Zoledronic acid associated orbital inflammation

A 59-year-old female patient had an intravenous zoledronic acid infusion (5 mg Aclasta; Novartis New Zealand, Auckland, New Zealand) for the treatment of osteoporosis. The next day, she developed a headache, bilateral retro-orbital pain and mild photosensitivity. On the second day, she developed swelling and redness of left eyelids, along with discomfort on eye movements. This was treated as conjunctivitis with chloramphenicol eye drops in the community. It did not resolve and progressed to more swelling with pain on eye movement, and diplopia in all gaze positions other than primary. She denied any history of trauma or sinusitis, and had no recent fever. She has history of trigeminal neuralgia, for which she takes pregabalin. The visual acuities were 6/4.8 in the right eye and 6/6 in the left eye. The intraocular pressures were 22 mmHg in the right eye and 26 mmHg in the left eye. There was marked swelling of left periorbital area, with gross proptosis of 4 mm on Hertel exophthalmometry. The left eye had restricted movement in all gazes (Figure 1). The left upper lid was erythematous with mild tender swelling. On Ishihara colour plates, the patient scored equally in both eyes. There were normal pupillary reflexes, with no relative afferent pupillary defect. Slit lamp examination showed marked conjunctival chemosis, but the anterior chamber and posterior segment were quiet. There were no signs of uveitis or scleritis. Urgent blood tests were done. These showed a normal white blood cell and platelet count, but a mildly elevated Creactive protein of 29 mg/L (reference range < 5). Thyroid stimulating hormone was within the normal range. An orbital computed tomography showed extensive pre-septal oedema and retro-orbital fat stranding. The extraocular muscles were of normal sizes. The paranasal sinuses were normal (Figure 2). The diagnosis of orbital inflammation secondary to zoledronic acid was made. The patient was given intravenous 500 mg methylprednisolone. The signs and symptoms rapidly improved after initial steroid within 24 hours, and the patient was switched to oral prednisone 60 mg daily (1 mg/kg dose). She returned for review 2 weeks after the initial presentation. The left-sided orbital inflammation had completely settled, and there was a full range of eye movement, with no proptosis. The prednisone course was rapidly tapered. Zoledronic acid is a bisphosphonate medication, commonly used for prevention and treatment of osteoporosis and also hypercalcaemia, metastatic bone disease and Paget's disease of bone. Prevalence of osteoporosis in Australia is estimated to be “5.9% for men and 22.8% for women aged 50 years and over, and 12.9% for men and 42.5% for women aged 70 years and over.” Zoledronic acid is considered the first-line prevention and treatment therapy of osteoporosis. Bisphosphonates reduces bone resorption through several mechanisms. It targets osteoclasts, where it reduces recruitment to bone surfaces, inhibits the activity and shortens the osteoclast life span. Ocular side effects of bisphosphonates are uncommon. They can affect any layer of the eye and can cause conjunctivitis, scleritis and uveitis. Bisphosphonate-related orbital inflammation is an uncommon event. The mechanism of inflammation is postulated to be due to the pro-inflammatory nature of subtypes of bisphosphonate. Zoledronic acid,