To examine the risk of age-related macular degeneration (AMD) with oral bisphosphonates.

Three study designs were used: (1) disproportionality analysis; (2) case-control study; (3) self-controlled case series (SCCS).

setting: (1) Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Database; (2) 2 patient cohorts from British Columbia, Canada. study population: (1) All reports of AMD to the FDA with oral bisphosphoantes; (2) patients with wet AMD in British Columbia (2009–2013) and 1 million controls (2000–2007). intervention: Oral bisphosphonates. main outcome measures: (1) Reports of AMD to the FDA; (2) first diagnosis of wet AMD verified by a retina specialist in British Columbia.

In the disproportionality analysis there were 133 cases of AMD reported with alendronate, 20 with ibandronate, and 14 with risedronate. The reported odds ratios (RORs) for alendronate, ibandronate, and risedronate were 3.82 (95% CI: 2.94–4.96), 2.40 (95% CI: 1.49–3.86), and 2.87 (95% CI: 1.58–5.19), respectively. In the case-control analysis there were 6367 cases and 6370 corresponding controls. The adjusted OR for wet AMD among regular users of bisphosphonates in the 1, 2, and 3 years prior to the index date were 1.24 (1.12–1.38), 1.38 (1.22–1.56), and 1.59 (1.38–1.82), respectively. In the SCCS analysis there were 198 cases of wet AMD on continuous bisphosphonate therapy. The rate ratio for wet AMD for continuous bisphosphonate use was 1.99 (95% CI: 1.41–2.79). We did not have information on intravenous bisphosphonates.

Continuous users of oral bisphosphonates are at a higher risk of developing wet AMD. Given the observational nature of this study and limitation of the data, future studies are needed to confirm these findings.