Endogenous endophthalmitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]
Synonyms and Keywords: Endogenous fungal endophthalmitis; Endogenous bacterial endophthalmitis


Overview

Endogenous endophthalmitis is a rare but sight-threatening complication that can be caused by the hematologic dissemination of bacterial/fungal infections to the eyes or direct spread from adjacent contagious sites. Most common extraocular foci of infection include liver abscess, pneumonia, endocarditis, and soft tissue infection. Endogenous endophthalmitis is commonly associated with immunosuppression or procedures that increase the risk for blood-borne infections, such as diabetes, HIV, malignancy, intravenous drug use, transplantation, immunosuppressive therapy, and catheterization. Common causes of endogenous endophthalmitis include Streptococcus pneumoniae, Staphylococcus aureus, Bacillus cereus, and Klebsiella spp. Additionally, endogenous endophthalmitis may be caused by the hematologic dissemination of fungal infections into the eye commonly Candida spp (>50%) following by Aspergillus, and Fusarium spp. Endophthalmitis is a medical emergency. If left untreated, It may lead to panophthalmitis, corneal perforation, and ultimately permanent vision loss. [1] The prognosis of endogenouse endophthalmitis varies with the offending organism and the systemic status of the patient. Late detection and late treatment of systemic infection of endogenouse endophthalmitis is associated with a poor prognosis.[2][3][4] The diagnosis of endogenous endophthalmitis may be difficult because of the variability in the clinical signs and symptoms. Patients with endogenous endophthalmtis usually appear extremely ill and lethargic. Therefore, eye examination in extremely ill patients, such as those in intensive care units (ICU), seems necessary. Most common eye examination findings in endogenous endophthalmitis may include decreased vision, ocular pain, eyelid edema, cloudy cornea, and decreased red reflex. Bacterial and fungal cultures from vitreous samples are necessary in the management of endophthalmitis However, positive cultures from vitreous samples can be achieved much less frequently in endogenous endophthalmitis. Identification of the causative pathogen by blood, urine, or cerebrospinal fluid culture is successful in more than 75% of endogenous endophthalmitis cases.[2][5]

  • The patient needs urgent examination by an expert ophthalmologist and/or vitreo-retina specialist who will usually decide for urgent intervention to provide intravitreal injection of potent antibiotics and also prepare for an urgent pars plana vitrectomy as needed. Enucleation may be required to remove a blind and painful eye.

Systemic antimicrobial and anti-fungal agents are recommended in endogenous endophthalmitis because the source of the infection is distant from the eye.[2][5]

Historical Perspective

In 1916, Dr. Leonard Weakly published a case report which detailed a patient with endophthalmitis concurrent with meningitis.[6]

Classification

Endogenous enophthalmitis may be classified according to causative organisms into 2 subtypes: bacterial or fungal.[7][8]

Pathophysiology

Pathogenesis

Endogenous endophthalmitis is mainly caused by hematologic dissemination of the organism from a primary site of infection in the setting of bacteremia or fungemia. Endogenous endophthalmitis is commonly associated with immunosuppression or procedures that increase the risk for blood-borne infections, such as diabetes, HIV, malignancy, intravenous drug use, transplantation, immunosuppressive therapy, and catheterization. Under normal circumstances, the blood-ocular barrier provides a natural resistance against invading organisms. In the high risk patients, following bacteremia the blood-borne organisms permeate the blood-ocular barrier by:[2][3][4][9]

Most common extraocular foci of infection include liver abscess, pneumonia, endocarditis, and soft tissue infection.

Additionally, direct spread from contagious sites can occur in cases of central nervous system (CNS) infection via the optic nerve.[10]

Endogenous fungal endophthalmitis is also associated with procedures or conditions that increase the risk for blood-borne fungal infections, such as abdominal surgery, diabetes mellitus, and indwelling central venous catheter. It is thought immunosuppression alone does not increase the risk of fungemia and subsequent fungal endophthalmitis.[11]

Gross Pathology

Microscopic histopathological analysis

  • On microscopic histopathological analysis, infiltration of polymorphonuclear leukocytes and destruction of ocular structures are characteristic findings of endogeouse bacterial endophthalmitis.
  • On microscopic histopathological analysis, random vitreous, choroid , and retinal lesions (which demonstrate [[polymorphonuclear leukocytes], lymphocytes, budding yeast, and pseudohyphae) are characteristic findings of candida endophthalmitis.[12]
  • On microscopic histopathological analysis, mixed acute and chronic inflammatory cells infiltration, retinal and choroidal vessel invasion, and subretinal pigment epithelial infection are characteristic findings of aspergillus endophthalmitis.[13] [14]

Causes

Bacterial

Common causes of endogenous bacterial endophthalmitis include:[2][3][4]

Fungal

Common causes of endogenous fungal endophthalmitis include:[2][3][4]

Differentiating endogenous Endophthalmitis from Other Diseases

Endogenous bacterial endophthalmitis must be differentiated from:[15]

  • Aspergillus endophthalmitis
  • Candida endophthalmitis

Candida endophthalmitis must be differentiated from:[16][17]

Aspergillus endophthalmitis must be differentiated from:[18]

Epidemiology and Demographics

Incidence

The incidence of endogenous endophthalmitis is estimated to be 50 cases per 100,000 hospitalized patients.[3][19]

Age

Endogenous bacterial endophthalmitis affects men and women equally.[3]

Geographical Distribution

In East Asian populations, liver abscess caused by Klebsiella pneumoniae is estimated to be the source of 60.000 cases per 100,000 individuals with endogenous endophthalmitis.[4]

Risk Factors

Endogenous bacterial endophthalmitis

Common risk factors in the development of endogenous bacterial endophthalmitis include:[2][3][4]

Endogenous fungal endophthalmitis

Common risk factors in the development of endogenous fungal endophthalmitis include:[8][20]

Screening

Screening for endogenous endophthalmitis is not recommended in hospitalized patients.[21]

Natural History, Complications, and Prognosis

Natural History

Exogenous endophthalmitis is a medical emergency. If left untreated, It may lead to panophthalmitis, corneal infiltration, corneal perforation, retinal detachment, and ultimately permanent vision loss.[1]

Complications

Common complications of bacterial endophthalmitis include:[1]

Prognosis

The prognosis of endogenouse endophthalmitis varies with the offending organism and the systemic status of the patient.

  • Late detection and late treatment of systemic infection of endogenouse bacterial endophthalmitis is associated with a poor prognosis.[2][3][4]
  • The prognosis of candida endophthalmitis is good if prompt systemic amphotericin B treatment is received.[22]
  • Despite of aggressive treatment, aspergillus endophthalmitis is associated with poor prognosis.[23]

Diagnosis

The diagnosis of endogenous endophthalmitis may be difficult because of the variability in the clinical signs and symptoms.

History

Specific areas of focus when obtaining a history from the patient with endogenous endophthalmitis include:.[2][3][4]

Symptoms

Symptoms of endogenous endophthalmitis may include the following:[24][25]

Physical Examination

  • Patients with endogenous endophthalmtis usually appear extremely ill and lethargic. Therefore, eye examination in extremely ill patients, such as those in intensive care units (ICU), seems necessary.
  • A thorough examination seems necessary to identify the primary source of infection in patient with endogenous endophthalmitis.

Eye examination

Ophthalmologic examination of patients with endogenoous endophthlamitis is usually remarkable for:

Laboratory Findings

Laboratory studies consistent with the diagnosis of endogenous bacterial endophthalmitis include:[2][5][26]

Laboratory studies consistent with the diagnosis of endogenous candida endophthalmitis include:[27]

Laboratory studies consistent with the diagnosis of endogenous aspergillus endophthalmitis include:

Imaging Findings

X Ray

There are no diagnostic x ray findings associated with endogenous endophthalmitis. X ray may be helpful in the diagnosis of underling medical conditions or source of infection.

CT

There are no diagnostic CT scan findings associated with endogenous endophthalmitis. Ct scan may be helpful in the diagnosis of underling medical conditions or source of infection.

MRI

There are no diagnostic MRI findings associated with endogenous endophthalmitis. Abdominal and chest MRI may be helpful in the diagnosis of underling medical conditions or source of infection.

Ultrasound

  • On ocular ultrasonography, endophthalmitis may characterized by anterior vitreous haze echoes and retinochoroidal thickening.[2][3][28]

Dense and hyper-reflective echoes in the vitreous cavity suggestive of exudates (yellow arrow). The membrane-like echo in the scan marked by yellow triangles suggests presence of a total retinal detachment.

Other Imaging Findings

Other Diagnostic Studies

Other diagnostic studies for endogenous endophthalmiatis include:[2][3][4]

Treatment

The patient needs urgent examination by an expert ophthalmologist and/or vitreo-retina specialist who will usually decide for urgent intervention to provide intravitreal injection of potent antibiotics and also prepare for an urgent pars plana vitrectomy as needed. Enucleation may be required to remove a blind and painful eye.

  • Bacterial and fungal cultures from vitreous samples are necessary in the management of endophthalmitis
  • Systemic antimicrobial and antifungal treatments are recommended in endogenous endophthalmitis because the source of the infection is distant from the eye
  • Vitrectomy is recommended in severe cases of endogenous endophthalmitis with marked vitreous infiltration

Antimicrobial Regimens

  • Infectious endophthalmitis[2]
  • 1. Causative pathogens
  • 2. Empiric antimicrobial therapy
  • Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Vancomycin 1 g IV bid for 2 weeks AND Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 1 g IV bid for 2 weeks AND Clindamycin 600-1200 mg IV bid to qid for 2 weeks
  • Note (1): Re-injection should be considered if the infection does not improve beyond 48 hours of the first injection. Re-injection significantly increases the risk of retinal toxicity.
  • Note (2): In addition to intravitreal and systemic antibiotic therapy, vitrectomy is usually necessary
  • Note (3): Intravitreal and intravenous Amphotericin B may be added to the regimen if fungal endophthalmitis is suspected
  • 3. Pathogen-directed antimicrobial therapy
  • 3.1 Bacillus spp.
  • Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Vancomycin 1 g IV bid for 2 weeks AND Clindamycin 600-1200 mg IV bid to qid for 2 weeks
  • Note: In addition to antimicrobial therapy, vitrectomy is usually necessary
  • 3.2 Non-Bacillus gram-positive bacteria
  • Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Vancomycin 1 g IV bid for 2 weeks
  • Note: In addition to antimicrobial therapy, vitrectomy is usually necessary
  • 3.3 Gram-negative bacteria
  • Preferred regimen: Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 1 g IV bid for 2 weeks
  • Note: In addition to antimicrobial therapy, vitrectomy is usually necessary
  • 3.4 Candida spp.
  • Preferred regimen: (Fluconazole 400-800 mg IV/PO qd for 6-12 weeks OR Voriconazole 400 mg IV/PO bid for 2 doses followed by 200-300 mg IV/PO bid for 6-12 weeks OR Amphotericin B 0.7-1.0 mg/kg IV qd for 6-12 weeks) AND Amphotericin B 5-10 microgram in 0.1 mL in normal saline intravitreal injection, single dose
  • Note (1): In addition to antimicrobial therapy, vitrectomy is usually necessary
  • 3.5 Aspergillus spp.
  • Preferred regimen: Amphotericin B 5-10 microgram in 0.1 mL normal saline intravitreal injection, single dose AND Dexamethasone 400 microgram intravitreal injection, single dose
  • Note (1): In addition to antimicrobial therapy, vitrectomy is usually necessary
  • Note (2): Repeat antimicrobial regimen in 2 days post-vitrectomy

Surgery

Vitrectomy

Vitrectomy surgically debrides the vitreous humor, similarly to draining an abscess, and is the fastest way of clearing infection in eyes with fulminant endophthalmitis.[2][5][29][30]

  • Vitrectomy is recommended in severe cases of endogenous endophthalmitis with marked vitreous infiltration (either fungal or bacterial)

The benefits of vitrectomy include:

  • Better vitreous sample
  • Rapid and complete sterilization of the vitreous
  • Removal of toxic bacterial products
  • Enhancement of systemic antimicrobial or antifungal penetration in to the eye

Prevention

Primary Prevention

Effective measures for the primary prevention of endogenous endophthalmitis include:

  • Effective treatment of underlying medical conditions

Secondary prevention

There are no secondary preventive measures available for endogenous endophthalmiatis. Endophthalmiatis is a medical emergency.

References

  1. 1.0 1.1 1.2 Doft BM, Kelsey SF, Wisniewski SR (2000). "Retinal detachment in the endophthalmitis vitrectomy study". Arch Ophthalmol. 118 (12): 1661–5. PMID 11115260.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 Durand ML (2013). "Endophthalmitis". Clin Microbiol Infect. 19 (3): 227–34. doi:10.1111/1469-0691.12118. PMC 3638360. PMID 23438028.
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 Kernt M, Kampik A (2010). "Endophthalmitis: Pathogenesis, clinical presentation, management, and perspectives". Clin Ophthalmol. 4: 121–35. PMC 2850824. PMID 20390032.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Wong JS, Chan TK, Lee HM, Chee SP (2000). "Endogenous bacterial endophthalmitis: an east Asian experience and a reappraisal of a severe ocular affliction". Ophthalmology. 107 (8): 1483–91. PMID 10919895.
  5. 5.0 5.1 5.2 5.3 5.4 Barza M, Pavan PR, Doft BH, Wisniewski SR, Wilson LA, Han DP; et al. (1997). "Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study". Arch Ophthalmol. 115 (9): 1142–50. PMID 9298055.
  6. {{cite journal| author=Weakley AL| title=METASTATIC ENDOPHTHALMITIS IN A CASE OF CEREBRO-SPINAL MENINGITIS. | journal=Br Med J | year= 1916 | volume= 1 | issue= 2871 | pages= 47-8 | pmid=20767965 | doi= | pmc=2346850 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?
  7. Lim HW, Shin JW, Cho HY, Kim HK, Kang SW, Song SJ; et al. (2014). "Endogenous endophthalmitis in the Korean population: a six-year retrospective study". Retina. 34 (3): 592–602. doi:10.1097/IAE.0b013e3182a2e705. PMID 24056527.
  8. 8.0 8.1 Schiedler V, Scott IU, Flynn HW, Davis JL, Benz MS, Miller D (2004). "Culture-proven endogenous endophthalmitis: clinical features and visual acuity outcomes". Am J Ophthalmol. 137 (4): 725–31. doi:10.1016/j.ajo.2003.11.013. PMID 15059712.
  9. Greenwald MJ, Wohl LG, Sell CH (1986). "Metastatic bacterial endophthalmitis: a contemporary reappraisal". Surv Ophthalmol. 31 (2): 81–101. PMID 3541265.
  10. Samiy N, D'Amico DJ (1996). "Endogenous fungal endophthalmitis". Int Ophthalmol Clin. 36 (3): 147–62. PMID 8989607.
  11. Rao NA, Hidayat AA (2001). "Endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared with aspergillosis". Am J Ophthalmol. 132 (2): 244–51. PMID 11476686.
  12. Rao, Narsing A., and Ahmed A. Hidayat. "Endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared with aspergillosis." American journal of ophthalmology 132.2 (2001): 244-251.
  13. Rao, Narsing A., and Ahmed A. Hidayat. "Endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared with aspergillosis." American journal of ophthalmology 132.2 (2001): 244-251.
  14. Hunt, LCDR Kerry E., and Ben J. Glasgow. "Aspergillus endophthalmitis: an unrecognized endemic disease in orthotopic liver transplantation." Ophthalmology 103.5 (1996): 757-767.
  15. Yonekawa Y, Chan RV, Reddy AK, Pieroni CG, Lee TC, Lee S (2011). "Early intravitreal treatment of endogenous bacterial endophthalmitis". Clin Experiment Ophthalmol. 39 (8): 771–8. doi:10.1111/j.1442-9071.2011.02545.x. PMID 22050564.
  16. Menezes, Allison V., et al. "Mortality of hospitalized patients with Candida endophthalmitis." Archives of internal medicine 154.18 (1994): 2093-2097.
  17. Hidalgo, Jose A., et al. "Fungal endophthalmitis diagnosis by detection of Candida albicans DNA in intraocular fluid by use of a species-specific polymerase chain reaction assay." Journal of Infectious Diseases 181.3 (2000): 1198-1201.
  18. Weishaar, Paul D., et al. "Endogenous Aspergillus endophthalmitis: clinical features and treatment outcomes." Ophthalmology 105.1 (1998): 57-65.
  19. Essex RW, Yi Q, Charles PG, Allen PJ (2004). "Post-traumatic endophthalmitis". Ophthalmology. 111 (11): 2015–22. doi:10.1016/j.ophtha.2003.09.041. PMID 15522366.
  20. Essman TF, Flynn HW, Smiddy WE, Brod RD, Murray TG, Davis JL; et al. (1997). "Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis". Ophthalmic Surg Lasers. 28 (3): 185–94. PMID 9076791.
  21. US Preventivre Services Task Force http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=endophthalmitis Accessed on August 5, 2016
  22. Essman, Thomas F., et al. "Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis." Ophthalmic Surgery, Lasers and Imaging Retina 28.3 (1997): 185-194.
  23. Weishaar, Paul D., et al. "Endogenous Aspergillus endophthalmitis: clinical features and treatment outcomes." Ophthalmology 105.1 (1998): 57-65.
  24. Sadiq MA, Hassan M, Agarwal A, Sarwar S, Toufeeq S, Soliman MK; et al. (2015). "Endogenous endophthalmitis: diagnosis, management, and prognosis". J Ophthalmic Inflamm Infect. 5 (1): 32. doi:10.1186/s12348-015-0063-y. PMC 4630262. PMID 26525563.
  25. Oude Lashof AM, Rothova A, Sobel JD, Ruhnke M, Pappas PG, Viscoli C; et al. (2011). "Ocular manifestations of candidemia". Clin Infect Dis. 53 (3): 262–8. doi:10.1093/cid/cir355. PMID 21765074.
  26. Seal D, Reischl U, Behr A, Ferrer C, Alió J, Koerner RJ; et al. (2008). "Laboratory diagnosis of endophthalmitis: comparison of microbiology and molecular methods in the European Society of Cataract & Refractive Surgeons multicenter study and susceptibility testing". J Cataract Refract Surg. 34 (9): 1439–50. doi:10.1016/j.jcrs.2008.05.043. PMID 18721702.
  27. Breit, Sean M., et al. "Management of endogenous fungal endophthalmitis with voriconazole and caspofungin." American journal of ophthalmology 139.1 (2005): 135-140.
  28. Affeldt JC, Flynn HW, Forster RK, Mandelbaum S, Clarkson JG, Jarus GD (1987). "Microbial endophthalmitis resulting from ocular trauma". Ophthalmology. 94 (4): 407–13. PMID 3495766.
  29. "Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group". Arch Ophthalmol. 113 (12): 1479–96. 1995. PMID 7487614.
  30. Breit, Sean M., et al. "Management of endogenous fungal endophthalmitis with voriconazole and caspofungin." American journal of ophthalmology 139.1 (2005): 135-140.

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