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 [102]. 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 [103]. Conversely, a study from Hong Kong identified bacteria as a more common cause [104]. 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].

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 [3]. 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 [108] (Table 15.2). Bleb-related endophthalmitis (BRE) presents similarly, although a relative afferent pupillary defect can also be seen [109]. 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 [28]. 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 [112].

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 [3]; 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) [3].

Common masqueraders of endophthalmitis include several conditions associated with a pseudohypopyon such as Behcet’s disease, rifabutin use [115], HLA-B27 uveitis, toxic anterior segment syndrome (TASS), multiple myeloma [116], retinoblastoma [117], 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 [123], and injection of intravitreal aflibercept which produces a sterile inflammatory reaction that often lacks pain or conjunctival erythema and typically responds to topical steroids [124].

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 [125]. 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 [126]. 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 [115]. 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 [115]. 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 [108]. 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.

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%) [108].

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 [151]. 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 [127].

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 [108]. 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 [108]. If sufficient material is available, specific polymerase chain reaction (PCR) studies should also be ordered based on clinical suspicions [115].

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.