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Recent eLetters

Displaying 1-10 letters out of 524 published

  1. Re:Comment on: Short-term choroidal thickness changes in patients treated with either ranibizumab or aflibercept: a comparative study

    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

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  2. Comment on: Population-based assessment of vision-related quality of life in corneal disease: results from the CORE study

    eLetter Comment on: Population-based assessment of vision-related quality of life in corneal disease: results from the CORE study 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 Vashist and associates [1] assessing the impact of corneal disease on vision-related quality of life (VR-QoL) in a rural North Indian population. We herein address important issues, some of which warrant further discussion. Firstly, as the authors stated "The Vision Related Quality of Life (VR-QoL) was assessed in 435 cases with corneal disease and 435 controls without any ophthalmic disease". However, in Table 1, under the subheading of 'marital status'; the total number of controls add upto 436. Secondly, in the present study, there was no statistically significant difference in VR-QoL scores between unilateral and bilateral corneal conditions. We strongly believe that patients with bilateral corneal involvement may have significantly more effect on the quality of life as compared to the unilateral [2] cases. Activities of daily living, as well as the ability to drive vehicles would be affected more in bilateral cases. Thirdly, no mention has been made of the variance of quality of life with the grade of corneal opacity. Lastly, an interesting observation in the present study was that in the cases with corneal disease, married patients had better scores on the IND-VFQ-33 questionnaire as compared to unmarried or widows/widowers in contrast to the study by Onakoya et al [3] carried out in glaucoma patients, in whom marital status had no significant effect on QoL scores. No competing interests References 1. Vashist P, Gupta N, Tandon R. Population-based assessment of vision- related quality of life in corneal disease: results from the CORE study. Br J Ophthalmol 2016;100:588-593. 2. Vu HTV, Keeffe JE, McCarty CA, Taylor HR. Impact of unilateral and bilateral vision loss on quality of life. Br J Ophthalmol 2005;89:360-363 3. Onakoya AO, Mbadugha CA, Aribaba OT, Ibidapo OO. Quality of life of primary open angle glaucoma patients in lagos, Nigeria: clinical and sociodemographic correlates. J Glaucoma. 2012;21(5):287-95.

    Conflict of Interest:

    None declared

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  3. The role of enhanced depth imaging optical coherence tomography in chronic Vogt-Koyanagi-Harada disease

    Dear Editor, We have read and reviewed the article entitled "The role of enhanced depth imaging optical coherence tomography in chronic Vogt-Koyanagi-Harada disease''which was written by Jap and Chee with great interest [1]. The authors evaluated 52 patients with chronic Vogt-Koyanagi-Harada (VKH) disease using indocyanine green angiograms (ICGAs) and optical coherence tomography (OCT). They discovered that the subfoveal choroidal thickness (SFCT) was thinner when ICGA was calm and thicker when the ICGA was active. Jap and Chee suggested that the positive correlation of SFCT measurements with ICGA score supporting that it might be used to monitor disease activity in chronic VKH in addition to ICGA, possibly reducing the number of ICGAs required. We would like to congratulate the authors for the valuable studies of them and ask them to give more details and contribute to the article.

    Firstly, choroidal thickness (CT) gets affected from various local and systemic factors. For example, many local diseases (glaucoma, age- related macular degeneration, strabismus, etc.), and systemic diseases (diabetes mellitus, hypertension, hyperlipidemia, vasculapathies, etc.) and physiological conditions (such as menstrual cycle and pregnancy) may have an effect on CT. Average age of 52 patients have been mentioned to be 51.7?14.1 years and 26 of them have been mentioned to be females. We would like to ask the authors if they have taken local/systemic diseases and their drug used for their treatment and physiological conditions of the patients into consideration.

    Secondly, it is known that many factors in relation with eyes such as axial length of eye, intraocular pressure, and refractive error certainly affect CT [2,3]. We think that these parameters must be stated in the article.

    Thirdly, we also would like to learn body mass indexes, systemic blood pressure measurements, fasting and postprandial, sleeping and exercising conditions of the patients, and their consumption of caffeinated/non-caffeinated beverages before OCT measurements, since all these parameters are known to be apparently affecting CT [2,3].

    Fourthly, CT demonstrates considerable diurnal alteration. The thickness of choroid is able to increase by 50% in an hour, and increase its thickness by four times in few days [2]. It has been demonstrated by Kee et al. that the choroid can get thinner very fast, by about 100 micrometer in 3-4 hours in chicks [4]. CT in 12 healthy humans was measured in another prospective study by Tan et al. with intervals of two hours between 9:00 AM-5:00 PM on two different days, and significant differences in CT were determined within all measurement points [5]. It has been found by Tan et al. that mean diurnal amplitude of CT was 33.7?21.5 micrometer (range: 3-67 micrometer). The alteration in CT was also correlated with alterations in systemic blood pressure.

    In consideration of those literature data, we are of the opinion that all local and systemic factors must be considered in the studies in which CT is evaluated.

    Competing interests: None

    References

    1 Jap A. Chee S-P. The role of enhanced depth imaging optical coherence tomography in chronic Vogt-Koyanagi-Harada disease. Br J Ophthalmol 2016;0:1-4. 2 Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res 2010;29:144-68. 3 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. 4 Kee CS, Marzani D, Wallman J. Differences in time course and visual requirements of ocular responses to lenses and diffusers. Invest Ophthalmol Vis Sci 2001;42:575-83. 5 Tan CS, Ouyang Y, Ruiz H, Sadda SR. Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 2012;53:261-6.

    Conflict of Interest:

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  4. Re:Comment on: Changes observed in diabetic retinopathy: eight-year follow-up of a Spanish population

    Response to E-letter. Thank very much for reading our article. It is true that oral insulin analogues can lead to increased growth hormone, increasing its effect over diabetic retinopathy, but previously it should exist a blood-retina barrier (BRB), despite in patients with preexisting diabetic retinopathy the BRB rupture exist in some amount. It is possible that oral insulin analogues can affect the diabetic retinopathy level, but in patients without diabetic retinopathy the BRB should be intact. In the present study we demonstrate two findings, the first is the number of patients with any-DR who increased selectively in two age groups: in patients with age between 41-50 and patients with age between 51-60; and the second finding is that patients with advanced-DR, showed an increase in the 31- 40, 41-50, 51-60 and 61-70 age groups. In all groups the HbA1c increased progressively since 2008 to 2014. Can the insulin analogues do any effects? It is difficult to give an answer. Attending our knowledge is a possibility, but I say you a question. What is the more important effect over the diabetic retinopathy the bad glycemic levels or the treatment by insulin or analogues, due this bad control? In fact, is very difficult to answer this question, in our initial studies long time ago ( ), the insulin is an independent factor in diabetic retinopathy development, but when we apply multivariate analysis using logistic regression the insulin is a confounding risk factor overlapped to glycemic levels. Respect our conclusion about a poor control of glycemic levels in the previously cited age groups is a reality in our Country, it seems it exists a relaxation in diabetes control exercised by patients, and all staff involved in the treatment of diabetes should strive to re-educate patients with diabetes, reminding how important is the glycemic control to prevent serious complications such as diabetic retinopathy. Finally thank you very much for your contribution to our problem. References. 1. Romero-Aroca P, Salvat-Serra M, Mendez-Marin I, Martinez-Salcedo I. [Is microalbuminuria a risk factor for diabetic retinopathy?]. J Fr Ophtalmol. 2003;26(7):680-4. 2. Romero-Aroca P, Calvino-Dominguez O, del Castillo-Dejardin D. [Epidemiologic study of diabetic retinopathy in a primary care unit]. Arch Soc Esp Oftalmol. 2000;75(3):147-52. 3. Romero-Aroca P, Espeso-Sentis O, Sarda-Aure P, del Castillo-Dejardin D. [Relationship between microalbuminuria and diabetic retinopathy in type 1 diabetes mellitus]. Rev Clin Esp. 2000;200(7):351-4.

    Conflict of Interest:

    None declared

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  5. Predictive value of QFT-G alone in cases of presumed ocular tuberculosis

    Dear Editor,

    We read with interest the article titled "Predictive factors for treatment failure in patients with presumed ocular tuberculosis in an area of low endemic prevalence" by Agarwal et al published in Br J Ophthalmol 2016;100:348-355.

    We wanted to point out few things regarding the article - The diagnosis of ocular tuberculosis was presumptive in most cases. The authors have used clinical guidelines from an article by Gupta et alignment published in 2007.[1]The same authors have published revised criterion in 2010.[2]It would have been more appropriate to use the latter more recent guidelines. The authors do not provide a break-up of the morphological forms of posterior uveitis considered as tubercular in the present series. Few categories of posterior uveitis such as serpiginous choroiditis and vasculitis may have been included as ocular tuberculosis only on basis of Quantiferon gold test positivity. All patients with these diagnosis may not actually be due to active tubercular infection.[3] Rather only a subset of these patients may be due to active tuberculosis. Thus it is difficult to analyse treatment failure in cases where the aetiology is not very certain. The findings of the authors of higher failure rate of Anti-tubercular therapy (ATT) in those given higher doses of immunosuppressives could also indicate that the disease process is not due to active tubercular infection. The ATT has probably no role in the management of these disorders and it is actually the immunosuppression that is working. The failure may be due to inadequate or rapid withdrawal of immunosppression. Thus it may not be prudent to attribute failure to some property of tubercular infection when the diagnosis of tuberculosis itself is probable or questionable. The authors donot mention if any cases had side-effects of the anti- tubercular medication or if any patients dropped out. The authors mention that the decision to start ATT was based on discretion of physician. Although from the article it appears that the onus of starting ATT was with the treating ophthalmologist as it was started only on basis of ocular findings and QFT-G positivity even in the absence of systemic evidence of tuberculosis. The authors mention in the end that the evidence base for benefit of oral steroids in TB-associated uveitis is weak. However we feel that the contrary, i.e. evidence of benefit of ATT in certain cases of presumed ocular tuberculosis is weak as in most studies ATT has been given in combination with steroids and not alone.

    References 1: Gupta V,Gupta A,Rao NA.Intraocular tuberculosis--an update.Surv Ophthalmol 2007;52:561-87. 2: Gupta A, Bansal R, Gupta V, Sharma A, Bambery P. Ocular signs predictive of tubercular uveitis.Am J Ophthalmol. 2010 Apr;149(4):562-70. doi: 10.1016/j.ajo.2009.11.020. Epub 2010 Feb 10. 3: Nazari Khanamiri H, Rao NA.Serpiginous choroiditis and infectious multifocal serpiginoid choroiditis. Surv Ophthalmol. 2013 May- Jun;58(3):203-32.

    Conflict of Interest:

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  6. Comment on: Changes observed in diabetic retinopathy: eight-year follow-up of a Spanish population

    I read with great interest the article by Romero- Aroca et al. titled "Changes observed in diabetic retinopathy: eight-year follow-up of a Spanish population" [1]. Insulin usage has found to be a risk factor for progression of DRP. Authors conclude this result as relaxation of patients in metabolic control. Beside this conclusion, insulin analogues may directly cause progression of DRP. Insulin and its analogues stimulate insulin like growth hormone-1 (IGF-1) receptors, like growth hormone. There is a strong relationship between growth hormone and progression of DRP. Diabetic retinopathy regresses after surgical ablation or spontaneous infarction of pituitary gland [2]. Growth hormone deficiency is a protective factor for development of diabetic retinopathy in dwarfs [3]. Development of diabetic retinopathy is significantly higher in pubertal subjects than pre -pubertal subjects, despite the same glycemic control [4]. Thus, insulin analogues may cause progression of DRP through growth hormone-like effect. But I hypothesize that insulin analogues may cause progression of DRP only after deterioration of inner blood retinal barrier [5]. Hyperglycemia is a major risk factor for development of DRP. High blood glucose levels cause inner blood-retinal barrier deterioration by polyol pathway, non-enzymatic protein glycation and oxidative stress. Insulin analogues decrease blood glucose level and protect pericytes and inner blood-retinal barrier. When inner blood-retinal barrier is intact, insulin analogues may pass into the retinal tissue in very small amounts. After impairment of inner blood retinal barrier, insulin analogues may pass into the retinal tissue in much more amounts. Thus, insulin analogues may pass retinal tissue after impairment of inner blood retinal barrier and cause progression of DRP by growth hormone like effect. But before impairment, analogues can not pass through inner blood retinal barrier to cause progression of DRP, even delay onset of DRP by decreasing high blood glucose that impair pericytes.

    References 1. Romero-Aroca P, de la Riva-Fernandez S, Valls-Mateu A, Sagarra-Alamo R, Moreno-Ribas A, Soler N. Changes observed in diabetic retinopathy: eight- year follow-up of a Spanish population. Br J Ophthalmol. 2016 Jan 14. 2. Adams, D.A., Rand, R.W., Roth, N.H., Dashe, A.M., Gipstein, R.M., Heuser, G. Hypophysectomy in diabetic retinopathy. The relationship between the degree of pituitary ablation and ocular response. Diabetes. 1974;23:698???707. 3. Merimee, T.J. A follow-up study of vascular disease in growth-hormone-deficient dwarfs with diabetes. N Engl J Med. 1978;298:1217???1222. 4. Murphy, R.P., Nanda, M., Plotnick, L., Enger, C., Vitale, S., Patz, A. The relationship of puberty to diabetic retinopathy. Arch Ophthalmol. 1990;108:215???218. 5. Kaya A, Kar T, Aksoy Y, Ozalper V, Basbug B. Insulin analogues may accelerate progression of diabetic retinopathy after impairment of inner blood-retinal barrier. Med Hypotheses. 2013 Dec;81(6):1012-4. 4.

    Conflict of Interest:

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  7. Comment on: Short-term choroidal thickness changes in patients treated with either ranibizumab or aflibercept: a comparative study

    Dear Editor,

    We have read and reviewed the article entitled as "Short-term choroidal thickness changes in patients treated with either ranibizumab or aflibercept: a comparative study'' by Kim et al. with interest.1 The authors analyzed 240 eyes of 240 treatment-naive neovascular AMD patients who treated with three-monthly injections of either ranibizumab (ranibizumab group) or aflibercept (aflibercept group). They analyzed the choroidal thickness (CT) alterations between the time of diagnosis and 3 months later, and compared them between two groups. They demonstrated a greater decrease in CT in eyes treated with aflibercept compared to the eyes treated with ranibizumab. We would like to ask for further details, and contribute to the article.

    As mentioned in the discussion section of the paper, a number of factors including diurnal variation, refractive error, axial length (AL), diabetes mellitus, hypertension, and consumption of water or coffee might affect CT. However, we wonder intraocular pressure (IOP), use of local or systemic drugs, smoking, sleep and exercise status, consumption of alcohol before optical coherence tomography (OCT), and whether body mass index, and systemic blood pressure of the patients were taken into consideration. We also wonder lightening of the test room since all of the aforementioned factors have been shown to affect CT significantly.2 3

    For instance, Sanchez-Cano et al. demonstrated a strong negative correlation between subfoveal CT and AL in healthy adults.4 In addition Saeedi et al. showed a negative correlation between mean CT and IOP.5 On the other hand, intravitreal ranibizumab and aflibercept may cause a significant increase in IOP6-8, and a significant alteration in CT. Therefore, IOP must be analyzed on control examinations just before OCT measurements. Additionally CT shows a significant diurnal variation. The choroid could increase its thickness by 50% in an hour, and quadruple its thickness in a few days.4 Kee et al. found that the choroid could thin very rapidly, by about 100 micron, in 3-4 h in young chicks.9 Usui et al. showed that CT might show a diurnal variation up to 65 micron in healthy individuals.10

    It is highly likely that all those parameters could affect the data obtained from the study, and the results of the statistical tests. Therefore, one should act with suspicion towards the results of this study.

    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 Akay F, Gundogan FC, Yolcu U, et al. Choroidal thickness in systemic arterial hypertension. Eur J Ophthalmol 2016;26:152-7.

    3 Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res 2010; 29:144-68.

    4 Sanchez-Cano A, Orduna E, Segura F, et al. Choroidal thickness and volume in healthy young white adults and the relationships between them and axial length, ammetropy and sex. Am J Ophthalmol 2014;158:574-83.e1.

    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.

    6 Dedania VS, SJ Bakri. Sustained elevation of intraocular pressure after intravitreal anti-vegf agents: What is the evidence? Retina 2015;35:841-58.

    7 Freund KB, Hoang QV, Saroj N. Intraocular pressure in patients with neovascular age-related macular degeneration receiving intravitreal aflibercept or ranibizumab. Ophthalmology 2015;122:1802-10.

    8 Hoang QV, Tsuang AJ, Gelman R, et al. Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy. Retina 2013;33:179-87.

    9 Kee CS, Marzani D, Wallman J. Differences in time course and visual requirements of ocular responses to lenses and diffusers. Invest Ophthalmol Vis Sci 2001;42:575-83.

    10 Usui S, Ikuno Y, Akiba M, 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.

    Conflict of Interest:

    None declared

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  8. Comparison of trabeculectomy versus Ex-PRESS: 3-year follow-up.Gonzalez-Rodriguez et al.doi:10.1136/bjophthalmol-2015-307161.

    We read with great interest the study titled as "Comparison of trabeculectomy versus Ex-PRESS: 3-year follow-up" by Gonzalez-Rodriguez et al [1].We congratulate their efforts for conducting the study with a follow up of 3 years, making the results more significant.They concluded that success rates, mean IOP, number of anti-glaucoma medications and final visual acuities were similar between the two groups after 3 years. The positive points in favour of Ex-PRESS implant, are its standardized pore size leading to more predictable filtration and consequently avoidance of hypotony & other complications and a shorter learning curve.

    Interestingly many studies have also claimed that Ex-PRESS has a faster visual recovery. In fact, the authors showed from their first year data that by one month the Ex-PRESS group reached the baseline acuity whereas in the trabeculectomy group, acuity remained significantly lower from baseline at each study visit from day 1 to 6 months. However, when excluding patients who needed a repeat glaucoma procedure, the acuity was found to be better in Ex-PRESS group compared to Trabeculectomy group at all time points. In our opinion, this data would have been more promising had the authors mentioned the test-retest variability as well as the confidence intervals of the visual acuity measurements in either group. The e?ects of the Ex-PRESS device on cornea were previously evaluated by the authors in their 1 year results [2]. We are keen to know their findings with regards to corneal health at last follow-up.

    The results of this study are consistent with other published reports, proving that, there is actually no difference in success rates between Ex-PRESS and trabeculectomy [3,4]. Though Ex-PRESS implant is considered to be another good option in our surgical armamentarium, the significant cost difference needs to be considered in conjunction with e?cacy and safety, if Ex-PRESS is to supersede trabeculectomy [5].

    REFERENCES -

    1. Gonzalez-Rodriguez JM, et al. Br J Ophthalmol 2015

    2. Wagschal et al. Prospective Randomized Study Comparing Ex-PRESS to Trabeculectomy: 1-Year Results. J Glaucoma 2015;24:624-629.

    3. Netland PAet al. Randomized, prospective, comparative trial of EX- PRESS glaucoma filtration device versus trabeculectomy (XVT study). Am J Ophthalmol 2014;157:433-40.e3.

    4. Dahan E, Ben Simon GJ, Lafuma A. Comparison of trabeculectomy and Ex-PRESS implantation in fellow eyes of the same patient: a prospective, randomised study. Eye (Lond) 2012;26:703-10.

    5. Buys YM. Trabeculectomy with ExPRESS: weighing the benefits and cost. CurrOpin Ophthalmol 2013;24:111-18.

    Conflict of Interest:

    None declared

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  9. Characteristics and quantification of vascular changes in macular telangiectasia type 2 on optical coherence tomography angiography

    EDITOR:

    With great interest,We have read the article by Chidambara1 and partners on characteristics and quantification of vascular changes in macular telangiectasia type 2( MacTel 2) on optical coherence tomography angiography(OCTA).The authors concluded that OCTA helps understand the pathology and disease progression better in MacTel 2.We commend their interesting and important work on this subject.However, we have a question for the authors concerning intra- and inter-observer variation and the reproducibility of the OCTA examination.

    As far as I know, reproducibility and repeatability are indicators of the applicability of any instrument as a diagnostic tool in clinical practice2.OCTA is extremely sensitive to motion, some images had significant artifacts even with the motion correction algorithm. Operator learning curve, media opacity, and patient cooperation were factors in poor-quality images3.If the subjects had repeated instances of unstable fixation,the image would appear with white ambiguous lines.The analysis software would mistake these white ambiguous lines for blood vessels and would overestimate the retinal vessel density.Therefore,intra- and inter- observer variation would be relatively large. I think the authors should perform a reproducibility analysis to prove the stability of the OCTA system examination.If such an analysis had been performed and intra- and inter- observer variation exceeded a certain percent,the results of this study might have been shown to be unreliable.

    REFERENCES 1. Chidambara L, Gadde SGK, Yadav NK, et al. Characteristics and quantification of vascular changes in macular telangiectasia type 2 on optical coherence tomography angiography. Br J Ophthalmol 2016:2015- 307941. 2. Carpineto P, Mastropasqua R, Marchini G, et al. Reproducibility and repeatability of foveal avascular zone measurements in healthy subjects by optical coherence tomography angiography. Br J Ophthalmol 2015. 3. Hwang TS, Gao SS, Liu L, et al. Automated Quantification of Capillary Nonperfusion Using Optical Coherence Tomography Angiography in Diabetic Retinopathy. JAMA OPHTHALMOL 2016:1-7.

    Conflict of Interest:

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  10. Cigarette smoke extract-mediated oxidative stress and fibrotic-related genes expression may contribute to poor response to steroids therapy in Graves' ophthalmopathy

    We read with great interest the article entitled "Smoking was associated with poor response to intravenous steroids therapy in Graves' ophthalmopathy" by Xing et al [1]. Cigarette smoking is known to be the most important risk factor for the development or deterioration of GO, and it is associated with poor response to treatment for GO. However, the exact mechanisms which prove deleterious effect of cigarette smoking on GO remain poorly understood.

    It has been suggested that smoke-induced generation of reactive oxygen species (ROS) may play a role in the pathogenesis of GO, either through direct contact with the paranasal sinuses, or indirectly through the bloodstream [2]. Previously, we had revealed that smokers had significant higher urinary 8-OHdG (product of oxidative DNA damage) than never smokers in GO patients [3]. Recently , we observed that cigarette smoke extract (CSE)-induced more cytotoxicity and ROS accumulation in a dose-dependent manner in the GO orbital fibroblasts as compared to those of normal controls. The increased generation of ROS, especially the superoxide anions and hydrogen peroxide, can stimulate orbital fibroblasts proliferation and induce the production of pro-inflammatory cytokines, being key pathological features of GO [4]. More importantly, we also noted that cigarette smoke-mediated oxidative stress could induce fibrotic-related genes expression, including apolipoprotein J, fibronectin, and connective tissue growth factor (CTGF) in the GO orbital fibroblasts (169%, 180%, and 170%, respectively) , and these inductions could be inhibited by pretreatment with antioxidants.

    Apolipoprotein J, fibronectin, and CTGF are all important fibrogenic factors. Especially, CTGF is critical for TGF-beta-mediated fibroblast-myofibroblast transdifferentiation and subsequent extracellular matrix deposition [5], which may contribute to the tissue remodeling and fibrosis process in GO. Besides, CSE has been reported to stimulate adipocyte differentiation in GO orbital fibroblasts either by synergizing with ROS or interleukin -1 [2,6]. Collectively, previous reports and our current findings may explain, in part, why smoking is associated with poor response to immunosuppressive therapy in GO.

    References

    1. Xing L, Ye L, Zhu W, Shen L, Huang F, Jiao Q, Zhou X, Wang S, Wang W, Ning G. Smoking was associated with poor response to intravenous steroids therapy in Graves' ophthalmopathy. Br J Ophthalmol. 2015;99:1686- 91.

    2. Yoon JS, Lee HJ, Chae MK, Lee SY, Lee EJ. Cigarette smoke extract- induced adipogenesis in Graves' orbital fibroblasts is inhibited by quercetin via reduction in oxidative stress. J Endocrinol. 2013;216:145- 56.

    3. Tsai CC, Cheng CY, Liu CY, Kao SC, Kau HC, Hsu WM, Wei YH. Oxidative stress in patients with Graves' Ophthalmopathy: Relationship between oxidative DNA damage and clinical evolution. Eye (Lond). 2009;23:1725-30.

    4. Tsai CC, Cheng CY, Liu CY, Kao SC, Kau HC, Hsu WM, Wei YH. Oxidative stress in patients with Graves' Ophthalmopathy: Relationship between oxidative DNA damage and clinical evolution. Eye (Lond). 2009;23:1725-30.

    5. Folger PA, Zekaria D, Grotendorst G, Masur SK. Transforming growth factor-beta-stimulated connective tissue growth factor expression during corneal myofibroblast differentiation. Invest Ophthalmol Vis Sci. 2001;42; 2534-41.

    6. Cawood TJ, Moriarty P, O'Farrelly C, O'Shea D. Smoking and thyroid -associated ophthalmopathy: a novel explanation of the biological link. Journal of Clinical Endocrinology and Metabolism. 2007;92:59-64.

    Conflict of Interest:

    None declared

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