Corneal Ulcer: Causes and Treatment

A corneal ulcer is an epithelial defect with inflammatory infiltrate and necrosis of the corneal stroma, most often occurring as a complication of infectious keratitis. It is an emergency: a delay in treatment of even 24-48 hours increases the risk of perforation and irreversible vision loss. The most common causes are bacteria in contact lens wearers, fungi after injury from plant material, Acanthamoeba when lenses come into contact with water, and the herpes simplex virus. [1]

The disease burden is significant worldwide: infectious keratitis is among the leading causes of cortical blindness and persistent corneal opacities. In developed countries, bacterial ulcers, often associated with contact lenses, predominate, while in countries with hot climates and agricultural work, the proportion of fungal ulcers is higher. Early diagnosis with microbiological verification and aggressive topical therapy determine the prognosis. [2]

The key clinical sign is a painful, unilateral, red palpebral fissure with photophobia, lacrimation, decreased vision, and a focal infiltrate with an epithelial defect visible with fluorescein staining. Pus in the anterior chamber, or hypopyon, indicates a pronounced inflammatory reaction and the severity of the process. Any patient with these symptoms should be examined by an ophthalmologist within a few hours. [3]

Without treatment, the ulcer can progress to decemethocele and perforation, leading to endophthalmitis. Even with infection control, scarring and irregular astigmatism often develop, requiring optical rehabilitation, including keratoplasty. [4]

Code according to ICD 10 and ICD 11

In the International Classification of Diseases, Tenth Revision, the code for corneal ulcer is H16.0. National clinical versions may use additional sub-items reflecting the location, presence of hypopyon, and perforation, but the basic code remains H16.0. [5]

In the International Classification of Diseases, Eleventh Revision, corneal ulcer is classified under the "Corneal Disorders" section with the code 9A76 "Corneal Ulcer." The description emphasizes infectious causes and lists inclusions such as central ulcer, annular ulcer, hypopyon ulcer, marginal ulcer, Mooren's ulcer, and perforated ulcer. [6]

Table 1. ICD codes

Classifier	Code	Name
ICD-10	H16.0	Corneal ulcer
ICD-11	9A76	Corneal ulcer
ICD-10 clinical clarifications	H16.01, H16.02, H16.03, H16.04, H16.06, H16.07	Central ulcer, annular ulcer, ulcer with hypopyon, and other clarifications in clinical versions
[7]

Epidemiology

The global incidence of infectious keratitis leading to ulceration varies from 2.5 to 799 cases per 100,000 people per year, depending on the region and risk factors. In high-income countries, rates are typically 11–35 per 100,000, while in tropical rural areas, rates are significantly higher. [8]

In the United States, estimates of 11.0–27.6 cases per 100,000 people per year are traditionally given, with contact lens wearers at particularly high risk. In British cohort data, the rate was approximately 34.7 per 100,000, highlighting the persistent burden of disease even with good access to health care. [9]

Contact lenses are responsible for 52-65% of new cases of microbial keratitis; the risk is approximately 80 times higher in contact lens wearers compared to non-wearers. Overnight lens wear, poor hygiene, contact with water, and storing lenses in water are significant contributors. [10]

In clinics in Europe and North America, bacterial ulcers predominate, whereas in South and Southeast Asia, fungal etiology is frequently identified in patients with plant injury. These differences should be considered when choosing empirical therapy. [11]

Table 2. Epidemiological landmarks

Indicator	Meaning
Global incidence	2.5-799 per 100,000 per year
Developed countries	11-35 per 100,000 per year
UK, Nottingham	34.7 per 100,000 per year
Proportion of cases associated with contact lenses	52-65%
Relative risk in contact lens wearers	about 80 times higher
[12]

Reasons

Bacterial corneal ulcers are most often associated with gram-negative rods in contact lens wearers and gram-positive cocci in blepharitis and ocular surface disorders. Microtrauma to the epithelium and hypoxia during overnight lens wear can stimulate bacterial colonization. [13]

Fungal corneal ulcers are common after injury from plant material and in hot climates. Fungal threads penetrate the stroma, forming "feathered" edges of the infiltrate; ulcers caused by Fusarium species are particularly severe. This determines the preference for natamycin as a first-line therapy. [14]

Acanthamoeba ulcers are often associated with contact between lenses and water, the use of tap water to rinse the lens case, and bathing with the lenses in. Clinically, they are characterized by severe pain out of proportion to the modest findings, perineural infiltrates, and annular infiltration in the later stages. [15]

Herpes simplex virus causes dendritic ulcers with branching lines of staining and terminal "nodules." Treatment with antiviral drugs is effective for the epithelial form, while the stromal form requires a combination of antiviral drugs and cautious use of corticosteroids. [16]

Table 3. Etiology, clinical clues, and initial therapy

Etiology	Frequent tips	Empirical initiation of treatment
Bacterial	Contact lenses, central infiltrate, hypopyon	Topical fluoroquinolone with high frequency for small peripheral ulcers; enhanced antibiotics for large or central ulcers
Fungal	Trauma by plant material, “feathered” edges of the infiltrate	Natamycin 5% topical as first line for filamentous fungi
Acanthamoeba	Contact of lenses with water, severe pain, perineural infiltrates	Polyhexamethylene biguanide 0.02% or chlorhexidine 0.02-0.06% plus diamidines
Herpes simplex virus	Dendritic ulcers, terminal "tubercles"	Ganciclovir 0.15% gel as per regimen, avoid steroids in epithelial form
[17]

Risk factors

The main modifiable risk factor is contact lens use, particularly overnight wear, contact with water, and improper cleaning and storage. Most adolescents and adults engage in at least one risky habit that increases the risk of infection. [18]

Traumatic factors include microdamage to the epithelium, most often during agricultural work and contact with plant material. The use of protective eyewear significantly reduces the risk of injury and subsequent infectious keratitis. [19]

Important ocular surface diseases include dry eye syndrome, blepharitis, lagofalmos, and neurotrophic keratitis. Systemic factors include diabetes mellitus, immunodeficiency, and the use of topical corticosteroids without anti-infective coverage. [20]

After keratorefractive surgery and corneal transplantation, the risk of ulceration increases due to impaired innervation, dryness and suture complications, which requires increased follow-up. [21]

Table 4. Risk factors and risk mitigation measures

Risk factor	How to reduce the risk
Contact lenses and overnight wear	Maintain hygiene, do not sleep in lenses, and avoid contact with water.
Injury by plant material	Use safety glasses, contact with any erosion
Dry eye, blepharitis	Treatment of eyelid inflammation, regular artificial tear therapy
Immunodeficiency and corticosteroids	Monitor the underlying condition, do not use steroids without anti-infective protection
[22]

Pathogenesis

Damage to the epithelium allows microorganisms to adhere to the corneal surface and penetrate the stroma. In response, innate immunity and an inflammatory cascade are activated, releasing cytokines and proteases, which exacerbates tissue damage. An imbalance between antimicrobial defense and proteolysis leads to "melting" of the stroma. [23]

In bacterial infections, toxic factors and matrix metalloproteinases destroy collagen lamellae, creating a deep defect. Gram-negative bacteria in contact lens wearers produce enzymes and biofilms that hinder eradication. [24]

Fungal threads grow into the stroma and along the nerve sheaths, causing perineural spread and slow clinical progression. This explains the more protracted course and poorer response to therapy compared to bacterial ulcers. [25]

Acanthamoeba, in the form of trophozoites and cysts, are resistant to many drugs; inflammation is maintained by proteases and the host immune response. Late diagnosis correlates with a worse prognosis and a high rate of keratoplasty. [26]

Symptoms and signs

Typical complaints include sharp pain, redness, lacrimation, photophobia, a foreign body sensation, and blurred vision. When using contact lenses, a rapid increase in symptoms is often observed, especially with overnight wear. [27]

Slit-lamp examination reveals a stromal infiltrate, an epithelial defect with fluorescein staining, corneal edema, precipitates, and possible hypopyon. An aqueous humor filtration test, also known as the Seidel test, is performed if perforation is suspected. [28]

Clinical clues to etiology: feathered edges and stromal confusion in fungal ulcers, ring infiltration and perineural tracts in acanthamoeba ulcers, dendritic form with terminal thickenings in epithelial herpetic ulcers. [29]

Systemic symptoms are rare, but in immunocompromised patients with plant material injury, the general response and possible endophthalmitis requiring surgical intervention should be assessed with caution.[30]

Table 5. Red flags for corneal ulcers

Sign	Clinical significance
Rapidly progressing pain and decreased vision	An aggressive bacterial infection is likely
Hypopyon	Severe inflammation of the anterior chamber
Annular infiltrate or severe pain with a modest picture	Acanthamoeba suspected
"Feathered" edges of the infiltrate	There is a high probability of fungal etiology
[31]

Classification, forms and stages

Based on etiology, ulcers are classified as infectious, caused by bacteria, fungi, acanthamoeba, and the herpes simplex virus, and non-infectious ulcers, such as marginal sterile infiltrates and Mooren's ulcer. Etiological verification determines the choice of therapy and prognosis. [32]

Based on location, a distinction is made between central ulcers in the optical zone and peripheral ulcers; central defects carry a greater risk of persistent visual acuity loss. Based on depth, a distinction is made between superficial defects, deep ulcers, decemethocele, and perforation. [33]

Clinical assessments of infiltrate size, depth, presence of hypopyon, and pain are used to determine severity, helping to plan drug dosage and monitoring frequency. Severe ulcers require enhanced antibiotics and daily monitoring. [34]

Ulcers after surgical interventions and against the background of neurotrophic keratitis are singled out separately: these conditions tend to heal slowly and require protective and regenerative technologies, for example, amniotic membrane. [35]

Table 6. Corneal ulcer severity assessment

Sign	Light	Moderate	Heavy
Infiltrate size	less than 2 mm	2-5 mm	more than 5 mm or multiple foci
Localization	peripheral	paracentral	central
Depth	superficial	up to half of the stroma	deep, decemetocele
Reaction in the chamber	No	cells and fla	hypopyon
[36]

Complications and consequences

Late complications include persistent opacities and irregular astigmatism, leading to decreased visual acuity and image distortion. In some cases, keratoplasty is required to restore corneal transparency and shape. [37]

Corneal perforation is accompanied by fluid leakage, pain, and the risk of endophthalmitis. Small perforations are closed with tissue adhesive and a bandage lens, while large defects and corneal melting require emergency keratoplasty. [38]

Secondary glaucoma, cataracts after long-term corticosteroid use, synechiae and chronic inflammatory response are common complications of severe and long-standing ulcers, requiring multidisciplinary management. [39]

A poor prognosis is associated with late initiation of therapy, central location, large surface area, and fungal or acanthamoeba etiology. These factors should be considered when informing the patient of risks and planning follow-up. [40]

When to see a doctor

An immediate consultation with an ophthalmologist is indicated in the event of severe eye pain, redness, photophobia, sudden decrease in vision, or the appearance of a whitish spot on the cornea. Contact lens wearers should remove the lens immediately and not reinsert it until an examination. [41]

Danger signs requiring urgent examination within hours: hypopyon, marked decrease in vision, inability to open the eye due to pain, signs of perforation, injury by plant material and the presence of systemic immunodeficiency. [42]

Prior to the visit, local anesthetics and corticosteroids should not be used without a doctor's prescription. Do not tape the eye or rinse it with tap water. Cycloplegics are permitted for pain relief as prescribed by a doctor. [43]

Patients with plant material trauma and contact lens wearers exposed to water are particularly vulnerable and should seek medical attention even with moderate symptoms, as fungal and acanthamoeba ulcers are insidious and may be diagnosed late. [44]

Diagnostics

The first step is to collect an anamnesis: contact lens type and wear schedule, water exposure, trauma, corticosteroid use, concomitant ocular surface diseases, and immune status. A full ophthalmological examination with a slit lamp is then performed. [45]

The second step is a fluorescein test to map the epithelial defect and a Seidel test if perforation is suspected. The size of the infiltrate and the depth of the lesion are measured, and the reaction in the anterior chamber and the presence of hypopyon are recorded. [46]

The third step is microbiological verification: scraping from the edge and bottom of the ulcer for staining with Gram, Giemsa, potassium alkali with fluorescent dye if fungal flora is suspected, sowing on appropriate media, and in case of acanthamoeba - sowing on agar without nutrients with Escherichia coli. The sensitivity of stains, according to literary data, reaches 60-75% for bacterial and 35-90% for fungal etiology. [47]

The fourth step involves additional methods: confocal microscopy to detect double-contour Acanthamoeba cysts, polymerase chain reaction in atypical cases, and anterior segment optical coherence tomography to assess depth. Indications for culture are increased in the presence of central, large, deep ulcers, hypopyon, and immunodeficiency. [48]

Table 7. Diagnostic tests and what they show

Test	What does it show?	When especially needed
Gram stain	Rapid preliminary identification of bacteria	Any suspicious ulcer before starting therapy
Staining with potassium alkali and fluorescent dye	Threads of mushrooms	Plant injury, tropics
Confocal microscopy	Acanthamoeba cysts	Severe pain with poor contact of lenses with water
Crops	Etiology and susceptibility	Central, large, deep ulcers, hypopyon
Polymerase chain reaction	Atypical and mixed infections	Refractory course, preoperative assessment
[49]

Differential diagnosis

Corneal erosion without infection typically heals rapidly with the use of lubricants and prophylactic antibiotics, without stromal infiltrate. The appearance of infiltrate and pain disproportionate to the surface requires ruling out infection and Acanthamoeba. [50]

Marginal sterile infiltration associated with staphylococcal blepharitis has a peripheral location and a small epithelial defect. Treatment is aimed at controlling eyelid inflammation and degranulating the immune response. [51]

Neurotrophic ulcers and exposure keratopathy are characterized by low corneal sensitivity and "sluggish" epithelialization, often without pain. Here, the emphasis is on protective and regenerative approaches rather than antibacterial escalation. [52]

Mooren's ulcer and peripheral ulcerative keratitis in systemic vasculitis mimic an infectious process but have an autoimmune basis. Cultures and biomicroscopic examination are crucial, and treatment includes immunosuppression. [53]

Table 8. How an infectious ulcer differs from a sterile one

Sign	Infectious ulcer	Sterile infiltrate
Pain	Expressed	Moderate
Epithelial defect	Significant	Small or none
Reaction in the chamber	Often there is	Usually no
Microbiology	Often positive	Negative
[54]

Treatment

The first principle is immediate initiation of empirical therapy with a high instillation frequency and subsequent de-escalation based on microbiological results. Small peripheral ulcers in low-risk patients often respond to monotherapy with a fluoroquinolone; large or central ulcers require enhanced antibiotics. [55]

For severe bacterial ulcers, enhanced antibiotics are prescribed: tobramycin 14 mg per milliliter alternately with cefazolin 50 mg per milliliter, or vancomycin 25-50 mg per milliliter if resistant gram-positive cocci are suspected; hourly instillations with a loading phase in the first 30-60 minutes. Therapy is then titrated based on the clinical response. [56]

For small peripheral ulcers, treatment may begin with fourth-generation fluoroquinolones, such as moxifloxacin or gatifloxacin, with high instillation frequency and mandatory early monitoring. Failure to improve within 24–48 hours requires escalation and re-diagnosis. [57]

Cycloplegics, such as pupil dilators, are indicated for pain relief and prevention of posterior adhesions. Dressings and bandage lenses are contraindicated during active infection, except for the use of tissue adhesive for minor perforations.[58]

The use of corticosteroids for bacterial ulcers is considered after 48-72 hours of adequate antimicrobial therapy and when there are signs of infection control, as early administration may worsen outcomes. The decision is made by an ophthalmologist based on clear antibacterial protection. [59]

Fungal corneal ulcers are treated with natamycin 5% as the drug of choice for filamentous fungi; in randomized trials, natamycin demonstrated better clinical and microbiological outcomes and a lower need for keratoplasty compared with voriconazole. For yeast infections, amphotericin B 0.15% is used topically. [60]

Acanthamoeba ulcer requires a combination of biguanides, such as polyhexamethylene biguanide 0.02% or chlorhexidine 0.02-0.06%, with diamidines, such as propamidine, in an intensive regimen with a gradual reduction in frequency. Early diagnosis improves outcomes and reduces the need for therapeutic keratoplasty. [61]

Epithelial herpetic ulcers are treated with 0.15% ganciclovir gel as follows: 1 drop 5 times daily until epithelialization, then 1 drop 3 times daily for another 7 days; for the stromal form, corticosteroids are added under the cover of an antiviral drug. Topical steroids are contraindicated for the epithelial form without cover. [62]

Adjuvant approaches include oral doxycycline and ascorbic acid to reduce the risk of melting, amniotic membrane for surface protection and regeneration, tissue glue for small perforations, and temporary tarsorrhaphy for exposure. These methods increase the likelihood of eye salvage until reconstruction.[63]

Photobiological technologies are advancing: photoactivated chromophoric corneal cross-linking for keratitis and photodynamic therapy with rose bengal are being studied as adjuncts to standard therapy, particularly for refractory bacterial and fungal ulcers. Data are mixed, but some series have observed a reduced need for keratoplasty and accelerated infection resolution. [64]

Table 9. Starting tactics depending on the situation

Situation	First line	Alternatives and additions
Minor peripheral bacterial ulcer	Fluoroquinolone topical with high frequency	Escalation to stronger antibiotics if there is no response
Large central bacterial ulcer	Strengthened antibiotics alternately every hour	Hospitalization, corticosteroids later to control infection
Fungal ulcer	Natamycin 5%	Amphotericin B 0.15%; surgery for perforation
Acanthamoeba ulcer	Polyhexamethylene biguanide 0.02% or chlorhexidine 0.02-0.06% plus diamidines	Adjuvant technologies, keratoplasty in case of ineffectiveness
Herpetic epithelial ulcer	Ganciclovir 0.15% according to the scheme	Oral acyclovir for intolerance to local therapy
[65]

Table 10. Common mistakes and how to avoid them

Error	Consequence	How to avoid
Delay in initiation of local therapy	Progression to perforation	Initiate empirical treatment immediately, then de-escalate
Early corticosteroids without infection control	Ulcer aggravation	Consider only after response to anti-infective therapy
Contact of lenses with water during treatment	Superinfection	Strict hygiene rules and avoiding contact lenses until complete recovery
Lack of microbiology in severe ulcers	Incorrect therapy	Perform scraping, cultures, additional methods
[66]

Prevention

Contact lens wearers should practice good hand hygiene, avoid sleeping in lenses unless specifically intended, never use water to rinse, and avoid swimming with lenses. The lens case should be cleaned with solution and changed at least every 3 months. [67]

Avoid storing lenses in water, as the risk of infection increases dramatically due to contamination with waterborne microorganisms and Acanthamoeba. If any signs of irritation occur, remove the lens immediately and consult an ophthalmologist. [68]

Agricultural workers and people prone to eye injuries should wear protective eyewear. Any erosion requiring fluorescein staining should be treated and monitored to prevent secondary infection. [69]

Control of eyelid inflammation, treatment of dry eye, careful use of corticosteroids, and regular preventive examinations in contact lens wearers reduce the risk of primary ulceration and recurrence.[70]

Table 11. Rules for “healthy habits” for contact lenses

Rule	Brief explanation
Wash and dry your hands before handling	Reducing microbial load
Do not sleep in lenses unless prescribed.	Reduction of hypoxia and biofilms
Avoid contact with water	Acanthamoeba prevention
Change the container regularly	Minimizing biofilms
Remove lenses if you feel discomfort.	Seek medical attention in a timely manner
[71]

Forecast

The prognosis is determined by the size and location of the defect, the time to treatment, and the etiology. Central ulcers greater than 3-5 mm in diameter and deep defects with hypopyon have an increased risk of scarring and vision loss. [72]

Fungal and acanthamoeba ulcers heal more slowly and require longer treatment, often leading to the need for keratoplasty. Early diagnosis and targeted treatment improve the chances of preserving corneal transparency. [73]

With bacterial ulcers treated early and treated according to modern guidelines, the likelihood of complete infection resolution is high, and the risk of perforation is low. Regular monitoring and appropriate de-escalation of therapy reduce toxicity and accelerate epithelialization. [74]

Post-healing visual rehabilitation includes the selection of glasses and hard contact lenses, and in the case of opacities in the optical zone, consideration of keratoplasty with an assessment of the risk of recurrence of infection. [75]

Questions and Answers

Is it possible to treat the condition with home remedies and over-the-counter drops?
No. Self-medication delays the initiation of adequate therapy and increases the risk of perforation and vision loss. Immediate consultation with an ophthalmologist is required. [76]

When can I wear contact lenses again?
Only after complete epithelialization, the infiltrate has disappeared, and the inflammation has resolved, according to my doctor's conclusion. Strict hygiene rules must be observed and the lens case must be replaced. [77]

Are corticosteroids necessary for corneal ulcers?
Corticosteroids should only be used after the bacterial infection has been controlled and under the supervision of an ophthalmologist. They are contraindicated for epithelial herpetic ulcers without antiviral coverage. [78]

Do "new" light-based treatments help?
Photoactivated cross-linking (PACT) technologies for keratitis and photodynamic therapy with rose bengal are being considered as adjuncts in resistant cases. The evidence base is growing, but results are still mixed. [79]