A Case of Sustained Intraocular Pressure Elevation after Multiple Intravitreal Injection of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration

Abstract

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop.

Contamination of Anti-Vegf Drugs for Intravitreal Injection

“…Intravitreal injection of anti-VEGF drugs can lead to an increased long-term IOP. 4,5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20] Several mechanisms to explain this phenomenon including the possibility that protein aggregates and silicone oil microdroplets are responsible for the IOP elevation are discussed. [22][23][24] Protein aggregates can be formed Fig.…”

“…7 Several studies with different number of patients followed reporting prevalence of long-term IOP rise after treatment with ranibizumab, bevacizumab, or aflibercept injections. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] Recent retrospective analysis of the VIEW 1 and 2 data of 2,457 patients showed significant higher IOP elevation in ranibizumab than in aflibercept injected eyes. 21 This study showed for the first time in a high number of patients a statistically significant IOP elevation difference between these two agents.…”

Immediate Rise in Intraocular Pressure After First-Time Intravitreal Injection of Bevacizumab

“…A meta-analysis of 46 articles by De Varies et al reported a mean rise of 23.4 mmHg returning to baseline after one week [20]. On the contrary, multiple other studies have shown IOP returning to safer levels within half an hour after the injection without any intervention [21,22]. These varying results can be because of the different types of patient cohorts used in the studies.…”

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

“…17 Over the years, several other studies have been published with varying numbers of patients reporting the prevalence of longterm IOP increase after treatment with bevacizumab, ranibizumab or aflibercept injections. [17][18][19][20][21][22][23][24][25][26][27][28][29][30] One of the studies with the largest number of patients (retrospective analysis of VIEW 1 and 2 study data from a total of 2457 patients) showed a significantly higher IOP increase in eyes after ranibizumab treatment than in patients after aflibercept treatment. 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.…”