Dear Editor, We have read and reviewed the article entitled as "Choroidal structure in eyes with drusen and reticular pseudodrusen determined by binarisation of optical coherence tomographic images" by Corvi et al. with great interest [1]. The authors compared luminal and stromal areas of the choroid in eyes with drusen and reticular pseudodrusen (RPD), and investigated their changes over 24 months using optical coherence tomography (OCT). They found that the mean total choroidal, luminal, and stromal areas decreased similarly in eyes with drusen and RPD over the period of 24 months. The mean total choroidal, luminal, and stromal areas were reduced more in eyes with RPD when compared to the eyes with drusen, and the controls. We express our gratitude to the authors for this valuable study, and we would like to ask the authors some important points that may affect the study results.

Owing to its unique anatomic structure, choroid is one of the most excessively vascularized tissues in the body. Accordingly, various local, systemic or environmental factors that affect vascular system influence choroid [2,3]. Although Corvi et al. referred a number of factors affecting choroid, we suggest that some important points should also be addressed in the paper.

First, choroidal thickness (CT) has a significant diurnal variation. Animal studies have demonstrated that CT might increase up to 50% in an hour, and might decrease 100 ?m within 3-4 hours [3]. In a study, Usui et al. analyzed subfoveal CT of healthy individuals at three hours intervals, and discovered that CT demonstrated significant differences at all measurement points [4]. In that study, Usui et al. indicated that diurnal variation in CT might be up to 65 ?m (ranging between 8 and 65 ?m). Another study by Lee et al. that included 100 adults reported the mean amplitude of the diurnal variation in CT as 20.32 ? 10.40 ?m (ranging between 4 and 60 ?m) [5]. Therefore we would like to ask the authors whether they have considered diurnal variation of CT at baseline, and 24- month choroid measurements.

Second, various systemic diseases (endocrine, cardiovascular, rheumatologic, and inflammatory), and their medications may significantly affect CT [2]. Since the participants of the study are old, those points should be indicated in the paper.

Third, intraocular pressure and refractive status, which have well known effects on CT, should be indicated in the paper, and compared between the groups.

Fourth, we suggest that some important parameters that affect CT like systemic blood pressure, and body mass index of the participants should also be addressed in the paper. Moreover, alcohol, smoking, and caffeinated beverage consuming of the participants should be asked for before OCT measurements.

In summary, we suggest that the aforementioned factors affecting CT may also affect stromal and luminal areas of the choroid as well, and change the results of the study. We want to get the opinions of the authors in this regard.

References 1 Corvi F, Souied EH, Capuano V, Costanzo E, Benatti L, Querques L, et al. Choroidal structure in eyes with drusen and reticular pseudodrusen determined by binarisation of optical coherence tomographic images. Br J Ophthalmol. 2016; doi: 10.1136/bjophthalmol-2016-308548. 2 Tan KA, Gupta P, Agarwal A, Chhablani J, Cheng CY, Keane PA, et al. State of science: Choroidal thickness and systemic health. Surv Ophthalmol 2016; doi: 10.1016/j.survophthal.2016.02.007. 3 Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res 2010;29:144-68. 4 Usui S, Ikuno Y, Akiba M, Maruko I, Sekiryu T, Nishida K, et al. Circadian changes in subfoveal choroidal thickness and the relationship with circulatory factors in healthy subjects. Invest Ophthalmol Vis Sci 2012;53:2300-7. 5 Lee SW, Yu SY, Seo KH, Kim ES, Kwak HW. Diurnal variation in choroidal thickness in relation to sex, axial length, and baseline choroidal thickness in healthy Korean subjects. Retina 2014;34:385-93.

Conflict of Interest:

None declared

eLetter Comment on: Clinical outcomes of amniotic membrane transplantation in the management of acute ocular chemical injury Parul Chawla Gupta, MS; Jagat Ram, MS, FAMS Department of Ophthalmology Post Graduate Institute of Medical Education and Research, Chandigarh, India, 160012 Corresponding author Dr. Jagat Ram, MS, FAMS Professor and Head Department of Ophthalmology Post Graduate Institute of Medical Education and Research, Chandigarh, India, 160012 Email id: drjagatram@gmail.com Conflict of interest and source of funding- None declared

Dear Editor, We read with interest the recent paper by Westekemper and associates [1] analysing the morphological and functional outcomes of patients receiving AMT after ocular chemical burns. While the study is indeed interesting, we herein address important issues, some of which warrant further discussion. Firstly, as the authors stated in the abstract "In 37 eyes (51.4%), AMT was applied within the first 6 days after injury". However, in the manuscript it is mentioned that," thirty-seven eyes (50.0%) received the AMT within 6 days after trauma". Secondly, in the present study, the patients treated at University of Duisburg-Essen, Germany and the Newcastle University, UK were not matched as far as the treatment protocol was concerned. In Essen, oral ascorbic acid 1g twice daily, oral prednisolone starting at 150mg/day orally and artificial tear substitutes (hyaluronic acid 0.15%) up to every hour were given in addition to the what the patients received at Newcastle; which might have influenced the final outcomes after AMT. Hence, the beneficial outcomes reported in the study may not be completely attributed by the use of AMT alone. However, we strongly believe that the once a day dose of dexamethasone 0.1% or prednisolone 1% given to patients in Essen was grossly inadequate since frequent topical steroids [2] remain the mainstay of treatment in ocular chemical burns primarily in the early stages since they reduce inflammatory cell infiltration and stabilize neutrophilic cytoplasmic and lysosomal membranes. Thirdly, repeated AMTs were necessary in 27 eyes (37.5%) due to Persistent Epithelial Defect (PEDs) and 12 eyes (16.6%) required more than 2 AMTs. Interestingly, an alternative non-surgical approach to the management of acute ocular chemical burn can be fingerprick autologous blood which can be used for early healing of persistent epithelial defects as shown in a recent study by Wawrzynski et al [3].

References 1. Westekemper H, Figueiredo FC, Siah WF, et al. Clinical outcomes of amniotic membrane transplantation in the management of acute ocular chemical injury. Br J Ophthalmol 2016;0:1-5. 2. Davis AR, Ali QH, Aclimandos WA, Hunter PA. Topical steroid use in the treatment of ocular alkali burns. Br J Ophthalmol 1997;81(9):732-734. 3. Wawrzynski J, H Mukherjee H, J Moore J, et al. Fingerprick autologous blood for dry eyes and persistent epithelial defects. Eye 2016;30:635-636.

Conflict of Interest:

None declared

The third point the authors raise is the variance of quality of life with the grade of corneal opacity. The grade of corneal opacity in the present study was graded as per the type (nebular, macular, leucoma), location, size and depth of involvement. A total of 571 eyes of 435 patients were detected with corneal opacity. For the purpose of analysis, the corneal opacity was divided into three grades ranging from mild to severe. As the VFQ scores were recorded per person and the corneal opacity was recorded eyewise, some cases had to be excluded from analysis. All unilateral cases and bilateral cases with same grade of corneal opacity in both eyes were used to compute VFQ scores in different grades of corneal opacity. Forty cases with dissimilar grade of corneal opacity in two eyes were excluded. The table below shows the variance of VR-QoL with grade of corneal opacity and demonstrates that VR-QoL varies significantly in the first two domains of vision function.? Table 2: Vision Function scores by grade of corneal opacity in the study population (n=395)*

Again, we would like to reiterate that the results presented in our paper are a part of a well planned population-based epidemiological study and demonstrate the findings in this rural population. It is possible that married population in our study had better quality of life as compared to unmarried or widows/widowers in contrast to other populations described in earlier reports. We further explored reasons for this observation and we found that the married population was younger (Mean age=57.5 vs 69.9 of unmarried/divorced population). Hence, age could play as a confounding factor in this association.

References: 1. Vashist P, Gupta N, Tandon R, Gupta SK, Dwivedi S, Mani K. Population- based assessment of vision-related quality of life in corneal disease: results from the CORE study. Br J Ophthalmol. 2016 May;100(5):588-93.

Conflict of Interest:

None declared

Dear Editor,

We would like to thank Dr. Uzun and Dr. Pehlivan for showing interest in our study.[1] It is well-known that various factors may influence choroidal thickness. In our study,[1] there was no significant difference in the age, sex, spherical equivalents, and incidence of diabetes mellitus and hypertension between the ranibizumab and aflibercept groups. As mentioned, the limitation of our retrospective study was that all potential influencing factors could not be perfectly controlled. Therefore, we agree with the opinion of Dr. Uzun and Dr. Pehlivan that these uncontrolled factors could influence the data obtained from our study. Dr. Uzun and Dr. Pehlivan particularly focused on the intraocular pressure (IOP) and diurnal variation on choroidal thickness. Unfortunately, the exact time of optical coherence tomography (OCT) scanning is normally not recorded in our institution. Thus, it is not possible to show whether the diurnal variation influenced our study result. In our institution, IOP is routinely measured during every visit using a pneumo-tonometer.

To evaluate whether IOP significantly influences the study result, we reviewed the IOP values before and after the treatment. Since the primary outcome of our study was to compare the difference in changes in choroidal thickness between eyes treated with ranibizumab and aflibercept, the IOP values were compared between the ranibizumab and aflibercept group. In all the included eyes, the IOP at diagnosis and one month after the third intravitreal anti-vascular endothelial growth factor (VEGF) injection was 13.6 +/- 3.2 and 13.6 +/- 3.0, respectively. In typical neovascular AMD, the IOP at diagnosis and that after treatment in the ranibizumab group was 13.7 +/- 3.4 and 12.8 +/ - 2.8, respectively. The values in the aflibercept group were 14.0 +/- 3.0 and 13.9 +/- 3.1, respectively. There was no significant difference in the IOP at diagnosis (P = 0.571) and after treatment (P = 0.406) between the two groups. In polypoidal choroidal vasculopathy, the IOP at diagnosis and after treatment in the ranibizumab group was 13.8 +/- 3.3 and 14.1 +/- 3.1, respectively, while the values in the aflibercept group were 13.2 +/- 3.3 and 13.2 +/- 2.9, respectively. There was no significant difference in the IOP at diagnosis (P = 0.297) and after treatment (P = 0.374) between the two groups. In retinal angiomatous proliferation, the IOP values at diagnosis and after treatment in the ranibizumab group were 13.5 +/- 2.5 and 14.5 +/- 3.1, respectively, while those in the aflibercept group were 13.5 +/- 3.8 and 13.1 +/- 3.1, respectively. There was no significant difference in the IOP at diagnosis (P = 0.983) and after treatment (P = 0.194) between the two groups. Although the matter is controversial,[2,3] several studies have shown that there is an association between IOP and subfoveal choroidal thickness.[4,5] The result of the additional analysis on IOP shows that IOP may not significantly influence the result of our study. We hope further studies with a more controlled design may better elucidate the difference in the changes in choroidal thickness after injection of different anti-VEGF agents.

REFERENCES

1.Kim JH, Lee TG, Chang YS, et al. Short-term choroidal thickness changes in patients treated with either ranibizumab or aflibercept: a comparative study. Br J Ophthalmol 2016. doi: 10.1136/bjophthalmol-2015- 308074. [Epub ahead of print] 2.Pekel G, Acer S, Yagci R, et al. Relationship Between Subfoveal Choroidal Thickness, Ocular Pulse Amplitude, and Intraocular Pressure in Healthy Subjects. J Glaucoma 2016. doi: 10.1097/IJG.0000000000000401. [Epub ahead of print] 3.Wei WB, Xu L, Jonas JB, et al. Subfoveal choroidal thickness: the Beijing Eye Study. Ophthalmology 2013;120:175-80. 4.Wang YX, Jiang R, Ren XL, et al. Intraocular pressure elevation and choroidal thinning. Br J Ophthalmol 2016. doi: 10.1136/bjophthalmol-2015-308062. [Epub ahead of print] 5.Saeedi O, Pillar A, Jefferys J, et al. Change in choroidal thickness and axial length with change in intraocular pressure after trabeculectomy. Br J Ophthalmol 2014;98:976-9.

Conflict of Interest:

None declared