Endogenous endophthalmitis
For the main page on endophthalmitis, please click here
For more information on bacterial endophthalmitis, please click here
For more information on post-operative endophthalmitis, please click here
For more information on post-traumatic endophthalmitis, please click here
For more information on bleb-related endophthalmitis, please click here
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. 
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.
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.
- 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.

# Historical Perspective
In 1916, Dr. Leonard Weakly published a case report which detailed a patient with endophthalmitis concurrent with meningitis.

# Classification
Endogenous enophthalmitis may be classified according to causative organisms into 2 subtypes: bacterial or fungal.

# 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:
- Direct invasion (septic emboli reaches the eye through the posterior segment vasculature)
- Change in vascular endothelium (caused by inflammatory mediators released during infection)
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.
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.

### Gross Pathology
- On gross pathology, eyelid swelling, eyelid erythema, conjunctival injection, chemosis, and mucoprulunt dischage are characteristic findings of endogenous endophthalmitis.

### 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 , lymphocytes, budding yeast, and pseudohyphae) are characteristic findings of candida endophthalmitis.
- 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. 

# Causes

## Bacterial
Common causes of endogenous bacterial endophthalmitis include:
- Gram-positive bacteria
Streptococcus spp
Staphylococcus aureus
Bacillus cereus (primary bacterial cause in intravenous drug users)
- Streptococcus spp
- Staphylococcus aureus
- Bacillus cereus (primary bacterial cause in intravenous drug users)
- Gram-negative bacteria
Neisseria meningitidis (pre-antibiotic era)
Escherichia coli
Klebsiella spp (in the Asian population with liver abscess)
- Neisseria meningitidis (pre-antibiotic era)
- Escherichia coli
- Klebsiella spp (in the Asian population with liver abscess)

## Fungal
Common causes of endogenous fungal endophthalmitis include:
- Candida albicans
- Candida tropicalis
- Aspergillus spp
- Fusarium spp

# Differentiating endogenous Endophthalmitis from Other Diseases
Endogenous bacterial endophthalmitis must be differentiated from:
- Aspergillus endophthalmitis
- Candida endophthalmitis
Candida endophthalmitis must be differentiated from:
- Cytomegalvirus retinitis
- Toxoplasmosis retinochoroiditis
- Primary intraocular lymphoma
- Syphilitic choroiditis
- Aspergillus endophthalmitis
- Endogenous bacterial endophthalmaitis
Aspergillus endophthalmitis must be differentiated from:
- Cytomegalvirus retinitis
- Toxoplasmosis retinochoroiditis
- Coccidiomycosis choroiditis
- Endogenous bacterial endophthalmitis

# Epidemiology and Demographics

## Incidence
The incidence of endogenous endophthalmitis is estimated to be 50 cases per 100,000 hospitalized patients.

## Age
Endogenous bacterial endophthalmitis affects men and women equally.

## 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.

# Risk Factors

## Endogenous bacterial endophthalmitis
Common risk factors in the development of endogenous bacterial endophthalmitis include:
- Recent hospitalization
- Immunosuppression
- Diabetes mellitus
- Urinary tract infection
- Immunosuppression (associated with underlying malignancy, neutropenia, and HIV)
- Intravenous drug use
- Catheterization
- Long-term use of broad-spectrum antibiotics or immunosuppressive drugs
- Liver abscess
- Infective endocarditis (IE)

## Endogenous fungal endophthalmitis
Common risk factors in the development of endogenous fungal endophthalmitis include:
- Recent abdominal surgery
- Diabetes mellitus
- Indwelling central venous catheter.
- Chemotherapy
- Organ transplantation
- Immunosuppressive therapy and impaired neutrophil function
- History of chronic pulmonary diseases
- Intravenous drug abuse
- Alcoholism

# Screening
Screening for endogenous endophthalmitis is not recommended in hospitalized patients.

# 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.

## Complications
Common complications of bacterial endophthalmitis include:
- Panophthalmitis
- Decrease or loss of vision
- Chronic pain
- Cataract development
- Retinal detachment
- Vitreous hemorrhage
- Hypotony and phthisis bulbi
- Proptosis and a corneal abscess
- Sepsis (specific for endogenous endophthalmit)
- Suprachoroidal hemorrhage (specific for endogenous endophthalmit)

## 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.
- The prognosis of candida endophthalmitis is good if prompt systemic amphotericin B treatment is received.
- Despite of aggressive treatment, aspergillus endophthalmitis is associated with poor prognosis.

# 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:.
- History of diabetes mellitus
- Immunosuppression (associated with underlying malignancy, neutropenia, and HIV)
- History of cardiac disease
- History of abdominal surgery
- intravenous catheters
- Intravenous drug use
- Immunosuppressive therapy
- History of chronic pulmonary diseases

## Symptoms
Symptoms of endogenous endophthalmitis may include the following:
- Decreased vision
- Eyelid edema
- Conjunctival injection
- Eye pain
- Photophobia
- Presence of floaters

## 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:
- Decreased vision
- Conjunctival injection
- Eyelid edema
- Cloudy cornea
- Decreased red reflex

## Laboratory Findings
Laboratory studies consistent with the diagnosis of endogenous bacterial endophthalmitis include:
- Culture and gram stain of aqueous humor as well as the vitreous humor (not often sensitive)
- Polymerase chain reaction (PCR)  of aqueous humor as well as the vitreous humor
- Blood cultures (it is positive in 75% of cases of endogenous endophthalmitis)
Laboratory studies consistent with the diagnosis of endogenous candida endophthalmitis include:
- Vitreaus cultures and biopsy (required to confirm the diagnosis)
- Vitreous polymerase chain reaction (PCR)
- Positive cultures of blood for Candida
Laboratory studies consistent with the diagnosis of endogenous aspergillus endophthalmitis include:
- Vitreous biopsy and cultures (Grocott or Periodic acid-Schiff)
- Anterior chamber and vitreous aspiration (unreliable)
- Positive cultures of blood for aspergillosis (coexisting systemic aspergillosis)

## 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.
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
- Echocardiography may be helpful (assessed the possibility of endocarditis)

## Other Diagnostic Studies
Other diagnostic studies for endogenous endophthalmiatis include:
- Slit lamp examination
Mild to moderate anterior chamber reaction
Hypopyon
Roth's spots and retinal periphlebitis
White and fluffy choriodoretinal lesions (candida endophthalmitis)
Snowball-like opacities in vitreous (candida endophthalmitis)
- Mild to moderate anterior chamber reaction
- Hypopyon
- Roth's spots and retinal periphlebitis
- White and fluffy choriodoretinal lesions (candida endophthalmitis)
- Snowball-like opacities in vitreous (candida endophthalmitis)
- Testing for human immunodeficiency virus (HIV)
- Culture of urine or cerebrospinal fluid is often necessary
- Cultures of other sites (catheter tip, surgical wounds, and body fluids)

# 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
- 1. Causative pathogens
- Staphylococcus epidermidis
- Staphylococcus aureus
- Bacillus spp.
- Escherichia coli
- Neisseria meningitidis
- Candida spp.
- Aspergillus spp.
- Fusarium spp.
- 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.
- 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.