Two-time champion Venus Williams was knocked out of the U.S. Open in the second round by sixth-seeded Angelique Kerber of Germany, completing a year of early-round Grand Slam exits for the 32-year-old American.

Williams, unseeded this year and ranked 46th in the world, has struggled for the past two years with Sjogren’s syndrome, an energy-sapping autoimmune disease.

Williams, who lost 6-2, 5-7, 7-5 to Kerber, was a second- round loser at the French Open and was defeated in the first round at Wimbledon. The seven-time Grand Slam champion, who has been ranked No. 1 in the world on three separate occasions, did not play in this year’s Australian Open.

Williams, who once was among the best servers in women’s tennis, lost her first five service games against Kerber. She had 16 double faults and one ace in the match, which ended after midnight.

To contact the editor responsible for this story: Rob Gloster at rgloster@bloomberg.net