This course has expired. You can still review the content but course credit is no longer available.
This certified CME activity is designed for retina specialists, glaucoma specialists and general ophthalmologists involved in the management of patients with retinal and glaucomatous disease.
Upon completion of this activity, the participant should be able to:
• Understand the potential for corticosteroid therapy to induce complications, including elevated IOP
• Distinguish between the different classes of corticosteroid therapy and relate the risks for complications associated with each
• Explain the early warning signs of elevated IOP
• Identify effective management strategies for patients requir- ing intervention
Intravitreal corticosteroid therapy has a broad range of applicability for retinal and ocular pathology. Because steroids have anti-inflammatory and antiangiogenic properties, they are beneficial for treating several retinal conditions, including diabetic and vasculoocclusive macular edema, exudative macular degeneration, pseudophakic cystoid macular edema, and pos- terior uveitis.1 Corticosteroid therapy has been associated with some potential complications, notably corneal opacification and intraocular pressure (IOP) elevation, which may be a barrier to its acceptance as a suitable treatment modality. This may be to patients’ detriment if an effective treatment strategy is underutilized, especially given that these complications can be effectively managed before visual symptoms become irreversible.
The most popular types of corticosteroids for ocular or retinal applications are triamcinolone acetonide, dexamethasone, and fluocinolone. Each has unique pharmacodynamic, pharma- cokinetic, and safety profiles. Nevertheless, several large clinical trials have documented a risk for IOP elevation associated with each class of corticosteroid. Use of topical ocular hypotensive therapy during subsequent clinical care after a single or mul- tiple intravitreal injections of triamcinolone acetonide (a sur- rogate marker for elevated IOP) has been documented as high as 20% to 60%.2-7 Transient and self-limiting IOP elevations have also been associated with intravitreal triamcinolone acetonide injections.8
Sustained-release corticosteroid intraocular implants are a relatively new addition to this category, offering the potential for durable drug delivery that is not dependent on patients’ compliance and eliminating instillation-associated complica- tions. However, the risk of an IOP spike after corticosteroid use may be both dose-dependent and associated with prolonged exposure. In one study, 24% of uveitis patients treated with the dexamethasone implant (Ozurdex, Allergan) needed topical therapy 6 months after implantation.9 After 3 years of follow-up of patients implanted with the fluocinolone device (Retisert, Bausch + Lomb), 70% of patients needed some form of glau- coma topical therapy.10 Topical therapy was required by 29% of patients within 1 year of implantation with the fluocinolone device (Iluvien, Alimera Sciences).11 Some studies have noted the need for filtration glaucoma surgery between 5% and 27% among patients implanted with the Iluvien11 and Retistert10 devices, respectively.
Given that there is still a strong rationale for corticosteroid therapy for the care of ocular and retinal pathologies, retina specialists using corticosteroids in any capacity should be aware of the risk factors for IOP elevation, as well as appropriate man- agement strategies for patients displaying the clinical signs or symptoms associated with elevated IOP. Retina specialists also must be aware of when it may be appropriate to work closely with a colleague in the glaucoma field on the management of a complex case. This could entail referral, either for incisional surgery or for long-term follow-up with diagnostic devices that may not be in a typical retina practice.
There may presently be a significant knowledge gap in retina specialists’ understanding of the dynamics of steroid-induced IOP elevation. An understanding of the dose- and exposure- dependent relationship between corticosteroid use and IOP elevation would be beneficial for the total care of patients. Equally, knowledge of appropriate management strategies would equip ophthalmologists who regularly use corticosteroid therapy with confidence in dealing with the most common potential complication.
Left untreated, elevation of IOP has the potential to damage the optic nerve, which, in turn, may lead to irreversible loss of visual acuity. However, most cases of corticosteroid-induced IOP elevation can be effectively managed with topical therapy, similar to that used for treating glaucoma.3,4,9,12 In each of these studies, the initiation of antihypotensive therapy was deemed necessary for some patients, and the initiation of this strategy was effective in reducing pressures to acceptable levels.
Incisional surgery to manage IOP elevation secondary to corticosteroid use may still be required in some cases.3,4,9,12 Discussions of surgical intervention may engender additional fears of intra- and postoperative complications. However, new understanding of the surgical management of glaucoma may add context to the associated risk when weighing a patient’s candidacy for surgery. For example, long-term follow up in the Tube Versus Trabeculectomy (TVT) Study suggests that shunts may confer a comparatively lower failure rate and a reduced rate of postoperative complications.13 Thus, even if IOP eleva- tion secondary to corticosteroid use is deemed serious enough to warrant surgical intervention, there are strategies available to minimize the attendant risks.
A full knowledge of the dynamics of corticosteroid-induced complications will be beneficial for arming clinicians who use these drugs with a more complete understanding when counseling patients and for knowing when to initiate additional therapeutic options. It is hoped that providing this education would remove a potential barrier to greater acceptance of this class of drugs. Finally, in the interest of more complete care to patients, providing clinicians with insight into the management strategies for corticosteroid-induced complications might engender greater collaboration with colleagues in other sub- specialties.
1. Kiernan DF, Mieler WF. The use of intraocular corticosteroids. Expert Opin Pharmacother. 2009;10(15):2511-2525.
2. BaathJ,EllisAL,ChrichtonA,etal.Safetyprofileoftriamcinoloneacetonide.JOculPharacolTher.2007;23(3):304-310. 3. Gillies MC, Sutter FK, Simpson JM, et al. Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial. Ophthalmology. 2006;113(9):1533-1538.
4. Gillies MC, Simpson JM, Billson FA, et al. Safety of an intravitreal injection of triamcinolone: results from a randomized clinical trial. Arch Ophthalmol. 2004;122(3):336-340.
5. Elman MJ, Aiello LP, Beck RW, et al. Diabetic Retinopathy Clinical Research Network. Randomized trial evaluat- ing ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117(6):1064-1077.
6. Goff MJ, Jumper JM, Yang SS, et al. Intravitreal triamcinolone acetonide treatment of macular edema associated with central retinal vein occlusion. Retina. 2006;26(8):896-901.
7. Sallam A, Sheth HG, Habot-Wilner Z, Lightman S. Outcome of raised intraocular pressure in uveitic eyes with and without a corticosteroid-induced hypertensive response. Am J Ophthalmol. 2009;148(2):207-213.
8. Tammewar AM, Cheng L, Kayikcioglu OR, et al. Comparison of 4 mg versus 20 mg intravitreal triamcinolone acetonide injections. Br J Ophthalmol. 2008;92(6):810-813.
9. Haller JA, Bandello F, Belfort R Jr, et al. OZURDEX GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117(6):1134-1146.
10. Goldstein DA, Godfrey DG, Hall A, et al. Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants. Arch Ophthalmol. 2007;125(11):1478-1485.
11. Campochiaro PA, Hafiz G, Shah SM, et al. Famous Study Group. Sustained ocular delivery of fluocinolone acetonide by an intravitreal insert. Ophthalmology. 2010;117(7):1393-1399.
12. Jonas JB, Degenring RF, Kreissig I, et al. Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology. 2005;112(4):593-598.
13. Gedde SJ, Schiffman JC, Feuer WJ, et al. The Tube Versus Trabeculectomy Study Group. Three-year follow up of the tube versus trabeculectomy study. Am J Ophthalmol. 2009;148(5):670-684.
In accordance with the disclosure policies of the Dulaney Foundation and to conform with ACCME and US Food and Drug Administration guidelines, anyone in a position to affect the content of a CME activity is required to disclose to the activity participants (1) the existence of any financial interest or other relationships with the manufacturers of any commercial products/devices or providers of commercial services and (2) identification of a commercial product/device that is unlabeled for use or an investigational use of a product/device not yet approved.