Neil Lagali1, Bogumil Wowra2, Fabian Norbert Fries3, Lorenz Latta3, Kayed Moslemani3, Tor Paaske Utheim4, Edward Wylegala2, Berthold Seitz3, Barbara Käsmann-Kellner3. 1. Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linköping, Sweden; Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway. Electronic address: neil.lagali@liu.se. 2. Clinical Department of Ophthalmology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Poland. 3. Klinik für Augenheilkunde, Universitätsklinikum des Saarlandes UKS, Homburg, Germany. 4. Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
Abstract
PURPOSE: To investigate corneal phenotype in aniridia-associated keratopathy (AAK) including its earliest manifestations, in relation to PAX6 mutational status. METHODS: 46 subjects (92 eyes) with congenital aniridia from a German registry were examined using slit lamp biomicroscopy, anterior segment optical coherence tomography, contact esthesiometry and in vivo confocal microscopy. Cytogenetic analysis was conducted by Sanger sequencing of PAX6 exons and/or MLPA analysis. Measured parameters included AAK grade, distance-corrected visual acuity (DCVA), central corneal thickness (CCT), corneal sensitivity, subbasal nerve density, mature dendritic cell (DC) density and corneal epithelial phenotype. RESULTS: 46 subjects (age range: 1-64 years) were examined, including 23 (50%) children under the age of 18. Five subjects (11.1%) with absent PAX6 coding mutation (non-PAX6 cases) had mild AAK (Grade 0-1) into the fourth decade of life and maintained corneal epithelial phenotype, greater subbasal nerve density (16.8 mm/mm2 vs. 3.58 mm/mm2, P = 0.01) and better corneal sensitivity (41 ± 11 mm vs. 28 ± 12 mm, P = 0.03) relative to those with PAX6 coding mutations. In five subjects, corneal endothelial cell density ranged from 3245 to 4399 cells/mm2. Independent of mutational status, an increased CCT, over tenfold increased mature DC density and reduced corneal sensitivity characterized all subjects. CONCLUSIONS: PAX6 coding mutations influence AAK phenotype and progression from the earliest stages of life. A minimal keratopathy present in 100% of congenital aniridia cases is independent of the specific mutation and consists of increased corneal thickness, reduced touch sensitivity, and increased ocular surface immune activity.
PURPOSE: To investigate corneal phenotype in aniridia-associated keratopathy (AAK) including its earliest manifestations, in relation to PAX6 mutational status. METHODS: 46 subjects (92 eyes) with congenital aniridia from a German registry were examined using slit lamp biomicroscopy, anterior segment optical coherence tomography, contact esthesiometry and in vivo confocal microscopy. Cytogenetic analysis was conducted by Sanger sequencing of PAX6 exons and/or MLPA analysis. Measured parameters included AAK grade, distance-corrected visual acuity (DCVA), central corneal thickness (CCT), corneal sensitivity, subbasal nerve density, mature dendritic cell (DC) density and corneal epithelial phenotype. RESULTS: 46 subjects (age range: 1-64 years) were examined, including 23 (50%) children under the age of 18. Five subjects (11.1%) with absent PAX6 coding mutation (non-PAX6 cases) had mild AAK (Grade 0-1) into the fourth decade of life and maintained corneal epithelial phenotype, greater subbasal nerve density (16.8 mm/mm2 vs. 3.58 mm/mm2, P = 0.01) and better corneal sensitivity (41 ± 11 mm vs. 28 ± 12 mm, P = 0.03) relative to those with PAX6 coding mutations. In five subjects, corneal endothelial cell density ranged from 3245 to 4399 cells/mm2. Independent of mutational status, an increased CCT, over tenfold increased mature DC density and reduced corneal sensitivity characterized all subjects. CONCLUSIONS:PAX6 coding mutations influence AAK phenotype and progression from the earliest stages of life. A minimal keratopathy present in 100% of congenital aniridia cases is independent of the specific mutation and consists of increased corneal thickness, reduced touch sensitivity, and increased ocular surface immune activity.
Authors: Anna Voskresenskaya; Nadezhda Pozdeyeva; Yevgeniy Batkov; Tatyana Vasilyeva; Andrey Marakhonov; Richard A West; Jeffrey L Caplan; Ales Cvekl; Yan Wang; Melinda K Duncan Journal: Exp Eye Res Date: 2020-11-26 Impact factor: 3.467