20 Endophthalmitis, Toxic Anterior Segment Syndrome, and Vitritis Abstract Postoperative endophthalmitis (POE) is one of the most dreadful complications of intraocular surgery. It is crucial to take right and quick decisions in order to achieve optimal clinical results and restore the best possible visual acuity. The differential diagnosis of POE should always be considered; however, in case of any doubt, the patient should be regarded as having infectious endophthalmitis and treated with no delay. The role of preoperative instillation of topical antibiotics as a prophylactic measure for prevention of POE is controversial as it does not have any specific benefit over the usage of chlorhexidine or povidone–iodine preoperatively and intraoperative injection of intracameral antibiotics. The main treatment of POE is injection of intravitreal antibiotics preceded by either vitreous tap biopsy or vitrectomy. The antibiotics of first line of preference are vancomycin (1 mg) and ceftazidime (2 mg). Second choice is a combination of vancomycin (2 mg) and amikacin (400 µg). At the same time, dexamethasone (400 µg) is often administered by intravitreal injection. Toxic anterior chamber syndrome (TASS) can also produce marked sterile inflammation due to toxic substances that enter the anterior chamber during or after surgery. The outbreak of TASS requires thorough analysis of each surgical step and all possible risk factors (especially newly introduced medical substances and devices, its sterilization, storage, and transport conditions) to identify and eradicate the causative agent. There are also various conditions presenting with vitritis, which may mimic as infectious endophthalmitis. They should always be differentiated from endophthalmitis; however, it is important to remember that concomitant endophthalmitis also may be present. Keywords: intraocular infections, endophthalmitis, toxic anterior segment syndrome, vitritis, postoperative endophthalmitis prophylaxis, antisepsis, antibiotics, intracameral antibiotics, cefuroxime, intravitreal antibiotics, pars plana vitrectomy, endophthalmitis vitrectomy study Intraocular infections and inflammations are significant complications of cataract surgery, limiting the visual potential of the eye. In severe cases, they can even lead to blindness. Over the recent years, improvements of surgical technology, techniques, and procedures have significantly reduced the incidence of postoperative infections; however, it is impossible to eliminate this problem completely. Therefore, accurate diagnosis and prompt treatment are crucial to achieve optimal clinical results with recovery of useful vision. Endophthalmitis ( Fig. 20.1 Postoperative endophthalmitis. (a) Post cataract extraction, endophthalmitis with corneal clouding, and hypopyon in anterior chamber is noted. (b) Post pars plana vitrectomy, cornea clears up with resolving of hypopyon. (c) B-scan image depicting the posterior segment involvement with opacities in the vitreous. (d) Posterior segment clears up with improved view of the retina and other structures. The vision of the case improved from counting fingers to 20/40 after 2 weeks of performing pars plana vitrectomy. The incidence of postcataract endophthalmitis varies in several countries from 0.03 to 0.7%1,2,3,4,5,6,7,8,9,10,11,12,13 as presented in The symptoms of POE vary according to its severity, the most common being pain and visual loss. Patients often demonstrate blurred vision, red eye, swollen eyelids, chemosis, conjunctival injection and discharge, as well as corneal haze, media haze, fibrinous exudate or hypopyon, and vitritis with an impaired view of the fundus. Early recognition leads to better clinical outcomes. The differential diagnosis includes toxic anterior segment syndrome (TASS), retained lens material in the anterior chamber or vitreous, vitreous hemorrhage, postoperative uveitis, and viral retinitis. If there is any doubt about the diagnosis, patients should always be regarded as having infectious endophthalmitis and immediately treated. Endophthalmitis is initially a clinical diagnosis, and have to be proven by gram stain, culture, or polymerase chain reaction (PCR), although a negative culture may occur in up to 30% of cases. This situation does not necessarily rule out the infection and the treatment should be continued. The samples for culture should be obtained from aqueous and vitreous. If the eye media is opaque, the B-scan ultrasound biomicroscopy should be performed to confirm the changes in vitreous and to rule out retinal detachment or other complications that may coexist. An anterior chamber tap should be performed to obtain aqueous sample where 0.1 to 0.2 mL of aqueous is aspirated via limbal paracentesis using a 25-gauge needle. Vitreous samples might be obtained by either needle tap, vitreous biopsy, or pars plana vitrectomy (PPV). The European Society of Cataract and Refractive Surgeons (ESCRS) guidelines favor vitrectomy technique as it allows obtaining larger sample of vitreous, and at the same time removes bacterial load in the vitreous and reduces the need for reoperation.15 The specimens obtained should be immediately sent to the microbiology laboratory for detailed analysis. Common sources of infection in POE are microorganisms derived from conjunctival sac, contaminated devices, irrigating solutions, the implanted IOL, or airborne contamination. According to the Endophthalmitis Vitrectomy Study (EVS),16 if only analysis was possible, the intraocular isolates in most cases of patients with bacterial POE were indistinguishable from conjunctival and lid specimens. Microbial spectrum of POE is dependent on environmental, geographical, or climatic factors and varies significantly in different countries.7,11,17,18,19,20,21,22,23 Prophylaxis regimens against infectious POE differ in several countries.24,25,26 In 2013, the ESCRS have published guidelines on prevention and treatment of POE.15 Surgical procedures should be performed in specially prepared operating theaters (proper air-flow design, sterile and/or single-used equipment); washing hands with an antiseptic soap solution, mask, gowning, and sterile gloves are recommended. Topical povidone–iodine (PVI) should be used for antisepsis of the periocular skin area, cornea, and conjunctival sac. The 5 to 10% PVI solution should be left in place at the skin surface to act for at least 3 minutes. In case of any contraindications (allergy or hyperthyroidism), it can be replaced with the 0.05% solution of chlorhexidine. The surgical site should be scrupulously prepared and lids should be thoroughly draped to ensure adequate eyelash coverage. For conjunctiva and cornea antisepsis, 5% PVI solution should be left in the conjunctival sac for at least 3 minutes. It is important not to use PVI solution containing a detergent as it irreversibly coagulates the cornea. ESCRS guidelines also recommend applying 1-mg cefuroxime in 0.1-mL saline (0.9%) by intracameral injection at the end of surgery, as it has been proven that this maneuver reduces the POE rates by severalfold.15 In 2012, specific commercial cefuroxime sodium at the necessary concentration (0.1 mg/mL) for intracameral use called Aprokam (Laboratories Théa, Clermont-Ferrand, France) received approval by the European Medicines Agency (EMA) and was introduced to the European market. By now, it is officially approved for intracameral antibiotic-prophylaxis of POE after cataract surgery in most European countries. Each vial contains 50 mg of cefuroxime to be reconstituted with 5 mL of saline solution and administered in the amount of 0.1 mL into the anterior chamber at the end of cataract surgery. Aprokam is a broad-spectrum antibiotic and covers most gram-positive and gram-negative organisms commonly associated with postoperative infectious endophthalmitis, including staphylococci, streptococci (except methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, and Enterococcus faecalis), gram-negative bacteria (except Pseudomonas aeruginosa), and P. acnes. It is also important to treat properly preexisting infections, such as blepharitis, conjunctivitis, or dacryocystitis as well as infections in contralateral eye and socket. The role of topical antibiotics in POE as preoperative prophylaxis is controversial and the regime differs in several countries.27,28 It has been shown that the addition of topical antibiotics to PVI does not provide additional reduction in bacterial colonization of conjunctival sac.27,28,29,30 ESCRS guidelines state that the use of topical antibiotics preoperatively and/or postoperatively does not have any specific benefit over the use of chlorhexidine or PVI preoperatively and over intracameral antibiotics injected at the close of surgery.15 Although postoperative topical antibiotics are used in majority of European countries for 5 to 7 days, their preoperative use has declined in recent years. In Sweden and Denmark, most surgeons avoid using topical antibiotics before and after cataract surgery, as they are not recommended by national guidelines in standard cases. Topical antibiotics reduce selected sensitive conjunctival flora, unlike antiseptics, that is, PVI that reduces all conjunctival bacterial growth. Furthermore, topical PVI is the only intervention that has been demonstrated by a randomized clinical trial (RCT) to reduce the risk of POE.31 The choice of postoperative antisepsis should be at the surgeon’s discretion, after evaluating the postoperative state of a patient and assessment of complications that occurred. In a noninflamed eye, the antibiotic weakly penetrates inside the globe; thus, intravenous antibiotic prophylaxis is not recommended. Oral antibiotic prophylaxis is recommend exclusively in cases of coexisting severe atopic disease, as the lid margins are more frequently colonized with S. aureus. The EVS, conducted in the early 1990s, is to date the only multicenter, prospective, RCT evaluating the roles of PPV and vitreous tap (VT) in the management of POE after cataract surgery. The EVS study concluded that vitrectomy is of substantial benefit for patients with initial visual acuity no better than light perception only.16 However, more recent studies have shown that early vitrectomy is beneficial for patients with better visual acuity, as it immediately reduces the inflammatory debris in vitreous cavity, removes nontransparent medium allowing inspection of the retina, provides better access of intravitreally administered drugs to the tissues and also provides an adequate specimen for microbiological diagnosis (
20.1 Introduction
20.2 Endophthalmitis
20.2.1 Classification
Fig. 20.1) is a serious inflammation due to an infectious process from bacteria, fungi, or parasites that enter the eye during the perioperative period. It affects the vitreous cavity and is one of the most dreaded complications of ophthalmic surgery, as it may cause severe visual acuity loss, or even loss of the eye. Endophthalmitis may be divided into several categories depending upon the cause of infection, the onset of symptoms, or the degree of inflammation. Most cases of endophthalmitis are exogenous, and occur after eye surgery (postoperative endophthalmitis [POE]), after penetrating ocular trauma (posttraumatic endophthalmitis), or as an extension of keratitis. Usually POE develops after cataract surgery; however, it can be also a complication of glaucoma surgery (associated with either conjunctival filtering bleb, or glaucoma drainage devices) or intravitreal injections. Endogenous endophthalmitis is an uncommon condition that can arise from bacteremic or fungemic seeding of the eye via the bloodstream. However, endophthalmitis is never a source of bacteremia or fungemia. Common risk factors are intravenous drug abuse, diabetes mellitus, immune compromise, malignancy, and chronic diseases with long hospital stays, catheters, and prolonged intravenous antibiotic therapy. The most common pathogens in endophthalmitis vary by category. Most frequently reported organisms causing acute-onset postcataract endophthalmitis are coagulase-negative staphylococci (CNS), whereas Propionibacterium acnes usually cause chronic postcataract endophthalmitis. CNS and viridans streptococci are the most common pathogens in endophthalmitis following intravitreal injections, whereas Streptococcus species, Haemophilus influenzae and Staphylococcus species usually cause endophthalmitis following glaucoma surgery. Posttraumatic endophthalmitis, in most of the cases, is caused by Bacillus and Staphylococcus species. Candida species, Staphylococcus aureus, and gram-negative bacteria are, in turn, the most common causes of endogenous endophthalmitis. Regardless of category, the most important component of treatment is intravitreal injection of antibiotics, along with vitrectomy in some cases.
20.2.2 Epidemiology
Table 20.1. The recommendations of the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) have set the maximum acceptable level of incidence for POE after cataract extractions as 0.05%.14 Surgical complications (wound leak, posterior capsule rupture, vitreous loss, or zonular complications) are related with higher incidence of POE. The elderly patients (older than 85 years), those with clear corneal incisions versus scleral tunnel incisions, and those without intracameral injection of cefuroxime have a higher risk of infection. Moreover, the type of intraocular lens (IOL) implanted is also considered a risk factor. Patients with silicone IOLs have higher probability of endophthalmitis compared to those with acrylic (or other material) IOLs.
20.2.3 Diagnosis
20.2.4 Etiology
Table 20.2 presents the etiology of POE in different regions of the world. In Europe, most commonly isolated organisms in postcataract endophthalmitis are gram-positive bacteria, including Staphylococcus epidermidis, Staphylococcus aureus, and Streptococcus pneumoniae, while gram-negative bacteria are in the minority. However, there are significant differences in a rate of enterococcal infections in Sweden (30–31%) compared with other European countries (2% in the Netherlands and United Kingdom), or the United States (3%).7,11,17,18,19 This may be connected with extensive use of intracameral cefuroxime in Sweden and increased proportion of cefuroxime-resistant species. In the United States, as in Europe the rate of streptococcal infections is lower, whereas CNS is the most commonly identified microorganism. In tropical regions of Asia, the reported percentage of gram-negative and fungal cases is much higher than in Europe and the United States.20,21,22,23 It should be emphasized that the main prognostic factor predictive of the final visual result in patients with POE is bacterial virulence level. Streptococcal strains are often virulent, producing exotoxins, and thus are associated with poor visual outcome.
20.2.5 Prophylaxis
20.2.6 Treatment
Fig. 20.2). The decision to perform a surgery should always be driven by the clinical appearance and course. ESCRS guidelines on prevention, investigation, and management of POE (2013) consider an immediate PPV performed by a vitreoretinal surgeon as a gold standard of treatment of acute POE.15 When a vitreoretinal surgeon and a vitreoretinal operating room are not available immediately, the silver standard would be a vitreous biopsy with a vitreous cutter and not with a syringe and needle. Subsequently, antibiotics should be injected intravitreally and repeated as necessary according to the clinical response at intervals of 48 to 72 hours. Full vitrectomy should be considered later. It should be emphasized that EVS showed no harmful effect of vitrectomy compared with the VT; however, the study excluded the most severe cases of POE.
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