Orbital and periorbital amyloidosis: A systematic review of clinical characteristics, radiological features, management, and systemic correlations.

We performed comprehensive systematic review of orbital and periorbital non-familial amyloidosis, including clinical features, radiology, histopathology, management and outcomes. We included English-language articles describing biopsy-proven orbital and periorbital amyloidosis published from inception to February, 2025. Cases without ocular histopathology and familial amyloidosis were excluded. We included 120 studies detailing 168 cases. Most were primary localized amyloidosis. The clinical presentation was variable, resulting in diagnostic uncertainty. Amyloidosis most commonly affects superficial structures, such as the eyelid and conjunctiva. Amyloidosis also affects orbital structures, including extraocular muscles, lacrimal gland, and orbital nerves. Computed tomography typically shows enlargement of the affected structures, sometimes with calcifications. On magnetic resonance imaging, amyloidosis appears iso- to hypo-intense on T1-weighted images and hypointense with heterogeneous signal on T2-weighted sequences, often presenting as an infiltrative or mass-like lesion. Amyloid plaques characteristically demonstrate apple-green birefringence on Congo-red staining. Following diagnosis, systemic evaluation helps identify potential severe complications of disease, including visceral damage, dysfunction, and malignancies. Early diagnosis, consideration of surgical or radiotherapy, and close monitoring are important in preventing disease progression and minimising symptoms. Orbital and periorbital amyloidosis is an important differential for non-specific eyelid mass, conjunctival haemorrhage, or periorbital ecchymosis. Careful evaluation is necessary, especially to identify features of systemic disease.