December 2011
Volume 52, Issue 13
Letters to the Editor  |   December 2011
Author Response: Anterior Corneal Pathology in Chronic Corneal Edema
Author Affiliations & Notes
  • Thaer S. Alomar
    Division of Ophthalmology and Visual Sciences, School of Clinical Sciences, University of Nottingham, United Kingdom.
  • Harminder S. Dua
    Division of Ophthalmology and Visual Sciences, School of Clinical Sciences, University of Nottingham, United Kingdom.
Investigative Ophthalmology & Visual Science December 2011, Vol.52, 9612-9613. doi:
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      Thaer S. Alomar, Harminder S. Dua; Author Response: Anterior Corneal Pathology in Chronic Corneal Edema. Invest. Ophthalmol. Vis. Sci. 2011;52(13):9612-9613.

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      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements
We are pleased to respond to the letter written by Drs. Patel and McLaren in relation to our paper correlating in vivo confocal microscopy (IVCM) findings with histologic findings in corneas with chronic edema. 1 We thank them for their generous commendation of our work in their opening sentences. They have essentially raised two issues. 
First, they contend that we have made “first claim” to the IVCM demonstration of subepithelial fibrosis. They have challenged this by quoting their own work, which is unpublished, and providing another reference. 2 The latter paper was designed to establish the normative database for corneal backscatter analysis by IVCM. They have included one patient, which was not normal, of Fuchs endothelial dystrophy where a reticular network of subepithelial fibrosis was demonstrated. This was a passing reference as it was not the main thrust of the paper. Moreover, the paper was published in August 2011, and our paper was published in September 2011. Clearly, there was no means by which we could have known of the content of this article before we submitted ours. 
Patel and McLaren go on to quote one of their papers 3 wherein they refer to the IVCM demonstration of subepithelial fibrosis in chronic edema as “S.V.P, unpublished data 2008.” We feel that a reference to unpublished data is not a bona fide claim to priority. We would like to add here that we first presented our preliminary data at the European Association for Vision and Eye Research (EVER) congress held in Portoroz, Slovenia, on October 4, 2008. 4 The published abstract 5 includes a statement on the presence of subepithelial fibroblasts in Fuchs endothelial dystrophy. Dr. McLaren and another eminent ophthalmologist attended the presentation and discussed the findings with Dr. Alomar. It thus appears that our “first claim” to the IVCM demonstration of subepithelial fibrosis in chronic corneal edema is justified, although others may have made the same observation contemporaneously. 
Their second contention is that we did not convincingly demonstrate that the subepithelial fibroblasts were derived from keratocytes, although they go on to discuss why this is most likely to be the case. We do not think that examination of keratocytes in serial sections, either transverse or coronal, would give an accurate measure of keratocyte nuclei as the orientation, of the nuclei within the cells can be in any direction. We presented similarities in shape, orientation, and size as circumstantial evidence in support of the keratocyte origin of the subepithelial cells. Moreover, we have provided evidence of keratocyte migration through breaks in Bowman's zone in a previously published paper, 6 which was quoted in our manuscript. We do not believe that keratocytes can migrate through an intact Bowman's zone; only in the presence of breaks does this occur. Bowman's zone breaks are known to occur in chronic edema, as we demonstrated in Figure 5 of our paper. 1 Patel and McLaren hypothesize in their letter that depletion of anterior stromal keratocytes in chronic corneal edema, as demonstrated in their elegant paper, 7 supports the notion that keratocytes migrate into the subepithelial region. Interestingly, however, in their paper, they argued that keratocyte depletion from the anterior corneal stroma is due to apoptosis of keratocytes. They made no comment on the possible anterior migration of keratocytes into the subepithelial region. It is surprising and intriguing that they made no mention of the subepithelial location of fibroblasts by histology or IVCM, despite their unpublished observations of 2008. These corneal samples would have provided them with an ideal opportunity to study this phenomenon and support their recent hypothesis that depletion of keratocytes from the anterior stroma is related to their anterior migration and accumulation in the subepithelial space. Careful scrutiny of their paper made it clear that, unlike our study, they did not perform histology and IVCM on the same corneal samples. Histology can be properly correlated with IVCM only if the same tissue samples (and preferably the same sites) are compared. Hence our “first claim” of histologic correlation with IVCM features is also sustained. 
Alomar TS Al-Aqaba M Gray T Lowe J Dua HS . Histological and confocal microscopy changes in chronic corneal edema: implications for endothelial transplantation. Invest Ophthalmol Vis Sci. 2011;52(11):8193–8207. [CrossRef] [PubMed]
Hillenaar T Cals RHH Eilers PHC Wubbels RJ van Cleynenbreugel H Remeijer L . Normative database for corneal backscatter analysis by in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2011;52(10):7274–7281. [CrossRef] [PubMed]
Patel SV Baratz KH Hodge DO Maguire LJ McLaren JW . The effect of corneal light scatter on vision after Descemet stripping with endothelial keratoplasty. Arch Ophthalmol. 2009;127(2):153–160. [CrossRef] [PubMed]
Alomar TS Lowe J Dua HS . In vivo confocal microscopy of abnormal cornea: a clinical and pathological correlation. Abstracts from the 2008 European Association for Vision and Eye Research. Acta Ophthalmol. 2008;86(suppl 243):6231. [CrossRef]
European Association for Vision and Eye Research. Ever2008, Portoroz, Slovenia, October 2008 Abstract 6231:129 (cited September 6, 2008). Available at: .
Said DG Nubile M Alomar T . Histologic features of transplanted amniotic membrane: implications for corneal wound healing. Ophthalmology. 2009;116(7):1287–1295. [CrossRef] [PubMed]
Hecker LA McLaren JW Bachman LA Patel SV . Anterior keratocyte depletion in Fuchs endothelial dystrophy. Arch Ophthalmol. 2011;129(5):555–561. [CrossRef] [PubMed]

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