**5. Pathogenesis of bacterial endophthalmitis**

#### **5.1. Protective mechanisms in eye**

## *5.1.1. Blood–ocular fluid barrier*

**Figure 2.** Endophthalmitis affecting the cornea

28 Advances in Common Eye Infections

ring infiltrate and dense hypopyon

**Figure 3.** White bleb with intense conjunctival injection suggestive of bleb-associated endophthalmitis

**Figure 4.** Post-traumatic endophthalmitis caused by *Bacillus cereus* showing prominent conjunctival congestion, corneal

Under normal circumstances, the blood–ocular barrier provides a natural resistance against invading organisms and it ensures proper functioning of intra-ocular tissues and is essential for immune privilege [10]. The blood–ocular fluid barrier consists of inner and outer blood– retina barriers and the blood–aqueous humour barrier. The inner blood–retina barrier is formed by tight junctions between the endothelial cells and basement membrane of retinal capillaries and retinal pericytes, which control the blood supply for the inner retinal layers, preventing leakage of plasma constituents into the vitreous. The tight junctions between retinal pigment epithelial cells constitute the outer blood–retina barrier and control the blood supply to retinal photoreceptor cells and the choriocapillaris. The blood aqueous humour barrier is formed by the iris and ciliary epithelium and thus divides the highly perfused iris from its neighbouring compartments, the anterior chamber and the anterior vitreous [41]. Certain cytokines, such as transforming growth factor β, α-melanocyte stimulating hormone and vasoactive intestinal peptide, are known to have immunosuppressive property and have been detected in healthy aqueous humour [10].

#### *5.1.2. Anterior Chamber-Associated Immune Deviation (ACAID)*

Ocular antigen presenting cells, namely macrophages and dendritic cells, are found in the iris and the choriocapillaris [42]. In most cases of post-operative endophthalmitis, bacteria enter the eye via the anterior chamber, where antigen presentation initially occurs and hence antigen presenting cells residing in the iris are the most likely to first encounter these pathogens. This process may be facilitated by the mild inflammatory reaction in the anterior segment, resulting from tissue manipulation of surgery. Retinal and uveal antigen present‐ ing cells may not have access to antigen under physiological conditions but can activate during the later stages of infection, if the microbes have gained access to the posterior segment. When the defense mechanisms of immune privilege are overwhelmed, then only fulminant inflammation occurs [10].

#### *5.1.3. Invading mechanisms of organisms*

Organisms causing endophthalmitis are mostly part of conjunctival flora. They adhere to IOLs and create microcolonies through biofilm formation and within biofilms they are protected from host inflammatory responses, both physically and through multiple genetic changes that alter antigenicity. Organisms in the biofilm are thus difficult to eradicate and may persist despite antibiotic treatment, resulting in relapsing endophthalmitis [43].

Various toxins and enzymes are produced and secreted by the invading organisms causing destruction of protective mechanisms in the eye in case of fulminant infection in eye. *B. cereus* produces a number of cytolysins and enzymes that could contribute to the rapid course and severity of endophthalmitis, including haemolysins, lipases, enterotoxins and proteases [30]. *E. faecalis* strains frequently harbour conjugative plasmids that encode a cytolysin which effectively lyses both eukaryotic and prokaryotic cells [44]. Cytolysin causes destructive changes in retinal architecture and vitreal structures. Adhesin, aggregation substance, produced by enterococci is a virulence-enhancing factor and helps them to attach to membra‐ nous vitreous structures. *S. aureus* secretes cell wall-associated products and adhesions (e.g. clumping factor, fibronectin-binding protein and protein A) and extracellular virulence factors (e.g. toxins such as alpha-toxin, beta-toxin, gamma-toxin and leukocidin, proteases and lipases) which are responsible for high virulence of this organism in endophthalmitis. These virulence factors are controlled by quorum-sensing systems namely, *agr* (accessory gene regulator) and *sar* (staphylococcal accessory regulator) [45]. Hence, therapeutics designed to inactivate global regulation of *S. aureus* during the early stages of infection may be more effective in arresting tissue damage than targeting individual toxins.
