Neovascular glaucoma

This common, severe type of secondary angle closure is characterized by anterior segment neovascularization along with a fibrovascular membrane on the surface of the iris, pupillary margin, and trabecular meshwork. It is caused by a variety of disorders that involve retinal or ocular ischemia or ocular inflammation (Table 10-2), most commonly diabetic retinopathy, central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), and ocular ischemic syndrome. Anterior segment neovascularization can also occur with metastatic or other tumors of the eye, such as retinoblastomas, medulloepitheliomas, and choroidal melanomas, as well as following radiation treatment, resulting in neovascular glaucoma.

Table 10-2 Disorders Predisposing to Neovascularization of the Iris and Angle

The pathophysiology of neovascular glaucoma most often involves secretion of angiogenic factors, especially vascular endothelial growth factor (VEGF), from ischemic retinal tissue. These angiogenic factors can diffuse into the anterior chamber and cause iris and angle neovascularization. In rare instances, anterior segment neovascularization may occur without demonstrable retinal ischemia, as in Fuchs uveitis syndrome and other types of uveitis, pseudoexfoliation syndrome, or isolated iris melanomas. When an ocular cause cannot be found, carotid artery occlusive disease should be considered.

Clinically, patients often present with acute IOP elevation together with reduced vision, ocular pain, conjunctival hyperemia, and microcystic corneal edema. In establishing a diagnosis, the clinician should distinguish dilated iris vessels associated with inflammation from neovascularization. Neovascularization of the anterior segment usually develops in a classic pattern, beginning with fine vascular tufts at the pupillary margin. As these vessels grow, they extend radially over the iris (Fig 6-10). Unlike dilated stromal vessels, these vessels are delicate and lacy and do not adhere to the normal anterior segment vasculature. Further, when they involve the angle, they cross the ciliary body face and scleral spur as fine single vessels that branch as they reach the trabecular meshwork (Fig 7-10). Often, the trabecular meshwork takes on a reddish coloration. With contraction of the fibrovascular membrane, PAS develop and coalesce, gradually closing the angle. Although the fibrovascular membrane can cause ectropion uveae, it typically does not grow over healthy corneal endothelium (Figs 10-8, 10-9). Thus, the PAS end at the Schwalbe line, distinguishing this condition from iridocorneal endothelial syndrome, which also features ectropion uveae. When performing gonioscopy in patients with possible neovascularization, the clinician may find it helpful to use a bright slit-lamp beam and high magnification to better visualize the fine vessels.

Figure 10-6 Iris neovascularization usually begins at the pupillary margin. Here there is more extensive iris neovascularization with radial extension along the iris surface.

(Courtesy of Angelo P. Tanna, MD.)

Figure 10-7 Iris neovascularization. With progressive angle involvement, peripheral anterior synechiae (PAS) develop with contraction of the fibrovascular membrane, resulting in secondary neovascular glaucoma.

(Courtesy of H. Dunbar Hoskins, MD. From the Glaucoma Center of San Francisco archives.)

Figure 10-8 With end-stage neovascular glaucoma, total angle closure occurs, obscuring the iris neovascularization. The PAS end at the Schwalbe line because the fibrovascular membrane does not grow over healthy corneal endothelium.

(Courtesy of Wallace L.M. Alward, MD. From the Iowa Glaucoma Curriculum [curriculum.iowaglaucoma.org]. © The University of Iowa.)

Figure 10-9 With vessel growth, iris neovascularization extends from the pupillary margin radially toward the anterior chamber angle.

(Courtesy of Wallace L.M. Alward, MD. From the Iowa Glaucoma Curriculum [curriculum.iowaglaucoma.org]. © The University of Iowa.)

Figure 10-10 Effect of bevacizumab on iris neovascularization. A, Slit-lamp photograph of florid iris neovascularization taken prior to injection of bevacizumab. B, Regression of iris neovascularization 4 days after treatment with bevacizumab.

(Courtesy of Nicholas P. Bell, MD.)

Because the prognosis for neovascular glaucoma is typically poor, prevention and early diagnosis are essential. In CRVO, angle neovascularization develops without iris neovascularization in approximately 4% of patients. Thus, gonioscopy is important for early diagnosis. Since the most common cause of iris neovascularization is ischemic retinopathy, the definitive treatment when the ocular media are clear is panretinal photocoagulation (PRP). However, intravitreal anti-VEGF therapy can be used to acutely reduce the neovascular stimulus. The regression of neovascularization after PRP, anti-VEGF therapy, or both may reduce or normalize IOP, depending on the extent of PAS. Even in the presence of total synechial angle closure, PRP may improve the success rate of subsequent glaucoma surgery by eliminating the angiogenic stimulus and may decrease the risk of hemorrhage at the time of surgery. More recently, anti-VEGF agents have been successfully employed to promote regression of the neovascular tissue prior to filtering surgery (Fig 10-10) and to improve outcomes. Although anti-VEGF treatment can substantially delay surgery, studies have shown that PRP is the most important factor in obviating the need for IOP-lowering surgery for neovascular glaucoma.

Medical management of neovascular glaucoma yields variable success and is sometimes only a temporizing measure until more definitive incisional or laser surgery is undertaken. Topical β-adrenergic antagonists, α2-adrenergic agonists, carbonic anhydrase inhibitors, cycloplegics, and corticosteroids may be useful in reducing IOP and decreasing inflammation, either as a long-term therapy or prior to filtering surgery. Incisional glaucoma surgery is more likely to be successful if performed after the neovascularization has regressed following PRP or anti-VEGF therapy. In many cases, tube shunt surgery, usually with a valved device, is the surgical procedure of choice. If these therapies fail or if the eye has poor visual potential, either endoscopic or transscleral cyclophotocoagulation can be considered as an alternative. See Chapter 13 for discussion of these procedures.

• Havens SJ, Gulati V. Neovascular glaucoma. Dev Ophthalmol. 2016;55:196–204.

Iridocorneal endothelial syndrome

Iridocorneal endothelial (ICE) syndrome is a group of disorders characterized by abnormal corneal endothelial cells that behave like epithelial cells in that they proliferate, migrate, and fail to exhibit contact inhibition. These abnormal endothelial cells cause variable degrees of iris atrophy, secondary angle closure, and corneal edema. (See also BCSC Section 8, External Disease and Cornea.) Three clinical variants have been described:

• Chandler syndrome

• essential (progressive) iris atrophy

• Cogan-Reese syndrome (sometimes called iris nevus syndrome)

Chandler syndrome is the most common type, accounting for approximately 50% of the cases of ICE syndrome.

ICE syndrome is clinically unilateral, occurs more often in women, and most commonly presents between 20 and 50 years of age. No consistent association has been found with other ocular or systemic diseases, and familial cases are very rare. A viral etiology has been postulated for ICE syndrome after lymphocytes were observed on the corneal endothelium of affected individuals. Patients typically present with elevated IOP, decreased vision due to corneal edema, secondary chronic angle-closure glaucoma, or an abnormal iris appearance. In each of the 3 clinical variants, the abnormal corneal endothelium takes on a “beaten bronze” appearance similar to cornea guttata, as seen in Fuchs corneal endothelial dystrophy. Microcystic corneal edema may be present without elevated IOP, especially in Chandler syndrome. The unaffected eye may have subclinical irregularities of the corneal endothelium detectable with confocal or specular microscopy without other manifestations of the disease.

High PAS are characteristic of ICE syndrome (Fig 11-10), and they often extend anterior to the Schwalbe line. The extent of angle closure does not always correlate with the IOP because some angles may be functionally closed by the endothelial membrane without overt PAS formation.

Various degrees of iris atrophy and corneal changes distinguish the specific clinical entities. The essential iris atrophy variant of ICE syndrome is characterized by severe progressive iris atrophy resulting in heterochromia, corectopia, ectropion uveae, iris stromal and pigment epithelial atrophy, and hole formation (Fig 12-10). In Chandler syndrome, minimal iris atrophy and corectopia occur, and the corneal and angle findings predominate (Fig 13-10). Iris atrophy also tends to be less severe in Cogan-Reese syndrome, a condition distinguished by tan pedunculated nodules or diffuse pigmented lesions on the anterior iris surface.

Glaucoma develops in approximately 50% of patients with ICE syndrome and may be more severe in those with essential iris atrophy or Cogan-Reese syndrome. In ICE, the corneal endothelium migrates posterior to the Schwalbe line, onto the trabecular meshwork and iris. Electron microscopy has shown the endothelium to vary in thickness, with areas of single and multiple endothelial cell layers and surrounding collagenous and fibrillar tissue. Unlike normal corneal endothelium, filopodial processes and cytoplasmic actin filaments are present, allowing cellular motility. PAS are formed when this migratory endothelium and its surrounding collagenous fibrillar tissue contract.

Figure 10-11 The classic high PAS of iridocorneal endothelial syndrome. These PAS extend anterior to the Schwalbe line in this patient with essential iris atrophy.

(Courtesy of Steven T. Simmons, MD.)

Figure 10-12 Clinical photograph showing corectopia and hole formation, typical findings in essential iris atrophy.

(Courtesy of Steven T. Simmons, MD.)

Figure 10-13 Clinical photograph showing ectropion uveae in a patient with Chandler syndrome.

(Courtesy of Steven T. Simmons, MD.)

The diagnosis of ICE syndrome must always be considered in young to middle-aged patients who present with unilateral secondary angle closure. It is particularly important to maintain a high index of suspicion for this condition because it can mimic primary open-angle glaucoma when the iris and corneal features are subtle. Specular microscopy can confirm the diagnosis by demonstrating an asymmetric loss of endothelial cells and atypical endothelial cell morphology in the involved eye.

Therapy is directed toward the corneal edema and IOP reduction. Hypertonic saline solution and medications to reduce the IOP, when elevated, can be effective in controlling the corneal edema. IOP can be lowered with aqueous suppressants and prostaglandin analogues. Miotics are often ineffective. When medical therapy fails, trabeculectomy or tube shunt surgery can be effective. Late failures have been reported with trabeculectomy secondary to endothelialization of the fistula. The fistula can be reopened with the Nd:YAG laser in some cases. Laser trabeculoplasty has no therapeutic role in ICE syndrome.

Epithelial and fibrous ingrowth

Epithelial and fibrous proliferations are rare surgical complications that can cause severe secondary glaucoma. Epithelial and fibrous ingrowth occurs when epithelium, fibroblasts, or both invade the anterior chamber through a defect in a wound site. Fortunately, improved surgical and wound closure techniques have greatly reduced the incidence of these entities. Although both types are potential causes of corneal graft failure, fibrous ingrowth is more common than epithelial ingrowth. Risk factors for developing ingrowth include prolonged inflammation, wound dehiscence, delayed wound closure, and a Descemet membrane tear. Epithelial ingrowth has also been reported following Descemet-stripping automated endothelial keratoplasty.

Epithelial ingrowth presents as a grayish, sheetlike membrane on the trabecular meshwork, iris, ciliary body, and posterior surface of the cornea. It is often associated with vitreous incarceration, wound gape, ocular inflammation, hypotony secondary to choroidal effusions, and corneal edema (Figs 10-14, 10-15). The ingrowth consists of nonkeratinized stratified squamous epithelium with an avascular subepithelial connective tissue layer.

Application of green laser produces characteristic white burns on the epithelial membrane on the iris surface and can help to confirm the diagnosis of epithelial ingrowth and to determine the extent of involvement. If the diagnosis remains in question, cytologic examination of an aqueous humor aspirate can be performed. Cryotherapy is an option for the treatment of epithelial ingrowth. Radical surgery is sometimes necessary to remove the intraocular epithelial membrane and affected tissues and to repair the fistula, but the prognosis remains poor. Thus, the decision to intervene is based on the extent of disease, the visual potential, the status of the fellow eye, and sociomedical circumstances relevant to the affected individual.

Fibrovascular tissue may also proliferate into an eye from a penetrating wound. Unlike epithelial proliferation, fibrous ingrowth progresses slowly and is often self-limited. Fibrous ingrowth appears as a thick, gray-white, vascular retrocorneal membrane with an irregular border. The ingrowth often involves the angle, resulting in PAS formation with destruction of the trabecular meshwork (Fig 16-10) and ectropion uveae.

Figure 10-14 Epithelial ingrowth appears as a grayish, sheetlike growth on the endothelial surface of the cornea, usually originating from a surgical incision or traumatic wound. The epithelial ingrowth shown here originated from a glaucoma surgery incision, causing peripheral anterior synechiae.

(Courtesy of Robert Ritch, MD.)

Figure 10-15 Epithelial ingrowth. The precipitating causes of epithelial ingrowth include vitreous incarceration in corneal and scleral wounds, as seen in this photograph, as well as wound gape, ocular inflammation, and hypotony secondary to choroidal effusions.

(Courtesy of Steven T. Simmons, MD.)

Figure 10-16 Fibrous ingrowth appears as a thick, grayish, retrocorneal membrane that results in high PAS and obstruction of the trabecular meshwork.

(Courtesy of Steven T. Simmons, MD.)

Trauma

Angle closure without pupillary block may develop after trauma, as a result of PAS formation associated with angle recession or from contusion, hyphema, and inflammation. See Chapter 8 for discussion of trauma.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.