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Recent eLetters

Displaying 1-10 letters out of 540 published

  1. Comment on: Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole

    eLetter Comment on: Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole 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 Rose- Nussbaumer and associates [1] determining the risk factors for low vision-related quality of life in patients with fungal keratitis. While the study is indeed interesting, we herein address important issues, some of which warrant further discussion. First, the authors stated in the abstract "Those who required therapeutic penetrating keratoplasty had an average of 25.2 points decrease on VFQ after correcting for treatment arm (95% CI ?31.8 to ?18.5, p<0.001).". However, in the manuscript it is mentioned that "study participants who required therapeutic penetrating keratoplasty (TPK) had significantly worse VFQ scores than those who did not, with those having undergone TPK scoring on average 25.5 points lower on VFQ (95% CI ?32.0 to ?18.9, p<0.001)." Second, since marital status is one of the robust predictor of health outcomes, it should have been taken into account as it may affect the quality of life in the study patients. It has been seen that divorced and widowed men report higher rates of depressive symptoms than married men [2]. Third, presence of other comorbidities like diabetes, cancer, organic disorders/cognitive impairment or current use of any medication due to a psychiatric disorder eg. antidepressants should be ruled out. Moreover, use of topical nonselective beta-blockers or intake of oral lipophilic beta blockers for hypertensives should also be considered since they may lead to depression [3, 4] and subsequently affect quality of life. References 1. Rose- Nussbaumer J, Prajna NV, Krishnan T, et al. Br J Ophthalmol 2016;100:929-932. 2. Jang SN, Kawachi I, Chang J et al. Marital status, gender, and depression: Analysis of the baseline survey of the Korean Longitudinal Study of Ageing (KLoSA). Soc Sci Med 2009; 11(12): 1608-15. 3. Verbeek DE, van Riezen J, de Boer RA, van Melle JP, de Jonge P. A review on the putative association between beta-blockers and depression. Heart Fail Clin. 2011;7(1):89-99. 4. Augustin A, Sahel JA, Bandello F et al. Anxiety and depression prevalence rates in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2007;48(4):1498-503.

    Conflict of Interest:

    None declared

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  2. Comment on: The impact of donor age and endothelial cell density on graft survival following penetrating keratoplasty

    eLetter Comment on: The impact of donor age and endothelial cell density on graft survival following penetrating keratoplasty 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 Wakefield and associates [1] analysing if donor age and preoperative endothelial cell density (ECD) affects corneal endothelial failure following penetrating keratoplasty (PK). While the study is indeed interesting, we herein address important issues, some of which warrant further discussion. First, the authors have determined the overall 5-year graft survival rate due to endothelial failure in all recipients. No mention has been made of the endothelial cell density/loss at 5 years after surgery in all age groups. Was there any significant difference in the endothelial cell density in all groups? Second, diabetic status has been few of the factors affecting corneal endothelial cell counts. In patients with diabetes (after adjusting age), the cell count is lesser by 66 cells (95% CI, 6.3-125.9) compared with controls [2]. Did the authors take into consideration the presence or absence of diabetes mellitus in all groups since higher prevalence of diabetes in the younger age group donors could have decreased the graft survival ultimately making it comparable with the graft survival of corneas from elderly donors. Third, cigarette smoking reduces endothelial cell counts [3]. Smoking history should also have been considered while comparing the graft survival rates in all the groups. Moreover, advanced nuclear cataract and chronic pulmonary disease are significant risk factors for reduced endothelial density. Although the mechanisms are unknown, patients with these risk factors may have a poor endothelial reserve [4]. The authors should therefore rule out all the aforementioned factors before analyzing the results. References 1. Wakefield MJ, Armitage WJ, Jones MNA, et al. Br J Ophthalmol 2016;100:986-989. 2. Sudhir RR, Raman R, Sharma T. Changes in the Corneal Endothelial Cell Density and Morphology in Patients With Type 2 Diabetes Mellitus: a Population Based Study, Sankara Nethralaya Diabetic Retinopathy And Molecular Genetics Study (SN-DREAMS, Report 23). Cornea 2012; 0:1-4. 3. Ilhan N, Ilhan O, Coskun M, et al. Effects of Smoking on Central Corneal Thickness and the Corneal Endothelial Cell Layer in Otherwise Healthy Subjects. Eye Contact Lens. 2015; 10.1097/ICL.0000000000000212 4. Ishikawa A. Risk factors for reduced corneal endothelial cell density before cataract surgery. J Cataract Refract Surg. 2002;28(11):1982-92.

    Conflict of Interest:

    None declared

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  3. Intravitreal bevacizumab for diabetic macular edema: 5-year results of the Pan-American collaborative retina study group

    Intravitreal bevacizumab for diabetic macular oedema: 5-year results of the Pan-American collaborative retina study group. Dan Calugaru, Mihai Calugaru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania

    Re: Intravitreal bevacizamab for diabetic macular oedema: 5-year results of the Pan-American collaborative retina study group. Arevalo et al. Br J Ophthalmol published online on February 24, 2016;doi:10.1136/bjophthalmol-2015-307950.

    Dear Editor The article by Arevalo et al [1] has several shortcomings that prevent the validation and extrapolation of their results and that can be specifically summarized as follows:

    1. The study was retrospectively conducted with the existence of a selection bias due to the lack of a uniform clear treatment schedule for injections and reinjections, the decision to treat being left at the discretion of the treating physicians. Additionally, a total of 113 eyes were diagnosed with proliferative diabetic retinopathy and treated with panretinal photocoagulation at least 6 months before undergoing intravitreal bevacizumab (IVB) for diabetic macular oedema (DME).

    2. The assessment of the final outcomes should be made taking into account the current assertion whereby evaluation of the outcomes has to be guided by the anatomical measure data with the visual changes as a secondary guide [2]. Accordingly, the visual and anatomic improvements of this study were poor. Thus, while early visual gains due to IVB were not maintained 5 years after treatment, the central macular thickness (CMT) decreased significantly from 403.5 to 313.7 microns over 5 years follow- up. Importantly, this value is much more than the cutoff (252 microns) for the upper level of normal foveal thickness (212 ? 20 ?m)(3) plus 2 standard deviations. Of note, the proportion of eyes considered "dry" on optical coherence tomography as per criterion of foveal thickness ? 260 ?m was 29.4%, the rest of the eyes having unresolved macular oedema.

    3. The results of this study could be explained by the low frequency of injections (a mean of 8.4 IVB injections per eye over 5 years) as well as the long duration of diabetes (a mean of 15.8 years). Most likely there was a chronic retinal capillaropathy due to permanent irreversible breakdown of the inner and outer blood retinal barriers. The vascular endothelial growth factor (VEGF) is one proven contributor to macular oedema in diabetic retinopathy. Besides, a panoply of proinflammatory and proangiogenic cytokines, chemokines, and growth factors may be associated with pathophysiology of DME [4,5].

    Altogether, the specific anti-VEGF drugs represent the front-line therapy for the treatment of DME but VEGF inhibition only may not be sufficient to decrease inflammatory response. Therefore, addition of a non -specific anti-VEGF substance, i.e., intravitreal steroid injection is mandatory. Otherwise, patients will be impeded to achieve maximal visual and anatomic benefits. References 1. Arevalo JF, Lasave AF, Wu L, et al. Intravitreal bevacizumab for diabetic macular oedema: 5-year results of the Pan American collaborative retina study group. Br J Ophthalmol 2016, online first published on February 24, 2016; doi:10.1136/bjophthalmol-2015-307950. 2. Freund KB, Korobelnik JF, Deveny R, et al. Treat-and-extend regimens with anti-VEGF agents in retinal diseases. A literature review and consensus recommendations. Retina 2015;35:1489-1506. 3. Chan A, Duker JS, Ko TH, et al. Normal macular thickness measurements in healthy eyes using optical coherence tomography. Arch Ophthalmol 2006;124:193-198. 4. Sohn HJ, Han DH, Kim IT, et al. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol2011;152:686-694. 5. Shah SU, Harless A, Bleau L, et al. Prospective randomized subject- masked study of intravitreal bevacizumab monotherapy versus dexamethasone implant monotherapy in the treatment of persistent diabetic macular edema. Retina 2016, online first published on April 27, 2016; doi:10.1097/IAE 0000000000001038.

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  4. Comment on: Morphological features in anterior scleral inflammation using swept-source optical coherence tomography with multiple B-scan averaging.

    Dear Editor,

    I read with interest the article by Kuroda et al.[1] The authors explored new possibilities of anterior segment imaging using a posterior segment swept-source optical coherence tomography device without noteworthy modifications. Interestingly, it was possible to obtain high- resolution images of the conjunctiva, episclera, and the sclera near the limbus that seemingly allow unequivocal identification of anatomical boundaries. The authors used this technique to examine eyes with anterior scleritis/episcleritis.

    However, I was not so impressed when I read through the methods section of the paper. Contralateral eyes of patients were included as controls. This is certainly problematic, considering that some of the subjects had systemic inflammatory disease. In patients with overt bilateral disease, both eyes were included in the analysis. As a result, the measurements are not independent,[2] and the use of basic statistical tests such as the Mann-Whitney or Kruskal-Wallis tests is not legitimate. All these tests require independence of observations. Advanced statistical methods[3] such as generalized estimating equations[4] or paired comparison[5] would be necessary to obtain statistically valid results.

    Another significant weakness of the methodology is that the thickness of tissues was not measured perpendicularly to the ocular surface. This makes data prone to bias and increases the variability. Moreover, the internal limits of the sclera in Figures 2B and 4B are not very distinct, and one wonders how accurate the measurements of this boundary are in other eyes in the study, if these photos are representative.

    To sum up, the images displayed are promising, yet, the scientific rigour of the paper is much less compelling.

    References

    1. Kuroda Y, Uji A, Morooka S, et al. Morphological features in anterior scleral inflammation using swept-source optical coherence tomography with multiple B-scan averaging. Br J Ophthalmol Published Online First: 7 July 2016. doi: 10.1136/bjophthalmol-2016-308561

    2. Ray WA, O'Day DM. Statistical analysis of multi-eye data in ophthalmic research. Invest Ophthalmol Vis Sci 1985; 26:1186-8.

    3. Fan Q, Teo YY, Saw SM. Application of advanced statistics in ophthalmology. Invest Ophthalmol Vis Sci 2011; 52:6059-65.

    4. Hanley JA, Negassa A, Edwardes MD, et al. Statistical analysis of correlated data using generalized estimating equations: an orientation. Am J Epidemiol 2003; 157:364-75.

    5. Murdoch IE, Morris SS, Cousens SN. People and eyes: statistical approaches in ophthalmology. Br J Ophthalmol 1998; 82:971-3.

    Conflict of Interest:

    None declared

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  5. Re:Comment on: Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase III trials

    Dear Editor, We thank Drs Gupta and Ram for their interest in our recent paper on the anatomical effects of dexamethasone intravitreal implant (DEX implant) in eyes with diabetic macular oedema [1] and appreciate the opportunity to respond to their comments. Their letter highlights various patient- and treatment-related factors that potentially might have influenced the retinal findings described in our analysis. We provide here some further clarification on the specific points raised in their letter. Firstly, the MEAD study data do not allow us to determine with certainty the treatment-free interval preceding DEX implant injection. However, we can confirm that all enrolled patients were required to discontinue intravitreal anti-VEGF and triamcinolone treatment at least 3 and 6 months, respectively, prior to study entry. Also, ranibizumab was not available at the start of the study (2004) and only 7% of patients had received prior anti-VEGF therapy. Moreover, randomization is likely to have minimized any imbalance between the treatment groups. Secondly, patients presenting with epiretinal membrane or vitreomacular traction syndrome at the initial screening visit were excluded from study entry. Thirdly, regarding the issue of insulin and oral hypoglycaemic use and changes in antidiabetic treatment during the study, randomization presumably minimized any influence these factors might have had on study outcomes. Fourthly, the study was not designed to assess the comparative efficacy of the 0.35 mg and 0.7 mg implants. However, since HbA1c assays over the course of the study showed no significant difference in glycaemic control between the three treatment arms, the MEAD findings indicate that the two implants are of comparable efficacy in reducing macular oedema. Finally, for information on the effects of DEX implant on lens status the reader is referred to the primary paper of the MEAD Study Group [2].

    Ronald P. Danis, M.D. Srinivas Sadda, M.D. Xiao-Yan Li, M.D. Harry Cui, MS. Yehia Hashad, M.D. Scott M. Whitcup, M.D.

    Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, 2870 University Avenue, Madison, Wisconsin 53711. E-mail: rpdanis@wisc.edu

    References 1. Danis RP, Sadda S, Li XY, et al. Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3- year phase III trials. Br J Ophthalmol 2016;100:796-801. 2. Boyer DS, Yoon YH, Belfort R, et al. Three-year, randomized, sham- controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 2014;121:1904-14.

    Conflict of Interest:

    RPD and SS have received grant support and consulting fees from Allergan, Inc. X-YL and YH are employees of Allergan, Inc.

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  6. Re:Diurnal variations in luminal and stromal areas of choroid in normal eyes

    Dear Editor,

    We thank Drs. Uzun and Pehlivan for their interest and comments to our article.[1] We compared and correlated the central choroidal thickness to the different choridal parameters at different times between 9:00 h and 18:00 h. We compared the findings between 09:00 h and 12:00 h, 09:00 h and 15:00 h, 09:00 h and 18:00 h, 12:00 h and 15:00 h, 12:00 h and 18:00 h, and 15:00 h and 18:00 h. There were significant strong correlations between the fluctuation range of central choroidal thickness (fCCT) and those of luminal area and total choroidal area at all times (r >0.8, P <0.001). There was no significant correlation between the fCCT and the fluctuation range of stromal area (fSA) at 09:00 h and 18:00 h, 12:00 h and 18:00 h, and 15:00 h and 18:00 h (P >0.1). There were significant correlations between the fCCT and the fSA at 09:00 h and 12:00 h, 09:00 h and 15:00 h but the correlations were relatively weak (r = 0.428, P = 0.010; r = 0.383, P = 0.023; respectively). There was a moderate correlation between fCCT and fSA at 12:00 h and 15:00 h (r = 0.635, P <0.001), however, no significant difference in the mean choroidal parameters was found during this interval (P = 1.000 for all choroidal parameters, repeated ANOVA with the Bonferroni test for post hoc analysis). Thus, these results reconfirm our main conclusion that that the diurnal variations in the choroidal thickness are mainly due to the fluctuations in the luminal area.

    There was no significant correlation between age and the choroidal parameters in the partial regression analyses in which the axial length was set as the control variable. However, we reported earlier that the age was significantly and negatively correlated with the total choroidal area, luminal area, stromal area, and the ratio of luminal to stromal area.[2] The differences in the distribution of age of the participants and the sample size between the two studies may explain this discrepancy. The mean age of 30.5 ? 9.11 (mean ? SD) years (range, 21 - 52 years) in the present study was younger with a smaller range than that in the previous report with a mean age of 55.9 ? 18.8 years (range 22 - 90 years). The sample size of the previous study was 180 which was larger than that of the present study (n = 38). No significant difference in the choroidal parameters was found between the sexes.

    Again, we thank you for your interest.

    1. Kinoshita T, Mitamura Y, Shinomiya K, et al. Diurnal variations in luminal and stromal areas of choroid in normal eyes. Br J Ophthalmol. 2016 Jun 13. pii: bjophthalmol-2016-308594. doi: 10.1136/bjophthalmol-2016- 308594. 2. Sonoda S, Sakamoto T, Yamashita T, et al. Luminal and stromal areas of choroid determined by binarization method of optical coherence tomographic images. Am J Ophthalmol 2015;159:1123-31.

    Conflict of Interest:

    None declared

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  7. Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration

    Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration Dan C?lug?ru, Mihai C?lug?ru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania

    Re: Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration. Barthelmes et al. Br J Ophthalmol published online on March 18, 2016;doi:10.1136/bjophthalmol- 2015-308090.

    Dear Editor

    The interesting article by Barthelmes et al [1] carries several shortcomings that prevent the validation and extrapolation of their results and that can be specifically summarized as follows:

    1. The study was retrospectively conducted with the existence of a bias due to the lack of a uniform definite treatment scheme for injections and reinjections, the decision to treat being left at the discretion of the treating physicians, Additionally, 26 eyes were switched back to the original treatment and two different treatment regimens were chosen, namely, the treat-and-extend approach in 59% of the eyes and the monthly pro re nata algorithm to the rest of the eyes.

    2 The aggressiveness of the neovascular age-related macular degeneration (nAMD) was graded taking into account the fluoreiscein angiography features. The assessment process should have included the optical coherence tomography (OCT) data as well.

    3. The analysis of the final outcomes of this study should have been carried out considering the current assertion according to which evaluation of the outcomes has to be guided by the anatomical measure data with the visual changes as a secondary guide [2] and not vice versa as Barthelmes et al [1] have approached.

    4. There were no data on the proportion of eyes considered "dry" on OCT as per criterion of foveal thickness < 320 ?m [3] nor on the anatomical types of the macular edema (subretinal fluid/cystic changes within neurosensory retina). Except for the morphological types of the choroidal neovascular membrane lesions presented in details, nothing was stated referring to the other anatomical types of the neovascular maculopathy including serous and/or hemorrhagic detachment of the neurosensory retina or retinal pigment epithelium (RPE), retinal hard exudates, subretinal and sub-RPE fibrovascular proliferation, and subretinal fibrosis, before and after switching to aflibercept (Eylea; Regeneron Pharmaceuticals Tarrytown, NY, USA.

    5. The design of this study has been deprived of a real washout period which is essential between the two periods of treatment in terms of aliased effects. Given that this washout period was not precisely delimited, the impact of the significant carryover effects may be confounded with direct treatment effects, in the sense that these effects could not be estimated separately being able to bias the interpretion of data analysis.

    Altogether, regardless of the anti-VEGF agents used (ranibizumab [Lucentis, Genentech Inc., South San Francisco, CA, USA]/bevacizumab [Avastin, Genentech Inc.,]/aflibercept), the efficacy of therapy depends primarily on the precociousness of the therapy after nAMD onset. References 1. Barthelmes D, Campain A, Nguyen P, et al. Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration. Br J Ophthalmol2016, online first published on March 18, 2016;doi:10.1136/bjophthalmol-2015-308090.. 2. Freund KB, Korobelnik JF, Deveny R, et al. Treat-and-extend regimens with anti-VEGF agents in retinal diseases. A literature review and consensus recommendations. Retina 2015;35:1489-1506.. 3. Gover S, Murthy RK, Brar VS, et al. Normative data for macular thickness by high-definition spectral-domain optical coherence tomography (spectralis).Am J Ophthalmol2009;148:266-271.

    Conflict of interest: None declared

    Conflict of Interest:

    None declared

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  8. Diurnal variations in luminal and stromal areas of choroid in normal eyes

    Dear Editor, We have read and reviewed the article entitled as "Diurnal variations in luminal and stromal areas of choroid in normal eyes'' by Kinoshita et al. with great interest [1]. The authors analyzed systemic blood pressure, heart rate, intraocular pressure, central choroidal thickness (CCT), total cross-sectional choroidal area, the luminal areas, stromal areas and the ratio of luminal area to total choroidal area (L/C ratio) of 38 healthy participants every 3 hours between 06:00 and 21:00. They found that there were significant diurnal variations in the CCT, total choroidal area, luminal area and L/C ratio with the maximum values at 6:00 hours and the minimum values at 15:00 hours. We express our gratitude to the authors, and appreciate their valuable contributions to the literature. However, we would like to ask the authors two important points regarding the study.

    Choroid is the most vascular structure of the eye, and it has the highest blood flow of any tissue per unit weight in human body. Additionally, numerous studies have demonstrated that choroid has a unique anatomical structure, and neurovascular configuration [2]. Owing to advancements in technology, ability to obtain fast, high-resolution, high- quality imaging of choroid with reproducible results made the investigators to focus on this important structure.

    Kinoshita et al. investigated the choroid, and the relationship of structure of choroid with systemic and local factors, and demonstrated the diurnal variation of those parameters. They compared all those investigated parameters, and particularly the parameters measured between 06:00 and 15:00 with each other. It is a fact that the vast majority of the studies investigating the choroid were performed during working hours. Accordingly, we would like to ask the authors whether they investigated the parameters, particularly the ones related to choroid in different time intervals, for instance between 09:00 and 12:00, or 09:00 and 15:00, or 12:00 and 15:00; since we suppose that such an assessment may guide investigators for further studies on choroid.

    Second, we suggest that considering age and gender differences of the participants regarding choroid-related parameters might provide significant contribution to the paper and the literature. References 1 Kinoshita T, Mitamura Y, Shinomiya K, et al. Diurnal variations in luminal and stromal areas of choroid in normal eyes. Br J Ophthalmol 2016; doi: 10.1136/bjophthalmol-2016-308594. 2 Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res 2010;29:144-68.

    Conflict of Interest:

    None declared

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  9. Re:Comment on: Choroidal structure in eyes with drusen and reticular pseudodrusen determined by binarisation of optical coherence tomographic images

    Dear Editor We thank Drs Uzun and Pehlivan for their interest in our article,1 and we welcome this opportunity to address their concerns. As pointed out, there are several factors that may induce fluctuation of choroidal thickness such as the diurnal effect, systemic diseases (endocrine, cardiovascular, rheumatologic, and inflammatory), intraocular pressure, refractive status, systemic blood pressure, body mass index, alcohol, smoking, and caffeinated beverage consuming.2-8 A limitation of our study is the retrospective design, therefore all of these parameters cannot be tested. In our series, the refractive error should not be considered as a potential confounding factor because we included patients with an axial length between 23.5 and 26.5 mm. Regarding intraocular pressure, a recent study 5 showed a significant diurnal fluctuation, but no correlation with choroidal thickness was detected in other reports.3,7 All of the studies 2-8 determining the diurnal variation of choroidal thickness were conducted in healthy subjects with healthy choroid while in our series we evaluated patients with drusen and reticular pseudodrusen in which remodeling of the choroid has been demonstated.1,9 In particular in patients with reticular pseudodrusen the choroid is significantly thinner compared to control subjects.1,9 As a result, thinner choroid with less blood supply may be less influenced by diurnal variation or systemic, local and environmental factors. Of note, a recent publication evaluated the diurnal variations in luminal and stromal areas of choroid in normal eyes by binarisation technique and demonstrated significant variations in the central choroidal thickness and luminal area but not in the stromal area.9 In our study we found that the stromal area was more represented in eyes with reticular pseudodrusen, suggesting less influence by diurnal variation or systemic, local and environmental factors and a possible role of choroidal vascular depletion and fibrotic replacement in the pathogenesis and disease progression.1 The insightful comments of Drs Uzun and Pehlivan are worth of considerable for further prospective studies with larger sample size, especially in patients with early age related macular degeneration and reticular pseudodrusen, and longer follow-up periods are needed to confirm if systemic, local and environmental factors should be considered as potential confunding effects on the choroid examination. ? References 1. Corvi F, Souied EH, Capuano V, et al. Choroidal structure in eyes with drusen and reticular pseudodrusen determined by binarisation of optical coherence tomographic images. Br J Ophthalmol. 2016. pii: 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. Toyokawa N, Kimura H, Fukomoto A, Kuroda S. Difference in morning and evening choroidal thickness in Japanese subjects with no chorioretinal disease. Ophthalmic Surg Lasers Imaging. 2012;43:109e14 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. 6. Chakraborty R, Read SA, Collins MJ. Diurnal variations in axial length, choroidal thickness, intraocular pressure, and ocular biometrics. Invest Ophthalmol Vis Sci. 2011;52:5121e9. 7. 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;53:261e6 8. Kinoshita T, Mitamura Y, Shinomiya K, et al. Diurnal variations in luminal and stromal areas of choroid in normal eyes. Br J Ophthalmol. 2016 Jun 13. pii: bjophthalmol-2016-308594.6 9. Querques G, Querques L, Forte R, et al. Choroidal changes associated with reticular pseudodrusen. Invest Ophthalmol Vis Sci 2012;53:1258-63.

    Conflict of Interest:

    None declared

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  10. Comment on: Predicting outcomes to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular oedema: a review of the literature

    Dear Editor, We read and reviewed the article entitled as "Predicting outcomes to anti- vascular endothelial growth factor (VEGF) therapy in diabetic macular oedema: a review of the literature'' by Ashraf et al. with great interest [1]. In that comprehensive study, the authors reviewed the studies that investigated demographic, clinical, optical coherence tomography (OCT), and fluorescein angiography results that could predict the outcomes of the anti-VEGF agents in patients with diabetic macular edema.

    Ashraf et al. suggested that choroidal thickness (CT) might also be utilized as a novel marker to predict outcomes of the treatment with anti- VEGF agents in patients with diabetic macular edema. However, we disagree with the authors at some important points.

    As Ashraf et al. have already indicated in their paper, CT is significantly variable in the patients with diabetic retinopathy. Although some studies stated that CT increased significantly, some others demonstrated that CT decreased significantly in patients with diabetic retinopathy. Even in some studies, CT has been found to be the same in the diabetic patients and the normal control group. Then what may be the causes of such conflicting results in CT measurements?

    First, choroid has a unique vascular anatomy and physiology [2]. It is one of the tissues that has the most excessive per-gram blood supply in the body. Therefore, various local, systemic, and environmental factors significantly affect CT [2,3].

    Second, various anatomic and pathological factors associated with eye significantly affect CT. In the literature, it has been indicated that local factors such as intraocular pressure, axial length, and refractive errors may affect CT [2,3]. Moreover, glaucoma, amblyopia, strabismus, and many other eye diseases and their treatments may affect CT.

    Third, many neurologic, rheumatologic, inflammatory, hematologic, endocrine, and vascular disease and their medications may significantly affect CT [3]. Additionally, physiologic conditions such as pregnancy and menstrual cycle also affect CT.

    Fourth, smoking, alcohol and caffeinated/decaffeinated beverages, diurnal variations as well as lightening conditions of the room where the CT measurement is performed may significantly affect CT [2,3].

    In contrast to Ashraf et al., we do not suggest CT as a suitable marker for patient follow-up, or a predictor for treatment outcomes. If the CT would be considered as a criterion, all local, systemic, and environmental factors should be standardized and optimized.

    References 1 Ashraf M, Souka A, Adelman R. Predicting outcomes to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular oedema: a review of the literature. Br J Ophthalmol. 2016; doi: 10.1136/bjophthalmol-2016-308388. 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.

    Conflict of Interest:

    None declared

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