Lipid nanoparticles, as a nucleic acid delivery system, have been used as an alternative to treat ocular diseases, since they can cross the ocular barrier and efficiently transfecting nucleic acids to various cells of the eye. The size influences the transfection of genes, biological distribution, diffusion, and cellular uptake. It is therefore important to establish a relationship between size, formulation, and encapsulation percentage. In this review, we used a search strategy to compare studies of nanomedicine systems aimed at eye diseases where the size of the nanoparticles and the efficiency of encapsulation of genetic material are reported based on the criteria of Preferred Reporting Items for Systematic Reviews (PRISMA ScR 2020 guidelines). Out of the initial 5932, 169 studies met the inclusion criteria and were included to form the basis of the analysis. Nanoparticles reported are composed mainly of PEG-modified lipids, cholesterol, and cationic lipids, that in combination with messenger or interference RNA, allow the formulation of a nanoparticle with an encapsulation efficiency greater than 95%. The diseases treated mainly focus on conditions related to the retina and cornea. Certain characteristics of nanoparticles increase encapsulation efficiency, such as the size of the nanoparticle and the charge of the outer layer of the nanoparticle. It is still unknown what characteristics lipid nanoparticles should have to successfully treat human eye illnesses. The in vitro and in vivo investigations covered in this review, however, present encouraging results. To improve encapsulation effectiveness and disease gene silencing, nanoparticle formulation is essential. The most stable nanoparticles are those made mostly of cationic lipids, PEG lipids, and cholesterol, which also effectively encapsulate RNA. The encapsulation efficiency is not only influenced by size, but also by other factors such as methods of preparation.