Endophthalmitis
For more information on bacterial endophthalmitis, please click here
For more information on post-operative endophthalmitis, please click here
For more information on bleb-related endophthalmitis, please click here
For more information on post-traumatic endophthalmitis, please click here
For more information on endogenous endophthalmitis, please click here

# Overview
Endophthalmitis is an inflammation of the internal coats of the eye. It is a dreaded complication of all intraocular surgeries, particularly cataract surgery, with possible loss of vision. The most common etiology is infectious. Various bacteria and fungi have been isolated as the cause of infectious endophthalmitis. Other causes include penetrating trauma and retained intraocular foreign bodies.

# Historical Perspective

# Classification
Endophthalmitis may be classified according to causative organisms into 2 subtypes:
- Bacterial endophthalmitis
- Fungal endophthalmitis
Additionally, endophthalmitis may be classified as either endogenous or exogenous based on the route of infection.
- Exogenous endophthalmitis
Post-operative endophthalmitis
Bleb-related endophthalmitis
Post-traumatic endophthalmitis
- Post-operative endophthalmitis
- Bleb-related endophthalmitis
- Post-traumatic endophthalmitis
- Endogenous endophthalmitis

# Pathophysiology

## Pathogenesis
Endophthalmitis is an ocular inflammation resulting from the introduction of an infectious agent, either bacterial or fungal, into the posterior segment of the eye. 
Infectious agents are introduced to the anterior and posterior segments of the eye exogenously or endogenously.
Exogenous endophthalmitis occurs following a penetrating ocular injury or ocular surgery.
Besides cataract (approximately 90% of all cases), nearly all other type of ocular surgery such as glaucoma, retinal, radial keratotomy, and intravitreal injections may be able to disturb the integrity of the eye globe and contaminate the aqueous humor and/or vitreous humor.
Endogenous endophthalmitis is caused by the hematologic dissemination of an infection to the eyes. The most common extraocular foci of infection include liver abscess, pneumonia, and endocarditis. 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.

### Gross Pathology
On gross pathology, eyelid swelling, eyelid erythema, injected conjunctiva and sclera, hypopyon, chemosis, and mucopurulunt discharge are characteristic findings of bacterial endophthalmitis.

### Microscopic Pathology
On microscopic histopathological analysis, infiltration of polymorphonuclear leukocytes or chronic inflammatory cells (depending on the duration of the inflammation) and destruction of ocular structures are characteristic findings of endophthalmitis.

# Causes

## Infectious
Common causes of endophthalmitis include:
- Bacterial
Staphylococcus epidermidis
Staphylococcus aureus
Streptococci spp.
Enterococci spp.
Bacillus spp.
Escherichia coli
Neisseria meningitidis
Klebsiella spp.
Propionibacterium spp.
Corynebacterium spp.
Pseudomonas aeruginosa
Candida spp.
Aspergillus spp.
Fusarium spp.
- Staphylococcus epidermidis
- Staphylococcus aureus
- Streptococci spp.
- Enterococci spp.
- Bacillus spp.
- Escherichia coli
- Neisseria meningitidis
- Klebsiella spp.
- Propionibacterium spp.
- Corynebacterium spp.
- Pseudomonas aeruginosa
- Candida spp.
- Aspergillus spp.
- Fusarium spp.
- Fungal
Candida spp.
Aspergillus spp.
Fusarium spp.
- Candida spp.
- Aspergillus spp.
- Fusarium spp.

## Drug-induced
Dexamethasone implant

# Differentiating Endophthalmitis from Other Diseases
Post-operative endophthalmitis must be differentiated from:
- Toxic anterior segment syndrome (TASS)
- Retained lens material
- Flare-up of pre-existing uveitis
- Dehemoglobinized vitreous hemorrhage
Bleb-related endophthalmitis must be differentiated from:
- Blebitis (bleb-related endophthalmitis is characterized by severe loss of vision, marked pain, and presence of vitritis)
- Anterior uveitis
- Uveitis-glaucoma-hyphema syndrome

# Epidemiology and Demographics
In the United States, post-cataract endophthalmitis is the most common form of endophthalmitis. The incidence of post-cataract endophthalmitis is estimated to range from 80 to 360 cases per 100,000 individuals.

# Risk Factors

## Exogenous Endophthalmitis
Common risk factors in the development of exogenous endophthalmitis include:
- Post-cataract 
Secondary intraocular lens placement
Intra-ocular lenses (IOLs) with polypropylene
Intracapsular cataract extraction
Clear corneal incisions
- Secondary intraocular lens placement
- Intra-ocular lenses (IOLs) with polypropylene
- Intracapsular cataract extraction
- Clear corneal incisions
- Post-traumatic
Retained intraocular foreign bodies
Injury in a rural setting
Delay in repair more than 24 hours
- Retained intraocular foreign bodies
- Injury in a rural setting
- Delay in repair more than 24 hours
- Bleb related
Bleb leakage (increase the risk of bleb infection 26 fold)
Inappropriate use of antifibrotic agents (such as 5-fluorouracil (5-FU) and mitomycin C (MMC))
Inferior and nasal placement of bleb
Bleb manipulation/trauma
- Bleb leakage (increase the risk of bleb infection 26 fold)
- Inappropriate use of antifibrotic agents (such as 5-fluorouracil (5-FU) and mitomycin C (MMC))
- Inferior and nasal placement of bleb
- Bleb manipulation/trauma

## Endogenous Endophthalmitis
Common risk factors in the development of endogenous endophthalmitis include:
- Recent hospitalization
- Immunosuppression

# Screening
There is no recommended screening guideline for endophthalmitis.

# Natural History, Complications, and Prognosis

## Natural History
Endophthalmitis is a medical emergency. If left untreated, it may lead to panophthalmitis, corneal infiltration, corneal perforation, and permanent vision loss.

## Complications
Common complications of endophthalmitis include:
- Panophthalmitis
- Decrease or loss of vision
- Chronic pain
- Cataract development
- Retinal detachment
- Vitreous hemorrhage
- Hypotony and phthisis bulbi

## Prognosis
Early diagnosis and treatment with antimicrobial therapy are fundamental to optimize visual outcome.

# Diagnosis
Endophthalmitis is a clinical diagnosis supported by culture of intra-ocular fluids.

## History and Symptoms

### History
A history of recent intraocular surgery or penetrating ocular trauma is usually elicited. Endogenous endophthalmitis is more commonly seen in patients with immunocompromised states such as AIDS and also in diabetes.

### Symptoms
The condition is usually accompanied by severe pain, loss of vision, and redness of the conjunctiva and the underlying episclera. Hypopyon may also be observed in endophthalmitis patients by a slit lamp examination.

## Physical Examination

## Laboratory Findings
Laboratory studies consistent with the diagnosis of post-cataract endophthalmitis include:
- Culture and gram stain of aqueous humor as well as the vitreous humor
- Polymerase chain reaction (PCR)  of aqueous humor as well as the vitreous humor

## Imaging Findings

## Other Diagnostic Studies

### Slit Lamp Examination Findings
- Hypopyon ( >80% of cases)
- Anterior chamber and vitreous inflammation
- Cloudy cornea
- Clumps of exudate in the anterior chamber (around the pupillary margin)
- Cloudy cornea
- Decreased red reflex
- Anterior chamber inflammation, mild corneal edema, and hypopyon in bacterial endophthalmitis
- Exogenous fungal endophthalmitis with corneal ulcer
- Hypopyon
- (A) Severe conjunctival injection, subconjunctival hemorrhage, corneal stromal edema, and hypopyon (B) Fundus photograph shows a mild pale color of optic disc & macular degeneration
- Corneal edema and severe anterior chamber exudation

# Treatment
Patients require urgent examination by an expert ophthalmologist and vitreo-retinal specialist who will determine the need for intravitreal injection of antibiotics and possible urgent pars plana vitrectomy. Enucleation may be required to remove a blind and painful eye. Systemic antibiotics are recommended in endogenous bacterial endophthalmitis because the source of the infection is extraocular. Immediate vitrectomy is often necessary

## Medical Therapy

### Antimicrobial Regimens
- Infectious endophthalmitis
- 1. Causative pathogens
- Staphylococcus epidermidis
- Staphylococcus aureus
- Streptococci
- Enterococci
- Bacillus spp.
- Escherichia coli
- Neisseria meningitidis
- Klebsiella spp.
- Propionibacterium spp.
- Corynebacterium spp.
- Pseudomonas aeruginosa
- 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
- 4. Special Considerations
- 4.1 Endogenous endophthalmitis
- 4.1.1 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
- 4.2 Bleb-related endophthalmitis
- 4.2.1 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
- 4.3 Post-operative endophthalmitis
- 4.3.1 Empiric antimicrobial therapy
- Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose
- Note (1): In addition to intravitreal antibiotic therapy, vitrectomy is necessary
- Note (2): If there is no improvement in 48 h, a repeat intravitreal injection may be administered
- Note (3): Late post-operative endophthalmitis is often caused by Propionibacterium acnes (several years post-op)
- 4.3.2 Pathogen-directed antimicrobial therapy
- 4.3.2.1 Gram-positive bacteria
- Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose
- 4.3.2.2 Gram-negative bacteria
- Preferred regimen: Amikacin 0.4 mg per 0.1 mL normal saline intravitreal injection, single dose
- Note: Intravitreal amikacin is associated with the development of retinal microvasculitis
- 4.4 Post-traumatic endophthalmitis
- 4.4.1 Empiric antimicrobial therapy
- Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose AND Amphotericin B 5-10 microgram in 0.1 mL in normal saline intravitreal injection, single dose
- Note (1): Removal of foreign bodies and debridement of necrotic tissue is necessary
- Note (2): In addition to antimicrobial therapy, vitrectomy is necessary
- Note (3): Systemic broad spectrum antibiotics are recommended in post-traumatic endophthalmitis

## Surgery

### Vitrectomy
Vitrectomy surgically debrides the vitreous humor, similarly to draining an abscess, and is the fastest way of clearing the infection in eyes with fulminant endophthalmitis.

# Prevention

## Primary prevention
Common effective measures for the primary prevention of endophthalmitis include:
- Proper sterile preparation of the surgical site
- Sterile preparation of the skin surrounding the surgical eye with Povidone-Iodine 10%
- Povidone-Iodine 5% onto the ocular surface (3-5 minutes prior to surgery)
- Removal of foreign bodies and debridement of necrotic tissue after penetrating eye injury
- Intracameral or intravitreal antibiotic injection after penetrating eye injury
- Effective treatment of underlying medical conditions

## Secondary prevention
There are no secondary preventive measures available for post-operative endophthalmiatis, endophthalmiatis is a medical emergency.