Panophthalmitis is a rapidly progressive purulent infection in which inflammation spreads to all structures of the eye (choroid, retina, vitreous, aqueous humor, cornea, and sclera) as well as the periorbital tissues. The term originates from Latin “pan-” (all), “ophthalmo-” (eye), and “-itis” (inflammation). Simply put, it is endophthalmitis accompanied by orbital cellulitis.
Infection routes are broadly classified as exogenous and endogenous.
According to a 2018 report, among cases that progressed from endophthalmitis to panophthalmitis, the most common cause was ocular trauma (39.9%), followed by microbial keratitis (27.7%), endogenous causes (21.2%), and post-cataract surgery (9.1%). No racial or sex predilection has been reported. Over 80% of cases are unilateral, but in endogenous cases, the right eye is affected approximately twice as often as the left eye7). This is thought to be because blood flow from the right carotid artery to the right eye is more direct7).
If treatment is delayed, it can lead to devastating outcomes such as phthisis bulbi, permanent vision loss, as well as cavernous sinus thrombosis, meningitis, encephalitis, sepsis, and death.
Endophthalmitis is inflammation within the eye primarily involving the vitreous and aqueous humor. Panophthalmitis refers to a condition where inflammation extends beyond this to include the sclera and periorbital tissues. It is accompanied by eyelid edema, proptosis, and restricted eye movement, presenting with clinical features of orbital cellulitis, which distinguishes it from endophthalmitis.
Panophthalmitis progresses rapidly and presents with the following symptoms.
Intraocular Findings
Hypopyon and fibrin: Marked anterior chamber inflammation is observed, sometimes accompanied by hyphema7).
Corneal edema and opacity: Severe corneal edema makes it difficult to visualize the fundus.
Vitreous opacity: Dense diffuse vitreous opacity is observed, often assessable only by ultrasound6).
Retinal detachment and choroidal detachment: Detachment due to exudative changes is visualized on B-scan.
Orbital findings
Proptosis: An important sign indicating inflammation spreading into the orbit 1).
Restricted eye movement: Inflammatory swelling of the extraocular muscles causes partial to complete ophthalmoplegia.
Relative afferent pupillary defect: Indicates progression of optic neuropathy 7).
Conjunctival injection and chemosis: Severe ciliary injection and marked edema are observed.
Systemic findings include fever, leukocytosis, and elevated CRP. An increase in procalcitonin, a serum marker for severe bacterial infection, is also observed. In advanced cases, perforation of the cornea or sclera may occur.
Both present similar orbital signs, but panophthalmitis is distinguished by the presence of intraocular inflammation such as hypopyon and marked vitreous opacity. If CT or MRI images show scleral thickening, globe deformity, or intraocular abscess formation, panophthalmitis is suggested 6).
The causative microorganisms of panophthalmitis are diverse.
Bacteria:
Fungi:
Others:
In diabetes, the permeability of the blood-retinal barrier is increased, creating an environment where bacteria can easily reach the eye via the bloodstream7). Additionally, reduced immune function weakens the ability to fight infection, so once an infection occurs, it tends to progress rapidly.
The diagnosis of panophthalmitis is primarily based on clinical findings. A detailed medical history (history of eye surgery, trauma, systemic infection, drug use, and travel history) is important.
| Specimen | Test Method | Notes |
|---|---|---|
| Aqueous humor / Vitreous fluid | Smear / Culture / PCR | Essential for definitive diagnosis |
| Blood | Culture | Positive rate approximately 56% |
| Urine | Culture | Search for infection focus |
Differentiation from orbital cellulitis and scleritis is important. It may be misdiagnosed as acute angle-closure glaucoma.5) If it worsens under steroid treatment, suspect fungal infection.3).
Panophthalmitis is an ophthalmic emergency requiring rapid multidisciplinary management.
If the causative organism is unknown, broad-spectrum antibiotics should be started empirically.
Once the causative organism is identified, the drug is selected based on susceptibility testing. The treatment duration is approximately 3 weeks for uncomplicated bacteremia and 6–8 weeks when metastatic infection is present1).
There are reports that combined multiple intravitreal and periocular antibiotic injections with dexamethasone administration achieved eye preservation even in cases with no light perception and scleral abscess5). However, since many cases ultimately require enucleation or evisceration, early multidisciplinary collaboration and aggressive treatment initiation are important.
The main route of endogenous panophthalmitis is that microorganisms released from an infectious focus in the body reach the inside of the eye hematogenously through the short posterior ciliary arteries. There are about 20 short posterior ciliary arteries, which enter the eye near the optic nerve entrance and supply the choroid (up to the equator), ciliary processes, and the circle of Zinn-Haller.
When the blood-ocular barrier first breaks down, an infectious focus forms in the choroid. Subsequently, it progresses from choroidal lesions to retinal lesions and vitreous opacities, eventually spreading inflammation to the anterior chamber, sclera, and periorbital area, resulting in panophthalmitis. Bacterial endophthalmitis worsens rapidly within hours, so early-stage findings are rarely captured.
Microorganisms enter the eye through physical disruption of the blood-ocular barrier, such as surgical incisions, perforating wounds, or implants. Microbial toxins propagate the inflammatory response from the vitreous to the entire eye, leading to panophthalmitis. Bacillus cereus and Clostridium species produce potent exotoxins (lecithinase) that can cause rapid tissue necrosis within 48 hours of inoculation.
Clostridium septicum is a Gram-positive anaerobic bacterium that proliferates in environments with low redox potential 4). This condition does not occur in a healthy intestinal tract, but in the presence of colorectal cancer, necrotic tissue within the tumor provides a suitable environment for growth. Therefore, C. septicum infection is an important sign requiring investigation for gastrointestinal malignancies 4).
Diabetes is the most important underlying disease for endogenous endophthalmitis and panophthalmitis. Animal experiments have shown that a diabetic environment increases the permeability of the blood-retinal barrier and promotes the development of endogenous endophthalmitis 7). Hyperglycemia reduces neutrophil function, leading to delayed infection control. In reported cases, HbA1c levels are often markedly poor, ranging from 8.8% to 13.8% 1)3)5).
Panophthalmitis caused by multidrug-resistant and extensively drug-resistant (XDR) gram-negative bacteria is a serious challenge with limited treatment options.
Wang et al. (2023) reported a case of XDR Pseudomonas aeruginosa panophthalmitis due to contaminated artificial tears. This strain, carrying VIM-80 and GES-9 genes, was resistant to almost all antibiotics except piperacillin-tazobactam. The novel siderophore cephalosporin cefiderocol (1.5 g every 8 hours for 14 days) was used, resulting in improvement of orbital cellulitis2).
Cefiderocol utilizes iron to be actively taken up into bacterial cells like a “Trojan horse,” thereby evading resistance due to efflux pumps and porin channel mutations. Currently, it is FDA-approved only for complicated urinary tract infections, but data on intravitreal penetration are scarce, and further research is awaited2).
Chen et al. reported a case of endogenous bacterial panophthalmitis with loss of light perception and scleral abscess, in which enucleation and evisceration were avoided by multiple intravitreal and periocular antibiotic injections combined with dexamethasone5).
This method has not yet been validated by large-scale clinical trials and is not applicable to all cases, but it suggests the possibility of eye preservation through aggressive drug administration.
Azzopardi et al. (2022) reported a case of sterile endogenous panophthalmitis in a patient with diabetes. Blood culture, vitreous culture, and PCR were all negative, but marked inflammation and glycemic abnormalities were observed with CRP 181 mg/L and HbA1c 138 mmol/mol. PET-CT also did not identify any malignancy or infectious focus7).
Even in culture-negative panophthalmitis, it is difficult to completely rule out infection, and continued aggressive antimicrobial therapy is recommended7).
