636 e-Letters

  • Collaborative Efforts for Improving Statistical Practice of Ophthalmic Data

    We thank Dr. Bunce et al for their interest in our paper.1 We would like to apologize for not mentioning the Statistics Notes Series2-12 from the UK Ophthalmology Research Section of the NIHR Statistics group. Given that our paper’s purpose is to evaluate whether the correlated eye data were analyzed properly in published ophthalmic clinical science papers, we did not cite these papers because we think most of them serve as introductions of general statistical methods instead of specific statistical methods for correlated eye data.

    We agree these Statistics Notes Series are very helpful to the vision research community to improve the statistical analysis and interpretation of ophthalmic data. We applaud the UK Ophthalmology Research Section of the NIHR Statistics group for their collaborative efforts in improving the quality of statistics for ophthalmic research through these series of publications and workshops. Similarly in the USA, we have been promoting the proper analysis of correlated eye data through tutorial papers13-14 and the ARVO short course. We believe all these efforts will lead to improvement in the statistical practice for ophthalmic data.

    We also agree that there are varying degrees of misuse of statistical methods in analyzing correlated eye data. Ignoring the inter-eye correlation when data from both eyes are analyzed is very bad practice as it can lead to the invalid conclusion, while analyzing correlated ocular data at person-level does...

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  • Reply to: Benign positional "vertical opsoclonus", or "upbeat nystagmus"?

    We thank Drs. Robert and Vidal for their comments. After carefully reading their original series of 5 patients and observing their videos [1], our impression was that both series could definitely refer to the same unique phenomenon.
    As stated before [2], a drawback of our series was the inability to acquire eye movement recordings for any of our patients due to technical obstacles and parental refusal. We found Robert and Vidal’s ability to do so in one of their patients very important to the understanding and definition of the phenomenon [1]. Clearly their recordings demonstrate an upbeating nystagmus that would be expected in patients with tonic downgaze, assuming the eyes drift down while saccadic correcting movements are upward towards primary gaze. Hopefully, additional supporting recordings will be added to the literature in the future, allowing us to conclude that this is a representing finding for all of these patients.
    This condition was apparently described under different titles over the years owing to scarce descriptions in the literature and difficulty providing convincing support for one definition over the other. This is an important step in that direction. We agree that with their addition of data, the term should include “upbeat nystagmus” and therefore suggest the term “benign infantile positional tonic downgaze with upbeat nystagmus”.

    1. Robert MP, Michel S, Adjadj E, Boddaert N, Desguerre I, Vidal PP. Benign intermittent upbeat nystag...

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  • Benign positional "vertical opsoclonus", or "upbeat nystagmus"?

    Dear Editor,

    We read with great interest the nice series from Sternfeld et al. about so-called “benign positional vertical opsoclonus in infants”. [1] As stated by the authors, the very specific condition they describe is not uncommon in the population, yet still poorly described in the scientific literature. Additionally, it is called differently by different authors, one reason for it being the difficulty to assess through the naked eye the very nature of the high frequency eye movements, as shown in video n°1.
    The condition combines a positional tonic downgaze and abnormal vertical eye movements. Oculomotor recordings of infants presenting with this clinical picture do actually confirm that these movements comprise downbeating slow phases and upbeating saccades 2, as clinically seen in video n°2, and are therefore a vertical kind of nystagmus. We therefore proposed to refer to them as benign intermittent upbeat nystagmus in infancy. [2] As stated by the authors, the association of a tonic downgaze and an upbeat nystagmus is logical and has been related to posterior semicircular canal predominance. [3]
    In addition to the evidence of slow phases in this condition and to the fact that, to the best of our knowledge, no pulse of purely vertical saccades has ever been recorded, the very possibility for the oculomotor system to produce such movements is questionable. Opsoclonus, by definition, designates a succession of multidirectional saccades. We therefo...

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  • Better collaboration to optimise research

    We read with great interest the recent paper by Zhang and Ying exploring statistical approaches in published ophthalmic clinical science papers.1 We very much agree with the main conclusion drawn by the authors that collaborative efforts should be made in the vision research community to improve statistical practise for ocular data. In this vein, however, we were disappointed not to see reference to the Statistics Notes Series that has been published in this very journal. These have been written with a view to tackling some of the more prevalent statistical issues within ophthalmology and we would encourage readers to make use of these.2- 12. Within the UK this view that there needs to be greater collaboration in the vision research community has led to the formation of the Ophthalmology Research Section of the NIHR Statistics group which is championing cross- professional collaboration and active discussion in relation to statistical issues. It is always important when reviewing misuse of statistics in biomedical research to distinguish between misuse that leads to distorted or incorrect results and those methods which do not fully use data to maximum potential given that this loss of information might be viewed as unethical. In this regard we find the results from Zhang et al pleasing in that the proportion of papers which analysed at the level of the individual because of the nature of the observation rose from 15.2 % in 1995 to 50 % in 2017. A finding which is...

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  • Response to Monfermé et al., 2018

    To the Editor:

    We read the recent article in the journal by Monfermé and coauthors (1) on phenotypic associations of TYR R402Q compound heterozygosity with keen interest. Given our own and others previous findings (2-4) that the R402Q-S192Y haplotype seemed to have a stronger biological effect, we were surprised that a triallelic effect was not supported in the clinical discussion by Monfermé et al. When we examined these results more closely, we noted that their sample included 52 S192Y variant allele carriers out of the entire collection of 69 patients, of whom 31 (44.9%) carried the R402Q-S192Y double variant haplotype. In our own collections from the Australian general population (BNMS and BLTS, Duffy et al., in submission), only 6% of R402Q carriers also carried S192Y in cis. When we examined the European 1000 Genomes subsamples, there too only 7% of R402Q haplotypes had the 192Y rather than 192S wild type allele. So, even though Monfermé et al could not detect a statistically significant additive effect on OCA trait severity due to the S192Y polymorphism within their sample, it is clear that the S192 variant allele is markedly overrepresented compared to the general population, suggesting that it must have some relationship to albinism. This genetic association of the TYR R402Q-S192Y double variant haplotype with OCA1 is now clearly causative (2, 3), and explains some of the missing heritability that has previously been seen in OCA patients (4).


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  • Re: Comparative Effectiveness and harms of intravitreal antivascular endothelial growth factor agents for three retinal conditions: a systematic review and meta-analysis

    To the Editor,
    Intravitreal antivascular endothelial growth factor (VEGF) agents undeniably have many clinical applications and we read with great interest the recent meta-analysis published in your journal by Low et al1 comparing the effectiveness and harms of these agents in three retinal disorders.
    We would first like to thank the authors for their exhaustive review and synthesis of the evidence in this area. The conclusions they reached served to confirm what many of us had already suspected.2 Nevertheless, the article features some important methodological flaws and inadequate reporting of data that we would like to highlight to ensure that readers are in a position to interpret the findings of the meta-analysis correctly.
    In relation to reporting issues, we were surprised to see that Table 1, which is quite creative and unique in terms of systematic review tables, does not include a list of the studies analyzed for each section. The authors, for example, state that they included two clinical trials comparing aflibercept and ranibizumab, but they do not specify which ones. This detracts from the transparency of the study and makes it difficult to review the findings. We also noticed a lack of uniformity within the figures, as some of the studies are listed by author name and others by author name and year of publication. In addition, Figure 3 shows data from the 2011 study by Biswas P, Sengupta S, Choudhary R, et al for the 18-24–month but not the 12...

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  • Choroidal Thickness in Macular Telangiectasia Type 2

    We read with great interest the article titled “Choroidal thickness and vascular density in macular telangiectasia type 2 using en face swept-source optical coherence tomography” by Wang et al.[1] This is an interesting study in which the authors performed multimodal imaging for the diagnosis of macular telangiectasia (MacTel) type 2 and reported similar choroidal thickness (CT) between MacTel type 2 and control eyes using swept-source optical coherence tomography (SS-OCT).[1]
    There are a few concerns that we would like to highlight. Although the authors control for confounders like age and spherical equivalent, axial length is another important confounder that has not been evaluated in this prospectively conducted study. The subfoveal CT has been reported to decrease by up to 58µm per one mm increase in the axial length after adjusting for age and sex.[2] Ignoring the axial length in choroidal thickness analysis may have untoward consequences.
    Although the number of cases was small (n=39 eyes), the stagewise distribution of CT may be of help. A recent study by Kumar et al. using SS-OCT reported different subfoveal CT in non-proliferative and proliferative stages of the disease, although the results were not statistically significant.[3] If a varied distribution is observed between different stages, this may support the role of the choroid in the pathophysiology of this disease.
    Inter-ocular asymmetry does exist in CT[4] as well as in the pr...

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  • Author response to “Collaterals or telangiectasias?”

    Dear Editor,

    We appreciate the valuable comments from Dr. Sato regarding our recently published article.1 Dr. Sato’s comments raise important points about definition of collateral vessels in eyes with branch retinal vein occlusion (BRVO).
    As previously reported,2 collateral vessels develop from the pre-existing retinal capillary network to drain a blood flow from an obstructed vein into an adjacent area in eyes with BRVO. Therefore, in the current study, we defined collateral vessels as dilated and tortuous capillaries occurring in pre-existing capillary beds and linking the obstructed vessel with the nearest patent vessel. Thus, the adjacent vessels also seemed to be dilated and tortuous, which had been similarly observed in our previous study.3 We speculate that the pressure gradient between an obstructed vein and neighbouring unobstructed vessels causes collateral vessels formation. The collaterals detection rate in the current study was higher than in the previous study.3 This is because wider optical coherence tomography angiography (OCTA) images, the size of which was 6 ✕ 6 mm in area, were used in the current study.
    Regarding the other comment about the location of collateral vessels, Freund et al4 reported that collateral vessels were observed in only deep retinal capillary layer. However, we confirmed that the collateral vessels were present in both the superficial and the deep capillary layers on B scan images of OCTA. Additionally, fluoresc...

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  • reply to Previous Reports of Tyr437His mutation

    Dear Editors,
    Thanks for your email and comments for John H Fingert et al.
    In our work, we aim to characterize the genotype(s), phenotype(s) and age-related penetrance in a Chinese family with primary open-angle glaucoma (POAG). We recruited a four-generation Chinese family with 22 participants and identified a novel heterozygous MYOC gene mutation (exon3 c.1309T>C p.Y437H) only among seven POAG patients and one ocular hypertension (OHT) patient. Further, we summarized the exact phenotype characterization of MYOC Y437H mutation and calculated the age-related penetrance of this family. Hopefully, we can do a favor in establishing genotype–phenotype correlations, which play a significant role in predicting the range of phenotypic variation of a specific mutation, in managing the disease better and in genetic counselling.
    To the best of our knowledge, this is the first report of Y437H mutation in Chinese.Thus, we titled our work as “A novel MYOC gene mutation in a Chinese family with primary open-angle glaucoma”, which we really mean is a novel mutation only in Chinese population. We are very sorry about the misunderstanding the inappropriate title of our article may cause. In “Molecular analysis” section, we have affirmed that the Y437H mutation has been reported and referred previous article titled” Identification of a gene that causes primary open angle glaucoma” and so on.
    To avoid above misunderstanding ever happening, if it is possible we’d li...

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  • Reply

    We thank Dr. Sarnicola and family for their interest in our work and at the same time we apologize for not mentioning their preliminary results published in 2010; in this regard, some issues need be clarified.
    We used an acronym to shorten the text and facilitate the readers of our article by eliminating this way long descriptive wording of the procedure. This did not imply by any means an attempt at modifying the terminology of surgical techniques, which is usually a task of the ophthalmological community. In fact, a particular acronym becomes a standard only when it is cited as such by numerous papers in the literature. This is not seeming the case, for the acronym “AVB”, that has never been used after its initial introduction by Sarnicola et al., thus failing to achieve the purpose aimed at.
    In addition, we had a reason to introduce a new acronym because of a substantial difference in the surgical technique: in fact, instead of creating a new corneal tunnel into the emphysematous tissue, we inject ophthalmic viscoelastic device (OVD) in the same track created for pneumatic dissection, thus increasing surgical reproducibility and safety.
    The lack of previous data we indicated (“…little data are available on the success rate…type of cleavage obtained, visual results and complications of this approach”) was simply related to the new concept of performing the injection of the OVD in the same corneal path where the air had failed.
    In our series visual...

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