Bibliographic Source(s)

• Cornea/External Disease Panel Preferred Practice Patterns Committee. Bacterial keratitis. San Francisco (CA): American Academy of Ophthalmology (AAO); 2005. 20 p. [60 references]

Guideline Status

Note: This guideline has been updated. The National Guideline Clearinghouse (NGC) is working to update this summary.

Guideline Category

Diagnosis
Evaluation
Management
Treatment

Intended Users

Health Plans
Physicians

Guideline Objective(s)

To minimize visual loss relieve pain eliminate the infectious agent and minimize structural damage to the cornea by addressing the following goals:

• Recognize and reduce risk factors that predispose patients to bacterial infection of the cornea
• Establish the diagnosis of bacterial keratitis differentiating it from other causes of keratitis
• Utilize appropriate diagnostic tests
• Deliver appropriate therapy
• Relieve pain
• Prevent complications such as intraocular infection cataract perforation and loss of vision
• Educate patients and their families about treatment and ways to reduce risk factors in the future

Target Population

Individuals of all ages who present with symptoms and signs suggestive of bacterial keratitis

Interventions and Practices Considered

Diagnosis/Evaluation

1. Comprehensive eye evaluation including detailed history and examination (e.g. visual acuity external examination slit-lamp biomicroscopy)
2. Diagnostic tests (e.g. cultures and smears corneal biopsy)
3. Follow-up evaluation

Treatment/Management

1. Antibiotics (topical drops and ointments subconjuntival systemic)
2. Corticosteroid therapy
3. Patient education
4. Referral to specialist for visual rehabilitation if indicated

Major Outcomes Considered

• Rate of disease progression
• Effectiveness of treatments
• Adverse effects of treatments

Methods Used to Collect/Select Evidence

Searches of Electronic Databases

Description of Methods used to Collect/Select the Evidence

In the process of revising this document a detailed literature search of MEDLINE for articles in the English language was conducted on the subject of bacterial keratitis for the years 2000 to February 2005.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence

Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence

Ratings of Strength of Evidence

• Level I includes evidence obtained from at least one properly conducted well-designed randomized controlled trial. It could include meta-analyses of randomized controlled trials.
• Level II includes evidence obtained from the following:
  • Well-designed controlled trials without randomization
  • Well-designed cohort or case-control analytic studies preferably from more than one center
  • Multiple-time series with or without the intervention
• Level III includes evidence obtained from one of the following:
  • Descriptive studies
  • Case reports
  • Reports of expert committees/organization
  • Expert opinion (e.g. Preferred Practice Pattern panel consensus)

Methods Used to Analyze the Evidence

Systematic Review

Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations

Expert Consensus

Description of Methods Used to Formulate the Recommendations

The results of a literature search on the subject of bacterial keratitis were reviewed by the Cornea/External Disease Panel and used to prepare the recommendations which they rated in two ways. The panel first rated each recommendation according to its importance to the care process. This "importance to the care process" rating represents care that the panel thought would improve the quality of the patient's care in a meaningful way. The panel also rated each recommendation on the strength of the evidence in the available literature to support the recommendation made.

Rating Scheme for the Strength of the Recommendations

Ratings of Importance to the Care Process

Level A most important
Level B moderately important
Level C relevant but not critical

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation

Internal Peer Review

Description of Method of Guideline Validation

These guidelines were reviewed by Council and approved by the Board of Trustees of the American Academy of Ophthalmology (September 2005).

Major Recommendations

Note: This guideline has been updated. The National Guideline Clearinghouse (NGC) is working to update this summary. The recommendations that follow are based on the previous version of the guideline.

Ratings of importance to the care process (A-C) and ratings of strength of evidence (I-III) are defined at the end of the "Major Recommendations" field.

Diagnosis

History

Obtaining a detailed history is important in evaluating patients with bacterial keratitis. Pertinent information includes the following:

• Ocular symptoms [A:III] (e.g. degree of pain redness discharge blurred vision photophobia duration of symptoms circumstances surrounding the onset of symptoms)
• Review of prior ocular history [A:III] including risk factors such as contact lens wear [A:II] swimming or using a hot tub while wearing contact lenses herpes simplex virus keratitis herpes zoster virus keratitis previous bacterial keratitis previous ocular surgery including refractive surgery trauma and dry eye
• Review of other medical problems [A:III]
• Current ocular medications and medications recently used [A:III]
• Medication allergies [A:III]

Examination

Visual Acuity

In many cases patient discomfort tearing and inflammation will compromise visual acuity. It is useful however to document baseline visual acuity and to ascertain that it is consistent with the anterior segment examination. [A:III]

External Examination

An external examination should be performed with particular attention to the following:

• General appearance of the patient including skin conditions [B:III]
• Facial examination [B:III]
• Eyelids and lid closure [A:III]
• Conjunctiva [A:III]
• Nasolacrimal apparatus [B:III]
• Corneal sensation [A:III]

Slit-Lamp Biomicroscopy

Slit-lamp biomicroscopy should include evaluation of the following:

• Eyelid margins: [A:III] inflammation ulceration eyelash abnormalities including trichiasis irregularities lacrimal punctal anomalies
• Conjunctiva: [A:III] discharge inflammation morphologic alterations (e.g. follicles papillae cicatrization keratinization membrane pseudomembrane ulceration prior surgery) ischemia foreign bodies filtering blebs
• Sclera: [A:III] inflammation (e.g. infectious versus autoimmune) ulceration scarring/thinning nodules ischemia
• Cornea: [A:III] epithelium including defects and punctate keratopathy edema; stroma including ulceration thinning perforation and infiltrate (location [central peripheral perineural surgical or traumatic wound] density size shape [ring] number [satellite] depth character of infiltrate margin [suppuration necrosis feathery soft crystalline] color) edema; endothelium; foreign bodies including sutures; signs of corneal dystrophies (e.g. epithelial basement membrane dystrophies); previous corneal inflammation (thinning scarring or neovascularization); signs of previous corneal surgery (e.g. corneal transplantation radial keratotomy astigmatic keratotomy or limbal relaxing incision LASIK or other refractive surgery)
• Anterior chamber: [A:III] depth; inflammation including cell and flare hypopyon fibrin hyphema
• Anterior vitreous; [A:III] presence of inflammation

Clinical features suggestive of bacterial keratitis include dense suppurative stromal infiltrate (particularly those greater than 1 mm in size) with indistinct edges edema and white cell infiltration in surrounding stroma. An epithelial defect is typically present. An anterior chamber reaction is often seen.

Diagnostic Tests

Cultures and Smears

• Smears and cultures are indicated in cases with a corneal infiltrate that is large and extends to the middle to deep stroma that is chronic in nature or unresponsive to broad spectrum antibiotic therapy or that has clinical features suggestive of fungal amoebic or mycobacterial keratitis (Wilhelmus et al. 1994). [A:III]
• The hypopyon that occurs in eyes with bacterial keratitis is usually sterile and aqueous or vitreous taps should not be performed unless there is a high suspicion of microbial endophthalmitis. [A:III]
• Prior to initiating antimicrobial therapy cultures are indicated in sight-threatening or severe keratitis of suspected microbial origin. [A:III]
• Corneal scrapings for culture should be inoculated directly onto appropriate culture media in order to maximize culture yield (see Appendix 2 in the original guideline document) (Waxman et al. 1999). [A:III] If this is not feasible specimens should be placed in transport media (Kaye et al. 2003). [A:III] In either case cultures should be immediately incubated or taken promptly to the laboratory. [A:III] Cultures of contact lenses lens case and solution may be useful in situations where acanthamoeba is suspected or corneal cultures are negative. The material for smear is applied to clean class microscope slides in an even thin layer (see Appendix 3 in the original guideline document for specific diagnostic stains).

Corneal Biopsy

• Corneal biopsy may be indicated if there has been a lack of response to treatment or if cultures have been negative on more than one occasion and the clinical picture continues to strongly suggest an infectious process. It may also be indicated if the infiltrate is located in the mid or deep stroma with overlying uninvolved tissue.
• The biopsy specimen should be delivered to the laboratory in a timely fashion. [A:III]

Treatment

Initial

• Topical antibiotic eye drops are capable of achieving high tissue levels and are the preferred method of treatment in most cases. [A:III] Ocular ointments may be useful at bedtime in less severe cases and also may be useful for adjunctive therapy.
• Subconjunctival antibiotics may be helpful where there is imminent scleral spread or perforation or in cases where adherence to the treatment regimen is questionable. Systemic therapy may be useful in cases of scleral or intraocular extension of infection or systemic infection such as gonorrhea. Collagen shields or soft contact lenses soaked in antibiotics are sometimes used and may enhance drug delivery. They may also be useful in cases where there is an anticipated delay in initiating appropriate therapy but these modalities have not been fully evaluated in terms of the potential risk for inducing drug toxicity.
• Topical broad-spectrum antibiotics are used initially in the empiric treatment of bacterial keratitis [A:III] (see Table 2 in the original guideline document). For severe keratitis (e.g. deep stromal involvement or a defect larger than 2 mm with extensive suppuration) a loading dose every 5 to 15 minutes for the first hour followed by applications every 15 minutes to 1 hour around the clock is recommended. [A:III] For less severe keratitis a regimen with less frequent dosing is appropriate. Cycloplegic agents may be used to decrease synechia formation and to decrease pain in more severe cases of bacterial keratitis and are indicated when significant anterior chamber inflammation is present.
• Systemic antibiotics are rarely needed but may be considered in severe cases where the infectious process has extended to adjacent tissues (e.g. the sclera) or when there is impending or frank perforation of the cornea. Systemic therapy is necessary in cases of gonococcal keratitis. [A:III]
• Frequency of re-evaluation of the patient with bacterial keratitis depends on the extent of disease but severe cases (e.g. deep stromal involvement or larger than 2 mm with extensive suppuration) initially should be followed at least daily until clinical improvement or stabilization is documented. [A:III]

Modification of Therapy

• In general the initial therapeutic regimen should be modified when the eye shows a lack of improvement or stabilization within 48 hours. [A:III] Keratitis due to Pseudomonas and other gram-negative organisms may exhibit increased inflammation during the first 24 to 48 hours despite appropriate therapy. Several clinical features suggest a positive response to antibiotic therapy:
  • Reduction in pain
  • Reduced amount of discharge
  • Lessened eyelid edema or conjunctival injection
  • Consolidation and sharper demarcation of the perimeter of the stromal infiltrate
  • Decreased density of the stromal infiltrate in the absence of progressive stromal loss
  • Reduced stromal edema and endothelial inflammatory plaque
  • Reduced anterior chamber cell fibrin or hypopyon
  • Initial re-epithelialization
  • Cessation of progressive corneal thinning
• Modification of therapy may mean a change in the type concentration or frequency of antibiotic treatment. Adjunctive therapy such as a temporary or permanent tarsorrhaphy may also be considered.
• Topical therapy is tapered according to clinical response taking into account the severity of the initial clinical picture and the virulence of the pathogen. Specific tapering recommendations are difficult to make due to wide variability in the severity of the infectious process in individual cases. Factors that may mandate more prolonged therapy include the presence of virulent or indolent organisms or presence of immunocompromise.

Indications for Reculture

Lack of a favorable clinical response particularly in the setting of negative culture results suggest the need for reculture and/or biopsy.

Corticosteroid Therapy

• Topical corticosteroid therapy may have a beneficial role in treating some cases of infectious keratitis.
• Patients being treated with ocular topical corticosteroids at the time of presentation of suspected bacterial keratitis should have their corticosteroid regimen reduced or eliminated until the infection has been controlled. [A:III]
• The objective in topical corticosteroid therapy is to use the minimum amount of corticosteroid required to achieve control of inflammation. Successful treatment requires optimal timing careful dose regulation use of adequate concomitant antibacterial medication and close follow-up. Patient compliance is essential and the intraocular pressure must be monitored frequently. The patient should be examined within 1 to 2 days after initiation of topical corticosteroid therapy. [A:III]

Therapy for Complicated Cases

• Additional treatment is necessary in cases where the integrity of the eye is compromised such as an extremely thin corneal surface or impending or frank perforation or where there is progressive or unresponsive disease or endophthalmitis. Application of tissue adhesive lamellar keratoplasty and penetrating keratoplasty are among the treatment options.

Provider and Setting

• The diagnosis and management of patients with bacterial keratitis require the clinical training and experience of an ophthalmologist because the disease has the potential to cause visual loss or blindness and because the ophthalmologist is familiar with medical conditions associated with bacterial keratitis. [A:III] Severe cases or those that fail to respond to treatment may be best managed by an ophthalmologist who has extensive expertise with bacterial keratitis.
• The majority of patients with bacterial keratitis can be treated on an outpatient basis. Hospitalization may be necessary if the keratitis is severe or vision threatening if compliance is impractical or if pain is severe.

Counseling/Referral

• Patients and care providers should be educated about the destructive nature of bacterial keratitis and the need for strict adherence to the therapeutic regimen. [A:III]
• The possibility of permanent visual loss and need for future visual rehabilitation should be discussed. [A:III]
• Patients who wear contact lenses should be educated about the increased risk of infection associated with contact lens wear overnight wear and the importance of adherence to techniques that promote contact lens hygiene (Larkin Kilvington & Easty 1990; Stern 1998). [A:III]
• Patients with significant visual impairment or blindness should be referred for vision rehabilitation if they are not candidates for surgical visual rehabilitation (American Academy of Ophthalmology 2001). [A:III]

Definitions:

Ratings of Importance to Care Process:

Level A most important
Level B moderately important
Level C relevant but not critical

Ratings of Strength of Evidence:

• Level I includes evidence obtained from at least one properly conducted well-designed randomized controlled trial. It could include meta-analyses of randomized controlled trials.
• Level II includes evidence obtained from the following:
  • Well-designed controlled trials without randomization
  • Well-designed cohort or case-control analytic studies preferably from more than one center
  • Multiple-time series with or without the intervention
• Level III includes evidence obtained from one of the following:
  • Descriptive studies
  • Case reports
  • Reports of expert committees/organization
  • Expert opinion (e.g. Preferred Practice Pattern panel consensus)

Clinical Algorithm(s)

None provided

References Supporting the Recommendations

• American Academy of Ophthalmology (AAO). Vision rehabilitation for adults. San Francisco (CA): American Academy of Ophthalmology (AAO); 2001 Feb. 32 p. (Preferred practice pattern). [42 references]



• Kaye SB Rao PG Smith G Scott JA Hoyles S Morton CE Willoughby C Batterbury M Harvey G. Simplifying collection of corneal specimens in cases of suspected bacterial keratitis. J Clin Microbiol 2003 Jul;41(7):3192-7. PubMed



• Larkin DF Kilvington S Easty DL. Contamination of contact lens storage cases by Acanthamoeba and bacteria. Br J Ophthalmol 1990 Mar;74(3):133-5. PubMed



• Stern GA. Contact lens associated bacterial keratitis: past present and future. CLAO J 1998 Jan;24(1):52-6. [59 references] PubMed



• Waxman E Chechelnitsky M Mannis MJ Schwab IR. Single culture media in infectious keratitis. Cornea 1999 May;18(3):257-61. PubMed



• Wilhelmus K Liesegang TJ Osato MS Jones DB. Laboratory diagnosis of ocular infections. Washington (DC): American Society for Microbiology; 1994.  (Cumitech series; no. 13A).

Type of Evidence supporting the Recommendations

The type of supporting evidence is identified and graded for most recommendations (see "Major Recommendations" field).

Potential Benefits

Effective therapy of bacterial keratitis eradicates the causative agent and minimizes structural damage to the cornea thereby relieving pain preserving vision and ameliorating the socioeconomic impact of the disease.

Subgroups Most Likely to Benefit:

Patients fall into four categories of risk factors that predispose them to bacterial keratitis:

• Exogenous factors: contact lens wearers (especially with extended wear lenses); trauma; ocular and eyelid surgery; loose sutures medicamentosa; immunosuppression (topical and systemic); factitious disease including anesthetic abuse.
• Ocular surface disease: misdirection of eyelashes; abnormalities of lid anatomy and function; tear film deficiencies adjacent infection (conjunctivitis including gonococcal blepharitis canaliculitis dacryocystitis).
• Corneal epithelial abnormalities: neurotrophic keratopathy; corneal epithelial edema especially bullous keratopathy; disorders predisposing to recurrent erosion of the cornea; viral keratitis.
• Systemic diseases: diabetes mellitus; debilitating illness especially malnourishment and/or respirator dependence; collagen vascular disease; substance abuse; dermatological/mucus membrane disorders (Stevens Johnson syndrome ocular cicatricial pemphigoid); immunocompromised status; atopic dermatitis/blepharoconjunctivitis; gonococcal infection with conjunctivitis; vitamin A deficiency.

Potential Harms

• Collagen shields and soft contact lenses can become displaced or lost leading to unrecognized interruption of drug delivery
• Potential disadvantages of corticosteroid therapy include recrudescence of infection local immunosuppression inhibition of collagen synthesis predisposing to corneal melting and increased intraocular pressure.

Qualifying Statements

• Preferred Practice Patterns provide guidance for the pattern of practice not for the care of a particular individual. While they should generally meet the needs of most patients they cannot possibly best meet the needs of all patients. Adherence to these Preferred Practice Patterns will certainly not ensure a successful outcome in every situation. These guidelines should not be deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed at obtaining the best results. It may be necessary to approach different patients' needs in different ways. The physician must make the ultimate judgment about the propriety of the care of a particular patient in light of all of the circumstances presented by that patient. The American Academy of Ophthalmology is available to assist members in resolving ethical dilemmas that arise in the course of ophthalmic practice.
• Preferred Practice Patterns are not medical standards to be adhered to in all individual situations. The Academy specifically disclaims any and all liability for injury or other damages of any kind from negligence or otherwise for any and all claims that may arise out of the use of any recommendations or other information contained herein.

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools

Personal Digital Assistant (PDA) Downloads
Quick Reference Guides/Physician Guides

For information about availability see the "Availability of Companion Documents" and "Patient Resources" fields below.

IOM Care Need

Getting Better
Living with Illness

IOM Domain

Effectiveness
Patient-centeredness

Bibliographic Source(s)

• Cornea/External Disease Panel Preferred Practice Patterns Committee. Bacterial keratitis. San Francisco (CA): American Academy of Ophthalmology (AAO); 2005. 20 p. [60 references]

Adaptation

Not applicable: The guideline was not adapted from another source.

Source(s) of Funding

American Academy of Ophthalmology (AAO)

Guideline Committee

Cornea/External Disease Panel; Preferred Practice Patterns Committee

Composition of Group that Authored the Guideline

Cornea/External Disease Panel Members: Christopher J. Rapuano MD (Chair); Robert S. Feder MD; Matthew R. Jones MD; Francis S. Mah MD; Ayman Naseri MD; Audrey R. Talley-Rostov MD; Andrew J. Velazquez MD; Jayne S. Weiss MD; David C. Musch PhD MPH Methodologist

Preferred Practice Patterns Committee Members: Sid Mandelbaum MD (Chair); Emily Y. Chew MD; Linda M. Christmann MD; Douglas E. Gaasterland MD; Stephen D. McLeod MD; Samuel Masket MD; Christopher J. Rapuano MD; Donald S. Fong MD MPH Methodologist

Academy Staff: Flora C. Lum MD; Nancy Collins RN MPH; Doris Mizuiri

Financial Disclosures/Conflicts of Interest

The following authors have received compensation within the past 3 years up to and including August 2005 for consulting services regarding the equipment process or product presented or competing equipment process or product presented:

Francis S. Mah MD: Alcon Allergan -- Contribution to research or research funds.

Christopher J. Rapuano MD: Alcon Allergan -- Ad hoc consulting fees.

Audrey R. Talley-Rostov MD: Addition Technologies Allergan -- Ad hoc consulting fees.

Andrew J. Velazquez MD: Alcon -- Unrestricted educational grant.

Jayne S. Weiss MD: Alcon -- Reimbursement of travel expenses for presentation at meetings or courses.

Other authors have no financial interest in the equipment process or product presented or competing equipment process or product presented.

Guideline Status

Note: This guideline has been updated. The National Guideline Clearinghouse (NGC) is working to update this summary.

Guideline Availability

Electronic copies of the updated guideline: Available from the American Academy of Ophthalmology (AAO) Web site.

Print copies: Available from American Academy of Ophthalmology P.O. Box 7424 San Francisco CA 94120-7424; telephone (415) 561-8540.

Availability of Companion Documents

The following is available:

• Summary benchmarks for preferred practice patterns. San Francisco (CA): American Academy of Ophthalmology; 2006 Nov. 21 p.

Available in Portable Document Format (PDF) from the American Academy of Ophthalmology (AAO) Web site.

Print copies: Available from American Academy of Ophthalmology P.O. Box 7424 San Francisco CA 94120-7424; telephone (415) 561-8540.

Patient Resources

None available

NGC STATUS

This summary was completed by ECRI on December 1 1998. The information was verified by the guideline developer on January 11 1999. The summary was updated by ECRI on January 29 2001. The updated information was verified by the guideline developer on March 12 2001. This NGC summary was updated by ECRI on January 6 2006. The updated information was verified by the guideline developer on February 9 2006.

COPYRIGHT STATEMENT

This NGC summary is based on the original guideline which is subject to the guideline developer's copyright restrictions. Information about the content ordering and copyright permissions can be obtained by calling the American Academy of Ophthalmology at (415) 561-8500.

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