Histopathologic evidence of VEGF in early neovascular AMD: from a 1992 hypothesis to a 1994 discovery - a historical perspective.

BACKGROUND

In the early1990s, neovascular age-related macular degeneration (nAMD) was the leading cause of irreversible vision loss in older adults, yet its molecular basis remained unknown. In 1992, a hypothesis was proposed in which localized hypoxia could trigger vascular endothelial growth factor (VEGF)-mediated choroidal neovascularization in nAMD. Although hypoxia was recognized in ischemic retinopathies, nAMD was not considered a hypoxia-mediated retinal vascular disease.

MAIN BODY: In 1994, this hypothesis was tested using antigen retrieval immunohistochemistry on paraffin-embedded whole human eye sections with early nAMD. The study demonstrated strong VEGF immunoreactivity in the retinal pigment epithelium in the macular area but not in normal control eyes, providing the first direct histopathologic evidence of VEGF expression at the site of disease in intact human eyes with early nAMD. Until that point, the role of VEGF in ischemic retinopathies was being uncovered, but its involvement in early-stage nAMD had not yet been demonstrated.

CONCLUSION

The 1992-1994 work established both the hypothesis and the first direct tissue evidence linking VEGF to early nAMD. This discovery, made just over a decade before the advent of anti-VEGF therapy, anticipated one of ophthalmology's most transformative achievements, preserving vision for millions worldwide.