PURPOSE. Reduced retinal nerve fiber layer (RNFL) thickness has been demonstrated in patients with diabetic peripheral neuropathy (DPN) in cross-sectional studies. This prospective study defines longitudinal alterations to the RNFL thickness in individuals with type 1 diabetes without (DPN-ve) and with (DPNþve) DPN and in relation to risk factors for nerve damage. METHODS. A cohort of 105 individuals with type 1 diabetes (20% DPNþve) with predominantly mild or no retinopathy and no previous retinal photocoagulation underwent spectral-domain optical coherence tomography (SD-OCT) at baseline, 2 years, and 4 years. SD-OCT scans were acquired at 3.45-mm diameter around the optic nerve head and the overall RNFL and RNFL in the nasal, superior, temporal, and inferior quadrants were quantified. By including serial quantified RNFL parameters, linear mixed models were applied to assess the change in RNFL thickness over time and to explore the associations with other clinical variables. RESULTS. There was a significant decline in the overall RNFL thickness (-0.7 lm/y, P ¼ 0.02) and RNFL in the superior quadrant (-1.9 lm/y, P < 0.01) in the DPNþve group compared with DPN-ve group. The overall RNFL thickness and RNFL in the superior and nasal quadrants were inversely associated with age (b ¼ -0.29, -0.41, and -0.29, respectively; P ≤ 0.02). Sex, retinopathy, diabetes duration, hemoglobin A 1c, lipid profile, blood pressure, cigarette use, alcohol consumption, and body mass index did not show any significant effects (P > 0.05). CONCLUSIONS. Individuals with DPN showed a progressive RNFL thinning overall and in the superior quadrant, which was more pronounced in older individuals. There may be common pathways for retinal and peripheral neurodegeneration that are independent of conventional DPN risk factors.