Hormones and Dry Eye Syndrome
Hormones and Dry Eye Syndrome
Ocular surface and tear film changes are very common in patients with thyroid disease. It is also clinically relevant to consider occult thyroid disease in the differential diagnosis of DES patients.
There is some ambiguity in the medical literature pertaining to identifying the association between thyroid disease and involvement of DES. Sometimes the terminology does not clarify the exact disease and in other instances an assignment is not definitive because groups of different diseases are lumped together as a single entity ( Table 3 ).
Although DES in thyroid disorders is usually considered as complication of an autoimmune condition related to Hashimoto's thyroiditis and/or Graves' ophthalmopathy, there are several causes of a thyroid disorder with diverse underlying mechanisms probably contributing to induce DES in those patients.
In these diseases, a combination of events contributes to manifesting DES in the patients. The most obvious one is an ocular surface disturbance due to enhanced environmental exposure and lid mechanical impairment in Graves' ophthalmopathy. Inappropriate lid closure is caused by superior eyelid retraction, eye globe proptosis, and impaired blinking. All these factors are contributory to inadequate tear film surface spreading and higher evaporation (Fig. 1).
(Enlarge Image)
Figure 1.
Aspect of the lid opening (a) and ocular surface (b) of a patient with Graves' ophthalmopathy.
In recent years, the concomitance between thyroid diseases and Sjögren's syndrome and more detailed descriptions of ocular surface inflammatory responses in patients with thyroid diseases made it likely that DES in those patients is an autoimmune-induced response. Although there are no known reports on lacrimal gland pathology in DES individuals afflicted with a thyroid disease, computed tomography analysis revealed that those glands were larger than controls. The biopsies of salivary glands revealed infiltrating lymphocytes (mainly CD3 T) with a CD4/CD8 ratio of 2 : 1, activation markers, human leukocyte antigen (HLA) class II molecules, and interleukin (IL)-2 receptor (CD25). In some patients, HLA class II was inappropriately expressed in the epithelial gland cells.
Autoantibodies against thyroid stimulating hormone (TSH) receptor are expressed in individuals with thyroid-associated ophthalmopathy and these TSH receptors are present in human lacrimal gland (LG). In addition, autoantibodies against thyroid hormone were observed in thyroid diseases such as Hashimoto's thyroiditis and Graves' disease, but also in Sjögren's syndrome. These observations suggest a mechanism whereby autoimmunity disrupts hormone and tissue interaction, due to antibody binding to hormones and/or their cognate receptors, leading to LG dysfunction.
Impaired thyroid hormone activity, per se, can be responsible for LG impairment and DES, since in rats LG express thyroid hormone receptor beta-1. Furthermore, the antithyroid drug thiamazole, given systemically to rats, induced tear secretion reduction and cornea epithelial metaplasia. A clinical study revealed also that thyroid hormone regulates lipid exocrine secretion, which suggests its impact on meibomian glands and evaporative DES.
The thyroid hormone disorder treatments include thyroid hormone replacement, iodine suppression, immunomodulators specific for the orbit and ocular disease, local radiotherapy, and oculoplastic and orbit surgical interventions. It is difficult to identify in the present medical literature whether each one of them contribute to DES development and/or progression. This uncertainty exists since clinical trials targeted to address these two questions are not available and the data are only from case reports. In a study involving a follow-up for 9 years of patients receiving various treatments for Graves' ophthalmopathy, about 25% of them presented with DES complaints. In another study, testing surgical millerectomy for eyelid retraction caused by Graves' ophthalmopathy, DES, identified by Schirmer test measurement, was observed in 7 of the 12 patients. In response to orbit radiotherapy, also for Graves' ophthalmopathy, persistent DES symptoms were reported in 10 and 12% of patients.
Taken together, these findings reveal that various factors present in the spectrum and long-term progression of ocular surface findings associated to thyroid diseases. Some of the contributory factors to DES include increased exposure, inflammatory responses, and hormonal level reduction (Fig. 2).
(Enlarge Image)
Figure 2.
Mechanisms of disease related to DES in thyroid diseases. DES, dry eye syndrome.
These considerations indicate that in every DES case lacking a clear cause, these individuals should also be evaluated for thyroid disease. Such screening entails a clinical exam and serum analysis for thyroxin (T4) and TSH. Moreover, in these cases, apart from ocular topical treatment, the patients may benefit from endocrine treatment, but the ophthalmologist needs to be aware of possible ocular side effects resulting from Graves' ophthalmopathy treatment.
Thyroid Hormone-related Diseases and Dry Eye Syndrome
Ocular surface and tear film changes are very common in patients with thyroid disease. It is also clinically relevant to consider occult thyroid disease in the differential diagnosis of DES patients.
There is some ambiguity in the medical literature pertaining to identifying the association between thyroid disease and involvement of DES. Sometimes the terminology does not clarify the exact disease and in other instances an assignment is not definitive because groups of different diseases are lumped together as a single entity ( Table 3 ).
Although DES in thyroid disorders is usually considered as complication of an autoimmune condition related to Hashimoto's thyroiditis and/or Graves' ophthalmopathy, there are several causes of a thyroid disorder with diverse underlying mechanisms probably contributing to induce DES in those patients.
In these diseases, a combination of events contributes to manifesting DES in the patients. The most obvious one is an ocular surface disturbance due to enhanced environmental exposure and lid mechanical impairment in Graves' ophthalmopathy. Inappropriate lid closure is caused by superior eyelid retraction, eye globe proptosis, and impaired blinking. All these factors are contributory to inadequate tear film surface spreading and higher evaporation (Fig. 1).
(Enlarge Image)
Figure 1.
Aspect of the lid opening (a) and ocular surface (b) of a patient with Graves' ophthalmopathy.
In recent years, the concomitance between thyroid diseases and Sjögren's syndrome and more detailed descriptions of ocular surface inflammatory responses in patients with thyroid diseases made it likely that DES in those patients is an autoimmune-induced response. Although there are no known reports on lacrimal gland pathology in DES individuals afflicted with a thyroid disease, computed tomography analysis revealed that those glands were larger than controls. The biopsies of salivary glands revealed infiltrating lymphocytes (mainly CD3 T) with a CD4/CD8 ratio of 2 : 1, activation markers, human leukocyte antigen (HLA) class II molecules, and interleukin (IL)-2 receptor (CD25). In some patients, HLA class II was inappropriately expressed in the epithelial gland cells.
Autoantibodies against thyroid stimulating hormone (TSH) receptor are expressed in individuals with thyroid-associated ophthalmopathy and these TSH receptors are present in human lacrimal gland (LG). In addition, autoantibodies against thyroid hormone were observed in thyroid diseases such as Hashimoto's thyroiditis and Graves' disease, but also in Sjögren's syndrome. These observations suggest a mechanism whereby autoimmunity disrupts hormone and tissue interaction, due to antibody binding to hormones and/or their cognate receptors, leading to LG dysfunction.
Impaired thyroid hormone activity, per se, can be responsible for LG impairment and DES, since in rats LG express thyroid hormone receptor beta-1. Furthermore, the antithyroid drug thiamazole, given systemically to rats, induced tear secretion reduction and cornea epithelial metaplasia. A clinical study revealed also that thyroid hormone regulates lipid exocrine secretion, which suggests its impact on meibomian glands and evaporative DES.
The thyroid hormone disorder treatments include thyroid hormone replacement, iodine suppression, immunomodulators specific for the orbit and ocular disease, local radiotherapy, and oculoplastic and orbit surgical interventions. It is difficult to identify in the present medical literature whether each one of them contribute to DES development and/or progression. This uncertainty exists since clinical trials targeted to address these two questions are not available and the data are only from case reports. In a study involving a follow-up for 9 years of patients receiving various treatments for Graves' ophthalmopathy, about 25% of them presented with DES complaints. In another study, testing surgical millerectomy for eyelid retraction caused by Graves' ophthalmopathy, DES, identified by Schirmer test measurement, was observed in 7 of the 12 patients. In response to orbit radiotherapy, also for Graves' ophthalmopathy, persistent DES symptoms were reported in 10 and 12% of patients.
Taken together, these findings reveal that various factors present in the spectrum and long-term progression of ocular surface findings associated to thyroid diseases. Some of the contributory factors to DES include increased exposure, inflammatory responses, and hormonal level reduction (Fig. 2).
(Enlarge Image)
Figure 2.
Mechanisms of disease related to DES in thyroid diseases. DES, dry eye syndrome.
These considerations indicate that in every DES case lacking a clear cause, these individuals should also be evaluated for thyroid disease. Such screening entails a clinical exam and serum analysis for thyroxin (T4) and TSH. Moreover, in these cases, apart from ocular topical treatment, the patients may benefit from endocrine treatment, but the ophthalmologist needs to be aware of possible ocular side effects resulting from Graves' ophthalmopathy treatment.
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