A study on immunoglobulin G4-related ophthalmic disease (IgG4-ROD) with destructive changes in periorbital soft tissues was presented. The patient was an 89-year-old-man who developed a left-sided orbital lesion involving the globe, lacrimal gland, and extraocular muscles. A diagnosis of definite IgG4-ROD was made based on clinical and histopathologic findings. The patient was started on oral prednisolone, which afforded good response initially. However, when tapering was initiated, full-thickness destruction developed on the lateral half of the lower eyelid margin. Steroid dose was increased, and the patient underwent a series of surgeries (suspension of the lower eyelid and lateral tarsorrhaphy, subtotal exenteration, and debridement and endonasal sinus surgery) in an attempt to manage the progression and recurrence of the condition. Medical management consisting of antibiotics and anti-fungal was administered to control the disease process. With close follow-up, repeated ancillary testing, and continuous management, the periocular and systemic findings were stable for 3 months after the last surgery.