We analysed the 100 top cited articles in ophthalmology to identify and characterise the most influential articles of the past four decades. Two independent investigators searched the database to determine the 100 most frequently cited articles in ophthalmology (T100-Eye) and general non-ophthalmology journals (T100-Gen) published from 1975 to December 2017. The T100-Eye list consisted of 83 original articles and 17 reviews, and the number of citations ranged from 582 to 2833. Seventy-eight of these articles were published in three journals alone (impact factor (IF): 5.05-8.2), led by the The T100-Gen list consisted of 84 original articles and 16 reviews and the number of citations ranged from 358 to 3272. Forty-five of these articles were published in four journals alone (IF: 9.66-72.41). In both lists, majority of the first authors were from the USA (T100-Eye, n=80; T100-Gen, n=66), and were men (n=76 in T100-Eye; n=72 in T100-Gen). With regard to the article type, in the T100-Eye, among the 83 original research articles, most were randomised controlled trials (n=26) or clinical observational studies related to description of a new condition or new management (n=26). In the T100-Gen, of the 84 original research articles, many were clinical observational studies (n=27) or basic science research (n=26). In both lists, the most frequently examined diseases were age-related macular degeneration, diabetic retinopathy and glaucoma. Our analysis reveals landmark articles, trends and medical advancements in ophthalmology over the past four decades. It also highlights gender disparity and influence of the USA in seminal ophthalmic research.