System and method for determining the position and orientation (P&O) of a tool-tip relative to an eye tissue of interest. The system includes and imaging and tracking module coupled with a processor. The imaging and tracking module at least includes an imager. The imager acquires at least one image of at least one tissue-reference-marker. The imaging and tracking module further determines information relating to the P&O of the tool. The processor determines the P&O of the tissue-reference-marker according to the acquired image of the tissue-reference-marker. The processor determines the P&O of the eye tissue of interest, according to the P&O of the tissue-reference-marker, and a predetermined relative P&O between the tissue-reference-marker and the eye tissue of interest. The processor also determines the P&O of a tool-tip according to a tool-marker and determines the relative P&O between the tool-tip and the eye tissue of interest.