stenosis, cranial arteritis, and coronary artery disease.99,100 Carotid artery obstruction accounts for about 75% of these patients, with other risk factors being diabetes mellitus, systemic hypertension, and a history of cerebrovascular accident.101 Doppler imaging of the carotids should be considered if any of the symptoms or signs associated with the ocular ischemic syndrome are manifest. Treatment proposals have included oral verapamil, panretinal photocoagulation, and carotid endarterectomy, although the latter intervention does not always effect a significant clinical improvement.102,103

Central retinal artery occlusion

Other vascular occlusive diseases of the eye may also be associated with neovascular glaucoma. Seven per cent to 15% of patients with

a central retinal artery occlusion will develop neovascular glaucoma.104,105 Some, but not all, have concomitant carotid artery

occlusive disease.106 Again, the preponderance of ischemic and disrupted retina is felt to be causative. Although panretinal photocoagulation may have some effect in reducing the incidence of neovascular glaucoma, it is not as effective as in retinal vein occlusion or diabetes mellitus.107

Miscellaneous

Neovascular glaucoma occurs after a variety of therapeutic interventions, including radiotherapy,108,109 microwave thermoradiotherapy,110 and retinal detachment surgery.111 Neovascular glaucoma occurs after radiation therapy for uveal melanoma between 8.5% and 25% of the time and is dose and time dependent.112 Cataract extraction in eyes that have had radiation is a risk factor for the acceleration of neovascular glaucoma, as it is in eyes with diabetes.113 Clearly, many of the eyes requiring these therapies have underlying diseases producing ischemia of the retina or tumors capable of producing vasoproliferative factors. Intraocular tumors also can be associated with neovascular glaucoma.114

Clinical presentation

Neovascular glaucoma often presents with an acute onset of pain, tearing, redness, and blurred vision. In some cases, depending on the underlying disease, patients report diminished vision for weeks to months before the onset of the pain and redness. When first seen, an affected eye may have ciliary injection, a hazy cornea from epithelial edema, a deep anterior chamber with moderate flare, a hyphema, a small pupil, and new vessels on the iris and in the angle. The first sign of rubeosis iridis is increased permeability of the blood vessels at the pupillary margin as detected by fluorescein angiography or fluorophotometry.115 Clinically the new vessels are first detected as small tufts at the pupillary margin. Occasionally new vessels are seen first in the angle if the tufts near the pupil are obscured by dark iris pigment (Fig. 16–4A).The neovascularization progresses over the iris surface and into the angle. The new ves-

sels extend from the iris root across the ciliary body and scleral spur, where they arborize over the trabecular meshwork117–119 (Fig.

16–4B). At times it may be difficult to distinguish new vessels from normal iris vessels, especially in inflamed eyes. Normal iris vessels have a uniform size and a radial course, and they do not branch within the iris. In contrast, new vessels have an irregular size and an irregular course, and they branch frequently. New vessels also lie on the iris surface rather than in the stroma as normal vessels do.

When the fibrovascular membrane covers a substantial portion of the trabecular meshwork, outflow facility falls and IOP rises.With time, the membrane pulls the peripheral iris up into the angle (Fig. 16–4C). The rate at which this occurs is quite variable, ranging from days to years.

In the late stages of neovascular glaucoma the eye is painful with bullous keratopathy, a sealed angle, and intractable glaucoma. Traction from the fibrovascular membrane lifts the iris anteriorly, gives the stroma a compacted appearance, and produces ectropion

uveae and a fixed, dilated pupil. At this stage, the new vessels may be much less visible, especially those in the angle (Fig. 16–4D).

Treatment

Historically, eyes with neovascular glaucoma had a poor prognosis, and enucleation for chronic pain was a frequent outcome.This dismal picture has changed remarkably over the past several decades, and in many instances neovascular glaucoma can be prevented or treated satisfactorily in terms of patient comfort, although restoration of visual function is uncommon.

Despite recent improvements in therapy, it is always far more effective to prevent neovascular glaucoma than to treat the disease once it is established.We have already mentioned the use of prophylactic panretinal photocoagulation (or retinal cryoablation) to deter neovascular glaucoma following ischemic central retinal vein occlusion. In similar fashion, photocoagulation can prevent neovascular glaucoma in eyes with proliferative diabetic retinopathy or nonproliferative retinopathy and large areas of capillary non-perfusion. Immediate panretinal photocoagulation may also prevent rubeosis iridis from progressing to neovascular glaucoma.

When a patient is seen with an acute episode of neovascular glaucoma, including markedly elevated IOP, the initial treatment consists of maximal IOP-reduction medical therapy, atropine for relief and to maximally dilate the pupil before iris mobility is lost, and corticosteroid. In this situation, miotic agents, prostaglandins, and adrenaline (epinephrine) are usually ineffective in lowering IOP, and may exacerbate pain and conjunctival injection.120 In most cases it is important to proceed rapidly with panretinal

photocoagulation or retinal cryoablation to prevent total angle clo- sure.121–124 Following this treatment, new vessels in the angle begin

to regress within a few days to a few weeks. Depending on the extent of the PAS, the retinal treatment may abort the glaucoma, or leave a stable form of residual angle closure that may be responsive to medical therapy or surgery.125

If extensive PAS are present after retinal ablation, and if IOP is not controlled by medical treatment, the clinician’s choice of therapy is usually based on the visual potential of the eye. If the eye has good visual potential, and if the neovascular membrane has

regressed, filtering surgery can be successful, especially when augmented with antimetabolites.126,127 Wet field cautery or underwater

diathermy to the sclera and iris may be useful to reduce intraoperative bleeding;128,129 but particularly helpful is preoperative intravitreal bevacizimab.36,130 Postoperatively, these eyes are often inflamed and require extensive topical, periocular, and systemic corticosteroid treatment.

Other authorities believe that there is a high failure rate of standard filtering surgery in eyes with neovascular glaucoma, even after the angiogenic stimulus has been reduced or eliminated, and despite antimetabolite agents. Today, many clinicians attempt

to control the glaucoma with some type of posterior glaucoma drainage device.131–137 Glaucoma drainage implants appear to be

successful in controlling pressures and preserving vision in approximately two-thirds of patients with neovascular glaucoma, dramatically reducing the need for enucleation in these otherwise doomed eyes.138 In aphakic eyes it is possible to implant the tube through the pars plana, so long as the anterior vitreal skirt has been removed by pars palna vitrectomy.139

There are a number of therapeutic options for eyes with neovascular glaucoma and poor visual potential. Eyes with limited or no vision can often be made comfortable using cycloplegic agents and topical corticosteroids regardless of the IOP.140 Cyclodestructive

procedures may be appropriate if the patient is too infirm for

of attempting to reduce aqueous production by means of ciliary destruction is a long one.

Cyclocryotherapy often reduces IOP and makes patients

more comfortable after an initial period of pain lasting 1–7 days, but this treatment is less effective in maintaining vision.141–144

Cyclocryotherapy is usually applied at 60°C to 80°C, using a large-tip probe with its anterior edge 2.5 mm posterior to the limbus. Six to eight 60-second freezes are placed over half of the circumference of the ciliary body. Frequent complications of this treatment include iridocyclitis, hypotony, pain, cataract, and phthisis bulbi. If cyclocryotherapy fails to reduce IOP, the treatment can be repeated over the same quadrants of the ciliary body and extended slightly. At least one-quarter of the ciliary body should remain untouched to reduce the incidence of phthisis bulbi. In the past, cyclodiathermy was used for the same purpose as cyclocryotherapy.145,146 Cyclodiathermy was largely abandoned and replaced by cryotherapy, which had a higher rate of success and a lower rate of complications. More recently, cyclocryotherapy itself has been replaced by either trans-scleral laser cyclophotocoagulation or endocyclophotocoagulation.147–154 One can expect approximately 65% success after 1 year in controlling pressures and pain with this modality. The results seem comparable with those achieved with posterior glaucoma drainage device implantation. In our hands, diode laser cyclodestruction with a contact delivery probe is a relatively safe and effective procedure for patients with poor vision or poor visual prognosis and for those for whom a glaucoma drainage device operation may be inadvisable (e.g., previous encircling band, poor physical condition). Retrobulbar alcohol injections and enucleation are appropriate treatments for eyes either with no useful vision or with intractable pain that does not respond to medical therapy and ciliodestructive procedures.

Some have advocated direct laser treatment to new vessels in the angle, a technique referred to as goniophotocoagulation, if neovascularization of the iris is encountered before PAS have formed.155 Low-energy argon laser treatments (0.2 seconds, 50–100  m, 100– 200 mW) are applied to the neovascular tufts as they cross the scleral spur.The laser therapy often must be repeated because these vessels may re-open minutes to days after treatment. Although goniophotocoagulation is inadequate treatment for neovascular glaucoma by itself, it may be a useful adjunct to panretinal photocoagulation in certain situations. For example, goniophotocoagulation can reduce angle neovascularization and synechia formation temporarily while panretinal photocoagulation takes effect and reduces the angiogenic stimulus. Finally, goniophotocoagulation can be applied when full panretinal photocoagulation is not totally successful in reducing the angiogenic stimulus. Its efficacy, however, is perhaps less than that of intravitreal angiogenic inhibitors; both modalities, however, may provide only temporary relief of weeks to months.

In neovascular glaucoma eyes secondary to central retinal vein occlusion, clinicians recommend intravitreal bevacizumab (1.25 mg/0.05 ml) (Avastin) to be administered through the pars plana 24–78 hours preceding surgery, with near total regression of iris neovascularization within 48 hours and some IOP lowering, an effect lasting for some weeks. This rapid regression of new vessels

allows both for panretinal photocoagulation and glaucoma surgery with reduced risk of bleeding.36,130 Similarly focal laser or intraoc-

ular surgery can be enhanced with temporary regression of new vessels by such intervention. When used with combined surgical