Anti-vascular endothelial growth factor (VEGF) drugs are widely used in modern ophthalmology, especially in treating macular disorders like age-related macular degeneration or diabetic macular edema. Protocols for such treatments include repeated administration of intravitreal injections, with the volume of drug injected into the vitreous chamber seemingly high enough to cause an increase in intraocular pressure. Hence, questions might arise if such therapeutic approaches are safe for ocular tissue. Moreover, anti-VEGF compounds may theoretically harm the retinal nerve fibers due to the inhibition of VEGF and its neuroprotective effects. Thus, this manuscript aims to review the literature regarding studies evaluating the retinal nerve fiber layer (RNFL) in eyes receiving anti-VEGF treatment due to age-related macular degeneration. The RNFL was chosen as a subject of this review, as it is the innermost retinal layer exposed to the direct action of intravitreally administered drugs. The results of the available studies remain inconclusive. Most researchers seem to confirm the safety of the anti-VEGF treatment in wet age-related macular degeneration, at least regarding the retinal nerve fiber layer. However, some authors noticed that the influence of anti-VEGFs on RNFL could become apparent after more than thirty injections. Nonetheless, the authors of all studies agree that further, long-term observations are needed to help clinicians understand the effect of anti-VEGF treatment on the dynamics of changes in the thickness of retinal nerve fibers in patients with the wet form of age-related macular degeneration.