Postoperative Endophthalmitis - Cataract Surgery, 3rd Edition

Cataract Surgery, 3rd Edition

PART VII – Management of Complications

Chapter 55 – Postoperative Endophthalmitis

David A. Eichenbaum, MD,
Robert I. Park, MD,
Trexler M. Topping, MD

Contents

	•	Epidemiology
	•	Clinical Presentation
	•	Symptoms
	•	Examination
	•	Differential Diagnosis
	•	Endophthalmitis Vitrectomy Study
	•	Organisms
	•	Investigations
	•	Treatment
	•	Clinical Course
	•	Prognosis
	•	Prevention
	•	Chronic Postoperative Endophthalmitis
	•	Conclusion

CHAPTER HIGHLIGHTS

	≫	Clinical signs and symptoms
	≫	Differential diagnosis
	≫	Lessons from the Endophthalmitis Vitrectomy Study
	≫	Treatment protocols

Postoperative endophthalmitis is a rare but much feared complication of cataract surgery. The potential sequelae of untreated or late treated endophthalmitis include loss of vision, severe ocular damage, and, in some cases, phthisis bulbi or enucleation. However, early detection and treatment of endophthalmitis may limit damage, and patients may regain good vision. Early identification and prompt treatment or referral of endophthalmitis cases are thus crucial factors in salvaging a patient's vision.

This chapter addresses the issue of post-cataract extraction endophthalmitis and should not be directly extrapolated to cases of trauma or glaucoma filtration-related endophthalmitis because the mode of infection and the causative organisms are very different. Emphasis is placed on the results of the Endophthalmitis Vitrectomy Study (EVS), a randomized, prospective, multicenter trial evaluating the treatment of endophthalmitis following cataract surgery (see later description).

Epidemiology

A number of retrospective studies have been undertaken to define the incidence of endophthalmitis following cataract extraction.^[1–7] The overall results appear in Table 55-1. The incidence of endophthalmitis has been reported to be between 0.04 and 0.22%.^[1–5] It is worthy to note that incidences have been decreasing since the early 1990s, and in the more recent series, the majority of the surgeries have been performed using small-incision phacoemulsification. The most comprehensive review was performed by Javitt et al.,^[4] who reviewed billing records for approximately 50% of all Medicare beneficiaries over the age of 65 who underwent cataract extraction in 1984. The incidence of endophthalmitis was found to be 0.17% for intracapsular cataract extraction and 0.12% for extracapsular cataract extraction. The primary criticism of Javitt's study is that it was based on a review of Medicare billing records. Although the results are likely to be unbiased, clinical information about each case was limited; that is, no data regarding the organisms or culture positivity or negativity were available. Although the exact incidence of endophthalmitis varied from study to study, all reported the incidence of endophthalmitis to be well below 0.5% following cataract surgery.

Table 55-1 -- Incidence of endophthalmitis after cataract surgery

Year	Author	Number of Charts	Overall Incidence	Culture (+) Incidence	Location
2004	Wong et al	44,804	0.076%	0.040	Singapore
2005	Miller et al	15,920	0.04%	0.03%	Miama, FL
1998	Aaberg et al^[1]	41,654	0.082%	NA	Miami, FL
1991	Menikoff et al^[2]	24,105	0.22%	0.17%	New York, NY
1991	Kattan et al^[3]	30,002	0.089%	0.072%	Miami, FL
1991	Javitt et al^[4]	338,141	0.13%	NA	Medicare database
1974	Allen and Mangiaracine^[5]	36,000	NA	0.086	Boston, MA

NA, Not applicable.

A number of factors that increase the risk of postoperative endophthalmitis have been identified. Diabetes mellitus, chronic alcoholism, complicated surgery, wound complications, intracapsular vs. extracapsular cataract extraction, capsular rupture, amount and duration of instrumentation, history of prior surgery, vitreous loss, and intraocular lens (IOL) type have been implicated with regard to the increased rate of endophthalmitis.^[11–15] An interesting finding from Miller's recent study is that an increased incidence of endophthalmitis was found in right-eye surgery performed by right-handed surgeons through a temporal approach. This finding implicates an inferior incision location as an additional risk factor. Of particular note are data from Javitt's review of the Medicare database in 1991, which demonstrated that the incidence of endophthalmitis after cataract extraction with anterior vitrectomy was significantly higher than for cataract surgery alone (0.58% for cataract extraction with anterior vitrectomy vs. 0.13% for cataract surgery alone, P <0.0001). Javitt's conclusion that complicated surgery increases the risk of infection has been supported in subsequent studies.^[4,][7–9]

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Clinical presentation

A high level of clinical suspicion must be maintained during the examination of postoperative patients. A detailed history including the time course of onset of symptoms and a careful examination may increase the rate of early detection of endophthalmitis. The circumstances of the surgery and any intraoperative complications should be known to the examiner. Patients should be well informed of the signs of possible infection on the day of surgery, as well as during the postoperative visit, and should be instructed to contact the surgeon's office immediately should they develop postoperative problems. Early detection by patients may give the best hope for a good outcome. The surgeon should not fear overdiagnosis, because the sequelae of a missed diagnosis are severe.

Symptoms

Blurred vision, a red eye, and pain are common complaints of patients developing endophthalmitis. Counterintuitively, blurred vision and a red eye were more common than pain as the presenting symptom in the EVS.^[16] Table 55-2 summarizes the presenting symptoms in the EVS.

Table 55-2 -- Patients presenting with type of symptom in Endophthalmitis Vitrectomy Study^[11]

Symptom	Percentage
Blurred vision	94.3%
Red eye	82.1%
Pain	74.3%
Swollen lid	34.5%

The median time to presentation in the EVS was 6 days after cataract extraction, with a majority presenting within 2 weeks of cataract extraction. However, a significant number of patients (22%) presented after 2–6 weeks. Table 55-3 shows the distribution of time to presentation in the EVS.

Table 55-3 -- Patients presenting at given periods after cataract extraction in Endophthalmitis Vitrectomy Study

Number of Days Post-cataract Extraction	Percentage of Endophthalmitis Patients
0–3 days	24%
4–7 days	37%
8–13 days	17%
2–6 weeks	22%

Data from 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 113:1479–1496, 1995.

Other studies demonstrate a similar time course, with a majority presenting between 3 and 10 days of surgery and 88% presenting within 6 weeks of surgery.^{[6,][7,][17,][18]} Late-onset endophthalmitis is discussed later in the chapter.

Examination

A thorough ocular examination should be performed. Common presenting signs in the EVS are listed in Table 55-4. Anterior segment examination may reveal conjunctival injection or chemosis, significant anterior segment inflammation, a hypopyon, an afferent pupillary defect, and a loss of red reflex. Corneal ring ulcers may be present in infections with streptococci, clostridia, and bacilli; in rare cases of Clostridium endophthalmitis, a gas bubble may be seen in the anterior chamber. Any abnormalities of the surgical wound(s) should be noted. Wound gape, vitreous wick, wound leaks, or torn or broken sutures, because they have been found to be associated with endophthalmitis. The wound should always be checked with a Seidel test.^[19–23] Examination of the retina should be performed to assess the clarity of the ocular media and to determine the status of the retina. If no view of the retina is possible, ultrasound examination should be performed to assess for retinal detachment, retained lens fragments, choroidal thickening, or vitreous membranes.

Table 55-4 -- Incidence of ocular signs in Endophthalmitis Vitrectomy Study

Sign	Incidence
Hypopyon	85.7%
Red eye	82.1%
No view of retinal vessel	79.1%
Loss of red reflex	68.0%
Corneal infiltrate or ring ulcer	4.8%

Differential diagnosis

A number of conditions may present with clinical findings similar to endophthalmitis, and a distinction between early endophthalmitis and other entities may be difficult to find. Retained nuclear fragments or a posteriorly displaced lens nucleus may cause severe intraocular inflammation.^[24] The surgeon is generally aware of dislocation of any lens fragments; however, in the case of inadvertent lens particle dislocation, intraocular pressure may be useful in distinguishing lens particle inflammation from endophthalmitis. The intraocular pressure is more often elevated with lens particle retention than with endophthalmitis. Careful examination of the retina and vitreous for retained lens fragments, either by visualization or ultrasound, must be performed. Other causes of intraocular inflammation must be considered. Severe anterior segment inflammation and a hypopyon may accompany corneal ulcers without endophthalmitis (Figure 55-1). Incarceration of vitreous in the surgical wound may cause an intraocular inflammation that is generally less severe than endophthalmitis but may be mistaken for early endophthalmitis. Intraocular blood may be mistaken for inflammation. Reaction to IOL materials and processing chemicals is rare today but must be considered; during the early days of IOLs, reactions to residual polishing compounds and sterilizing agents were reported.^[25,][26]



Figure 55-1 Hypopyon in patient with postoperative endophthalmitis.

Alternative sources of endophthalmitis must also be considered during history taking. Concurrent infections, including dental abscesses, and previous surgery, especially glaucoma filtration surgery, are potential sources of seeding of bacteria into the eye and have broad implications regarding the infecting organism and potential clinical course.

Unfortunately, there is no specific combination of signs and symptoms that a surgeon may use to definitively diagnose endophthalmitis, especially early cases. It is especially imperative not to disregard inflammation following complicated surgery with posterior capsule rupture and lens particle loss as non-infectious, since data support complicated surgery as being a significant risk factor for infectious endophthalmitis.^[4,][7–9] Given the severity of the damage that may be inflicted by endophthalmitis, questionable cases should be treated empirically as endophthalmitis.

Endophthalmitis vitrectomy study

The EVS^[16] was a National Eye Institute-funded multicenter, prospective, randomized trial evaluating the effectiveness of immediate vitrectomy and intravenous antibiotics in the treatment of postoperative bacterial endophthalmitis. Specifically, the EVS looked at 420 cases of endophthalmitis occurring after cataract extraction. Patients were randomized to either pars plana vitrectomy or vitreous needle biopsy, and intravenous antibiotics or no intravenous antibiotics. Study end-points were media clarity and visual acuity. All patients received the following:

	1.	Intravitreal vancomycin (1mg/0.1mL) and amikacin (0.4mg in 0.1mL)
	2.	Subconjunctival vancomycin (25mg/0.5mL), ceftazidime (100mg/0.5mL), and dexamethasone sodium phosphate (6mg in 0.25mL). Subconjunctival amikacin (25mg/0.1mL) was substituted for ceftazidime if the patient was allergic to penicillin
	3.	Topical vancomycin, 50mg/mL; amikacin, 20mg/mL; cycloplegic; and prednisolone acetate 1%
	4.	Oral prednisone, 30mg bid, for 5–10 days.

Patients randomized to the intravenous antibiotic arm received the following:

	1.	Ceftazidime, 2g q8h, or ciprofloxacin, 750mg PO bid, if allergic to penicillin
	2.	Amikacin, 7.5mg/kg IV loading dose and then 6mg/kg every 12h. Doses were adjusted to keep peak and trough levels within an acceptable level.

The EVS demonstrated several important points:

	1.	There was no difference in final visual acuity or media clarity whether or not intravenous antibiotics were used. The findings were consistent across all subsets of patients.
	2.	Patients with light perception vision who received pars plana vitrectomy had a threefold increase in the likelihood of achieving 20/40, a twofold chance of achieving 20/100 vision, and a 50% decrease in the likelihood of severe visual loss as compared with patients receiving vitreous needle biopsy.
	3.	Patients with hand-motions vision or better demonstrated no significant difference in final visual acuity or media clarity whether or not immediate vitrectomy was performed.

The EVS should be used as a general guide to the care of postoperative endophthalmitis patients. Clinical judgment should, however, be used to determine care on a case-by-case basis. Coverage of the details of the EVS is beyond the scope of this chapter; for more information, see EVS journal articles.^{[16,][27–33]}

Organisms

Identification of the infectious organism has been reviewed in a number of studies. The distribution of organisms causing endophthalmitis in the EVS appears in Table 55-5.^[27]Microbiologic culture growth was demonstrated in 69.3% of samples, and Gram-positive coagulase-negative organisms predominated.

Table 55-5 -- Incidence of inciting organisms in Endophthalmitis Vitrectomy Study

Organism	Incidence
Gram positive, coagulase negative (Staphylococcus epidermidis)	70.0%
Staphylococcus aureus	9.9%
Streptococcus	9.0%
Miscellaneous Gram-positive	3.1%
Enterococcus	2.2%
Gram-negative	5.9%

Data from Han DP, Wisniewski SR, Wilson LA et al: Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study, Am J Ophthalmol 122:1–17, 1996.

Although the exact percentages of organisms causing endophthalmitis varies through other smaller studies, the trends seen in the EVS are upheld.^{[6,][7,][10,][18,][19,][37,][38]} Gram-positive, coagulase-negative bacteria, Staphylococcus aureus, and Streptococcus species are reported to be the three leading infecting organisms in post-cataract extraction endophthalmitis. The vast majority of culture-positive infections yield a single organism. ^[10]

Late-onset endophthalmitis associated with glaucoma filtration surgery presents a very different microbiologic spectrum. Several studies have reported a predominance ofStreptococcus and Gram-negative bacteria in bleb-associated endophthalmitis.^[38–41] Because of the virulence of the causative organisms, patients with bleb-associated endophthalmitis carry a much poorer visual prognosis than early post-cataract extraction endophthalmitis. The virulence of the causitive organisms for bleb associated endophthalmitis leads to poorer visual results, and evidence supports more aggressive intervention for patients with bleb-associated endophthalmitis, with patients receiving prompt pars plana vitrectomy having better visual outcomes.^[40] Fungal endophthalmitis is generally uncommon but must be considered as a potential cause.

Investigations

Once the clinical diagnosis of endophthalmitis has been made, anterior-chamber and vitreous samples should be obtained for Gram staining and culture because the results from the vitreous and anterior chamber biopsies will guide antibiotic selection during postoperative treatment. Vitreous samples have been demonstrated to show growth at a greater rate than anterior-chamber samples.^[42] However, in early cases of endophthalmitis with an intact capsule and posterior-chamber (PC) IOL, anterior-chamber biopsies have been found to show growth even with no growth from vitreous biopsies.^[43]

The EVS guidelines should be followed, although with some caveats. Patients presenting with hand-motions vision or better may receive anterior chamber and vitreous needle biopsy with an injection of intravitreal antibiotics. Patients with light perception or nonlight perception vision should receive an anterior-chamber biopsy with pars plana vitrectomy and intravitreal antibiotics. Clinical judgment, however, must be used to temper the decision to perform or not perform pars plana vitrectomy. Patients with a rapidly worsening clinical picture should be considered for immediate vitrectomy because the etiologic organism may be extremely virulent. A low threshold for vitrectomy should be used for diabetic and immunocompromised patients. In the EVS, diabetic patients with endophthalmitis demonstrated a nonstatistically significant trend toward better outcome with pars plana vitrectomy than with needle biopsy.^[32] The samples size, however, was small; a larger study is required to further investigate this trend.

Collection and antibiotic injection

Needle biopsy

Needle biopsy samples may be taken in the operating room or in the office setting if the appropriate equipment is available. Virtually all samples may be taken under local anesthesia; only in rare cases of severe periorbital inflammation is general endotracheal anesthesia required. Occasionally, a retrobulbar or subconjunctival block with 2% lidocaine is performed, although subconjuctival anesthesia with 2% lidocaine is usually adequate. The eye is then prepared in the usual sterile fashion, and a lid speculum is placed. Conjunctival cultures are generally not taken. Next, several drops of 5% povidone-iodine are instilled into the fornices, and the eye is not disturbed for several minutes to allow antimicrobial action by the povidone-iodine.

Table 55-6 lists the steps taken in obtaining samples. A 27- or 30-gauge needle is inserted into the anterior chamber through the peripheral clear cornea, and 0.1mL of fluid is aspirated into a tuberculin syringe. Care is taken to avoid any previous surgical incisions. If a capsule or PC IOL is present, a pars plana needle biopsy may be obtained by passing a 25-gauge needle 3.5mm posterior to the limbus into the midvitreous. In either case, 0.2–0.3mL should be gently aspirated. If a sample cannot be aspirated with a 25-gauge needle, a 23-gauge needle passed in the same location can be used. If no sample can be obtained during needle-tap vitreous biopsy, the patient should receive a standard three-port pars plana vitrectomy. Otherwise, antibiotics should be injected into the midvitreous through a 25-gauge, ½-inch needle placed 3.5mm posterior to the limbus. The intraocular pressure is checked, and a second anterior chamber paracentesis can be performed if the pressure is elevated. The anterior chamber and vitreous samples are sent for Gram staining and culture.

Table 55-6 -- Treatment of endophthalmitis: anterior chamber and vitreous biopsy and injection of antibiotics

Needle biopsy

Anterior chamber

	1.	Insert 30-gauge needle attached to a tuberculin syringe. Avoid previous surgical incisions.
	2.	Withdraw 0.1ml aqueous solution.

Vitreous chamber

	1.	Insert a 25-gauge, ½-inch needle into the midvitreous chamber through a point 3.5mm posterior to the limbus.
	2.	Gently withdraw 0.2–0.3mL fluid.
	3.	Use a 23- or 22-gauge needle if there is no vitreous aspirated with moderate suction. If the yield continues to be poor, proceed to three-port vitrectomy.
	4.	Otherwise, inject antibiotics through a 30-gauge, ½-inch needle into the midvitreous through a point 3.5mm posterior to the limbus.
	5.	Check intraocular pressure and repeat anterior chamber paracentesis to relieve pressure, if necessary.

Pars plana vitrectomy

Prepare a three-port pars plana vitrectomy using a 6-mm infusion cannula.

Anterior chamber

	1.	Insert 30-gauge needle attached to a tuberculin syringe. Avoid previous surgical incisions.
	2.	Withdraw 0.1mL aqueous solution.

Vitreous chamber

	1.	Perform a core vitrectomy.
	2.	Close two of three sclerotomies.
	3.	Inject antibiotics and then close final sclerotomy.
	4.	Check intraocular pressure and perform anterior chamber paracentesis, if necessary, to relieve pressure.

Pars plana vitrectomy

Pars plana vitrectomy should be performed in the operating room under local or general anesthesia. Generally, a retrobulbar block with 2% lidocaine and 0.75% bupivacaine is performed. The eye is then prepared in the usual sterile fashion, and a lid speculum is placed. Conjunctival cultures are not routinely taken. Table 55-6 lists the steps taken in obtaining samples.

The eye is prepared for a standard three-port vitrectomy. A 6mm infusion cannula is placed because the view into the vitreous is often very poor. To obtain anterior-chamber samples, a 25- or 27-gauge needle is inserted into the anterior chamber at the limbus, and 0.1mL of fluid is aspirated into a tuberculin syringe. Care is taken to avoid any previous surgical incisions. The pars plana vitrectomy is performed. On initiation of the pars plana vitrectomy, prior to turning on the infusion, 0.2–0.3mL of undiluted vitreous fluid is withdrawn. This fluid is often manually aspirated into a syringe connected to the infusion line. The infusion is then opened, and the core vitrectomy is carried out. Two of the three sclerotomies are closed, and antibiotics are injected before closure of the final sclerotomy. All surgical wound abnormalities from the initial surgery, including wound gape, exposed sutures, vitreous wick, and so on, should be corrected before antibiotic injection and closure. In addition to the anterior-chamber and vitreous sample, the vitrectomy cassette is sent for concentration, culture, and Gram staining.

Other surgical techniques have been explored for managing postoperative endophthalmitis. Use of intraocular endoscopy has been reported as an adjunct in surgery.^[34] There is limited literature that performing more aggressive procedures, including scleral buckling, at the time of initial vitrectomy decrease the incidence of additional procedures.^[35] Small-gauge vitrectomy, which is theoretically a less-traumatic procedure with better preservation of the conjunctive, has been described for treatment in this setting.^[36] Our recommendation is to limit surgical intervention to standard pars plana vitrectomy at the time of initial surgery unless more evidence emerges supporting the facility of more aggressive surgery.

Culture

Specimens obtained from anterior-chamber aspiration and vitreous needle biopsy or pars plana vitrectomy should be cultured and stained separately. Cassette washings from pars plana vitrectomy should be concentrated by centrifuge or filtration before culture and staining. Samples should be plated on blood agar, chocolate agar, Sabouraud, and thioglycolate broth and should be cultured in aerobic and anaerobic conditions. Samples should be placed on slides and stained using Gram and Giemsa stains. A positive culture result is defined as growth on two or more media or confluent growth on one solid medium at the site of inoculation.

Treatment

Initial treatment

Initial treatment is directed toward the sterilization of the eye using intravitreal, topical, and oral antibiotics. Most vitreoretinal surgeons agree that intravitreal antibiotics are crucial for maximizing chances for a good outcome. The authors choose to inject two antibiotics: vancomycin (1mg in 0.1mL) and ceftazidime (2.5mg in 0.1mL). In cases of penicillin or cephalosporin allergy, we inject vancomycin (1mg in 0.1mL) and amikacin (0.4mg in 0.1mL). Table 55-7 summarizes the combination of medications recommended.

Table 55-7 -- Initial therapeutic regimen for endophthalmitis

Intravitreal injection for endophthalmitis

	1.	Vancomycin 1mg in 0.1mL normal saline
	2.	Ceftazidime 2.5mg in 0.1mL normal saline
	3.	Dexamethasone 400μg in 0.1mL normal saline is reasonable to consider as an adjunct.
	4.	Substitute amikacin 0.4mg in 0.1mL water for ceftazidime in patients allergic to penicillin or cephalosporin

Topical regimen

	1.	Vancomycin 25–50mg/mL with Gentamicin 11–14mg/mL hourly if the patient has been receiving fourth-generation quinolones
	2.	Consider topical gatifloxacin 0.3% or topical moxifloxacin 0.5% hourly in lieu of fortified antibiotics if the patient has not received fourth-generation fluoroquinolones
	3.	Scopolamine 0.25% twice daily
	4.	Prednisolone acetate 1% hourly

Oral regimen

Moxifloxacin or Gatifloxacin 400mg once each day

Dilutions must be performed carefully, especially in the case of amikacin, because higher concentrations may be toxic to the eye or may cause systemic complications. Although dilutions can be performed by the surgeon, intraocular antibiotics may be safer when performed by the pharmacist.

Choice of antibiotics

Controversy exists regarding the choice of antibiotics for intravitreal injection. The EVS used a combination of antibiotics, including intravitreal vancomycin and amikacin, subconjunctival vancomycin, ceftazidime (amikacin if patients were allergic to penicillin or cephalosporin), and dexamethasone, and topical vancomycin and amikacin postoperatively. The EVS's empiric choice to use multiple antibiotics has been shown to be best in clinical evaluation. In a review of culture-proven endophthalmitis cases, it was confirmed that no single antibiotic covered all microbes isolated.^[44]

Vancomycin is very effective in the treatment of endophthalmitis for a number of reasons. First, vancomycin has been found to be active against most Gram-positive organisms found in endophthalmitis. Second, vancomycin is cleared from the eye anteriorly, resulting in a long half-life. Data from rabbit studies demonstrated a vitreal half-life of 20–40h in uninfected rabbit eyes and 38–54h in infected rabbit eyes.^{[44,][45–47]}

Vancomycin appears to be well tolerated by ocular structures.

The choice of an agent for coverage of Gram-negative organisms remains controversial. Although the EVS used amikacin, an aminoglycoside, a number of vitreoretinal surgeons have advocated the use of other antibiotics. The potential benefits of amikacin include a good Gram-negative spectrum of coverage, a long half-life, a synergistic effect with vancomycin against Gram-positive cocci, and concentration-dependent bactericidal activity.^[48] Potential problems are ocular toxicity (including macular infarction), ototoxicity, and nephrotoxicity.^[50]

Intravitreal ceftazidime (a beta-lactam) has also been used for treatment of endophthalmitis. Ceftazidime has a similar spectrum of coverage and a similar half-life as amikacin.^[52]Although ceftazidime does not have the synergistic effect with vancomycin against Gram-positive cocci that amikacin has, neither does it carry the potential risk of ocular and systemic toxicity. Additionally, the high intravitreal concentration of each individual intravitreal antibiotic decreases the importance of antibiotic synergy.^[51]

Fluoroquinolones have been considered for intravitreal injection. Ciprofloxacin has a similar spectrum of coverage to amikacin and ceftazidime, but several problems preclude its use in intravitreal injection. Doses higher than 100μg injected into rabbit vitreous have been demonstrated to cause retinal and corneal toxicity,^[53] and the half-life of ciprofloxacin is short (~2h in the rabbit).^[54] Intravitreal moxifloxacin, a fourth-generation fluoroquinolone, has also been studied in animal eyes. It shows similar pharmacokinetics as ciprofloxacion. ^[49]

On the basis of the preceding evidence, the authors' choice is to inject vancomycin and ceftazidime. The authors do not routinely treat for fungal endophthalmitis and limit antifungal agents to culture-proven cases.

Intravitreal steroid injection

Controversy exists concerning the use of intravitreal injection of steroids. A number of studies have been performed in animal models, as well as in humans. Some studies demonstrate an improvement in clinical inflammation and visual outcome with concurrent intravitreal injection of steroids and antibiotics,^[57–60] whereas others demonstrate worsened inflammation and visual outcome.^[61–65] Histopathologic studies have shown similarly contradictory results for intravitreal steroids.^{[57,][58,][61]} The study designs, including type of antibiotic, dose of steroid injected, and type of bacterium injected (in the animal models), were not consistent across studies; therefore, comparison of results is difficult. Intravitreal triamcinolone has been shown to exhibit a beneficial effect for postoperative endophthalmitis when combined with intravitreal antibiotics.^[66] On the basis of the existing studies, the authors do not support the injection of intravitreal steroids at the time of antibiotic injection but await a comprehensive evaluation of the efficacy of intravitreal steroids in endophthalmitis.

Adjuvant treatment

The EVS used subconjunctival antibiotics for eradication of any anterior segment infection and many surgeons advocate their use in the treatment of endophthalmitis. The authors believe that the application of subconjunctival antibiotics is redundant when an aggressive postoperative topical antibiotic regimen is planned and do not generally use subconjunctival antibiotics or steroids.

Our recommendations for postoperative treatment with topical antibiotics is the use of fortified medications, with the EVS trial as a guiding principal, if the patient presents with an apparent infection while taking fourth-generation fluoroquinolones topically, as they are often prescribed in the postoperative regimen. Topical fortified vancomycin (25 or 50mg/mL) is used to treat any Gram-positive infection, whereas topical fortified amikacin (20mg/mL) or ceftazidime (100mg/mL) are good choices to treat any Gram-negative organisms. Although unused in the EVS, topical fortified gentamicin (11 or 14mg/mL) is also a reasonable choice for Gram-negative coverage. If a patient has not received a topical fourth-generation quinolone, one may be started as treatment for both Gram-positive and Gram-negative coverage following intravitreal antibiotics. Both aqueous and vitreous penetration of these topical fluoroquinolones has been reported.^[62,][63]

Oral administration of fourth-generation fluoroquinolones have also been shown to achieve high intravitreal concentrations in the noninflamed eye. Following oral administration, both gatifloxacin and moxifloxacin have been shown to penetrate the vitreous of the non-inflamed eye within hours, exceeding MIC therapeutic levels gains a wide range of both Gram-positive and Gram-negative organisms causative of endophthalmitis.^[55,][56] Oral fourth-generation fluoroquinolones certainly represent a significant advance in endophthalmitis treatment, and we recommend prescribing them at the time of diagnosis.

On the basis of EVS data, no intravenous antibiotics are recommended.

Aggressive postoperative administration of prednisolone acetate 1% is started 1 day after surgery. The EVS utilized oral prednisone at 30mg/day. This dose may be started if the patient has no contraindications to steroid use, but the authors rarely use it. Cycloplegic drops are used postoperatively to relieve discomfort and synechiae formation.

Clinical course

The clinical course varies on a case-by-case basis. Often, the clinical appearance is worse 1 day after surgery than on the day of surgery. Generally speaking, 2 days after surgery, the eye should appear clinically improved, although a hypopyon and media opacities may be present. Although the eye may be sterilized, aggressive anti-inflammatory therapy is imperative to prevent late sequelae. It is important to evaluate and reevaluate the anterior and posterior segments for development of complications such as posterior synechiae with iris bombé, vitreous membranes, retinal traction, and retinal detachment. As long as the media is hazy, the posterior segment should be followed with ultrasound. The surgeon should not hesitate to bring the patient back to the operating room should further complications develop or should a persistent infection be suspected.

Prognosis

The final outcome depends on a number of factors, including appearance at presentation, the inciting organism, and the baseline medical condition. Patients infected with coagulase-negative Staphylococcus generally have the best outcome, whereas those with streptococcal infections have a worse prognosis. Gram-negative endophthalmitis carries a poor prognosis. Recent data from the EVS demonstrate a trend toward worsened outcomes for diabetic patients; the surgeon should consider earlier, more aggressive intervention for diabetics.^[67] Some surgeons advocate vitrectomy following injection of antibiotics if media haze persists and examination continues to reveal vitreous haze and membranes, despite vision better than LP. Early detection and treatment may be the best hope for a good outcome.

Prevention

Evidence exists that the use of topical 5% povidone-iodine applied to the ocular surface preoperatively decreases the incidence of culture-positive endophthalmitis,^[68] and the authors advocate its use. There has been a recent trend toward the use of antibiotics within the irrigating solution. Studies involving animal models and retrospective chart reviews have not definitively demonstrated a benefit to the use of antibiotics within irrigating solutions during cataract surgery, but a recent large multicenter study showed a fivefold reduction in the risk of endophthalmitis following cataract surgery with intracameral cefuroxime. Based upon the emerging risk-reduction data, it is the authors' recommendation to consider adding intracameral cefuroxime to cataract surgery.^[69–73]

Chronic postoperative endophthalmitis

Although most of this chapter has focused on early postoperative endophthalmitis, the surgeon should be aware of the signs of chronic postoperative endophthalmitis. A number of weakly virulent organisms may produce a late, chronic infection that may mimic a chronic uveitis. Organisms that have been reported to produce such a reaction includePropionibacterium acnes, Staphylococcus epidermidis, and fungi, such as Candida species.

acnesis a commensal anaerobic diphtheroid bacterium that is found on the skin. P. acnesendophthalmitis has been reported to present with an equatorial white plaque on the lens capsule after extracapsular cataract extraction, low-grade chronic inflammation, granulomatous keratic precipitates, fibrin strands or beaded infiltrates in the anterior vitreous, and an intermittent hypopyon. The inflammation associated with P. acnes infection often responds to steroid treatment, but recurs once treatment is withheld.^[74–76] The authors' experience has been that P. acnes generally produces a chronic low-grade inflammation with a white plaque seen within the capsular bag but without hypopyon or other changes. Patients have often been treated chronically with steroids, which may mask the development of classic findings.

A number of treatments for patients with P. acnes endophthalmitis have been used, including various combinations of topical, intravenous, and intraocular antibiotics with or without vitrectomy.^[76] Data have supported treating P. acnes infection with vitrectomy, capsulectomy, and IOL extraction with intravitreal antibiotics to yield the greatest chance of cure. However, if less aggressive intervention fails, studies do not show that visual acuity decreases as more aggressive steps are taken. It is the authors' recommendation to consider initial intervention with vitrectomy, posterior capsulectomy, and injection of antibiotics, whereas consideration of IOL removal is reasonable if primary intervention fails.^[77,][78] A planned secondary IOL placement after complete resolution of inflammation is reasonable. In all cases, the vitreous washings and capsular remnant are sent for culture and staining.

A patient with suspected chronic late endophthalmitis that is not believed to be P. acnes or has not proven culture-positive for the organism is treated with a pars plana vitrectomy, anterior chamber biopsy, and injection of intravitreal antibiotics. The authors elect to use intravitreal vancomycin, 1mg in 0.1mL, and ceftazidime, 2mg in 0.1mL. Coagulase-negative staphylococcal species can mimic P. acnes, and often respond to this treatment regimen without IOL removal. Postoperatively, patients receive anti-inflammatory drops, cycloplegics, and fourth-generation fluoroquinolone drops supplemented by an oral fourth-generation quinolone. The authors do not start antifungal therapy until cases are culture proven, although one can consider submission of the posterior capsule for fungal culture in cryptic cases of chronic endophthalmitis.^[79]

Conclusion

Postoperative endophthalmitis is a greatly feared complication of cataract surgery with potentially devastating results. However, early diagnosis and prompt treatment of endophthalmitis can result in the preservation of good vision. Surgeons should remain vigilant during their evaluation of the postoperative patient and should treat or refer the patient for immediate treatment if endophthalmitis is suspected.

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