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Previous Volume 359:1410-1411 September 25, 2008 Number 13 Next

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To the Editor: Bisphosphonates are being used increasingly for the prevention and treatment of osteoporosis, hypercalcemia of malignant disease, and other disorders of bone metabolism. Known ocular complications of bisphosphonates include conjunctivitis, anterior uveitis, episcleritis, and scleritis.¹

A 57-year-old man presented with a 4-day history of increasing orbital pain and swelling in the right eye. Three days before the onset of symptoms, he had received an infusion of zoledronic acid bisphosphonate for spontaneous osteonecrosis of the knee. His medical history was otherwise unremarkable.

On examination, his visual acuity was 20/60 in his right eye (corrected to 20/16 with the use of a pinhole occluder) and 20/16 in his left eye. There was marked orbital swelling and 2 mm of proptosis in the right eye on Luedde proptometry.² His right-eye movements were reduced in all directions. He had conjunctival chemosis and inferior corneal punctate erosions in the right eye (Figure 1), with a subtle, relative afferent pupillary defect.

View larger version (57K): [in this window] [in a new window]   Figure 1. Conjunctival Chemosis and Proptosis of the Right Eye on Initial Presentation.

 
An orbital computed tomographic scan showed extensive preseptal and postseptal fat stranding with proptosis in the right eye (Figure 2). There was no orbital collection or sinus disease. Despite high-dose intravenous antibiotic therapy for 5 days, there was no improvement.

View larger version (88K): [in this window] [in a new window]   Figure 2. Orbital CT Scan Showing Extensive Preseptal and Postseptal Fat Stranding and Proptosis in the Right Eye.

 
A diagnosis of orbital inflammatory disease due to bisphosphonate infusion was made. Treatment with intravenous pulse methylprednisolone was initiated, with immediate improvement. After three doses, the patient's pain had resolved completely and the swelling had improved markedly. He was discharged while receiving decreasing doses of oral prednisone, and his condition continued to improve.

To our knowledge, there have been only three previously reported cases of orbital inflammatory disease due to bisphosphonates, and in each case, the associated agent was intravenous pamidronate.^3,4 In all cases, the onset of ocular pain and swelling occurred within 6 days after the bisphosphonate infusion, and these symptoms responded rapidly to corticosteroid therapy.

The mechanisms of orbital inflammatory disease due to bisphosphonates are uncertain. Bisphosphonates may stimulate the release of acute-phase reactants and cytokines, including interleukin-1 and interleukin-6.⁵ The release of these cytokines with extraocular muscle inflammation might be the mechanism in orbital inflammatory disease.³

Physicians should be aware of this rare complication of bisphosphonates. We recommend taking a thorough history, with specific questions about recent bisphosphonate therapy, for all patients presenting with symptoms of orbital inflammatory disease. Bisphosphonate infusions should be used with caution, or avoided altogether, in patients with acute ocular inflammation or a history of inflammatory eye disease or uveitis.

Neil S. Sharma, M.B., B.S., M.P.H.
Ju-Lee Ooi, M.B., B.S., M.P.H.
Sydney Eye Hospital
Sydney, NSW 2000, Australia

Katherine Masselos, M.B., B.S.
University of New South Wales
Sydney, NSW 2033, Australia

Michael J. Hooper, M.D.
University of Sydney
Sydney, NSW 2006, Australia

Ian C. Francis, M.B., B.S., Ph.D.
Prince of Wales Hospital
Sydney, NSW 2031, Australia
iancfrancis{at}gmail.com

Dr. Hooper reports receiving consulting and lecture fees from Merck, Novartis, and AstraZeneca and lecture fees from Servier. No other potential conflict of interest relevant to this letter was reported.

References

1. Fraunfelder FW, Fraunfelder FT. Bisphosphonates and ocular inflammation. N Engl J Med 2003;348:1187-1188. [Free Full Text]
2. Chang AA, Bank A, Francis IC, Kappagoda MB. Clinical exophthalmometry: a comparative study of the Luedde and Hertel exophthalmometers. Aust N Z J Ophthalmol 1995;23:315-318. [CrossRef][Web of Science][Medline]
3. Ryan PJ, Sampath R. Idiopathic orbital inflammation following intravenous pamidronate. Rheumatology (Oxford) 2001;40:956-957. [CrossRef][Medline]
4. Subramanian PS, Kerrison JB, Calvert PC, Miller NR. Orbital inflammatory disease after pamidronate treatment for metastatic prostate cancer. Arch Ophthalmol 2003;121:1335-1336. [Free Full Text]
5. Kunzmann V, Bauer E, Wilhelm M. / T-cell stimulation by pamidronate. N Engl J Med 1999;340:737-738. [Free Full Text]

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