Ординатура / Офтальмология / Английские материалы / Shields Textbook of Glaucoma, 6th edition_Allingham, Damji, Freedman_2010

Figure 19.1 Clinicopathologic stages of neovascular glaucoma. A: Preglaucoma stage (i.e., rubeosis iridis), characterized by new vessels on the surface of the iris (a) and in the anterior chamber angle (b). B: Open-angle glaucoma stage, characterized by an increase in neovascularization and a fibrovascular membrane on the iris (c) and in the anterior chamber angle (d). C: Angle-closure glaucoma stage, characterized by contracture of the fibrovascular membrane, causing corectopia, ectropion uvea (e), flattening of the iris (f), and peripheral anterior synechiae (g).

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Figure 19.2 A: Slitlamp view of a diabetic patient with neovascular glaucoma. Neovascularization of the iris is seen through the edematous cornea that is secondary to uncontrolled IOP. B: Fluorescein angiographic view of another patient demonstrates fluorescein leakage along the superior papillary margin. In subsequent frames, the area of fluorescein leakage enlarges. (From Reiss GR, Sipperley JO. Glaucoma associated with retinal disorders and retinal surgery. In: Tasman W, Jaeger EA, eds. Duane's Clinical Ophthalmology. Vol. 3. Philadelphia, PA: Lippincott Williams & Wilkins:chap 54E.)

Despite evidence of good perfusion and a low risk for iris neovascularization by any of the noted techniques, all patients with central retinal vein occlusion should be followed for the possibility of rubeosis iridis and neovascular glaucoma. In some patients, perfused retinas will progress to nonperfusion. In one study, this was seen in 15% of cases (57). Time and age appear to influence this percentage. In one study, the cumulative probability of converting from nonischemic to ischemic central retinal vein occlusion in 6 and 18 months was 13.2% and 18.6%, respectively, in persons 65 years or older and 6.7% and 8.1%, respectively, in persons 45 to 64 years of age (21). The study also found that 83% of patients with indeterminate perfusion eventually developed nonperfusion or neovascularization of the iris or anterior chamber angle (58).

Preglaucoma Stage: Rubeosis Iridis Clinical Features

The preglaucoma stage is characterized by a normal IOP, unless preexisting chronic open-angle glaucoma (COAG) is present. Slitlamp biomicroscopy early in the disease process typically reveals dilated tufts of preexisting capillaries and fine, randomly oriented vessels on the surface of the iris near the pupillary margin (Fig. 19.3). The new vessels are also characterized by leakage of fluorescein. Neovascularization in most cases is first seen on the peripupillary iris, although it may be first seen in the anterior chamber angle in patients with diabetes and central retinal vein occlusion (45, 59). Gonioscopy therefore may reveal a normal anterior chamber angle or may show a variable amount of angle neovascularization. The latter is characterized by single vascular trunks crossing the ciliary body band and scleral spur and arborizing on the trabecular meshwork.

Figure 19.3 Slitlamp view of iris in a patient with rubeosis iridis shows tortuous vessels on the surface of the iris.

Histopathologic Features

The rubeosis iridis begins intrastromally and then develops on the surface of the iris (37, 60). Experimental retinal vein occlusion in monkey eyes indicates that the rubeosis iridis begins with dilatation of normal iris vessels and marked increase in metabolism of vascular endothelial cells followed by new vessel formation (61). Silicone-injection studies indicate that the new vessels on the iris arise from normal iris arteries and drain primarily into iris and ciliary body veins, whereas new vessels in the angle arise from arteries of the iris and ciliary body and connect with the peripheral neovascular network on the iris (62). Although the clinical appearance of rubeosis iridis is said to be the same in cases of diabetes and central retinal vein occlusion, the silicone injections show tighter and more evenly distributed neovascularization in the diabetic eye (62). The silicone-injection studies also show that new vessels in the angle run circumferentially in the trabecular meshwork, with branches coursing into the fibrosed Schlemm canal and occasionally into collector channels (62). The new vessels are characterized histologically as having thin fenestrated walls and are arranged in irregular patterns (60). The ultrastructure of iris neovascularization associated with sickle-cell retinopathy is said to be similar to that in diabetes and retinal occlusive disease with open interendothelial cell junctions, attenuated intraendothelial cytoplasm, and pericyte formation (63).

Open-Angle Glaucoma Stage Clinical Features

Neovascular glaucoma does not invariably follow the development of rubeosis iridis (40, 41, 63, 64), and the latter condition may rarely resolve spontaneously, especially that associated with diabetic retinopathy (40). The reported incidence of

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neovascular glaucoma in diabetic patients with rubeosis iridis ranges from 13% to 41% (40, 41, 64), whereas that associated with central retinal vein occlusion is probably significantly higher. The latter condition typically occurs 8 to 15 weeks after the vascular occlusive event (63). It has been called 90day glaucoma because the average time interval was thought to be 3 months. However, the glaucoma

Figure 19.4 Slitlamp appearance of the iris in a patient with neovascular glaucoma shows marked rubeosis and hyphema.

The rubeosis iridis is typically more florid in this stage, and biomicroscopic examination of the aqueous often reveals an inflammatory reaction and sometimes a hyphema (Fig. 19.4). By gonioscopy, the anterior chamber angle is still open, but the neovascularization may be intense (Fig. 19.5). The IOP is elevated and may rise suddenly, causing the patient to present with acute-onset glaucoma. Histopathologic Features

The hallmark of the open-angle glaucoma stage is a fibrovascular membrane that covers the anterior chamber angle and anterior surface of the iris and may even extend onto the posterior iris (60, 65). Chronic inflammatory changes are also typically seen on histologic examination (60, 65). The glaucoma in this stage probably results from obstruction of the trabecular meshwork by the fibrovascular membrane, with variable contribution from the inflammation and hemorrhage. One histopathologic report of an eye with neovascular glaucoma and without a fibrovascular membrane covering the iridocorneal angle found that the spaces between the trabecular beams were lined by a single layer of vascular endothelium and were filled with red blood cells in this patient, suggesting that neovascular tissue found in the trabecular spaces might be one of the factors responsible for IOP elevation in eyes with neovascular glaucoma (66).

Figure 19.5 A: Angle neovascularization in a patient with a central retinal vein occlusion. Note vessels are superficial and found on the ciliary body band and trabecular meshwork. The angle is open although aqueous outflow is impaired. B: Neovascular glaucoma has progressed to angle closure in this patient. (A, B, courtesy of Joseph A. Halabis, OD.) C: A patient with open-angle neovascular glaucoma, with heavy neovascularization of the open angle. The angle, however, is beginning to close, as seen by the low synechia to the left of the view.

Angle-Closure Glaucoma Stage Clinical Features

In the angle-closure glaucoma stage, the stroma of the iris has become flattened, with a smooth, glistening appearance. Ectropion uvea is frequently present, and the iris is often dilated and pulled anteriorly from the lens (Fig. 19.6). In the anterior chamber angle, the contracture leads to formation of peripheral anterior synechia, with eventual total synechial closure of the angle. The glaucoma in this stage is typically severe and usually requires surgical intervention.

Histopathologic Features

The clinically observed alterations of the iris and anterior chamber angle in this stage result from contracture of tissue overlying these structures. Histopathologic studies reveal peripheral anterior synechiae and flattening of the anterior iris surface by a confluent fibrovascular membrane (67, 68). Overlying the new vessels is a clinically inapparent, superficial layer of myofibroblasts (i.e., fibroblastic cells with smooth-muscle differentiation), which may be responsible for the tissue contraction (67). A layer

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of endothelium, continuous with the corneal endothelium at the pseudoangle, is also seen in some cases and has been observed to possess features of myoblastic differentiation (68, 69), which may explain the origin of these cells.

Figure 19.6 Slitlamp view of a patient with the angle-closure stage of neovascular glaucoma shows numerous new vessels on the iris, with pupillary dilatation and ectropion uvea due to contracture of the fibrovascular membrane.

Differential Diagnosis

In the open-angle stage, neovascular glaucoma must be distinguished from other glaucomas with acute onset, such as angleclosure glaucoma and glaucoma associated with anterior uveitis. This differentiation can usually be made on the basis of new vessels on the iris and in the anterior chamber angle with neovascular glaucoma, although eyes with uveitis often have dilatation of normal iris vessels that may be confused with neovascularization, especially with blue irides. Patients with Fuchs heterochromic iridocyclitis also typically have new vessels in the anterior chamber angle (see Chapter 22). In the angleclosure stage of neovascular glaucoma, the new vessels may be less apparent, and the differential diagnosis must include other causes of iris distortion and peripheral anterior synechiae, such as the iridocorneal endothelial syndrome (see Chapter 16) and old trauma (see Chapter 25).

Management

Panretinal Photocoagulation

Ablation of the peripheral retina with laser (usually argon) photocoagulation is the first line of therapy for most cases of neovascular glaucoma. This procedure has been shown to significantly reduce or eliminate anterior segment neovascularization in many cases and to reduce the chances of developing rubeosis iridis in eyes with diabetic retinopathy or central retinal vein occlusion (47, 64, 70, 71, 72, 73, 74, 75, 76, 77, 78 and 79). The mechanism by which panretinal photocoagulation influences neovascularization is uncertain, although it may be related to decreasing the retinal oxygen demand, which is consistent with the reported observation that the photoreceptor-retinal pigment epithelial complex accounts for two thirds of the total retinal oxygen consumption (80). This may reduce the stimulus for release of an angiogenesis factor or may reduce the hypoxia in the anterior ocular segment. However, in 27 eyes with ischemic central retinal vein occlusion treated with panretinal photocoagulation, 5 developed posterior neovascularization, which had not been present preoperatively, suggesting that photocoagulation does not always eliminate retinal ischemia (81).

Prophylactic Therapy

Panretinal photocoagulation is most effective as prophylaxis against the development of neovascular

glaucoma. It was once thought by some surgeons that photocoagulation should be performed during the prerubeosis stage in central retinal vein occlusion, if the risk for rubeosis iridis was sufficiently high. However, a multicenter, randomized clinical trial revealed that prophylactic photocoagulation does not totally prevent iris and angle neovascularization and that prompt regression of the rubeosis is more likely to occur in response to photocoagulation in eyes that have not been treated previously (82). With regard to central retinal vein occlusion, it is apparently better to follow patients closely and intervene promptly with panretinal photocoagulation at the early signs of rubeosis.

The risk for rubeosis iridis is more difficult to predict in eyes with diabetic retinopathy than in those with central retinal vein occlusion, but vitrectomy or lensectomy, especially in association with peripupillary fluorescein leakage, may be indications for prophylactic therapy. The latter is often performed as endophotocoagulation in conjunction with pars plana vitrectomy for diabetic retinopathy. By the time rubeosis iridis appears (preglaucoma stage), panretinal photocoagulation is indicated in all cases, including those resulting from central retinal artery occlusion and carotid artery insufficiency (83). Although neovascular glaucoma does not invariably follow rubeosis iridis, it does so with sufficient frequency that prophylactic laser therapy is justified in nearly all of these cases.

Treatment of Glaucoma

Panretinal photocoagulation may reverse IOP elevation in the open-angle glaucoma stage and in some cases of early angleclosure neovascular glaucoma, provided that the synechial closure has not exceeded 270 degrees (70, 71, 73, 84). Even in the latter situation, panretinal photocoagulation may be useful in reducing anterior segment neovascularization before intraocular surgery (85). However, one study showed that panretinal photocoagulation before vitrectomy for diabetic retinopathy did not prevent postoperative rubeosis iridis (86). In these cases, intraocular panretinal photocoagulation at the time of vitrectomy may be the procedure of choice (87).

Panretinal Cryotherapy

When cloudy media preclude panretinal photocoagulation, transscleral panretinal cryotherapy, often combined with cyclocryotherapy, in eyes with neovascular glaucoma can control the IOP and reduce or abolish the neovascularization (88, 89).

Anti-VEGF Agents

Many case reports have attempted to ascertain the value of intraocular anti-VEGF therapy with bevacizumab as an adjunctive treatment of iris neovascularization associated with

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glaucoma (36). These reports in patients with either diabetes or central retinal vein occlusion and associated neovascular glaucoma involved injecting 1.25-mg bevacizumab in the vitreous cavity or 1.0- to 1.25-mg bevacizumab in the anterior chamber before or concomitant with panretinal photocoagulation. Virtually all treated eyes had significant regression of anterior segment neovascularization within 48 hours, many with a concomitant reduction in IOP. The injected medication was reported to be safe and well tolerated. The effect of bevacizumab lasted for a number of weeks, and thereafter, new vessel formation was noted to resume in some eyes. Hence, it is important to proceed with panretinal photocoagulation as soon as practical to help prevent recurrent neovascularization. Intraocular injections of bevacizumab can be repeated, but how often eyes can be reinjected remains to be determined (90).

Medical Management of Glaucoma and Inflammation

When the IOP begins to rise, medical therapy is usually required and is frequently sufficient to control the pressure during the open-angle glaucoma stage. The mainstay of the therapy at this stage is drugs that reduce aqueous production, such as carbonic anhydrase inhibitors, topical (ß-blockers, and a 2-

agonists. Prostaglandin analogues are rarely effective because access to the uveoscleral route is generally compromised from angle closure, and there is a theoretical concern regarding exacerbation of inflammation. Miotics are not helpful in the acute situation and should usually be avoided because they may increase the inflammation and discomfort. Topical corticosteroids may be useful in minimizing the inflammation and pain (91). Intravitreal triamcinolone has reduced retinal neovascularization in rabbit

eyes (92), raising the question of a possible direct benefit of topical steroids on rubeotic vessels. In faradvanced or blind eyes, atropine is helpful for relief of pain. Hyperosmotic agents may also be required for temporary control of cases with marked IOP elevation.

Glaucoma Surgical Procedures Cyclodestructive Procedures

If the disease follows its natural course to the angle-closure glaucoma stage, medical therapy usually becomes ineffective and surgical intervention is required. Even at this stage, panretinal photocoagulation may be beneficial by reducing the anterior segment neovascularization to allow filtration surgery. With active rubeosis, however, standard filtering surgery has a low chance of success, and a cyclodestructive procedure may be preferable.

Although good results have been reported by some surgeons with the use of cyclocryotherapy for neovascular glaucoma (93, 94), other reports have been less encouraging (95, 96 and 97). In one 2-year follow-up of 50 eyes, one third were uncontrolled and one third developed phthisis (95). Alternative cyclodestructive procedures include transscleral Nd:YAG cyclophotocoagulation and diode laser cyclophotocoagulation (98). Preliminary experience suggests that diode laser cyclophotocoagulation provides less postoperative inflammation and better IOP control than Nd:YAG cyclophotocoagulation and has become the surgical procedure of choice for neovascular glaucoma when filtering surgery is not thought to be indicated (99, 100).

Filtering Surgery

It has been a general belief that standard filtering procedures in eyes with neovascular glaucoma are rarely successful, primarily because of the high risk for intraoperative bleeding and postoperative progression of the fibrovascular membrane. However, a successful panretinal photocoagulation, combined with anti-VEGF treatment, can reduce neovascularization sufficiently to make it possible to perform a standard filtering operation, such as trabeculectomy. In one study, the adjunctive use of 5- fluorouracil provided success rates of 71% and 67% in the first and second postoperative years, respectively, although this fell to 41% and 28% by the fourth and fifth years, respectively (101). In another study, the use of mitomycin C during trabeculectomy yielded success rates of 62.6%, 58.2%, and 51.7% at 1, 2, and 5 years, respectively. Younger age and previous vitrectomy were prognostic factors for surgical failure (102). Other techniques for filtering surgery in neovascular glaucoma that may be helpful include a modified trabeculectomy with intraocular bipolar cautery of peripheral iris and ciliary processes and creation of a small iridectomy or avoidance of an iridectomy if the chamber is deep and pupillary block is absent (103, 104).

Glaucoma Drainage-Device Surgery

Encouraging results have been reported with the implantation of drainage tubes or valves into the anterior chamber and through the pars plana (when combined with a vitrectomy) in eyes with neovascular glaucoma (105, 106 and 107). Adjunctive bevacizumab may improve the success of glaucoma drainage-device surgery in these eyes (108). (Details regarding the techniques and reported results of these procedures are considered in Section III.)

Other Surgical Procedures

Several other techniques have been evaluated for the treatment of neovascular glaucoma. Endoscopic cyclophotocoagulation (see Chapter 41) may be helpful in lowering IOP, particularly in eyes that have reasonable visual potential and are not good candidates for aqueous drainage procedures. Silicone oil injection during revision of vitrectomy after unsuccessful diabetic vitreous surgery achieved stabilization or regression of anterior ocular neovascular changes in 83% of eyes in one study (109). Intravitreal injection of crystalline triamcinolone acetonide has also been demonstrated to decrease the degree of rubeosis iridis in neovascular glaucoma attributable to peripheral diabetic retinopathy or central retinal vein occlusion (110). Exposure to 100% oxygen under hyperbaric conditions significantly increases the partial pressure of oxygen in the aqueous humor of animal eyes, a mechanism that may have an application in treating hypoxic diseases of the anterior segment, including rubeosis iridis (111). P.302

ALTERATIONS OF IOP ASSOCIATED WITH RETINAL DETACHMENT Reduced IOP and Retinal Detachment

An eye with a rhegmatogenous retinal detachment typically has a reduced IOP. Experimental studies with retinal detachments in monkeys suggest that an early, transient pressure drop may result from inflammation and reduced aqueous production (112), whereas more prolonged hypotony may be caused by posterior flow of aqueous through the retinal hole (113). A study with kinetic vitreous fluorophotometry indicated a posterior flow, presumably through a break in the retinal pigment epithelium, in patients with vitreous and rhegmatogenous retinal detachments (114). Campbell (115) described a condition, the iris retraction syndrome, in which a patient presents with a rhegmatogenous retinal detachment, a secluded pupil, and angle closure with iris bombé. Pharmacologic suppression of aqueous production in these individuals leads to hypotony and a posterior retraction of the iris, presumably due to a shift in the predominant direction of aqueous flow toward the subretinal space. Glaucomas Associated with Retinal Detachment

The coexistence of glaucoma and a retinal detachment in the same eye occurs under three circumstances: (a) glaucoma associated with retinal detachment, for which a cause-and-effect relationship is uncertain; (b) glaucoma directly related to retinal detachment; and (c) glaucoma after treatment of retinal detachment. (The first two situations are discussed in this chapter, and the third is considered in Chapter 26.)

Chronic Open-Angle Glaucoma and Retinal Detachment Epidemiology

COAG is more common in eyes with a rhegmatogenous retinal detachment than in the general population. In one study of 817 cases of retinal detachment, COAG was present in 4%, and an additional 6.5% had elevated IOP without glaucomatous damage (116).

Theories of Mechanism

It is not known why COAG and rhegmatogenous retinal detachment occur in the same eye more frequently than would be anticipated on the basis of chance occurrence. Neither myopia nor the use of miotics has been found to be the common denominator (116). In 30 cases of spontaneous rhegmatogenous retinal detachment, 53% had a cup-to-disc ratio greater than 0.3, and 20% were high topical steroid responders (117). These values are significantly higher than those in the general population and resemble the findings in groups of patients with COAG, which led investigators to suggest that the two diseases might be related genetically by multifactorial inheritance.

Management

When COAG and retinal detachment coexist, one disorder may mask the presence of the other, necessitating careful attention to certain details during the management of either condition. When following a patient with COAG, the peripheral retina should be examined before initiating therapy and at least annually or whenever warning signs appear, such as floaters, flashing lights, loss of peripheral vision, or a sudden decrease in the IOP. Although the role of miotics in the pathogenesis of rhegmatogenous retinal detachment has not been clearly established, circumstantial evidence indicates that particular caution is warranted when these drugs are used (118).

In an eye with a rhegmatogenous retinal detachment, the reduced IOP may mask a preexisting glaucoma. Applanation tonometry should be performed before and after retinal detachment surgery, and the optic nerve head should be carefully inspected during the fundus examination to avoid missing coexisting glaucoma.

The success of retinal detachment surgery is not adversely affected by the presence of glaucoma, although the visual outcome may be worse because of the concomitant glaucomatous optic atrophy (116, 119). After retinal detachment surgery, particularly in nondiabetic patients, regression of iris neovascularization may occur (120). After surgery, special caution should be given to the use of topical steroids because of the increased incidence of high topical steroid responders (117), and miotics should be used with caution in either eye.

Pigmentary Glaucoma and Retinal Detachment

Patients with the pigment dispersion syndrome, with or without glaucoma, may have an increased

incidence of retinal detachment. Patients with retinal detachment are reported to have various degrees of pigment dispersion in the anterior chamber angle in a significant number of cases (121). As in the case of COAG, no definite cause-and-effect relationship has been established, but the same considerations as mentioned earlier must be employed in the management of coexisting pigmentary glaucoma and retinal detachment.

Schwartz Syndrome

A rhegmatogenous retinal detachment is typically associated with a slight reduction in the IOP. However, Schwartz described a rare condition in which the patient presents with unilateral pressure elevation, a retinal detachment, and an open anterior chamber angle with aqueous cells and flare (122). The condition is generally known as Schwartz syndrome.

Theories of Mechanism

Photoreceptor outer segments with few inflammatory cells have been demonstrated by Matsuo and colleagues in the aqueous of patients with Schwartz syndrome (123), and the injection of rod outer segments into human autopsy and living cat eyes has been shown to significantly reduce outflow facility by obstructing the trabecular meshwork (124). Other mechanisms that have been considered include ocular trauma with concomitant damage to the trabecular meshwork, anterior uveitis from the retinal detachment and obstruction of the trabecular meshwork by pigment from the retinal pigment epithelium, or glycosaminoglycans from the visual cells (122, 125, 126).

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Management

Treatment of rhegmatogenous retinal detachment and the associated glaucoma is repair of the detachment, which typically results in resolution of the glaucoma within a few days (122). In the differential diagnosis, it is important to remember that an eye with a retinal detachment and glaucoma may harbor a malignant melanoma.

Glaucoma Associated with Other Forms of Retinal Detachment

In addition to rhegmatogenous retinal detachment, several other forms of retinal detachment may be associated with glaucoma. These include traction detachments, as with proliferative diabetic retinopathy and retinopathy of prematurity (discussed in this chapter); exudative retinal detachments (see Chapter 22); and detachments associated with neoplasia, such as melanomas and retinoblastoma (see Chapter 21). Each of these conditions may lead to neovascular or angle-closure glaucoma.

ANGLE-CLOSURE GLAUCOMAS ASSOCIATED WITH DISORDERS OF THE RETINA, VITREOUS, AND CHOROID

Central Retinal Vein Occlusion

Neovascular glaucoma occurring after retinal vascular occlusive disease was discussed earlier in this chapter. A few cases have been described in which shallowing of the anterior chamber after a central retinal vein occlusion led to transient angleclosure glaucoma (127, 128, 129 and 130).

Examination typically reveals a forward shift of the lens-iris diaphragm in the involved eye and a normal anterior chamber depth in the fellow eye. The mechanism of the angle closure is uncertain, although it has been postulated that transudation of fluid from the retinal vessels into the vitreous leads to forward displacement of the lens with a subsequent pupillary block (128). The differential diagnosis should include pupillary block glaucoma, which may lead to occlusion of the central retinal vein, and neovascular glaucoma, which can cause synechial closure of the anterior chamber angle. The former situation may be recognized by a potentially occludable angle in the fellow eye, and the latter can usually be identified by the presence of rubeosis iridis.

Treatment should usually be medical, because the angle returns to normal depth over several weeks. In general, aqueous suppressants, such as topical or oral carbonic anhydrase inhibitors, topical (ß-block ers, and a2-agonists, in conjunction with topical cycloplegic agents are generally effective (129). Hemorrhagic Retinal or Choroidal Detachment

Acute angle-closure glaucoma may follow a spontaneous massive hemorrhagic retinal or choroidal detachment (131). The hemorrhagic detachment is typically caused by a disciform macular lesion, and