Zoledronate, a bisphosphonate, is an inhibitor of osteoclastic bone resorption, indicated for treatment of osteolytic bone lesions from multiple myeloma and other solid tumors. The most common adverse effect of zoledronate is a transient flu-like syndrome. Ocular adverse effects of bisphosphonates include conjunctivitis, uveitis, episcleritis, and scleritis.1 Cases of orbital inflammatory disease have been reported after treatment with another bisphosphonate, pamidronate sodium.2,3 There have been no reported cases of orbital inflammatory disease after treatment with zoledronate. We describe a case of a man developing orbital inflammation after intravenous treatment with zoledronate for bone-involving metastases from renal cell carcinoma.
A 55-year-old white man with bone metastases from renal cell carcinoma developed a transient fever (temperature, ≤ 38°C) with scleral injection in both eyes, more in the left eye than the right, one day following an infusion of 4 mg of zoledronate. By day 6, he noted the onset of significant periocular pain and edema in his left eye with diplopia. Visual acuity was 20/20 OU. Visual fields were full. Upper and lower lids were edematous with prolapsed chemosis, ptosis, and significant proptosis in his left eye. Extraocular movement was restricted in all left-eye gazes, greatest in the elevated gaze (Figure 1). There was no afferent pupillary defect. Mild cell and flare were present in the anterior chamber of the left eye. The fundus examination results were normal. A computed tomography scan demonstrated diffuse nonspecific inflammation with a focus involving the superior orbit surrounding the superior rectus muscle (Figure 2). We diagnosed orbital inflammatory disease in the patient.
Nine cardinal positions of gaze. A, At presentation, the right eye is proptotic and chemotic with decreased motility in all directions, most notably in elevation and adduction. B, At day 3 after treatment with 60 mg of oral prednisone, the proptosis and chemosis have resolved with normal motility.
Computed tomography scan of the orbits. A, Coronal section demonstrating diffuse edema nasally and superiorly involving the extraocular muscles and displacing the globe anteriorly and inferiorly. B, Axial section demonstrating edema with noticeable thickening of the sclera consistent with scleritis.
Treatment with 60 mg of oral prednisone lead to rapid clinical resolution of symptoms (Figure 1). The prednisone treatment was tapered during 10 weeks. Monthly treatments with zoledronate were continued. There were no recurrences of orbital inflammation.
Orbital inflammation has been reported in 3 patients treated with pamidronate.2,3 In all cases, the patients experienced complete recovery after withdrawal of treatment and initiation of oral steroids. The more common ocular adverse effects (scleritis, conjunctivitis) generally resolve once the bisphosphonate is discontinued, but may recur following rechallenge.4 No rechallenge occurred in these previous reports of orbital inflammation. The close temporal relationship of the infusion of zoledronate and the occurrence of orbital inflammation in our patient agrees with prior reports of orbital inflammation following bisphosphonate therapy.2,3 The demonstration that a rechallenge does not necessarily lead to a recurrence of disease when treated with steroids implies that orbital inflammation following treatment with zoledronate may not contraindicate the continued use of this quality of life–improving medication.
Bisphosphonates activate antigenic receptor T cells, whose activation releases cytokines. This may contribute to an immunologic or toxic ocular reaction in some patients.1 The T-cell rise occurring after treatment with bisphosphonates is less pronounced with each successive treatment. This may explain the lack of recurrence of orbital inflammation on successive treatments in our patient. Clearly, immune suppression with steroids aids in the resolution of orbital inflammation. Additional experience with rechallenge of bisphosphonate therapy following steroid treatment of orbital inflammation will help clarify the likelihood of successful retreatment.
Correspondence: Dr Phillips, PO Box 800715, Charlottesville, VA 22908-0715 (firstname.lastname@example.org).
Financial Disclosure: None reported.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Ophthalmology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Purchase Online Access to this article for 24 hours
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 7
Customize your page view by dragging & repositioning the boxes below.
and access these and other features:
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.