Novak Djokovic lost the opener 6-3 during which he appeared to complain about a problem with his right eye.
The retirement represents the first time the 28-year-old has failed to make a final since Doha in January 2015.
"It's very sad when one of the greatest players ever has to retire from a match like that," Lopez told reporters while adding that Djokovic had told him he was suffering from an eye infection.
At one point, Novak Djokovic asked for the doctor to come on court, but refused the eye drops offered to him.
Novak Djokovic committed 18 unforced errors in the nine games played, offering his hand to his Spanish rival after just half an hour on court.
Australian Open champion Djokovic, who racked up his 700th career win on Wednesday, was booed by some fans as he walked off court having suffered his first loss in 15 matches in 2016
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