Intravitreal Aflibercept in Japanese Patients with Neovascular Glaucoma: The VEGA Randomized Clinical Trial

Masaru Inatani, Tomomi Higashide, Kenji Matsushita, Atsuya Miki, Mari Ueki, Yuji Iwamoto, Masato Kobayashi, Sergio Leal, VEGA Investigators, Tomomi Higashide, Masaru Inatani, Chie Sotozono, Shigeru Kinoshita, Kenji Matsushita, Mari Ueki, Kanji Takahashi, Toshiaki Kubota, Takashi Koto, Yasuyuki Takai, Shinichiro Teranishi, Katsuyoshi Suzuki, Toru Nakazawa, Tomoyasu Shiraya, Tomohiro Oshiro, Hitoshi Takagi, Daisuke Nagasato, Hideyasu Oh, Masaru Inatani, Tomomi Higashide, Kenji Matsushita, Atsuya Miki, Mari Ueki, Yuji Iwamoto, Masato Kobayashi, Sergio Leal, VEGA Investigators, Tomomi Higashide, Masaru Inatani, Chie Sotozono, Shigeru Kinoshita, Kenji Matsushita, Mari Ueki, Kanji Takahashi, Toshiaki Kubota, Takashi Koto, Yasuyuki Takai, Shinichiro Teranishi, Katsuyoshi Suzuki, Toru Nakazawa, Tomoyasu Shiraya, Tomohiro Oshiro, Hitoshi Takagi, Daisuke Nagasato, Hideyasu Oh

Abstract

Introduction: Neovascular glaucoma is characterized by neovascularization of the iris and the anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may improve intraocular pressure (IOP) and neovascularization.

Methods: The VEGA trial assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma in a 13-week, randomized, double-masked, sham-controlled, phase 3 study performed at multiple sites in Japan that enrolled patients with anterior segment neovascularization and IOP > 25 mmHg. Patients received background therapy plus IVT-AFL (2 mg) or sham injection at baseline. Patients were re-treated if presenting with IOP > 21 mmHg and incomplete regression of iris neovascularization, receiving additional sham or IVT-AFL injections at week 1 and IVT-AFL injections at weeks 5 and/or 9. Double-masking was maintained throughout. The primary endpoint was change in IOP from baseline to week 1.

Results: Fifty-four patients were randomly assigned (full analysis set); the per-protocol set comprised 52 patients. At week 1, the least squares mean change in IOP was -9.9 mmHg for IVT-AFL versus -5.0 mmHg for sham [full analysis set: difference -4.9 mmHg (95% confidence interval -10.2 to 0.3; P = 0.06); per-protocol set: -5.5 mmHg (95% CI -10.8 to -0.2; P = 0.04)]. At week 1, a greater proportion of patients administered IVT-AFL versus sham achieved IOP ≤ 21 mmHg and had improved neovascularization grades. Patients in the sham group who met re-treatment criteria and received IVT-AFL at week 1 [n = 22 (81.5%)] had an additional mean IOP decrease of 9.2 mmHg by week 2, and the proportion with improvement in neovascularization grades increased from 11.5% to 69.2%. Increases in the proportion of patients with improved neovascularization grades and the proportion who achieved IOP control (≤ 21 mmHg) were also observed by week 2 in this group. Overall, 77.8% and 74.1% of patients treated with IVT-AFL and sham/IVT-AFL, respectively, received a single IVT-AFL injection. The most common ocular treatment-emergent adverse event was punctate keratitis (9.3%: 7.4% and 11.1% in the IVT-AFL and sham/IVT-AFL groups, respectively).

Conclusions: IVT-AFL was associated with clinically meaningful improvements in IOP control, indicating that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma.

Trial registration: Clinicaltrials.gov identifier, NCT02396316.

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
Patient flowchart; IVT-AFL intravitreal aflibercept
Fig. 2
Fig. 2
Mean change in IOP from baseline to week 1 (a) and mean IOP from baseline to week 13 (b). aA sensitivity analysis of the primary endpoint was performed on the PPS. bCalculated using ANCOVA model, with treatment group and stage of NVG randomization as fixed effects, with baseline value as covariate; ANCOVA analysis of covariance, FAS full analysis set, IOP intraocular pressure, IVT-AFL intravitreal aflibercept, NVG neovascular glaucoma, PPS per-protocol set
Fig. 3
Fig. 3
Improvements (≥ 1 grade) in NVI (a) and NVA (b) from baseline to week 13 aCalculated using Mantel–Haenszel weights adjusted for stage of NVG for randomization (FAS, LOCF). FAS full analysis set, IVT-AFL intravitreal aflibercept, LOCF last observation carried forward, NVA neovascularization of the angle, NVG neovascular glaucoma, NVI neovascularization of the iris

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