Title: Type of the Recurrent Exotropia after Bilateral Rectus Recession for Intermittent Exotropia

Transcription

1 Author s response to reviews Title: Type of the Recurrent Exotropia after Bilateral Rectus Recession for Intermittent Exotropia Authors: Kwan Hyuk Cho (whmed@hanmail.net) Hee Weon Kim (khw402@hanmail.net) Dong Gyu Choi (eyechoi@hallym.or.kr) Joo Yeon Lee (kimleejy@hallym.or.kr) Version: 1 Date: 23 Dec 2015 Author s response to reviews: BOPH-D Type of the Recurrent Exotropia after Bilateral Rectus Recession for Intermittent Exotropia Kwan Hyuk Cho, M.D.; HeeWeon Kim, M.D.; Dong Gyu Choi, PhD; JooYeon Lee, PhD BMC Ophthalmology Dear Editor and reviewers I appreciate you giving the thoughtful comments to improve and revise my manuscript. Here is my answer with a point-by-point response to the comments. I wrote my opinion (answer) with blue colored letters next to your comment (question).

2 All changes to the manuscript are indicated in the revised manuscript by highlighting with red colored letters. I look forward to receiving your favorable answer. Sincerely, JooYeon Lee, M.D Ph.D (Professor of Hallym University Medical College Department of Ophthalmology, division of pediatric ophthalmology & strabismus) P.S : Kwan Hyuk Cho, M.D. transferred to the Seoul National University Bundang Hospital in Seongnam, South Korea. Therefore, he added his new affiliation in the revised manuscript Editor's Additional Comments: Please clarify whether informed consent covers the study as well as surgery. Consent for the study can be waived in cases of the retrospective clinical research that conformed to the Declaration of Helsinki. This study was appoved by the Institutional Review Board(IRB No ) with an understanding on exemption from the study consent. Manuscript before revision (p3) ; All the procedures in this study conformed to the Declaration of Helsinki, and this study was approved by the Institutional Review Board (IRB) of the Hallym University Sacred Heart Hospital (IRB No I025).

3 -->revised manuscript (p4 ) ; All the procedures in this study conformed to the Declaration of Helsinki, and this study was approved by the Institutional Review Board (IRB) of the Hallym University Sacred Heart Hospital (IRB No I025) with an understanding on exemption from the informed consent for the study of retrospective collection of the clinical data. About informed consent for the surgery, it was described in the manuscript before revision, and I left it with no change in the revised manuscript. -- manuscript before revision (p3) & revised manuscript (p4 ) : The written informed consent of all the patients and their legal guardians to the surgical procedure was obtained Reviewer reports: Reviewer #1: Abstract. 1.Background "to find out the possibility of secondary convergence insufficiency (CI)-type strabismus". Is there evidence that patients develop CI after initial LR recession or this is the author's conclusion? are the authors claiming their conclusion in the background? (Answer ) manuscript (abstract) before revision was ;

4 Background To investigate the type of exotropia (XT) based on the distance-near (D/N) difference in recurrent XT after bilateral lateral rectus (BLR) recession to treat intermittent XT (IXT) and to find out the possibility of secondary convergence insufficiency (CI)-type strabismus. That never meant a conclusion or any evidence. That was a purpose. I aimed to find out the possibility of secondary convergence insufficiency (CI)-type strabismus. I think the expression might cause a mis-understanding. So I changed the part of abstract in the revised manuscript as below ; Background The aim of this study was to investigate the type of exotropia (XT) based on the distance-near (D/N) difference in recurrent XT after bilateral lateral rectus (BLR) recession to treat intermittent XT (IXT) to look into the possibility of secondary convergence insufficiency (CI)-type strabismus. 2. Results. Based on the results here presented LR recessions increase the changes of divergence excess and CI type of XT. Not just CI. Authors must discuss this. 3. Conclusion. Just reflect half of their findings. Increased CI but no the increase (duplicated the total number of patients with DE type of XT (Answer to Question# 2 & 3 ) -- Before revision ;

5 Conclusion The XT type composition changed after the BLR recession. The XT types in recurrent XT after BLR recession showed an increasing proportion of CI-type. -- In the revised manuscript ; Conclusion The XT type composition changed after the BLR recession. The XT types in recurrent XT after BLR recession showed an increasing proportion of CI-type. We suspect that an individual fusion mechanism might also influence the XT-type in recurrent XT in view of somewhat increased DE-types of recurrent XT. Also, I added more discussion for this issue in the body of the revised manuscript, because the abstract has a limitation of space and number of characters. Please see the Answer to question # 16, 17, 18, 19 Introduction 4. "Choi et al.3 compared the long-term surgical outcomes of BLR recession and R&R, and found that they were better in the eyes treated using BLR recession than in those treated with R&R." this paragraph is incomplete. The previous paragraph refers to both basic and DE types of XT. Please clarify what do you refer to "they were better" are you referring only to basic or only DE or both. The study by Choi et al.3 compared the surgical outcomes between BLR recession and R&R in the basic-type exotropia. I am sorry for the mistake that I missed the word in the basic-type exotropia for the sentence. I put right the sentence as below (p 3) ;

6 Choi et al.3 compared the long-term surgical outcomes of BLR recession and R&R in the basictype intermittent exotropia, and found that they were better in the eyes treated using BLR recession than in those treated with R&R. 5. "BLR recession also has several advantages. The procedure is short and simple; and unlike R&R, a larger amount of surgery procedures can be performed with BLR recession without causing significant lateral incomitancy.14,15 These are potential complications. However large LR recessions may also increase the chances of esotropia in lateral gazes. Authors must use appropriate language such as potential advantages. Debatable. I agree on that large LR recessions may also cause an abduction deficit. But bilateral lateral incomitance were generally asymptomatic, particularly when symmetrical. Asymmetrical lateral incomitance after monocular R&R is known to have the risk of symptomatic diplopia in lateral gaze to the side of operated eye. It should be one of the important reasons why many physicians prefer a symmetrical BLR recessions over R&R.(references : Wright KW, Strube YNJ, Pediatric Ophthalmology and Strabismus, 3rd edition, Oxford, p / Schwartz RL, Calhoun JH, Surgery of large angle exotropia, J Pediatr Ophthalmol Strabismus 1980;17: / Currie ZI, Shipman T, Burke JP, Surgical correction of largeangle exotropia in adults. Eye (Lond) ;17:334-9 ) That I intended to say was that BLR recession does not induce symptomatic asymmetrical lateral incomitance. In the revision, the new paragraph is as below, to clarify the meaning (p 3) ; The procedure is short and simple; and unlike R&R, a larger amount of surgery procedures can be performed with BLR recession without causing symptomatic asymmetrical lateral incomitance Asymmetrical lateral incomitance after monocular R&R is known for the risk of symptomatic diplopia in ipsilateral side-gaze. The large LR recession can also cause lateral incomitance, but bilateral lateral incomitance is generally asymptomatic, particularly when symmetrical. Wright & Strube said that BLR recession works well for all the basic, pseudo DE,

7 and true DE types of XT, and is usually preferred over a monocular R&R as R&R produce significant lateral incomitance in the side of the operated eye.16 Methods 6. Authors are free to include and exclude patients. However the rationale to exclude the following patients "The cases in which they had shown early surgical success were included in this study, by exclusion of those with 5PD consecutive esotropia in one month after surgery or 10PD residual exotropia within one month after surgery" So which cases were included. Early alignment in intermittent exotropia is meaningless. Many studies support this. In fact patients with early overcorrection more than 66% of the them result in ortho or recurrent XT. Those with residual XT of more than 10 in the first months are very typical. In other words only patients aligned within less than 5 pd of ET and less than 10 pd of XT in the first month were included. Also not clear if that criteria was for near or for distance deviation.] You mentioned that early alignment after surgery is meaningless. I also agree that the early alignment is not so important in exotropia surgery. Many authors reported that an initial overcorrection after XT surgery is necessary for a good results and a lower probability of early recurrence. But the importance of an initial overcorrection for long-term outcomes remain uncertain and many studies have reported that the amount of early overcorrection after intermittent exotropia surgery could not predict the occurrence of consecutive esotropia and recurrent exotropia and it could not predict long-term motor outcomes.( references : Lee SY and Lee YC. Relationship between motor alignment at postoperative day 1 and at year 1 after symmetric and asymmetric surgery in intermittent exotropia. Jpn J Ophthalmol 2001;45: doi: /s (00) / Oh JY and Hwang JM. Survival analysis of 365 patients with exotropia after surgery. Eye 2006;20: / Choi J, Kim SJ and Yu YS. Initial postoperative deviation as a predictor of long-term outcome after surgery for intermittent exotropia. J AAPOS 2011;15: / Scott WE, Keech R and Mash AJ. The postoperative results and stability of exodeviations. Arch Ophthalmol 1981;99: / Raab EL, Parks MM. Recession of the lateral recti. Early and late postoperative alignments. Arch Ophthalmol 1969;82: / Ruttum MS. Initial versus subsequent postoperative motor alignment in intermittent exotropia. J AAPOS 1997;1: )

8 Regardless of the above explanations, the matter that I concerned in my present study was not the early alignment after surgery. The reason why I made the exclusion criteria of 5PD consecutive esotropia in one month after surgery or 10PD residual exotropia within one month after surgery was that I wanted to enroll the cases of recurrent exotropia which occurred in patients who they got a surgical success. Residual exotropia after exotropia surgery and consecutive esotropia after exotropia surgery are surgical failures. And I wanted to exclude the cases of surgical failure. To exclude them, in my present study, I defined the consecutive esotropia as 5PD esotropia in one month after surgery. By my previous research, postoperative overcorrection at 1st day after surgery was meaningless and mean 5.4PD esodeviation at 1 month after surgery was significant risk factor for persistent esotropia that require additional surgery.(reference; Choi YM, Lee JY et al. Risk Factors Predicting the Need for Additional Surgery in Consecutive Esotropia. J Pediatr Ophthalmol Strabismus 2013;50:335-9.) And I defined the residual exotropia as 10PD residual exotropia within one month after surgery. Exodeviation of 10PD after surgery was considered as the surgical failure in most studies, and patients with a residual exotropia greater than 10PD in the early postoperative weeks will probably not improve(wright KW, Strube YNJ, Pediatric Ophthalmology and Strabismus, 3rd edition, Oxford, p ). The sentence of only patients aligned within less than 5 pd of ET and less than 10 pd of XT in the first month were included. you recommended, was a precise explanation for the inclusion and exclusion criteria. And you also asked Also not clear if that criteria was for near or for distance deviation. So, according to your advice, I revised the paragraph as below (manuscript p3) ; The cases of recurrent exotropia, which occurred in patients who had aligned within < 5 PD of distant angle of esotropia and < 10 PD of distant angle of exotropia in the first postoperative month, were included.

9 7. "The FCGX data collected from the medical records were graded as good or poor at a fixation target of 6 m. The FCGX was graded good when the patient manifested the deviation after the cover test and resumed the fusion rapidly with blinking or with a refixation. The patients who exhibited the deviation spontaneously, without any form of fusion disruption, were defined as having had a poor FCGX.16,17" Who recorded the FCGX. I already described it on page No. 4 in manuscript before revision ; The surgeon assessed the fusion control grade of the exodeviation (FCGX) at a fixation target of 6 m. As you asked Who recorded the FCGX., I added the word recorded in the sentence. In the revised manuscript (p4); The surgeon assessed and recorded the fusion control grade of the exodeviation (FCGX) at a fixation target of 6 m. 8. Please clarify the following. "The type change between the primary XT and recurrent XT was evaluate according to the D/N deviation angles. Then the IXT type was assigned based on the reference D/N difference. In the patients with a distance deviation greater than 30 PD, the reference value of the D/N difference was 10 PD; and in the patients with a distance deviation less than 30 PD, the reference value was one-third the distance deviating angle." It is not clear if Preoperative criteria were more severe with larger differences between near and distance explaining the postoperative findings.

10 We applied the same reference value to divide the exotropia type in preoperative and postoperative type exotropia when we performed the retrospective data review. I added the word in both of primary and recurrent exotropia in the revised manuscript. In the revised manuscript(p4) ; The IXT type was assigned based on the same reference D/N difference in both of primary and recurrent exotropia. The reference value that we used (one-third the distance deviating angle in the patients with a distance deviation 30 PD, and, 10 PD in the patients with a distance deviation > 30 PD ) is one that was already used in previously published articles (reference ; Suh YW, Kim SH, Lee JY, et al. Conversion of Intermittent Exotropia Types Subsequent to Part-time Occlusion Therapy and Its Sustainability. Graefes Arch Clin Exp Ophthalmol 2006;244: doi: /s ). For your information, 26 patients out of 121 primary extropia had XT > 30 PD, and 3 patients out of 121 recurrent exotropia had XT > 30 PD. The differences of XT angle size between primary and recurrent exotropia (that is, smaller angle in the recurrent exotropia) is no wonder at all. And it was the reason why I used the reference value that is different according to the distant deviating angle. For example, if we apply the 10PD reference value to both of 45PD XT and 12PD XT, the criteria will be more severe for the case of 12 PD XT. If there is a patient with 12PD distant XT / 20 PD near XT, the D/N difference in the patient should be worthy to be considered as a larger D/N differences than that in a patient who have 45PD distant XT / 53PD near XT. In the manuscript, I already discussed as below ; (discussion in the manuscript) ; --We used the reference value of the D/N differences described by Suh et al.23 to avoid underestimating the change in the XT type in cases of recurrent XT with a low-grade distance angle. In cases with a distance angle greater than 30 PD, the reference value of the D/N difference was 10 PD; and in cases with a distance angle less than 30 PD, the reference value was one-third of the distance angle.

11 9. "The pseudo- DE type was preoperatively differentiated from the DE type in all the patients using the patch test, but the test was not performed in the patients with recurrent XT.8,16" It is no defined how many of these patients that preoperatively were selected as basic after the patch test were postoperatively selected as CI but because they were not patched the distance angle of deviation did not change. Your question how many of these patients that preoperatively were selected as basic after the patch test were postoperatively selected as CI this means how many patients of preoperative pseudo-divergence excess type were postoperatively selected as CI ; One patient among 11 patients with pseudo-de type XT showed CI type recurrent exotropia. We added Table 2 according to your advice (question # 12, 13, 14 ) and the table include the number of patients who were postoperative CI type from preoperative pseudo-de type. 10. There is a concern that preoperative measurements were rigorous in selecting patients into different groups. But postoperatively were is expected that patients somehow measured less XT because of the surgery criteria were not as rigorous. Two examples. No patching postoperatively. And applying the criteria that patients with less than 30 PD of XT at distance require less difference between near an distance to be considered CI or DE types of XT. -Your concern No patching postoperatively ; This study is a retrospective study. No patch test in recurrent exotropia was an inevitable limitation of the retrospective study. I already mentioned about the limitation in the last paragraph of the discussion part of the manuscript. ( the last paragraph was ; As far as we know, this is the first study that compared the distribution of the XT types according to the D/N difference between primary and recurrent XT after BLR recession to find out the possibility of secondary CI-type IXT. Limitation of this study is that it was a single-center study, which collected data retrospectively. Future studies should be

12 contemplated as multicenter and prospective studies in a large number of patients. Another limitation of this study is that the DE-type category included both the pseudo-de and true DE types and we did not perform a patch test to differentiate the pseudo-de type from the true DE type in the recurrent XT cases, as mentioned above. ) -Your concern applying the criteria that patients with less than 30 PD of XT at distance require less difference between near an distance to be considered CI or DE types of XT ; Please see the answer to question # In the pseudo DE type the D/N becomes minimal after the patch test". This is not clear at all. Patients with tenacious fusion break at near after patching one eye and those are consider pseudo DE XT. Please explain. Are you trying to say that those patients in whom the patch test resulted in no increase of the near deviation were excluded The sentence in my manuscript was In the pseudo-de-type IXT, the D/N difference becomes minimal after the patch test; and in IXT with a high AC/A ratio, the D/N difference becomes minimal in the D lens test after the patch test.4,8,16. It was a description of the general knowledge. To clarify the meaning, I changed the sentence as below ; In revised manuscript (p4); The pseudo-de-type IXT is generally differentiated from true DE type by the occlusion test. After the occlusion test, the near deviation increases and it becomes basic type. Meanwhile, IXT with a high AC/A ratio can be diagnosed when the near deviation increases in the D lens test after the occlusion.4,8,19 Your question Are you trying to say that those patients in whom the patch test resulted in no increase of the near deviation were excluded No, I didn t exclude preoperative true

13 divergence excess type( the patch test resulted in no increase of the near deviation that you said ). In my subject, there were 3 patients of true DE type and 11 patients of pseudo DE type after the occlusion test (See the results and the new table = table 2 in revised manuscript). 12. Is there a reason why authors did not also create another groups: preoperative Basic to postoperative DE, and preoperative DE to postoperative DE (this by the way seems to be the real control group here because preoperatively those patients had no near deviation at all. 13. How many preoperatively truly DE type of XT became CI type XT postoperatively? (Answer for question # 12 & 13) Your question Is there a reason why authors did not also create another groups ; There was already an explained reason in my manuscript (method part, p5) This categorization could not be performed in the preoperative DE-type XT because there were too few patients and there was no discrimination between the pseudo-de and true DE types in recurrent XT. Although we did not create groups in the preoperative DE type, we made a new table to show the data according to your advice. -- the part of results and added Table 2 in revised manuscript (p5) as below ; In the 14 preoperative DE types, four patients converted to the basic type, and one patient, to the CI type. These 5 patients were all pseudo-de type XT and all three of the true DE type XT maintained DE type in recurrent exotropia(table 2).

14 Results 14. The information presented shows that overall patients were basic and continue basic (Preoperative mean preoperative distance 27.54±9.75 PD, and the mean near-deviation angle was 26.22±11.71 PD. The mean postoperative distance deviation angle was 15.01±4.81 PD, and the mean near-deviation angle was 15.69±8.91 PD. However we do not information per group. Minimal changes could have moved patients around. Authors are not including important information. What were the preoperative and postoperative deviations per group DN deviations per group: Preoperative Basic POP Basic, Preoperative Basic POP CI, Preoperative Basic POP DE, Preoperative DE POP Basic, Preoperative DE POP Basic, Preoperative DE POP Basic. What are the differences between preoperative angles and postoperative angles. These information will help to understand those changes that could be very small (overall preoperative and post op who basic deviation I added the preoperative and postoperative deviations per group in the new table. (Table 2) 15. Discussion. There are several concerns 16. Authors indicate that postoperatively XT type composition changed. And showed an increased number of CI not seen preoperatively. But why did the authors ignore that the numbers of patients in the DE group increased by more than 100% patients in the basic type became DE postoperatively. Methodology authors indicate that they patched patients preoperatively, not postoperatively. Many of those postoperative DE patients could have been basic postoperatively if patching test was done. Something similar could had happened if the patients with CI would have been patched postoperatively. The distance deviation could have changed.

15 18. Only 1/14 patients with DE had a larger deviation. But 32/107 basic. This actually a strong indicator that recessing LR unlikely results in CI (assuming all other DE 13 continue as DE, fisher exact test 0.3) 19. A Fisher exact test indicates that the postoperative outcomes for both CI and DE were statically significant. (Answer to question # 16, 17, ) All 4 questions (# 16, 17, 18, 19) were concerns about the matter of the increased proportion of DE type XT in recurrent exotropia. The near fusion in intermittent exotropia is generally well-reserved(references; Wilson ME. Intermittent exotropia: When to observe and when to treat. J AAPOS 2011;15:518. von Noorden GK, Campos EC. Binocular vision and ocular moyility, 6th edition, Mosby, p ). Dr. Jampolsky typically made the point that, with rare exceptions, exodeviations begin as an exophoria that may deteriorate into intermittent exotropia and constant exotropia, and such deterioration usually occur first at distance. Therefore, pseudo-divergence excess is quiet common (references; von Noorden GK, Campos EC. Binocular vision and ocular moyility, 6th edition, Mosby, p , Wright KW, Strube YNJ, Pediatric Ophthalmology and Strabismus, 3rd edition, Oxford, p ). We can expect recurrent exotropia that occurred after the successful surgery can have a strong near fusion or maintain near exophoria state. The relative brief period of monocular occlusion in routine alternate cover test might be not enough to break up the strong and tonic near fusional convergence and might be not enough to disclose the full near deviation in the recurrent exotropia patients. If we performed occlusion test in the recurrent exotropia in our Basic to DE group, the near fusional convergence would have been broken and the basic pattern would have been revealed in DE type recurrent XT. All the preoperative conditions (in primary exotropia) were the state of indication for surgery. However, the recurrent exotropia cases were not. Even they had exotropia over 10PD and they had a recurrence, but most of them were still early to be indication of reoperation. So, we can suggest the increased DE type is very natural phenomenon in the recurrent exotropia which maintain a favorable fusional state. But the convergence insufficiency type in our recurrent exotropia deserves to be suspected that it is a secondary CI type affected by the BLR recession. The follow-up to recurrence or last follow-up years in Basic to CI group were not longer than Basic to Basic group and Basic to DE group(table 3 in previous manuscript = Table 5 in revised manuscript). In

16 addition, their near stereopsis and distant fusion control state(fcgx) were not worse than two other groups(fig 1). There were no other reasons they became CI type from the basic type. You also said Many of those postoperative DE patients could have been basic postoperatively if patching test was done. Something similar could had happened if the patients with CI would have been patched postoperatively. The distance deviation could have changed. in your Question #17. You are saying about the possibility of the presence of pseudo-ci type. If it can be possible(pseudo-ci type), the chance must be little as I ve explained above(; the recurrent exotropia that occurred after the successful surgery can be expected to maintain good fusion and the deterioration in IXT usually occur first at distance.). In most physician s clinical practice, the occlusion test is aimed to select pseudo DE types of XT and not to confirm the pseudo-ci types because it is relatively rare. In most cases of IXT, the near deviation control is usually preserved even when distance control is poor(reference; Wilson ME. Intermittent exotropia: When to observe and when to treat. J AAPOS 2011;15:518. ). Burian also mentioned that convergence insufficiency type develops in those with a basic exotropia that have a tendency for the deviation to increase(reference; von Noorden GK, Campos EC. Binocular vision and ocular moyility, 6th edition, Mosby, p ). We may, therefore, guess at the rareness of pseudo CI type. Also, Kushner & Morton had reported a result of occlusion test in exotropia patients and it showed 80 cases of pseudo DE types after occlusion test among 98 DE types before the test and only 2 cases of pseudo CI types after occlusion test among 26 CI types before the test (reference ; Kushner BJ and Morton GV. Distance/Near Differences in Intermittent Exotropia. Arch Ophthalmol 1998;116: doi: /archopht ). So we suggest a BLR recession effect in our results of the occurrence of the 33 CI types in the recurrent exotropia (no CI type in primary XT preop.). In addition, we added a sentence to the discussion as your recommend ; We suspect that an individual fusion mechanism might also influence the XT-type in recurrent XT in view of somewhat increased DE-types of recurrent XT. as described in the answer to the Question #2, 3. (Please see the answer to the Question #2, 3 ) We already discussed this issue in the manuscript. Please read paragraph given below ( from the discussion part of the manuscript p6 ). ; Twenty cases out of the 107 preoperative Basic-type XT were also converted into the DE type. However, we think that the Basic-to-DE groups didn t experience significant type change. We did not perform a patch test to differentiate the pseudo-de type from the true DE type in the recurrent XT cases. Although we did not confirm the cases using the patch test, recurrent DEtype XTs in Basic-to-DE group are actually pseudo-de-type XTs with the tenacious proximal

17 fusion (TPF) mechanism because a true DE type has inherent nature with unique features of large proximal convergence4,7 and there was a bare possibility that it was newly occurred postoperatively. Besides, many patients had a relatively small distance deviation angle in the Basic-to-DE group, even though there were no differences in time to the recurrence or total follow-up period between the three groups (Table 5). We suggested the Basic-to-DE group didn t demonstrate XT type change and it was a group representing good surgical outcome. But, the Basic-to-CI group didn t showed inferior surgical outcomes in the distance deviation angle, FCGX, and near stereopsis when compared to the Basic-to-Basic group and had the similar length of time to the recurrence and similar follow-up time to the other groups. We concluded the type change in the Basic-to-CI group could be surgically induced and the Basic-to-CI group was not merely a group of poor postoperative state. Also, we already discussed about your concern in question # 18 of Only 1/14 patients with DE had a larger deviation. But 32/107 basic. Please read paragraph given below ( from the discussion part of the manuscript p6 ). ; Also, only one CI-type XT (7.1%) was occurred in the 14 preoperative DE-type XTs. It is thought that a strong near fusion mechanism may maintain the near deviation in DE-type XT. This finding could support the hypothesis of Kushner that patients with the TPF(tenacious proximal fusion) mechanism fare better after LR recession than patients without the TPF mechanism. Figure 20. A B C are not really adding any information that is not in table 3 Figure 1 and Table 3(=Table 5 in revised manuscript) were not linked. The two were independent of each other. Please see the explanation below.

18 **The Table 3(=Table 5 in revised manuscript) demonstrates that there were no differences in Follow-up to recurrence, Last follow-up years, and amount of BLR recession among the three groups. **The Figure 1 demonstrates the postoperative sensory-motor outcomes according to the postoperative type change in recurrent exotropia from the preoperative basic-type exotopia. A shows Stereoacuity: no differences among the three groups / B shows Fusion control grade of the exodeviation (FCGX): no differences among the three groups. / C shows Distance deviation angle: The Basic-to-DE group had a significantly smaller angle deviation than the other groups. Reviewer #2: This is an interesting study which should be worthy to be published after adequate revision. However I have several concerns. 1. The study only evaluate those recurrent XT across 10 year period, and to study those preoperative characteristics of these recurrent XT. One of the major limitation is that those cases after BLR recession without recurrence are not included. It would be of higher interest and impact if these cases are also included, and that the actual proportion of cases developed into different types of recurrent XT can be compared with those without recurrence. If not possible to include these cases, these should be mentioned as the major limitation of the paper. Your concern ; those cases after BLR recession without recurrence are not included. The concept of types of exotropia is thing for the IXT, not for the exophoria. The concept of vergence abnormality including convergence excess, convergence insufficiency and divergence insufficiency is different concept from the type of IXT. In the exophoria less than 10 PD at

19 distance, the type should be hard to be mentioned. If there is a patient with 2PD x / 6PD x, I can t make any decision whether he has a convergence insufficiency or not. Also if there is a patient with 4PD x / 2 PD x, I cannot be sure that he is a DE type or basic type. So I don t think it will be possible the direct comparison between the actual proportion of cases developed into different types of recurrent XT and those without recurrence that you asked. Occasionally, I meet the case, for example, who has 4PD x / 15 x in my clinic and he may be suspected to be a convergence insufficiency after the exotropia surgery without recurrence at distance. I agree on your opinion that the occurrence of this kind of convergence insufficiency with exophoria after BLR recession would be of high interest and impact. But the analysis of this kind of cases is not linked with the purpose and title of this study ( to investigate the type of exotropia (XT) based on the distance-near (D/N) difference in recurrent XT after bilateral lateral rectus (BLR) recession ) I also have a great interest in the issue of exophoria patients who showed a pattern of convergence insufficiency that had a recurrence only in the deviation at near without recurrence in the deviation at distance. I will analyze about the issue in the future. Thank you for your comment and I am very happy you talked about the issue that I was very interested in. 2. I cannot understand p.4 line 33-36: "To compare the cases of primary and recurrent XT, nine patients with preoperative pseudo-de-type XT were assigned to the DE-type group, even though the pseudo-de type is actually a subset of the basic type." Any reason? The reason why nine patients with preoperative pseudo-de-type XT were assigned to the DEtype group is described as below (manuscript p4) The pseudo-de type was preoperatively differentiated from the DE type in all the patients using the patch test, but the test was not performed in the patients with recurrent XT. To compare the cases of primary and recurrent XT, nine patients with preoperative pseudo-de-type XT were assigned to the DE-type group, even though the pseudo-de type is actually a subset of the basic type. ; That means, DE group in recurrent XT should have presumed pseudo DE that was not be confirmed for the lack of postoperative occlusion test, so we made the preop DE group contain pseudo DE although pseudo DE was already differentiated by preop occlusion test.

20 Also, please see the newly added table (Table 2 in revised manuscript ) that showed the type from the preop true DE and preop pseudo DE, separately. 3. For table 2, multiple logistic regression are used to identify factors affecting the types changes. Why FCGX, distance deviation angle, stereoacuity, and corrective glasses are included? I would advice can conduct a univariate analysis between the two types changes to give you a preliminary idea whether any of the factors are potentially corrected. the results of the multivariate analysis depends a lot of the factors you have input. According to your recommend, I added a new table including statistical analysis between the two type changes separately. (Please see the Table 3 in revised manuscript) And for your question Why FCGX, distance deviation angle, stereoacuity, and corrective glasses are included? ; Convergence insufficiency type of IXT tends to be considered as a form of IXT with inferior binocularity. Dr. Jampolsky also said that, with rare exceptions, exodeviations begin as an exophoria that may deteriorate into intermittent exotropia and constant exotropia, and such deterioration usually occur first at distance.(reference; von Noorden GK, Campos EC. Binocular vision and ocular moyility, 6th edition, Mosby, p ) Burian mentioned that convergence insufficiency type develops in those with a basic exotropia that have a tendency for the deviation to increase(reference; von Noorden GK, Campos EC. Binocular vision and ocular moyility, 6th edition, Mosby, p ). In IXT, the ocular deviation can be controlled by the instinctive drive for binocular vision(reference; Wilson ME. Intermittent exotropia: When to observe and when to treat. J AAPOS 2011;15:518. ). Therefore, the preoperative clinical characteristics which I consider that they can affect the binocularity in IXT patients were selected and analyzed. In results, none of them affect the change in the XT type in the Basic-to-CI group and the Basic-to- DE group

21 4. The fusional control grade of the exodeviation (FCGX) is not standardized. Only two grade? You may consider grading it by Newcastle Control Score or using fusional parameters such as fusional reserve. Please consider adding reference to the paper: Yam JC, Chong GS, Wu PK, Wong US, Chan CW, Ko ST. A prospective study of fusional convergence parameters in Chinese patients with intermittent exotropia.j AAPOS Aug;17(4): Yes, I added the reference that you recommend. (new reference No. 21 in revised manuscript) I know that the fusion control grade can be subdivided into more grades than two grades. The grades were different in references (references ; Rosenbaum AL, Santiago AP. Intermittent Exotropia: Clinical Strabismus Management. Philadelphia: WB Saunders 1999: / Stathacopoulos RA, Rosenbaum AL, Zanoni D et al. Distance stereoacuity: assessing control in intermittent exotropia. Ophthalmology 1993;100: / Haggerty H, Richardson S, Hrisos S et al. The Newcastle Control Score: a new method of grading the severity of intermittent distance exotropia. Br J ophthalmology 2004;88:233-5.). I routinely assess the objective control grade in my office using the Rosenbaum s grading(reference; Rosenbaum AL, Santiago AP. Intermittent Exotropia: Clinical Strabismus Management. Philadelphia: WB Saunders 1999: ). -- Good control when the fusion breaks only after cover test and resumes fusion rapidly without need for a refixation / Fair control when a patient refixate other target to resume the deviation control after the cover test / Poor control when the fusion breaks spontaneously without any form of fusion disruption including the cover test. For this study, I bound good and fair from the medical record into one as good and designated poor from the medical record as poor based on the presence(poor) or absence(good & fair) of the spontaneous deviation at distance without any form of fusion disruption.

22 I already described the definition of good (actually good and fair in medical record) and poor grade for this study in the manuscript as below (p4); ; The FCGX data collected from the medical records were graded as good or poor at a fixation target of 6 m. The FCGX was graded good when the patient manifested the deviation after the cover test and resumed the fusion rapidly with blinking or with a refixation. The patients who exhibited the deviation spontaneously, without any form of fusion disruption, were defined as having had a poor FCGX. -the patient manifested the deviation after the cover test and resumed the fusion rapidly with blinking good in the medical record - ; above two were bound into one as good grade in my manuscript -patients who exhibited the deviation poor in both of the medical record and in the manuscript 5. Another limitation of the paper is the RETROSPECTIVE NATURE. Please add back to the limitation. I already described about the limitation in the manuscript. Please see the last paragraph of discussion. ; Limitation of this study is that it was a single-center study, which collected data retrospectively. 6. In the background, line 14-16, consider adding reference of the paper:

23 Yam JC, Wu PK, Chong GS, Wong US, Chan CW, Ko ST. Long-term ocular alignment after bilateral lateral rectus recession in children with infantile and intermittent exotropia.j AAPOS Jun;16(3): Yes, I added the reference that you recommend. (new reference No. 14 in revised manuscript) Editorial Requests Please note that all submissions to BMC Ophthalmology must comply with our editorial policies. Please read the following information and revise your manuscript as necessary. If your manuscript does not adhere to our editorial requirements this will cause a delay whilst the issue is addressed. Failure to adhere to our policies may result in rejection of your manuscript. Ethics: If your study involves humans, human data or animals, then your article should contain an ethics statement which includes the name of the committee that approved your study. If ethics was not required for your study, then this should be clearly stated and a rationale provided. Consent: If your article is a prospective study involving human participants then your article should include a statement detailing consent for participation. If individual clinical data is presented in your article, then you must clarify whether consent for publication of these data was obtained.

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