587 e-Letters

  • Response to AML after OAC

    Dear Sir,

    We are writing this letter in response to a “letter to the editor” from Drs. Leahey and Meadows about our recently published paper “Second primary malignancies in retinoblastoma patients treated with intra-arterial chemotherapy: the first 10 years”.1 There are a number of incorrect statements in their letter and we hope this letter will clarify those errors made by them.

    1) Drs. Leahey and Meadows state that…”the author’s report is profoundly misleading with regard to the risk of SPMs following OAC”. To prove that they then state that the median follow-up range is 2.5 years with a maximum follow-up of 12 years. How is that “profoundly misleading”? In the same paragraph they then state that patients failing OAC required radiation therapy and suggest that all of these second neoplasms are a consequence of radiation. That is not true. In our paper (page 273, Table 3) we documented that not one of the children who developed a second tumor had received radiation. How could radiation be the cause of a second tumor if the patients never received radiation? Dr. Leahey and Meadows also wrote that…”patients failing OAC require radiation”. That’s not true. On page 272 we stated that…”patients who received external beam radiation prior to presentation at our clinic were excluded from analysis”. None of the patients in this series received radiation after OAC and no patient in our center has received radiation in the past 10 years. We do not dispute that radia...

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  • Acute Myeloid Leukemia following OAC

    Having read the article of secondary primary malignancies (SPM) in patients treated with ophthalmic artery chemosurgery (OAC) (1), we wish to update Dr. Habib’s report. A patient with unilateral Group D heritable retinoblastoma (RB) treated by their team with 5 OAC treatments in 2012 through 2013 developed acute myeloid leukemia (AML) on 4/26/2017 and died 3 months later.
    Following an intraocular recurrence after OAC and subsequent enucleation the patient’s care was transferred to our institution. Despite adjuvant chemotherapy he developed widespread bone and marrow metastases 8 months after enucleation. He then underwent intensive chemotherapy and an autologous stem cell transplant. Twenty eight months later he developed AML with a fms-like tyrosine kinase 3 (FLT3) mutation. Melphalan administered during all OAC treatments and the drugs administered following that failure must be implicated in this outcome (2). By failing to eradicate retinoblastoma, metastatic disease ensued requiring further treatment and subsequently, AML.
    The author’s report is profoundly misleading with regard to the risk of SPMs following OAC. Although the maximum period of follow-up is 12 years, the median is 2.5 years. Patients failing OAC required radiation therapy and are known to be 3 times more likely to develop additional cancers (3). We await that follow-up.
    The goal of RB care is cure. This patient’s course illustrates the danger of failing to prevent metastatic disease wi...

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  • Combination therapy for Fungal keratitis: Should we go for it?

    We read with interest the report by Sradhanjali et al(1) demonstrating more effective antifungal activity of combination of Natamycin and voriconazole than single-use in vitro treatment. It should be noted, however, that given the small sample size, these results should be confirmed with a larger dataset.

    Caution should be exercised when inferring results from in vitro studies because it always do not translate to in vivo models and are inconsistent. In our hands, we found treatment success when adding topical voriconazole 1% with natamycin 5% in recalcitrant full thickness infiltrate cases of fungal keratitis. This may be because topical natamycin acts superficially whereas voriconazole, though not as effective as Natamycin, takes care of the deeper infiltration because it has better penetration than Natamycin. Sharma et al (2) also concluded that topical voriconazole seems to be a useful adjunct to natamycin in fungal keratitis not responding to topical natamycin. Debridement of ulcer also helps in these cases giving way for the drug to act and reducing the fungal load.

    Given the poor susceptibility and clinical outcomes among Fusarium ulcers treated with voriconazole, Sun et al(3) recommended against using voriconazole as a first-line therapy for Fusarium keratitis. Li et al(4) recommends against combination therapy because of possible interactions in mechanism of drugs. We believe that combination therapy as a first line of treatment may compound the pr...

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  • Reply to 'Big data, selection bias and clinical significance

    We thank the authors for their comments and insights on our paper ‘Pterygia are indicators of an increased risk of developing cutaneous melanomas’.
    We agree that there was selection bias within the pterygium cases. All cases were identified as hospital in-patients and therefore represent that small select portion of the population who were receiving treatment for (or removal of) their pterygium. We made no assumptions about whether these cases were more or less severe than untreated pterygia or whether the removals were performed for cosmetic or other reasons. The strengths of this study are that it included all in-hospital cases treated in Western Australia over a 30 year time period, without prejudice.
    While melanoma is an uncommon problem in China, it is a major health issue in Australia and New Zealand. The clinical relevance of this study should be viewed against the background of the world’s highest incidence rates of cutaneous melanoma that currently exist, with up to 60 cases per 100,000 population1-3 in Australia and New Zealand. Contrast this with the incidence rates of East Asian countries of approximately 0.7 cases per 100,000 population.4 Both non-melanoma and melanoma skin cancers are a major health priority for cancer prevention research. We are not suggesting that pterygium be used as the sole indicator for a population wide screening program. There are well established major screening and surveillance programs in place in Australia. Our study a...

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  • Spurious elevations in serum IgG2 may be seen by immunonephelometry in IgG4-RD - response to Chan et al [1]

    Chan et al report on marked elevations in serum IgG2 that are observed in patients with orbital IgG4 related disease (IgG4-RD), with or without systemic involvement.

    Using ROC area under the curve comparisons, the authors show that the serum IgG2 concentration has a higher AUC (0.9) than serum IgG4 (0.8) in detecting IgG4-RD in their cohort (comprised of 33 subjects: 20 with orbital IgG4-RD with or without systemic involvement, and 13 with non-IgG4-RD orbital inflammation).

    Our group has noted this paper by Chan et al with interest as we have observed the same phenomenon of marked serum IgG2 elevations in patients with IgG4-RD, who have concomitantly low serum IgG4 concentrations. Like the patients presented by Chan et al, our IgG4-RD patients uniformly had serum IgG2 concentrations that were greater than the serum IgG4 concentration, even when the serum IgG4 concentration was very high.

    Our interpretation of the apparent superior clinical utility of the serum IgG2 test in this context, is that this observation is only made when using an immunonephelometric methodology subject to two different types of analytical error:
    i) antigen excess, leading to falsely low serum IgG4 measurement in a patient who in fact has a marked elevation of serum IgG4 [2] and
    ii) cross reactivity of the reagent used to measure IgG2 with serum IgG4, leading to falsely high serum IgG2 measurement (this may be due to a direct and specific recognition of IgG4 epitop...

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  • Big data, selection bias and clinical significance

    Title Page

    Letter to the Editor

    The article in question:
    Crewe JM, Threlfall T, Clark A, Sanfilippo PG, Mackey DA. Pterygia are indicators of an increased risk of developing cutaneous melanomas. Br J Ophthalmol 2017.

    Jingjing Shen
    Minqian Shen
    Yuanzhi Yuan

    Corresponding author:
    Yuanzhi Yuan

    Address:#180 Fenglin Rd., Department of Ophthalmology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China
    Email: yuan.yuanzhi@zs.hospital.sh.cn
    Phone: +86-186 1688 1220 or +86-21-64041990 ext. 2684

    Dear Editor,

    We read with great interest the paper by Crewe et al.1 The authors showed that patients with pterygium had higher risk of cutaneous melanomas (CM) in a large retrospective matched-cohort study in Western Australia (WA), and suggested pterygium as an indicator for CM. The finding was interesting. However, we doubt the conclusion and its clinical relevance and public health significance.

    Compared to control group, patients with pterygium had a 20% or 24% increased risk of developing CM in terms of odds ratio(OR) or incidence rate ratio (IRR), respectively. The incidence rate difference(IRD), however, was only 27.7/100 000 person-years (PY) (Table 5., by subtracting the IR of the control group from that of the pterygium group, i.e. (186.5-158.8)/100 000 PY). The rate difference corres...

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  • Reply

    We read with interest the insightful comments in the e-letter submitted by Dr. Gain, Dr. He, Dr. Garcin, and Dr. Thuret on our recently published article.1 As stated in their letter, they previously reported that by using a similar triple staining (i.e., Hoechst 33342, ethidium homodimere and calcein-AM) on the endothelium of whole donor corneas stored in long-term organ culture, the endothelial cell (EC) density in the whole pool of viable ECs in the cornea is routinely, and quite substantially, overestimated.2,3 We completely agree with the authors regarding the importance of assessing the whole pool of viable ECs in corneal grafts.

    We first reported at the 2009 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) that triple-staining a donor graft with propidium iodide, calcein-AM, and Hoechst 33342 allowed for a distinct discrimination between living cells and dead cells. In that report, we hypothesized that the existence of dead cells on the endothelium of the donor cornea suggests an association with the rapid loss of corneal ECs, at least at the early phase, post keratoplasty. However, Gauthier and associates reported3 that there was no difference between the density of viable ECs at day 0 and at day 5 postoperative, thus suggesting that very early EC loss in the host recipient is almost negligible. However, similar to Gain and associates, we believed that it was quite important to measure viable ECD, not to calculate just ECD by...

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  • eletter

    We noticed the article entitled “The existence of dead cells in donor corneal endothelium preserved with storage media” by Kitazawa with interest (Br J Ophthalmol 2017. Oct 5).
    Authors clearly demonstrated, using a triple staining with Hoechst, Propidium Iodide and Calcein-AM, that corneas stored at 4°C in Optisol-GS for 3 to 7 days, the technic most used worldwide, bear a significant number of dead endothelial cells (ECs). They underlined that these non-viable ECs are not recognized by specular cell count done by the eye bank and that this could explain the “cell loss” inevitably noticed post graft. Our team applied, for the first time in 2011 [1] and again in 2016 [2], a similar triple staining on the endothelium of whole corneas stored in long-term organ culture at 31°C, the dominant technic in Europe. We made the same findings as Kitazawa et al. and defined the notion of viable ECD (vECD) as the number of viable ECs per surface unit. Areas without ECs (especially in Descemetic folds), dead and dying EC (that will not survive the storage) clearly explain the important discrepancy between the cell count done by the eye bank (unable to spot them) and the very early postoperative ECD. Our team also demonstrated long ago that vital Trypan blue staining used by certain eye bank is unable to spot all dying cells because its time window of positivity is very narrow, corresponding only to ECs near to desquamate [3]. Viable ECD determined by triple staining therefore appea...

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  • Re: e Letter for bjophthalmol-2017-310312; Comments on article “Impact of Surgical Timing of Postoperative Ocular Motility in Orbital Blowout Fractures”

    Dr. Jost Jonas

    British Journal of Ophthalmology


    Dear Dr. Jonas:


    With great interest, we read the e letter (E-Letter 1) submitted by Ankita Anil Patil, Srikanth Ramsubramanian, and Bipasha Mukherjee, entitled “Comments on article ‘Impact of surgical timing on postoperative ocular motility in orbital blowout fractures’” illustrating their analysis and opinions on our article that was recently published in the British Journal of Ophthalmology. Please know that we greatly appreciate the authors’ cogent and helpful comments.


    It should be noted that in our opinion, in order to normalize ocular motility, the most important aspect is to restore the orbital tissues for the appropriate location. It is quite well known that the transcaruncular approach is suitable for small fractures of the medial wall. Since the transcaruncular approach provides surgeons with only a narrow view, it is difficult to restore the orbital tissues for the appropriate location for a large depressed fracture. On the other hand, the Lynch incision provides a substantial advantage for the repair of an orbital fracture, as it allows for a wide view during surgery and makes it easy to restore the orbital tissues for the orbit and insert the reconstruction implant. In additi...

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  • Building a reliable evidence base in eyes and vision

    Dear Editors,

    We are writing to express concerns about an article published recently in BJO. (1) While Joksimovic and colleagues claim to have conducted a systematic review, they did not. Rather, they describe a cross-sectional study of randomized trials in ophthalmology with two comparison (or “exposure”) groups: trials published in ophthalmology journals, and trials published in general medical journals. In contrast, a systematic review (also a cross sectional study) has been defined as "… a scientific investigation that focuses on a specific question and uses explicit, prespecified scientific methods to identify, select, assess, and summarize the findings of similar but separate studies." (2)

    To minimize mislabeling of systematic reviews, among other purposes, Cochrane Eyes and Vision (CEV) is partnering with individual ophthalmology and optometry journals to appoint a knowledgeable associate editor responsible for editorial functions related to systematic reviews at each journal (http://eyes.cochrane.org/associate-editors-eyes-and-vision-journals). Our research has indicated that many published eye and vision articles billed as “systematic reviews” do not adhere to accepted criteria, and are not reliable. (3)

    In addition to adding associate editors for systematic reviews to their team, journal editors can insist that authors adhere to reporting standards, f...

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