PURPOSE: To validate a new computer-aided diagnosis (CAD) imaging program for the assessment of nuclear lens opacity. METHODS: Slit-lamp lens photographs from the Singapore Malay Eye Study (SiMES) were graded using both the CAD imaging program and manual assessment method by a trained grader using the Wisconsin Cataract Grading System. Cataract was separately assessed clinically during the study using Lens Opacities Classification System III (LOCS III). The repeatability of CAD and Wisconsin grading methods were assessed using 160 paired images. The agreement between the CAD and Wisconsin grading methods, and the correlations of CAD with Wisconsin and LOCS III were assessed using the SiMES sample (5547 eyes from 2951 subjects). RESULTS: In assessing the repeatability, the coefficient of variation (CoV) was 8.10% (95% confidence interval [CI], 7.21-8.99), and the intraclass correlation coefficient (ICC) was 0.96 (95% CI, 0.93-0.96) for the CAD method. There was high agreement between the CAD and Wisconsin methods, with a mean difference (CAD minus Wisconsin) of -0.02 (95% limit of agreement, -0.91 and 0.87) and an ICC of 0.81 (95% CI, 0.80-0.82). CAD parameters were also significantly correlated with LOCS III grading (all P < 0.001). CONCLUSIONS: This new CAD imaging program assesses nuclear lens opacity with results comparable to the manual grading using the Wisconsin System. This study shows that an automated, precise, and quantitative assessment of nuclear cataract is possible.