1. Foreign body reaction against intracameral Triamcinolone: Clinicopathological case report Amy L. Wong, MRCSEd; Hunter K. L. Yuen FRCS; Christopher K.S. Leung, MD; Dennis S.C. Lam, MD. Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong

2. Introduction o Triamcinolone acetonide (TA) is a corticosteroid suspension with potent anti-inflammatory effect. o Intravitreal TA has been advocated in the treatment of various conditions including o refractory macular edemas1-2 o choriodal neovascularizations secondary to AMD o pathological myopia3 o enhancing visualization of vitreous during vitrectomy4-5 and ERM peeling operations o Common adverse effects of intravitreal injection of TA are o transient elevated intraocular pressure o cataract progression7 o Endophthalmitis is a rare but devastating8-9 o Non-infectious endophthalmitis or pseudoendophthalmitis as a result of toxic reaction10- 12 o Here, we report a patient who had persistent pseudohypopyon five weeks after intracameral TA injection following cataract surgery

3. Case report o 72/F; Good past medical health o Underwent an uneventful phaco + IOL operation of the right eye in February 2007 o Immediately after the surgery, intracameral injection of 2 mg triamcinolone (40mg/ml, Kenacort A, Bristol- Myer, Squibb, Agani, Italy) was given for the control of postoperative inflammation. oPost op Day 1: o On the next day, the TA was noted in the inferior part of the anterior chamber mimicking a shallow hypopyon (Fig. 1) o BCVA: 0.4; IOP: normal; ACQ and no ocular pain o The patient was managed conservatively with close observation

4. Case report oPost op 4 weeks: o Pseudohypopyon persisted and anterior segment optical coherence tomography (Visante OCT, Carl Zeiss Meditec, Dublin, CA, USA) revealed that the pseudohypopyon covered 3 clock hours inferiorly and measured 0.78 mm in height (Fig. 2) o A similar finding was noted one week later and there was no change in the extension and height of this pseudohypopyon o The anterior chamber washout was performed because of the persistent of pseudohypopyon o Intraoperatively, the pseudohypopyon was found to be a soft mass like lesion instead of liquid o The patient had an uneventful recovery thereafter o BCVA: 0.7; IOP: normal; ACQ

5. Histopathological analysis o Numerous birefrigence particles consistent with TA crystals were identified when the pseudohypopyon was examined under polarized light (Fig. 3A) o Microscopic examination disclosed numerous histiocytes with numerous clear dropout spaces of different sizes o These dropout spaces were presumably caused by removal of TA crystals during processing (Fig. 3B) o The histiocytes were highlighted by CD163 immunstaining (Fig. 3C) o The overall features were compatible with foreign body reaction against the injected TA

6. Fig. 1 Slit-lamp photo showing a shallow pseudohypopyon (arrow) located at 5 to 7 o’clock region of right eye.

7. Fig. 2 ASOCT showing hyperreflective signal with vertical height of 0.78mm at inferior anterior chamber angle of right eye 4 weeks after intracameral triamcinolone injection.

8. Fig. 3 Histopathology of the ‘pseudohypopyon’. (A) Multiple birefrigence particles compatible with triamcinolone crystals (polarized light x 40). (B) The pseudohypopyon is composed of histiocytes with numerous clear dropout spaces of different sizes and brownish iris pigment ( H&E, x 400). (C) The histiocytes are confirmed by CD163 immunostaining (x 400).

9. Discussion o Non infectious endophthalmitis or pseudoendophthalmitis is a condition that mimics infectious endophthalmits and can post a diagnostic challenge10. It was postulated that pseudoendophthalmitis was probably an inflammatory reaction to some substances in the formulation of TA. o We have, for the first time, demonstrated by histopathology that intracameral triamcinolone usage can cause foreign reaction and pseudohypopyon formation in human eye. The presence of histiocytes surrounding the TA molecules in our specimen indicated that the intracamerally injected unfiltered Kenacort could have induced foreign body reaction. o Theorectically, triamcinolone will suppress inflammation and the exact reason for the development of foreign body reaction is unknown. We postulate that such inflammatory response could be a non infectious reaction to the drug or its vehicle.

10. Discussion o To differentiate infectious from noninfectious endophthalmitis, clinicians should closely monitor the clinical symptoms and signs, like eye pain, visual acuity, intraocular pressure, progression of anterior chamber reaction and the level of hypopyon o Anterior segment optical coherence tomography is also useful in monitoring the progression of hypopyon as demonstrated o This can objectively monitor the level, location and extension of the hypopyon in a non invasive, non contact manner with high resolution, cross sectional images of the anterior segment (18um).

11. Conclusion o Intracameral injection of TA could trigger foreign body reaction in a healthy human eye o Using a preservative free formulation or filtered suspension for injection could be considered as an alternative for intraocular injection in order to prevent the unwanted inflammatory response.

12. References o Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002; 109( 5): 920–927 o Greenberg PB, Martidis A, Rogers AH, et al. Intravitreal triamcinolone acetonide for macular oedema due to central retinal vein occlusion. Br J Ophthalmol 2002; 86( 2): 247–248. o Gillies MC, Simpson JM, Luo W, et al. A randomized clinical trial of a single dose of intravitreal triamcinolone for neovascular age-related macular degeneration. One year results. Arch Ophthalmol 2003; 121:667-73 o Peyman GA, Cheema R, Conway MD, et al. Triamcinolone actinide as an aid to visualization of the vitreous and the posterior hyaloids during pars plana vitrectomy. Retina 2000; 20:554-555 o Yamakiri K, Uchino E, Kimura K, Azad RV. Intracameral triamcinolone helps to visualize and remove the vitreous body in anterior chamber in cataract surgery. Am J Ophthalmol 2004; 138:650-52 o Gills JP, Gill P. Effect of intracameral triamcinolone to control inflammation following cataract surgery. J Cat Refract Surg. 2005;31: 1670-1. o Akduman L, Kolker AE, Black DL, Del Priore LV, Kaplan HJ. Treatment of persistent glacuma secondary to periocular corticosteroids. Am J Ophthalmol 1996; 122:275-7 o Moshfeghi DM, Kaiser PK, Scott IU, et al. Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 2003; 136:791- 6 o Sakamoto T, Enaida H, Kubota, et al. Incidence of acute endophthalmitis after triamcinolone-assisted pars plana vitrectomy. Am J Ophthalmol 2004; 138:137- 8 o Roth DB, Chieh J, spirn MJ, Green SN et al. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol. 2003; 121: 1279-82