Endophthalmitis

Diagnostic approach

• Visual acuity
• External eye examination
• Pupillary examination
• Tonometry
• Slit-lamp examination
• Fundoscopic exam
• Ocular ultrasound
• Vitreous sampling by ophthalmology
• Endogenous endophthalmitis: studies to evaluate for a primary source of infection (e.g., blood cultures, urine culture)

Red flag features

• Acute onset of severe eye pain
• Rapidly progressive vision loss
• Hypopyon
• Loss of red reflex
• Relative afferent pupillary defect
• Signs of sepsis

Management checklist

• Consult ophthalmology urgently.
• Empiric intravitreal antimicrobial therapy administered by ophthalmology.
• Consider adjunctive systematic antimicrobial therapy based on suspected etiology.
• Endogenous endophthalmitis: Manage underlying source.

Endophthalmitis is a rare, potentially sight-threatening inflammation of the aqueous and vitreous humor that may be infectious (resulting from bacterial or fungal infection) or noninfectious (an inflammatory reaction to a drug administered via intravitreal injection). Infectious endophthalmitis may be exogenous (e.g., following ocular surgery or penetrating trauma) or endogenous (hematogenous spread). Acute endophthalmitis typically manifests with rapidly progressive ocular pain and, possibly, vision loss, while chronic endophthalmitis has a slower onset of milder symptoms. Other clinical features include conjunctival hyperemia, corneal haziness, and hypopyon. Endophthalmitis is primarily a clinical diagnosis. Management is directed by specialists (e.g., ophthalmology, infectious diseases). Intravitreal antimicrobial therapy is indicated in most patients with infectious endophthalmitis; systemic antimicrobial therapy and vitrectomy are indicated in selected cases. Noninfectious endophthalmitis is typically managed with topical corticosteroids. Complications include panophthalmitis, corneal rupture, and permanent vision loss.

Infectious endophthalmitis ^[1][2]

Causative organisms

• Bacteria (usually manifests as acute endophthalmitis) ^[2]
  • Coagulase-negative staphylococci (most common)
  • Staphylococcus aureus
  • Streptococci
  • Bacillus cereus (in posttraumatic endophthalmitis)
• Fungi (usually manifests as chronic or subacute endophthalmitis) ^[2]
  • Candida spp.
  • Mold (Aspergillus spp. and Fusarium spp.)

Route of entry

Exogenous endophthalmitis

Exogenous endophthalmitis is the most common type of endophthalmitis and is caused by direct inoculation of the aqueous and/or vitreous humor following, e.g.: ^[1]

• Surgery (postoperative endophthalmitis): e.g., cataract surgery (most common), glaucoma surgery, corneal transplant
• Intravitreal injections
• Penetrating trauma
• Corneal ulcers
• Keratitis

Postoperative endophthalmitis is the most common form of endophthalmitis. ^[1]

Endogenous endophthalmitis

• Accounts for ∼ 15% of all cases of endophthalmitis ^[1]
• Caused by hematogenous spread of infection from a primary source (e.g., endocarditis, indwelling lines, solid organ abscess)
• Risk factors include immunocompromised state, indwelling catheters, and intravenous drug use. ^[1][3]

Noninfectious endophthalmitis ^[4]

• An inflammatory reaction to drugs injected into the vitreous
• Examples: endophthalmitis after intravitreal triamcinolone injection and intravitreal anti-VEGF therapy

Ocular pain and decreased visual acuity are the main symptoms of endophthalmitis. In general, clinical features of noninfectious endophthalmitis are less severe than those in infectious endophthalmitis. ^[5]

Acute endophthalmitis ^[1][6]

• Acute onset of symptoms (usually within 6 weeks of surgery in postoperative endophthalmitis) ^[1]
• Red painful eye
• Visual disturbance (e.g., photopsia, floaters, vision loss)
• Conjunctival hyperemia and chemosis
• Hypopyon
• Signs of sepsis (in endogenous endophthalmitis)

Suspect endogenous endophthalmitis in patients with systemic symptoms. ^[1]

Chronic endophthalmitis ^[1]

• Insidious onset of symptoms
• Mild erythema and/or swelling
• Less painful than acute endophthalmitis
• Visual disturbance (e.g., floaters and slow, progressive vision loss)

Endophthalmitis is a clinical diagnosis supported by imaging and microbiological studies on a vitreous and/or aqueous humor sample.

Bedside examination

Bedside examination should include a focused examination of the eyes on all patients and ocular ultrasound if indicated.

Visual acuity and pupillary examination ^[1]

• Visual acuity: decreased
• Swinging flashlight test: relative afferent pupillary defect

Slit lamp examination ^[1]

• Corneal edema and/or haziness
• Hypopyon and/or hazy aqueous chamber
• Vitreous chamber
  • Signs of inflammation (e.g., cells and flare)
  • Fungal endophthalmitis: white and fluffy retinal infiltrates ^[7]

Fundoscopy ^[1]

• Reduced or absent red reflex
• Obscured fundus and possible nonvisualization of retinal vessels
• Fungal endophthalmitis ^[7]
  • Candida endophthalmitis: clumps of inflammation that appear as creamy white retinal nodules
  • Aspergillus endophthalmitis: retinal necrosis, retinal hemorrhage

Ocular ultrasound ^[1][6][7]

• Indications
  • Difficulty establishing a clinical diagnosis (e.g., due to inability to visualize the vitreous chamber)
  • Assessment for complications
• Techniques
  • Ocular POCUS
  • B-scan
• Supportive findings
  • Vitreal exudates that appear as scattered echogenic stranding and/or membranes
  • Choroidoretinal thickening
  • Complications (e.g., choroidal abscess, retinal detachment)

Laboratory studies

• Confirmatory studies (obtained by ophthalmology): e.g., vitreous or aqueous sample for culture, Gram stain, PCR testing ^[8][9]
• Suspected endogenous endophthalmitis: additional studies to evaluate for a primary source of infection (e.g., blood cultures, urine culture) ^[1]
• Diagnostic uncertainty: Consider studies to rule out differential diagnoses of endophthalmitis (e.g., diagnostics for uveitis, diagnostics for optic neuritis). ^[7][10]

Negative cultures and normal ultrasound findings do not rule out endophthalmitis. ^[1][2]

Advanced imaging

• CT orbits may be obtained for suspected intraocular foreign bodies or suspected complications (e.g., abscess) ^[1]
• Suspected endogenous endophthalmitis: imaging as needed to evaluate for a primary source of infection (e.g., echocardiogram for infectious endocarditis, abdominal ultrasound for liver abscess) ^[10]

• Uveitis
• Orbital cellulitis
• Orbital apex syndrome
• Optic neuritis
• Acute angle-closure glaucoma
• Keratitis
• Open globe injury

The differential diagnoses listed here are not exhaustive.

Infectious endophthalmitis ^[1][6][7]

Approach ^[11]

• Immediately consult ophthalmology for diagnostic confirmation and administration of empiric intravitreal antimicrobial therapy.
• Consider adjunctive systemic antimicrobial therapy based on suspected etiology.
• Consult infectious diseases to tailor antimicrobial agents and treatment duration based on culture results.
• Admit for further management, including:
  • Monitoring response to therapy
  • Pars plana vitrectomy for severe or refractory disease
  • Treatment of the underlying infection in patients with endogenous endophthalmitis

Early initiation of treatment (within hours) is critical to preserve eyesight in patients with acute endophthalmitis.

Empiric intravitreal antimicrobial therapy ^[1][2][11]

• Bacterial endophthalmitis: intravitreal vancomycin AND ceftazidime
• Fungal endophthalmitis: intravitreal amphotericin B OR voriconazole ^[7][12]

Adjunctive systemic antimicrobial therapy ^[1][11]

• Postoperative bacterial endophthalmitis: not routinely indicated ^[13]
• Posttraumatic bacterial endophthalmitis
  • Ciprofloxacin (off-label) OR moxifloxacin (off-label) ^[11]
  • AND cefazolin (off-label) ^[11]
• Endogenous bacterial endophthalmitis:
  • Initiate antibiotic therapy based on suspected underlying source of bacteremia.
  • See "Empiric antibiotic therapy for sepsis."
• Fungal endophthalmitis: systemic antifungal agents (e.g., voriconazole, amphotericin B) for a minimum of 4–6 weeks ^[1][12]

Pars plana vitrectomy ^[1]

• Surgical removal of infected vitreous humor
• Indications
  • Severe vision loss (e.g., light perception only)
  • Insufficient improvement 24–48 hours after administration of intravitreal antibiotics in patients with bacterial endophthalmitis

Noninfectious endophthalmitis

Treatment for noninfectious endophthalmitis should be initiated in consultation with ophthalmology.

• Consider topical corticosteroids (e.g., prednisolone). ^[4][14]
• Diagnostic uncertainty or symptoms that worsen with corticosteroids ^[4]
  • Initiate empiric treatment for infectious endophthalmitis.
  • Pars plana vitrectomy may be considered.

• Permanent vision loss
• Panophthalmitis ^[15]
• Retinal detachment ^[16]
• Phthisis bulbi

We list the most important complications. The selection is not exhaustive.