Endophthalmitis

Definition and Epidemiology

Definition

Endophthalmitis is an inflammatory process of the intraocular cavities (e.g., aqueous and/or vitreous humor) usually caused by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview or fungi Fungi Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi. Mycology: Overview.

Epidemiology

• The incidence between men and women is equal.
• More common in the elderly and after cataract surgery
• Exogenous endophthalmitis is the most common form:
  • 60% of exogenous cases occur after intraocular surgery.
  • Occurs in 0.1%–0.3% of cataract operations
  • 25%–30% of cases are posttraumatic.
• Endogenous endophthalmitis:
  • More common in immunocompromised individuals
  • Candidal infections are increasing in IV drug users.
  • Rare (2%–15% of all cases)

Etiology

Sterile endophthalmitis

• Complication of intravitreal injection (triamcinolone, anti-vascular endothelial growth factor (anti-VEGF), methotrexate)
• Retained native lens after an operation

Infectious endophthalmitis

Exogenous: 

• Acute-onset postoperative endophthalmitis:
  • Occurs within 6 weeks of an ocular procedure
  • Cataract surgery is the most common cause.
  • Organism:
    • Coagulase-negative Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus (most common) 
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus
• Delayed-onset postoperative endophthalmitis:
  • Less common than the acute-onset variety
  • Occurs more than 6 weeks after surgery
  • Organisms:
    • Propionibacterium acnes (predominant)
    • Coagulase-negative Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus
    • Fungal infections (16%–27% of cases)
• Bleb-associated endophthalmitis:
  • Following trabeculectomy
  • Organisms:
    • Coagulase-negative Staphylococcus
    • Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae
    • Moraxella Moraxella Moraxella is a genus of gram-negative diplococci, with M. catarrhalis being the most clinically relevant species. M. catarrhalis is part of the normal flora of the upper respiratory tract, but it can cause infection in susceptible individuals. The infection is transmitted through respiratory droplets and can lead to chronic obstructive pulmonary disease (COPD) exacerbations in adults and otitis media in children. Moraxella catarrhalis 
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus
• Post-intravitreal injection endophthalmitis:
  • Occurs following injection of anti-VEGF medications (e.g., bevacizumab) or corticosteroids
  • Organisms:
    • Coagulase-negative Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus 
• Posttraumatic endophthalmitis:
  • Occurs following penetrating trauma to the eye
  • Organisms:
    • Bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus cereus (one of the most common organisms) 
    • Gram-positive cocci 
    • Gram-negative organisms

Endogenous:

• Hematogenous spread of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview/ fungi Fungi Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi. Mycology: Overview from a distant source (e.g., endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis, indwelling catheter)
• Caused by:
  • Gram-positive organisms (in the United States)
  • Fungi: Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis albicans is the most common, followed by Aspergillus and Fusarium.

Pathogenesis

Normally, the ocular-blood barrier naturally resists invasive organisms.

Exogenous endophthalmitis

Pathophysiology:

• Disruption of globe integrity:
  • Cataract operations
  • Radial keratotomy
  • Intravitreal injections
  • Retinal or glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma operations
  • Penetrating foreign bodies
• Introduction of causative organisms

Risk factors:

• Blepharitis Blepharitis Blepharitis is an ocular condition characterized by eyelid inflammation. Anterior blepharitis involves the eyelid skin and eyelashes, while the posterior type affects the meibomian glands. Often, these conditions overlap. Blepharitis
• Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
• Older age
• Wound contamination
• Traumatic lens rupture
• Delayed wound closure
• Compounded medication usage

Endogenous endophthalmitis

Pathophysiology:

In unilateral cases, the right eye is twice as likely as the left eye to become infected.

• Hematogenous spread from distant sites
• Blood-borne organisms breach the blood-ocular barrier by:
  • Direct invasion
  • Changes in vascular endothelium as a result of substrates released during an infection

Risk factors: 

• Immunocompromised conditions
• Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
• Malignancies
• IV drug use
• Indwelling catheters
• Urinary tract infections Urinary tract infections Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections
• Organ transplant
• End-stage liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver or renal disease

Clinical Presentation

Exogenous

Acute:

• Usually bacterial
• Occurs within days after an inciting event
• Presents with: 
  • Decreased visual acuity
  • Eye pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Eyelid edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Conjunctival injection
  • Hypopyon (WBCs in the anterior chamber)
  • Corneal-ring ulcer (traumatic)
  • Absent red reflex

Chronic:

• Usually from fungi Fungi Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi. Mycology: Overview or less-virulent bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
• Gradual onset
• Visual acuity may be preserved until late in the presentation
• Corneal infiltrates with fuzzy or feathery borders

Endogenous

• Subacute onset
• Signs of a systemic infection may be present (e.g., fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever).
• Presentation may include:
  • Decreased vision
  • Eye pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Hypopyon
  • Subconjunctival hemorrhage
  • Conjunctival injection
  • Corneal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Reduced or absent red reflex

Diagnosis

Endophthalmitis diagnosis is based on clinical presentation with confirmation by laboratory testing of aqueous and/or vitreous humor.

History

• Focus on risk-increasing practices or procedures:
  • Recent ocular procedures
  • Trauma
  • IV drug use
  • Immunosuppression
  • Sepsis risk
• Ocular symptoms:
  • Pain and irritation
  • Photophobia
  • Headache
  • Redness
  • Decreased visual acuity
• Fever

Physical exam

Fundoscopy:

• Reduced fundal view
• Loss of red reflex
• Roth spots:
  • Retinal hemorrhages
  • Occurs in endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis

Slit-lamp examination:

• Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation in the anterior chamber:
  • Cells
  • Fibrin
• Infiltrates in the vitreous cavity
• Thick, clumpy material in aqueous humor (fungal)
• Puff–ball-like lesions in the vitreous cavity (fungal)

Diagnostic testing

• Ultrasound-B scan:
  • Use when the posterior segment is not visualized.
  • Findings: vitreous debris, retinochoroidal thickening
• CT scan: cases of orbital trauma (avoid MRI due to potential of foreign bodies of metal)
• Collection of ocular fluid (vitreous/aqueous) for microbiological study: 
  • Real-time PCR:
    •  Identify both bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview and fungi Fungi Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi. Mycology: Overview
    •  Preferred over Gram stain
  • Gram stain 
  • Culture
• Culture of the penetrating object if traumatic injury

Workup support by diagnostic testing

Diagnostic testing supports workup to search for the source of endogenous endophthalmitis:

• Echocardiogram to rule out infective endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
• Chest X-ray to evaluate the source of infection
• Blood cultures to identify potential hematogenous seeding agent
• CBC with differential to evaluate for signs of infection
• Erythrocyte sedimentation rate (ESR)
• Urine culture to evaluate for urinary tract infection as the cause
• Culture of the indwelling catheter tip to identify if a catheter-related source

Management

Management depends on the underlying cause and outcome is extremely dependent on timely diagnosis and treatment. 

Sterile endophthalmitis

• Usually resolves without further treatment
• Topical steroids may be used.
• Treat with antibiotics in severe disease.

Infectious endophthalmitis

Fungal:

• Intravitreal injections: 
  • Achieves a high concentration of the drug in the vitreous cavity without systemic side effects
  • Options: amphotericin B or voriconazole
• Systemic therapy: 
  • Used in all cases of endogenous endophthalmitis (part of systemic infection)
  • Used in addition to intravitreal injections for exogenous endophthalmitis
  • Options: IV fluconazole or voriconazole
• Pars plana vitrectomy (PPV): 
  • For severe disease 
  • Removes the vitreous humor 

Bacterial:

• Hospital admission
• Intravitreal injections:
  • Vancomycin plus ceftazidime 
  • Amikacin is an alternative (may cause retinal toxicity).
• IV antibiotics: 
  • Vancomycin 
  • Fluoroquinolone or a 3rd-generation cephalosporin
• Topical steroids
• PPV

Traumatic endophthalmitis

• Hospital admission
• Treat ruptured globe (if present).
• Intravitreal antibiotics
• Systemic antibiotics:
  • Vancomycin plus ceftazidime
  • Consider clindamycin if soil contamination (covers Bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus).
• PPV

Differential Diagnosis

• Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea: inflammation of the uvea. Patients usually present with decreased visual acuity, photophobia, and periocular pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea is often idiopathic but may be caused by genetic, immune, traumatic, or infectious etiologies. An examination may show hypopyon and vitritis, or macular edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. Management depends on the etiology. Steroids are used in idiopathic uveitis. Infectious uveitis is treated with antibiotics or antiviral therapy.
• Vitreous hemorrhage: the leakage of blood into the vitreous body. Patients present with dramatic vision loss, floaters, visual haze, and blurring. Slit-lamp examination shows blood floating in the vitreous cavity. Management is based on the disease severity and the underlying etiology. Photocoagulation or PPV may be performed.
• Toxic anterior segment syndrome (TASS): a sterile inflammation of the anterior segment occurring 12–24 hours after ocular surgery, resulting as a reaction to a sterile toxin or contaminant of surgery. Patients present with ocular pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and mildly decreased visual acuity. Slit-lamp examination shows conjunctival injection, corneal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, and fibrin deposition in the anterior segment. Hypopyon and intravitreal inflammation are not present. Management includes the administration of topical steroids.
• Corneal ulcer Corneal ulcer Corneal ulcers are classified as corneal epithelial defects. These defects are differentiated from other corneal lesions according to their depth: ulcers extend into the underlying stroma. Corneal Abrasions, Erosion, and Ulcers: an epithelial defect commonly associated with corneal inflammation. Most corneal ulcers are infectious (bacterial and viral causes). Noninfectious ulcers may be autoimmune or due to toxins/chemical burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns. The presentation includes conjunctival erythema, discharge, foreign-body sensation, and decreased vision. Slit-lamp evaluation is mandatory, and the condition is considered an ocular emergency. Management is with antibiotic topical agents.