Education Committee Highlights WGC-2021 | part 5.1

Update on Neovascular Glaucoma

Anti-VEGF and Photocoagulation
Dr. Leopold Magacho explained that proliferative retinopathy, central vein occlusion, ocular ischemic syndrome, retinal artery occlusion, and carotid arterial obstruction are the most common causes of neovascular glaucoma. Retinal ischemia leads to increased vascular endothelial growth factor (VEGF), a key molecule in ocular neovascularization (NV).

He emphasized the importance of considering paretinal coagulation in all cases of neovascular glaucoma (NVG) in which VEGF levels are reduced indirectly. If PRP cannot be performed because of media opacity, pars plana vitrectomy and PRP can be used in combination. In diabetic retinopathy cases, additional PRP sessions may be needed as new vessels may continue to grow, and their regression can take weeks after PRP is completed.

He presented the various anti-VEGF agents used in NVG therapy. He stated that in situations of high-risk diabetic retinopathy, intravitreal bevacizumab injection resulted in a high percentage of disease regression. Intracameral administration of Anti-VEGF was effective in reducing anterior chamber NV and the IOP-lowering effect can be seen 1 week after the injection but is limited to approximately 3 weeks. Frequent gonioscopy is considered important in the follow-up as some patients may have recurrent angle neovascularization. Potential retinal complications, such as macular edema or retinal NV are not directly addressed with intracameral administration.

He finished by suggesting that rapid diagnosis and treatment with anti-VEGF and PRP are crucial to avoid or delay glaucoma surgery in NVG patients. Even after therapy, NV may recur; therefore, it is crucial to continuously follow the patient.

I prefer cyclo-photocoagulation (CPC)
Dr. Alfonso Anton López introduced the cyclophotocoagulation (CPC) delivery methods: Trans-scleral, endoscopic and transpupillary. He explained that CPC shows similar IOP lowering effect than drainage devices, as they are simple, provide short surgical time with no wound, no sutures, and maybe repeated if needed. However, the procedure is not preferred by most surgeons because of lack of evidence-based data and complications. According to the 2017 Preferred Practice Patterns for glaucoma surgery (AGS), CPC is the least applied method for neovascular glaucoma. In literature, there is very limited solid data with few controlled prospective clinical trials. The most commonly reported adverse events across studies were hypotony, phthisis bulbi, prolonged inflammation, and vision loss. He underlined that large well-designed randomized studies are needed.

Subsequently, he discussed the advantages and disadvantages of the procedure. The short and simple nature of the treatment, the absence of a wound, the ease of postoperative management, and the avoidance of drainage device-related complications (exposure, blockage, diplopia, etc.) are its benefits. The inability to see target tissues restricts the predictability of the transscleral diode laser. As a result, it carries the risk of sight-threatening complications.

Dr. López prefers CPC based on AAO and EGS recommendations, particularly in patients with low vision or in cases where drainage devices are likely to fail, have failed, or are not feasible, in patients with no visual potential and need pain relief, or if the patient’s general medical condition precludes invasive surgery, and if the patient refuses more aggressive surgery.

Dr. López concluded that there is a need for randomized controlled studies to better assess the role of CPC in neovascular glaucoma.

I prefer trabeculectomy
Dr. Ahmet Akman begins by discussing the pre-anti-VEGF era in NVG patients, and how trabeculectomy outcomes were poor even with antimetabolite use. Most surgeons preferred tube shunts, and cyclo-destruction was an option if the visual prognosis was poor. In the current anti-VEGF era, anti-VEGF injections combined with PRP may prevent glaucoma surgery and improve trabeculectomy and tube shunt success rates.

Dr. Akman outlined the stages of wound healing after trabeculectomy, and VEGF is a key mediator in the acute phase. VEGF increases in the early stages after trabeculectomy and promotes fibroblast migration, proliferation, and collagen production. It also directly stimulates vascular endothelial cells and fibroblasts, resulting in enhanced bleb vascularity and scar formation. VEGF is a cause of bleb failure in all glaucoma eyes, although it is a more serious issue in NVG.

He added that anti-VEGF injections when combined with anti-fibrotics increase success rates, albeit re-injections may be required. Unlike in other types of glaucoma, anti-VEGF injections may be useful in NVG since VEGF is the primary cause of neovascularization, fibrosis, and bleb failure. Trabeculectomy became a feasible alternative to tube shunt surgery for NVG patients after anti-VEGF injections became available.

Dr. Akman listed anti-VEGF agents and injection protocols such as intravitreal anti-VEGF injection 15 days before trabeculectomy, as well as intracameral, subconjunctival, and topical routes as alternatives. He discussed his NVG treatment strategy, which he described as intravitreal anti-VEGF injection initially, followed by complete PRP if possible. If PRP is not applicable, he recommends cataract surgery and/or pars plana vitrectomy with PRP, followed by trabeculectomy with MMC and subsequent anti-VEGF therapy if neovascularization persists. Tight post-operative follow-up is essential, and if the bleb fails, tube shunts and CPC are viable options.

He believes that trabeculectomy is preferable in NVG since anti-VEGF injections increased success rates equivalent to tube shunts and visual prognosis is better than cyclodestructive treatments.

I prefer drainage devices
Dr. Lineu Shiroma emphasized that managing NVG includes controlling the underlying ischemic process as well as lowering IOP. PRP and intravitreal anti-VEGF injection decrease the ischemic drive which leads to the development of new blood vessels, while medical therapy and surgery lower IOP.

He described that glaucoma drainage devices (GDD) have different specificities, ranging from different plate sizes, materials, and valved and non-valved mechanisms. Tube shunts have shown good efficacy in reducing NVG in studies comparing GDDs, trabeculectomy, and CPC. GDD implants may be advised as a major surgical procedure in NVG treatment strategy, particularly in eyes with significant inflammation. He recommends that trabeculectomy be avoided in younger patients, those who have had a previous vitrectomy, and those who have a fellow eye with NVG due to diabetic retinopathy, as the likelihood of failure is significant in these people. He also did not advocate CPC in eyes that have had vitreoretinal surgery, have extensive inflammation, or have good visual potential due to the risk of hypotony and phthisis.

In summary, the reduction of the ischemic stimulus is critical for long-term control of the disease. Anti-VEGF intravitreal injections provide a useful adjunct for the treatment of NVG when given prior to surgery that helps to reduce the risk of hemorrhage. Although trabeculectomy with antimetabolites, GDDs, or CPC are options for the surgical management of NVG, there is currently no superior surgical approach. According to Dr. Shiroma, if there is active neovascularization, trabeculectomy should be avoided and a GDD should be considered.

Prevention and management of complications
Dr. Xiulan Zhang explained that the etiology of NVG includes more than 40 causes, the most common of which are diabetic retinopathy, retinal vein occlusion, central retinal artery occlusion, and ocular ischemia syndrome. She classified progressive NGV into three stages: stage 1 (iris or angle rubeosis with normal IOP), stage 2 (open-angle with trabecular meshwork damage and high IOP), and stage 3 (closed-angle with markedly elevated IOP).

She highlighted the significance of the proper approach to NVG prevention and management. According to Dr. Zhang, if IOP decreases after treatment of retinal ischemia with PRP and anti-VEGF therapy (stage 2), antiglaucoma management should involve medical treatment as well as trabeculectomy with MMC. If IOP remains high (stage 3), tube shunt surgery should be considered. She noted that trabeculectomy has the lowest success rate in NVG eyes and that the efficacy diminishes with time. She discussed two studies showing a better success rate in tube implantation, and she believes that tubes should be the first option for NVG.

To improve surgical success, she discussed how to treat conjunctiva in trabeculectomy, how to apply MMC, how to prevent shallow anterior chamber in tube surgery, how to insert the tube correctly and precisely, and how to prevent exposure of the drainage tube.

She believes that the treatment of the underlying causes for the development of NVG is essential. Following glaucoma surgery, continuous PRP or anti-VEGF injections are critical. Otherwise, the recurrence of neovascularization will further damage the trabecular meshwork and lead to IOP elevation. Complications of neovascular proliferation will take place, including neovascular membrane traction, anterior chamber shallowing, and obstruction of the filtering pathway or drainage tube.

Dr. Zhang concluded that NVG is a refractory and challenging disease, and saving the visual potential is the ultimate goal. Every step in the treatment is crucial for increasing the success rate and reducing complications.

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