Mastering the Eye: Clinical Paradigm Shifts from Optical Restoration to Genomic Correction

Historically, the main operation for cataract was couching, and the interior of the living eye could not be examined until Hermann von Helmholtz introduced the ophthalmoscope in 1851. Since the mid-twentieth century, seven advances have reshaped ophthalmic care. Harold Ridley implanted the first intraocular lens in 1949, and the ophthalmologist Charles Kelman and the engineer Anton Banko developed phacoemulsification, reported in 1967. Robert Machemer performed the first pars plana vitrectomy in 1970, while David Huang and colleagues described optical coherence tomography in 1991. Endothelial keratoplasty, developed by Gerrit Melles and others between 1998 and 2006, replaced only the failing corneal endothelium instead of the full thickness of the cornea. Anti-VEGF therapy followed the purification of VEGF by Napoleone Ferrara and colleagues in 1989 and the approval of ranibizumab in 2006. Minimally invasive glaucoma surgery has spread since 2012, and in 2017 voretigene neparvovec became the first approved gene therapy for an inherited retinal disease. Five of these advances enabled a new type of intervention, whereas endothelial keratoplasty and minimally invasive glaucoma surgery made existing operations safer. For each advance we summarize the best available evidence of benefit to patients and its certainty, which is high for some, such as anti-VEGF therapy, and low for others, such as the effect of imaging on patient outcomes. Each advance created new burdens, from chronic injections to dependence on donor tissue, and routine adoption depended on manufacturing, regulation, cost, reimbursement, and health-system capacity.