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Columnar Keratopathy an Early Manifestation of Limbal Stem Cell

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Columnar Keratopathy an Early Manifestation of Limbal Stem Cell Journal of EuCornea 3 (2019) 1–4 Contents lists available at ScienceDirect Journal of EuCornea journal homepage: www.elsevier.com/locate/xjec Columnar keratopathy: An early manifestation of limbal stem cell deficiency T Veronica Mas Tura,b, Amna AlMaazmia,b, Ahmed AlSaadic, Mario Nubiled, Dalia G. Saida,b, ⁎ Leonardo Mastropasquad, Harminder S. Duaa,b, a Section of Academic Ophthalmology, Larry A Donoso Laboratory for Eye Research, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK b Department of Ophthalmology, Nottingham University Hospitals NHS Trust, UK c Department of Ophthalmology, Zayed Military Hospital, Abu Dhabi, United Arab Emirates d Ophthalmology Clinic, National Centre of High Technology (CNAT) in Ophthalmology, University of “G d'Annunzio”, Chieti-Pescara, Italy ARTICLE INFO ABSTRACT Keywords: Background/Purpose: Stem cells of the corneal epithelium reside in the limbal palisades and associated limbal Columnar keratopathy epithelial crypts. The limbus constitutes a barrier between the conjunctival and corneal phenotype of cells. When Limbus the limbal barrier is breached, stem cell deficiency (LSCD) results with conjunctivalisation of the cornea. The fi Stem cell de ciency purpose of this study was to document an early manifestation of LSCD which is consistent and distinct across several causes of LSCD. Methods: Seventeen eyes of 11 consecutive patients with diverse known causes of LSCD were included. Patients were examined clinically with the slit lamp and fluorescein staining, and by in vivo confocal microscopy. All corneas were photographed with a slit lamp camera. Seven patients underwent in vivo confocal microscopy examination. Results: There were 6 males and 5 females. Six cases had bilateral involvement and the other 5 were unilateral. All patients showed predominantly superior loss of limbal anatomy with effacement of the palisades of Vogt, superficial vascularization encroaching on the peripheral cornea and alternating columns, 6–20 in number, of late fluorescein staining conjunctivalised and normal epithelium extending for a variable distance towards the corneal centre. These were related to prolonged contact lens wear, atopic keratoconjunctivitis, superficial ocular surface burns, ocular cicatricial pemphigoid, rosacea keratoconjunctivitis, old trachoma and neurotrophic ker- atopathy. In vivo confocal microscopy confirmed features of LSCD. Conclusion: Alternating columns of conjunctivalized and normal epithelia encroaching on the cornea from the superior limbus is a distinct manifestation of early LSCD across a diverse range of causes. The reason for this manifestation is unclear but could be related to the random dysfunction or loss of the palisade architecture. 1. Introduction manifesting as irregular epithelium with late fluorescein staining [5,7]. We report a series of cases where columns of late fluorescein The palisades of Vogt and the inter-palisade rete ridges that are staining cells alternating with columns of normal cells were seen in the distributed along the sclero-corneal limbus serve as repositories of the superior limbus and cornea. The condition has been termed ‘Columnar limbal stem cells (SC) [1]. The palisades of Vogt together with the keratopathy’ and is an early sign of LSCD. limbal epithelial crypts provide the anatomical and physiological basis for the limbal stem cell niche [2–4]. The palisades are better defined in 2. Methods the superior and inferior limbus. Several diseases of the ocular surface can lead to limbal SC deficiency (LSCD) [5]. When the insult is acute Consecutive case series of 17 eyes of 11 patients, 6 males and 5 with extensive destruction of the limbus, the signs of LSCD manifest in females, presenting with ocular surface discomfort and signs of altered the form of a thick fibrovascular pannus or persistent epithelial defect limbal anatomy and conjunctivalisation of the cornea were studied. The [6]. When the underlying pathology or injury is mild, chronic and patients presented with one or more of the following symptoms; dry slowly progressive; subtle signs of LSCD appear in the form of con- eye, irritation and blurred vision. History of ocular and systemic health junctivalisation of the cornea with or without vascularization was elicited, visual acuity was recorded and slit lamp examination ⁎ Corresponding author. E-mail address: [email protected] (H.S. Dua). https://doi.org/10.1016/j.xjec.2019.10.001 Received 25 April 2019; Accepted 16 October 2019 Available online 18 October 2019 2452-4034/ © 2019 Published by Elsevier Inc. on behalf of European Society of Cornea & Ocular Surface Disease Specialists. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). V. Mas Tur, et al. Journal of EuCornea 3 (2019) 1–4 carried out without and with fluorescein (one drop of 2% fluorescein symptoms of dry eyes and blurred vision. Both wore lenses for 10–12 h minims, Bausch & Lomb, Laboratoire Chauvin, Aubenas, France); fol- a day. Visual acuity with contact lenses in situ was 6/9 and 6/7.5 (RE), lowed 5 s later with 2 drops of normal saline minims (Bausch & Lomb). and 6/9 and 6/6 (LE) respectively. Patients were advised to stop Slit lamp clinical findings were recorded. Anterior segment images were wearing contact lenses and treated with lubricant eye drops and a taken with the Topcon slit lamp camera (Topcon SL-7F slit lamp, course of topical preservative free prednisolone 0.5% starting at four Topcon 4059). The Heidelberg Retina Tomograph II Rostock Corneal times a day and tapering to once a day. Corneal findings are illustrated Module (Heidelberg Engineering GmBH, Dossenheim, Germany) was in Fig. 1(a-b) [8]. used to perform in vivo confocal microscopy (IVCM) examination in 7 Two males and one female aged 53, 41 and 40 years had bilateral cases. chronic atopic keratoconjunctivitis with eczema and history of asthma. Ocular symptoms were present over a duration 15 to 36 months. They complained of intermittent blurred vision but maintained visual acuity 3. Results between 6/6 and 6/12. The eyes had received treatment with different medications over the duration of the condition. These included car- Six cases had bilateral involvement and the other 5 were unilateral. mellose 0.5% lubricant drops, steroids (prednisolone phosphate 0.5% Two cases, one bilateral, were related to contact lens wear; three cases, and dexamethasone 0.1%) and tacrolimus skin cream (protopic 0.03%) two bilateral, had atopic keratoconjunctivitis; two cases were secondary to the lid margins. Two patients showed corneal signs in both eyes and fi to super cial ocular surface burns and one each had ocular cicatricial one in the right eye only as illustrated in Fig. 1(c, d). pemphigoid (bilateral), rosacea keratoconjunctivitis (bilateral), old A 45 years old female with old history of chemical injury with hy- trachoma (bilateral) and neurotrophic keratopathy. All had the drogen peroxide on the right eye 18 months previously. Best corrected fi fl common corneal ndings of uorescein staining and non-staining al- visual acuity with RGP contact lens was 6/12 on the right eye and 6/6 fi ternating columns of cells from the superior limbus. Corneal ndings on the left eye. She had chronic symptoms of irritation and photophobia are collectively described below after the patient demographics, with in the affected eye. illustrations in Fig. 1. A 45 years old male had suffered from superficial ocular surface Two females aged 56 and 32 years who had been using soft contact burn in the left eye with household cleaning liquid one year prior to lenses for correction of myopia for over 5 years presented with bilateral Fig. 1. Clinical presentation of Columnar Keratopathy, manifesting as alternating columns of fluorescein stained and unstained columns of epithelial cells of varying width and length extending from the superior limbus towards the pupil. (a,b) Contact lens related limbal stem cell deficiency (LSCD) demonstrating curvilinear extensions of stained epithelium from the limbus to the centre. The central cornea shows extensive punctate erosions. (c,d) LSCD secondary to atopic kerato- conjunctivitis showing parallel alternating columns of fluorescein stained and unstained epithelium. (e) LSCD secondary to chemical injury with multiple columns of fluorescein stained epithelial cells. The inferior cornea shows a segment of conjunctivalisation. (f) LSCD secondary to herpes simplex keratitis with a central persistent epithelial defect and alternating fluorescein stained and unstained columns superiorly. (g) LSCD secondary to rosacea with superior ‘columnar keratopathy’ asso- ciated with superficial vascularization of the cornea (h) LSCD secondary to old trachoma with columns of fluorescein stained and unstained epithelium at the superior limbus. These columns are relatively shorter in length than in the other examples. (i) LSCD secondary to ocular cicatricial pemphigoid with visible broad columns of fluorescein staining at the base and trapper to a fine line centrally. There was peripheral and associated central vascularization. (some figures are from the authors own previous publications that are referenced in the text). 2 V. Mas Tur, et al. Journal of EuCornea 3 (2019) 1–4 presentation. He showed evidence of conjunctivalisation of the cornea reflective metaplastic cells and normal cells in the remainder (Fig. 2 e, inferiorly and superonasally with superficial vascularization (Fig. 1e). f). An 87 years old male with a central persistent epithelial defect
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