Ocular Surface and Lacrimal Gland Study in Graves’ Ophthalmopathy
Date Issued
2011
Date
2011
Author(s)
Hsuan, Wei-Yi
Abstract
Purpose:
Graves’ ophthalmopathy (GO) is an autoimmune inflammatory disorder of the orbital adipose, connective tissues and the extraocular muscles. The characteristic clinical manifestations of GO include proptosis, periorbital edema, extraocular muscle dysfunction, eyelid retraction and dry eye. However, the pathogenesis of Graves’ ophthalmopathy is still not clear.
Just like many autoimmune diseases, dry eye is an important clinical manifestation in GO. Lacrimal dysfunction can result from many autoimmune diseases, such as Sjögren''s syndrome, sarcoidosis, and thyroid disease. The pathogenesis of dry eye in GO is still uncelar. Increased palpebral fissure width in GO can accelerate tear film evaporation and result in increasing tear film osmolarity and ocular surface damage. Many inflammatory cytokines have been implicated in dry eye syndrome either on the ocular surface or in the lacrimal gland. Inflammatory cytokines alone have been reported to cause damages to the lacrimal gland. It has been demonstrated that lacrimal acinar cells physiologically express thyroid stimulating hormone receptor (TSHR). The lacrimal gland can become a target of the immune system and show signs of inflammation.
The purpose of this study is to investigate the ocualr surface changes and gene expressions in the lacrimal gland of GO patients. It may give a new insight for the understanding of dry eye in GO and may offer a new strategy for the management of dry eye in GO.
Methods:
In ocular surface study, we recruited 15 GO patients and 15 normal volenteers in control group. We collected clinical data from the two groups, including Ocular Surface Disease Index (OSDI), marginal reflex distance (MRD1 and MRD2), severity of exophthalmos, palpebral fissure length, severity of lagophthalmos, Schirmer’s test, tear break-up time (TBUT), and ocular surface fluorescein staining.
We used in vivo confocal microscopy and impression cytology to examine the upper and temporal bulbar conjunctiva in the two groups. We analyzed the conjunctival thickness, and the density of superficial epithelial cells, basal epithelial cells, Langerhans cells, and goblet cells. The grading of squamous metaplasia of conjunctival epithelum was also recorded.
In lacrimal gland study, we collected the specimens of lacrimal gland from 10 GO patients and 10 normal cases. We used real time RT-PCR to compare the gene expression between the two groups, including genes of cytokines, chemokine, autoantigens, PPAR-γ, and COX-2. The results were analyzed by Mann-Whitney U test.
Results:
The severity of exophthalmos, palpebral fissure length, and severity of lagophthalmos were significantly increased in the GO group. The results of Schirmer’s test and tear break-up time were significantly decreased in the GO group. The grading of ocular surface fluorescein staining was significantly increased in the GO group.
In vivo confocal microscopy study showed decreased superficial epithelial cell density of upper bulbar conjunctiva in the GO group. This difference was noted in the temporal bulbar conjunctiva. The conjunctival thickness and basal epithelial cell density were not significantly different between the two groups. The density of Langerhans cells was increased, and the density of goblet cell was decreased in the GO group. The impression cytology of conjunctival epithelium showed squamous metaplasia change in the GO group.
The superficial epithelial cell density of upper bulbar conjunctiva showed negative correlation to MRD1, and positive correlation to TBUT in the GO group. However, no significant correlration was noted between superficial epithelial cell density and the severity of exophthalmos, the result of Schirmer’s test, or the grading of ocular surface fluorescein staining.
The gene expression of PPAR-γ and COX-2 were significantly upregulated in the lacrimal gland of GO patients. The gene expressions of cytokines or autoantigenes have no statistical difference between the two groups.
Conclusions:
The changes of conjuncitval epithelium were demostrated in GO patients using in vivo confocal microscopy and impression cytology. The change was correlated to lid retraction, which maybe the important factor causing dry eye in GO patients. The gene associated with adipogenesis showed increased expression in the lacrimal gland of GO patients. The lacrimal dysfunction may play a role in the pathogenesis of GO-associated dry eye.
Subjects
Graves’ophthalmopathy
thyroid eye disease
in vivo confocal microscopy
impression cytology
conjunctival epithelial cell
dry eye
lid retraction
lacrimal gland
Type
thesis
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