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• W2401509953 abstract "We thank Boto-de-los-Bueis et al for their interest in our article1Hillenaar T. van Cleynenbreugel H. Remeijer L. How normal is the transparent cornea? Effects of aging on corneal morphology.Ophthalmology. 2012; 119: 241-248Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar and for sharing a complementary case featuring salt and pepper alterations of the corneal endothelium. This novel phenotype has recently been described in 2 asymptomatic men with transparent corneas, whereas Boto-de-los-Bueis et al have found similar endothelial changes in a 72-year-old woman who developed visual complaints during a follow-up of 6 years. Although the 3 cases bear certain similarities, several remarks remain.First, we agree with the authors that the images acquired with specular microscopy resemble the morphologic changes shown in our cases. However, because the transverse resolution of specular microscopy is inferior to confocal microscopy, comparison of images acquired with both techniques is difficult. Differences in image quality exist even among different confocal microscope types.2Szaflik J.P. Comparison of in vivo confocal microscopy of human cornea by white light scanning slit and laser scanning systems.Cornea. 2007; 26: 438-445Crossref PubMed Scopus (44) Google Scholar Highest quality is obtained using a laser scanning technique when the superficial corneal layers are observed. For morphologic assessment of the endothelial layer, however, a white light confocal microscope is superior. The confocal image shown by Boto-de-los-Bueis et al seems to be acquired with a laser scanning device, whereas a white light confocal microscope would offer better means for comparison of cases.Second, by viewing the consecutive images in a single scan, the granular hyperreflective structures described in all 3 cases can be interpreted as deposits on the endothelial layer. Following this assumption, the granular deposits correspond with the brown pigmented deposits seen with the slit lamp. Nevertheless, the consistence of the pigmented granules remains unknown. The same goes for the causative factor of the variable-sized discoloration of the endothelial cells. The exact nature of the pigmented granules and the specific endothelial alterations can only be ascertained by “correlative microscopy,”3Masters B.R. Correlation of histology and linear and nonlinear microscopy of the living human cornea.J Biophotonics. 2009; 2: 127-139Crossref PubMed Scopus (23) Google Scholar which compares in vivo images with ex vivo histopathologic and immunohistochemical examinations. Until this multidimensional approach is performed, one can only speculate whether the salt and pepper appearance is elicited by accumulation of intracellular material, cellular vacuolization or changes at the cellular surface. With further visual deterioration, the case described by Boto-de-los-Bueis et al may provide the opportunity for correlative microscopy.Third, we have recently obtained the 3-year follow-up results of our cases. Neither of our patients experienced any visual complaints and visual acuity was still ≥20/16 in all 4 eyes. On slit-lamp examination, corneas were clear except for some pigmented granules distributed on the endothelial layer in both eyes of the 73-year-old man (Fig 1, available at http://aaojournal.org). In contrast with Boto-de-los-Bueis et al, we could not establish any birefringent particles at endothelial level that would indicate a crystalline deposition. In vivo confocal microscopy demonstrated that the density of the endothelial cells was unchanged and their salt and pepper appearance was similar to the previous examinations in the past 3 years (Fig 2, available at http://aaojournal.org).Although not all features are similar among the 3 cases and different imaging techniques were used, they all display a salt and pepper endothelium. The bilateral alterations seem to be gender independent, do not compromise endothelial function, and may remain stationary or progress very slowly. In our opinion, histologic evidence of cellular changes is required, before the term “salt and pepper endothelium” can be changed to “salt and pepper endotheliopathy.” We thank Boto-de-los-Bueis et al for their interest in our article1Hillenaar T. van Cleynenbreugel H. Remeijer L. How normal is the transparent cornea? Effects of aging on corneal morphology.Ophthalmology. 2012; 119: 241-248Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar and for sharing a complementary case featuring salt and pepper alterations of the corneal endothelium. This novel phenotype has recently been described in 2 asymptomatic men with transparent corneas, whereas Boto-de-los-Bueis et al have found similar endothelial changes in a 72-year-old woman who developed visual complaints during a follow-up of 6 years. Although the 3 cases bear certain similarities, several remarks remain. First, we agree with the authors that the images acquired with specular microscopy resemble the morphologic changes shown in our cases. However, because the transverse resolution of specular microscopy is inferior to confocal microscopy, comparison of images acquired with both techniques is difficult. Differences in image quality exist even among different confocal microscope types.2Szaflik J.P. Comparison of in vivo confocal microscopy of human cornea by white light scanning slit and laser scanning systems.Cornea. 2007; 26: 438-445Crossref PubMed Scopus (44) Google Scholar Highest quality is obtained using a laser scanning technique when the superficial corneal layers are observed. For morphologic assessment of the endothelial layer, however, a white light confocal microscope is superior. The confocal image shown by Boto-de-los-Bueis et al seems to be acquired with a laser scanning device, whereas a white light confocal microscope would offer better means for comparison of cases. Second, by viewing the consecutive images in a single scan, the granular hyperreflective structures described in all 3 cases can be interpreted as deposits on the endothelial layer. Following this assumption, the granular deposits correspond with the brown pigmented deposits seen with the slit lamp. Nevertheless, the consistence of the pigmented granules remains unknown. The same goes for the causative factor of the variable-sized discoloration of the endothelial cells. The exact nature of the pigmented granules and the specific endothelial alterations can only be ascertained by “correlative microscopy,”3Masters B.R. Correlation of histology and linear and nonlinear microscopy of the living human cornea.J Biophotonics. 2009; 2: 127-139Crossref PubMed Scopus (23) Google Scholar which compares in vivo images with ex vivo histopathologic and immunohistochemical examinations. Until this multidimensional approach is performed, one can only speculate whether the salt and pepper appearance is elicited by accumulation of intracellular material, cellular vacuolization or changes at the cellular surface. With further visual deterioration, the case described by Boto-de-los-Bueis et al may provide the opportunity for correlative microscopy. Third, we have recently obtained the 3-year follow-up results of our cases. Neither of our patients experienced any visual complaints and visual acuity was still ≥20/16 in all 4 eyes. On slit-lamp examination, corneas were clear except for some pigmented granules distributed on the endothelial layer in both eyes of the 73-year-old man (Fig 1, available at http://aaojournal.org). In contrast with Boto-de-los-Bueis et al, we could not establish any birefringent particles at endothelial level that would indicate a crystalline deposition. In vivo confocal microscopy demonstrated that the density of the endothelial cells was unchanged and their salt and pepper appearance was similar to the previous examinations in the past 3 years (Fig 2, available at http://aaojournal.org). Although not all features are similar among the 3 cases and different imaging techniques were used, they all display a salt and pepper endothelium. The bilateral alterations seem to be gender independent, do not compromise endothelial function, and may remain stationary or progress very slowly. In our opinion, histologic evidence of cellular changes is required, before the term “salt and pepper endothelium” can be changed to “salt and pepper endotheliopathy.” Supplementary dataFigure 2Three year follow-up of 2 cases with salt and pepper endothelium using in vivo confocal microscopy. The morphologic appearance of all 4 eyes remained remarkably unchanged. A–B, 73-year-old man. A, Endothelial cell density (ECD) of the right eye changed from 2373 to 2333 cells/mm2 at 3 years follow-up. B, ECD of the left eye changed from 2054 to 2100 cells/mm2. C–D, 60-year-old man. C, ECD of the right eye changed from 2442 to 2719 cells/mm2. D, The left eye showed a single guttate lesion (arrow). ECD changed from 2529 to 2557 cells/mm2.View Large Image Figure ViewerDownload Hi-res image Download (PPT) “Salt and Pepper” Corneal EndotheliumOphthalmologyVol. 120Issue 3PreviewWe report a symptomatic patient who resembles the “salt and pepper endothelium” described by Hillenaar et al his “How Normal Is the Transparent Cornea? Effects of Ageing on Corneal Morphology.”1 Full-Text PDF" @default.
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