Neovascular Glaucoma

The anterior chamber angle, formed by the iris root, ciliary body, scleral spur, and trabecular meshwork, is where aqueous humor normally drains. In neovascular glaucoma (NVG), abnormal new blood vessels grow across the iris surface (rubeosis iridis) and into this angle, eventually forming a fibrovascular membrane that can contract and pull the angle closed.

NVG is a severe, vision-threatening secondary glaucoma most commonly arising from ischemic retinal disease, and despite advances in anti-VEGF therapy, it remains associated with high rates of vision loss, ocular morbidity, and surgical failure.¹

NVG originates from retinal ischemia, which elevates intraocular VEGF and other proangiogenic/inflammatory mediators, inducing rubeosis iridis and fibrovascular membrane formation at the angle.¹ In diabetic retinopathy specifically, hyperglycemia-induced capillary occlusion causes retinal hypoxia, stabilizing HIF-1α and upregulating VEGF-A and PlGF, while downregulation of endogenous inhibitors like PEDF may further exacerbate abnormal angiogenesis.² Inflammation followed by TGF-β-driven fibrotic angle closure collectively produces refractory IOP elevation and optic nerve damage — the progression from open, functioning angle to fibrovascular contraction and angle closure defines the disease's clinical staging.²

Early NVG may be asymptomatic, with rubeosis noted incidentally on slit-lamp exam. As angle involvement progresses, patients develop pain, redness, photophobia, and decreased vision; advanced disease can progress to a chronically painful, blind eye. Staging ranges from early rubeosis with normal IOP and open angle, through intermediate angle involvement with rising IOP, to advanced synechial angle closure with markedly elevated, often refractory IOP.¹

Differential diagnosis includes uveitic glaucoma with iris vessel dilation (mimics mild rubeosis but lacks a true neovascular membrane), iridocorneal endothelial syndrome, angle-recession glaucoma from prior trauma, and other causes of acute angle closure — distinguished by the absence of neovascularization.

Diagnosis requires careful slit-lamp examination and gonioscopy to detect early rubeosis and angle neovascularization, supplemented by multimodal imaging: ultrawidefield fluorescein angiography to quantify retinal nonperfusion, and anterior-segment OCT or ultrasound biomicroscopy to delineate fibrovascular membrane extent and angle architecture.¹

Management relies on two parallel goals: rapid suppression of anterior segment neovascularization and definitive treatment of the underlying retinal ischemia.¹ Intravitreal anti-VEGF injections rapidly regress neovascularization and improve surgical conditions but are only temporizing unless combined with panretinal photocoagulation (PRP) or other ischemia-directed therapy.¹ Anti-VEGF monotherapy is limited by its inability to control fibrosis and inflammation, highlighting the need for multifaceted strategies in advanced disease.²

Surgical management with a glaucoma drainage device (generally preferred over trabeculectomy given friable neovascular tissue) is often needed once synechial angle closure has occurred, ideally after anti-VEGF pretreatment to reduce intraoperative bleeding risk. Anti-VEGF therapy carries recognized systemic and ocular adverse effects that should be considered with repeated dosing.³

• Always perform gonioscopy in patients with retinal ischemia risk factors — early rubeosis can be subtle and easily missed
• Anti-VEGF injection is temporizing, not curative — it must be paired with definitive ischemia-directed therapy (typically PRP)
• Glaucoma drainage devices are generally preferred over trabeculectomy in NVG given friable, neovascular tissue
• Common pitfall: treating anti-VEGF injection as a one-time definitive treatment rather than a bridge to PRP
• Common pitfall: missing early rubeosis because gonioscopy was skipped or the exam focused only on the posterior segment