Displaying 1-10 letters out of 469 published
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
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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.
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Comment on : Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant infectious keratitis: a randomised clinical studyDear 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 (firstname.lastname@example.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: email@example.com; Srikant_sahu1@yahoo.co.in)
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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.
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Re: Comparison of umbilical cord serum and amniotic membrane transplantation in acute ocular chemical burns
Dear Editor; We have read the article entitled "Comparison of Umbilical Cord Serum and Amniotic Membrane Transplantation in Acute Ocular Chemical Burns" by Sharma et al. with interest.1 The authors compared the efficacy of amniotic membrane transplantation (AMT) and umbilical cord serum (UCS) in patients with ocular chemical burns. They found that UCS treatment was superior to AMT in maintaining a better ocular surface. The authors also emphasized that UCS treatment offers the benefit of avoiding a surgical maneuver in already inflamed eyes. Human tear film contain multiple biologically active growth factors and essential components secreted by the lacrimal gland. These substances include transforming growth factor-?, basic fibroblast growth factor, epidermal growth factor, neurotrophic factors and vitamin A. These componenets play critical roles in maintaining the health of ocular surface structures.2 It has been revealed that UCS includes many neurotrophic factors, essential tear components and growth factors. It is a more valuable adjunct than autologous serum in the management of persistent epithelial defects and severe dry eye syndrome.3 In addition to these biological effects, it acts as a lubricant due to physical characteristics similar to tears. We assume that the superiority of UCS to AMT may be attributed to those features mentioned above. A recent study showed that amniotic membrane is able to remove reactive oxygen species due to the presence of abundant hyaluronic acid.4 That property may be advantageous in distinct clinical entities in which oxidative stress is involved in the pathogenesis. For example; the role of oxidative stress in mustard-induced chemical injury is well-defined. Therefore; AMT may be preferred to UCS in the treatment of chemical ocular surface burns especially in the acute phase.
1. Sharma N, Lathi SS, Sehra SV, et al. Comparison of umbilical cord serum and amniotic membrane transplantation in acute ocular chemical burns. Br J Ophthalmol. 2014; 2. Klenkler B, Sheardown H, Jones L. Growth factors in the tear film: role in tissue maintenance, wound healing, and ocular pathology. Ocul Surf. 2007; 5:228-239. 3. Yoon KC, Im SK, Park YG, et al. Application of umbilical cord serum eyedrops for the treatment of dry eye syndrome. Cornea. 2006; 25:268-272. 4. Lockington D, Agarwal P, Young D, et al. Antioxidant properties of amniotic membrane: novel observations from a pilot study. Can J Ophthalmol. 2014; 49:426-430.
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Outcomes of epiretinal membrane surgery in highly myopic eyes: a case-control studyThe published study by Conart and colleagues is described as a nested case-control study; however, this is incorrect.1 Participants were selected based on the presence or absence of high myopia and were matched with respect to time of surgery, duration of symptoms, and preoperative visual acuity. The participants were followed up prospectively to compare anatomical and functional outcomes following epiretinal membrane (ERM) surgery among patients with and without high myopia. This describes a matched cohort study, not a nested case-control study. This error has implications for the appropriate statistical analysis, and therefore, the proper interpretation of the observed results. In addition, the statistical tests employed do not account for the matched nature of the study design and therefore are not appropriate. Statistical procedures that account for the matched nature of the study should have been employed. Furthermore, the authors also compared the mean change in best corrected visual acuity and central macular thickness from baseline to 1-year post-surgery within each exposure group (in the text, pages 3-4); however, none of the statistical tests used accounted for the within-person correlation that occurs when taking multiple measurements from the same subject. Specifically, the authors used Student's t-test when paired t-tests should have been used. Authors are strongly encouraged to conduct a reanalysis of their study data using statistical procedures suitable for this study design and provide readers with the appropriate p-values, amending their interpretation as warranted. References 1. Conart J-B, Favel C, Selton J, et al. Outcomes of epiretinal membrane surgery in highly myopic eyes: a case-control study. Br J Ophthalmol. 2014.
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Quantifying Symptomatology in Convergence Insufficiency Using the Convergence Insufficiency Symptom Survey
We are in agreement with Horwood and associates that the Convergence Insufficiency Symptom Survey (CISS) was not designed as a screening tool for convergence insufficiency (CI) and thus should not be used as such. However, we would like to point out that their conclusion from their recent paper(1) that the "majority of subjects with clinical signs of CI (reduced convergence and fusional ranges) have no symptoms," is not supported by their data. Unfortunately, their study design severely limits any conclusions that can be made regarding symptoms in young adults with CI because 1) the study specifically recruited "asymptomatic" subjects, 2) the study excluded subjects who would clearly meet the clinical diagnosis of CI, and 3) the CISS was not administered as designed and validated.
In regards to subject selection, only university students "who considered their eyes normal" and had not sought treatment for visual symptoms in the past were invited to participate. They were asked to complete the CISS to "confirm the absence of significant visual symptoms" during the recruitment phase of another study for which they were to be paid. There is little doubt that eliminating students with visually- related symptoms and those who had been informed in the past about a binocular vision anomaly (including CI) and associated symptoms, resulted in significant selection bias for a study evaluating the presence of symptoms in those with and without CI.
Another troublesome issue is that those with a near exophoria greater than 8 prism diopters (pd) were excluded, meaning that none of those diagnosed with CI had a large exophoria at near. We are perplexed why a patient with a near exophoria of 10 pd, a receded near point of convergence, and poor convergence amplitudes at near would be excluded from a study of CI. A high exophoria at near is usually considered to be one of the hallmark clinical signs of CI (2-4) For example, in a CITT study of young adults with symptomatic CI the mean near exophoria was 10.6 (SD=4.8).(5)
Of further concern is that rather than administering the CISS as designed and validated, the authors administered the CISS using a non- standard testing approach. The survey was emailed to students who were told that the purpose was to "confirm the absence of significant visual symptoms in a quantifiable fashion." In addition, supplemental questions (e.g., "Do you think it was because you were tired at the time?" or "Do you think it was because your eyes have made it necessary?") were added for 5 of the 15 survey items and adjusted scores were derived. Apparently, the authors assumed that the students could distinguish whether their symptoms were directly related to their visual system and that altering the presentation of CISS questions would not impact the validity of the instrument. Certainly, a golden rule when administering a validated questionnaire is that it should not be modified because even very small changes can negatively impact its validity. As emphasized by E. Juniper, "it is beholden to each one of us to ensure that we use only authorized versions in our clinical practice and research."(6) The only way to know with any certainty if a questionnaire can be improved with modifications is if the validity and reliability are established for the modified version. Lastly, we are disappointed that the authors presented their modified version in their Figure 1 as the "convergence insufficiency symptom survey" when it is obviously not the copyrighted version of the test. This is bound to lead to confusion for readers, especially those who are unfamiliar with the CISS.
As correctly noted by the authors, the CISS was developed as a method of quantifying and monitoring symptoms in persons with CI; it was never intended, nor have we promoted it to be used as a screening instrument for CI. However, the presence of symptoms associated with reading is often the critical factor used when optometrists and ophthalmologists recommend treatment for CI. If the CISS is administered and scored as designed, it can be a useful tool for "quantifying" symptoms in children and adults with CI before and after treatment in clinical studies or in clinical practice. The answer to the question of what proportion of university students with CI are symptomatic remains unanswered.
1. Horwood AM, Toor S, Riddell PM. Screening for convergence insufficiency using the CISS is not indicated in young adults. Br J Ophthalmol. 2014;98(5):679-83.
2. Convergence Insufficiency Treatment Trial (CITT) Study Group. Randomized clinical trial of treatments for symptomatic convergence insufficiency in children. Arch Ophthalmol. 2008;126:1336-49.
3. Dusek WA, Pierscionek BK, McClelland JF. An evaluation of clinical treatment of convergence insufficiency for children with reading difficulties. BMC Ophthalmol. 2011;11:21.
4. Scheiman M, Gwiazda J, T L. Non-surgical interventions for convergence insufficiency. Cochrane Database of Systematic Reviews 2011(Issue 3. Art.No.: CD006768. DOI: 10.1002/14651858.CD006768.pub2.).
5. Rouse MW, Borsting EJ, Mitchell GL, Scheiman M, Cotter SA, Cooper J, et al. Validity and reliability of the revised convergence insufficiency symptom survey in adults. Ophthalmic Physiol Opt. 2004;24(5):384-90.
6. Juniper EF. Validated questionnaires should not be modified. Eur Respir J. 2009;34(5):1015-7.
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Recent trends in glaucoma surgery, accurately assessed? - A case for updated coding?
We read with interest the recent article by Murphy, et al*. The authors report a six-fold increase in the use of glaucoma drainage devices (GDDs) between 2003 and 2012. They also note that non-penetrating glaucoma surgery (NPGS) and minimally-invasive glaucoma surgery (MIGS) were not analyzed due to the small numbers being undertaken. One confounder is MIGS have the same code as for GDDs & have been in the UK since 2009. Consequently, the analysis and conclusions in the paper may be inaccurate. The manufacturers of MIGS devices were asked if they knew of any other codes being used, to which they responded, "No." The increase in numbers of GDDs in paediatric populations is most likely accurate. However, this may not reflect adult surgery.
It is hard to support the authors' comment that the number of NPGS is small. Several newly-appointed Consultant Glaucoma Surgeons perform NPGS; it is offered as part of subspecialty training in certain centres, thereby cascading the likelihood the procedure is performed. There is no clear code for NPGS, hence it is hard to know how many NPGS are actually being performed. A poll of UK surgeons undertaking NPGS found that 3-4000 procedures were undertaken during the timescale of the Murphy study. Six recently appointed Consultants reported having performed approximately 700 last year. These are not small numbers. It is unfortunate they cannot be extracted from the overall number of procedures. We also thought it was interesting there was no mention of trabeculotomy or goniotomy in the paediatric group. Trabeculotomy is the most common procedure for childhood glaucomas in the United States and GDDs would be used if these failed.
Whilst the authors are to be congratulated on an interesting review, an update of the OPCS codes may help us obtain more meaningful data in the future.
* Murphy C, Ogston S, Cobb C, et al. Recent trends in glaucoma surgery in Scotland, England and Wales Br J Ophthalmology. Published Online First 10 September 2014
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Details of participants in the study are incomplete.
I have read the article with great interest as it is one of the early reports of this emerging technology. Going through the article I noticed that though the inclusion criteria describe that the patients with refractive error less than 10 diopter of myopia and astigmatism less than 5 diopter were included, the results show only the average myopia and standard deviation. The range of spherical myopia is not given, though the range of astigmatism is provided.
i will be keen to know the range of myopia included as it is obvious that a very thin lenticule will be difficult to create and retrieve in case of low myopia.
Kindly comment on the following points, 1. the range of myopic refractive error included in the study. 2. Any limitation in including patients with low myopia. 3. Was there any difficulty in handling a thin lenticule in the patients with low refractive error?
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Dua's Layer and Success of Non Penetrating Glaucoma Filtering surgery
We read with interest the article on extension of Dua's layer into trabecular meshwork.(1)This knowledge has implications also in success of newer surgeries like deep sclerectomy. Deep Sclerectomy is a safer option to trabeculectomy but is known to fail in some cases (2)(3). Guedes et al(4) have investigated the factors affecting the success of this surgery. George Kistos et al (5) have discussed a modified deep sclerectomy to deal with failure and they postulated an external removal of the inner wall of Schlemm's canal and the external layers of the trabecular meshwork with external trabeculectomy . Iordanidou et al (6) have shown how the bio mechanics of the cornea changes after deep sclerectomy and this may be responsible for success in stabilising field defects independent of the intra ocular pressure . Dua's layer has been shown by Dua et al to affect the corneal biomechanics.It now seems that the removal of the Dua's layer may be central to success of deep sclerectomy due to various reasons, one being imperviousness of this layer ( which gets confused with Descemet's layer) and the other being the fact that the biomechanics of the cornea changes with removal of this layer. We have been doing modified deep sclerectomy since 5 years at our hospitals and go a little ahead anteriorly into the cornea and create a Descemet's window without perforating that window and sometimes we do not see egress of fluid at the removal of deep scleral flap and deroofing of the schlemm's canal and the Descemet's window. We routinely do a video audit of our cases. In our video audit we have noted that in cases where there is no fluid egress the "descemet's membrane" withstands pressure and the air bubble in the anterior chamber is visible and even on increasing the anterior chamber pressure with a large bubble the "descemets membrane" does not rupture. Dua et al (7)have discussed the properties of this layer and it is said to be impervious to air and known to withstand pressures upto 200kPa.We postulate that this is a combination of descemet's layer and Dua's layer which has not been removed. These are the cases in which the deep sclerectomy fails and needs a gonio puncture. In other cases the "descemet's membrane" is very thin and shows egress of fluid spontaneously and sometimes ruptures if the anterior chamber pressure is high due to large air bubble, releasing a small air bubble but no prolapse of iris or sometimes leading to iris prolapse without the membrane being touched. In these cases there is good egress of fluid even from the area of schlemm's canal.These cases of deep sclerectomy are successful. These are the cases where the Dua's layer has been removed and hence the layer remaining in the eye is purely Descemet's layer and allows egress of fluid and cannot withstand pressure. We postulate that the thick membrane that withstands pressure and does not allow egress of fluid easily is a sclerosed peripheral part of Dua's layer which if not removed causes failure of deep sclerectomy necessitating a gonio puncture later. Removing this layer is probably the key to success of Deep Sclerectomy. Further evaluation is needed to substantiate this hypothesis though our video audit shows that, cases in which the layer has not been removed ,fail and need a gonio puncture and the cases in which the Dua's layer is removed are successful and do not need a gonio puncture suggesting that removal of Dua's Layer is essential for success of Deep Sclerectomy, modified or otherwise.
1)Harminder S Dua, Lana A Faraj,Matthew J Branch,Aaron M Yeung,Mohamed S Elalfy,Dalia G Said,Trevor Gray,and James Lowe.The collagen matrix of the human trabecular meshwork is an extension of the novel pre-Descemet's layer (Dua's layer)Br J Ophthalmol 2014 98:691-697;
2)El Sayyad F(1), Helal M, El-Kholify H, Khalil M, El-Maghraby A.Nonpenetrating deep sclerectomy versus trabeculectomy in bilateral primary open-angle glaucoma.Ophthalmology. 2000 Sep;107(9):1671-4.
3)Zsolt Varga and Tarek Shaarawy.Deep Sclerectomy: Safety and Efficacy.Middle East Afr J Ophthalmol. 2009 Jul-Sep; 16(3): 123-126.
4)Guedes RA(1), Guedes VM, Chaoubah A. Factors associated with non-penetrating deep sclerectomy failure in controlling intraocular pressure.Acta Ophthalmol. 2011 Feb;89(1):58-61.
5)George Kitsos,Miltiades Aspiotis, Yannis Alamanos, Konstantinos Psilas. A modified deep sclerectomy with or without external trabeculectomy: a comparative studyClinical Ophthalmology 2010:4 557-564
6)Iordanidou V(1), Hamard P, Gendron G, Labb? A, Raphael M, Baudouin C.Modifications in corneal biomechanics and intraocular pressure after deep sclerectomy.J Glaucoma. 2010 Apr-May;19(4):252-6.
7)Dua HS, Faraj LA, Said DG, Gray T, Lowe J (September 2013). "Human corneal anatomy redefined: a novel pre-Descemet's layer (Dua's layer)". Ophthalmology 120 (9): 1778-85
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