BACKGROUND AND OBJECTIVE Laser photocoagulation is a mainstay or adjuvant treatment for a variety of common retinal diseases. Automated laser photocoagulation during intraocular surgery has not yet been established. The authors introduce an automated laser photocoagulation system for intraocular surgery, based on a novel handheld instrument. The goals of the system are to enhance accuracy and efficiency and improve safety. MATERIALS AND METHODS Triple-ring patterns are introduced as a typical arrangement for the treatment of proliferative retinopathy and registered to a preoperative fundus image. In total, 32 target locations are specified along the circumferences of three rings having diameters of 1, 2, and 3 mm, with a burn spacing of 600 μm. Given the initial system calibration, the retinal surface is reconstructed using stereo vision, and the targets specified on the preoperative image are registered with the control system. During automated operation, the laser probe attached to the manipulator of the active handheld instrument is deflected as needed via visual servoing in order to correct the error between the aiming beam and a specified target, regardless of any erroneous handle motion by the surgeon. A constant distance of the laser probe from the retinal surface is maintained in order to yield consistent size of burns and ensure safety during operation. Real-time tracking of anatomical features enables compensation for any movement of the eye. A graphical overlay system within operating microscope provides the surgeon with guidance cues for automated operation. Two retinal surgeons performed automated and manual trials in an artificial model of the eye, with each trial repeated three times. For the automated trials, various targeting thresholds (50-200 μm) were used to automatically trigger laser firing. In manual operation, fixed repetition rates were used, with frequencies of 1.0-2.5 Hz. The power of the 532 nm laser was set at 3.0 W with a duration of 20 ms. After completion of each trial, the speed of operation and placement error of burns were measured. The performance of the automated laser photocoagulation was compared with manual operation, using interpolated data for equivalent firing rates from 1.0 to 1.75 Hz. RESULTS In automated trials, average error increased from 45 ± 27 to 60 ± 37 μm as the targeting threshold varied from 50 to 200 μm, while average firing rate significantly increased from 0.69 to 1.71 Hz. The average error in the manual trials increased from 102 ± 67 to 174 ± 98 μm as firing rate increased from 1.0 to 2.5 Hz. Compared to the manual trials, the average error in the automated trials was reduced by 53.0-56.4%, resulting in statistically significant differences (P ≤ 10(-20) ) for all equivalent frequencies (1.0-1.75 Hz). The depth of the laser tip in the automated trials was consistently maintained within 18 ± 2 μm root-mean-square (RMS) of its initial position, whereas it significantly varied in the manual trials, yielding an error of 296 ± 30 μm RMS. At high firing rates in manual trials, such as at 2.5 Hz, laser photocoagulation is marginally attained, yielding failed burns of 30% over the entire pattern, whereas no failed burns are found in automated trials. Relatively regular burn sizes are attained in the automated trials by the depth servoing of the laser tip, while burn sizes in the manual trials vary considerably. Automated avoidance of blood vessels was also successfully demonstrated, utilizing the retina-tracking feature to identify avoidance zones. CONCLUSION Automated intraocular laser surgery can improve the accuracy of photocoagulation while ensuring safety during operation. This paper provides an initial demonstration of the technique under reasonably realistic laboratory conditions; development of a clinically applicable system requires further work.