• My Dashboard My Education Find an Ophthalmologist
  • Home
  • Coronavirus
  • For Ophthalmologists
    • Meetings
      • AAO 2022
        • Meeting Information
          • Past and Future Meetings
          • Mobile Meeting Guide
          • Contact Information
          • Annual Meeting News
          • Health and Safety
          • Policies and Disclaimers
        • Program
          • Program Highlights
          • Subspecialty Day
          • Virtual Meeting
          • Program Committees
          • CME
          • Meeting Archives
        • Expo
        • Registration
        • Hotels & Travel
          • Hotel Reservation Information
          • Chicago
          • International Attendees
          • Hotel Meeting Space
        • Presenter Central
          • Presenter Central
          • Abstract Selection Process
          • Submission Policies
          • Subject Classification/Topics
          • Instruction Courses and Skills Transfer Labs
          • Papers and Posters
          • Videos
          • Grand Rounds Symposium
          • Program Participant and Faculty Guidelines
          • Faculty Development Program
        • Exhibitors
          • Exhibitor Central
          • Exhibitor Portal Information
          • Exhibitor Prospectus
          • New Exhibiting Companies
          • Exhibitor Resources
          • International Exhibitors
          • Promotional Opportunities
          • Exhibitor Hotel Reservations
      • Mid-Year Forum
        • Registration and Travel
        • Congressional Advocacy Day
        • Advocacy Ambassador Program
        • Program
        • Schedule
        • Sponsored Attendees
        • News
      • Codequest
        • Codequest Instructors
        • Claim Codequest CME or CEU Credit
      • Eyecelerator
    • Clinical Education
      • COVID-19
      • Education
        • Browse All Education
        • Courses
        • Cases
        • Learning Plans
        • Interactive
        • Focal Points
        • Wills Eye Manual
        • Disease Reviews
        • Clinical Webinars
        • Diagnose This
        • Self-Assessments
        • Educational Centers
          • Glaucoma Education Center
          • Pediatric Ophthalmology Education Center
          • Laser Surgery Education Center
          • Myopia Resources
          • Oculofacial Plastic Surgery Center
          • Redmond Ethics Center
      • Journals
      • Guidelines
        • Browse All Practice Guidelines
        • Preferred Practice Patterns
        • Clinical Statements
        • Compendium Guidelines
        • Complementary Therapy Assessments
        • Medical Information Technology
        • Ophthalmic Technology Assessments
        • Patient Safety Statements
        • Choosing Wisely
        • Low Vision
        • Eye Care for Older Adults
        • Eye Disease Statistics
        • About the Hoskins Center
      • Video and Image Library
        • Browse All Videos
        • Clinical and Surgical Videos
        • Presentations and Lectures
        • 1-Minute Videos
        • Master Class Videos
        • Basic Skills Videos
        • Interviews
        • Images
        • Submit an Image
        • Submit a Video
      • Podcasts
        • Browse All Audio and Podcasts
        • Experts InSight
        • Ophthalmology Journal
      • News
        • Browse All Clinical News
        • Editors' Choice
        • Headlines
        • Current Insight
      • CME Central
        • Browse All CME Activities
        • Claim CME Credit and View Transcript
        • CME Planning Resources
        • Complete Your Financial Disclosure
        • Joint Sponsorship Portal
        • LEO Continuing Education Recognition Award
        • Safe ER/LA Opioid Prescribing
        • Check Your Industry Payment Records
      • MOC
      • Resident Education
        • Resident Education Home
        • Browse All Resident Content
          • Courses
          • Flashcards
          • Interactive Cases and Simulations
          • Videos
          • Webinars
        • OKAP and Board Exam Resources
          • OKAP Exam
          • Board Prep Resources
          • OKAP and Board Review Presentations
          • Study Flashcards
        • Cataract Master
        • Diversity and Inclusion Education
        • News and Advice from YO Info
        • Pediatric Ophthalmology Education Center
        • PGY-1 and PGY-2 Resources
        • Simulation in Resident Education
    • Membership
      • Join
      • Renew
      • Current Member
      • Volunteer
      • Physician Wellness
      • Member Directory
      • Member Obituaries
      • AAOE Membership
    • Advocacy
      • Advocacy News
      • Get Involved
        • Ways to Give
        • How to Get Involved
        • Congressional Advocacy
        • Support the Academy's Agenda
        • Research Legislation
        • Find Your Legislators
        • I Am an Advocate
        • Advocacy at Home
        • Advocate Tools
        • Best Practices for Advocating at Home
        • Social Media Toolkit
        • Letter to Editor
        • Town Hall Guide
        • Guide to Engaging With New Lawmakers
        • Resources
        • Attending a Political Fundraiser
      • OPHTHPAC
        • About Us
        • Join OPHTHPAC
        • OPHTHPAC Blog
      • Surgical Scope Fund
        • Support Surgery By Surgeons
        • Surgery By Surgeons Blog
    • Publications
      • EyeNet Magazine
        • Latest Issue
        • Archive
        • Subscribe
        • Advertise
        • Write For Us
        • Corporate Lunches
        • Contact
        • MIPS 2022
      • Focal Points
      • Ophthalmology
      • Ophthalmology Glaucoma
      • Ophthalmology Retina
      • YO Info
      • Scope
    • Subspecialties
      • Cataract/Anterior Segment
      • Comprehensive Ophthalmology
      • Cornea/External Disease
      • Glaucoma
      • Neuro-Ophthalmology/Orbit
      • Ocular Pathology/Oncology
      • Oculoplastics/Orbit
      • Pediatric Ophthalmology/Strabismus
      • Refractive Management/Intervention
      • Retina/Vitreous
      • Uveitis
    • IRIS Registry
      • About
      • Using the Registry
        • User Guide
        • Medicare Reporting
        • Maintenance of Certification
        • Non-EHR Reporting
      • Sign Up
        • Application Process
        • Why Participate
        • Once You've Applied: Getting Started
        • What Practices Are Saying About the Registry
      • Requirements
        • EHR Systems
        • Data & Technical Needs
      • Research
      • Registry Dashboard
      • News
      • Medicare & MIPS
    • Medicare Information
    • Diversity, Equity, and Inclusion
  • For Practice Management
    • Managing Your Practice
      • Managing Your Practice Topics
      • Coronavirus Resources
      • Reopening & Recovery
      • Practice Forms Library
      • Practice Management News and Advice
      • AAOE-Talk
      • Video Library
      • Ophthalmology Job Center
      • Benchmarking and Salary Tools
      • Academy Consultations
      • Consultant Directory
    • Coding
      • Coding Topics
      • Codequest Events
      • Ask the Coding Experts
      • Coding Updates and Resources
      • Coding for Injectable Drugs
      • EM Documentation
      • ICD-10-CM
      • Ophthalmic Coding Specialist (OCS) Exam
      • Retina
      • Savvy Coder
    • Webinars and Events
      • Annual Meeting
      • Codequest Courses
      • Mid-Year Forum
      • Webinar Recordings
    • IRIS Registry
      • Merit-Based Incentive Payment
    • Medicare and MIPS
      • MIPS
        • Quality
        • Promoting Interoperability
        • Improvement Activities
        • Cost
        • Avoid a Penalty
      • Resources
      • Medicare Participation Options
      • Medicare Advantage Plans
      • New Medicare Card
      • Provider Enrollment, Chain and Ownership System (PECOS)
    • Regulatory Compliance
      • HIPPA Resources
      • Office of Inspector General
      • Audits
      • OSHA
    • AAOE Membership
      • Join AAOE
      • Membership Benefits
      • Renew/Pay Dues
    • About AAOE
      • AAOE Board of Directors
      • AAOE Content Committee
      • Volunteer Opportunities
  • For Public & Patients
    • Eye Health A-Z
    • Symptoms
    • Glasses & Contacts
    • Tips & Prevention
    • News
    • Ask an Ophthalmologist
    • Patient Stories
    • No Cost Eye Exams
    • Español
      • A - Z de Salud Ocular
      • Síntomas
      • Anteojos y Lentes de Contacto
      • Consejos y Prevención
      • Noticias
      • Relatos de Pacientes
      • Exámenes de la vista sin costo
      • English
  • AAO 2022
    • Meeting Information
      • Past and Future Meetings
      • Mobile Meeting Guide
      • Contact Information
      • Annual Meeting News
      • Health and Safety
      • Policies and Disclaimers
    • Program
      • Program Highlights
      • Subspecialty Day
      • Virtual Meeting
      • Program Committees
      • CME
      • Meeting Archives
    • Expo
    • Registration
    • Hotels & Travel
      • Hotel Reservation Information
      • Chicago
      • International Attendees
      • Hotel Meeting Space
    • Presenter Central
      • Presenter Central
      • Abstract Selection Process
      • Submission Policies
      • Subject Classification/Topics
      • Instruction Courses and Skills Transfer Labs
      • Papers and Posters
      • Videos
      • Grand Rounds Symposium
      • Program Participant and Faculty Guidelines
      • Faculty Development Program
    • Exhibitors
      • Exhibitor Central
      • Exhibitor Portal Information
      • Exhibitor Prospectus
      • New Exhibiting Companies
      • Exhibitor Resources
      • International Exhibitors
      • Promotional Opportunities
      • Exhibitor Hotel Reservations
  • About
    • Who We Are
      • What We Do
      • About Ophthalmology
      • The Eye Care Team
      • Ethics and the Academy
      • History
      • Museum of Vision
      • Values
    • Governance
      • Council
      • Board of Trustees
      • Committees
      • Academy Past Presidents
      • Secretariats
      • Elections
      • Academy Blog
      • Academy Staff Leadership
    • Leadership Development
    • Awards
      • Laureate Recognition Award
      • Outstanding Advocate Award
      • Outstanding Humanitarian Service Award
      • International Blindness Prevention Award
      • Distinguished Service Award
      • Guests of Honor
      • Secretariat Award
      • Straatsma Award
      • Achievement Award Program
      • Artemis Award
      • EnergEYES Award
      • International Education Award
      • International Scholar Award
      • Commitment to Advocacy Award
      • Visionary Society Award
    • Financial Relationships
    • Policy Statements
    • Related Organizations
      • Subspecialty/Specialized Interest Society Directory
      • State Society Directory
      • Subspecialty/Specialized Interest Society Meetings
      • State Society Meetings
      • Resources for Societies
    • Year in Review
      • 2020 Year in Review
  • Foundation
    • About
      • 2020-2021 Annual Report
      • Annual Report Archives
      • News From the Chair
      • Foundation Staff
    • Our Impact
      • Partners for Sight
      • Donor Spotlights
      • Global Ophthalmic Community
      • Sponsorships
      • Patients and the Public
    • Giving Options
      • Our Supporters
      • Estate and Planned Giving
      • Ophthalmic Business Council
      • Parke Center Campaign
      • Minority Ophthalmology Mentoring Campaign
      • Museum of the Eye Campaign
    • Orbital Gala
      • Why Attend
      • Photo Recap
      • Corporate Support Opportunities
      • Tribute Gifts
      • Silent Auction
      • Corporate Sponsors
    • Donate
    • Museum of the Eye Campaign
      • Museum Supporters
  • Museum of the Eye
    • Visit
    • What's On
      • Museum Galleries
      • Special Exhibitions
      • Current Events
      • Past Events
    • Explore
      • Research and Resources
      • Collection Search
      • Previous Exhibits
      • Oral Histories
      • Biographies
    • Volunteer
    • Mailing List
    • Donate
    • About the Museum
      • Museum Blog
  • Young Ophthalmologists
    • YO Info
    • Learn to Bill
    • Engage with the Academy
  • Senior Ophthalmologists
    • Scope
    • Practice Transitions
  • International Ophthalmologists
    • Global Programs and Resources for National Societies
    • Awards
    • Global Outreach
  • Residents
  • Medical Students
×
Shop
Log In Create an Account
  • For Ophthalmologists
  • For Practice Management
  • For Public & Patients
  • Coronavirus
  • About
  • Foundation
  • Museum of the Eye
  • COVID-19
  • Journals
  • Education
    • Education
    • Courses
    • Cases
    • Learning Plans
    • Interactive
    • Focal Points
    • Wills Eye Manual
    • Disease Reviews
    • Clinical Webinars
    • Diagnose This
    • Self-Assessments
    • Education Centers
      • Glaucoma Education Center
      • Pediatric Ophthalmology Education Center
      • Laser Surgery Education Center
      • Oculofacial Plastic Surgery Center
      • Redmond Ethics Center
      • Myopia Resources
      • Thyroid Eye Disease Resources
  • Guidelines
    • Practice Guidelines
    • Preferred Practice Patterns
    • Clinical Statements
    • Ophthalmic Technology Assessments
    • Patient Safety Statements
    • Complementary Therapy Assessments
    • Compendium Guidelines
    • Medical Information Technology
    • Low Vision
    • Choosing Wisely
    • Eye Care for Older Adults
    • Eye Disease Statistics
    • About the Hoskins Center
    • Artificial Intelligence
    • Premium IOLs
    • Patient-Reported Outcomes with LASIK Symptoms and Satisfaction
  • Multimedia
    • Multimedia Library
    • Video
      • 1-Minute Videos
      • Presentations and Lectures
      • Master Class Videos
      • Basic Skills Videos
      • Clinical and Surgical Videos
      • Interviews
      • Resident Lectures
      • Submit a Video
      • YO Video Contest
    • Podcasts
      • Browse Podcast Archive
      • Experts InSight Podcast
      • Ophthalmology Journal Podcast
    • Images
      • Submit an Image
  • News
    • Clinical News
    • Editors' Choice
    • Headlines
    • Current Insight
  • CME
    • CME Central
    • Claim CME Credit and View Transcript
    • CME Planning Resources
    • Complete Your Financial Disclosure
    • Joint Sponsorship Portal
    • LEO Continuing Education Recognition Award
    • Safe ER/LA Opioid Prescribing
    • Check Your Industry Payment Records
  • MOC
  • Residents
    • Resident Education Home
    • Browse All Resident Content
      • Courses
      • Flashcards and Study Presentations
      • Interactive Cases and Simulations
      • Videos
      • Webinars
    • Cataract Master
    • Diversity and Inclusion Education
    • News and Advice from YO Info
    • OKAP and Board Exam Resources
      • OKAP Exam
      • Board Prep Resources
      • OKAP and Board Review Presentations
      • Study Flashcards
    • Pediatric Ophthalmology Education Center
    • PGY-1 and PGY-2 Resources
    • Resident Knowledge Exchange
    • Simulation in Resident Education
    • Clinical Education /
    • Book Excerpts /
    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    8 External Disease and Cornea

    Chapter 10: Infectious Diseases of the External Eye: Microbial and Parasitic Infections

    Microbial and Parasitic Infections of the Cornea and Sclera

    Primary Infectious Keratitis

    Contact lens–related infectious keratitis

    In the United States, the most frequent risk factor for bacterial keratitis is contact lens wear, which has been identified in 19%–42% of patients with culture-proven microbial keratitis and accounts for up to one-third of emergency department visits for corneal infection. Epidemiologic studies in Australia have estimated the annual incidence of cosmetic contact lens–related ulcerative keratitis at 0.21% for individuals using extended-wear soft lenses and 0.02% for patients using daily-wear soft lenses; this incidence is unaltered by the use of newer lens materials or variation in hygiene practices. The risk of corneal infection is increased nearly tenfold in contact lens wearers; it is even higher in patients who wear their contact lenses overnight, and it is positively correlated with the number of consecutive days that lenses are worn without removal.

    PATHOGENESIS

    Contact lens wear predisposes the cornea to infection through a number of mechanisms, including introduction of a contaminated foreign body to the corneal surface; interruption of the normal tear flow, which is essential to corneal immunity; induction of corneal epithelial microtrauma; alteration of ocular surface immunity; and induction of corneal hypoxia. Various hygiene-related factors increase the risk of both infectious and noninfectious corneal inflammatory events. See BCSC Section 3, Clinical Optics, for further discussion of noninfectious contact lens–related disease.

    MANAGEMENT

    Eliciting a history of contact lens wear is critical in the evaluation of corneal inflammation, and a history of lens wear should raise the suspicion of corneal infection. Bacteria are both the most common pathogen and the most immediate threat to vision. Therefore, unless otherwise indicated, initial management should provide coverage for the most common bacterial pathogen in contact lens–related keratitis, P aeruginosa, as is done in empiric therapy for bacterial keratitis unrelated to contact lens wear. Acanthamoeba and fungal pathogens should be suspected if the clinical presentation or clinical course is atypical.

    Cortina MS, Tu EY. Antibiotic use in corneal and external eye infections. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2011, module 6.

    Bacterial keratitis

    Bacterial infection of the eye is a common sight-threatening condition. Some cases have explosive onset and rapidly progressive stromal inflammation. Untreated, it often leads to progressive tissue destruction with corneal perforation or extension of infection to adjacent tissue. Bacterial keratitis is frequently associated with risk factors that disturb the corneal epithelial integrity. Common predisposing factors include

    • contact lens wear (see the section “Contact lens–related infectious keratitis”)

    • trauma

    • contaminated ocular medications

    • impaired defense mechanisms

    • altered structure of the corneal surface

    PATHOGENESIS

    Although bacterial keratitis restricted to the epithelial layer only has been reported, corneal pathogens generally must first adhere to the cornea and then invade and proliferate in the corneal stroma. Certain risk factors will often select for specific pathogens, based on their particular mechanism of adherence. For example, P aeruginosa becomes more pathogenic in lens-related biofilms, in turn enabling enhanced binding to molecular receptors exposed on injured epithelial cells. Once adherent, bacteria will proliferate and invade the corneal stroma, often with the aid of bacteria-specific proteases. Reactive host inflammation begins with the expression of various cytokines and chemokines, recruitment of inflammatory cells from the tears and limbal vessels, and subsequent secretion of matrix metalloproteinases leading to characteristic corneal necrosis. Reduction of bacterial loads and, potentially, direct control of the inflammatory response may reduce keratolysis. See BCSC Section 1, Update on General Medicine, for further discussion.

    CLINICAL PRESENTATION

    Rapid onset of pain is accompanied by conjunctival injection, photophobia, and decreased vision in patients with bacterial corneal ulcers. The rate of progression of these symptoms depends on the virulence of the infecting organism. Bacterial corneal ulcers are typically a single infiltrate and show a sharp epithelial demarcation with underlying dense, suppurative stromal inflammation that has indistinct edges and is surrounded by edema. P aeruginosa typically causes stromal necrosis with a shaggy surface and adherent mucopurulent exudate (Fig 10-15). An endothelial inflammatory plaque, marked anterior chamber reaction, and hypopyon frequently occur.

    Figure 10-15 Suppurative ulcerative keratitis caused by P aeruginosa.

    Patients with infections caused by slow-growing, fastidious organisms such as mycobacteria or anaerobes may have a nonsuppurative infiltrate and intact epithelium. Infectious crystalline keratopathy, for example, presents as densely packed, white, branching aggregates of organisms in the virtual absence of a host inflammatory response, shielded by the bacterial biofilm coating. Risk factors include corticosteroid use, contact lens wear, and previous corneal surgery. Infectious crystalline keratopathy has been reported with a number of bacterial and fungal species, most commonly α-hemolytic Streptococcus species (Fig 10-16).

    LABORATORY EVALUATION

    The prevalence of a particular causative organism depends on the geographic location and risk factors for the infection. Causative organisms in bacterial keratitis are listed in Table 10-5.

    Studies indicate that for bacterial keratitis, clinical appearance of the infection is an unreliable guide in determining the causative pathogen. The successful use of topical fluoroquinolones in the 1990s led to a reduction in the number of cultures performed for cases of presumed infectious keratitis. The American Academy of Ophthalmology practice guidelines continue to recommend that initial cultures be obtained for infiltrates extending to the middle of the cornea, into deep stroma, or across a large area (>2 mm), as well as for patients whose history or clinical features suggest fungal, amebic, mycobacterial, or drug-resistant organisms as the causative agents. In addition to corneal culture, it may be helpful to culture contact lenses, contact lens cases and solutions, and any other potential sources of contamination, such as inflamed eyelids. Some correlation has been shown between cultures of such sources and corneal scrapings.

    Figure 10-16 Infectious crystalline keratopathy in a corneal graft caused by α-hemolytic Streptococcus species.

    Table 10-5 Causes of Bacterial Keratitis

    The yield for corneal cultures and smears is significantly higher before the initiation of antibiotic treatment, but cases unresponsive to such therapy should still be cultured, with some suggesting discontinuation of antibiotics for 12–24 hours to encourage yield. However, a positive smear result at any point does not obviate the need for broad-spectrum coverage, although it may cause coverage to be weighted toward a different class of microorganism and/or provide guidance for later treatment in the absence of a positive culture. (See Chapter 9 in this volume and BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors, for discussion of specimen collection, culturing, staining, and interpretation.)

    MANAGEMENT

    In any keratitis, the primary goal of therapy is preservation of sight and corneal clarity. Bacterial pathogens can produce irreversible corneal scarring over a period of hours because of their rapid growth, keratolytic enzymes, and stimulation of destructive host immune responses. Therefore, therapy must be initiated before definitive diagnosis is obtained in order to rapidly reduce the bacterial load and minimize later visual disability.

    Initial therapy consists of empiric, broad-spectrum topical antibiotics. In routine corneal ulcers, monotherapy with topical fluoroquinolones provides outcomes equivalent to those of combination therapy, because of the excellent penetration achieved with commercially available concentrations of fluoroquinolones. These antibiotics should initially be given every 30–60 minutes and then tapered in frequency according to the clinical response. In severe cases, administration of antibiotics every 5 minutes for 30 minutes as a loading dose can more rapidly achieve therapeutic concentrations in the corneal stroma. Second-generation fluoroquinolones (ciprofloxacin, ofloxacin) continue to have excellent Pseudomonas coverage but lack useful gram-positive activity. Third- and fourth-generation fluoroquinolones (eg, moxifloxacin, gatifloxacin, levofloxacin, and besifloxacin) have improved gram-positive and atypical mycobacterial coverage but limited activity against MRSA.

    Alternatively, topical combination therapy with an agent active against gram-positive bacteria and another agent active against gram-negative bacteria can be used as initial therapy (Table 10-6). Although “fortified” antibiotics (compounded at increased concentrations compared with their commercial formulations in order to achieve therapeutic levels in the corneal stroma) are more difficult to obtain and may have a greater toxic effect on the ocular surface, the clinician should consider using them, especially in combination with vancomycin for gram-positive coverage when MRSA is suspected, with large or vision-threatening ulcers, or with prior antibiotic failure. Effectively treated, most infectious keratitis is culture negative after 48–72 hours. Once the offending microbe is identified or the clinical response shows improvement, appropriate monotherapy may be considered (see Table 10-6) to maintain coverage and reduce toxicity. However, laboratory sensitivities are based on antibiotic tissue levels achievable by systemic administration, and the levels achieved by topical administration are much higher. Often, a bacterial keratitis will respond in vivo even when in vitro data suggest resistance. Any changes in medical therapy should therefore be based primarily on clinical response. Several clinical parameters are useful for monitoring clinical response to antibiotic therapy:

    Table 10-6 Initial Therapy for Bacterial Keratitis

    • blunting of the perimeter of the stromal infiltrate

    • decreased density of the stromal infiltrate

    • reduction of stromal edema and endothelial inflammatory plaque

    • reduction in anterior chamber inflammation

    • reepithelialization

    • cessation of corneal thinning

    Systemic antibiotics—especially the fluoroquinolones, which have excellent ocular penetration—and intensive topical antibiotics are indicated in cases with suspected scleral and/or intraocular extension of infection.

    The role of corticosteroid therapy for bacterial keratitis remains controversial. Tissue destruction results from a combination of the direct effects of the bacteria and an exuberant host inflammatory response consisting of polymorphonuclear leukocytes and proteolytic enzymes, which predominate even after corneal sterilization. Corticosteroids are effective at modifying this response, but they also inhibit the host response to infection. The literature strongly suggests that corticosteroid therapy administered prior to appropriate antibiotic therapy worsens prognosis. The literature is inconclusive, though, about steroid therapy used concomitantly with antibiotic therapy or after it is initiated, as demonstrated in a randomized clinical trial in which topical corticosteroids were given 48 hours after initiation of topical antibiotics for bacterial keratitis. At 3 months, no effect on final visual outcome or complication rate was seen, but a trend toward improved outcomes was noted in those patients with the worst initial vision who received corticosteroids and for the corticosteroid group at 1-year follow-up. Notably in this study, Nocardia keratitis, which is uncommon in the United States, fared worse with corticosteroid treatment.

    The indiscriminate or universal use of corticosteroids is, therefore, unsupported but does not appear to increase the general risk of poor outcomes or complications in treated bacterial keratitis. In fact, certain patients may benefit from the addition of corticosteroids to antibiotic therapy. Future study of the appropriate timing and dosage may further refine the indications for corticosteroid use. As there is still significant risk associated with corticosteroid use in patients with bacterial or other forms of infectious keratitis not appropriately treated, following are recommended criteria for instituting corticosteroid therapy for bacterial keratitis:

    • Corticosteroids should not be used in the absence of appropriate antibiotic therapy.

    • The patient must be able to return for frequent follow-up examinations and demonstrate adherence to appropriate antibiotic therapy.

    • No other associated virulent or difficult-to-eradicate organism is found or suspected.

    Corticosteroid drops may be started in moderate dosages (prednisolone acetate or phosphate 1% every 6 hours), and the patient should be monitored at 24 and 48 hours after initiation of therapy. If the patient shows no adverse effects, the frequency of administration may be adjusted based on clinical response. Collagen crosslinking is increasingly used as an adjunctive therapy for bacterial keratitis, with anecdotal success; as this technology becomes more available in the United States, its precise role and application are evolving.

    Penetrating keratoplasty (PK) for treatment of bacterial keratitis is indicated if the disease progresses despite therapy, descemetocele formation or perforation occurs, or the keratitis is unresponsive to antimicrobial therapy. The involved area should be identified preoperatively and an attempt made to circumscribe all areas of infection. Peripheral iridectomies are indicated, because seclusion of the pupil may develop from inflammatory pupillary membranes. Interrupted sutures are recommended. The patient should be treated with appropriate antibiotics, cycloplegics, and intense topical corticosteroids postoperatively. See Chapter 15 in this volume for a more detailed discussion of PK and BCSC Section 2, Fundamentals and Principles of Ophthalmology, for an in-depth discussion of ocular pharmacology.

    American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. Bacterial Keratitis. San Francisco: American Academy of Ophthalmology; 2013. Available at www.aao.org/ppp.

    Price MO, Tenkman LR, Schrier A, Fairchild KM, Trokel SL, Price FW Jr. Photoactivated riboflavin treatment of infectious keratitis using collagen cross-linking technology. J Refract Surg. 2012;28(10):706–713.

    Schein OD, Glynn RJ, Poggio EC, Seddon JM, Kenyon KR. The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. A case-control study. Microbial Keratitis Study Group. N Engl J Med. 1989;321(12):773–778.

    Srinivasan M, Mascarenhas J, Rajaraman R; Steroids for Corneal Ulcers Trial Group. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol. 2012;130(2):143–150.

    Srinivasan M, Mascarenhas J, Rajaraman R; Steroids for Corneal Ulcers Trial Group. The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial. Am J Ophthalmol. 2014;157(2):327–333.

    Atypical mycobacteria

    Atypical mycobacteria are important pathogens in infections following laser in situ keratomileusis (LASIK) (Fig 10-17). The most common pathogens are Mycobacterium fortuitum and Mycobacterium chelonae, which may be found in soil and water. These organisms should be suspected in delayed-onset postrefractive infections, classically with recalcitrant, nonsuppurative infiltrates. The diagnosis may be confirmed with acid-fast stain or culture on Löwenstein-Jensen medium. Medical treatment options include oral and topical clarithromycin, amikacin, linezolid, and the fluoroquinolones with antimycobacterial activity, including moxifloxacin, besifloxacin, and gatifloxacin.

    Figure 10-17 Atypical mycobacterial infection following laser in situ keratomileusis (LASIK).

    (Courtesy of Elmer Y. Tu, MD.)

    Chang MA, Jain S, Azar DT. Infections following laser in situ keratomileusis: an integration of the published literature. Surv Ophthalmol. 2004;49(3):269–280.

    Hyon JY, Joo MJ, Hose S, Sinha D, Dick JD, O’Brien TP. Comparative efficacy of topical gatifloxacin with ciprofloxacin, amikacin, and clarithromycin in the treatment of experimental Mycobacterium chelonae keratitis. Arch Ophthalmol. 2004;122(8):1166–1169.

    Fungal keratitis

    PATHOGENESIS

    Fungal keratitis is less common than bacterial keratitis, generally representing less than 5%–10% of corneal infections in reported clinical series in the United States. Filamentous fungal keratitis occurs more frequently in warmer, more humid parts of the United States than in other regions of the country. Trauma to the cornea with plant or vegetable material is the leading risk factor for fungal keratitis. Contact lens wear has emerged as another risk factor for the development of fungal keratitis. Topical corticosteroids are a major risk factor as well, as they appear to activate and increase the virulence of fungal organisms in part by reducing the cornea’s resistance to infection. Candida species cause ocular infections in immunocompromised hosts and in corneas with chronic erosions/ulceration from other causes. Systemic corticosteroid and immunosuppressant use in these patients may suppress the host immune response, thereby predisposing to fungal keratitis. Other common risk factors include corneal surgery (eg, PK, radial keratotomy) and chronic keratitis (eg, herpes simplex virus, herpes zoster, or vernal/allergic conjunctivitis).

    In early 2006, an outbreak of contact lens–associated Fusarium keratitis was observed, first in Singapore and the Pacific Rim and then in the United States. The epidemic occurred in association with the use of Renu with MoistureLoc solution (Bausch + Lomb, Rochester, NY). Bausch + Lomb withdrew the solution from the world market on May 15, 2006, with a subsequent steep decline in Fusarium cases across the United States.

    Chang DC, Grant GB, O’Donnell K, et al; Fusarium Keratitis Investigation Team. Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution. JAMA. 2006; 296(8):953–963.

    CLINICAL PRESENTATION

    Patients with fungal keratitis tend to have fewer inflammatory signs and symptoms during the initial period than those with bacterial keratitis and may have little or no conjunctival injection upon initial presentation. On the other hand, pain in fungal keratitis can be out of proportion to the relatively uninflamed cornea. Filamentous fungal keratitis frequently manifests as a gray-white, dry-appearing infiltrate that has irregular feathery or filamentous margins (Fig 10-18). Superficial lesions may appear gray-white; elevate the surface of the cornea; and have a dry, rough, or gritty texture detectable at the time of diagnostic corneal scraping. Occasionally, multifocal or satellite infiltrates may be present, although these are less common than previously reported. In addition, a deep stromal infiltrate may occur in the presence of an intact epithelium. An endothelial plaque and/or hypopyon may also occur if the fungal infiltrate(s) is sufficiently deep or large or has penetrated into the anterior chamber.

    As the keratitis progresses, intense suppuration may develop, and the lesions may resemble those of bacterial keratitis. At this point, rapidly progressive hypopyon and anterior chamber inflammatory membranes may develop. Extension of fungal infection into the anterior chamber is often a cause of rapidly progressive anterior chamber inflammation. Occasionally, fungus may invade the iris or posterior chamber, and angle-closure glaucoma may develop from inflammatory pupillary block.

    Yeast keratitis is most frequently caused by Candida species. This form of fungal keratitis frequently presents with superficial white, raised colonies in a structurally altered eye. Although most cases tend to remain superficial, deep invasion may occur with suppuration resembling keratitis induced by gram-positive bacteria.

    Figure 10-18 Fungal keratitis caused by F solani with characteristic dry-appearing, white stromal infiltrate with feathery edges.

    LABORATORY EVALUATION

    The fungal cell wall stains with Gomori methenamine silver but, except for Candida, does not take up Gram stain. Blood agar, Sabouraud dextrose agar, and brain–heart infusion agar are the preferred media for fungal culture. Because of progressive enhancements to in vitro antifungal sensitivity testing, these tests are better correlated with clinical outcomes for fungal keratitis and should be pursued. Confocal microscopy is very useful in detecting branching filaments in the cornea, as well as the individual septa found in the majority of corneal mold pathogens.

    MANAGEMENT

    Natamycin 5% suspension is recommended for the treatment of most cases of filamentous fungal keratitis, particularly those caused by Fusarium species, which are the most common causative agents for exogenous fungal keratitis occurring in the humid areas of the southern United States. Most clinical and experimental evidence suggests that topical amphotericin B (0.15%–0.30%) is the most efficacious agent available to treat yeast keratitis; most corneal yeast infections respond readily to the drug. Amphotericin B is also recommended for filamentous keratitis caused by Aspergillus species. Topical voriconazole 1% is increasingly utilized and has been effective in treating some cases of fungal keratitis unresponsive to other therapy; however, significant resistance has been reported, and a recent prospective, randomized clinical trial concluded that this agent is inferior to natamycin for empiric therapy, especially for F solani.

    Systemic administration may be considered for treatment of more severe keratitis or keratitis with intracameral extension. The use of older azoles, including ketoconazole (200–600 mg/day), fluconazole (200–400 mg/day), and itraconazole (200 mg/day), for this purpose has been described. Oral voriconazole (200–400 mg/day) and posaconazole (800 mg/day) are rapidly replacing other oral antifungals because of their excellent intraocular penetration and broader spectrum of coverage. Alternatively, intrastromal administration of aqueous-soluble amphotericin B (5–10 μg/0.1 cc) or voriconazole (50–100 μg/0.1 cc) as primary or secondary treatment of deep fungal keratitis, and intracameral injection of either agent for intraocular extension are becoming more widely validated. Unresponsive cases of culture-proven or histologically proven fungal keratitis require definitive speciation of the pathogen as well as antifungal sensitivity testing. As classic morphologic identification is often inaccurate, a look-alike species or P insidiosum (discussed earlier) can be suspected in these cases. Collagen crosslinking has been investigated as an adjunctive therapy for fungal keratitis; it appears to have no role in deeper stromal disease and achieves mixed results in superficial fungal infections.

    When the smear result is negative and fungal infection is suspected, repeated scrapings or biopsy may be necessary to identify fungal material. Furthermore, mechanical debridement may be beneficial for cases of superficial fungal keratitis. Fungal infiltration of the deep corneal stroma may not respond to topical antifungal therapy, because the penetration of these agents is reduced in the presence of an intact epithelium. Penetration of natamycin or amphotericin B has been shown to be significantly enhanced by debridement of the corneal epithelium, and animal experiments indicate that frequent topical application (every 5 min) for 1 hour can readily achieve therapeutic levels. Cases with progressive disease despite maximal topical and/or oral antifungal therapy may require therapeutic PK to prevent scleral or intraocular extension of the fungal infection. Both of these latter conditions carry a very poor prognosis for salvaging the eye.

    Bunya VY, Hammersmith KM, Rapuano CJ, Ayres BD, Cohen EJ. Topical and oral voriconazole in the treatment of fungal keratitis. Am J Ophthalmol. 2007;143(1):151–153.

    Loh AR, Hong K, Lee S, Mannis M, Acharya NR. Practice patterns in the management of fungal corneal ulcers. Cornea. 2009;28(8):856–859.

    Prajna NV, Krishnan T, Mascarenhas J; Mycotic Ulcer Treatment Trial Group. The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol. 2013;131(4):422–429.

    Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

  • Most Commented
    Loading, please wait...
    There are no comments available.
    Most Viewed
    Loading, please wait...
    Most Viewed content is not available.
  • The Academy Store
    2022-2023 Basic and Clinical Science Course, Complete Print Set
    2022-2023 Basic and Clinical Science Course, Complete eBook Set
    2022-2023 Basic and Clinical Science Course, Complete Print and eBook Set
    2022-2023 Basic and Clinical Science Course, Residency Print Set
    2022-2023 Basic and Clinical Science Course, Residency eBook Set
    2022-2023 Basic and Clinical Science Course Complete Set
    2022-2023 Basic and Clinical Science Course Residency Set
    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
    2022-2023 Basic and Clinical Science Course, Section 02: Fundamentals and Principles of Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision Rehabilitation
    2022-2023 Basic and Clinical Science Course, Section 04: Ophthalmic Pathology and Intraocular Tumors
    2022-2023 Basic and Clinical Science Course, Section 05: Neuro-Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 06: Pediatric Ophthalmology and Strabismus
    2022-2023 Basic and Clinical Science Course, Section 07: Oculofacial Plastic and Orbital Surgery
    2022-2023 Basic and Clinical Science Course, Section 08: External Disease and Cornea
    2022-2023 Basic and Clinical Science Course, Section 09: Uveitis and Ocular Inflammation
    2022-2023 Basic and Clinical Science Course, Section 10: Glaucoma
    2022-2023 Basic and Clinical Science Course, Section 11: Lens and Cataract
    2022-2023 Basic and Clinical Science Course, Section 12: Retina and Vitreous
    2022-2023 Basic and Clinical Science Course, Section 13: Refractive Surgery
    The Technician Point System: How to Improve Practice Accountability and Bottom Line (Free Member Webinar)
    Transitioning Your Practice: Retiring, Selling or Buying a Practice (Free Member Webinar)
    2022 IRIS Registry (Intelligent Research in Sight) Preparation Kit
    Advances in Medical and Surgical Management: The 2022 Update on Glaucoma
    Presbyopia-Correcting IOLs
    2022 Codequest - Multistate (Recorded March 29)
    2022 Codequest Virtual (Multistate)
    Retina Patient Education Video Collection
    Cataract and Refractive Surgery Patient Education Video Collection
    Glaucoma Patient Education Video Collection
 
  • Contact Us
  • About the Academy
  • Jobs at the Academy
  • Financial Relationships with Industry
  • Medical Disclaimer
  • Privacy Policy
  • Terms of Service
  • Help
  • For Advertisers
  • For Media
  • Ophthalmology Job Center

OUR SITES

  • EyeWiki
  • International Society of Refractive Surgery

FOLLOW THE ACADEMY

Medical Professionals

  • Facebook
  • Twitter
  • LinkedIn
  • YouTube

Public & Patients

  • Facebook
  • Twitter
  • Instagram
  • YouTube

Museum of the Eye

  • Facebook
  • Twitter
  • Instagram
  • YouTube
  • Trip Advisor
  • Yelp
© American Academy of Ophthalmology 2022