Efficacy of Intravitreal Ranibizumab Combined With Ahmed Glaucoma Valve Implantation for the Treatment of Neovascular Glaucoma

Min Tang; Yang Fu; Ying Wang; Zhi Zheng; Ying Fan; Xiaodong Sun; Xun Xu


BMC Ophthalmol. 2016;16(7) 

In This Article


Patients with early NVG have an open angle and normal or slightly elevated IOP. Aggressive treatment with glaucoma medications and laser therapy can bring the disease under control in some of these patients. However, as the disease progresses, the angle is gradually closed and IOP often continues to rise, leading to a poor response to medications or laser, and surgery is usually required. AGV implantation is an effective method for the treatment of NVG, especially for patients with angle closure; however, NVG is associated with unfavorable outcomes.[2] In this study, success was achieved in 71.4 % of the 22 patients in the control group at six months and 68.4 % at 12 months. Some clinical studies using the same surgical procedure have reached similar results. For instance, Yalvac IS et al.[8] performed AGV implantation alone in 38 patients with NVG and achieved success in 63.2 % of the patients at one year. Shen CC et al.[9] reported a success rate of 70 % and 60 % at one year and two years, respectively. In a retrospective study, Netland PA et al.[2] reported a success rate of 73.1 % at one year, 61.9 % at two years, and only 20.6 % at five years, and considered NVG a high risk factor of AGV implantation failure.

The course of NVG depends on the occurrence and development of new vessels in the iris and the anterior chamber angle. Anti-VEGF factors can inhibit intraocular neovascularization, promote atrophy, and mitigate damage to the blood-ocular barrier as a result of leakage from new vessels. A study shows that ranibizumab can lower IOP and alleviate rubeosis in patients with NVG.[10] Therefore, anti-VEGF factors have been used alone or in combination for the treatment of NVG. However, currently available clinical evidence is inconclusive to establish the effectiveness of such drugs, especially in the medium- and long-term.[11,12] Our study examined the efficacy of AGV implantation with or without a single preoperative injection of 0.5 mg ranibizumab in patients with NVG. After a follow-up period of six months to one year, the results showed that there was no significant difference between the two groups in terms of IOP control, success rate, or anti-glaucoma medications.

Currently available studies on glaucoma treatment have reported the use of anti-VEGF factors under the conjunctiva[13] and in the anterior chamber[7] and vitreous cavity,[14–16] and even reported that topical eye drops containing ranibizumab (2 mg/mL) after filtering surgery can reduce the formation of bleb scarring.[17] However, there are large discrepancies in the conclusions reached by a number of small-scale clinical studies on NVG. Elmekawey H et al.[7] injected 0.5 mg ranibizumab into the anterior chamber in 13 patients once and two patients twice, and performed trabeculectomy at four weeks when the new vessels resolved on the surface of the iris. Success was achieved in 93.3 % of the patients at six months. Lüke J et al.[10] used repeated intravitreal injections of ranibizumab for the treatment of iris neovascularization (2.3 times/year) and neovascular glaucoma (3.6 times/year), in combination with traditional therapies such as laser photocoagulation, cryotherapy, and vitrectomy. This treatment approach improved rubeosis and angle closure and achieved effective control of IOP. However, in a retrospective study, Ma KT et al.[18] analyzed the outcomes of NVG patients who received AGV implantation combined intraoperative vitreous injection of 1.25 mg bevacizumab, and found that its one-year success rate did not differ significantly from AGV implantation alone. As our point of view, the possible reasons for the discrepancies of the above studies may include different usages of anti-VEGF factors (especially single or repeated injections) and baseline differences in patients.

Intravitreal injection of anti-VEGF factors can help reduce macular edema and improve vision in patients with RVO and DR.[19–21] Our data showed that early postoperative BCVA improved from baseline in the two groups, because IOP was brought under control and corneal edema was alleviated in most patients. However, with the extension of the follow-up period, BCVA gradually declined, which may be caused by retinal deterioration and worsened cataracts. In comparison, postoperative BCVA improved more notably and this improvement lasted longer in patients administered with ranibizumab (about three months). The average BCVA in the injection group at three months was higher than that in the control group, which is positive for the quality of life and compliance of patients. Nevertheless, the beneficial effect from ranibizumab disappeared thereafter and BCVA started to move closer between the two groups, with no significant difference in medium- and long-term vision outcomes between the two groups. Collectively, our results suggest that single IVR before surgery can only enhance vision in the early period after surgery.

We observed that ranibizumab alleviated rubeosis in patients and this effect started to appear two to three days after administration as measured by slit lamp examination. However, there was no marked difference in the incidence of postoperative complications between the two groups. Early postoperative complications after AGV implantation surgery for NVG included hyphema, choroidal detachment, vitreous hemorrhage, and obstruction of drainage valves. The occurrence of these complications was associated with a number of factors such as the severity of neovascularization of the iris and the anterior chamber angle, the severity of underlying diseases, the level of baseline IOP, and changes in perioperative IOP (especially during surgery). For this reason, we sought to achieve success in our first attempt when preparing a scleral tunnel to avoid sharp IOP decline as a result of repeated puncture of the anterior chamber. Meanwhile an appropriate amount of viscoelastic was injected into the anterior chamber to bring IOP slightly higher than normal levels. The drainage tube was partially ligated using absorbable suture. These measures contribute to the maintenance of anterior chamber and IOP during surgery and within a short period after surgery. Therefore, no serious complications occurred in early postoperative periods in both groups, which, therefore, rendered the role of ranibizumab less significant. Nakatake S et al.[22] studied a group of NVG patients who had received trabeculectomy and also found that the use of bevacizumab injections had no notable effect on the incidence of preoperative complications such as hyphema and choroidal detachment. However, as ranibizumab was applied for a short time, our study failed to establish a correlation between ranibizumab and medium- and long-term complications after AGV implantation, such as drainage valve exposure or fiber encapsulation.

As a non-randomized study, anti-VEGF treatment was assigned at the discretion of the subjects, and the sample size was relative small, so bias would be inevitable between groups. To some extent, our study demonstrates that single IVR before AGV implantation has no significant effect on the medium- and long-term outcomes of NVG patients. As these drugs act in a very time-dependant manner, it is necessary to carry out repeated injections to control the progression of the disease according to changes in rubeosis, IOP, BCVA or the fundus during follow-up. Further studies are needed to explore how to choose and evaluate clinical indicators used to determine the timing of repeated administration. However, we presume that the use of anti-VEGF factors as needed may signal the direction of single or combined treatment modalities for NVG in the future.