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Summary Table

Category	Details
Risk Factors	Recent intraocular surgery (cataract surgery is the most common, typically within 6 weeks), intravitreal injection, penetrating ocular trauma, retained intraocular foreign body, microbial keratitis, immunocompromise, indwelling catheters, intravenous drug use, recent bacteremia or fungemia
Etiology	Acute postoperative cases are most often *Staphylococcus epidermidis(coagulase-negative staph), followed by Staphylococcus aureus* and streptococci. Post-traumatic cases often involve *Bacillus cereus. Bleb-associated* cases often involve streptococci and *Haemophilus influenzae. Endogenous cases often involve Candida albicans, Klebsiella pneumoniae* (especially in Asia, with liver abscess), or Aspergillus
Patient Presentation	Rapid onset of ocular pain, decreased vision, and redness, classically a few days to weeks after intraocular surgery or trauma. Endogenous cases present with painful red eye in a febrile or septic patient
Classic Physical Exam	Conjunctival injection, eyelid swelling, corneal edema, hypopyon (layered white cells in the anterior chamber), severe vitritis obscuring the fundus, loss of red reflex, decreased visual acuity often to hand motion or light perception
Key Diagnostic Results	Vitreous tap with culture and Gram stain is the gold standard. B-scan ultrasound shows vitreous opacities when the view is blocked. In endogenous cases, blood cultures and source workup (echocardiogram, abdominal imaging) are essential
Management	Urgent referral to ophthalmology. Intravitreal antibiotics (vancomycin 1 mg in 0.1 mL + ceftazidime 2.25 mg in 0.1 mL) are the cornerstone. Pars plana vitrectomy is indicated when vision is light perception or worse. Intravitreal amphotericin or voriconazole for fungal cases. Systemic antibiotics or antifungals for endogenous disease
Keywords	Hypopyon, post-cataract surgery, sudden pain and vision loss, loss of red reflex, vitritis, "white blood layer in the anterior chamber," intravitreal vancomycin and ceftazidime, vitreous tap and inject

1. Pathophysiology

Endophthalmitis is an infection of the intraocular fluids, the aqueous and the vitreous, with inflammation that extends into adjacent structures. The eye is normally an immune-privileged compartment protected by the blood-ocular barrier, so once organisms breach this barrier they encounter a sheltered environment with limited host defenses, allowing rapid microbial proliferation and devastating tissue damage.

There are two principal routes of entry. Exogenous endophthalmitis is far more common and results from organisms gaining direct access through a break in the eye wall. The classic setting is acute postoperative endophthalmitis after cataract surgery, where flora from the patient's own eyelids and conjunctiva (especially coagulase-negative staphylococci) enter through the surgical wound. Other exogenous causes include intravitreal injection, penetrating trauma, retained foreign bodies, and infected filtering blebs after glaucoma surgery. Endogenous endophthalmitis is uncommon and arises when organisms reach the eye hematogenously from a distant source such as endocarditis, a liver abscess, an indwelling catheter, or intravenous drug use.

The clinical picture is driven by the inflammatory response to organisms within the closed ocular cavity. Neutrophil influx into the anterior chamber produces the hypopyon, a layered collection of white cells visible at the slit lamp. Vitreous involvement produces vitritis, which scatters light and obscures the fundus, accounting for the loss of red reflex and severely reduced vision. Toxins and inflammatory mediators damage the retina and optic nerve, and irreversible photoreceptor injury can occur within hours, which is why endophthalmitis is an ophthalmic emergency.

The timing of onset offers strong clues to the organism. Acute postoperative endophthalmitis appears within 1 to 6 weeks of surgery and is usually caused by bacteria. Chronic or delayed-onset endophthalmitis appearing months later is classically caused by Propionibacterium acnes (now Cutibacterium acnes) or fungi, with a more indolent granulomatous picture. Post-traumatic endophthalmitis has a higher rate of Bacillus cereus, which is particularly aggressive and associated with rapid vision loss and a ring corneal infiltrate.

2. Diagnostic Workup

Test	Role	Key Findings
Visual acuity and slit-lamp exam	Best initial assessment	Reduced acuity, hypopyon, conjunctival injection, corneal edema, fibrin in anterior chamber
Dilated fundoscopy	Assesses vitreous and retina	Vitritis, loss of red reflex, retinal hemorrhages, fluffy white vitreous infiltrates in fungal cases
B-scan ultrasound	Used when fundus view is obscured	Vitreous opacities, membranes, possible retinal detachment
Vitreous tap for culture and Gram stain	Gold standard, confirmatory test	Identifies organism, guides targeted therapy. Performed simultaneously with intravitreal antibiotic injection ("tap and inject")
Aqueous tap	Adjunct to vitreous sampling	Lower yield than vitreous but useful when vitreous tap is not feasible
Blood cultures	Mandatory in suspected endogenous disease	Identifies bacteremia or fungemia
Systemic source workup	Endogenous cases	Echocardiogram for endocarditis, abdominal imaging for liver abscess (especially Klebsiella in Asian patients), urinalysis, catheter cultures
Complete blood count, inflammatory markers	Supportive	Leukocytosis, elevated CRP in endogenous disease

The diagnosis of endophthalmitis is fundamentally clinical. Any patient with pain, decreased vision, and hypopyon after recent intraocular surgery, injection, or trauma has endophthalmitis until proven otherwise, and treatment cannot wait for cultures. The best initial test is a careful slit-lamp examination, which reveals the hypopyon, anterior chamber cells and flare, and severe vitritis.

When the vitreous is too cloudy to see the retina, B-scan ultrasonography is performed to look for vitreous opacities, membranes, and any associated retinal detachment, and to rule out a retained intraocular foreign body in trauma cases.

The most accurate (confirmatory) test is the vitreous tap with culture and Gram stain. This is performed at the same sitting as the first intravitreal antibiotic injection, a procedure called "tap and inject." The vitreous yields a higher microbiologic yield than the aqueous and identifies the organism in roughly two-thirds of acute postoperative cases. Cultures should be plated for bacteria and fungi, and PCR may be used for low-yield or fastidious organisms.

In endogenous endophthalmitis, the eye is the metastatic site, not the primary infection. Workup must therefore include blood cultures, echocardiography, and imaging directed at the suspected source. In Southeast Asian patients with a painful red eye and fever, Klebsiella pneumoniae liver abscess is a classic association and abdominal imaging is mandatory.

3. Management and Treatment

Treatment	Indication	Notes
Intravitreal vancomycin 1 mg in 0.1 mL plus ceftazidime 2.25 mg in 0.1 mL	First-line empiric therapy for all bacterial cases	Covers gram-positive (vancomycin) and gram-negative (ceftazidime) organisms. Amikacin 0.4 mg can substitute for ceftazidime in cephalosporin allergy
Intravitreal amphotericin B 5 to 10 micrograms or voriconazole 100 micrograms	Suspected or confirmed fungal endophthalmitis	First-line for Candida and mold infections
Pars plana vitrectomy	Vision of light perception or worse, severe or worsening cases, fungal disease, post-traumatic disease	Removes infected vitreous, improves antibiotic penetration, allows definitive sampling
Systemic antibiotics	Endogenous disease, post-traumatic disease, bleb-associated disease	Tailored to organism and source
Systemic antifungals (voriconazole, fluconazole)	Endogenous fungal disease	Voriconazole has good vitreous penetration
Topical or systemic corticosteroids	Adjunct after antimicrobials are established	Reduces inflammatory damage, controversial and avoided in fungal disease

Acute management is an emergency and follows a clear sequence. The next best step in any patient with suspected endophthalmitis is immediate referral to ophthalmology for vitreous tap and intravitreal antibiotic injection. Do not delay for culture results. Standard empiric intravitreal therapy is vancomycin 1 mg in 0.1 mL combined with ceftazidime 2.25 mg in 0.1 mL, which together cover the gram-positive organisms responsible for most postoperative cases and the gram-negative organisms that can cause more aggressive disease. In patients with cephalosporin allergy or hypersensitivity, amikacin 0.4 mg in 0.1 mL is the alternative, although it carries a risk of macular toxicity. Injections are typically repeated every 48 to 72 hours based on clinical response.

The decision regarding pars plana vitrectomy is guided by the landmark Endophthalmitis Vitrectomy Study. In acute postoperative endophthalmitis, immediate vitrectomy is recommended when presenting visual acuity is light perception or worse. When vision is hand motions or better, tap and inject alone is sufficient. Modern practice has expanded vitrectomy indications, and most surgeons now offer early vitrectomy for severe disease, post-traumatic cases, fungal disease, and any case that fails to improve within 48 hours.

Systemic antibiotics are not routinely added to acute postoperative cases because the Endophthalmitis Vitrectomy Study showed no benefit from systemic ceftazidime and amikacin. They are essential, however, in endogenous endophthalmitis (treat the source), post-traumatic endophthalmitis (broad-spectrum coverage including Bacillus), and bleb-associated disease.

Fungal endophthalmitis is treated with intravitreal amphotericin B or voriconazole, often combined with systemic voriconazole or fluconazole, and pars plana vitrectomy for moderate to severe disease. Candida chorioretinitis without vitritis can be treated with systemic therapy alone, but once the vitreous is involved intravitreal therapy is required.

Long-term management focuses on monitoring for complications including retinal detachment, persistent inflammation, glaucoma, and phthisis bulbi, and on treating residual macular pathology. Patients require close follow-up over weeks to months.

Contraindications and cautions: aminoglycosides are avoided when possible due to retinal toxicity. Intravitreal corticosteroids are contraindicated in fungal endophthalmitis because they worsen infection. In pregnancy, voriconazole and fluconazole are category D and require careful risk-benefit consideration; amphotericin B is preferred for systemic fungal therapy.

4. Differential Diagnosis and Distractors

Differential Diagnosis	Why it is similar	Key Discriminator
Toxic anterior segment syndrome (TASS)	Hypopyon, anterior chamber inflammation, decreased vision after cataract surgery	Onset within 12 to 48 hours of surgery (very rapid), no pain, no vitritis, responds to topical steroids alone. Endophthalmitis presents days later with severe pain and vitritis
Acute anterior uveitis	Painful red eye with hypopyon, photophobia	No vitritis, no recent surgery or trauma. Often associated with HLA-B27 disease, sarcoidosis, or Behcet disease. Vision is usually less severely affected
Acute angle-closure glaucoma	Sudden painful red eye with decreased vision	Mid-dilated non-reactive pupil, rock-hard eye on palpation, intraocular pressure greater than 40 mmHg. No hypopyon, no vitritis. Halos around lights and nausea common
Retained lens fragments after cataract surgery	Postoperative inflammation and vision loss	Lens material visible in anterior chamber or vitreous, negative cultures, slower onset, less pain
Postoperative inflammation (sterile)	Hypopyon and inflammation after surgery	Mild pain, gradual onset, responds rapidly to topical steroids. Endophthalmitis is severe and progressive
Vitreous hemorrhage	Sudden vision loss with poor fundus view	Painless, no hypopyon, no inflammation. B-scan distinguishes blood from inflammatory debris
Orbital cellulitis	Painful red eye with eyelid swelling	Proptosis, restricted ocular motility, pain with eye movement. Inflammation is orbital, not intraocular. Hypopyon and vitritis are absent

5. Traps and High-Yield Pearls

The most common way students miss endophthalmitis questions is failing to act with sufficient urgency. The vignette gives you a patient three to five days after cataract surgery with pain, redness, and a hypopyon, and the trap is to choose "topical antibiotics and ophthalmology follow-up tomorrow" or "oral fluoroquinolone." The correct answer is always immediate referral for vitreous tap and intravitreal antibiotic injection, because retinal damage accumulates within hours and a delay of even one day can cost the eye. Remember the mantra: tap and inject, do not delay for cultures.

A second trap is confusing acute postoperative endophthalmitis with toxic anterior segment syndrome. Timing is the discriminator. TASS appears within 12 to 48 hours, is painless, and lacks vitritis, while endophthalmitis appears several days to weeks after surgery, is painful, and shows florid vitritis. A third trap is missing endogenous endophthalmitis in a septic patient. If the vignette describes an intravenous drug user, a patient with indwelling catheters, or a patient with a liver abscess (especially Klebsiella in an Asian diabetic), and they develop a painful red eye with hypopyon, the eye is a metastatic infection and the correct workup includes blood cultures, echocardiography, and source imaging in addition to vitreous tap.

A fourth trap involves fungal endophthalmitis after intravenous drug use or in immunocompromised patients. The exam may describe fluffy white "string-of-pearls" vitreous lesions in a Candida albicans infection. Reaching for vancomycin and ceftazidime is wrong; the answer is intravitreal amphotericin or voriconazole plus systemic antifungal therapy, and steroids are avoided.

A fifth trap is post-traumatic endophthalmitis, particularly with soil-contaminated injuries, where the high-yield organism is Bacillus cereus. This organism is aggressive, causes a ring corneal infiltrate, and often results in vision loss within 24 hours. Empiric coverage must include vancomycin (the drug of choice for Bacillus), and many experts add a fluoroquinolone systemically.

The core competency being tested is recognizing that any patient with pain, hypopyon, and vision loss after recent intraocular surgery, injection, or trauma has endophthalmitis until proven otherwise, and that the next best step is always urgent ophthalmology referral for tap and inject, not waiting, not topical drops, not oral antibiotics. The exam rewards speed, correct empiric drug choice (vancomycin plus ceftazidime intravitreally), and the ability to recognize the few situations (light perception vision, fungal disease, endogenous source, severe trauma) where vitrectomy and systemic therapy must be added.

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