An ophthalmic laser surgical system uses a confocal detector assembly to continuously detect a confocal signal during laser treatment, and based on the confocal signal, detects in real time a loss of tissue contact with the patient interface (PI) output surface. The detection is partly based on the change of reflectivity at the PI output surface when the optical interface changes from a lens-tissue interface to a lens-air interface. The behavior of the confocal signal upon loss of tissue contact is dependent on the treatment laser scan pattern being performed at the time of tissue contact loss. Thus, different confocal signal analysis algorithms are applied to detect tissue contact loss during different scans, such as the bed cut and side cut for a corneal flap. The real time confocal signal may also be used during eye docking to detect the establishment of tissue contact with the PI output surface.