Acute postoperative endophthalmitis Pathogenesis

The estimated incidence of acute endophthalmitis following cataract surgery is approximately 0.3%. Toxins produced by the infecting bacteria and the host inflammatory responses cause rapid and irreversible photoreceptor damage, and these effects can continue long after the ocular contents have been rendered sterile.

Possible risk factors include operative complications such as posterior capsule rupture, prolonged procedure time, combined procedure (e.g. with vitrectomy), clear corneal sutureless incision, temporal incision, wound leak on the first day, delaying postoperative topical antibiotics until the day after surgery, topical anaesthesia, adnexal disease and diabetes.
Pathogens. About 90% of isolates are of fre$uency they include% ram!positive and "0% ram!negative. #n order

Coagulase negative staphylococci (S. epidermidis). !ther "ram positive organisms (S. aureus and Streptococcus spp.). "ram negative organisms (Pseudomonas spp. and Proteus spp.). 3 The source of infection usually cannot be identified with certainty. #t is thought that the flora of the eyelids and con$unctiva are the most fre%uent source, including contamination via incisions in the early postoperative stages. !ther potential sources include contaminated solutions and instruments, environmental air, and the surgeon and other operating room personnel. Prophylaxis
&ecause of the low rate of endophthalmitis it is very difficult to prove that any method of prophylaxis is effective or superior to any other. The following are li'ely to be beneficial%

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Instillation of 5% povidone-iodine into the con$unctival fornices and leaving this undisturbed for at least & minutes prior to surgery. Scrupulous preparation of the surgical site, with re draping if eyelash coverage is inade%uate. Treatment of pre-e istin! infections such as blepharitis, con$unctivitis, chronic dacryocystitis and infection in the contralateral eye or socket.
Prophylactic antibiotics

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Pre operative topical fluoro%uinolone antibiotics are fre%uently given in regimens from ' hour to & days before surgery. #ntracameral cefuroxime (' mg in (.' m)) in$ected into the AC at the end of surgery. Postoperative subcon$unctival in$ection can achieve bactericidal levels in the anterior chamber for at least '*+ hours. ,ewer generation %uinolones such as moxifloxacin penetrate the eye effectively to give concentrations inhibitory to bacterial growth. #arl$ resuturin! of leaking wounds rather than observation may be prudent. &evie'in! personal sur!ical practice to eliminate potentially risk prone elements, particularly if a significant rate of endophthalmitis is encountered. S$mptoms are pain and visual loss.
Signs vary according to severity.

(linical features

-yelid swelling, chemosis, con$unctival in$ection and discharge. A relative afferent pupillary defect is common. Corneal ha.e (/ig. 0.'1A) /ibrinous exudate and hypopyon (/ig. 0.'12). 3itritis with an impaired view of the fundus (/ig. 0.'1C). 4evere vitreous inflammation and debris (/ig. 0.'15) with loss of the red reflex.

5ifferential diagnosis
#f there is any doubt about the diagnosis, treatment should be that of infectious endophthalmitis. )arly recognition leads to a better outcome.

&etained lens material in the anterior chamber or vitreous may precipitate a severe uveitis, corneal oedema and raised intraocular pressure. 2 (itreous haemorrha!e, especially if blood in the vitreous is depigmented. 3 Postoperative uveitis. A confident diagnosis of infection is not always straightforward. #f signs of inflammation are mild a trial of topical steroid therapy and early review (6*+7 hours) is appropriate. #f there is no substantial improvement management should be that of endophthalmitis. " To ic reaction to the use of inappropriate or contaminated irrigating fluid or viscoelastic. An intense fibrinous reaction with corneal oedema may develop although other signs of infectious endophthalmitis are absent. 8reatment is with intensive topical steroids combined with cycloplegics. Corneal decompensation may be permanent. 5 )omplicated or prolon!ed sur!er$ may result in corneal oedema and uveitis. #dentification of pathogens
*amples for culture should be obtained from a$ueous and vitreous to confirm the diagnosis. +owever, negative culture does not necessarily rule out infection and treatment should be continued. An operating theatre with experienced staff is the best setting, but samples can be ta'en in a minor procedures operating room if necessary to avoid delay, ma'ing sure that all e$uipment is available prior to starting.

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*-scan ultrasound should be performed prior to vitreous sampling to exclude retinal detachment if there is no clinical view.
Preparation

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Povidone iodine 9: is instilled. 8opical and subcon$unctival, sub 8enon;s or peribulbar anaesthesia is administered. 8he eye is draped as for cataract surgery, with insertion of a speculum. 2etween (.' m) and (.+ m) of a%ueous is aspirated via a limbal paracentesis using a +9 " needle on a tuberculin syringe. 8he syringe is capped and labelled. A + m) syringe and a +& " needle may be used, or optimally a disposable vitrector (/ig. 0.'0A). 8he distance from the limbus for the scleral incision is measured with callipers and marked (/ig. 0.'02)< & mm (pseudophakic eye), 7 mm (phakic eye).

Aqueous samples

Vitreous samples are more li'ely to yield a positive culture than a$ueous.

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(.+*(.7 m) is aspirated from the mid vitreous cavity (/ig. 0.'0C). #f using a disposable vitrector, cap off the tubing securely and place in a specimen bag. 5o not disconnect the vitrector from its tubing. )on+unctival s'abs may be taken as well, as significant culture may be helpful in the absence of a positive culture from intraocular samples. -icrobiolo!$. 4pecimens should be sent to the microbiology laboratory immediately= most prefer to receive a sample in the apparatus used for ac%uiring the specimen and will divide the specimen for microscopy and culture. Polymerase chain reaction (PC>) can be helpful in identifying unusual organisms, the cause of culture negative disease, and organisms after antibiotic treatment has been started. ?owever, its high sensitivity means that contamination can lead to false positive results.

Treatment 1 Intravitreal antibiotics are the 'ey to management because they achieve levels above the minimum inhibitory concentration of most pathogens, and these are maintained for days. They should be administered immediately after culture specimens have been obtained. Two antibiotics commonly used in combination are cefta,idime, which will 'ill most ram!negative organisms -including Pseudomonas aeruginosa. and vancomycin to address coagulase!negative and coagulase!positive cocci -including methicillin! resistant S. aureus..

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8he concentrations are cefta.idime + mg in (.' m) and vancomycin + mg in (.' m)= amikacin (.7 mg in (.' m) can be used as an alternative to cefta.idime in patients allergic to penicillin but is more toxic to the retina. 4ee 8able 0.+ for details of preparation. 8he antibiotics are in$ected slowly into the mid vitreous cavity using a +9 " needle (/ig. 0.'05). After the first in$ection has been given, the syringe may be disconnected but the needle left inside the vitreous cavity so that the second in$ection can be given through the same needle. Alternatively, a second needle can be used. Periocular antibiotic in+ections are often given but are of doubtful additional benefit if intravitreal antibiotics have been used. 4uggested doses are vancomycin 9( mg and cefta.idime '+9 mg (or amikacin 9( mg). Topical antibiotics are of limited benefit and are often used only 7*6 times daily in order to protect the fresh wounds from contamination. 3ancomycin 9: (9( mg@m)) or cefta.idime 9: (9( mg@m)) applied intensively may penetrate the cornea in therapeutic levels. 8hird or fourth generation fluoro%uinolones achieve effective levels in the a%ueous and vitreous, even in uninflamed eyes, and may be considered. /ral antibiotics. /luoro%uinolones penetrate the eye well and moxifloxacin 7(( mg daily for '( days is recommended= clarithromycin 9(( mg twice daily may be helpful for culture negative infections. -vidence suggests these may attack bacterial biofilm. /ral steroids. 8he rationale for the use of steroids is to limit the destructive complications of the inflammatory process. Prednisolone ' mg@kg daily should be started in severe cases after '+*+7 hours provided fungal infection has been excluded from examination of smears. 2eware contraindications, prescribe gastric protection (e.g. lansopra.ole &( mg once daily) and monitor appropriately including baseline blood tests= if necessary re%uest general medical advice. Periocular steroids. 5examethasone or triamcinolone should be considered if systemic therapy is contraindicated.

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Topical de amethasone (.': + hourly initially for anterior uveitis. Topical m$driatic such as atropine ': twice daily. Intravitreal steroids may reduce inflammation in the short term but they do not influence the final visual outcome= some studies even suggest a detrimental effect. Conversely, improvement in outcome in some bacterial sub groups has been reported. 12 Pars plana vitrectom$. 8he -ndophthalmitis 3itrectomy 4tudy (-34) showed a benefit for immediate pars plana vitrectomy in eyes with a visual acuity of perception of light (,!8 hand movements vision or better) at presentation, with a 9(: reduction in severe visual loss. #f vitrectomy is not readily available, it is prudent to give intravitreal antibiotics in the interim. 8he conclusions of the -34 in post cataract surgery eyes cannot readily be extrapolated to other forms of endophthalmitis. Table 1.2 -- Preparation of antibiotics for intravitreal in+ection )efta3idime (broad spectrum, including Pseudomonas) 45 2egin with a 9(( mg ampoule. *5 Add '( m) water for in$ection (A/#) or saline and dissolve thoroughly (for a +9( mg vial add 9 m) A/# or saline, for a ' g vial add +( m) A/# or saline). )5 5raw up ' m) of the solution, containing 9( mg of antibiotic. 65 Add '.9 m) A/# or saline giving 9( mg in +.9 m). #5 5raw up about (.+ m) (excess to facilitate priming) into a ' m) syringe. Ahen ready to in$ect fit the >ycroft cannula or the needle to be used, and discard all but (.' m) (contains + mg of antibiotic) for in$ection. (ancom$cin (action primarily against "ram positive organisms) !nly saline, not A/#, should be used with vancomycin As A*- above, again preferably starting with a 9(( mg ampoule. 4mikacin (alternative to cefta.idime= as carries a higher risk of retinal infarction, use only if well defined penicillin or cephalosporin allergy)= lower intravitreal dose than cefta.idime and vancomycin ,ote different dilution procedure to cefta.idime and vancomycin 45 Presentation< vial contains 9(( mg of amikacin in + m) of solution. *5 Bse a +.9 m) syringe to draw up ' m) of amikacin solution then '.9 m) of A/#. )5 #n$ect (.7 m) of the solution, containing 7( mg of antibiotic, into a '( m) syringe and dilute to '( m) (giving 7 mg per m)). #5 5raw up about (.+ m) (excess to facilitate priming) into a ' m) syringe. Ahen ready to in$ect fit the >ycroft cannula or the needle to be used, and discard all but (.' m) (contains (.7 mg of antibiotic) for in$ection. 4ubse%uent management
*ubse$uent management proceeds according to culture results and clinical findings. /ltrasonography may be useful in assessing response to treatment.

Si!ns of improvement include contraction of fibrinous exudate and reduction of anterior chamber cellular activity and hypopyon. #n this situation treatment is not modified irrespective of culture results.

If the clinical si!ns are 'orsenin! after 71 hours antibiotic sensitivities should be reviewed and therapy modified accordingly. Par plana vitrectomy should be considered if not previously performed. #ntravitreal antibiotics can be repeated after + days= if amikacin has previously been used, repeated administration should probably be avoided to reduce the risk of retinal toxicity.
The outcome is related to the duration of the infection prior to treatment and the virulence of organisms.

#f visual acuity at presentation is light perception &(: of eyes achieve 6@'+ following treatment. #f visual acuity is better than light perception this figure increases to 6(:. #nfection with Bacillus cereus and streptococci has a poor visual outcome despite aggressive and appropriate therapy, with C(: and 99:, respectively, achieving a final visual acuity of 6@6( or less. 8his poor visual outcome may be related to early retinopathy from exotoxins.

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Late problems

Persistent vitreous opacities. Aggressive and extended topical, periocular and, if necessary, oral steroid treatment will often lead to resolution. 3itrectomy can be considered if unresolving and severe. b Maculopathy in the form of epimacular membranes, cystoid oedema and ischaemia. c Hypotony. Aound leak should be excluded and persistent inflammation addressed. Choroidal effusions should be identified and drained if necessary. >etinal detachment and anterior vitreous membranes may re%uire vitrectomy. d Other problems include chronic uveitis, secondary glaucoma, retinal detachment and phthisis. 5elayed onset postoperative endophthalmitis Pathogenesis 5elayed onset endophthalmitis following cataract surgery develops when an organism of low virulence becomes trapped within the capsular bag (;saccular endophthalmitisD). !rganisms can become se%uestered within macrophages, protected from eradication but with continued expression of bacterial antigen. #t has an onset ranging from 7 weeks to years (mean of 0 months) postoperatively and typically follows uneventful cataract extraction with a posterior chamber intraocular lens. #t may rarely be precipitated by ,d<EA" laser capsulotomy, which releases the organism into the vitreous. 8he infection is caused most fre%uently by P. acnes and occasionally S. epidermidis, Corynebacterium spp. or Candida parapsilosis.
0iagnosis

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Presentation is with painless mild progressive visual deterioration which may be associated with floaters.
Signs

)ow grade anterior uveitis, sometimes with mutton fat keratic precipitates (/ig. 0.+(A). 8he inflammation initially responds well to topical steroids (/ig. 0.+(2), but recurs when treatment is stopped and eventually becomes steroid resistant (/ig. 0.+(C). 3itritis is common but hypopyon infre%uent. An enlarging capsular pla%ue composed of organisms se%uestrated in residual cortex within the peripheral capsular bag is characteristic (/ig. 0.+(5).

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"onioscopy under mydriasis may identify an e%uatorial pla%ue. Initial mana!ement involves a '(*'7 day course of oral moxifloxacin= clarithromycin is an alternative. Investi!ations consisting of cultures or a%ueous and vitreous should be considered, if oral antibiotics are ineffective. Anaerobic culture should be re%uested if P. acnes infection is suspected, and isolates may take '(*'7 days to grow. 8he detection rate can be greatly improved with the use of polymerase chain reaction (PC>).
Treatment if persistent

#ntravitreal antibiotics alone are usually unsuccessful in resolving the infection. >emoval of the capsular bag, residual cortex and #!), re%uiring pars plana vitrectomy. 4econdary #!) implantation may be considered at a later date. #ntravitreal antibiotics are combined< vancomycin (' mg in (.' m)) is the antibiotic of choice and can also be irrigated into any capsular remnant. P. acnes is also sensitive to methicillin, cefa.olin and clindamycin.