Pathophysiology Mechanism of Disease

TED pathogenesis: A “complex” story of disordered signaling

Though the exact autoimmune triggers of thyroid eye disease are unknown, emerging evidence does identify two co-localized receptors expressed on orbital fibroblasts, acting together as a receptor signaling complex, as a key gatekeeper of the pro-inflammatory cascade and downstream effects.6

Watch how TED autoantibodies activate a receptor signaling complex
made up of the insulin-like growth factor 1 receptor (IGF‑1R) and the thyroid‑stimulating hormone receptor (TSHR) to mediate inflammation

TED damage begins behind the eye

Inflammatory changes behind the eye

Before erythema or proptosis is visible, TED autoantibodies are targeting the orbital fibroblasts, the specialized cells responsible for tissue and cell repair, via the IGF-1R/TSHR signaling complex.1,6 The resulting inflammatory cascade causes muscle tissue within the orbit to swell.7 Adipose tissue at the back of the orbit also expands.7 These tissue changes within the rigid, bony space of the orbit force the eye forward (exophthalmos) and put dangerous pressure on the optic nerve.7

Image showing thyroid eye disease targeting orbital fibroblasts before proptosis is visibleImage showing thyroid eye disease targeting orbital fibroblasts before proptosis is visible

MRI studies can provide objective confirmation of the substantial inflammatory changes in and around the orbit and show the involvement of individual muscles, including early in the course of disease.8 In one study, MRI revealed extraocular muscular swelling in 70% of patients who had Graves’ disease but no visible signs of TED.9,10

The swelling of muscle and expansion of orbital fat seen on these types of imaging studies can cause ocular tenderness, pain, and pressure.7 As TED progresses, the increased intraorbital volume puts pressure on the eye and optic nerve as more pronounced signs begin to appear, such as proptosis/exophthalmos, vision changes, and signs of corneal exposure.7

Inflammatory eye damage icon Inflammatory eye damage icon

The inflammatory damage of TED begins before clinical signs
are visible. Close monitoring of patient-reported symptoms is key to uncovering early disease.

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