Abstract
The objective of this study is to systematically review and compare the visual symptoms, temporal characteristics, associated features, and pathophysiological mechanisms of retinal migraine (RM) and migraine with aura (MA) to facilitate clinical differentiation. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, databases (PubMed, Google Scholar, Web of Science, and Scopus) were searched from January 1985 to July 2025 for studies on adult patients with RM or MA. A large language model assisted in extracting data on study design, visual symptoms, diagnostic criteria, and frequencies. Inclusion criteria focused on studies differentiating conditions, with preference given to case series of at least five patients and to systematic reviews or meta-analyses that encompassed at least 10 studies. Two-stage screening yielded 171 papers, with 65 unique studies analyzed qualitatively. RM is characterized by monocular (90%), negative symptoms (e.g., scotoma 84% and transient vision loss up to 100%), variable duration (less than 60 minutes in 89%, but prolongable), and vascular pathophysiology, with rare permanent loss. MA features bilateral/homonymous (75%), positive symptoms (e.g., scintillating scotoma 77% and zigzag 53%), stereotyped duration (five to 60 minutes in 79%), and cortical spreading depression, often with additional neurological symptoms. Overlaps include transient phenomena (less than one hour) and gradual spread. The International Classification of Headache Disorders, 3rd Edition (ICHD-3) criteria predominate, but debate persists for RM's reversibility requirement. MA evidence is robust from large cohorts, while RM data are limited and heterogeneous. Key differentiators include laterality, symptom type, and duration variability. Accurate history-taking emphasizing monocularity and exclusion of vascular mimics is crucial; RM may warrant aggressive prophylaxis to prevent infarction. Future research should standardize RM criteria and explore underreported acephalgic cases.