Types of endophthalmitis categorized by route of infection
Routes of Infection
Postoperative endophthalmitis can be classified into two broad categories: acute-onset (<6 weeks after surgery) and delayed-onset (>6 weeks after surgery). The overall incidence of acute-onset postoperative endophthalmitis is approximately 0.1% [1–3]. Endophthalmitis can occur after any type of surgery; the most common procedures associated with postoperative endophthalmitis are discussed below.
Acute Post-cataract Surgery Endophthalmitis
Cataract surgery is one of the most common intraocular procedures and accounts for the majority of postoperative endophthalmitis cases [2, 4, 5]. The incidence of acute postoperative endophthalmitis (POE) after cataract extraction ranges from 0.028 to 0.16% in the literature [1, 2, 4, 6–12]. A variety of factors are associated with the risk of acute endophthalmitis including extracapsular or intracapsular extractions, surgeries combined with lacrimal or eyelid procedures, postoperative wound defects, preoperative eyelid abnormalities, and intraoperative complications, namely, posterior capsular rupture, which can increase the risk 8- to 11-fold [11, 13–16]. Nonsurgical risk factors for endophthalmitis after cataract surgery include age over 80 and diabetes [4, 16].
The pathogenic microorganisms are most commonly innate bacteria that reside on the eyelid margin and within the tear film [17, 18]. Coagulase-negative Staphylococcus is the most commonly isolated organism comprising 54–70% of culture-positive cases of POE [19–21]. Staphylococcus aureus and Streptococcus species also cause a significant number of cases [1, 19, 20, 22–24]. Negative cultures account for 16.7–35% of cases in the United States [1, 20, 21, 24, 25].
Chronic Post-cataract Surgery Endophthalmitis
Chronic post-cataract endophthalmitis is less common than acute POE and is marked by insidious inflammation. It can manifest weeks to months after surgery and is typically associated with less virulent bacterial and fungal pathogens. The incidence of chronic post-cataract endophthalmitis is 0.017% based on a single-center study . Propionibacterium acnes is the most commonly isolated pathogen comprising 41.2–63% of positive cultures [26–30]. Coagulase-negative Staphylococcus [27, 31], Corynebacterium , Candida , Actinomyces , and Nocardia  species can also produce a similar chronic, smoldering presentation to that of P. acnes .
The incidence of bleb-related endophthalmitis (BRE ) after trabeculectomy ranges from 0.061 to 2.6% [4, 34–40] for early-onset POE and 0.19–0.6% for late-onset POE [38–40]. Antiproliferative agent use [38, 39, 41, 42] and inferiorly-located trabeculectomies [35, 42, 43] significantly increase the risk of BRE. The most significant postoperative risk factor is bleb leakage [41–43]. Gram-positive organisms, most commonly Staphylococcus and Streptococcus species, are responsible for the majority of cases [44–46]. Culture positivity is present in 64–86% of BRE cases, notably higher than rates associated with other causes of POE [45–47].
Post-corneal Transplantation Endophthalmitis
The incidence of endophthalmitis after penetrating keratoplasty (PK) ranges from 0.08 to 0.67% [1, 2, 4, 8, 48–51]. A downward trend in the incidence of post-PK endophthalmitis has been observed since 1991, probably due to increased iodine use on the donor tissue prior to harvest as well as on the recipient tissue prior to surgery. Other factors that may have contributed to the decrease in post-PK endophthalmitis include the addition of antibiotics for gentamycin-resistant species in the tissue storage media and use of fluoroquinolones for surgical prophylaxis .
Risk factors for post-PK endophthalmitis include death of donor by infection and high-risk graft indications such as ulcerative keratitis and trauma . A positive donor rim culture significantly increases the risk of the recipient developing endophthalmitis [52, 53]. Postoperative risk factors including graft ulceration , suture abscess, and wound gape . Gram-positive bacteria, such as Streptococcus species, are the most common culprit of post-PK endophthalmitis cases where an organism is identified [49, 50, 53, 56–58]. Negative cultures account for approximately 10.9% of cases based on a single-center study .
Post-intravitreal Injection Endophthalmitis
There has been exponential growth in the use of intravitreal injections over the past decade. This can be attributed primarily to the advent of anti-vascular endothelial growth factor (anti-VEGF) agents which are used to treat numerous conditions like exudative age-related macular degeneration and diabetic macular edema. Although one study found that intravitreal injections accounted for 8.5% of all endophthalmitis cases , most studies estimate the incidence of postinjection endophthalmitis to be much lower, ranging from 0.00 to 0.095% [60–74]. The largest study evaluating this issue analyzed 316,576 injections and observed 65 cases of endophthalmitis, equating to an incidence of 0.021% . Gram-positive organisms are the most frequent culprit of postinjection endophthalmitis cases, and coagulase-negative Staphylococcus and Streptococcus species are the most commonly isolated organisms [66, 72, 75]. Negative culture rates vary significantly in the literature. Postinjection endophthalmitis generally presents earlier and has poorer visual outcomes compared to post-cataract endophthalmitis .
Risk factors for post-intravitreal injection endophthalmitis have been difficult to identify due to the low overall incidence of endophthalmitis and the wide variety of injection techniques. Suggested preventative measures include administering postinjection topical antibiotics, wearing a face mask, and utilizing a speculum; however, there is no definitive evidence to support the efficacy of any of these methods [66, 68–71, 77]. The only practice with substantial evidence for endophthalmitis prevention is the use of povidone-iodine in the preparation process [69, 78–81].
Post-traumatic endophthalmitis accounts for 20–30% of infectious endophthalmitis cases [3, 82]. Its incidence following penetrating trauma ranges from 0.0 to 12% [83–90], although this can be as high as 30% in rural settings [85, 90]. Lens violation, contamination of the wound, delayed primary globe repair, and retained intraocular foreign bodies are the most commonly identified risk factors for development of post-traumatic endophthalmitis [83, 84, 86, 91, 92]. Traumatic endophthalmitis is frequently caused by polymicrobial infections [85, 93, 94]; coagulase-negative Staphylococcus and Bacillus cereus are the most commonly cultured organisms [85, 93–97]. Bacillus cereus infections are common in penetrating eye injuries contaminated by soil and are characterized by rapid destruction of the intraocular contents and dismal visual outcomes resulting from a severe enterotoxin-mediated reaction [82, 94].
Endogenous endophthalmitis (EE) accounts for 2–11% of all cases of infectious endophthalmitis [98–100]. Risk factors include diabetes mellitus, gastrointestinal disorders, hypertension, cardiac disorders, malignancy, AIDS, immunosuppressive therapy, renal failure, intravenous drug abuse, indwelling catheters, and history of invasive surgery [98, 101]. The liver, lung, and endocardium are common sources of endogenous infection . Causative organisms vary based on geography and population demographics (Table 15.1). In the developed world, fungal organisms account for most endogenous cases. One study reported fungal pathogens in 66% of culture-positive cases, with a predominance of Candida albicans . Conversely, a study from Hong Kong identified bacteria as a more common cause . In the context of bacterial EE, gram-positive organisms are more prevalent in the Western world, whereas gram-negatives are more prevalent in Asian countries [98, 100, 103, 104]. For instance, Klebsiella endophthalmitis is frequently seen in patients with liver abscesses, a condition frequently seen in Asia [30, 105–107].
Most common causative organisms for the various types of endophthalmitis
Causative organisms in various endophthalmitis types
Coagulase-negative Staph. (54–70%)
Staphylococcus aureus (6.8–13%)
Streptococcus species (8.2–9%)
Propionibacterium acnes (41.2–63%)
Staph. species (16–17.6%)
Post-penetrating keratoplasty 
Streptococcus pneumoniae (27%)
Staphylococcus epidermidis (21.8%)
Propionibacterium acnes (14.5%)
Staphylococcus aureus (12.7%)
Post-intraocular injection 
Streptococcus species (30–55%)
Coagulase-negative Staphylococcus (14.6–20%)
Staphylococcus epidermidis (21.5–21.8%)
Bacillus species (18.5%)
Gram-positive (e.g., Staph., Strep.)
Gram-negative (e.g., Klebsiella)
Clinical Assessment and Diagnosis of Endophthalmitis
Signs and Symptoms
The classic presentation of endophthalmitis is a red, painful eye accompanied by a significant inflammatory reaction that often manifests as a hypopyon (Fig. 15.2) with vitritis . However, different etiologies of endophthalmitis may cause slight variations in the presenting signs and symptoms of a patient. In the Endophthalmitis Vitrectomy Study (EVS), 94% of patients with acute-onset endophthalmitis following cataract surgery or secondary intraocular lens implantation presented with decreased visual acuity, 82% with conjunctival injection, 74% with eye pain, and approximately 35% with eyelid edema  (Table 15.2). Bleb-related endophthalmitis (BRE) presents similarly, although a relative afferent pupillary defect can also be seen . In contrast, delayed-onset postoperative endophthalmitis typically progresses more slowly and may induce only mild inflammation. The provider must look carefully for white plaques within the remaining capsule where the infectious nidus may dwell . Post-intravitreal injection endophthalmitis usually manifests acutely within the first few days following injection. While anterior chamber cells are often present, a hypopyon and vitritis can initially be subtle [64, 110, 111]. Post-traumatic endophthalmitis may be the most highly variable in terms of presentation. While similar signs and symptoms are seen [88, 112], their onset can range anywhere from hours to years after the injury depending on the mechanism of injury, foreign body presence, and type of microorganisms involved .
External photograph of patient with a hypopyon, conjunctival injection, and corneal edema in the setting of endophthalmitis, postoperative week 1 following cataract surgery
Symptoms and signs of endophthalmitis
Classic symptoms and signs of endophthalmitis
Systemic symptoms including nausea,vomiting, chills, and fever (endogenous endophthalmitis)
Anterior chamber cells/fibrin
Deposits on remaining lens capsule
Reduced/absent red reflex
Endogenous endophthalmitis (EE) presents in a similar fashion, but due to hematogenous spread of infection in 19–33% of cases [88, 113, 114], the patient may also have constitutional symptoms such as fever, chills, or vomiting. The clinical presentation of EE may also depend on the immune status of the patient. A blunted clinical appearance in immunocompromised patients can lead to a delay in diagnosis ; in these circumstances, a detailed patient history can help identify risk factors such as intravenous drug use, sickle cell disease, foreign bodies including intravenous catheters, malignancy, neutropenia, diabetes, corticosteroid use, and acquired immunodeficiency syndrome (AIDS) .
Common masqueraders of endophthalmitis include several conditions associated with a pseudohypopyon such as Behcet’s disease, rifabutin use , HLA-B27 uveitis, toxic anterior segment syndrome (TASS), multiple myeloma , retinoblastoma , and certain leukemias and lymphomas [118, 119]. Other conditions include the use of intravitreal triamcinolone acetonide [120, 121], heavy oil emulsification [120, 122], retained lens fragments following cataract surgery , and injection of intravitreal aflibercept which produces a sterile inflammatory reaction that often lacks pain or conjunctival erythema and typically responds to topical steroids .
Diagnosis and Further Evaluation
Once endophthalmitis is suspected, it is considered an emergency given the potential for severe ophthalmic damage and vision loss. As such, a complete clinical evaluation and work-up should commence immediately. Focus should be placed on identifying the causative microbe and initiating treatment with broad-spectrum intravitreal antibiotics. To address the former, a sample of intraocular fluid must be collected for analysis. The most common and widely accepted method is a vitreous humor tap. Tapping through areas with scleral thinning or hardware (e.g., tube shunt) should be avoided if possible.
Given the severe inflammation associated with endophthalmitis, affected patients are extremely sensitive to pain, and anesthesia is critical. Some providers use topical proparacaine (0.5%) or hold localized pressure on the globe with a proparacaine-soaked cotton-tip applicator. Subconjunctival lidocaine (2%) without epinephrine can be injected on a 30-gauge 0.5-in. needle. Peribulbar or retrobulbar blocks (2% lidocaine/0.5% bupivacaine) injected on a 25-gauge 1.5-in. needle may be considered in patients with extreme discomfort, although these injections can be painful in themselves. It is important to note that due to the severe degree of inflammation often present, the penetration and efficacy of anesthesia—regardless of route—can be lower than that typically observed in routine settings.
Once the eye is anesthetized, the actual vitreous tap is done. The steps utilized by the retina providers in our department are described next. The patient is reclined into a supine position. Gloves are worn by the provider and the patient is asked not to talk so as to avoid contamination by oral flora. Povidone-iodine (5%) is dropped directly onto the ocular surface, and then 10% povidone-iodine swabs are used to clean the eyelids, eyelashes, and periorbital skin . An eyelid speculum is inserted. Calipers are used to mark the position of entry through the pars plana (3.5 mm posterior to the limbus for pseudophakic patients, 4.0 mm for phakic patients), and another drop of povidone-iodine (5%) is applied over the mark. A 23- or 25-gauge needle attached to a 3-mL syringe is inserted perpendicular to the ocular surface. Slow, steady aspiration of 0.1–0.3 mL of vitreous humor is conducted . In young patients with formed vitreous, gentle aspiration is especially important in order to avoid an iatrogenic retinal break or detachment. Once the specimen has been collected, the syringe is withdrawn while rolling a cotton-tip applicator over the site to prevent vitreous reflux; generally, injection of intravitreal antibiotics will follow, as discussed below.
An anterior chamber paracentesis (tap) can be beneficial in certain situations. Vitreous taps in young patients can be dry with no yield; these patients should undergo an aqueous tap or vitreous biopsy . Collection of aqueous can also be done to increase sample yield for cultures. Finally, aqueous taps can be considered in endophthalmitis cases with concurrent retinal detachment or tractional membranes so as to avoid further retinal damage. An anterior chamber tap is performed by entering the anterior chamber through the limbus and parallel to the iris plane with a 30-gauge 0.5-in. needle on a 1-mL syringe . Care should be taken to avoid contact of the needle with the lens.
Another method for sample retrieval is a vitreous biopsy. This invasive approach is usually reserved for cases unresponsive to broad-spectrum antibiotics with a prior unsuccessful vitreous tap or negative culture results. Moreover, in cases of trauma or severe inflammation where a complete pars plana vitrectomy (PPV) will be performed anyway, a concurrent biopsy can be done for organism identification [115, 127]. Details of the technique will be described below.
Collected specimen must be carefully handled to avoid contamination, and physicians must be aware of their specific laboratory facility’s specifications for processing specimens. Although specific tests should be individualized to the patient based on clinical suspicions, the specimen should at least be sent for Gram stain as well as aerobic and anaerobic cultures . Specifically, it can be plated on chocolate agar, enriched thioglycolate broth, anaerobic blood agar, and fresh Sabouraud dextrose agar. One should also send for KOH prep and fungal culture if fungal endophthalmitis is a concern.
Imaging and Other Ancillary Testing
Although the clinical examination and vitreous tap are the primary components of the work-up, ancillary testing can assist in the diagnosis of endophthalmitis. B-scan ultrasonography can further characterize the extent of posterior involvement if direct visualization is limited; it can also detect potential complications such as a retinal detachment or be used serially to monitor treatment response (Fig. 15.3).
B-scan ultrasound images of a patient with endophthalmitis, illustrating consolidated vitritis and fibrinous debris
If endogenous endophthalmitis is suspected, the work-up may also include an echocardiogram, gastrointestinal endoscopy, chest X-ray, abdominal ultrasound, and CT scan. Cultures of blood, urine, cerebrospinal fluid, sputum, and indwelling catheters should also be performed . Lastly, orbital or intracranial CT scan may be done to differentiate endophthalmitis from panophthalmitis .
Management of Bacterial Endophthalmitis
Early treatment of endophthalmitis is critical in optimizing visual outcomes and preventing loss of the eye. Endophthalmitis was historically treated with intravenous antibiotics in the 1940s–1960s, but suboptimal visual outcomes were observed due to poor drug penetration into the ocular tissues [3, 130, 131]. Advances in management such as intraocular sampling, intravitreal antimicrobial injections, and early surgical intervention have brought improved outcomes [3, 108].
Since their advent in the 1940s and subsequent development over decades, intravitreal antibiotics have replaced systemic antibiotics as the primary treatment for exogenous endophthalmitis [131, 132]. Even as supplemental treatment, systemic antibiotics do not seem to provide additional benefits [106, 133]. In endogenous endophthalmitis, however, systemic antibiotics are a critical adjunctive therapy to intravitreal injections. Oral or parenteral antibiotics are able to target the primary source of infection, while local intravitreal antibiotics address the endophthalmitis itself .
Intravitreal antibiotics are the mainstay of endophthalmitis treatment (Table 15.3). These allow for high concentrations of therapeutic agents to be delivered directly to the vitreous cavity while limiting systemic toxicity and side effects [134, 135]. Unfortunately, due to their short duration of action, multiple injections are sometimes required.
Common intravitreal antibiotics used to treat bacterial endophthalmitis
Common intravitreal antibiotics
Mechanism of action
1 mg/0.1 mL
Inhibits cell wall synthesis
Gram-positive (e.g., Staphylococcus aureus)
2.25 mg/0.1 mL
First-generation cephalosporin: inhibits cell wall synthesis
Gram-positive and some Gram-negative
2.25 mg/0.1 mL
Third-generation cephalosporin: inhibits cell wall synthesis
Gram-positive and some Gram-negative
0.4 mg/0.1 mL
Aminoglycoside: binds 30S ribosomal unit to inhibit protein synthesis
Gram-negative (e.g., Pseudomonas, Serratia)
200 μg/0.1 mL
Aminoglycoside: binds 30S ribosomal unit to inhibit protein synthesis
Gram-positive and Gram-negative (e.g., Pseudomonas, Klebsiella)
400 μg/0.1 mL
Fluoroquinolone: inhibits DNA gyrase
Gram-positive, Gram-negative, and anaerobes
Generally, broad-spectrum coverage is initiated to cover both Gram-positive organisms, the predominant pathogen of exogenous endophthalmitis, as well as Gram-negative organisms, which can be more virulent and convey a poorer prognosis. Most providers use intravitreal vancomycin (1 mg/0.1 mL), and a third-generation cephalosporin such as ceftazidime (2.25 mg/0.1 mL) until treatment can be tailored based on bacterial sensitivity studies [115, 127, 130, 131]. Injection of antibiotics typically immediately follows the vitreous tap, so the field is usually already prepared; if not, details for preparing the semi-sterile field are discussed above. The 0.1-mL injections should be delivered sequentially via a 30-gauge needle through the pars plana (3.5–4.0 mm posterior to the limbus in pseudophakic or phakic patients, respectively) directed toward the optic nerve. The needle should be withdrawn while rolling over the site with a cotton-tip applicator to prevent vitreous reflux. If the intraocular pressure is subsequently elevated, an anterior chamber paracentesis can be done.
Sensitivities of Gram-positive organisms to vancomycin were previously thought to be approximately 99% [4, 21], while sensitivities of Gram-negative organisms to ceftazidime ranged from 63 to 90% [108, 136]. Unfortunately, resistance to these medications may be emerging [137–139]. Fluoroquinolones and aminoglycosides (e.g., amikacin) are other treatment options and can be used in patients with a penicillin allergy. However, the growing use of fluoroquinolones has contributed to increasing resistance of S. aureus and other Gram-positive organisms to this drug class [5, 140–142]. Aminoglycosides have waned in popularity due to their potential retinal toxicity that can induce macular infarction [143, 144, 154].
Topical antibiotics are far inferior to intravitreal therapies for treating endophthalmitis due to their poor penetration and resultant low intravitreal concentrations. Still, they can be beneficial as an adjunctive treatment. In bleb-related and keratitis-associated endophthalmitis, it is recommended that intravitreal antibiotics be used alongside topical therapies such as fortified vancomycin (50 mg/mL), fortified ceftazidime or cefazolin (50 mg/mL), fortified tobramycin (14 mg/mL), or a fluoroquinolone (gatifloxacin 3 mg/mL, ciprofloxacin 3 mg/mL, or moxifloxacin 5 mg/mL) [145, 146].
Other topical therapies to consider are cycloplegics to help control pain and prevent synechia formation and topical intraocular pressure-lowering medications if the intraocular pressure is elevated. Topical steroids may be considered to help control inflammation .
Intravitreal and Periocular Steroids
The use of intravitreal or periocular steroids in the treatment of bacterial endophthalmitis remains controversial given the lack of convincing data [147, 148]. A prospective randomized clinical trial described early improvement in intraocular inflammation at 1 and 4 weeks following adjunctive administration of intravitreal dexamethasone 400 μg; however, there was no significant difference in the level of inflammation or visual acuity at 12 weeks between eyes that had received intravitreal steroid and those which did not . Another smaller prospective study showed trends of improvement in visual acuity 3 months and 12 months after intravitreal dexamethasone, but results were not statistically significant .
Aside from those outlined in the Endophthalmitis Vitrectomy Study (EVS) , no general guidelines exist as to when surgical intervention is indicated in patients with endophthalmitis. The EVS was a multicenter randomized controlled study which included patients who developed endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation. In this study, there was no apparent benefit in performing an immediate vitrectomy (versus tap/inject) if patients had hand motions visual acuity (Va) or better. For patients with light perception Va, an immediate vitrectomy (versus tap/inject) led to a threefold increase in the frequency of achieving Va 20/40 or better (33% vs. 11%), twofold improved likelihood of achieving Va 20/100 or better (56% vs. 30%), and a 50% decrease in the frequency of severe vision loss (20% vs. 47%) .
Under real-world conditions that may not mimic those of the study, whether or not to proceed with pars plana vitrectomy (PPV ) for endophthalmitis is left to the discretion of the treating physician. Surgical intervention might be considered in patients who do not respond to medical therapy or in those with chronic post-cataract endophthalmitis due to Propionibacterium acnes in which a PPV along with a total capsulectomy and intraocular lens explantation are recommended . For endogenous endophthalmitis, there is data to suggest that earlier surgical intervention when the Va is counting fingers or better may be beneficial [115, 152]. Regardless of the endophthalmitis type, patients can develop a large intraocular pus-like consolidation. In these cases, a PPV may be advantageous in order to debulk the eye and remove necrotic tissue and bacteria. Doing so can lessen inflammation, maintain vitreous transparency, and hasten visual recovery .
During a PPV , a vitreous sample can also be collected for culture. One technique involves a three-port setup where the infusion line is placed, but deliberately left off . The aspiration tubing is disconnected, and a syringe with in-line stopcock is attached. The cutter is introduced into the mid-vitreous cavity and then 1 mL of vitreous is cut and aspirated while the assistant gently draws back on the syringe; the assistant should be directed to suction only while active cutting is occurring. The surgeon should expect to see mild collapse of the ocular walls, and care should be taken not to insult retinal tissue. Once the undiluted specimen has been collected, the syringe is handed off and a new one is attached. The infusion line is turned on and the process is repeated to collect the diluted specimen. Finally, the aspiration tubing is reconnected to the cassette and the remainder of the vitrectomy is completed.
Intraoperative visualization is often poor due to corneal edema, hypopyon, lens opacity, or a profound fibrinous reaction. The view sometimes improves with anterior chamber washout or lensectomy (intraocular lens placement should be deferred). If it does not, an endoscope can be utilized. As a last resort, a surgeon can perform a blind vitrectomy where the cutter is held in the mid-vitreous cavity without much manipulation. If the view permits, careful evaluation for retinal tears should be performed. Sclerotomies should be sutured given compromised tissue integrity and risk for postoperative hypotony. Finally, intravitreal antibiotics with or without steroids should be injected at case conclusion. The vitreous aspirate collected in the cassette should be sent for culture along with the diluted and undiluted specimens. Each specimen is filtered through a sterile 0.45-μm membrane filter and then plated on culture media as discussed earlier . If sufficient material is available, specific polymerase chain reaction (PCR) studies should also be ordered based on clinical suspicions .
The decision for surgical intervention is multifactorial and case-dependent. While there are advantages to debulking the intraocular debris, addressing retinal pathology, and obtaining an abundant vitreous sample for microbial identification, disadvantages also exist (Table 15.4). There are anesthesia risks and surgical complications, and patients can experience immense postoperative pain and hypotony as a result of operating on an inflamed eye. The surgeon must weigh these carefully and remember that surgery may not improve the ultimate outcome.
Advantages and disadvantages associated with pars plana vitrectomy in the treatment of bacterial endophthalmitis
Pars plana vitrectomy for endophthalmitis treatment
Debulk infectious nidus and debris
Improve view to retina
Address concurrent retinal pathologyPremium Wordpress Themes by UFO Themes
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