NONINFECTIOUS ENDOPHTHALMITIS OCCURRING AFTER INTRAVITREAL TRIESENCE INJECTION Sophie J. Bakri, MD, Albert O. Edwards, MD, PhD, Steven M. Couch, MD
Purpose: To report a case of noninfectious endophthalmitis occurring after intravitreal Triesence (preservative-free triamcinolone acetonide) injection. Method: Case report. Results: A 62-year-old patient with macular edema occurring after cataract surgery received 0.1 mL (4 mg) of intravitreal Triesence to the left eye. His vision was 20/60. One day later, he presented with a decrease in vision to light perception upon awakening. He denied ocular pain, and the eye was not red. Clinical examination was remarkable for orbital proptosis, minimal fibrin on the anterior chamber intraocular lens, and a white hypopyon. There was no view of the retina due to vitreous opacities. A vitreous tap and injection of intravitreal Ceftazidime and Vancomycin were performed. Microbiology showed no organisms on gram stain, and the cultures were negative. The endophthalmitis resolved, and the patient recovered vision to 20/70. Conclusions: Noninfectious endophthalmitis can occur after preservative-free commercially available intravitreal Triesence. This case suggests that noninfectious endophthalmitis can occur in the absence of the benzyl alcohol found in preserved preparations of Kenalog. RETINAL CASES & BRIEF REPORTS 3:316 –318, 2009
From the Department of Ophthalmology, The Mayo Clinic, Rochester, Minnesota.
servative-free Kenalog because this was thought to reduce the incidence of noninfectious endophthalmitis.3 Triesence is a recently approved, commercially available preservative-free intravitreal triamcinolone formulation that is increasing in popularity in the United States. The advantage of using a commercially prepared formulation is that it may be a safer and a more standard procedure than using a compounded preparation.5 We report noninfectious endophthalmitis occurring after intravitreal Triesence.
I
ntravitreal Triesence (Alcon, Fort Worth, TX) is a preservative-free triamcinolone acetonide preparation that was recently approved by the Food and Drug Administration in the United States.1 It is approved for the treatment of ocular inflammatory conditions as well as other rare diseases such as sympathetic ophthalmia. In addition to 4% weight/volume triamcinolone acetonide, the only other ingredients are polysorbate 80 (0.015% w/v) and carboxymethylcellulose (0.5% w/v). Before intravitreal Triesence was available, Kenalog-40 (Bristol-Myers Squibb, Teepack, NJ) was the most commonly used intravitreal steroid. However, this contains the preservative benzyl alcohol, which is toxic to the retina and has been thought to contribute to development of noninfectious endophthalmitis in some patients.2–5 Compounding pharmacies have been manufacturing pre-
Case Report We present a 62-year-old white male patient treated with 0.1 mL (4 mg) of intravitreal Triesence for macular edema. His ocular history includes a pars plana vitrectomy and membrane peeling for an epiretinal membrane in the left eye and a distant history of LASIK. His vision before surgery was 20/150 –1 on the Snellen chart. After this, he underwent phacoemulsification with posterior chamber intraocular lens implantation in the left eye. After cataract surgery, the posterior chamber intraocular lens dislocated, and he underwent further surgery to remove the posterior chamber intraocular lens implant and to place an anterior chamber intraocular lens implant. After the anterior chamber intraocular lens implantation, he developed macular edema. He was initially treated with poste-
The authors have no proprietary interest in any of the products mentioned in this paper. Reprint requests: Sophie J. Bakri, MD, Mayo Clinic, 200 First Street, S.W., Rochester, MN 55905; e-mail: [email protected]
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Ceftazidime and 0.1 mL (1 mg) of Vancomycin were injected intravitreally. Vitreous samples were sent for gram stain and culture. Gram stain showed no organisms, and cultures exhibited no growth. The patient’s hypopyon (Figure 2) and vitreous haze resolved 10 days later. His vision returned to 20/70, and his macular edema resolved on OCT (not shown).
Discussion
Fig. 1. Acute presentation of endophthalmitis with hypopyon and minimal anterior chamber fibrin in the absence of conjunctival inflammation. Typical infectious endophthalmitis would produce a dense fibrin reaction that would obscure the iris details.
rior subTenon triamcinolone 40 mg. Optical coherence tomography (OCT) was performed and did not show a decrease in the macular edema at 6 weeks, and his vision at the time was 20/60. The patient was then treated with intravitreal Triesence 0.1 mL (4 mg). Topical anesthesia, using tetracaine, was achieved, and the eye was prepped with 5% povidone iodine on the conjunctiva and 10% povidone iodine on the lids. An eyelid speculum was placed. The injection was performed intravitreally 3.5 mm posterior to the limbus. One day later, the patient presented with a dramatic decrease of vision. On examination, his visual acuity was light perception in the left eye. The cornea was clear. The anterior chamber showed a 1.5-mm white hypopyon, minimal fibrin with circulating cells, and drug particles in the anterior chamber (Figure 1). There was no conjunctival, scleral, or limbal hyperemia, and the patient denied pain. The vitreous cavity was full of nonpigmented cells and drug particles obscuring the view to the posterior pole. Ultrasonography showed the retina to be attached. A diagnosis of possible noninfectious endophthalmitis was made based on the rapid onset and extensive early anterior chamber reaction but was treated for infectious endophthalmitis due to the safety of treatment compared with the risk to the eye if the endophthalmitis was infectious. Under noninfectious technique and prepping the eye with povidone iodine, a vitreous sample was obtained using a 25-gauge needle on a tuberculin syringe. Next, 0.1 mL (2 mg) of
Noninfectious or infectious endophthalmitis can occur after intravitreal injections.6 –9 A higher incidence of noninfectious endophthalmitis after triamcinolone injection has been noted in vitrectomized patients and patients with an open posterior lens capsule.6,10,11 Noninfectious endophthalmitis usually presents with a quiet, painless eye with loss of vision due to vitreous haze and a prominent anterior chamber reaction. It usually occurs between 1 day and 5 days after injection. The hallmarks for infectious endophthalmitis are loss of vision after 5 days and a painful, red eye. Although our patient presented with a picture similar to noninfectious endophthalmitis, we elected to treat it as infectious given the safety of the therapy and the risk to his eye if the process was eventually determined to be infectious. As more experience with intravitreal Triesence is gained, we may develop greater confidence in not treating possible noninfectious cases with intravitreal antibiotics. Noninfectious endophthalmitis has been reported to occur after intravitreal Kenalog-40 injection and compounded intravitreal preservative-free Kenalog.2–5,8,9 This is the first reported case of noninfectious endophthalmitis with a commercially available triamcinolone acetonide preparation that does not contain the toxic preservatives that were thought to contribute to the inflammatory reaction. It is important to remember that our patient had risk factors for postinjection noninfectious endophthalmitis, namely vitrectomy and an open posterior capsule. The role of triamcinolone acetonide itself or the polysorbate 80 and carboxymethlycellulose carriers in causing the sterile inflammation is not yet known. This case describes the key features of noninfectious endophthalmitis from Triescence for the first time (rapid onset, no red eye or pain, and prominent anterior chamber reaction). Future experience will allow for studies to assess its incidence and enable a comparison to previous experience with preserved triamcinolone preparations. Key words: culture-negative, endophthalmitis, inflammation, noninfectious, preservative-free, triamcinolone, triesence. References
Fig. 2. Resolution of hypopyon and fibrin 10 days later.
1.
Nevitt MP. Clinical Review NDA 22-048, Triesence (triamcinolone acetonide injectable suspension). Available at: http://
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RETINAL CASES & BRIEF REPORTSℜ
www.fda.gov/cder/foi/ped㛭review/2008/022048㛭Acetonide㛭 Clinical㛭PREA.pdf. Accessed August 1, 2008. 2. Lorenzo CJ, Gonza´lez BM, Pe´rez FI. Sterile endophthalmitis after benzyl alcohol filtered triamcinolone acetonide injection. Arch Ophthalmol 2008;126:142–143. 3. Bakri SJ, Shah A, Falk NS, Beer PM. Intravitreal preservative-free triamcinolone acetonide for the treatment of macular oedema. Eye 2005;19:686 – 688. 4. Moshfeghi DM, Kaiser PK, Bakri SJ, et al. Presumed sterile endophthalmitis following intravitreal triamcinolone acetonide injection. Ophthalmic Surg Lasers Imaging 2005;36: 24 –29. 5. Maia M, Farah ME, Belfort RN. Effects of intravitreal triamcinolone acetonide injection with and without preservative. Br J Ophthalmol 2007;91:1122–1124. 6. Bhavsar AR, Ip MS, Glassman AR. The risk of endophthalmitis following intravitreal triamcinolone injection in the
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11.
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DRCRnet and SCORE clinical trials. Am J Ophthalmol 2007; 144:454 – 456. Moshfeghi DM, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 2003;136:791–796. Nelson ML, Tennant MT, Sivalingam A, et al. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina 2003;23:686 – 691. Jonas JB, Kreissig I, Spandau UH, Harder B. Infectious and noninfectious endophthalmitis after intravitreal high-dosage triamcinolone acetonide. Am J Ophthalmol 2006;141:579 –580. Roth DB, Flynn HW Jr. Distinguishing between infectious and non-infectious endophthalmitis after intravitreal triamcinolone injection. Am J Ophthalmol 2008;146:346 –347. Roth DB, Chieh J, Spirn MS, et al. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol 2003;121:1279 –1282.
Purpose: To report a case of noninfectious endophthalmitis occurring after intravitreal Triesence (preservative-free triamcinolone acetonide) injection. Method: Case report. Results: A 62-year-old patient with macular edema occurring after cataract surgery received 0.1 mL (4 mg) of intravitreal Triesence to the left eye. His vision was 20/60. One day later, he presented with a decrease in vision to light perception upon awakening. He denied ocular pain, and the eye was not red. Clinical examination was remarkable for orbital proptosis, minimal fibrin on the anterior chamber intraocular lens, and a white hypopyon. There was no view of the retina due to vitreous opacities. A vitreous tap and injection of intravitreal Ceftazidime and Vancomycin were performed. Microbiology showed no organisms on gram stain, and the cultures were negative. The endophthalmitis resolved, and the patient recovered vision to 20/70. Conclusions: Noninfectious endophthalmitis can occur after preservative-free commercially available intravitreal Triesence. This case suggests that noninfectious endophthalmitis can occur in the absence of the benzyl alcohol found in preserved preparations of Kenalog. RETINAL CASES & BRIEF REPORTS 3:316 –318, 2009
From the Department of Ophthalmology, The Mayo Clinic, Rochester, Minnesota.
servative-free Kenalog because this was thought to reduce the incidence of noninfectious endophthalmitis.3 Triesence is a recently approved, commercially available preservative-free intravitreal triamcinolone formulation that is increasing in popularity in the United States. The advantage of using a commercially prepared formulation is that it may be a safer and a more standard procedure than using a compounded preparation.5 We report noninfectious endophthalmitis occurring after intravitreal Triesence.
I
ntravitreal Triesence (Alcon, Fort Worth, TX) is a preservative-free triamcinolone acetonide preparation that was recently approved by the Food and Drug Administration in the United States.1 It is approved for the treatment of ocular inflammatory conditions as well as other rare diseases such as sympathetic ophthalmia. In addition to 4% weight/volume triamcinolone acetonide, the only other ingredients are polysorbate 80 (0.015% w/v) and carboxymethylcellulose (0.5% w/v). Before intravitreal Triesence was available, Kenalog-40 (Bristol-Myers Squibb, Teepack, NJ) was the most commonly used intravitreal steroid. However, this contains the preservative benzyl alcohol, which is toxic to the retina and has been thought to contribute to development of noninfectious endophthalmitis in some patients.2–5 Compounding pharmacies have been manufacturing pre-
Case Report We present a 62-year-old white male patient treated with 0.1 mL (4 mg) of intravitreal Triesence for macular edema. His ocular history includes a pars plana vitrectomy and membrane peeling for an epiretinal membrane in the left eye and a distant history of LASIK. His vision before surgery was 20/150 –1 on the Snellen chart. After this, he underwent phacoemulsification with posterior chamber intraocular lens implantation in the left eye. After cataract surgery, the posterior chamber intraocular lens dislocated, and he underwent further surgery to remove the posterior chamber intraocular lens implant and to place an anterior chamber intraocular lens implant. After the anterior chamber intraocular lens implantation, he developed macular edema. He was initially treated with poste-
The authors have no proprietary interest in any of the products mentioned in this paper. Reprint requests: Sophie J. Bakri, MD, Mayo Clinic, 200 First Street, S.W., Rochester, MN 55905; e-mail: [email protected]
316
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ENDOPHTHALMITIS AFTER TRIESENCE
Ceftazidime and 0.1 mL (1 mg) of Vancomycin were injected intravitreally. Vitreous samples were sent for gram stain and culture. Gram stain showed no organisms, and cultures exhibited no growth. The patient’s hypopyon (Figure 2) and vitreous haze resolved 10 days later. His vision returned to 20/70, and his macular edema resolved on OCT (not shown).
Discussion
Fig. 1. Acute presentation of endophthalmitis with hypopyon and minimal anterior chamber fibrin in the absence of conjunctival inflammation. Typical infectious endophthalmitis would produce a dense fibrin reaction that would obscure the iris details.
rior subTenon triamcinolone 40 mg. Optical coherence tomography (OCT) was performed and did not show a decrease in the macular edema at 6 weeks, and his vision at the time was 20/60. The patient was then treated with intravitreal Triesence 0.1 mL (4 mg). Topical anesthesia, using tetracaine, was achieved, and the eye was prepped with 5% povidone iodine on the conjunctiva and 10% povidone iodine on the lids. An eyelid speculum was placed. The injection was performed intravitreally 3.5 mm posterior to the limbus. One day later, the patient presented with a dramatic decrease of vision. On examination, his visual acuity was light perception in the left eye. The cornea was clear. The anterior chamber showed a 1.5-mm white hypopyon, minimal fibrin with circulating cells, and drug particles in the anterior chamber (Figure 1). There was no conjunctival, scleral, or limbal hyperemia, and the patient denied pain. The vitreous cavity was full of nonpigmented cells and drug particles obscuring the view to the posterior pole. Ultrasonography showed the retina to be attached. A diagnosis of possible noninfectious endophthalmitis was made based on the rapid onset and extensive early anterior chamber reaction but was treated for infectious endophthalmitis due to the safety of treatment compared with the risk to the eye if the endophthalmitis was infectious. Under noninfectious technique and prepping the eye with povidone iodine, a vitreous sample was obtained using a 25-gauge needle on a tuberculin syringe. Next, 0.1 mL (2 mg) of
Noninfectious or infectious endophthalmitis can occur after intravitreal injections.6 –9 A higher incidence of noninfectious endophthalmitis after triamcinolone injection has been noted in vitrectomized patients and patients with an open posterior lens capsule.6,10,11 Noninfectious endophthalmitis usually presents with a quiet, painless eye with loss of vision due to vitreous haze and a prominent anterior chamber reaction. It usually occurs between 1 day and 5 days after injection. The hallmarks for infectious endophthalmitis are loss of vision after 5 days and a painful, red eye. Although our patient presented with a picture similar to noninfectious endophthalmitis, we elected to treat it as infectious given the safety of the therapy and the risk to his eye if the process was eventually determined to be infectious. As more experience with intravitreal Triesence is gained, we may develop greater confidence in not treating possible noninfectious cases with intravitreal antibiotics. Noninfectious endophthalmitis has been reported to occur after intravitreal Kenalog-40 injection and compounded intravitreal preservative-free Kenalog.2–5,8,9 This is the first reported case of noninfectious endophthalmitis with a commercially available triamcinolone acetonide preparation that does not contain the toxic preservatives that were thought to contribute to the inflammatory reaction. It is important to remember that our patient had risk factors for postinjection noninfectious endophthalmitis, namely vitrectomy and an open posterior capsule. The role of triamcinolone acetonide itself or the polysorbate 80 and carboxymethlycellulose carriers in causing the sterile inflammation is not yet known. This case describes the key features of noninfectious endophthalmitis from Triescence for the first time (rapid onset, no red eye or pain, and prominent anterior chamber reaction). Future experience will allow for studies to assess its incidence and enable a comparison to previous experience with preserved triamcinolone preparations. Key words: culture-negative, endophthalmitis, inflammation, noninfectious, preservative-free, triamcinolone, triesence. References
Fig. 2. Resolution of hypopyon and fibrin 10 days later.
1.
Nevitt MP. Clinical Review NDA 22-048, Triesence (triamcinolone acetonide injectable suspension). Available at: http://
318
RETINAL CASES & BRIEF REPORTSℜ
www.fda.gov/cder/foi/ped㛭review/2008/022048㛭Acetonide㛭 Clinical㛭PREA.pdf. Accessed August 1, 2008. 2. Lorenzo CJ, Gonza´lez BM, Pe´rez FI. Sterile endophthalmitis after benzyl alcohol filtered triamcinolone acetonide injection. Arch Ophthalmol 2008;126:142–143. 3. Bakri SJ, Shah A, Falk NS, Beer PM. Intravitreal preservative-free triamcinolone acetonide for the treatment of macular oedema. Eye 2005;19:686 – 688. 4. Moshfeghi DM, Kaiser PK, Bakri SJ, et al. Presumed sterile endophthalmitis following intravitreal triamcinolone acetonide injection. Ophthalmic Surg Lasers Imaging 2005;36: 24 –29. 5. Maia M, Farah ME, Belfort RN. Effects of intravitreal triamcinolone acetonide injection with and without preservative. Br J Ophthalmol 2007;91:1122–1124. 6. Bhavsar AR, Ip MS, Glassman AR. The risk of endophthalmitis following intravitreal triamcinolone injection in the
7.
8.
9.
10.
11.
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2009
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VOLUME 3
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NUMBER 3
DRCRnet and SCORE clinical trials. Am J Ophthalmol 2007; 144:454 – 456. Moshfeghi DM, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 2003;136:791–796. Nelson ML, Tennant MT, Sivalingam A, et al. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina 2003;23:686 – 691. Jonas JB, Kreissig I, Spandau UH, Harder B. Infectious and noninfectious endophthalmitis after intravitreal high-dosage triamcinolone acetonide. Am J Ophthalmol 2006;141:579 –580. Roth DB, Flynn HW Jr. Distinguishing between infectious and non-infectious endophthalmitis after intravitreal triamcinolone injection. Am J Ophthalmol 2008;146:346 –347. Roth DB, Chieh J, Spirn MS, et al. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol 2003;121:1279 –1282.
