Repeated intravitreal injections of antivascular endothelial growth factor in patients with neovascular age-related macular degeneration may increase the risk of ischemic optic neuropathy

Abstract

BackgroundPrevious case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD).MethodsA population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10–15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma).ResultsIn total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32–2.76) and 2.20 (95% CI, 1.42–3.43), respectively, compared with those in the first-level group.ConclusionsAmong patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.

Risk Factors for Non-arteritic Anterior Ischemic Optic Neuropathy: A Large Scale Meta-Analysis

“…The studies were published between 1991 and 2019. A total of 38 studies were case-control studies ( 10 , 11 , 13 , 19 , 22 – 29 , 31 – 35 , 37 , 39 – 43 , 46 – 60 ) and 11 were retrospective cohort studies ( 9 , 17 , 18 , 20 , 21 , 30 , 36 , 38 , 44 , 45 , 61 ). About 12 of them were studied in the Asian populations, 24 in Europeans, and the remaining 13 in mixed ethnicities.…”

“…In three studies ( 9 , 10 , 58 ) concerning glaucoma, no significant association was found ( OR = 0.74, 95% CI : 0.11–5.00, P = 0.76) with heterogeneity ( I 2 = 90%, P < 0.00001). Microaneurysm/retinal hemorrhage, small optic cup, high intraocular pressure ( 29 ), small cup to disc ratio (CDR) ( 60 ), age-related macular degeneration, retinal vein occlusion ( 9 ), anti-vascular endothelial growth factor injection times ( 17 ), and post-cataract surgery ( 18 ) were all studied in one literature, which is listed in Table 2 .…”

Can intravitreal injections with higher volume cause higher intraocular eye pressure? Considerations for anti-complement injections in normal and glaucomatous eyes

“…Besides some unanticipated drug-related predisposing factor, a reduced ocular blood flow secondary to an increased IOP should be regarded as a plausible cause. In agreement with this hypothesis, Chen et al ( 2019) have shown that a greater number of IVI of antiangiogenic agents leads to increased likelihood of developing ischemic optic neuropathy, and they also attributed it to a higher IOP [17].…”

The Risk of Non-arteritic Ischemic Optic Neuropathy Post-intravitreal Bevacizumab Injection

“…In addition to multiple injections, such a category of patients usually has less controlled diabetes, which further increases the risk of developing NAION. Chen et al reported that patients with age-related macular degeneration who received a higher number of intravitreal anti-VEGF injections were at a higher risk for developing NAION [ 20 ]. Table 3 also shows the onset of NAION in relation to the time of injection.…”