What is endophthalmitis?

• Endophthalmitis is a vision-threatening condition associated with severe inflammation of intraocular tissue (vitreous and aqueous humor).
• Divided into endogenous and exogenous forms.
• May result in irreversible blindness within hours to days.

What are the most common causes?

• Exogenous: over 85% of cases.
  • Due to infection from microbes on the ocular surface (keratitis, bleb-related, glaucoma drainage device-related, postinjection, contact lens wear, or postoperative) or the environment (posttraumatic).
  • Most common form of endophthalmitis is postoperative endophthalmitis; typically occurs within 6 weeks of surgery.
  • Chronic postoperative endophthalmitis presents after 6 weeks following intra-ocular surgery (glaucoma filtering blebs, corneal sutures, glaucoma shunt, or cataract surgery).
• Endogenous: approximately 10-15% of all cases.
  • Due to hematogenous spread of an organism to the affected eye from a distant site (indwelling line, endocarditis, liver abscess, or other infection).
• Specific microbe is based on the cause. Coagulase negative staph most common. Candida and Aspergillus species associated with injection drug use and indwelling catheters.

What are the numbers?

• Uncommon but incidence varies based on the type of endophthalmitis.
  • Incidence of postoperative endophthalmitis is 0.036-0.36% of ocular surgeries (0.04-0.3% for cataracts, 0.2% for glaucoma surgery and intraocular lens implantation, and 0.03% for pars plana vitrectomy).
  • Risk of endophthalmitis per intravitreal injection is 0.05%.
  • Endophthalmitis may occur in 0.9-18% of adult patients with penetrating eye injuries, but rates range between 5-54% in children.

What are the outcomes?

• Outcomes depend on specific cause, microbes involved, and presenting visual acuity (worse presenting visual acuity = lower likelihood of recovery).
  • Around 50% of postoperative endophthalmitis cases recover 20/40 vision, but 10% will have 20/800 vision.
  • Risk of vision loss worsens with delays in diagnosis and care.

Are there risk factors?

• Depends on host factors and etiology (exogenous versus endogenous).
• Host factors: immunocompromised state, lacrimal drainage system disease, chronic blepharitis, contact lens wear, contralateral ocular prosthesis, contaminated ocular drops, another infection within the body.
  • Immunocompromise: extremes of age, malignancy, use of systemic corticosteroids or non-corticosteroid immunosuppressive agents, end-stage renal disease, human immunodeficiency virus, diabetes mellitus.
  • Injection drug use, indwelling catheters, endocarditis, other infections (GI and GU) increase risk of endogenous form.
• Operative and post operative risk factors: secondary intraocular lens implantation, vitreous loss, iris prolapse, posterior capsular rupture, contaminated irrigating solutions, vitreous incarceration, wound leaks, and provider failure to prescribe or patient non-adherence to postoperative antibiotics.
• Posttraumatic endophthalmitis risk factors: injuries exposed to soil, retained foreign bodies, lens capsule breach, lack of prophylactic antibiotics, and repair delayed beyond 24 hours.

How do these patients present?

• Most commonly present with vision changes (blurry vision, floaters, decreased visual acuity), eye pain/redness/drainage, and headache.
  • Vision changes are present in 90% of cases.
• Systemic findings may be present: fever in over 35%, malaise/fatigue/chills/rigors in up to 20% of cases.
  • Systemic symptoms more common in the endogenous form compared to the exogenous form.
• Chronic or fungal endophthalmitis more commonly presents with less inflammation and pain, more indolent course.
• If associated with open globe, often presents with severe vision loss and pain.

What do we need to do on exam?

• Based on ocular exam, starting with visual acuity. Perform slit lamp if possible, but this may not be available in all EDs. If not, evaluate with magnification with white light, then fluorescein staining with woods lamp.
• Up to 90% have vision changes.
• Hypopyon (layered collection of inflammatory cells in the anterior chamber) present in 35% of overall cases and 80% of postcataract cases.
• Vitritis and anterior chamber inflammation present in one-third of patients.
• Slit and lamp common reveals “cell and flare” microscopic inflammatory and cellular debris in the anterior chamber).
• Fundoscopic exam usually limited due to intraocular inflammation causing vitreous haze.
• Suggestive findings of endophthalmitis: uveal tissue abscess, hypopyon ≥ 1.5 mm, vitreous exudates, arteriolar septic emboli, necrotizing retinitis, perivascular hemorrhages with inflammatory infiltrate, panophthalmitis, and corneal infiltrates or ulcer.
  • Other findings may include periorbital edema, ocular drainage or discharge, and a relative afferent pupillary defect.
• Do not just focus on the ocular exam; also evaluate for other site of infection, IVDU, lines.
• Key: Hypopyon, vitritis, cell and flare suggestive, but normal retinal examination in the ED does not rule out the disease.

Post cataract endophthalmitis with hypopyon, scleral injection, lid swelling.

Are labs helpful?

• Labs not sensitive or specific, but mild leukocytosis and elevated CRP and ESR common.
• Blood cultures are usually negative in exogenous form but should be obtained for cases of endogenous endophthalmitis associated with another infection (positive in 75%).
• Vitreal cultures are recommended (obtained by ophthalmology) with sensitivities; negative culture does not exclude diagnosis.

What about imaging?

• Not necessary in all cases but may be used as an adjunct for diagnosis.
• POCUS can be useful.
  • Evaluate for foreign body; most common findings are mobile vitreous exudates (increased echogenicity of the vitreous), vitreous membranes, choroidoretinal thickening, retinal or choroidal effusion or abscess, retinal detachment, and retinal and vitreous hemorrhag
  • Do not use to rule in or out the diagnosis.
• CT may help identify radiopaque foreign bodies acting as a nidus for infection
• MRI has superior deep soft tissue resolution of the globe and retro-orbital area. Findings often subtle early, but may show enhanced uveal thickness. In advanced disease, imaging is typically significant for retinal/choroidal detachment, vitreous exudates, and peribulbar inflammation.
• If concerned about endogenous disease, look for primary infection, which may need imaging.

What does management entail?

• Early recognition essential to optimize outcomes; consult ophthalmology, and if unavailable, transfer to center with ophtho on call.
• Outcomes based on initial presenting visual acuity (best predictor), virulence of infecting agent, and time to appropriate treatment.
• Management mainstay is broad-spectrum intravitreal antibiotics (not necessarily intravenous); the sooner the better.
  • Intravitreal antibiotics achieve the highest concentration of drug in the vitreous cavity. Systemic antibiotics alone are not definitively effective due to the blood-ocular barrier.
  • Treatment of choice: Intravitreal injection (performed by the ophthalmology) with third-generation cephalosporin with expanded Pseudomonal coverage or aminoglycoside plus coverage for
    • Example: ceftazidime (2.25 mg/0.1 mL) and vancomycin (1 mg/0.1 mL).
  • Efficacy of systemic plus intravitreal antimicrobials is controversial.
  • Systemic antibiotics are recommended in posttraumatic and postoperative endophthalmitis and endogenous endophthalmitis due to the significant risk of fulminant endophthalmitis.
    • Vancomycin (20 mg/kg intravenous [IV] and ceftazidime (1g IV) or a fluoroquinolone like moxifloxacin (400 mg IV or per os).
  •  Systemic antimicrobials with intravitreal antimicrobials also recommended for suspected fungal endophthalmitis.
    • Amphotericin B or voriconazole recommended for fungal endophthalmitis due to Candida or Aspergillus and for immunocompromised patients.
•  Vitrectomy may be needed for severe vision loss (defined as light perception or worse) or patients who fail to improve 24-48 hours after initial intravitreal injection.
  • Associated with 3-fold increase in chance of achieving 20/40 visual acuity or better, 2-fold chance of achieving 20/100 visual acuity or better, and 50% decrease in the frequency of severe visual loss worse than 5/200 visual acuity.

What are the key takeaways?

• Endophthalmitis is an infection associated with severe inflammation of intraocular tissue, specifically the vitreous and aqueous humor.
• Most common etiology is exogenous (extrinsic) from direct inoculation associated with surgery or trauma.
• High-risk patients include those with a history of recent ocular trauma or procedures, immunosuppression, injection drug use, recent ocular procedures, diabetes mellitus, ocular pain, vision changes.
• Look for vision changes, eye redness, hypopyon, eye drainage, and lid or periorbital edema.
• Serum laboratory analysis is not definitive; aqueous or vitreous culture is recommended.  Imaging can suggest the disease but should not be used to exclude it.
• Consult ophthalmology and transfer if necessary.
• Treatment for all types of endophthalmitis includes intravitreal antibiotics with consideration of vitrectomy in severe cases. Systemic antimicrobials are recommended in posttraumatic, endogenous, post-surgical, and fungal etiologies.

References/Further Reading:

1. Gunalda J, Williams D, Koyfman A, Long B. High risk and low prevalence diseases: Endophthalmitis. Am J Emerg Med. 2023 Sep;71:144-149.
2. Durand ML. Bacterial and fungal endophthalmitis. Clin Microbiol Rev. 2017 Jul;30(3):597-613.
3. Schwartz SG, Flynn Jr HW, Das T, Mieler WF. Ocular infection: endophthalmitis. Dev Ophthalmol. 2016;55:176–188.
4. Durand ML. Endophthalmitis. Clin Microbiol Infect. 2013 Mar;19(3):227-34.
5. Lemley CA, Han DP. Endophthalmitis: a review of current evaluation and management. Retina. 2007 Jul-Aug;27(6):662-80.
6. Rahmani S, Eliott D. Postoperative endophthalmitis: a review of risk factors, prophylaxis, incidence, microbiology, treatment, and outcomes. Semin Ophthalmol. 2018;33(1):95-101.
7. Wade CI, Whitescarver TD, Ashcroft CR, et al. Endophthalmitis: a bibliographic review. Int Ophthalmol. 2021;41:4151–4161.
8. Relhan N, Forster RK, Flynn Jr HW. Endophthalmitis: then and now. Am J Ophthalmol. 2018 Mar;187:xx-xxvii.
9. Schwartz SG, Flynn Jr HW, Das T, Mieler WF. Ocular infection: endophthalmitis. Dev Ophthalmol. 2016;55:176–188.
10. Durand ML. Bacterial endophthalmitis. Curr Infect Dis Rep. 2009;11(4):283-288.
11. Radhika M, Mithal K, Bawdekar A, et al. Pharmacokinetics of intravitreal antibiotics in endophthalmitis. J Ophthalmic Inflamm Infect. 2014 Sep 10;4:22.
12. Grzybowski A, Turczynowska M, Schwartz SG, et al. The role of systemic antimicrobials in the treatment of endophthalmitis: a review and an international perspective. Ophthalmol Ther. 2020 Sep;9(3):485-498.