Neovascular glaucoma (NVG) results from hypoxic ocular tissues and is commonly associated with retinal vascular diseases such as vein occlusions and diabetic retinopathy. Other, less common causes include ocular ischemic syndrome, chronic retinal detachments, ocular neoplastic processes, and chronic ocular inflammation.1,2 Before treating NVG, it is imperative that, when possible, the ophthalmologist have a firm understanding of the underlying etiology. Incisional glaucoma surgery should be avoided in the setting of an untreated and/or unrecognized ocular tumor.

PATHOPHYSIOLOGY

The underlying pathophysiology of NVG begins with oxygen deprivation, which leads to angiogenesis and neovascularization (NV). The new blood vessels that form are abnormal and grow within the intraocular structures.2,3 Initially, fine vessels can be seen within the iris stroma or at the pupil's margin (neovascularization of the iris [NVI]) or in the anterior segment angle (neovascularization of the angle [NVA]). Evidence of NV of the retina is common but not always present or appreciated. If unrecognized or untreated, the fine vessels will typically become a dense fibrovascular membrane that occludes the trabecular meshwork and leads to the broad formation of peripheral anterior synechiae. NVG occurs once the inherent drainage system of the eye is sufficiently compromised and the IOP increases.2-4

TREATMENT OPTIONS

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Traditionally, NVG has been treated with extensive panretinal photocoagulation (PRP), which causes NVI and NVA to regress over the course of at least several weeks.2,3 PRP destroys ischemic retinal cells, thereby decreasing the stimulus for NV.2,3 Vascular endothelial growth factor (VEGF) has been identified as one of the main ocular angiogenic signals (although others have been found), and it is the target of most clinical interventions.4,5 Although several anti-VEGF medications are currently available, this article focuses on bevacizumab (Avastin; Genentech). This drug is the most common anti-VEGF agent used to treat NVG, and it has been evaluated extensively in studies.4 Although a widespread practice supported by many studies, delivering bevacizumab as an intravitreal injection is an off-label treatment not approved by the FDA.

When treating hypoxic retinal vascular diseases, it is useful to separate patients into two categories, NVG and NV without glaucoma. Several studies have demonstrated that, in patients with NV but not glaucoma, intravitreal bevacizumab (IVB) injections with or without PRP can sufficiently treat NV and cause regression of NVI and NVA (within days to weeks) without damaging the inherent drainage structures of the eye.5,6 Glaucoma surgery is required when NVG cannot be controlled with antiglaucoma medications. Several studies have demonstrated that IVB alone does not sufficiently control NVG.5,7 NV must be controlled as much as possible before incisional glaucoma surgery to minimize intra- and postoperative bleeding and inflammation. Often in the acute setting, inflammation, corneal edema, hyphema, and/or vitreous hemorrhage prevents PRP treatment.

There is currently no consensus in the field as to which incisional glaucoma surgery best treats NVG. Given the challenging nature of this patient population, NVG was an exclusion criterion in the Tube Versus Trabeculectomy (TVT) Study.8 Many glaucomatologists feel that trabeculectomy with mitomycin C (with or without bevacizumab) is the best approach to treating NVG.9,10 Others believe that a glaucoma drainage device best controls the disease.3,6 The topic of which glaucoma drainage device to use is beyond the scope of this article but depends on the patient's preoperative IOP, age, and visual potential as well as the health of the optic nerve. In the setting of uncontrolled NVG with an IOP greater than 30 mm Hg on maximal medical treatment, I prefer to use a valved glaucoma drainage device to control IOP. Extra precautions must be taken, however, to ensure the use of adequate patch graft material over the tube. Moreover, the tube must be placed through at least a 1.5-mm scleral tunnel incision (Figure 1) to minimize the chance of erosion, because this population is at high risk of this challenging complication.11

When an eye does not have reasonable visual potential or the risk of an incisional surgery is too great, a nonincisional glaucoma procedure should be considered. In a blind hypertensive eye, diode laser cyclophotocoagulation has been demonstrated to be highly successful, safe, and low risk.12 Additionally, if the patient has a blind, painful, hypertensive eye, a retrobulbar chlorpromazine injection in addition to cyclophotocoagulation is highly effective at controlling pain in NVG.13

MY TREATMENT PROTOCOL

My general approach to treating uncontrolled NVG despite maximally tolerated glaucoma medication is first to have the patient undergo an IVB injection 1 to 2 weeks prior to glaucoma surgery to allow for regression of NVI and NVA. I then place a valved glaucoma drainage implant, with the tube inserted through a 1.5- to 2-mm scleral tunnel and covered by a partial-thickness corneal patch graft. I purposefully keep the tube long in the anterior chamber, because a blood clot can form around the insertion of the tube and occlude the tip (Figure 2). This typically occurs when extensive peripheral synechiae are encountered when the tube is inserted into the anterior chamber. Once the IOP is controlled, the patient's retinal specialist or primary ophthalmologist uses IVB injections and PRP to minimize the NV stimulus. I personally counsel diabetic patients about the importance of controlling their blood sugar.

Davinder S. Grover, MD, MPH, is an ophthalmologist at Glaucoma Associates of Texas in Dallas. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Grover may be reached at dgrover@glaucomaassociates.com

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