PURPOSE: Anti-vascular endothelial growth factor (VEGF) agents have been used for the last 10 years, but their safety profile, including cytotoxicity against various ocular cells such as retinal pigment epithelial (RPE) cells, remains a serious concern. Safety studies of VEGF agents conducted to date have primarily relied on healthy RPE cells. In this study, we assessed the safety of three anti-VEGF agents, namely, ranibizumab, bevacizumab, and aflibercept, on senescent RPE cells. METHODS: Senescent human induced pluripotent stem cell-derived RPE cells were generated by continuous replication and confirmed with senescence biomarkers. The viability, proliferation, protein expression, and phagocytosis of the senescent RPE cells were characterized 3 days after anti-VEGF treatment with clinical doses of ranibizumab, bevacizumab, or aflibercept. RESULTS: Clinical doses of ranibizumab, bevacizumab, or aflibercept did not decrease the viability or alter proliferation of senescent RPE cells. In addition, the anti-VEGF agents did not induce additional senescence, impair the protein expression of zonula occludens-1 and RPE65, or reduce the phagocytosis capacity of senescent RPE cells. CONCLUSIONS: Clinical dosages of ranibizumab, bevacizumab, or aflibercept do not induce significant cytotoxicity in senescent RPE cells.
Aging ; Bevacizumab* ; Biomarkers ; Endothelial Growth Factors ; Epithelial Cells* ; Humans ; Phagocytosis ; Ranibizumab* ; Retinaldehyde* ; Vascular Endothelial Growth Factor A

Purpose: We report three cases of asymptomatic pseudo-optic discs in chorioretinal colobomas highlighted on visual fields patterns.Case summary: (Case 1) A 36-year-old man was found to have a pseudo-optic disc below the optic nerve with a relatively intact neurosensory retina over the lesion. There were no obvious abnormalities on the visual field test, so he underwent no treatment and was followed up every 6 months. (Case 2) A 37-year-old woman diagnosed with glaucoma had abrupt convergence of the neurosensory retinal layers on the boundary of the pseudo-optic disc and a focal retinal nerve fiber layer defect in the inferior sector. An antiglaucoma eyedrop was used to manage the superior hemifield defect, and no significant progression was observed in the structural and functional tests during the 5-year follow-up. (Case 3) A 57-year-old man had a pseudo-optic disc with diffuse retinal nerve fiber layer atrophy in both the superior and inferior sectors. The pseudo-optic disc had protruded into the vitreous cavity. Antiglaucoma eyedrops were used to manage both the superior and inferior hemifield defects, and no significant progression was observed using the structural and functional tests during the 6-year follow-up period. Conclusions Various visual field results may occur with pseudo-optic discs in chorioretinal colobomas depending on the status of residual retinal tissues and underlying glaucoma. Further evaluations and management options should be considered according to the patient’s condition.