LETTERS

Incidence of Peters Anomaly and Congenital Opacity To the Editor: Although I agree that information concerning the true incidence and prevalence of Peters anomaly is lacking and would be useful, I question the validity of the methodology for this purpose as used by Kurilec and Zeidman in their article.1 Regardless of the presence or absence of “medical problems that interfere with their ability to have a cornea transplant,” many corneal surgeons when presented with cases of severe opacity and associated dysgenesis do not believe that these cases are appropriate for transplantation. This is particularly true in monocular instances in which the fellow eye appears normal. Thus, eye bank data are inappropriate for purposes of incidence estimation and for the larger issue of determining the success rate of transplantation in Peters anomaly because a significant number of cases are excluded from consideration. New York State Department of Health data in this regard are also suspect because the initial reporting is made by delivery room staff. Although this is subject to subsequent modification by pediatricians, there is no evidence of frequency with which this actually occurs in the context of a busy pediatric practice. Given the small number of cases, infrequency of updating can have a large impact on the final numbers. New York State has one of the most robust reporting systems, with no evidence that this can be approximated by other states, thus using New York State data to extrapolate the national incidence would also be erroneous. In addition, my personal observation is that the most frequent source of the initial diagnosis is the mother, when at some point after discharge, she is able to see into the now open lids. Conflicts of interest: None reported. James V. Aquavella, MD University of Rochester Flaum Eye Institute, Rochester, NY

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TO THE

EDITOR

REFERENCE 1. Kurilec JM, Zaidman GW. Incidence of Peters anomaly and congenital corneal opacities interfering with vision in the United States. Cornea. 2014;33:848–850.

Reply: We thank Dr Aquavella for his comments; however, we disagree. In our article, we addressed the difficulties in obtaining accurate data to answer the question of what is the incidence of Peters anomaly and congenital corneal opacity (CCO) interfering with vision in the United States. These difficulties led us to look at various sources of data. For example, after we received the preliminary data from the Eye Bank for Sight Restoration in New York, we contacted surgeons who had performed corneal transplants in children to clarify the indications for transplant surgery. We understood that the data from the State of New York Health Department may be somewhat inaccurate because the delivery room staff makes the diagnosis. However, delivery room personnel (including obstetricians) are trained to identify congenital anomalies and report them to the state and appropriate physicians. They are probably more accurate in this than parents. Additionally, we obtained confirmation of our data from the members of the Pediatric Keratoplasty Association, all of whom are corneal surgeons or pediatric ophthalmologists. They took part in our survey, reviewed their data regarding their incidence of CCO and corneal transplants, and submitted them to us. Finally, as we discussed in our article, Dr Bermejo analyzed congenital eye malformations in over one million births in Spain from 1980 to 1995. He found that the incidence of CCO was 3.11 of 100,000 births, which is equal to about 1 of 32,000. Data from the New York State Department of Health, as we reported, were 2.2 CCO of 100,000 births. Considering the difficulties in getting accurate data, these 2 results are relatively comparable. If we used Dr Bermejo’s data, there would be 125 infants born every year with CCO. Our data would give 167 CCO born every year in the United States, a difference of only about 40 cases, in the approximately 4 million annual births in the United

States. In summary, although it may not be possible to determine the exact incidence of CCO, our data give pediatric ophthalmologists and corneal surgeons an idea of how often these conditions occur, and what they can tell parents of these children. Conflicts of interest: None reported. Gerald W. Zaidman, MD Jeffrey M. Kurilec, MD Department of Ophthalmology, Westchester Medical Center, New York Medical College, Valhalla, NY

Accurate Use of Neutrophil/ Lymphocyte Ratio in Patients With Keratoconus To the Editor: We read with great interest the recently published article by Karaca et al,1 in which the authors aimed to compare the neutrophil/lymphocyte ratio (NLR) between nonprogressive and progressive keratoconus patients and healthy controls. In conclusion, it was reported that patients with progressive keratoconus have a higher NLR compared with nonprogressive patients and controls, and the NLR was not different between patients with nonprogressive keratoconus and controls. However, there are some points that we would like to address from this study. First, the NLR test is easy to perform from the white blood cell count, which integrates detrimental effects of neutrophilia (an indicator of inflammation) and lymphopenia (an indicator of physiologic stress). However, the NLR itself without other inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, tumor necrosis factor-alpha, interleukin-6, etc) may lead to insufficiency of evidence confirming the presence of inflammation and may

Cornea  Volume 34, Number 2, February 2015

Cornea  Volume 34, Number 2, February 2015

not accurately provide information about the prognosis of the patients.2 In such studies aimed to determine predictive markers by using laboratory results, it should be better to evaluate and compare the value and efficacy of these markers with widely used inflammation markers. Second, in the methods section of the original study, the authors stated that 25 patients with keratoconus were using rigid gas-permeable contact lenses and were asked to discontinue using contact lenses for at least 4 weeks before the topographic examination. However, as is known, the time for contact lens–induced corneal changes to reach a steady state after cessation of lens wear is highly variable. According to a study involving 55 eyes of 28 patients using rigid gaspermeable contact lenses, 31 eyes achieved refractive stability by the sixth week and 24 eyes required more than 6 weeks to achieve stability.3 And, among the variables examined, including those indicating corneal warpage, the factor that correlated with the required time to refractive stability after discontinuation of rigid gas-permeable contact lens wear was the length of time of contact lens use.3 The use of rigid gas-permeable contact lenses may lead to patient selection bias. Therefore, it should be better if the authors detailed the patients using rigid gas-permeable contact lenses. Also, this issue should be mentioned as a limitation of the study. Third, it is hypothesized that oxidative by-products released by neutrophils may activate proteolytic enzymes and matrix metalloproteinases which may contribute to progression of keratoconus in the original study. This means that progression of keratoconus is a result of higher levels of neutrophils. It is not clear whether the higher levels of neutrophils are a result of progression or the progression is a result of higher levels of neutrophils, and this is an issue that should be clarified. Financial disclosures/conflicts of interest: None reported. Cem Ozgonul, MD Department of Ophthalmology, Van Military Hospital, Van, Turkey

Letters to the Editor

Erdim Sertoglu, MD Ankara Mevki Military Hospital, Anittepe Dispensary, Biochemistry Laboratory, Ankara, Turkey

Gokcen Gokce, MD Department of Ophthalmology, Kayseri Military Hospital, Kayseri, Turkey

REFERENCES 1. Karaca EE, Ozmen MC, Ekici F, et al. Neutrophil-to-lymphocyte ratio may predict progression in patients with keratoconus. Cornea. 2014;33:1168–1173. 2. Sertoglu E, Uyanik M. Accurate use of neutrophil/lymphocyte ratio from the perspective of laboratory experts. Vasc Health Risk Manag. 2014;10:13–14. 3. Tsai PS, Dowidar A, Naseri A, et al. Predicting time to refractive stability after discontinuation of rigid contact lens wear before refractive surgery. J Cataract Refract Surg. 2004;30:2290–2294.

cause–effect relationship between NLR and progression. However, we observed that systemic inflammation has no cause–effect relationship with the progression of keratoconus. We hypothesized that patients with progression of keratoconus have a high degree of inflammation, in terms of NLR, and this finding may be a clue for the impact of systemic inflammation on the pathogenesis of keratoconus, which is widely unknown. Financial disclosures/conflicts of interest: None reported. Emine Esra Karaca, MD Department of Ophthalmology, Sorgun State Hospital, Yozgat, Turkey

Mehmet Cüneyt Özmen, MD Reply: We thank the authors of the letter for their interest and criticism about our study published in the November issue of Cornea.1 Neutrophil-to-lymphocyte ratio (NLR) was proposed to be an important measure of systemic inflammation.2 The relationship between NLR and systemic diseases has been studied several times and a strong correlation was found in terms of poor prognosis. Other inflammatory factors such as Creactive protein,3 interleukin (IL)-1b, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, interferon g, chemokine C-C motif ligand 5, and tumor necrosis factor a in serum samples of patients with keratoconus were previously investigated. Thus, this research is just a pilot study for emphasizing the impact of NLR, a simple marker for inflammation, in patients with keratoconus. The cross correlation between NLR and other systemic inflammatory markers, with regard to progression of keratoconus, would be a second step for future studies. We agree that the time for contact lens–induced corneal changes to reach a steady state after cessation of contact lens wear is highly variable and this issue could be considered as a limitation. Another issue raised by the authors of the letter is the probable

Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.

Department of Ophthalmology, Gazi University Medical Faculty, Ankara, Turkey

Feyzahan Ekici, MD Department of Ophthalmology, Medical Faculty, Recep Tayyip Erdo gan University, Rize, Turkey

Erdem Yüksel, MD Department of Ophthalmology, Medical Faculty, Gazi University, Ankara, Turkey

Zülal Türko glu, MS Department of Statistics, Faculty of Science, Gazi University, Ankara, Turkey

REFERENCES 1. Karaca EE, Ozmen MC, Ekici F, et al. Neutrophil-to-lymphocyte ratio may predict progression in patients with keratoconus. Cornea. 2014;33:1168–1173. 2. Imtiaz F, Shafique K, Mirza SS, et al. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med. 2012;5:2. 3. Xu L, Wang YX, Guo Y, et al; Beijing Eye Study Group. Prevalence and associations of steep cornea/keratoconus in Greater Beijing. The Beijing Eye Study. PLoS One. 2012;7: e39313.

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