GLAUCOMA OPHTHALMIC PEARLS

Diagnosis and Management of Neovascular Glaucoma

eovascular glaucoma (NVG), with ischemia that may drive neovascu­ a secondary glaucoma that has larization and, potentially, NVG. Nsignificant potential to cause visual loss, is characterized by neovas­ Underlying Conditions cularization of the iris (NVI) and of the Proliferative diabetic retinopathy. angle (NVA) as well as elevated intra­ Poor glycemic control in patients with ocular pressure (IOP). George Coats diabetes may lead to PDR, which may first described the condition in 1906, be associated with neovascularization identifying the presence of NVI in eyes of the anterior segment. Notably, PDR with prior central retinal vein occlusion is the most common cause of bilateral (CRVO). In 1963, the name neovascular NVG.3 glaucoma was proposed by Daniel Weiss The time interval between the onset et al., replacing older terms such as of PDR and the development of NVG thrombotic, congestive, rubeotic, and is difficult to predict, ranging from 1 hemorrhagic glaucoma.1 month to several years. Patients with ADVANCED NVI. This eye of a patient

NVG presents most commonly in elevated HbA1c should have frequent with NVG shows vessels traversing most elderly patients and, in more than 95% ophthalmologic examinations to moni­ of the iris. Also note the iridotomy at of cases, is secondary to conditions that tor for progression of diabetic eye the top. cause retinal ischemia, including pro­ disease. liferative diabetic retinopathy (PDR), Central retinal vein occlusion. may, paradoxically, have either normal CRVO, and carotid artery occlusive dis­ Ischemic CRVO is the second leading or low IOP, confounding the diagnosis ease (CAOD).2 Early identification and cause of NVG. This type of NVG is of NVG. Thus, it is important to look treatment of NVG is critical in order to sometimes called “90-day glaucoma” for other features that suggest CAOD- avoid irreversible vision loss. because it commonly presents around 3 induced NVG, including absence of any months after the initial ischemic event. apparent ocular cause of NVI or stark Pathophysiology Although NVG can take from 2 weeks asymmetry of retinopathy.3 Retinal ischemia acts as a stimulus for to several years to develop after CRVO, Central retinal artery occlusion. proangiogenic growth factors (includ­ the majority of cases develop within the CRAO, an uncommon cause of NVG, ing vascular endothelial growth factor, first 6 months.3 can occasionally lead to neovascular­ or VEGF). The subsequent neovascu­ Carotid artery occlusive disease. ization. In such cases, new vessels are larization begins at the pupillary border CAOD can lead to ocular ischemic syn­ typically seen early; thus, post-CRAO and eventually invades the iridocorneal drome caused by ocular arterial hypo­ NVG was historically referred to as “30- angle, disrupting drainage of aqueous perfusion, with symptoms including day glaucoma.”1 fluid through the trabecular meshwork amaurosis fugax and reduced vision.4 Other uncommon causes. Other and leading to elevated IOP. Because the resulting ciliary body potential causes include retinal detach­ Several ocular and systemic disor­ hypoperfusion leads to decreased aque­ ment, intraocular tumors, and uveitis.5 ders, discussed below, are associated ous humor production, these patients Diagnosis To make an accurate diagnosis of NVG, BY OWEN J. DRINKWATER, BS, BA, AND JOSEPH PANARELLI, MD. EDITED the physician should consider the pa­

Paul A. Sidoti, MD Paul BY SHARON FEKRAT, MD, AND INGRID U. SCOTT, MD, MPH. tient’s symptoms and clinical signs in

EYENET MAGAZINE • 39 conjunction with common risk factors. of the retina reduces the angiogenic outcome with filtering surgery. A high index of suspicion should be stimulus. PRP has been shown to cause In addition, patients with NVG maintained in patients with a history lasting regression of NVI and NVA and often require subsequent surgeries for of systemic or ocular disease that may is used in cases of neovascularization problems such as vitreous hemorrhage result in retinal ischemia, including both with and without further signs of and tractional retinal detachment. poorly controlled diabetes, hyperten­ progression to NVG.6 These later procedures can jeopardize sion, or arteriosclerosis, as well as PDR, PRP can be performed only if there the functioning of the bleb. CRVO, CAOD, and CRAO. is an adequate view of the retina. Finally, because of the intensive Symptoms. Patients may be asymp- Anti-VEGF agents may be valuable in postoperative follow-up required after tomatic early on. When symptoms improving visibility in patients with trabeculectomy, compliance is often an develop, the most common are ocular vitreous hemorrhage, significant media issue for patients who have undergone pain and decreased vision.4 opacities, or poor pupillary dilation. this procedure.5,6 Clinical signs. When evaluating a Anti-VEGF agents. Intravitreal However, trabeculectomy combined patient with possible NVG, a complete injection of anti-VEGF agents, such with anti-VEGF pretreatment and use ophthalmologic examination of both as bevacizumab, ranibizumab, and of adjunctive antimetabolites such as eyes should be performed. The condi­ aflibercept, has been shown to decrease mitomycin C has shown moderate tion of the fellow eye can provide useful angiogenesis. These agents may be success rates. This approach may be information, especially in cases of pro­ used for neovascularization alone or useful for patients with NVG refractory liferative disease due to diabetes. for NVG and have been successful both to PRP and medical management.5 The clinician should examine the as monotherapy and as an adjunct to Drainage implants. Glaucoma drain­ cornea for microcystic edema, the ante­ procedures such as PRP.5 age implants have gained increasing rior chamber for hyphema, and the iris However, if the angle is completely popularity in recent years as a surgical and anterior chamber angle for NVI/ closed with 360 degrees of synechiae, management option for glaucoma.7 NVA. In the vast majority of cases, NVI anti-VEGF therapy may reduce the Types of shunts. Two basic drainage and NVA occur before IOP increases; neovascularization without lowering implant designs—valved (e.g., Ahmed) thus, early recognition and prompt the IOP. and nonvalved (e.g., Baerveldt)—are treatment of neovascularization may Cautions. Anti-VEGF agents should available in a range of sizes. Smaller prevent progression to NVG.3,4 be used with caution in eyes with con­ valved implants may yield better results Abnormal blood vessels. Early on, current and significant neovasculariza­ in NVG patients, allowing early IOP tufted vessels can be visualized at the tion elsewhere (NVE), as rapid invo­ control while minimizing the risk of pupillary margin. Unlike normal iris lution of NVE may lead to tractional hypotony (common in eyes with signif­ vessels, which are distributed radially, retinal detachment. icant ischemia). these pathologic vessels grow in a me­ Moreover, the long-term effects of A valved shunt is functional upon andering pattern. NVA will first appear anti-VEGF treatment in NGV have yet implantation. Cohesive viscoelastic as vessels crossing the scleral spur and to be studied, and definitive treatment can be left in the anterior chamber at trabecular meshwork.1 with laser photocoagulation is still nec­ the end of the case to help tamponade As the disease progresses, NVA essary for most patients with NVG.5 bleeding that occurs during the proce­ becomes more prominent, and the Medical therapy. When IOP is ele­ dure; it also prevents delayed hemor­ fibrovascular membrane that develops vated, various topical agents are used rhage that may result from a sudden will disrupt the functioning of the tra­ to lower the pressure, including beta- drop in IOP. becular meshwork, leading to increased blockers, carbonic anhydrase inhibitors, In contrast, nonvalved shunts are IOP. If left untreated, the membrane alpha-agonists, and prostaglandin not functional for 4 to 6 weeks, until contracts, causing synechial angle clo­ ana­logues. Topical atropine and topical the implant has become encapsulated. sure and permanently compromising corticosteroids are useful for managing During this time, the shunt must either the outflow pathway.1,4 inflammation and pain.4 be tied off with a suture or have the Corneal edema. If corneal edema is Medical therapy often functions as tube lumen occluded. Various methods present in the affected eye, it can limit a bridge to surgical therapy for patients to control the IOP during the early visualization of the anterior chamber who present with significant synechial post­operative phase have been employed structures. In these cases, B-scan angle closure. (fenestrations, orphan trabeculectomy, echography can be performed to look etc.), but most are inconsistent and for vitreous opacities, tractional retinal Surgical Procedures unpredictable. detachment, or intraocular tumor. Trabeculectomy. Although commonly Our choice. Therefore, the authors used for open-angle glaucoma, trab­ prefer placement of valved implants Management Options eculectomy is less effective for NVG. initially for all cases of active NVG. If Panretinal photocoagulation. PRP is Patients with NVG often present with a this does not achieve adequate long- considered the mainstay of treatment “hot eye,” and significant inflammation term IOP control, a nonvalved implant for NVG. Ablation of ischemic areas reduces the likelihood of a successful can be placed in a different quadrant,

40 • APRIL 2018 or cyclophotocoagulation (CPC) can be performed. Cyclodestruction. If the eye has limited visual potential, cyclodestructive laser therapies such as CPC provide another option for IOP management. Either continuous wave or micropulse CPC can be offered; the advantage of micropulse is that the tissue is allowed to cool between the pulses of laser delivery, preventing damage from ther­ mal build-up. Complications of laser cyclodestruction include hypotony and phthisis as well as inflammation caused 6 by the procedure. High-quality Addressing the Causes research from the Because NVG is a secondary glaucoma, it is essential for the patient to receive world’s leading treatment for the underlying cause of ophthalmic journal ischemia. This may involve multidisci­ plinary management with a cardiolo­ gist, vascular surgeon, or primary care physician, depending on the specific etiology.

Complications NVG typically results in severe vision loss and carries a poor prognosis, underscoring the importance of early recognition and prevention. A blind, painful eye can be a common, but un­ fortunate, outcome of refractory NVG. When this occurs, retrobulbar alcohol injection can be administered for pain The Academy’s newest scientific management, but enucleation may be publication, Ophthalmology® necessary to relieve intractable pain.3 Retina, focuses on advances in 1 Shazly TA, Latina MA. Semin Ophthalmol. 2009; medical drug treatment, surgery 24(2):113-121. 2 Sivak-Callcott JA et al. Ophthalmology. 2001; and technology for retina-related 108(10):1767-1776; quiz1777, 1800. disesases and conditions. 3 Havens SJ, Gulati V. Dev Ophthalmol. 2016;55: 196-204. Subscribe at aao.org/store. 4 Rodrigues GB et al. Int J Retina Vitreous. 2016; 2:26. 5 SooHoo JR et al. Semin Ophthalmol. 2013;28(3): 165-172. 6 Olmos LC, Lee RK. Int Ophthalmol Clin. 2011; 51(3):27-36. 7 Vinod K et al. J Glaucoma. 2017;26(8):687-693.

Mr. Drinkwater is a medical student at Weill Cornell Medicine, and Dr. Panarelli is assistant professor of ophthalmology at the New York Eye & Ear Infirmary of Mount Sinai, both in New York, N.Y. Relevant financial disclosures: None.

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