Eyes with apparent infection may not grow out bacteria when appropriately subjected to culture. These cases are commonly called sterile endophthalmitis and accounted for 31% of the post-cataract surgery infected eyes entered into the Endophthalmitis Vitrectomy Study (EVS).^1,2 Polymerase chain reaction (PCR) evidence indicates that many of these cases may be the result of bacteria present in the eye that do not grow on culture.^3,4 Another syndrome, commonly referred to as a Toxic Anterior Segment Syndrome, is a reaction to intraocular foreign material, such as intraocular lenses or toxic irrigating solutions.⁵ The term pseudo-endophthalmitis also has been used, probably incorrectly, to designate accumulation of injected corticosteroid in the anterior chamber producing a white layering called a pseudohypopyon.

In cases of endophthalmitis after cataract extraction, a significant relationship to operative and postoperative complications has been identified. Capsular rupture, vitreous loss, wound leaks, postoperative filtering blebs, and vitreous wick have been identified as associated with the postoperative infection.¹⁸ The type of incision may contribute to the incidence of postoperative infection. In a recent case-control study from an ASC, a threefold greater risk of and optimize with clear corneal incisions was identified compared to scleral tunnel incisions.¹⁹ A higher incidence of infection has been noted in temporal incisions that was superior incisions in another study.²⁰ In secondary intraocular lens (IOL) implantation, a case-control study showed an association of infection with diabetes mellitus, propylene haptics, scleral suture fixation of posterior chamber IOLs, preoperative eyelid abnormalities, postoperative wound defects, and re-entry of the eye through a previous wound.²¹

Intraocular injections of corticosteroid and antibiotics have become increasingly common and will undoubtedly increase in the future, because intraocular injections are being introduced for treatment of macular degeneration. A review of 4,382 eyes that received 14,866 injections documented 38 cases of endophthalmitis for risk of 0.2% per injection.²²

After filtration bleb surgery the immediate incidence of infection is similar to cataract surgery or higher, but the eye remains at risk as long as the bleb is present. Studies suggest that the rate of infection on a yearly basis may be as much as 1% to 7.9%.^23–25 Glaucoma drainage devices also may become infected.²⁶

Posttraumatic cases account for roughly 25% of all cases of endophthalmitis.^6–9 The likelihood of infection is at least 100 to 300 times higher than after elective cataract surgery. Rates of infection after penetrating injury are approximately 2% to 3%,²⁷ rising to 11% to 20% with retained intraocular foreign body.^28–30 The National Eye Trauma Registry System surveyed 429 cases of intraocular foreign bodies and documented an incidence of endophthalmitis of 6.9%. There was no significant difference in risk depending on whether the foreign body was metallic, nonmetallic, or organic material.²⁹ Thirty percent of injuries in rural environments in one study became infected.³¹

The relevant group for incidence studies for endogenous endophthalmitis is not clear. Patients with known fungal septicemia frequently develop white dots in the choroid and retina that respond as a systemic disease is treated. Frank endogenous infection is relatively uncommon.

ACUTE POSTOPERATIVE ENDOPHTHALMITIS

Acute postoperative endophthalmitis may follow any intraocular surgery. Because cataract surgery is by far the most common ophthalmologic procedure, infections following lens extraction and IOL implantation are most often encountered. Infection may follow minor manipulations such as cutting sutures in corneal grafts or cataract incisions.³² Infection usually begins within the first 6 weeks, often within the first 1 to 2 weeks. More virulent organisms generally produce symptoms earlier. There is also a subgroup, termed delayed or chronic endophthalmitis, in which the onset of infectious symptoms may be delayed for 2 to 4 months.^33,34

The EVS was a National Eye Institute supported multicenter randomized clinical trial that evaluated four treatment regimens in post-cataract endophthalmitis. The study is important in understanding the current demographics and clinical parameters of post-cataract infection in United States. The study also served to validate proper diagnostic techniques and establish certain treatment regimens as most likely to be successful.²

Patients typically notice increased pain, sometimes beginning with a scratchy or irritated sensation. This usually is accompanied by blurred vision. Patients may notice increased exudates as well. In the EVS approximately 75% of patients had pain as a presenting symptom.³⁵ The time of onset of symptoms is correlated with the organism's virulence. In a large study of Staphylococcus epidermis endophthalmitis by Omerod^36,37 58% of the cases had the onset within the first week after surgery, whereas 42% were delayed into the second week or later. In the EVS there was a tendency for infections produced by more virulent organisms such as Staphylococcus aureus, Streptococcus, and gram-negative infections to present in the first two days after surgery.³⁸ The eye has varying degrees of redness, exudate, and lid edema. Slit-lamp examination may reveal wound complications or wound infiltrate, although in the phacoemulsification era these are relatively less common than identified previously. Increased anterior chamber flare and cell is almost always present; as the condition becomes more severe, variable degrees of fibrin are noted. Hypopyon is considered the hallmark of infection but it was only seen at presentation in 75% of the EVS patients.³⁵ In early cases when the fundus may still be seen, vasculitis has been described as one of the earliest findings.³⁹ Vitreous inflammation, however, is an invariable part of the presenting picture and usually is severe enough to obscure a clear fundus detail. Eyes with more virulent organisms are more likely to present with swollen eyelids, have light perception-only vision, demonstrate an afferent papillary defect, a corneal infiltrate, and loss of the red reflex.³⁸

In the EVS, 69% of the eyes were culture positive, but 31% were culture-negative. Of culture-positive eyes, 70% grew coagulase-negative staphylococci. Only 6% of eyes grew gram-negative organisms. Polymicrobial infections were identified in 9% of the cases.^2,40

After most intraocular surgery the major differential is between infection and an exaggerated inflammatory reaction to the surgery. When there is significant retained lens material, inflammation usually is greater than expected.⁴¹ Retained cortical material may produce an increased inflammation, which usually is evident from seeing pieces of cortex in the peripheral portion of the capsular bag or displaced into the vitreous or anterior chamber. Retained nuclear material usually creates less inflammation.

DELAYED-ONSET POSTOPERATIVE ENDOPHTHALMITIS

Endophthalmitis may present some weeks after the initial surgical procedure. Less virulent bacteria and fungi usually are suspected. Propionibacterium acnes produce a particular syndrome that may be suspected from the clinical presentation.^42–44 In the initial description of this disorder the average interval between cataract surgery and microbiological confirmation of the infection was 12 months. Most cases present 2 months or later after the initial surgery. The majority of patients present with granulomatous anterior uveitis, although nongranulomatous reactions also are observed, and some patients can even have hypopyon. A finding that is almost pathognomonic is a white plaque found on the capsule. These may be observed to increase in size under serial observation.^45,46 Some relatively nonvirulent bacteria can produce a chronic inflammatory response as do fungi. There is no other constellation of findings that can distinguish between fungal infection and less virulent bacteria. Culture and stains are necessary to make the diagnosis in these cases. The laboratory must be notified that the specimen must be specifically analyzed for fungi; for those in which P. acnes is suspected that the culture must be held for 2 weeks because the organism is slow growing.

BLEB-RELATED ENDOPHTHALMITIS

Most cases of bleb-related endophthalmitis occur months to years after the original procedure. Both intentional filtration blebs and traumatic blebs are susceptible to infection. Patients may have a prodrome of browache and/or headache. There often is an antecedent conjunctivitis manifested as redness of the eye with some degree of exudation.^{23–25,47,48} Patients who have inferior bleb and those in whom antifibrotic agents have been used are more susceptible to infection.^23–25 Although some blebs are Seidel-positive, intact blebs also may become infected. Thin blebs may be at higher risk. A recent report documented that bleb manipulations and bleb revisions are significant risk factors for the creation of bleb-related endophthalmitis.⁴⁹

The clinical presentation is classically described as “white-on-red” because the bleb is filled with white or yellow material in contrast with the surrounding conjunctival erythema. Examination findings of the cornea, anterior chamber, iris, and vitreous are similar to that in postoperative endophthalmitis.

An important differential diagnosis is that of blebitis versus bleb-related endophthalmitis. Absence of vitreous involvement indicates the diagnosis of blebitis.^48,50 Bleb-related infections have a very different bacterial spectrum than those from endophthalmitis following cataract surgery Streptococcus sp. are identified in 31% to 57% of eyes.⁴⁹ More recently, Staphylococcus and Enterococcus have been reported increasingly as the causative organisms, and gram-negative species also are found.^49,51

TRAUMATIC ENDOPHTHALMITIS

In traumatic endophthalmitis bacteria are introduced into the eye by traumatic penetration of the sclera or cornea. Studies have shown that not all patients who are culture-positive at vitrectomy for trauma develop endophthalmitis, possibly as the result of removal of the organism by the vitrectomy.^30,52 The differential diagnosis is between posttraumatic uveitis and true infection; severe inflammatory signs from the initial injury may make the diagnosis of endophthalmitis more difficult.

Typically patients have increased pain and redness postoperatively. Gram-positive organisms are responsible for approximately two-thirds of postoperative infections. Gram-negative organisms may cause 10% to 15% of the infections. However, several series have indicated that Bacillus infections are a responsible for 20% to 25% of posttraumatic infections, and most of these are associated with intraocular foreign bodies.^{28,31,53–55}

The rapidity of onset of symptoms may offer some clue to bacteriologic diagnosis, because Bacillus spp. produce a rapidly progressive infection. Findings in Bacillus infection include marked chemosis and exudates, a ring infiltrate of the cornea, diffuse opacification of the cornea, and severe intraocular inflammation. In other cases of endophthalmitis, a hypopyon appears and the vitreous may become more clouded after otherwise successful surgery.

Fungal infections may have a late onset and are seen in as many as 15% of cases of traumatic endophthalmitis. In the clinical presentation of these infections there may be the appearance of yellow or white fluffy material in the anterior chamber and/or vitreous cavity. Other cases are indolent and have progressively increased inflammatory changes in the anterior chamber and vitreous cavity.

ENDOGENOUS ENDOPHTHALMITIS

Endogenous endophthalmitis occurs primarily in patients with systemic illness. Many of these individuals are immune compromised; others may have systemic illness including endocarditis, urinary tract infections, recent gastrointestinal surgery, or hepatobiliary infections.^56–59 In a large series of endogenous fungal endophthalmitis, important predisposing factors were intravenous hyperalimentation, a history of cancer, and a fever of unknown origin.⁶⁰ The presenting symptoms and signs depend on the series being reviewed. Illness may be detected in an outpatient setting where ocular symptoms are the first presenting signs of the generalized illness. Others present as a complication in patients with known systemic sepsis or immunosuppression. In two series most initial contact was made with an ophthalmologist, whereas in another series most of the patients were hospitalized at diagnosis. Initial symptoms may be mild with decreased vision and redness, pain, and photophobia. Because patients may be quite ill, sometimes these symptoms are not adequately stressed to the caregivers on an acute medical service.⁵⁹ The initial misdiagnosis rate approaches 50% in some series.^56,58 Initial incorrect diagnoses included iritis and uveitis, conjunctivitis, glaucoma, and cellulitis. Therefore, diagnosis is frequently delayed until the disease has become more advanced. Bilateral presentation is fairly common and is reported in 15% to 26% of cases.^56–59

When endogenous endophthalmitis is considered, an internist or infectious disease specialist usually is consulted to search for the systemic source of infection. Blood cultures are frequently critical in establishing the diagnosis. A wide range of organisms are causative for this infection and 50% to 62% of the cases have been reported owing to fungal agents. Candida spp. are the most common isolate in some series, whereas Aspergillus has been noted by other authors. Gram-positive organisms are more prevalent than gram-negative organisms.^56–59

For unequivocal diagnosis samples of the aqueous and vitreous must be obtained for culture, sensitivity, and stain using the techniques described in the following. Samples from the vitreous are more often positive that are samples from aqueous.^61,62 Vitreous samples are positive as frequently from a tap/biopsy as they are after vitrectomy to obtain the specimen.²² Undiluted vitreous and aqueous may be placed on the following media for culture: enriched thioglycolate liquid medium, chocolate agar, Sabouraud's agar. Anaerobic cultures typically use either thioglycolate enriched broth or blood agar enriched with hemin and vitamin K. In some institutions material from the vitreous cassette after vitrectomy is filtered through a 0.45μ membrane filter. The filter is subsequently divided into three pieces under sterile conditions and used for culture.²

Stains are prepared from anterior chamber and vitreous specimens. In the EVS, the findings of a positive gram stain were associated with significantly worse final media clarity and visual acuity. The gram stain result did not reveal any subgroups in which vitrectomy had a beneficial value and therefore was of little consequence in making initial therapeutic decisions.⁶³ In the EVS there was no difference between the positive rate for culture between samples obtained by tap and those which were obtained by vitrectomy. There was no significant difference in operative complication between the two methods.

ANTIMICROBIAL THERAPY

Choice of Antimicrobial Agent

Because endophthalmitis therapy must be initiated emergently, the identity of the organism is unlikely to be known at the time antimicrobial agents must be chosen. The vast majority of endophthalmitis infections are gram-positive in origin.^2,66,67 As noted, the clinical setting often determines which organisms are more likely to be present. Because it is almost impossible initially to rule out gram-negative organisms as the cause of most infections on clinical examination, broad-spectrum antibiotic coverage usually is chosen.³⁸ In practice, this usually means empiric treatment with two separate antimicrobial agents as the initial choice.

Desirable characteristics for antimicrobial agents for treatment of bacterial endophthalmitis include the following:⁶⁸

1. Broad spectrum of coverage. Gram-positive organisms including methicillin-resistant staphylococci and Bacillus as well as gram-negative organisms must be covered.
   
2. Bactericidal properties. A bactericidal drug is preferable because the eye is an immune-privileged site.
   
3. Excellent therapeutic ratio (activity/toxicity) after intravitreal injection. The therapeutic window is the dose range between the lowest potentially efficacious dose and the upper limits established by tissue toxicity in the host. In evaluation of drugs for intraocular injection, the usual parameters studied for indications of toxicity are electroretinographic testing, histologic sectioning, and electron microscopic studies. Toxicity may be increased by repeated injections of certain antibiotics, a phenomenon that has not been extensively studied at this time.^69–71
   
4. Excellent therapeutic ratio after systemic administration. Medications administered orally or parenterally typically have poor penetration from the bloodstream into the eye.^68,72,73 There are several blood–eye barriers that reduce the ability of the antimicrobial to achieve access to intraocular structures. The concentration of antimicrobial in the aqueous humor is typically higher than that in the vitreous cavity. Intravitreal antimicrobial levels do not reach or exceed the minimum inhibitory concentration (MIC) in the vitreous cavity for many of the target organisms after systemic administration. Lipid-soluble compounds penetrate into the eye better than the hydrophilic antibiotics such as aminoglycosides. . Inflammation may break down blood–eye barriers allowing increased penetration.^68,74–76 Aminoglycosides and amphotericin have significant systemic toxicity, limiting their effectiveness.⁷⁷ Combinations of antibiotics such as vancomycin and aminoglycosides may improve coverage, but have additive toxicities.
   
5. Pharmacodynamics. The most favorable pharmacokinetic parameters are for a drug to access the eye readily from the bloodstream but to be retained within the eye for long periods of time after intraocular injection. This combination of characteristics is rarely, if ever, seen.
   

The highest possible initial dose is chosen whenever possible so that the drug remains above the MIC for the longest period of time. Drugs with longer half-lives are also preferred because the effective dose of drug is thought to be eliminated from the drug by the expiration of five half-lives. The upper limit of drug concentration is defined by the toxicity, usually in the form of retinal deterioration. If other characteristics are equivalent, then choice of the drug exceeding the MIC by the greatest degree is preferable. Some authors have suggested that concentrations of 10 to 30 times the MIC are necessary to effectively treat infections elsewhere in the body.

Intraocular Injections

The standard of care for most cases of endophthalmitis is intraocular injection of antimicrobial agents. Antibiotics injected into the vitreous cavity are eliminated from the eye by either an anterior or posterior route. β-Lactam antimicrobials were removed posteriorly, whereas the aminoglycosides exit through the anterior (trabecular meshwork) route.^78,79 The removal of the vitreous shortens the half-life of antimicrobials, whereas lens removal also can shorten the half-life of those using an anterior route of elimination. Inflammation breaks down blood–retinal barriers and also decreases the half-life of anteriorly eliminated drugs.^80–83

Although some controversy exists, there is a short half-life of most injected antimicrobials, so that effective duration of action of many antibiotics may be somewhere between 36 and 72 hours. Toxicity has been demonstrated in the form of retinal vascular shutdown by intravitreal aminoglycosides^84–87 and retinal necrosis in the case of other antibiotics.^70,71 Combinations of antimicrobials such as vancomycin and amikacin may increase their toxicities.^70,71 The antimicrobials usually chosen for intraocular injections at this time are the following agents:

1. Vancomycin. Vancomycin is considered the antibiotic of choice for gram-positive coverage. One study of 246 gram-positive endophthalmitis isolates demonstrated all to be susceptible to vancomycin.⁸⁸ Vancomycin inhibits cell wall assembly and RNA synthesis, and damages protoplasts. The spectrum of coverage is entirely gram-positive but includes all the staphylococcal species, streptococci, P. acnes, and Bacillus organisms. Although some vitreous sampling after intraocular injections in human infected eyes has demonstrated persistent therapeutic levels for 3 to 4 days after initial injection,^89–91 in animal studies the half-life suggests that therapeutic concentrations should be maintained for only about 48 hours after intravitreal injection.^80,92
   
2. Cephalosporins. Cephalosporins are synthetic penicillins that damage bacterial cell walls. Both cefazolin and ceftazidime have been extensively studied for intraocular injection and seem relatively safe when 2.25 mg are injected intravitreally.⁹³ First-generation cephalosporins are weak against enterococcus and methicillin-resistant staphylococcal organisms. Ceftazidime is a third-generation agent often used for enhanced gram-negative coverage. One study of 37 gram-negative isolates from cases of endophthalmitis found 80% to be susceptible to ceftazidime.⁸⁸ As with vancomycin, the effective dosage lasts only 2 to 3 days after injection.⁶⁸
   
3. Aminoglycosides. Aminoglycosides have been popular with ophthalmologists for treatment because of their gram-positive and -negative coverage. They inhibit protein synthesis but after intraocular injection may produce retinal vascular infarction. This complication has been noted both with gentamicin and amikacin.^22,84–87 The half-life of amikacin in inflamed vitrectomized eyes is approximately 8 hours.⁸² Because toxicity limits total injected dose, the concentration of antimicrobials remains above the MIC for only 24 to 36 hours after intraocular injection.
   
4. Antifungal Agents. Until recently amphotericin was considered the gold standard for treatment of intraocular fungal infection by intraocular injection. The usual recommended dose is 5 μg/mL. The half-life is long, reportedly as much as 9 days. However, the half-life is decreased by inflammation and vitreous removal.⁸¹
   

Systemic Antimicrobials

Systemic antimicrobials were once considered crucial for the treatment of endophthalmitis, but now their efficacy is debated. Because inflammation breaks down the blood–eye barriers, greater penetration into inflamed eyes occurs after systemic administration.^{68,72,74–76} Vitrectomy enhances the penetration of some medications (cefazolin,⁷⁵ vancomycin,⁷⁶ and ceftazidime^68,74) into the eye. Repeat intravenous dosing likewise contributes to progressive increase in intraocular concentrations.^{68,72,74–76}

Antimicrobials may be administered either orally or intravenously. Although studies have demonstrated response in staphylococcus endophthalmitis and other more virulent organisms to intravenous antibiotics only,⁹⁴ the EVS did not demonstrate any improvement in visual outcome in patients given intravenous therapy along with intraocular therapy as compared to patients given intraocular therapy only.² However, in that study the intravenous antibiotic given for gram-positive coverage was amikacin, which has very poor penetration into the vitreous cavity after intravenous injection and would not be expected to provide a significant effect.⁷³ Newer data indicates that fluoroquinolones, particularly fourth-generation agents, may have improved intraocular penetration due to their ability to cross the blood–eye barriers.^95,96 Most antimicrobials are more likely to be able to achieve intravitreal levels if the eye is inflamed because of a breakdown of the blood–ocular barrier. Specific antimicrobials often considered for systemic therapy include vancomycin, fluoroquinolones, and cephalosporins.

1. Vancomycin. Vancomycin is a large molecule must be an administered intravenously. After a single intravenous dose variable but small intraocular concentrations have been found in noninflamed human eyes. In inflamed eyes after repeated dosing in animal models, there is modest penetration in the vitreous cavity sufficient to be above the MIC for target organisms.⁷⁶ High intravenous doses run the risk of systemic toxicity that may be additive with intravenous aminoglycosides.
   
2. Cephalosporins. Penetration of cefazolin into inflamed vitrectomized eyes can be achieved after repeated intravenous doses. Levels above MICs for gram-positive pathogens for endophthalmitis have been demonstrated.⁷⁵ Ceftazidime has an even greater penetration particularly into inflamed eyes.^74,75 It has better Pseudomonas coverage than cefazolin does, but it is not as good as for some gram-positive organisms.
   
3. Quinolones. The fourth-generation quinolones have been recently suggested for their potential effectiveness to prevent and treat endophthalmitis. Fluoroquinolones have both gram-positive and gram-negative coverage. Inhibition of DNA synthesis is their usual mode of action. Ciprofloxacin was initially promoted for its penetration into the eye after oral administration but a number of ocular pathogens have developed resistance to it.^97–99 The fourth-generation quinolones, gatifloxacin, and moxifloxacin, have good levels of penetration and require two alterations to their genetic mechanism in order to produce resistance. Because of this mechanism, it is hoped that resistance will prove to be a less important issue. Penetration of gatifloxacin in noninflamed eyes undergoing vitreous surgery demonstrated that two doses of oral medication delivered 12 hours apart produced significant intraocular concentrations as a percentage of serum levels. The vitreous ratio to serum concentration was 26.17% and the ratio of aqueous concentration to vitreous was 21.01%. For most of the pathogens producing intraocular disease, the levels achieved were above the MIC 90.^96,100 Initial studies suggest that the fourth-generation quinolones cover the bacterial resistance that developed to the second- and third-generation agents. Moxifloxacin may be the most potent fluoroquinolone for gram-positive bacteria, whereas moxifloxacin and gatifloxacin may be equivalent for gram-negative organisms.¹⁰¹
   
4. Antifungal Agents. Amphotericin B has been the time-honored medication for intravenous administration for antifungal therapy. Recent reports have demonstrated good results for vitrectomy and fluconazole.¹⁰² Recent studies of voriconazole have demonstrated intraocular penetration sufficient to suggest possible efficacy.¹⁰³

Subconjunctival Injections

Frequent subconjunctival injections were previously advocated as a mainstay of therapy, but the entry of antimicrobials into the eye after subconjunctival injection is marginal.^104–108 Vitreous levels of antimicrobial after subconjunctival injection rarely reached therapeutic levels and are essentially insignificant by comparison to the concentration produced by intravitreal injections. Subconjunctival injections may release antimicrobial onto the surface of the eye and therefore may be useful for any external aspect of the infection such as bleb infection or wound infection.

Topical Antimicrobials

Topical antimicrobials have the same limitations as do subconjunctival injections. Attempts are made to overcome this problem by producing highly concentrated formulations and administering the drops frequently during the day. Some authors recommend topical vancomycin (25 mg/mL), aminoglycosides (9 to 14 mg/mL) or ceftazidime (50 mg/mL). Like subconjunctival injections, these may have some benefit for external aspects of the infection but the amount of drug delivered to the vitreous cavity is marginal

SURGICAL PROCEDURES

Two basic procedures are used for initial treatment of endophthalmitis: a) vitreous tap with injection of intraocular antibiotics, and b) pars plana vitrectomy.

Tap and Inject

A vitreous tap is usually done through the pars plana because most cases of endophthalmitis occur in eyes that have a posterior chamber intraocular lens (PCIOL) in position or that are phakic. The anterior chamber may be tapped to obtain aqueous culture, or may be the entrance site for a tap to sample the vitreous cavity in an aphakic eye. To tap the anterior chamber, topical anesthesia is usually employed. The eye may be stabilized with a Q-tip or forceps in one hand and entered with a 30-gauge needle at the limbus with the operative hand. A tuberculin syringe often is used for convenience, and as much as 0.2 cc of fluid may be withdrawn. If there is significant fibrin in the anterior chamber, the small-bore needle may not be sufficient to achieve a good sample, and an entry must be made with a 25- or 27-gauge needle. A small puncture incision with a blade may facilitate use of the larger gauge needles.

Tap of the vitreous cavity usually is made through the pars plana 3.5 to 4 mm posterior to the limbus. Depending on the amount of inflammation and the pain tolerance, this may be done with a conjunctival injection or retrobulbar injection. A topical anesthetic of choice may be placed in the eye and supplemented if desired with a pledget of lidocaine placed over the area for injection for a few moments. A bleb may be raised with subconjunctival lidocaine 2% in the area if the topical anesthesia does not seem to produce sufficient analgesia. In the case of very inflamed eyes, this may not be sufficient, and retrobulbar or peribulbar injection of lidocaine 2% to 4% may be chosen.

Topical povidone iodine 5% is instilled in the conjunctival sac for 1 to 2 minutes prior to the injection. A lid spectrum usually is helpful to prevent blinking. The eye then is stabilized with forceps or a Q-tip and a position 3.5 mm posterior to the limbus is identified. A 22- to 27-gauge needle may be used for the initial penetration and inserted with a slight screwing motion. Once in the eye, it should be advanced far enough to be clear of the vitreous base and then suction should be applied. If the medium is clear enough, it is best to visualize the position of the needle in the vitreous cavity before suctioning. Suction without clear visualization is dangerous and should be avoided if possible. The goal should be to obtain 0.2 to 0.3 cc of fluid for gram stain, culture, and sensitivity. Needles as large as 20 to 22 gauge sometimes are necessary because of the viscous nature of an inflamed vitreous. The tap should be aborted if liquid vitreous is not obtained. A single port vitrectomy then may be used to obtain material for analysis. Once the needle is withdrawn, pressure is placed over the sclerotomy site with a cotton tip. Material is submitted immediately to the laboratory. After the tap has been done, injection is performed often through the same incision site if possible. Typically, 0.1 cc of each of two antimicrobials is injected into the vitreous cavity. The usual antibiotic injections are vancomycin 1 mg in 0.1 cc and either amikacin 200 γg in 0.1 cc or ceftazidime 2.25 mg in 0.1 cc.

Pars Plana Vitrectomy

Pars plana vitrectomy was adopted early for treatment of intraocular infection shortly after its introduction and acceptance as a surgical procedure.^109,110 Pars plana vitrectomy allows application of the principles of incision and drainage of an abscess. This intervention allows for the removal of the infected organisms, removal of opacified vitreous and debris, and potentially reduction of toxins.

Pars plana vitrectomy for infection is performed under local or general anesthesia, although it may be somewhat difficult to achieve adequate local anesthesia in a very inflamed eye. Standard conjunctival cutdowns are performed and an infusion port placed into the inferotemporal sclera 3.5 mm posterior to the limbus. It is important to visualize the port inside before turning on infusion.

The anterior chamber may be quite opaque. In these cases pars plana infusion is put in position but not turned on. Another infusion is carried through the limbus and the vitrectomy cutting probe introduced into the anterior chamber to clear debris. It is often necessary to strip away fibrin membrane from the surface of the iris and intraocular lens. In some instances iris retractors may be beneficial if the pupil will not dilate properly. Material obtained from the anterior chamber is submitted for culture and sensitivity.

Once the vitreous cavity may be examined, the infusion is identified and turned on so that a light source and cutting probe may be introduced into the posterior segment. Before turning on the posterior infusion the vitrectomy probe is hooked up to a small syringe and an undiluted sample is taken, cutting the opaque vitreous and sucking the material into the syringe: 0.5 to 1 cc may be safely removed in this manner and submitted for culture and stains.

Vitrectomy is carried further into the vitreous cavity using simultaneous fluid infusion. Once the central cavity is clear, whitish material on the surface of the retina may be noted. It is important to be careful not to apply traction either with suction or direct pulling on areas of necrotic retina. Sometimes white material represents white cells layered on the surface of the retina which can be vacuumed free. White material trapped in membrane often clears within the first few days without being stripped away if the infection has been adequately treated. In cases of Propionibacterium acnes there may be small plaque of white material sequestered in the capsule that is thought to be the nidus of infection. It is then necessary to remove this plaque in most eyes in order to cure the infection. Removal of the entire lens capsule and even removal of the lens and/or IOL exchange is sometimes necessary to effect a cure in these cases.^42–44,111

One sclerotomy is closed and then a stitch put into the second sclerotomy. Intraocular antibiotics are injected into the eye through the second sclerotomy before closure.

INDICATIONS.

There are a variety of indications for pars plana vitrectomy in the treatment of endophthalmitis. The EVS demonstrated that in eyes with light perception there is a 33% chance of achieving 20/40 vision at the initial intervention with vitrectomy and intraocular antibiotic injection versus only 11% likelihood if the initial intervention was a vitreous tap and injection only. For eyes with hand motion or better vision, there was no difference in visual outcome between these two initial strategies.² Subsequent analysis of the data demonstrated that eyes of patients with diabetes mellitus had a tendency to fare better with a vitrectomy as an initial intervention, but the trend did not reach statistical significance.¹¹² This study was an analysis of a factor identified retrospectively which was not part of the randomization scheme.

Vitrectomy also may be elected for eyes with acute infections not responding to the initial strategy of tap and inject.¹¹³ In the EVS, over 10% of eyes were subjected to additional surgery within a week of the initial therapeutic intervention. Early secondary interventions were undertaken in 8% of eyes undergoing initial vitrectomy and in 14% of eyes treated with tap and inject. Surgeons should consider a vitrectomy in eyes that do not respond to initial therapeutic intervention, because it is clear from laboratory^113–117 and clinical studies^113,118,119 that a single injection of antimicrobials does not cure all endophthalmitis. Furthermore, in animal studies the strategy of initial vitrectomy is more effective in sterilizing the vitreous cavity as an initial strategy than is an injection of antibiotics alone.^114,115 In the EVS cultures obtained in 33 eyes operated for worsening inflammation were positive 42% of the time. Eyes initially treated with vitrectomy were positive in only 13% of the cases, whereas eyes treated with tap and inject initially were positive 71% of the time.¹¹³

In eyes that have apparent cure of the infection some vitreous opacities may persist for several months interfering with the patient's ability to see. Only a few of these eyes eventually require a vitrectomy to clear the media.¹¹³

Vitrectomy and intraocular antibiotic injection may be elected as initial intervention in other circumstances when vision is better than light perception. In cases with severe bleb infections, for example, the incidence of virulent organisms is high and the onset may be rapid. In such instances the suspicion of rapid progression of a more severe infection may tip the balance toward vitrectomy as an initial intervention. Vitrectomy also may be elected in situations where there is an indication for vitreous surgery in addition to the infection. These might include infection associated with retained intraocular foreign body or retained lens material.

Chronic indolent cases of endophthalmitis have been demonstrated to respond better to vitrectomy than initial antibiotic injection. This is particularly true for Propionibacterium acnes infections that have a very low rate of cure with injection of antibiotic injection only.^42–44,111 Fungal cases also may require vitrectomy with an intraocular injection of amphotericin B.¹²⁰

COMPLICATIONS.

In most instances, an eye treated with vitrectomy shows as much or more inflammation the following day than it did at presentation because of the addition of surgical trauma. Aggressive anti-inflammatory therapy is often indicated. In the immediate postoperative period, the cornea is often edematous if the inflammation has been severe. Persistent epithelial defects occur in some patients and sometimes require management with a bandage contact lens.

Intraocular pressure may be elevated in the postoperative period usually responding to medical management. If there has been severe inflammation, hypotony may occur, associated with persistent inflammation, and lead to a downhill course. A leaking wound site may be suspected, but in general the cause of this complication is ciliary body shutdown.

In eyes that are phakic at the time of infection and therapy, cataract often develops in the postoperative period. Usually time is allowed to pass for the inflammation to clear before cataract surgery is undertaken. If there is apparent vitreous opacity on clinical examination or ultrasound, pars plana lensectomy combined with vitrectomy may be elected.

The most feared complication of endophthalmitis with or without vitrectomy is retinal detachment. In the EVS, retinal detachment occurred in 8.3% of the eyes; there was no significant difference in incidence between eyes treated with initial vitrectomy and those treated with tap and inject as the first intervention.¹²¹ Retinal detachment may occur because of breakdown of necrotic retina or because of traction on the vitreous or vitreous base during vitrectomy or vitreous tap. Detachments are a major cause of failure in many series,¹²² but in the EVS series, 78% of cases were successfully repaired. There was a correlation of retinal detachment and poor visual outcome.¹²¹

In eyes of the retinal detachment, proliferative retinopathy is a significant complication. Sympathetic ophthalmia has been reported.

CORTICOSTEROIDS.

In laboratory studies concomitant corticosteroid use almost always leads to better clinical outcomes than controls not treated with corticosteroids. The proper route of administration remains a source of some controversy.

In the EVS patients were routinely treated with prednisone 30 mg PO twice daily for 5 days following surgical intervention.² In animal studies similar treatment has proven effective in many models of gram-positive infections.^114,123

Intraocular corticosteroids are advocated by some authors.^124–127 In many animal models, this route of administration is associated with better clinical outcomes than no corticosteroid treatment at all. However, neither laboratory nor clinical studies demonstrate a clear-cut advantage for intraocular injection over systemic administration. Retrospective clinical studies have provided conflicting results. Das and co-workers, in a prospective randomized trial, demonstrated an earlier reduction of intraocular inflammation after injection intraocular corticosteroids, but there was no lasting benefit on visual outcome compared to controls.¹²⁸ Two retrospective studies reached differing conclusions. Shah and co-workers reported that those patients receiving intravitreal corticosteroids had a reduced chance of achieving a three-line improvement of visual acuity in the postoperative period.¹²⁹ All patients had treatment with intraocular antibiotic. At another institution a retrospective analysis of 42 patients demonstrated no difference between those treated with intraocular corticosteroids and those without intraocular corticosteroids.¹³⁰ None of these studies, however, is a randomized trial, so there is no data to indicate clearly the superiority of this technique over systemic administration. A single laboratory evaluation has demonstrated worse outcomes in an animal model of Staphylococcus aureus given intraocular corticosteroids when compared to systemic administration of corticosteroids.¹¹⁴

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.^42–44,111

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 coagulase-negative Staphylococcus 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%.^56–59

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 self-sterilize 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 coagulase-negative 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 of Streptococcus 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 perception^{53,148,150,151} 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 post-cataract 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

1. Endophthalmitis Vitrectomy Study Group: Results of the Endophthalmitis Vitrectomy Study: A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol 113:1479, 1995

2. Endophthalmitis Vitrectomy Study Group: Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol 113:1479, 1995

3. Okhravi N, Adamson P, Carroll N, et al: PCR-based evidence of bacterial involvement in eyes with suspected intraocular infection. Invest Ophthalmol Vis Sci 41:3474, 2000

4. Okhravi N, Adamson P, Matheson MM, Towler HM, Lightman S: PCR-RFLP-mediated detection and speciation of bacterial species causing endophthalmitis. Invest Ophthalmol Vis Sci 41:1438, 2000

5. Jehan FS, Mamalis N, Spencer TS, et al: Postoperative sterile endophthalmitis (TASS) associated with the Memory Lens. J Cataract Refract Surg 26:1773, 2000

6. Bohigian G: A study of the incidence of culture-positive endophthalmitis after cataract surgery in an ambulatory care center. Ophth Surg Lasers 30:295, 1999

7. Forster RK, Zachary IG, Cottingham AJ Jr, Norton EWD: Further observations on the diagnosis, cause, and treatment of endophthalmitis. Am J Ophthalmol 81:52, 1976

8. Forster RK, Abbott RL, Gelender H: Management of infectious endophthalmitis. Ophthalmology 87:313, 1980

9. Rowsey JJ, Newson DL, Sexton DJ, Harms WK: Endophthalmitis current approaches. Ophthalmology 89:1055, 1982

10. Bannerman TL, Rhoden DL, McAllister SK, Miller JM, Wilson LA: The source of coagulase-negative staphylococci in the Endophthalmitis Vitrectomy Study. A comparison of eyelid and intraocular isolates using pulsed-field gel electrophoresis. Arch Ophthalmol 115:357, 1997

11. Speaker MG, Milch FA, Shah MK: Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology 98:639, 1991

12. Montan P, Lundstrom M, Stenevi U, Thorburn W: Endophthalmitis following cataract surgery in Sweden. The 1998 national prospective survey. Acta Ophthalmol Scand 80:258, 2002

13. Sandvig KU, Dannevig L: Postoperative endophthalmitis: Establishment and results of a national registry. J Cataract Refract Surg 29:1273, 2003

14. Allen HF, Mangiaracine AB: Bacterial endophthalmitis after cataract extraction. II. Incidence in 36,000 consecutive operations with special reference to preoperative topical antibiotics. Trans Am Acad Ophthalmol Otolaryngol 77:581, 1973

15. Kattan HM, Flynn HW, Pflugfelder SC, Robertson C, Forster RK: Noscomial endophthalmitis survey: Current incidence of infection following intraocular surgery. Ophthalmol 98:227, 1991

16. Eifrig CW, Flynn HW Jr, Scott IU, Newton J: Acute-onset postoperative endophthalmitis: review of incidence and visual outcomes (1995–2001). Ophthalmic Surg Lasers 33:373, 2002

17. Ho PC, Tolentino FI: Bacterial endophthalmitis after closed vitrectomy. Arch Ophthalmol 102:207, 1984

18. Driebe WT Jr, Mandelbaum S, Forster RK, Schwartz LK, Culbertson WW: Pseudophakic endophthalmitis: diagnosis and management. Ophthalmology 93:442, 1986

19. Cooper BA, Holekamp NM, Bohigian G, Thompson PA: Case-control study of endophthalmitis after cataract surgery comparing scleral tunnel and clear corneal wounds. Am J Ophthalmol 136:300, 2003

20. Nagaki Y, Hayasaka S, Kadoi C, et al: Bacterial endophthalmitis after small-incision cataract surgery: effect of incision placement and intraocular lens type. J Cataract Refract Surg 29:20, 2003

21. Scott IU, Flynn HW, Feuer WJ: Endophthalmitis after secondary intraocular lens implantation. Ophthalmology 102:1925, 1995

22. Jager RD, Aiello LP, Patel SC, Cunningham ET Jr: Risks of Intravitreal Injection: A Comprehensive Review. Retina 24, 676: 2004

23. Greenfield DS, Suner IJ, Schiffman J: Endophthalmitis after filtering surgery with mitomycin. Arch Ophthalmol 114:943, 1996

24. Higginbotham EJ, Stevens RK, Musch DC: Bleb-related endophthalmitis after trabeculectomy with mitomycin C. Ophthalmology 103:650, 1996

25. Wolner B, Liebmann JM, Sassani JW: Late bleb-related endophthalmitis after trabeculectomy with adjunctive 5-fluorouracil. Ophthalmology 98:1053, 1991

26. Gedde SJ, Scott IU, Tabandeh H, et al: Late endophthalmitis associated with glaucoma drainage implants. Ophthalmology 108:1323, 2001

27. Gilbert CM, Soong HK, Hirst LW: A two-year prospective study of penetrating ocular trauma at the Wilmer Ophthalmological Institute. Ann Ophthalmol 19:104, 1987

28. Brinton GS, Topping TM, Hyndiuk RA, et al: Posttraumatic endophthalmitis. Arch Ophthalmol 102:547, 1984

29. Thompson JT, Parver LM, Enger CL, Mieler WF, Liggett PE: Infectious endophthalmitis after penetrating injuries with retained intraocular foreign bodies. Ophthalmology 100:1468, 1993

30. Williams DF, Mieler WF, Abrams GW, Lewis H: Results and prognostic factors in penetrating ocular injuries with retained intraocular foreign bodies. Ophthalmology 95:911, 1988

31. Boldt HC, Pulido JS, Blodi CS, Folk JC, Weingeist TA: Rural endophthalmitis. Ophthalmology 96:1722, 1989

32. Gelender H: Bacterial endophthalmitis following cutting of sutures after cataract surgery. Am J Ophthalmol 94:528, 1982

33. Ficker L, Meredith TA, Wilson LA, Kaplan HJ, Kozarsky AM: Chronic bacterial endophthalmitis. Am J Ophthalmol 103:745, 1987

34. Fox GM, Jooneph BC, Flynn HW: Delayed-onset pseudophakic endophthalmitis. Am J Ophthalmol 111:163, 1991

35. Wisniewski SR, Capone A, Kelsey SF, et al: Characteristics after cataract extraction or secondary lens implantation among patients screened for the Endophthalmitis Vitrectomy Study. Ophthalmology 107:1274, 2000

36. Ormerod LD, Ho DD, Becker LE, et al: Endophthalmitis caused by the coagulase-negative staphylococci. 1. Disease spectrum and outcome. Ophthalmology 100:715, 1993

37. Ormerod LD, Becker LE, Cruise RJ, et al: Endophthalmitis caused by the coagulase-negative staphylococci 2. Factors influencing presentation after cataract surgery. Ophthalmology 100:72, 1993

38. Johnson MW, Doft BH, Kelsey SF, et al: The Endophthalmitis Vitrectomy Study. Relationship between clinical presentation and microbiologic spectrum. Ophthalmology 104:261, 1997

39. Packer AJ, Weingeist TA, Abrams GW: Retinal periphlebitis as an early sign of bacterial endophthalmitis. Am J Ophthalmol 96:66, 1983

40. Han DP, Wisniewski SR, Wilson LA, et al: Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study. Am J Ophthalmol 122:1, 1996

41. Irvine WE, Flynn HW, Murray TG, Rubsamen PE: Retained lens fragments after phacoemulsification manifesting as marked intraocular inflammation with hypopyon. Am J Ophthalmol 114:610, 1992

42. Aldave AJ, Stein JD, Deramo VA, et al: Treatment strategies for postoperative Propionibacterium acnes endophthalmitis. Ophthalmology 106:2395, 1999

43. Winward KE, Pflugfelder SC, Flynn HW Jr, Roussel TJ, Davis JL: Postoperative Propionibacterium endophthalmitis. Treatment strategies and long-term results. Ophthalmology 100:447, 1993

44. Zambrano W, Flynn HW Jr, Pflugfelder SC, et al: Management options for Propionibacterium acnes endophthalmitis. Ophthalmology 96:1100, 1989

45. Meisler DM, Palestine AG, Vastine DW: Chronic Propionibacterium endophthalmitis after extracapsular cataract extraction and intraocular lens implantation. Am J Ophthalmol 102:733, 1986

46. Meisler DM, Zakov ZN, Bruner WE, Hall GS: Endophthalmitis associated with sequestered intraocular Propionibacterium acnes. Am J Ophthalmol 104:428, 1987

47. Mandelbaum S, Forster RK, Gelender H, Culbertson W: Late onset endophthalmitis associated with filtering blebs. Ophthalmology 92:964, 1985

48. Poulsen EJ, Allingham RR: Characteristics and risk factors of infections after glaucoma filtering surgery. J Glaucoma 9:438, 2000

49. Song A, Scott IU, Flynn HW Jr, Budenz DL: Delayed-onset bleb-associated endophthalmitis: Clinical features and visual acuity outcomes. Ophthalmology 109:985, 2002

50. Brown RH, Yang LH, Wlaker SD, et al: Treatment of bleb infection after glaucoma surgery. Arch Ophthalmol 112:57, 1994

51. Mandelbaum S, Forster RK: Endophthalmitis associated with filtering blebs. Int Ophthalmol Clin 27:107, 1987

52. Lieb DF, Scott IU, Flynn HW Jr, Miller D, Feuer WJ: Open globe injuries with positive intraocular cultures: Factors influencing final visual acuity outcomes. Ophthalmology 110:1560, 2003

53. Davey RT, Tauber WB: Posttraumatic endophthalmitis: the emerging role of Bacillus cereus infection. Rev Infect Dis 9:110, 1987

54. Puliafito CA, Baker AS, Haaf J, Foster CS: Infectious endophthalmitis: A review of 36 cases. Ophthalmology 89:921, 1982

55. Schemmer GB, Driebe WT: Posttraumatic Bacillus cereus endophthalmitis. Arch Ophthalmol 105:342, 1987

56. Binder MI, Chua J, Kaiser PK, Procop GW, Isada CM: Endogenous endophthalmitis: An 18-year review of culture-positive cases at a tertiary care center. Medicine (Baltimore) 82:97, 2003

57. Greenwald MJ, Wohl LG, Sell CH: Metastatic bacterial endophthalmitis: A contemporary reappraisal. Surv Ophthalmol 31:81, 1986

58. Okada AA, Johnson RP, Liles WC, D'Amico DJ, Baker AS: Endogenous bacterial endophthalmitis. Report of a ten-year retrospective study. Ophthalmology 101:832, 1994

59. Schiedler V, Scott IU, Flynn HW Jr, et al: Culture-proven endogenous endophthalmitis: Clinical features and visual acuity outcomes. Am J Ophthalmol 137:725, 2004

60. Tanaka M, Kobayashi Y, Takebayashi H, Kiyokawa M, Qiu H: Analysis of predisposing clinical and laboratory findings for the development of endogenous fungal endophthalmitis. A retrospective 12-year study of 79 eyes of 46 patients. Retina 21:203, 2001

61. Barza M, Pavan PR, Doft BH, et al: Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study. Arch Ophthalmol 115:1142, 1997

62. Donahue SP, Kowalski RP, Jewart BH, Friberg TR: Vitreous cultures in suspected endophthalmitis. Biopsy or vitrectomy? Ophthalmology 100:452, 1993

63. Endophthalmitis Vitrectomy Study Group: Microbiologic factors and visual outcome in the endophthalmitis vitrectomy study. Am J Ophthalmol 122:830, 1996

64. Baum J, Peyman GA, Barza M: Intravitreal administration of antibiotic in the treatment of bacterial endophthalmitis. III. Consensus. Surv Ophthalmol 26:204, 1982

65. Baum JL: Antibiotic administration in the treatment of bacterial endophthalmitis. I. Periocular injections. Surv Ophthalmol 21:332, 1977

66. Bohigian GM, Olk RJ: Factors associated with a poor visual result in endophthalmitis. Am J Ophthalmol 101:332, 1986

67. Rowsey JJ, Stonecipher KG, Jensen H, Krueger R, Parmley VC: Culture and sensitivities of infectious endophthalmitis: A microbiological analysis of 302 intravitreal biopsies. Invest Ophthalmol Vis Sci 33(Suppl):745, 1992

68. Meredith TA: Antimicrobial pharmacokinetics in endophthalmitis treatment studies of ceftazidime. Trans Am Ophthalmol Soc 91:653, 1993

69. Meredith TA, Abdala C, Aguilar HE, Chanping L, Hageman GS: Toxicity of intravitreal ceftazidime and vancomycin. Invest Ophthalmol Vis Sci 36:3647, 1995

70. Oum B, D'Amico DJ, Kwak HW, Wong KW: Intravitreal antibiotic therapy with vancomycin and aminoglycoside: Examination of the retinal toxicity of repetitive injections after vitreous and lens surgery. Graefe's Arch Clin Exp Ophthalmol 230:56, 1992

71. Oum BS, D'Amico DJ, Wong KW: Intravitreal antibiotic therapy with vancomycin and aminoglycoside. An experimental study of combination and repetitive injections. Arch Ophthalmol 107:1055, 1989

72. Barza M: Factors affecting the intraocular penetration of antibiotics. The influence of route, inflammation, animal species and tissue pigmentation. Scan J Infect Dis 14(Suppl):151, 1978

73. El-Massry A, Meredith TA, Aguilar HE, et al: Aminoglycoside concentrations in the vitreous cavity after intravenous administration. Am J Ophthalmol 121:684, 1996

74. Aguilar HE, Meredith TA, Shaarawy A, Kincaid M, Dick J: Vitreous cavity penetration of ceftazidime after intravenous administration. Retina 15:154, 1995

75. Martin DF, Ficker LA, Aguilar HA, et al: Vitreous cefazolin levels after intravenous injection. Effects of inflammation, repeated antibiotic doses, and surgery. Arch Ophthalmol 108:411, 1990

76. Meredith TA, Aguilar HE, Shaarawy A, et al: Vancomycin levels in the vitreous cavity after intravenous administration. Am J Ophthalmol 119:774, 1995

77. Wilson L: Endophthalmitis. Trans Ophthalmol Soc UK 105:56, 1986

78. Barza M, Kane A, Baum J: Pharmacokinetics of intravitreal carbenicillin, cefazolin, and gentamicin in rhesus monkeys. Invest Ophthalmol Vis Sci 24:1602, 1983

79. Barza M: Animal models in the evaluation of chemotherapy of ocular infections. In Experimental Models in Antimicrobial Chemotherapy. London: Harcourt Brace Jovanovich, 1986:187

80. Aguilar HE, Meredith TA, el Massry A, et al: Vancomycin levels after intravitreal injection. Effects of inflammation and surgery. Retina 15:428, 1995

81. Doft BH, Weiskopf J, Nillson-Ehle I, Wingard L: Amphotericin clearance in vitrectomized versus non-vitrectomized eyes. Ophthalmology 92:1601, 1985

82. Mandell BA, Meredith TA, Aguilar E, et al: Effects of inflammation and surgery on amikacin levels in the vitreous cavity. Am J Ophthalmol 115:770, 1993

83. Meredith TA, Mandell BA, Aguilar EA, et al: Amikacin levels after intravitreal injection: Effects of inflammation and surgery. Invest Ophthalmol Vis Sci 33/4:747, 1992

84. Campochiaro PA, Conway BP: Aminoglycoside toxicity: A survey of retinal specialists. Arch Ophthalmol 109:946, 1991

85. Campochiaro PA, Lin JI, Group AS: Aminoglycoside toxicity in the treatment of endophthalmitis. Arch Ophthalmol 112:48, 1994

86. Conway BP, Campochiaro PA: Macular infarction after endophthalmitis treated with vitrectomy and intravitreal gentamicin. Arch Ophthalmol 104:367, 1986

87. Conway BP, Tabatabay CA, Campochiaro PA, et al: Gentamicin toxicity in the primate retina. Arch Ophthalmol 107:107, 1989

88. Benz MS, Scott IU, Flynn HW, Unonius N, Miller D: Endophthalmitis isolates and antibiotic sensitivities: A 6-year review of culture-proven cases. Am J Ophthalmol 137:38, 2004

89. Ferencz JR, Assia EI, Diamantstein L, Rubinstein E: Vancomycin concentration in the vitreous after intravenous and intravitreal administration for postoperative endophthalmitis. Arch Ophthalmol 117:1023, 1999

90. Gan IM, van Dissel JT, Beekhuis WH, Swart W, van Meurs JC: Intravitreal vancomycin and gentamicin concentrations in patients with postoperative endophthalmitis. Br J Ophthalmol 85:1289, 2001

91. Haider SA, Hassett P, Bron AJ: Intraocular vancomycin levels after intravitreal injection in post-cataract extraction endophthalmitis. Retina 21:210, 2001

92. Pflugfelder SC, Hernandez E, Fleisler SJ, et al: Intravitreal vancomycin. Arch Ophthalmol 105:831, 1987

93. Campochiaro PA, Green WR: Toxicity of intravitreal ceftazidime in primate retina. Arch Ophthalmol 110:1625, 1992

94. O'Day DM, Jones DB, Patrinely J, Elliott JH: Staphylococcus epidermidis endophthalmitis: visual outcome following noninvasive therapy. Ophthalmology 89:354, 1982

95. Fiscella RG, Shapiro MJ, Solomon MJ, et al: Ofloxacin penetration into the eye after intravenous and topical administration. Retina 17:535, 1997

96. Hariprasad SM, Mieler WF, Holz ER: Vitreous and aqueous penetration of orally administered gatifloxacin in humans. Arch Ophthalmol 121:345, 2003

97. El Baba FZ, Trousdale MD, Gauderman WJ, Wagner DB, Liggett PE: Intravitreal penetration of oral ciprofloxacin in humans. Ophthalmology 99:483, 1992

98. Kowalski RP, Karenchak LM, Eller AW: The role of ciprofloxacin in endophthalmitis therapy. Am J Ophthalmol 116:695, 1993

99. Lesk MR, Ammann H, Marcil G, et al: The penetration of oral ciprofloxacin into the aqueous humor, vitreous and subretinal fluid of humans. Am J Ophthalmol 115:623, 1993

100. Hariprasad SM, Mieler WF, Holz ER: Vitreous penetration of orally administered gatifloxacin in humans. Trans Am Ophthalmol Soc 100:153, 2002

101. Mather R, Karenchak LM, Romanowski EG, Kowalski RP: Fourth generation fluoroquinolones: New weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol 133:463, 2002

102. Christmas NJ, Smiddy WE: Vitrectomy and systemic fluconazole for treatment of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers 27:1012, 1996

103. Hariprasad SM, Mieler WF, Holz ER, et al: Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch Ophthalmol 122:42, 2004

104. Barza M, Kane A, Baum JL: Regional differences in ocular concentration of gentamicin after subconjunctival and retrobulbar injection in the rabbit. Invest Ophthalmol Vis Sci 83:407, 1977

105. Barza M, Kane A, Baum J: Intraocular penetration of gentamicin after subconjunctival retrobulbar injection. Am J Ophthalmol 85:541, 1978

106. Barza M, Kane A, Baum JL: Intraocular levels of cefamandole compared with cefazolin after subconjunctival injection in rabbits. Invest Ophthalmol Vis Sci 18:250, 1979

107. Barza M, Kane A, Baum J: Ocular penetration of subconjunctival oxacillin, methicillin, and cefazolin in rabbits with staphylococcal endophthalmitis. J Infect Dis 145:899, 1982

108. Barza M, Lynch E, Baum JL: Pharmacokinetics of newer cephalosporins after subconjunctival and intravitreal injection in rabbits. Arch Ophthalmol 111:121, 1993

109. Irvine AR: The role of vitrectomy in endophthalmitis. Trans Pac Coast Oto-Ophthalmol Soc 58:185, 1977

110. Peyman GA, Raichand M, Bennett TO: Management of endophthalmitis with pars plana vitrectomy. Br J Ophthalmol 64:472, 1980

111. Clark WL, Kaiser PK, Flynn HW Jr, et al: Treatment strategies and visual acuity outcomes in chronic postoperative Propionibacterium acnes endophthalmitis. Ophthalmology 106:1665, 1999

112. Doft BH, Wisniewski SR, Kelsey SF, Fitzgerald SG: Diabetes and postoperative endophthalmitis in the endophthalmitis vitrectomy study. Arch Ophthalmol 119:650, 2001

113. Doft BH, Kelsey SF, Wisniewski SR: Additional procedures after the initial vitrectomy or tap-biopsy in the Endophthalmitis Vitrectomy Study. Ophthalmology 105:707, 1998

114. Aguilar HE, Meredith TA, Drews CD, et al: Treatment of experimental S. aureus endophthalmitis with vancomycin, cefazolin and corticosteroids. Invest Ophthalmol Vis Sci 31(Suppl):308, 1990

115. Aguilar HE, Meredith TA, Drews C, et al: Comparative treatment of experimental Staphylococcus aureus endophthalmitis. Am J Ophthalmol 121:310, 1996

116. Davey PG, Barza M, Stuart M: Dose response of experimental Pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence of resistance to “late” treatment of infections. J Infect Dis 155:518, 1987

117. Forster RK: Experimental postoperative endophthalmitis. Trans Am Ophthalmol Soc 505, 1992

118. Shaarawy A, Grand MG, Meredith TA, Ibanez H: Persistent infection after intravitreal antimicrobial therapy. Ophthalmology 102:382, 1995

119. Stern GA, Engel HM, Driebe WT: Recurrent postoperative endophthalmitis. Cornea 9:102, 1990

120. Essman TF, Flynn HW Jr, Smiddy WE, et al: Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers 28:185, 1997

121. Doft BM, Kelsey SF, Wisniewski SR: Retinal detachment in the endophthalmitis vitrectomy study. Arch Ophthalmol 118:1661, 2000

122. Nelsen PT, Marcus DA, Bovino JA: Retinal detachment following endophthalmitis. Ophthalmology 92:1112, 1985

123. Meredith TA, Aguilar HE, Miller MJ, et al: Comparative treatment of experimental Staphylococcus epidermidis endophthalmitis. Arch Ophthalmol 108:857, 1990

124. Coats ML, Peyman GA: Intravitreal corticosteroids in the treatment of exogenous fungal endophthalmitis. Retina 12:46, 1992

125. Maxwell DP Jr, Brent BD, Diamond JG, Wu L: Effect of intravitreal dexamethasone on ocular histopathology in a rabbit model of endophthalmitis. Ophthalmology 98:1370, 1991

126. Peyman GA, Herbst R: Bacterial endophthalmitis: Treatment with intraocular injection of gentamicin and dexamethasone. Arch Ophthalmol 91:416, 1974

127. Yoshizumi MO, Lee GC, Equi RA, et al: Timing of dexamethasone treatment in experimental Staphylococcus aureus endophthalmitis. Retina 18:130, 1998

128. Das T, Jalali S, Gothwal VK, Sharma S, Naduvilath TJ: Intravitreal dexamethasone in exogenous bacterial endophthalmitis: Results of a prospective randomised study. Br J Ophthalmol 83:1050, 1999

129. Shah GK, Stein JD, Sharma S, et al: Visual outcomes following the use of intravitreal steroids in the treatment of postoperative endophthalmitis. Ophthalmology 107:486, 2000

130. Dev S, Gonzalez-Vivas , Han DP, et al: The role of intravitreal dexamethasone as an adjunct in the management of postoperative bacterial endophthalmitis. 2004 In press

131. Narang S, Gupta A, Gupta V, et al: Fungal endophthalmitis following cataract surgery: Clinical presentation, microbiological spectrum, and outcome. Am J Ophthalmol 132:609, 2001

132. Reynolds AC, Skuta GL, Monlux R, Johnson J: Management of blebitis by members of the American Glaucoma Society: A survey. J Glaucoma 10:340, 2001

133. Ciulla TA, Beck AD, Topping TM, Baker AS: Blebitis, early endophthalmitis, and late endophthalmitis after glaucoma-filtering surgery. Ophthalmology 104:986, 1997

134. Affeldt JC, Flynn HW Jr, Forster RK, et al: Microbial endophthalmitis resulting from ocular trauma. Ophthalmology 94:407, 1987

135. Reynolds DS, Flynn HW Jr: Endophthalmitis after penetrating ocular trauma. Curr Opin Ophthalmol 8:32, 1997

136. Ariyasu RG, Kumar S, La Bree LD, Wagner DG, Smith RE: Microorganisms cultured from the anterior chamber of ruptured globes at the time of repair. Am J Ophthalmol 119:181, 1995

137. Sabaci G, Bayer A, Mutlu FM, Karagul S, Yildirim E: Endophthalmitis after deadly-weapon-related open-globe injuries: Risk factors, value of prophylactic antibiotics, and visual outcomes. Am J Ophthalmol 133:62, 2002

138. Meredith TA, Trabelsi A, Miller MJ, Aguilar E, Wilson LA: Spontaneous sterilization of experimental Staphylococcus epidermidis endophthalmitis. Invest Ophthalmol Vis Sci 31:181, 1990

139. Smith MA, Sorenson JA, D'Aversa G, et al: Treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis with intravitreal vancomycin and intravitreal dexamethasone. J Infect Dis 175:462, 1997

140. Osato MS, Jensen HG, Trousdale MD: The comparative in vitro activity of ofloxacin and selected ophthalmic agents against ocular bacterial isolates. Am J Ophthalmol 108:380, 1989

141. Bode DD Jr, Gelender H, Forster RK: A retrospective review of endophthalmitis due to coagulase-negative staphylococci. Br J Ophthalmol 69:915, 1985

142. Ficker LA, Meredith TA, Wilson LA, Kaplan HJ: The role of vitrectomy in staphylococcus epidermitis endophthalmitis. Br J Ophthalmol 72:386, 1987

143. Mao LK, Flynn HW, Miller D, Pflugfelder SC: Endophthalmitis caused by Staphylococcus aureus. Am J Ophthalmol 116:584, 1993

144. Jett BD, Jensen HG, Atkuri RV, Gilmore MS: Evaluation of therapeutic measures for treating endophthalmits caused by isogenic toxin-producing and toxin-nonproducing Enterococcus faecalis strains. Invest Ophthalmol Vis Sci 36:9, 1995

145. Mao LK, Flynn HW Jr, Miller D, Pflugfelder SC: Endophthalmitis caused by streptococcal species. Arch Ophthalmol 110:798, 1992

146. Miller JJ, Scott IU, Flynn HW Jr, et al: Endophthalmitis cause by Streptococcus pneumoniae. Am J Ophthalmol 138:231, 2004

147. Eifrig CW, Scott IU, Flynn HW Jr, Miller D: Endophthalmitis caused by Pseudomonas aeruginosa. Ophthalmology 110:1714, 2003

148. Vahey J, Flynn HW: Results in the management of Bacillus endophthalmitis. Ophthal Surg 22:681, 1991

149. Beecher DJ, Pulido JS, Barney NP, Wong ACL: Extracellular virulence factors in Bacillus cereus endophthalmitis: Methods and implication of involvement of hemolysin BL. Infect Immunol 63:632, 1995

150. Foster RE, Martinez JA, Murray TG, et al: Useful visual outcomes after treatment of Bacillus cereus endophthalmitis. Ophthalmology 103:390, 1996

151. O'Day DM, Smith RS, Gregg CR, et al: The problem of Bacillus species infection with special emphasis on the virulence of Bacillus cereus. Ophthalmology 88:833, 1981

152. Chen JC, Roy M: Epidemic Bacillus endophthalmitis after cataract surgery II: Chronic and recurrent presentation and outcome. Ophthalmology 107:1038, 2000