Background

Corneal ulcer, also known as corneal keratitis, is a relatively common eye condition characterized by inflammation and open soreness on the surface of the cornea—the transparent, dome-shaped protective layer at the front of the eye. An infection, injury, or underlying disease typically causes it.

The cornea plays a crucial role in focusing light onto the retina, and any damage or infection to this structure can lead to vision problems and discomfort. Corneal ulcers can affect people of all ages. Still, they are more common in individuals who wear contact lenses, have compromised immune systems, or live in environments with poor hygiene or high levels of pollutants.

Certain common factors may contribute to the development of corneal ulcers:

• Infection: Bacterial, viral, fungal, or parasitic infections are a primary cause of corneal ulcers. Bacterial infections, most commonly caused by Staphylococcus aureus or Pseudomonas aeruginosa, are often associated with contact lens wear and poor lens hygiene.
• Eye trauma: Any injury to the cornea, such as scratches, cuts, or foreign objects entering the eye, can create an opening for bacteria to enter and cause an ulcer.
• Dry eyes: Insufficient tear production or poor tear quality can lead to dryness of the cornea, making it more susceptible to damage and infections.
• Immune system disorders: Certain conditions that weaken the immune system, such as diabetes, HIV/AIDS, or autoimmune diseases, can increase the risk of corneal ulcers.
• Eye conditions: Pre-existing eye conditions like blepharitis (inflammation of the eyelids), conjunctivitis (pink eye), or corneal dystrophies can make the cornea more vulnerable to ulceration.

The symptoms of corneal ulcers can vary but often include:

• Eye redness
• Eye pain or discomfort
• Blurred or decreased vision
• Sensitivity to light (photophobia)
• Excessive tearing
• Foreign body sensation/gritty feeling in the eye
• Pus or discharge from the eye

Epidemiology

• Keratitis, which precedes corneal ulceration, leads to nearly 1 million visits to clinics and also emergency departments in the American States each year.
• A retrospective research study conducted in California revealed that the greatest rate of the bacterial corneal ulcers, which was observed in females of age 25-34, with an incidence rate of 60.3/100,000 person-years.
• Mycotic keratitis, particularly in tropical and also in subtropical environments, may account for >50% of all cases of culture-proven microbial keratitis. In a research study which is conducted in Britain, the Mycotic keratitis incidence was 0.32 cases/million individuals for a year.
• Peripheral ulcerative keratitis (PUK), whether occurring as isolated condition or as a manifestation of a primary autoimmune disorder, which has an estimated annual incidence of 3 cases/million individuals.
• In developed countries, the estimated incidence of the ocular herpes infection is between 5-20 cases/10,000 individuals annually. HSV-1 is the primary causative agent in over 95% of these infections. Bilateral cases represent only 1.3%-12% of all cases, and they typically occur in younger individuals and tend to be more severe in nature.

Anatomy

Pathophysiology

The pathophysiology of corneal ulcers involves a complex interplay of various factors, including infectious agents, immune responses, and tissue damage. Here is an overview of the critical processes involved:

• Epithelial disruption: Corneal ulcers often begin with an injury or breach in the corneal epithelium, the cornea’s outermost layer. This disruption can result from trauma, foreign bodies, contact lens-related issues, or underlying eye conditions.
• Entry of pathogens: Once the epithelium is compromised, microorganisms such as bacteria, viruses, fungi, or parasites can enter the cornea. Bacterial infections are the most common etiology, mainly caused by Staphylococcus aureus or Pseudomonas aeruginosa. Viral infections, like herpes simplex virus (HSV) or varicella-zoster virus (VZV), can also cause corneal ulcers.
• Inflammatory response: Pathogens trigger an immune response in the cornea. Immune cells, such as neutrophils and macrophages, migrate to the site of infection to combat against the invading microorganisms. These immune cells release various inflammatory mediators, including cytokines and chemokines, leading to localized inflammation.
• Collagen degradation: Inflammatory mediators and enzymes released during the immune response can lead to collagen degradation in the cornea. Collagen, a significant component of the cornea, provides its structural integrity. Degradation of collagen weakens the cornea, making it susceptible to further damage and ulceration.
• Neovascularization: In response to inflammation and tissue damage, new blood vessels (neovessels) may grow into the cornea from the surrounding conjunctiva. Neovascularization can provide a route for immune cells and nutrients to reach the infected area but can also contribute to scarring and impaired vision.
• Corneal tissue destruction: Pathogens and the associated immune response can directly damage corneal tissue, forming an open sore or ulcer. The ulceration may extend deeper into the corneal layers, involving the stroma—the cornea’s middle layer—and potentially progressing to more severe complications, such as corneal perforation.
• Healing and scarring: The healing process of corneal ulcers involves migrating healthy epithelial cells to cover the ulcerated area. However, depending on the severity of the ulcer and the extent of tissue damage, scarring may occur during the healing process. Corneal scarring can impair vision and require further interventions to restore visual acuity.

Etiology

The etiology of corneal ulcers can be diverse, with various factors contributing to their development. The primary causes of corneal ulcers include:

• Infectious agents: Infections are a common cause of corneal ulcers. They can be bacterial, viral, fungal, or parasitic in nature. Bacterial infections, particularly those caused by Staphylococcus aureus or Pseudomonas aeruginosa, are commonly associated with corneal ulcers, especially in individuals who wear contact lenses and have poor lens hygiene. Viral infections, like herpes simplex virus (HSV) or varicella-zoster virus (VZV), can also lead to corneal ulcers, often associated with a history of recurrent ocular herpetic disease.
• Trauma: Physical trauma to the cornea can cause ulcers. This includes scratches, cuts, or puncture wounds from foreign objects entering the eye. Corneal abrasions resulting from contact lens wear or improper removal can also create a pathway for infection and ulceration.
• Dry eyes: Insufficient tear production or poor tear quality can lead to dryness of the cornea, making it more prone to damage and ulceration. Dry eye syndrome can arise from various factors, including aging, hormonal changes, certain medications, or underlying systemic conditions.
• Immune system disorders: The conditions that weaken the immune system can increase the risk of corneal ulcers. Examples include diabetes, HIV/AIDS, systemic autoimmune diseases (such as rheumatoid arthritis or lupus), or local autoimmune conditions like Mooren’s ulcer.
• Eye conditions: Pre-existing eye conditions can contribute to developing corneal ulcers. These may include chronic blepharitis (inflammation of the eyelids), recurrent corneal erosions, corneal dystrophies, or certain inflammatory conditions like vernal keratoconjunctivitis or ocular rosacea.
• Contact lens-related factors: Improper use and maintenance of contact lenses can lead to corneal ulcers. Factors such as poor hygiene, extended wear of lenses beyond recommended durations, using expired solutions, or wearing contact lenses while swimming or in contaminated environments can increase the risk of infection and ulceration.
• Environmental factors: Environmental conditions can also contribute to corneal ulcers. Exposure to high levels of pollutants, dust, or chemicals, particularly in occupational settings, can irritate the cornea and make it susceptible to infections or ulceration.

Genetics

Prognostic Factors

Prognostic factors in corneal ulcers refer to the factors that can help predict the likely outcome and potential complications associated with the condition. These factors can vary depending on the underlying cause, severity, and individual patient characteristics. Here are some common prognostic factors for corneal ulcers:

• Size and depth of the ulcer: The size and depth of the corneal ulcer can influence its prognosis. More extensive and deeper ulcers are generally associated with a poorer prognosis as they may take longer to heal and have a greater risk of complications.
• Underlying cause: The underlying cause of the corneal ulcer can impact the prognosis. For example, ulcers caused by bacterial infections tend to respond well to appropriate antibiotic treatment. In contrast, viral or fungal ulcers may be more challenging to manage and have a potentially long course.
• Time to diagnosis and treatment: Early diagnosis and prompt initiation of appropriate treatment are critical in improving the prognosis of corneal ulcers. Delayed diagnosis or delayed treatment can lead to the progression of the ulcer, increased risk of complications, and poorer visual outcomes.
• Infection severity: The severity of the infectious process associated with the corneal ulcer can influence prognosis. Severe infections, particularly those involving aggressive or antibiotic-resistant microorganisms, can be more challenging to manage and may have a higher risk of vision-threatening complications.
• Presence of complications: Complications such as corneal perforation, significant scarring, or associated conditions like hypopyon can impact the prognosis. Complications often require additional interventions, leading to prolonged healing time and reduced visual acuity.
• Patient factors: Certain patient factors can influence the prognosis of corneal ulcers. These include the patient’s overall health, immune status, and ability to comply with treatment. Patients with compromised immune systems, such as diabetes or immunodeficiency disorders, may have a higher risk of complications and slower healing.
• Response to treatment: The response to initial treatment is an important prognostic factor. If the ulcer shows a positive response to treatment, such as a decrease in size, reduced inflammation, and improved symptoms, it generally indicates a better prognosis. Lack of response or worsening despite treatment may suggest the need for alternative management strategies.
• Compliance with follow-up care: Regular follow-up visits and adherence to prescribed medications and treatment regimens are crucial for monitoring the progress of corneal ulcers. Patients actively engaged in their care and following the recommended treatment plan have a better chance of achieving a favorable outcome.

Clinical History

Clinical history

The clinical presentation of corneal ulcers can vary depending on several factors, including the age group of the individual, associated comorbidities or activities, and the acuity of presentation. Here are some critical aspects of the clinical presentation:

• Age group: Corneal ulcers can occur in individuals of all ages, including children, adults, and elder people. The specific age group affected may provide insights into the potential underlying causes. For example, in children, corneal ulcers may be associated with conditions like viral conjunctivitis or trauma, whereas in older adults, underlying systemic diseases or age-related changes may play a role.

Physical Examination

Physical examination

During the physical examination of a corneal ulcer, an eye care professional will assess various aspects of the affected eye to determine the characteristics and severity of the ulcer. Here are some critical components of the physical examination:

• Visual Acuity: The eye care professional will evaluate the patient’s visual acuity using an eye chart or other appropriate methods. This helps determine the extent of visual impairment caused by the corneal ulcer.
• Slit-lamp Examination: A slit-lamp biomicroscope, a specialized microscope with a high-intensity light source, is used to examine the front structures of eye, including the cornea. This examination allows for a detailed assessment of the corneal ulcer and associated findings. The eye care professional may use special techniques such as fluorescein staining to enhance the visibility of the ulcer.
• Evaluation of Corneal Integrity: The eye care professional will examine the integrity of the cornea, looking for any epithelial defects or erosions. These can be visualized with fluorescein staining, where a dye is applied to the eye and illuminated with a blue light. The dye highlights any areas of damage or loss of the corneal epithelium.
• Corneal Infiltrates and Opacity: The presence and characteristics of corneal infiltrates, which are areas of inflammatory cells within the cornea, are assessed. The eye care professional will examine the infiltrates’ size, location, density, and any associated corneal opacity or cloudiness.
• Neovascularization: The growth of new blood vessels (neovascularization) around the corneal ulcer is evaluated. Neovascularization indicates the body’s attempt to supply oxygen and nutrients to the damaged cornea but can also contribute to scarring and impaired vision.
• Anterior Chamber Examination: The eye care professional may assess the eye’s anterior chamber for signs of inflammation or infection, such as pus (hypopyon) or cells in the fluid-filled space between the cornea and the iris.
• Evaluation of Conjunctiva and Eyelids: The conjunctiva and eyelids are examined for any signs of inflammation, infection, or associated conditions that may contribute to the corneal ulcer, such as conjunctivitis or blepharitis.

Age group

Associated comorbidity

Associated comorbidity or activity:

Certain comorbidities or engagement in specific activities can influence the clinical presentation of corneal ulcers. For instance, individuals with a history of contact lens use or recently experienced eye trauma may be at a higher risk for developing corneal ulcers.

Patients with underlying conditions such as diabetes, autoimmune disorders, or immunodeficiency may be more susceptible to infections and potentially more severe ulcers.

Associated activity

Acuity of presentation

The acuity of presentation:

The acuity of presentation refers to how rapidly the symptoms develop and the seriousness of the symptoms at the time of examination. Corneal ulcers can have acute or chronic presentations.

Acute presentations may involve sudden-onset symptoms such as eye pain, redness, photophobia (sensitivity to light), blurred vision, tearing, and a foreign body sensation in the eye.

Differential Diagnoses

Differential Diagnosis

The differential diagnosis of a corneal ulcer involves considering other conditions that can present with similar symptoms and signs. Some common conditions that may mimic a corneal ulcer include:

• Corneal Abrasion: Corneal abrasions are superficial injuries to the corneal epithelium caused by trauma or foreign bodies. They can produce symptoms similar to corneal ulcers, such as eye pain, redness, tearing, and blurred vision. However, corneal abrasions typically heal within a few days without developing an open sore.
• Herpes Simplex Keratitis: Herpes simplex virus (HSV) infection of the cornea, known as herpes simplex keratitis, can cause recurrent corneal ulcers. These ulcers may have a characteristic branching pattern and are often associated with a prior history of earlier episodes of ocular herpetic disease and additional symptoms like eye pain, redness, and blurred vision. Laboratory tests and clinical findings can help differentiate herpes simplex keratitis from other causes of corneal ulcers.
• Acanthamoeba Keratitis: It is a rare but severe cornea infection caused by a microscopic organism called Acanthamoeba. It typically occurs in contact lens wearers who have poor hygiene practices. Symptoms include severe eye pain, redness, photophobia, blurred vision, and corneal infiltrates. Diagnosis often requires specific laboratory tests to identify the presence of Acanthamoeba.
• Fungal Keratitis: Fungal keratitis is a fungal cornea infection that can present with symptoms similar to bacterial or viral corneal ulcers. It is commonly associated with trauma or improper contact lens use. Risk factors include living in a tropical environment or having a history of ocular surface disease. A fungal culture is typically required to confirm the diagnosis.
• Bacterial Keratitis: Bacterial infections of the cornea can cause ulcers similar in appearance to other types of corneal ulcers. Common causative organisms include Staphylococcus aureus and Pseudomonas aeruginosa. A detailed history, examination findings, and sometimes microbiological testing are used to differentiate bacterial keratitis from other conditions.
• Peripheral Ulcerative Keratitis (PUK): PUK is a rare inflammatory condition involving thinning and cornea inflammation. It is often associated with underlying systemic conditions, such as autoimmune diseases (e.g., rheumatoid arthritis, Wegener’s granulomatosis) or collagen vascular disorders. PUK can present with corneal ulceration and is typically associated with additional findings like scleritis and inflammation of the surrounding tissues.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Treating corneal ulcers involves multiple approaches, including modifying the environment, administering pharmaceutical agents, and sometimes intervention with a procedure. The management of corneal ulcers can be divided into several phases. Here is an overview:

Modification of environment:

• Thorough evaluation by an eye care professional to determine the corneal ulcer’s cause, severity, and extent.
• Identification and management of underlying risk factors or contributing factors.
• Stabilizing the ocular surface with lubricating eye drops or ointments reduces friction and promotes healing.
• Protection of the eye with a patch or bandage contact lens to prevent further damage and promote a moist environment.

Administration of a pharmaceutical agent:

• Administration of topical antibiotics to treat or prevent bacterial infection. The choice of antibiotic based on the suspected or identified causative organism and may be adjusted based on culture and sensitivity results.
• Use antiviral or antifungal medications if a viral or fungal infection is suspected or confirmed.
• Anti-inflammatory medications, like corticosteroids or non-steroidal anti-inflammatory drugs, might be prescribed to reduce inflammation and promote healing.
• Lubricating eye drops or ointments to relieve symptoms and maintain corneal hydration.

Intervention with a procedure

• Debridement: Removal of necrotic tissue or loose epithelium from the ulcer to promote healing and stop further infection.
• Amniotic membrane transplantation: Application of a thin, transparent membrane from the placenta onto the corneal ulcer to enhance healing and reduce scarring.
• Corneal glue or sutures: Used to close perforations or deep ulcers that do not respond to medical treatment alone.
• Tarsorrhaphy: Partial or complete closure of the eyelids to protect the cornea and promote healing in severe or non-healing ulcers.

Phase of management:

• Regular follow-up visits with an eye care professional to monitor the healing progress, adjust medications if necessary, and address any complications.
• Additional interventions or treatments may be required based on the response to initial treatment, complications, or underlying factors that may prolong healing.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Future Trends

Media Gallary

References

Contact Lens-Related Corneal Infections – United States, 2005-2015 – PubMed (nih.gov)

Corneal Ulcer – StatPearls – NCBI Bookshelf (nih.gov)

Mycotic keratitis: epidemiology, diagnosis and management – PubMed (nih.gov)