Combating posterior capsular opacification: From conventional intraocular lens modifications to proactive defense via...

Posterior capsular opacification (PCO), the most common complication after intraocular lens (IOL) implantation, can be mitigated but is not fully prevented using conventional IOL strategies. These strategies include material optimization (e.g., hydrophobic acrylate), mechanical barrier design (e.g., sharp edges), and biological modifications (e.g., heparin surface-modified IOLs). In this review, we discuss the pathological mechanisms of PCO, briefly trace the evolution of traditional functional IOLs, and critically analyze their limitations in terms of passive defense. We then systematically elaborate on proactive interface engineering-driven strategies, including drug-delivering IOLs, biofunctionalized IOLs, and stimuli-responsive IOLs, that precisely regulate lens epithelial cell (LEC) activity and microenvironment remodeling through surface functionalization. Challenges in efficacy evaluation and clinical translation, such as key in vitro/in vivo metrics, model limitations and issues in manufacturing, are discussed. The integration of smart responsive materials with interdisciplinary assessment frameworks will bridge the gap between laboratory innovation and clinical safety for next-generation IOLs.