AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Several different drugs have the potential to cause the elevation of intraocular pressure (IOP), which can occur via an open-angle mechanism or a closed-angle mechanism. Steroid-induced glaucoma is a form of open-angle glaucoma that usually is associated with topical steroid use, but it may develop with inhaled, oral, intravenous, periocular, or intravitreal steroid administration. Medications prescribed for a variety of systemic conditions (eg, depression, allergies, Parkinson disease) can produce pupillary dilation and precipitate an attack of acute angle-closure glaucoma in anatomically predisposed eyes that have narrow angles.

Open angle

Drug-induced elevation of IOP is more common by an open-angle mechanism. Corticosteroids are a class of drugs that may produce IOP elevation by this mechanism. Not all patients taking corticosteroids will develop elevated IOP. Risk factors include preexisting primary open-angle glaucoma, a family history of glaucoma, high myopia, diabetes mellitus, and history of connective tissue disease (especially rheumatoid arthritis).

Additionally, the number of people responding with an elevated IOP varies with the route of administration. More people respond from topically applied drops (including topically applied creams to the periorbital area) or intravitreal injection. In order of decreasing frequency, incidence of elevated IOP is less with intravenous, parenteral, and inhaled routes of administration. Patients on chronic corticosteroid therapy can remain undiagnosed with an elevated IOP, which can result in glaucomatous optic nerve damage.

Steroid-induced IOP elevation typically occurs within a few weeks of beginning steroid therapy. In the majority of cases, the IOP lowers spontaneously to the baseline within a few weeks to months upon stopping the steroid. In rare instances, the IOP remains elevated. Additionally, there may be some patients whose underlying condition necessitates the continued use of corticosteroids despite the elevated IOP. These patients are treated identically to those with primary open-angle glaucoma.

Closed angle

The majority of categories of drugs that list glaucoma as a contraindication or adverse effect are concerned with inducing acute angle-closure glaucoma. These medications will incite an attack only in those individuals with occludable angles (ie, very narrow anterior chamber angles). The classes of medications that have the potential to induce angle closure are topical anticholinergic or sympathomimetic dilating drops, tricyclic antidepressants, monoamine oxidase inhibitors, antihistamines, antiparkinsonian drugs, antipsychotic medications, and antispasmolytic agents.

Sulfa containing medications may induce angle-closure glaucoma by a different angle-closure mechanism, involving anterior rotation of the ciliary body. Typically, the angle closure is bilateral and occurs within the first several doses of the sulfonamide-containing medication. Patients with narrow or wide open angles are potentially susceptible to this rare and idiosyncratic reaction.

Pathophysiology

Open angle

Exact pathophysiology of steroid-induced glaucoma is unknown. It is known that steroid-induced IOP elevation is secondary to increased resistance to aqueous outflow. Some evidence indicates that the defect could be increased accumulation of glycosaminoglycans or increased production of trabecular meshwork-inducible glucocorticoid response (TIGR) protein, which could mechanically obstruct outflow. Other evidence points toward corticosteroid-induced cytoskeletal changes that could inhibit pinocytosis of aqueous humor or inhibit the clearing of glycosaminoglycans, resulting in the accumulation of this substance.

Closed angle

The pathophysiology of drug-induced angle-closure glaucoma is usually increased pupillary block (ie, increased iris-lens contact at the pupillary border) from pupillary dilation. Medications have a direct or secondary effect, either to stimulate sympathetic or inhibit parasympathetic activation causing pupillary dilation, which can precipitate acute angle-closure glaucoma in patients with occludable angles. The other possible mechanism is dilation in patients with plateau iris syndrome. See Glaucoma, Acute Angle Closure.

A notable exception is the angle closure resulting from sulfa containing medications. The mechanism involves anterior rotation of the ciliary body and/or choroidal effusions, resulting in shallowing of the anterior chamber and blockage of trabecular meshwork by the iris. Pupillary dilation and a preexisting shallow anterior chamber angle are not necessary. The exact defect that causes the ciliary body swelling is unknown.

Frequency

United States

Open angle: Incidence of steroid-induced IOP elevation in patients on systemic corticosteroids is unknown because most of these patients do not have their IOP checked. These patients may be discovered during a routine eye exam while on their medication, or the glaucoma may have progressed to the point of causing visual symptoms. Patients taking topical steroid drops usually receive follow-up care by an ophthalmologist who monitors IOP. Risk of developing steroid-induced glaucoma is related to its potency and frequency of administration. People with preexisting primary open-angle glaucoma have a much greater potential to experience an elevated IOP from topical corticosteroids. Patients with primary chronic angle closure and patients with secondary open-angle glaucoma behave similarly to normal eyes with regard to steroid response.

Studies completed by Armaly indicated that approximately one third of normal eyes and more than 90% of patients with primary open-angle glaucoma respond with greater than 6 mm Hg of IOP elevation after receiving a 4-week course of topical dexamethasone 0.1%. Following intravitreal injection of triamcinolone, over 50% of nonglaucomatous eyes will have an increase in IOP; this increase in IOP can occur as long as 6 months after the injection.

Closed angle: Prevalence of occludable angles in whites from the Framingham study is 3.8%. Narrow angles are more common in the Asian population. A study of a Vietnamese population estimated a prevalence of occludable angles at 8.5%.

Mortality/Morbidity

Glaucoma is the third leading cause of blindness in the US. The risk of becoming legally blind in one eye from open-angle glaucoma is approximately 20%, with bilateral blindness occurring in 9%.

Race

No racial predilection exists for steroid-responsive IOP.

Sex

No gender predilection exists for steroid-responsive IOP.

Age

Steroid-responsive IOP elevations can occur in people of all ages, although children less frequently are reported to have IOP elevation with steroids.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Elicit the patient's current medications.

• Symptoms
• • With steroid-induced glaucoma, the pressure elevation is gradual. Therefore, like primary open-angle glaucoma, very few symptoms exist.
  • Visual symptoms of drug-induced acute angle-closure glaucoma are the same as primary acute angle-closure glaucoma.
• Past ocular history/past medical history
• • Elicit history of systemic medical disease, which could require chronic corticosteroid use (eg, uveitis, collagen vascular disease, asthma, dermatitis).
  • Patients with preexisting primary open-angle glaucoma, a family history of primary open-angle glaucoma, diabetes mellitus, high myopia, or connective tissue diseases are at greater risk to be steroid responders.

Physical

Complete ophthalmic examination

• Vision and refraction - Patients with hyperopia are at an increased risk for narrow angles.
• Pupils - Test for the presence of an afferent pupillary defect (APD) if topical use has been unilateral or attack has only occurred in one eye.
• External examination - Flashlight test to identify an anatomically narrow angle
• Slit lamp examination - Exclude stigmata of other causes of secondary glaucoma
• • Cornea - Krukenberg spindle (eg, pigmentary glaucoma), keratic precipitates (eg, uveitic glaucoma, Fuchs heterochromic iridocyclitis)
  • Anterior chamber - Anterior chamber depth to indicate narrow angle
  • Iris - Heterochromia (ie, Fuchs heterochromic iridocyclitis), iris transillumination defects (eg, pseudoexfoliation [PXF], pigment dispersion, previous episodes of intermittent angle closure)
  • Lens - Pseudoexfoliation material (pseudoexfoliation glaucoma)
• Gonioscopic evaluation - Examine angle anatomy to determine if the angle is at risk for occlusion with dilation.
• Dilated examination - Inspect the optic nerve for glaucomatous optic nerve damage (see Glaucoma, Primary Open Angle for description of glaucomatous patterns).

Causes

Drug-induced glaucoma can occur via two mechanisms. Open-angle glaucoma is generally steroid induced, and closed-angle glaucoma is generally from pupillary dilation.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Steroid therapy (eg, posterior subcapsular cataracts)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No lab studies are indicated.

Imaging Studies

• No imaging studies are indicated for glaucoma.

Other Tests

• Formal visual field testing (ie, Humphrey, Octopus, Goldmann)

Procedures

• No procedures are indicated for glaucoma.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Open angle
• • If the patient's underlying medical condition can tolerate discontinuation of corticosteroids, then cessation of the medication usually will result in normalization of IOP.
  • In the case of topical corticosteroid drops, consider using a lower potency steroid medication, such as the phosphate forms of prednisolone and dexamethasone, rimexolone, loteprednol etabonate, fluorometholone, or medrysone. These lower potency drugs have a lesser chance of raising IOP, but they usually are not as effective as an anti-inflammatory drug. Topical nonsteroidal anti-inflammatory medications (eg, diclofenac, ketorolac) are other alternatives that have no potential to elevate IOP, but they may not have enough anti-inflammatory activity to treat the patient's underlying condition.
  • In the occasional cases in which the patient's IOP does not normalize upon cessation of the steroid or in those patients who must continue on corticosteroid medications, use standard antiglaucoma medications as described in Glaucoma, Primary Open Angle.
• Closed angle
• • If the etiology is because of sulfa containing medications, the increase in IOP generally will resolve upon stopping the medication. However, severe cases of sulfonamide-induced angle closure (ie, IOP >45 mm Hg) may not respond to simply discontinuing the offending medication. These cases may respond to intravenous solumedrol and mannitol.
  • For other etiologies, treat the same as primary acute angle-closure glaucoma.

Surgical Care

• Open angle
• • When medical therapy is ineffective at lowering the IOP to target pressure or the patient is intolerant of medical therapy, then surgical therapy is indicated.
  • In patients with an open angle and the absence of ocular inflammation, argon laser trabeculoplasty can be attempted to lower the IOP.
  • In patients whom both medical and laser therapy have failed to lower the IOP adequately, surgical therapy is warranted. Usually, trabeculectomy (guarded filtration procedure), with or without intraoperative antimetabolites, is the primary procedure. In cases of eyes with active neovascularization or inflammation, a glaucoma drainage implant may be used as the primary procedure.
• Closed angle: Treat the same as primary acute angle-closure glaucoma.

Consultations

If not able to control IOP, refer the patient to a glaucoma specialist.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goal of pharmacotherapy is to reduce morbidity and to prevent complications.

Bimatoprost (Lumigan) and travoprost (Travatan) are newer ophthalmic prostaglandin analogs recently approved in the United States. Bimatoprost is a prostamide analog with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Travoprost and bimatoprost are prostaglandin F2-alpha (ie, dinoprost) analogs similar to latanoprost. They are selective FP prostanoid receptor agonists believed to reduce IOP by increasing uveoscleral outflow. They are indicated for the lowering of IOP in patients with open-angle glaucoma or ocular hypertension who are intolerant of other IOP-lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another IOP-lowering medication.

Bimatoprost and travoprost are each administered once daily at bedtime (ie, 1 gtt in affected eye[s] hs); they have not been studied in pediatric patients.

They are contraindicated if hypersensitivity has been documented. No drug interactions have been reported. All are classified as pregnancy category C (ie, safety for use during pregnancy has not been established).

Like latanoprost, all demonstrate the unusual adverse effect of permanent increase in pigment of the iris (ie, increases brown pigment) and eyelid, and they may increase eyelash growth. Bacterial keratitis may occur. Use is cautioned in uveitis or macular edema. They should not be used if inflammation is present.

Drug Category: Adrenergic agonists

Topical agents (sympathomimetics) decrease aqueous production and reduce resistance to aqueous outflow. Often used with cholinergic agonists like pilocarpine. Adverse effects include dry mouth and allergenicity.

Drug Category: Beta-blockers

Topical beta-adrenergic receptor antagonists decrease aqueous humor production by the ciliary body. Adverse effects are due to systemic absorption of the drug, decreased cardiac output, and bronchoconstriction. In susceptible patients, this may cause bronchospasm, bradycardia, heart block, or hypotension. Monitor the patient's pulse rate and blood pressure; patients may be instructed to perform punctal occlusion after administering the drops. Depression or anxiety may be experienced in some patients, and sexual dysfunction may be initiated or exacerbated.

Drug Category: Sympathomimetics

Increase outflow of aqueous humor through trabecular meshwork and possibly through uveoscleral outflow pathway, probably by a beta2-agonist action. Up to one third of patients will not respond to these drugs.

Drug Category: Carbonic anhydrase inhibitors

Reduce secretion of aqueous humor by inhibiting carbonic anhydrase in the ciliary body. In acute angle-closure glaucoma, administer systemically; apply topically in patients with open-angle glaucoma. These drugs are less effective, and their duration of action is shorter than many other classes of drugs. Adverse effects are relatively rare but include superficial punctate keratitis, acidosis, paresthesias, nausea, depression, and lassitude.

Drug Category: Miotic agents (parasympathomimetics)

Contract the ciliary muscle, tightening the trabecular meshwork and allowing increased outflow of aqueous. Miosis results from the action of these drugs on pupillary sphincter. Adverse effects include brow ache, induced myopia, and decreased vision in low light.

Drug Category: Prostaglandin analogs

Increase uveoscleral outflow of aqueous. One mechanism of action may be through induction of metalloproteinases in the ciliary body, which breakdown the extracellular matrix, reducing resistance to outflow through the ciliary body. They can be used in conjunction with beta-blockers, alpha-agonists, or topical carbonic anhydrase inhibitors. Many patients respond well to these agents; others do not respond at all. Adverse effects include iris pigmentation, cystoid macular edema, and uveitis.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Open angle
• • It is recommended that all patients who use chronic corticosteroid medications in any capacity should have a full ophthalmologic evaluation.
  • Patients on topical corticosteroid therapy should receive follow-up care at regular intervals by an ophthalmologist to monitor their ocular condition and IOP. Steroid-induced IOP elevation typically occurs within 2-6 weeks of beginning steroid therapy.
  • Upon stopping corticosteroids, the IOP usually normalizes in a few weeks to months. For patients on medical therapy alone, interval of follow-up care is determined by the extent of the IOP elevation and degree of optic nerve and visual field damage.
  • Patients who have had surgical intervention should have follow-up care consistent with routine postoperative care for the appropriate procedure.
• Closed angle
• • It is recommended that people older than the 40 years should have routine eye examinations to screen for various conditions. One of these conditions should be the presence of narrow anterior chamber angles.
  • Treat the same as primary acute angle-closure glaucoma.

In/Out Patient Meds

• See Medication.

Deterrence/Prevention

• Drugs that have the potential of inducing glaucoma should only be used if truly indicated.
• If drugs must be used, IOP should be monitored closely.

Complications

• Untreated glaucoma can lead to permanent visual damage and blindness.

Prognosis

• A favorable outlook exists if IOPs are controlled.

Patient Education

• It is recommended that all patients who use chronic corticosteroid medications in any capacity should have a full ophthalmologic evaluation.
• For excellent patient education resources, visit eMedicine's Glaucoma Center. Also, see eMedicine's patient education articles Glaucoma Overview, Glaucoma FAQs, Understanding Glaucoma Medications, and Angle Recession Glaucoma.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Patients taking drugs that have the potential to increase IOP should have tests to detect this condition and to allow early diagnosis.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Armaly MF. Effect of corticosteroids on intraocular pressure and fluid dynamics. I. The effect of dexamethasone in the normal eye. Arch Ophthalmol. 1963;70:482.
• Armaly MF. Effect of corticosteroids on intraocular pressure and fluid dynamics. II. The effect of dexamethasone in the glaucomatous eye. Arch Ophthalmol. 1963;70:492.
• Nguyen N, Mora JS, Gaffney MM, et al. A high prevalence of occludable angles in a Vietnamese population. Ophthalmology. Sep 1996;103(9):1426-31. [Medline].
• Ohji M, Kinoshita S, Ohmi E. Marked intraocular pressure response to instillation of corticosteroids in children. Am J Ophthalmol. Oct 15 1991;112(4):450-4. [Medline].
• Polansky JR. Side effects of ophthalmic therapy with anti-inflammatory steroids. Curr Opin Ophthalmol. 1992;3:259-272.
• Wolfs RC, Grobbee DE, Hofman A. Risk of acute angle-closure glaucoma after diagnostic mydriasis in nonselected subjects: the Rotterdam Study. Invest Ophthalmol Vis Sci. Nov 1997;38(12):2683-7. [Medline].

Article Last Updated: Jun 18, 2006