Efficacy and Safety of Intravitreal Aflibercept Injection in Japanese Patients with Neovascular Glaucoma: Outcomes from the VENERA Study

Masaru Inatani, Tomomi Higashide, Kenji Matsushita, Daisuke Nagasato, Hitoshi Takagi, Mari Ueki, Yasuyuki Takai, Ken Miyazaki, Yuji Iwamoto, Masato Kobayashi, Sergio Leal, Masaru Inatani, Tomomi Higashide, Kenji Matsushita, Daisuke Nagasato, Hitoshi Takagi, Mari Ueki, Yasuyuki Takai, Ken Miyazaki, Yuji Iwamoto, Masato Kobayashi, Sergio Leal

Abstract

Introduction: Neovascular glaucoma is characterized by neovascularization of the iris and anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may decrease intraocular pressure (IOP) and improve neovascularization. The VENERA study assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma.

Methods: This was a 5-week, single-arm, nonrandomized, open-label, phase 3 study performed at 7 study sites in Japan that enrolled Japanese patients with anterior segment neovascularization and IOP > 25 mmHg who had not undergone (within 30 days prior), nor were imminently scheduled to undergo (within 8 days following) intraocular surgeries, including panretinal photocoagulation (PRP). Patients received background therapy plus 2 mg IVT-AFL at baseline. Background therapy with systemic IOP-lowering drugs was prohibited for 3 days before day 1 and until IOP evaluation at week 1. The primary endpoint was the change in IOP from baseline to week 1 and the secondary endpoint was the proportion of patients with an improvement of ≥ 1 grade of neovascularization of the angle (NVA) from baseline to week 1.

Results: Sixteen patients received treatment (full analysis set); the per-protocol set comprised 15 patients. The mean IOP decreased from 34.1 mmHg at baseline to 25.8 mmHg at week 1 (mean change, -8.3 mmHg [95% confidence interval; CI -12.2 to -4.4; P = 0.0004]). At week 1, 81.3% of patients had an improvement in the grade of neovascularization of the iris (NVI) and 50.0% of patients had an improvement in NVA grade. The proportion of patients with controlled IOP (≤ 21 mmHg) was 43.8% (95% CI 19.8-70.1) at week 1, and increased to 56.3% at week 2 and 86.7% at week 5. The most common ocular treatment-emergent adverse event was eye pain, which occurred in 4 patients (25.0%).

Conclusions: IVT-AFL was associated with statistically significant and clinically meaningful IOP reductions, without concomitant use of systemic IOP-lowering drugs or PRP. The safety profile was consistent with the known safety profile of IVT-AFL. These findings supplement those from the previous VEGA study, and suggest that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma.

Trial registration: Clinicaltrials.gov identifier NCT03639675.

Keywords: Anti-VEGF; Anti-vascular endothelial growth factor; Intraocular pressure; Intravitreal aflibercept; NVG; Neovascular glaucoma; Neovascularization of the angle; Neovascularization of the iris.

Figures

Fig. 1
Fig. 1
Mean IOP (mmHg) from baseline to week 5 (PPS). *n = 15. The 2-sided 95% CI and P value were estimated using 1-sample t statistics. 3 patients received acetazolamide and 2 patients underwent surgery after evaluation at week 1. IOP intraocular pressure, IVT-AFL intravitreal aflibercept, PPS per-protocol set, SD standard deviation
Fig. 2
Fig. 2
Proportion of patients with IOP ≤ 21 mmHg per visit up to week 5 (PPS). IVT-AFL intravitreal aflibercept, PPS per-protocol set
Fig. 3
Fig. 3
Proportion of patients with improved, maintained, or worsened NVI (a) and NVA (b) grade from baseline to week 1 (PPS). Improved = improvement by ≥ 1 grade from baseline; stable = no change in grade from baseline; worsened = worsened by  ≥ 1 grade from baseline. IVT-AFL intravitreal aflibercept, NVA neovascularization of the angle, PPS per-protocol set

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