ESCRS Guidelines on prevention, investigation and management of

<strong>ESCRS</strong> <strong>Guidelines</strong> on prevention,
investigation
and management of
post-operative endophthalmitis
Version 2
August 2007
Editors
Peter Barry, Wolfgang Behrens-Baumann,
Uwe Pleyer & David Seal
Supported by

Contents
1. INTRODUCTION 1
1.1 Endophthalmitis 1
1.2 Pathophysiology 1
1.3 Microbial spectrum 2
1.4 Incidence of endophthalmitis after different types of surgery 3
2. PROPHYLAXIS 8
2.1 Operating theatre 8
2.2 Antisepsis 8
2.3 Antibiotics 9
2.4 Limitations of the <strong>ESCRS</strong> Study 12
2.5 FLOW CHART – PROPHYLAXIS GUIDELINES 14
3. DIAGNOSIS 15
3.1 Commencement and symptoms 15
3.2 FLOW CHART – DIAGNOSTIC GUIDELINES FOR ACUTE
VIRULENT ENDOPHTHALMITIS 16
3.3 FLOW CHART – DIAGNOSTIC GUIDELINES FOR CHRONIC ENDOPHTHALMITIS 17
3.4 Differential diagnosis – the toxic anterior segment syndrome 18
4. INVESTIGATION 19
4.1 AC tap, vitreous tap, vitrectomy for Gram stain, culture and PCR tests 19
4.2 Epidemiology 19
5. TREATMENT 20
5.1 Surgical management of endophthalmitis. Diagnostic and therapeutic vitrectomy 20
5.2 Anti-microbial therapy 22
5.3 Anti-inflammatory therapy 25
5.4 Other types of post-operative endophthalmitis 25
5.5 Limitations of EVS study 26
5.6 FLOW CHART – TREATMENT GUIDELINES FOR
ACUTE VIRULENT ENDOPHTHALMITIS 27
5.7 FLOW CHART – TREATMENT GUIDELINES FOR
CHRONIC ENDOPHTHALMITIS 28
6. REFERENCES 29
7. APPENDIX (Addresses of Contributors) 36

1. Introduction
1.1 Endophthalmitis
Endophthalmitis is an inflammatory reaction occurring as a result of intraocular colonisation by bacteria,
fungi or rarely parasites. It can be exogenous (post-operative, post-traumatic) due to microbial contamination
spreading from the ocular surface or open incision (wound) or contaminated instruments, intraocular lenses
(IOLs) or intraocular foreign bodies or endogenous (septicaemia) in origin.
These guidelines on the prophylaxis and treatment of post-operative endophthalmitis are supported in detail
with literature references, which were classified according to the criteria of the Arbeitsgemeinschaft der
Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) [Association of the Scientific Medical
Societies in Germany] and the Ärztliches Zentrum für Qualität [Agency for Quality in Medicine] for evidencebased
medicine (EBM) (Table 1.1). This enables the reader to form an accurate opinion of the value of the
individual views stated. At the same time, he or she is able to form an opinion him/herself from the
extensive literature. Ultimately, it is apparent that there is a lack of well-founded prospective and controlled
studies of many procedures - an important task for the future. Results of the recently completed <strong>ESCRS</strong>
Study on the Antibiotic Prophylaxis of Post-operative Endophthalmitis (<strong>ESCRS</strong> Study) have been included in
these <strong>Guidelines</strong>.
Table 1.1 Classification of evidence type of studies
Stage Evidence based on:
I a meta-analysis of randomised controlled studies
I b at least one randomised controlled study
II a at least one well-designed controlled study without randomisation
II b at least one well-designed, quasi-experimental study
III well-designed, non-experimental descriptive studies
(e.g. comparative studies, correlative studies, case-control studies)
IV reports/opinions of expert circles, consensus conferences
and/or clinical experience of acknowledged authorities
1.2 Pathophysiology
The occurrence, severity and clinical course of endophthalmitis depends on the route of infection, the
virulence and number of inoculated pathogens as well as the patient's immune state and the time of
examination [205]. In 29 to 43 per cent of cataract operations, intraocular contamination occurs with
facultative pathogenic bacteria from the ocular surface without the development of endophthalmitis [41],
[68], [106]. Protective mechanisms, which have been summarised as the “immune privilege of the eye“
(anterior or posterior chamber-associated immune deviation, ACAID or POCAID) [205], are particularly
effective in the anterior part of the eye, act as a protective barrier and can limit the inflammatory reaction
[191], [198]. If this privilege is compromised, e.g. by an intra-operative capsular defect with vitreous loss,
the risk of endophthalmitis increases by a factor of 14 [98].
In microbial endophthalmitis, three phases of infection can be observed: an incubation phase, an
acceleration phase and a destructive phase [173]. A clinically inapparent incubation phase is observed
initially, which lasts at least 16 to 18 hours, even with virulent micro-organisms. Intraocular bacterial
inoculation above a critical level then leads to breakdown of the aqueous barrier with fibrin exudation and
cellular infiltration by neutrophilic granulocytes [24]. The incubation phase is determined mainly by the
generation time of the pathogen (e.g. Staphylococcus aureus and Pseudomonas aeruginosa up to 10 min,
Propionibacterium sp. > 5 h) and the specific characteristics of the pathogen such as toxin production. With
the commonest pathogens, Staphylococcus epidermidis (CNS) and Staphylococcus aureus, the greatest
infiltration is observed only three days after infection [24], [39].
In the case of primary infection of the posterior part of the eye, inflammation of the anterior chamber occurs
initially and this is accompanied within seven days by a specific immune response with macrophages and
lymphocytes in the vitreous cavity. Just three days after intraocular infection, pathogen-specific antibodies
can be detected, which contribute to pathogen elimination by opsonisation and phagocytosis within about
1

10 days. This can produce negative laboratory culture results but severe inflammatory disease within the eye
[39]. The inflammatory mediators of infiltrating cells, especially cytokines, not only recruit further leukocytes
but can directly result in destructive effects, retinal injury and vitreoretinal proliferation (destructive phase)
[30], [205].
It has been suggested that the use of phacoemulsification increases pressure within the eye forcing bacteria
backwards into the vitreous, where early multiplication gives rise to the anterior vitritis characteristically seen
behind the posterior capsule (refer to Investigation Section below).
Intraocular lenses are a potential vector for bacteria. There are differences in adherence to different lens
materials. Staphylococcus epidermidis adheres more to polypropylene haptics than to polymethyl methacrylate,
(PMMA) [69], [98], [190]. Hydrophilic heparin-coated lenses demonstrate lower adherence for staphylococci
[52]. The clinical effects have been variously interpreted [106]. A recent retrospective study has suggested,
but not proven, that use of foldable IOLs inserted via a sterile injector lowers the incidence of post-operative
endophthalmitis [95].
1.3 Microbial spectrum
This is described in the table of post-operative endophthalmitis below. The spectrum is dependent on various
factors including environmental, geographic and climatic conditions and which type of surgery is performed.
Table 1.2: Microbial spectrum of post-operative endophthalmitis
In summary, the most important pathogens causing post-operative phacoemulsification endophthalmitis are:
Post-operative (cataract surgery) endophthalmitis [46], [70], [81], [100], [102], [105], [134], [205], [207]
33 - 77 % CNS (coagulase-negative staphylococci)
10 - 21 % Staphylococcus aureus
9 - 19 % BHS (ß-haemolytic streptococci), S. pneumoniae, ∂-haemolytic
streptococci including S. mitis and S. salivarius
6 - 22 % Gram-negative bacteria including Ps. aeruginosa (occurs rarely)
up to 8 % Fungi (Candida sp., Aspergillus sp., Fusarium sp.)
Delayed post-operative saccular or capsule bag endophthalmitis with IOL implantation
Propionibacterium acnes, corynebacteria including C. macginleyi [164], [175], [205] and fungi [205]
Post-operative (glaucoma surgery) endophthalmitis [116], [124]
up to 67 % CNS
Delayed post-operative (glaucoma surgery) endophthalmitis [78], [142]
Streptococci
Gram-negative bacteria (especially Haemophilus influenzae)
Post-traumatic endophthalmitis
Single pathogen identified in 62–65%, mixed infection in 12–42% [57], [91], [125], [130], [205],
[207], [208]
16 - 44 % CNS
17 - 32 % Bacillus sp.
10.5 - 18 % Gram-negative bacteria
8 - 21 % Streptococci
4 - 14 % Fungi
4 - 8 % Corynebacterium sp.
1 - 2 % Clostridum perfringens and other soil bacteria
2

In the <strong>ESCRS</strong> Study, 29 patients presented with presumed post-operative endophthalmitis, of whom 20 were
classified as having proven infective endophthalmitis. The causative bacteria were identified by
microbiological methods and polymerase chain reaction (PCR) [11]. From 19 cases the following bacteria
have been confirmed:
Staphylococcus epidermidis 6
CNS 4
Staphylococcus aureus 2
other staphylococci 1
Streptococcus pneumoniae 2
other streptococci 6
Propionibacterium acnes 1
Gemella haemolysans 1
In summary, the most important pathogens causing post-operative phacoemulsification endophthalmitis are:
Acute
■ BHS, S. mitis, S. pneumoniae, E. faecalis
■ S. aureus, CNS, (MRSA, MRSE)
■ Gram-negative rods (GNR) including Haemophilus influenzae and Pseudomonas aeruginosa
Chronic
■ P. acnes
■ Diphtheroids
■ CNS
■ Fungi
1.4 Incidence of endophthalmitis after different types of surgery
Phacoemulsification
At the start of the 20th century (c1910), the incidence of endophthalmitis after cataract operations was 10
per cent. In the period of ECCE via a scleral or limbal incision and improved hygiene conditions (1970-
1990), the infection rate fell to 0.12 per cent in Europe [90] and to 0.072 per cent in the US [88].
However, since the introduction of phacoemulsification and clear cornea incisions, the retrospective data
with phacoemulsification are between 0.3 to 0.5 and 0.015 per cent (Table 1.3).
Table 1.3: Reported incidence for endophthalmitis after cataract surgery
Country [reference] Year of Publication Incidence (%) No. of Operations
USA [98] 1991 0.22 24105
USA [203] 1992 0.015 27181
France [40] 1992 0.32 ~ 34690
Germany [126] 1999 0.15 ~ 103090
Netherlands [135] 2000 0.10 ~ 25330
Canada [64] 2000 0.01 to 0.18 13886
Sweden [37] 2002 0.10 54666
Australia [110] 2003 0.16 to 0.36 83677
Japan [8] 2003 0.05 to 0.29 11595
USA [86] 2005 0.29 9079
Ireland [87] 2005 0.5 8763
UK [105] 2007 0.099 101920
Sweden [94] 2007 0.048 225471
Europe [5] 2007 0.05 to 0.35 16211
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While in the majority of studies patients received various additional forms of prophylaxis, the higher
incidence rate reported by the <strong>ESCRS</strong> [5] may be regarded as the true background rate when only povidoneiodine
is administered pre-operatively.
Risk factors for endophthalmitis following cataract surgery
The clear cornea incision is thought to have contributed to the increase in the number of endophthalmitis
cases following phacoemulsification surgery [8], [64], [197], [205]. Taban (2005) performed a metaanalysis
of 215 studies that addressed post-cataract surgical endophthalmitis which met his selection
criteria [129]. A total of 3,140,650 cataract extractions were pooled from ECCE and phacoemulsification
surgery giving an overall incidence of 0.128 per cent for post-operative endophthalmitis. He found this
incidence varied with time from 0.265 per cent in 2000/2003, 0.087 per cent in the 1990s, 0.158 per
cent in the 1980s to 0.327 per cent in the 1970s. He found the clear corneal incision of
phacoemulsification to be a risk factor between 1992 and 2003 with an increased rate of 0.189 per cent
compared to 0.074 per cent for scleral tunnel incision. However, Taban reviewed the limitations of his metaanalysis
study depending mostly on retrospective studies with limited statistical power. He commented on
the paucity of prospective randomised case-controlled studies.
Wallin et al. identified potential risk factors in a study of 27 endophthalmitis cases compared with 1525
patients in the cohort control. Main factors found to be statistically associated with endophthalmitis
included i) wound leak on the first post-operative day (p

In a case-control study of post-operative endophthalmitis cases in Sweden between 1994 and 2000, Wejde et al. found
that silicone intraocular lenses carried a higher risk than heparin surface modified PMMA implants [138]. Likewise, in
the prospective <strong>ESCRS</strong> study, the type of IOL material was found to be a risk factor which was significantly associated
with endophthalmitis. Patients receiving a silicone intraocular lens were 3.13 times more likely to experience
endophthalmitis than patients receiving an acrylic (or other material) lens. The hydrophobic nature of silicone may not
be the main characteristic explaining the apparent increased risk; the explanation is likely to be more subtle involving
an understanding of how differing biofilms are formed based on the surface properties of varying types of IOLs [5].
Finally, the <strong>ESCRS</strong> study demonstrated that surgical complications contribute to a higher incidence of contracting
endophthalmitis following phacoemulsification cataract surgery. Patients experiencing complications at the time of
surgery had a 4.95 times higher risk of infection [5].
There are no definite data with regard to other factors such as duration of operation, tissue trauma, and choice of
viscoelastic and irrigation solution [127], while there is limited retrospective data for use of injectors for lens (IOL)
implantation, suggesting they reduce the infection rate [95], and operative experience, suggesting a higher complication
rate by junior staff. All these factors have been assessed prospectively in the multi-centre <strong>ESCRS</strong> study (Table 1.4).
Because of the low incidence of childhood cataract, an exact estimate of the endophthalmitis risk in this patient
population is not possible. In 1990, Good et al. found three cases of endophthalmitis after 671 operations for
paediatric or congenital cataract (0.45 per cent). Two of the three cases occurred within the first 24 hours and Grampositive
bacteria were isolated as the cause (S. aureus, S. epidermidis, Strep. pneumoniae) [76]. Wheeler et al. reported
11 cases of endophthalmitis after cataract surgery out of 24,000 cataract or glaucoma operations in children [139].
Table 1.4: Risk factors for endophthalmitis following phacoemulsification surgery being
investigated in the <strong>ESCRS</strong> multi-centre study
Risk Factor Odds Ratio
Intra-cameral injection of cefuroxime – given or not given 4.92
Clear cornea (and position) versus scleral tunnel incision 5.88
Type of wound closure – suture or sutureless no evidence found
Insertion of IOL – injector or forceps not retained as a risk factor
Type of IOL material 3.13
Diabetic or non-diabetic no evidence found
Immuno-suppression or not no evidence found
Equipment sterilisation – disposable vs reusable no evidence found
Complications of surgery 4.95
Glaucoma surgery
Early post-operative endophthalmitis following glaucoma surgery has an incidence of about 0.1 per cent [89], [142].
However, the majority of cases of endophthalmitis after glaucoma surgery occur after months or years; the incidence is
about 0.2 per cent to 0.7 per cent [89], [142]. The risk of endophthalmitis when using anti-metabolites depends,
among other things, on the location of the filter bleb, where the inferior position has a markedly higher risk (Wolner:
three per cent with superior vs. 9.4 per cent with inferior position, Greenfield: 1.3 per cent with superior vs. 7.8 per
cent with inferior position, Caronia: 11.9 per cent with inferior position, Higginbotham: 1.1 per cent with superior vs. 8
per cent with inferior position) [59], [78], [82], [142]. After 5-FU the incidence of endophthalmitis is 5.7 per cent
[142].
In children, six cases of endophthalmitis after glaucoma surgery were reported after 24,000 cataract and glaucoma
filtering operations [139]. However, it is not reported how many of the 24,000 operations were glaucoma surgeries
alone.
Endophthalmitis after filter bleb operation commences within four weeks in about 19 per cent, so the majority of cases
occur later [92], [123]. In about half of the cases, the infection is due to streptococci and Gram-negative bacteria
including Moraxella sp. [55], [60], [181]. The endophthalmitis is sometimes preceded for days or weeks by eyebrow
pain, headache, blepharitis and conjunctivitis [123]. Filter bleb infection can still occur after many years [60], [78],
[142].
5

Penetrating keratoplasty
The incidence of post-operative endophthalmitis after penetrating keratoplasty reported in the literature is
between 0.08 per cent and 0.2 per cent (Eifrig: 0.08 per cent, Kattan: 0.11 per cent, Somani: 0.2 per
cent) [71], [88], [127]. Contamination of the donor cornea appears to be an important risk factor [152].
Fungal endophthalmitis after keratoplasty tends to be rare [99], [151], [189].
Pars plana vitrectomy
The incidence of post-operative endophthalmitis reported in the literature after pars plana vitrectomy is
between 0.05 per cent and 0.14 per cent [83], [88]. A few authors assumed that there was an increased
incidence of endophthalmitis after pars plana vitrectomy, as the patient often suffers at the same time from,
for example, diabetes mellitus. However, this assumption has not been confirmed.
The largest sample size comes from Cohen et al. in 1995 with 12,216 vitrectomies in eight centres; nine
cases of endophthalmitis were reported with an incidence of 0.07 per cent [63]. Since then, Jager et al.
have presented a retrospective review for 1972-2002 with 10,563 intravitreal taps in 1326 eyes from 42
published reports [171]; the overall incidence of endophthalmitis was 0.17 per cent (18 cases). For those
vitrectomies performed in the operating theatre, the rate was 0.11 per cent (4/3720) while for those
performed in out-patients, the rate was 0.17 per cent (5/2965) which was not statistically significant.
However, when there was use of topical povidone iodine prior to the tap, the incidence rate was 0.14 per
cent (9/6314), which increased to 0.69 per cent (6/869) when iodine was not used - this is statistically
significant at p = 0.0009, but relates to multiple taps in non-inflamed eyes.
Post-traumatic endophthalmitis
Post-traumatic endophthalmitis, along with post-operative endophthalmitis, is the second commonest form
of endophthalmitis. The incidence of endophthalmitis after perforating injury is between two per cent and
17 per cent [75], [154].
Trauma due to an intraocular foreign body involves a greater risk of endophthalmitis than trauma without a
foreign body [131]. The signs of infection usually occur early, but are often masked by the post-traumatic
reactions of the injured tissue.
An exact history (e.g. “did the accident happen in the country or in the city?”, type of foreign body,
symptoms) enables an early diagnosis to be made. In rural districts, the occurrence of post-traumatic
endophthalmitis was reported in 30 per cent of 80 patients after an injury. In contrast, post-traumatic
endophthalmitis occurred in 11 per cent of 204 patients in non-rural districts [154].
The start, course and symptoms of endophthalmitis after trauma are very varied, corresponding to the
causative organisms. The initial symptoms are usually pain, intraocular inflammation, hypopyon and vitreous
clouding. Similar to post-operative endophthalmitis, two thirds of the bacteria in post-traumatic
endophthalmitis are Gram-positive and 10 to15 per cent are Gram-negative [25]. In contrast to postoperative
endophthalmitis, virulent Bacillus species are the commonest pathogens in post-traumatic
endophthalmitis. They were isolated in 20 per cent of all cases of post-traumatic endophthalmitis. In the
rural population, they are found in 42 per cent of cases of post-traumatic endophthalmitis. They are the
second commonest cause of all cases of endophthalmitis. Most Bacillus infections are associated with
intraocular foreign bodies [154]. Infections that are caused by Bacillus species usually commence with rapid
loss of vision together with severe pain.
Fungi are the causative organisms in 10 to 15 per cent of cases of endophthalmitis after trauma. Fungal
endophthalmitis usually commences only weeks to months after the injury. While mixed infections tend to be
rarer in post-operative endophthalmitis, they were isolated in 42 per cent of the trauma-associated cases of
endophthalmitis [154].
Compared to post-operative endophthalmitis, the prognosis of post-traumatic endophthalmitis is usually
poor. This is due to a spectrum of more virulent pathogens, to mixed infections, to the degree of tissue
injury caused by the preceding trauma and to the failure to instil prophylactic intravitreal antibiotics at the
time of surgery. While final vision of 20/400 or better occurs in 85 per cent of cases of post-operative
endophthalmitis, patients with post-traumatic endophthalmitis achieve a final vision of 20/400 or better in
only 26 to 54 per cent with the remaining losing all vision [49], [57], [114], [131].
6

Medical conditions
Diabetes mellitus
About 14 to 21 per cent of all patients who develop post-operative endophthalmitis after cataract
operations are diabetic [67], [122]. However, pre-existing diabetes mellitus has not been confirmed as an
isolated risk factor for post-operative endophthalmitis after cataract extraction [4], [5]. If endophthalmitis
occurs in diabetics after cataract extraction, however, the functional prognosis must be regarded as poorer
especially if diabetic retinopathy is present pre-operatively [67]. Endophthalmitis in diabetics is caused
more often by Gram-negative bacteria than in non-diabetics [122]. In the EVS, endophthalmitis patients
with diabetes mellitus benefited particularly from vitrectomy even when their initial vision was better than
light perception [4].
Immune-suppression
Patients on topically or systemically administered immuno-suppressant therapy (corticosteroids, antimetabolites)
at the time of intraoperative procedures have a significantly higher risk of endophthalmitis
[106]. A change in the local pre-operative flora was not confirmed in patients on immuno-suppressant
therapy, nor was there an alteration in the spectrum of the organisms causing the endophthalmitis [185].
Altered bacterial flora
Atopic patients and those with rosacea have altered conjunctival and lid bacterial flora with a preponderance
of Staphylococcus aureus [12]; in addition rosacea patients have enhanced systemic cell-mediated immunity
to S. aureus which is thought to contribute to their blepharitis and keratitis [12]. While no trial data exists
for an increased incidence of endophthalmitis after cataract surgery in these patients, anecdotal evidence
does exist and it is prudent to give them anti-staphylococcal prophylaxis prior to and after surgery [207].
7

2. Prophylaxis
2.1 Operating theatre
Air flow design
There are no current guidelines or data for the type of airflow best required to prevent post-operative
endophthalmitis after phacoemulsification. For ECCE operations, it has been shown in the past that 85 per
cent of endophthalmitis cases could be traced to the patient by comparing DNA profiles of vitreous isolates
of bacteria with those collected from the lid and skin flora of the patient [42]. Nevertheless, a risk remains
of infecting the eye with bacterial flora from the surgical team by the airborne route.
Old data on aerobiology has suggested that a hospital operating theatre should have a minimum of 20 air
changes per hour to reduce the airborne bacterial count, but this is arbitrary as all the airborne bacteria,
attached to skin scales, will settle to the floor in still air after 30 minutes. Research on ultra-clean air for
hip surgery has shown that a fast laminar flow of air in an operating theatre can remove airborne bacteria
within seconds, rather than minutes with traditional airflow systems at 20 air changes per hour, but is this
required for phacoemulsification surgery through a very small incision? This question has been investigated
by the <strong>ESCRS</strong> multi-centre study of endophthalmitis after phacoemulsification surgery, as some clinical
partners operate with minimal airflow, others 20 air changes per hour and others have ultraclean air systems
with either horizontal or vertical laminar flow. However, the result of this investigation was inconclusive, a
relationship between air changes per hour and incidence of endophthalmitis has not been established [5].
Equipment – sterilisation and single-use
All instruments for surgery should be sterile. Single-use is even more robust, as there have been occasions
recently when instruments have not been washed properly prior to sterilising which itself may have been
faulty. Care is required with both washing the instruments and autoclaving them, as the latter is never
absolute nor an exact science! Both matters should be investigated if there is an ongoing 'epidemic' of postoperative
endophthalmitis with different types of skin bacteria viz. coagulase-negative staphylococci within a
surgical unit for no obvious reason.
Single-use of tubing and other equipment that becomes wet within the operative procedure is always
preferable, if cost allows. Tubing is not easy to effectively sterilise unless an ethylene oxide gas steriliser is
available. Bottles of solution containing BSS (balanced salt solution) etc. should never be kept or used for
more than one operating session. Any air vent applied to these bottles should be protected by a bacterial
filter. Wet areas are easily contaminated with Pseudomonas aeruginosa, which can then cause devastating
endophthalmitis.
2.2 Antisepsis
The goal of pre-operative antisepsis is to reduce the likelihood of a wound infection by reducing the total
bacterial count in the wound area and immediate wound environment. In view of the low incidence of
endophthalmitis, controlled studies comparing the effectiveness of different antiseptics are hardly feasible
because of the random sample sizes required.
For peri-orbital skin antisepsis, a five to 10 per cent povidone-iodine solution is recommended which should
be allowed to act for a minimum of 3 min, as the skin contains many sebaceous glands. If this is
contraindicated (allergy or hyperthyroidism), an aqueous solution of chlorhexidine (0.05 per cent) should be
used instead [212]. Single use of chlorhexidine is non-toxic at this concentration.
For antisepsis of the conjunctiva and cornea, povidone-iodine is the chemical preparation of choice. The
numbers of bacteria on the conjunctiva and cornea can be reduced by 1 log10 count (10 fold) to a
maximum of 2 log10 count (100 fold) in the pre-operative phase by a five per cent povidone-iodine solution
left in place for a minimum of three minutes [22], [23], [27], [28], [85]; a 10 per cent solution of
povidone-iodine can be diluted 1:1 with BSS or isotonic saline. Post-operatively, a significant reduction in
bacterial count in the conjunctival sac can also be achieved by antisepsis with a 1.25 per cent povidoneiodine
solution [28].
Schmitz et al. in their questionnaire survey of 469 ophthalmic surgical institutions in Germany, came to the
conclusion that the pre-operative use of povidone-iodine on the conjunctiva significantly reduced the risk of
endophthalmitis [126]. However, the survey gave no indication of the method of application, contact time,
or concentration of the povidone-iodine solution employed, so the conclusion remains unproven. In an
analysis of the literature from 1966 to 2000 listed in Medline, the benefit of povidone-iodine antisepsis is
also confirmed, even if only with category EbM III (= moderately important to clinical outcome) [61].
8

In 1991, Bohigian was able to show in a retrospective analysis of a total of 19,269 cataract extractions that
the incidence of endophthalmitis fell from 0.08 per cent to 0.03 per cent following the introduction of
antisepsis with five per cent povidone-iodine. This difference indicates a benefit but was not statistically
significant and it is doubtful whether it can be attributed exclusively to povidone-iodine antisepsis [56]. In
the same year, Speaker and Menikoff in their study of 8,083 patients showed a significant difference, at the
0.05 level, between the incidence of endophthalmitis with antisepsis using five per cent povidone-iodine
(0.06 per cent) and the control group in which silver-protein solution was used (0.24 per cent) [18].
The optimum concentration of povidone-iodine for use in pre-operative eye antisepsis has not been
established at present. From the aspect of tolerability, there is evidence that even a 10 per cent povidoneiodine
solution (without the addition of detergent) is associated with low external corneal toxicity [177]. On
the other hand, considerable side effects can be expected if even a five per cent povidone-iodine solution
gets into the anterior chamber [145]. In animal experiments, the healing of skin wounds is significantly
delayed even by two per cent povidone-iodine [211], while it is tolerated by the sensitive nasociliary
epithelium in a concentration of 1.25 per cent [17] and by adult cartilage at one per cent [16] without the
efficacy in vitro being restricted at these dilutions even with a large protein and blood load [38].
Studies of the use of chlorhexidine digluconate on the conjunctiva or cornea give conflicting results. A four
per cent chlorhexidine solution induces corneal damage and should NOT be used [177], [200].
Complications have also been described for the 0.02 per cent chlorhexidine solution [188], but when used
as long-term therapy (four times daily for eight weeks in the presence of a corneal ulcer presumed due to
Acanthamoeba) rather than as single-use prophylaxis on an intact epithelium prior to surgery. On the other
hand, pre-operative conjunctival irrigation with 0.05 per cent chlorhexidine diacetate solution [107], as used
by Per Montan and all colleagues in Sweden, is found satisfactory.
Application of 10ml of five per cent povidone-iodine onto a sponge pad one hour prior to surgery clamped
against the closed lids was associated with significantly fewer positive conjunctival cultures immediately
prior to surgery (p = 0.02) and at the conclusion of the surgery (p = 0.05) compared with the application of
two drops of five per cent povidone-iodine [35].
Clinicians should avoid use of large bottles of readily diluted povidone-iodine or chlorhexidine whenever
possible, and use single-use sachets or vials instead, as both antiseptics can become contaminated with
Ps. aeruginosa.
In conclusion, it can be stated on the basis of the available clinical studies that only povidone-iodine in a
concentration of five per cent in BSS or isotonic saline can be recommended at present as the pre-operative
antiseptic of choice. It has not been established whether similar results can be obtained with a lower
concentration, such as 2.5 or 1.25 per cent. However, a significant effect for a reduction in the conjunctival
bacterial count after surgery has been confirmed when 1.25 per cent povidone-iodine was used [28].
Povidone iodine solution containing a detergent must NOT be used as it coagulates the cornea irreversibly.
2.3 Antibiotics
Pre-operative prophylaxis
Pre-operative topical antibiotic prophylaxis appears rational to reduce the number of bacteria in the
conjunctival sac. Various antibiotics have been used in the past including fluoroquinolones,
chloramphenicol, aminoglycosides, fusidic acid and combination products of polymyxin / bacithracin /
neomycin, but their use, including current use of topical fluoroquinolones, is not yet scientifically proven to
reduce the rate of post-operative endophthalmitis [53], [61], [77], [146], [178]. However, a recent
retrospective analysis has suggested a lower endophthalmitis rate following use of topical ofloxacin compared
to topical ciprofloxacin [86].
The randomised, placebo-controlled prospective multi-centre <strong>ESCRS</strong> study has investigated if use of perioperative
topical levofloxacin, which reaches significantly higher concentrations in the anterior chamber than
ofloxacin and ciprofloxacin [2], [3], [7], can prevent post-operative endophthalmitis. Patients were
administered one drop of levofloxacin 0.5 per cent solution one hour before surgery, one drop 30 minutes
before surgery and three drops at five-minute intervals immediately following surgery. Dosing was interrupted
until the following day to study the effect of peri-operative prophylaxis only. Although there appeared to be
some benefit from the use of peri-operative levofloxacin, the effect was smaller than for intracameral
injection of cefuroxime (see below) and did not reach statistical significance [5]. To maintain an adequate
level of levofloxacin in the anterior chamber it may be considered continuing to dose every two hours postoperatively
on the day of surgery [43].
9

In a retrospective analysis of 20,013 cataract surgeries, the effect of gatifloxacin 0.3 per cent and moxifloxacin
0.5 per cent given three times within one hour before surgery and four times daily for one week after surgery
was shown to be comparable with other prophylactic measures. Estimated endophthalmitis rates of 0.06 per
cent for gatifloxacin and 0.1 per cent for moxifloxacin, respectively, were reported. The authors concluded that
older fluoroquinolones may be used instead and these newer ones be reserved for frank infections [112].
Combining prophylaxis for three days by the oral route with short-term prophylaxis by the topical route (1 h)
provides higher antibiotic levels in the anterior chamber than either alone [44]. However, a reduction in
intraocular bacterial contamination using this approach has not been proven [74], [157]. From considerations
of principle (development of resistance, allergies) and because of the higher efficacy of antiseptics in vitro,
equivalent results can be expected with antiseptics (e.g. povidone-iodine) on the ocular surface, but with the
major disadvantage of a lack of an antibiotic effect within the anterior chamber.
The effect of a combined antiseptic and antibiotic approach with ciprofloxacin, ofloxacin and povidone-iodine
has been investigated in vitro [174], but large numbers of patients are needed for a prospective clinical trial.
Ofloxacin and levofloxacin are absorbed through the cornea into the anterior chamber to give an antibiotic
effect which does not happen with povidone iodine. Topical levofloxacin four times on the day prior to surgery
and three drops within one hour before surgery in combination with povidone-iodine irrigation was shown to be
highly effective in reducing the bacterial conjunctival flora compared to the use of povidone-iodine prophylaxis
alone. This schedule may be prudent in reducing bacteria from the surgical field in order to minimise the risk
of endophthalmitis [36].
Vancomycin and other reserve antibiotics should not be used for prophylaxis [156].
Systemic antibiotic prophylaxis
Intravenous antibiotic prophylaxis is not used for conventional intra- and extra-ocular procedures and is not
proven to be of benefit against post-operative endophthalmitis. As low levels of antibiotic penetrate the globe in
the non-inflamed eye, this route is NOT recommended. Oral quinolones, however, penetrate the globe to give
concentration levels (up to 1.3 µg/ml after three doses of 200mg levofloxacin), which increase up to 1.86
µg/ml with topical therapy pre-operatively [6]. However, routine cataract surgery does not require oral
prophylaxis unless the patient has severe atopic disease when the lid margins are more frequently colonised
with S. aureus [133].
After a penetrating injury, a prophylactic antibiotic is given systemically, as well as by the intravitreal route, and
the same drug should be used. This has been reviewed recently [150], [205]. Antibiotic cover must include
Bacillus sp., with vancomycin, gentamicin or clindamycin, as well as CNS, S. aureus and Clostridium sp. The
importance of intravitreal antibiotic was shown in two recent studies. In the first study, at the end of wound
repair, vancomycin (1mg) plus ceftazidime (2.25mg) were injected intravitreally in 32 eyes, whereas 38 eyes
remained without this prophylaxis. Seven of the latter 38 eyes (18.42 per cent) developed endophthalmitis
compared to only two of the prophylaxis group (6.25 per cent), which had an initially undetected intraocular
foreign body (cilia) in the vitreous cavity [9]. In the second study, 179 eyes were randomly assigned to either
intracameral injections of 40µg of gentamicin and 45µg of clindamycin or to injection of balanced salt solution.
Endophthalmitis developed within two weeks postop in eight eyes (2.3 per cent) in the control group, compared
to one eye (0.3 per cent) in the study group. [13]. A significant association was also noted between
endophthalmitis and the presence of an intraocular foreign body (IOFB). Endophthalmitis developed in seven of
25 control eyes with an IOFB, but in none of the 27 antibiotic-treated eyes with an IOFB.
Irrigation of the lacrimal passages
Pre-operative irrigation of the lacrimal passages has no significant effect on the contamination of investigated
aqueous aspirates. However, it should not be performed immediately before the operation, as then even more
bacteria are washed from the lacrimal sac into the conjunctival sac [51].
Covering the periorbital area
With regard to the endophthalmitis risk, there has been no randomised controlled study of pre-operative cutting
of the eyelashes.
The information available in the literature suggests that cutting the lashes is not associated with a reduction of
risk [126], and demonstrates that the periocular flora is not influenced on the day of the operation or in the
immediately succeeding days [194].
Taping back the lashes with adhesive tape nevertheless appears recommendable after PVP treatment of the skin
[53], as in this way a conceivable additional risk is eliminated without side effects, all the more so as the
annoying presence of lashes in the operating area can be avoided.
10

Intra-operative prophylaxis
Addition of antibiotic to irrigating solutions
According to Questionnaire Reporting Surveys in various countries, antibiotics are used in the irrigating solution
by approximately 60 per cent of responding cataract surgeons in Germany [126], 35 per cent in the US [182],
16 per cent in New Zealand [163], 8.5 per cent in England [161] and 8 per cent in Australia [186]. However,
while these surveys can be used for crude comparative rates, they are not accurate because of a limited
response rate around the 65 per cent limit [205]. Antibiotics added to the irrigating solution include
vancomycin and gentamicin.
While it is suggested in various surveys that the addition of antibiotics to the irrigating solution has a protective
effect, it has not been possible to reduce the incidence of endophthalmitis in any prospective scientific study.
All information on the incidence of endophthalmitis comes either from retrospective studies or from studies of
antibiotic use where there was no control group [108], [167], [169].
Anterior chamber contamination at the end of a cataract operation varies between 0 per cent (0 of 98 eyes) and
an extreme figure of 43 per cent (13 of 30 eyes) [68], [93], but even with a greater number of investigated
eyes it is between 0.18 per cent (1/552) and 13.7 per cent (98/700) [104], [187]. Whether the reduction in
the contamination rate from 12/100 to 5/100 when vancomycin is used in the irrigation solution [97] and from
22/110 to 3/110 with vancomycin/gentamicin [54] is meaningful remains doubtful, especially as no difference
was found in another corresponding study (8/190 control, 9/182 vancomycin) [72].
In any case, the onset of action of various antibiotics, but in particular vancomycin, in vitro is observed only
after three to four hours and full activity only occurs after about one day [31], [58], [79], [174]. This contrasts
with the half-life of the drug in the anterior chamber of three hours. In animal studies of pars plana vitrectomy,
antibiotic prophylaxis can be established only for low but not for moderate numbers of bacteria [33].
There is also the risk of overdose (aminoglycoside retinal toxicity) and the danger of developing resistance,
which is disturbing particularly with the reserve antibiotic vancomycin. Relevant scientific organisations and
authors therefore advise against giving prophylactic antibiotics in the irrigating solutions or call this in question,
especially as a benefit has not so far been proven (Center for Disease Control in 1995 regarding vancomycin
[156], American Academy of Ophthalmology in 1999 regarding vancomycin [144] and May et al. in 2000
regarding aminoglycosides [184]).
Addition of antibiotic as an intra-cameral injection in 0.1ml at the end of surgery
All Swedish cataract surgeons now routinely give an intra-cameral injection of 1mg cefuroxime in 0.1ml at
the end of phacoemulsification surgery before closing the wound [108], [109]. This technique has been
developed in Sweden and data from over 400,000 Swedish patients both retrospective and prospective
demonstrate the efficacy of intracameral cefuroxime [94][137]. The technique has now been proven by the
results of the prospective, randomised and controlled multi-centre <strong>ESCRS</strong> study [1], [5], [10]. Cefuroxime is
very active against staphylococci and streptococci (except MRSA, MRSE and Enterococcus faecalis), Gramnegative
bacteria (except Pseudomonas aeruginosa) and P. acnes.
The study found that the risk for contracting endophthalmitis following phacoemulsification cataract surgery
was significantly reduced (five fold) by an intracameral injection of cefuroxime at the end of surgery,
p=0.001 for presumed endophthalmitis and p=0.005 for proven endophthalmitis [1], [5], [10]. The lowest
observed incidence rates were in Group D of this four-arm study [10], which received both intracameral
cefuroxime and peri-operative topical levofloxacin. These rates were 0.049 per cent for presumed
endophthalmitis and 0.025 per cent for proven endophthalmitis.
It must be remembered that some patients still developed post-operative endophthalmitis even after they
received intracameral cefuroxime in both Sweden and the <strong>ESCRS</strong> study. There were three isolates of
coagulase-negative staphylococci in the <strong>ESCRS</strong> study that were shown to be resistant to cefuroxime. On subanalysis,
the evidence for benefit of cefuroxime against CNS endophthalmitis appears to be weaker than
against streptococcal endophthalmitis, while intensive peri-operative antibiotic eye drops are likely to work
synergistically with cefuroxime.
The risk of an allergic reaction to cefuroxime in patients with a known allergy to penicillin is present but
small [195] and must be weighed up against the increased risk of endophthalmitis if the cefuroxime
injection is withheld. In these patients, an antihistamine tablet 15 minutes before surgery may be
considered. There has been a case report of severe anaphylactic reaction attributed to intracameral injection
of cefuroxime [199]. In patients with a known allergy to cephalosporins, cefuroxime should not be used and
11

as an exception an intracameral injection of vancomycin should be considered instead. Intensive topical
quinolones, e.g. levofloxacin, may be a useful adjunct for coverage of Gram-negative bacteria.
Besides cefuroxime, other antibiotics that have been given intracamerally include vancomycin (effective
against all Gram-positive bacteria only) [168], gentamicin (effective against staphylococci, but not
streptococci and P. acnes, and effective against Gram-negative bacteria including Ps. aeruginosa) and
clindamycin in combination with gentamicin [13], [14]. Anecdotal evidence from those who use antibiotics
in this way suggests that they prevent post-operative or post-traumatic endophthalmitis but no scientific
study has been mounted in their support.
The intracameral application of antibiotics, including cefuroxime, vancomycin and aminoglycosides, is not
licensed by regulatory authority and it is given at the surgeon's discretion. Clinicians should be aware of
country specific implications as regards liability, medical insurance and reimbursement.
Subconjunctival antibiotic injection prophylaxis
This technique has been much used over the last 30 years, especially in the UK, but probably has little
prophylactic effect on the prevention of endophthalmitis [61], [205]. While there has been no formal study
to establish the technique, there have been plenty of studies, including the EVS, in which patients who
develop endophthalmitis have received a prophylactic subconjunctival injection. One of the reasons why this
might have occurred is that many surgeons used gentamicin which has no antibiotic effect on streptococci
and Propionibacterium acnes. Researchers have investigated the pharmacokinetics of cefuroxime when
125mg given by the subconjunctival route gave levels of 20 µg/ml in the anterior chamber [29], which is
far lower than that (3,000 µg/ml) which occurs when injected by the intracameral route. However, one
recent retrospective uncontrolled study from Canada found one case of endophthalmitis in 8856 surgeries
using subconjunctival antibiotics and nine cases of endophthalmitis out of 5030 surgeries not using them
[64]. While this was statistically significant (p < 0.009), the study was open to bias as regards surgeon,
incision and type of patient; such data needs to be repeated in a controlled prospective study.
Post-operative prophylaxis
In order to minimise the risk of infection, particularly after clear cornea incisions (see above) until wound
healing is secure, use of the pre-operatively applied topical antibiotic (a quinolone or other drug - see below)
is recommended for up to two weeks but is not proven. Longer application (more than two weeks) is
discouraged unless there are other medical reasons for it. Post-operative quinolone drops should be applied
every one to two hours after surgery to sleeping and from the next day on four times daily, from first waking
in the morning to just before sleeping, with one drop well placed in the conjunctival sac [193]. Alternatively,
topical chloramphenicol has been demonstrated to be safe for use for one week, without the risk of causing
aplastic anaemia [45], or a combination product such as polymyxin/bacithracin/neomycin may be used,
which has broad spectrum, low resistance and is not used systemically.
2.4 Limitations of the <strong>ESCRS</strong> Study
One of the objectives of the study was to assess the true background rate of post-operative endophthalmitis
in Europe when no antibiotics were given on the days before or at the time of surgery. Patients in Group A,
the control group, received instead peri-operative placebo eye drops without the cefuroxime injection [10].
However, it was considered unethical to withhold povidone iodine at the time of study design as it was the
only prophylaxis for which there was a true evidence base [18]. Hence, all patients received povidone-iodine
antisepsis following a standard protocol, which the background rate was established with. Topical
levofloxacin was given as standardised medication for six days beginning on the first post-operative day, to
prevent wound infection [149], but this was considered irrelevant for testing, whether or not an antibiotic
administered at the time of surgery was effective.
The study did not evaluate the role of pre-operative antibiotics, which are normally administered anywhere
between one hour to three days before surgery. Instead, it tested intensive peri-operative antibiotic drops
versus intensive peri-operative placebo drops, commencing one hour before and concluding 15 minutes after
the surgery.
Cefuroxime was chosen for the study, because its benefit had been demonstrated in more than 32,000
procedures in Sweden by the time of study design [109], [149], and it is effective against the majority of
organisms that cause post-operative endophthalmitis [10]. The objective of the study was to prove the
efficacy of the technique of intracameral cefuroxime in a prospective, randomised controlled trial. Although
other intracameral agents or alternative systems of drug delivery might be superior to cefuroxime, they would
have required additional safety studies prior to their use in this trial.
12

Levofloxacin was chosen as a topical antibiotic for similar reasons. It is well absorbed into the anterior
chamber and has enhanced antibacterial activity compared to older fluoroquinolones [10]. Whilst newer
fluoroquinolones, such as moxifloxacin and gatifloxacin may have a higher potency against Gram-positive
bacteria and are widely used pre-operatively in the US, their use, like that of intracameral vancomycin,
raises ethical questions about the utilisation of reserve antibiotics for prophylaxis as opposed to treatment
[149]. Furthermore, both antibiotics are not yet available for topical ophthalmic use in Europe.
The applied dosing regimen of topical levofloxacin was based upon studies investigating its ocular
penetration with four or five drops pre-operatively [2], [3], [7]. There has been a lack of specific
pharmacokinetic data of fluoroquinolones in the anterior chamber and the PK study by Sundelin et al. [43]
was conducted only after completion of the <strong>ESCRS</strong> study. The results of this latter study suggest a
continued dosing on the day of surgery to maintain adequate drug levels in the aqueous humour. This is
endorsed by Wallin et al., who showed that commencing post-operative topical antibiotics as late as one day
after surgery is associated with a higher risk of contracting endophthalmitis [136].
Preparation of cefuroxime solution for intra-cameral injection
The use of cefuroxime should be discussed with the hospital pharmacist and, in particular, the
method agreed about how to make the dilution to 10 mg/ml.
It is recommended to use ZINACEF (GlaxoSmithKline) or an equivalent preparation containing
cefuroxime as cefuroxime sodium in powder form, without any excipients. It MUST be diluted in
sterile 0.9 per cent sodium chloride solution (saline) and NOT sterile water for injection as stated in
the product data sheet, to achieve the correct pH of approx. 7.4 and osmolality of approx. 310
mOsm/kg for ocular injection [109]. 250mg cefuroxime are dissolved in 2.5ml of 0.9 per cent saline.
1ml of this solution is mixed with 9ml of 0.9 per cent saline to obtain a cefuroxime concentration of
10 mg/ml. 0.4ml of this solution are drawn up in a 1ml syringe and a fine metal cannula is attached
to it. The first 0.1ml is displaced through the cannula for disposal. The cannula is inserted through
the clear corneal wound or the corneo-scleral tunnel to the location of the intra-ocular lens and 0.1ml
is injected intra-camerally.
13

14
2.5 FLOW CHART – PROPHYLAXIS GUIDELINES
(Based on the results of <strong>ESCRS</strong> multi-centre study [1], [5], [10] as well as Healy et al. 2004 [26],
Jensen et al. 2005 [86] and Peyman, Lee & Seal 2004 [205]
Consider use of topical quinolone (levofloxacin* or ofloxacin one drop four times daily) or a topical
combination of polymyxin B/bacithracin/neomycin for 24 or 48 hours prior to surgery
and/or Apply topical quinolone (same type) to cornea and conjunctiva with one drop
one hour prior to surgery and one drop one half-hour prior to surgery
It is mandatory to apply one drop povidone iodine five per cent [61], or 10ml povidone iodine five
per cent on a sponge pad [35], or aq. chlorhexidine 0.05 per cent [107], to the cornea and
conjunctival sac for a minimum of three minutes prior to surgery – preferably this is done in the
preparation room prior to taking the patient into the operating theatre (OT)
Apply 10 per cent povidone iodine or 0.05 per cent chlorhexidine to the peri-orbital area in the OT
as skin antisepsis, and allow to spill over into the conjunctival sac
Surgeon washes hands with antiseptic soap solution (povidone iodine or chlorhexidine), gowns up
and wears sterile gloves and a mask. Check that theatre airflow is running and that doors are closed
Apply surgical drapes and taping of eyelids to remove eye lashes
from the surgical field (do not cut eyelashes)
Perform phacoemulsification surgery. Consider using foldable IOLs
that can be inserted through a sterile injector
Apply 1mg cefuroxime in 0.1ml saline (0.9 per cent) by intra-cameral injection [108], [109] at the
end of surgery. This is an unlicensed use of cefuroxime given at the surgeon's discretion.
Use of vancomycin (or gentamicin) in the irrigation fluid or by intra-cameral injection
is not proven and is not encouraged (refer to text)
Re-apply topical quinolone (same type) at the end of surgery as one drop stat, one drop
five minutes later and one drop five minutes later again, or reapply polymyxin B/
bacithracin/neomycin or apply topical chloramphenicol (1 drop stat)
Use of subconjunctival antibiotic (gentamicin, cefuroxime) is not thought to offer effective
prophylaxis (refer to text)
Give post-operative topical prophylaxis with the same quinolone as one drop every one to two hours
on the day of surgery. From the next day, give four times daily (six hourly) for one week if scleral
tunnel or sutured clear cornea incision was used, and for two weeks if an unsutured clear cornea
incision was used. If not using quinolones, give topical chloramphenicol or polymyxin B/
bacithracin/neomycin using the same regimen as with quinolones.
* gives three to four times higher levels of the active isomer in the
anterior chamber than ofloxacin [7], [26], [205]

3. Diagnosis
3.1 Commencement and symptoms
Acute early endophthalmitis after cataract operations commences between the first post-operative day and
approximately two weeks after the operation. It is associated in 74 to 85 per cent with ocular pain and in >
90 per cent with reduced vision [15], [122]. It is characterised in 75 to 86 per cent by hypopyon, in > 80
per cent by a red eye and in 35 per cent by lid swelling [141]. Additionally, there can be corneal oedema
and involvement of the posterior segment (refer to chart below) [205].
Chronic late endophthalmitis after cataract operations commences only after two weeks but may also take
many months to appear [50], [96], [113], [117]. It is usually caused by Propionibacterium acnes, S.
epidermidis (CNS), diphtheroids and fungi [15], [122]. In P. acnes endophthalmitis, whitish plaques are
found in the capsular sac in 40 to 89 per cent [50], [62], [205]. Hypopyon is found in 67 per cent, corneal
oedema in 48 per cent and keratitis in 26 per cent of cases of fungal endophthalmitis [113], [124];
pyramid-shaped hypopyon is typical of a mycotic cause [204], [210]. Refer to chart below.
The course and final outcome depend on the type and number of pathogens. In 44 to 53 per cent there is
an achievement of only one metre vision with bacterial infection [15], [122], and similar for fungal infection
in 41 to 70 per cent of patients [113], [151]. Endophthalmitis after pars plana vitrectomy has a poorer
prognosis than after cataract or glaucoma surgery [46], [63].
The diagnosis of acute bacterial endophthalmitis is a medical emergency requiring an immediate vitreal tap
and instillation of intravitreal antibiotics and corticosteroid.
Figure 3.1 Early presentation of acute endophthalmitis
due to Streptococcus mitis
(Courtesy of Suleyman Kaynak)
Figure 3.2 Presentation of acute endophthalmitis
due to Staphylococcus aureus
(Courtesy of Uwe Pleyer)
15

16
3.2 FLOW CHART – DIAGNOSTIC GUIDELINES FOR
ACUTE VIRULENT ENDOPHTHALMITIS [205]
Observe the patient for:
■ pain
■ blurring or loss of vision, which may appear as a darkened image
due to developing vitritis, down to perception of light
■ swollen lids
■ inflamed or oedematous conjunctiva
■ discharge into conjunctiva
■ corneal oedema sometimes with an infiltrate or ring abscess
■ cloudy anterior chamber with cells, hypopyon or fibrin clot
■ afferent pupillary defect
■ vitreous clouding (vitritis) from inflammation precluding a view of the retinal vessels
■ involvement of posterior segment with retinitis, and/or retinal periphlebitis, retinal oedema and
papillary oedema
■ absent red reflex when the vitreous is viewed through the pupil may be a poor guide to the state of
the vitreous, which may be most opaque anteriorly where the inflammatory process has begun. If
the pupil is observed while transilluminating the sclera, the red reflex may become apparent and
can then form a better guide to control of the disease.
Check B-scan ultrasonography for vitritis and retinal detachment – this is a useful adjunct
for the clinical evaluation of infectious endophthalmitis especially in an eye with opaque media.
MAKE A CLINICAL DIAGNOSIS OF ENDOPHTHALMITIS (with photography if possible)
BEWARE OF DELAYING THE DIAGNOSIS WITH A TRIAL OF CORTICOSTEROID DROPS
(refer to Section 5.3)
THIS IS A MEDICAL EMERGENCY!
PERFORM AN INTRAVITREAL TAP WITHIN ONE HOUR!
■ Perform a vitreous tap in the OT using a vitrector or phaco/vitrector or use a portable vitrector
(BD Visitrec 5100) in the outpatient clinic (refer to text)
■ Also, perform an anterior chamber tap for microbiology
■ Collect samples of vitreous and aqueous for microbiology (Gram stain, culture & PCR*)
■ Inject empirical choice of antibiotics** (refer to text and flow diagram below) AND dexamethasone
(400 µg unpreserved drug in 0.1ml) into vitreous with separate syringes and needles
* Expert PCR (polymerase chain reaction) for bacteria and fungi causing acute and chronic endophthalmitis is
available from Dr Udo Reischl, Institute for Medical Microbiology and Hygiene, University Hospital, 93053
Regensburg, Germany (udo.reischl@klinik.uni-regensburg.de; Tel: +49-941-944-6450, Fax: -6402) or from Prof
Jorge Alio & Dr Consuelo Ferrer, VISSUM-Instituto Oftalmologico de Alicante, 03016 Alicante, Spain
(cferrer@vissum.com; Tel: + 34-9651-50025, Fax: -60468) at a cost of 250 EUR per sample. Collect samples
of one drop of aqueous and one drop of vitreous, each placed in a separate sterile Eppendorf plastic tube or
other sealable tube. Specimens should be stored at + 4°C for up to 24 hours and sent by next-day courier
service to the laboratory or stored at -20°C for longer periods. Do not send by courier over a weekend. It is
advisable to contact the units by telephone, email or fax before sending any samples.
** ALWAYS have a chosen empirical regime of antibiotics ready in advance for intravitreal use in a clinic or OT
setting. Have instructions prepared for making-up correct dilutions and have necessary sterile equipment (bottles
and syringes) available in an 'endophthalmitis pack' within the operating theatre.

3.3 FLOW CHART – DIAGNOSTIC GUIDELINES FOR
CHRONIC ENDOPHTHALMITIS [205]
Observe the patient for:
■ pain
■ blurring or loss of vision
■ cloudy anterior chamber with cells
■ recurrent hypopyon uveitis that fails to respond to corticosteroids
■ plaque in the capsular bag (= saccular or granulomatous endophthalmitis)
■ vitreous clouding (vitritis) from chronic inflammation reducing a view of the retinal vessels
Check B-scan ultrasonography for vitritis and retinal detachment
MAKE A CLINICAL DIAGNOSIS OF CHRONIC ENDOPHTHALMITIS
INVESTIGATE FOR A MICROBIAL SOURCE
■ perform an anterior chamber tap for microbiology (Gram stain, culture & PCR) (refer above for
details) – PCR is often positive here when culture is negative as bacteria are intra-cellular
■ perform a vitreous tap, if vitritis is present, for microbiology (Gram stain, culture & PCR)
■ if a decision is made to remove the IOL, then collect and send the capsule fragments to the
microbiologist and to the histopathologist for paraffin-section based Gram stained films which
will reveal the presence of intra-cellular Gram-positive bacteria within macrophages lining the
capsule [47], [205]. Also collect a sample into glutaraldehyde to perform election microscopy,
which can identify the intra-cellular bacteria [205].
Figure 3.3 Gram stain of vitreous tap from acute endophthalmitis
due to Streptococcus salivarius
(Courtesy of Roland Koerner)
17

3.4 Differential diagnosis – the toxic anterior segment syndrome
The toxic anterior segment syndrome (TASS) is an acute inflammation of the anterior chamber of the eye.
TASS may be related to any of the irrigating solutions, medications, or materials that gain access to the eye
during anterior segment surgery. In addition, factors related to the cleaning and sterilisation of instruments
may be a major problem causing TASS. Some cases have been related to heat stable endotoxins from
overgrowth of Gram-negative bacilli in water baths of ultrasonic cleaners.
TASS rarely occurs in one patient only, but usually in three or more, because most or all the patients have
been exposed to the incriminating toxin during one or two operating sessions. If an outbreak occurs, then
the surgeon must stop operating and investigate for the source of the problem.
The common signs noted in the patients in a recent outbreak of TASS in the US included blurred vision,
marked increase in anterior segment inflammation, including hypopyon formation as well as fibrin in the
anterior chamber of the eye. It is always Gram stain and culture negative. There may be diffuse corneal
oedema, classically from limbus to limbus, with endothelial cell damage. Patients present within 12 to 48
hours of cataract surgery and seem to respond well to intense topical corticosteroid treatment [147],
[148], [179].
18

4. Investigation
4.1 AC tap, vitreous tap, vitrectomy for Gram stain, culture and PCR tests
The previous section describes diagnostic guidelines. A medical emergency exists as soon as the clinical
diagnosis is made of acute bacterial endophthalmitis. There is a need to perform an anterior chamber tap and a
vitreous tap within ONE hour of clinical diagnosis and to instil intravitreal antibiotics. The acute bacterial
process is very 'unforgiving', giving rise to massive inflammation within the posterior segment with a breakdown
of the blood-ocular barrier. Hence, to save vision there is need to stop the acute bacterial process but also to
minimise the acute inflammation that it has caused, hence the current opinion that unpreserved dexamethasone
400 µg in 0.1ml should be injected intravitreally at the same time as the antibiotics. The full arguments for and
against this approach, based on a scientific review, are considered by Peyman, Lee & Seal [205].
The question arises how to carry out the urgent taps and antibiotic instillation. In some hospitals it is not
possible to take the patient to the operating theatre (OT) at any given time because of use of the OT by others. It
is not advisable to keep the patient waiting for more than three hours, because the chances of retaining
reasonable vision are diminishing fast. For this reason, a portable vitrector has been developed by Peyman and
Visitec (Figure 5.1) to make an intravitreal tap within the outpatient clinic and to instil intravitreal antibiotics
and dexamethasone at the same time in the clinic (refer to surgical section below). Jager et al. [171] have found
that it is safe to perform vitrectomy in the outpatient (OP) clinic providing that antiseptic prophylaxis is used
with povidone iodine; they found no statistical difference in acquired endophthalmitis rates after vitrectomy
between the two sites – OT and OP (refer to incidence section above).
Use of the phaco/vitrector equipment, for a partial or full vitrectomy, is considered below in the treatment
(surgical) section. It can be used for both sample collection and a full vitrectomy.
Antibiotics (refer below) are instilled with separate syringes and 25 or 30 G needles for each drug, either
injecting directly through the pars plana or by injecting through the sclerotomy wound if present. The scleral
wound is usually self-sealing and does not need to be sutured.
Identification of the pathogen in infectious endophthalmitis is rational as this allows targeted antibiotic therapy.
The sampling should be done as soon as possible, and within ONE hour, after the diagnosis is made. Enlist the
help of the microbiologist.
Microscopy and Gram stain results are available after one hour, pathogen culture results after 24 h, and
antibiotic sensitivity testing results after six to 10 hours when the RAST method is used, or after 24 to 48 h
with conventional methods [103].
The highest rate of pathogen identification is obtained with microscopic and microbiological processing of
vitreous material, obtained either using the vitrectomy cutter before switching on the irrigation or as an aspirate,
or using the portable vitrector. Use of a syringe and needle gives an unreliable sample that is often dry and
culture-negative.
Pathogen identification from the anterior chamber is less successful and also potentially contaminated by the
vitrectomy cassette [20], [101]. Conjunctival and corneal swabs are pointless, as the correlation with the microorganisms
isolated is too low [42]. The culture media should be inoculated directly in the operating theatre
[189]. Transportation of material on cotton buds produces a high loss of pathogens and reduces the detection
rate, which ideally is about 90 per cent [102].
The polymerase chain reaction (PCR) method offers much improved pathogen detection especially in the case of
chronic endophthalmitis with low pathogen counts [34], [205]. However, the increased risk of contamination
because of the high sensitivity of the method, the lack of antibiotic sensitivity testing and the partial lack of
quality control standards in routine diagnostic laboratories have limited its routine use so far. PCR has been
evaluated in depth in the multi-centre <strong>ESCRS</strong> study by the two expert laboratories mentioned above. Results of
this cross-validation study are not yet published [11].
4.2 Epidemiology
For detailed discussion on how to investigate an outbreak of cataract-surgery-associated post-operative
endophthalmitis, the reader is referred to Chapter 4 of Peyman, Lee & Seal's book [205]. This chapter
considers the epidemiology of post-operative endophthalmitis in detail and has tables from which actual
numbers of cases of endophthalmitis can be compared with predicted numbers for different incidence rates
of infection, and thus determine whether the number of cases is greater-than-expected statistically, requiring
the unit to close for detailed investigations. One of the most important aspects to then determine is whether
there is a common source outbreak or whether it is due to a selection of different types of bacteria out of
those normally found on the lid margin or in the conjunctival sac [214]. The former is often associated with
a staff carrier for Staphylococcus aureus or Pseudomonas aeruginosa if contaminated solutions are involved,
while the latter is more often associated with failures of either washing the instruments or with their
sterilisation or with a failure of the air conditioning system in summer, causing the surgeons to shed
excessive numbers of bacteria. It may be necessary to introduce an intra-cameral injection of antibiotic when
the unit reopens if the source cannot be found.
19

5. Treatment
5.1 Surgical management of endophthalmitis.
Diagnostic and therapeutic vitrectomy
The GOLD STANDARD of treatment of acute post-operative endophthalmitis is immediate (within a few
hours) "complete" three port pars plana vitrectomy by a vitreoretinal surgeon. First, the infusion port is
inserted through the pars plana, 3.5mm from the limbus, but is NOT TURNED ON. The vitreous cutter is
inserted through a separate 3.5mm sclerotomy and directly visualised through the pupil. A hand-held syringe
is attached to the aspirating line and the surgical assistant aspirates whilst the surgeon activates the cutter
until the eye visibly softens and the cutter is disappearing from view. The infusion is turned on to reform the
globe and the cutter removed. The syringe and the tubing now contain 1-2ml of infected but undiluted
vitreous and the two together are promptly sent to the laboratory for immediate Gram stain, culture and PCR
analysis.
The microbiologist has previously been informed the sample is en route.
The vitreous cutter is now connected to the machine for aspiration control and a light pipe is inserted
through the pars plana. A standard three-port vitrectomy is performed within the limits of visualisation. It is
useful to perform a posterior capsulotomy with the cutter and aspirate the fibrin and pus from the anterior
chamber and intraocular lens surface. This procedure not only improves visualisation but permits flow
through the entire eye and facilitates recovery.
Caution must be exercised against too aggressive surgery. These eyes have concomitant retinal vasculitis and
retinal oedema and the inadvertent creation of a retinal break can be catastrophic. Iatrogenic retinal
detachment in eyes with acute endophthalmitis is comparable to that of AIDS.
Once the vitrectomy is as complete as possible, the intravitreal antibiotics (see text) are injected. Note that
the dose is reduced by 50 per cent if a full vitrectomy has been performed. This injection should be given
SLOWLY, over minutes, and the needle pointed away from the macula. Separate syringes and separate
needles are used through an existing entry site. Intravitreal dexamethasone (preservative free) is then
injected.
The procedure is performed under general, peribulbar or retrobulbar anaesthesia but not topical.
The authors favour general anaesthesia as the patients are usually old, frail, sick, and in pain. Furthermore,
the eyes are inflamed, hyperaemic and bleed.
While the above GOLD STANDARD achieves immediate diagnostic and therapeutic vitrectomy and reduces
the need for re-operation, it is often not possible due to the lack of a vitreoretinal surgeon and a vitreoretinal
operating room. The duty surgeon frequently does not have the required skill.
As TIME is of the essence, a SILVER STANDARD may be the practical option. The basic fundamental
requirement is the intravitreal injection of the antibiotics. This should be preceded by vitreous biopsy.
Simple aspiration with a needle is frequently unsuccessful unless the needle fortuitously enters the syneretic
vitreous cavity; infected vitreous cannot be aspirated with a syringe and needle. Every duty surgeon must be
taught to perform a vitreous biopsy with a vitreous cutter. The simplest technique is with the portable
vitrector with a microvitreoretinal (MVR) blade at its tip as marketed by Visitec (Becton Dickinson Visitrec
Vitrectomy System 5100 Visitrec Surgical Vitrectomy Unit) and Insight Instruments, Inc. (The Intrector®
Portable Office-based Drug Injection/Vitrectomy System). Following the sampling, antibiotics and
corticosteroids are injected through the sclerotomy as above. The incision does not require suture closure
and no conjunctival incision is necessary.
This SILVER STANDARD has the advantage of time over completeness. While it ignores the fundamental
surgical principle of "Ubi pus, ibi evacuat" (where there is pus, let it out) and it provides a smaller sample, it
permits the earlier injection of intravitreal antibiotics and earlier microbiology. It also buys time pending the
availability of a vitreoretinal surgeon and vitreoretinal operating room and the technique should be
mandatory for all cataract surgeons.
The portable vitrector consists of a battery box, with 'off/on' and cutting speed switches, and a handheld
vitrector (Figure 5.1). The vitrector has a 23 G guillotine probe, for use through a sclerotomy puncture site.
In addition, a 20 G bevel needle can be placed on it, to allow direct puncture and use at the pars plana.
The micro-guillotine cutter is controlled with a switch on the hand-piece. There is also an irrigating and
aspiration module, to allow collection of the vitreous sample (Figure 5.1). The portable vitrector is designed
for sample collection only and not for use for a therapeutic vitrectomy. These techniques are also described
by Peyman et al. [206].
20

Figure 5.1 Portable Vitrector* – Becton Dickinson Visitrec Vitrectomy
System 5100 Visitrec
* PORTABLE VITRECTOR – Becton Dickinson Visitrec Vitrectomy System 5100 Visitrec TM Surgical
Vitrectomy Unit marketed by Visitec, Waterloo Industrial Estate, Bidford-on-Avon, Warwickshire B50 4JH, UK.
Tel: +44-1789-490909 Fax: +44-1789-490511
Figure 5.2 Site of insertion of vitrector guillotine
21

The patient is supine (lying flat). The eye is prepared with povidone iodine and then anaesthetised by
topical, peri- or retro-bulbar anaesthetic. A lid speculum is inserted and an anterior chamber tap is made for
Gram stain, culture and PCR.
For the portable vitrector, the biopsy probe is inserted through the pars plana transconjunctivally. The probe
has a MVR blade at its tip so no incision is necessary. The single instrument provides one-step sclerotomy,
cutting and aspiration. A mini-core vitrectomy can also be performed with slow manual aspiration of up to
1ml vitreous for microbiology and PCR.
The cutting probe is removed from the eye. Antibiotics and corticosteroids are injected with a 30mm (30 G)
needle through the same incision site with separate syringes and needles. The incision is small enough not
to need suture closure.
5.2 Anti-microbial therapy
An antibiotic combination is injected intravitreally and repeated as necessary according to the clinical
response at intervals of 48 to 72 hours, depending on the persistence of the drugs selected within the eye.
Intravitreal antibiotic doses are scaled down to avoid retinal toxicity but the margin for error between
chemotherapy and toxicity is narrow for the aminoglycosides (for gentamicin, 200 µg is effective but 400 µg
can be toxic, causing macular infarction); thus, the total dose injected must be highly accurate.
A combination of intravitreal antibiotics should be instilled as vancomycin (1mg) plus ceftazidime (2mg)
(first choice) [32] (cave: physical incompatibility of vancomycin and ceftazidime [165], [176]) or amikacin
(0.4mg) plus vancomycin (2mg) (second choice); 0.1ml of each of the two chosen antibiotics should be
injected separately intravitreally after the tap or vitrectomy has been performed. An intravitreal injection of
dexamethasone 0.4mg in 0.1ml should be given at the same time in most circumstances, again by a
separate syringe and needle.
Antibiotics that have been used relatively safely for intravitreal use are shown in Table 5.1 below. The table
lists the non-toxic doses of antibiotics, but the dose should be reduced by at least 50 per cent if given with
a full vitrectomy, since the vitreous prevents rapid diffusion of antibiotics towards the retina [205]; some
clinicians reduce the dose even by 90 per cent.
Table 5.1 - Doses of antibiotics for intra-vitreal treatment of acute
post-operative endophthalmitis
Antibiotic injection intravitreal dose* (micrograms) Duration (h)
Amikacin 400 24-48
Ampicillin 2000 24
Amphotericin 5 or 10 24-48
Cefazolin 2000 16
Ceftazidime 2000 16-24
Cefuroxime 2000 16-24
Clindamycin 1000 16-24
Erythromycin 500 24
Gentamicin 200 48
Methicillin 2000 16-24
Miconazole 5 or 10 24-48
Oxacillin 500 24
Vancomycin 1000 48-72
* maximum intravitreal injection volume is usually 0.3ml but give each drug separately in 0.1ml amounts (use the
intrathecal preparation when available because they are preservative free); intravitreal ciprofloxacin has been used
[205], while the use of intravitreal levofloxacin is still experimental [19]. Intravitreal concentrations of 625µg or
less of levofloxacin and 400µg or less of gatifloxacin appeared to be non-toxic in rabbit eyes [172].
22

How To Make Up The Antibiotics
The antibiotics should be supplied freshly diluted by the hospital pharmacy department. However, for
emergency cases, a method for diluting the drugs in the operating theatre is given below. The procedure
must use sterile equipment and be undertaken on a sterile surface; ideally, the hospital makes up sterile
packs with drugs, bottles for dilution and instructions in advance for this purpose. All drugs should be mixed
by inverting or rolling the bottle 25 times, avoiding frothing.
Some important “dos” and “don’ts” are:
■ Never return diluted drugs to the same or original vial for further dilution
■ Never dilute at greater than 1 in 10
■ Do not use syringes more than once
■ Do not reuse bottles
■ Avoid use of drugs with preservatives if possible
■ Do inject the drugs slowly over 1 to 2 minutes
Prior to preparing the dilutions it is mandatory to check the amount of the antibiotic in the vial as the same
antibiotic may be sold in different strengths in each EU country.
Vancomycin Dose for use = 1000µg. Reconstitute one vial of 250mg and make up to 10ml with sterile
normal (0.9 per cent) saline (SNS) in a sterile bottle with lid. Mix well. Withdraw 2ml accurately and add to
3ml of SNS in a sterile bottle with lid. Mix well (= 10mg/ml). Use 0.1ml = 1000µg.
Ceftazidime (or other cephalosporin) Dose for use = 2000µg. Reconstitute one vial of 500mg and make up
to 10ml with SNS in a sterile bottle with lid. Mix well. Withdraw 2ml accurately and add to 3ml of SNS in a
sterile bottle with lid. Mix well (= 20mg/ml). Use 0.1ml = 2000µg.
Note: the percentage of drug precipitation is less when using SNS instead of BSS [32].
Amikacin Dose for use = 400µg. Reconstitute one vial of 500mg and make up to 10ml with SNS or
balanced salt solution (BSS) in a sterile bottle with lid. Mix well. Withdraw 0.8ml, using a 1ml syringe, and
add to 9.2ml of SNS or BSS in a sterile bottle with lid. Mix well (= 4.0mg/ml). Use 0.1ml = 400µg.
Gentamicin Dose for use = 200µg. Method 1: Use a 'Minim' which contains 3000µg/ml. Dilute to
2000µg/ml by adding 2ml of the Minim formulation to 1ml SNS in a sterile bottle with lid. Mix well. Use
0.1ml = 200µg for injection. Method 2: Remove 0.5ml, using a 1ml syringe, from a vial containing
40mg/ml unpreserved gentamicin and place in a sterile bottle with lid. Add 9.5ml of SNS or BSS and mix
well (= 2.0mg/ml). Use 0.1ml = 200µg.
Clindamycin Dose for use = 1000µg. Transfer the contents of a 2ml ampule containing 300mg to a sterile
bottle and add 1ml SNS or BSS, replace lid, and mix well. Withdraw 1ml, using a 1ml syringe, and add to
9ml of SNS or BSS in a sterile bottle with lid. Mix well (=10mg/ml). Use 0.1ml = 1000µg.
Amphotericin Dose for use = 5µg. Reconstitute a 50mg vial with 10ml water for injection. Withdraw 1ml,
using a 1ml syringe, and add to 9ml of water in a sterile bottle with lid for injection. Mix well. Withdraw 1ml
of this dilution, using a 1ml syringe, and add to 9ml of dextrose five per cent in a sterile bottle with lid, to
complete a dilution of 1/100. Mix well (= 50µg/ml). Use 0.1ml = 5µg. (A dose of 10µg has been used by
some clinicians.)
Miconazole Dose for use = 10µg. Withdraw 1ml, using a 1ml syringe, from an ampule of intravenous
miconazole containing 10mg/ml and add to 9ml SNS or BSS in a sterile bottle with lid. Mix well. Withdraw
1ml, using a 1ml syringe, and add to 9ml SNS or BSS in a sterile bottle with lid. Mix well (= 100µg/ml).
Use 0.1ml = 10µg.
Within Europe, various manufacturers produce sterile bottles of saline of different volumes for injection with
side-ports, but many are not sold universally. For example in Spain and Portugal, the following method can
be used with Braun's 50ml bottles of saline, suitable for drug dilution with two rubber injection ports [159]:
Vancomycin - mix vial of 500mg with 5ml saline withdrawn from Braun 50ml bottle, shake well and then
return to Braun bottle. Dilution gives 10mg/ml (dose of 0.1ml contains 1mg).
Ceftazidime - mix vial of 1g (1000mg) with 5ml saline withdrawn from Braun 50ml bottle, shake well and
then return to Braun bottle. Dilution gives 20mg/ml (dose of 0.1ml contains 2mg).
Amikacin - add 2ml saline to vial of 500mg. Shake well and remove 0.8ml (= 200mg) to Braun 50ml bottle
and shake well. Dilution gives 4 mg/ml (dose of 0.1ml contains 400µg).
23

Acute purulent endophthalmitis should be treated with additional systemic antibiotic therapy with the same
drugs as used for intravitreal therapy. This adjunctive regimen will maintain effective intravitreal levels of the
drug for a longer period by reducing the diffusion gradient out of the eye as well as its penetration into the
inflamed eye [205]. High doses are required and there is a need to be aware of the risks of systemic toxicity.
Vancomycin levels should be assayed. Use of oral probenecid (dose 500mg every 12 hours) retards outward
transport of penicillins, cephalosporins and fluoroquinolones across the retinal capillary endothelial cells,
thus extending the half-life of the drug within the vitreous. Probenecid also raises the plasma level by
blocking secretion of these drugs by the proximal renal tubule.
Dexamethasone (preservative-free) is often given by intravitreal injection (dose = 400 µg in 0.1ml [use the
commercial preparation containing 4 mg/ml]) but should NOT be mixed with antibiotics in the same syringe.
Refer to section 5.3. Prednisolone can be added to the systemic regimen to reduce the vitreous
inflammatory response and subsequent vitreous organisation (oral prednisolone e.g. 200mg (see p. 21) daily
on a reducing scale).
Antibiotic therapy may be modified after 24 to 48 hours according to the clinical response and the
antibiotic sensitivity profile of the cultured organism. However, the inflammation usually becomes worse
before becoming better, even with the correct antibiotic regime, hence the need to give a broad-spectrum
antibiotic combination empirically by the intravitreal route that will be effective against most Gram-positive
and negative bacteria causing post-operative endophthalmitis.
Intravitreal administration of the antibiotic gives the highest drug concentration “at the target site” but only
lasts for a limited time period. Injection alone can be successful [119], but is usually combined with pars
plana vitrectomy (PPV). Vancomycin (1mg/ 0.1ml) is suitable for Gram-positive bacteria [15], [180] and is
above the MIC90 of Staphylococcus epidermidis (CNS) for > 48 h [80]; even 0.2mg/ 0.1ml vancomycin can
remain at a therapeutic level for three days [73]. For treating Gram-negative bacteria, many surgeons are
abandoning the use of aminoglycosides because of retinal toxicity and low therapeutic spectrum and are
instead giving ceftazidime 2mg/ 0.1ml [155], [166], [170]. Vancomycin is used for Propionibacterium
acnes [50], [62], but P. acnes is also very sensitive to cefuroxime.
Amphotericin B (5-7.5 µg) is the only fungicidal antibiotic available for intravitreal injection but its
spectrum does not cover all fungi; in particular, Scedosporium apiospermum (Pseudallescheria boydii) is
resistant to it but sensitive to miconazole which can be used instead [120], [121], [205], [210]. Miconazole
is fungistatic but can be given intravitreally (Table 5.1). Systemic anti-fungal therapy is also required and
the source of the infection needs to be identified.
How To Give The Antibiotics
UP TO 0.1ML CAN BE LOST IN THE HUB OF THE SYRINGE AND THE NEEDLE when drugs are diluted or
made up for injection into the eye. Always draw up sufficient drug to fill a 1ml syringe to at least the
halfway mark (0.5ml) and expel 0.1ml accurately from the syringe. Never expel the drug from the 0.1ml
mark, because of errors with the hub.
Adjunctive Routes
Systemic administration
According to the randomised, multi-centre “Endophthalmitis Vitrectomy Study” (EVS), systemic antibiotics
do not appear to have any effect on the course and outcome of endophthalmitis after cataract operations
[15]. However, the study design used different drugs systemically (amikacin and ceftazidime) to those used
intravitreally (vancomycin and ceftazidime [162], [196]), which does not contribute towards maintaining
effective antibiotic levels within the eye. Thirty-eight per cent of the endophthalmitic eyes demonstrated
Gram-positive cocci, against which ceftazidime has limited activity, whereas vancomycin would have been
much more effective. Thus, adjunctive systemic antibiotic therapy with the same antibiotics as those given
intravitreally is recommended for management of acute virulent bacterial endophthalmitis [162], [196],
[209] when the patient should be closely observed in hospital. This may not be needed for less severe cases
such as those caused by CNS.
Vancomycin provides good cover for Gram-positive bacteria including methicillin-resistant staphylococci
(MRSA, MRSE). Ceftazidime is used to cover the Gram-negative spectrum incl. Ps. aeruginosa [153], [158].
Imipenem, which is also suitable for Gram-positive bacteria, and fluoroquinolones for Gram-negative
bacteria, have not yet been fully evaluated for intravitreal use and should only be administered if there are
contraindications against vancomycin and ceftazidime [21], [48], [153]. Experimental studies have been
performed to show that levofloxacin can be used to kill bacteria causing experimental endophthalmitis in
24

abbits but the final dose to use, that is also non-toxic, has not yet been established [19], [205].
Clindamycin, vancomycin or cefuroxime are effective for Propionibacterium acnes endophthalmitis [47],
[140]. However, this must often be preceded by surgery [66], combined with intravitreal antibiotic injection
[50], [62].
For fungal infection, amphotericin should be used systemically if it has been given by the intravitreal route.
It is relatively toxic, but quite safe with experience, and the help of an infectious disease specialist should
be found. In addition, systemic imidazoles are often given but are more likely to be effective for systemic
infection than for the endophthalmitis. Voriconazole or fluconazole (for Candida albicans) or itraconazole (for
other Candida species, Aspergillus or Cryptococcus) can be given but are not usually as effective as
amphotericin [113], [205], [210]. 5-fluorocytosine can be used in combination therapy for Candida
albicans. Fusarium endophthalmitis is particularly difficult to treat requiring both surgical removal where
possible and chemotherapy (intravitreal, AC instillation or wash-outs, topical and systemic routes); Fusarium
is usually but not always sensitive to amphotericin and combination therapy is often given with imidazoles
[205].
5.3 Anti-inflammatory therapy
Effective anti-inflammatory therapy, e.g. with corticosteroids, is rational in order a) to limit tissue destruction
by infiltrating leukocytes, b) to stem the effect of antigens and highly inflammatory cell walls released by
bacterial disintegration after administration of antibiotics and c) to diminish the toxic effects of intraocular
cytokines. Intravitreal dexamethasone injection (400 µg in 0.1ml) at the end of the vitrectomy leads under
antimicrobial therapy to a more rapid subsidence of the intraocular inflammation [65], but without
improving the long-term functional outcome although this finding may reflect studies in which
dexamethasone or corticosteroid has been given later rather than initially with the first injection of
antibiotics.
Oral administration of prednisolone (1mg/kg body weight) one day after intravitreal antibiotic therapy with or
without vitrectomy has not shown any negative effect on the course of infection in bacterial endophthalmitis
[15]. There have also been case reports of systemic steroid administration with mycotic infections, likewise
without adverse effects [173]. 200mg prednisolone is often rationally given systemically in parallel with
intra-venous antibiotics; however, there are no published studies on this subject.
From reports of recent experience from others, there seems to be quite a widespread use of a trial of
corticosteroid drops in post-operative inflammation. Our view is that in uncomplicated phacoemulsification
surgery with significant post-operative inflammation the patients should have an immediate vitreous biopsy
and intravitreal antibiotics with no delay, and a trial of corticosteroid drops should not be performed.
To summarise, not only the microbes but also their interplay with the immune mechanisms, are important in
the outcome of endophthalmitis. Cell walls of dead bacteria, especially those of streptococci, and including
those recently killed by antibiotics, are highly inflammatory. As a direct consequence, anti-inflammatory
treatment with intravitreal dexamethasone (400 µg in 0.1ml) should be given along with specific intravitreal
anti-microbial therapy. In addition, surgical removal of a high bacterial load in the vitreous can also be
important to save vision, by removing the main source of the acute inflammatory effect.
5.4 Other types of post-operative endophthalmitis
Late cases of endophthalmitis after cataract operation are the second commonest form of endophthalmitis
accounting for 20 to 30 per cent in past studies following ECCE surgery; the symptoms are milder and
Propionibacterium acnes has been identified as the principal pathogen. There is difficulty in culturing it as
the bacterium is often enclosed in the synechised capsular sac. The high rate of recurrence is problematic,
which can only be reduced by vitrectomy, possibly combined with posterior capsulectomy [160]. A further
advantage of vitrectomy is that adequate material for culturing the causative organism can be obtained but
capsular bag material is needed as well (refer to Flow Chart 3.3). Early vitrectomy is advisable [111]. A trial
of therapy should be given with clarithromycin 250mg twice daily (refer to Flow Chart 5.7, [115]) which can
be effective without surgery because the drug is well absorbed and concentrated 200 times into
macrophages and other cells.
25

5.5 Limitations of EVS study
The Endophthalmitis Vitrectomy Study (EVS) [15] conclusions refer mostly to sub-acute post-operative
endophthalmitis due to coagulase negative staphylococci (CNS) (80 per cent of cases) and the advice and
conclusions overall do not relate to acute pyogenic pathogens such as Staphylococcus aureus, Streptococcus
pyogenes and Streptococcus pneumoniae. The conclusions also do not apply to late post-operative
(saccular), bleb-induced, post-traumatic or endogenous endophthalmitis. These forms of endophthalmitis
have a more aggressive bacterial spectrum and therefore require different operative techniques (vitrectomy),
and both intravitreal and systemic antibiotics [205], [206]. The principles of management are the same for
post-traumatic and endogenous endophthalmitis, as for acute post-operative endophthalmitis, but the visual
outcome is poorer [205].
According to the EVS, conducted in the US [15], patients with acute endophthalmitis after a cataract
operation with an initial vision of hand movements or better should be treated by vitreous biopsy and
intravitreal antibiotics. In patients whose vision consists only of light perception, immediate vitrectomy is
recommended. This advice however was based on the selection of patients admitted to the study and does
not reflect the management of acute streptococcal endophthalmitis, where there is good reason to proceed
with an immediate vitrectomy in order to remove the highly inflammatory bacterial cell walls from within the
vitreous milieu. Retrospective studies have shown that affected patients can profit from early vitrectomy
[192].
In the EVS, ceftazidime and amikacin were used systemically, while vancomycin and amikacin were used
intravitreally, which does not contribute towards maintaining effective drug levels within the eye. However,
38 per cent of the eyes with < 5/200 outcome were infected by gram-positive strains. Ceftazidime is not the
drug of choice for these bacteria. Therefore, the design of the EVS can not answer the question of
intravenous use of antibiotics [162], [196]. In fact, this was not the primary objective of this study.
Follow-up EVS analyses showed differences between diabetics and non-diabetics. Diabetics with a visual
acuity of hand movements or better obtained vision of 20/40 more often (57 per cent) by vitrectomy than
after biopsy (40 per cent) but the results ultimately were not statistically significant because of the low
number of diabetic participants in the study [4].
26

5.6 FLOW CHART – TREATMENT GUIDELINES FOR ACUTE
VIRULENT ENDOPHTHALMITIS
(presumed and not proven) [205]
Make clinical diagnosis of endophthalmitis
Perform ultrasonography of vitreous and retina
Perform aqueous and vitreous tap and/or vitrectomy, through the pars plana, collecting
samples for microbiology investigation (Gram stain, culture & PCR)
Inject antibiotics empirically into the vitreous using a combination of either vancomycin
1mg in 0.1ml and ceftazidime 2mg in 0.1ml (first choice) or amikacin 400 µg in 0.1ml
and vancomycin 2mg in 0.1ml (second choice).
USE A SEPARATE SYRINGE AND 30 G NEEDLE FOR EACH DRUG
AND DO NOT MIX DRUGS TOGETHER IN THE SAME SYRINGE.
Do NOT point the needle towards the retina but forwards instead
and inject very slowly into the mid-vitreous
Inject dexamethasone 400 µg (preservative-free) in 0.1ml into the vitreous
at the same time by a separate syringe and needle
For acute virulent endophthalmitis begin adjunctive systemic therapy with the same
antibiotics as those used intravitreally for 48 hours to maintain higher levels within the
posterior segment of the eye (measure serum levels for intravenous vancomycin therapy);
this may not be needed for less severe cases due to CNS
Consider beginning systemic therapy with corticosteroids
(prednisolone 1 or even 2 mg/kg/day)
Consider referral to a vitreoretinal surgeon for an opinion on a full vitrectomy
(refer to text) and repeated intravitreal antibiotics
OBSERVE PATIENT (inflammation becomes worse before better again,
hence need for a defined initial empirical approach)
27

28
5.7 FLOW CHART – TREATMENT GUIDELINES FOR
CHRONIC ENDOPHTHALMITIS
(presumed and not proven) [205]
Make a clinical diagnosis
Investigate for a microbial source
CONDUCT A TRIAL OF THERAPY WITH CLARITHROMYCIN 250mg twice daily for two weeks
(this derivative of erythromycin is well absorbed orally, penetrates well into the eye and is
concentrated 200 times into PMNs and macrophages, to kill intra-cellular Gram-positive bacteria
and Haemophilus sp., but not other Gram-negative rods; clarithromycin is also effective against
many atypical bacteria) [115], [201], [205]
If successful, retain IOL but if therapy fails, make a decision on whether to retain or remove the
IOL and consider performing a vitrectomy possibly combined with a posterior capsulectomy [160]
If IOL is retained, give trial of therapy with intravitreal vancomycin and cefazolin or cefuroxime,
together with intravenous therapy for one week
If combination anti-microbial therapy fails as well, remove the IOL – collect samples
of capsule fragment for histology, electron microscopy and microbiology investigation
(Gram stain, culture & PCR) [47], [202], [205]
Inflammation usually subsides after the IOL has been removed with the capsule but further
antibiotic therapy can be given, such as an oral quinolone, but may not be needed

6. References
References categorised as EbM IB
[1] Barry, P., Seal, D. V., Gettinby, G., Lees, F., Peterson, M., Revie, C. W.: <strong>ESCRS</strong> study of prophylaxis of post-operative
endophthalmitis after cataract surgery: Preliminary report of principal results from a European multi-centre study. J Cataract
Refract Surg. 32, 2006, 407 - 410
[2] Bucci, F. A.: An In Vivo Study Comparing the Ocular Absorption of Levofloxacin and Ciprofloxacin Prior to Phacoemulsification.
Am J Ophthalmol 137, 2004, 308 - 312
[3] Colin, J., Simonpoli, S., Geldsetzer, K., Ropo, A.: Corneal penetration of levofloxacin into the human aqueous humour:
a comparison with ciprofloxacin. Acta Ophthalmol Scand 81, 2003, 611 - 613
[4] Doft, B. H., Wisniewski, S. R., Kelsey, S. F., Fitzgerald, S. G., Endophthalmitis Vitrectomy Study Group: Diabetes and postoperative
endophthalmitis in the Endophthalmitis Vitrectomy Study. Arch Ophthalmol 119, 2001, 650 - 656
[5] <strong>ESCRS</strong> Endophthalmitis Study Group: Prophylaxis of post-operative endophthalmitis following cataract surgery: results of the
<strong>ESCRS</strong> multi-centre study and identification of risk factors. J Cataract Refract Surg. 33, 2007, 978 - 988
[6] Kobayakawa, S., Tochikubo, T., Tsuji, A.: Penetration of Levofloxacin into Human Aqueous Humor. Ophthalmic Res 35, 2003,
97 - 101
[7] Koch, H.-R., Kulus, S. C., Roessler, M., Ropo, A., Geldsetzer, K.: Corneal penetration of fluoroquinolones: aqueous humour
concentrations after topical application of levofloxacin 0.5% and ofloxacin 0.3% eyedrops. J Cataract Refract Surg 31, 2005,
1377 - 1385
[8] Nagaki, Y., Hayasaka, S., Kadoi, C., Matsumoto, M., Yanagisawa, S., Watanabe, Ka., Watanabe, Ko., Hayasaka, Y., Ikeda, N.,
Sato., S., Kataoka, Y., Togashi, M., Abe, T.: Bacterial endophthalmitis after small-incision cataract surgery. Effect of incision
placement and intraocular lens type. J Cataract Refract Surg 29, 2003, 20 - 26
[9] Narang, S., Gupta, V., Gupta, A., Dogra, M. R., Pandav, S. S., Das, S.: Role of prophylactic intravitreal antibiotics in open
globe injuries. Indian J Ophthalmol. 51, 2003, 39 - 44
[10] Seal, D. V., Barry, P., Gettinby, G., Lees, F., Peterson, M., Revie, C. W., Wilhelmus, K. R.: <strong>ESCRS</strong> study of prophylaxis of postoperative
endophthalmitis after cataract surgery: Case for a European multi-centre study. J Cataract Refract Surg. 32, 2006,
396 - 406
[11] Seal, D. V., Reischl, U., Behr, A., Ferrer, C., Alio, J., Koerner, R., Barry, P., <strong>ESCRS</strong> Endophthalmitis Study Group: Laboratory
management of endophthalmitis: comparison of microbiology and molecular biology methods in the European multi-centre
study and appropriate chemotherapy. Manuscript in preparation.
[12] Seal, D., Wright, P., Ficker, L., Hagan, K., Troski, M., Menday, P. : Placebo-controlled trial of fusidic acid gel and
oxytetracycline for recurrent blepharitis and rosacea. Br J Ophthalmol 79, 1995, 42 - 45
[13] Soheilian, M., Rafati N., Mohebbi, M. R., Yazdani, S., Habibabadi, H. F., Feghhi, M., Shahriary, H. A., Eslamipour, J., Piri, N.,
Peyman, G. A.: Traumatic Endophthalmitis Trial Research Group: Prophylaxis of acute posttraumatic bacterial endophthalmitis:
a multi-centre, randomized clinical trial of intraocular antibiotic injection, report 2. Arch Ophthalmol 125, 2007, 460 - 465
[14] Soheilian, M., Rafati N., Peyman, G. A.: Prophylaxis of acute posttraumatic bacterial endophthalmitis with or without
combined intraocular antibiotics: a prospective, double-masked randomized pilot study. Int Ophthalmol 24, 2001, 323 - 330
References categorised as EbM IIA
[15] Endophthalmitis Vitrectomy Study Group: Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate
vitrectomy and of intravenous antibiotics for the treatment of post-operative bacterial endophthalmitis. Arch Ophthalmol 113,
1995, 1479 - 1496
[16] Kramer, A., Below, H., Behrens-Baumann, W., Müller, G., Rudolph, P., Reimer, K.: New aspects of the tolerance of the
antiseptic povidone-iodine in different ex vivo models. Dermatol 204 (Suppl. 1), 2001, 86 - 91
[17] Rudolph, P., Reimer, K., Mlynski, G., Reese, M., Kramer, A.: Modell zur Ermittlung der Nasenverträglichkeit lokaler
Antiinfektiva mittels In-vitro-Bestimmung der Ziliaraktivität. Hyg Med 25, 2000, 500 - 503
[18] Speaker, M. G. and Menikoff, J. A.: Prophylaxis of endophthalmitis with topical povidone-iodine. Ophthalmology 98, 1991,
1769 - 1775
References categorised as EbM IIB
[19] Alio, J., Ferrer, C., Fernandez, J., Abad, J.L., Rodriguez, A.: Intravitreal levofloxacin monotherapy of endophthalmitis in an
experimental model. Presented at Winter <strong>ESCRS</strong> Meeting, Rome 2005. Abstract, manuscript submitted to BJO
[20] Barza, M., Pavan, P. R., Doft, B. H., Wisniewski, S. R., Wilson, L. A., Han, D. P., Kelsey, S. F.: Evaluation of microbiological
diagnostic techniques in post-operative endophthalmitis in the Endophthalmitis Vitrectomy Study. Arch Ophthalmol 115,
1997, 1142 - 1150
[21] Behrens-Baumann, W., Martell, J.: Ciprofloxacin concentrations in human aqueous humor following intravenous administration.
Chemoth 33, 1987, 328 - 330
[22] Binder, C. A., Miño de Kaspar, H., Engelbert, M., Klauß, V., Kampik, A.: Bakterielle Keimbesiedelung der Konjunktiva mit
Propionibacterium acnes vor und nach Polyvidon-Jod-Applikation vor intraokulären Eingriffen. Ophthalmologe 95, 1998,
438 - 441
[23] Binder, C. A., Miño de Kaspar, H., Klauß, V., Kampik, A.: Präoperative Infektionsprophylaxe mit 1%-iger Polyvidon-Jod-Lösung
am Beispiel von konjunktivalen Staphylokokken. Ophthalmologe 96, 1999, 663 - 667
[24] Engstrom, R. E. Jr., Mondino, B. J., Glasgow, B. J., Pitchekian-Halabi, H., Adamu, S. A.: Immune response to Staphylococcus
aureus endophthalmitis in a rabbit model. Invest Ophthalmol Vis Sci 32, 1991, 1523 - 1533
[25] Forster, R. K.: Experimental post-operative endophthalmitis. Trans Am Ophthalmol Soc 90, 1992, 505 - 559
[26] Healy, D. P., Holland, E. J., Nordlund, M. L., Dunn, S., Chow, C., Lindstrom, R. L., Hardten, D., Davis, E.: Concentrations of
levofloxacin, ofloxacin and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration.
Cornea 23, 2004, 255 - 263
29

[27] Isenberg, S. J., Apt, L., Yoshimori, R., Khwarg, S.: Chemical preparation of the eye in ophthalmic surgery. IV. Comparison of
povidone-iodine on the conjunctiva with a prophylactic antibiotic. Arch Ophthalmol 103, 1985, 1340 - 1342
[28] Isenberg, S. J., Apt, L., Yoshimori, R., Pham, C., Lam, N. K.: Efficacy of topical povidone-iodine during the first week after
ophthalmic surgery. Am J Ophthalmol 124, 1997, 31 - 35
[29] Jenkins, C.D.G., Tuft, S.J., Sheradiah, G., Buckley, R.: Comparative intra-ocular penetration of topical and injected cefuroxime.
Br J Ophthalmol 80, 1996, 685-688
[30] Kon, C. H., Occleston, N. L., Aylward, G. W., Khaw, P. T.: Expression of vitreous cytokines in proliferative vitreoretinopathy: a
prospective study. Invest Ophthalmol Vis Sci 40, 1999, 705 - 712
[31] Kowalski, R. P., Karenchak, L. M., Warren, B. B., Eller, A. W.: Time-kill profiles of Enterococcus to antibiotics used for
intravitreal therapy. Ophthalmic Surg Lasers 29, 1998, 295 - 299
[32] Kwok, A. K., Hui, M., Pang, C. P., Chan, R. C., Cheung, S. W., Yip, C. M., Lam, D. S., Cheng, A. F.: An in vitro study of
ceftazidime and vancomycin concentrations in various fluid media: implications for use in treating endophthalmitis. Invest
Ophthalmol Vis Sci 43, 2002, 1182 - 1188
[33] Liang, Ch., Peyman, G. A., Sonmez, M., Molinari, L. C.: Experimental prophylaxis of Staphylococcus aureus endophthalmitis
after vitrectomy. The use of antibiotics in irrigating solution. Retina 19, 1999, 223 - 229
[34] Lohmann, C. P., Linde, H. J., Reischl, U.: Improved detection of microorganisms by polymerase chain reaction in delayed
endophthalmitis after cataract surgery. Ophthalmology 107, 2000, 1047 - 1052
[35] Miño de Kaspar H., Chang R.T., Singh K., Egbert P.R., Blumenkranz M.S., Ta C.N.: Prospective randomized comparison of 2
different methods of 5 % povidone-iodine applications for anterior segment intraocular surgery. Arch Ophthalmol 123, 2005,
161 - 165
[36] Miño de Kaspar H., Kreutzer, T. C., Aguirre-Romo, I., Ta, C. N., Dudichum, J., Bayrhof, M., Klauss, V., Kampik, A.: A
prospective randomized study to determine the efficacy of pre-operative topical levofloxacin in reducing conjunctival bacterial
flora. Am J Ophthalmol. In press
[37] Montan, P. G., Lundstrom, M., Stenevi, U., Thorburn, W.: Endophthalmitis following cataract surgery in Sweden. The 1998
national prospective survey. Acta Ophthalmol Scand 80, 2002, 258 - 261
[38] Pitten, F. A., Werner, H. P., Kramer, A.: A standardized test to assess the impact of different organic challenges on the
antimicrobial activity of antiseptics. J Hosp Infect 55, 2003, 108 - 15
[39] Pleyer, U., Mondino, B. J., Adamu, S. A., Pitchekian-Halabi, H., Engstrom, R. E., Glasgow, B. J.: Immune response to
Staphylococcus epidermidis endophthalmitis in a rabbit model. Invest Ophthalmol Vis Sci 33, 1992, 2650 - 2663
[40] Salvanet-Bouccara, A., Forestier, F., Coscas, G., Adenis, J. P., Denis, F.: Bacterial endophthalmitis. Ophthalmological results of
a national multi-centre prospective survey. J Fr Ophtalmol 15, 1992, 669 - 678
[41] Sherwood, D. R., Rich, W. J., Jacobs, J. S., Hart, R. J., Fairchild, Y. L.: Bacterial contamination of intraocular and extraocular
fluids during extracapsular cataract extraction. Eye 3, 1989, 308 - 312
[42] Speaker, M. G., Milch, F. A., Shah, M. K., Eisner, W., Kreiswirth, B. N.: Role of external bacterial flora in the pathogenesis of
acute post-operative endophthalmitis. Ophthalmology 98, 1991, 639 - 649
[43] Sundelin, K., Stenevi, U., Seal, D., Gardner, S., Ropo, A., Geldsetzer, K.: Corneal penetration of topical levofloxacin 0.5% -
pharmacokinetic profile with aqueous humour concentrations after intensive pre- and post-operative dosing and implications
for prophylactic use. 2007, manuscript submitted to Acta Ophthalmol Scand.
[44] Ta, C. N., Egbert, P. R., Singh, K., Shriver, E. M., Blumenkranz, M. S., Miño de Kaspar, H.: Prospective randomized
comparison of 3-day versus 1-hour pre-operative ofloxacin prophylaxis for cataract surgery. Ophthalmology 109, 2002,
2036 - 2040
[45] Walker S., Diaper C. M., Bowman R., Sweeney G., Seal D. V., Kirkness C. M.: Lack of evidence for systemic toxicity following
topical chloramphenicol use. Eye 12, 1998, 875 - 879
References categorised as EbM III
[46] Aaberg, T. M., Flynn, H. W. Jr., Schiffman, J., Newton, J.: Nosocomial acute-onset post-operative endophthalmitis survey.
Ophthalmology 105, 1998, 1004 - 1010
[47] Abreu, J. A. and Cordovés, L.: Chronic or saccular endophthalmitis: diagnosis and management. J Cataract Refract Surg 27,
2001, 650 - 651
[48] Adenis, J. P., Mounier, M., Salomon, J. L., Denis, F.: Human vitreous penetration of imipenem. Eur J Ophthalmol 4, 1994,
115 - 117
[49] Affeldt, J. C., Flynn, H. W. Jr., Forster, R. K., Mandelbaum, S., Clarkson, J. G., Jarus, G. D.: Microbial endophthalmitis
resulting from ocular trauma. Ophthalmology 94, 1987, 407 - 413
[50] Aldave, A. J., Stein, J. D., Deramo, V. A., Shah, G. K., Fischer, D. H., Maguire, J. I.: Treatment strategies for post-operative
Propionibacterium acnes endophthalmitis. Ophthalmology 106, 1999, 2395 - 2401
[51] Amon, M., Hirschl, A. M., Freyler, H.: Unterschiede im Keimspektrum des Konjunktivalsackes vor und nach
Tränenwegsspülung. Klin Mbl Augenheilk 199, 1991, 330 - 332
[52] Arciola, C. R., Caramazza, R., Pizzoferrato, A.: in vitro adhesion of Staphylococcus epidermidis on heparin-surface-modified
intraocular lenses. J Cataract Refract Surg 20, 1994, 158 - 161
[53] Behrens-Baumann, W., Dobrinski, B., Zimmermann, O.: Bakterienflora der Lider nach präoperativer Desinfektion. Klin. Mbl.
Augenheilkd. 192, 1988, 40 - 43
[54] Beigi, B., Westlake, W., Chang, B., Marsh, C., Jacob, J., Riordan, T.: The effect of intracameral, per-operative antibiotics on
microbial contamination of anterior chamber aspirates during phacoemulsification. Eye 12, 1998, 390 - 394
[55] Berrocal, A. M., Scott, I. U., Miller, D., Flynn, H. W. Jr.: Endophthalmitis caused by Moraxella species. Am J Ophthalmol 132,
2001, 788 - 790
[56] Bohigian G. M.: A study of the incidence of culture-positive endophthalmitis after cataract surgery in an ambulatory care
centre. Ophthalmic Surg Lasers 30, 1999, 295 - 298
30

[57] Brinton, G. S., Topping, T. M., Hyndiuk, R. A., Aaberg, T. M., Reeser, F. H., Abrams, G. W.: Posttraumatic endophthalmitis.
Arch Ophthalmol 102, 1984, 547 - 550
[58] Caillon, J., Juvin, M. E., Pirault, J. L., Drugeon, H. B.: Activité bactéricide de la Daptomycine (LY 146032) comparée à celle
de la Vancomycine et de la Teicoplanine sur les bactéries à gram positif. Path Biol 37, 1989, 540 - 548
[59] Caronia, R. M., Liebmann, J. M., Friedman, R., Cohen, H., Ritch, R.: Trabeculectomy at the inferior limbus. Arch Ophthalmol
114, 1996, 387 - 391
[60] Ciulla, T. A., Beck, A. D., Topping, T. M., Baker, A. S.: Blebitis, early endophthalmitis, and late endophthalmitis after
glaucoma-filtering surgery. Ophthalmology 104, 1997, 986 - 995
[61] Ciulla, T. A., Starr, M. B., Masket, S.: Bacterial endophthalmitis prophylaxis for cataract surgery. Ophthalmology 109, 2002,
13 - 24
[62] Clark, W. L., Kaiser, P. K., Flynn, H. W. Jr., Belfort, A., Miller, D., Meisler, D. M.: Treatment strategies and visual acuity
outcomes in chronic post-operative Propionibacterium acnes endophthalmitis. Ophthalmology 106, 1999, 1665 - 1670
[63] Cohen, St. M., Flynn, H. W. Jr., Murray, T. G., Smiddy, W. E., Postvitrectomy Endophthalmitis Study Group: Endophthalmitis
after pars plana vitrectomy. Ophthalmology 102, 1995, 705 - 712
[64] Colleaux, K. M., Hamilton, W. K.: Effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after
cataract surgery. Can J Ophthalmol 35, 2000, 373 - 378
[65] Das, T., Jalali, S., Gothwal, V. K., Sharma, S., Naduvilath, T. J.: Intravitreal dexamethasone in exogenous bacterial
endophthalmitis: results of a prospective randomised study. Br J Ophthalmol 83, 1999, 1050 - 1055
[66] Deramo, V. A. and Ting, T. D.: Treatment of Propionibacterium acnes endophthalmitis. Curr Opin Ophthalmol 12, 2001,
225 - 229
[67] Dev, S., Pulido, J. S., Tessler, H. H., Mittra, R. A., Han, D. P., Mieler, W. F., Conno, T. B. Jr.: Progression of diabetic
retinopathy after endophthalmitis. Ophthalmology 106, 1999, 774 - 781
[68] Dickey, J. B., Thompson, K. D., Jay, W. M.: Anterior chamber aspirate cultures after uncomplicated cataract surgery. Am J
Ophthalmol 112, 1991, 278 - 282
[69] Dilly, P. N., Sellors, P. J.: Bacterial adhesion to intraocular lenses. J Cataract Refract Surg 15, 1989, 317 - 320
[70] Driebe W. T. Jr., Mandelbaum S., Forster R. K., Schwartz L. K., Culbertson W. W.: Pseudophakic endophthalmitis. Diagnosis
and management. Ophthalmology 93, 1986, 442 - 448
[71] Eifrig, C. W., Flynn, H. W. Jr., Scott, I. U., Newton, J.: Acute-onset post-operative endophthalmitis: review of incidence and
visual outcomes (1995-2001). Ophthalmic Surg Lasers 33, 2002, 373 - 378
[72] Feys, J., Salvanet-Bouccara, A., Emond, J. Ph., Dublanchet, A.: Vancomycin prophylaxis and intraocular contamination during
cataract surgery. J Cataract Refract Surg 23, 1997, 894 - 897
[73] Gan, I. M., van Dissel, J. T., Beekhuis, W. H., Swart, W., van Meurs, J. C.: Intravitreal vancomycin and gentamicin
concentrations in patients with post-operative endophthalmitis. Br J Ophthalmol 85, 2001, 1289 - 1293
[74] Gelfand, Y. A., Mezer, E., Linn, S., Miller, B.: Lack of effect of prophylactic gentamicin treatment on intraocular and
extraocular fluid cultures after pars plana vitrectomy. Ophthalmic Surg Lasers 29, 1998, 497 - 501
[75] Gilbert, C. M., Sooong, H. K., Hirst, L. W.: A two-year prospective study of penetrating ocular trauma at the Wilmer
Ophthalmological Institute. Ann Ophthalmol 19, 1987, 104 - 106
[76] Good, W. V., Irvine, A. R., Hoyt, C. S., Hing, S., Taylor, D. S. I.: Post-operative endophthalmitis in children following cataract
surgery. J Pediatr Ophthalmol Strabismus 27, 1990, 283 - 285
[77] Gray, T. B., Keenan, J.I., Clemett, R.S., Allardyce, R.A.: Fusidic acid prophylaxis before cataract surgery: patient selfadministration.
Aust N Z J Ophthalmol 21, 1993, 99 - 103
[78] Greenfield, D. S., Suñer, I. J., Miller, M. P., Kangas, T. A., Palmberg, P. F., Flynn, H. W. Jr.: Endophthalmitis after filtering
surgery with mitomycin. Arch Ophthalmol 114, 1996, 943 - 949
[79] Gritz, D. C., Cevallos, A. V., Smolin, G., Whitcher, J. P. Jr.: Antibiotic supplementation of intraocular irrigating solutions.
Ophthalmology 103, 1996, 1204 - 1209
[80] Haider, S. A., Hassett, P., Bron, A. J.: Intraocular vancomycin levels after intravitreal injection in post cataract extraction
endophthalmitis. Retina 21, 2001, 210 - 213
[81] Han, D. P., Wisniewski, S. R., Wilson, L. A., Barza, M., Vine, A. K., Doft, B. H., Kelsey, S. F., Endophthalmitis Victrectomy
Study Group: Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study. Am J
Ophthalmol 122, 1996, 1 - 17
[82] Higginbotham, E. J., Stevens, R. K., Musch, D. C., Karp, K. O., Lichter, P. R., Bergstrom, T. J., Skuta, G. L.: Bleb-related
endophthalmitis after trabeculectomy with mitomycin C. Ophthalmology 103, 1996, 650 - 656
[83] Ho, P. C. and Tolentino, F. I.: Bacterial endophthalmitis after closed vitrectomy. Arch Ophthalmol 102, 1984, 207 - 210
[84] Holland, G. N., Earl, D. T., Wheeler, N. C., Straatsma, B. R., Pettit, T. H., Hepler, R. S., Christensen, R. E., Oye, R. K.:
Results of inpatient and outpatient cataract surgery. A historical cohort comparison. Ophthalmology 99, 1992, 845 - 852
[85] Isenberg S. J., Apt, L., Yoshimuri, R.: Chemical preparation of the eye in ophthalmic surgery. I. Effect of conjunctival irrigation.
Arch Ophthalmol 101, 1983, 761 - 763
[86] Jensen, M.K., Fiscella, R.G., Crandall, A.S., Moshirfar, M., Mooney, B., Wallin, T., Olson, R.J. : A retrospective study of
endophthalmitis rates comparing quinolone antibiotics. Am J Ophthalmol 139, 2005, 141 - 148
[87] Kahn, R.I., Kennedy S., Barry, P.: Incidence of presumed post-operative endophthalmitis in Dublin for a 5 year period (1997-
2001). J Cataract Refract Surg 31, 2005, 1575 - 1581
[88] Kattan, H. M., Flynn, H. W. Jr., Pflugfelder, S. C., Robertson, C., Forster, R. K.: Nosocomial endophthalmitis survey. Current
incidence of infection after intraocular surgery. Ophthalmology 98, 1991, 227 - 238
[89] Katz, L. J., Cantor, L. B., Spaeth, G. L.: Complications of surgery in glaucoma: Early and late bacterial endophthalmitis
following glaucoma filtering surgery. Ophthalmology 92, 1985, 959 - 963
31

[90] Koc, F., Sen, E., Demirbay, P., Taskintuna, I., Teke, M. Y., Ozdal, P., Ortac, S., Oz, O., Tarkan, F., Firat, E.: Factors influencing
treatment results in pseudophakic endophthalmitis. Eur J Ophthalmol 12, 2002, 34 - 39
[91] Kunimoto, D. Y., Das, T., Sharma, S., Jalali, S., Majji, A. B., Gopinathan, U., Athmanathan, S., Rao, T. N.: Microbiologic
spectrum and susceptibility of isolates: part II. Posttraumatic endophthalmitis. Endophthalmitis Research Group. Am J
Ophthalmol 128, 1999, 242 - 244
[92] Lehmann, O. J., Bunce, C., Matheson, M. M., Marino, V., Khaw, P. T., Wormald, R., Barton, K.: Risk factors for development of
post-trabeculectomy endophthalmitis. Br J Ophthalmol 84, 2000, 1349 - 1353
[93] Leong, J. K., Shah, R., McCluskey, P. J., Benn, R. A., Taylor, R. F.: Bacterial contamination of the anterior chamber during
phacoemulsification cataract surgery. J Cataract Refract Surg 28, 2002, 826 - 833
[94] Lundström, M., Wejde, G., Stenevi, U, Thorburn, W., Montan, P.: Endophthalmitis after cataract surgery: a nationwide
prospective study evaluating incidence in relation to incision type and location. Ophthalmology 114, 2007, 866 - 870
[95] Mayer, E., Cadman, D., Ewings, P.: A 10 year retrospective study of cataract surgery and endophthalmitis in a single eye unit:
injectable lenses lower the incidence of endophthalmitis. Br J Ophthalmol 87, 2003, 867 - 869
[96] Meisler, D. M., Palestine, A. G., Vastine, D. W., Demartini, D. R., Murphy, B. F., Reinhart, W. J., Zakov, Z. N., McMahon, J. T.,
Cliffel, T. P.: Chronic Propionibacterium endophthalmitis after extracapsular cataract extraction and intraocular lens
implantation. Am J Ophthalmol 102, 1986, 733 - 739
[97] Mendivil Soto, A., Mendivil, M. P.: The effect of topical povidone-iodine, intraocular vancomycin, or both on aqueous humor
cultures at the time of cataract surgery. Am J Ophthalmol 131, 2001, 293 - 300
[98] Menikoff, J. A., Speaker, M. G., Marmor, M., Raskin, E. M.: A case-control study of risk factors for post-operative
endophthalmitis. Ophthalmology 98, 1991, 1761 - 1768
[99] Merchant, A., Zacks, C. M., Wilhelmus, K., Durand, M., Dohlman, C. H.: Candidal endophthalmitis after keratoplasty. Cornea
20, 2001, 226 - 229
[100] Miller, J.J., Scott, I.U., Flynn, H.W., Smiddy, W.E., Corey, R.P., Miller, D. : Endophthalmitis caused by Streptococcus
pneumoniae. Am J Ophthalmol 138, 2004, 231 - 236
[101] Miño de Kaspar, H., Grasbon, T., Kampik, A.: Automated surgical equipment requires routine disinfection of vacuum control
manifold to prevent post-operative endophthalmitis. Ophthalmology 107, 2000, 685 - 690
[102] Miño de Kaspar, H., Kollmann, M., Klauß, V.: Endophthalmitis: Bedeutung mikrobiologischer Untersuchungen für Therapie und
Prognose. Ophthalmologe 90, 1993, 726 - 736
[103] Miño de Kaspar, H., Neubauer, A. S., Molnar, A., Hoepfner, A. S., Ta, C. N., Grasbon, T., Engelbert, M., Thiel, M., Klauß, V.,
Kampik, A.: Rapid direct antibiotic susceptibility testing in endophthalmitis. Ophthalmology 109, 2002, 687 - 693
[104] Mistlberger, A., Ruckhofer, J., Raithel, E., Müller, M., Alzner, E., Egger, St. F., Grabner, G.: Anterior chamber contamination
during cataract surgery with intraocular lens implantation. J Cataract Refract Surg 23, 1997, 1064 - 1069
[105] Mollan, S. P., Gao, A., Lockwood, A., Durrani, O. M., Butler, L.: Postcataract endophthalmitis: Incidence and microbial isolates
in a United Kingdom region from 1996 through 2004. J Cataract Refract Surg 33, 2007, 265 - 280
[106] Montan, P. G., Koranyi, G., Setterquist, H. E., Stridh, A., Philipson, B. T., Wiklund, K.: Endophthalmitis after cataract surgery:
Risk factors relating to technique and events of the operation and patient history. A retrospective case-control study.
Ophthalmology 105, 1998, 2171 - 2177
[107] Montan, P. G., Setterquist, H., Marcusson, E., Rylander, M., Ransjo, U.: Pre-operative gentamicin eye drops and chlorhexidine
solution in cataract surgery. Experimental and clinical results. Eur J Ophthalmol 10, 2000, 286 - 292
[108] Montan, P. G., Wejde, G., Koranyi, G., Rylander, M.: Prophylactic intracameral cefuroxime. Efficacy in preventing
endophthalmitis after cataract surgery. J Cataract Refract Surg 28, 2002, 977 - 981
[109] Montan, P.G., Wejde, G., Setterquist, H., Rylander, M., Zetterström, C.: Prophylactic intra-cameral cefuroxime. Evaluations of
safety kinetics in cataract surgery. J Cat Refract Surg 28, 2002, 982 - 987
[110] Morlet, N., Li, J., Semmers, J., Ng, J. on behalf of team EPSWA: The endophthalmitis population study of Western Australia
(EPSWA): First report. Brit J Ophthalmol 87, 2003, 574 - 576
[111] Morse, L. S., Yip, P., Perkins, S. et al.: Treatment outcomes for chronic, delayed onset, indolent, culture negative
endophthalmitis following cataract surgery. 20th Annual Vitreous Society Meeting San Francisco 2002
[112] Moshirfar, M., Feiz, V., Vitale, A. T., Wegelin, J. A., Basavanthappa, S., Wolsey, D. H.: Endophthalmitis after uncomplicated
cataract surgery with the use of fourth-generation fluoroquinolones – a retrospective observational case series. Ophthalmology
114, 2007, 686 - 691
[113] Narang, S., Gupta, A., Gupta, V., Dogra, M. R., Ram, J., Pandav, S. S., Chakrabarti, A.: Fungal endophthalmitis following
cataract surgery: Clinical presentation, microbiological spectrum, and outcome. Am J Ophthalmol 132, 2001, 609 - 617
[114] Nobe, J. R., Gomez, D. R., Liggelt, P.: Post-traumatic and post-operative endophthalmitis: a comparison of visual outcomes.
Br J Ophthalmol 71, 1987, 614 - 617
[115] Okhravi, N., Guest, S., Matheson, M. M., Kees, F., Ficker, L. A., Tuft, S. J., Lightman, S.: Assessment of the effect of oral
clarithromycin on visual outcome following presumed bacterial endophthalmitis. Curr Eye Res 21, 2000, 691 - 702
[116] Olson, J. C., Flynn, H. W. Jr., Forster, R. K., Culbertson, W. W.: Results in the treatment of post-operative endophthalmitis.
Ophthalmology 90, 1983, 692 - 699
[117] Ormerod, L. D., Ho, D. D., Becker, L. E., Cruise, R. J., Grohar, H. I., Paton, B. G., Frederick, A. R. Jr., Topping, T. M., Weiter,
J. J., Buzney, S. M., Ling, R. A., Baker, A. S.: Endophthalmitis caused by the coagulase-negative staphylococci. 1. Disease
spectrum and outcome. Ophthalmology 100, 1993, 715 - 723
[118] Özer-Arasli, A., Schwenn, O., Dick, B., Pfeiffer, N.: Endophthalmitis nach Kataraktoperation: Langzeitverlauf. Klin Mbl
Augenheilk 211, 1997, 178 - 182
[119] Pavan, P. R., Oteiza, E. E., Hughes, B. A., Avni, A.: Exogenous endophthalmitis initially treated without systemic antibiotics.
Ophthalmology 101, 1994, 1289 - 1297
[120] Perraut, L. E. Jr., Perraut, L. E., Bleiman, B., Lyons, J.: Successful treatment of Candida albicans endophthalmitis with
intravitreal amphotericin B. Arch Ophthalmol 99, 1981, 1565 - 1567
32

[121] Pflugfelder, St. C., Flynn, H. W. Jr., Zwickey, T. A., Forster, R. K., Tsiligianni, A., Culbertson, W. W., Mandelbaum, S.:
Exogenous fungal endophthalmitis. Ophthalmology 95, 1988, 19 - 30
[122] Philipps, W. B. and Tasman, W. S.: Post-operative endophthalmitis in association with diabetes mellitus. Ophthalmology 101,
1994, 508 - 518
[123] Poulsen, E. J. and Allingham, R. R.: Characteristics and risk factors of infections after glaucoma filtering surgery. J Glaucoma
9, 2000, 438 - 443
[124] Puliafito, C. A., Baker, A. S., Haaf, J., Foster, C. S.: Infectious endophthalmitis. Review of 36 cases. Ophthalmology 89, 1982,
921 - 928
[125] Schmidseder, E., Miño de Kaspar, H., Klauß, V., Kampik, A.: Posttraumatische Endophthalmitis nach penetrierenden
Augenverletzungen. Risikofaktoren, mikrobiologische Diagnostik und funktionelle Ergebnisse. Ophthalmologe 95, 1998,
153 - 157
[126] Schmitz, S., Dick, H. B., Krummenauer, F., Pfeiffer, N.: Endophthalmitis in cataract surgery. Results of a German survey.
Ophthalmology 106, 1999, 1869 - 1877
[127] Somani, S., Grinbaum, A., Slomovic, A. R.: Post-operative endophthalmitis: incidence, predisposing surgery, clinical course
and outcome. Can J Ophthalmol 32, 1997, 303 - 310
[128] Stonecipher, K. G., Ainbinder, D., Maxwell, D. P., Caldwell, D., Diamond, J. G.: Infectious endophthalmitis: A review of
cases from the cornea and retina services at Tulane Medical Center from 1979 to present. J Invest Ophthalmol Vis Sci 31,
1990, 140
[129] Taban, M., Behrens, A., Newcomb, R.L., Nobe, M.Y., Saedi, G., Sweet, P.M., McDonnell, P.M.: Acute endophthalmitis
following cataract surgery. Arch Ophthalmol 123, 2005, 613 - 620
[130] Thompson, J. T., Parver, L. M., Enger, C. L., Mieler, W. F., Liggett, P. E. for the National Eye Trauma System: Infectious
endophthalmitis after penetrating injuries with retained intraocular foreign bodies. National eye trauma system. Ophthalmology
100, 1993, 1468 - 1474
[131] Thompson, W. S., Rubsamen, P. E., Flynn, H. W. Jr., Schiffman, J., Cousins, S. W.: Endophthalmitis after penetrating trauma:
risk factors and visual acuity outcomes. Ophthalmology 102, 1995, 1696 - 1701
[132] Thoms, S. S., Musch, D. C., Soong, H. K.: Post-operative endophthalmitis associated with sutured versus unsutured clear
corneal cataract incisions. Br J Ophthalmol 91, 2007, 728 - 730
[133] Tuft, S., Kemeney, M., Buckley, R., Ramakrishnan, M., Seal, D. Role of Staphylococcus aureus in chronic allergic
conjunctivitis. Ophthalmology 1992; 99: 180 - 184
[134] Verbraeken, H.: Treatment of post-operative endophthalmitis. Ophthalmologica 209, 1995, 165 - 171
[135] Versteegh, M. F. L. and van Rij, G.: Incidence of endophthalmitis after cataract surgery in the Netherlands. Documenta
Ophthalmologica 100, 2000, 1 - 6
[136] Wallin, T., Parker, J., Jin, Y., Kefalopoulos, G., Olson, R. J.: Cohort study of 27 cases of endophthalmitis at a single institution.
J Cataract Refract Surg 31, 2005, 735 - 741
[137] Wejde, G., Montan, P., Lundström, M., Stenevi, U., Thorburn, W.: Endophthalmitis following cataract surgery in Sweden:
national prospective survey 1999-2001. Acta Ophthalmol Scand 83, 2005, 7 - 10
[138] Wejde, G., Samolov, B., Seregard, S., Koranyi, G., Montan, P. G.: Risk factors for endophthalmitis following cataract surgery: a
retrospective case-control study. J Hosp Infect 61, 2005, 251 - 256
[139] Wheeler, D. T., Stager, D. R., Weakley, D. R.: Endophthalmitis following pediatric intraocular surgery for congenital cataracts
and congenital glaucoma. J Pediatr Ophthalmol Strabismus 29, 1992, 139 - 141
[140] Winward, K. E., Pflugfelder, St. C., Flynn, H. W. Jr., Roussel, T. J., Davis, J. L.: Post-operative Propionibacterium
endophthalmitis. Treatment strategies and long-term results. Ophthalmology 100, 1993, 447 - 451
[141] Wisniewski, St. R., Capone, A., Kelsey, S. F., Groer-Fitzgerald, S., Lambert, H. M., Doft, B. H.: Characteristics after cataract
extraction or secondary lens implantation among patients screened for the Endophthalmitis Vitrectomy Study. Ophthalmol 107,
2000, 1274 - 1282
[142] Wolner, B., Liebmann, J. M., Sassani, J. W., Ritch. R., Speaker, M., Marmor, M.: Late bleb-related endophthalmitis after
trabeculectomy with adjunctive 5-fluorouracil. Ophthalmology 98, 1991, 1053 - 1060
[143] Zell, K., Engelmann, K., Bialasiewicz, A. A., Richard, G.: Endophthalmitis nach Katarakt-Operation: Disponierende Faktoren,
Erreger und Therapie. Ophthalmologe 97, 2000, 257 - 263
References categorised as EbM IV
[144] AAO-CDC Task Force: The prophylactic use of vancomycin for intraocular surgery. Quality of Care Publications, Number 515,
American Academy of Ophthalmology, San Francisco, CA, October 1999
[145] Alp, B. N., Elibol, O., Sargon, M. F., Aslan, O. S., Yanyali, A., Karabas, L., Talu, H., Caglar, Y.: The effect of povidone iodine on
the corneal endothelium. Cornea 19, 2000, 546 - 550
[146] Apt, L., Isenberg, S.J., Yoshimori, R., Spierer, A.: Outpatient topical use of povidone-iodine in preparing the eye for surgery.
Ophthalmology 96, 1989, 289 - 292
[147] ASCRS Ad Hoc Task Force on Cleaning and Sterilization of Intraocular Instruments: ASCRS-ASORN Special Report;
Recommended Practices for Cleaning and Sterilizing Intraocular Surgical Instruments. 16 Feb 2007,
www.ascrs.org/9370_1.pdf
[148] ASCRS, Ad Hoc TASS Task Force: Toxic Anterior Segment Syndrome (TASS) Outbreak Final Report - September 22, 2006.
www.ascrs.org/press_releases/Final-TASS-Report.cfm
[149] Barry, P.: Endophthalmitis: Recommendations based on the <strong>ESCRS</strong> study. CRS Today, 7, 2007, 63 - 65
[150] Behrens-Baumann, W.: Antiinfektiva bei Augenverletzungen. Klin Monatsbl Augenheilkd 221, 2004, 674 - 676
[151] Behrens-Baumann, W., Lederer, C.: Meta-analysis of 73 eyes of retrospective studies until 1999, 2003 – unpublished
33

[152] Behrens-Baumann, W., Rüchel, R., Zimmermann, O., Vogel, M.: Candida tropicalis endophthalmitis following penetrating
keratoplasty. Brit J Ophthalmol 75, 1991, 565
[153] Behrens-Baumann, W.: Magdeburger Dreistufenplan. www.med.uni-magdeburg.de/augenklinik, 1991 - 2003 (regularly
updated)
[154] Boldt, H. C., Pulido, J. S., Blodi, C. F., Folk, J. C., Weingeist, T. A.: Rural endophthalmitis. Ophthalmology 96, 1989,
1722 - 1726
[155] Campochiaro, P., A., Lim, J. I., Aminoglycoside Toxicity Study Group: Aminoglycoside toxicity in the treatment of
endophthalmitis. Arch Ophthalmol 112, 1994, 48 - 53
[156] Center for Disease Control: Recommendations for preventing the spread of vancomycin resistance. Morb Mort Wkly Rep 44
(RR-12), 1995, 1 - 13
[157] Chitkara, D. K., Manners, T., Chapman, F., Stoddart, M. G., Hill, D., Jenkins, D.: Lack of effect of pre-operative norfloxacin on
bacterial contamination of anterior chamber aspirates after cataract surgery. Br J Ophthalmol 78, 1994, 772 - 774
[158] Ciulla, T. A.: Update on Acute and Chronic Endophthalmitis. Ophthalmology 106, 1999, 2237 - 2238
[159] Cordoves, L., Abreu, A., Seal, D., Barry, P.: Intravitreal antibiotics: The emergency kit. J Cataract Refract Surg 27, 2001,
971 - 972
[160] Deramo, V. A., Ting, T. D.: Treatment of Propionibacterium acnes endophthalmitis. Curr Opin Ophthalmol 2001; 12: 225 - 229
[161] Dinakaran, S., Crome, D. A.: Prophylactic measures prevalent in the United Kingdom. J Cataract Refract Surg 28, 2002,
387 - 388
[162] Durand, M. L.: The Post-Endophthalmitis Vitrectomy Study Era. Arch Ophthalmol 120, 2002, 233 - 234
[163] Elder, M., Tarr, K., Leaming, D.: The New Zealand cataract and refractive surgery survey. Clin Exp Ophthalmol 28, 2000,
89 - 96
[164] Ferrer C, Ruiz-Moreno JM, Rodriguez AE, Alio J.: Post-operative Corynebacterium macginleyi endophthalmitis. J Cataract
Refractive Surg 30, 2004, 2441 - 2444
[165] Fiscella, R.G.: Physical incompatibility of vancomycin and ceftazidime for intravitreal injection. Arch Ophthalmol 110, 1992,
1625 - 1629
[166] Galloway, G., Ramsay, A., Jordan, K., Vivian, A.: Macular infarction after intravitreal amikacin: mounting evidence against
amikacin. Br J Ophthalmol 86, 2002, 359 - 360
[167] Gills, J. P.: Filters and antibiotics in irrigating solution for cataract surgery. J Cataract Refract Surg 17, 1991, 385
[168] Gimbel, H. V.: Intracameral vancomycin - rationale and experience. CRS Today, 7, 2007, 71 - 74
[169] Gimbel, H. V., Sun, R., DeBrof, B. M.: Prophylactic intracameral antibiotics during cataract surgery: The incidence of
endophthalmitis and corneal endothelial cell loss. Eur J Implant Ref Surg 6, 1994, 280 - 285
[170] Jackson, T. L., Williamson, T. H.: Amikacin retinal toxicity. Br J Ophthalmol 83, 1999, 1199 - 1200
[171] Jager, R.D., Timothy, N., Coney, J., Keenan, H.A., Ariegg, P., Aiello, L.P. : Endophthalmitis as a complication of intravitreal
injection: a systemic review. Presented at ARVO, Ft. Lauderdale, 2004, abs. 2001
[172] Kazi, A. A., Jermak, C. M., Peyman, G. A., Aydin, E., Riazi-Esfahani, M.: Intravitreal toxicity of levofloxacin and gatifloxacin.
Ophthalmic Surg Lasers Imaging 37, 2006, 224 - 229
[173] Kain, H. L.: Prinzipien in der Behandlung der Endophthalmitis. Klin Monatsbl Augenheilkd 210, 1997, 274 - 288
[174] Keverline, M. R., Kowalski, R. P., Dhaliwal, D. K.: in vitro comparison of ciprofloxacin, ofloxacin, and povidone-iodine for
surgical prophylaxis. J Cataract Refract Surg 28, 2002, 915 - 916
[175] Kresloff, M. S., Castellarin, A.A., Zarbin, M.A.: Endophthalmitis. Surv Ophthalmol 43, 1998, 193 - 224
[176] Lifshitz, T., Lapid-Gortzak, R., Finkelman, Y., and Klemperer, I.: Vancomycin and ceftazidime incompatibility upon intravitreal
injection. Br J Ophthalmol 84, 2000, 117 - 118
[177] Mac Rae, S. M., Brown, B., Edelhauser, H. F.: The corneal toxicity of presurgical skin antiseptics. Am J Ophthalmol 97, 1984,
221 - 232
[178] Maeck, C.R., Eckardt, C., Höller, C.: Comparison of bacterial growth on the conjunctiva after treatment with gentamicin or
povidone-iodine. Fortschr Ophthalmol 88, 1991, 848 - 851
[179] Mamalis, N., Edelhauser, H. F., Dawson, D. G., Chew, J., LeBoyer, R. M., Werner, L.: Toxic anterior segment syndrome.
J Cataract Refract Surg 32, 2006, 324 - 333
[180] Mamalis, N., Kearsley, L., Brinton, E.: Post-operative endophthalmitis. Curr Opin Ophthalmol 13, 2002, 14 - 18
[181] Mandelbaum, S., Forster, R. K., Gelender, H., Culbertson, W.: Late onset endophthalmitis associated with filtering blebs.
Ophthalmology 92, 1985, 964 - 972
[182] Masket, S.: Preventing, diagnosing, and treating endophthalmitis. J Cataract Refract Surg 24, 1998, 725 - 726
[183] Masket, S.: Is there a relationship between clear corneal cataract incisions and endophthalmitis? J Cataract Refract Surg 31,
2005, 643 - 645
[184] May, L., Navarro, V. B., Gottsch, J. D.: First do no harm: Routine use of aminoglycosides in the operating room. Insight 25,
2000, 77 - 80
[185] Miller, B., Ellis, P. P.: Conjunctival flora in patients receiving immunosuppressive drugs. Arch Ophthalmol 95, 1977,
2012 - 2014
[186] Morlet, N., Gatus, B., Coroneo, M.: Patterns of peri-operative prophylaxis for cataract surgery: A survey of Australian
ophthalmologists. Aust NZJ Ophthalmol 26, 1998, 5 - 12
[187] Motschmann, M., Behrens-Baumann, W.: Antiseptik in der Kataraktchirurgie. Ophthalmo-Chirurgie 12, 2000, 9 - 14
[188] Murthy, S., Hawksworth, N. R., Cree, I.: Progressive ulcerative keratitis related to the use of topical chlorhexidine gluconate
(0,02%). Cornea 21, 2002, 237 - 239
[189] Neß, T., Pelz, K.: Endophthalmitis - Verbesserung des Keimnachweises. Ophthalmologe 97, 2000, 33 - 37
34

[190] Ng, E. W., Barrett, G. D., Bowman, R.: in vitro bacterial adherence to hydrogel and poly (methyl methacrylate) intraocular
lenses. J Cataract Refract Surg 22, Suppl. 2, 1996, 1331 - 1335
[191] Niederkorn, J. Y.: Immune privilege and immune regulation in the eye. Adv Immunol. 48, 1990, 191 - 226
[192] Okada, A. A., Johnson, R. P., Liles, W. P., D'Amico, D. J., Baker, A. S.: Endogenous bacterial endophthalmitis. Report of a
ten-year retrospective study. Ophthalmology 101, 1994, 832 - 838
[193] Olson R. J.: What do I do? CRS Today 7, 2007, 112
[194] Perry, L. D., Skaggs, C.: Pre-operative topical antibiotics and lash trimming in cataract surgery. Ophthalmic Surg 8, 1977,
44 - 48
[195] Pichichero, M. E.: Cephalosporins can be prescribed safely for penicillin-allergic patients. J Fam Pract 55, 2006, 106 - 112
[196] Sternberg, P. Jr. and Martin, D. F.: Management of endophthalmitis in the Post-Endophthalmitis Vitrectomy Study Era. Arch
Ophthalmol, 119, 2001, 754 - 755
[197] Stonecipher, K. G., Parmley, V. C., Jensen, H., Rowsey, J. J.: Infectious endophthalmitis following sutureless cataract surgery.
Arch Ophthalmol 109, 1991, 1562 - 1563
[198] Streilein, J. W.: Ocular immune privilege and the faustian dilemma. Invest Ophthalmol Vis Sci 37, 1996, 1940 - 1950
[199] Villada, J. R., Vicente, U., Javaloy, J. Alió, J. L.: Severe anaphylactic reaction after intracameral antibiotic administration
during cataract surgery. J Cataract Refract Surg 31, 2005, 620 - 621
[200] Varley, G. A., Meisler, D. M., Benes, S. C., McMahon, J. T., Zakov, Z. N., Fryczkowski, A.: Hibiclens keratopathy.
A clinicopathologic case report. Cornea 9, 1990, 341 - 346
[201] Warheker, P.T., Gupta, S.R., Mansfield, D.C., Seal, D.V.: Successful treatment of saccular endophthalmitis with clarithromycin.
Eye 12, 1998, 1017 - 1019
[202] Warheker, P.T., Gupta, S.R., Mansfield, D.C., Seal, D.V., Lee, W.R.: Post-operative saccular endophthalmitis caused by
macrophage-associated staphylococci. Eye 12, 1998, 1019 - 1021
[203] Williams, D. L., Gills, J. P.: Infectious endophthalmitis following sutureless cataract surgery. Arch Ophthalmol 110, 1992, 913
References to books
[204] Behrens-Baumann, W.: Pilzerkrankungen des Auges. Ferdinand Enke Verlag, Stuttgart 1991 (with a contribution by R. Rüchel)
[205] Peyman, G., Lee, P., Seal, D.V. Endophthalmitis – diagnosis and management. Taylor & Francis, London: 2004, pp 1 - 270
[206] Peyman, G.A., Meffert, S.A., Conway, M.D., Chou, F. Vitreoretinal Surgical Techniques. Martin Dunitz, London 2001,
pp 1 - 605
[207] Seal, D.V., Bron, A.J., Hay, J. Ocular infection – investigation and treatment in practice. Martin Dunitz, London 1998,
pp 1 - 275
[208] Spoor, T.C. An Atlas of Ophthalmic Trauma. Martin Dunitz, London 1997, pp 1 - 207
References to book chapters
[209] Aaberg, T. M. and Sternberg, P. Jr.: Trauma: principles and techniques of treatment. In: Ryan, St. R. (Ed.): Retina. Mosby, St.
Louis 2001, 2400 - 2426
[210] Behrens-Baumann, W.: Mycosis of the Eye and its Adnexa. In: Developments in Ophthalmology 32, S. Karger AG, Basel 1999
(with a contribution by R. Rüchel)
[211] Bolton, L., Oleniacz, W., Constantine, B., Kelliher, B. O., Jensen, D., Means, B., Rovee, D.: Repair and antibacterial effects of
topical antiseptic agents in vivo. In: Maibach, H., Lowe, I. (Eds.): Models in Dermatology 2, S. Karger AG, Basel 1985,
145-158
[212] Kramer, A. and Rudolph, P.: Efficacy and tolerance of selected antiseptic substances in respect of suitability for use on the
eye. In: Kramer, A. and Behrens-Baumann, W. (Eds.): Antiseptic Prophylaxis and Therapy in Ocular Infections. S. Karger AG,
Basel 2002, 117-144
[213] Meredith, T. A.: Vitrectomy for infectious endophthalmitis. In: Ryan, S. J. (Ed.): Retina. Mosby Year Book Inc 3, St. Louis
2001, 2242-2263
[214] Osato, M. S.: Normal ocular flora. In: Pepose, J., Holland, G. N., Wilhelmus, K. R. (Eds.): Ocular Infection and Immunity.
Mosby, St Louis 1995
35

7. Appendix (Addresses of Contributors)
Augusto Abreu
Servicio de Oftalmología
Hospital Universitario de Canarias
38320 La Laguna
Tenerife
Spain
Jorge Alió
Instituto Oftalmológico VISSUM,
Avda. de Denia s/n,
03016 Alicante
Spain
Albert J Augustin
Augenklinik des
Städtischen Klinikums
Moltkestr. 90
76133 Karlsruhe
Germany
Peter Barry
Royal Victoria Eye & Ear
and St. Vincent's University
Hospital,
Dublin 4
Republic of Ireland
Wolfgang Behrens-Baumann
Universitäts-Augenklinik
Leipziger Str. 44
39120 Magdeburg
Germany
Alexander Bialasiewicz
Department of Ophthalmology
Sultan Qaboos University Hospital
P.O. Box 38
Al-Khod 123
Sultanate of Oman
Stefano Bonini
Istituto di Oftalmologia
Università degli Studi di Roma
Campus BioMedico
Via Moscati 31
00168 Roma
Italy
Joseph Colin
Service d'Ophtalmologie
CHU Pellegrin
Place Amélie Raba Léon
33076 Bordeaux Cedex
France
36
Luis Cordoves
Servicio de Oftalmología
Hospital Universitario de Canarias
38320 La Laguna
Tenerife
Spain
Burkhard Dick
Knappschaftskrankenhaus
Bochum-Langendreer
Universitätsklinik, Augenklinik
In der Schornau 23-25
44892 Bochum
Germany
Ekkehard Fabian
Bahnhofstr. 12
83022 Rosenheim
Germany
Susanne Gardner
St. Joseph's Hospital/Research
4765 Woodvale Dr.
Atlanta, Ga. 30327
USA
Klaus Geldsetzer
Santen GmbH
Industriestrasse 1
82110 Germering
Germany
Veronika Huber-Spitzy
Augenambulanz der
Krankenanstalt Sanatorium Hera
Lustkandlgasse 24
1090 Wien
Austria
Suleyman Kaynak
Retina Ophthalmic Research
Centre
1488 Sok. No. 3
35220 Alsancak
Izmir
Turkey
Volker Klauß
Universitäts-Augenklinik
Mathildenstr. 8
80336 München
Germany
Hans-Reinhard Koch
Hochkreuz-Klinik
Godesberger Allee 90
53175 Bonn
Germany
Axel Kramer
Institut für Hygiene und
Umweltmedizin
Ernst-Moritz-Arndt-Universität
Hainstr. 26
17487 Greifswald
Germany
Franz-Albert Pitten
Institut für Hygiene und
Mikrobiologie der
Bayerischen Julius-Maximilians-
Universität
Josef-Schneider-Str. 2
97080 Würzburg
Germany
Uwe Pleyer
Charité - Universitätsmedizin
Berlin
Campus Virchow-Klinikum
Augenklinik
Augustenburger Platz 1
13353 Berlin
Germany
David Seal
Applied Vision Research Centre
City University
Northampton Square
London EC1V 0HB
England
Ulf Stenevi
SU/Mölndals sjukhus
Ogenkliniken
Göteborgsvägen 31
431 80 Mölndal
Sweden
Jerzy Szaflik
Kierownik Katedry i Kliniki
Okulistyki
II Wydz. Lek. Akademii
Medycznej w Warszawie
Samodzielny Publiczny Kliniczny
Szpital Okulistyczny
ul. Sierakowskiego 13
Warsaw 03-709
Poland
J. Zeitz
Berliner Allee 15
40212 Düsseldorf
Germany

Notes
37

Published by The European Society for Cataract & Refractive Surgeons
Copyright © The European Society for Cataract & Refractive Surgeons
ISBN 0-9550988-0-7