Sustained Elevation of Intraocular Pressure Associated with Intravitreal Administration of Anti-vascular Endothelial Growth Factor: A Systematic Review and Meta-Analysis

Abstract

This study aimed to assess whether repetitive intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) cause sustained elevation of intraocular pressure (SE-IOP). We conducted a systematic review and meta-analysis based on five randomized controlled trials (RCTs) assessing 1428 subjects and 17 non-RCTs evaluating 8358 cases. In the RCTs, an increased risk of SE-IOP was found in the anti-VEGF group (summary risk ratio [RR] = 3.00, 95% confidence interval [CI]: 1.63–5.53) compared with the sham injection or laser group. The increased risk of SE-IOP was correlated with follow-up duration (RR = 2.14, 95% CI 0.69–6.57 at 6 months; RR = 3.15, 95% CI 0.99–10.09 at 12 months; RR = 3.48, 95% CI 1.38–8.78 at 23 months). The risk of SE-IOP after non-exclusion of pre-existing glaucoma patients (RR = 3.48, 95% CI 1.38–8.78) was higher than that obtained after excluding pre-existing glaucoma patients (RR = 2.6, 95% CI 1.16–5.81). In non-RCTs, the pooled prevalence of SE-IOP was 4.7% (95% CI 3.7–5.8) regardless of diagnosis criteria. In conclusion, repeated intravitreal injections of anti-VEGF agents cause a 2-fold elevation in SE-IOP risk.

<p>Issues with Intravitreal Administration of Anti-VEGF Drugs</p>

“…31 In 2016 Zhou et al conducted a meta-analysis of 5 randomized controlled trials (RCT) in 1428 patients and 8358 patients from 17 non-RCTs. 32 The risk of a sustained increase in IOP after not excluding existing glaucoma patients was higher than the risk after excluding existing glaucoma patients. In non-RCTs, the pooled prevalence of elevated IOP was 4.7% regardless of the diagnostic criteria.…”

“…In conclusion, Zhou calculated a 2-fold risk of developing elevated IOP after repeated intravitreal injections of anti-VEGF agents. 32 Unfortunately, all published studies that evaluated IOP elevations after anti-VEGF injections have been retrospectively evaluated and are therefore of limited value.…”

Stellungnahme der DOG, der RG und des BVA zur Therapie des diabetischen Makulaödems

“…Die kumulative Wahrscheinlichkeit einer Druckerhöhung war auch unter der Behandlung mit Ranibizumab in einem 3-Jahres-Zeitraum auf 9,5 % gegenüber 2,9 % in der Lasergruppe leicht erhöht [173]. Auch wenn es weniger Daten zu Patienten mit diabetischem Makulaödem [174] im Vergleich zu Analysen von AMD-Patienten [171,172,175] gibt, wurde eine Risikoerhöhung für einen Druckanstieg gegenüber dem nicht behandelten Partnerauge beobachtet [176].…”

“…An morphologischen Kriterien der Funduskopie und v. a. der OCT kann die Therapie präziser und praktikabel festgelegt werden. Eine Stabilität unter Reduktion der Therapiefrequenz konnte außerdem alternativ in Studien auch mit 2-monatlicher Wiederbehandlung nach einer initialen monatlichen Upload-Phase erreicht werden; bei einem relevanten Patientenanteil kann jedes fixe Schema mit Über-und Untertherapie verbunden sein [200,274] Kontrollen des Augendrucks sollen nach der Gabe von VEGF-Inhibitoren und wegen der Gefahr eines Sekundärglaukoms auch in längeren Phasen ohne intravitreale Therapie erfolgen [174,176]. Nach der Gabe von Steroiden sind zusätzliche Druckkontrollen ca.…”

P53/DRAM/ autophagy - a new target for improving the therapeutic effect of anti-VEGF on intraocular neovascularization

“…At present, the main treatment is anti-vascular endothelial growth factor (anti-VEGF) in the treatment of intraocular neovascularization. Although anti-VEGF therapy has achieved good therapeutic effect, the recurrence of neovascularization is inevitable which increases the cost of treatment and adverse drug reactions, and also increase the incidence of complications such as endophthalmitis, lens damage, elevated intraocular pressure [4,5]. Therefore, How to control the formation of intraocular neovascularization more effectively and reduce the recurrence of intraocular neovascularization is particularly important.…”