Although an ophthalmology residency program existed at USC prior to that time, there were no full-time faculty members in the department.

[6] In 2011, USC and the Doheny Eye Institute fell into a dispute over renovations, permits, and other matters related to the building, which led to litigation.

[5] In 2013, the Doheny Eye Institute ended its relationship with USC and entered into an exclusive, long-term affiliation with University of California Los Angeles[7][8] Ronald E. Smith served as department chairman from 1995 to 2013,[9] and left USC to follow Doheny, and became vice chair of the department at UCLA.

[13][14][15] Dr. Mark Humayun, who joined the faculty of the Keck School of Medicine of USC in 2001,[16] was a co-inventor of a retinal prosthesis[17] that became the basis for the formation of the company, Second Sight, in 1998.

[20] In December 2013, David Hinton and Mark S. Humayun won a $19 million grant from the California Institute for Regenerative Medicine to conduct a clinical trial in which the use of embryonic stem cells to treat age-related macular degeneration will be tested.