Endophthalmitis: Diagnosis, clinical findings, and management

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CHAPTER 64 Endophthalmitis

Diagnosis, clinical findings, and management

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Introduction

Infectious endophthalmitis is defined as inflammation of intraocular fluids and tissues caused by microbial organisms. It may result in severe visual loss13. In this chapter the epidemiology, diagnosis, and clinical findings are discussed and medical and surgical management issues for infectious endophthalmitis are reviewed.

Epidemiologic consideration and terminology

Infectious endophthalmitis is classified by the events leading to the infection and by the timing of the clinical diagnosis13. 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

Postoperative endophthalmitis is the most frequent category, accounting for greater than 70% of cases3. 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 outcome9a. 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 bleb1012, 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 fungi1417.

In reported large clinical series1820, 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 abuse2531. 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.

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 specimen35. 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 diagnosis2,35,36. 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

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 promising39,40. 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 surgery1,46. 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 endophthalmitis43,44. 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 TASS45. 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 endophthalmitis4758

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