Endophthalmitis

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Article initiated by:

Sami Kamjoo, MD

All contributors:

David Xu, MD, Florence Valcourt, Robert F. Melendez, MD, MBA, Vinay A. Shah M.D., Koushik Tripathy, MD (AIIMS), Dr. Kabir Hossain, Alan Palestine, MD, Anna Murchison, MD, MPH, Jennifer Cao, MD, David Xu, MD, Jason Hsu, MD, Bharat Gurnani MBBS,DNB,FCRS,FICO(UK), FAICO (Cornea, AIIMS, AIOS), FAICO (Refractive Surgery, AIIMS, AIOS), MRCS (Ed), MNAMS, Sami Kamjoo, MD, Jennifer I Lim MD, Kevin Yang Wu, MD. DMD.

Assigned editor:

Jason Hsu, MD, Jennifer Cao, MD

Review:

Assigned status Update Pending

 by Jennifer Cao, MD on January 19, 2024.

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Contributing Editors:	add

Endophthalmitis

Hypopyon with hazy media

DiseasesDB

30828

ICD-10

H44.0

Definition

Endophthalmitis is a purulent inflammation of the intraocular fluids (vitreous and aqueous) usually due to infection. 

• Serious intraocular inflammatory disorder resulting from infection of the vitreous cavity
• Progressive vitritis is the hallmark of any form of endophthalmitis
• Histologically: massive infiltration of the vitreous cavity with inflammatory cells

Types of Endophthalmitis

Exogenous

• Acute Postoperative
• Chronic Postoperative
• Traumatic
• Filtering Bleb-Associated
• After Intravitreal Injections
• Corneal ulcer

Endogenous

• Bacterial or fungal endogenous chorioretinitis +/- vitritis

Acute Postoperative Endophthalmitis

• Refers to infectious endophthalmitis shortly after ocular surgery
• Most present within 1-2 weeks, usually 3-5 days after the surgery.
• Initial symptoms: rapidly progressive, including pain, red eye, ocular discharge, and worsening vision
• Common signs: decreased visual acuity, lid swelling, conjunctival and corneal edema, anterior chamber cells + fibrin, hypopyon, vitreous inflammation, retinitis, retinal hemorrhages and blunting of red reflex
• Retinal Periphlebitis – earliest sign

Endophthalmitis Vitrectomy Study (EVS)

EVS evaluated only the patients with acute endophthalmitis occurring within 6 weeks of cataract surgery or secondary intraocular lens implantation.

Symptoms

• 94.3% reported blurred vision
• 82.1% red eye
• 74% pain- It is important to note that almost 25% of patients did not have pain.
• 34.5% swollen lid
• Epiphora
• Photophobia

Signs

• 85% hypopyon- 15% of patients may not have a hypopyon.
• 79% hazy media
• 26% light perception (LP) vision only

When there is a doubt between post-operative inflammation and endophthalmitis with severe haze in the ocular media or vitreous opacities clinically, the possibility of an infection should be given priority given the potentially rapid and devastating consequences of delayed treatment.

Epidemiology

• Acute postoperative endophthalmitis is the most common form of endophthalmitis
• Incidence following cataract surgery: 0.08% - 0.68%
• Rates increasing since advent of clear corneal incisions
• Highest risk after secondary IOL (0.2-0.367%), and traditionally lowest after pars plana vitrectomy (0.03-0.046%). However, recent studies in the microincisional vitrectomy surgery era suggest increased rates up to 0.11-0.16%.

Evaluation

• Suspect in any eye with inflammation greater than the usual postop course
• Associations:
  • Wound leak or dehiscence- especially a leaking small incision cataract surgery (SICS) wound
  • Suture abscess
  • Vitreous incarceration in the wound
  • Eroding scleral sutures used to fixate IOLs
  • Exposed tube shunt

Presenting Visual Acuity

• When measuring VA, the technique of differentiating LP vs. hand motion (HM) vision is most important
  • Pars plana vitrectomy recommended in patients with visual acuity of LP or worse.
  • Tap and inject intravitreal antibiotics in patients with visual acuity of HM or better.

• EVS gave the standard criteria to evaluate visual acuity in endophthalmitis: 'If no letters could be read on the (ETDRS) chart at 4 m, then at 1 m, vision was tested for the ability to count fingers. If the patient was unable to count fingers, vision was tested for the ability to recognize hand motions. For this, the patient's opposite eye was occluded, and a light source, such as a lamp used for near vision, was directed from behind the patient to the examiner's hand that either was stationary or was moved at one motion per second in a horizontal or vertical direction at a distance of 60 cm from the eye. The patient was asked to identify whether the examiner's hand was still, moving sideways, or moving up and down. The presentation was repeated five times, and hand-motion visual acuity was considered present if the patient was able to identify the examiner's action on at least four of the presentations. If the examiner was not convinced that hand motions could be detected, LP was tested at 0.9 m with an indirect ophthalmoscope set at maximum intensity.'

Differential Diagnosis of Acute Endophthalmitis

1. Occult retention of lens cortex or nucleus
2. Non-infectious hypopyon uveitis (Behcet’s or rifabutin)
3. Infectious posterior uveitis (syphilitic, tuberculous, toxoplasmosis, toxocariasis in children)
4. Non-infectious posterior uveitis (Vogt-Koyanagi-Harada disease, collagen vascular disorders, systemic vasculitides, idiopathic)
5. Inflammatory reaction to intravitreal drug
6. Blebitis
7. Acute retinal necrosis
8. Keratitis
9. Toxic anterior segment syndrome (TASS)
   • Rapid onset (within 12-24 hours, often with limbus to limbus corneal edema)
   • Increased intraocular pressure
   • Absent vitreous inflammation
   • Iris damage
   • Response to steroid
10. Intraocular lymphoma (masquerade syndrome)

Testing

Ultrasound Evaluation

• Should be performed if significant vitritis or media opacity prevents adequate view of the fundus
• Findings consistent with endophthalmitis:
  1. Dispersed vitreous opacities with vitritis
  2. Chorioretinal thickening
• Assess for presence of: retinal or choroidal detachment, retained lens material, retained foreign bodies
• Retinal or choroidal detachment are poor prognostic factors.

Microbiological Characteristics

• Bacteria are the most common infecting agents
• Causative organisms typically represent bacteria from patient’s own periocular flora introduced during the procedure or gaining access later, usually in the early post-procedure period.
  • In cases of intravitreal injection associated endophthalmitis, additional causes include oral flora (from the treating physician or patient and appears to occur at a higher rate compared to postoperative endophthalmitis) or drug contamination. Therefore, it is important for providers and patients to not speak during injections and consider wearing a mask or using a drape.

• In the EVS, 94.2% of culture-confirmed cases involved gram positive bacteria
• 70% were gram positive, coagulase-negative staphylococci (Staphylococcus epidermidis)

Obtaining Specimens for Microbiological Studies

• In the EVS, vitreous samples yielded positive cultures more often than aqueous samples
• Aqueous samples yielded positive culture only in a small minority (4.2%) of eyes
• Given this, vitreous sampling is most often the first choice. Some surgeons obtain both vitreous and aqueous while others obtain an aqueous sample only if the vitreous tap is dry. A minority obtain only an aqueous sample.
• Eye should be prepped with 5% povidone-iodine. Lashes may be draped. An eyelid speculum may be used.
• Subconjunctival or periocular lidocaine anesthesia is usually required.

Vitreous Specimen

• Needle aspiration
  • A 22 to 27G needle attached to a syringe is inserted into the vitreous cavity through the pars plana (pull plunger back first to break the vacuum before inserting into the eye).
  • Slowly aspirate. If no fluid vitreous can be obtained with a needle tap, an anterior chamber (AC) tap or vitreous biopsy must be performed instead to avoid aspirating formed vitreous
• Vitrectomy
  • After conjunctival incision (if 20g), a vitrectomy probe attached to a syringe is inserted into the vitreous cavity through a sclerotomy placed 3-4 mm posterior to limbus
  • Approx 0.1-0.3mL of vitreous is removed from the anterior vitreous cavity by using the automated cutting mechanism of the probe and slow, manual aspiration.

Anterior Chamber Specimen

• A 27 to 30G needle is inserted near the limbus into the AC
• 0.05 to 0.1cc of fluid is withdrawn.
• Care should be taken to avoid the lens and iris. The AC should not be flattened. Do not aspirate the hypopyon as it is congealed and may not go through the needle.

Specimen Handling

• Culture inoculation by the surgeon or laboratory within minutes of obtaining specimens is ideal to maximize recovery of organisms
• Inject the specimen deeply into liquid media to ensure the sample is within the media
• Gram stain can help to determine the presence of infectious organisms and white cells acutely. Cultures (aerobic, anaerobic, and fungal) are useful for specific identification of organisms and sensitivity
• Antibiotic sensitivities (although in the EVS, vancomycin and amikacin empirically covered 99.4% of all infecting organisms)
• More recently, polymerase chain reaction (PCR) testing is being used more frequently to identify suspected pathogens in the sample. PCR testing requires the physician to specify the suspected organisms when requesting the test.

Treatment

Pars Plana Vitrectomy (PPV)

• Advantages: reduction of infecting organisms, toxins, inflammatory materials, and opacities. Allows a more robust collection of samples for culture
• Disadvantages: Need for sophisticated equipment and operating room time/staff. Visualization may be poor due to corneal edema/opacification, posterior synechiae, and dense vitreous debris.
• Vitrectomized eyes may have more rapid clearance of intravitreal antibiotics
• In inflamed, aphakic, vitrectomized rabbits, intravitreal vancomycin and ceftazidime half-lives are 7.5 and 5.1 hours, respectively, compared to 31.4 and 10.1 hours, respectively, in inflamed, phakic non vitrectomized rabbits
  

PPV – obtaining sample

• Standard 3 port setup
• A vitreous sample of 0.2-0.5mL is first obtained without infusion using gentle manual aspiration into a syringe - this yields an undiluted vitreous specimen
• Infusion is then initiated and core vitrectomy performed
• The AC is cleared for visualization as necessary
• In most cases, IOL need not be removed initially
• Aspiration of debris within the capsular bag if able to be performed safely is also helpful

• In the EVS, attempts were made to clear 50% or more of the vitreous
• Also in the EVS, no attempt was made to induce a posterior vitreous detachment if none was previously present

Immediate PPV vs. Tap & Inject

• In the EVS, patients who presented with LP only visual acuity had a significant, threefold improved chance of obtaining 20/40 vision after immediate vitrectomy (33%) compared to tap and inject (11%)
  • 56% of eyes achieved 20/100 or better after immediate PPV compared to only 30% after tap
• HM or better vision demonstrated no significant difference between the treatment groups in final visual acuity (consider earlier PPV for diabetics)

EVS Limitations

• Results may not apply to endophthalmitis after other ocular procedures (EVS only studied post cataract and IOL surgery)
  • For example, post-intravitreal injection, bleb related endophthalmitis or chronic postoperative endophthalmitis were not studied in the EVS
• Patients with no light perception (NLP) or significant opacification of AC obscuring iris tissue were excluded from the study. Therefore severe infections or virulent organisms were excluded
• Unknown whether PPV is superior in these circumstances

Intravitreal Antibiotics

Current recommendations for empirical therapy (bacterial)

• Vancomycin 1.0 mg/0.1 mL
• Ceftazidime 2.25 mg/0.1 mL
• Amikacin 400 μg/0.1 mL for Penicillin (PCN) allergic patients (although usually can still inject Ceftaz since there is low cross-reactivity between cephalosporins and PCN; keep in mind that most PCN "allergies" may not really be an allergic reaction; also low systemic absorption from ocular injection)
• 4th generation fluoroquinolones – intravitreal moxifloxacin has been tried in some studies
• Fungal: Amphotericin B 5-10 μg/0.1 mL or voriconazole 50-100 μg/0.1 mL

Complications of Intravitreal Antibiotics

• Corneal opacification and retinal toxicity
• Retinal toxicity with aminoglycosides, most notably gentamicin (even as low as 0.1mg)- macular infarction
  • Less common with amikacin and tobramycin
  • Amphotericin B can also cause retinal toxicity
• Hemorrhagic occlusive retinal vasculitis (HORV): rare but serious, associated with vancomycin injection

Systemic Antibiotics

• Usually too slow to enter the eye in adequate concentrations so not sufficient as monotherapy. Some surgeons use adjunctive oral antibiotics (i.e., oral moxifloxacin) in addition to intravitreals
• In the EVS, there was no difference in VA or media clarity with or without intravenous antibiotics (amikacin plus ceftazidime or amikacin plus ciprofloxacin) when given in addition to intravitreal antibiotics
• However, newer 4th generation fluoroquinolones with better ocular penetration were not available at the time the EVS was conducted. Systemic ceftazidime, cefazolin, ciprofloxacin, gatifloxacin³ and moxifloxacin have been shown to penetrate the blood ocular barrier efficiently.

Corticosteroids

• Goal is to modulate the host inflammatory response to the infection and minimize ocular damage from this response. Avoid when fungal infection is suspected.
• Intravitreal corticosteroids (dexamethasone) is controversial
• 2 retrospective nonrandomized studies showed 20/400 or better vision was achieved more often in patients who received 400 μg adjuvant intravitreal dexamethasone
• Randomized, prospective trial of 63 patients showed in no difference in visual acuity at 12 weeks
• Another retrospective, nonrandomized trial of 57 patients showed worse visual acuity

Reinjection

A minority of patients will require further treatment, mainly for worsening ocular infection. It typically requires more than 24 hours to observe an improvement in the clinical appearance after initial treatment. In many cases, the treated eyes look somewhat worse 1 day after treatment before improving subsequently.

Considerations of reinjection

• Should be considered if the infection fails to stabilize or improve more than 48 hours after the first injection
• Based on consensus view, the EVS protocol recommended reinjection if the infection was worsening at 36-60 hours after initial injection
• Often, 36 hours after treatment, culture results are available
• Decision to reinject antibiotics should not be taken lightly, since repeat injection may increase risk of retinal toxicity
• 100% retinal toxicity rates with 3 intravitreal doses of 1mg vanco combined with 400 μg amikacin or 200 μg gentamicin in rabbit eyes
• Patients with no culture growth, equivocal growth, or coagulase-negative Staphylococci had a 5% rate of additional procedures, compared to 30% in patients with cultures that grew gram negative or other gram positive organisms

Outcomes and Risk Factors for Poor Outcomes

• The most common cause of visual loss in the EVS was attributed to macular abnormalities, such as ERM, macular edema, pigmentary degeneration, and ischemia
• Strongest predictor of poor visual outcome was light perception only vision
• Other risk factors: older age, diabetes mellitus, corneal infiltrate or ring ulcer, compromised posterior capsule, low or high intraocular pressure, afferent pupillary defect, rubeosis, and absent red reflex

Virulence

Eyes with coagulase-negative Staphylococci were most likely to obtain 20/100 final visual acuity or better (84%). More virulent organisms, such as Staphylococcus aureus, Streptococcal species, and gram negative (Pseudomonas) organisms were associated with worse visual outcomes

Chronic Postoperative Endophthalmitis (> 6 weeks)

History

• Usually manifest several weeks or months after surgery
• Less common than acute variety
• Organisms isolated are less virulent bacteria and fungi
• 63% Propionibacterium acnes, 16% Staphylococcus epidermidis, 16% Candida parapsilosis

Clinical features

• Pain or discomfort may not be present
• Inflammation can be initially steroid responsive but recurrent after steroid taper
• Fungal infections demonstrate paradoxical worsening with steroids
• Frank hypopyon is often absent
• Granulomatous uveitis with large precipitates on cornea or IOL
• White intracapsular plaque with P. acnes
• Stringy white infiltrates and “fluff balls” or “pearls-on-a-string” near the capsular remnant are characteristic but not pathognomonic for fungal infection

Treatment for Chronic Cases

• Obtain AC and vitreous samples
• Identification of infectious organism is key in management of these infections
• Intravitreal injection
• However, vancomycin is often inadequate for P. acnes
• Often need PPV and removal of capsule and/or IOL

Filtering Bleb-Associated Endophthalmitis

• Occurs as a result of pathogenic organisms gaining entry to intraocular tissue through the conjunctival filtering bleb
• Mean time between surgery and endophthalmitis is 19.1 months (range 3-9 years)
• 0.2 – 9.6% of glaucoma filtering procedures
• Increased incidence with use of antifibrotic agents
• Thin, cystic, avascular conjunctiva
• Blebitis – if no uveitis or vitritis

Post-Trabeculectomy Endophthalmitis Treatment

• If only blebitis - conservative treatment with systemic and topical fortified antibiotic therapy
• If the vitreous is clear, examine these patients frequently, treating for endophthalmitis if vitritis or acute hypopyon develops
• Needle aspiration of the bleb is not advised
• Studies suggest possible benefit from PPV

Endophthalmitis after Intravitreal Injection

• Intravitreal injections have increased in volume worldwide, leading to increased prevalence of endophthalmitis
• Coagulase-negative Staphylococci is the most common organism, similar to acute postop endophthalmitis
• No infectious agent is identified in many cases
• Triamcinolone acetonide crystals can migrate into AC and mimic hypopyon
• Up to 1.4% after intravitreal triamcinolone injections
• 0.008% - 0.092% after anti-vascular endothelial growth factor injections
• Intravitreal triamcinolone may play a role in endophthalmitis potentiation

Intraocular Inflammation after Triamcinolone Injection or Intravitreal Anti-VEGF Injection

• Triamcinolone crystals in AC or vitreous cavity can be difficult to distinguish from inflammatory reaction
  • Use gravity-induced shifting of layered material and absence of AC flare or fibrin as a sign of a non-inflammatory cause
  • Triamcinolone crystals may shift from the inferior anterior chamber angle when the pt is placed on his or her side, a phenomenon that does not occur with sticky, fibrin-laden material in a true inflammatory hypopyon
• Reported cases of non-infectious intraocular inflammation after anti-VEGF injections
  • Cases can be difficult to distinguish from true endophthalmitis. Therefore, low threshold for immediate treatment with tap and inject.

Management options

• Close observation, topical steroids alone, oral fluoroquinolones alone

Traumatic Endophthalmitis

Etiology

• Approximately 25% of endophthalmitis cases
• After open globe injury, chance of developing endophthalmitis is approximately 7%
• Injuries including intraocular foreign body (IOFB) have higher rates

Risk factors

• Other risk factors: dirty wound, lens capsule rupture, age >50 years, delayed presentation of more than 24 hours after injury
• Bacillus and Staphylococcus species are common in penetrating trauma with IOFB

Workup

• Primary repair and removal of IOFB as soon as possible
• Exclude the possibility of occult, retained IOFB
• CT scan with thin 1mm cuts
• Obtain cultures
• Intravitreal vancomycin and ceftazidime
• Some advocate gentamicin + clindamycin for synergistic effect against Bacillus and Staphylococcus

Treatment considerations

• Application of EVS may not be appropriate, due to different organisms. In severe cases, vitrectomy should be strongly considered
• Some authors advocate therapeutic vitrectomy in all cases of traumatic endophthalmitis
• Others suggest performing vitrectomy only if patients do not respond after 48 hours or rapidly deteriorate in the first 24 hours following intravitreal antibiotics
• Post-traumatic endophthalmitis has worst visual prognosis than other categories

Prophylaxis after Penetrating Trauma

• Clinical evidence not established
• Some authors advocate intravitreal antibiotic administration in all cases of penetrating trauma, especially when associated with an IOFB
• Others recommend administration in the presence of risk factors (2 of 3: dirty wound, lens breach, or delay in closure over 24 hours)
• Systemic antibiotics: intravenous cefazolin (1g every 6 hours for 48-72 hours) followed by an oral agent such as gatifloxacin or moxifloxacin for 7 days

Endogenous Bacterial Endophthalmitis

For endogenous fungal endophthalmitis, please refer to the article on Fungal Endophthalmitis.

Etiology

• Originates from sources within the body
• Infectious extraocular focus can be found in 90% of the cases, such as tooth abscess, pneumonia, endocarditis, liver abscess, urinary tract infection and bacterial meningitis
• Bacterial causes are responsible for half of endogenous endophthalmitis while fungal origins are responsible for the other half
• Gram-positive organisms:
  • Streptococcus species: primary infection is often endocarditis which accounts for 40% of endogenous bacterial endophthalmitis in North America
  • Staphylococcus aureus often comes from a skin infection
  • Bacillus species are mostly seen in IV drugs users
  • Nocardia species are mostly seen in immunocompromised patients
• Gram-negative organisms:
  • Escherichia coli from urinary tract infection is the second leading cause and is responsible for about a third of cases in North America
  • Neisseria meningitidis and Haemophilus influenzae can both be associated with meningitis
  • Klebsiella species are often associated with liver abscess and are the leading cause of endogenous bacterial endophthalmitis in Asian population

Other Risk Factors

• Impaired immune status: HIV/AIDS, chronic disease (eg, diabetes mellitus, systemic malignancy, sickle cell anemia, systemic lupus erythematous), immunosuppressive treatment, neonates
• Recent invasive medical procedures: extensive gastrointestinal surgery, endoscopy, dental procedures

• Intravenous access lines and catheters

Diagnosis

• Anterior chamber paracentesis with vitrectomy: vitreous and aqueous cultures (e.g., aerobic, anaerobic, fungal) with stains (e.g., gram, giemsa)
• Identification of causative organism is made by systemic culture of blood, urine and/or cerebrospinal fluid in 75-80% of cases

Treatment

• In contrast to postoperative endophthalmitis, systemic antibiotics are central to the treatment of endogenous endophthalmitis
• Intravitreal antibiotics administered rapidly
• Initial empiric treatment with vancomycin 1 mg/0,1ml with ceftazidime 2,25 mg/0,1ml or amphotericin B 5-10 ug/0,1 ml in addition to systemic therapy
• Focal chorioretinitis and associated mild vitritis can respond to systemic therapy alone
• A late vitrectomy is preferred to additional antibiotics when the disease progresses under antibiotic therapy
• Additional antifungal therapy if there is doubt on the etiology
• Corticosteroids are controversial, but they may help to reduce enucleation and evisceration

Conclusions

• Early diagnosis and treatment with antimicrobial therapy are critical
• Usually diagnosis must be made on clinical grounds
• Treat with empirical therapy, usually vancomycin + ceftazidime if bacterial
• EVS showed that PPV was of benefit in patients with endophthalmitis following cataract surgery or secondary IOL placement who presented with LP only visual acuity
• Although the role of vitrectomy in other forms of endophthalmitis is less clear, it remains an accepted adjunct to intravitreal antibiotics for treatment of moderate to severe cases