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Recent eLetters

Displaying 1-10 letters out of 475 published

  1. SLET allograft in bilateral Limbal stem cell deficiency

    In routine keratoplasties, HLA matching and systemic immunosuppressive drugs are not employed, yet 90% of the uncomplicated transplants survive. (1) But allografts of stem cells may need to be taken from live HLA matched donors as cadaver stem cells have been reported to fail in the long term inspite of continued immunosuppressive treatment with cyclosporine A,steroids, FK 506 and mycophenolate mofetil.Also the success of the said procedure as described by Sangwan et al (2) needs to be tested as an allograft in cases of immune damage to stem cells too. We did an allograft SLET on a 29 year old patient's eye with vision of hand movements upto one feet ; by taking the stem cell from the patient's sister in the same manner as described by Sangwan et al but modified it and did a sandwich technique placing the stem cell on tissue glue between two layers of amniotic membrane and covered it with a bandage contact lens. The patient had bilateral Limbal stem cell deficiency due to a host graft rejection phenomena after a bone marrow transplant at the age of six with poor vision in both eyes. Post operatively he was maintained on immunosupression with steroids systemically and locally. The final visual acuity at two months post operatively was 6/36. There have been cases reports (3) of success with stem cell allografts but this probably needs to be further evaluated especially in cases which are bilateral like our case. Allograft stem cell has been used successfully in Limbal stem cell deficiency due to chemical burns (4). It has also been described for Steven Johnson syndrome (5) and authors have described that HLA nonmatched live relative donor's stem cell fail to reconstitute the corneal surface. But the efficacy of such a procedure when done as an allograft in Limbal stem cell deficiency after host graft rejection process due to bone marrow transplant in childhood needs to be further evaluated. We attempted to do the same and achieved reasonable success in the short term. Long term follow up should provide us with more information. In the meantime any advice would be welcome.

    References 1. Niederkorn JY, Kaplan HJ (eds): Immune Response and the Eye. Chem Immunol Allergy. Basel, Karger, 2007, vol 92, pp 290-299 . 2. Sangwan et al. Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. Br J Ophthalmol 2012 96:931-934; doi:10.1136/bjophthalmol- 2011-301164 3. Gardu?o -Vieyra L. * Gonzalez C.R. * Hernandez-Da Mota S.E. Limbal Stem Cell Allografts and Corneal Transplant in a Patient with Severe Corneal Perforation due to Thermokeratoplasty andCross-Linking Treatment Burn Case Rep Ophthalmol 2012;3:364-369 4. Huang T, Wang Y, Zhang H, Gao N, Hu A. Limbal allografting from living- related donors to treat partial limbal deficiency secondary to ocular chemical burns.Arch Ophthalmol. 2011 Oct;129(10):1267-73. doi: 10.1001/archophthalmol.2011.251. 5. Rao SK, Rajagopal R, Sitalakshmi G, Padmanabhan P. Limbal allografting fromrelated live donors for corneal surface reconstruction. Ophthalmology. 1999 Apr;106(4):822-

    Conflict of Interest:

    None declared

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  2. Outcomes of posterior-approach 'levatorpexy' in congenital ptosis repair

    Dear Editor We read with great interest the article entitled "Outcomes of posterior- approach 'levatorpexy' in congenital ptosis repair" by Al-Abbadi Z et al.(1) In their article, the authors described posterior-approach levatorpexy surgical technique for management of congenital ptosis. In this technique, the first suture was passed through the levator aponeurosis- levator muscle junction or above according to levator function. The second suture was passed 2 mm medial to first suture. (1) However, in their previous article the authors used the second suture 2 mm lateral to first suture for management of involutional aponeurotic ptosis. (2) The authors did not discuss the reason why they moved the second suture from lateral to medial.

    REFERENCES 1. Al-Abbadi Z, Sagili S, Malhotra R. Outcomes of posterior-approach 'levatorpexy' in congenital ptosis repair. Br J Ophthalmol. 2014 Dec;98(12):1686-90. 2. Patel V, Salam A, Malhotra R. Posterior approach white line advancement ptosis repair: the evolving posterior approach to ptosis surgery. Br J Ophthalmol. 2010 Nov;94(11):1513-8.

    Conflict of Interest:

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  3. RE: Alberti M, la Cour M. Face-down positioning versus non-supine positioning in macular hole surgery. Br J Ophthalmol 2015;99:2 236-239

    We read the paper by Alberti and la Cour [1] with great interest as we are shortly to commence a randomised controlled clinical trial to determine the value of face-down positioning following surgery for large (> 400 micrometres) macular holes [2]. We would urge readers to be mindful of the message recently emphasised by the Ophthalmic Statistics Group that absence of evidence is not evidence of absence, and that confidence intervals can be informative in such situations [3]. The data provided by Alberti and la Cour give an odds ratio of surgical success following face-down versus non supine positioning of 0.77 (0.06, 7.06). Whilst the data are entirely consistent with there being no difference, it is clear that there is much uncertainty. We have ignored unit of analysis issues [4] in computing this effect estimate. When developing our research proposal we discussed the issue of positioning with people who had recently undergone surgery for macular hole. Whilst they very much agreed that positioning could be arduous they also expressed the view that they would do whatever necessary to minimise any need for further surgery.

    1.Alberti M, la Cour M. Face-down positioning versus non-supine positioning in macular hole surgery. Br J Ophthalmol 2015;99:2 236-239 2.http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=17966 3.Bunce C, Patel KV, Xing W. Ophthalmic statistics note 2: absence of evidence is not evidence of absence. Br J Ophthalmol 2014;98:703-705 4.Bunce C, Patel KV, Xing W. Ophthalmic statistics note 1: unit of analysis. Br J Ophthalmol 2014;98:3 408-412

    Conflict of Interest:

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  4. Inconclusive treatment recommendations with ranibizumab in retinal vein occlusion by an expert panel

    Title page:

    Inconclusive treatment recommendations with ranibizumab in retinal vein occlusion by an expert panel

    Dan Calugaru, PhD 1 and Mihai Calugaru, PhD 2

    1Department of Ophthalmology, University of Medicine Cluj- Napoca/Romania

    Phone number: 0745 827 552

    Fax number: 0040 264 591468

    E-mail: dan.calugaru@ymail.com

    2Department of Ophthalmology, University of Medicine Cluj- Napoca/Romania

    Phone number: 0741 165 094

    Fax number: 00 40 264 591468

    E-mail: mihai.calugaru@mail.dntcj.ro Address of the Corresponding Author:

    Mihai Calugaru

    Strada Br??ncoveanu 11

    3400 Cluj-Napoca/Romania

    E-mail: mihai.calugaru@mail.dntcj.ro The manuscript has been seen and approved by all authors; None of the authors has conflict of interest with the submission; The authors have never received financial support for this article;

    Inconclusive treatment recommendations with ranibizumab in retinal vein occlusion by an expert panel Re: Ranibizumab in retinal vein occlusion: treatment recommendations by an expert panel. Gerding et al. Br J Ophthalmol 2015;99 (3): 298-304 doi:10.1136/bjophthalmol-2014-305041

    In their article, Gerding et al.1, developed treatment recommendations with ranibizumab (Lucentis, Genentech, Inc., South San Francisco, CA) in patients with macular edema secondary to retinal vein occlusions. For central retinal vein occlusion (CRVO), the authors' recommendations were based on evidence delivered mainly from the Cruise study.2 Of note, the conclusions described by Gerding et al. related only to nonischemic occlusions because 98.5% of the treated patients had had a perfused retinal status. Moreover, the authors' recommendations were not updated with the available long-term results 3,4 of the Cruise study, 2 which revealed a worsening of the initial remarkable outcomes achieved after aggressive treatment was applied for 12 months. Thus, the 12-month extension 3 of the Cruise study 2 showed a deterioration in the outcomes measures in all three groups of patients, i.e., sham/0.5 mg, 0.3 mg, and 0.5 mg of ranibizumab (decrease in the best corrected visual acuity [BCVA] with -4.2, -5.5, and -4.1 letters, respectively, and an increase in the foveal thickness with 63, 88.6, and 72.4 ?m, respectively). Furthermore, a study with an extension of the follow-up to 51.4 months 4 after the Cruise study baseline reported that 56% of patients still required frequent injections; 6 patients experienced a reduction in the BCVA of -33, -18, - 11, -4, -3, and -3 letters, having serious ischemic macular damages. Delayed deterioration of visual functions could be explained by the lower frequency of injections as well as the long period of time before the initiation of therapy, during which patients went without treatment (the CRVO diagnosis was made within 12 months before initiation of screening). These facts favored the delayed occurrence of irreversible and ischemic lesions of the macular retinal ganglion cells, close to the foveola. In conclusion, CRVO (both ischemic and nonischemic forms) should be considered an ophthalmic emergency, which has to be promptly treated with anti-angiogenic agents. Every delay of treatment adversely influences the delayed deterioration of visual functions, which are difficult to correct even with subsequent treatment.5

    References

    1. Gerding H, Mones J, Tadayoni R, et al. Ranibizumab in retinal vein occlusion: treatment

    reccomendations by an expert panel. Br J Ophthalmol 2015;99:297-304.

    2. Campochiaro PA, Brown DM, Awh CC, et al. Sustained benefits from ranibizumab for macular

    edema following central retinal vein occlusion: twelve-month outcomes in a phase III study.

    Ophthalmology 2011;118:2041-49.

    3. Heier JS, Campochiaro PA, Yau L, et al. Ranibizumab for macular edema due to retinal vein

    occlusion: long-term follow-up in the Horizon trial. Ophthalmology 2012;119:802-9.

    4. Campochiaro PA, Sophie R, Pearlman J, et al. Long-term outcomes in patients with retinal vein

    occlusion treated with ranibizumab. The Retain study. Ophthalmology 2014;121:209-19.

    5. Calugaru D, Calugaru M. Intravitreal bevacizumab in acute central/hemicentral retinal vein

    occlusions: three-year results of a prospective clinical study. J Ocul Pharmacol Ther. doi: 10.1089.

    /jop.2014.0037.

    Conflict of Interest:

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  5. Data accuracy in estimates of treatment incidence for retinopathy of prematurity

    We read the paper by Painter et al. with great interest. The authors have compiled important information about trends in the incidence and treatment of retinopathy of prematurity (ROP) in the United Kingdom (UK) [1]. The authors have used data linkage of routine NHS datasets which is an impressive example of data analysis to evaluate trends. Here the authors demonstrate the impact of improved survival of low-birth weight (LBW) neonates and recommendations for earlier treatment of ROP [2]. Data accuracy is of course key when conducting such exercises, and in fact birth statistics published by the Office for National Statistics for England and Wales (ONS) do allow separation into English and Welsh figures, so that tables from the ONS website with information on LBW infants for both countries are readily available. We would advise that the reported number of ROP treatments should be viewed as very minimum estimate - clinicians often have little or no input into data entry to the Hospital Episode Statistics (HES) system, and we have previously demonstrated that ROP data collected by non-ophthalmologists are incomplete and result in inaccurate national statistics [3]. This under- estimation is supported by our current study, kindly mentioned in Painter's paper. For the year starting 01/12/2013, our national study of ROP treatment, administered by the British Ophthalmic Surveillance Unit (BOSU) has recorded, in England alone, 273 babies undergoing at least one treatment episode for ROP, so the incidence (Poisson rate estimate) was 38.2 per 1,000 LBW infants; exact 95 % CI (33.81 to 43.02). In conclusion, data linkage with thorough assessment of validity can provide data essential for planning and commissioning services.

    1. Painter SL, Wilkinson AR, Desai P, Goldacre MJ, Patel CK. Incidence and treatment of retinopathy of prematurity in England between 1990 and 2011: database study. The British journal of ophthalmology 2014 doi: 10.1136/bjophthalmol-2014-305561

    2. Early Treatment For Retinopathy Of Prematurity Cooperative G. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Archives of ophthalmology 2003;121(12):1684-94 doi: 10.1001/archopht.121.12.1684

    3. Warden C, George J, Nithyanandarajah A, Dahlmann-Noor A. Inaccuracy of ROP screening data in National Neonatal Audit Programme report. Eye 2014;28(2):237-8 doi: 10.1038/eye.2013.251

    Conflict of Interest:

    The authors currently carry out a national active surveillance study on the topic of ROP treatment; this study is funded by Moorfields Special Trustees and the Birmingham Eye Foundation. The authors have no personal commercial interests to declare.

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  6. Re:Outcomes of epiretinal membrane surgery in highly myopic eyes: a case-control study

    Dear Editor,

    We thank Huisingh and McGwin, Jr for their comments on our study. We basically agree with their remark regarding the study design. We hypothesized that high myopia could affect surgical outcomes and considered it as a risk factor. Highly myopic eyes were selected based on axial length and were matched for potential confounding factors (i.e., duration of symptoms and preoperative visual acuity) with non-highly myopic eyes selected from the same cohort. This study actually describes a matched cohort study, not a case-control study, as Huisingh and McGwin, Jr suggested. As such, a paired t-test should have been used to compare final visual acuity and central macular thickness on the one hand, and on the other, mean change in visual acuity and macular thickness of matched pairs between the two groups. However, this error has no significant implication for the interpretation of the observed results (p=.563 and p=.365, p=.673 and p=.703, paired t-test). Furthermore, the statistical tests used to compare visual acuity and macular thickness before and after surgery in each exposure group seem to be appropriate when considering that only the 1-year visual acuity and macular thickness were considered for the statistical analysis and that each eye included belonged to a different patient.

    Conflict of Interest:

    None declared

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  7. Re:Data inconclusive to recommend oral azithromycin over oral doxycycline in meibomian gland dysfunction

    We would like to thank Michel J. Belliveau for the comments on our recently published trial(1) on comparing the oral Azithromycin with doxycycline. All the concerns regarding the data presentation are being addressed in the following paragraphs. The null hypothesis had been written in the study design (ClinicalTrials.gov; NCT01783860) which was not mentioned in the article because of word number limitation. It was a two-tail hypothesis: "there is not any difference in severity of disease (measured by sign and symptom checklist) at the last follow-up across two groups of treatment (Oral Azithromycin versus Doxycycline)." The sample size calculation was based on the references 12 and 14 of our article which have been cited in the method section. (1) Prior validation is recommended for a questionnaire and not for grading the signs and symptoms of a disease. While a standard questionnaire (like quality of life questionnaire) requires a prior validation because of different subjective feeling and responses to each question, symptom and sign grading could be differently used in different studies based on the aim of study. Furthermore, all of grading systems of symptoms and signs in our study have already been extensively used in the previous studies and workshops on blepharitis without a prior validation. Since cases with lost follow up were less than 10% of all participants, it does not violate the results. (2-4) In fact, drop out of samples up to 20% of sample size is acceptable and does not violate the results. (2-4) Regarding to writing all confidence intervals, table 3 shows a detailed statistical analysis of both groups expanding what has been mentioned in the text without a need to increase the word number of the text. (1) By applying The Bonferroni multiple comparisons test to the data in Table 4, there is still one significant (conjunctival redness) and one marginally significant (ocular surface staining) score favoring the Azithromycin group. (1) Such a significant difference (even in one sign score) was big enough to lead to a significantly better mean total sign score (of seven signs) in the azithromycin group(1) to which the conclusion was written. Whether a significantly better mean total sign score of azithromycin group has rooted from one or more than one of the signs does not violate the conclusion that azithromycin resulted in a significantly better total mean sign score and therefore is recommended over doxycycline. Even if there was no any significant differences between symptom and sign scores of two groups, azithromycin would still be recommended for its shorter duration of treatment, lesser side effects, and cheaper price. In conclusion, we believe the data are conclusive enough to recommend azithromycin over doxycycline in patients with meibomian gland dysfunction because of a significantly better improvement of sign score, shorter duration of treatment, lesser side effects, and lower price. References 1. Kashkouli MB, Fazel AJ, Kiavash V, Nojomi M, Ghiasian L. Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised double masked open label clinical trial. Br J Ophthalmol. 2014 Aug 19. [Epub ahead of print] 2. Peterson JC, Pirraglia PA, Wells MT, Charlson ME. Attrition in longitudinal random controlled trials: home visits make a difference. Medical Research Metodology 2012;12:178 3. Armijo-Olivo S, Warren S, Magee D. Intention to treat analysis, compliance, drop-outs and how to deal with missing data in clinical research: a review. Physical Therapy Review 20109;14:36-49 4. Fewtrell MS, Kennedy K, Singhal A, et al. How much loss to follow-up is acceptable in long-term randomized trials and prospective studies? Arch Dis Child 2008;93:458-461

    Conflict of Interest:

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  8. Retinal Tracking System Reduces Head Tilt Effect During Optical Coherence Tomography Examination

    Previously, I reported that head tilting during optical coherence tomography (OCT) image acquisition affects circumpapillary retinal nerve fibre layer (RNFL) and macular retinal thickness measurement.1 Although the subject's head and chin are appropriately positioned, a possibility of inter-test variation in head alignment still exists. A useful strategy to overcome this limitation is tracking the subsequent image to the prior image. Recently, Cirrus high-definition (HD) OCT (Carl Zeiss Meditec, Dublin, California, USA) introduced an eye-tracking system (FastTracTM retinal tracking system), which was developed to reduce the artifacts induced by eye movement during scan acquisition and to allow image capture at identical points during each visit. Till date, it is yet to be determined whether the retinal tracking system can reduce artifacts induced by head tilting during OCT examination.

    To test this hypothesis, 10 eyes from 5 healthy young subjects without ocular and neurologic disorders were recruited. RNFL thickness was measured at a baseline head position without head tilting and at the right and left head tilt positions as described previously.1 Differences in thicknesses and peak locations of RNFL between the baseline head position and head tilt positions were analysed using Wilcoxon signed rank test. When the retinal tracking system was not used, right and left head tilt induced significant changes in thicknesses and peak locations of RNFL. However, when the retinal tracking system was used, none of the RNFL parameters showed significant change during head tilting. This result suggests that the Cirrus HD-OCT retinal tracking system can reduce inter- test variation induced by head tilting during OCT image acquisition. To identify the range of head tilt degree in which the retinal tracking system can operate and its utility in patients with cyclotorsional eye movement disorders, further studies are needed.

    Reference 1. Hwang YH, Lee JY, Kim YY. The effect of head tilt on the measurements of retinal nerve fibre layer and macular thickness by spectral-domain optical coherence tomography. Br J Ophthalmol 2011;95:1547-51.

    Conflict of Interest:

    None declared

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  9. Comment on : Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant infectious keratitis: a randomised clinical study

    Dear sir, We read the article by Abdulhalim et al with great interest (1) . The article remind us that both CONJUNCTIVAL FLAP and AMNIOTIC MEMBRANE GRAFT are effective in corneal healing and can be an alternative to keratoplasty in cases of infectious keratitis. However we have some concerns: The way to assess the mean size of ulcer and depth and the healing time in the post operative period would have made the comparison more interesting. The outcome of both these procedures if compared with keratoplasty -which is the gold standard in treatment of recalcitrant ulcer would have given us an information regarding which ulcers will benefit from these two procedures.(2) If proved that they are equally effective or superior to keratoplasty then we can save some corneas which can be used for optical purposes in other patient. Patient will be free from post keratoplasty frequent follow up and long term steroid application. Since the study was started in 2011 and finished in 2012, there might have been patients who were amenable for keratoplasy for visual rehabilitation. Such an outcome would be interesting to look at and could have established both these procedures for treatment of recalcitrant ulcers. However this article has encouraged us to start these old but highly effective methods in our institution. We can leave a small band of conjunctiva while doing peritomy so that limbal stem cells remain undisturbed. We are thankful to author for such valuable information. CONFLICT OF INTEREST The authors have no conflict of interests disclose FUNDING SOURCE The authors have no funding source to disclose References- 1) Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant infectious keratitis: a randomised clinical study Bahaa-Eldin Hasan Abdulhalim,1 Mostafa Mohamed Wagih,1 Ahmed A M Gad,1 Ghada Boghdadi,2 Ragy R S Nagy3 ,BJO , July 22, 2014 2) J Kanski and B Bowling , Clinical Ophthalmology - A systematic approach( 7th ed), 240-244. Debasmita Majhi, Srikant Kumar Sahu (srikant@lvpei.org; Srikant_sahu1@yahoo.co.in), Danish Alam, L V Prasad eye institute, Bhubaneswar, India Correspondence: Srikant Kumar Sahu, MS, cornea and anterior segment services, L V Prasad Eye Institute, Bhubaneswar 751024, India. Tel: 91-9439488888 Emails: srikant@lvpei.org; Srikant_sahu1@yahoo.co.in)

    Conflict of Interest:

    None declared

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  10. Data inconclusive to recommend oral azithromycin over oral doxycycline in meibomian gland dysfunction

    Kashkouli and colleagues (1) have studied a subject with high clinical relevance. Meibomian gland dysfunction is prevalent and treatment often unsatisfactory. Oral azithromycin has advantages over oral doxycycline including dosing and side effects as reviewed in the article.

    There are a few problems with the methods to be highlighted so that readers can draw accurate conclusions, and validation studies be constructed appropriately. This is done in point form below.

    -Statement of a null hypothesis a priori would have been helpful to interpret the trial as a non-inferiority or superiority design. (2)

    -The sample size calculation was designed "to detect at least 1.8 differences". It is not clear why this number was chosen and cannot be gleaned from the cited articles. Was the trial adequately powered to meet the aims of assessing efficacy and safety?

    -Ideally, a new scale as used in the study should be validated before use in a trial.

    -Ten patients were lost to follow-up. Their baseline characteristics should be reported and compared to those who completed follow-up. (3) Intention-to-treat analysis can determine the maximum effect on the results of those lost to follow-up by assuming the extremes of outcome and recalculating. (4) The null hypothesis is important to assign the extremes appropriately.

    -"Symptoms significantly improved in both groups (p=0.001, 95%CI -2.2 to -0.7)". A similar statement exists for clinical signs. There are two groups and there should be a 95%CI for each. It cannot be determined to which group these values correspond.

    -The Bonferroni multiple comparisons test applies to the data shared in Table 4. With seven variables, the p value for significance is 0.007 (0.05/7). Therefore, ocular surface staining is no longer significant in this conservative model.

    The potential impact of repeated dosing of oral azithromycin on bacterial resistance was not addressed in the discussion and also deserves comment from the authors.

    In light of these concerns, conclusions from this study should be tempered until the results are validated.

    1. Kashkouli MB, Fazel AJ, Kiavash V, Nojomi M, Ghiasian L. Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomized double masked open label clinical trial. Br J Ophthalmol ePub 19 Aug 2014.

    2. Committee for Proprietary Medicinal Products. Points to consider on switching between superiority and non-inferiority. Br J Clin Pharmacol 2001; 52:223-228.

    3. Groenwold RHH, Moons KGM, Vandenbroucke JP. Randomized trials with missing outcome data: how to analyze and what to report. CMAJ 2014; 186:1153-1157.

    4. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 1993; 270:2598-2601.

    Conflict of Interest:

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