Particle-Induced Endophthalmitis: Possible Mechanisms of Sterile Endophthalmitis after Intravitreal Triamcinolone

PURPOSE. We determined the cause of sterile endophthalmitis after intravitreal triamcinolone acetonide (IVTA). METHODS. The clinical records of 21 eyes that had sterile endophthalmitis after IVTA were reviewed. Cytologic studies were performed, and cytokine and chemokine profiles in the aqueous humor were determined. The effects of a direct contact of triamcinolone acetonide (TA) particles with cultured lens epithelial cells (B3) or retinal pigment epithelial cells (ARPE-19) on cytokine production were determined. Noncontact culture studies were performed in a Boyden chamber; 11-deoxycortisol was used for nonbioactive particles. RESULTS. Inflammation appeared one day after the IVTA, and the incidence of severe sterile endophthalmitis was 13.0% (6/46), which was reduced to 4.3% (2/47) after switching to preservative-free TA. Most cells found in the aqueous humor were granulocytes. The concentrations of IL-6 (447.8-<5000 pg/mL) and IL-8 (47.2-<5000 pg/mL) were increased significantly, but IL-1 beta, IL-10, IL-12p70, and TNF-alpha were not significantly changed. In B3 cells, the level of IL-8 increased significantly when the cells made direct contact with TA particles (1.33 times that of PBS, P < 0.05, Student's t-test), but not in noncontact cultures. Similar reaction pattern was found in ARPE-19 cells. These effects also were observed when the cells were exposed to 11-deoxycortisol. CONCLUSIONS. Sterile endophthalmitis after IVTA is characterized by an immediate granulocytic infiltration and an increase of IL6/IL-8 in the aqueous humor. Preservatives may be a factor causing this condition, and mechanical/rheologic stress by particles presumably might be a new causative factor by increasing IL-6/IL-8. (Invest Ophthalmol Vis Sci. 2013; 54:1758-1766) DOI:10.1167/iovs.12-11247