Bacterial Endophthalmitis: Epidemiology, Therapeutics, and Bacterium-Host Interactions

Abstract

SUMMARY Endophthalmitis is a severe inflammation of the interior of the eye caused by the introduction of contaminating microorganisms following trauma, surgery, or hematogenous spread from a distant infection site. Despite appropriate therapeutic intervention, bacterial endophthalmitis frequently results in visual loss, if not loss of the eye itself. Although the pathogenicity of bacterial endophthalmitis has historically been linked with toxin production during infection, a paucity of information exists as to the exact mechanisms of retinal toxicity and the triggers for induction of the intraocular immune response. Recently, research has begun to examine the bacterial and host molecular and cellular events that contribute to ocular damage during endophthalmitis. This review focuses on the causative agents and therapeutic challenges of bacterial endophthalmitis and provides current data from the analysis of the role of bacterial virulence factors and host inflammatory interactions in the pathogenesis of eye infections. Based on these and related studies, a hypothetical model for the molecular pathogenesis of bacterial endopthalmitis is proposed. Identifying and understanding the basic mechanisms of these bacterium-host interactions will provide the foundation for which novel, information-based therapeutic agents are developed in order to prevent vision loss during endophthalmitis.

Bacterial endophthalmitis: Therapeutic challenges and host–pathogen interactions

“…Inflammation during infection is necessary for the clearance of organisms, but can result in bystander damage to the interior of the eye. Intraocular inflammation can occur following intravitreal injection of bacteria or their components, such as toxins or cell wall constitutents that are shed from the organisms during infection, either during bacterial replication (Callegan, et al, 1999a(Callegan, et al, ,2002bFox, et al, 1984;Kufoy, et al, 1990), or following treatment with cell wallactive antbiotics (Callegan, et al, 2002b). To minimize ocular inflammation during endophthalmitis, clinicians often use intravitreal injection of dexamethasone in conjunction with antibiotics.…”

“…In terms of the significance of individual toxins to pathogenicity, S. aureus alpha-toxin and beta-toxin appear to be important to intraocular virulence. Eyes infected with strains deficient in alpha-toxin, beta-toxin, or both toxins were less inflamed and retained greater retinal function than eyes infected with wild type S. aureus (Callegan, et al, 2002b). The global regulators agr and sar, which control the density-dependent production of S. aureus adhesins and toxins, are critical for the intraocular virulence of S. aureus.…”

“…Neutrophils are an essential component of innate immunity, and are the primary infiltrating cell type in the early phase of endophthalmitis (Callegan, et al, 2002b;Giese, et al, 2003;Ramadan, et al, 2006). However, the recruitment and activation of neutrophils within the eye represent an important biological dilemma.…”

“…Retinal structural changes during endophthalmitis, in addition to detachment in its entirety, include photoreceptor layer folding and detachment, and complete dissolution of retinal cell layers (Callegan, et al, 1999a(Callegan, et al, ,1999b(Callegan, et al, ,2002b. Motile organisms, such as Bacillus, have been observed within retinal folds by 8 hours postinfection (Callegan, et al, 1999b(Callegan, et al, ,2002b.…”

“…Retinal structural changes during endophthalmitis, in addition to detachment in its entirety, include photoreceptor layer folding and detachment, and complete dissolution of retinal cell layers (Callegan, et al, 1999a(Callegan, et al, ,1999b(Callegan, et al, ,2002b. Motile organisms, such as Bacillus, have been observed within retinal folds by 8 hours postinfection (Callegan, et al, 1999b(Callegan, et al, ,2002b. Retinal detachment and destruction of the retinal layers has also been observed in endophthalmitis caused by organisms which remain in the midvitreous, such as S. aureus, E. faecalis, or nonmotile Bacillus (Callegan, et al, 2002b).…”