Age-Related Macular Degeneration (AMD) is one of the leading causes of visual impairment in individuals over the age of 55 years in developed countries.1 The neovascular form of AMD, with vascular endothelial growth factor (VEGF) as one of the key factors, causes severe and irreversible vision loss, frequently resulting in legal blindness.2,3 In recent years, VEGF inhibition by anti-VEGF antibodies has significantly improved visual outcomes in patients with neovascular AMD. However, in many patients with neovascular AMD anti-VEGF needs to be continuously administered over many years to persistently suppress disease activity and maintain visual function.
The need for long-term treatment with anti-VEGF agents has also become evident in the extension studies, where long-term outcomes 7-8 years after initiation of intensive ranibizumab therapy suggest that many patients require long-term treatment with anti-VEGF agents.4 However, despite the beneficial effect of anti-VEGF therapy, long-term side effects are not clarified yet and are a matter of ongoing controversy. There is evidence that repeated long-term anti-VEGF treatment may accelerate atrophy of different ocular tissues. Retinal pigment epithelium atrophy,5 as well as scleral thinning, has been reported.6 In the last years, several studies have investigated the effect of intravitreal anti-VEGF injections on the peripapillary retinal nerve fiber layer (RNFL). There exists some controversy regarding the effect of anti-VEGF agents on retinal ganglion cells (RGCs). In mice, some reports suggest severe damage to RGCs after local treatment with VEGF binding agents,7 while another report did not find any changes within the retinal ganglion cell layer (RGCL) after VEGF receptor blockade in mice.8 Because most studies have analyzed peripapillary optical coherence tomography (OCT) scans, these reports have focused on RNFL change after antiVEGF treatment. However, several studies focusing on glaucoma patients have shown that RGCL thickness changes may be a more sensitive marker for global and regional visual field sensitivities.9,10
In the present study, we investigated RNFL and RGCL changes in the macular area in eyes receiving long-term intravitreal anti-VEGF treatment for neovascular AMD using spectral-domain optical coherence tomography (Spectralis SDOCT; Heidelberg Engineering, Heidelberg, Germany) and automated segmentation of macular scans.