Non-invasive corneal examination of individuals with PANK2 mutation

Abstract

Purpose: Pantothenate kinase-associated neurodegeneration is a progressive autosomal recessive disorder characterized by early onset neurological symptoms and iron deposition in the brain, particularly in globus pallidus. This is a very rare condition caused by mutations in the gene encoding pantothenate kinase 2 (PANK2), which is required for the phosphorylation of pantothenic acid and in the formation of coenzyme A. The heterozygotes were not reported to manifest any significant abnormalities. While the retinal involvement is well-accepted, there are no data in the literature dealing with the corneal alterations in this condition. The present study aimed to find any abnormalities in the corneal microstructure in patients with PANK2 mutations.

Methods: Patients, homozygous for the PANK2 mutation and asymptomatic heterozygous gene mutation carriers have been included in this preliminary study. The corneal examination was performed using in vivo confocal laser-scanning microscopy (CLSM). The corneal sensation was measured with Cochet-Bonnet esthesiometer.

Results: All examined corneae displayed a physiological sensation in Cochet-Bonnet esthesiometry. Both, in homozygous and heterozygous individuals the in vivo CLSM revealed a normal epithelium with very good distinguishable cell layers. The nerves in subbasal nerve plexus (SBP) revealed normal density and ordinary structure and distribution in both phenotypes. The number of antigen presenting cells, dendritic cells, was increased in the homozygous phenotype. Keratocytes nuclei appeared overall as bright oval objects, distributed through the entire stroma with a decreasing density in anterior-posterior direction. Intrastromal hyperreflective microdots occurred in the anterior stroma of all investigated subjects. The most striking finding of our study was the abundant presence of very small hyperreflective particles at the level of Bowman’s membrane, which were found only in homozygotes, but not in the heterozygous gene carriers.

Conclusions: This is the first study addressing the corneal features in individuals with PANK2 mutations. Here, we could show that despite absence of clinical signs, the cornea is involved in the pathology of disease. The nature and role of the particles observed at the Bowman’s membrane has to be appreciated in experimental studies, involving PANK2-mutant animals.

Keywords: 480 cornea: basic science