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Article
Peer-Review Record

Correlation Between Endocrine and Other Clinical Factors with Peripapillary Retinal Nerve Fiber Layer Thickness After Surgical Treatment of Pediatric Craniopharyngioma

Biomedicines 2026, 14(1), 239; https://doi.org/10.3390/biomedicines14010239
by Agnieszka Bogusz-Wójcik 1,*, Klaudia Rakusiewicz-Krasnodębska 2, Wojciech Hautz 2, Maciej Jaworski 3, Paweł Kowalczyk 4 and Elżbieta Moszczyńska 1
Reviewer 1:
Reviewer 2:
Reviewer 3:
Biomedicines 2026, 14(1), 239; https://doi.org/10.3390/biomedicines14010239
Submission received: 2 November 2025 / Revised: 21 December 2025 / Accepted: 13 January 2026 / Published: 21 January 2026
(This article belongs to the Special Issue Pediatric Tumors: Diagnosis, Pathogenesis, Treatment, and Outcome)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Bogusz-Wójcik et al presented a well-done descriptive case series related to the use of OCT in the Pre-Op setting for CP. My only recommendation is to carefully review some of the citations and try to be more concise with the introduction. Also, improve the image quality, as it is almost impossible to read the values. Besides that, it is very intersting, and certainly a good tool for the practice.

Author Response

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions and corrections, highlighted in the re-submitted files

Comments: Bogusz-Wójcik et al presented a well-done descriptive case series related to the use of OCT in the Pre-Op setting for CP. My only recommendation is to carefully review some of the citations and try to be more concise with the introduction. Also, improve the image quality, as it is almost impossible to read the values. Besides that, it is very intersting, and certainly a good tool for the practice.

Response: Thank you very much for your detailed review of the work and positive feedback. The citations have been rechecked and editorial errors corrected. We have made every effort to write a more concise introduction. We have added new, higher-resolution photos straight from the OCT machine to make them more transparent and more legible.

Reviewer 2 Report

Comments and Suggestions for Authors

The findings regarding RNFL thickness are interesting; however, the design of the OCT assessment presents significant limitations that affect the interpretation of the results.

The study exclusively reports post-operative OCT measurements. Without pre-operative baseline data, it is impossible to determine the true impact of the tumor itself and the subsequent surgical intervention on the RNFL. We cannot discern how much of the post-operative RNFL thickness represents surgical injury, pre-existing tumor-induced damage, or a combination of both. This absence of a pre-operative benchmark greatly limits the ability to attribute the observed outcomes specifically to the treatment.

The OCT scans were performed within a very broad time window of 1.5 to 5 years post-surgery (mean 3 years and 8 months). The RNFL is not static during this period; it may undergo progressive thinning due to ongoing degeneration or even potential recovery in the early phases. Grouping measurements from such disparate time points introduces a substantial "time-dependent variable" bias. Differences observed between groups could be conflated with differences in the time since surgery, rather than reflecting true, stable group characteristics.

 

I have a concern regarding the choice of statistical tests, which would benefit from further clarification. The manuscript states that the normality of continuous variables was assessed using the Shapiro-Wilk test, and consequently, these variables are reported as medians with interquartile ranges. This strongly suggests that the data for these continuous variables were not normally distributed. While the use of the non-parametric Mann-Whitney U test for two-group comparisons is entirely appropriate for non-normally distributed data, the use of ANOVA for comparisons of more than two groups appears inconsistent with this data characteristic.

 

The title "Clinical Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness in Pediatric Craniopharyngioma" is broad and could be interpreted as encompassing the natural history of the disease, including the pre-operative state.

 

I strongly recommend that all tables and in-text results for Spearman's correlations be amended to include the Spearman's R value alongside the p-value. This is a standard practice that greatly enhances the transparency, interpretability, and scientific rigor of the findings.

Author Response

Thank you very much for taking the time to review this manuscript.
Please find the detailed responses below and the corresponding revisions highlighted in the re-submitted files. 

Comments 1: The findings regarding RNFL thickness are interesting; however, the design of the OCT assessment presents significant limitations that affect the interpretation of the results.

The study exclusively reports post-operative OCT measurements. Without pre-operative baseline data, it is impossible to determine the true impact of the tumor itself and the subsequent surgical intervention on the RNFL. We cannot discern how much of the post-operative RNFL thickness represents surgical injury, pre-existing tumor-induced damage, or a combination of both. This absence of a pre-operative benchmark greatly limits the ability to attribute the observed outcomes specifically to the treatment.

The OCT scans were performed within a very broad time window of 1.5 to 5 years post-surgery (mean 3 years and 8 months). The RNFL is not static during this period; it may undergo progressive thinning due to ongoing degeneration or even potential recovery in the early phases. Grouping measurements from such disparate time points introduces a substantial "time-dependent variable" bias. Differences observed between groups could be conflated with differences in the time since surgery, rather than reflecting true, stable group characteristics.

Response 1Thank you very much for this important and insightful comment. We fully agree that the wide postoperative time window (1.5–5 years) introduces a potential time-dependent bias, given that RNFL thickness is not a static parameter and may undergo both progressive thinning and, in selected cases, partial recovery in the early postoperative period.

However, based on findings from larger cohorts and clinical experience, the most substantial structural changes typically occur in association with the tumour itself and with the acute effects of surgery. In clinically stable patients without tumour recurrence, OCT parameters are often relatively stable over longer follow-up periods. We acknowledge nonetheless that additional postoperative factors may influence RNFL measurements.

We are currently conducting a longitudinal study with preoperative and regular postoperative OCT assessments to more precisely characterise the temporal dynamics of these changes.

As suggested, we have also expanded the Limitations section by adding the following sentence:
“The interval between surgery and examination covered a relatively long time span; therefore, it cannot be excluded that additional factors may have influenced the RNFL parameters during this period, as well as the direction and magnitude of these effects.”

Comments 2: I have a concern regarding the choice of statistical tests, which would benefit from further clarification. The manuscript states that the normality of continuous variables was assessed using the Shapiro-Wilk test, and consequently, these variables are reported as medians with interquartile ranges. This strongly suggests that the data for these continuous variables were not normally distributed. While the use of the non-parametric Mann-Whitney U test for two-group comparisons is entirely appropriate for non-normally distributed data, the use of ANOVA for comparisons of more than two groups appears inconsistent with this data characteristic.

Response 2Thank you very much for your insight and comprehensive review of the work. Unfortunately, this is an editorial error. The analysis used in the work was a non-parametric ANOVA with a post-test when comparing more than two groups. The error has been corrected in the manuscript.

The corrected paragraph on statistical methods is below.

“The Mann–Whitney test was used for comparisons between two groups, and non-parametric ANOVA with post-test when comparing more than two groups.”

Comments 3: The title "Clinical Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness in Pediatric Craniopharyngioma" is broad and could be interpreted as encompassing the natural history of the disease, including the pre-operative state.

Response 3Thank you for this helpful observation. We agree that the original title may suggest inclusion of the natural history of the disease or pre-operative characteristics. To better reflect the actual scope of the study which focuses exclusively on postoperative OCT findings, we have revised the title accordingly.

Revised title:  Clinical Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness After Surgical Treatment of Pediatric Craniopharyngioma.

Comments 4: I strongly recommend that all tables and in-text results for Spearman's correlations be amended to include the Spearman's R value alongside the p-value. This is a standard practice that greatly enhances the transparency, interpretability, and scientific rigor of the findings.

Response 4Thank you very much for this comment regarding statistics. We didn't describe correlations in the manuscript because there were no correlations in the statistical results. You likely meant a comparison of two groups based on the presence of a given parameter, with p-values ​​provided. For greater clarity and reader readability, median values ​​for individual groups have been added.

“Preoperative clinical factors, such as the age below 5 years at diagnosis, were found to significantly influence RNFL damage in the IN (79 μm vs. 121 μm, p=0.02) and NU (56 μm vs. 96 μm, p=0.02) sectors, with more pronounced damage seen in children diagnosed before age 5. Children born domestically exhibited thinner RNFL and showed greater reductions, especially in the infRNFL (74 μm vs. 85 μm, p=0.03), IT (112 μm vs. 130 μmp=0.03), IN (78 μm vs. 130 μmp=0.04), NU (29 μm vs. 37 μmp=0.04), and SN (79 μm vs. 90 μm, p=0.004) regions. Additionally, the presence of optic disc oedema before surgery was significantly linked to avgRNFL (75 μm vs. 85 μm, p=0.02) (Figure 3), supRNFL (78 μm vs. 87 μm, p=0.03)  infRNFL (74 μm vs. 83 μm, p=0.03), IN (91 μm vs. 112 μm, p=0.04), and NL (51 μm vs. 62 μm p=0.04) thinning, indicating that optic disc oedema corresponded to more severe RNFL fiber loss in these areas. Delayed puberty before diagnosis was linked to increased RNFL thinning in several areas, including avgRNFL (75 μm vs. 91 μm, p=0.005) (Figure 4), supRNFL (77 μm vs. 92 μm, p=0.007), infRNFL (74 μm vs. 90 μm, p=0.007), ST (109 μm vs. 129 μm, p=0.03), TU (62 μm vs. 78 μm, p=0.007), IT (101 μm vs. 135 μm, p=0.007), NL (52 μm vs. 67 μm, p=0.02), and SN (81 μm vs. 91 μm, p=0.02). Growth hormone deficiency (GHD) detected before surgery also showed a significant association with thinner RNFL measurements in avgRNFL (73 μm vs. 96 μm, p=0.03), infRNFL (66 μm vs. 91 μm, p=0.03), IN (63 μm vs. 122 μm, p=0.03), NL (49 μm vs. 72 μm, p=0.03), NU (58 μm vs. 83 μm, p=0.03), and SN (83 μm vs. 127 μm, p=0.03), with GHD presence indicating more severe RNFL loss in these sectors. AVD diagnosed before surgery significantly influenced the thickening of avgRNFL (77 μm vs. 98 μm, p=0.02) (Figure 5), supRNFL (78 μm vs. 87 μm, p=0.04), infRNFL (76 μm vs. 95 μm, p=0.006), IN (78 μm vs. 119 μm, p=0.04), NU (57 μm vs. 78 μm, p=0.04), and SN (81 μm vs. 123 μm, p=0.008). Hyperprolactinemia before surgery was associated with more pronounced RNFL thinning in the infRNFL (66 μm vs. 78 μm, p=0.02), IN (64 μm vs. 80 μm, p=0.03), and NL (43 μm vs. 53 μm, p=0.003). Moreover TL (34 μm vs. 50 μm, p=0.001) and NL (42 μm vs. 56 μm, p=0.04) were thinner when there was no hypothalamic involvement [35].

Clinical factors after surgery, such as SIADH, had a significant impact on the greater damage in NL sector (49 μm vs. 61 μm, p=0.01). Additionally, the end of AVD in follow-up had a substantial effect on the IT sector. (98 μm vs. 115 μm, p=0.04). A thinner RNFL was observed when AVD was continuous after surgery. Postoperative clinical symptoms such as memory impairment had a significant impact on the RNFL reduction in the TL sector (55 μm vs. 48 μm, p=0.03) as well as hyperphagia in the IN sector (73 μm vs. 90 μm, p=0.002).”

Reviewer 3 Report

Comments and Suggestions for Authors

The authors present the series of children who underwent surgical resection of Craniopharyngioma had had subsequent evaluation of retinal nerve fiber layer by OCT several years after their primary surgical treatment and compared to an aged matched normal cohort. They demonstrate correlation with preoperative papilledema as well as delayed puberty, prolactinemia, diabetes isipidus, and hypothalamic involvement. It is an interesting concept to utilize retinal nerve fiber damage as a long-term marker of visual impairment and potentially monitoring children with residual disease in terms of potential recurrence before significant radiographic enlargement. Although the paper is well written, I believe there are several major areas that need to be addressed in a revision:

  1. From a pragmatic perspective, the authors do not indicate whether tumor size impacted their outcome. It would be useful to divide their study cohort by tumor size (less than 2 cm, 2-3 cm, greater than 3 cm) as well as location, prechiasmatic versus postchiasmatic. The authors intimate that hypothalamic involvement led to worse outcome suggesting counterintuitively but it is postchiasmatic compression however hypothalamic involvement may be more a marker of tumor size causing the impact on the retinal nerve fiber.
  2. Was the duration of postoperative symptoms associated with more severe retinal fiber loss. Typically there is a two year program of fall off in growth hormone/linear growth before tumors are diagnosed.  Were more acute presentations more or less likely the result in retinal nerve fiber loss?
  3. Was the degree of preoperative visual acuity deficit or visual field deficit associated with long-term retinal nerve fiber loss?
  4. Up to 25 to 40% of children undergoing surgery for   Craniopharyngioma may have some degree of visual deterioration postoperatively.Was the deterioration in visual function between  preoperative and postoperative ophthalmologic evaluations significantly associated with the long-term retinal nerve fiber loss?
  5. Was retinal nerve loss associated with recovery or lack of recovery after deterioration due to surgical intervention and manipulation of the optic apparatus.
  6. It is unclear whether radiation had any impact on retinal nerve fiber loss
  7. It would be a useful to have a chart with all the clinical variables (tumor characteristics, surgical characteristics, endocrine characteristics, etc.) Evaluated in univariant analysis and their P values 
  8. Some form of  multi-variant analysis would be appropriate as well. For example are the endocrine deficiencies simply a reflection of the hypothalamic involvement where do they stand alone in multi-variant analysis.
  9. The author supply but do not state in their discussion that retinal nerve fiber evaluation would be a useful tool both preoperatively and immediately postoperatively in prognosticating long-term visual function. They should expand upon this in the discussion

Author Response

Thank you very much for taking the time to review this manuscript.
Please find the detailed responses below and the corresponding revisions highlighted in the re-submitted files. 

Comments 1:

The authors present the series of children who underwent surgical resection of Craniopharyngioma had had subsequent evaluation of retinal nerve fiber layer by OCT several years after their primary surgical treatment and compared to an aged matched normal cohort. They demonstrate correlation with preoperative papilledema as well as delayed puberty, prolactinemia, diabetes isipidus, and hypothalamic involvement. It is an interesting concept to utilize retinal nerve fiber damage as a long-term marker of visual impairment and potentially monitoring children with residual disease in terms of potential recurrence before significant radiographic enlargement. Although the paper is well written, I believe there are several major areas that need to be addressed in a revision:

  1. From a pragmatic perspective, the authors do not indicate whether tumor size impacted their outcome. It would be useful to divide their study cohort by tumor size (less than 2 cm, 2-3 cm, greater than 3 cm) as well as location, prechiasmatic versus postchiasmatic. The authors intimate that hypothalamic involvement led to worse outcome suggesting counterintuitively but it is postchiasmatic compression however hypothalamic involvement may be more a marker of tumor size causing the impact on the retinal nerve fiber.

Response 2Thank you very much for this important and insightful comment. We fully agree that the size of the tumour is very important in assessing its impact on RNFL damage. We described the relationship between tumour size, location and morphology in an earlier paper published in Cancers, entitled “ Evaluation of the effect of optic nerve compression by Craniopharyngioma on retinal nerve fiber layer thickness in pediatric patients”, which is cited in the current paper. In our current work, we focused on clinical factors that affect RNFL thickness. As described in Table 3, RNFL damage scores were higher when the hypothalamus was not involved, as was rightly pointed out by the reviewer. In the results, we also added information about the impact of hypothalamic involvement on less severe damage to the RNFL.

“Moreover TL (34 μm vs. 50 μm, p=0.001) and NL (42 μm vs. 56 μm, p=0.04) were thinner when there was no hypothalamic involvement [35]. ”

Comments 2: Was the duration of postoperative symptoms associated with more severe retinal fiber loss. Typically there is a two year program of fall off in growth hormone/linear growth before tumors are diagnosed.  Were more acute presentations more or less likely the result in retinal nerve fiber loss?

Response 2: In our study group, at the time of tumour diagnosis, as many as 16 patients (42%) had a growth retardation prior to tumour diagnosis, but only in 4 patients (11%) was short stature the reason for consulting a doctor and starting diagnostics. The occurrence of acute tumour symptoms, such as optic nerve swelling had a significant impact on RNFL damage.

“Clinical parameters before surgery, such as gender, headache, vomiting, impaired visual acuity, visual field restriction, optic nerve disc atrophy, strabismus, double vision, unilateral blindness, drowsiness, altered consciousness, apathy, epileptic seizures, loss of consciousness, abdominal pain, and memory disturbances, did not affect RNFL parameters. Endocrinological parameters like BMI SD, growth retardation, hypothyroidism and adrenal insufficiency had no significant impact on RNFL parameters in individual sectors.”

Comments 3: Was the degree of preoperative visual acuity deficit or visual field deficit associated with long-term retinal nerve fiber loss?

Response 3: The relationship between preoperative RNFL thickness and both visual acuity and visual field outcomes before and after surgery is indeed an important and widely discussed topic. However, our patient cohort consists primarily of young children, for whom obtaining a reliable and diagnostically meaningful visual field examination is extremely challenging. Although visual acuity and visual field assessments are routinely performed at our centre preoperatively, postoperatively, and during follow-up visits, in most cases, the visual field results were of insufficient quality to be included in the analysis.

Similarly, visual acuity, being a subjective measure, is not an objective or reliable parameter in younger children. For these reasons, neither visual acuity nor visual field data could be incorporated into the present study.

In this work, we therefore focused on the more objective and reproducible structural parameter of RNFL thickness, along with relevant clinical factors.

Comments 4: Up to 25 to 40% of children undergoing surgery for Craniopharyngioma may have some degree of visual deterioration postoperatively.Was the deterioration in visual function between  preoperative and postoperative ophthalmologic evaluations significantly associated with the long-term retinal nerve fiber loss?

Response 4: We are currently conducting a longitudinal study with preoperative and regular postoperative OCT assessments to more precisely characterise the temporal dynamics of these changes.

Comments 5: Was retinal nerve loss associated with recovery or lack of recovery after deterioration due to surgical intervention and manipulation of the optic apparatus.

Response 5: The impact of surgical intervention on RNFL has been described in detail in a paper published in Cancers, which is cited in the current paper (Rakusiewicz-KrasnodÄ™bska, K.; Bogusz-Wójcik, A.; MoszczyÅ„ska, E.; Jaworski, M.; Kowalczyk, P.; Hautz, W. Evaluation of the Effect of Optic Nerve Compression by Craniopharyngioma on Retinal Nerve Fiber Layer Thickness in Pediatric Patients. Cancers 2025, 17, 2574. https://doi.org/10.3390/cancers17152574)

In our current work, we focused on clinical aspects affecting RNFL damage.

Comments 6: It is unclear whether radiation had any impact on retinal nerve fiber loss

Response 6: Thank you for this valuable question. Indeed, postoperative radiotherapy was used in only ten patients (low statistical value). And in our results, radiotherapy did not affect RNFL parameters in individual sectors. However, these parameters have already been presented in another published paper, which is cited in this regard (Rakusiewicz-KrasnodÄ™bska, K.; Bogusz-Wójcik, A.; MoszczyÅ„ska, E.; Jaworski, M.; Kowalczyk, P.; Hautz, W. Evaluation of the Effect of Optic Nerve Compression by Craniopharyngioma on Retinal Nerve Fiber Layer Thickness in Pediatric Patients. Cancers 2025, 17, 2574. https://doi.org/10.3390/cancers17152574). The methodology has been corrected and postoperative data whose results have not been described have been removed.

Comments 7: It would be a useful to have a chart with all the clinical variables (tumor characteristics, surgical characteristics, endocrine characteristics, etc.) Evaluated in univariant analysis and their P values

Response 7: We understand that including these data would certainly increase the value of the work; however, the submitted manuscript focuses on clinical parameters, particularly endocrine parameters, rather than tumour-related factors. The factors you mention, within our similarly heterogeneous patient group, are discussed in detail in the article we cited, published in Cancers. Rakusiewicz-KrasnodÄ™bska, K.; Bogusz-Wójcik, A.; MoszczyÅ„ska, E.; Jaworski, M.; Kowalczyk, P.; Hautz, W. Evaluation of the Effect of Optic Nerve Compression by Craniopharyngioma on Retinal Nerve Fiber Layer Thickness in Pediatric Patients. Cancers 2025, 17, 2574. https://doi.org/10.3390/cancers17152574

Comments 8: Some form of  multi-variant analysis would be appropriate as well. For example are the endocrine deficiencies simply a reflection of the hypothalamic involvement where do they stand alone in multi-variant analysis.

Response 8: Thank you very much for this valuable comment. A single-factor analysis was sufficient to establish ophthalmological recommendations, while a multi-factor analysis aimed at identifying independent factors was not the subject of the study.

A multi-factor analysis was planned when analyzing pre- and post-operative factors, for which we are currently collecting data.

Comments 9: The author supply but do not state in their discussion that retinal nerve fiber evaluation would be a useful tool both preoperatively and immediately postoperatively in prognosticating long-term visual function. They should expand upon this in the discussion

Response 9: Thank you very much for your valuable comment. We add and extend in discussion that retinal nerve fiber evaluation would be a useful tool both preoperatively and immediately postoperatively in prognosticating long-term visual function.

“This study highlights OCT's importance as a non-invasive and objective method for evaluating the optic nerve in children with CP. Measuring RNFL thickness helps clinicians identify subtle lesions at an early stage, making it especially useful for pediatric patients. OCT can also support ongoing monitoring to detect those at risk of worsening vision and inform specific treatment strategies. Retinal nerve fiber evaluation would be a useful tool both preoperatively and immediately postoperatively in prognosticating long-term visual function.”

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

I appreciate the authors' responses and the manuscript revisions. I remain concerned that the authors' hypothesis that "clinical factors" impact on retinal nerve fiber layer is spurious and that the" clinical factors", predominantly endocrine testing results, are an epiphenomena or marker of injury, but not the actual pathologic factor causing diminished nerve fiber layer. For example, the decrease in nerve fiber layer with delayed puberty may have nothing to do with the impact of gonadotropin deficit but rather a marker of the chronicity of the optic pathway compression.

I would suggest that a minimum that there needs to be significant discussion regarding whether the hormone abnormalities or directly impacting the optic pathway or if they represent a marker of other phenomena, primarily chronicity and degree of compression by the tumor and impact of surgical manipulation.

I would also suggest that the title of the article be modified to indicate that this is primarily correlation between endocrine deficiencies and retinal nerve fiber layer. These endocrine abnormalities have not been proven by this manuscript to be determinants (ie cause)of  decreased retinal nerve fiber layer but rather a correlate or clinical indicator nothing retinal nerve fiber layer has been diminished. Perhaps the title of the manuscript should be "Correlation between endocrine and other clinical factors with peripapillary retinal nerve fiber layer thickness after surgical treatment of pediatric craniopharyngioma"

 

Author Response

Comment 1: I appreciate the authors' responses and the manuscript revisions. I remain concerned that the authors' hypothesis that "clinical factors" impact on retinal nerve fiber layer is spurious and that the" clinical factors", predominantly endocrine testing results, are an epiphenomena or marker of injury, but not the actual pathologic factor causing diminished nerve fiber layer. For example, the decrease in nerve fiber layer with delayed puberty may have nothing to do with the impact of gonadotropin deficit but rather a marker of the chronicity of the optic pathway compression.

I would suggest that a minimum that there needs to be significant discussion regarding whether the hormone abnormalities or directly impacting the optic pathway or if they represent a marker of other phenomena, primarily chronicity and degree of compression by the tumor and impact of surgical manipulation.

Response 1: Thank you very much for your insightful analysis and valuable comments on our work. We agree with the reviewer that “the decrease in nerve fiber layer with delayed puberty may have nothing to do with the impact of gonadotropin deficit but rather a marker of the chronicity of the optic pathway compression”. The impact of AVD and gonadotropin deficiency on RNFL thinning has not been thoroughly investigated and described in detail in the literature. We added a paragraph to the discussion and limitations about the lack of scientific reports on the impact of these hormonal disorders in RNFL thickening.

We also agree with the reviewer that the most crucial is the effect of the degree of compression by the tumour and the impact of surgical manipulation on RNFL thickness in pediatric patients. Identifying clinical factors for RNFL damage has practical implications in everyday clinical practice with children.

Discussion line 368

The impact of AVD and gonadotropin deficiency on RNFL thinning has not been thoroughly investigated and described in detail in the literature. It seems likely that the pressure exerted by the tumour on the pituitary gland and hypothalamus is associated with the destruction of these structures and the failure to secrete pituitary hormones. The size and location of the tumour are important markers of the chronicity of optic pathway compression. It is also worth noting that the surgical procedure itself can lead to damage to nerve fibres, which is why a multifactorial assessment of the impact of clinical factors on the RNFL before and after surgery is essential. This study is currently being conducted at the CMHI in Warsaw, Poland. Identifying clinical factors for RNFL damage has practical implications in everyday clinical practice with children.

Limitations line 400

There is a lack of detailed studies in the literature on the effect of endocrine abnormalities such as  AVD  and gonadotropin deficiency on RNFL; further studies are needed to assess this relationship.

Comment 2: I would also suggest that the title of the article be modified to indicate that this is primarily correlation between endocrine deficiencies and retinal nerve fiber layer. These endocrine abnormalities have not been proven by this manuscript to be determinants (ie cause)of  decreased retinal nerve fiber layer but rather a correlate or clinical indicator nothing retinal nerve fiber layer has been diminished. Perhaps the title of the manuscript should be "Correlation between endocrine and other clinical factors with peripapillary retinal nerve fiber layer thickness after surgical treatment of pediatric craniopharyngioma"

Response 2: Thank you for pointing this out. We agree with this comment. Therefore, we have changed the title of the manuscript:

Correlation between endocrine and other clinical factors with peripapillary retinal nerve fiber layer thickness after surgical treatment of pediatric craniopharyngioma

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