Former champions Kei Nishikori and Tomas Berdych lost at the Japan Open on Wednesday.
Top-seeded Nishikori was forced to retire with a left glute problem in the first set of his second round match against Joao Sousa.
Third-seeded Berdych fell to Gilles Muller of Luxembourg 7-6(7), 6-1 in the first round.
Nishikori was 3-0 up when he received medical treatment on his left glute while lying face down on the court for several minutes.
The 2012 and 2014 champ served two weak double faults in the next game, and appeared in pain when chasing the ball. He held serve, but lost the next three games before calling a halt while leading 4-3 in his first matchup with Sousa.
Nishikori, ranked No. 5, saw a doctor after the match, and will have a scan on Thursday.
Sousa moved on to face fifth-seeded David Goffin, after the Belgian beat Jiri Vesely 6-3, 7-5.
Also, fourth-seeded Marin Cilic rallied to defeat Spanish baseliner Fernando Verdasco 4-6, 7-5, 7-5.
Berdych captured his first ATP title of the season when he retained his Shenzhen Open crown in China on Sunday, but his first-round defeat in Tokyo dented his bid for the ATP Finals. He lies ninth in the race for the elite eight-man finals, which he’s played for the last six years.
A weary Berdych, the 2008 champ, squandered three break points in the sixth game then failed to convert a set-point in the first tiebreaker.
After falling 3-0 behind in the second set, the Czech called for a trainer to treat a left glute complaint, and was unable to stop Muller, who fired 12 aces.
“At the beginning of the second set, my body gave me a bit of a sign I’ve been playing a little too much tennis in the last couple of weeks,” Berdych said.
Muller, a two-time finalist this year, next faces Marcos Baghdatis.
The results:
At Beijing: China Open: Men: Second round: Andy Murray bt Andrey Kuznetsov 6-2, 6-1; Alexander Zverev bt Jack Sock 6-4, 6-2; David Ferrer bt Fabio Fognini 6-3, 6-4; Kyle Edmund bt Roberto Bautista 6-4, 4-6, 6-4.
First round: Adrian Mannarino bt Albert Ramos 6-3, 4-6, 6-3; Richard Gasquet bt Sam Querrey 2-6, 6-3, 6-2; Malek Jaziri bt Guido Pella 6-4, 6-4; Pablo Carreno bt Bernard Tomic 6-3, 6-1.
Women: Third round: Madison Keys bt Svetlana Kuznetsova 7-6(2), 6-2.
Second round: Angelique Kerber bt Barbora Strycova 6-3, 7-6(4); Caroline Garcia bt Peng Shuai 6-3, 3-6, 7-6(4); Elina Svitolina bt Sabine Lisicki 6-4, 6-4; Daria Gavrilova bt Timea Bacsinszky 4-6, 6-0, 6-4; Karolina Pliskova bt Darya Kasatkina 3-6, 7-5, 7-6(7); Johanna Konta bt Timea Babos 7-5, 6-2.
At Tokyo: Japan Open: Men: Second round: David Goffin bt Jiri Vesely 6-3, 7-5; Joao Sousa bt Kei Nishikori 3-4 retd.; Marin Cilic bt Fernando Verdasco 4-6, 7-5, 7-5.
First round: Gilles Muller bt Tomas Berdych 7-6(7), 6-1.
