Initial management strategy depends on the type of endophthalmitis, the presenting findings, systemic conditions (including drug allergies,

systemic diagnosis, and systemic fitness for surgery), and the possibility of local infection elsewhere as the cause for infection. The outcome depends on the clinical characteristics of the infection and is largely dependent on the bacterial or fungal species creating the infection. ACUTE POSTOPERATIVE INFECTION In the EVS, four separate initial management strategies were evaluated. All eyes received intravitreal vancomycin 1 mg and amikacin 0.4 mg. Eyes were initially randomized to either a pars plana vitrectomy or tap and injection of antibiotics. The two groups were then randomized into those receiving intravenous amikacin, and those of receiving no intravenous antimicrobial. Visual outcome was evaluated at 9 to 12 months. Fifty-three percent of patients achieved visual acuity 20/40 or better, whereas 74% achieved vision of 20/100 or better. Only 15% had visual acuity worse than 5/200.2 Visual acuity at presentation had the most important impact on the strategy that achieved the best outcome, and on the final visual acuity. Eyes with light perception only vision at presentation had a three times greater chance of achieving 20/40 vision with vitrectomy compared to tap and inject (33% versus 11%). These eyes also had a 50% decrease in the frequency of severe visual loss (20% versus 47%) when treated with vitrectomy compared to those eyes treated without vitrectomy. More favorable outcomes were achieved in eyes with hand motion or better vision at presentation, and there was no statistically significant difference between initial tap/ biopsy or vitrectomy in the effect on outcome. Thus for these eyes an initial strategy of vitrectomy is not usually indicated. Almost two-thirds of these eyes achieved 20/40 or better vision and 85% achieved a 20/100 or better. The risk for severe visual loss was approximately 4%.2 Additional procedures were required in 10% of eyes within the first week of a surgical intervention. Thirteen percent of eyes undergoing initial tap and 8% of the vitrectomy eyes underwent additional procedures. Most were operated for indications of worsening inflammation. Cultures obtained from these eyes were positive in 42% of the cases. These secondary cultures were positive for eyes having an initial tap 71% of the time, but only 13% of the time in eyes which had an initial vitrectomy. Twenty-seven percent of patients required additional procedures after 7 days. These included posterior capsulectomy, vitrectomy, retinopexy, scleral buckling, and epiretinal membrane peeling.113 The type of bacteria isolated from the culture had an impact on visual acuity. Rates of achieving final visual acuity of 20/100 or better were: gram-positive, coagulase-negative micrococci, 84%; Staphylococcus aureus, 50%; streptococci, 30%; enterococci, 14%; and gram-negative organisms, 50%.63 Administration of intravenous antibiotics did not

change the outcome of treatment and therefore been abandoned for routine administration.2 The most common cause for final visual impairment was abnormality of the macula, accounting for approximately 50% of patients with vision less than 20/40. Risk factors predicting a poor visual outcome were worse initial vision, small pupil size after maximal dilatation, presence of rubeosis irides, and absence of a red reflex.2 Other clinical factors predicting decreased final visual acuity included an open posterior capsule, corneal infiltrate or ring ulcer, history of diabetes, older age, and abnormal intraocular pressure. DELAYED-ONSET POSTOPERATIVE INFECTION Eyes with delay of the onset of postoperative infection for 6 weeks to longer should be suspected of harboring P. acnes infection or fungal infection. Fungal infections also can present acutely.131 An initial tap may be elected for identification of the organism so that the surgical intervention may be staged. For eyes with P. acnes infection, vancomycin is the preferred initial antibiotic choice. Eyes treated only with intraocular antibiotic, however, have a very high rate of recurrence. Two studies have demonstrated that an initial strategy of pars plane vitrectomy and intraocular antibiotics also fails to eradicate infection in half the cases. Thus, for initial therapy, a vitrectomy with removal of capsular plaque (and in selected cases, the capsule) is the preferred intervention. IOL exchange is a safe approach to treat the primary infection in a single procedure, unlike treatment of other forms of bacterial endophthalmitis. Fifty percent of patients achieved vision equal to or better than 20/40, and 78% were at least 20/400 in one series, whereas in another the average vision was 20/30 to 20/40.4244,111 BLEBITIS A recent survey of members of the American Glaucoma Society indicated that approximately half of the respondents chose initial treatment with topical quinolones only.132 Systemic microbial therapy has been reported to be successful in treating blebitis before the vitreous cavity becomes involved.50 Because moderate levels of aqueous humor drug concentration can be achieved by systemic administration, systemic antimicrobials may be more effective. Such eyes should be examined frequently because extension of the infection to the vitreous cavity may herald a rapid downhill course. In studies of blebitis, good outcomes have been reported by Poulsen,48 Brown,50 and Ciulla.133 BLEB-RELATED ENDOPHTHALMITIS Bleb-related endophthalmitis usually is a late onset disease after the bleb has been present for some time. Because virulent organisms are frequently the causative agents, outcomes are poor. Pars plana vitrectomy should be considered as one option for early intervention even in the absence of visual decline to the light perception level.

Although not effective in the EVS, systemic antibiotics also may be considered because of the presence of infection in the bleb and anterior chamber. Furthermore, a modest vitreous cavity concentration may also be achieved. Review of five series of treatment of bleb-related endophthalmitis demonstrated that only 41% of eyes achieved vision equal to or better than 20/400. This was especially influenced by the number of eyes with streptococcal infection; only 33% of these eyes achieved vision at that level.Streptococcus infections accounted for 45% of the combined series.49 In the series by Song 22% of patients underwent enucleation or evisceration secondary to pain, and/or poor vision. Of the other eyes, pressure was poorly controlled in 11%. Eyes treated with vitrectomy had worse outcomes than those treated with tap and inject, presumably because selection bias. Worse eyes usually were chosen for vitrectomy as initial management.49 TRAUMATIC ENDOPHTHALMITIS In traumatic endophthalmitis early mild disease may be approached with a tap and injection strategy if it is clear there is no retained intraocular foreign body or significant amount of lens material in the eye. If these conditions are present, vitrectomy may be adopted as the initial strategy in order to rid the eye of these materials.134,135 Early onset severe endophthalmitis may herald a mixed infection or infection with a severe virulent organism such as Streptococcus or Bacillus. If such an infection is suspected, vitrectomy may be chosen because of its demonstrated ability to clear the infection more quickly.134,135 Systemic antimicrobials also should be considered if there an organism other than coagulasenegativeStaphylococcus is suspected. Studies of trauma have demonstrated that not all eyes with positive cultures at the time surgery will develop and infection.30,136 In a study of deadly weapon, open 11 injuries, 10% became infected. Only 21% of the infected eyes of had visual outcomes 5/200 or better. Slightly more than half of the globes were to develop phthisis, were enucleated, or eviscerated.137 Outcomes in this study were better if they were infected with less virulent bacteria. Eyes with retinal breaks or retinal it detachment have worse outcomes.28,134 One study examined eyes in which the culture was positive at the time of initial repair of trauma, and separated the eyes into two groups: those who developed endophthalmitis (44%) and those who did not (56%). There was no statistically significant difference in the visual outcomes between the two groups, and the median vision was less than 20/200 in both. The eyes had better outcomes if they: (a) had been better initial visual acuity, (b) were infected with nonvirulent bacteria, (c) did not have retinal detachment, (d) did not develop endophthalmitis, (e) had shorter initial wound length.52 ENDOGENOUS ENDOPHTHALMITIS Management of endogenous endophthalmitis involves early recognition of the clinical picture. Consultation with an infectious disease specialist in

the early stages may be very helpful if the patient is not already known to be septic. A search for systemic sepsis should be undertaken in cases of endophthalmitis, because the systemic condition might be life threatening. Management depends on the severity of the presenting infection and systemic condition. Essentially all patients require systemic therapy. Patients who present with a chorioretinitis with modest vitreous inflammation may be successfully managed with intravenous antimicrobial therapy alone. If there is any suggestion that this may not be sufficient then intravitreal injection and/or pars plana vitrectomy with intraocular antibiotic injection are chosen. Outcomes are variable depending on the infection organism and the systemic health of the patient. Patients with bacterial endophthalmitis may experience a reasonably good outcome depending on the organism and severity of the initial infection. In two series the final vision was 20/400 or better in approximately half the patients.56,59 On the other hand, a very poor outcome is not unusual. One series reported an outcome of no light perception in 37.5% of cases. 58 Others note evisceration or enucleation as the outcome in a number of eyes.58,59 In fungal cases, Candida may present as a mild peripheral infection and respond well to the systemic medication being used for systemic therapy. Aspergillosis, on the other hand, has a tendency to present as a posterior segment infection involving the macula, and often destroys central vision.59 It should be remembered that these cases are often harbingers of a severe systemic condition. Because these patients are systemically ill, the death rate in published series ranges between 7% and 29%. 5659 Back to Top

OUTCOME BY ORGANISM
COAGULASE-NEGATIVE STAPHYLOCOCCI Gram-positive coagulase negative micrococci accounted for 69% of the culture positive infections in the EVS. In older reports, these organisms were frequently grouped together and reported as Staphylococcus epidermidis. In a large series of 90 cases of gram-positive coagulase negative staphylococcal endophthalmitis, nonepidermis staphylococci counted for 28% of the infections. S. warneri, S. hominis, S. haemolyticus, and S. capitis were the most common nonepidermidis isolates.36 In laboratory studies, Staphylococcus epidermis may selfsterilize after injection into the vitreous cavity.138,139 This suggests that some cases of culture negative endophthalmitis may be caused by these organisms, a speculation supported by PCR data.3,4There is frequently a significant delay between the inciting surgical or traumatic event and the onset of symptoms. In two studies by Omerod, approximately one-third of the cases presented after the first week.36,37,140 Only a small minority presented with more florid physical signs such as marked lid swelling, chemosis, or purulent external ocular inflammation.36 Infection with

these organisms often can be treated with a good outcome. After cataract surgery, more than half of all cases infected with these organisms achieve 20/50 vision or better.66,94,141,142 In the EVS, 84% coagulase negative micrococci infected eyes achieved 20/100 or better vision, and 58% achieved 20/40 or better. STAPHYLOCOCCUS AUREUS Staphylococcus aureus endophthalmitis usually occurs after cataract surgery but can be found after endogenous spread or after penetrating trauma.66,143 Most cases have the onset within the first week after surgery.143 Eyes with Staphylococcus aureus endophthalmitis do not have as good outcome as those with gram-positive, coagulase-negative staphylococci. In the EVS, 50% of eyes achieved 20/100 or better and 36.7% achieved 20/40 or better.63 In laboratory studies Staphylococcus aureus is not always eradicated with a single injection of antimicrobial.114 This persistence of infection also has been noted by authors of clinical series including those of the EVS who found 47% of eyes re-tapped after staphylococcus aureus or Streptococcus infection remained culture positive.113,118,119 They noted that persistence of infection may be a feature of infection with more virulent organisms.113 STREPTOCOCCUS Streptococcal species produce a particular virulent form of endophthalmitis. The genus Streptococcus is subdivided by several different classifications and comprises over 20 organisms that may cause intraocular infection. Virulence varies from one organism to the next and is often conferred by toxin production.144 Streptococcal species are the predominant organisms in bleb related endophthalmitis, but it may also occur in acute postoperative endophthalmitis.47,49,145 In the EVS they accounted for 7% of post-cataract infections. The onset of the infection after surgery tends to be more rapid than after coagulasenegative Staphylococcus infections and produce worse initial symptoms.2,38 Visual outcomes also tend to be worse than after coagulase-negative Staphylococcus infections. In the EVS, Streptococcus and Staphylococcus aureus infections were grouped together and demonstrated that the prognosis was less favorable.63 A large series, from a teaching hospital of 48 patients, demonstrated that 50% of the cases were produced by Streptococcus viridans. In this series, only 10% of eyes achieved vision equal to or better than 20/50 and only 31% were 20/400 or better.143 A later series of 27 eyes ofStreptococcus pneumoniae, from the same institution, noted that the visual results were approximately the same as the larger mixed series. Thirty-seven percent had no light perception.146 PSEUDOMONAS Pseudomonas aeruginosa is perhaps the most common gram-negative

intraocular infection. Pseudomonas is a relatively uncommon cause of post-cataract extraction endophthalmitis and is perhaps more commonly seen in mixed infections and after trauma. In one laboratory study, infection persisted despite appropriate antimicrobial therapy with a variety of agents after single injection if the infection had been established for 48 hours or longer.116 In the EVS, 70% of the infections with gram-negative organisms that were re-cultured remained culture positive.113 The largest reported series consists of 28 eyes that developed Pseudomonas endophthalmitis associated with various clinical situations. Twenty-five percent required enucleation or evisceration at presentation because of no light perception vision and intractable pain. Sixty-eight percent of eyes had a final visual acuity of no light perception, and only 7% of eyes had a final visual acuity of 5/200 or better.147 BACILLI Infection with Bacillus species confers an extremely poor prognosis. The majority of cases occur after trauma and often are associated with intraocular foreign bodies.31,148 Most endophthalmitis is caused by Bacillus cereus.148 Infections are so severe that the patient may present both with fever and leukocytosis. Injection of some of the toxins produced by Bacillus produces severe intraocular inflammation.149 In the literature, very few eyes have final vision better than no light perception53,148,150,151 with the exception of one outbreak of epidemic of Bacillus spp. in a series of cataract extraction patients.152 PROPIONIBACTERIUM ACNES Even though not an acute infection, P. acnes infections can result in visual loss in some patients. The overall recovery rate is approximately the same as in Staphylococcus epidermis infections. Fifty percent of patients achieved vision equal to or better than 20/40, and 78% were at least 20/400 in one recent study.111 In another report the average visual acuity was 20/30 to 20/40 depending on the group examined.42 FUNGI The outcome of fungal infections depends on the series reported and the types of infection. In a review of endogenous fungal endophthalmitis from the United States, 13 of 17 eyes with Candida infection achieved vision of 20/400 or better. Aspergillus endophthalmitis occurred far less frequently but had a more unfavorable prognosis.120 In a large series of endogenous fungal endophthalmitis from Japan, at least one-third of the eyes saw 20/200 or less after therapy. Vitreous surgery was performed in 26 eyes; six of these ended up totally blind.60 In a series of postcataract cases from India, Aspergillus spp. were the most common isolates. Only one-third of the eyes achieved visual acuity of 3/60 or better. Initial corneal involvement was a poor prognostic sign.131