Investigation of Ocular Inflammation in Thyroid Orbitopathy (TO) Patients by Conjunctival Impression Cytology (CIC) and Ultrasound Biomicroscopy (UBM) of the Upper Eyelid Structures

Abstract

Thyroid-associated Orbitopathy (TAO or TO) or Graves’ Orbitopathy (GO) is an autoimmune inflammatory eye disease associated with thyroid disorders, which clinical manifestation occurr as a combination of inflammation, increase of orbital fat and extra ocular muscle volume within the orbital space. The incidence rate of this disease is 16 women and 3 men per 100,000 populations. Autoantibodies to both TSHr (Thyroid stimulating hormone-receptor) and IGF-1r (insulin-like growth factor 1 receptor) displayed in the orbital fibroblast contributed in the development of the orbital changes in TO. In this study, we described the inflammation in TO patient’s ocular surface by morphological and immunological impression cytology of conjunctival epithelium cells layer. We also evaluated the eyelid changes in TO including eyelid retraction and swelling using an ultrasound biomicroscopy (UBM) imaging features. This enables us to observe the correlation of eyelid’s structure thickness and the pathology of the aforementioned changes. We found the morphological changes of conjunctival epithelial cells including low quality of cell-to-cell adhesion, increased nucleo-cytoplasmic ratio of cells and absence of mucus and goblet cells. The positivity of pro-inflammatory cytokines-released from the cells (IL-1α, IL-1β and ICAM) was also observed in immunostaining examination. Ultrasound Biomicroscopy (UBM) measurement gave a significant different thickness of eyelid and levator aponeurosis (LA) layer in TO compare to normal subject, but LA thickness was less correlated with the clinically upper eyelid retraction. Since its causes are multifactorial, eyelid retraction could be seen as a restrictive problem where lid retractors (LPS and Muller muscle) may also become inflamed and subsequent fibrosis, scarring to the adjacent connective tissue might cause retraction. Eyelid swelling could not be clearly imaged by UBM, because eyelid skin (thin epidermis and dermis with subcutaneous tissue) was observed as an echo-dense line at the water cup medium-upper eyelid interface. We emphasized the inflammation of ocular surface in TO patient by using impression cytology method and the clinical use of UBM in eyelid structure study related to TO clinical finding. This model of study support the anti-inflammatory drug application for TO patients with severe dry eye and UBM study provides information about anatomy of TO eyelid.