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CLINICAL PRACTICE GUIDELINES
MANAGEMENT OF
POST-OPERATIVE
INFECTIOUS
ENDOPHTHALMITIS
BERSATU•BERUSAHA•BERBAKTI•
MINISTRY OF HEALTH MALAYSIA
ACADEMY OF MEDICINE
Statement of Intent
This clinical practice guideline is meant to be a guide for clinical practice, based on the best available evidence at the time of development. Adherence to these guidelines may not necessarily ensure the best outcome in every case. Every health care provider is responsible for the management of his/her unique patient based on the clinical picture presented by the patient and the management Review of the Guidelines
This guideline was issued in August 2006 and will be reviewed in August 2009 or sooner if new evidence becomes available.
GUIDELINE DEVELOPMENT AND OBJECTIVE
Guideline Development
Post-operative endophthalmitis, though infrequent, remains a serious andblinding complication following intraocular surgery. However, variations inthe management of post-operative infectious endophthalmitis still existamongst ophthalmologists in Malaysia. This national guideline has beencompiled by a committee comprising of ophthalmologists, a pharmacistand a nursing officer from the public and private sector. It aims to presentevidence-based recommendations as a guide for the prophylaxis andmanagement of post-operative infectious endophthalmitis.
Relevant key words ‘post-operative endophthalmitis’, ‘endophthalmitis’,‘endophthalmitis AND causative organism’, ‘endophthalmitis ANDprophylaxis’, ‘endophthalmitis AND infection control’, ‘endophthalmitis ANDclinical features’, ‘endophthalmitis AND management’ were used to generateliterature from the following databases (PubMed), Cochrane Database ofSystematic Reviews (CDSR), Database of Abstracts of Reviews andCochrane Controlled Trial Register via OVID search engine. Searcheswere also manually done in non-indexed journals and “grey literature”.
Existing guideline, mainly the ESCRS Guidelines on prevention,investigation and management of post-operative endophthalmitis wasincluded as reference. The experience and knowledge of the CPGdevelopment group was also considered when formulating the guideline.
Assessment of the evidence was conducted independently by individualmembers and discussed as a group before decisions were made. In eacharea considered, the best evidence available was given more weightage.
Less well designed studies were either merely mentioned or excluded unlessthey added a different perspective. Related articles were selected and outof these, relevant articles were chosen and graded using the modifiedversion of the Catalonian Agency for Health Technology Assessment andResearch (CAHTAR) model. The grading of recommendations was modifiedfrom the Scottish Intercollegiate Guideline Network (SIGN).
Objective
To provide guidelines to ophthalmic surgeons in the prophylaxis and
treatment of post-operative infectious endophthalmitis based on best
available evidence.
Clinical Questions
The clinical questions of these guidelines are:
What are the risk factors of post-operative infectiousendophthalmitis? What are the prophylactic measures for the condition? What are the clinical features and investigations required forpatients with post-operative infectious endophthalmitis? What is the management of post-operative infectiousendophthalmitis? Target Population
Patients undergoing intraocular surgery and patients who develop post-
operative infectious endophthalmitis.
Target Group
This guideline is applicable to doctors and eye care providers who perform
ocular surgery and are involved in the management of patients with post-
operative infectious endophthalmitis.
Clinical Indicators for Quality Management
: Rate of post-operative infectious endophthalmitis : Number of cases with post-operative infectious : Total number of intraocular surgery performed in the corresponding year, excluding surgery for penetratingeye injury Rate of post-operative infectious endophthalmitis= (Numerator/ Denominator) x 100% Dr. Mariam IsmailConsultant OphthalmologistSelayang HospitalSelangor Dr. Loh Swee SengConsultant OphthalmologistSultanah Aminah HospitalJohor Baru COORDINATORS
SPECIALIST REVIEWERS
The draft guideline was reviewed by a panel of independent expertreferees, who were asked to comment primarily on thecomprehensiveness and accuracy of interpretation of the evidencesupporting the recommendations in the guideline.
Consultant OphthalmologistGleneagles Medical Centre Penang1 Jalan Pangkor10500 Penang Consultant OphthalmologistMoorfields Eye HospitalCity RoadEV12 2PDLondonUnited Kingdom The draft guideline was also available on the websites of Ministry ofHealth Malaysia and Academy of Medicine to allow interested parties tosubmit opinions and comments of the guideline.
TABLE OF CONTENTS
Guideline Development And Objective
Clinical Practice Guidelines Development Group
Specialist Reviewers
INTRODUCTION
Definition
Magnitude of Problem
Causative Organism
Risk Factors
PROPHYLACTIC MEASURES
Antiseptic Measures
a. Preoperative povidone iodine on skin and conjunctival sac d. Preoperative irrigation of lacrimal passages e. Preoperative saline irrigation of conjunctival sac Antibiotics Prophylaxis
a. Intracameral antibioticb. Preoperative topical antibiotic c. Preoperative systemic antibiotic d. Post-operative subconjunctival antibiotic injection Heparinized Intraocular Infusion Solution and
Heparin Coated Intraocular Lens (IOL)
Operating Theatre
DIAGNOSIS AND INVESTIGATIONS
Clinical Features
a. Acute post-operative infectious endophthalmitis b. Chronic post-operative infectious endophthalmitis Investigations
MANAGEMENT
Treatment of Acute Post-operative Endophthalmitis
Treatment of Chronic Post-operative Endophthalmitis
CLINICAL AUDIT PARAMETERS
ALGORITHM
Algorithm for the Management of Acute Post-operative Algorithm for the Management of Chronic Post-operative APPENDIX
Appendix 2 : Procedure for Anterior Chamber Tap,Vitreous Tap and Intravitreal Antibiotic Injection Appendix 3 : Preparation of intravitreal drugs Appendix 4 : Preparation of intracameral cefuroxime REFERENCES
INTRODUCTION
Post-operative infectious endophthalmitis is an infrequent but
devastating complication of ophthalmic surgery. Its occurrence can
lead to poor visual prognosis, and increase in health care cost. The
rate of post-operative infectious endophthalmitis therefore is frequently
used as an indicator for quality assurance of ophthalmology services.
It is currently used as one of the national indicator approaches (NIA)
in the Ministry of Health Malaysia (MOH).
1.1 Definition
For practical purposes, post-operative infectious endophthalmitisis defined as intraocular inflammation caused by an infectiveprocess following intraocular surgery. Intra-ocular surgery isdefined as any ocular surgery where the full thickness of thecornea and / or sclera has been breached. This definitionexcludes patients with penetrating eye injury.
Acute infectious endophthalmitis usually presents within twoweeks of surgery, whereas chronic infectious endophthalmitisusually present a few weeks or months following surgery.
1.2 Magnitude of Problem
Over the past decades, the incidence of post-operative infectiousendophthalmitis has shown a decline due to improvements insurgical techniques and instrumentation. Emphasis on sterilityand prophylactic measures may also have a role in this decline.
The incidence of post-operative endophthalmitis ranges from0.07% (1, Level 8; 2, Level 8) to 1.8% (3, Level 8). Incidence rates differ withthe type of surgery. Cataract surgery, being the most commonlyperformed ocular surgery, is the most common type of surgerypreceding endophthalmitis, with incidences ranging from 0.07%to 0.13% (4, Level 8). The incidence following specific type of surgerywas : secondary intraocular lens (IOL) 0.30% to 0.40 %, extra-capsular cataract extraction (ECCE) with or without IOLimplantation 0.072% to 0.18%, phacoemulsification 0.015% to0.5%, penetrating keratoplasty 0.11 % to 0.18%, glaucomafiltering surgery 0.06% to 1.8%, pars plana vitrectomy 0.046% to0.07%, combined trabeculectomy and cataract surgery 0.11%,combined penetrating keratoplasty and cataract surgery 0.19%(4, Level 9, 5 Level 8 ).
In Malaysia, the rates of post-operative infectious endophthalmitisfollowing all intraocular surgery in MOH hospitals ranged from0% to 1.13%, with a mean of 0.26 % for 2 consecutive years(2003 and 2004) and a mean of 0.18% for the year 2005(Unpublished data, Annual MOH census).
The rate following cataract surgery based on the National CataractSurgery Registry of MOH hospitals was 0.19% in 2002, 0.24% in2003 and 0.16% in 2004 (6, Level 9 ; 7, Level 9; 8, Level 9 ).
1.3 Causative Organism
The microbial spectrum seen in post-operative endophthalmitisdepends on various factors including environmental, geographicclimatic conditions as well as types of surgery.
Table 1 : Causative Organism- Microbial Spectrum Based on Type
of Surgery
Type of surgery
Micro organism
Percentage
Coagulase negative staphylococcus i.e.
Beta haemolytic streptococcus, Streptococcus pneumoniae, alpha-haemolytic streptococciincluding S.mitis and S. salivarius Pseudomonas aeruginosa, Bacteroids species Fungi including Candida species, Aspergillus Propionibacterium acnes, Corynebacterium Streptococcus, gram negative bacteria (Adapted from ESCRS Guidelines 2005 with permission) 1.4 Risk Factors
The source of infection following intraocular surgery include lids,adnexa, ocular tear film, respiratory and skin flora of the surgeonsand assistants, surgical instruments including IOL, irrigatingsolutions and operating room air (9, Level 1). As sterile surgicaltechnique addresses many of these factors, the common sourcesof pathogens are thus from ocular surface and adnexa (10, Level 2; 11,Level 8).
Table 2 : General Risk Factors
Evidence / Level of Evidence
Preoperative risk factors include presence of blepharitis, conjunctivitis, dacryocystitis, lacrimal duct obstruction, contactlens wear, and ocular prosthesis in the fellow orbit (12, Level 9) Intra-operative risk factors include inadequate eyelid andconjunctival disinfection (13, Level 7), inadequate draping of lid andlashes (14, Level 9), prolonged surgery (13, Level 7) and presence of intra-operative complications (15, Level 7) Post-operative risk factors include wound leak and wounddehiscence, inadequately buried sutures, suture removal,vitreous incarceration in the surgical wound and occurrence offiltering bleb (4, Level 9) Systemic
Host immunosuppression, diabetes mellitus (16, Level 7; 1 Level 8, 17, Level 2) Presence of atopic dermatitis and keratoconjunctivitis sicca (18, Level 9) Patient on topical or systemic immunosuppressive drugs suchas corticosteroid and antimetabolites (19, Level 7) Respiratory and skin flora of the surgeons and assistants (9 , Level 1) Surgical instruments including intraocular lens (9, Level 1) Irrigating solutions and medications (9, Level 1) Table 3 : Specific Risk Factors In Relation to the Type of Intraocular Surgery
Evidence / Level of Evidence
Cataract
Surgery
Intracapsular cataract extraction (ICCE) has higher risk when compared to extracapsular cataract extraction (ECCE) (5, Level 8) ECCE has higher risk when compared to phacoemulsification(20, Level 8) Secondary IOL implantation has higher risk due to associatedfactors such as transcleral suture fixation of posterior chamberIOL, polypropylene haptics, re-entering the eye through aprevious wound and post-operative wound defects (21, Level 8) The risk is higher with clear cornea incision when compared to scleral tunnel incision (22, Level 8; 23, Level 2) The risk is higher with longer duration of surgery (13, Level7) Occurrence of posterior capsular rupture and vitreous loss, as well as performance of anterior vitrectomy is associated with complications higher risk ( 5, Level 8; 15, Level 6; 20, Level 8; 24, Level 8; 25, Level 8)and anteriorvitrectomy Polypropylene haptic IOL is associated with higher risk (13, Level 7) Silicon IOL has higher risk as compared topolymethylmethalcrylate (PMMA) and acrylic IOL (15, Level 7)Foldable lenses have higher risk when compared to injectablelenses (20, Level 8) Glaucoma
Inferiorly located bleb is associated with higher risk. (26, Level 9; 27,Level 8; 3, Level 8; 28, Level 7) Filtering
Surgery
The use of mitomycin C is associated with higher risk (26, Level 9; 29, Level 7)Performance of full thickness rather than a guarded filtrationprocedure (29, Level 7)Highly elevated or leaking bleb is associated with higher risk (29, Level 7) Penetrating Contaminated donor button is associated with higher risk (30, Level 8)
Keratoplasty
Patients who are exposed to any of the above risk factors should be monitoredclosely for symptoms and signs of infection.
PROPHYLACTIC MEASURES
The low incidence of post-operative infectious endophthalmitis makes
it difficult to assess accurately the efficacy of preventive measures.
Many studies either have low statistical power in assessing the
influence of a change in procedure on the incidence of post-operative
endophthalmitis, or measure surrogate outcomes such as change in
conjunctival flora or aqueous bacterial counts. In addition, most of
the studies on prophylaxis were related to cataract surgery and thus
its application to other forms of ocular surgeries may not apply.
As the ocular surface is a common source of pathogens (10, Level 2; 11, Level 8)various measures have been used to prepare the ocular surfacebefore surgery to reduce normal ocular surface flora.
2.1 Antiseptic Measures
Preoperative povidone iodine on skin and conjunctival sacPovidone iodine 5% solution has been shown to decrease thenumber of colonies isolated from the conjunctiva by 91% anddecrease the number of species by 50%. (9, Level I; 31, Level 3; 32, Level 7; 33,Level 7; 34, Level 7; 35, Level 4; 36, Level 8; 37, Level 8). Instillation of topical 5%povidone iodine solution into the conjunctival sac just beforesurgery significantly reduced the incidence of culture positiveendophthalmitis as compared to silver nitrate solution (38, Level 4; 9,Level I). Even when used at 1.25% preoperatively, topical povidoneiodine has shown a significant reduction in the conjunctivalbacterial counts (39, Level 4).
Its application to the eye at the end of surgery has also beenshown to be effective in reducing conjunctival bacterial flora andwas in fact more effective when compared to topical broadspectrum antibiotics (40, Level 7).
However, on the basis of available clinical studies, only povidoneiodine in a concentration of 5% in balanced salt solution (BSS)or isotonic saline can be recommended as the preoperativeantiseptic of choice (26, Level 9). Chlorhexidine 0.05% should be used asthe alternative in patients who are allergic to povidone iodine (26, Level 9).
The use of povidone iodine was not associated with significantadverse reactions (38, Level 4).
Inadequate draping of the periorbital areas with exposed lids andlashes to the surgical site might be a possible risk factor (14, Level 9).
Preoperative trimming of eyelashes is not associated with areduction of risk of post-operative endophthalmitis (22, Level 8; 9, Level 1).
Preoperative irrigation of lacrimal passages Preoperative irrigation of the lacrimal passages has no significanteffect as prophylactic measure (9, Level 1).
Preoperative saline irrigation of conjunctival sac Saline irrigation of conjunctival sac did not reduce the bacterialflora (9, Level 1; 34, Level 4).
2.2 Antibiotics Prophylaxis
Intracameral injection of cefuroxime at the end of surgery Intracameral injection of 1mg cefuroxime in 0.1 ml at the end ofphacoemulsification surgery has been shown to significantlyreduce the risk of post-operative endophthalmitis up to five foldsin a multicenter European study (41, Level 2). This prophylacticmeasure has been adopted by all Swedish cataract surgeons (42,Level 7). Refer Appendix 4 for the dilution of intracameral cefuroxime.
Careful dilution should be undertaken to ensure its safe use andto prevent potential toxicity.
Intracameral irrigation of antibiotic through addition of Anterior chamber contamination at the end of cataract surgeryvaries from 0.18% to 13.7% (26, Level 9; 43, Level 8). Although somestudies evaluating intraocular fluid contamination have shownthat irrigating solution with vancomycin have reduced positiveaqueous cultures (44, Level 9; 45, Level 8; 46, Level 2), whether the reduction ismeaningful remains doubtful (26, Level 9). Furthermore, it has beenshown that exposure to an antibiotic for a short duration during intraocular surgery has little effect on organisms commonlyresponsible for endophthalmitis (47, Level 9). As its use can causeretinal toxicity from inadvertent dilution error including irreversiblemacular infarct, as well as resulting in antibiotic resistance, it isgenerally not recommended (48, Level 9; 49, Level 9; 50, Level 9).
There is insufficient evidence to show that the use of preoperativetopical antibiotic significantly reduces the risk of post-operativeinfectious endophthalmitis (9, Level 1; 41, Level 2).
c. Preoperative systemic antibioticIntravenous antibiotic prophylaxis is not proven to be of benefitin preventing post-operative endophthalmitis (26, Level 9).
d. Post-operative subconjunctival antibiotic injectionSub-conjunctival antibiotic injection at the conclusion of surgerydoes not appear to prevent post-operative endophthalmitis (22, Level 9).
2.3 Heparinized Intraocular Infusion Solution and Heparin
Coated IOL
Heparin coats the lens and intraocular surface and thus preventbacterial adherence (51, Level 9). However there is no sufficientevidence to indicate benefits of both heparinized irrigating solutionand heparin coated IOL in preventing post-operative infectiousendophthalmitis (52, Level 3).
2.4 Operating Theatre
There are no current guidelines for the type of airflow best requiredto prevent post-operative infectious endophthalmitis forintraocular surgery. The ideal type of airflow system is beinginvestigated by the ESCRS multi-centre study on endophthalmitisafter phacoemulsification surgery (26, Level 9).
All equipment for surgery should be sterile. Care is required withboth washing and autoclaving the instruments. It is preferablethat tubing that becomes wet within the operative procedure should not be reused. Bottles of balanced salt solution (BSS)should never be kept overnight or used for more than oneoperating session. Operating theatre trolleys must be kept dryas wet areas are easily contaminated with Pseudomonasaeruginosa (26, Level 9).
Further details of prophylactic measures are given in Appendix 1.
Recommendations for prophylaxis
Use of povidone iodine 5% as an antiseptic agent for preparation ofskin and conjunctival sac preoperatively is recommended. (Grade A) Proper draping of the eyelid margin using an adhesive non porous drapeand the use of speculum to cover all the eyelashes is recommended.
Intracameral injection of 1 mg cefuroxime in 0.1ml at the end of surgeryis recommended. Careful dilution should be undertaken to preventpotential toxicity.
DIAGNOSIS AND INVESTIGATIONS
Patients who have undergone intraocular surgery and who develop
the following clinical features should be assessed and monitored
closely. Prompt management with intravitreal tap and intravitreal
antibiotic injection should be performed in clinically suspected cases
of post-operative infectious endophthalmitis.
3.1 Clinical Features
Acute post-operative endophthalmitis The symptoms and signs may include the following:- Ocular pain (74-85%) (53, Level 2; 16, Level 7; 26, Level 9; 50, Level 9) Reduced vision (>90%) (53, Level 2; 16, Level 7 ; 50, Level 9; 26, Level 9) Swollen lids (35%) (54, Level 8; 50, Level 9) Inflamed or oedematous conjunctiva (>80%) (54, Level 8; 50, Level 9;26, Level 9) Discharge into conjunctiva (26, Level 9; 50, Level 9) Corneal oedema (26, Level 9, 50, Level 9) Cloudy anterior chamber with cells, hypopyon or fibrin (75-85%) (54, Level 8; 26 , Level 9; 50, Level 9) Vitreous clouding (vitritis) (26, Level 9; 50, Level 9 ) Involvement of posterior segment with retinitis, and/or retinalperiphlebitis, retinal oedema and papillary oedema (26, Level 9; 50, Level 9) Involvement of posterior segment is virtually always accompaniedby severe anterior segment inflammation.
Chronic post-operative infectious endophthalmitis Patients may present with any of the symptoms and signs ofacute post-operative endophthalmitis. Features include:- Mutton fat keratic precipitates on IOL or corneal endothelium(4, Level 9) P e r s i s t e n t l o w g r a d e u v e i t i s t h a t m a y r e s p o n d t ocorticosteroids initially ( typical) (4, Level 9) Hypopyon – sometimes so small that it can only be visiblewith gonioscopy, or recurrent hypopyon that fails to respondto corticosteroid (4, Level 9; 26,level 9) White ‘string-of-pearl’ infiltrate in the anterior chamber andvitreous are sometimes seen in fungal infections (4, Level 9) Plaque located on the posterior capsule, IOL or retainedlens particles (40-89%) (56, Level 9; 57, Level 9; 4, Level 9) Vitreous clouding (vitritis) from chronic inflammation (4, Level9; 26, Level 9) 3.2 Investigations
When a clinical diagnosis of acute or chronic post-operative
infectious endophthalmitis is made, a vitreous tap should be
performed within ONE hour after clinical diagnosis, together
with administration of an intravitreal antibiotic injection (26, Level 9).
Anterior chamber tap is helpful in the identification of the causative
organism as some organisms grow from the aqueous but not
from the vitreous sample.
Aqueous and vitreous specimens should be sent for gram stain,culture and sensitivity. Polymerase chain reaction (PCR) methodsoffer much improved pathogen detection especially in the caseof chronic endophthalmitis with low pathogen counts (58, Level 8).
However, due to its high sensitivity, problems with availability andthe risk of contamination, its use as routine diagnostic test islimited (26, Level 9).
Vitreous biopsy has not been shown to have better microbialyield as compared to vitreous tap (59, Level 2).
Conjunctival and corneal swabs are usually not helpful in isolatingthe causative microorganisms (38, Level 4).
Refer Appendix 2 for the performance of anterior chamber tap,vitreous tap and intravitreal antibiotic injection.
TREATMENT
There is variation in the treatment of post-operative infectious
endophthalmitis and the treatment approach is usually based on
institutional protocol.
4.1 Treatment of Acute Post-operative Infectious
Endophthalmitis
Intravitreal antibiotics should be given as soon as possible afterclinical diagnosis has been made (4, Level 9; 26, Level 9; 50, Level 9). Thisshould be preceded by intravitreal tap. Intravitreal antibiotic maybe repeated as necessary judging by the clinical response, usuallyat an interval of 48-72 hours (50, Level 9). The time interval for repeatintravitreal antibiotic depends on the half-life of the antibiotic used.
A combination of broad-spectrum antibiotics covering both grampositive and negative organism is used. The choice of antibioticsshould be reviewed following the culture and sensitivity results.
The commonly used antibiotic combinations are:- Vancomycin (2mg in 0.1ml) AND Ceftazidime (2mg in 0.1ml)(60, Level 2; 4, Level 8; 61, Level 9) OR Vancomycin (2mg in 0.1ml) AND Amikacin (0.4mg in 0.1ml)(4, Level 8; 53, Level 2) Ceftazidime is preferred over amikacin in view of amikacin relatedretinal toxicity (53, level 2; 62, level 9; 48, Level 9; 4, Level 9).
Patient’s clinical progress should be observed and monitoredclosely. Early referral for a vitreoretinal opinion after intravitrealantibiotic injection is recommended.
Refer Appendix 3 for the preparation of intravitreal drugs usingaseptic technique.
Topical and subconjunctival injection of antibiotic The aim of topical and subconjunctival injection of broad spectrumantibiotics use is to treate possible ocular surface and anteriorsegment infection. Topical ceftazidime (5% or 50mg/ml), topicalvancomycin (5% or 50mg/ml) or other broad spectrum antibioticseye drops are used, either as monotherapy or combined therapy,hourly round the clock initially with subsequent tapering accordingto clinical response (50, Level 9). Subconjunctival injection of antibioticcan be used together with intravitreal antibiotics in the treatmentof post-operative endophthalmitis. This is done in the hope ofachieving higher concentration of antibiotics around the eye andin the anterior chamber, especially when the frequent round theclock instillation of topical antibiotics at the initial period is notpossible (4, Level 9). When giving subconjunctival antibiotic,subconjunctival mydricane can be given to get pupillary dilatationwhich helps the movement of antibiotic around the eye.
The Endophthalmitis Vitrectomy Study concluded that systemicceftazidime and amikacin did not have any effect on the courseand outcome of endophthalmitis after cataract surgery (53, Level 2).
In cases of severe, virulent endophthalmitis, systemic intravenousantibiotics of the same choice as intravitreal antibiotics shouldbe given (4, Level 9). Alternatively, oral moxifloxacin (400mg daily for10 days) or oral ciprofloxacin (750mg bd for 14 days) can begiven. However, systemic fluoroquinolones are to be used withcaution in children (50, Level 9).
Oral clarithromycin (500mg bd for 2 weeks) is recommended forpatients with acute post-operative endophthalmitis with a culture negative eye (66, Level 8; 67, Level 8). It acts as a biofilm reducing agent toenhance the efficacy of cefuroxime, ceftazidime and amikacin.
In view of a high incidence of resistance to ciprofloxacin, fourthgeneration fluoroquinolones, oral moxifloxacin (400mg daily for10 days) has been used (65, Level 9). In addition, moxifloxacin hasan anti-biofilm effect on coagulase- negative staphylococci, whichare one of the commonest infecting organisms following cataractsurgery. Besides, moxifloxacin has also been shown to havebetter penetration to inflamed ocular tissue (68, Level 9; 69, 2006, Level 8).
This may therefore improve the ocular prognosis. When oralmoxifloxacin is used, the use of oral clarithromycin is not indicated(65, Level 9).
There is limited evidence on the efficacy of intravitreal andperiocular corticosteroids in the treatment of post-operativeinfectious endophthalmitis. While intravitreal dexamethasonereduces early inflammation in bacterial endophthalmitis, it hasno independent influence on the visual outcome (63, Level 8; 64, Level 8).
Intensive topical prednisolone acetate 1% or dexamethasone 1%every 1 to 2 hours is recommended to control anterior chamberinflammation. Its use should begin soon after intravitreal injectionof antibiotics (65, Level 9).
Oral prednisolone one day after intra-vitreal antibiotic therapyhas not been shown to have any negative effect on the course ofinfection in bacterial endophthalmitis (53, Level 2). It may be used inthose who have no contraindications for corticosteroid (50, Level 9; 65,Level 9). The dosage of oral prednisolone is 1 mg/kg/day, to betapered by 10mg each week for a total duration of up to 3 weeks(65, Level 9). Tablet ranitidine is prescribed simultaneously for gastricprotection. Patients with fungal endophthalmitis should not begiven prednisolone.
Tissue Plasminogen Activator (TPA) TPA has only been reported to be useful as adjunctive therapy inanimal studies and in a small case series of endophthalmitis withsevere fibrinous anterior chamber reaction (70, Level 9; 71, Level 9; 72, Level 9).
There is insufficient evidence for its routine use for both acuteand chronic post-operative endophthalmitis. However,intracameral injection of 25 mg in 0.1 ml is recommended inpatients with severe fibrinous anterior chamber reactionsparticularly in eyes with pupils that do not dilate with mydriatics.
According to Endopthalmitis Vitrectomy Study (EVS), routineimmediate vitrectomy is not necessary in patients with better thanlight perception vision at presentation but is of substantial benefitfor those who have light perception- only vision (53, level 2; 73, Level 9).
However, limitations of EVS leave this conclusion open to futuremodification (26, Level 9; 74, Level 9).
Recommendation for treatment of acute post-operative
endophthalmitis
Intravitreal antibiotic should be given within 1 hour of diagnosis andrepeated when necessary.
Intensive topical antibiotic and steroid should be given round the clockinitially.
Subconjunctival antibiotic is given when indicated.
The use of oral or intravenous antibiotics is recommended forendophthalmitis patients with virulent infection.
Systemic corticosteroid may be given.
Oral clarithromycin (500mg bd for 2 weeks) is recommended in culturenegative cases with poor clinical response.
Intracameral tissue plasminogen activator (25mg in 0.1ml) isrecommended in patients with severe anterior chamber reaction.
Vitrectomy may have a role in improving prognosis. Therefore, earlyreferral for a vitreoretinal opinion is recommended.
Refer algorithm for the management of acute post-operative endophthalmitis Vitrectomy with or without silicone oil tamponade has been shownin recent case series, to increase the chance of surgical successand decrease the number of additional procedures in eyes withpost-operative infectious endophthalmitis (75, Level 7).
4.2 Tr e a t m e n t o f C h r o n i c P o s t - o p e r a t i v e I n f e c t i o u s
Endophthalmitis
Intravitreal antibiotic is given to all patients with chronic post-operative endophthalmitis. The choice of intravitreal antibiotic issimilar to that in acute post-operative endophthalmitis (76, Level 6; 4,Level 9).
The decision to use topical and systemic antimicrobials in chronicpost-operative infectious endophthalmitis is the same as that foracute post-operative infectious endophthalmitis (26, Level 9).
For suspected fungal endophthalmitis, intravitreal amphotericinB (5ug or 10ug in 0.1ml) has been proven to be effective.
Intravitreal miconazole (0.01mg in 0.1ml) should be consideredfor fungi resistant to amphotericin B (76, level 9; 4, Level 9).
Combined systemic therapy with amphotericin B and imidazoleis effective in infection with Fusarium sp. whereas voriconazoleor fluconazole is effective for Candida albicans. Itraconazolecan be used for other Candida species, Aspergillus orCryptococcus (77, Level 9).
The indication for he use of systemic clarithromycin is as peracute post-operative endophthalmitis (66, Level 8; 67, Level 8; 26, level 9).
There is insufficient evidence for or against vitrectomy in thetreatment of chronic post-operative endophthalmitis. However,in cases of suspected or confirmed Propionebacterium acnes orfungal endophthalmitis following cataract surgery, removal of IOLand posterior lens capsule with vitrectomy should be considered(4, Level 9; 18, Level 9).
Recommendation for treatment of chronic post-operative
endophthalmitis
Intravitreal antibiotic should be given promptly.
Intravitreal amphotericin B (5ug or 10ug in 0.1ml) is to be given if fungalendophthalmitis is suspected.
Topical antibiotics and steroid should be given.
Systemic anti-fungals to be given when indicated.
The use of oral or intravenous antibiotics is indicated in patients withsevere endophthalmitis.
Oral clarithromycin (500mg bd for 2 weeks) is recommended in culturenegative cases with poor clinical response.
Intracameral tissue plasminogen activator (25mg in 0.1ml) isrecommended in patients with severe anterior chamber reaction.
Early referral for vitreoretinal consultation is recommended. (Grade C) Refer algorithm for the management of chronic post-operative endophthalmitis 5. CLINICAL AUDIT INDICATOR
The incidence rate of post-operative infectious endophthalmitis should bemonitored as a performance indicator by all ophthalmic facilities. Currentlydata from MOH hospitals are being collected by the ophthalmology service,MOH.
ALGORITHM FOR THE MANAGEMENT OF ACUTE POST-OPERATIVE
INFECTIOUS ENDOPHTHALMITIS
CLINICAL DIAGNOSIS
History:Patient who presents within 2 weeks of intraocular surgery with signsand symptoms suspicious of endophthalmitis (refer to text) Examination1. Perform anterior and posterior segment examinations2. Perform B-scan ultrasonography if necessary INVESTIGATIONS
1. Perform vitreous tap +/- anterior chamber tap. Preferably to be done within ONE hour of clinical diagnosis
2. Send specimen for gram stain, culture and sensitivity, and PCR TREATMENT
1. Intravitreal antibiotic injections to be given within 1 hour of diagnosis 2. Begin intensive topical antibiotics and topical steroid soon after intravitreal antibiotic injection, round the clock initially 3. Systemic antibiotics for severe, virulent endophthalmitis4. Oral prednisolone to be considered and may be given 24 hours following intravitreal antibiotics injection 5. Review antibiotic regimen after microbiology results6. Repeat intravitreal antibiotics after 48 to 72 hours if indicated7. Consider oral clarithromycin in culture negative cases with poor 8. Early referral for a vitreoretinal opinion ALGORITHM FOR THE MANAGEMENT OF CHRONIC POST-
OPERATIVE INFECTIOUS ENDOPHTHALMITIS
CLINICAL DIAGNOSIS
History:Patient who presents after 2 weeks of intraocular surgery with signs andsymptoms suspicious of endophthalmitis (refer to text) Examination1. Perform anterior and posterior segment examinations2. Perform B-scan ultrasonography if necessary INVESTIGATIONS
1. Perform vitreous tap +/- anterior chamber tap2. Send specimen for gram stain, culture and sensitivity, and PCR test if 3. If decision is made to remove the IOL, then send the lens capsule fragments for gram stain, culture and sensitivity, and PCR test if indicated TREATMENT
vancomycin and ceftazidimeORvancomycin and amikacinAND/ORintravitreal amphotericin B if suspicious of fungal endophthalmitis 2. Begin topical steroid and topical antibiotics soon after intravitreal 3. Review antibiotic regimen after microbiology results4. Systemic anti-fungals if indicated5. Consider oral clarithromycin in culture negative cases with poor clinical 6. Consider intracameral tissue plasminogen activator in patients with 7. Early referral for a vitreoretinal opinion Appendix 1
PROPHYLACTIC MEASURES
Careful preoperative assessment of patients1.1. Treat patients who have predisposing risk factors such as eyelid infection, conjunctivitis, dacryocystitis and nasolacrimal ductobstruction.
1.2. Optimize patients’ medical conditions, which may affect wound healing such as diabetes mellitus and anemia.
Proper scrubbing of eyebrow, upper and lower eyelids, eyelashes, adjacentforehead, nose, cheek and temporal orbital areas with 5% povidone iodine*.
Use chlorhexidine 0.05% as an alternative in patients who are allergic topovidone iodine.
Apply 5% povidone iodine to the conjunctival sac before surgery begins.
Proper draping of eyelid margins, and with proper use of speculum to tuckin all eyelashes under the non porous adhesive drape.
Ensure sterility of surgical instrument especially the microsurgicalinstruments that enter the eyes. Only use properly sterilized microinstruments.
For cataract surgery7.1. Avoid unnecessary contact of IOL on possible areas of contamination 7.2. Use of injector for foldable lens is preferred.
7.3. Do not share viscoelastic material between patients.
7.4. Ensure incision is water tight at the end of surgery.
7.5. Consider intracameral injection of 1mg cefuroxime in 0.1 ml at the end of surgery. Careful dilution must be undertaken to prevent potentialtoxicity.
Replenishment of analgesic, steroid and antibiotic eye drops used in theOT at regular intervals to prevent contamination. Label date of opening onnew bottles.
Careful post-operative monitoring for high risk patients.
*Preparation of 5% povidone iodine is done with 1:1 dilution of the 10% solutionwith sterile balanced salt solution (BSS) or isotonic saline. It should be preparedon the day of surgery. The use of a large bottle of readily diluted povidone iodineor chlorhexidine should be avoided as both antiseptics can become contaminatedwith Pseudomonas aeruginosa. Povidone iodine solution containing detergentmust NOT be used as it coagulates the cornea irreversibly (26, level 9).
Appendix 2
PROCEDURE FOR ANTERIOR CHAMBER TAP, VITREOUS TAP AND
INTRAVITREAL ANTIBIOTIC INJECTION
Anterior Chamber Tap
Perform limbal paracentesis at the slit lamp, using a 1 ml syringe (notan insulin syringe) with a half inch 25 gauge needle. A larger boreneedle, e.g. 23 gauge needle, may be used if there is hypopyon. Loosenthe plunger first before entering the eye to ease the aspiration of aqueous.
Inoculate aqueous specimen onto culture plates and smear it on glass slide.
Label the syringe, culture plates, glass slide or culture bottle beforesending them to the laboratory.
Vitreous Tap
Prepare vitreous tap set consisting of eyelid retractor, caliper,conjunctival forceps, 5ml syringes, 23G needle, cotton buds, eye pad,and povidone iodine 5% solution.
Perform procedure using aseptic technique in a quiet and clean place,either at the outpatient clinic, ward or operating theatre.
Clean the periorbital skin and conjunctival sac with povidone iodine 5%.
Instill topical anaesthetic drops and subconjunctival injection of 2%lignocaine.
Perform vitreous tap using a 5ml syringe with 23G needle. Enter theeye about 4 mm posterior to the limbus for phakic eyes or 3.5 mm foraphakic or pseudophakic eyes.
Aspirate about 0.2ml to 0.4 ml of vitreous.
Inoculate vitreous specimen onto culture plates and smear it on aglass slide.
Label the syringe, culture plates, glass slide or culture bottle beforesending them to the laboratory Intravitreal Antibiotic Injection
Prepare and dilute intravitreal antibiotics using an aseptic technique.
Prepare different antibiotics in separate syringes.
Use 26G or 30G needle and inject 4 mm (phakic eyes) or 3.5 mm(pseudophakic/ aphakic eyes) posterior to the limbus into the midvitreous cavity, with the bevel of the needle pointing anteriorly.
Appendix 3
PREPARATION OF INTRAVITREAL DRUGS
Intravitreal drug preparation should be freshly diluted and preferably supplied by the
hospital pharmacy department. However, in case of emergency, it can be prepared
in the ward using an aseptic technique. The drug preparation guide is given below.
Drug (Recom-
Preparation
mended dosage)
1. The vial contains 500 mg vancomycin powder 2. Reconstitute the vial with 10 ml of 0.9% normal saline 3. Withdraw 4ml (200mg) and add 6ml of 0.9% NS4. Take 0.1 ml (=2 mg) 1. The vial contains 1000 mg ceftazidime powder.
2. Reconstitute the vial with 10 ml of 0.9% NS/water for 3. Withdraw 1 ml (100mg) and add 4ml of 0.9% NS/water solution of 500mg of
solution of 250mg of
1. The vial contains 50-mg of amphotericin B powder 2. Reconstitute the vial with 10ml sterile water for injection3. Withdraw 1ml (5mg) and add 9ml of sterile water for 4. Withdraw 1ml (0.5mg) and add 9ml of sterile water for 1. The ampoule contains 10mg/ml of miconazole 2. Withdraw 1ml (10mg) and add 9ml of 0.9% normal saline.
3. Withdraw 1ml (1mg) and add 9ml of 0.9% normal saline4. Take 0.1ml (=0.01mg) 1. The vial contains a solution of 4mg of dexamethasone in 1ml Appendix 4
PREPARATION OF INTRACAMERAL CEFUROXIME
Drug (Recom-
Preparation
mended dosage)
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ACKNOWLEDGEMENTS
The committee of this guideline would like to express their gratitude and appreciation to the following for their contribution: Panel of external reviewers who reviewed the draft.
Technical Advisory Committee for Clinical Practice Guidelines for their CPG Secretariat, particularly Datin Dr Rugayah Bakri, Head of Health Technology Assessment Unit, and Ms Hanita Muhsin, Nursing Manager, Medical Development Division, Ministry of Health Malaysia.
DISCLOSURE STATEMENT
The panel members have no potential conflict of interest to disclose.
SOURCES OF FUNDING
The development of the CPG on Management of Post-operative Infectious Endophthalmitis was supported financially in its entirety by the Ministry of Health Malaysia and was developed without any involvement of the LEVELS OF EVIDENCE SCALE
Strength of
Study Design
Evidence
Non-randomised controlled prospective trial Non-randomised controlled prospective trialwith historical control Non-controlled clinical series, descriptivestudies multi-centre Expert committees, consensus, case reportsanecdotes Adapted from Catalonian Agency for Health Technology Assessment & Research,(CAHTAR) Spain GRADES OF RECOMMENDATIONS
At least one meta analysis, systematic review, or RCT, or evidence rated as good and directly applicable to the target population Evidence from well conducted clinical trials, directly applicable tothe target population, and demonstrating overall consistency of results; or evidence extrapolated from meta analysis, systematicreview, or RCT Evidence from expert committee reports, or opinions and /or clinical experiences of respected authorities; indicates absenceof directly applicable clinical studies of good quality Source : Modified from Scottish Intercollegiate Guidelines Network (SIGN)

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