670 e-Letters

  • Reply to the letter of Dr. Tarannum Mansoori

    We would like to thank Dr. Tarannum Mansoori for the interest in our study, “Intraocular pressure change after injection of intravitreal dexamethasone (Ozurdex) implant in Korean patients” and highlighting important issues about the intraocular pressure (IOP) measurement methods and the correlation of IOP with age.1
    We used KT-800 Non-Contact Tonometer (Kowa, Tokyo, Japan) to measure IOP initially and rechecked with GAT if necessary. Unless the patient was diagnosed with glaucoma, NCT was initially used to measure both pre- and post-injection IOP.
    As Dr. Tarannum Mansoori has pointed out, we also agree that GAT is the gold standard for IOP measurement. If the IOP measured with NCT was found to be high, it was always rechecked with GAT. GAT was used in 2 situations in our study. First, when the patients had a previous history of glaucoma, and second, when the patients’ IOP as measured with NCT was high (greater than 20). Thus, in cases of high IOP, the measurement involved NCT and was also always double checked with GAT. Moreover, multiple IOP measurements were obtained with GAT in cases of high IOP, and the average value of the measurements was regarded as the final IOP.
    The range of age of the patients for injection of intravitreal dexamethasone was broad, from 16 to 88 years. We know that very young age (less than six years) or an older age are risk factors for steroid-induced glaucoma.2 However, regrettably, we have not performed any further analysis...

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  • Response to letter

    We thank the authors for their careful perusal of our study report and thoughtful observations. We agree that as demonstrated by the large population study1,2 referenced by us and by them, the rate of complications with cataract surgery is non-homogenous and increases dramatically with advanced stage cataracts – as much as 200%+ increase in rate of PCT in cases with high grade cataract, pseudoexfoliation and other comorbidities. In fact, with the co-existence of multiple factors, the compound rate can be even higher.

    Our pilot study was in patients with advanced cataracts and multiple co-existing ocular pathologies and given the small sample size we are not surprised that the study point estimate for the PCT rate may be on the higher end of the overall range demonstrated by the larger population study. In addition, the randomized control design of the clinical trial further validates a PCT rate which was similar for both treatment and control groups. Certainly, an informed reader would appreciate that such a small trial is underpowered to be conclusive regarding the small difference between the two groups so no claims should be made about the slightly better rate of PCT and lower trend demonstrated in the miLOOP group.

    What is important to appreciate from both the population study and our pilot data is that the rate of PCT is not the same for all cataract surgeries and there is a multiplier effect in certain subgroups and subpopulations. Our authorship team...

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  • Concerns regarding complication rates of recent prospective investigation

    We are interested in the work of Ianchulev et al in their recent interventional randomized controlled trial.[1] What piqued our interest was the rate of posterior capsular tears (PCT). 4/53 (7.5%) patients in the miLOOP+phaco group experienced PCT, and 5/48 (10.4%) phaco-alone controls with PCT. These rates are much higher than standard phacoemulsification reports. The authors refer to a large study that identified advanced cataracts increased risk of PCT at comparable levels.[2] That same group published investigations expounding upon this.[3-4] Advanced cataracts were specifically identified as brunescent/white cataracts, contrasting Grade 3-4 in the miLOOP study (curiously described as LOCSIII classification in the manuscript).

    Using the risk calculation,[3] the range of composite adjusted odds ratio (aOR) for the miLOOP study was 49.93 (25-28% risk) to an aOR of 0.87 (<1% surgical risk). The average patient from the miLOOP investigation had an aOR of 4.43, thus <5% PCT risk.

    Our concerns: First, the authors state that “There was a trend towards a lower rate of capsular tear during the phaco portion with miLOOP-assisted phaco (7.5%) compared to standard phaco (10.4%).” Given the numbers representing these percentages this is an inappropriate description of this relationship.

    Let us assume that a control group presented with a PCT rate similar to that reported in literature: <5%. Here, miLOOP-phaco PCT rate would be higher than the control...

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  • Author Response to Letter to the Editor

    To the Editor,

    We appreciate Francisco-Javier Carrera-Hueso, Pedro Vazquez-Ferreiro, and Jaime Poquet-Jornet's careful reading of this paper. This commissioned review had a necessarily broad scope in order to summarize benefits and harms across three available therapies for the most common clinical indications. We agree there was quite a bit of information to present and that doing so in a succinct format is a challenge. However, we disagree with their contention that we did not follow current methodologic systematic review standards. We did indeed follow PRISMA reporting guidelines, as described in the Methods.

    Regarding Table 1, the studies included in the summary table are the same as those described within the text and meta-analyses; we apologize for any confusion. In terms of format for the listing of studies in the meta-analyses, since studies are known primarily by their acronym, we used them in the figures whenever possible. The trials without specific names or acronyms were listed according to author and year.

    Biswas 2011 only reported the percentage of patients gaining ≥15 letters at the 18-month endpoint, not at 12 months, so the study could not be included in the 12-month analysis for this outcome. The study did report mean change in BCVA at both endpoints, so it is included in both the 12 month and 18-24 month analyses in Figure 2. In terms of analyzing cost-effectiveness, only two trials meeting inclusion criteria (CATT and DRCR) di...

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  • 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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