18

Management of Highly Elevated Intraocular Pressure

Joshua D. Stein, MD, MS; R. Rand Allingham, MD; and Pratap Challa, MD, MS

The patient with acutely elevated intraocular pressure (IOP) is usually symptomatic, whereas IOP that has gradually increased, even to relatively high levels, usually does not produce symptoms. Common symptoms from acutely elevated IOP include headache, usually dull or aching, blurred vision, perception of colored haloes, and nausea or vomiting. These symptoms of acutely elevated IOP may be accompanied by signs including conjunctival injection, microcystic corneal edema, pupillary abnormalities, and absence of central retinal arterial or venous pulsations. Although glaucomatous optic nerve damage or visual field loss may not be present in cases of acutely elevated IOP, we still refer to these as forms of glaucoma.

Most forms of glaucoma can cause extremely elevated IOP (Table 18-1). Of these, angle-closure glaucoma, either primary or secondary, is a common cause of acute symptomatic IOP elevation. Acute angle-closure crisis often produces the entire constellation of signs and symptoms of this group of disorders. Secondary angle-closure glaucoma, particularly neovascular glaucoma, is frequently encountered in practice. Secondary open-angle glaucomas, including angle recession, exfoliation, pigment dispersion, Posner-Schlossman syndrome, and steroid-induced glaucoma, occasionally cause a sudden, marked IOP increase. Juvenile open-angle glaucoma, although rare, is the most likely primary open-angle glaucoma to produce symptomatic highly elevated IOP.

DIAGNOSIS

History

A thorough medical history and ocular exam frequently provide diagnostic clues to the cause of highly elevated IOP. Often, the cause is obvious (eg, after laser or incisional surgery). In other cases, there may be no apparent cause. An asymptomatic patient usually has had a gradual increase in IOP, which suggests chronic angle-closure glaucoma or a form of open-angle glaucoma. Patients who have had recent eye surgeries and those with histories of ocular inflammation, trauma, or chronic inflammatory medical conditions (eg, asthma, rheumatoid arthritis) should be questioned about the use of topical or systemic corticosteroids. Histories of ocular trauma are often found in patients with angle-recession glaucoma.

Episodic pain or blurred vision occurring over months or years is more commonly observed with intermittent angle-closure glaucoma, whereas the sudden onset of severe unrelenting pain and blurred vision, particularly in a hyperopic patient, is most commonly seen with acute angle-closure crisis. A history of painless loss of vision in the affected eye can occur with a central retinal vein occlusion (CRVO), or a history of diabetes mellitus would suggest neovascular glaucoma as the cause of the IOP elevation.

The anterior chamber may contain flare or cells from ocular ischemia secondary to high IOP. However, more than a few cells would suggest a uveitic or infectious etiology, whereas red cells may indicate bleeding from ischemic tissue, trauma, neoplastic disorders, or vitreous hemorrhage (eg, ghost cell glaucoma). The anterior chamber depth both axially and peripherally should be noted. A peripherally shallow anterior chamber suggests glaucoma secondary to relative pupillary block and subsequent angle clo sure or plateau iris syndrome, whereas a centrally shallow anterior chamber suggests lens displacement or enlargement, posterior segment pathology, or malignant glaucoma.

Gonioscopy is of vital importance in these cases to determine a rational medical (or surgical) treatment strategy. In cases in which there is significant microcystic corneal edema, topical glycerin will often provide an adequate view of the iris and angle structures to assess whether the angle is open or closed. Alternatively, when the view is compromised due to corneal edema, a paracentesis can be performed to temporarily lower the IOP, permitting improved visualization of the angle structures.1 Compression gonioscopy can be performed to determine which portions of the angle are appositionally vs synechially closed. If gonioscopy is not possible due to corneal opacity, ultrasound biomicroscopy or anterior segment optical coherence tomography can be used to establish the anatomy of the anterior segment.

Fundus

If possible, the fundus should be examined acutely for evidence of CRVO, CRAO, proliferative diabetic retinopathy, retinal detachment or dialysis (Schwartz’s syndrome), and optic nerve damage. In patients with suspected acute angle-closure crisis, dilation should be deferred. In those cases in which a view of the fundus is not possible due to media opacity, B-scan ultrasonography should be strongly considered. Posterior segment tumors (eg, melanoma) and chronic retinal detachment can both present with neovascular glaucoma.

TREATMENT STRATEGY

The goal of treatment in these cases is to reduce the IOP as quickly as possible to a safe level for the optic nerve. After this has been accomplished, one can proceed with additional diagnostic tests and therapies. The approach to extremely elevated IOP can be broken down into a simple paradigm, depending on the diagnosis (Table 18-2). As stated, the treatment approach must be modified according to the patient’s medical and allergy history.

IOP can be reduced by increasing outflow or reducing inflow. Inflow drugs include beta-blockers, alpha-2 agonists, CAIs, and osmotic agents. Although not strictly inflow drugs, osmotic agents reduce IOP by dehydrating the vitreous and other ocular structures and are effective in the presence of a functionally closed angle. Miotics primarily increase conventional outflow through action on the trabecular meshwork and can open the angle in pupillary block glaucoma. However, because strong miotics can shift the lens-iris diaphragm forward and worsen pupillary block, these agents should be used with caution.

There is considerable overlap in the mechanism in which these agents reduce aqueous inflow. The IOP-lowering effect of the alpha-2 agonist apraclonidine is partially additive to timolol, when these agents are administered chronically.2 However, apraclonidine is not additive to timolol if both agents are given simultaneously.³ In other words, apraclonidine appears to restore the full potency of chronically administered timolol but is no more potent than timolol when it is given acutely. This may also be true for all nonselective beta-blockers. Therefore, either apraclonidine or nonselective beta-blocker therapy is adequate as initial treatment for patients on no previous glaucoma therapy. Apraclonidine would be the agent of choice in cases in which there is a contraindication to using a beta-blocker. The clinician should not be faulted for using alpha-agonists and beta-blockers concomitantly in patients with acutely elevated IOP. Beta-blockers should be given every 12 hours. Apraclonidine is given every 8 hours. There is no therapeutic benefit in treating more frequently.

Miotics

Direct-acting miotics like pilocarpine are useful in the treatment of glaucoma secondary to angle closure resulting from pupillary block, in addition to open-angle glaucomas in which there is no associated anterior segment inflammation. Indirect-acting agents (eg, echothiophate iodide) are long lasting, difficult to reverse, more likely to increase anterior segment inflammation, and frequently cause severe pain when administered acutely. Therefore, indirect-acting miotics should not be used in treating acute glaucomas.

Pilocarpine (1% to 2%) should be given 1 to 2 hours after aqueous suppressants have been administered. Miotics are frequently ineffective in the presence of extremely high IOP due to secondary ischemia of the iris dilator muscles. Generally, 1 or 2 applications are sufficient. More frequent administration is ineffective and can produce serious gastrointestinal and respiratory side effects.⁴

Miotics are contraindicated when the angle is structurally closed by synechiae or neovascularization, mechanically closed from a posterior pushing mechanism (eg, acute angle-closure after panretinal photocoagulation or malignant glaucoma), functionally closed by inflammatory debris (uveitis), or when elevated IOP has produced anterior segment ischemia and the iris sphincter is nonfunctional. In the latter case, delaying the addition of miotics for 1 or 2 hours until the IOP has been reduced by aqueous suppressants, hyperosmotics, or paracentesis is often more effective than starting miotic treatment initially.⁵

Miotics should be used judiciously in patients with acutely elevated IOP. If there is a question as to whether miotics should be used, withhold use until the effect of aqueous suppressant and osmotic therapy can be assessed.

Cycloplegic Agents

Whereas cycloplegics such as tropicamide and cyclopentolate are not used to directly reduce IOP, they are indicated for the treatment of secondary angle-closure glaucomas produced by swelling or rotation of the ciliary body and forward movement of the lens-iris diaphragm, such as malignant glaucoma or acute glaucoma after CRVO. These cases are worsened by miotic treatment. Cycloplegics may also help stabilize the blood-ocular barrier in patients with neovascularization of the iris or angle and in patients with hyphemas.⁶

Carbonic Anhydrase Inhibitors

CAIs, such as acetazolamide and methazolamide, reduce aqueous inflow in a manner that is partially additive to both beta-blockers and alpha-2 agonists. Methazolamide, 50 to 100 mg every 8 hours, or acetazolamide, 250 mg every 4 to 6 hours, should be given orally to adult patients. When using acetazolamide in the setting of acute high IOP, 2 250-mg tablets should be given rather than acetazolamide (Diamox Sequels), a 500-mg sustained release formulation, as the tablet formulation is more rapidly absorbed than the sustained-release preparation. Acetazolamide (500 mg) can be given intravenously for patients who have nausea.

When given systemically, CAIs produce metabolic acidosis and should be used with caution in patients with severe liver disease, renal impairment, or pulmonary insufficiency (see Chapter 14).

Although not as potent as the oral form, the topical CAIs dorzolamide and brinzolamide are available for selected patients (see Chapter 15).⁷ For example, they may be useful for treating acute glaucoma when nausea is present or an intravenous line cannot be placed.

Osmotics

Osmotic agents, such as mannitol, isosorbide, and glycerol, are thought to reduce IOP by decreasing the vitreous volume.⁸ There may be some effect mediated through the interaction of the central nervous system and optic nerve, although this remains poorly understood.⁹ These agents can be given orally or intravenously and are used for emergent control of dangerously elevated IOP. They should not be given chronically and can cause serious side effects.¹⁰

Glycerol (or glycerin) is administered orally as a 50% solution. The dose is 11.5 g/kg lean body weight. Glycerol is metabolized as a carbohydrate and, if given repeatedly, can cause serious metabolic disturbances in patients with diabetes.¹¹ Peak IOP reduction after glycerol administration is reached in approximately 30 minutes and lasts for 5 hours.¹²

Isosorbide is also an oral hyperosmotic agent. The dose is 11.5 g/kg lean body weight. Because it is excreted largely unmetabolized in the urine, it is safer for patients with diabetes than glycerin. The peak IOP reduction of isosorbide is reached 1 to 2 hours after administration and lasts for 3 to 5 hours.¹³

Mannitol is a potent osmotic agent that is administered intravenously. It is rapidly excreted unmetabolized in the urine. The recommended dose is 12 g/kg administered in a 20% solution over 20 to 30 minutes.14 The onset of action occurs within 1 hour and lasts for up to 6 hours. Due to the rapid infusion of a large volume of fluid, intra venous osmotic agents can precipitate renal or congestive heart failure, and consultation with an internist or family practitioner should be considered before administering mannitol to patients with significant cardiac or renal disease.^15,16

In general, due to concern about potentially severe systemic side effects, hyperosmotic agents are rarely used in practice today for the management of acutely elevated IOP.

Corticosteroids

If markedly increased IOP is due to ocular inflammation from uveitis in the presence of an open angle on gonioscopy, cautious use of topical corticosteroids may effectively lower the IOP in some cases.

Prostaglandin Analogs

Although prostaglandin analogs are the most commonly used first-line agents for lowering IOP in patients with open-angle glaucoma, there is little role for the use of these agents in patients who require acute IOP lowering. These agents often take 10 to 14 hours before they exert their peak effect on IOP. Furthermore, because they are proinflammatory, they can exacerbate inflammation caused by uveitis or acute angle-closure crisis.

MEDICAL MANAGEMENT

After the patient with extremely elevated IOP is examined, an initial working diagnosis is made. Patients can usually be placed into 1 of 2 groups: acutely elevated IOP with marked symptoms or acutely elevated IOP with few or mild symptoms. Treatment can be devised accordingly (see Table 18-2).

All patient groups benefit from maximal aqueous suppressant therapy. Topical beta-blockers, apraclonidine, and CAIs should all be used when the patient’s medical condition permits.

Miotics should only be used when the patient has pupillary block glaucoma or open-angle glaucoma without associated inflammation or angle recession. In all other cases, miotics should be deferred until the effect of aqueous suppressant therapy has been determined.

In the patient who is markedly symptomatic, especially one with acute angle-closure crisis in which nausea and vomiting are pronounced, promptly administering acetazolamide can produce a rapid reduction in IOP. Once IOP has been reduced to safer levels, definitive management of the underlying cause is pursued.

SURGICAL MANAGEMENT

Preparing for Surgery

When IOP cannot be lowered by using medications alone, in the acute setting, occasionally it is necessary to intervene surgically. In circumstances when surgery is necessary, administrating IOP-lowering medications prior to and at the time of surgery can minimize the risks of intraoperative bleeding, which may occur when operating on an eye that has markedly elevated IOP.

Depending on the cause of the IOP elevation, there are other interventions that can be administered that can reduce the risks associated with surgery. For example, for patients who have neovascular glaucoma, injecting anti–vascular endothelial growth factor (VEGF) agents such as bevacizumab or ranibizumab into the vitreous cavity or anterior chamber prior to surgical intervention can be beneficial.¹⁶ Occasionally, the use of these agents can cause regression of the angle neovascularization reestablishing outflow of aqueous from the eye. When neovascularization of the angle is long standing and permanent synechiae have developed, anti-VEGF agents are often ineffective at reestablishing outflow through the trabecular meshwork. However, there is still a role for the use of these agents to help cause regression of the iris neovascularization, which can limit the risk of intraoperative or postoperative bleeding. When possible, it is helpful to administer these agents 24 to 48 hours prior to performing incisional surgery. Patients with neovascular glaucoma may also benefit from topical corticosteroids and cycloplegics prior to surgery.

Surgical Interventions

Peripheral Iridotomy

The definitive treatment for pupillary block angle closure is the creation of a peripheral iridotomy. In most cases, this is accomplished using an argon or yttrium-aluminum-garnet laser. Rarely, it may be necessary to perform a surgical iridectomy. Most commonly, this occurs in cases where laser is not possible (eg, where media opacity or other anterior segment issues preclude adequate laser treatment). Less commonly, surgical intervention may be necessary where the patient is unable to cooperate for laser treatment or has nystagmus. Whenever possible, it is best to try to break the attack of acute angle-closure crisis using medications and wait a few days until the inflammation has decreased and the corneal edema has cleared before performing this procedure. However, in circumstances when the IOP cannot be reduced using medications alone or it is unsafe to use IOP-lowering medications, it may be necessary to intervene surgically in the setting of markedly elevated IOP.

It can be challenging to perform laser or incisional surgical interventions on patients with markedly elevated IOP because often these patients are very uncomfortable. Judicious use of analgesics and antiemetics can help reduce patient discomfort. A retrobulbar block can also help alleviate the discomfort associated with marked IOP elevation so that the clinician can more easily perform laser or surgical iridectomy.

The recommended technique for laser peripheral iridotomy and surgical iridectomy is described in Chapter 56. Chapter 58 describes how to perform laser iridoplasty, a technique that can be effective at acutely opening the angle when visualization of the iris to perform laser peripheral iridotomy is impaired.

Challenges associated with performing these procedures when the IOP is acutely elevated include reduced visualization of the iris and other structures in the anterior chamber, the need for increased laser energy to penetrate through a thickened inflamed iris, and the increased risk of intraoperative or postoperative bleeding. To improve visualization, a paracentesis can be performed to lower the IOP prior to performing the iridotomy.¹

Trabeculectomy/Glaucoma Drainage Device Insertion

In settings when the IOP is acutely elevated as a result of mechanisms other than pupillary block angle closure, it may be warranted to perform a trabeculectomy or implant a glaucoma drainage device. While it is beyond the scope of this chapter to discuss how to perform these procedures, this section will describe techniques that can improve the safety and effectiveness of these procedures in the setting of markedly elevated IOP.

When performing filtering surgery or implanting a glaucoma drainage device in a patient with markedly elevated IOP, it is often useful to gradually rather than abruptly lower the IOP during the surgery. This can be achieved through the use of intravenous acetazolamide or intravenous mannitol prior to surgery. Another effective strategy is to perform a paracentesis at the start of the procedure, creating a pathway for aqueous to gradually drain through over the course of the procedure. During trabeculectomy, once the sclerostomy is created, the IOP will abruptly drop, and the surgeon can control the IOP by adjusting the tension of the partial-thickness flap sutures. During glaucoma drainage device surgery, when using flow-restrictive devices, the IOP will normalize once the sclerostomy is created and the tube is inserted into the anterior chamber. Because nonflow-restrictive devices are usually tied-off until a capsule has formed around the plate of the implant, the IOP will remain elevated. There are several options for acutely lowering IOP when using non-flow-restrictive implants, such as the Baerveldt (Johnson & Johnson Vision) or Molteno (Nova Eye Medical) devices. One option is to include the creation of venting slits (small punctures in the lumen of the tube that allow aqueous to percolate through) in the implant. Other options include creation of an orphan trabeculectomy at the same time as implanting the nonvalved device or the simultaneous insertion of a flow-restricted device such as an Ahmed S3. The orphan trabeculectomy or Ahmed S3 will function to control the IOP for a few weeks until a capsule has formed around the flow-restricted device.

Cyclophotocoagulation

In eyes that have poor visual potential, an effective option for acutely lowering the IOP and helping reduce discomfort is the use of transscleral diode cyclophotocoagulation. Chapter 57 describes the preferred technique for performing this procedure.

REFERENCES

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2.      Gharagozloo NZ, Brubaker RF. Effect of apraclonidine in long-term timolol users. Ophthalmology. 1991;98:1543-1546.

3.      Koskela T, Brubaker RF. Apraclonidine and timolol. Combined effects in previously untreated normal subjects. Arch Ophthalmol. 1991;109:804-806.

4.      Greco JJ, Kelman CD. Systemic pilocarpine toxicity in the treatment of angle closure glaucoma. Ann Ophthalmol. 1973;5:57-59.

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10.    Grabie MT, Gipstein RM, Adams DA, et al. Contraindications for mannitol in aphakic glaucoma. Am J Ophthalmol. 1981;91:265-267.

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13.    Mehra KS, Singh R. Lowering of intraocular pressure by isosorbide. Effects of different doses of drug. Arch Ophthalmol. 1971;86(6):623-625.

14.    Smith EW, Drance SM. Reduction of human intraocular pressure with intravenous mannitol. Arch Ophthalmol. 1962;68:734-737.

15.    Havener WH. Ocular Pharmacology. 4th ed. St Louis, MO: CV Mosby; 1978:440.

16.    Chalam KV, Gupta SK, Grover S, Brar VS, Agarwal S. Intracameral Avastin dramatically resolves iris neovascularization and reverses neovascular glaucoma. Eur J Ophthalmol. 2008;18(2):255-262.