**8. Prevention of endophthalmitis**

The most effective therapy for endophthalmitis is prevention. Sterile technique during any type of ocular surgery is important. All instruments for surgery should be thoroughly sterilized with autoclaving; tubing is preferably sterilized with ethylene oxide gas sterilizer. BSS (balanced salt solution) bottles should never be kept or used for more than one operating session. Proper preparation before any intra-ocular surgery including peri-ocular and ocular surface (cul-de-sac) sterilization with povidone iodine 5% applied for 3 min is the best means for prevention of endophthalmitis (superior to topical antibiotics) [54]. In allergic patients, 0.05% chlorhexidine can be used. Large bottles of diluted povidone iodine or chlorhexidine should be avoided and single-use vials be used as they get contaminated with *P. aeruginosa*. A prophylactic antibiotic like topical 0.5% levofloxacin or ofloxacin one drop 1 h and one drop 30 min before surgery and three drops at 5 min intervals immediately following surgery is effective in reducing the rate of post-operative endophthalmitis according to the European Society of Cataract and Refractive Surgery (ESCRS) study [55]. Topical antibiotic should be continued four times a day for two weeks post-operatively. The use of antibiotics in the irrigation and infusion fluid is also an option. In addition, washing the surgical gloves whether containing talc or not, after wearing them in sterile saline and washing any surgical instrument before introducing it into the eye and avoiding touching any non-sterile place including the body surface with anything. Biodegradable scleral plugs impregnated with antibiotics, antiviral and anti-inflammatory drugs have been tested for drug release *in vitro*. Scleral plugs containing vancomycin, amikacin and dexamethasone have been used for slow delivery of drugs in the vitreal cavity at a concentration well above MIC (minimum inhibitory concen‐ tration) for a period of time needed to treat bacterial endophthalmitis in place of repeated vitreal injections [56, 57]. All patients with ocular penetration injuries should be treated with IV broad-spectrum antibiotics for 3 days. The common regimen is cefazolin 1 g tds and gentamycin 80 mg BD. If injury is through contaminated object, vancomycin 1 g bd (in slow infusion to prevent "red man" syndrome) should substitute cefazolin. In patients allergic to penicillins or cephalosporins, moxifloxacin 400 mg once a day may be used.

#### **8.1. Treatment strategy for endophthalmitis**

paper that concentrates the microorganisms and particulate matter and filter paper is sectioned and distributed on the appropriate media or vitrectomy specimen is directly inoculated into standard blood culture bottle [49]. Specimens can be inoculated on 5% sheep blood agar for recovery of the most common bacterial and fungal isolates. Sabouraud dextrose agar is also inoculated for recovery of fungal isolates. Chocolate agar: can be used for the recovery of fastidious organisms (i.e. *Neisseria gonorrhoeae* and *Hemophilusinfluenzae*). Thioglycollate broth and anaerobic blood agar are useful for recovery of small numbers of aerobic or anaerobic (including *Propionibacterium acnes*) organisms from ocular fluids and tissues. Blood culture bottles contain specially prepared medium for the recovery of both aerobic and anaerobic bacteria and fungi and it can be directly inoculated by intra-ocular fluids. Immunologic and molecular genetic technologies enable rapid and specific identification of infectious agents. In culture negative cases, the additional use of polymerase chain reaction was reported to aid in the identification of the organism [49]. These real-time techniques have been used in both clinical and experimental settings, and their future use in this area appears promising [50, 51].

In the Endophthalmitis Vitrectomy Study (EVS), Gram stain result did not reveal any sub‐ groups in which vitrectomy had a beneficial value and therefore is not useful in making initial therapeutic decisions [26]. Also in EVS, there was no difference in the culture positivity rate and operative complications between samples obtained by tap and those obtained by vitrec‐

In B-scan ultrasound of the posterior pole, choroidal thickening and ultrasound echoes in the vitreous support the diagnosis of endophthalmitis. Retained lens material and associated retinal detachment are also visible. The ultrasound also provides a baseline prior to intra-ocular intervention and allows assessment of the posterior vitreous face and areas of possible traction [53]. In traumatic cases, a CT scan can be performed, which may show thickening of the sclera and uveal tissues associated with various degrees of increased density in the vitreous and periocular soft tissue structures. In endogenous cases, imaging modalities like two-dimensional echocardiography and chest x-ray can be done to rule out potential sources of infection.

The most effective therapy for endophthalmitis is prevention. Sterile technique during any type of ocular surgery is important. All instruments for surgery should be thoroughly sterilized with autoclaving; tubing is preferably sterilized with ethylene oxide gas sterilizer. BSS (balanced salt solution) bottles should never be kept or used for more than one operating session. Proper preparation before any intra-ocular surgery including peri-ocular and ocular surface (cul-de-sac) sterilization with povidone iodine 5% applied for 3 min is the best means for prevention of endophthalmitis (superior to topical antibiotics) [54]. In allergic patients, 0.05% chlorhexidine can be used. Large bottles of diluted povidone iodine or chlorhexidine should be avoided and single-use vials be used as they get contaminated with *P. aeruginosa*. A

tomy [52].

*7.1.2. Imaging studies*

32 Advances in Common Eye Infections

**8. Prevention of endophthalmitis**

Endophthalmitis is an ocular emergency, and urgent treatment is required to reduce the potential of significant visual loss. Microbial endophthalmitis is a therapeutic challenge due to delicate anatomy and physiology of ocular tissues. Retina has a rich blood supply, but the vitreous and anterior chambers are avascular and are isolated from systemic circulation via blood–ocular fluid barrier [4]. These features represent a barrier for the delivery of cellular and humoral mediators of host immunity and also antimicrobial or anti-inflammatory agents administered systemically. This leaves clinicians with few treatment options like injecting drug directly into intra-ocular space, but there is a risk of vitreous or sub-retinal haemorrhaging, retinal toxicity, corneal abrasions, central artery occlusion, uveitis or lens opacification [58]. Also, retinal photoreceptor cells are highly sensitive not only to the offending pathogen and the resulting inflammatory response but also to antimicrobial agents administered locally to treat the infection [59].

#### **8.2. Antimicrobial agents and anti-inflammatory agents**

Outcome of endophthalmitis management depends on several factors, including the respon‐ sible pathogen, the patient's age, the duration between injury and treatment, the therapy chosen and the condition of the eye upon presentation [60]. Delay in therapy results in poor visual outcome, especially in severe cases of endophthalmitis. Bacterial endophthalmitis is treated with repeated injection of antibiotics into the vitreous concurrently with systemic antibiotics, although some potentially effective antibiotics like vancomycin and aminoglyco‐ sides do not penetrate readily into the vitreous, due to the protective effect of the blood–ocular fluid barrier; however, intra-ocular inflammation increases the permeability of the blood– ocular fluid barrier, enhancing penetration of systemic antibiotics into the vitreous cavity [61]. Another reason for poor systemic antibiotic effect in endophthalmitis is poor penetration through the blood flow because of the inflammation and necrosis of blood vessels. Because of variable penetration into the vitreous cavity of aminoglycosides, vancomycin and cephalo‐ sporins, the EVS evaluated their clinical efficacy in a post-cataract surgery endophthalmitis controlled trial and found that systemic antibiotics did not enhance visual outcomes in these patients. However, this recommendation does not hold true following other types of ocular surgery, trauma or suspected endogenous endophthalmitis [62]. Systemic antibiotics are important for therapeutic management of endogenous endophthalmitis where there is concomitant bacteremia, while intravitreal antibiotic is a key component for clinical manage‐ ment of exogenous bacterial endophthalmitis. Fluoroquinolones are currently used by many clinicians in combination with intravitreal antibiotics like vancomycin, amikacin and ceftazi‐ dime for severe endophthalmitis cases. The two drug regimens commonly used by clinicians include vancomycin (1 mg/0.1 ml) to cover Gram-positive organisms and a third-generation cephalosporin (ceftazidime 2 mg /0.1 ml) or amikacin (0.4 mg/0.1 ml) to cover Gram-negative organisms [63]. Repeated intravitreal injections of antibiotics may be necessary if there is no response to the initial therapy.

Fungal endophthalmitis carries a poor prognosis and there is no standard management available for treating this condition. In fungal endophthalmitis cases, systemic antifungal agents namely amphotericin with or without flucytosine or fluconazole are used. In flucona‐ zole-resistant strains voriconazole may be helpful; however, information on new antifungal agents for endophthalmitis is limited. It is seen that chorioretinitis infections can be more readily cured with systemic antifungal agents, whereas more aggressive treatment including pars plana vitrectomy with intravitreal amphotericin (5–10mg/0.1mL) or voriconazole and systemic antifungal is required for patients with vitritis. Topical antifungal agents (natamycin 5%) are also included, especially in cases of corneal involvement [64].

The use of corticosteroids is controversial. In endophthalmitis, ocular inflammation is induced by growing bacteria and also due to breakdown of cell wall or other components due to use of antibiotics. This overt inflammatory response can damage sensitive neurologic tissues. They should not be administered without proper coverage of all infective microorganisms and when the infection is not controlled. Intravitreal dexamethosone in the concentration of 400 micro‐ gram in 0.1 ml has been used, but is contraindicated in fungal endophthalmitis [65].

#### **8.3. Pars plana vitrectomy**

Although intravitreal antibiotic therapy can provide effective bacterial killing during endoph‐ thalmitis, vitrectomy is an appealing adjunct to management. Vitrectomy (surgical cutting and aspiration of vitreous contents and replacement with balanced salt solution) (Figure 6) debrides the vitreous cavity of bacteria, inflammatory cells and other toxic debris; promotes better diffusion of antibiotics; helps in obtaining adequate sampling for microanalysis and helps in speedy recovery of vision [66, 67]. Timing of vitrectomy is controversial, and inves‐ tigators advocate aggressive early treatment with early vitrectomy in suspected bacterial metastatic endophthalmitis, and more conservative approach in suspected fungal cases. Also, 3 port pars plana 23 or 25 gauge complete vitrectomy is preferred over core vitrectomy. However, in an inflamed eye certain complications like retinal detachment, hypotony and pthisis bulbi can occur. The definite indications for vitrectomy include worsening of signs and symptoms, rapid progression, infections uncontrolled by systemic and /or intravitreal antibiotics, retinal necrosis, extensive subretinal abscess, retinal detachment and intra-ocular foreign body [65].

**Figure 6.** showing Cutting and aspiration of vitreous contents in pars plana vitrectomy
