B isphosphonates are used to inhibit bone absorption as a treatment for hypercalcemia associated with osteolytic bone cancer, bony metastasis, Paget disease, and osteoporosis. There have been 7 reported cases of bisphosphonate-induced orbital inflammation (1–7). We describe another case and document MRI abnormalities. An 89-year-old woman was well until 20 minutes after receiving her first dose of 4 mg zoledronic acid intravenously when she developed acute, severe lower extremity arthralgias, followed by ascending arthralgias and a left-sided headache. Three days later she developed bilateral periocular pain associated with intense sharp pain provoked by eye movement, blurred vision in the left eye, and binocular horizontal diplopia with image separation greater in lateral gaze. Best-corrected visual acuity was 20/40 in the right eye and 20/50 in the left eye without a relative afferent pupil defect. In primary gaze position, she had 10 prism-diopters (PD) of esotropia which increased to 25 PD in right and left gaze (Fig. 1). Confrontation visual fields were full. Slit-lamp examination showed diffuse conjunctival injection and bullous chemosis with no sign of anterior uveitis. Ophthalmoscopy disclosed no abnormalities. MRI showed diffuse fat stranding, optic nerve sheath enhancement, posterior scleral enhancement, and slight enlargement of extraocular muscles bilaterally (Fig. 2). Bisphosphonate-induced orbital inflammation was diagnosed and treated with 1 g methylprednisolone intravenously per day for 3 days followed by prednisone on a tapered dose regimen. Over the next 3 days, headache, double vision, chemosis, and orbital pain dramatically improved. One month later, ophthalmic abnormalities had largely resolved (Fig. 3). This is the first reported case of orbital inflammation caused by bisphosphonate treatment for osteoporosis. In all reported cases of bisphosphonate-induced orbital inflammation, the onset of ocular symptoms has varied from 1 to 6 days after drug administration. The symptoms have included orbital pain, diplopia, and lid swelling. The common signs have been periocular edema, chemosis, conjunctival injection, proptosis, reduced ocular ductions, and minimal anterior chamber inflammation. The treatment of this adverse event has been discontinuation of the offending drug and use of high-dose systemic corticosteroids. All reported patients have had rapid and complete resolution. Although discontinuation of bisphosphonate alone may be sufficient (1,2,3,4,5), corticosteroids may hasten the recovery process. The mechanism of orbital inflammation in this setting is unsettled. Inflammatory factors have been implicated, given that augmented levels of tumor necrosis factor(TNF-),