Infectious endophthalmitis is classified by the events leading to the infection and by the timing of the clinical diagnosis ¹^–³. The broad categories include postoperative endophthalmitis (acute onset, chronic or delayed-onset, conjunctival filtering bleb associated), post-traumatic endophthalmitis, intravitreal injection-associated endophthalmitis, and endogenous endophthalmitis (Table 64.1). Rare categories include cases associated with microbial keratitis or suture removal. These categories are important in predicting the causative organisms and guiding therapeutic decisions before microbiological confirmation of the clinical diagnosis.

Table 64.1 Classification of endophthalmitis – most frequent organisms in various clinical settings

1 Postoperative:

a Acute-onset postoperative endophthalmitis: coagulase-negative staphylococci, Staphylococcus aureus, Streptococcus species, Gram-negative bacteria

b Delayed-onset (chronic) pseudophakic endophthalmitis (>6 weeks postop): P. acnes, coagulase-negative staphylococci, fungi

c Conjunctival filtering bleb-associated endophthalmitis: Streptococcus species, Haemophilus influenzae, Staphylococcus species

2 Post-traumatic: Bacillus species, Staphylococcus species

3 Intravitreal injection-associated endophthalmitis: Staphylococcus and Streptococcus species

4 Endogenous endophthalmitis: Candida species, S. aureus, Gram-negative bacteria

5 Miscellaneous (keratitis associated): Pseudomonas, Staphylococcus species

Postoperative endophthalmitis is the most frequent category, accounting for greater than 70% of cases ³. In a nosocomial survey (2002–2009) of a university-based hospital reviewing over 56 672 intraocular surgical procedures with or without intraocular lens implantation, acute-onset endophthalmitis occurred in 14 cases (0.025%)⁴. In this survey of intraocular surgical cases, the rates of endophthalmitis were highest after penetrating keratoplasy (0.108% of 2788 cases) and lowest after pars plana vitrectomy (0.01% or 2 of 18 492 cases). Despite concerns that clear corneal sutureless temporal incision cataract surgery may increase the risk of endophthalmitis, this and most other studies do not substantiate this⁵. Comparing the rate of endophthalmitis at the same university-based hospital to studies from prior time periods, there has been a steady decline in the incidence of endophthalmitis⁶. Another study reviewed 440 000 consecutive cataract surgeries in Canada from 2002 to 2006 and determined the rate of endophthalmitis to be 0.14%. They found the rate to be higher in men, cases with capsular rupture, and older patients⁷. There is an increased incidence of endophthalmitis in patients with diabetes mellitus that can possibly be explained by known immune compromise in diabetic patients⁸. Endophthalmitis from an intravitreal injection is a more recently recognized category of endophthalmitis due to the increased utilization of intravitreal medications to treat retinal disease. Intravitreal injections are currently the most common procedure in the Medicare system. Vascular endothelial growth factor inhibitors (VEGF) (bevacizumab, ranibizumab) and depot-steroids (triamcinolone acetonide) are the two main drug groups injected intravitreally for treatment purposes. The VEGF inhibitors are mainly used for treating exudative macular degeneration, but have also been shown to be effective for treatment of macular edema resulting from retinal vascular diseases and retinal and iris neovascularization resulting from retinal ischemia in diabetic retinopathy and retinal vein occlusions. Intravitreal triamcinolone acetonide is used to treat macular edema from various causes, as well as intraocular inflammatory diseases. In a meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor(VEGF) agents, endophthalmitis occurred in 52 of 105 536 injections (0.049%)⁹. 52% of these were culture positive. Of the culture positive cases, coagulase-negative Staphylococcus accounted for 65.4%, Streptococcus species for 30.8% and Bacillus cereus for 3.8%. The frequency of Streptococcus was approximately 3 times higher than that reported after cataract surgery related endophthalmitis. The authors recommended strategies to minimize oropharyngeal droplet transmission including avoiding talking, coughing, and sneezing or wearing surgical masks during injections. In another large study from a single medical center and satellite clinics, the rate of endophthalmitis following intravitreal injection of anti VEGF agents was 0.02% (12/60 322). Streptococcus species was the most common organism isolated and was associated with a poorer visual outcome^9a. The infectious endophthalmitis incidence data from triamcinolone acetonide also suggests that it is an uncommon complication. It is reported to occur in from 0.05–0.87% of cases. Combining data from the diabetic retinopathy clinical research network diabetic macular edema trial and the standard care vs. triamcinolone acetonide for retinal vein occlusion (SCORE) there was one case of endophthalmitis in 2009 injections (0.05%)^9b. In 2004, a panel of experienced researchers and clinicians met and created a “Best Practice” guide for intravitreal injections to minimize the incidence infection. Although there was some disagreement among panel members, a list of guidelines accepted by most of the panel members has been published (Table 60.5). Use of a lid speculum and application of topical povidone-iodine are highly recommended for all injections. The needle should avoid contact with the patient’s eyelid prior to entering the eye. There is no evidence that pre or postoperative antibiotics reduce the rate of infectious endophthalmitis following an intravitreal injection. Endophthalmitis may also occur infrequently in the setting of a conjunctival filtering bleb¹⁰^–¹², wound dehiscence, or vitreous wick¹³. Chronic or delayed-onset endophthalmitis may be caused by less virulent bacteria (e.g. Propionibacterium acnes, Staphylococcus epidermidis) or by fungi¹⁴^–¹⁷.

In reported large clinical series ¹⁸^–²⁰, endophthalmitis after penetrating ocular trauma represents approximately 25% of all endophthalmitis cases. In one large study of penetrating ocular trauma, endophthalmitis occurred in 10.7% of cases with a retained intraocular foreign body and 5.2% of cases without a retained intraocular foreign body²¹. The National Eye Trauma System Registry reported an endophthalmitis incidence of 6.9% (34 of 492 cases) after penetrating ocular injuries with retained intraocular foreign bodies²². Metallic intraocular foreign bodies were as likely to be associated with infectious endophthalmitis (7.2%) as non-metallic foreign bodies (7.3%) and organic matter (6.3%) foreign bodies²². Rupture of the crystalline lens capsule is also a risk for endophthalmitis in open-globe injuries²³. More recent data indicate that the incidence of endophthalmitis after penetrating trauma may be declining²⁴.

Compared with the postoperative and post-trauma categories, endogenous endophthalmitis cases occur with the least frequency and more often occur in debilitated or immunocompromised patients or in patients with a history of intravenous drug abuse ²⁵^–³¹. The incidence of intravitreal injection-associated endophthalmitis is less than 0.1% in most reported series³².

Clinical features, diagnosis, and differential diagnosis

The diagnostic features of infectious endophthalmitis can be divided into two aspects: clinical recognition and microbiological confirmation. The clinical signs of endophthalmitis vary depending on the preceding events or surgery, the infecting organism, the associated inflammation, and the duration of the disease prior to diagnosis. In acute-onset postoperative endophthalmitis when bacteria are the etiologic agents, the hallmark of the clinical diagnosis is marked intraocular inflammation with hypopyon (Fig. 64.1)^1,². Other signs of acute postoperative bacterial endophthalmitis include fibrin in the anterior chamber and on the intraocular lens (IOL), corneal edema, marked conjunctival congestion, lid edema, and vitreitis. Retinal periphlebitis is another clinical sign that is diagnostically more helpful in eyes with relatively clear media³³. The clinical features of endophthalmitis after clear cornea cataract surgery are similar to those in cases following scleral incision cataract surgery, except the time of diagnosis may be later with clear corneal surgery cases³⁴. Endophthalmitis cases caused by fungal organisms generally have less inflammation, a more indolent course, and less ocular pain. Endogenous Candida cases often manifest as isolated white infiltrates in the formed vitreous overlying a focal area of chorioretinitis²⁷.

Fig. 64.1 Clinical features of a patient with acute-onset endophthalmitis after cataract surgery: marked intraocular inflammation with hypopyon, conjunctival congestion, corneal haze.

The clinical diagnosis of endophthalmitis is confirmed by obtaining intraocular (aqueous and vitreous) specimens. A vitreous specimen is much more likely to yield a positive culture result than is a simultaneously acquired aqueous specimen ³⁵. The vitreous specimen can be obtained either by needle biopsy or by the use of an automated vitrectomy instrument. A needle biopsy or limited vitrectomy approach can be performed in a treatment room, but a three-port pars plana vitrectomy usually requires the use of the operating room and ancillary equipment. One report of 138 culture-proven endophthalmitis cases showed a positive culture result in 34.8% of anterior chamber specimens, 58.2% of vitreous tap specimens, and 80% of vitrectomy fluid specimens³⁵.

The technique for culturing intraocular specimens depends on the volume of the specimen and the suspected clinical diagnosis ^2,^35,³⁶. Direct inoculation of the intraocular fluid specimen onto culture media is a traditional approach and remains a very practical technique. The specific media used for direct inoculation are listed in Table 64.2. This approach is especially important when limited specimens (such as a needle vitreous or aqueous aspiration) are obtained. These specimens can be directly inoculated onto the appropriate media, including anaerobic media in cases of suspected P. acnes endophthalmitis. Specimens obtained by the use of automated vitrectomy instruments are diluted by the infusion fluid but can be processed by two methods. One method for processing the vitrectomy specimen uses a membrane filter system in which the vitrectomy specimen is passed through 0.45 mm filter paper that concentrates the microorganisms and particulate matter. This filter paper is then sectioned and distributed on the appropriate media. An alternative method involves direct inoculation of the initially aspirated vitrectomy specimen into standard blood culture bottles³⁶. The latter technique is particularly useful at night or on the weekend when the microbiology laboratory staff are not available to assist in processing the vitrectomy specimen. In a retrospective review of 83 cases, this blood culture bottle method for processing vitrectomy specimens yielded a 91% incidence of positive culture results³⁶. This rate of positive culture resulting from clinically diagnosed endophthalmitis cases was similar to simultaneously processed specimens using the membrane filter system. In another study this method yielded positive cultures in 34 of 48 vitreous specimens (70.8%)³⁷. Direct inoculation of vitreous onto the BancTec Peds Plus F broth has also been shown to be a simpler and effective alternative culture method³⁸.

Table 64.2 Culture media used for endophthalmitis specimens

1 Chocolate agar: an enriched medium for the recovery of fastidious organisms (i.e. Neisseria gonorrhoeae and Haemophilus influenzae) from clinical specimens. The chocolate agar should be used as a general purpose medium and as the medium of choice for the recovery of common endophthalmitis isolates when only a few drops of intraocular fluid are available for culture. It must be placed in a CO₂ jar or bag.

2 5% Sheep blood agar: a general purpose medium for the recovery of the most common bacterial and fungal endophthalmitis isolates. It should be placed in a CO₂ jar or bag.

3 Thioglycollate broth: an enriched medium for the recovery of small numbers of aerobic or anaerobic (including P. acnes) organisms from ocular fluids and tissues. The broth dilutes the effects of antibiotics and other inhibitory substances. The broth should be kept a minimum of 5 days.

4 Anaerobic blood agar: a general purpose medium for the recovery of anaerobic and facultative anaerobic organisms. This medium should be included for all chronic cases of endophthalmitis and/or where P. acnes is suspected. The viridans and B-hemolytic streptococci may grow better and faster on this plate. This medium is placed in an anaerobic jar or bag.

5 Sabouraud agar: a selective medium used to promote the growth of fungi (yeasts and molds) from clinical materials.

6 Blood culture bottles: contain specially prepared medium for the recovery of both aerobic and anaerobic bacteria and fungi. Intraocular fluids may be inoculated directly into blood culture bottles. Undiluted fluids should be inoculated into pediatric bottles; diluted fluids (6–12 ml of vitrectomy specimen), into a set of routine (adult) bottles. Identification is made after growth is established.

Immunologic as well as molecular genetic technologies enable rapid and specific identification of infectious agents. These techniques have been used in both clinical and experimental settings, and their future use in this area appears promising ^39,⁴⁰. Molecular genetic technology has made available specific DNA probes that will interact with the unique DNA sequence for a particular pathogen³⁹. Polymerase chain reaction (PCR) uses a primer set and DNA polymerase to amplify small amounts of DNA. It shows clinical potential as a rapid and sensitive diagnostic technique to aid in the confirmation of clinical observations and as an adjunct to conventional culture techniques⁴¹. Clinical application of PCR techniques for the more rapid diagnosis of bacterial endophthalmitis is currently under investigation⁴⁰.

The differential diagnosis of marked intraocular cellular inflammation after ocular surgery includes sterile inflammation related to retained lens fragments, iris trauma, pre-existing uveitis, and foreign material introduced during surgery ^1,⁴^–⁶. Retained cortical lens remnants have been reported to cause more inflammation than nuclear remnants⁴². Retained lens fragments may occasionally cause a marked inflammatory reaction with hypopyon, which may clinically resemble infectious endophthalmitis^43,⁴⁴. Blood in the anterior chamber or vitreous cavity may also be confused with endophthalmitis, especially when the blood is long-standing and associated with anterior segment trauma during preceding surgery. Similarly, difficult or prolonged surgery, which often includes vitreous loss or vitreous incarceration in the cataract incision, may increase postoperative inflammation.

Toxic anterior segment syndrome (TASS) can mimic infectious endophthalmitis and the incidence of this has risen in recent years. It is probably caused by multiple factors but, as the name implies, is presumed to be due to a toxin entering the eye at the time of surgery. The American Society of Cataract and refractive Surgeons found many different possible causes of TASS ⁴⁵. The use of toxic single use materials and instruments as well as the sterilization and processing of reusable instruments are possible causes. The inflammatory response is usually seen within the first 24 hours after surgery. It can be intense and associated with a hypopyon and fibrin formation in the anterior chamber. Corneal edema can be severe. The vitreous is typically not involved, as is the case with an infectious endophthalmitis. In addition other differentiating features between TASS and infectious endophthalmitis include minimal to no pain, lid edema or purulent discharge with TASS, and onset within 24 hours as opposed to 4–7 days with infection⁴⁶.

In eyes with mild to moderate postoperative inflammation without hypopyon, intensive therapy with topical corticosteroids may be used initially. The careful sequential observation of such eyes will allow appropriate diagnostic and treatment approaches to be employed. Acute-onset postoperative endophthalmitis when caused by more virulent organisms, such as Streptococcus species or Gram-negative bacteria, will usually present with rapidly progressive clinical signs aiding in the early diagnosis of infectious endophthalmitis. Endophthalmitis caused by the coagulase-negative staphylococci may have less inflammatory signs, often creating difficulty in distinguishing between an infectious and a non-infectious etiology.

Goals of management

Antibiotics

The management goal for endophthalmitis is first and foremost to eradicate the infection and sterilize the intraocular contents. Antibiotics are the mainstay of therapy. Antibiotics can be delivered to the eye by several routes, including direct intravitreal injection, periocular injection, and topical application (Table 64.3). Endophthalmitis management, like the management of infections elsewhere in the body, requires selection of safe and effective antimicrobial agents. The antibiotics selected should cover the broad range of Gram-positive and Gram-negative organisms causing infectious endophthalmitis. Systemic antibiotics may be used to supplement local ocular treatment in selected cases. Injection of intravitreal antibiotics is the primary means of achieving this goal. Of all the available antimicrobial agents evaluated for intravitreal injection, only a few are used regularly in clinical practice. In the Endophthalmitis Vitrectomy Study (EVS), intravitreal vancomycin 1 mg in combination with amikacin 0.4 mg was used for the initial empiric treatment of acute-onset endophthalmitis⁴⁷^–⁵⁸. An alternative to the aminoglycosides for coverage of Gram-negative organisms is the use of intravitreal ceftazidime 2.25 mg, a third-generation cephalosporin^59,⁶⁰. Although ceftazidime may precipitate when used with vancomycin, this has not been shown to alter its effectiveness in the clinical setting⁵⁸. These two antibiotics should not be mixed in the same syringe. These antibiotic combinations provide broad coverage for nearly all of the organisms causing bacterial endophthalmitis, including staphylococci, streptococci, Bacillus species, and the Gram-negative organisms.

Table 64.3 Antibiotics considered for endophthalmitis treatment: concentration and dosages of principal agents used for treatment of endophthalmitis*

Vancomycin is generally considered to be the drug of choice for Gram-positive bacterial coverage. Vancomycin has excellent activity against coagulase-negative staphylococci and other Gram-positive organisms. In the EVS, coagulase-negative micrococci were the most commonly cultured bacteria in acute-onset post-cataract surgery cases ⁴⁷^–⁵⁷. Vancomycin has been reported to be consistently effective for the broad range of streptococcal organisms as well as nearly all Gram-positive organisms.

Repetitive injections of intravitreal antibiotics may cause significant retinal toxicity. In a rabbit model, eyes treated with a second or third intraocular vancomycin/aminoglycoside injection at 48-hour intervals showed progressive toxicity ⁶¹. In view of the low rate of persistent infection after initial combination therapy, repeat injection of intravitreal antibiotics are considered only in those cases with progressive inflammation caused by virulent organisms⁶². Based on the initial culture report, a single intravitreal antibiotic may be selected for this repeat injection.

Vitrectomy

The potential advantages of vitrectomy for infectious endophthalmitis include the ability to obtain an adequate vitreous specimen without the theoretically harmful tractional effects of needle aspiration on formed vitreous. Vitrectomy also debulks the vitreous cavity, allowing removal of most of the infecting organisms and other inflammatory mediators. Finally, the vitrectomized eye should allow improved drug circulation throughout the vitreous cavity.

Disadvantages of vitrectomy include the requirement for more sophisticated instrumentation, possibly available only in an operating room, a setting that can be associated with a delay in initiating treatment. The view of the posterior segment is frequently obscured by fibrin and inflammatory debris on the surface of the IOL or in the anterior chamber, making vitrectomy surgery difficult and potentially hazardous. The view of the posterior segment can frequently be improved by either aspirating or peeling the inflammatory material from the anterior segment or surface of the IOL ⁶³.

Another disadvantage of vitrectomy is its effect on reducing the half-life of injected intravitreal antibiotics ⁶⁴. Doft and associates studied the ocular clearance of amphotericin B injected into the vitreous in a rabbit model of unmodified phakic eyes, Candida-infected phakic eyes, aphakic eyes, and aphakic vitrectomized eyes. The half-lives of drug disappearance after a single amphotericin B 10 µg intravitreal injection were 9.1, 8.6, 4.7, and 4.1 days, respectively. The authors summarized that this rapid disappearance of amphotericin B from vitrectomized eyes must be considered in the clinical management of patients with fungal endophthalmitis.

Vitrectomy for endophthalmitis can be performed using either a standard 20-gauge three-port system or a transconjunctival cannulated 23 or 25-gauge system depending on the surgeon’s preference and the clinical circumstances. Possible advantages of the small gauge technique over the 20-gauge approach include shorter operating time, reduced postoperative inflammation from sutures in an already inflamed eye, and possibly reduced incidence of postoperative retinal tears and detachments ⁶⁵. In the setting of post-cataract surgery endophthalmitis, a pars plana vitrectomy is generally recommended for endophthalmitis cases with light perception vision. The inflammatory response is usually severe and, in such cases, preoperative echography should be performed to rule out retinal detachment and to document the presence or absence of a posterior vitreous detachment. When there is a posterior vitreous detachment, the vitrectomy surgeon can remove more opaque vitreous near the posterior pole and have greater confidence in avoiding contact with the retina.

A more concentrated vitreous specimen can be obtained at the beginning of the procedure using manual aspiration into a syringe attached to the aspiration line of the vitrectomy hand piece. The intraocular specimens are evaluated by microbiology laboratory using stained smears and cultures.

Indications for surgery

The indications for performing vitreoretinal surgery for endophthalmitis as opposed to vitreous tap and intravitreal antibiotics were defined in the Endophthalmitis Vitrectomy Study (EVS). The EVS was a multicenter, National Eye Institute (NEI)-sponsored trial that evaluated pars plana vitrectomy and systemic antibiotics in acute postoperative endophthalmitis ⁴⁷^–⁵⁷. The EVS also evaluated a variety of clinical and microbiologic factors relating to endophthalmitis. The study enrolled 420 patients with symptoms and signs of endophthalmitis occurring within 6 weeks of cataract extraction or secondary IOL implantation. Patients were randomized to treatment with pars plana vitrectomy or to vitreous tap/biopsy, and to treatment with or without systemic antibiotics. All patients in the study received intravitreal antibiotic therapy (vancomycin 1 mg and amikacin 0.4 mg), and topical and systemic corticosteroids. Patients who appeared clinically worse after 36–60 hours after presentation underwent re-injection of intravitreal antibiotics. Similarly, patients who were initially randomized to tap/biopsy and had worsening also underwent vitrectomy. The main endpoint of the study was best-corrected visual acuity at 9 to 12 months after presentation. A secondary endpoint was media clarity.

Visual acuity results

The EVS demonstrated that immediate pars plana vitrectomy was beneficial for patients who presented with visual acuity of light perception only ⁴⁷. In this subgroup of patients, vitrectomy was associated with a threefold increase in the frequency of achieving 20/40 or better acuity (33% vs. 11%), approximately a twofold chance of achieving 20/100 or better acuity (56% vs. 30%), and a 50% decrease in the frequency of severe visual loss to worse than 5/200 acuity (20% vs. 47%). There was no difference in outcome between immediate pars plana vitrectomy and tap/biopsy for patients with an initial visual acuity of hand motions or better. In this subgroup, patients had about the same chance of achieving 20/40 or better acuity (66% vs. 62%) and 20/100 or better acuity (86% vs. 84%), and a similar risk for severe visual loss to worse than 5/200 acuity (5% vs. 3%), whether they had immediate three-port pars plana vitrectomy or vitreous tap/biopsy. However, there was a possible exception. Diabetic patients with initial visual acuity of hand motions or better obtained somewhat better visual acuity outcome with vitrectomy compared with tap/biopsy. Final visual acuity of 20/40 or better was obtained in 57% of vitrectomy patients and 40% of tap biopsy patients. The difference was not statistically significant. It was suggested that either vitrectomy or tap/biopsy could be considered reasonable for diabetic patients⁴⁸.

At 9–12 months after presentation, clear media, as judged by a 20/40 view of the fundus by indirect ophthalmoscopy, was achieved slightly less frequently in the tap/biopsy eyes (83%) than in the vitrectomized eyes (90%), but this difference was not statistically significant. In no cases were vitreous opacities judged to be a principal cause of impaired vision at the final examination ⁵².

Systemic antibiotics (amikacin, ceftazidime) were observed to have no effect on visual outcome or media clarity in the EVS, even when subgroup analysis that considered microbiologic susceptibilities was performed ^47,⁵⁷. The study concluded that systemic antibiotics provided no additional benefit to intravitreally administered antibiotics.

Recent studies have confirmed the relevance of the EVS to similar cases in the modern era of clear corneal surgery ⁵¹. In spite of newer systemic antibiotics, the traditional intravitreal antibiotics remain effective and are the mainstay of therapy.

Preoperative assessment

The preoperative evaluation should start with a careful history focusing on the nature and onset of symptoms in relation to previous eye surgery or trauma. The medical history including chronic diseases, medications, and allergies should be obtained. A complete ocular examination is important with a careful attention to determining whether visual acuity is hand motions or better, as this may determine the method of treatment. The degree of inflammation in both the anterior segment and vitreous should be assessed clinically. If visualization of the posterior segment is limited by either inflammatory material or corneal edema, a B-scan ultrasound is necessary prior to treatment to assess the degree of vitreous inflammation, and the presence of either choroidal or retinal detachment. It is also important to examine the surgical wound for leakage and vitreous incarceration, which may need to be addressed at the time of surgery.

Anesthesia

The treatment of endophthalmitis is usually performed using retrobulbar or peribulbar anesthesia. The specific local anesthetic agent is up to the discretion of the surgeon, but often includes a short-acting drug such as 2% plain lidocaine combined with a longer-acting agent such as 0.75% bupivicaine. This can be combined with hyaluronidase for better tissue penetration. If a tap and inject is indicated, this can be performed in the office or clinic procedure room without the need for sedation. If vitreoretinal surgery is indicated this is usually performed in the operating room with anesthesia personnel administering sedation during the procedure. Children or adults unable to cooperate or tolerate a local anesthetic with sedation may need to be placed under general anesthesia. This may be supplemented by a retrobulbar block to facilitate the general anesthesia and to aid with pain management in the immediate postoperative period. General anesthesia may also be considered in situations where a retrobulbar block is considered high risk such as in recent trauma with an open globe, recent cataract surgery with a large or inadequately closed incision, or patients on anti-coagulant medication.

Surgical technique

Tap and inject

A sterile prep of the eye and eyelids is performed using povidone iodine and a sterile lid speculum is placed. A syringe attached to a 23-gauge butterfly needle is preferred for the aspiration. A 23-gauge butterfly needle is usually readily available in the clinic and works well for this purpose. The needle is inserted approximately 3 mm from the limbus into the mid vitreous and moderate aspiration is applied (Fig. 64.2). If vitreous does not aspirate initially the needle tip can be carefully moved in an attempt to locate a pocket of liquid vitreous. If after several attempts a vitreous specimen cannot be obtained the procedure should be terminated as excessive aspiration can lead to development of iatrogenic retinal tears. Another option if vitreous aspiration is not successful is the use of a portable battery operated small gauge vitrector.

Fig. 64.2 An eye with suspected postoperative bacterial endophthalmitis undergoing a diagnostic vitreous tap. Note the 23-gauge butterfly needle used for the procedure.

An anterior chamber paracentesis to obtain an aqueous specimen may be obtained at the same time. After intraocular specimens have been obtained intravitreal antibiotics are injected. Ceftazidime 2.25 mg in 0.1 ml and vancomycin 1.0 mg in 0.1 ml are injected into the vitreous through at separate pars plana sites approximately 3 mm from the limbus. In most cases dexamethasone 0.4 mg in 0.1 ml is also injected at a separate pars plane site. All specimens should be immediately sent for Gram stain, culture, and sensitivity as detailed above.

Vitrectomy

A traditional ocular sterile prep is performed using povidone iodine antiseptic and surgical drapes (Fig. 64.3). An infusion canula is inserted but infusion should not begin until one can visualize the canula in the vitreous cavity. This may require clearing inflammatory material from the anterior chamber by placing the vitrector into the anterior chamber through a limbal incision. Usually the material can be cut and aspirated but in some cases removal of fibrin is facilitated by twirling the material around the vitrectomy probe, similar to twirling spaghetti around a fork. An anterior chamber specimen can be obtained at this time.

Fig. 64.3 An eye prepped for surgery with povidone iodine scrub and plastic eye drape covering the lashes.

Once visualization of the vitreous is possible a more concentrated vitreous specimen is acquired. This can be done by ‘breaking’ the aspiration line from the vitrector and inserting a 10 ml syringe. As the vitreous cutter is activated an assistant can slowly aspirate approximately 0.5 ml of concentrated vitreous into the syringe (Fig. 64.4). The infusion can be turned on after the specimen is obtained and a complete vitrectomy performed. The extent of vitreous removal may depend on adequacy of visualization during the vitrectomy. An inadequate view to the posterior segment because of corneal edema, or residual inflammatory material in the anterior segment may limit the extent of vitrectomy that can be performed.

Fig. 64.4 Photograph demonstrating the technique used to obtain a concentrated vitreous specimen by inserting a syringe at the break point in the vitrector aspirating line.

Postoperative care, additional procedures, and results of treatment (EVS data)

Immediately after the procedure an antibiotic ointment is applied to the eye and a patch and plastic ocular shield are placed. The patient is instructed to keep this in place until the exam the following day. An exam in the office or clinic is performed on the first post-treatment day. The eyes are usually markedly inflamed and frequent topical steroids are initiated. A topical broad-spectrum antibiotic such as a fourth generation fluoroquinolone is usually started at this time as well. A cycloplegic agent such as atropine 1.0% can also be used. Frequent follow-up exams are important until one is certain that the infection is eradicated and there are signs of clinical improvement as evidenced by reduced intraocular inflammation. In eyes in which visualization of the posterior segment is obscured, B-scan ultrasound should be performed to determine whether the inflammation is improving and to rule out a retinal or choroidal detachment.

Early and late additional procedures

The EVS also evaluated the frequency of additional intervention following initial treatment ⁵². Within 1 week of presentation, additional procedures were required in 8% of vitrectomized eyes versus 13% of those treated with tap/biopsy. Of 44 eyes (10% overall) that required repeat procedures, most (9%) underwent such procedures for worsening inflammation, and the remainder (1.4%, six eyes) for other complications after the initial treatment procedure. These complications included glaucoma, wound leak, and retinal detachment. Eyes that required additional procedures soon after initial presentation had a worse visual outcome, with only 15% of eyes achieving 20/40 or better visual acuity compared with 57% of eyes that did not require such procedures. The poorer outcome in eyes requiring secondary procedures could be attributed to the worse early course in such eyes, rather than to the secondary procedures themselves.

The incidence of late additional surgical procedures was 27% overall, and did not differ whether or not vitrectomy was performed or intravenous antibiotics were administered. Overall, late additional procedures included posterior capsulotomy in 9% of patients, vitrectomy in 7%, retinopexy in 2%, scleral buckling in 1%, and glaucoma procedures in 1%. Macular pucker was operated on in about 2% of patients. Including early additional surgical procedures, approximately one-third of EVS patients required repeated surgical intervention after initial treatment.

Clinical presentation and visual outcome

Clinical factors on presentation can be correlated with final visual outcome in the EVS. The single most important predictor of visual outcome was presenting visual acuity. Patients with LP visual acuity at presentation had twice the risk of decreased vision compared with those with hand motions or better. Overall, 23% of patients with light perception acuity achieved 20/40 or better final acuity, compared with 64% of patients who had hand motions or better acuity ⁴⁷. The data confirmed that early treatment of endophthalmitis prior to severe visual loss is critical to maximize visual outcome, and that such treatment is more important in influencing outcome than any other factor, including vitrectomy. Other clinical factors that independently predicted decreased final visual acuity were older age, history of diabetes, corneal infiltrate or ring ulcer, abnormal intraocular pressure, rubeosis, an absent red reflex, and an open posterior capsule⁵⁵.

Microbiological factors and outcomes

The EVS evaluated the microbiological spectrum and susceptibilities of infecting organisms in acute postoperative endophthalmitis after cataract surgery. The findings provided a basis for choosing initial empiric antibiotic therapy and for evaluating subsequent changes in microbiological spectrum in this disease. Because both Gram-positive and Gram-negative organisms were encountered, antibiotic coverage for both types of organisms is recommended. Sensitivity testing of the intraocular isolate is recommended. It is important in determining the virulence of the organism and detecting possible resistant organisms. In addition knowing the specific isolate may be helpful in distinguishing an epidemic of endophthalmitis due to a common source.

The European Society of Cataract and Refractive Surgeons (ESCRS) Endophthalmitis Study

Although the Endophthalmitis Vitrectomy Study (EVS) provided valuable information from the 1990s, the ESCRS added additional and updated data regarding the management of post-cataract endophthalmitis ⁶⁹. The study was conducted at 24 centers in nine European countries from 2003 to 2006. It was a partially masked randomized placebo-controlled study evaluating the prophylactic effect of intracameral cefuroxime injection and/or perioperative levofloxacin eye drops on the incidence of endophthalmitis after cataract surgery. Data on 16 211 patients were published in June of 2007. The rate of endophthalmitis was 4.92 times higher in the control group than the cefuroxime treated group. Although perioperative topical levofloxacin was associated with a reduced incidence of endophthalmitis, it did not achieve statistical significance. Other identified risk factors for proven infective endophthalmitis in the study were silicone IOL material and male sex.

This was a landmark study and contributed valuable information regarding the treatment of post-cataract endophthalmitis, but concerns have been raised:

1 The control group rate of endophthalmitis was higher than the reported incidence in most United States studies. It was over 0.2 % in the ESCRS study and 0.05% in most recent large other studies. The patients in the study were treated with topical levofloxacin but not the fourth generation fluoroquinolones currently used as standard treatment for prophylaxis in the United States. This may have influenced the results.

2 The potential for toxicity from dilution errors during preparation of the intracameral cefuroxime in clinical practice is a concern since a prediluted commercially available preparation is not available in the US.

Currently intracameral cefuroxime has not become the standard practice for endophthalmitis prevention in the United States or in Europe ⁷⁰.

Systemic antibiotics

Controversy has existed in the literature over whether systemic antibiotics are necessary for successful treatment of infectious endophthalmitis. Intraocular inflammation and/or performance of a vitrectomy may alter the blood–retina barrier in a manner to allow better intravitreal penetration of systemically administered antibiotics. Prior to the EVS, successful treatment results in culture-positive cases of exogenous bacterial endophthalmitis without the use of systemic antibiotic therapy were published ⁷¹. One series included 16 endophthalmitis cases caused by S. epidermidis or more virulent organisms. Repeat intravitreal antibiotic injections were performed in seven cases because of suspected initial treatment failure, but in all patients the infection was ultimately cured without the use of systemic antibiotics. Three arguments against the use of intravenous antibiotics are the potential systemic toxicity, the variable intravitreal penetration, and the high cost of some antibiotics. Certain limitations of the EVS with respect to systemic antibiotic therapy should be recognized. First amikacin and ceftazidime were the only systemic antibiotics evaluated in the EVS. Second, whereas patients with acute-onset endophthalmitis following cataract surgery derived no additional benefit from the EVS systemically administered antibiotics, the study made no recommendations regarding systemic antibiotics for endophthalmitis prophylaxis, or for chronic, traumatic, bleb-related, fungal, or endogenous endophthalmitis.

Since the conclusion of the EVS, oral antibiotics in the fluoroquinolone class with a broad spectrum of activity and excellent intravitreal penetration have become available. These oral fluoroquinolones, include gatifloxacin (Tequin) (no longer commercially available) and moxifloxacin (Avelox; Bayer Pharmaceuticals Corp, West Haven, Conn). Moxifloxacin hydrochloride (Avelox; Bayer Pharmaceuticals Corp, West Haven, Conn) was shown to achieve therapeutic levels in the aqueous and vitreous for a wide variety of Gram-positive and Gram-negative pathogens following oral administration in non-inflamed eyes ⁷². Although resistant organisms causing endophthalmitis are becoming more prevalent⁷³, this drug may be considered in the management of endophthalmitis as a supplement to local ocular therapy. Although the fluoroquinolones are overall a relatively safe class of drugs, side effects must be considered and weighed against the benefit of the drug. Tendon rupture can occur with the fluoroquinolones, particularly in patients over 60 and those on corticosteroids⁷⁴.

Periocular antibiotic therapy

Conflicting data regarding the intravitreal penetration after periocular antibiotic injection have been reported ⁷⁵. Causes for the variability in these experiments include the inflammatory status of the eye and, possibly, sampling technique. The physiochemical properties of the drug may affect transscleral and transcorneal permeability. Of the antibiotics now in use, the third generation cephalosporins (ceftazidime and ceftriaxone) achieve the highest vitreous levels. A study comparing the effectiveness of treating endophthalmitis cases with periocular antibiotic injection in addition to intravitreal antibiotic with cases treated without periocular antibiotics demonstrated no statistical difference in outcomes⁷⁶.

Topical antibiotic therapy

Most studies concerning the efficacy of topically applied antibiotics pertain to corneal infections and cataract surgery prophylaxis. Significant intraocular levels of antibiotics can be achieved with frequent administration ⁷⁷. Alternative topical antibiotics include fortified antibiotics (vancomycin, and ceftazidime or amikacin) versus standard commercially available fourth generation fluoroquinolones.

Corticosteroid therapy

Marked infiltration of the anterior chamber and vitreous cavity by polymorphonuclear cells often occurs in endophthalmitis caused by bacteria. These white blood cells are implicated as mediators of tissue-destructive events by liberating oxygen metabolites such as superoxide and hydrogen peroxide, as well as proteolytic enzymes (elastase, collagenase, gelatinase). Theoretically, corticosteroids should reduce this inflammation-induced ocular damage associated with endophthalmitis.

Corticosteroids can be administered to the eye by several routes (intravitreal, systemic, periocular, and topical). Clinical studies have reported no adverse effect when using intravitreal dexamethasone in conjunction with intraocular antibiotics ⁷⁸^–⁸⁰. Intravitreal triamcinolone acetonide has also been shown to reduce inflammation without exacerbating the infection in a small series of endophthalmitis cases⁸¹. A study using a rabbit model of endophthalmitis demonstrated better clinical outcomes, post-treatment ERGs, and less histopathologic evidence of tissue destruction when intravitreal dexamethasone was used compared with antibiotics alone⁸².

In addition to intravitreal corticosteroids, periocular corticosteroids are also commonly used in the treatment of endophthalmitis. The periocular dosage may include dexamethasone 12 mg or more, administered together with periocular antibiotics ¹. Topical corticosteroids are usually started on the first morning after the initial treatment of endophthalmitis. These drops may be alternated on an hourly basis with the use of topical antibiotics.

Systemic corticosteroids were used in the EVS in the treatment of all study patients with postoperative endophthalmitis. In one study, a combination of topical and systemic corticosteroids gave better results than no corticosteroids or only topical corticosteroid administration ⁸³. Because many patients with endophthalmitis also have diabetes mellitus⁸, caution is advised when using higher dosages of systemic corticosteroids.