STERILE ENDOPHTHALMITIS FOLLOWING INTRAVITREAL INJECTION OF PRESERVATIVE-FREE TRIAMCINOLONE ACETONIDE Andrew Lam, MD, Sunir J. Garg, MD, Marc J. Spirn, MD, Mitchell S. Fineman, MD, Arunan Sivalingam, MD

Purpose: To describe two cases of sterile endophthalmitis following intravitreal injection of preservative-free triamcinolone acetonide. Methods: Chart review. Results: Two patients with histories of sterile inflammatory reaction to intravitreal Kenalog (triamcinolone acetonide) subsequently were treated with intravitreal injections of preservative-free triamcinolone. Both patients presented 2 to 3 days after injection with significant anterior chamber cell reaction without pain or inflammation-related conjunctival injection. The intraocular inflammation of both patients resolved completely using only topical steroids and antibiotics. Conclusions: An inflammatory reaction to the vehicle has been the leading hypothesis for the etiology of the sterile inflammatory response following intravitreal Kenalog injections. The use of preservative-free triamcinolone is intended to eliminate this potential source of toxicity. These cases demonstrate that noninfectious endophthalmitis can develop even with preservative-free triamcinolone. RETINAL CASES & BRIEF REPORTS 2:228 –230, 2008

From The Retina Service of Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania.

been singled out as the most likely stimulus for inflammation, and some investigators have advocated removing this additive to prevent noninfectious endophthalmitis.5,6 We describe two cases of presumed sterile endophthalmitis following intravitreal injections of preservative-free triamcinolone.

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ntravitreal injection of Kenalog (triamcinolone acetonide) is used to treat several retinal diseases, including macular edema and chronic uveitis. In addition to the risk of infectious endophthalmitis that accompanies any intraocular procedure, there have been several reports of presumed sterile, noninfectious endophthalmitis after intravitreal Kenalog injection.1–3 This reaction is thought to be related to the vehicle in which Kenalog is suspended.1,4 The vehicle in Kenalog (Bristol-Myers Squibb, Princeton, NJ), the most commonly available commercial form of triamcinolone acetonide, contains the additives benzyl alcohol, carboxymethylcellulose sodium, and polysorbate. A reaction to the preservative benzyl alcohol has

Case 1 A 52-year-old man with a history of proliferative diabetic retinopathy underwent three vitrectomies in his right eye. He subsequently developed sympathetic ophthalmia in his left eye and the right eye was enucleated. The patient deferred systemic treatment of his sympathetic ophthalmia in favor of intravitreal injections of Kenalog (4 mg, 0.1 cc). After nearly 2 years of injections, he developed significant vitritis following an uncomplicated Kenalog injection. Although this was believed to be a sterile inflammatory reaction, a vitreous tap with injection of intravitreal antibiotics was performed. The vitreous specimen was culture negative and his inflammation resolved within 10 days. A month later, he underwent another intravitreal Kenalog injection with a similar inflammatory response that completely resolved in 11 days with topical treatment alone. After these two inflammatory reactions, he received an

Reprint requests: Sunir J. Garg, MD, Assistant Professor of Ophthalmology, The Retina Service of Wills Eye Institute, Thomas Jefferson University, 840 Walnut Street, Suite 1020, Philadelphia, PA 19107; e-mail: [email protected]

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ENDOPHTHALMITIS AFTER INTRAVITREAL PRESERVATIVE-FREE TRIAMCINOLONE ACETONIDE

Fig. 1. Case 1. External photograph of the left eye shows a mild subconjunctival hemorrhage at the inferotemporal injection site, but the eye is otherwise white.

injection of preservative-free triamcinolone acetonide (New England Compounding Center, Framingham, MA) with no postinjection inflammation. Three days after a second preservative-free triamcinolone injection, he returned complaining of sudden, painless vision loss. His vision had decreased from 20/200 to hand motions. The eye was white other than a subconjunctival hemorrhage at the injection site (Figure 1). He had 3⫹ anterior chamber cells with 2⫹ vitritis. This was presumed to be a sterile inflammatory response and he was treated with fortified vancomycin and tobramycin, prednisolone acetate, and cycloplegic drops. By the next day, his inflammation had begun to improve and it completely resolved within 9 days.

Case 2 A 70-year-old woman underwent a vitrectomy in her right eye for an epiretinal membrane. Intravitreal Kenalog was injected intraoperatively. The next day she had a 0.5 mm hypopyon. This was believed to be a sterile inflammatory reaction to the Kenalog and she was treated with topical prednisolone acetate and ofloxacin. Her inflammation resolved completely within 10 days. She later developed cystoid macular edema and opted for an intravitreal injection of preservative-free triamcinolone (New England Compounding Center). Two days after this injection she returned complaining of decreased vision. Her vision had declined from 20/70 preinjection to counting fingers. She had a hypopyon, but the conjunctiva was uninflamed (Figure 2). Treatment with topical prednisolone acetate and ofloxacin resulted in resolution of the inflammation within 2 weeks.

Comment Distinguishing between infectious and noninfectious endophthalmitis after intravitreal triamcinolone injection can be difficult. Presumed sterile inflammatory endophthalmitis often presents within 2 days, which is often sooner than infectious endophthalmitis presents, but, as Case 1 demonstrates, this is not always

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Fig. 2. Case 2. External photograph of the right eye shows a small hypopyon but the conjunctiva is otherwise uninflamed.

the case.1 Minimal pain and lack of conjunctival injection are also suggestive but not ideal markers as the injected steroid can mask the typical presentation of infectious endophthalmitis. As there is no way to be absolutely certain an inflammatory response is not infectious, physicians are motivated to find ways to minimize the incidence of sterile endophthalmitis. An inflammatory reaction to preservatives such as benzyl alcohol has been the leading hypothesis for the etiology of the sterile inflammatory response following intravitreal Kenalog injections.6 Specifically, attention has been drawn to benzyl alcohol, and the use of preservative-free triamcinolone without additives like benzyl alcohol is intended to eliminate this potential source of toxicity.5,6 The formulation of preservative-free triamcinolone used (New England Compounding Center) has a shelf-life of 45 days and contains the following ingredients: triamcinolone acetonide, polysorbate 80 (a surfactant), polyglycol (suspending agent), dibasic sodium phosphate and monobasic sodium phosphate, and sodium chloride 0.22% (components of balanced salt solution).7 The 0.99% benzyl alcohol present in Kenalog-40 is absent. These cases demonstrate that noninfectious endophthalmitis can develop even with preservative-free triamcinolone. Other possible etiologies for noninfectious endophthalmitis include the presence of a contaminant in the drug suspension and the formation of a pseudohypopyon composed of the triamcinolone particles. In the first case, the compounding pharmacy tested samples from the lot and found no contaminants and there have been no similar reported complications from that lot. Furthermore, multiple retinal specialists examined these patients and agreed that the anterior chamber in-

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flammation was cellular and not triamcinolone particles. Both are presumed cases of noninfectious endophthalmitis as we did not culture the vitreous. However, the clinical presentation and rapid resolution without intravitreal injection of antibiotics strongly suggests that these were noninfectious. There are recent studies that suggest that triamcinolone may be toxic to the retina and these two cases suggest that patients can develop an inflammatory reaction to triamcinolone itself.8 Clinicians should be aware that sterile endophthalmitis might still develop even with preservative-free triamcinolone. Key words: endophthalmitis, Kenalog, preservative-free, sterile, triamcinolone.

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References 1.

Nelson ML, Tennant TS, Sivalingam A, et al. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina 2003;23:686–691.

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Sterile endophthalmitis following intravitreal injection of preservative-free triamcinolone acetonide.

To describe two cases of sterile endophthalmitis following intravitreal injection of preservative-free triamcinolone acetonide...
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