Hyperthyroidism associated with intraocular pressure and dry eye

Graves’ orbitopathy/ophthalmopathy (GO) also known as thyroid eye disease (TED),dysthyroid/thyroid-associated ophthalmopathy (TAO), is an autoimmune disorder representing thecommonest and most important extrathyroidal manifestation of Graves’ disease. Materials andMethods: This is a prospective study conducted for 2 years. A total of 60 established cases ofHyperthyroidism of all Age groups with either gender subjects who were diagnosed with Thyroidorbitopathy at hospitals were included in this study. History of ocular surgery or medications, thosedemonstrating the recent use of contact lenses, pregnant or lactating women. All the cases withsimilar presentation not proved to be Thyroid Orbitopathy and patients who did not report for thefollow-up were excluded from the study. Result: A total of 60 patients were examined. Of the 60cases analyzed, female preponderance was noted and 41-60 years age group had the highestincidence of thyroid orbitopathy. The most common presentation was found to be unilateral. Inferiorrectus muscle was the commonest muscle involved with 48.3% followed by Medial rectus muscle38.3%, Superior rectus muscle 23.3%, and Lateral rectus muscle involved least with 11.6% indescending order. None of the patients reported a loss of vision. Conclusions: Dry eye andincreased IOP have commonly seen outcomes that should be managed diligently. This potentialsight-threatening condition is seen worldwide and has many functional and cosmetic consequencesthat need to be recognized. Hyperthyroidism was significantly associated with the severity.


Introduction
Graves' orbitopathy/ophthalmopathy (GO) also known as thyroid eye disease (TED), dysthyroid/ thyroid-associated ophthalmopathy (TAO), is an autoimmune disorder representing the commonest and most important extrathyroidal manifestation of Graves' disease, but it may occur in patients without current or prior hyperthyroidism ( Graves' disease is a common disorder with an annual incidence in women of one per 1,000 population. In addition to hyperthyroidism, clinical involvement of the eyes develops in 25% to 50% of individuals with Graves' disease [5]. The annual incidence of Graves's ophthalmopathy in women is approximately 16 in 100,000 and men 3 in 100,000.
There appears to be a female preponderance in which women are affected 2.5-6 times more frequently than men; however, severe cases occur more often in men than in women [6]. The underlying pathophysiology is thought to be an antibody-mediated reaction against the TSH receptor with orbital fibroblast modulation of T-cell lymphocytes. The T-cell lymphocytes are believed to react against thyroid follicular cells with shared antigenic epitopes in the retrobulbar space [10].
The lymphocytic infiltration leads to the activation of cytokine networks and inflammation and interstitial edema of the extraocular muscles [11]. Excess secretion of glycosaminoglycans by orbital fibroblasts seems to be an important contributor.
The result is the expansion of the volume of extraocular muscles, retrobulbar fat, and connective tissue. Similar changes affect the eyelids and anterior periorbital tissues [12].
Risk factors of progressive and severe thyroidassociated orbitopathy: Aims and Objectives 2. To assess the risk factors associated with TED

Materials and Methods
This is a prospective study conducted over 2 years (September 2018 -August 2020).
Inclusion criteria: All the Age groups with either gender subjects who were diagnosed with Thyroid orbitopathy at hospitals were included in this study.   According to Table 2, 41-60 years age group had the highest incidence of thyroid orbitopathy, the patients were arbitrarily divided into four groups, and at least one less than 20 years of age group. Intraocular pressure was seen in hyperthyroid patients and the association was found to be statistically significant in Table 3. In table 4, the Laterality status of orbitopathy was analyzed. The most common presentation was found to be unilateral.  None of the patients reported a loss of vision. The most common sign refractive error and the least one was restrictive myopathy in Table 6. As per Table 7, the most common presenting eye sign was found to be decreased vision during the study period in patients of Hyperthyroidism which was found to be statistically significant. (p<0.05).  (Table 8).

Discussion
The involvement of the eyes in thyroid disease is a well-acknowledged entity. In the present study, our objective was to determine the association of hyperthyroidism with raised IOP and Dry eye in a patient population is based on different age groups and gender. Most studies around the world have shown a higher female to male ratio [13].
The present study had a female to male was 2.1:1.
Besharati et al. also found a higher frequency in females but Kashkouli et al reported more prevalent thyroid eye disease in males [14].
More than 80% of our patients were under the age of 50. Etezad-Razavi reported a mean of 34.7 years for females and 44.7 years for males, which is slightly different from our mean of 33.0 and 38.1 years for females and males, respectively [15].
As per the present study raised Intraocular pressure and Dry eyes were seen in our female population, our results were clinically significant (P<0.05) One notable finding in this study was the elevation of IOP.
The orbit is a bony structure and an increase in intra-orbital volume will cause both displacements of the globe anteriorly and increased intraocular pressure [16]. The association of Hyperthyroidism with increased IOP has been known for more than a century.
Increased IOP in up gaze is commonly seen in hyperthyroidism however it is not specific and can be seen in any infiltrative orbitopathy due to mechanical compression of the globe. Besides, it has been proposed that thyroid-related ocular hypertension may be caused by increased episcleral venous pressure or glycosaminoglycan deposition in the trabecular meshwork [17].
In a study by Haefliger et al., performed on 500 patient charts, the prevalence of increased IOP was noted to be 24% [18]. In 2007, Behrouzi et al.
reported a prevalence of 11%, and He reported an incidence of 31.3% in Chinese patients [18]. With the persistence of exophthalmos, there was an increased chance of development and progression of glaucoma signs such as cupping of the disc and visual field defects. The present study had (36.6%) cases of increased IOP in the primary position.
An increase in IOP can be explained by increased pressure on the globe by enlarging muscle masses and by the impediment of episcleral outflow.
Persistence of hyperthyroidism may lead to a progressive increase of IOP, leading to overt manifestations of glaucoma such as cupping of the disc and visual field loss, therefore, follow-up of patients in this regard is warranted.
The studies by Besharati, Perros, and Lee also demonstrated the same trend [19,20,21]. It appears that even though dry eyes and raised intraocular pressure was more frequently seen in females, a more aggressive form is seen with increasing age and the male gender.

Patil M. et al: Hyperthyroidism associated with intraocular
Tropical Journal of Ophthalmology and Otolaryngology 2020;5(7) The ocular complaint was observed in 44.27% of patients; foreign body sensation being the most common presenting symptoms in 61.79%. In a study done by Kashkouli et al., bilateral proptosis (9.9%), burning sensation (5.4%), pain behind the eye (5.3%), and puffiness (4.7%) were the most common signs and symptoms [22]. According to Carlson SE, the frequency of decreased vision is 67% of having common symptoms [23].
Dry eye has historically been explained by increased tear evaporation from proptotic eyes [24,25].
Nonetheless recently it has been shown that the lacrimal gland may also be a target of TSH antibodies [26]. Clinical evidence of dry eye was noted in 12 (17%) of our patients significant in women when compared to males.
When the dry eye was cross-referenced with the presence of proptosis, it was not found to be significant, indicating that lacrimal gland dysfunction should be considered as an entity by itself and not merely a consequence of proptosis. Interestingly, it has been shown by Gupta et al. that in patients presenting with dry eyes, previously undiagnosed thyroid dysfunction may be the underlying cause [27].

Conclusions
The prevalence of dry eye and raised Intraocular pressure in patients of hyperthyroidism was high and was more common in males. Dry eye and increased IOP have commonly seen outcomes that should be managed diligently.
What does the study add to the existing knowledge This potential sight-threatening condition is seen worldwide and has many functional and cosmetic consequences that need to be recognized. Hyperthyroidism was significantly associated with the severity.