Intraocular Steroids in the Office
New formulations offer preservative-free triamcinolone without relying on compounding pharmacies.
JULIA A. HALLER, MD
The intraocular use of steroids dates back to the 1970s, when these agents were used as an adjunctive therapy for endophthalmitis.1 Intravitreal triamcinolone acetonide (IVTA) has been a part of clinical ophthalmology for more than a decade, and has been used to treat a wide range of ocular pathology, including choroidal neovascularization, macular edema and uveitis.2,3 The peer-reviewed literature contains scores of publications assessing the effectiveness and side effects of IVTA in various disease states. Although the introduction of intravitreal anti-VEGF agents may have tempered its use, IVTA is still commonly employed in the office to treat macular edema associated with diabetic retinopathy (DME), retinal vein occlusions, and cataract surgery. The approval of 2 sterile, preservative-free preparations of triamcinolone acetonide suspension – TRIESENCE® (Alcon, Fort Worth, TX) and more recently TRIVARIS® (Allergan, Irvine, CA) — suggests demand still exists for an ocular-friendly triamcinolone formulation.
The first of these formulations to become available was TRIESENCE® suspension, a preservative-free suspension of TA, designed for intraocular administration. It was approved by the FDA in late 2007 for clinical use in sympathetic ophthalmia, temporal arteritis, uveitis, and ocular inflammatory conditions unresponsive to topical corticosteroids. It is also approved for enhancing tissue visualization during vitrectomy.
TRIESENCE® suspension is packaged as a single-use 1 ml vial, at a concentration of 40 mg/ml. This is the same concentration as KENALOG®-40 (Bristol-Myers Squibb, Princeton, NJ), a preserved formulation of TA, as well as commonly used preservative-free formulations obtained from compounding pharmacies. TRIVARIS®, a triamcinolone acetonide injectable suspension, is available at a concentration of 80 mg/mL. Neither KENALOG® nor compounded TA is FDA-approved for intraocular use; intravitreal injections of these formulations for any indication are thus all off-label. Early reports suggest that clinicians are using both TRIESENCE® suspension and TRIVARIS® in a manner similar to their use of previously available TA formulations. Because the most common retinal uses for IVTA are DME and edema associated with venous occlusive disease, and neither TRIVARIS® nor TRIESENCE® suspension is approved for these indications, most intravitreal steroid injections continue to be performed in an off-label manner, despite the introduction of the new intravitreal formulations of TA.
|Julia A. Haller, MD, is ophthalmologist-in-chief at Wills and professor and chair of the Department of Ophthalmology at Thomas Jefferson University, Philadelphia, PA.|
USE AND SAFETY OF TRIESENCE® SUSPENSION, THE FIRST TA FORMULATION APPROVED INTRAVITREAL INJECTION
The approved indications for TRIESENCE® suspension seem unusual at first glance. For example, IVTA is rarely, if ever, used as a treatment for temporal arteritis, yet this is an approved indication for TRIESENCE® suspension. In contrast, the drug is not approved for such common uses of IVTA as DME. Further probing of this issue reveals that FDA approval of TRIESENCE® was based on a "paper application," a process by which the approved indications for KENALOG® were simply transferred to TRIESENCE®. In addition, Alcon conducted a visualization study on 60 patients to show that TRIESENCE® was safe and effective for use in visualization during vitrectomy.
The ocular indications for KENALOG® are for intramuscular use, so the indications for TRIESENCE® suspension simply mirror the approved ocular indications for intramuscular KENALOG®. The only exception to this is the indication for visualization during vitrectomy, which required the small clinical trial on 60 patients.
Color fundus photo (a) and corresponding OCT (c) of a patient after a branch vein occlusion in the right eye prior to any intervention. The patient was treated with 4mg of intravitreal TRIESENCE® suspension and 7 weeks post-injection photo (b) and OCT (d) reveal significant improvement of macular edema with restoration of the foveal contour.
Intravitreal injection of preserved TA or preservative-free TA obtained from compounding pharmacies has been associated with cases of infectious and noninfectious (or sterile) endophthalmitis.4-6 Noninfectious endophthalmitis has been presumed to be an inflammatory reaction to the preservative (benzyl alcohol) or other excipients in KENALOG®.7 However, noninfectious endophthalmitis also has been reported with non-preserved TA generated by a compounding pharmacy, which does not contain benzyl alcohol.8 The stimulus for ocular inflammation in these cases is unclear. Further experience will clarify whether culture-negative endophthalmitis, a vexing issue for the treating clinician, is eliminated by the use of steroids formulated specifically for intravitreal administration, such as TRIESENCE® suspension and TRIVARIS®. The side effect profile of these agents should otherwise be very similar to that of other IVTA formulations, the most common sequelae of which are increased intraocular pressure (IOP) and increased rate of cataract formation.
The cost of TRIESENCE® suspension is $124 per vial, and is reimbursed by Medicare and most insurers. Pricing was not available for TRIVARIS® as of this writing. A new J-Code was created to help simplify billing and expedite reimbursement of TRIESENCE® suspension. Effective January 1, 2009, physicians can use J3300 (injection, triamcinolone acetonide, preservative free 1mg).
Sterile, preservative-free preparations of TA that are designed for intraocular use represent a welcome addition to the market. The precise role of TRIESENCE® suspension, and the more recent arrival TRIVARIS®, in clinical practice is still evolving as physicians and patients gain experience with their use. While steroid preparations specifically designed for intraocular use are clearly of value, further study is needed to clarify the use and cost-benefit profile of TRIESENCE® relative to other preservative-free TA formulations, both TRIVARIS® and preparations from compounding pharmacies. In addition, these shorter acting steroid formulations will need to be compared to the longer acting steroid treatments already available or in clinical testing, such as the RETISERT® implant (Bausch and Lomb, Rochester, NY), with its long-term delivery of fluocinolone to the posterior segment, the POSURDEX® implant (Allergan), which provides extended delivery of dexamethasone, and others. Comparison of the efficacy of these corticosteroid formulations, and their respective rates of post-injection inflammation, IOP elevation and cataract formation, is an important clinical priority as physicians gain experience with the expanding retinal pharmacopoeia. RP
- Peyman, G.A. and R. Herbst, Bacterial endophthalmitis. Treatment with intraocular injection of gentamicin and dexamethasone. Arch Ophthalmol. 1974;91(5):p.416-8.
- Jermak, C.M., et al., Triamcinolone acetonide in ocular therapeutics. Surv Ophthalmol. 2007;52(5):p.503-22.
- Penfold, P.L., et al., Exudative macular degeneration and intravitreal triamcinolone. A pilot study. Aust N Z J Ophthalmol. 1995;23(4):p.293-8.
- Nelson, M.L., et al., Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina. 2003;23(5):p.686-91.
- Roth, D.B., et al., Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol. 2003;121(9):p.1279-82.
- Westfall, A.C., et al., Acute endophthalmitis incidence: intravitreal triamcinolone. Arch Ophthalmol. 2005;123(8):p.1075-7.
- Jonas, J.B., Effects of triamcinolone acetonide injections with and without preservative. Br J Ophthalmol. 2007;91(9):p.1099-101.
- Lam A, G.S., Spirn M, Fineman M, Sivalingam A., Sterile Endophthalmitis Following Intravitreal Injection of Preservative-free Triamcinolone Acetonide. Retina Cases and Brief Reports. In Press.