Title:Clinical and Optic Coherence Tomography Findings of Focal Choroidal Excavation in Chinese Patients

Transcription

1 Author's response to reviews Title:Clinical and Optic Coherence Tomography Findings of Focal Choroidal Excavation in Chinese Patients Authors: Jie Guo Lu Zhong Chunhui Jiang Xin Zhou Gezhi Xu Wenji Wang Yuliang Wang Version:2Date:15 April 2014 Author's response to reviews: see over

2 Clinical and Optic Coherence Tomography Findings of Focal Choroidal Excavation in Chinese Patients point-by-point response to the comments: Reviewer:Bruno Lumbroso **Discretionary Revisions I recommend the authors to read and add informations and conclusions from the following article: I observed with my co Authors positive correlation between Epstein-Barr virus infection and focal choroidal excavation. Observed positive correlation between Epstein-Barr virus infection and focal choroidal excavation. Authors Savastano MC, Rispoli M, Di Antonio L, Mastropasqua L, Lumbroso B.Journal: Int Ophthalmol Nov 6. [Epub ahead of print] Thanks. We added the following in our discussion (Discussion, 1st paragraph, line 12): On the other hand, recently Savastano MC et al found a positive correlation between Epstein-Barr virus infection and focal choroidal excavation, and Lee CS reported the changes of focal choroidal excavation in their observation[9,10], so further study is required to reveal the etiology of this entity, and the reference was modified correspondingly. Reviewer:Christopher Seungkyu Lee Major Compulsory Revision **1 Result, 4th paragraph: 8 with local retinal detachment (likely 7 CSCR and 1 nonconforming) There seems to be some confusion about how many CSC patients were included in this series. Authors stated in the abstract and other places that there were 4 CSC cases. I assume that out of these 7 CSC-looking OCT cases, only 4 cases were confirmed by fluorescein angiography. Authors may want to elaborate on these CSC-like nonconforming type FCE, perhaps with figures, since special attention was given to the characteristics of excavations with CSCR as stated in the introduction. What was the difficulty in differentiating active CSC from uncomplicated nonconforming FCE on OCT? Yes, out of the 7 eyes, 4 were confirmed to have CSC by FFA, other 3 were CSC-looking. What was the difficulty in differentiating active CSC from uncomplicated nonconforming FCE on OCT? That is a good question. Actually, it is not well described how to differentiate active CSC from uncomplicated nonconforming FCE by OCT. Since in both of these entities a localized retinal detachment is present on OCT, then FFA might be necessary to make the diagnosis. Our paper tried to present the characteristic of them in the discussion (Discussion, 4th paragraph, line 4), so OCT might be helpful in the differentiating. **Could choroidal thickness (if can be measured) help differentiating these eyes? Choroidal thickness in FCE was initially thought to be thickened (Margolis et al. Archives of ophthalmol 2011), but more recent reports found that it is not significantly thickened unless complicated by CSC.

3 That is a very good idea. It is a pity that choroidal thickness was not included in this study. This is a retrospective study and our OCT system did not have the EDI software until recently, so choroidal thickness was not included this time. The findings of recently studies are really interesting, and we added these in our discussion: And since recent study found that choroidal thickness was increased in FCE patients if complicated by CSC, so this could be another point that could be helpful in the differentiating (Discussion, 4th paragraph, line 17). **Authors described four differences between CSC-associated RD and nonconforming FCE-associated RD in the discussion (i.e. RD extent, location of ELM/IS/OS line, RPE changes, and association with type 1 FCE). Authors may want to use these points to address this issue. Please refer to some of the recent publications on CSC in FCE for further discussion. (Suzuki et al. Characteristics of Central Serous Chorioretinopathy Complicated by Focal Choroidal Excavation, Retina 2013; Ellabban et al. Focal Choroidal Excavation in Eyes With Central Serous Chorioretinopathy, AJO Lee CS et al. Clinical and Spectral-Domain Optical Coherence Tomography Findings in Patients with Focal Choroidal Excavation. ophthalmology, 2014) Thanks for that we referred to the publications in our discussion and made some mortification in our discussion : Also Ellabban A et al did not observe any change in the focal choroidal excavation during the follow-up. (Discussion, 1st paragraph, line 9). and Lee CS reported the changes of focal choroidal excavation in their observation, (Discussion,1st paragraph, line 14). The OCT images and the width and depth of the focal choroidal excavation in our series were similar to those of others, (Discussion, 3rd paragraph, line 1). The nonconforming cases that Ron Margolis, John C. Chen, Suzuki M and Ellabban A demonstrated were type 1 (Discussion, 3rd paragraph, line 9). And since recent study found that choroidal thickness was increased in focal choroidal excavation patients if complicated by CSC, so this could be another point that could be helpful in the differentiating, (Discussion, 4th paragraph, line 17) In the former reports, changes of RPE and abnormal choroidal circulation at focal choroidal excavation were found. So abnormality at the level of RPE or choroid might contribute to the pathogenesis of CSC or CNV in these patients. (Discussion, 5th paragraph, line 6) **2. Another issue with CSC. Authors may want to describe whether their CSC cases were in active phase or not. Good suggestion, in our result we wrote: A leaking spot within the excavation was observed in 4 patients who underwent FFA (Result, 5th paragraph, line 9). And in the discussion we highlighted that In our series, FFA confirmed acute CSCR in 4 eyes. (Discussion, 4th, line 8) **I have seen a nonconforming CSC/FCE with serous RD becoming a conforming type FCE after resolution of serous RD.Conversely, some cases remained nonconforming even after complete resolution of serous RD. The latter would represent an originally no originally conforming FCE

4 that assumed the appearance of nonconforming FCE with the development of CSC. Active CSC and nonconforming FCE may not be mutually exclusive. The true nature of FCE could be masked by active CSC or other RD-causing pathologies. That is really a very good question. As we had described in our paper, in 7 CSC-looking cases, only 4 was confirmed by FFA. And only these 4 cases were included in analyzing the characteristic of FCE cases accompanied with CSC. Just as the reviewer said if most of the subretinal fluid got absorbed, and only a very shallow layer was found within the choroidal excavation, it is really a challenge, if ever possible, to tell the nature of the case was an originally nonconforming case or a not-fully-recoveried CSC case by only OCT. FFA might be helpful if a positive leaking point could be found. On the other hand, it is said that the FFA findings in chronic CSC cases might be non-specific, so as you just pointed out choroidal thickness might be helpful. And longer follow-up and more cases might find out if this kind of cases (a very shallow layer of subretinal fluid within the choroidal excavation, and no leaking point on FFA) will actually turn into a confirming one or remain nonconforming. There is also possibility that there might be no nonconforming type at all, but only cases during the recovery from a former episode of CSC. Our knowledge in this field still needs to be improved. **3. An idea for typing FCE into 2 types based on steepness of excavation is interesting. Authors may want to describe the criteria for this typing in detail in the method section. Did you arbitrarily determine the type by gross evaluation of lesion contour on OCT? Yes, actually two doctors made the judge separately, if there is disagreement, the corresponding author made the final discussion. We added that in the method. (Data Collection, 2rd paragraph, line 7) **Was the ratio between lesion diameter and depth considered, perhaps? Could an angle (acute vs. obtuse, etc) formed between lateral margin of FCE and transverse line be used for some objectivity maybe? What was the implication of this typing? Authors stated that nonconforming FCE was more associated with steep FCE. Further analysis on this issue (perhaps with statistics and a table) would help highlight this interesting point. That is a very good suggestion. The angle and the ratio might be telling the same story, since we already have the data of the transverse diameter and depth, we calculated the ratio (transverse diameter/depth). And The ratio (transverse diameter/depth) was calculated, the ratio of type 1 was 4.57±1.65 and type ±5.2, significantly different was found between the two types(p=0.000). (Result, 4th paragraph, line 9). The implication of the typing is trying to analyze why the findings of OCT were different in different cases, like why someone was nonconforming, which might develop from a conforming one, and why others developed CSCR or CNV. But as we only had one nonconforming case, so the statistic analysis of the incidence of conforming and nonconforming in excavation cases of different types did not make any sense. We discussed the relationship between the contour of the excavation and other findings of OCT in the discussion (Discussion, 3rd paragraph, line 5-12).

5 Minor Essential Revisions **1. Abstract, Results: Abnormal changes in these eyes were more prominent Please clarify what these eyes refer to (type 1? Or type 2?). these eyes refer to all the eyes with focal choroidal excavation. It has been revised to in these eyes with choroidal excavation and this sentence was put ahead (Abstract, line 8) **2. Abstract, Results: There are growing interests in CNV associated with FCE (Lee JH et al. Choroidal neovascularization associated with focal choroidal excavation, AJO 2014; Xu H et al. Focal Choroidal Excavation Complicated by Choroidal Neovascularization, Ophthalmology 2013). Brief mention of 2 CNV cases in the abstract would benefit readers. The sentence Concomitant CNV was found in another 2 cases. was added in the abstract (Abstract, line 14) **3. Result : Table of demography and clinical features would help. Since we had 31 cases, the table would be quite large. We made one, but are not so sure if it is proper to put it in the article, so we put it in the supplement. **4. Result, 4th paragraph. Please clarify trans-illumination of the choroid at the choroidal excavation area (figure 1). Does it refer to fundus photograph? OCT? It would be better if this can be shown in figure 1 with legend. Thanks for the suggestion, we added on OCT in the sentence, and the legend too (Result, 4th paragraph, line 14) (fig 1B)( legend Fig1,line 8). **5. Discussion, 1st paragraph: Our series, which is the largest ever reported, This sentence needs to be readdressed, since there is a recent article with 41 FCE eyes of 38 patients. (Lee CS et al. Clinical and Spectral-Domain Optical Coherence Tomography Findings in Patients with Focal Choroidal Excavation. ophthalmology, 2014) We changed the sentence to Our series included 31 Chinese patients. (Discussion, 1st paragraph, line 2) Discretionary Revisions **1. Discussion, 1st paragraph: please put the citation number for Ron Margolis et al Thanks. The citation number has been added. (Discussion, 1st paragraph, line 12) **2. Putting % in parenthesis by some important figures (eg. % associated with CSC) would help readers to appreciate the finding. Thanks for your advice and the % had been added, refer to the percentage of CSCR and CNV, and different FCE types. (Result, 4th paragraph, line 1-3)