| disease | Pseudomonas Aeruginosa Corneal Ulcer |
Pseudomonas corneal ulcer is a fulminant suppurative infection of the cornea caused by Pseudomonas aeruginosa. It was first reported by Sattler in 1981. The 1938 edition of Duke-Elder's Textbook of Ophthalmology documented only a few cases, while the 1965 edition of System of Ophthalmology cited approximately 100 cases. In China, apart from the 100 cases reported by Fan Dezhang and others in 1965, there have been numerous reports in recent years from Beijing, Guangzhou, Nanjing, Henan, and other regions. Both domestically and internationally, the incidence of this disease appears to be increasing. This trend may be attributed to the emergence of microbial substitution due to the development of chemotherapy, leading to a rise in Gram-negative bacterial infections.
bubble_chart Epidemiology
This disease is more common in summer and autumn, possibly related to bacterial living conditions and natural temperatures. Additionally, summer and autumn are busy farming seasons with increased outdoor activities, which also raises the chances of eye injuries. Gender is not a significant factor, though males are generally more affected.
Age: Cases occur across all age groups. In our observations, the youngest patient was 1 year old, and the oldest was 78. However, most reported cases involve young and middle-aged adults engaged in labor-intensive work. Pediatric patients often have underlying conditions such as nutritional deficiencies or corneal softening, while elderly patients may be prone due to unhealthy corneal epithelium, making them more susceptible to epithelial injuries.
Occupation: Workers, farmers, teachers, and students are all affected, but workers have the highest incidence, particularly those in machinery and steel factories. Occupations like lathe operators and fitters are at higher risk because these jobs often involve corneal foreign bodies, especially in summer when strong fans blow metal debris onto the corneal surface. Farmers rank second, as they frequently suffer from injuries caused by rice stalks, cotton stems, or grain splashes. Other occupational cases are also linked to eye injuries. Recently, there have been reports of the disease occurring after wearing hydrophilic silicone contact lenses. Thomas et al. (1980) reported 60 cases of Pseudomonas aeruginosa corneal ulcers, of which only 13 had a history of trauma, while 20 cases without trauma history occurred after wearing contact lenses (8 with rigid lenses and 12 with soft lenses).
bubble_chart EtiologyThis disease is caused by the direct invasion of Pseudomonas aeruginosa into the cornea, leading to infection. The bacterium is a small Gram-negative bacillus with low nutritional requirements. It is widely distributed in soil, sewage, and air in nature, and can also colonize the body surface or even the conjunctival sac. The optimal temperature for its reproduction is 30–37°C, and it can produce fluorescein and pyocyanin. It should be noted that Pseudomonas aeruginosa can be present in many types of eye drops, such as fluorescein, dicaine, cortisone, idoxuridine, or atropine solutions, all of which can become contaminated with Pseudomonas aeruginosa.
Pseudomonas aeruginosa has strong virulence but weak invasiveness. It can only infect corneal tissue by penetrating damaged epithelium. Therefore, any condition that compromises the health of the corneal epithelium—such as various forms of corneal trauma, keratitis, keratomalacia, radiation therapy for head and facial tumors, chemical burns, or exposure keratitis—can predispose to infection.
In addition to its high toxicity, Pseudomonas aeruginosa produces a proteolytic enzyme, and the ulcer itself generates collagenase. Both proteolytic enzymes and collagenase have collagenolytic effects on the corneal stroma. The activity of collagenase depends on the concentration of calcium ions, with higher activity at concentrations similar to serum calcium levels. Tears and aqueous humor continuously replenish calcium ions, making collagenase even more active. This leads to extensive and rapid dissolution and necrosis of corneal tissue, often resulting in early corneal perforation.
bubble_chart Clinical Manifestations
The incubation period of this disease is very short, generally half a day to one day, with cases below half a day or exceeding two days being rare. Patients typically complain of eye redness, swelling, pain, tearing, visual impairment, and increased discharge.
Ocular findings: In the early stages, corneal infiltrates can be observed, with varying locations, often occurring at sites of trauma or unhealthy cornea. The infiltrates are approximately 1 mm in diameter and appear grayish-white. Under slit-lamp examination, the corneal infiltrates are slightly elevated, with diffuse edema in the surrounding and deeper areas. Some cases may exhibit folds in the corneal endothelium and Descemet's membrane. Fine grayish-brown precipitates may appear behind the cornea. Tyndall's phenomenon is often positive.
Within 1–2 days of onset, the infiltrates rapidly form round, ring-shaped, or semicircular translucent, greasy, and grade I elevated grayish-white necrotic areas. The necrotic tissue is highly adhesive, clinging to the ulcer's periphery or the corneal surface. A small amount of light yellow hypopyon may appear in the anterior chamber, accompanied by severe eye pain, visual impairment, significant eyelid edema, and ciliary congestion. After 2–3 days, the ulcer rapidly expands toward the central area and deepens, eventually forming a necrotic zone 5–8 mm in diameter, leaving only a 1–2 mm wide transparent margin at the corneal periphery. Large amounts of grayish-white, viscous corneal necrotic tissue may adhere to the eyelashes, forming purulent discharge. Once the necrotic tissue sloughs off, the corneal surface becomes ground-glass-like, grayish-white, and slightly flattened. The anterior chamber may fill with a large amount of yellow pus, sometimes occupying the entire chamber.
bubble_chart Treatment Measures
The work focuses on protecting the normal cornea from injury, preventing the spread of ulcers, and eliminating sources of bacterial infection.
Those engaged in physical labor should take appropriate protective measures to prevent corneal trauma. All ophthalmic examination or treatment medications and instruments must be strictly sterilized, stored properly, replaced regularly, and protected from contamination, especially tools used for removing foreign bodies. For all mechanical, chemical, or physical corneal injuries, routine use of anti-Pseudomonas medications (commonly 0.5% streptomycin) is necessary to prevent infection. Cotton balls and dressings used for Pseudomonas patients should be specially handled or incinerated.
This disease is one of the most severe corneal ulcers with a poor prognosis. However, if an early diagnosis can be made and effective treatment is promptly administered, the impact on vision may not be significant. Our hospital has systematically observed over 100 cases of this disease. Among those who sought early medical attention and received a clear diagnosis, the ulcers healed with scars after undergoing the aforementioned treatment methods, typically with diameters not exceeding 1–2 mm and mostly confined to the superficial stroma. If the scar is not located in the pupillary area, it generally does not significantly affect vision. Even in some cases where the scar is located in the central cornea, vision can remain above 0.5. However, in cases where medical attention is sought at an advanced stage or treatment is inadequate, larger nebulas or leucomas often form. The diameter of these scars usually ranges from 3–8 mm, with dense scarring involving the entire thickness of the cornea. The tissue becomes thinner, approximately 1/3 to 3/4 of the normal corneal thickness, and the surface is flattened, sometimes accompanied by neovascularization, significantly impairing vision. If the leucoma exceeds 8 mm in diameter or is accompanied by anterior synechiae, vision may decrease to light perception or hand motion, and secondary glaucoma may occasionally develop, resulting in an even worse prognosis. If the ulcer has already perforated by the time of consultation, accompanied by extensive iris prolapse or secondary intraocular infection, enucleation or evisceration may be necessary.
In recent treatments, the application of polymyxin has enabled the control of infections. The following goals should be prioritized during treatment: ① Prevent the ulcer from expanding further. ② Prevent perforation of the ulcer. ③ Avoid complications of iridocyclitis, primarily the occurrence of posterior synechiae. Treatment should be tailored according to the specific conditions at each stage of the disease.
During the ulcer stage, bacteria proliferate rapidly, and the primary task is to eliminate or inhibit their activity. When clinical suspicion of the disease arises, emergency treatment should be initiated even before bacterial culture results are confirmed. Based on our experience, polymyxin is the most effective antibiotic, followed by gentamicin or streptomycin. Recently, there have been reports of using Chinese medicinals such as purpleflower holly leaf via intravenous drip for treatment. Sulfobenzylpenicillin (SB-PC) eye drops have also shown some efficacy. Some advocate using domestically produced gentamicin as the primary treatment combined with lamellar keratoplasty for Pseudomonas aeruginosa-induced corneal ulcers. For subconjunctival injections, the dosages are: polymyxin 170,000 units, gentamicin 20,000–40,000 units, or streptomycin 0.3–0.5 grams, administered once daily. Typically, 3–6 injections are sufficient to control the infection. Recently, we have adopted the method of instilling high-concentration antibiotics into the conjunctival sac with satisfactory results. The preferred drugs are polymyxin (50,000 units/mL) or 1% sulbenicillin solution, followed by gentamicin (8,000 units/mL) and 5% streptomycin.
**Administration method:** Initially, administer the medication every 5–10 minutes for the first four hours, then reduce to every half-hour. Once the ulcer begins healing, switch to hourly administration. Generally, infection can be controlled within 1–2 days of starting treatment. The ulcer typically heals in 10–15 days, with results comparable to subconjunctival injections. A 5–10% streptomycin solution also shows some efficacy. However, systemic intravenous drip or intramuscular injections have no significant effect. At this stage, the pupil must be dilated with atropine. Improvement is indicated by reduced pain and irritation, decreased discharge, localization of the corneal ulcer, shedding of necrotic tissue, a cleaner ulcer surface, and diminished hypopyon. Bacterial cultures may then turn negative.
From the point when bacterial cultures turn negative and the ulcer localizes until complete epithelial healing, the focus shifts to repair and recovery. The treatment aims to prevent Pseudomonas aeruginosa recurrence or secondary infections by other bacteria and to promote ulcer healing. In addition to continuing the aforementioned medications (with reduced frequency), 15–30% sulfacetamide sodium solution should be applied multiple times, along with appropriate ophthalmic ointments in the conjunctival sac, local hot compresses, pupil dilation, and oral vitamin supplements.
From the point of surface healing until complete scar formation, the focus is on stromal recovery. The goal of medication during this phase is to promote the absorption of residual stromal infiltrates and edema while minimizing scar formation. Topical corticosteroids may be added.
For cases where the ulcer fails to heal over time, significant hypopyon accumulates, perforation occurs, severe ocular pain persists, or vision is completely lost, palliative therapy should still be pursued whenever possible. Enucleation or evisceration should not be hastily performed. Pathological reports indicate that inflammation may sometimes be confined to the anterior segment, leaving the vitreous and retina intact. We believe that destructive surgeries like enucleation should only be considered in cases of panophthalmitis or when the corneal ulcer perforation exceeds 40%, inevitably leading to staphyloma formation. In recent years, for large perforated ulcers, we have attempted penetrating keratoplasty to salvage the eye, avoiding enucleation or corneal staphyloma. Postoperatively, some patients not only retained their eyeballs but also preserved light perception vision.
