Malignant Glaucoma 

Updated: Sep 20, 2018
Author: Mauricio E Pons, MD; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

In 1869, von Graefe first used the term malignant glaucoma to describe an entity characterized by elevated intraocular pressure (IOP) with a shallow or flat anterior chamber in the presence of a patent peripheral iridectomy. In its classic form, malignant glaucoma is rare but one of the most serious complications of glaucoma filtration surgery in patients with narrow-angle or angle-closure glaucoma.

The term malignant glaucoma refers to a sustained ongoing process that is difficult to treat and characteristically progresses to blindness. It is sometimes unresponsive and occasionally worsened with conventional management. Modern vitreoretinal surgical techniques, as well as a better understanding of the disease, have improved the prognosis to some extent.

Many different terms, including ciliovitreal block and aqueous misdirection syndrome, have been proposed based on diverse unproven pathophysiological and anatomical mechanisms.

Pathophysiology

A blockage of the normal aqueous flow at the level of the ciliary body, lens, and anterior vitreous face is believed to cause malignant glaucoma. Posterior misdirection of aqueous humor into the vitreous cavity occurs producing a continuous expansion of the vitreous cavity and increased posterior segment pressure. This accumulation of aqueous fluid in the vitreous cavity causes anterior displacement of the lens-iris diaphragm in phakic and pseudophakic eyes or forward displacement of the anterior hyaloid in aphakic patients. Corneal edema is a frequent finding.[1] The resulting shallow or flat chamber (athalamia)[2] is believed to exacerbate the condition because of the decreased access of aqueous to the trabecular meshwork. The IOP is often markedly increased but may be normal.[3, 4]

Phakic malignant glaucoma. Phakic malignant glaucoma.

Epstein et al proposed that forward displacement of the vitreous into apposition with the posterior ciliary body caused a decrease in available hyaloid surface, increasing the resistance to flow from the vitreous body.[5] Small hyperopic eyes are at higher risk for malignant glaucoma.

Malignant glaucoma has been described following: cataract surgery with or without intraocular implant (aphakic or pseudophakic malignant glaucoma), implantation of a large posterior chamber intraocular lens, cessation of topical cycloplegic therapy, induction of miotic therapy, laser iridotomy, laser capsulotomy, Nd:YAG cyclophotocoagulation, laser sclerotomy, Molteno implantation, Baerveldt glaucoma drainage device implantation, viscoelastic use, intravitreal injection of triamcinolone acetonide, Aspergillus flavus intraocular infection, and acute hydrops in Down syndrome.[6] Malignant glaucoma has also been described spontaneously in an eye with no antecedent of surgery or miotics. Surgical iridectomy had a 2% complication before YAG laser largely replaced the procedure. A pseudomalignant glaucoma syndrome has been reported after pars plana vitrectomy.

Malignant glaucoma subsequently developed in a 70- Malignant glaucoma subsequently developed in a 70-year-old man with a history of nanophthalmos who underwent cataract extraction with spherical piggyback IOL implantation.

Malignant glaucoma with a low IOP has been described after trabeculectomy.[7] In these cases, the pressure in the anterior chamber is lower than the pressure in the vitreous, causing shallowing of the anterior chamber. A functioning iridectomy and sclerotomy must be present for the fluid to escape and keep the pressure low. Anterior rotation of the ciliary processes has been observed. Choroidal effusion may not be present.[7] In a different case, trabeculectomy was complicated with unplanned zonulectomy and ciliovitreal block caused by vitreous herniation through the peripheral iridectomy. High IOP and a flat anterior chamber were observed.[8]

Epidemiology

Frequency

United States

Malignant glaucoma has been reported to occur in 0.6-4% of eyes following filtration surgery for angle-closure glaucoma. Trope et al reported that 71% of 14 patients with malignant glaucoma had chronic angle-closure glaucoma.[9]

International

In Germany, Duy and Wollensak reported 2 cases of ciliary block in 9000 patients following cataract extraction.[10] However, both patients had previous filtration procedures with temporary shallowing of the anterior chamber postoperatively. In China, Wu et al reported an incidence of 2% in patients with chronic angle-closure glaucoma surgery.[11]

Mortality/Morbidity

Malignant glaucoma remains a difficult clinical problem that results in irreversible blindness if not promptly treated. The surgeon should be aware preoperatively of eyes at risk and observe them closely postoperatively. Early recognition is the most important step to prevent irreversible vision loss.[12]

Age

Trope et al reported that the average age of patients with malignant glaucoma was 70 years.[9]

Prognosis

The prognosis depends on the length and the severity of the attack. In patients with relatively healthy optic nerves, the prognosis can be good if the attack is abated and intraocular pressure is controlled.[13]

Patient Education

For patient education resources, see the Glaucoma Center, as well as Glaucoma FAQs and Understanding Glaucoma Medications.

 

Presentation

History

Typically, patients with narrow-angle or acute or chronic angle-closure glaucoma, who recently underwent filtration surgery, present shortly after surgery; however, it can develop months later or even in the absence of surgery.

Patients may present with pain and discomfort, increasing redness, blurring, or decreased visual acuity.

Pain may be severe enough to cause nausea and induce vomiting, similar to an attack of acute angle-closure glaucoma.

Precipitating factors are suture lysis, initiation of miotic therapy, or discontinuation of cycloplegics.

Shallowing of the anterior chamber due to wound leak must be ruled out by performing a Seidel test during slit lamp examination.

Physical

In malignant glaucoma, slit lamp examination reveals anterior displacement of the lens-iris diaphragm in phakic patients and the anterior hyaloid face in aphakic patients, shallowing of the central and peripheral anterior chamber, and elevated intraocular pressure with a patent iridectomy present.

Optically clear spaces can be observed within the vitreous cavity and have been interpreted as pockets of fluid.

With the Goldman lens, a completely closed angle can be observed. Choroidal detachments or suprachoroidal hemorrhage should be ruled out using the goniolens mirrors and indirect ophthalmoscopy. The retina should be evaluated for vascular occlusions, and the vitreous should be evaluated for possible hemorrhages. B-mode ultrasound can be extremely useful if direct visualization is not possible.

Malignant glaucoma is not caused by pupillary block where laser iridotomy can relieve the flow obstruction. In malignant glaucoma, a patent iridectomy must be demonstrated. If not, a new laser iridotomy must be performed.

Ultrasound biomicroscopy has demonstrated anterior rotation of the ciliary body with apposition to the ciliary process in contact with the lens equator and anterior displacement of the ciliary body and lens, causing iridocorneal touch and appositional angle closure in these patients.

Causes

The exact mechanism that leads to malignant glaucoma is not clearly understood. Movement of aqueous humor from the posterior chamber into the vitreous instead of draining to the anterior chamber may be the cause.

Malignant glaucoma may occur within hours to days or years after surgery. Most commonly, it is seen after trabeculectomy or surgical iridectomy. This condition may be noted after the cessation of cycloplegic drops or the initiation of miotic therapy after surgery for angle-closure glaucoma.

The fellow eye is predisposed strongly to develop malignant glaucoma.

In 1954, Shaffer proposed that misdirection of aqueous humor into the vitreous body or around it was the pathogenic mechanism.[14]

In 1972, Levene suggested that malignant glaucoma results from forward movement of the lens with direct closure of the angle intensified by surgery, and it represents a more severe form of angle-closure glaucoma.[15] The tone of the ciliary body muscle and the tension of the zonules could explain the anterior movement of the lens.

Epstein et al hypothesized that a sustained expansion in total vitreous volume moves available peripheral anterior hyaloid into apposition with the posterior ciliary body increasing the resistance for anterior fluid transfer and causing forward displacement of the lens-iris diaphragm and shallowing of the anterior chamber.[5]

In 1980, Quigley incorporated data from Fatt into this theory and proposed that dehydrated and compressed vitreous with a decreased fluid conductivity establishes a vicious circle of elevated pressure and anterior chamber shallowing.[16, 17]

 

DDx

 

Workup

Imaging Studies

A-mode ultrasound is used to measure axial length.

B-mode ultrasound can discover occult choroidal effusions or hemorrhages or vitreous hemorrhage.

Ultrasound biomicroscopy (UBM) is used to obtain cross-sectional images of the anterior segment, cornea, iris, lens, and ciliary body at 25-50 µm resolution with a tissue penetration of 5 mm. UBM can help to differentiate the anatomic mechanisms responsible for different forms of glaucoma.[18]

OCT anterior segment imaging may be used to evaluate anterior chamber depth and corneal thickness.[19] Structures behind the iris are not clearly seen because the iris pigment epithelium acts as a barrier to the OCT laser beam.

Other Tests

The Seidel Test is used to evaluate the existence of anterior chamber leakage in the cornea.

Electronic indentation tonometry, such as the Tono-Pen (Reichert, Inc) or AccuPen (Accutome, Inc), can be used to measure intraocular pressure.

Procedures

Bleb or wound leaks should be identified and treated first.

Because of its simplicity, a new laser iridotomy should be performed if suspicion of pupillary block exists.

 

Treatment

Medical Care

The first line of treatment should be medical.[19] The goal is to decrease aqueous humor production, shrink the vitreous body, and move the iris-lens diaphragm backward.

Cycloplegic agents, including tropicamide, cyclopentolate, and topical atropine, paralyze the sphincter muscle of the ciliary body, increasing zonular tension with flattening and posterior movement of the lens and deepening the anterior chamber.

Topical phenylephrine is used to tighten the zonules by stimulating the longitudinal muscle of the ciliary body.

Topical beta-blockers, alpha-adrenergic agonists, and topical and oral carbonic anhydrase inhibitors are effective in decreasing aqueous humor production and lowering intraocular pressure, presumably decreasing aqueous misdirection.

Osmotic agents used to decrease vitreous volume include oral glycerol or isosorbide, or intravenous mannitol. Hyperosmotic agents are very effective in lowering intraocular pressure and have an onset of action in minutes reaching its maximum peak at 60 minutes. They should be used with caution due to possible metabolic disorders and intravascular volume overload; they are contraindicated in patients with renal or heart failure.

Medical treatment works in approximately one half of patients. Medical management should be continued unless intraocular pressure is higher than acceptable, given the state of the optic nerve. Also, flat anterior chamber with lens-corneal touch and increased intraocular pressure is an indication to proceed with surgical therapy. Once the condition resolves, medications can be withdrawn gradually. The condition may recur when therapy is decreased. Atropine may be required indefinitely to prevent recurrences.

Bimatoprost, travoprost, tafluprost, and latanoprost are effective new medications for lowering intraocular pressure in patients with glaucoma and ocular hypertension. Prostaglandin analogues reduce intraocular pressure by increasing uveoscleral aqueous outflow; however, their role in the treatment of malignant glaucoma is not clearly defined.

Malignant glaucoma with a low IOP is treated in the same way as malignant glaucoma.

Surgical Care

Argon laser can be used through a peripheral iridectomy to diminish the volume of ciliary processes and, therefore, ciliolenticular block. In 1980, Herschler reported that transpupillary laser shrinkage of ciliary processes in aphakic patients was successful in reversing the posterior secretion of aqueous humor and restoring anterior chamber depth.[20]

YAG laser can break the anterior hyaloid to allow free movement of fluid from the vitreous cavity to the anterior chamber. Hyaloidotomy is preferably performed in the peripheral hyaloid through a large peripheral iridectomy to avoid lens injury in phakic patients and to prevent lens capsule or retained cortical material to obstruct the fluid path in pseudophakic patients. Clear media is required to perform laser treatment for optimal focusing.

If medical or laser treatment fails or if lens-corneal touch occurs, surgery should be considered.

Pars plana vitrectomy, with or without lensectomy, disrupts the impermeable anterior vitreous face and reduces the vitreous volume. The goal is to create a direct communication between the vitreous cavity and the anterior chamber. In phakic eyes, anterior vitreous is difficult to remove without damaging the lens; therefore, treatment is less likely to succeed.

Pars plana vitrectomy combined with pars plana insertion of an aqueous shunt can lower the intraocular pressure and prevent an increase in vitreous volume, reducing the recurrence of malignant glaucoma.[21]

Byrnes et al reviewed the medical records of 21 patients with pars plana vitrectomy surgery for malignant glaucoma.[22] Vitrectomy was unsuccessful in alleviating glaucoma in 6 eyes, 5 of them were phakic. Zacharia and Abboud reported a case of malignant glaucoma after pars plana vitrectomy in which the hyaloid face was left intact.[23]

Debrouwere et al reported that complete vitrectomy, iridectomy, zonulectomy, and phacoemulsification when appropriate were more successful than other forms of therapy.[24] Sclerectomy combined with phacoemulsification, zonulectomy, hyaloidectomy, and anterior vitrectomy have been used in patients with nanophthalmos and malignant glaucoma.[25]

Because pseudophakic patients often have retained cortex in the peripheral capsule, core vitrectomy, anterior hyaloidectomy, and removal of peripheral cortical elements are necessary to create a fluid path from the posterior segment to the anterior chamber. Lynch et al proposed such a method to surgically treat malignant glaucoma in pseudophakic patients.[26] A pars plana approach is advised. A core vitrectomy and peripheral anterior hyaloidectomy are performed. A small area of lens zonules and capsule is excised. This is accomplished using low suction with a high-cutting frequency. Visualization through a previous iridectomy reduces complications and risk to the lens optic and haptics. When visualization is poor in spite of the presence of a peripheral iridectomy, the probe tip can be used to gently push against the posterior capsule and lens optic. The haptics can be identified because they distort the iris anteriorly.

Zarnowski et al described a new surgical approach consisting of anterior vitrectomy performed through the clear cornea, zonulectomy, peripheral capsulectomy, and iridectomy in patients with pseudophakic malignant glaucoma.[27]

Prevention

Trabeculectomy surgery modification, including releasable sutures, the use of viscoelastics during the surgery, and the postoperative use of atropine, has been proposed to prevent malignant glaucoma.

The fellow eye is at increased risk of developing malignant glaucoma postoperatively. Hyperopic eyes and eyes with short axial length also are at increased risk. Prophylactic iridotomy is recommended if support for occludable angle exists, preferably with avoidance of the use of miotics.

Prophylactic anterior vitrectomy has been used during cataract surgery in eyes at increased risk for malignant glaucoma.[28]

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Beta-adrenergic receptor blocking agents

Class Summary

The exact mechanism of ocular antihypertensive action is not established, but it appears to be a reduction of aqueous humor production.

Timolol ophthalmic (Timoptic, Timoptic-XE, Betimol, Istalol)

First-line treatment. Precise mechanism by which timolol decreases IOP is not well established, although it is thought to be through reduction of aqueous formation.

Betaxolol ophthalmic (Betoptic-S)

Cardioselective beta1-adrenergic receptor blocking agent with minimal effect on pulmonary and cardiovascular parameters. Precise mechanism by which betaxolol decreases IOP is thought to be through reduction of aqueous formation.

Carteolol ophthalmic

Nonselective beta-adrenergic receptor blocking with intrinsic sympathomimetic activity. Precise mechanism by which carteolol decreases IOP is thought to be through reduction of aqueous formation.

Levobunolol (Betagan)

Noncardioselective beta-adrenergic receptor blocking agent. Precise mechanism by which levobunolol decreases IOP is thought to be through reduction of aqueous formation.

Metipranolol

Nonselective beta-adrenergic receptor blocking agent. Precise mechanism by which metipranolol decreases IOP is thought to be through reduction of aqueous formation.

Alpha2-adrenergic receptor agonists

Class Summary

May decrease IOP by reducing aqueous humor production.

Apraclonidine (Iopidine)

Reduces elevated, as well as normal, IOP whether accompanied by glaucoma or not. Apraclonidine is a relatively selective alpha-adrenergic agonist that does not have significant local anesthetic activity. It has minimal cardiovascular effects. Generally used in short-term therapy.

Brimonidine (Alphagan P)

This medication lowers pressure by allowing better fluid drainage from within the eye and also by reducing the amount of fluid formed in the eye.

Oral carbonic anhydrase inhibitors

Class Summary

By slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, it may inhibit carbonic anhydrase in the ciliary processes of the eye. This effect decreases aqueous humor secretion, reducing IOP.

Acetazolamide (Diamox)

Inhibits enzyme carbonic anhydrase, reducing rate of aqueous humor formation, which, in turn, reduces IOP.

Topical carbonic anhydrase inhibitor

Class Summary

Agents in this class slow the formation of bicarbonate ions, causing a reduction in sodium and fluid transport. These agents may inhibit carbonic anhydrase in the ciliary processes of the eye, which decreases aqueous humor secretion, thereby reducing IOP. Carbonic anhydrase inhibitors typically have a weaker effect than beta blockers.

Brinzolamide (Azopt)

Brinzolamide catalyzes a reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. It may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, administer them at least 10 minutes apart.

Dorzolamide (Trusopt)

Dorzolamide is a reversible carbonic anhydrase inhibitor that may decrease aqueous humor secretion, causing a decrease in IOP. Presumably, it slows bicarbonate ion formation, producing a subsequent reduction in sodium and fluid transport.

Hyperosmotic agents

Class Summary

Osmotic diuretics increase the osmolarity of the glomerular filtrate and induce diuresis. This in turn hinders the tubular reabsorption of water, causing sodium and chloride excretion to increase as well. The diuretic effect of these agents can subsequently reduce IOP by creating an osmotic gradient between ocular fluids and plasma. They are not for long-term use.

Mannitol (Resectisol, Osmitrol)

Lowers IOP by increasing the osmotic gradient between blood and ocular fluids, resulting in loss of water from the vitreous.

Prostaglandins, ophthalmic

Class Summary

Prostaglandin analogs reduce intraocular pressure by increasing uveoscleral outflow. These agents typically lower IOP by 25%-30%.

Latanoprost (Xalatan, Xelpros)

Latanoprost may decrease IOP by increasing the outflow of aqueous humor. Patients should be informed about possible cosmetic effects to the eye/eyelashes, especially if uniocular therapy is to be initiated.

Bimatoprost (Lumigan)

This agent is a prostamide analog with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Bimatoprost ophthalmic solution is used to reduce IOP in open-angle glaucoma and ocular hypertension.

Travoprost ophthalmic (Travatan Z)

This agent is a prostaglandin F2-alpha analog. It is a selective FP prostanoid receptor agonist that is believed to reduce IOP by increasing uveoscleral outflow. Travoprost ophthalmic solution is used to treat open-angle glaucoma and ocular hypertension.

Tafluprost (Zioptan)

Tafluprost is a topical, preservative-free, ophthalmic prostaglandin analog that is indicated for elevated IOP associated with open-angle glaucoma or ocular hypertension. The exact mechanism by which it reduces IOP is unknown, but it is thought to increase uveoscleral outflow.

Latanoprostene bunod ophthalmic (Vyzulta)

Latanoprostene bunod is rapidly metabolized to latanoprost, which may lower IOP by increasing outflow of aqueous humor through both the trabecular meshwork and the uveoscleral pathway.

Rho kinase (ROCK) inhibitors

Class Summary

Agents in this class are small GTP-binding proteins that belong to the Rho family. Although their exact mechanism of action is unknown, they may reduce intraocular blood pressure by increasing the outflow of aqueous humor through the trabecular meshwork route.

Netarsudil ophthalmic (Rhopressa)

Netarsudil is believed to work differently than other widely used IOP-lowering medications by improving outflow of aqueous humor through the trabecular meshwork.