Endophthalmitis

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Endophthalmitis

Endophthalmitis is an extensive, potentially devastating inflammation of the intraocular contents - principally the vitreous and aqueous humors - caused most often by infectious organisms. It is an ophthalmic emergency requiring prompt diagnosis and treatment to salvage vision.

Definition and Classification

Endophthalmitis is classified by route of entry:

Type	Route	Common Triggers
Exogenous	Direct inoculation through the globe	Cataract surgery, intravitreal injection, penetrating trauma, filtering bleb
Endogenous (metastatic)	Hematogenous spread from a distant focus	Septicemia, IV drug use, immunosuppression, indwelling catheters

Goldman-Cecil Medicine, p. 451

Etiology

Postoperative (most common exogenous)

After cataract surgery:

Most common: Staphylococcus epidermidis
Common: S. aureus, streptococcal species
Less common: Gram-negatives (Pseudomonas, Klebsiella, E. coli, Bacillus, H. influenzae), anaerobes
Incidence: approximately <0.03% of surgical cases

Bleb-associated (after trabeculectomy): Streptococcus spp. and Gram-negatives predominate - organisms tend to be significantly more virulent than those seen after cataract surgery, and prognosis is worse.

Postvitrectomy: S. epidermidis most common.

Post-intravitreal injection: S. epidermidis and oral flora (notably streptococcal species).

Post-traumatic: Staphylococcus spp. and Bacillus spp. account for ~90% of culture-positive cases. Develops in approximately 1 in 10 penetrating injuries with retained intraocular foreign body (IOFB).

Chronic/subacute postoperative:

Cutibacterium acnes (formerly P. acnes): indolent course, recurrent anterior uveitis, white plaque on lens capsule, granulomatous KP, only transient steroid response
S. epidermidis, fungi (Aspergillus, Candida, Cephalosporium, Penicillium)

Fungal Endophthalmitis

Accounts for ~7% of microbial endophthalmitis. Primary organisms: Candida, Aspergillus, Coccidioides. Access via traumatic introduction or hematogenous spread. Multiple abscesses suggest fungal; a solitary abscess is more likely bacterial.

Goldman-Cecil, p. 571
Wills Eye Manual, pp. 996-1001

Clinical Features

Symptoms

Sudden onset of decreased vision (the initial symptom)
Ocular pain (follows)
Floaters; red eye in advanced cases

Signs

Critical:

Hypopyon (highly characteristic)
Severe anterior chamber reaction - fibrin, cells
Vitreous cells and haze - impaired red reflex
White milky bleb (in bleb-related cases)

Other:

Eyelid edema, corneal edema
Intense conjunctival injection, chemosis (highly variable)
Severe anterior uveitis

Slit-lamp biomicroscopy is required to visualize aqueous and vitreous cells.

C. acnes: presents insidiously with recurrent granulomatous anterior uveitis, a white capsular plaque, and minimal injection - easily missed.

Wills Eye Manual, pp. 4893-4896
Goldman-Cecil, p. 451

Differential Diagnosis

Condition	Distinguishing Feature
Toxic anterior segment syndrome (TASS)	Onset 6-24h after surgery; diffuse corneal edema; responds to topical steroids
Sterile endophthalmitis	After intravitreal triamcinolone or anti-VEGF injection; no organisms
Lens-particle uveitis	Retained lens fragment in vitreous/angle
Acute noninfectious uveitis flare	History of prior uveitis; HLA-B27
IOL-induced uveitis	Iris transillumination, IOL decentration

Wills Eye Manual, pp. 4920-4928

Diagnosis

Slit-lamp examination and dilated fundoscopy - establish severity, check red reflex
B-scan ultrasound - if posterior segment not visible; confirms vitritis, membrane formation, excludes retinal detachment before vitreous tap
Vitreous tap (preferred) - more likely to yield positive culture than aqueous tap
- 0.2-0.4 mL from mid-vitreous cavity via 23-gauge needle or disposable vitrector
Aqueous tap - 0.1-0.2 mL via limbal paracentesis if vitreous cannot be obtained
Microbiology: Gram stain, Giemsa stain, methenamine-silver stain; cultures on blood agar, chocolate agar, Sabouraud (fungal), thioglycolate (anaerobic), solid anaerobic medium
- C. acnes requires anaerobic culture held for 14 days
PCR - useful for unusual organisms or culture-negative cases (high sensitivity; beware false positives)
Conjunctival swabs - additional, supplementary

Kanski, pp. 7378-7401
Wills Eye Manual, p. 4939

Treatment

Prevention

Preoperative 5% povidone-iodine to conjunctiva (proven to reduce risk)
Intracameral antibiotics at end of cataract surgery (proven benefit)
Perioperative topical broad-spectrum antibiotics reduce bacterial load but have not been proven to lower endophthalmitis rates and may promote resistance

Intravitreal Antibiotics (cornerstone of treatment)

Achieve and maintain levels above the MIC of most pathogens for days. Administer immediately after obtaining cultures.

Drug	Dose	Coverage
Vancomycin	1-2 mg/0.1 mL	Gram-positives including MRSA
Ceftazidime	2-2.25 mg/0.1 mL	Gram-negatives including Pseudomonas
Amikacin	0.4 mg/0.1 mL	Alternative to ceftazidime (penicillin allergy) - higher risk of retinal infarction
Dexamethasone	0.4 mg/0.1 mL	Adjunct for severe vitreous inflammation (select cases)

Regimen is refined based on culture results, sensitivity, and clinical course.

Kanski, pp. 7406-7408
Wills Eye Manual, p. 4946
Goldman-Cecil, p. 458

Role of Vitrectomy - the Endophthalmitis Vitrectomy Study (EVS)

The landmark EVS demonstrated:

Immediate pars plana vitrectomy (PPV) is beneficial when presenting VA is light perception (not hand movements) in postcataract endophthalmitis
For VA of hand movements or better, vitreous aspiration (tap) alone is acceptable initially
For other causes (bleb-related, trauma, endogenous), vitrectomy may benefit select cases; the EVS did not study these
Kanski, p. 7467

Additional Treatments

Topical:

Intensive topical steroids: prednisolone acetate 1% q1h (for anterior inflammation)
Fortified topical antibiotics (vancomycin + tobramycin q1h) for bleb leaks or wound dehiscence

Systemic:

Oral fluoroquinolones (moxifloxacin 400 mg daily for 10-14 days) - penetrate vitreous; recommended especially for bleb-related endophthalmitis or trauma
Oral steroids (prednisolone 1 mg/kg/day) - consider 12-24h after antibiotic initiation once fungal infection excluded; gastroprotection required
IV antibiotics not routinely indicated

Cycloplegia: Atropine 1% b.i.d.-t.i.d.

Subconjunctival antibiotics: Vancomycin 50 mg + ceftazidime 125 mg - of doubtful additional benefit once intravitreal antibiotics given.

Kanski, pp. 7414-7421
Wills Eye Manual, pp. 4944-4964

Bleb-Related (Fistula) Endophthalmitis

Treat aggressively:

Immediate vitreous and aqueous sampling
Intravitreal ceftazidime 2 mg + vancomycin 2 mg
Repeat intravitreal antibiotics at 48 hours; consider PPV
Topical steroids after 48 hours
Oral fluoroquinolones 10-14 days

Kanski, pp. 3655-3673

Chronic/Subacute Endophthalmitis (C. acnes)

Treat initially as acute postoperative (no steroids)
Immediate PPV beneficial if VA is light perception
IOL and capsular remnant removal may be required for diagnosis and treatment
Sensitive to intravitreal penicillin, cefoxitin, clindamycin, or vancomycin

Wills Eye Manual, pp. 5039-5053

Fungal Endophthalmitis Treatment

Localized abscesses: systemic antifungals - fluconazole 100-200 mg daily for 2 months
Vitreous involvement: vitrectomy + intravitreal antifungals
- Intravitreal amphotericin B: 5-10 μg/0.1 mL
- Intravitreal voriconazole: 100 μg/0.1 mL
Candida endophthalmitis with IOL: IOL removal + vitrectomy + local amphotericin B + systemic fluconazole or voriconazole
Hematogenous Candida: IV polyene + flucytosine (25 mg/kg q.i.d.) when lesions threaten the macula
Goldman-Cecil, p. 571; Wills Eye Manual, p. 5047; Harrison's, p. 789

Follow-Up

Monitor q12-24h initially
Relief of pain is a useful early sign of response
After 48 hours: expect improvement - decreased pain, inflammation, and hypopyon
If no improvement: re-inject intravitreal antibiotics; consider PPV if deteriorating
Oral steroids (prednisone 60 mg/day x 5 days) were part of EVS protocol; use depends on organism, comorbidities, and severity
Antibiotic regimen refined as culture results return

Prognosis

Virulence of organism is the most important prognostic factor
S. epidermidis: relatively favorable; Streptococcus and Gram-negatives: poor
Bleb-related endophthalmitis carries a significantly worse prognosis than postcataract surgery (more virulent organisms; may result in blindness or enucleation)
Traumatic endophthalmitis with Bacillus cereus: particularly destructive course

Recent Evidence (2024-2026)

Two recent meta-analyses (PMIDs 40154909 and 39922542) compare chlorhexidine vs. povidone-iodine for antisepsis before intravitreal injections - these are directly relevant to endophthalmitis prevention in the intravitreal injection era. A 2026 network meta-analysis (PMID 41043517) examines prefilled syringes and post-intravitreal injection endophthalmitis rates.

Sources: Kanski's Clinical Ophthalmology 10th Ed. | Wills Eye Manual | Goldman-Cecil Medicine | Harrison's Principles of Internal Medicine 22E | Tintinalli's Emergency Medicine

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