Isner, Thompson set up quarter-final meeting
The headline match of the second round was top seed Isner and Aussie Bernard Tomic. In what proved to be a very close contest, the world number nine prevailed, saving a set point in the first set en route to a 7-6 (7), 6-4 victory.
Thompson took on Eubanks on Grandstand and after the American qualifier edged out the opening set, the seventh-seeded Aussie rolled through the second set before navigating his way past the American 4-6, 6-1, 6-4.
Johnson, Karlovic fall victim to upsets
Third seed Johnson lost his ninth straight match dating back to last year, ousted from the tournament by qualifier Brayden Schnur 6-4, 4-6, 7-6 (5). After the Canadian broke midway through the first set, Johnson hit back to win the second.
After assuming a 5-3 lead, the world number 34 held a match point, but Schnur ultimately saved it and forced a tiebreaker that the world number 154 edged out to reach his first tour-level quarterfinal. Karlovic also fell, losing to Radu Albot 6-7 (4), 7-6 (4), 7-6 (5).
Other Wednesday results and Thursday look ahead
Harrison lost a close three-setter to Paolo Lorenzi, the 37-year old Italian claiming a 4-6, 6-4, 6-4 victory to set up a last-eight meeting with Schnur. McDonald was defeated by Denis Istomin 4-6, 6-2, 6-3.
Thursday's action is highlighted by Sam Querrey facing Albot while second seed Frances Tiafoe gets his tournament underway against Jason Jung as well as Bob Bryan and Mike Bryan in doubles action.