Joshua Gould,
Cynthia Mattox
Abnormalities of the crystalline lens may incite elevation of intraocular pressure often accompanied by significant intraocular inflammation. These pathologic conditions are traditionally known as phacogenic or lens-induced glaucomas.[1] Three of these entities, namely phacolytic glaucoma, lens particle glaucoma and lens-induced uveitis or phacoanaphylaxis are associated with obstruction of aqueous outflow at the level of the trabecular meshwork and are therefore considered secondary open-angle glaucomas. Phacomorphic glaucoma and lens displacement glaucoma involve pretrabecular obstruction to outflow through anterior displacement of the lens-iris diaphragm or pupillary block with resultant narrowing of the iridocorneal angle. These entities are considered secondary narrow-angle glaucomas.
With the introduction and increasing use of phakic intraocular lenses for high myopia, a new and unique population of phakic patients are encountered in whom secondary lens-induced glaucoma may be observed.
PHACOLYTIC GLAUCOMA
Phacolytic glaucoma is a clinical entity named by Flocks et al in 1955.[2] It is associated with hypermaturity of the crystalline lens with liquefaction of lens cortex and passage of lens proteins through the lens capsule (see Fig. 207.1). Patients are typically elderly and present with sudden onset of unilateral pain and diminution of vision in an eye with a prior history of poor vision due to cataract. Examination reveals elevated intraocular pressure, injection, corneal edema and prominent flare reaction with few anterior chamber cells. The anterior chamber is typically deep. Gonioscopy may be difficult due to corneal edema but shows an open iridocorneal angle. The lens exhibits advanced cataractous change which may be Morgagnian in nature with liquefied cortex and a brunescent nucleus. The anterior lens capsule may be dotted with white flecks representing collections of macrophages engulfing liberated lens material or may be wrinkled in appearance as the lens material beneath the capsule decreases in volume.
|
|
|
|
FIGURE 207.1 Hypermature cataract that caused phacolytic glaucoma. |
The mechanism of intraocular pressure elevation historically focused on the obstruction of the trabecular meshwork by macrophages with foamy cytoplasm swollen by ingestion of lens protein. These macrophages may be isolated after aqueous paracentesis through a millipore filtration technique and this technique has been proposed as a means of confirming the diagnosis of phacolytic glaucoma.[3]Specular microscopy has also been used in vivo to identify foamy macrophages on the corneal endothelium.[4] Chemotaxis of blood monocytes to lens proteins has been demonstrated in vitro with the gamma crystalline fraction being the strongest stimulus for monocyte chemotaxis.[5] While macrophages, when present, may themselves obstruct the trabecular meshwork, considerable attention has been given to heavy molecular weight proteins as a source of trabecular obstruction. Cases of phacolytic glaucoma have been reported in which few or no macrophages have been isolated.[6] In a series of six patients one exhibited no macrophages and two had a very small number of the characteristic cells in the aqueous. Epstein, Jedziniak, and Grant found a 14-fold higher concentration of heavy-molecular weight proteins (HMW) in the hypermature lenses of phacolytic patients compared to patients with immature cataracts. Aqueous samples obtained at the time of surgery showed HMW proteins comprising 35% of the total aqueous protein in the phacolytic patients. No HMW protein was isolated from the aqueous of the six control subjects with immature cataracts.[7] The same group of investigators in a series of elegant experiments demonstrated a 60% reduction in aqueous outflow in cadaveric eyes when irrigated with HMW proteins. This was similar to the 68% reduction in outflow observed with 1% whole lens homogenate. Low-molecular weight proteins did not cause observable obstruction to fluid flow. Aqueous aspirate from patients with phacolytic glaucoma has also been reported to contain calcium oxalate crystals.[8]
The treatment of phacolytic glaucoma is primarily surgical. Preoperative medical efforts to lower intraocular pressure through the use of topical beta-blockers, alpha-agonists and topical and oral carbonic anhydrase inhibitors should be employed. Additionally topical corticosteroids should be administered frequently and oral corticosteroids may be considered.[9] Historically, intracapsular cataract extraction was the treatment of choice however the role of extracapsular cataract extraction (ECCE) with implantation of a posterior chamber intraocular lens is now well established.[9,10] Use of trypan blue dye for anterior capsular staining may greatly increase facility in creating an anterior capsulorrhexis. Liquefied cortex liberated at the initiation of the capsulorrhexis may be gently aspirated with a hand-held Simcoe irrigation-aspiration (IA) unit or other IA handpiece. The depleted volume of the capsular bag should then be reestablished with viscoelastic and the capsulorrhexis completed in a continuous curvilinear fashion. Radial relaxing incisions in the circular capsulorrhexis created with a cystotome or Gill's scissors may be necessary prior to the expression of the lens nucleus, if the nucleus is large. An appropriate intraocular lens may be implanted at the time of surgery.
The postoperative course is generally associated with resolution of inflammation and normalization of the intraocular pressure usually without glaucoma medication.
A visual acuity of 20/40 or better was reported in 76.5% of 28 eyes undergoing ECCE with posterior chamber intraocular lens (PCIOL) for phacolytic glaucoma.[10]
|
Key Features: Phacolytic Glaucoma |
|||||||||||||||
|
LENS PARTICLE GLAUCOMA
Elevation of intraocular pressure in the context of retained lens material in the aqueous is known as lens particle glaucoma (see Figs 207.2 and 207.3). Lens particle glaucoma is associated with antecedent trauma with disruption of the lens capsule or intraocular surgery such as ECCE or phacoemulsification. Lens particle glaucoma has been reported 12 years after cat-aract extraction in association with subluxation of a PCIOL and liberation of residual lens cortex.[11] Dislocation of a Soemmering's ring into the anterior chamber may also precipitate lens particle glaucoma years after lensectomy.[12]
|
|
|
|
FIGURE 207.2 (a) Low-magnification image of granulomatous reaction surrounding lens material in the anterior chamber after traumatic lens rupture. H&E. (b) High-magnification image of foamy macrophages ingesting lens material. H&E. |
|
|
|
|
FIGURE 207.3 Lens particle glaucoma. |
Lens particle glaucoma is recognized by the characteristic lens fragments in the anterior chamber. The eye is injected with elevated intraocular pressure. Localized or diffuse corneal edema and a marked cell and flare reaction are present in the anterior chamber, as are portions of the crystalline lens. Gonioscopy may reveal obvious lens particles overlying the trabecular meshwork.
The mechanism of aqueous outflow impairment is direct obstruction of the trabecular meshwork by lens fragments. It is likely that cellular reaction to the lens particles contributes to trabecular obstruction as well. Experiments with cadaveric eyes have demonstrated markedly diminished trabecular outflow when the anterior chamber is perfused with whole lens homogenate.[6]
With modern phacoemulsification techniques, small fragments of lens may be left behind during routine cataract surgery. Eyes with prolonged low-grade inflammation requiring treatment with topical steroids after cataract surgery may harbor an unnoticed fragment. If the eye also has elevated intraocular pressure, differentiation from steroid-induced glaucoma is sometimes difficult.
If the diagnosis is in question lens particle glaucoma can be confirmed by anterior chamber paracentesis. Aqueous samples should reveal fragments of lens material along with macrophages. Ultrasound biomicroscopy may aid in locating lens fragments sequestered behind the iris.
Treatment involves medical therapy with topical beta-blockers, alpha-agonists and topical or oral carbonic anhydrase inhibitors to control intraocular pressure. Miotics should be avoided to prevent synechiae and further compromise of the blood-aqueous barrier. Topical corticosteroids are desirable to reduce the amount of inflammation but should not be administered so frequently as to suppress the phagocytosis of lens material by inflammatory cells. Topical cycloplegics may also be used.
Surgical intervention may be required in eyes that do not respond well to medical therapy. If the eye has an underlying glaucoma or is at risk for corneal decompensation and a fragment of lens is noticed early postoperatively, prompt removal may save the eye from prolonged inflammation, corneal edema, and glaucoma. Prompt removal will also prevent loculation of lens material within inflammatory membranes further complicating surgery.[13]
|
Key Features: Lens Particle Glaucoma |
||||||||||||
|
LENS-INDUCED UVEITIS (PHACOANAPHYLAXIS)
Lens-induced uveitis also known as phacoanaphylactic glaucoma and phacoantigenic endophthalmitis is the most confounding of the three open-angle, lens-induced glaucomas. This entity was first termed endophthalmitis phacoanaphylactica by Verhoeff in 1922.[14] With regard to its mechanism, it is most clear and appropriate to use the term lens-induced uveitis. This name reinforces the fact that the inflammation seen is due to an abnormal intolerance to self-antigens with intense intraocular inflammation incited by residual lens material in the eye. Most frequently this disorder is associated with hypotony rather than elevation in intraocular pressure and here again the term lens-induced uveitis is most appropriate as 'glaucoma' is excluded from this name. Likewise the exclusion of the term anaphylaxis is appropriate as neither IgE, basophils, nor mast cells serve a role in this inflammatory response.
Lens-induced uveitis is a rare entity characterized histopathologically by the formation of concentric layers of polymorphonuclear leukocytes, lymphocytes, epithelioid cells and multinucleated giant cells surrounding lens material. These are known as zonal granulomas.[15]
It has been demonstrated that normal control subjects possess antibodies to lens antigens and this suggests that lens antigens are not sequestered throughout embryonic development but are recognized as self.[16] Lens-induced uveitis may be considered an autoimmune response as there is an acquired intolerance to self-antigens rather than sensitization to new, formerly sequestered antigens.
Patients may present within hours to months after surgery or trauma.[17] Lens-induced uveitis may be seen in the initial postsurgical or traumatized eye or later in the patient's fellow eye following cataract extraction or other cause for liberation of lens protein.[18,19] Inflammation may be severe with marked injection, keratic precipitates and aqueous cell and flare. A sterile hypopyon may also be present. Intraocular pressure is most commonly low until later in the course when peripheral synechial angle closure or pupillary block due to seclusio pupillae may develop. Residual lens material may or may not be visible clinically but is always present.
Medical therapy with topical or systemic corticosteroids and cycloplegics may suppress inflammation for a period however medical treatment is characterized by a relapsing and remitting course of intraocular inflammation rarely leading to synechial sequelae, cyclitic membrane formation and phthisis bulbi. Definitive treatment involves surgical removal of all residual lens material ideally by pars plana vitrectomy.
|
Key Features: Lens-Induced Uveitis |
||||||||||||||||||
|
PHACOMORPHIC GLAUCOMA
The name of this entity stems from the Greek root morphos meaning shape or form. This condition involves an abnormality in the size of the lens associated with secondary angle-closure glaucoma. Phacomorphic glaucoma presents in the context of an advanced senile cataract or traumatic cataract that becomes intumescent (see Fig. 207.4). It is seen more commonly in areas with limited access to ophthalmic care in which more advanced cataracts are frequently encountered. The mechanism involves anterior displacement of the lens-iris diaphragm by the swollen cataractous lens with pretrabecular occlusion to aqueous outflow by the peripheral iris. In addition to peripheral occlusion of the iridocorneal angle due to an anterior pushing force from the intumescent lens, there is usually a component of pupillary block in phacomorphic glaucoma. The inability of aqueous to flow through the pupil and into the anterior chamber results in a positive pressure gradient between the posterior and anterior chamber leading to iris bombé and further closure of the iridocorneal angle.
|
|
|
|
FIGURE 207.4 Mature cataract causing phacomorphic glaucoma. |
It may be vexing to distinguish phacomorphic glaucoma from primary angle-closure glaucoma. Both are generally seen in hyperopic eyes with relatively short axial lengths and crowding of the anterior segment structures. Usually the affected eye has a more shallow anterior chamber. Gonioscopy of the fellow eye in cases of unilateral angle-closure glaucoma is critical diagnostically. A nonoccludable, contralateral angle makes primary angle closure unlikely and one should consider other mechanisms by which the lens-iris diaphragm may become rotated anteriorly such as a choroidal mass, choroidal effusion, scleral buckle, plateau iris, iris and ciliary body cysts or lens subluxation or dislocation. Ultrasound biomicroscopy can be used to diagnose these posterior mechanisms.
The need to distinguish primary angle closure from phacomorphic glaucoma is important from a therapeutic standpoint. If one observes an advanced cataract in an eye with acute angle closure, it is wise to avoid miotic therapy as this may worsen the anterior rotation of the lens-iris diaphragm further obstructing outflow. Likewise, angle closure caused by choroidal effusion, choroidal mass or scleral buckle are appropriately treated with cycloplegic agents and may be worsened by cholinergic medications.
Initial therapy for phacomorphic glaucoma consists of topical beta-blockers, alpha-agonists, carbonic anhydrase inhibitors and frequent administration of topical corticosteroid. In patients with phacomorphic glaucoma there is nearly always some component of pupillary block and thus performing a peripheral laser iridotomy after medical therapy is initiated is appropriate but not curative. Definitive treatment involves extraction of the intumescent cataract. Cataract extraction in these inflamed eyes presents a higher risk of complication and surgical therapy is ideally delayed until control of inflammation and intraocular pressure is achieved to lessen corneal edema and improve visualization during surgery. Phacomorphic glaucoma is frequently a disease of the elderly and therefore the use of oral or intravenous carbonic anhydrase inhibitors or osmotics to lower intraocular pressure may present an unacceptable risk to the patient. The use of argon laser peripheral iridoplasty (ALPI) has been advocated as a temporizing measure. A retrospective review of 21 eyes with phacomorphic glaucoma found success in temporizing 17 out of 21 eyes (80.95%) with ALPI and topical medication. Success was defined as an IOP less than 30 mmHg at 2 h and IOP less than 20 mmHg at 24 h after ALPI.[20]
Persistent elevation of intraocular pressure following cat-aract extraction in patients with phacomorphic glaucoma may be the result of peripheral anterior synechiae (PAS) formation. Goniosynechiolysis during cataract surgery may alleviate the angle obstruction and improve the prognosis for those eyes with angle closure existing for less than 6 months. Patients with chronic angle closure due to PAS may require concomitant or subsequent filtering or tube shunt surgery following cataract extraction.
|
Key Features: Phacomorphic Glaucoma |
|||||||||||||||||||||
|
LENS DISPLACEMENT GLAUCOMA
Ectopia lentis involves subluxation or dislocation of the crystalline lens and may be associated with acute, intermittent or chronic elevations in intraocular pressure. Subluxation of the lens implies a partial dehiscense of the zonules with alteration in the normal position of the lens within the eye. Dislocation of the lens is seen when there is a total lack of zonular support.
Lens subluxation may be a subtle clinical finding with iridodonesis and phacodonesis seen at the slit lamp. More obvious cases may present with readily apparent decentration of the lens. Lens dislocation may occur into the vitreous cavity or anterior chamber (Fig. 207.5).
|
|
|
|
FIGURE 207.5 Angle-closure glaucoma caused by a congenitally dislocated lens. |
A variety of mechanisms account for increased intraocular pressure associated with ectopia lentis. Anterior displacement of the lens may obstruct aqueous flow through the pupil causing pupillary block. Likewise the intact hyaloid face may lead to pupillary block in the setting of posterior or anterior lens dislocation. Anterior displacement of the lens may cause narrowing of the iridocorneal angle with acute elevation in intraocular pressure or over time lead to the formation of PAS and chronic angle-closure glaucoma. Complete posterior dislocation of the lens into the vitreous cavity usually has a benign course and lenses may be observed in the vitreous cavity for years without sequelae. Rarely phacolytic glaucoma may develop as the lens matures releasing heavy molecular weight proteins and inciting an inflammatory response. This type of phacolytic glaucoma has been reported as early as age 32 in a woman with homocystinuria and posterior lens dislocation.[21]
|
Key Features: Lens Displacement Glaucoma |
||||||||||||||||||
|
Several heritable disorders are commonly associated with ectopia lentis namely, Marfan's syndrome, homocystinuria, simple ectopia lentis, Weill-Marchesani syndrome, ectopia lentis et pupillae, sulfite oxidase deficiency and isolated microspherophakia. There are myriad other heritable disorders in which ectopia lentis has been reported. Acquired ectopia lentis may be due to trauma, pseudoexfoliation syndrome, High myopia, intraocular tumor, mature cataract, buphthalmos, uveitis or syphilis.[22] Pseudoexfoliation syndrome associated anterior lens displacement is common and may be present in the absence of frank phacodonesis. It manifests as subtle shallowing of the anterior chamber with narrowing of the angle, and often requires prophylactic laser iridotomy. It is particularly important to recognize to prepare for the zonular weakness that will be encountered during cataract surgery.
Treatment of glaucoma due to ectopia lentis is highly individualized and is aimed at the underlying pathophysiologic mechanism of intraocular pressure elevation. Acute angle-closure glaucoma may be due to anterior displacement of the lens-iris diaphragm secondary to lens subluxation with peripheral narrowing of the angle or due to pupillary block by the ectopic lens with peripheral iris bombé. Miotics are not used in this context. Laser peripheral iridotomy is useful in relieving pupillary block and cycloplegia may help relax the zonules achieving posterior rotation of the lens-iris diaphragm.
Anterior dislocation of the lens into the anterior chamber must be addressed emergently as lenticular-corneal touch may lead to fusion of the anterior capsule with the corneal endothelium with attendant corneal decompensation. It may be possible to manage anterior lens dislocation medically with mydriasis and supine positioning of the patient with the intent of causing posterior dislocation of the lens.
Posterior dislocation of the crystalline lens into the vitreous which is complicated by phacolytic glaucoma is treated by pars plana vitrectomy and lensectomy by phacofragmentation.
GLAUCOMA ASSOCIATED WITH PHAKIC INTRAOCULAR LENSES
Phakic intraocular lenses were first introduced in the 1950s.[23] Implantation of an intraocular lens in a phakic patient is employed in the setting of high myopia as a refractive procedure. Phakic intraocular lenses have the advantage of preserving accommodative function as compared to clear lens extraction. They are also free of the limitations of keratorefractive surgery in correcting highly myopic patients. Early lenses were associated with unacceptable rates of corneal decompensation and uveitis-glaucoma-hyphema syndrome.
Various models of phakic IOLs that have been approved by the Food and Drug Administration (FDA) and in Europe are placed either behind or in front of the iris.[24,25] Those models that are placed behind the iris and vault over the crystalline lens are particularly prone to causing pupillary block and require preoperative laser iridotomies. Early postoperative IOP elevation may be seen due to inadequate removal of viscoelastic material. Early onset of malignant glaucoma has also been reported.[26] Phakic patients in whom intraocular lenses are implanted may present with elevated intraocular pressure due to narrowing of the iridocorneal angle by anterior displacement of the peripheral iris by lens haptics or secondary to pupillary block.[23,25,27-29] Secondary open-angle mechanisms should also be considered including pigmentary, uveitic or steroid-induced glaucoma. Patients with phakic intraocular lenses should be monitored closely for elevated intraocular pressure, gonioscopic changes in the iridocorneal angle and glaucomatous optic neuropathy for an indefinite period of time postoperatively. Optic disk changes may be particularly difficult to appreciate in high myopes receiving these lenses and thus the potential for undetected glaucomatous optic neuropathy in these patients is of great concern. Further studies to establish the long-term safety of these lenses are ongoing.
|
Key Features: Phakic Intraocular Lenses |
|||||||||||||||
|
REFERENCES
1. Appleton B, Lowrey Jr A: Phacogenic glaucoma. Am J Ophthalmol 1959; 47:682.
2. Flocks M, Littwin CS, Zimmerman LE: Phacolytic glaucoma. Arch Ophthalmol 1955; 54:37.
3. Goldberg MF: Cytological diagnosis of phacolytic glaucoma utilizing Millipore filtration of the aqueous. Br J Ophthalmol 1967; 51:847.
4. Brooks AMV, Grant G, Gillies WE: Comparison of specular microscopy and examination of aspirate in phacolytic glaucoma. Ophthalmology 1990; 97:85.
5. Rosenbaum JT, Samples JR, Seymour B, et al: Chemotactic activity of lens proteins and the pathogenesis of phacolytic glaucoma. Arch Ophthalmol 1987; 105:1582.
6. Epstein DL, Jedziniak JA, Grant WM: Obstruction of aqueous outflow by lens particles and by heavy-molecular-weight soluble lens proteins. Invest Ophthalmol Vis Sci 1978; 17:272.
7. Epstein DL, Jedziniak JA, Grant WM: Identification of heavy-molecular-weight soluble protein in aqueous humor in human phacolytic glaucoma. Invest Ophthalmol Vis Sci 1978; 17:398.
8. Bartholomew RS, Rebello PF: Calcium oxalate crystals in aqueous. Am J Ophthalmol 1979; 88:1026.
9. Lane SS, Kopietz LA, Lindquist TD, et al: Treatment of phacolytic glaucoma with extracapsular cataract extraction. Ophthalmology 1988; 95:749.
10. Mandal AK, Gothwal VK: Intraocular pressure control and visual outcome in patients with phacolytic glaucoma managed by extracapsular cataract extraction with or without posterior chamber intraocular lens implantation. Ophthalmic Surg Lasers 1998 Nov; 29:880-889.
11. Lim MC, Doe EA, Vroman DT, et al: Late onset lens particle glaucoma as a consequence of spontaneous dislocation of an intraocular lens in pseudoexfoliation syndrome. Am J Ophthalmol 2001; 132:261-263.
12. Epstein DL: Diagnosis and management of lens-induced glaucoma. Ophthalmology 1982; 89:227.
13. Richter C, Epstein DL: Lens-induced open-angle glaucoma. In: Ritch R, Shields MB, Krupin T, ed. The glaucomas, St Louis: CV Mosby; 1989.
14. Verhoeff FH: Endophthalmitis phacoanaphylactica. Proceedings International Congress of Ophthalmology, Washington DC. 1922, p 177.
15. Apple DJ, Mamalis N, Steinmetz RL, et al: Phacoanaphylactic endophthalmitis associated extracapsular cataract extraction and posterior chamber intraocular lens. Arch Ophthalmol 1984; 102:1528.
16. Nissen SH, Anderson P, Anderson HMK: Antibodies to lens antigen in cataracts after cataract surgery. Br J Ophthalmol 1981; 65:63.
17. Perlman EM, Albert DM: Clinically unsuspected phacoanaphylaxis after ocular trauma. Arch Ophthalmol 1977; 95:244.
18. Irvine SR, Irvine Jr AR: Lens-induced uveitis and glaucoma. I: Endophthalmitis phacoanaphylactica. Am J Ophthalmol 1952; 35:177.
19. deVeer JA: Bilateral endophthalmitis phacoanaphylacta. Arch Ophthalmol 1953; 49:607.
20. Yip PP, Leung WY, Hon CY, Ho CK: Argon laser peripheral iridoplasty in the management of phacomorphic glaucoma. Ophthalmic Surg Lasers Imaging 2005; 36:286-291.
21. Smith GT, Vakalis AN, Brittain GP, Casswell AG: Related Articles, Links Vitrectomy for phacolytic glaucoma in a patient with homocystinuria. Am J Ophthalmol 1999; 128:762-763.
22. Liebman JM, Ritch R: Glaucoma secondary to lens intumescence and dislocation. In: Ritch R, Shields MB, Krupin T, ed. The glaucomas, St Louis: CV Mosby; 1989.
23. Apple DJ, Mamalis N, Steinmetz RL, et al: Phacoanaphylactic endophthalmitis associated extracapsular cataract extraction and posterior chamber intraocular lens. Arch Ophthalmol 1984; 102:1528.
24. Alio JL, de la Hoz F, Perez-Santonja JJ, et al: Phakic anterior chamber lenses for the correction of myopia: a 7-year cumulative analysis of complications in 263 cases. Ophthalmology 1999; 106:458-466.
25. Sanders DR, Vukich JA, Doney K, Gaston MImplantable Contact Lens in Treatment of Myopia Study Group: U.S. Food and Drug Administration clinical trial of the Implantable Contact Lens for moderate to high myopia. Ophthalmology 2003; 110:255-266.
26. Kodjikian L, Gain P, Donate D, et al: Malignant glaucoma induced by a phakic posterior chamber intraocular lens for myopia. J Cataract Refract Surg 2002; 28:2217-2221.
27. Trindade F, Pereira F: Gonioscopic changes after ICL implantation in myopic eyes. J Cataract Refract Surg 2002; 28:1896-1897.
28. Smallman DS, Probst L, Rafuse PE: Pupillary block glaucoma secondary to posterior chamber phakic intraocular lens implantation for high myopia. J Cataract Refract Surg 2004; 30:905-907.
29. Pineda-Fernandez A, Jaramillo J, Vargas J, et al: Phakic posterior chamber intraocular lens for high myopia. J Cataract Refract Surg 2004; 30:2277-2283.
