the tear meniscus. The decision to skip AS-OCT introduces bias and needs to be addressed as a limitation.

Response 4: We appreciate the reviewer’s valuable comment. We agree that anterior segment optical coherence tomography (AS-OCT) provides a more objective assessment of tear meniscus parameters and is increasingly used in contemporary ophthalmic research. In the present study, ophthalmologic evaluation was based on routinely performed clinical and functional tests available during standard clinical care. We acknowledge that the absence of AS-OCT may have introduced measurement variability and potential bias, and this limitation has now been added to the manuscript.

 

Comment 5: Lack of Clinical Utility: The authors boast a model AUC of 0.89. However, the model relies on obvious clinical signs, like symptom duration and purulent discharge, to predict surgery. Any ophthalmologist knows these signs point straight to the OR without needing a CT-DCG. Exposing patients to radiation to confirm what a standard clinical exam already tells us is not a clinical breakthrough. The discussion needs a realistic defence of how this imaging actually changes standard surgical triage.

Response 5: We thank the reviewer for this thoughtful and clinically important comment. We agree that clinical features such as prolonged symptom duration and purulent discharge are well-recognized indicators of significant nasolacrimal drainage pathology and may strongly influence surgical decision-making in routine ophthalmic practice. The purpose of this study was not to propose CT-DCG as a replacement for standard clinical evaluation or as a universal imaging modality for all patients with epiphora. In response to the reviewer’s comment, we revised the manuscript to clarify that the role of CT-DCG is primarily complementary and adjunctive. We emphasized that CT-DCG may be most useful in selected patients with diagnostically uncertain, complex, or mixed presentations, where additional anatomical characterization may assist in distinguishing structural from functional causes of epiphora and support surgical planning. We also softened the interpretation of the regression model and acknowledged the need to balance the potential diagnostic benefit of CT-DCG against radiation exposure.

 

Minor Concerns

Comment 6: Incomplete Reference: Reference 4 (“Li R, Li Y, McArdle B") is missing publication details and needs proper formatting.

Response 6: We thank the reviewer for noting this formatting issue. The reference has been corrected and updated to include the complete publication details in accordance with the journal reference style.

 

Comment 7: Low-Resolution Images: Figure 2 is blurry. The authors should provide high-resolution versions and add arrows pointing directly to the stenoses or obstructions.

Response 7:

 

Comment 8: Selection Bias: Figure 1 shows that only patients already suspected of having nasolacrimal duct involvement were sent for a CT-DCG. This introduces a selection bias right from the start. They mention it briefly in the limitations, but they need to explore how it inflates their specificity.

Response 8: We thank the reviewer for this important observation. We agree that the study population was inherently preselected, as CT-DCG was performed only in patients with clinically suspected nasolacrimal drainage system involvement. This may have enriched the cohort for structural lacrimal pathology and introduced selection bias, potentially influencing the apparent diagnostic performance of imaging findings and limiting generalizability to broader populations with epiphora. In response, we expanded the limitations section to more clearly acknowledge this issue and its potential impact on interpretation of the results.

 

Comment 9: Final Note: The revisions I have outlined above, particularly crucial matters like methodological contradictions and ethics committee inconsistencies, must be meticulously corrected. The study's ability to serve scientific merit and patient safety depends on the resolution of these fundamental issues.

Response 9: We thank the reviewer for the careful and detailed evaluation of our manuscript. We have thoroughly revised the manuscript to address the methodological, statistical, and ethical concerns raised during peer review. In particular, we clarified the retrospective study design and ethics approval timeline, revised the inclusion criteria and interpretation of clinical subgroups, reassessed the regression analysis with additional multicollinearity diagnostics, and expanded the limitations section to better acknowledge potential sources of bias and model instability. We also revised the discussion to provide a more balanced interpretation of the clinical role of CT-DCG. We appreciate the reviewer’s comments, which have substantially improved the clarity and rigor of the manuscript.

 

 

 

 

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

This study addresses a clinically relevant topic: the evaluation of chronic epiphora and the potential role of CT-dacryocystography (CT-DCG) in supporting surgical decision-making. The manuscript is generally well organized, and the focus on combining clinical signs with imaging findings is potentially useful for ophthalmologists and lacrimal surgeons.

However, several important issues should be addressed before the manuscript can be considered further.

1. The study population is inconsistent. The Methods and flow diagram state that 127 patients were included, whereas the Results section states that 128 patients were analyzed. This discrepancy should be corrected throughout the manuscript and tables.

2. The primary and secondary outcomes need clarification. The Methods state that the primary outcome was structural NLDS obstruction on CT-DCG, while much of the Results and Discussion focus on predictors of surgical management. The authors should clearly distinguish whether the study aims to predict anatomical obstruction, clinical decision for surgery, or actual surgical outcomes.

3. Surgical management may be affected by the same clinical and imaging findings used as predictors. Therefore, the outcome “surgical intervention” may partly reflect physician decision-making rather than an independent disease outcome. This should be discussed more explicitly, and the authors should avoid implying that the model predicts true surgical necessity unless postoperative outcomes or treatment response are available.

4. The CT-DCG findings are central to the title and objective, but they are not included in the multivariable logistic regression model shown in Table 4. The authors should explain why imaging variables such as NLDS stenosis, NLDS obstruction, dacryocystitis, or punctal eversion were excluded from the final model, or provide an additional model including clinically relevant CT-DCG variables.

5. The change in direction of the association for ENT comorbidity is concerning. In univariate analysis, ENT comorbidity appears more frequent in the non-surgical group, but in multivariable analysis it is associated with higher odds of surgery. The authors should assess and report possible confounding, interaction, multicollinearity, or model instability.

6. The Methods require more detail regarding surgical indications. The manuscript should specify which procedures were performed, how the decision for surgery was made, whether a standardized protocol was used, and whether the treating surgeon was blinded to any part of the assessment.

7. The statistical analysis should be strengthened. The authors should report how variables were selected for the regression model, whether assumptions were checked, whether collinearity was assessed, and whether the ROC AUC was internally validated. Without validation, the reported AUC of 0.89 may overestimate model performance.

8. Laterality should be clarified. Patients may have unilateral or bilateral epiphora, but the analysis appears to be patient-based. The authors should state how bilateral cases were handled and whether both eyes or one eye per patient contributed to imaging and clinical variables.

9. The ethical approval timing requires clarification. The study period was December 2022 to May 2024, but the ethics approval date is reported as July 1, 2024. The authors should clarify whether the study was retrospective, whether approval covered retrospective data use, and how informed consent was obtained.

10. Some conclusions should be toned down. The findings support CT-DCG as a complementary anatomical tool, but the current design does not prove that CT-DCG improves patient outcomes or accurately identifies patients who truly require surgery.

11. Figures and tables are generally understandable, but Figure 3 duplicates the information in Table 2 and may not add substantial value. Table 3 and Table 4 should be checked carefully for consistency in patient numbers and interpretation.

Comments on the Quality of English Language

The English is understandable, but several sentences would benefit from editing for clarity, grammar, and concision. Minor formatting issues are also present, including spacing in the author contribution section and placeholder supplementary material text.

Author Response

Reviewer 2

Comment 1: This study addresses a clinically relevant topic: the evaluation of chronic epiphora and the potential role of CT-dacryocystography (CT-DCG) in supporting surgical decision-making. The manuscript is generally well organized, and the focus on combining clinical signs with imaging findings is potentially useful for ophthalmologists and lacrimal surgeons.

However, several important issues should be addressed before the manuscript can be considered further.

1. The study population is inconsistent. The Methods and flow diagram state that 127 patients were included, whereas the Results section states that 128 patients were analyzed. This discrepancy should be corrected throughout the manuscript and tables.

Response 1: We thank the reviewer for identifying this inconsistency. The discrepancy in patient numbers resulted from a typographical error in the Results section. The manuscript, tables, and figure legend have now been carefully revised to ensure consistency throughout, and the correct number of analyzed patients (n = 127) is reported uniformly across the manuscript.

 

Comment 2: 2. The primary and secondary outcomes need clarification. The Methods state that the primary outcome was structural NLDS obstruction on CT-DCG, while much of the Results and Discussion focus on predictors of surgical management. The authors should clearly distinguish whether the study aims to predict anatomical obstruction, clinical decision for surgery, or actual surgical outcomes.

Response 2: We thank the reviewer for this important comment. In the revised manuscript, we clarified that the primary focus of the study was the evaluation of clinical and imaging factors associated with surgical management in patients with chronic epiphora. The Outcome Measures section and corresponding parts of the Results and Discussion were revised to more clearly distinguish structural CT-DCG findings from management-related outcomes.

 

Comment 3: 3. Surgical management may be affected by the same clinical and imaging findings used as predictors. Therefore, the outcome “surgical intervention” may partly reflect physician decision-making rather than an independent disease outcome. This should be discussed more explicitly, and the authors should avoid implying that the model predicts true surgical necessity unless postoperative outcomes or treatment response are available.

Response 3: We thank the reviewer for this important observation. We agree that surgical management in this study reflected real-world clinical decision-making based on combined clinical and imaging findings rather than an independent measure of confirmed disease severity or surgical necessity. In response, we revised the Discussion section to clarify this distinction, avoided predictive wording implying definitive surgical need, and added a limitation acknowledging the absence of postoperative outcome and treatment response data.

 

Comment 4: 4. The CT-DCG findings are central to the title and objective, but they are not included in the multivariable logistic regression model shown in Table 4. The authors should explain why imaging variables such as NLDS stenosis, NLDS obstruction, dacryocystitis, or punctal eversion were excluded from the final model, or provide an additional model including clinically relevant CT-DCG variables.

Response 4: We appreciate the reviewer’s thoughtful observation. In the present study, CT-DCG findings were included primarily to characterize the anatomical spectrum of lacrimal drainage abnormalities in patients with chronic epiphora. Imaging variables were not extensively incorporated into the final multivariable model because several CT-DCG subgroups contained relatively small numbers of patients, increasing the risk of model instability and overfitting. In response to the reviewer’s comment, we clarified this rationale in the Statistical Analysis and Discussion sections and emphasized the complementary anatomical role of CT-DCG within the study design.

 

Comment 5: 5. The change in direction of the association for ENT comorbidity is concerning. In univariate analysis, ENT comorbidity appears more frequent in the non-surgical group, but in multivariable analysis it is associated with higher odds of surgery. The authors should assess and report possible confounding, interaction, multicollinearity, or model instability.

Response 5: We appreciate the reviewer’s important observation. In response, we assessed multicollinearity among variables included in the regression model using variance inflation factors (VIFs), which did not demonstrate severe collinearity (all VIF values < 5). We also revised the Discussion section to acknowledge that the change in direction of the association for ENT comorbidity may reflect residual confounding, interaction between clinical variables, or model instability related to the relatively limited sample size. The interpretation of this finding has been softened accordingly.

 

Comment 6: 6. The Methods require more detail regarding surgical indications. The manuscript should specify which procedures were performed, how the decision for surgery was made, whether a standardized protocol was used, and whether the treating surgeon was blinded to any part of the assessment.

Response 6: We thank the reviewer for this important comment. In the revised manuscript, we expanded the Methods section to clarify that surgical decisions were made during routine clinical care based on combined clinical, functional, and imaging findings. We also specified the types of lacrimal drainage procedures performed and clarified that no predefined surgical protocol or blinding procedures were applied due to the retrospective observational design of the study.

 

Comment 7: 7. The statistical analysis should be strengthened. The authors should report how variables were selected for the regression model, whether assumptions were checked, whether collinearity was assessed, and whether the ROC AUC was internally validated. Without validation, the reported AUC of 0.89 may overestimate model performance.

Response 7: We appreciate the reviewer’s comment. The Statistical Analysis section was revised to clarify variable selection, assessment of multicollinearity using VIFs, and evaluation of model fit using the Hosmer–Lemeshow test. We also added a limitation acknowledging that the regression model was not internally validated and that the reported AUC may overestimate model performance.

 

Comment 8: 8. Laterality should be clarified. Patients may have unilateral or bilateral epiphora, but the analysis appears to be patient-based. The authors should state how bilateral cases were handled and whether both eyes or one eye per patient contributed to imaging and clinical variables.

Response 8: We thank the reviewer for highlighting this important point. The analysis was performed at the patient level rather than the eye level. In patients with bilateral epiphora, retrospective clinical and imaging assessment was based on the side considered more clinically significant according to the medical records. This clarification has been added to the Methods section.

 

Comment 9: 9. The ethical approval timing requires clarification. The study period was December 2022 to May 2024, but the ethics approval date is reported as July 1, 2024. The authors should clarify whether the study was retrospective, whether approval covered retrospective data use, and how informed consent was obtained.

Response 9: We appreciate the reviewer’s important comment and have clarified this issue in the revised manuscript. The study was retrospective and involved analysis of anonymized clinical and imaging data obtained during routine clinical care between December 2022 and May 2024. Ethics approval granted on July 1, 2024 specifically covered the retrospective use of existing clinical data for research purposes. We also clarified that written informed consent for diagnostic procedures was obtained during routine clinical care, and consent for the use of anonymized clinical and imaging data for research purposes was obtained in accordance with institutional ethical requirements.

 

Comment 10:10. Some conclusions should be toned down. The findings support CT-DCG as a complementary anatomical tool, but the current design does not prove that CT-DCG improves patient outcomes or accurately identifies patients who truly require surgery.

Response 10: We appreciate the reviewer’s comment and have revised the manuscript to provide a more cautious interpretation of the findings. Throughout the Discussion and Conclusion sections, CT-DCG is now described as a complementary or adjunctive imaging modality rather than a tool that definitively identifies surgical necessity or improves outcomes. We also added limitations regarding the absence of postoperative outcome data.

 

Comment 11:11. Figures and tables are generally understandable, but Figure 3 duplicates the information in Table 2 and may not add substantial value. Table 3 and Table 4 should be checked carefully for consistency in patient numbers and interpretation.

Response 11: We thank the reviewer for this helpful comment. Figure 3 was removed because it duplicated information already presented in Table 2 and did not substantially add to data interpretation. In addition, Tables 3 and 4 were carefully reviewed and revised to ensure consistency in patient numbers, statistical reporting, and interpretation throughout the manuscript.

 

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I thank the authors for their thorough responses. The transition to a retrospective observational design and the clarification regarding "acute on chronic" symptoms have resolved my primary methodological concerns. 

To finalise the manuscript, please address the following technical points:

Multicollinearity Diagnostics: In Table 4, the ENT comorbidity variable flips from being protective in the univariate analysis to a risk factor in the multivariable model. While you noted interaction effects in your response, please explicitly list the Variance Inflation Factor (VIF) values for all variables in the final model within the text to demonstrate statistical stability.

Model Interpretation: The very wide confidence intervals in Table 4 still suggest potential model overfitting. Please add a brief sentence to the "Limitations" section acknowledging that high odds ratios and wide CIs for certain variables (such as purulent discharge) should be interpreted with caution due to the sample distribution.

Author Response

Reviewer 1

Comment 1: Multicollinearity Diagnostics: In Table 4, the ENT comorbidity variable flips from being protective in the univariate analysis to a risk factor in the multivariable model. While you noted interaction effects in your response, please explicitly list the Variance Inflation Factor (VIF) values for all variables in the final model within the text to demonstrate statistical stability.

Response 1: We thank the reviewer for this helpful suggestion. In the revised manuscript, we added the individual variance inflation factor (VIF) values for all variables included in the final multivariable model. The calculated VIF values did not indicate severe multicollinearity, supporting acceptable model stability.

 

Comment 2: Model Interpretation: The very wide confidence intervals in Table 4 still suggest potential model overfitting. Please add a brief sentence to the "Limitations" section acknowledging that high odds ratios and wide CIs for certain variables (such as purulent discharge) should be interpreted with caution due to the sample distribution.

Response 2: We appreciate the reviewer’s comment. In the revised manuscript, we expanded the Limitations section to acknowledge that the high odds ratios and wide confidence intervals observed for certain variables, particularly purulent discharge, may reflect limited model stability and sample distribution effects, and should therefore be interpreted cautiously.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed several important concerns raised in the previous review. The revised manuscript now more clearly describes the retrospective design, corrects the study population to 127 patients, clarifies that surgical management was the primary outcome, explains the patient-level analysis in bilateral cases, and appropriately tones down the conclusion regarding CT-DCG.

I have only a few remaining comments.

1. The conclusion is now more balanced, but the authors should continue to avoid implying that the model predicts true surgical necessity. Since postoperative outcomes were not available, the findings should be interpreted as factors associated with real-world surgical decision-making rather than confirmed benefit from surgery.

2. The regression model still requires cautious interpretation. The authors report good AUC performance, but the manuscript also notes a significant Hosmer–Lemeshow test and wide confidence intervals for some variables. This limitation should be mentioned briefly in the Results as well as in the Discussion.

3. CT-DCG findings are mainly analyzed descriptively because of small subgroup sizes. This is acceptable, but the authors should make this limitation clear in the Abstract or Conclusion, since CT-DCG is emphasized in the title.

4. Please check the reference formatting. Several references contain duplicated numbering, such as “ 1 [1]”, and some references lack consistent spacing after the reference number.

5. The author contribution section still contains minor spacing and formatting errors, for example “Dautbayevaand”, “Zh.S.Abdrakhmanova”, “Rakhimzhanova;data”, and “Dautbayeva, Z.U.” These should be corrected.

Comments on the Quality of English Language

The English is generally understandable and has improved compared with the previous version. Minor editing is still recommended to improve clarity, concision, and formatting consistency, particularly in the author contribution section, reference list, and manuscript template text.

Author Response

Comment 1: 1. The conclusion is now more balanced, but the authors should continue to avoid implying that the model predicts true surgical necessity. Since postoperative outcomes were not available, the findings should be interpreted as factors associated with real-world surgical decision-making rather than confirmed benefit from surgery.

Response 1: We thank the reviewer for this important clarification. The Conclusion section was revised to further emphasize that the identified factors were associated with real-world surgical management decisions rather than confirmed surgical necessity or postoperative benefit. We also highlighted the need for future studies incorporating postoperative outcomes.

 

Comment 2: 2. The regression model still requires cautious interpretation. The authors report good AUC performance, but the manuscript also notes a significant Hosmer–Lemeshow test and wide confidence intervals for some variables. This limitation should be mentioned briefly in the Results as well as in the Discussion.

Response 2: We thank the reviewer for this important observation. In the revised manuscript, we added a brief statement in the Results section acknowledging that, despite the good discriminative performance of the model, the significant Hosmer–Lemeshow test and wide confidence intervals for some variables indicate that the regression findings should be interpreted cautiously. This limitation was also retained in the Discussion section.

 

Comment 3: 3. CT-DCG findings are mainly analyzed descriptively because of small subgroup sizes. This is acceptable, but the authors should make this limitation clear in the Abstract or Conclusion, since CT-DCG is emphasized in the title.

Response 3: We appreciate the reviewer’s comment. In the revised manuscript, we clarified in the Abstract that CT-DCG findings were analyzed primarily descriptively because several imaging subgroups contained relatively small numbers of patients. This limitation is also discussed in the main text.

 

Comment 4: 4. Please check the reference formatting. Several references contain duplicated numbering, such as “ 1 [1]”, and some references lack consistent spacing after the reference number.

Response 4: We thank the reviewer for identifying these formatting inconsistencies. The reference list was carefully revised to remove duplicated numbering, standardize spacing, and ensure consistent formatting throughout the manuscript.

 

Comment 5: 5. The author contribution section still contains minor spacing and formatting errors, for example “Dautbayevaand”, “Zh.S.Abdrakhmanova”, “Rakhimzhanova;data”, and “Dautbayeva, Z.U.” These should be corrected.

Response 5: We thank the reviewer for identifying these formatting issues. The Author Contributions section was carefully revised to correct spacing, punctuation, and formatting inconsistencies throughout the manuscript.