In rare cases, bisphosphonates are well established to cause ocular inflammation, presenting as uveitis, episcleritis, scleritis, orbital inflammation, and/or conjunctivitis. Some reports of bisphosphonate-associated neuro-ophthalmic complications also exist. We identified 101 reports in the literature relating to bisphosphonate-associated ocular complications. In a great majority of cases, symptoms resolve after discontinuation of the drug and anti-inflammatory treatment. Many cases recur if rechallenged with the same bisphosphonate. First-generation nonamino bisphosphonates, including clodronate and etidronate, are not associated with ocular inflammation. Only 2nd- and 3rd-generation amino bisphosphonates, including pamidronate, alendronate, risedronate, ibandronate, and zoledronate are associated with these complications. The mechanism of bisphosphonate-induced ocular inflammation may be related to activation of γ/δ T cells or M1 macrophages. Intravenous forms, such as pamidronate and zoledronate, tend to have higher rates and faster onset of ocular inflammation, generally presenting within days of infusion. In oral bisphosphonates, such as alendronate and risedronate, these complications present with more sporadic timing. Rates of complications are also higher when bisphosphonates are used for malignancy, as doses tend to be higher compared with doses for osteoporosis.

Ocular Side Effects of Bisphosphonates: A Review of Literature.

Metabolic bone disease includes a variety of disorders, including Paget's Disease, osteogenesis imperfecta, and osteoporosis which is the most prevalent. This chapter reviews publications from January 2021 through December 2022 that include adverse reactions to the following drugs/drug classes: bisphosphonates, burosumab, calcitonin, denosumab, romosozumab, teriparatide, and abaloparatide. Included are data from meta-analyses, systematic reviews, clinical trials, observational studies, and case reports. 

Drugs for metabolic bone disease

Bisphosphonates such as zoledronic acid are an important part of adjuvant therapy to reduce the risk of recurrence in early-stage breast cancer. Uveitis remains one of the lesser-known side effects of zoledronic acid; prompt recognition is essential to ensure patients receive appropriate and timely care to help prevent permanent vision loss. We report a case of anterior uveitis in a postmenopausal woman who presented with visual symptoms after receiving the first dose of zoledronic acid. This case report serves to educate and increase awareness of the risk of uveitis in patients who are given zoledronic acid. This is the first and only reported case of zoledronic acid when used in the adjuvant setting for the treatment of breast cancer. 

Uveitis, a rare but important complication of adjuvant zoledronic acid for early-stage breast cancer

The most frequently reported adverse reaction to zoledronic acid is an acute phase reaction resembling influenza. While rarer adverse events such as osteonecrosis of the jaw and atypical femoral fractures have gained significant recognition, the ocular adverse effects, particularly scleritis, are not yet fully comprehended. Here, we present the case of a 75-year-old female patient with osteoporosis who developed bilateral redness and intense eye pain 48 h after receiving a 5 mg intravenous dose of zoledronic acid. Clinical presentation suggested bilateral conjunctivitis, but treatment with levofloxacin eye drops and acyclovir ophthalmic gel exacerbated the symptoms over 2 days, predominantly affecting the left eye. Ocular ultrasonography revealed thickening of the left eyeball wall with a "T" sign, while an orbital CT scan showed increased thickness of the left sclera. Treatment with methylprednisolone 80 mg intravenous infusion twice daily led to gradual symptom improvement and eventual resolution of inflammation. This report, based on a review of relevant literature, investigates the treatment and outcomes of zoledronic acid-induced scleritis, emphasizing the importance for clinicians to promptly identify and manage this rare and serious ocular adverse reaction. 

Posterior scleritis following a single infusion of zoledronate for osteoporosis: A case report and literature review

/pdf/case-report-acute-unilateral-uveitis-induced-by-infusion-of-1syvqejr.pdf

Case Report: Acute Unilateral Uveitis Induced by Infusion of Zoledronic Acid

This three-case report aims to highlight the ocular adverse effects induced by bisphosphonate therapy and to call clinicians’ attention. Three cases of acute anterior uveitis secondary to the initial dose of zoledronate infusion were reported with focus on their symptoms, treatment regimens, and outcomes. A review of published reports provided a basis for discussion. Three cases of acute anterior uveitis were either bilateral or unilateral. They demonstrated typical manifestations of bisphosphonate-induced acute anterior uveitis such as eye pain, blurred vision, conjunctival and ciliary hyperemia, keratic precipitates, and flare in the anterior chamber. After topical corticosteroid-containing comprehensive treatments, these symptoms resolved completely without any vision loss and long-term sequelae. Acute anterior uveitis may be part of the acute phase reaction induced by zoledronate. Patients should be informed of its symptoms in advance and be monitored closely during and after administration. Clinicians should have a good awareness of the zoledronate-associated acute anterior uveitis and to treat it in a prompt and appropriate manner.

/pdf/zoledronate-induced-acute-anterior-uveitis-a-three-case-neot4orfp7.pdf

Zoledronate-induced acute anterior uveitis: a three-case report and brief review of literature.

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Zoledronate-induced acute anterior uveitis: a three-case report and brief review of literature.