Panophthalmitis - Ophthalmology Residency Viva: Case Presentation Q&A

SECTION 1: Definition and Classification

1. Exogenous - organism enters from outside the body:
   • Penetrating globe trauma (most common; especially organic matter, wood, soil-contaminated metal)
   • Post-operative (cataract surgery, glaucoma filtering surgery - bleb-associated, intravitreal injections)
   • Corneal ulcer with perforation
   • Descemetocele rupture
2. Endogenous (metastatic) - hematogenous seeding from a distant focus:
   • Infective endocarditis (vegetations on heart valves)
   • IV drug use (Candida, gram-negatives)
   • Liver abscess (Klebsiella pneumoniae - especially in diabetics from Southeast Asia)
   • Meningococcemia, pneumococcemia
   • Immunocompromised states (HIV, transplant, chemotherapy)

SECTION 2: Etiology and Microbiology

• Post-traumatic: Staphylococcus aureus, Streptococcus spp., Bacillus cereus (soil/organic matter injury - notoriously virulent, can destroy eye in 24-48 hours), gram-negatives, anaerobes
• Post-operative: Staphylococcus epidermidis (CoNS - most common), S. aureus, Streptococcus spp.
• Bleb-associated: Streptococcus spp., Haemophilus influenzae, gram-negatives (more virulent than post-cataract organisms)
• Endogenous: Klebsiella pneumoniae (diabetics, liver abscess), Streptococcus pneumoniae, gram-negative rods

• Candida albicans - IV drug users, immunocompromised
• Aspergillus spp.
• Rhizopus - mucormycosis (diabetic ketoacidosis)

• Herpes simplex virus, Varicella zoster virus - herpetic panophthalmitis
• Dengue virus

SECTION 3: Pathogenesis

1. Organisms gain access to the eye (exogenous: via wound; endogenous: blood-ocular barrier breakdown)
2. Bacterial toxins + host inflammatory response destroy the blood-retinal barrier
3. Suppurative inflammation begins in vitreous/aqueous (endophthalmitis stage)
4. Infection extends through scleral emissaria (vessels/nerves) into episclera and orbit
5. Orbital involvement causes proptosis, ophthalmoplegia, periorbital edema
6. Without treatment: global architectural destruction, phthisis bulbi, or spread to cavernous sinus/meninges

SECTION 4: Clinical Features

• Recent penetrating trauma, ocular surgery, intravitreal injection, or systemic infection/sepsis
• Rapid progression over hours to days
• Diabetic, immunocompromised, or IV drug user history (for endogenous)

• P - Pain (severe, throbbing, disproportionate to examination findings)
• A - Absent/reduced vision
• N - Nausea/vomiting (from severe pain)
• O - Orbital signs (proptosis, restricted movements)
• P - Photophobia
• H - Headache
• T - Temperature (fever, malaise, systemic features)

• Eyelid edema and erythema
• Chemosis (severe conjunctival edema)
• Conjunctival injection
• Purulent discharge
• Corneal edema, corneal opacity
• Hypopyon (pus in anterior chamber)
• Anterior uveitis
• Perforated cornea (in advanced cases)

• Absent red reflex
• Vitritis (hazy vitreous)
• Retinal infiltrates, flame-shaped hemorrhages with white centers
• Retinal/subretinal/choroidal abscesses

• Proptosis
• Ophthalmoplegia (partial or complete - indicates orbital spread)
• Afferent pupillary defect (APD)
• Raised or reduced IOP

• Fever, leukocytosis
• Signs of sepsis in endogenous cases

SECTION 5: Investigations

• Vitreous tap + culture (most important) - vitreous biopsy has higher yield than aqueous tap
• Aqueous tap - additional sample
• B-scan ultrasonography - shows vitreous opacities (snowball opacities/echogenic vitreous), thickened posterior coats, choroidal effusions, retinal detachment, subretinal fluid; essential when fundus not visible
• OCT - retinal involvement, choroidal infiltrates (if media allows)
• Corneal scraping (if corneal ulcer present)

• CT orbit with thin cuts (1-3 mm) with and without contrast - extent of orbital involvement, subperiosteal abscess, foreign body localization, sinus disease, intracranial extension
• MRI orbit - superior soft tissue delineation, cavernous sinus assessment

• Blood cultures (minimum 2 sets) - before starting antibiotics
• CBC with differential (leukocytosis)
• Fasting blood glucose / HbA1c (diabetes)
• Transthoracic echocardiogram (TTE) - rule out infective endocarditis
• Liver function tests, liver ultrasound (if Klebsiella endogenous endophthalmitis suspected)
• HIV serology
• Urine culture, chest X-ray (identify primary source)
• Coagulation profile

SECTION 6: Management

• Hospital admission - panophthalmitis is a medical emergency
• IV access, blood cultures before antibiotics
• Urgent orbital imaging (CT)
• Vitreous + aqueous tap for smear and culture

• Vancomycin 1-2 mg/0.1 mL (gram-positive coverage)
• Ceftazidime 2 mg/0.1 mL (gram-negative coverage)
• Repeat at 48-72 hours if not improving; consider pars plana vitrectomy

• IV broad-spectrum: vancomycin + piperacillin-tazobactam OR carbapenem (meropenem) for severely ill
• Adjust based on culture sensitivities
• Duration typically 2-4 weeks for bacterial; longer for fungal

• Topical antibiotics (fortified: vancomycin 50 mg/mL, ceftazidime 50 mg/mL) hourly
• Cycloplegics (atropine 1%) - for pain and prevent posterior synechiae
• Topical steroids after 48 hours of antibiotics (controversial)
• Oral fluoroquinolones (excellent ocular penetration) for 10-14 days

• Intravitreal voriconazole (100 mcg/0.1 mL) OR amphotericin B (5-10 mcg/0.1 mL)
• IV voriconazole or amphotericin B systemically

• Indicated when: no improvement after 48-72 hours of intravitreal antibiotics, severe vitreous involvement, vision better than light perception (EVS trial for post-cataract endophthalmitis), trauma-associated endophthalmitis/panophthalmitis, fungal cases
• Advantage: removes the infected vitreous scaffold, allows direct antibiotic delivery, provides sample for culture, possible visual rehabilitation

• Panophthalmitis with no perception of light AND globe is intact
• Preferred over enucleation in active infection (lower risk of CNS spread through orbital tissues vs. cutting optic nerve)
• Allows fitting of orbital implant
• Contraindication: suspected intraocular malignancy (use enucleation then)

• When sclera is also destroyed or perforated
• Suspected intraocular tumor with panophthalmitis
• Failed evisceration
• Caution in panophthalmitis: cutting the optic nerve sheath may risk spread of infection to meninges and cavernous sinus

• Rare, severe cases with fungal panophthalmitis (mucormycosis) with extensive orbital invasion, particularly in diabetic ketoacidosis

SECTION 7: Complications and Prognosis

• Permanent vision loss (most common)
• Phthisis bulbi (shrunken, atrophic, non-functional globe - end-stage)
• Corneal scarring/perforation
• Retinal detachment
• Cyclitic membrane
• Hypotony
• Secondary glaucoma

• Subperiosteal abscess
• Orbital abscess

• Cavernous sinus thrombosis (high mortality)
• Meningitis
• Encephalitis
• Brain abscess
• Stroke (septic emboli)

• Septicemia
• Septic shock
• Death (rare with modern treatment but reported)

• Organism virulence (worst: Bacillus cereus, Streptococcus spp.; better: CoNS)
• Time to presentation and treatment (every hour matters)
• Route of infection (post-traumatic with soil > post-operative)
• Patient's immune status (immunocompromised fare worse)
• Extent of involvement at presentation
• Adequacy of initial treatment

SECTION 8: High-Yield Viva Points

• Immediate vitrectomy + intravitreal antibiotics was better than vitreous tap + intravitreal antibiotics ONLY in patients with light perception only (LP) - 3x better chance of achieving 20/40 vision
• In patients with hand motion (HM) or better vision, no significant difference between the two approaches
• Systemic antibiotics (IV amikacin + vancomycin) showed NO benefit over intravitreal alone
• Important: EVS excluded traumatic endophthalmitis/panophthalmitis - these are always managed aggressively with PPV

• Diagnosis: Post-operative panophthalmitis (extension beyond endophthalmitis to orbital involvement)
• Distinguish from endophthalmitis: proptosis and ophthalmoplegia confirm orbital spread = panophthalmitis

1. Admit as emergency
2. Blood cultures x2 stat
3. CT orbit (thin cuts, with/without contrast) - assess orbital extension, foreign body
4. Tap vitreous + aqueous simultaneously, send for Gram stain + culture
5. Intravitreal vancomycin 2 mg/0.1 mL + ceftazidime 2 mg/0.1 mL IMMEDIATELY
6. IV vancomycin + piperacillin-tazobactam
7. Topical fortified antibiotics hourly + cycloplegics
8. If no improvement in 48-72 hours: PPV
9. If no light perception + failed medical management: evisceration
10. Infectious disease consult

• Diagnosis: Endogenous panophthalmitis/endophthalmitis secondary to Klebsiella pneumoniae bacteremia (classic scenario in Asian diabetic patients with liver abscess)
• This syndrome is called Klebsiella liver abscess-associated endophthalmitis and is particularly common in Taiwan/Southeast Asia

1. Admit for systemic infection control
2. Blood cultures
3. CT abdomen (confirm liver abscess), CT orbit
4. Echo (rule out endocarditis)
5. Vitreous tap + intravitreal antibiotics (ceftazidime covers Klebsiella well)
6. IV third-generation cephalosporin (ceftriaxone) OR carbapenem
7. Drainage of liver abscess (IR-guided)
8. PPV if no improvement
9. Prognosis is poor - most endogenous Klebsiella endophthalmitis results in loss of vision

• Intravitreal dexamethasone (400 mcg/0.1 mL) - used by some alongside intravitreal antibiotics to reduce inflammatory damage, but not universally recommended
• Topical steroids - started AFTER 48 hours of confirmed antibiotic response, not initially (risk of worsening infection)
• Systemic steroids - generally avoided in active panophthalmitis due to immunosuppression risk
• Rationale for use: The inflammatory response itself (not just the organism) causes significant retinal damage; modulating it may preserve some visual function
• EVS trial did not include intravitreal steroids in its protocol

• Almost exclusively post-traumatic (soil, vegetation, organic material)
• Onset within 12-24 hours of injury
• Characterized by: ring corneal abscess (pathognomonic), rapid corneal perforation, severe hypopyon, total loss of vision often within 24-48 hours
• Produces potent toxins: metalloprotease, phospholipase C, cereulide - direct tissue destruction beyond inflammation
• Despite aggressive treatment, most eyes are lost
• Key management point: Aggressive PPV + intravitreal antibiotics as EMERGENCY, do not wait

• Shows: echogenic vitreous (vitritis), vitreous membranes, snowball opacities (fungal)
• Retinal detachment (flat or funnel-shaped)
• Choroidal thickening, choroidal detachment
• Subretinal/subchoroidal collections
• Posterior coats thickening (>2mm is significant for posterior scleritis/panophthalmitis)
• Can help plan vitrectomy approach
• Serial B-scans guide response to treatment

• Diabetes mellitus (most common - Klebsiella, Candida, mucor)
• IV drug use (Candida, Bacillus, gram-negatives)
• Infective endocarditis (bacterial seeding)
• HIV/AIDS (Candida, CMV, Aspergillus)
• Immunosuppression (transplant, chemotherapy, biologics)
• Neonates (group B Streptococcus, gram-negatives)
• Chronic liver disease / liver abscess (Klebsiella pneumoniae)
• Post-sepsis / bacteremia from any source
• Indwelling IV catheters / TPN (Candida)

Quick-Reference Summary Card

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p.1216 - definition and pathology of endophthalmitis vs panophthalmitis
• Kanski's Clinical Ophthalmology, 10th ed. - intravitreal antibiotic protocols
• Wills Eye Manual - clinical signs and differential diagnosis
• EyeWiki - Panophthalmitis - comprehensive clinical reference
• Tintinalli's Emergency Medicine - orbital complications