Thyroid Eye Disease (TED), also known as Graves’ orbitopathy, is a self-limiting autoimmune condition commonly associated with dysthyroid states. Its clinical presentation varies widely, ranging from mild cases to severe, sight-threatening complications. ^[1] TED is the most frequent orbital disease, occurring in approximately 25% of patients with Graves’ disease when eyelid signs are excluded and up to 40% when they are included. It typically manifests in the fourth and fifth decades of life but can also affect neonates and the elderly. ^[2]

Hyperthyroidism, a condition characterized by excessive thyroid hormone production, impacts multiple body systems, including the eyes. TED, a common extra-thyroidal manifestation of hyperthyroidism, significantly affects patients’ quality of life. ^[3] The ocular changes result from immune-mediated inflammation and fibrosis of orbital tissues, leading to a spectrum of symptoms and functional impairments. ^[4]

TED symptoms include proptosis, dry eye, upper lid retraction, diminished vision, and ptosis. These signs range from mild discomfort to severe complications threatening vision. The prevalence and severity of TED vary across demographic and clinical groups, emphasizing the need for tailored care and early intervention. ^[5]

Graves’ disease, the most common form of hyperthyroidism, is an autoimmune disorder wherein IgG antibodies bind to thyroid-stimulating hormone (TSH) receptors, stimulating excessive thyroid hormone production. ^[6] It is more prevalent in females, commonly occurring in the third and fourth decades of life, and is frequently linked to other autoimmune disorders. Clinical features include lid retraction, conjunctival chemosis, unequal pupil dilation, ocular motility issues, exophthalmos, exposure keratitis, optic neuropathy, and ocular surface discomfort. Dry eye is particularly common in patients with Hashimoto’s thyroiditis. ^[7]

In TED, inflammation affects extraocular muscles, orbital fat, and lacrimal glands, causing cellular infiltration, glycosaminoglycan accumulation, and fluid retention. ^[8] This results in muscle enlargement—sometimes up to eight times their normal size—and can lead to optic nerve compression, subsequent muscle fiber degeneration, fibrosis, restrictive myopathy, and diplopia. ^[9] Increased intraorbital pressure from fluid retention further exacerbates symptoms. ^[10]

This was an observational, cross‑sectional study conducted at a tertiary eye care hospital. Patients diagnosed with TED as per the Bartley and Gorman criteria amongst those who presented to the out‑patient department were included in the study. If lid retraction was seen, the presence of laboratory evidence of thyroid dysfunction, exophthalmos, optic nerve dysfunction or extra ocular muscle involvement was considered as TED. In case of no lid retraction in a patient with laboratory evidence of thyroid dysfunction, the presence of exophthalmos, optic nerve involvement or restrictive myopathy was considered as TED.

Patients in whom diagnosis was uncertain or who refused complete ocular examination were excluded from the study.

Data were collected using a self‑administered questionnaire and complete ocular examination was recordedas perthe ITEDS case proforma. This included demographic data and a history of smoking andcomorbidities with an emphasis on autoimmune diseases, systemic thyroidstatus,orbitopathystatuswithregards to onset, duration and laterality of symptoms.

Objective clinical assessment was done using the VISA (vision, inflammation strabismus and appearance) score assessment. Vision (aided/ unaided) was recorded using the Snellen chart; color vision using the Ishihara plates (15 of 38 plates). The afferent pupillary defect was assessed by swinging flashlight test. Optic disc was assessed by slit‑lamp biomicroscopy forthe presence of edema and/or pallor. Slit‑lamp examination was done to look for signs of inflammation namely caruncular oedema, chemosis, conjunctival redness, lid redness and lid edema Ocular ductions were graded using the Hirschberg reflex.

Various measurements such as margin reflex distance1 (MRD1), palpebral fissure height (PFH), scleral show, levator function and lagophthalmos were recorded in millimeters. Proptosis was measured using Hertel’s exophthalmometer. The eyeball was said to be proptosed if Hertel’s reading was over 20 mm or there was a greaterthan 2 mm difference in degree of proptosis. Schirmer’s test without topical anaesthesia (for 5 minutes) was done to detect dry eyes.

Based on the VISA score calculated, a score over >4/10 was classified as clinically significant active disease, while a VISA score of ≤4/10 was defined as clinically insignificant quiescent disease. Grading of severity was done by EUGOGO classification for severity and patients were classified to have mild, moderate to severe and sight‑threatening disease. Various clinical presentations of TED are depicted

Statistical analyses

Statistical analyses were performed using Microsoft excel office version 2016 and SPSS trial version 23.0 (SPSS Inc., Chicago, IL, USA) software. Quantitative data were expressed as mean ± SD, whereas qualitative data were expressed as percentage and proportions. A significance of difference in means was inferred by student’s t‑test and paired‑T test, whereas a significance of difference in proportions was inferred by Chi‑square test. Risk factors for severe disease were assessed using univariate and multivariate logistic regression. For significance, P ≤ 0.05 was considered and all P values were two sided.

Table 1: Demographic Details and Clinical Characteristics of Study Participants (N=90)

*Significance at p < 0.05.

According to Table 1, a total of 90 patients with established hyperthyroidism were studied. The study showed a female preponderance, with females comprising approximately 55.6% of the hyperthyroid patients. The mean age in males was 42.5 ± 22.4 years, while in females it was 44.6 ± 16.6 years, which was found to be statistically significant (p < 0.05). Increased intraocular pressure was observed in a significant proportion of hyperthyroid patients, and the association was found to be statistically significant (p = 0.01)

Table 2: Distribution of Presenting Eye Signs in Hyperthyroid Patients (N=90)

*P < 0.05 is statistically significant.

As per Table 2, the most common presenting eye sign was diminished vision, observed in 66.7% of hyperthyroid patients, which was found to be statistically significant (p < 0.01). Other frequently reported signs included ptosis (65.6%) and proptosis (58.9%), both of which were also statistically significant.

Table 3: Prevalence of Hyperthyroid Eye Signs According to Different Age Groups (N=90)

P < 0.05 is statistically significant

As shown in Table 3, it is evident that with increasing age, the prevalence of hyperthyroid eye signs tends to rise. Diminished vision was the most common eye sign across all age groups, being statistically significant (p < 0.01). This was followed by upper lid retraction and ptosis, which also showed significant associations with increasing age (p < 0.05).

Table 3 highlights the prevalence of hyperthyroid eye signs distributed across different age groups among 90 patients. The data reveals a clear trend of increasing eye signs with advancing age in hyperthyroid patients. Proptosis was observed in 9 patients under 20 years, 15 patients aged 20–39 years, 13 patients aged 40–59 years, and 16 patients aged over 60 years. Although prevalent, the difference across age groups was not statistically significant (p = 0.21). Dry eye symptoms were more prominent in older patients, affecting 2 individuals in both the under 20 and 20–39 age groups,²³4 individuals aged 40–59 years, and 8 individuals over 60 years. However, this trend was not statistically significant (p = 0.11). Upper lid retraction showed a notable increase with age, affecting 3 patients under 20, 5 in the 20–39 age group, 11 in the 40–59 group, and 15 patients over 60 years. This association was statistically significant (p = 0.02). Diminished vision was the most common sign across all age groups, with 6 cases under 20 years, 15 cases aged 20–39 years, 13 cases aged 40–59 years, and 16 cases in those over 60 years. This trend was highly significant (p = 0.01). Similarly, ptosis was a frequent finding, with prevalence rising from 6 cases under 20 years, 15 cases in the 20–39 age group, 13 cases in the 40–59 age group, ²³to 25 cases in those over 60 years, showing a statistically significant correlation (p = 0.01).

Table 4:

Intraocular pressure was significantly higher in participants with hyperthyroidism compared to the normal reference range. The mean IOP was 19.4 ± 2.8 mmHg, with 28% of participants exhibiting IOP levels above 21 mmHg. This elevation was more pronounced in individuals with longer disease duration (>2 years), suggesting a potential link between chronic hyperthyroidism and elevated IOP.

Dry eye symptoms were reported in 68 participants (75.6%). Clinical evaluation using the Schirmer’s test revealed that 72.2% of participants had reduced tear production (<10 mm in 5 minutes), and the Tear Break-Up Time (TBUT) test confirmed instability of the tear film in 78.9% of cases. Subjective complaints of eye discomfort, irritation, and visual disturbance were consistent with these findings.

Involvement of the eyes in thyroid disease is a wellac knowledged entity. In the present study, our objective was to determine the association of hyperthyroidism with raised IOP and Dry eye in a patient population in based on different age groups and gender. Most studies around the world have shown a higher female to male ratio ^[11]. The present study had a male to female ratio of 1: 1.3. Besharati ^[12] also found a higher frequency in females but Kashkouli et al reported more prevalent thyroid eye disease in males. ^[13] More than 80% of our patients were under the age 50.

As per the present study raised Intraocular pressure and Dry eyes were seen in our female population, our results were clinically significant intraocular pressure. ^[14] 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. In addition, it has been proposed that thyroid related ocular hypertension may be caused by increased episcleral venous pressure or glycosaminoglycan deposition in the trabecular meshwork ^[15].

In a study by Haefliger et al., performed on 500 patient charts, the prevalence of increased IOP was noted to be 24%. ^[16] In 2007, Behrouzi et al. reported a prevalence of 11%, and He reported an incidence of 31.3% in Chinese patients. ^[17] With 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 primary position. Increase in IOP can be explained by increased pressure on the globe by enlarging muscle masses and by impediment of episcleral outflow.

Persistence of hyperthyroidism may lead to 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. ^[18,19] 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. 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. ^[20]

Dry eye has historically been explained by increased tear evaporation from proptotic eyes. ^[21] Nonetheless recently it has been shown that the lacrimal gland may also be a target of TSH antibodies. ^[22] Clinical evidence of dry eye was noted in 12 (17%) of our patients significant in women when compared to male. When dry eye was crossreferenced with 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. ^[23-25].

Thyroid eye disease affects the majority of thyroid disease patients. The ocular manifestation ranges from mildest to the most severe form. Early diagnosis and intervention can be beneficial in saving sight and globe. Hence a proper referral system between ophthalmologists and physician is mandatory. Also, many thyroid disorders are first time diagnosed form ocular manifestations so a regular health check-up including eye check-up is needed to pick the cases in early stage and referred among each other for better treatment outcome

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