Prospective Case-crossover Study Investigating the Possible Association Between Nonarteritic Anterior Ischemic Optic Neuropathy and Phosphodiesterase Type 5 Inhibitor Exposure.
To evaluate the association between intermittent phosphodiesterase type 5 inhibitor (PDE5i) exposure and risk of acute nonarteritic anterior ischemic optic neuropathy (NAION) using a case-crossover design.



Male adults with suspected NAION were enrolled at 41 US ophthalmology sites from 2010 to 2015 and were interviewed regarding risk factors for NAION, medical history, and PDE5i use before NAION onset (index date of onset [IDO]). An adjudication committee confirmed the NAION cases. The primary analysis, using the person-time method, examined the rate of PDE5i exposure within 5 half-lives of NAION onset relative to PDE5i exposure over a 30-day study period preceding the IDO in men exposed to PDE5i intermittently as a measure of NAION risk associated with PDE5i exposure. Rate ratios were estimated using the Mantel-Haenszel estimator. Secondary analyses included person-time analyses over the 12-months preceding the IDO and matched-interval analyses over 42 days preceding the IDO.



Of 279 men with confirmed NAION, 22 were exposed to PDE5i intermittently within 30 days of IDO. The Mantel-Haenszel rate ratio for risk of NAION associated with PDE5i exposure within 5 half-lives of IDO was 2.27 (95% confidence interval [CI]: 0.99-5.20) over the 30-day period (n = 22) and 3.52 (95% CI: 1.59-7.79) over the 12-month period (n = 26). Sensitivity analyses showed similar results and were statistically significant. The matched-interval method found no association (hazard ratio = 1.64 [95% CI: 0.60-4.51]).



Overall, the study suggests an increased risk of NAION associated with PDE5i use. Patients and health-care providers should continue to weigh the risks and benefits of PDE5i use, including the potential for NAION.
Eli Lilly and Company Limited, Surrey, United Kingdom. Electronic address: eva_flahavan@lilly.com.
Evelyn M
EM
Flahavan
Eli Lilly and Company, Indianapolis, IN.
Hu
H
Li
Eli Lilly and Company, Indianapolis, IN.
Komal
K
Gupte-Singh
Eli Lilly and Company, Indianapolis, IN.
Rosemary T
RT
Rizk
Eli Lilly and Company, Indianapolis, IN.
Dustin D
DD
Ruff
Eli Lilly and Company, Indianapolis, IN.
Jennie Lin
JL
Francis
Eli Lilly and Company, Indianapolis, IN.
Kraig S
KS
Kinchen
D000208:Acute Disease; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D007172:Erectile Dysfunction / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced* / Q000175:diagnosis*; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects*; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States
D058986:Phosphodiesterase 5 Inhibitors