Endophthalmitis

Endophthalmitis is an inflammatory process of the inner layers of the eye, which may be either infectious or sterile. Infectious endophthalmitis can lead to irreversible vision loss if not treated quickly. Based on the entry mode of the infectious source, endophthalmitis is divided into endogenous and exogenous types. Exogenous endophthalmitis occurs via direct inoculation of infectious organisms during cataract surgery, ocular trauma, or intravitreal injection. Endogenous endophthalmitis results from hematogenous seeding. Sterile endophthalmitis may result from toxins or retained lens material after an ocular operation. Clinical features vary depending on the type and course of the disease. Features may include decreased vision, conjunctival injection, ocular pain, hypopyon, and corneal edema. The diagnosis primarily depends on history and ophthalmological examination, and treatment is based upon the underlying cause. Sterile endophthalmitis generally resolves spontaneously while infectious endophthalmitis is treated with antimicrobials (antibiotics or antifungals). Vitrectomy may be needed in severe disease.

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Definition and Epidemiology

Definition

Endophthalmitis is an inflammatory process of the intraocular cavities (e.g., aqueous and/or vitreous humor) usually caused by bacteria or fungi.

Epidemiology

  • The incidence between men and women is equal.
  • More common in the elderly and after cataract surgery
  • Exogenous endophthalmitis is the most common form:
    • 60% of exogenous cases occur after intraocular surgery.
    • Occurs in 0.1%–0.3% of cataract operations
    • 25%–30% of cases are posttraumatic.
  • Endogenous endophthalmitis:
    • More common in immunocompromised individuals
    • Candidal infections are increasing in IV drug users.
    • Rare (2%–15% of all cases)

Etiology

Sterile endophthalmitis

  • Complication of intravitreal injection (triamcinolone, anti-vascular endothelial growth factor (anti-VEGF), methotrexate)
  • Retained native lens after an operation

Infectious endophthalmitis

Exogenous: 

  • Acute-onset postoperative endophthalmitis:
    • Occurs within 6 weeks of an ocular procedure
    • Cataract surgery is the most common cause.
    • Organism:
      • Coagulase-negative Staphylococcus (most common) 
      • Staphylococcus aureus
      • Streptococcus
  • Delayed-onset postoperative endophthalmitis:
    • Less common than the acute-onset variety
    • Occurs more than 6 weeks after surgery
    • Organisms:
      • Propionibacterium acnes (predominant)
      • Coagulase-negative Staphylococcus
      • Fungal infections (16%–27% of cases)
  • Bleb-associated endophthalmitis:
    • Following trabeculectomy
    • Organisms:
      • Coagulase-negative Staphylococcus
      • Haemophilus influenzae
      • Moraxella catarrhalis 
      • Staphylococcus aureus
  • Post-intravitreal injection endophthalmitis:
    • Occurs following injection of anti-VEGF medications (e.g., bevacizumab) or corticosteroids
    • Organisms:
      • Coagulase-negative Staphylococcus
      • Streptococcus 
  • Posttraumatic endophthalmitis:
    • Occurs following penetrating trauma to the eye
    • Organisms:
      • Bacillus cereus (one of the most common organisms) 
      • Gram-positive cocci 
      • Gram-negative organisms

Endogenous:

  • Hematogenous spread of bacteria/fungi from a distant source (e.g., endocarditis, indwelling catheter)
  • Caused by:
    • Gram-positive organisms (in the United States)
    • Fungi: Candida albicans is the most common, followed by Aspergillus and Fusarium.

Pathogenesis

Normally, the ocular-blood barrier naturally resists invasive organisms.

Exogenous endophthalmitis

Pathophysiology:

  • Disruption of globe integrity:
    • Cataract operations
    • Radial keratotomy
    • Intravitreal injections
    • Retinal or glaucoma operations
    • Penetrating foreign bodies
  • Introduction of causative organisms

Risk factors:

  • Blepharitis
  • Diabetes mellitus
  • Older age
  • Wound contamination
  • Traumatic lens rupture
  • Delayed wound closure
  • Compounded medication usage

Endogenous endophthalmitis

Pathophysiology:

In unilateral cases, the right eye is twice as likely as the left eye to become infected.

  • Hematogenous spread from distant sites
  • Blood-borne organisms breach the blood-ocular barrier by:
    • Direct invasion
    • Changes in vascular endothelium as a result of substrates released during an infection

Risk factors: 

  • Immunocompromised conditions
  • Diabetes mellitus
  • Malignancies
  • IV drug use
  • Indwelling catheters
  • Urinary tract infections
  • Organ transplant
  • End-stage liver or renal disease

Clinical Presentation

Exogenous

Acute:

  • Usually bacterial
  • Occurs within days after an inciting event
  • Presents with: 
    • Decreased visual acuity
    • Eye pain
    • Eyelid edema
    • Conjunctival injection
    • Hypopyon (WBCs in the anterior chamber)
    • Corneal-ring ulcer (traumatic)
    • Absent red reflex

Chronic:

  • Usually from fungi or less-virulent bacteria
  • Gradual onset
  • Visual acuity may be preserved until late in the presentation
  • Corneal infiltrates with fuzzy or feathery borders
Hypopyon and track of pus with endophthalmitis associated with glaucoma shunt intraluminal stent exposure

Hypopyon and track of pus with endophthalmitis associated with glaucoma shunt intraluminal stent exposure

Image: “Hypopyon and track of pus from tube at presentation with endophthalmitis” by Jaypee Brothers Medical Publishers (P) Ltd. License: CC BY 3.0

Endogenous

  • Subacute onset
  • Signs of a systemic infection may be present (e.g., fever).
  • Presentation may include:
    • Decreased vision
    • Eye pain
    • Hypopyon
    • Subconjunctival hemorrhage
    • Conjunctival injection
    • Corneal edema
    • Reduced or absent red reflex

Diagnosis

Endophthalmitis diagnosis is based on clinical presentation with confirmation by laboratory testing of aqueous and/or vitreous humor.

History

  • Focus on risk-increasing practices or procedures:
    • Recent ocular procedures
    • Trauma
    • IV drug use
    • Immunosuppression
    • Sepsis risk
  • Ocular symptoms:
    • Pain and irritation
    • Photophobia
    • Headache
    • Redness
    • Decreased visual acuity
  • Fever

Physical exam

Fundoscopy:

  • Reduced fundal view
  • Loss of red reflex
  • Roth spots:
    • Retinal hemorrhages
    • Occurs in endocarditis
A fundoscopic examination of a patient with endogenous fungal endophthalmitis

A fundoscopic examination of a patient with endogenous fungal endophthalmitis demonstrates a yellow retinal lesion medial to the optic nerve.

Image: “Endogenous fungal endophthalmitis: risk factors, clinical features, and treatment outcomes in mold and yeast infections.” by Sridhar J, Flynn HW, Kuriyan AE, Miller D, Albini T. License: CC BY 2.0

Slit-lamp examination:

  • Inflammation in the anterior chamber:
    • Cells
    • Fibrin
  • Infiltrates in the vitreous cavity
  • Thick, clumpy material in aqueous humor (fungal)
  • Puff–ball-like lesions in the vitreous cavity (fungal)

Diagnostic testing

  • Ultrasound-B scan:
    • Use when the posterior segment is not visualized.
    • Findings: vitreous debris, retinochoroidal thickening
  • CT scan: cases of orbital trauma (avoid MRI due to potential of foreign bodies of metal)
  • Collection of ocular fluid (vitreous/aqueous) for microbiological study: 
    • Real-time PCR:
      •  Identify both bacteria and fungi
      •  Preferred over Gram stain
    • Gram stain 
    • Culture
  • Culture of the penetrating object if traumatic injury

Workup support by diagnostic testing

Diagnostic testing supports workup to search for the source of endogenous endophthalmitis:

  • Echocardiogram to rule out infective endocarditis
  • Chest X-ray to evaluate the source of infection
  • Blood cultures to identify potential hematogenous seeding agent
  • CBC with differential to evaluate for signs of infection
  • Erythrocyte sedimentation rate (ESR)
  • Urine culture to evaluate for urinary tract infection as the cause
  • Culture of the indwelling catheter tip to identify if a catheter-related source

Management

Management depends on the underlying cause and outcome is extremely dependent on timely diagnosis and treatment. 

Sterile endophthalmitis

  • Usually resolves without further treatment
  • Topical steroids may be used.
  • Treat with antibiotics in severe disease.

Infectious endophthalmitis

Fungal:

  • Intravitreal injections: 
    • Achieves a high concentration of the drug in the vitreous cavity without systemic side effects
    • Options: amphotericin B or voriconazole
  • Systemic therapy: 
    • Used in all cases of endogenous endophthalmitis (part of systemic infection)
    • Used in addition to intravitreal injections for exogenous endophthalmitis
    • Options: IV fluconazole or voriconazole
  • Pars plana vitrectomy (PPV): 
    • For severe disease 
    • Removes the vitreous humor 

Bacterial:

  • Hospital admission
  • Intravitreal injections:
    • Vancomycin plus ceftazidime 
    • Amikacin is an alternative (may cause retinal toxicity).
  • IV antibiotics: 
    • Vancomycin 
    • Fluoroquinolone or a 3rd-generation cephalosporin
  • Topical steroids
  • PPV

Traumatic endophthalmitis

  • Hospital admission
  • Treat ruptured globe (if present).
  • Intravitreal antibiotics
  • Systemic antibiotics:
    • Vancomycin plus ceftazidime
    • Consider clindamycin if soil contamination (covers Bacillus).
  • PPV

Differential Diagnosis

  • Uveitis: inflammation of the uvea. Patients usually present with decreased visual acuity, photophobia, and periocular pain. Uveitis is often idiopathic but may be caused by genetic, immune, traumatic, or infectious etiologies. An examination may show hypopyon and vitritis, or macular edema. Management depends on the etiology. Steroids are used in idiopathic uveitis. Infectious uveitis is treated with antibiotics or antiviral therapy.
  • Vitreous hemorrhage: the leakage of blood into the vitreous body. Patients present with dramatic vision loss, floaters, visual haze, and blurring. Slit-lamp examination shows blood floating in the vitreous cavity. Management is based on the disease severity and the underlying etiology. Photocoagulation or PPV may be performed.
  • Toxic anterior segment syndrome (TASS): a sterile inflammation of the anterior segment occurring 12–24 hours after ocular surgery, resulting as a reaction to a sterile toxin or contaminant of surgery. Patients present with ocular pain and mildly decreased visual acuity. Slit-lamp examination shows conjunctival injection, corneal edema, and fibrin deposition in the anterior segment. Hypopyon and intravitreal inflammation are not present. Management includes the administration of topical steroids.
  • Corneal ulcer: an epithelial defect commonly associated with corneal inflammation. Most corneal ulcers are infectious (bacterial and viral causes). Noninfectious ulcers may be autoimmune or due to toxins/chemical burns. The presentation includes conjunctival erythema, discharge, foreign-body sensation, and decreased vision. Slit-lamp evaluation is mandatory, and the condition is considered an ocular emergency. Management is with antibiotic topical agents.

References

  1. Vaziri, K., et al. (2015). Endophthalmitis: state of the art. Clinical ophthalmology (Auckland, N.Z.). 9, 95–108. https://doi.org/10.2147/OPTH.S76406
  2. Sheu, S. J. (2017). Endophthalmitis. Korean journal of ophthalmology. 31(4), 283–289. https://doi.org/10.3341/kjo.2017.0036
  3. Kernt, M., & Kampik, A. (2010). Endophthalmitis: Pathogenesis, clinical presentation, management, and perspectives. Clinical ophthalmology (Auckland, N.Z.). 4, 121–135. https://doi.org/10.2147/opth.s6461
  4. Relhan, N., et al. (2018). Endophthalmitis: Then and Now. American journal of ophthalmology. 187, xx–xxvii. https://doi.org/10.1016/j.ajo.2017.11.021
  5. Durand, M. (2021). Bacterial endophthalmitis. UpToDate. Retrieved April 25, 2021, from https://www.uptodate.com/contents/bacterial-endophthalmitis
  6. Egan, D. (2018). Endophthalmitis. Medscape. Retrieved April 25, 2021, from https://reference.medscape.com/article/799431-overview
  7. Simakurthy, S., and Tripathy, K. (2021). Endophthalmitis. StatPearls. Retrieved June 2, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK559079/
  8. Lowth, M. (2014). Endophthalmitis. In Tidy, C. (Ed.), Patient. Retrieved June 2, 2021, from https://patient.info/doctor/endophthalmitis

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