Post-cataract surgery endophthalmitis

# Overview
Acute post-cataract endophthalmitis is an ocular inflammation resulting from the introduction of an infectious agent, most commonly coagulase-negative staphylococci, into the posterior segment of the eye.
Nearly every type of ocular surgery may be able to disturb the eye globe integrity and contaminate the aqueous humor and/or vitreous. Cataract surgery accounts for approximately 90% of all cases of post-operative enndophthalmitis.

# Historical Perspective

# Classification
Based on the latancy of onset, post-cataract endophthalmitis may be classified into:
- Acute post-catarct endophthalmitis
- Delayed post-cataract endophthalmitis
Additionally, post-cataract enophthalmitis may be classified according to causative organisms into 2 subtypes: bacterial or fungal.

# Pathophysiology

### Pathogenesis
Acute post-cataract endophthalmitis is an ocular inflammation, which may occur within hours to few days after cataract surgery.
Acute post-cataract endophthalmitis is mainly caused by the introduction of an infectious agent, most commonly coagulase-negative staphylococci, into the posterior segment of the eye.
Nearly every type of ocular surgery may be able to disturb the eye globe integrity and contaminate the aqueous humor and/or vitreous. Cataract surgery accounts for approximately 90% of all cases of post-operative enndophthalmitis.
Preoperative topical antimicrobial agents can decrease colony counts in the tear film, but they do not sterilize the area. The exact low rate of clinical infection following eye surgery (despite the relatively high prevalence of microorganisms in the eye) is not fully understood. It is thought that low rate of clinical infection following surgical procedure is explained by combination of low inoculum levels, low pathogenicity, and the innate ocular defenses against infection.
Post-operative endophthalmitis may also occur weeks to years following surgery. 
It presents as a low-grade inflammation in the anterior chamber.
The exact pathogenesis of delayed post-operative endophthalmitis is not fully understood. It is thought that delayed post-operative endophthalmitis is caused by either sequestration of low-virulence organisms introduced at the time of surgery or delayed inoculation of organisms to the eye through wound abnormalities, suture tracks, or filtering blebs.
Propionibacterium acnes is the most common microorganism encountered in delayed post-operative bacterial endophthalmitis. 

### Gross Pathology
On gross pathology, eyelid swelling, eyelid erythema, injected conjunctiva and sclera, hypopyon, chemosis, and mucoprulunt dischage are characteristic findings of post-cataract endophthalmitis.

### Microscopic histopathological analysis
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 post cataract bacterial endophthalmitis.

# Causes

## Acute Post-operative Endophthalmitis
Post-operative endophthalmitis has been reported following nearly every type of ocular surgery. 
Common causes of acute post-cataract endophthalmitis include:
Bacterial
- Gram-positive bacteria
Coagulase-negative staphylococci
Staphylococcus epidermidis (most of the cases)
Staphylococcus aureus
Streptococcus spp
Enterococcus spp
- Coagulase-negative staphylococci
Staphylococcus epidermidis (most of the cases)
- Staphylococcus epidermidis (most of the cases)
- Staphylococcus aureus
- Streptococcus spp
- Enterococcus spp
- Gram-negative bacilli
Proteus spp
Pseudomonas aeruginosa
Haemophilus spp.
- Proteus spp
- Pseudomonas aeruginosa
- Haemophilus spp.
Fungal
- Candida spp
- Aspergillus spp

## Delayed Post-operative Endophthalmitis
Common causes of delayed post-operative endophthalmitis include:
Bacterial
- Propionibacterium acnes (most common)
- Streptococcus spp
- Corynebacterium spp
- Xanthomonas maltophilia
- Alcaligenes xylosoxidans
Fungal
- Candida spp
- Aspergillus spp
- Paecilomyces spp
- Acremonium spp

# Differentiating Post-cataract Surgery Endophthalmitis from Other Diseases
Acute post-cataract endophthalmitis must be differentiated from:
- Phacoanaphylactic endophthalmitis
- Toxic anterior segment syndrome (TASS)
Delayed post-cataract endophthalmitis must be differentiated from:
- Uveitis
- Sterile inflammation
- Rebound inflammation (related to abrupt discontinuation of steroid drops)
- Iris or vitreous incarceration in the wound (low-grade inflammation)
- Uveitis-glaucoma-hyphema syndrome
- Fungal endophthalmitis

# Epidemiology and Demographics

## Prevalence and Incidence
- In 1910, the incidence of post-cataract endophthalmitis was estimated 10,000 cases per 100,000 individuals with cataract surgery.
- Between 1970 to 1990, the incidence of post-cataract endophthalmitis was estimated to range from 72  to 120 cases per 100,000 individuals with cataract surgery.
- Since the introduction of phacoemulsification and clear cornea incision, the incidence of post-cataract endophthalmitis was estimated to range from 300 to 500 cases per 100,000 individuals with cataract surgery.

## Age
- Post-operative endophthalmitis (following cataract surgery) commonly affects patients older than 85 years.

## Gender
- Post-operative endophthalmitis affects men and women equally.

## Geographical Distribution
In tropical regions such as India, 1020% of all cases of acute post-cataract endophthalmitis are caused by fungi.

## Developed Country
- In the United States, post-cataract endophthalmitis is the most common form of bacterial endophthalmitis.
- In the United States, the incidence of cataract endophthalmitis was estimated to range from 80 to 360 cases per 100,00 individuals with ocular surgery.
- In the  United States and Europe, nearly all cases of acute post-cataract endophthalmitis are caused by bacteria.
- In the United States, the incidence of culture-proven postoperative endophthalmitis caused by cataract surgery with or without intraocular lens (IOL) was estimated to be 80 cases per 100,000 individuals.
- In the United States, the incidence of culture-proven postoperative endophthalmitis caused by secondary IOL placement was estimated to be 360 cases per 100,000 individuals.

# Risk Factors
Common risk factors in the development of post-catarct endophthalmitis include:
- Secondary intraocular lens placement
- Intra-ocular lenses (IOLs) with polypropylene
- Intracapsular cataract extraction
- Clear corneal incisions
- Vitreous contamination following cataract surgery (break in the posterior lens capsule)
- Implantation of an intraocular lens without a heparinized surface
- Diabetes
- immunosuppressive therapy
- Wound dehiscence or leak
- Age 85
- Eyelid abnormalities (blepharitis, conjunctivitis, cannuliculitis, lacrimal duct obstructions, and contact lens wear)

# Screening
Screening for post cataract surgery endophthalmitis is not recommended.

# Natural History, Complications, and Prognosis

## Natural History
Post-cataract endophthalmitis is a medical emergency. If left untreated, It may lead to panophthalmitis, corneal infiltration, corneal perforation, and ultimately permanent vision loss.

## Complications
Common complications of post-catarsct 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.
Overall, 50% of eyes with post-cataract endophthalmitis obtain a final visual acuity 20/40 vision, and 10% obtain a final visual acuity of 20/400.
The visual outcome of post cataract endophthalmitis is highly correlated with the bacteriology.
- Post-operative endophthalmitis caused by any type of streptococci is associated with very poor visual outcome.
- Post-operative endophthalmitis caused by coagulase-negative staphylococcus (cause milder endophthalmitis) is associated with better visual outcome than strepcocci.
- Delayed post-operative endophthalmitis is associated with particularly good prognosis with treatment.

# Diagnosis

## Diagnostic Criteria
Endophthalmitis is a clinical diagnosis, supported by culture of intra-ocular fluids.

## History
A detailed and thorough history from the patient is necessary. Specific areas of focus when obtaining a history from the patient with post-cataract surgery endophthalmitis include:
- History of previous cataract surgery
- History of chronic, recurrent, steroid responsive idiopathic uveitis (most patients with delayed post-operative endophthalmitis are characterized by this presentation)

## Symptoms
- Acute post-cataract endophthalmitis may occur within hours to few days after  cataract surgery in 75% of cases.
- Delayed post-operative endophthalmitis may occur several weeks or month after surgery and often include less virulent bacteria and only of the patients may present with eye pain.
Symptoms of post-cataratc endophthalmitis may include the following:
- Deep pain
- Decreased vision
- Lid swelling
- Red eye
- Photophobia
- Eye discharge

## Physical Examination
A thorough physical and eye examination from the patient is necessary. 
Common ophthalmoscope examination findings of post-operative endophthalmitis include:
- Visual acuity less than 5/200
- Conjunctival injection
- eyelid edema
- Decreased red reflex

## 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 (not often sensitive)
- Polymerase chain reaction (PCR)  of aqueous humor as well as the vitreous humor (much more sensitive than culture (70% vs. 9%)
- Conjunctival and eyelid cultures in patients with blepharitis and wound dehiscence may indicated
Vitreous cultures are more likely to be positive after vitrectomy than vitreous aspirate (90% vs. 75%), and aqueous cultures are positive in 40% of all cases with endophthalmitis.

## Imaging Findings

### X Ray
There are no diagnostic x ray findings associated with post-cataract endophthalmitis.

### CT
There are no diagnostic CT scan findings associated with post-cataract endophthalmitis.

### MRI
There are no diagnostic MRI findings associated with post-cataract endophthalmitis.

### Ultrasound
On ocular ultrasonography, endophthalmitis may characterized by anterior vitreous haze echoes and retinochoroidal thickening.

### Other Imaging Findings
Orbital echography is helpful for assessment of vitreous opacification, status of the posterior hyaloid face, and retinal detachment in a patient with post-operative.

## Other Diagnostic Studies

### Slit lamp finding
- 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
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
- In addition to intravitreal antibiotic therapy, immediate vitrectomy is often necessary
- Repeat antimicrobial regimen in 2 days post-vitrectomy is necessary
- Systemic antibiotics are not recommended, but may be considered in severe cases, especially with orbital involvement.
- In delayed post-operative endophthalmitis, treatment should include vitrectomy with posterior capsulectomy and intravitreal injection.

## 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 OR 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
- 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 for all patients who develop post cataract endophthalmitis
- A vitrectomy is almost always indicated in all patients with delayed post-operative endophthalmitis
The benefits of vitrectomy include:
- Better vitreous sample
- Rapid and complete sterilization of the vitreous
- Removal of toxic bacterial products
- Enhancement of systemic antimicrobial penetration in to the eye

## Prevention

### Primary prevention
Effective measures for the primary prevention of post-cataract surgery 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)
- preoperative antibiotic propylaxis (timing, routs of delivery, and antibiotic choice in not clear)
- Proper construction of wound, injectable intraocular lenses
- Preoperative clinical assessment of the patient before proceeding for surgery

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