The purpose of this study was to evaluate central and parafoveal inner retinal layer thickness in patients with subretinal drusenoid deposits (SDD) or conventional drusen (CD). Participants underwent comprehensive ophthalmoscopic examination. Evidence of SDD or CD was evaluated with near infrared reflectance and spectral domain optical coherence tomography. Quantification of subfoveal lesions was made through a qualitative analysis of vertical and horizontal SD-OCT scans centered on the fovea. Inner retinal layer macular thickness measurements were obtained for central circles with 1, 3, and 5 mm diameter. Continuous variables were compared by the analysis of covariance (ANCOVA) with post-hoc Tukey HSD correction for multiple comparison analysis. Fifty-five patients were included in the study; 18 eyes with SDD alone, 19 eyes with CD alone, and 18 eyes of healthy age-matched subjects. Eight eyes with SDD (44%) and 13 eyes with CD (68%) had subfoveal lesions. There was significant reduction in the inner retinal layer thickness in the central 1mm area and in the superior 3 mm area in the SDD and CD group compared to controls. In conclusion the inner retinal layer is thinner in the central macula and in the superior parafovea in eyes.