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

have surgery within a week or so of symptom onset. If, however, symptoms have persisted for more than a week, combining trabeculectomy with cataract extraction to prevent a postoperative rise in IOP and to decrease the need for systemic hypotensive medications is reasonable to consider.

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Figure 18.9 “ Fluffed-up” lens cortical material is retained in the anterior chamber in this patient with lens particle glaucoma. (Courtesy of Brooks W. McCuen II, MD.)

Lens Particle Glaucoma Terminology

It was once thought that a primary toxicity of cataractous lens material caused an inflammatory reaction called phacotoxic uveitis and that it led to glaucoma in some cases. Subsequent studies have not supported the concept that liberated lens material is toxic (48). Cases incorrectly given this diagnosis are actually caused by liberation of lens particles and debris after disruption of the lens capsule, and the term “lens particle glaucoma” has been proposed for this entity (35).

Clinical Features

Lens particle glaucoma is typically associated with disruption of the lens capsule by cataract extraction or a penetrating injury. The onset of IOP elevation usually occurs soon after the primary event and is generally proportional to the amount of “fluffed-up ” lens cortical material in the anterior chamber (F ig. 18.9). Uncommon clinical variations include an onset of glaucoma many years after capsular disruption or after a spontaneous rupture in the lens capsule. The latter condition may be hard to distinguish from phacolytic glaucoma, although cases of lens particle glaucoma tend to have a greater inflammatory component, often associated with posterior and anterior synechiae and inflammatory pupillary membranes (35).

Theories of Mechanism

Perfusion studies with enucleated human eyes have demonstrated that small amounts of free particulate lens material significantly reduce outflow (33). This is presumed to be the principal mechanism of trabecular meshwork obstruction in cases of lens particle glaucoma. However, the associated inflammation, whether in response to the surgery, trauma, or retained lens material, may contribute to the glaucoma in this condition.

Differential Diagnosis

In its typical form, lens particle glaucoma is usually easy to diagnose on the basis of history and physical findings. In atypical forms, such as delayed onset or spontaneous capsule rupture, the condition might be confused with phacoanaphylaxis, phacolytic glaucoma, or uveitic conditions with associated open-angle glaucoma. When doubt exists, microscopic examination of aqueous from an anterior chamber tap may help to diagnose lens particle glaucoma by demonstrating leukocytes and macrophages along with lens cortical material (35).

Management

In some cases, the IOP is possible to control medically with drugs that reduce aqueous production. Because inflammation is also present, the pupil should be dilated and topical steroids used, although it may be advisable to use the latter only in moderate amounts because steroid therapy may delay absorption of the lens material (35). The IOP usually returns to normal after the lens material has been absorbed. When the IOP cannot be adequately controlled medically, the residual lens material should be surgically removed by irrigation if the material is loose or with vitrectomy instruments when it is adherent to ocular structures.

Phacoanaphylaxis Terminology

In 1922, Verhoeff and Lemoine (49) reported that a few individuals were hypersensitive to lens protein and that rupture of the lens capsule in these cases led to an intraocular inflammation, which they called endophthalmitis phacoanaphylactica. Although such cases are apparently rare, evidence shows that a true phacoanaphylaxis does occur in response to lens protein antigen (50), with subsequent inflammation and occasional open-angle glaucoma.

Clinical Features

As in the case of lens particle glaucoma, a preceding disruption of the lens capsule by extracapsular cataract surgery or penetrating injury usually occurs (51). The distinguishing feature, however, is a latent period during which sensitization to lens protein occurs. A particularly likely setting for the development of phacoanaphylaxis is when lens material, especially the nucleus, is retained in the vitreous. The typical physical finding is a chronic, relentless, granulomatous-type inflammation that centers on lens material in the primarily involved eye or in the fellow eye after it has undergone extracapsular cataract surgery or phacoemulsification. Associated glaucoma is only rarely a feature of phacoanaphylaxis.

Theories of Mechanism

It has been demonstrated in rabbits that autologous lens protein is antigenic (50), and the lens capsule was assumed to isolate the lenticular antigens from the immune response, with sensitization occurring only when the capsule is violated. This concept was not supported by human studies, which failed to demonstrate lens antibodies after injury to the lens and showed an equal incidence of antibody in patients with cataracts and controls (52). The same study did show a higher prevalence of antibodies in a small group with hypermature cataracts and more frequent postoperative uveitis in patients with antibodies in preoperative

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blood specimens, although the latter observation was not statistically significant. In the rabbit study, considerable variation in the response to autologous lens antigen was observed, which may explain the infrequency with which phacoanaphylaxis is seen clinically (50). The cellular appearance of the immune response is characterized by polymorphonuclear leukocytes and lymphoid, epithelioid, and giant cells, usually around a nidus of lens material. The occasional glaucoma in phacoanaphylaxis may be related to the accumulation of these cells in the trabecular meshwork, although lens protein or particles may also be present and could account for the glaucoma.

Differential Diagnosis

Other chronic forms of uveitis, especially sympathetic ophthalmia, may occur in association with phacoanaphylaxis. Phacolytic and lens particle glaucomas must also be considered. Microscopic

examination of the aqueous may be helpful, although variations in cytology have not been fully studied in this condition and the diagnosis may require histologic examination of the surgically removed lens material.

Management

Steroid therapy should be used to control the uveitis, with antiglaucoma medication administered as required. When medical measures are inadequate, the retained lens material should be surgically removed.

Intumescent Lens Phacomorphic Glaucoma

In some eyes with advanced cataract formation, the lens may become swollen or intumescent, with progressive reduction in the anterior chamber angle eventually leading to a form of angle-closure glaucoma (Fig. 18.10). This condition has been referred to as phacomorphic glaucoma (53). The angle closure may be caused by an enhanced pupillary block mechanism or by forward displacement of the lens-iris diaphragm. In either case, the condition is usually diagnosed by observing a mature, intumescent cataract associated with a central anterior chamber depth that is significantly shallower than that of the fellow eye. The treatment is initial medical reduction of the IOP with hyperosmotics, carbonic anhydrase inhibitors, and topical (ß-blockers or a 2-agonists, followed by extraction of the cataract (54).

However, in a small study of patients with phacomorphic glaucoma, the acute angle-closure glaucoma attack was relieved in all cases by laser iridotomy (55), which may help to bring the pressure under control before proceeding with cataract surgery. If the mechanism of glaucoma is felt to be partly related to chronic angle closure with formation of peripheral anterior synechiae, goniosynechialysis in conjunction with cataract extraction can be considered.

Figure 18.10 Phacomorphic glaucoma caused by an intumescent lens in an older adult. Note the extremely shallow anterior chamber centrally and peripherally. (From Mandelcorn E, Gupta N. Lensrelated glaucomas. In: Tasman W, Jaeger EA, eds. Duane's Clinical Ophthalmology. Vol 3. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:chap 54A.)

KEY POINTS

The lens may be associated with glaucoma when it is dislocated, which may occur with trauma or

certain inherited disorders, such as Marfan syndrome, homocystinuria, and Weill-Marchesani syndrome.

Mechanisms by which a dislocated lens may be associated with glaucoma include pupillary block, degenerative changes of the lens, and concomitant damage of the anterior chamber angle.

A cataractous lens may also lead to glaucoma by obstruction of the trabecular meshwork with lens protein and macrophages (i.e., phacolytic glaucoma), lens particles and debris (i.e., lens particle glaucoma), or inflammatory cells as part of an immune response (i.e., phacoanaphylaxis). An intumescent lens may lead to pupillary block and secondary angle-closure glaucoma.

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Shields > SECTION II - The Clinical Forms of Glaucoma >

19 - Glaucomas Associated with Disorders of the Retina, Vitreous, and Choroid

Authors: Allingham, R. Rand

Title: Shields Textbook of Glaucoma, 6th Edition Copyright ©2011 Lippincott Williams & Wilkins

> Table of Contents > SECTION II - The Clinical Forms of Glaucoma > 19 - Glaucomas Associated with Disorders of the Retina, Vitreous, and Choroid

19

Glaucomas Associated with Disorders of the Retina, Vitreous, and Choroid

Several types of glaucoma are associated with diseases of the retina. The most common of these is neovascular glaucoma, which is usually associated with one of several retinal disorders, although some cases are associated with other ocular or extraocular conditions. Retinal detachments and a variety of less common disorders of the retina, vitreous, or choroid may cause or occur in association with various forms of glaucoma.

NEOVASCULAR GLAUCOMA Terminology

In 1906, Coats (1) described new vessel formation on the iris in eyes with central retinal vein occlusion. This neovascularization of the iris is commonly known as rubeosis iridis and is now recognized as a complication of many diseases of the retina and other ocular and extraocular disorders. Rubeosis iridis is frequently associated with a severe form of glaucoma, which has been given different names on the basis of various clinical features: hemorrhagic glaucoma, referring to the hyphema that is present in some cases; congestive glaucoma, describing the frequently acute nature of the condition; and thrombotic glaucoma, implying an underlying vascular thrombotic cause. However, none of these terms accurately describes the glaucoma in all cases, and more nonspecific names are preferable, such as rubeotic glaucoma or neovascular glaucoma, which was proposed by Weiss and colleagues and is the term found most often in the current literature (2, 3).

Factors Predisposing to Rubeosis Iridis

Most cases of rubeosis iridis are preceded by hypoxic disease of the retina. Diabetic retinopathy, central retinal vein occlusion, and carotid ischemic disease are the most common causes (4). However, many

additional retinal diseases and certain other ocular or extraocular disorders have been recognized, resulting in a long list of conditions that may predispose to rubeosis iridis (Table 19.1).

Diabetic Retinopathy

Approximately one third of patients with rubeosis iridis have diabetic retinopathy. Tight metabolic control of blood glucose results in delayed onset of diabetic retinopathy and slows or prevents progression to nonproliferative and proliferative retinopathy (5). The frequency with which rubeosis iridis is associated with diabetic retinopathy is greatly influenced by surgical interventions. After pars plana vitrectomy for diabetic retinopathy, the reported incidence of rubeosis iridis ranges from 25% to 42%, whereas that for neovascular glaucoma ranges from 10% to 23% (6, 7 and 8), with most of these cases developing during the first 6 months after surgery (9). In these cases, rubeosis iridis and neovascular glaucoma occur more often in aphakic eyes (7, 8, 10). In one series, vitreous cavity lavage of hemorrhage after pars plana vitrectomy for diabetic retinopathy was associated with rubeosis iridis in 76% of aphakic eyes and 14% of phakic eyes (10). Postoperative neovascular glaucoma is also more common when rubeosis iridis is present before vitrectomy (11).

An unrepaired retinal detachment after vitrectomy for diabetic retinopathy is also a risk factor for postoperative rubeosis iridis. The acute onset or exacerbation of rubeosis iridis after diabetic vitrectomy can indicate the presence of a peripheral traction retinal detachment (12). Successful surgical reattachment of the retina during vitrectomy for diabetic retinopathy often leads to regression of preoperative rubeosis iridis, especially in phakic patients (13). A completely attached retina and aggressive anterior or peripheral photocoagulation therapy are the most important factors in controlling or preventing neovascular glaucoma after vitrectomy for proliferative diabetic retinopathy (12, 14). Intraocular silicone oil also reduces the incidence of anterior segment neovascularization, possibly by acting as a diffusion or convection barrier to the posterior movement of oxygen from the anterior chamber or the anterior movement of an angiogenesis factor (15).

Nonproliferative and preproliferative diabetic retinopathy may progress after cataract surgery (4). Intracapsular cataract surgery alone in eyes with diabetic retinopathy has been associated with an increased incidence of postoperative rubeosis iridis and neovascular glaucoma. The incidence is similar with extracapsular extraction and a primary capsulotomy. Leaving the posterior capsule intact appears to reduce the likelihood of this complication, although a subsequent laser capsulotomy in patients with diabetes may lead to neovascular glaucoma.

Retinal Vascular Occlusive Disorders

Central retinal vein occlusion accounted for 28% of all cases of rubeosis iridis in one series (16). Elevated intraocular pressure (IOP), with or without glaucomatous damage, is thought by most (17, 18 and 19) investigators to be a predisposing factor for retinal vein occlusion. Optic disc cupping was reported to be a significant risk factor for central and branch retinal vein occlusions in the Beaver Dam Eye Study (20). Other risk factors for central or branch retinal vein occlusion include systemic hypertension, diabetes, and male sex (19). Retinal vein occlusion may occur in a

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wide range of ages (14 to 92 years in one large study, although 51% of these patients were 65 years or older) (21).

Table 19.1 Conditions Predisposing to Rubeosis Iridis and Neovascular Glaucoma Retinal Ischemic Disease

Diabetic retinopathy

Central retinal vein occlusion Central retinal artery occlusion Branch retinal vein occlusion Branch retinal artery occlusion Retinal detachment Hemorrhagic retinal disorders Coat exudative retinopathy

Eales disease

Leber congenital amaurosis

Retinopathy of prematurity

Persistent hyperplastic primary vitreous

Sickle-cell retinopathy

Syphilitic retinal vasculitis

Retinoschisis

Stickler syndrome (inherited vitreoretinal degeneration)

Optic nerve glioma with subsequent venous stasis retinopathy

Irradiation

Photoradiation

External beam

Charged particle: proton, helium ion radiation

Plaques

Tumors

Choroidal melanoma

Ring melanoma of the ciliary body

Iris melanoma

Retinoblastoma

Large-cell lymphoma

Inflammatory Diseases

Uveitis: chronic iridocyclitis, Behçet disease

Vogt-Koyanagi-Harada syndrome

Sympathetic ophthalmia

Endophthalmitis

Crohn disease with retinal vasculitis

Surgical Causes

Carotid endarterectomy

Cataract extraction

Pars plana vitrectomy or lensectomy

Nd:YAG capsulotomy

Laser coreoplasty

Extraocular Vascular Disorders

Carotid artery obstructive disease

Carotid-cavernous fistula

Internal carotid artery occlusion

Adapted from Sivak-Callcott JA, O'Day DM, Gass DM, et al. Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma. Ophthalmology. 2001;108:1767-1778.

Rubeosis iridis and neovascular glaucoma are associated with central retinal artery occlusion, and they are less commonly associated with central vein occlusion. In two series of patients with central retinal artery occlusion, the incidence of rubeosis iridis was 16.67% and 18.2%, respectively (22, 23). Patients who develop neovascular glaucoma in association with central retinal artery occlusion are usually elderly with severe carotid artery disease and atherosclerosis, which may be predisposing factors for retinal artery occlusion and, in some cases, ocular neovascularization (24, 25). Branch retinal vein occlusion may rarely cause rubeosis iridis and neovascular glaucoma (16). Branch retinal artery occlusion has also been reported as a rare cause of rubeosis iridis (25, 26), although the association with neovascular glaucoma is uncertain.

Other Retinal Disorders

Rubeosis iridis may be associated with a rhegmatogenous retinal detachment (27), especially when complicated by proliferative vitreoretinopathy (28). In some cases, the detachment may overlie a choroidal melanoma. A chronic retinal detachment with associated glaucoma should always raise the

suspicion of melanoma. Neovascular glaucoma may also be associated with sickle-cell retinopathy and many other retinal disorders, which are listed in Table 19.1.

Other Ocular Disorders

Uveitis was present in 11% of rubeotic eyes in one series and in 1.5% of another study (16, 29). An iris melanoma has also been associated with neovascular glaucoma, which resolved after the tumor was excised (30). End-stage glaucoma (open-angle or angle-closure) has been said to give rise to rubeosis iridis (16), which may be related to associated central retinal vein occlusion.

Extraocular Vascular Disorders

Carotid artery obstructive disease is probably the third most common cause of neovascular glaucoma, accounting for 13% of all cases in one series (29). These eyes may initially be normotensive or even hypotensive as a result of decreased perfusion of the ciliary body with reduced aqueous production, and fluorescein angiography may reveal an increased arm-to-retina time and leakage from the major retinal arterioles. A carotid-cavernous fistula may also cause rubeosis iridis and neovascular glaucoma as a result of decreased arterial flow and subsequent reduction in the ocular perfusion pressure, which may occur before or after treatment of the fistula (31, 32). Internal carotid artery occlusion may create an ophthalmic artery steal phenomenon with associated rubeosis iridis (33).

Theories of Neovasculogenesis

The mechanisms by which the aforementioned clinical situations lead to rubeosis iridis are not fully understood, although the following theories have been proposed (4).

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Retinal Hypoxia

Because most of the conditions associated with rubeosis iridis involve diminished perfusion of the retina, retinal hypoxia may be one factor in the formation of new vessels on the iris and anterior chamber angle and on the retina and optic nerve head. This concept is supported by the clinical observation that rubeosis iridis in association with proliferative diabetic retinopathy or central retinal vein occlusion is more likely to occur when significant capillary nonperfusion is present. Angiogenesis Factors

The existence of an angiogenic substance regulating normal development of retinal blood vessels was hypothesized in 1948 (34). It has since been demonstrated that tumors possess a diffusible factor, tumor angiogenesis factor, that can elicit new vessel growth toward the tumor (35). Subsequent studies have suggested that human and animal retinas and other vascular ocular tissues have similar angiogenic activity related to a key angiogenic peptide, vascular endothelial growth factor (VEGF), which explains why ocular neovascularization can occur in areas remote from the site of retinal capillary nonperfusion. Several cell types in the retina synthesize VEGF, but under conditions of retinal ischemia, Müller cel ls appear to be the primary source. Four VEGF isoforms (VEGF121, VEGF165, VEGF189, and VEGF206)

have been identified, which are generated by alternative mRNA splicing from the same gene (36). VEGF165 is the most abundant form in the majority of tissues. VEGF is a potent angiogenic stimulator,

promoting several steps of angiogenesis, including proliferation, migration, proteolytic activity, and capillary tube formation, thus playing a crucial role in both normal and pathologic angiogenesis. It is also known as a vascular permeability factor on the basis of its ability to induce vascular hyperpermeability and endothelial cell proliferation as well as migration.

Vasoinhibitory Factors

It has been postulated that ocular tissues may produce substances that inhibit neovascularization. The vitreous and lens are possible sources of these vasoinhibitory factors (37, 38), which could explain why vitrectomy or lensectomy increases the risk for rubeosis iridis in eyes with diabetic retinopathy. Retinal pigment epithelial cells release an inhibitor of neovascularization (39).

Clinicopathologic Course

The clinical and histologic events that lead from a predisposing factor through rubeosis iridis to advanced neovascular glaucoma may be thought of in four stages (Fig. 19.1).

Prerubeosis Stage

In patients with a predisposing factor, such as diabetic retinopathy or central retinal vein occlusion, it is helpful to understand what the likelihood is for development of rubeosis iridis and what the chances are for progression to neovascular glaucoma. Additional circumstances, especially with the two mentioned predisposing factors, may increase the risk for neovascular glaucoma to the extent that treatment may be indicated even before rubeosis is detected.

Diabetic Retinopathy

The prevalence of rubeosis iridis among patients with diabetes mellitus ranges from 0.25% to 20% according to various reports (40). Diabetes usually exists for many years before rubeosis develops, and concomitant proliferative diabetic retinopathy is usually found. In populations of patients with proliferative diabetic retinopathy, rubeosis iridis is reported to occur in approximately one-half of the cases (40, 41). Rubeosis iridis may rarely occur in an eye with nonproliferative retinopathy (40), although other predisposing factors, such as carotid artery disease, should be considered in these cases. The risk for rubeosis iridis and neovascular glaucoma in patients with diabetic retinopathy is greatly increased when arteriolar or capillary nonperfusion is present or after vitrectomy or lensectomy. There is also a highly significant correlation between rubeosis iridis and optic disc neovascularization (42) as well as a rhegmatogenous retinal detachment (13, 14). The demonstration of peripupillary leakage by iris fluorescein angiography correlates with the presence of abnormal iris vessels and the risk for rubeosis iridis after vitrectomy for diabetic retinopathy (Fig. 19.2). Slitlamp biomicroscopy is less reliable than angiography in detecting the presence of diabetic iris lesions (43). It is important to pay close attention to the pupillary margin of the iris, where neovascularization is typically seen first (44), when looking for the earliest biomicroscopic evidence of anterior segment rubeosis. However, gonioscopy is also important, because angle neovascularization may occasionally precede that of the iris (45).

Central Retinal Vein Occlusion

During the early months after a central retinal vein occlusion, hypotony may develop (46). The explanation for this is unclear, although the possible influences of anterior segment ischemia or an angiogenic factor have been proposed.

As in diabetic retinopathy, the incidence of rubeosis iridis and neovascular glaucoma in eyes with central retinal vein occlusion is significantly correlated with the extent of retinal capillary nonperfusion. In one study, the incidence of rubeosis iridis after central retinal vein occlusion was 60% when retinal ischemia was demonstrated by fluorescein angiography, compared with 1% in eyes with good capillary perfusion (47).

Fluorescein angiography is the most direct method of evaluating capillary nonperfusion but is not always feasible because of obstruction of visualization by blood or other media opacities. The ophthalmoscopic findings may be helpful in determining the risk for neovascular glaucoma, which has been reported in 14% to 27% of eyes with hemorrhagic retinopathy (complete venous occlusion) but in no cases of venous stasis retinopathy (incomplete occlusion) (48, 49). Several other techniques have predictive value. Fluorescein angiography of the iris reveals abnormal, leaking vessels in virtually all eyes with extensive retinal capillary closure after central retinal vein occlusion (50). Aqueous protein and cell concentrations, as indicated by a laser flare-cell meter, have been shown to correlate with fluorescein angiographic findings and the severity of retinal vein occlusion (51). A relative afferent P.297

pupillary defect also indicates an increased risk for rubeosis iridis after central retinal vein occlusion (52), and infrared pupillometry is an objective method of documenting this finding (53). Electroretinography also has useful predictive value (54). The most diagnostic findings include a B- wave implicit time delay and a reduced B-wave-A-wave amplitude ratio. Flicker electroretinography also has diagnostic value (55). Blood-flow velocities of the central retinal vein and artery can be measured with color Doppler imaging and provide a high degree of predictability regarding the risk for iris neovascularization (56).