Representative patient images. (A) Representative images of patients 1 to 5 with KRAS-mutant isolated orbital histiocytosis. External photographs of the external adnexa and involved eye: eyelid edema and ptosis (i), conjunctival histiocytic infiltration (ii), exophthalmos, and scleral show (iii), lower eyelid swelling with xanthelasma (iv), exophthalmos and scleral show (v). MRI of representative patients: arrows showing bilateral diffusely enlarged lacrimal glands (vi), arrow showing thickening of the left lateral rectus (vii), arrow showing mass lesion involving the right lateral rectus muscle (viii), arrow showing infiltration and involvement of the lacrimal gland, superior muscle complex and lateral rectus (ix), and arrow showing bulky disease in the inferior orbit with diffuse involvement of the inferior rectus muscle (x). (B) Representative patient images demonstrating disease response to treatment in KRAS-mutant isolated orbital disease. T1-weighted MRI coronal image of patient 2 demonstrating predominantly inferior and medial histiocytosis infiltration of the right orbit before treatment (i) and marked response after cobimetinib treatment (ii). T1-weighted MRI axial image of patient 5 showing right infiltration of the inferolateral orbit with exophthalmos (iii), with marked improvement following intra-arterial chemotherapy with melphalan (iv).