Venus Williams is out of the U.S. Open, leaving the tournament with only a few big-name stars. (Charles Krupa/AP)

Williams’ departure leaves the 2011 draw with just three remaining former champions: 2004 winner and No. 15 seed Svetlana Kuznetsova, 2006 winner and No. 3 seed Maria Sharapova and three-time winner and No. 28 seed Serena Williams.

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Through three days if play, eight seeded players have already been ousted including French Open champion Li Na (6), Wimbledon champion Petra Kvitova (5) and Marion Bartoli (8). And strangely in a week that has not featured the usual blistering heat and soul-sucking humidity of past tournaments, four players had already retired from matches before Venus announced her withdrawal.

So who’s the favorite the rest of the way? Many will say Serena if she can stay healthy and well-behaved. Or Sharapova if her shrieking doesn’t get in the way. Or perhaps world No. 1 and top seed Caroline Wozniacki if she can finally prove she has what it takes to win a major.

Just like each of the previous 2011 Grand Slam events, the U.S. Open draw is officially wide open.

Now back to Venus...

In a statement explaining her abrupt withdrawal from the tournament, Williams said she is suffering from Sjogren’s syndrome — an autoimmune disorder that causes fatigue and joint pain.

According to the Sjogren’s Syndrome Foundation Web site, the disease causes white blood cells to attack their moisture-producing glands, and today affects as many as four million Americans. Nine out of 10 patients are women.

How will this impact the waning career of one of the sport’s most dominant figures? In a story in Thursday’s Washington Post, tennis writer Liz Clarke suggests the condition, “need not be career-ending” in the case of a world-class athlete.

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While a virus kept her off the hard court circuit in the lead up to the U.S. Open this summer, dating back to 2004, the 31-year-old Williams had only missed two Grand Slam events before missing the French Open this spring. But her durability appears to be on the decline, and in a sport as demanding and fluid as tennis, this condition could signal the beginning of the end for one of the game’s brightest stars.

That’s not to say she cannot and will not continue to compete for Grand Slam titles, but the days of the Williams sisters owning the WTA tour throughout the season appear to be long gone.

“A lot of the battle is just trying to be fit and stay healthy,” Williams said. “Sometimes I’ve been losing that battle a lot. . . . No one is more in one-match-at-a-time mode than me now at this tournament. It will just be one match at a time, for sure.”