Bacterial keratitis, also referred to as corneal ulcer, is an infection of the corneal tissue caused by diverse bacterial pathogens. It may manifest as an acute, chronic, or transient process, affecting different topographical and anatomical regions of the cornea [1]. Clinically, it may present as a slowly progressive ulceration or as a rapidly advancing suppurative lesion involving any corneal layer. Although viruses, fungi, protozoa, and bacteria can invade the cornea, bacterial infections are particularly concerning due to their aggressive course, frequently resulting in severe, irreversible visual impairment [2].

Microbial keratitis develops when the natural anatomical, mechanical, and antimicrobial defense mechanisms of the cornea are compromised, predisposing to vision-threatening infections. Over recent decades, the global rise in contact lens use has been strongly associated with an increased incidence of bacterial keratitis [3,4]. Diagnosis relies on both clinical assessment and microbiological confirmation. Despite advances in diagnostic modalities, molecular investigations, and targeted antimicrobial strategies that have reduced morbidity, bacterial keratitis continues to be a major cause of sight-threatening disease, particularly in rural and resource-limited regions worldwide [5].

Etiology

Protective Barriers against Microbial Infection

• Anatomical Barriers: bony orbital rim, eyelids, intact conjunctival and corneal epithelium

• Mechanical Barriers: tear film mucus layer, lacrimal drainage system

• Antimicrobial Barriers: tear film components (IgA, complement factors, lactoferrin, lysozyme) and conjunctiva-associated lymphoid tissue (CALT)       

Disruption of these barriers predisposes to bacterial keratitis [6]

Risk Factors for Bacterial Keratitis

Contact Lens–Associated Factors [7]

• Bandage contact lenses

• Sharing of lenses

• Swimming with lenses

• CL-induced trauma

• Overnight wear or extended use

Extrinsic Causes [8]

• Previous ocular or eyelid surgery

• Immunosuppression

• Prolonged corticosteroid or NSAID use

• Substance abuse

• Ocular trauma or foreign body injury

• Chemical, thermal, or mechanical insults

• Insect entry

Ocular Surface Disorders (Local Factors) [9]

• Dry eye disease

• Corneal suture-related infection

• Eyelid malpositions [ectropion, entropion, lagophthalmos]

• Blepharitis, trichiasis, chronic dacryocystitis, conjunctivitis

• Recurrent corneal erosions

• Neurotrophic keratopathy

• Bullous keratopathy

• Secondary bacterial keratitis following viral keratitis

Systemic Conditions [10]

• Diabetes mellitus

• Malnutrition

• Autoimmune/connective tissue disorders

• Stevens–Johnson syndrome (SJS)

• Ocular mucous membrane pemphigoid (OMMP)

• Atopic dermatitis

• Xerophthalmia, blepharoconjunctivitis

• Cranial nerve palsy (V, VII)

• Graft-versus-host disease

• Acquired immunodeficiency syndrome (AIDS)

• Chronic alcoholism

• Immunosuppression

Epidemiology

The incidence and prevalence of bacterial keratitis exhibit substantial geographic variation influenced by socioeconomic, environmental, climatic factors [12]. 

Marked differences are observed between developed regions such as the Europe and USA and developing countries including Bangladesh India, Nepal, and Pakistan [5]. This disparity is partly attributed to the lower prevalence of contact lens use in rural regions, resulting in less incidence of contact lens–associated keratitis [13] (Table 1).

In the USA, the incidence is approximately 11 per 100,000 users, whereas Nepal reports a significantly higher incidence of 799 per 100,000 users. The annual incidence of microbial keratitis in the USA is estimated at nearly 71,000 cases [14,15]. However,the healthy cornea exhibits inherent resistance to bacterial invasion, several studies have identified the predominant causative organisms. Ormerod et al. reported Staphylococcus spp., Pseudomonas, and Streptococcus as the principal pathogens in North America [16]. Similarly, Neuman et al identified Staphylococcus epidermidis and Staphylococcus aureus as the most common Gram-positive organisms and Pseudomonas as the leading Gram-negative pathogen [17].

Epidemiological data indicate a progressive increase in corneal ulceration, rising from negligible levels in the early 1960s to approximately 52% in the 1990s. Erie et al. also documented a marked increase in ulcerative keratitis between 1950 and 1980 (5.3% to 435%), largely associated with contact lens use. The annual incidence among contact lens users ranges from 4 to 21 cases per 10,000 users, with extended-wear soft lenses conferring greater risk. Overall, Staphylococcus spp. and Pseudomonas remain the predominant etiological agents [18].

Other studies from U.K. and Italy observed that contact lens wearer serve as a major predisposing factor, while hospital-based studies from Los Angeles document Gram-positive organisms as the principal isolates [19].

• A dual-hospital study in Los Angeles identified coagulase-negative staphylococci as the most common Gram-positive pathogens and Pseudomonas aeruginosa as the predominant Gram-negative isolate [20]. Another study from the USA reported a higher prevalence of Gram-negative organisms in southern states compared with northern regions [21], Gram-negative bacteria was identified as the predominant isolates on a Texas based analysis [9].

Polymicrobial keratitis has also been reported, with one study identifying multiple bacterial isolates in 43% of culture-positive cases. Fusarium and Staphylococcus epidermidis were frequently detected, with ocular trauma identified as the primary risk factor [22]. The Steroids for Corneal Ulcers Trial (SCUT) conducted in South India reported Streptococcus pneumoniae (51.5%), Pseudomonas (22.7%), and Nocardia (11.5%) as the principal etiological agents [23].

Table 1: Bacterial Pathogens Causing Keratitis [11]

Pathophysiology of Focal Bacterial Keratitis

Bacterial keratitis is initiated when the integrity of the corneal epithelium is disrupted, allowing microorganisms to invade the underlying tissue [1]. The disease typically progresses through four sequential stages:

• Active ulceration

• Regression

• Cicatrization

• .Progressive infiltration [24]

The clinical outcome is determined by the virulence of the causative pathogen, the host immune response, and the adequacy of therapeutic intervention.

Pathophysiology of Perforated Bacterial Corneal Ulcer

Perforation occurs as a result of accelerated keratolysis and stromal melting, extending the ulcerative process to the Descemet membrane (DM). Despite its relative resistance, the DM may bulge outward, forming a descemetocele. At this stage, any transient increase in intraocular pressure (e.g., from sneezing, coughing, or straining) may precipitate rupture. Following perforation, aqueous humor escapes rapidly, leading to a reduction in intraocular pressure, immediate relief of pain ,forward displacement of the iris–lens diaphragm.The prognosis depends largely on the size and location of the perforation. Small perforations, particularly those adjacent to iris tissue, are often sealed by iris incarceration, promoting rapid healing and the development of an adherent leucoma [25].

Pathophysiology of Anterior Staphyloma Formation and Sloughed-Out Corneal Ulcer
In cases of infection with highly virulent bacteria and inadequate host defense, widespread stromal necrosis may result in, , sparing only a peripheral rim complete corneal sloughing, and often associated with total iris prolapse. This is followed by iritis and obstruction of the pupil by fibrinous exudates, which simulate the appearance of a false cornea. Subsequent organization of these exudates, combined with epithelial and fibrovascular ingrowth, leads to the formation of a pseudocornea. However, the pseudocornea is structurally weak and unable to withstand intraocular pressure, resulting in progressive ectasia and protrusion of the plastered iris tissue. This culminates in the development of an anterior staphyloma, which may be partial or total, depending on the extent of corneal involvement [26].

Evaluation

Corneal Scraping

Indications
Corneal scraping is recommended in the following situations:

• History of prior corneal surgery

• Presence of atypical clinical features

• Multiple infiltrates located at different corneal sites

• Large, centrally located corneal infiltrates with stromal involvement or tissue melt

• Keratitis that is chronic or unresponsive to broad-spectrum antimicrobial therapy

Procedure
The procedure is performed under preservative-free topical anesthesia using 0.5% proparacaine or 0.5% proxymetacaine. Preservative-free agents are preferred as preservatives may reduce bacterial viability for culture. Tetracaine may also be used, although it possesses additional bacteriostatic activity.

Scraping is carried out using a sterile Bard-Parker blade (No. 11 or 15), a 26-gauge bent hypodermic needle, a sterile Kimura spatula, or a platinum spatula. Prior to scraping, necrotic tissue, mucus, and debris are removed from the ulcer surface. Samples are collected from both the ulcer margin and base.

The collected material is smeared onto one or more sterile glass slides for direct microscopic evaluation, including Gram staining. As a standard convention, the labeling surface is positioned on the upper side of the slide. Smears are air-dried and mounted on slide carriers. Repeat scraping is then inoculated onto different culture media, such as blood agar, chocolate agar, potato dextrose agar, brain–heart infusion broth, or Lowenstein–Jensen medium. In patients with prior antibiotic exposure, scraping is ideally delayed for at least 12 hours. Recently, calcium alginate swabs in trypticase soy broth have been employed to improve bacterial yield. Special caution is required in cases of corneal melt, descemetocele, or deep stromal keratitis [27].

Culture Techniques

Solid media are inoculated using conventional multiple “C”-shaped streaks without cutting the agar surface.

In liquid media, the instrument tip (needle or spatula) is immersed directly in liquid media,

Microbiological Evaluation

Staining Methods

• Gram Stain: Differentiates bacteria based on cell wall composition; Gram-positive organisms retain crystal violet and appear purple, whereas Gram-negative organisms take up the counterstain and appear pink.

• Acridine Orange Stain: A fluorescent stain used for rapid detection of bacteria, in which microorganisms emit yellow-green fluorescence under ultraviolet illumination.

• Acid-Fast Stain: Utilized for the identification of Mycobacterium species, which retain the primary stain and appear pink to red due to the presence of mycolic acids in their cell wall.

Culture Media and Their Applications

• Blood agar (35 °C): Aerobic and facultative anaerobic bacteria.

• Chocolate agar (35 °C): Moraxella, Haemophilus ,Aerobic bacteria, Neisseria

• Thioglycolate broth (35 °C): Aerobic and anaerobic bacteria.

• Sabouraud’s dextrose agar (Room temperature): Nocardia.

• Brain–heart infusion broth (Room temperature): Nocardia.

• Middlebrook–Cohn agar (35 °C, 3–10% CO₂): Mycobacterium and 

Nocardia 

• Cooked meat broth (35 °C): Anaerobic bacteria.

• Thayer–Martin blood agar (35 °C): Neisseria.

• Lowenstein–Jensen medium (35 °C, 3–10% CO₂): Mycobacterium species [28]

• Conjunctival Swab Culture: In cases where conventional cultures yield negative results, conjunctival swab culture can serve as a valuable adjunctive diagnostic tool. Swabs made of calcium alginate have been shown to provide optimal recovery of organisms [29]

• Contact Lens Culture: Culturing contact lenses and their associated solutions can provide important microbiological information, provided the lenses have not been cleaned or disinfected by the patient prior to sampling.[30]

• Culture and Sensitivity Analysis: Culture and sensitivity testing guides targeted antimicrobial therapy and helps identify bacterial resistance and susceptibility patterns. Clinicians may need to adjust treatment regimens based on these results to optimize therapeutic outcomes [31]

• Anterior Chamber Paracentesis: Anterior chamber paracentesis may be indicated when corneal scrapings and cultures are negative, yet the ulcer continues to progress despite appropriate antibacterial therapy. This procedure can also help differentiate bacterial keratitis from other microbial etiologies. A side port incision is created, and 0.1–0.2 mL of aqueous humor is aspirated using a 25-gauge needle [32]

• Corneal Biopsy: Corneal biopsy is considered when smear and culture results remain negative after repeated testing and the ulcer shows clinical progression despite optimal therapy. Tissue is obtained using polyfilament braided 6-0 or 8-0 silk sutures from both normal and affected areas of the cornea [33]

• Ultrasound B-Scan: B-scan ultrasonography is typically performed post-therapeutic keratoplasty when visualization of the fundus is obstructed by hyphema, or anterior chamber exudates, corneal edema, haze, fibrinous membranes. It assists in detecting complications such as endophthalmitis, panophthalmitis, dislocated lens or nuclear fragments, and vitritis ,retinal or choroidal detachment.

• Emerging Diagnostic Modalities: Advanced techniques including radioimmunoassays are emerging diagnostic tools for enzyme immunoassays, bacterial keratitis, immunohistochemistry, polymerase chain reaction (PCR) though their routine clinical use remains limited [34]

Medical Management of Bacterial Keratitis

Immediate Initiation of Therapy: Treatment should commence promptly upon patient presentation. Smear results are typically available within 1 hour, allowing early guidance for therapy. Broad-spectrum topical antibiotics covering both Gram-positive and Gram-negative organisms should be initiated immediately. Once culture results are available, generally within 48–72 hours, therapy should be adjusted to targeted antibacterial treatment. For small peripheral ulcers (<3 mm) that do not involve the visual axis, monotherapy is usually sufficient. In contrast, larger or deep stromal ulcers require dual antibiotic therapy to prevent irreversible vision-threatening complications [35].

Topical Antibiotics

• Cephalosporins: Fortified cefazolin 5% is commonly used and effective against non-penicillinase-producing Gram-positive bacteria.

• Aminoglycosides: Fortified topical tobramycin 0.3%, gentamicin 0.3%, and amikacin 1 g/ml injections are effective against Gram-negative bacteria, streptococci, and staphylococci, but show limited activity against pneumococci. Commercially, cefazolin and tobramycin are available in combination and are widely employed in bacterial keratitis.

• Glycopeptides: Fortified vancomycin 5% is indicated for methicillin-resistant Staphylococcus aureus (MRSA).

• Fluoroquinolones: Agents include moxifloxacin 0.5%, and gatifloxacin 0.3%, ciprofloxacin 0.3%, ofloxacin 0.3%, primarily administered as monotherapy. Increasing resistance to ofloxacin and ciprofloxacin and has led to preferential use of gatifloxacin and moxifloxacin [36]

Systemic Antibiotics

Systemic therapy has a limited role, reserved for cases such as scleritis, endophthalmitis, or progressive non-resolving ulcers. Commonly used agents include ciprofloxacin 750 mg twice daily or an aminoglycoside combined with a cephalosporin (37)

Adjunctive Medications

• Cycloplegics: pain, posterior synechiae, and anterior chamber inflammation , while improving antibody migration and anterior uveal blood flow.

• Antiglaucoma Agents: Aid in controlling intraocular pressure and hypopyon drainage by enhancing trabecular outflow. Timolol 0.5% twice daily is preferred; miotics and prostaglandin analogs should be avoided due to pro-inflammatory effects.

• Lubricating Eye Drops: reduce irritation, remove debris, and maintain corneal surface integrity, promote epithelial healing Commonly used agents include 0.5% carboxymethylcellulose and 0.3% hydroxypropyl methylcellulose.

• Systemic Anti-inflammatory Drugs: Reduce pain and inflammation, such as diclofenac 50 mg combined with serratiopeptidase 10 mg twice daily, or ibuprofen 200 mg twice daily.

Protective Measures

Supportive care is essential and includes the use of dark goggles, avoidance of direct sunlight, prevention of eye rubbing, minimizing exposure to water or soap, adequate rest, nutrition, and hot fomentation.

Surgical Management

Gundersen Conjunctival Flap: Used when donor cornea is unavailable for perforated corneal ulcers. A thin conjunctival flap is dissected and sutured over the cornea, providing metabolic support [37]

Therapeutic Penetrating Keratoplasty (TPK)

Indicated for non-healing corneal ulcers (≥2 weeks). The procedure removes the diseased cornea and replaces it with a healthy donor corneal button. Key steps include: trephination with a 0.5 mm margin, graft sizing slightly larger than the host cornea, anterior chamber exudate removal, release of peripheral anterior synechiae, peripheral iridectomy, and lens removal if necessary. Suturing is performed with 16 interrupted 9-0 or 10-0 nylon sutures, though continuous sutures may also be used. An intact posterior capsule is preferred to prevent expulsive hemorrhage; anterior vitrectomy is required if the capsule is breached [38].

Penetrating Keratoplasty [PKP]

Performed once the cornea has scarred and infection has resolved, aiming to restore vision. Technique mirrors TPK with emphasis on graft-host alignment and suture radiality. In cataractous lenses, a triple procedure [PKP, cataract extraction, and IOL implantation] may be performed. PKP is generally undertaken after 6–8 months of quiescence [38].

Prognosis

The prognosis of bacterial keratitis is influenced by multiple clinical factors. Ulcers confined to the superficial corneal layers or limited to the anterior one-third of the stroma generally exhibit favorable healing outcomes. In contrast, ulcers extending beyond two-thirds of the stromal depth, those affecting the visual axis or cases with stromal melting and corneal thinning are associated with poor prognosis. Additional prognostic determinants include adherence to prescribed medications, patient compliance, presence of scleral extension or endophthalmitis, and the consistency of follow-up and counseling.

Bacterial keratitis is a major cause of vision-threatening corneal infection worldwide. Prompt treatment early diagnosis, prompt treatment, and close follow-up are essential for preserving vision. Ophthalmologists establish the diagnosis and initiate targeted therapy, while optometrists aid in early detection and referral. Nurses play an important role in patient education, particularly regarding medication adherence and contact lens hygiene and medication adherence, and pharmacists ensure timely drug availability. Effective inter professional collaboration is therefore essential for achieving favorable visual outcomes.

Financial Support and Sponsorship

None. 

Conflicts of Interest

None.

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