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

the lens (3) (Fig. 18.2). The condition is associated with a wide variety of other ocular abnormalities, including severe axial myopia with related fundus changes, enlarged corneal diameters, iris transillumination defects, poor pupillary dilation, persistent pupillary membranes, iridohyaloid adhesions, prominent iris processes, cataracts, retinal detachment, and glaucoma (4). The condition is usually bilateral, although marked variation may be seen between eyes of the same patient. The pathogenesis of this disorder is unknown, but an ultrasound biomicroscopic study of an affected patient demonstrated a lack of definition of the ciliary processes except in the quadrant toward which the pupil was displaced and a membrane-like structure extending from the proximal pupillary margin over the tips of the ciliary processes to a more posterior origin (5). The investigators proposed a localized abnormality of the secondary vitreous with persistence of the marginal bundle of Drualt, resulting in a mechanical tethering of the iris or pupil margin to the vitreous base or anterior vitreous face and localized zonular disruption. Others have suggested a neuroectodermal defect resulting in hypoplasia or absence of the posterior pigment epithelium layer and dilator

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muscle of the iris or a mesodermal defect with persistence of the anterior and lateral elements of the tunica vasculosa lentis (4). The ultrasound biomicroscopy findings are consistent with histopathologic case reports in the German literature from the beginning of the past century (6, 7 and 8).

Figure 18.1 Dislocation or subluxation of the lens can result from various disorders that can lead to glaucoma. In this case, the lens is dislocated superotemporally in a patient with ectopia lentis et papillae, which is characterized by small, subluxed lenses and oval or slit-like pupils that are displaced in the opposite direction of the lens.

Figure 18.2 Patient with ectopia lentis et pupillae, showing typical displacement of pupils.

It has been suggested that simple ectopia lentis may be an incomplete expression of ectopia lentis et pupillae, because both may occur in the same family and have peripheral iris transillumination (4). Some patients with ectopia lentis et pupillae may have mild systemic changes suggestive of Marfan syndrome. Marfan Syndrome

This autosomal dominant disorder is characterized by a tall, slender individual with long, slender fingers and toes (i.e., arachnodactyly) and frequent cardiovascular disease (3). Marfan syndrome and ectopia lentis have been linked to a single fibrillin gene on chromosome 15, and arachnodactyly was linked to the fibrillin gene on chromosome 5 (9). In a review of 160 consecutive patients, the most striking ocular abnormality was enlargement of the globe, presumably caused by scleral stretching (10). The lens was dislocated in 193 of the eyes, and this correlated with increased ocular axial length, suggesting that stretching and rupture of the zonular fibers lead to the dislocation. The ectopia lentis typically appears in the fourth to fifth decade of life and is rarely complete, but it is usually seen as an upward subluxation (Fig. 18.3). Bilateral spontaneous lens dislocation has been described in early childhood with associated glaucoma (11). Glaucoma may result from the lens dislocation, but it is also associated with surgical aphakia or occurs as an anomaly of the anterior chamber angle. In one review of 573 patients, 29 (5%) had glaucoma, and the most common mechanisms were chronic open angle and glaucoma following lens extraction or scleral buckling procedure (12). Retinal detachment is also a common finding in the phakic or aphakic eye of a patient with Marfan syndrome.

Homocystinuria

Patients with homocystinuria may resemble those with Marfan syndrome in habitus and ocular problems, but they differ by having an autosomal recessive inheritance pattern and frequently having mental retardation (3, 13). Homocystinuria may result from one of several enzyme deficiencies in homocysteine metabolism. The diagnosis can be confirmed by the demonstration of homocysteine in the urine. The differentiation between Marfan syndrome and homocystinuria is important because the patient with homocystinuria is subject to thromboembolic episodes, which can lead to death in early adulthood and creates a significant surgical risk. If the condition is diagnosed in a newborn, appropriate dietary treatment and vitamin supplementation can substantially reduce the risk for ocular complications (14). The lens dislocation occurs earlier in life than in the Marfan syndrome and is more often in a downward direction, and complete dislocation into the vitreous or anterior chamber is frequent.

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Glaucoma is more commonly related to the lens dislocation than is the case with Marfan syndrome. Retinal detachment is a common problem.

Figure 18.3 Upward lens subluxation in a patient with Marfan syndrome.

One article examined the results of medical versus surgical treatment for lens subluxation or dislocation in a retrospective case series of 45 patients (15). Medical therapy was attempted initially in all patients and was the sole therapy used for five patients. Eighty-two procedures were performed with the patients under general anesthesia, and two surgical complications and one postoperative complication occurred. Lens dislocation into the anterior chamber was the most frequent indication for surgery (50%), followed by pupillary block glaucoma (12%). Prophylactic peripheral iridectomy was not successful in preventing lens dislocation into the anterior chamber in five patients. The investigators recommend that surgical treatment should be considered, especially for cases of repeated lens dislocation into the anterior chamber or pupillary block glaucoma.

Weill-Marchesani Syndrome

Weill-Marchesani syndrome is the antithesis of the aforementioned conditions with respect to habitus; these patients are short and stocky (16, 17). The principal features of the syndrome are short fingers (i.e., brachydactyly); muscular hypertrophy; and small, round lenses (i.e., microspherophakia) (Fig. 18.4). Lens dislocation in these patients occurs as frequently as in patients with Marfan syndrome and homocystinuria, and glaucoma is more common than in either of the latter two conditions (18). In his original publication, Marchesani (17) hypothesized that an overdevelopment or hyperplasia of the ciliary P.287

body might be the reason for spherophakia. However, an ultrasonographic biomicroscopy study of three patients with this syndrome and normal axial lengths demonstrated that the ciliary body actually appeared smaller than normal (19). The investigators hypothesized that the small ciliary body represents the underlying reason for elongated zonules and that it may be exerting less force on the lens, giving rise to the spherical shape of the lens. An ultrastructural study of the lens from a patient with the WeillMarchesani syndrome revealed degeneration and necrosis of the epithelial cells and destruction of cortical fibers, which was thought to result, in part, from the trauma and irritation of a highly mobile lens in close contact with the iris (20). The small, round lens in this condition also has loose zonules, and

the glaucoma may be related to lens dislocation or a forward shift of the lens, causing pupillary block glaucoma (18), which can be precipitated or aggravated by miotic therapy. Bilateral angle-closure glaucoma has also been reported after middilatation with cyclopentolate in a child with the WeillMarchesani syndrome but without lens subluxation (21). Angle-closure glaucoma may be treated with laser iridectomy or peripheral iridoplasty depending on the relative proportion of pupillary block as the mechanism of the angle closure (22).

Figure 18.4 Partial lens dislocation in a patient with Weill-Marchesani syndrome. The loose zonules allow the lens to assume a typical, small round shape (i.e., microspherophakia).

Spontaneous Dislocation

In some middle-aged or older individuals, dislocation of the lens may occur spontaneously, usually in association with cataract formation (1). Spontaneous dislocation has also been reported in eyes with high myopia, uveitis, buphthalmos, or megalocornea.

Other Conditions with Associated Ectopia Lentis

Other rare congenital disorders associated with lens dislocation include Ehlers-Danlos syndrome, hyperlysinemia, sulfite oxidase deficiency, and aniridia. Additional conditions associated with ectopia lentis are included in Table 18.1.

Examination and Investigation

Slitlamp examination may reveal lenticular subluxation and dislocation. If zonules are weak, then phacodonesis or iridodonesis may also be present. Even with these signs, the nature of the accompanying zonular defect may be uncertain. Ultrasonographic biomicroscopy enables in vivo imaging of the zonules and can detect zonular loss and stretching directly (Fig. 18.5) (23). In a study of 18 eyes with clinically suspected zonular abnormalities, ultrasonographic biomicroscopy demonstrated evidence of missing zonules in 11 eyes and evidence of zonular stretch in 11 eyes. All of the eyes examined demonstrated increased lenticular sphericity in the area of the zonular disorder, and nine eyes showed ciliary body flattening.

Table 18.1 Conditions Associated with Ectopia Lentis

Trauma

Simple ectopia lentis

Ectopia lentis et pupillae

Marfan syndrome

Homocystinuria

Weill-Marchesani syndrome

High myopia

Uveitis

Buphthalmos

Megalocornea

Ehlers-Danlos syndrome

Hyperlysinemia

Sulfite oxidase deficiency

Aniridia

Scleroderma

Alport syndrome

Mandibulofacial dysostosis

Klinefelter syndrome

Retinitis pigmentosa

Persistent pupillary membrane

Axenfeld-Rieger syndrome

Dominantly inherited blepharoptosis and high myopia

Marfan-like syndrome with hyaloretinal degeneration

Sturge-Weber syndrome

Syphilis

Crouzon disease

Refsum syndrome

Modified from Refs. 3 and 27.

Mechanisms of Glaucoma Associated with Subluxated or Dislocated Lens

Subluxation or complete dislocation of the lens in any of the aforementioned clinical conditions may lead to glaucoma by various mechanisms. In general, these mechanisms of glaucoma apply to all forms of ectopia lentis.

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Figure 18.5 A: Ultrasonographic biomicroscopy showing stretched zonules. B: Ultrasonographic biomicroscopy showing broken zonules with rounding up of the ciliary body and adjacent lens equator. Pupillary Block

The lens may block aqueous flow through the pupil if it is dislocated into the pupil or anterior chamber or subluxed or tilted forward against the iris without entering the anterior chamber. This mechanism is particularly common with microspherophakia, as in the Weill-Marchesani syndrome, because of loose zonules of the lens. Pupillary block in the latter condition is often worsened by miotic therapy, which allows further relaxation of zonular support, and cycloplegic agents may help by pulling the lens posteriorly. Pupillary block may also be associated with a dislocated lens due to herniation of vitreous into the pupil. Peripheral anterior synechiae may develop from a long-standing pupillary block and produce chronic IOP elevation.

Phacolytic Glaucoma

In some cases, the lens may dislocate completely into the vitreous cavity and later undergo degenerative changes with release of material that obstructs aqueous outflow (24). In one reported case, this condition was associated with retinal perivasculitis, which cleared along with the glaucoma after removal of the lens (25). (Phacolytic glaucoma without dislocation is discussed later in this chapter.)

Concomitant Trauma

In cases of traumatic dislocation of the lens, concomitant trauma to the anterior chamber angle from the initial injury may be the cause of the associated glaucoma (1, 3). A transient pressure elevation of uncertain origin may persist for days or weeks after traumatic dislocation of the lens. (The mechanisms of glaucoma associated with trauma are considered in more detail in Chapter 25.)

Management

If the lens is displaced anteriorly in the anterior chamber or partially through the pupil, the condition may be relieved by dilating the pupil and allowing the lens to reposit back into the posterior chamber (26). A miotic agent may then be used to keep the lens behind the iris, but miotic therapy should be avoided when the pupillary block is caused by loose zonules, because contraction of the ciliary muscle further relaxes the zonular support, making the pupillary block worse (27). If the lens is completely dislocated in the anterior chamber, it is probably better to constrict the pupil and surgically remove the lens, rather than letting it fall back into the vitreous. Cycloplegic agents may help to break the attack by pulling the lens posteriorly. Hyperosmotic agents, carbonic anhydrase inhibitors, or topical (ß-blocke rs may also be useful in breaking the attack. The definitive treatment, however, is laser iridotomy (or incisional iridectomy, if necessary). The iridotomy should be placed peripherally to avoid subsequent obstruction by the lens. Prophylactic iridotomy in cases of microspherophakia has also been advocated to avoid pupillary block glaucoma (27). Laser peripheral iridoplasty may also be helpful in some cases of angle-closure glaucoma without a significant pupillary block component (22). The extraction of a subluxated lens is associated with increased surgical risk and should usually be avoided unless the lens is in the anterior chamber or lens extraction is needed to relieve the glaucoma or improve vision. Phacolytic Glaucoma

Phacolytic glaucoma is the only situation in cases of lens dislocation in which cataract extraction is the procedure of choice (28). Subluxated lenses can be successfully removed through a pars plana approach with vitreous instruments (25).

Chronic Glaucomas

Chronic glaucoma due to peripheral anterior synechiae or concomitant trauma in eyes with dislocated lenses is generally managed by standard medical measures. Laser trabeculoplasty has a low success rate in eyes with open-angle glaucoma associated with trauma, although this approach is often reasonable to try when medical therapy is no longer adequate before recommending incisional surgical intervention. P.289

Figure 18.6 High-magnification slitlamp view showing iridescent particles in the aqueous in a patient with phacolytic glaucoma. The white, cloudy cornea is seen to the right, and the dark iris to the left, of the photograph. (Courtesy of L. Frank Cashwell Jr, MD.)

GLAUCOMAS ASSOCIATED WITH CATARACT FORMATION

It has long been recognized clinically that several forms of glaucoma may occur in association with the formation of cataracts. However, an incomplete understanding of the various mechanisms for these glaucomas has led to a plethora of terms and considerable controversy and confusion. Later observations have provided new explanations and terminology for several of the glaucomas associated with cataract formation.

Phacolytic (Lens Protein) Glaucoma Terminology

In 1900, Gifford (29) described a form of open-angle glaucoma associated with a hypermature cataract. Among the terms subsequently suggested for this condition were phacogenic glaucoma and lens-induced uveitis (30, 31). Flocks and colleagues (32) reported histologic findings suggesting that the glaucomainducing mechanism was a macrophagic response to lens material. They proposed that this condition be called phacolytic glaucoma, which is the term most often used today. However, Epstein and colleagues (33, 34) have provided evidence that high-molecular-weight lens protein may be primarily responsible for the obstruction to aqueous outflow in this disorder, and the term lens protein glaucoma has been suggested (35).

Figure 18.7 A: Mature cataract in a patient with phacolytic glaucoma. B: B-scan ultrasonography shows a lens dislocated in the vitreous cavity.

Clinical Features

The typical patient presents with an acute onset of monocular pain and redness. There is usually a history of gradual reduction in visual acuity over the preceding months or years. Vision at the time of presentation may be reduced to light perception. The examination reveals a high IOP, conjunctival hyperemia, and diffuse corneal edema. The anterior chamber angle is open and usually grossly normal. A heavy flare is typically seen in the anterior chamber and is often associated with iridescent or hyperrefringent particles (Fig. 18.6). The latter have been variably reported to represent calcium oxalate or cholesterol crystals and are a helpful diagnostic sign in phacolytic glaucoma (36, 37 and 38). Chunks of white material may also be seen in the aqueous and on the anterior lens capsule and corneal endothelium. In five cases, specular microscopy revealed regular, round cells, about three times the size of an erythrocyte, which were found by histologic study of aqueous aspirates to represent macrophages (37). Rare cases of vitreous opacification have been reported (39). The opacities were observed at the time of cataract surgery and resolved spontaneously over 12 weeks. The cataract is typically mature and opaque (Fig. 18.7A) or hypermature (i.e., liquid cortex), but it may, rarely, be immature. A less common variation of phacolytic glaucoma is the previously discussed situation in which the lens has dislocated into the vitreous and undergone phacolysis (Fig. 18.7B). The latter cases differ clinically in that the glaucoma tends to be more subacute.

Theories of Mechanism

It is generally accepted that part of the pathogenesis in phacolytic glaucoma is the release of soluble lens protein into the aqueous through microscopic defects in the lens capsule.

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However, theories vary as to how this protein leads to the elevated IOP.

Figure 18.8 Light microscopic photograph of the trabecular meshwork area in a patient with phacolytic glaucoma demonstrates numerous macrophages in the anterior chamber angle (bottom) adjacent to the meshwork.

It has been postulated that macrophages, laden with phagocytosed lens material, block the trabecular

meshwork to produce the acute glaucoma (Fig. 18.8) (33). This theory has been supported by the demonstration of macrophages in the aqueous and trabecular meshwork of eyes with phacolytic glaucoma (40, 41). By electron microscopic study, these macrophages were found to have phagocytized, degenerated lens material (42). Electron microscopy has also demonstrated free-floating degenerated lens material in the aqueous and trabecular meshwork of an eye with phacolytic glaucoma (42). Against the macrophage theory is the observation that lens-laden macrophages in the anterior chamber do not invariably lead to elevated IOP. For example, a macrophagic cellular reaction has been found in the anterior chamber aspirate after needling and aspiration of a cataract but did not appear to obstruct aqueous outflow (43). However, the number of macrophages in the aqueous may be greater in phacolytic glaucoma.

An alternative theory is that high-molecular-weight soluble protein from the lens directly obstructs the outflow of aqueous (33, 34 and 35). Such protein has been shown to cause a significant decrease in outflow when perfused in enucleated human eyes (33). High-molecular-weight soluble protein is known to increase in the cataractous lens and has been demonstrated in the aqueous of eyes with phacolytic glaucoma in quantities sufficient to obstruct aqueous outflow (34, 44). High-molecular-weight protein is rare in childhood lenses, which may explain why phacolytic glaucoma rarely occurs in children. Differential Diagnosis

Several forms of glaucoma manifest with the sudden onset of pain and redness, creating diagnostic confusion with phacolytic glaucoma. Acute angle-closure glaucoma must be ruled out on the basis of the gonioscopic examination. Open-angle glaucoma associated with uveitis may be more difficult to distinguish. In some cases, a paracentesis and microscopic examination of the aqueous may be helpful by demonstrating amorphous protein-like fluid and occasional macrophages in eyes with phacolytic glaucoma (38). A therapeutic trial of topical steroids can produce only temporary remission when phacolysis is the underlying problem, which may help to distinguish it from a primary uveitis. Other conditions, such as neovascular glaucoma, trauma, and rarely, an occult posterior segment tumor, may also present with a similar clinical picture. Usually, these causes can be readily distinguished on the basis of history or clinical findings. It is always wise to perform B-scan ultrasonography when the view of the posterior segment is obscured by media opacity.

Management

Phacolytic glaucoma should be handled as an emergency, ultimately by removal of the lens (45). It is desirable to first bring the IOP under medical control with hyperosmotics, carbonic anhydrase inhibitors, and topical ß-blockers or a 2-agonists and possibly to minimize associated inflammation with topical

steroid therapy (38). When the pressure cannot be lowered medically, it may be necessary to accomplish this at the time of surgery by gradual release of aqueous through a paracentesis incision. Phacoemulsification or traditional extracapsular cataract extraction with posterior chamber intraocular lens implantation can often be performed with good results. The anterior chamber should be thoroughly irrigated and all lens material removed to avoid postoperative IOP rise. After uncomplicated cataract surgery, the glaucoma usually clears, and there is often a return of good vision despite a significant preoperative reduction.

In a retrospective study of eyes with phacolytic glaucoma in which trabeculectomy was added to standard cataract surgery if symptoms endured for more than 7 days or if preoperative control of IOP with maximal medical treatment was inadequate, IOP was significantly lower in the combinedsurgery group compared with the group receiving cataract surgery only (46). At 6 months, IOP and visual acuity did not differ between the two groups. Another study of patients with phacolytic glaucoma and cataract surgery found IOP was less than 21 mm Hg in all patients without use of any antiglaucoma medication (47). This included a group of eyes that underwent extracapsular cataract extraction with posterior chamber intraocular lens implantation and another group of eyes that underwent only extracapsular cataract extraction. Eighteen of the 45 patients initially presented with light perception without projection, and 44% of these patients regained a visual acuity of 20/40 or better. There were no significant intraoperative or postoperative complications. In view of the previously described studies, it seems reasonable to proceed with cataract extraction alone in patients with phacolytic glaucoma who