The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma

Abstract

Purpose: To assess the effect of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents on immediate and long-term intraocular pressure (IOP) elevation and glaucoma.Methods: Literature searches of the PubMed and Cochrane databases, last conducted in April 2018, yielded 253 unique citations. Of these, 41 met the inclusion criteria and were rated according to the strength of evidence. Two articles were rated level I, 17 were rated level II, and 15 were rated level III; an additional 7 were excluded because of poor study design and lack of relevance to the topic under evaluation.Results: The studies that reported on short-term IOP elevation (i.e., between 0 and 60 minutes) showed that an immediate increase in IOP is seen in all patients when measured between 0 and 30 minutes of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; 7 studies reported that between 4% and 15% of patients developed sustained elevation of IOP at 9 to 24 months after injection, whereas 6 studies found no long-term change in IOP from 1 to 36 months after injection. Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection. Data were mixed on the relationship between IOP increase and the type of intravitreal injection, number of intravitreal injections, preexisting glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment.Conclusions: Intravitreal injection of anti-VEGF agents results in an immediate and transient increase in IOP. A long-term increase in IOP also may be seen, and further studies are needed to determine at-risk populations. Although there is some suggestion in the literature, there is currently insufficient data to determine the impact of intravitreal anti-VEGF injections on glaucoma progression. Although pretreatment with glaucoma medications, performing anterior chamber paracentesis, or increasing the interval between injections may reduce the impact of transient IOP elevation, the clinical significance and associated risks of these interventions are unknown.

Sustained Intraocular Pressure Rise after the Treat and Extend Regimen at 3 Years: Aflibercept versus Ranibizumab

“…AMD was a risk factor for IOP rise independent of number of injections in our study. Also, the potential role of vein occlusions in IOP rise has been suggested in past analyses [1,2].…”

“…Sustained IOP rise with aflibercept and ranibizumab use for AMD has been documented and studied [15]; studies have thrown up conflicting reports as regards the risk factors studied for IOP rise. Indeed, some studies do not report of any sustained IOP rise following anti-VEGF injections [1,2,6,8]. e most oft studied and documented risk factors are the number of injections and the treatment interval, followed by lens status, presence of vein occlusion [2], preexisting glaucomatous disease, and angle chamber depth.…”

“…Sustained intraocular pressure rise following intravitreal anti-VEGF injections is a known phenomenon, with several publications addressing this issue in part or whole [1][2][3][4][5].…”

“…ere is a certain measure of discrepancy in reporting insofar as the potential risk factors as well as definitions of intraocular pressure (IOP) rise are concerned [6][7][8]. With numerous publications on the subject, it is only natural that contrasting outcomes are noted in studies conducted across the globe [1][2][3][4][5][6][7][8], the most disputed amongst risk factors for IOP rise being the number of injections administered and the treatment interval [2] between consecutive injections. When one factor in the indication, the anti-VEGF agent used, the phakic status, the anterior chamber angle status, family history of glaucoma, and other characteristics [1,2], it is evident that the condition (IOP rise) and analysis thereof is a complex phenomenon.…”

“…Despite a plethora of literature on the subject, a recently published review [1] highlights the lack of readily identifiable risk factors for IOP rise following intravitreal injections. Additionally, a literature search on PubMed, Scopus, and the Cochrane Database on 11 th May 2019 using the key words "anti-VEGF agents, diabetic macular edema, retinal vein occlusion, age-related macular degeneration, choroidal neovascular membrane, intraocular pressure rise, ocular hypertension, ethnicity, anti-VEGF drug volume, shortterm intraocular pressure rise, treat and extend regimen, aflibercept, ranibizumab, bevacizumab, dexamethasone implant, therapy switch, glaucoma progression, RNFL thickness, visual fields and optic disc changes" revealed a paucity of data on a comprehensive overview and hazard analysis of risk factors and IOP rise, especially between ranibizumab and aflibercept.…”