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Peripheral Hypertrophic Subepithelial Corneal Degeneration Presenting Eye (2015) 29, 88–97 & 2015 Macmillan Publishers Limited All rights reserved 0950-222X/15 www.nature.com/eye 1,2 3 4 CLINICAL STUDY Peripheral MSchargus , C Kusserow ,USchlo¨ tzer-Schrehardt , C Hofmann-Rummelt4, G Schlunck1 hypertrophic and G Geerling1,5 subepithelial corneal degeneration presenting with bilateral nasal and temporal corneal changes Abstract 1 Department of Purpose To characterise the history, clinical transmission electron microscopy showed Ophthalmology, University of Wuerzburg, Wuerzburg, and histopathological features of patients histological features that are similar to Germany with bilateral nasal and temporal peripheral Salzmann’s corneal changes without any hypertrophic subepithelial corneal inflammation. We hypothesise that light 2Department of degeneration in a German population. exposure and a localised limbal insufficiency Ophthalmology, University Methods A detailed ophthalmological and could be involved in the pathogenesis. of Bochum, Bochum, dermatological history and clinical findings Eye (2015) 29, 88–97; doi:10.1038/eye.2014.236; Germany were recorded of nine patients with bilateral published online 3 October 2014 3Department of simultaneous nasal and temporal peripheral Ophthalmology, University corneal degeneration from two centers in of Luebeck, Lu¨ beck, Germany. Excised tissues were studied by Introduction Germany histopathology, immunohistochemistry, and transmission electron microscopy. Salzmann’s nodules (SN) are subepithelial, 4 Department of Results Foreign body sensation and need elevated bluish-white corneal opacities of non- Ophthalmology, University inflammatory origin, with a specific peripheral of Erlangen-Nuernberg, of artificial tear substitutes were the only 1–7 Erlangen, Germany symptoms reported regularly. Schirmer’s and circular pattern. What has been termed Jones-test were normal in all, but fluorescein Salzmann’s degeneration is predominantly 5Department of break-up time of 410 s was found in five eyes unilateral, presenting at any time in life with Ophthalmology, University of four patients. Best corrected visual acuity a female preponderance. Although the of Duesseldorf, Duesseldorf, was reduced only under glare conditions. pathophysiology remains undefined until Germany Corneal topography revealed irregular present, chronic ocular surface irritation or inflammation are thought to be the initiating Correspondence: astigmatism in 13 of 14 eyes. Follow-up Marc Schargus, University median time was 35 months. Most cases were conditions. The corneal nodules can be Eye Hospital Bochum, In stable within the follow-up period. Light and associated with a peripheral pannus. More der Schornau 23–25, electron microscopy revealed the findings of common differential diagnosis of such 44892 Bochum, Germany superficial vascularised corneal hypertrophic prominent subepithelial nodules associated Tel: +49 234 2993113; with peripheral corneal vascularisation include Fax: +49 234 2993109. scars, oxytatlan fibers, and discontinued E-mail: marc.schargus@ Bowmans layer. posttraumatic scars and pterygium. Less well gmx.de Conclusion In this series of German known are two entities that present with patients with peripheral hypertrophic bilateral peripheral changes similar to a Received: 16 December subepithelial corneal degeneration, the pterygium, which were classified as peripheral 2013 changes were predominantly located in the hypertrophic subepithelial corneal degeneration Accepted in revised form: 1 (PHSCD) and autosomal dominant pterygoid August 2014 palpebral aperture and often present in both Published online: 3 October eyes. No associated surface disease could corneal dystrophy, which clinically show also 2014 be established in this study. Light and features of SN. Peripheral hypertrophic subepithelial corneal degeneration M Schargus et al 89 Between 2003 and 2011, we observed a pattern of tetroxide, dehydrated in graded alcohol concentrations, peripheral pterygium-like corneal changes in nine and embedded in epoxy resin. Semithin sections (1 mm) patients that showed none of the conjunctival changes of were stained with toluidine blue, ultrathin sections were a typical pterygium, but included Salzmann’s like stained with uranyl acetate-lead citrate and examined corneal opacities. Strikingly these were all bilateral as with a transmission electron microscope (TEM) (EM well as both nasal and temporal. None of the previous 906E; Zeiss, Oberkochen, Germany). descriptions in literature showed these high numbers of For light microscopy, specimens were fixed in 4% strict nasal and temporal affections. We performed a paraformaldehyde/0.1% glutaraldehyde in 0.1 M thorough examination of the ocular surface of these phosphate buffer and embedded in paraffin according to patients with this distinct corneal pathology. Here, we standard protocols. 5-mm thick paraffin sections were describe the typical clinical and microscopic findings of stained with periodic acid-Schiff (PAS), hematoxylin- what may be considered a subtype of PHSCD with a eosin, Masson trichrome stain, van Gieson’s stain bitemporal and binasal pattern. for elastin, Congo red for amyloid, and acid mucopolysaccharides (AMP). Immunohistochemistry was performed by the peroxidase-labeled streptavidin- Subjects and methods biotin method, using the LSAB Plus-kit according to Between 2003 and 2011 we examined nine patients (seven the manufacturer‘s instructions (DAKO, Glostrup, female, two male; median age 43 years (29–55, ±10 Denmark). Briefly, sections were incubated with primary years) at two centers (University Eye Hospital antibody dilutions, biotinylated link antibody, and Wuerzburg, Germany and University Eye Hospital peroxidase-conjugated streptavidin for 30 min each. As a Luebeck, Germany) who uniformly presented with a chromogenic substrate, 3-Amino-9-ethyl carbazole was bilateral, nasal and temporal superficial pannus, that is, used, and Mayer‘s hemalum was used as a counter intra- or subepithelial neovascularisation and scar tissue, stain. Monoclonal antibodies against pan-cytokeratin in the palpebral aperture (Figure 1). This extended over (clone 80, Abcam, Cambridge, UK), corneal epithelial approximately two limbal clock hours. Central to the cytokeratin 3/12 (clone AE5, Merck-Millipore, pannus, elevated white subepithelial opacities similar to Darmstadt, Germany), cytokeratin 10 (clone DE-K10, SN were located. Median follow-up period was 35 Abcam), cytokeratin 13 (clone KS-1A3, Novocastra, months (range 20–82 months), only one patient showed Newcastle upon Tyne, UK), cytokeratin 19 (clone BA17, progression of changes after excision. Merck-Millipore), fibrillin-1 (clone 26, Merck-Millipore), The medical history and clinical findings of all patients vimentin (clone V9, DAKO), and alpha-smooth muscle were recorded following a questionnaire and protocol. actin (clone 1A4, Sigma, St Louis, MO, USA) were used at This included the family history, systemic and concentrations of 1:50 À 1:100. In negative control ophthalmic history of diseases, drug use, known experiments, the primary antibody was omitted or allergies, and any signs of ocular disease. We specifically replaced by an irrelevant primary antibody. searched for any signs and symptoms of dermatological disorders. The ophthalmic history assessed any previous trauma, including eye surgery, use of eye drops, and Results contact lenses. Best corrected spectacle visual acuity History (BCVA) using decimal charts in 5 m distance and brightness acuity test were recorded. The family, general and drug histories were A full clinical ophthalmic examination was performed unremarkable in all patients. Two reported a history of including measurement of the vertical and horizontal seasonal allergies. Two patients had occasionally used palpebral aperture, exophthalmometry, corneal soft contact lenses until several years before consultation. topography, aesthesiometry, Fluoresceine break-up time, Schirmer test with and without anaesthesia over 5 min Symptoms and signs and syringing of the lacrimal drainage system. In addition all patients were assessed by a dermatologist. All except one patient suffered of foreign body In three patients the superficial corneal opacification symptoms and applied topical artificial lubricants and pannus were easily stripped off the underlying regularly two to six times a day. Automated refraction corneal surface by manual superficial keratectomy and revealed an against the rule astigmatism in 15 of 16 eyes processed for light and electron microscopy. For electron (median ¼À2.0 D, min À 0.25 D to À 10.75 D max). microscopy, specimens were fixed in 4% Corneal topography confirmed the irregularity of the paraformaldehyde/0.1% glutaraldehyde in 0.1-M astigmatism. Median spectacle best corrected decimal phosphate buffer, postfixed in 2% buffered osmium visual acuity was 0.9 (min 0.2–1.25 max). Two patients Eye Peripheral hypertrophic subepithelial corneal degeneration M Schargus et al 90 Figure 1 (a, b) OD/OS Patient 7, 55 years, C þ D: OD/OS Patient 1, 29 years. showed reduced brightness acuity well below the BCVA Vertical (median 8.5 mm, min 7–12 mm max) as well as under room light conditions (Table 1). horizontal palpebral aperture (median 25.5 mm, min In all patients, slitlamp biomicroscopy revealed a 25–27 mm max) were equally unremarkable. Lacrimal bilateral nasal and temporal pannus with vascularisation drainage and all intraocular findings were normal. extending over one to three limbal clock hours almost All except one patient showed no progression of the exclusively in the
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