Ocular Surface Pathology in Patients Suffering from Mercury Intoxication

Pilar Cañadas; Yrbani Lantigua; Amalia Enríquez-de-Salamanca; Itziar Fernandez; Salvador Pastor-Idoate; Eva M Sobas; Antonio Dueñas-Laita; José Luis Pérez-Castrillón; Jose C Pastor Jimeno; Margarita Calonge

doi:10.3390/diagnostics11081326

Ocular Surface Pathology in Patients Suffering from Mercury Intoxication

Diagnostics (Basel). 2021 Jul 23;11(8):1326. doi: 10.3390/diagnostics11081326.

Affiliations

¹ IOBA (Institute of Applied Ophthalmobiology), University of Valladolid, 47011 Valladolid, Spain.
² CIBER-BBN (Biomedical Research Networking Center Bioengineering, Biomaterials and Nanomedicine), Carlos III National Institute of Health, 28029 Madrid, Spain.
³ Department of Toxicology, Medical School, University of Valladolid, 47003 Valladolid, Spain.
⁴ Department of Internal Medicine, Medical School, University of Valladolid, 47003 Valladolid, Spain.

Abstract

Purpose: To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication.

Design: Cross-sectional study.

Participants: Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects.

Methods: The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM).

Results: Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (<7 s) in 22.7% of patients. Schirmer test and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal esthesiometry showed patient mechanical (mean 147.81 (53.36) mL/min) and thermal thresholds to heat (+2.35 (+1.10) °C) and cold (-2.57 (-1.24) °C) to be significantly higher than controls. Corneal IVCM revealed lower values for nerve density (6.4 (2.94) n/mm²), nerve branching density (2 (2.50) n/mm²), and dendritic cell density (9.1 (8.84) n/mm²) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels.

Conclusions: Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.

Keywords: cornea toxic effects; corneal esthesiometry; corneal innervation; corneal nerves; in vivo confocal microscopy; mercury poisoning; neurogenic dry eye; occupational exposure; tear biomarkers; tear cytokines.