Endophthalmitis

OVERVIEW: What every practitioner needs to know

Are you sure your patient has endophthalmitis? What should you expect to find?

• The key symptoms are pain, photophobia, ocular and periocular redness, lid swelling, conjunctival discharge, and blurring or decreased vision.

• The key physical findings are: erythematous and swollen eyelids; injected conjunctiva and sclera; corneal edema; reduced visual acuity; anterior chamber cells and flare (slit lamp exam), hypopyon (dependent layering of inflammatory cells and exudate); fibrin membrane formation; vitritis (vitreous clouding precluding view of retinal vessels); cotton-wool spots; reduced or absent red reflex (See Figure 1).

Figure 1.

How did the patient develop endophthalmitis? What was the primary source from which the infection spread?

• Endophthalmitis implies infection by bacteria and fungi of the intraocular cavities (i.e. vitreous or aqueous humors). There are two main types of endophthalmitis: endogenous (metastatic) and exogenous.

  Endogenous endophthalmitis accounts for about 2-15% of all cases. It results from hematogenous spread from a distant, concurrent source in the host (e.g. endocarditis) or from an indwelling external source (e.g. intravenous line or catheter). Endogenous endophthalmitis ipsilateral in 14-25%, often with one eye (right eye is twice as likely) more heavily affected. Endogenous fungal endophthalmitis has been reported in the range of 3-45% of patients with disseminated fungal infection. The higher numbers were from several decades ago; this is much less frequently seen now that recommendations are to treat all patients with candidemia with antifungal agents.

  Exogenous endophthalmitis results most commonly from intraocular surgery (70%), penetrating ocular trauma with or without a foreign body (20%), blunt trauma, bleb-associated, and as extension from severe microbial keratitis. In addition, there are rare reports of endophthalmitis associated with glaucoma shunts and keratoprostheses.

Which individuals are of greater risk of developing endophthalmitis?

• Endogenous endophthalmitis occurs with an incidence of 5 per 10,000 in hospitalized patients. The most important host sources of infectious agents include endocarditis, gastrointestinal (GI) tract, genitourinary (GU) tract/pyelonephritis, skin and wound infection, pulmonary infections, meningitis, and septic arthritis/osteomyelitis. External sources include invasive procedures with predisposing factors such as hemodialysis, bladder catheterization, gastrointestinal endoscopy, total parental nutrition, chemotherapy, dental procedures, and intravenous drug abuse.

• Endogenous bacterial endophthalmitis accounts for 2-8% of all cases, usually due to S. aureus and Gram-negative bacteria. Many patients are diagnosed with medical conditions including diabetes, hypertension, gastrointestinal disorders, cardiac disorders, malignancy, and immunosuppression or prolonged surgical complications. Systemic symptoms (fever) rather than acute ocular symptoms have been the most common reason to present and many cases are misdiagnosed with loss of vision.

• Endogenous fungal endophthalmitis has been reported over a wide range of 3-45% of patients with disseminated fungal infection. Candida albicans endophthalmitis is the most frequent (75-80% of fungal cases), but with a changing epidemiology. It has become more common in patients with long-term indwelling lines and catheters. Overall, it is less common because of the now standard practice of treating all patients who have candidemia. Aspergillosis is the second most common especially in intravenous drug users.

• Exogenous endophthalmitis results most commonly from intraocular surgery (60-70%), followed by penetrating trauma. The incidence of post-cataract surgery endophthalmitis is 0.05 – 0.3%; risk factors include loss of vitreous, disrupted posterior capsule, poor wound closure, and prolonged surgery. In the early, acute post-operative period (<6 weeks), the vast majority are Gram-positive bacteria including coagulase-negative staphylococci (70%), Staphylococcus aureus (10%), Streptococcus species (11%), and Gram-negatives only account for 6%. In the delayed, chronic post-operative period (>6 weeks) (also called chronic pseudophakic referring to infection of the implanted intraocular lens), Propionibacterium acnes (41-63%), coagulase-negative staphylococci (16%), and fungi (21%) (mostly Candida, then Aspergillus sp.) are the most common. Gram-negatives (6%), atypical mycobacteria (3%), and Nocardia occur rarely.

• In conjunctival filtering bleb-associated endophthalmitis, the onset may be after several years, and the etiologic agents include Streptococcus sp. (47%), coagulase-negative staphylococci (22%), and Haemophilus influenzae (16%).

• The incidence of post-traumatic endophthalmitis after a perforating injury is 2-17%, but the presence of a foreign body at least doubles the risk of endophthalmitis (7-31%) with the higher incidence in rural compared to non-rural settings. Risk factors include retained intraocular foreign body, delayed surgery (>24 hours), rural setting with soil contamination, and disrupted crystalline lens. The signs of infection occur early, but are often masked by the injured inflamed tissue. The rapidly destructive Bacillus sp. (B. cereus) accounts for 24%, while Staphylococcus sp. (39%) and Gram-negative organisms (7%) account for less. Fungi (particularly filamentous fungi) may play an important role in soil, wood, or organic matter contaminated wounds.

Beware: there are other diseases that can mimic endophthalmitis:

• Uveitis (inflammation of any of three components of uveal tract: iris, ciliary body, or choroid)

• Sterile inflammation (prolonged intraoperative surgical manipulations, especially involving the vitreous)

• Retained lens material

• Rebound inflammation after sudden decrease in postoperative steroids

• Toxic anterior segment syndrome (TASS; acute postoperative anterior chamber reaction and corneal edema due to contaminants from surgical instruments, intraocular [IOL] solutions, or IOL implant) – usually within 1-2 days post-surgery

• Intraocular foreign body

• Intraocular tumor

• Sympathetic ophthalmia

• Anterior segment ischemia (from carotid artery disease) (ocular ischemia syndrome)

• Rectus muscle surgery (usually on multiple rectus muscles on the same eye at the same surgery)

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

• If endogenous endophthalmitis is suspected, peripheral WBC and differential, C-reactive protein, sedimentation rate, and several blood cultures. In exogenous endophthalmitis, less than one-third of patients have elevated WBC.

Results that confirm the diagnosis

• Vitreous (0.2-0.3mL) and Aqueous (0.1-0.2mL) fluid aspirates: One drop each on blood, chocolate, Sabouraud media, anaerobic media, and meat broth and one drop for Gram-stain. If vitrectomy is performed, 3mL of the vitreous wash should be centrifuged, the pellet smeared on a slide for a Gram stain, and calcofluor white stain if fungus is suspected. The remainder of the washing is filtered through 0.45-micron membrane and the filter paper should then be plated on the above media. Vitreous WBC is performed if sample is adequate.

• Aqueous aspirate cultures are positive in only 40%, vitreous aspirate cultures are positive in 75%, while vitrectomy obtained vitreous cultures are 90% yield. Gram stains are positive in only 45% of cases.

• Consider PCR of vitreous sampling or washing with the universal eubacterial (and fungal) primers, particularly in chronic endophthalmitis (CPE). In CPE, if tap not diagnostic, mechanical biopsy of the vitreous through pars plana vitrectomy. The highest diagnostic yield is by sampling the white plaque in the posterior lens capsule if present, utilizing specialized culture media, as well as prolonging the culture time to several weeks to cover slow-growing organisms. Contamination limits its usefulness and refers to (ocular) specialty molecular biology centers that handle smaller volumes.

What imaging studies will be helpful in making or excluding the diagnosis of endophthalmitis?

• B-scan (ultrasound of the eye) to look for vitreous debris (increased echogenicity of the vitreous) and retinal detachment. $

• Optional computed tomography (CT) scan of the orbits to assess for foreign bodies, displaced glaucoma shunts, concurrent orbital cellulitis or sinusitis. $$

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has endophthalmitis, what therapies should you initiate immediately?

Intravitreal injection of antibiotics is the cornerstone of treatment.

Key principles of therapy

• Check B-scan ultrasonography for vitritis and retinal detachment.

• Perform prior to therapy: intravitreal tap, mini-vitrectomy (vitreous ’biopsy’), or core vitrectomy within one hour

• Obtain anterior chamber and vitreous fluid (Gram-stain and cultures)

When to perform vitreous aspiration (’tap and inject’) versus vitrectomy

• Vitreous tap may be used for initial diagnosis in vision loss less than light perception or if obtaining vitrectomy (best by retinal specialist) would lead to delay in diagnosis and delivery of intravitreal antibiotics.

• Anterior or pars plana (core) vitrectomy for severe vision loss (light perception); loss of red reflex; rapidly, fulminant infection; Gram-negative or fungal infection; or failure of initial therapy over 24-48 hours.

• Intravitreal antibiotic injection may be repeated in 24-48 hours, and even a third time 48-72 hours with more targeted therapy.

• Intravitreal dexamethasone is used in fulminant bacterial infections (if diagnosis known); contraindicated in fungal infections.

• The intraocular lens implant does not need to be removed, except in chronic pseudophakic (P. acnes), fungal, or atypical mycobacteria endophthalmitis.

*Benefit of systemic antibiotics benefit is controversial. We recommend initial systemic vancomycin until cultures are final. The EVS study did not evaluate vancomycin, and suggested no benefit to intravenous therapy (studied amikacin and ceftazidime). EVS study examined post-cataract surgery endophthalmitis; they did not examine post-traumatic, bleb-associated or endogenous endophthalmitis.

1. Anti-infective agents

If I am not sure what pathogen is causing the infection what anti-infective should I order?

Table I. Etiology of Endophthalmitis, Usual Pathogens and Suggested Initial Therapy