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Neovascular Glaucoma

Jeffrey R. SooHoo, MD; David Dueker, MD; and Malik Y. Kahook, MD

Neovascular glaucoma (NVG) is a potentially devastating secondary glaucoma that results from the growth of a fibrovascular membrane over the trabecular meshwork (TM) in the anterior chamber angle.

PREDISPOSING CONDITIONS

The changes in the anterior segment that lead to NVG arise in response to a predisposing condition elsewhere—most commonly to a disturbance of the retinal circulation resulting in ischemia. The 3 most common predisposing conditions are diabetic retinopathy, occlusion of the central retinal vein (ischemic type), and ocular ischemic syndrome. Other forms of retinal vascular disease (eg, Eales’ disease, sickle cell retinopathy), intraocular neoplasm, chronic retinal detachment, and severe intraocular infection or inflammation are among numerous other disorders that have also been associated with NVG. Thus, a patient presenting with this disorder may require a rather broad-based diagnostic work-up to determine the underlying cause.^1,2 Any patient with a clinical condition known to predispose an eye to NVG deserves careful monitoring to detect the process in its earliest stages.

The conditions that predispose to NVG show large differences in their tendency to produce the disease. The incidence of NVG after ischemic central retinal vein occlusion (CRVO) is probably best known because both CRVO and NVG usually have clear signs and symptoms, and, when they occur in association, the time interval is short.^3–11 Classically known as 90-day glaucoma, a high percentage of eyes that develop NVG after ischemic CRVO do so within the first 3 to 4 months after the CRVO. The overall risk of NVG after ischemic CRVO is 45%, with approximately 40% occurring in the first 7 months.³

Fluorescein angiography has been advocated as a way to distinguish the 2 forms of CRVO.^7–10 The ischemic form of CRVO shows large areas of retinal capillary nonperfusion, a sign of severe retinal ischemia. When the capillaries are not filled, the retina remains dark (nonfluorescent), except for the major vascular branches. Because the risk of subsequent NVG resides almost entirely with the ischemic type of CRVO, identifying the type of occlusion is very helpful in guiding further management. However, a single angiogram showing well-perfused retinal capillary beds does not ensure against all risk of NVG, because a percentage (approximately 15%) of nonischemic CRVOs later convert to the ischemic form.⁵

Furthermore, definitive angiograms may be unobtainable because of media opacities, widespread retinal hemorrhage, or failure to include peripheral capillary beds. Hayreh recommends a careful assessment of visual function (Table 32-1) as an aid in accurately separating ischemic from nonischemic CRVOs.¹¹

The incidence of NVG in eyes with diabetic retinopathy is not as well defined as in CRVO. In unselected populations of people with diabetes, the incidence of NVG is low. However, in the presence of proliferative retinopathy, the incidence is similar to that found with CRVO and may actually be higher.^12,13

Among patients with one of the predisposing diseases, we do not yet know how to predict precisely which individual will develop neovascularization of the anterior segment. And if neovascularization of the iris or the angle develops, we do not yet know what factors determine which eyes will progress to clinically significant NVG. Finally, in different patients with differing predisposing causes, the progression to full-blown NVG may take weeks, months, or years.

Against this background of multiple different causes and widely varying time course, the only sure method of detecting the earliest signs of anterior segment neovascularization is appropriate vigilance based on knowledge of the potential causes and knowledge of the early clinical signs of anterior segment neovascularization. The reward for this vigilance is the opportunity to intervene at a relatively harmless stage of the process, slowing or even arresting it with appropriate therapy. Most often, the intervention takes the form of retinal ablation, though in certain cases, other forms of therapy are also useful with particular interest in recent years on the promise of antiangiogenic factors. The rationale for retinal ablation and antiangiogenic therapy derives from clinical observation and theoretical models of the disease (Figure 32-1).

NATURAL CLINIC HISTORY OF NEOVASCULAR GLAUCOMA

Although the pathologic conditions predisposing to NVG are numerous and varied, the sequence of anterior segment change is sufficiently uniform to suggest that the various causes of NVG act through a common pathway, though with variable intensities. When a patient has a disorder with known potential to cause NVG, the first sign that new vessel growth in the anterior segment is beginning is leakage of intravenously injected fluorescein dye from vessels at the pupillary margin. This leakage of dye may be conspicuous even when the iris appears completely normal on careful slit-lamp examination at high magnification. This abnormal permeability to fluorescein reflects an alteration of the preexisting vasculature—an opening of the tight junctions normally found between endothelial cells in iris vessels, which is probably a necessary prelude to neovascular proliferation. When vascular proliferation occurs, it is observable by clinical slit-lamp biomicroscopy without fluorescein, though one cannot appreciate by regular slit-lamp examination as much abnormality as is revealed by fluorescein angiography (Figure 32-2).

Vascular proliferation is usually first evident at the pupil. Careful attention to the pupillary margin is therefore of great clinical importance for early detection of neo vascularization. When an abnormality in vessels of the pupillary margin is suspected, gonioscopy should be done to search for vessels in the chamber angle. In a small proportion of patients (especially those with dark irides), there may be significant vascular proliferation in the angle before any change at the pupil is recognized by slit-lamp examination. Therefore, any patient at risk of developing NVG in a useful eye should have not only a careful and repeated high-magnification slit-lamp examination of the iris (with an undilated pupil) but also a periodic inspection of the anterior chamber angle by gonioscopy.

When proliferating vessels are limited to the iris surface, they do not seem to cause clinically significant disturbance in the anterior chamber, even though they show an abnormal permeability to fluorescein during angiography. But when vessels proliferate in the angle, they cause a progressive decrease of outflow facility and eventually severe glaucoma. New vessels growing in the chamber angle develop from the base of the iris as individual trunks that cross the ciliary body and scleral spur in a direct path to the filtration area of the corneoscleral TM. On the meshwork, the individual vessels branch into a complex pattern of fine vessels that eventually involve the entire circumference, intertwining with branches from other trunk vessels.14 This fibrovascular tissue may severely compromise aqueous outflow, with resultant glaucoma, even while the angle remains open.¹⁵ Next, a contractile process begins along one or more of the major vessels that run from the iris base to the TM, producing localized anterior synechiae that tend to spread and ultimately to join, causing complete closure of the angle (Figure 32-3).

The rate at which peripheral synechiae spread to involve the whole circumference is remarkably variable. In some eyes, once the formation of synechiae is started, the angle may become fully closed within a week. In other eyes, the process is much slower, for reasons unknown. The onset of high pressure is often acute and painful, whether or not the angle has been closed by neo vascular tissue or synechiae, and frequently the patient comes for attention as an emergency with a red eye, edematous cornea, and rubeosis of the iris.

DIAGNOSIS

A patient with acute NVG occasionally presents a challenge in diagnosis because the cornea may be so hazy that it obscures a view of details in the anterior chamber. Under such circumstances, the differential diagnosis includes acute angle-closure glaucoma or acute glaucoma secondary to an inflammatory disease. A careful history is frequently helpful in diagnosing the underlying problem. For instance, most patients developing glaucoma after CRVO recall a pain less blurring or loss of vision in the affected eye weeks or months prior to developing pain. Likewise, a patient with diabetes with retinal vasculopathy sufficient to cause NVG is almost sure to be aware that he or she has diabetes. Also, a patient with diabetes frequently, but not always, has a history of reduced vision before development of glaucoma. Careful examination of the patient’s other eye can also provide valuable information, particularly regarding the appearance of the chamber angle, the intraocular pressure (IOP), and the condition of the retina. For example, most patients with acute primary angle closure have a predisposition to the same problem in the opposite eye (especially if the refractive error of both eyes is similar). Therefore, gonioscopy of the opposite eye will usually show a narrow angle. An elevated IOP in the opposite eye, coupled with a normal gonioscopic appearance, will suggest open-angle glaucoma, a common finding in the eye opposite one with NVG after a CRVO. When diabetic retinopathy is the underlying cause for NVG in one eye, the opposite retina will almost always show some evidence of retinopathy as well.

Carotid artery disease may produce NVG (Table 32-2). These patients may demonstrate only peripheral retinal hemorrhages and a relatively low IOP despite advanced angle closure. If carotid artery disease is treated surgically, the IOP may markedly increase due to improved ocular perfusion.

Even a severely edematous cornea in the involved eye can usually be cleared enough with topical glycerin to allow some of the superficial new vessels on the iris and angle to be seen. Occasionally, an acute iritis will cause a rubeotic appearance because the major vessels, and even the capillaries, may dilate markedly, becoming much more visible and imparting a red hue to the iris. But these in flamed vessels, though dilated and tortuous, are still within the iris stroma and still in a predominantly radial pattern consistent with normal iris vasculature. One must differentiate this finding from the rubeosis associated with a true vasoproliferative response that derives from the growth of irregular networks of newly formed vessels on the iris surface. Frequently, a contractile element associated with these new surface vessels causes an ectropion of the posterior iris pigment epithelium; this finding can be a useful clinical clue to the diagnosis.

Having determined that the case is a true NVG, the clinician will then want to ensure that the underlying cause has been correctly identified. This is important because the underlying pathologic condition may require specific treatment (eg, diabetes, systemic hypertension, carotid artery occlusion, retinal detachment; Table 32-3). Diagnostic ultrasound is uniquely helpful in revealing occult malignancy or retinal detachment presenting as NVG and should be considered for all cases in which the cause of anterior neovascularization is unclear or the fundus cannot be seen.

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