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Angle-closure glaucoma
Disease-a-Month 60 (2014) 254–262
Contents lists available at ScienceDirect
Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth
Angle-closure glaucoma Krishna Patel, BS, Shuchi Patel, MD
Introduction Glaucoma is defined as an optic neuropathy causing peripheral vision loss. The etiology of glaucoma can be divided according to its pathophysiology. The broad classifications of glaucoma include open-angle and closed-angle glaucoma. As determined in the 2000 US census, it is estimated that primary open-angle glaucoma affects 2.22 million US citizens. Owing to the rapidly aging population, the number with open-angle glaucoma will increase by 50% to 3.36 million in 2020.1 In contrast, angle-closure glaucoma is not as common in the United States, as it accounts for only 10% of all glaucoma. However, it is more prevalent worldwide with estimates that 5.3 million people will be blinded by primary angle-closure glaucoma by 2020.2 Angle-closure glaucoma is caused by apposition of the peripheral iris to the trabecular meshwork, resulting in reduced drainage of aqueous humor through the anterior chamber angle. This usually occurs because the iris is either pushed or pulled anteriorly into the angle. Based on these anatomic definitions, angle-closure glaucoma can be further classified into primary angleclosure glaucoma or secondary angle closure. As the name indicates, primary angle closure has no causative mechanism leading to appositional angle closure. Secondary angle closures have identifiable mechanisms for the apposition of the iris to the angle or closure of the angle by direct blockage of the trabecular meshwork.
Primary angle-closure glaucoma Primary angle-closure glaucoma (PACG) is caused by pupillary block in 90% of cases. Pupillary block is caused by apposition of the iris against the lens restricting the efflux of aqueous from the posterior chamber to the anterior chamber and subsequent drainage through the trabecular meshwork (Fig. 1). The accumulation of the aqueous in the posterior aspect causes bowing of the iris anteriorly and eventual closure of the angle. This can happen acutely, intermittently, or chronically. There are multiple risk factors for PACG. Patients with hyperopia, or a short axial length of the eyeball, and an anterior chamber length of less than 2.5 mm are at an increased risk. The disease is more common in Eskimos and Southeast Asians populations with individuals over 40 years being at an increased risk as the lens thickens (due to cataract formation) and the anterior chamber depth shallows. Females are at a higher risk as they tend to have shallower anterior chambers,3 and those with a family history of PACG are also at an increased risk for the disease. http://dx.doi.org/10.1016/j.disamonth.2014.03.005 0011-5029/ Published by Mosby, Inc.
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Fig. 1. Pupillary block. (Woo E, Pavlin C, Slomovic A, Taback N, Buys Y. Ultrasound biomicroscopic quantitative analysis of light-dark changes associated with pupillary block. Am J Ophthalmol. 1999;127:43–47.)
Acute primary angle closure Acute primary angle closure is caused by a sudden block of the trabecular meshwork by the iris. Acute primary angle closure may be caused iatrogenically by mydriatics, and patients should be evaluated for narrow angles prior to using dilating drops. Symptoms include blurred vision, pain, colored halos around lights, nausea, emesis, and frontal headaches. Patients with acute primary angle closure may present clinically with increased intraocular pressure (IOP), a mid-dilated, non-reactive, or irregular pupil. On physical exam, corneal edema may be seen in these patients secondary to the extreme sudden elevation in pressure. Additionally, these patients may present with congested episcleral and conjunctival vessels, shallow anterior chambers, and mild cell and flare in the anterior chamber, indicative of an inflammatory process. Glaucomaflecken, which are anterior subcapsular or capsular opacities due to epithelial infarct, may be present as well. On gonioscopy, or examination of the angle, the contralateral eye usually has narrow angles as well, and there is a 40–80% chance of an acute attack in the other eye in 5–10 years. A study showed that without treatment, 51.3% (58/113) of patients developed an acute attack in the contralateral eye.4 Therefore, a prophylactic laser peripheral iridotomy (LPI) should be performed in the fellow eye relatively soon after treatment is started for the eye with angle closure. The elevation in pressure should first try to be reduced by using topical glaucoma drops, such as beta-blockers, carbonic anhydrase inhibitors, and alpha-agonists. Parasympatheticomimetics, such as pilocarpine, can also be used. Systemic hyperosmotic agents and topical steroids can be used as well. If the attack is recent, corneal indention with a gonioscopy lens can break the pupillary block and open the angle. Apraclonidine and nonselective adrenergic agonists should be avoided, as they may cause pupillary dilation/vasoconstriction and worsen the condition. These patients should be referred to an ophthalmologist for determination of further surgical interventions. Definitive treatment is a LPI performed with either an argon or YAG laser, although sometimes the procedure has to be delayed until the cornea is clear and the procedure can be performed safely.5
Intermittent (sub-acute) angle closure Patients with intermittent angle closure have periodic episodes of blurred vision, halos, and mild pain. These patients often have normal IOP in between episodes, and episodes often resolve during sleep due to miosis of the pupils. Treatment options include laser peripheral iridotomy, cataract extraction (if present), and goniosynechiolysis.
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Chronic angle closure Chronic angle closures occur after an episode of acute angle closure, or due to frequent intermittent angle closures. Most occur gradually, making them difficult to diagnose. These patients may have a lack of subjective findings. Gonioscopy is needed to accurately diagnose this, as chronic angle closure can be mistaken for primary open-angle glaucoma. Iridotomy is still needed in order to remove any component of pupillary block, and these patients may still require ocular medications or further surgery. Narrow anterior chamber angle A narrow anterior chamber is an anatomic finding that is a risk for angle closure. To determine if the patient is at high risk for pupillary block, and if a prophylactic LPI is indicated, provocative testing can be performed. There are three different tests that can be done. The darkroom test is performed by having the patient stay in a dark room causing the pupil to dilate. After 45 min, the pressure should be checked again. This method can identify about 50% of patients at risk. Another test that can be done is the prone test in which the patient lies face down for 1 h. It is more sensitive test with a sensitivity of 70%. Lastly, a phenylephrine test can be performed. The IOP should be rechecked at 1 h after dilation or when the pupil is at least 4 mm dilated. In any of these tests if the IOP increases by more than 8 mmHg from baseline, this is considered a positive test and a risk factor for acute angle closure. Plateau iris Plateau iris the only type of primary angle closure without pupillary block. It is an anatomic variation in which the iris root angulates forward from its insertion point, and then again centrally6 (Fig. 2). The abnormal configuration of the anterior chamber angle may result in acute or chronic angle-closure glaucoma. Plateau iris is most often caused by anteriorly positioned ciliary processes that push the peripheral iris forward, which can block the trabecular meshwork. Plateaus iris with acute angle closure is seen more commonly in young patients with myopia (near-sightedness).
Fig. 2. Plateau iris caused anterior rotation of ciliary body. (Tran H, Liebmann J, Ritch R. Iridociliary apposition in plateau iris syndrome persists after cataract extraction. Am J Ophthalmol. 2003;135(1):40–43.)
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In these patients, it should be noted that the central chamber depth is deeper than seen with the patients described previously. The definitive diagnosis of plateau iris can be made if angle closure continues to persist after iridotomy. These patients can be further treated by laser gonioplasty and chronic treatment with miotic agents.7
Secondary angle closure with pupillary block Lens-induced glaucoma Phacomorphic glaucoma Phacomorphic glaucoma is due to a large swollen lens that pushes the iris forward, leading to an intermittent pupillary block angle closure. The initial treatment is most often with topical medications such as beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors.8 Phacomorphic glaucoma can be treated by iridotomy for temporary relief and with cataract extraction for definitive treatment (Fig. 3). Microspherophakia Microspherophakia is an abnormally shaped lens. It is often familial and can be an isolated condition or part of other conditions such as Weill–Marchesani or Marfan syndrome. The anterior lens position and round shape lead to pupillary block angle-closure glaucoma. Medical treatment includes cycloplegics to flatten the lens and pull it more posteriorly. Conversely, miotics worsen the condition. A LPI or lens extraction is curative.9 Ectopia lentis Ectopia lentis occurs when there is displacement of the lens from the normal anatomic position. It can lead to intermittent pupillary block. An ophthalmologist can treat this by creating two laser peripheral iridotomies that are 1801 apart. Other diseases that should be kept in the differential include pseudoexfoliation syndrome, trauma, Marfan’s syndrome, homocystinuria, microspherophakia, and Weill–Marchesani10 (Fig. 4). Aphakic or pseudophakic angle-closure glaucoma In aphakic patients without a LPI, angle closure can occur from pupillary block by the contact between the iris and the intact anterior hyaloid face. In pseudophakic patients pupillary block can also occur. With an anterior chamber intraocular lens (ACIOL), the lens may directly block the pupil as it rests on the iris and therefore a peripheral iridectomy is usually made at the time
Fig. 3. Phacomorphic glaucoma. (Sowka J. Phacomorphic glaucoma. J Am Optom Assoc. 2006;77(12):586–589.)
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Fig. 4. Ectopia Lentis, with upward displacement of the lens, in a patient with Marfan’s syndrome. (Konradsen T, Koivula A, Kugelberg M, Zetterströ m C. Accommodation measured with optical coherence tomography in patients with Marfan’s syndrome. Ophthalmology. 2009;116(7):1343–1348.)
of ACIOL placement. Occasionally pupillary block can occur with a posterior chamber intraocular lens (PCIOL) due to the formation of posterior synechiae that result in iris bombe. Vitrectomy with intraocular gas/silicone oil Intraocular gas or silicone oil filling the posterior chamber for treatment of a retinal detachment can also be space occupying and cause a pupillary block. Since these substances are lighter than aqueous, an inferior LPI should be performed.
Secondary angle closure without pupillary block Neovascular glaucoma Neovascular glaucoma is usually caused by growth of new vessels within the angle, often due to ocular ischemia or ocular inflammation. Some causes of neovascular glaucoma include diabetic retinopathy, ischemic retinal vessel occlusions, and ocular ischemic syndrome.11 In cases of neovascular glaucoma, fine arborizing blood vessels can grow at the pupil margin, extend over the surface of the iris, and also into the angle (Fig. 5). The vessels then cross the ciliary body and scleral spur and branch over the trabecular meshwork but never onto endothelium. A fibrous membrane may also grow on the trabecular meshwork, which eventually contracts leading to peripheral anterior synechia and thus the development of secondary angleclosure glaucoma. Patients with neovascular glaucoma present with increased intraocular pressure and the symptoms that are associated with that including pain, injection, corneal edema, and anterior chamber reaction. A gonioscopy should always be performed on these patients. Overall, 10% of the time, patients may have neovascularization within the angle without having any neovascularization of the iris. It is important to distinguish dilated iris blood vessels due to inflammation from neovascularization. If neovascular glaucoma is caught early and the vitreous is clear, an ophthalmologist can perform a pan-retinal photocoagulation laser, but the effect of the laser can take weeks. Therefore, intravitreal anti-VEGF (endothelial growth factors) medications should be considered. If the neovascularization has regressed, but IOP remains elevated then a surgical procedure, such as a glaucoma drainage device, may be warranted. In cases of late disease with poor visual potential, a cyclodestructive procedure may be used.
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Fig. 5. Neovasculization of the angle leading to glaucoma. (Iliev M, Domig D, Schnurrbursch U, Wolf S, Sarra G. Intravitreat Bevacizumab (Avastins) in the treatment of neovascular glaucoma. Am J Ophthalmol. 2006;142(6):1054– 1056.)
Iridocorneal endothelial syndrome (ICE) There are multiple iridocorneal endothelial syndromes (ICE), including iris nevus syndrome, Chandler’s, and essential iris atropy. All of these disorders involve the corneal endothelium, which has a “beaten bronze” look. The endothelium starts to behave like epithelium and profilerates. On specular microscopy, the endothelium appears atypical with large spaces between cells and a low cell count. An endothelial membrane can grow over the angle, iris, and other structures. The layer of endothelial cells pulls the iris up to the cornea, leading to peripheral anterior synechia. This results in glaucoma in about 50% of the cases. The disease is almost always unilateral. The incidence of ICE is higher in women, and more common in people aged 20–50 years. Treatment options include hypertonic saline and glaucoma medications, but usually it is difficult to manage medically. Glaucoma surgery may therefore be indicated and multiple surgeries may be needed due to a higher failure rate of these procedure compared to other conditions.12 Epithelial downgrowth Epithelial downgrowth is a condition in which non-keratinized, stratified, squamous cell epithelium covers corneal endothelium, trabecular meshwork, iris, and the ciliary processes (Fig. 6). Epithelial cells can be seen in cytologic examination of the aqueous aspirate. Another way to confirm that there are indeed epithelial cell on surfaces that they do not belong on is to place a spot of argon laser in the area suspected to have this growth. If there are epithelial cells there, the argon causes whitening of the tissue and helps to identify the presence of the abnormal growth. The cells are usually present secondary to a penetrating wound or intraocular surgery and can cause a severe secondary glaucoma by blocking the trabecular meshwork. The treatment is by removing the epithelial membrane and affected tissues by curettage, intraocular cryotherapy, or laser therapy. The overall prognosis of this disease is poor despite surgical treatment of the underlying cause. Medical or surgical treatment to manage the increased pressure is usually needed because the primary etiology is difficult to cure. Fibrous ingrowth Fibrous ingrowth is caused by fibroblast proliferation following a penetrating wound in the anterior chamber. It is not as aggressive as epithelial downgrowth but can cause corneal
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Fig. 6. Epithelial downgrowth. (Nemi A, Bahadur R, Randleman J. Traumatic epithelial downgrowth after radial keratotomy. J Cataract Refract Surg. 2008;34(2):327–329.)
decompensation and a secondary glaucoma.13 The treatment is first by medical therapy for the increased pressure followed by surgical intervention if needed. Intraocular tumors Intraocular tumors can cause glaucoma by different mechanisms depending on the location of the tumor. If the tumor is found in the posterior segment, the tumor may cause the iris–lens diaphragm to be pushed forward, resulting in a secondary angle closure. If the tumor is in the anterior segment, it may cause a secondary glaucoma via direct tumor invasion of the angle, rotation of the ciliary body, intraocular heme, rubeosis iridis, deposition of tumor cells, or inflammatory or cellular debris within the trabecular meshwork. The most common type of intraocular tumors leading to glaucoma is uveal melanoma. Treatment of the underlying cause is usually more important than treating just the high pressure, but the pressure is managed medically, and if needed, surgically as well. Inflammation Inflammation can cause posterior synechia and then iris bombe leading to secondary angle closure. The peripheral anterior synechia seen secondary to inflammation is often inferior and non-uniform in shape and height. This is different than synechia that occur with primary angle closure, in which case the peripheral anterior synechia is often superior. Treatment should be aimed at reducing the inflammation and then the pressure should be managed either medically or surgically. Aqueous misdirection Aqueous misdirection, also known as malignant glaucoma, is a rare cause of glaucoma. It almost always presents after ocular surgery, often in patients with pre-existing angle-closure glaucoma or peripheral anterior synechia. Aqueous misdirection usually has a uniform flattening of the central and peripheral anterior chamber, and elevated intraocular pressure. Aqueous misdirection is caused by an anterior rotation of the ciliary body with posterior misdirection of the aqueous, combined with a block to aqueous movement into the anterior chamber. A patent peripheral iridotomy is needed in order to make the diagnosis.
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Medical management of aqueous misdirection should be with mydriatics, aqueous suppressors, and hyperosmotic agents. Miotic agents should be avoided as they worsen the condition by causing further anterior rotation of the ciliary body. YAG laser to disrupt the anterior hyaloid face or argon laser to shrink the ciliary processes may reverse the condition. Definitive treatment is pars plana vitrectomy.14 Retinal surgery/retinal vascular disease A scleral buckle is one of the ways to treat a retinal detachment. The buckle encircles the eye and pushes the sclera towards the middle of the eye to relieve the pull on the retina, placing the retina and underlying tissue in proximity to allow the tear to heal. However, the encircling band can cause congestive swelling with forward motion of the ciliary body and subsequent occlusion of the angle. There can also be an increase in IOP due to obstruction to venous outflow into vortex system by the encircling band. This can be treated by cycloplegics, carbonic anhydrase inhibitors, and topical steroids. Iridectomy is of little benefit. The chamber usually deepens over several weeks with medical therapy. Central retinal vein occlusion Central retinal vein occlusions (CRVO) can be a cause of glaucoma, independent of causing neovascular glaucoma by causing early shallowing of the chamber angle, presumably due to swelling of the choroid and ciliary body. With resolution of the CRVO, the chamber deepens. Nanophthalmos Nanophthalmos can be defined as a normal-shaped, but small eye. The axial length of the eye is less than 20 mm. In this case, the lens of the eye is relatively large in comparison to the volume of the eye. This can lead to angle closure. Also, the thickened sclera impedes vortex vein drainage, also increasing IOP. Glaucoma in this instance can be treated by laser iridectomy, laser iridoplasty, and medical therapy. Caution during surgical intervention needs to be taken as there is a high risk for choroidal effusions in nanophthalmic eyes.15 Retinopathy of prematurity (ROP)/persistant fetal vasculature/persistent primary hyperplastic vitreous (PFV/PHPV) ROP is a disease affecting premature babies. Babies who are born before 31 weeks are at an increased risk. Contracting retrolental tissue in ROP can cause progressive shallowing of the anterior chamber and angle closure. In cases of PFV/PHPV, there is a unilateral microphthalmos and elongated ciliary processes. Glaucoma can occur due to contracture of the primary vitreous and swelling of the cataractous lens. Drug-induced secondary angle-closure glaucoma Certain medications can lead to secondary angle-closure glaucoma.16 One such medication is topiramate, which is a sulfamate-substituted monosaccharide. It can lead to an acute myopic shift and bilateral angle-closure glaucoma due to ciliochoroidal effusion.17 Symptoms usually begin within 1 month of initiating therapy. The first step to treat drug-induced secondary angleclosure glaucoma is cessation of the offending agent, followed by using aqueous suppressants and cycloplegics. An iridotomy is not indicated for this cause of glaucoma. Interestingly enough, acetazolamide, which is a medication used to reduce intraocular pressure, can induce this type of secondary angle closure. Other sulfonamides, such as hydrochlorathiazide,18 can have similar effects.
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Conclusion In the US, POAG is more common than angle closure, yet angle closure still constitutes a large portion of glaucoma worldwide. Despite the cause, the symptoms are usually similar due to a significantly increased IOP and subsequent irreversible damage to the vision. Therefore, recognition of angle closure and the specific type is important for timely treatment to minimize both patient discomfort and permanent visual damage. References 1. Friedman DS, Wolfs RC, O’Colmain BJ, et al. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122(4):532–538. 2. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–267. 3. Lim AS. Primary angle-closure glaucoma in Singapore. Aust J Ophthalmol. 1979;7(7):23–30. 4. Henrietta H, Chew P, Sng C, Huang H, Aung T, Perera S. A comparison of two approaches to managing acute primary angle closure in Asian eyes. Clin Ophthalmol. 2013;7(7):1205–1210. 5. Ang L, Ang L. Current understanding of the treatment and outcome of acute primary angleclosure glaucoma: an Asian perspective. Ann Acad Med Singapore. 2008;37(3):210–214. 6. Diniz F, Cronemberger S, Merula RV, Calixto N. Plateau iris. Arg Bras Oftalmol. 2008;71(5):752–758. 7. Ang GS, Bochmann F, Azuara-Blanco A. Argon laser peripheral iridoplasty for plateau iris associated with iridociliary cysts: a case report. Cases J. 2008;1(1):368. 8. Kaplowitz1 K, Kapoor K. An evidence-based approach to phacomorphic glaucoma. J Clinic Exp Ophthalmol. 2011. 9. Senthil S, Rao HL, Hoang NT, et al. Glaucoma in microspherophakia: presenting features and treatment outcomes. J Glaucoma. 2014;23(4):262–267. 10. Tsilou E, MacDonald IM. Weill–Marchesani syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, eds. GeneReviews: Seattle, WA; University of Washington, Seattle (1993-2013). 2007. 11. Hayreh S. Neovascular glaucoma. Prog Retin Eye Res. 2007;26:470–485. 12. Doe EA, Budenz DL, Gedde SJ, Imami NR. Long-term surgical outcomes of patients with glaucoma secondary to the iridocorneal endothelial syndrome. Ophthalmology. 2001;108(10):1789–1795. 13. Smith MF, Doyle JW. Glaucoma secondary to epithelial and fibrous downgrowth. Semin Ophthalmol. 1994;9(4): 248–253. 14. Debrouwere V, Stalmans P, Van Calster J, Spileers W, Zeyen T, Stalmans I. Outcomes of different management options for malignant glaucoma: a retrospective study. Graefes Arch Clin Exp Ophthalmol. 2012;250(1):131–141. 15. Steijns D, Bijlsma WR, Van der Lelij A. Cataract surgery in patients with nanophthalmos. Ophthalmology. 2013;120(2): 266–270. 16. Lachkar Y, Bouassida W. Drug-induced acute angle closure glaucoma. Curr Opin Ophthalmol. 2007;18(2):129–133. 17. Panday VA, Rhee DJ. Review of sulfonamide-induced acute myopia and acute bilateral angle-closure glaucoma. Compr Ophthalmol Update. 2007;8(5):271–276. 18. Geanon JD, Perkins TW. Bilateral acute angle-closure glaucoma associated with drug sensitivity to hydrochlorothiazide. Arch Ophthalmol. 1995;113(10):1231–1232.
Contents lists available at ScienceDirect
Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth
Angle-closure glaucoma Krishna Patel, BS, Shuchi Patel, MD
Introduction Glaucoma is defined as an optic neuropathy causing peripheral vision loss. The etiology of glaucoma can be divided according to its pathophysiology. The broad classifications of glaucoma include open-angle and closed-angle glaucoma. As determined in the 2000 US census, it is estimated that primary open-angle glaucoma affects 2.22 million US citizens. Owing to the rapidly aging population, the number with open-angle glaucoma will increase by 50% to 3.36 million in 2020.1 In contrast, angle-closure glaucoma is not as common in the United States, as it accounts for only 10% of all glaucoma. However, it is more prevalent worldwide with estimates that 5.3 million people will be blinded by primary angle-closure glaucoma by 2020.2 Angle-closure glaucoma is caused by apposition of the peripheral iris to the trabecular meshwork, resulting in reduced drainage of aqueous humor through the anterior chamber angle. This usually occurs because the iris is either pushed or pulled anteriorly into the angle. Based on these anatomic definitions, angle-closure glaucoma can be further classified into primary angleclosure glaucoma or secondary angle closure. As the name indicates, primary angle closure has no causative mechanism leading to appositional angle closure. Secondary angle closures have identifiable mechanisms for the apposition of the iris to the angle or closure of the angle by direct blockage of the trabecular meshwork.
Primary angle-closure glaucoma Primary angle-closure glaucoma (PACG) is caused by pupillary block in 90% of cases. Pupillary block is caused by apposition of the iris against the lens restricting the efflux of aqueous from the posterior chamber to the anterior chamber and subsequent drainage through the trabecular meshwork (Fig. 1). The accumulation of the aqueous in the posterior aspect causes bowing of the iris anteriorly and eventual closure of the angle. This can happen acutely, intermittently, or chronically. There are multiple risk factors for PACG. Patients with hyperopia, or a short axial length of the eyeball, and an anterior chamber length of less than 2.5 mm are at an increased risk. The disease is more common in Eskimos and Southeast Asians populations with individuals over 40 years being at an increased risk as the lens thickens (due to cataract formation) and the anterior chamber depth shallows. Females are at a higher risk as they tend to have shallower anterior chambers,3 and those with a family history of PACG are also at an increased risk for the disease. http://dx.doi.org/10.1016/j.disamonth.2014.03.005 0011-5029/ Published by Mosby, Inc.
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Fig. 1. Pupillary block. (Woo E, Pavlin C, Slomovic A, Taback N, Buys Y. Ultrasound biomicroscopic quantitative analysis of light-dark changes associated with pupillary block. Am J Ophthalmol. 1999;127:43–47.)
Acute primary angle closure Acute primary angle closure is caused by a sudden block of the trabecular meshwork by the iris. Acute primary angle closure may be caused iatrogenically by mydriatics, and patients should be evaluated for narrow angles prior to using dilating drops. Symptoms include blurred vision, pain, colored halos around lights, nausea, emesis, and frontal headaches. Patients with acute primary angle closure may present clinically with increased intraocular pressure (IOP), a mid-dilated, non-reactive, or irregular pupil. On physical exam, corneal edema may be seen in these patients secondary to the extreme sudden elevation in pressure. Additionally, these patients may present with congested episcleral and conjunctival vessels, shallow anterior chambers, and mild cell and flare in the anterior chamber, indicative of an inflammatory process. Glaucomaflecken, which are anterior subcapsular or capsular opacities due to epithelial infarct, may be present as well. On gonioscopy, or examination of the angle, the contralateral eye usually has narrow angles as well, and there is a 40–80% chance of an acute attack in the other eye in 5–10 years. A study showed that without treatment, 51.3% (58/113) of patients developed an acute attack in the contralateral eye.4 Therefore, a prophylactic laser peripheral iridotomy (LPI) should be performed in the fellow eye relatively soon after treatment is started for the eye with angle closure. The elevation in pressure should first try to be reduced by using topical glaucoma drops, such as beta-blockers, carbonic anhydrase inhibitors, and alpha-agonists. Parasympatheticomimetics, such as pilocarpine, can also be used. Systemic hyperosmotic agents and topical steroids can be used as well. If the attack is recent, corneal indention with a gonioscopy lens can break the pupillary block and open the angle. Apraclonidine and nonselective adrenergic agonists should be avoided, as they may cause pupillary dilation/vasoconstriction and worsen the condition. These patients should be referred to an ophthalmologist for determination of further surgical interventions. Definitive treatment is a LPI performed with either an argon or YAG laser, although sometimes the procedure has to be delayed until the cornea is clear and the procedure can be performed safely.5
Intermittent (sub-acute) angle closure Patients with intermittent angle closure have periodic episodes of blurred vision, halos, and mild pain. These patients often have normal IOP in between episodes, and episodes often resolve during sleep due to miosis of the pupils. Treatment options include laser peripheral iridotomy, cataract extraction (if present), and goniosynechiolysis.
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Chronic angle closure Chronic angle closures occur after an episode of acute angle closure, or due to frequent intermittent angle closures. Most occur gradually, making them difficult to diagnose. These patients may have a lack of subjective findings. Gonioscopy is needed to accurately diagnose this, as chronic angle closure can be mistaken for primary open-angle glaucoma. Iridotomy is still needed in order to remove any component of pupillary block, and these patients may still require ocular medications or further surgery. Narrow anterior chamber angle A narrow anterior chamber is an anatomic finding that is a risk for angle closure. To determine if the patient is at high risk for pupillary block, and if a prophylactic LPI is indicated, provocative testing can be performed. There are three different tests that can be done. The darkroom test is performed by having the patient stay in a dark room causing the pupil to dilate. After 45 min, the pressure should be checked again. This method can identify about 50% of patients at risk. Another test that can be done is the prone test in which the patient lies face down for 1 h. It is more sensitive test with a sensitivity of 70%. Lastly, a phenylephrine test can be performed. The IOP should be rechecked at 1 h after dilation or when the pupil is at least 4 mm dilated. In any of these tests if the IOP increases by more than 8 mmHg from baseline, this is considered a positive test and a risk factor for acute angle closure. Plateau iris Plateau iris the only type of primary angle closure without pupillary block. It is an anatomic variation in which the iris root angulates forward from its insertion point, and then again centrally6 (Fig. 2). The abnormal configuration of the anterior chamber angle may result in acute or chronic angle-closure glaucoma. Plateau iris is most often caused by anteriorly positioned ciliary processes that push the peripheral iris forward, which can block the trabecular meshwork. Plateaus iris with acute angle closure is seen more commonly in young patients with myopia (near-sightedness).
Fig. 2. Plateau iris caused anterior rotation of ciliary body. (Tran H, Liebmann J, Ritch R. Iridociliary apposition in plateau iris syndrome persists after cataract extraction. Am J Ophthalmol. 2003;135(1):40–43.)
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In these patients, it should be noted that the central chamber depth is deeper than seen with the patients described previously. The definitive diagnosis of plateau iris can be made if angle closure continues to persist after iridotomy. These patients can be further treated by laser gonioplasty and chronic treatment with miotic agents.7
Secondary angle closure with pupillary block Lens-induced glaucoma Phacomorphic glaucoma Phacomorphic glaucoma is due to a large swollen lens that pushes the iris forward, leading to an intermittent pupillary block angle closure. The initial treatment is most often with topical medications such as beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors.8 Phacomorphic glaucoma can be treated by iridotomy for temporary relief and with cataract extraction for definitive treatment (Fig. 3). Microspherophakia Microspherophakia is an abnormally shaped lens. It is often familial and can be an isolated condition or part of other conditions such as Weill–Marchesani or Marfan syndrome. The anterior lens position and round shape lead to pupillary block angle-closure glaucoma. Medical treatment includes cycloplegics to flatten the lens and pull it more posteriorly. Conversely, miotics worsen the condition. A LPI or lens extraction is curative.9 Ectopia lentis Ectopia lentis occurs when there is displacement of the lens from the normal anatomic position. It can lead to intermittent pupillary block. An ophthalmologist can treat this by creating two laser peripheral iridotomies that are 1801 apart. Other diseases that should be kept in the differential include pseudoexfoliation syndrome, trauma, Marfan’s syndrome, homocystinuria, microspherophakia, and Weill–Marchesani10 (Fig. 4). Aphakic or pseudophakic angle-closure glaucoma In aphakic patients without a LPI, angle closure can occur from pupillary block by the contact between the iris and the intact anterior hyaloid face. In pseudophakic patients pupillary block can also occur. With an anterior chamber intraocular lens (ACIOL), the lens may directly block the pupil as it rests on the iris and therefore a peripheral iridectomy is usually made at the time
Fig. 3. Phacomorphic glaucoma. (Sowka J. Phacomorphic glaucoma. J Am Optom Assoc. 2006;77(12):586–589.)
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Fig. 4. Ectopia Lentis, with upward displacement of the lens, in a patient with Marfan’s syndrome. (Konradsen T, Koivula A, Kugelberg M, Zetterströ m C. Accommodation measured with optical coherence tomography in patients with Marfan’s syndrome. Ophthalmology. 2009;116(7):1343–1348.)
of ACIOL placement. Occasionally pupillary block can occur with a posterior chamber intraocular lens (PCIOL) due to the formation of posterior synechiae that result in iris bombe. Vitrectomy with intraocular gas/silicone oil Intraocular gas or silicone oil filling the posterior chamber for treatment of a retinal detachment can also be space occupying and cause a pupillary block. Since these substances are lighter than aqueous, an inferior LPI should be performed.
Secondary angle closure without pupillary block Neovascular glaucoma Neovascular glaucoma is usually caused by growth of new vessels within the angle, often due to ocular ischemia or ocular inflammation. Some causes of neovascular glaucoma include diabetic retinopathy, ischemic retinal vessel occlusions, and ocular ischemic syndrome.11 In cases of neovascular glaucoma, fine arborizing blood vessels can grow at the pupil margin, extend over the surface of the iris, and also into the angle (Fig. 5). The vessels then cross the ciliary body and scleral spur and branch over the trabecular meshwork but never onto endothelium. A fibrous membrane may also grow on the trabecular meshwork, which eventually contracts leading to peripheral anterior synechia and thus the development of secondary angleclosure glaucoma. Patients with neovascular glaucoma present with increased intraocular pressure and the symptoms that are associated with that including pain, injection, corneal edema, and anterior chamber reaction. A gonioscopy should always be performed on these patients. Overall, 10% of the time, patients may have neovascularization within the angle without having any neovascularization of the iris. It is important to distinguish dilated iris blood vessels due to inflammation from neovascularization. If neovascular glaucoma is caught early and the vitreous is clear, an ophthalmologist can perform a pan-retinal photocoagulation laser, but the effect of the laser can take weeks. Therefore, intravitreal anti-VEGF (endothelial growth factors) medications should be considered. If the neovascularization has regressed, but IOP remains elevated then a surgical procedure, such as a glaucoma drainage device, may be warranted. In cases of late disease with poor visual potential, a cyclodestructive procedure may be used.
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Fig. 5. Neovasculization of the angle leading to glaucoma. (Iliev M, Domig D, Schnurrbursch U, Wolf S, Sarra G. Intravitreat Bevacizumab (Avastins) in the treatment of neovascular glaucoma. Am J Ophthalmol. 2006;142(6):1054– 1056.)
Iridocorneal endothelial syndrome (ICE) There are multiple iridocorneal endothelial syndromes (ICE), including iris nevus syndrome, Chandler’s, and essential iris atropy. All of these disorders involve the corneal endothelium, which has a “beaten bronze” look. The endothelium starts to behave like epithelium and profilerates. On specular microscopy, the endothelium appears atypical with large spaces between cells and a low cell count. An endothelial membrane can grow over the angle, iris, and other structures. The layer of endothelial cells pulls the iris up to the cornea, leading to peripheral anterior synechia. This results in glaucoma in about 50% of the cases. The disease is almost always unilateral. The incidence of ICE is higher in women, and more common in people aged 20–50 years. Treatment options include hypertonic saline and glaucoma medications, but usually it is difficult to manage medically. Glaucoma surgery may therefore be indicated and multiple surgeries may be needed due to a higher failure rate of these procedure compared to other conditions.12 Epithelial downgrowth Epithelial downgrowth is a condition in which non-keratinized, stratified, squamous cell epithelium covers corneal endothelium, trabecular meshwork, iris, and the ciliary processes (Fig. 6). Epithelial cells can be seen in cytologic examination of the aqueous aspirate. Another way to confirm that there are indeed epithelial cell on surfaces that they do not belong on is to place a spot of argon laser in the area suspected to have this growth. If there are epithelial cells there, the argon causes whitening of the tissue and helps to identify the presence of the abnormal growth. The cells are usually present secondary to a penetrating wound or intraocular surgery and can cause a severe secondary glaucoma by blocking the trabecular meshwork. The treatment is by removing the epithelial membrane and affected tissues by curettage, intraocular cryotherapy, or laser therapy. The overall prognosis of this disease is poor despite surgical treatment of the underlying cause. Medical or surgical treatment to manage the increased pressure is usually needed because the primary etiology is difficult to cure. Fibrous ingrowth Fibrous ingrowth is caused by fibroblast proliferation following a penetrating wound in the anterior chamber. It is not as aggressive as epithelial downgrowth but can cause corneal
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Fig. 6. Epithelial downgrowth. (Nemi A, Bahadur R, Randleman J. Traumatic epithelial downgrowth after radial keratotomy. J Cataract Refract Surg. 2008;34(2):327–329.)
decompensation and a secondary glaucoma.13 The treatment is first by medical therapy for the increased pressure followed by surgical intervention if needed. Intraocular tumors Intraocular tumors can cause glaucoma by different mechanisms depending on the location of the tumor. If the tumor is found in the posterior segment, the tumor may cause the iris–lens diaphragm to be pushed forward, resulting in a secondary angle closure. If the tumor is in the anterior segment, it may cause a secondary glaucoma via direct tumor invasion of the angle, rotation of the ciliary body, intraocular heme, rubeosis iridis, deposition of tumor cells, or inflammatory or cellular debris within the trabecular meshwork. The most common type of intraocular tumors leading to glaucoma is uveal melanoma. Treatment of the underlying cause is usually more important than treating just the high pressure, but the pressure is managed medically, and if needed, surgically as well. Inflammation Inflammation can cause posterior synechia and then iris bombe leading to secondary angle closure. The peripheral anterior synechia seen secondary to inflammation is often inferior and non-uniform in shape and height. This is different than synechia that occur with primary angle closure, in which case the peripheral anterior synechia is often superior. Treatment should be aimed at reducing the inflammation and then the pressure should be managed either medically or surgically. Aqueous misdirection Aqueous misdirection, also known as malignant glaucoma, is a rare cause of glaucoma. It almost always presents after ocular surgery, often in patients with pre-existing angle-closure glaucoma or peripheral anterior synechia. Aqueous misdirection usually has a uniform flattening of the central and peripheral anterior chamber, and elevated intraocular pressure. Aqueous misdirection is caused by an anterior rotation of the ciliary body with posterior misdirection of the aqueous, combined with a block to aqueous movement into the anterior chamber. A patent peripheral iridotomy is needed in order to make the diagnosis.
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Medical management of aqueous misdirection should be with mydriatics, aqueous suppressors, and hyperosmotic agents. Miotic agents should be avoided as they worsen the condition by causing further anterior rotation of the ciliary body. YAG laser to disrupt the anterior hyaloid face or argon laser to shrink the ciliary processes may reverse the condition. Definitive treatment is pars plana vitrectomy.14 Retinal surgery/retinal vascular disease A scleral buckle is one of the ways to treat a retinal detachment. The buckle encircles the eye and pushes the sclera towards the middle of the eye to relieve the pull on the retina, placing the retina and underlying tissue in proximity to allow the tear to heal. However, the encircling band can cause congestive swelling with forward motion of the ciliary body and subsequent occlusion of the angle. There can also be an increase in IOP due to obstruction to venous outflow into vortex system by the encircling band. This can be treated by cycloplegics, carbonic anhydrase inhibitors, and topical steroids. Iridectomy is of little benefit. The chamber usually deepens over several weeks with medical therapy. Central retinal vein occlusion Central retinal vein occlusions (CRVO) can be a cause of glaucoma, independent of causing neovascular glaucoma by causing early shallowing of the chamber angle, presumably due to swelling of the choroid and ciliary body. With resolution of the CRVO, the chamber deepens. Nanophthalmos Nanophthalmos can be defined as a normal-shaped, but small eye. The axial length of the eye is less than 20 mm. In this case, the lens of the eye is relatively large in comparison to the volume of the eye. This can lead to angle closure. Also, the thickened sclera impedes vortex vein drainage, also increasing IOP. Glaucoma in this instance can be treated by laser iridectomy, laser iridoplasty, and medical therapy. Caution during surgical intervention needs to be taken as there is a high risk for choroidal effusions in nanophthalmic eyes.15 Retinopathy of prematurity (ROP)/persistant fetal vasculature/persistent primary hyperplastic vitreous (PFV/PHPV) ROP is a disease affecting premature babies. Babies who are born before 31 weeks are at an increased risk. Contracting retrolental tissue in ROP can cause progressive shallowing of the anterior chamber and angle closure. In cases of PFV/PHPV, there is a unilateral microphthalmos and elongated ciliary processes. Glaucoma can occur due to contracture of the primary vitreous and swelling of the cataractous lens. Drug-induced secondary angle-closure glaucoma Certain medications can lead to secondary angle-closure glaucoma.16 One such medication is topiramate, which is a sulfamate-substituted monosaccharide. It can lead to an acute myopic shift and bilateral angle-closure glaucoma due to ciliochoroidal effusion.17 Symptoms usually begin within 1 month of initiating therapy. The first step to treat drug-induced secondary angleclosure glaucoma is cessation of the offending agent, followed by using aqueous suppressants and cycloplegics. An iridotomy is not indicated for this cause of glaucoma. Interestingly enough, acetazolamide, which is a medication used to reduce intraocular pressure, can induce this type of secondary angle closure. Other sulfonamides, such as hydrochlorathiazide,18 can have similar effects.
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Conclusion In the US, POAG is more common than angle closure, yet angle closure still constitutes a large portion of glaucoma worldwide. Despite the cause, the symptoms are usually similar due to a significantly increased IOP and subsequent irreversible damage to the vision. Therefore, recognition of angle closure and the specific type is important for timely treatment to minimize both patient discomfort and permanent visual damage. References 1. Friedman DS, Wolfs RC, O’Colmain BJ, et al. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122(4):532–538. 2. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–267. 3. Lim AS. Primary angle-closure glaucoma in Singapore. Aust J Ophthalmol. 1979;7(7):23–30. 4. Henrietta H, Chew P, Sng C, Huang H, Aung T, Perera S. A comparison of two approaches to managing acute primary angle closure in Asian eyes. Clin Ophthalmol. 2013;7(7):1205–1210. 5. Ang L, Ang L. Current understanding of the treatment and outcome of acute primary angleclosure glaucoma: an Asian perspective. Ann Acad Med Singapore. 2008;37(3):210–214. 6. Diniz F, Cronemberger S, Merula RV, Calixto N. Plateau iris. Arg Bras Oftalmol. 2008;71(5):752–758. 7. Ang GS, Bochmann F, Azuara-Blanco A. Argon laser peripheral iridoplasty for plateau iris associated with iridociliary cysts: a case report. Cases J. 2008;1(1):368. 8. Kaplowitz1 K, Kapoor K. An evidence-based approach to phacomorphic glaucoma. J Clinic Exp Ophthalmol. 2011. 9. Senthil S, Rao HL, Hoang NT, et al. Glaucoma in microspherophakia: presenting features and treatment outcomes. J Glaucoma. 2014;23(4):262–267. 10. Tsilou E, MacDonald IM. Weill–Marchesani syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, eds. GeneReviews: Seattle, WA; University of Washington, Seattle (1993-2013). 2007. 11. Hayreh S. Neovascular glaucoma. Prog Retin Eye Res. 2007;26:470–485. 12. Doe EA, Budenz DL, Gedde SJ, Imami NR. Long-term surgical outcomes of patients with glaucoma secondary to the iridocorneal endothelial syndrome. Ophthalmology. 2001;108(10):1789–1795. 13. Smith MF, Doyle JW. Glaucoma secondary to epithelial and fibrous downgrowth. Semin Ophthalmol. 1994;9(4): 248–253. 14. Debrouwere V, Stalmans P, Van Calster J, Spileers W, Zeyen T, Stalmans I. Outcomes of different management options for malignant glaucoma: a retrospective study. Graefes Arch Clin Exp Ophthalmol. 2012;250(1):131–141. 15. Steijns D, Bijlsma WR, Van der Lelij A. Cataract surgery in patients with nanophthalmos. Ophthalmology. 2013;120(2): 266–270. 16. Lachkar Y, Bouassida W. Drug-induced acute angle closure glaucoma. Curr Opin Ophthalmol. 2007;18(2):129–133. 17. Panday VA, Rhee DJ. Review of sulfonamide-induced acute myopia and acute bilateral angle-closure glaucoma. Compr Ophthalmol Update. 2007;8(5):271–276. 18. Geanon JD, Perkins TW. Bilateral acute angle-closure glaucoma associated with drug sensitivity to hydrochlorothiazide. Arch Ophthalmol. 1995;113(10):1231–1232.