Article Review: "Radiation Therapy" for Thyroid Eye Disease

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Thyroid-related ophthalmopathy (TAO) is an organ-specific autoimmune disease characterized by infiltrative lesions of the retro-ocular and periorbital eye tissue, and is one of the most common extrathyroid manifestations of
thyroid disease.

TAO is more common in patients with Graves disease (GD), also known as Graves eye disease (GO), and can also be seen in a small number of patients with Hashimoto's thyroiditis and normal
thyroid function.
This article summarizes the contents of radiation therapy related to "thyroid eye disease" for readers
.

Principles of treatment of thyroid-related eye diseases

Treatment of thyroid-associated eye disease (TAO) includes medication, orbital radiation therapy, and surgery
.

Drug treatment mainly includes glucocorticoids, biologics and traditional immunosuppressants, and requires full control of risk factors, stable thyroid function, and ocular symptomatic support
.
Orbital radiation therapy is one of
the second-line treatments for moderately to severely active TAO.

The choice of treatment should take into account factors such as the course and condition (staging and grading) of TAO, the efficacy of treatment, the safety and cost of treatment, access to drugs, and patient preference (Figure 1).

Note: CAS, showing clinical activity score; QOL, quality of life score

Fig.
1 Treatment flow of thyroid-related eye disease (TAO).

"Radiation therapy" strategies for thyroid-related eye disease

Orbital radiation therapy is one of
the second-line treatments for moderately to severely active TAO.

1.
Mechanism

Orbital radiation therapy can promote apoptosis of lymphocytes in extraocular muscle tissue, and at the same time promote the production of free radicals in cells, inactivate activated T lymphocytes, thereby reducing the activity of orbital fibroblasts, stopping inflammation, and reducing glycosaminoglycans
.
Low-dose orbital radiation therapy allows for terminal differentiation of fibroblasts
.
In addition, orbital radiation therapy can stop the nitric oxide pathway and reduce inflammatory pain
.

2.
Indications

(1) moderately severe active TAO that is insensitive to glucocorticoids; (2) moderately severe active TAO with glucocorticoid intolerance; (3) Glucocorticoid-dependent moderate-to-severe active TAO
.

3.
Contraindications

Gestational and diabetic retinopathy are absolute
contraindications.
Use
with caution in patients younger than 20 years.

4.
Scheme

Three-dimensional intensity-modulated radiation therapy is
recommended.
GENERALLY USING 6MV X-RAY, MASK TO FIX THE HEAD POSITION, SUPINE POSITION, MRI OR CT POSITIONING, THE TOTAL IRRADIATION DOSE IS 20 Gy, 1 TIME / d, 2 Gy EACH TIME, 5 TIMES A WEEK, THE TOTAL COURSE OF TREATMENT IS 2 WEEKS
.
Low-dose radiation therapy regimens of 1 Gy once weekly for a total dose of 20 Gy for 20 weeks
of completion may also be used.
The target area is the retroorbital bulbar contents and does not affect the pituitary, lacrimal glands, and anterior chamber
of the eye.
The cornea and lens should be protected as much as possible during irradiation, and the average irradiation dose in the area should be less than 2 Gy
.
Orbital radiation therapy combined with intravenous or oral corticosteroids may yield better results
.

5.
Effectiveness

Most of the research results show that orbital radiation therapy 2 weeks has a significant effect on active TAO, with an effective rate of 52%~67%.

Especially for the extraocular muscle thickening type active TAO effect is obvious, can improve eye mobility, restrictive strabismus, diplopia symptoms, etc.
, but also can prevent TAO optic neuropathy
.
For TAO who has developed TAO optic neuropathy, orbital radiation therapy can significantly improve ocular symptoms and delay or even avoid orbital decompression surgery
.
The literature recommends a low-dose radiation regimen (20 weeks), which has an effective rate of 67% and a lower incidence of adverse reactions, but the course of treatment is long and the patient cooperation is poor
.
In addition, some studies compared the efficacy of 2.
4 Gy (0.
3 Gy/time, 1 dose/day, 8 doses) with 16 Gy (2 Gy/dose, 1 dose/day, total 8 doses), and there was no clear difference between the two, suggesting that low-dose radiation therapy regimens are effective, but more studies are needed
.

6.
Adverse reactions

Adverse effects of orbital radiation therapy are divided into early acute radiation injury (within 3 months) and late radiation injury (more than 3 months).

Early acute radiation injury includes hair loss in the irradiated field (27%), blurred vision, periorbital edema, conjunctival hyperemia (14.
5%), and TAO optic neuropathy, which can be recovered
after stopping orbital radiation therapy.
Advanced radiation injury includes radiation retinopathy (1%), cataract (2.
25%), and secondary malignancy (occasionally).

Modern 3D intensity modulated radiation therapy techniques provide adequate protection of critical organs, making orbital radiation therapy an effective second-line treatment
.