In recent years, intravitreal triamcinolone acetonide (IVTA) has been used for the treatment of pseudophakic macular edema, exudative macular degeneration, macular edema following central retinal vein occlusion, diffuse diabetic macular edema, iris neovascularization, and idiopathic juxtafoveal telangiectasis. Although surgical intervention is uncommon for IVTA associated glaucoma, the prevalence of an IOP elevation following IVTA is estimated to be around 50% (Br J Ophthalmol. 2006;90:999-1003. Epub 2006 Apr 5). As ophthalmologists are seeing a resurgence of steroid-induced glaucoma due to the increased use of IVTA to treat macular edema from a variety of causes, they should be equipped to anticipate, recognize, and manage the condition via age-appropriate IOP lowering treatments.
Pathophysiology
Steroid-induced ocular hypertension was first reported in 1950 when McLean described an increase in IOP associated with the systemic administration of adrenocorticotrophic hormone (ACTH) (Trans Am Ophthalmol Soc. 1950;48:293-296). The first report of increased IOP caused by the local administration of cortisone was published 4 years later (Ann D’Oculist. 1954;187:805). The intraocular potency and mode of administration is important in initiating an ocular hypertensive response.4-13
The mechanism of steroid-induced IOP elevations is an increased resistance to aqueous outflow. Researchers have observed accumulations of extracellular matrix (ECM) consisting of abnormal collagen with lamellar thickening arranged in a fingerprint-like pattern resembling basement membrane and dense homogenous material adjacent to the inner wall of Schlemm’s canal.14-16 These ECM changes are different from the ECM changes seen in primary open-angle glaucoma (POAG) (Arch Ophthalmol. 1997;115:375-383). Experimental studies of cultured human eyes or trabecular meshwork endothelial cells indicate that corticosteriods change the proteoglycans of the extracellular matrix,18,19 increase elastin and fibronectin expression,20,21 decrease protease and matrix metalloproteinase activities,22,23 change the synthesis of specific proteins (Invest Ophthalmol Vis Sci. 1989;30:1843-1847), increase nuclear size and DNA content (Exp Eye Res. 1989;49:259-270), stabilize the actin microfilament network of trabecular meshwork cells (Invest Ophthalmol Vis Sci. 1994;35:281-294), and decrease the phagocytic capacity.27,28
Risk Factors
Several variables have been identified as predisposing risk factors for steroid-induced ocular hypertension. Approximately one-third of glaucoma suspects and more than 90% of POAG patients responded with an IOP elevation greater than 6 mm Hg after receiving a 4-week course of topical dexamethasone 0.1%.29,30 Others have found that first-degree relatives of POAG patients increased one’s susceptibility to being a steroid-responder.31,32
IOP elevations are more prominent in older adults compared with younger adults. 29,30 However, children are also at risk for an increased IOP in response to steroids. Lam et al found that 71% and 59% of children receiving topical dexamethasone 0.1% (q.i.d. and b.i.d. respectively) had a subsequent IOP measurement greater than 21 mm Hg (Clin Experiment Ophthalmol. 2005;33:252-258). Of those children receiving dexamethasone q.i.d. or b.i.d., 36% and 21% respectively had an IOP greater than 30 mm Hg. Age, as a risk factor, appears to occur in a bimodal distribution peaking first at age 6. As one progresses through adulthood, the risk rises again in late adulthood.
Patients with type 1 diabetes mellitus (Am J Ophthalmol. 1971;1:1-16), high myopia (Am J Ophthalmol. 1966;62:1038-1043), and connective tissue disease (Br J Ophthalmol. 1983;67:487-490) have also been shown to be at greater risk of an elevated IOP from steroids.
Clinical Course
Both the speed and frequency of IOP elevation are related to the route of administration: the more rapid the onset, the greater prevalence of steroid responders occurring with intravitreal > subtenons > topical > intravenous > parenteral > periorbital dermal application > inhaled. Ophthalmologists are most likely to encounter topical and intravitreal routes of administration. When treated with topical steroids for 4-6 weeks, 5% of the population demonstrates a rise in IOP > 16 mm Hg, and 30% have a rise of 6-15 mm Hg.37,38 With intravitreal triamcinolone, an IOP elevation may be seen in up to 40-60% of individuals.1,39
In the majority of cases, medical management is all that is required to resolve IOP elevation. In patients with preexisting glaucoma and glaucoma suspects, Becker and Mills found significant increases in IOP in 2-4 weeks with the use of topical betamethasone 0.1% (Arch Ophthalmol. 1963;70:500-507). However, the IOP returned to baseline approximately 1 week after the discontinuation of steroid treatment. This and a wealth of other anecdotal observations have led to the general belief that IOP will normalize after about one-third to one-half the duration of the topical administration.
Treatment
Steroid-induced glaucoma is defined as an elevated IOP that occurs as a result of a person’s use of corticosteroids, causing optic nerve and visual field changes typical of open-angle glaucoma. People whose IOP increases following exposure to corticosteroids are often called “steroid-responders.” Increased IOP can occur as a consequence of oral, intravenous, inhaled, topical, periocular, or intravitreal corticosteroid therapy.4-12,37,38
Age-appropriate IOP lowering treatments (e.g. avoiding laser trabeculoplasty in children and younger adults or avoiding alpha-agonists in children) are employed to temporize or permanently treat elevated IOP that persists indefinitely. Following IVTA induced ocular hypertension, the need for surgical treatment is approximately 1% following a single IVTA injection and approximately 2%, if the IOP elevation occurred in an eye that had received more than one IVTA injection (Br J Ophthalmol. 2006;90:999-1003. Epub 2006 Apr 5). When medications are utilized, the average duration of IOP lowering treatment was 6 months for a single IVTA injection and 8 months for multiple IVTA injections. However, some eyes required continued treatment through the study follow-up period of 12 months (Br J Ophthalmol. 2006;90:999-1003. Epub 2006 Apr 5).
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Author Disclosure
Dr. Rhee discloses a financial interest as a recipient of recent clinical research funding from Pharmacia, Allergan, Santen, and as a consultant for Johnson & Johnson. He also participates on the speaker panels for Allergan, Alcon, and Merck. He has no proprietary interest in any of the products discussed in this article.