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 (euthyroid or ophthalmic Graves’ disease) or in patients who are hypothyroid due to chronic autoimmune (Hashimoto’s) thyroiditis [1].

Clinical symptoms and signs are usually mild, consisting of ocular irritation with redness and tearing, stare due to lid retraction and exophthalmos, and periorbital swelling [2]. Approximately 28% of GO cases are severe, with restricted motility leading to diplopia, exposure keratopathy, and optic neuropathy [3]. Patients with severe GO may have lower rates of remission of their thyroid disease compared to mild GO patients [4].

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].

Also, most patients are aged 30-50 years, with severe cases appearing to be more frequent in those older than 50 years. It is the most common cause of bilateral exophthalmos, accounting for ~ 85% of cases [7]. GO also presents as unilateral exophthalmos, accounting for 15-28% of cases [8]. Although many patients are thought to have unilateral disease based on clinical findings, radiographic evidence of bilateral disease is present in a majority [8]. Cigarette smoking has been considered the strongest risk factor for developing GO [9].

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].

A comprehensive ophthalmic examination was performed in a standardized way for all patients. Best-corrected visual acuity was documented by the Snellen chart. Intraocular pressure (IOP) was measured by Goldmann applanation tonometry in the primary position. Eyelid, conjunctiva, and ocular motility were assessed. Tear status was evaluated with the Schirmer test and tear break-up time. considered Schirmer <10 mm and tear break-up time <10 seconds as tear dysfunction. The degree of proptosis was measured by the Hertel ophthalmometer. Proptosis was defined as the measurement of protrusion of the globe >20 mm from the lateral orbital rim in either eye or any discrepancy in the degree of protrusion of the 2 eyes by >2mm. The fundus examination was done for the evaluation of the disc and retina.

Apart from the routine hematological examinations, the patient was subjected to serological investigations which include the Thyroid profile was also done. Once the case was confirmed to be of thyroid orbitopathy, depending on the stage of clinical presentation, the patients were reassured and observed. All patients were referred to an endocrinologist for management of thyroid dysfunction and then they were followed for 6 months. The first follow-up was in the 1^st week and then at 1^st, 3^rd, and 6^th months.

Statistical analysis: The recorded observations were analyzed using SPSS Version 20. Categorical variables were expressed as counts and percentages. The Chi-square test for independent proportions or Fisher’s exact test was used. P<0.05 is considered statistically significant

A total of 60 patients were examined. Of the 60 cases analyzed, female preponderance was noted as shown in Table 1.

Table-1: Sex distribution of patients.

Table-2: Age distribution of patients.

As table 5 shows the Inferior rectus muscle was the commonest muscle involved with 48.3% followed by the Medial rectus muscle 38.3%, Superior rectus muscle 23.3%, and Lateral rectus muscle involved least with 11.6% in descending order.

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.

Table-7: Distribution of presenting ocular signs in Hyperthyroid Patients (N=70).

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: Prevalence of hyperthyroid eye signs according to different age groups.

It has been clear as the age progresses the signs tend to increase in hypothyroidism patients. the decreased vision was found to be the most common eye sign among all age groups which was statistically significant. (p<0.05) followed by Upper lid retraction (Table 8).

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].

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].

• Since our sample size was small due to the lesser number of patients attending the outpatient department, this was insufficient to estimate the exact prevalence of ocular manifestations of thyroid disease
• Smoking has been shown to correlate with the severity of hyperthyroidism but in the present study there was only 13 smoker who had hyperthyroidism, yet there was not enough data to make a statistical statement.
• Some patients with TD were taking systemic steroid and other immunosuppressive drugs due to some other systemic disease, these drugs are known to be having anti-inflammatory effects, and this can be a confounding factor in the present study
• The presence of a severe degree of eye involvement in our set up may be due to late presentation and due to unawareness of their disease process at presentation. It may be due to our center being a tertiary eye center, and since the majority of complicated and referred cases are reported.