To evaluate the safety of SNJ-1656, ophthalmologic findings and physiological conditions were examined during the trials. The palpebral and bulbar conjunctiva, cornea, anterior chamber, iris, and lens were examined with slitlamp microscopy at 9 AM, 10 AM, 1 PM, 5 PM, and 9 PM daily during the trial. Also, the ocular findings were scored according to the following criteria: 0 indicates no significant changes; 0.5, slight changes regarded as physiological; 1, mild changes requiring no treatment; 2, moderate changes requiring any treatment; and 4, severe changes requiring hospitalization. Pupil diameter was measured at constant illumination at 9 AM, 10 AM, 11 AM, 5 PM, and 9 PM. General physiological factors, including blood pressure, pulse, and body temperature, were also monitored at 9 AM, 10 AM, 1 PM, 5 PM, and 9 PM. Electrocardiograms were obtained at 9 AM and 11 AM. Ocular examinations included determination of best-corrected visual acuity, retinal fundus examination, full -field flash electroretinography (LE-1000; Tomey, Nagoya, Japan), examination of the corneal and conjunctival surfaces with fluorescein and rose bengal dye, the Schirmer lacrimal test, corneal endothelial cell count with a specular microscope (Noncon Robo Pachy SP-9000; Konan Medical Inc, Tokyo), determination of corneal thickness using pachymetry (Noncon Robo Pachy SP-9000), and hematological and urine examinations, all performed at 9 AM. In the repeated-instillation trial, slitlamp examination, Schirmer lacrimal and rose bengal tests, the measurement of pupil diameter and the monitoring of physiological factors were performed on the first, third, fifth, and seventh days of the trial. An electrocardiogram was obtained on the first, second, fourth, sixth, and seventh days. All examinations were reperformed on the last day of the trial and 1 week after the trial. Slitlamp photography was performed at baseline and whenever abnormal findings were obtained on slitlamp examination results. If volunteers experienced abnormal ocular symptoms, the volunteers indicated them on the patient data sheets. To minimize the adverse effects of SNJ-1656 in the subjects, the study was performed in ascending order from steps 1 to 5 in the single-instillation trial and steps 1, 2-1, 2-2, and 3 in the repeated-instillation trial.