Background: To compare early visual changes in amyotrophic lateral sclerosis (ALS) patients with healthy controls in a baseline exploration, to follow-up the patients after 6 months, and to correlate these visual changes with neurological disability. Methods: All patients underwent a comprehensive neurological and ophthalmological examination. A linear mixed analysis and Bonferroni p-value correction were performed, testing four comparisons as follows: Control baseline vs. control follow-up, control baseline vs. ALS baseline, control follow-up vs. ALS follow-up, and ALS baseline vs. ALS follow-up. Results: The mean time from the diagnosis was 10.80 ± 5.5 months. The analysis of the optical coherence tomography (OCT) showed: (1) In ALS baseline vs. control baseline, a macular significantly increased thickness of the inner macular ring temporal and inferior areas; (2) in ALS follow-up vs. ALS baseline, a significant macular thinning in the inner and outer macular ring inferior areas; (3) in ALS follow-up vs. ALS baseline, a significant peripapillary retinal nerve fiber layer (pRNFL) thinning in the superior and inferior quadrants; and (4) ALS patients showed a moderate correlation between some OCT pRNFL parameters and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Conclusion: The OCT showed retinal changes in patients with motoneuron disease and could serve as a complementary tool for studying ALS.