PURPOSE: To investigate a relationship between the inner segment-outer segment (IS-OS) junctional layer integrity and the overlying retinal sensitivity assessed by Spectral OCT/SLO (spectral-domain optical coherence tomography) and microperimetry testing in patients with dry and wet forms of age-related macular degeneration (AMD). METHODS: Spectral-domain optical coherence tomography examination and microperimetry testing were performed in 55 eyes of 43 consecutive patients with AMD. Microperimetry maps were registered onto three-dimensional retinal topography maps, and point-to-point analysis of correlation between microperimetric retinal sensitivities and corresponding status of the underlying IS-OS junctional layer was performed. In addition, the analysis of correlation between the best-corrected visual acuity and the integrity of IS-OS layer in the center of the fovea also was performed. RESULTS: Retinal sensitivity was inversely and strongly correlated with the integrity of IS-OS layer in both dry and wet forms of AMD (correlation coefficient [r] = -0.75 [95% confidence interval, 0.49-0.88], P < 0.001, and -0.79 [95% confidence interval, 0.61-0.89], P < 0.001, respectively). The correlation between the best-corrected visual acuity and the integrity of IS-OS layer in the center of fovea was less significant (r = -0.58 [95% confidence interval, 0.19-0.79], P = 0.02, for dry AMD, and r = -0.6 [95% confidence interval, 0.32-0.78], P = 0.015, for wet AMD). CONCLUSION: Retinal sensitivity consistently correlated with the status of underlying IS-OS junctional layer in both dry and wet forms of AMD. Loss of IS-OS layer is significantly associated with poor retinal sensitivity, assessed by microperimetry. Compared with visual acuity, functional testing with microperimetry appears to more consistently correlate with changes in the outer retina, such as IS-OS junctional integrity, especially, in patients with wet AMD.