Infectious Keratitis


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By Dr. Noel Rosado

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  • ,with estimated costs of US$50 million in annual expenditures for medical care of this condition.
  • These natural defenses include the eyelid, tear film, corneal epithelium, and normal ocular flora.
  • and they depend on the virulence of the organism, duration of infection, pre-existing corneal conditions, immune status of the host, and previous use of antibiotics or corticosteroids.
  • such as bullouskeratopathy, chronic herpetic keratitis, keratoconjunctivitissicca, ocular rosacea, or atopic keratoconjunctivitis.
  • Inclusion bodies of Chlamydia by Giemsa stain.
  • Corneal surface irradiance was approximately 3 mW/cm2 for a period of 30min. In all cases [23-25,27-29,34-38], during the induction period, 0.1% riboflavin and 20% dextran T500 drops were topically administered to the cornea for a period of 20 to 30min at intervals of 2 to 3min.
  • Infectious Keratitis

    1. 1. Noel Rosado MD Visionary Ophthalmology September 8, 2013
    2. 2.  Microbial keratitis or infectious corneal ulcer is due to the proliferation of microorganisms (including bacteria, fungi, viruses, and parasites) and associated inflammation and tissue destruction within the cornea.  It is a potentially sight-threatening condition and frequently presents as an ocular emergency.  Bacterial keratitis is the most common cause of suppurative corneal ulceration, which rarely occurs in the normal eye because of the human cornea's natural resistance to infection.
    3. 3.  The accurate incidence of bacterial keratitis is not known.  It is estimated that 30 000 cases of microbial keratitis occur in the USA annually.[  An estimated 10 to 30 individuals per 100 000 contact lens wearers develop microbial keratitis annually in the USA  Bacterial keratitis is one of the leading causes of corneal blindness in developing nations, usually caused by ocular trauma.  Occasionally, severe or refractory bacterial keratitis requires surgery. Statistics from the Eye Bank Association of America demonstrate that approximately 1% of all corneal transplants are performed as a result of microbial keratitis.
    4. 4.  Bacterial keratitis usually occurs in patients with predisposing factors, which can compromise normal ocular surface defenses.  Eyelid trauma or any abnormality of the lid closure can compromise this defense mechanism.  Abnormalities of tear components, tear volume, or tear drainage system are the principal causes of a compromised ocular surface.  Chronic colonization and infection of the eyelid margin or lacrimal outflow system can predispose cornea to bacterial infection when minor trauma occurs.
    5. 5.  An intact corneal epithelium is an important defense factor of the eye.  Compromised corneal epithelial integrity caused by contact lens wear, corneal trauma, or corneal surgery is an important predisposing factor to bacterial ulcers.  Also, inappropriate use of topical antibiotics could eliminate the natural protection by the normal flora and predispose the cornea to the development of opportunistic infections, particularly when combined with corneal disease or trauma.
    6. 6.  Trauma, including chemical and thermal injuries, foreign bodies, and local irradiation can predispose to bacterial keratitis.  Corneal infection can occur from contamination of topical solutions and the tips or caps of eye dropper bottles.  Chronic abuse of topical anesthetics can disrupt the corneal epithelium and render it at risk for microbial infection
    7. 7.  The most common risk factor for bacterial keratitis in developed countries.  All types of contact lenses, including hard, gas-permeable, soft, disposable, and cosmetic lenses, have been implicated in microbial keratitis.  Contact lens users have a 1.5% chance of developing infectious keratitis during a lifetime of contact lens wear.  Three groups of patients have an increased risk of contact lens-related infectious keratitis:  Aphakes  Patients with a corneal transplant  Patients wearing a bandage lens for chronic keratopathy.
    8. 8.  Ocular surface diseases such as cicatricialpemphigoid, Stevens-Johnson syndrome, atopic keratoconjunctivitis, radiation and chemical injury, and vitamin A deficiency can lead to squamousmetaplasia of the ocular surface epithelium and cause an unstable tear film, which can predispose to bacterial infection.  Bacterial keratitis can complicate corneal epithelial erosions associated with corneal epithelial basement membrane dystrophy,lattice corneal dystrophy, and vernal or atopic keratoconjunctivitis
    9. 9.  Bacterial keratitis after corneal transplantation can occur at any time postoperatively.  Postkeratoplasty use of extended wear soft contact lenses has been a major risk factor.  Loose, broken, or exposed sutures can harbor ocular flora and permit an entry site for microbes
    10. 10.  Systemic conditions such as malnutrition, diabetes, collagen vascular diseases, or chronic alcoholism may also compromise the ocular surface and increase the risk of microbial keratitis caused by unusual organisms  In patients with AIDS (acquired immunodeficiency syndrome), microbial keratitis does not appear to be more prevalent than in the normal population.  However, the keratitis tends to be more severe and more resistant to therapy in these patients.
    11. 11.  Clinical signs and symptoms of microbial keratitis are variable.  Severe bacterial keratitis usually has a history of rapid onset of pain, photophobia, decreased vision, conjunctival injection, anterior chamber reaction, and/or hypopyon.  The clinical findings usually cannot readily distinguish the causing organism.  Nonetheless, clinical diagnosis is possible when a pertinent history is available or the organisms present with characteristic features.  However, many microorganisms such as fungi or Acanthamoebacan cause masquerading syndromes mimicking bacterial keratitis.
    12. 12.  Differential diagnosis of bacterial keratitis includes infectious and noninfectious causes of corneal infiltrates.
    13. 13.  Include fungi (both yeast and mold), parasites (including protozoa such as Acanthamoeba), nematodes (such as Onchocerca), and viral infection.
    14. 14.  Viruses including herpes simplex virus (HSV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV) produce immunologically mediated corneal infiltrates that may resemble a bacterial, fungal, or Acanthamoeba keratitis.  Viruses can also cause a true suppurativekeratitis, as in necrotizing stromal disease.
    15. 15.  Collagen vascular disorders (e.g. rheumatoid arthritis, systemic lupus erythematosus), vasculitic disorders (e.g. polyarteritisnodosa, Wegener's granulomatosis), and other inflammatory disorders such as sarcoidosis may produce infiltrative keratitis.
    16. 16.  Other causes include dermatologic disorders (e.g. severe ocular rosacea) and allergic conditions (e.g. vernal and atopic keratoconjunctivitis).
    17. 17.  The purpose of the clinical evaluation is to:  Evaluate predisposing or aggravating factors in order to construct a differential diagnosis,  To assess the severity of the disease and the associated complications  To initiate appropriate management in a timely manner.  Obtaining a detailed history is important and should include ocular symptoms (e.g. degree of pain, redness, discharge, blurred vision, photophobia, duration of symptoms, circumstances surrounding the onset of symptoms) and review of prior ocular history (including previous infectious keratitis, ocular surgery, contact lens wear,trauma, and dry eye)
    18. 18.  Important to document baseline visual acuity  An external examination should be performed with particular attention to the followings:  General appearance of the patient, including skin conditions  Eyelids and lid closure  Conjunctiva  Nasolacrimal apparatus  Corneal sensation (assess prior to instillation of topical anesthetic).
    19. 19.  Eyelid margins (meibomian gland dysfunction, ulceration, eyelash abnormalities including trichiasis, irregularities, nasolacrimal obstructions or punctal anomalies)  Tear film (dry eye or debris)  Conjunctiva (discharge, erythema, follicles, papillae, cicatrization, keratinization, membrane, pseudomembrane, ulceration, scars, foreign bodies)  Sclera (inflammation, ulceration, nodules or ischemia)  Cornea (epithelial defects, punctatekeratopathy, edema, stromal infiltrates, thinning, or perforation).
    20. 20.  The location, density, size, shape, depth, character of infiltrate margin (suppurative, necrotic, feathery, soft, crystalline), and color of the corneal ulcer should be carefully evaluated and documented.  The endothelium and associated anterior chamber inflammation (cell, flare, hypopyon, or fibrin) should not be overlooked.  Fluorescein or rose Bengal staining may provide additional information, such as the presence of dendrites, pseudodendrites, loose or exposed sutures, and epithelial defects.  Attention should also be directed to the contralateral eye for clues to etiology as well as possible similar pathology.
    21. 21.  Clinical features suggestive of bacterial keratitis include suppurativestromal infiltrate (particularly those greater than 1 mm in size) with edema, and white cell infiltration in surrounding stroma.  An epithelial defect is typically present.  An anterior chamber reaction is often seen.
    22. 22.  The corneal ulcer is considered to be severe if  The lesion progresses rapidly  Has an infiltration dimension larger than 6 mm  Involves deeper than one- third of the corneal thickness  Presents with impending or overt perforation  Has scleral involvement.
    23. 23.  Pseuodmonasaeruginosa is the most common Gram-negative pathogen isolated from severe keratitis.  The increasing prevalence of Pseudomonas keratitis in otherwise healthy individuals has been largely associated with the use of soft contact lenses.  Rapid progression, dense stromal infiltrate, marked suppuration, liquefactive necrosis, and descemetocele formation or corneal perforation are the characteristics of this pathogen .  Despite appropriate treatment, the keratitis may progress rapidly into a deep stromal abscess and stromalkeratolysis with perforation may occur.  A corneal ring infiltrate, which is a dense accumulation and aggregation of polymorphonuclear leukocytes, can also be present .
    24. 24.  Staphylococcus, the most common Gram-positive organism, is usually present in normal ocular flora.  Staphylococcus keratitis occurs more frequently in compromised cornea cases.  S. aureus tends to produce a rapidly progressive corneal infiltration and moderate anterior chamber reactions with endothelial plaques or hypopyon.  The corneal lesions usually are round or oval with dense infiltration and a distinct border .  Coagulase-negative staphylococci usually cause opportunistic infection in the compromised cornea. More than 85% of eyelid cultures from the normal population are positive for nonaureus staphylococcus,  The infection tends to progress slowly and the infiltrates are usually superficial, localized with the surrounding cornea clear. However, severe ulcers with dense infiltrates can occur if untreated
    25. 25.  Streptococcus pneumoniae keratitis usually occurs after corneal trauma, dacryocystitis, or filtering bleb infection.  The ulcer tends to be acute, purulent, and rapidly progressive with a deep stromal abscess .  The anterior chamber reaction is usually severe with marked hypopyon and retrocorneal fibrin coagulation.  Perforation secondary to ulcer is common.
    26. 26.  This is a class of rapidy growing and acid- fast mycobacteria.  The most common pathogens are Mycobacterium fortuitumand M. chelonei, which may be found in soil and water.  These organisms tend to cause a slowly progressive keratitis, and usually occur after a corneal foreign body, corneal trauma or following corneal surgery, particularly after LASIK  Keratitis from nontuberculousmycobacteria is often associated with delayed onset of symptoms, and severe ocular pain can develop from 2 to 8 weeks after exposure to the organism.  Infiltrates are typically nonsuppurative and can be solitary or multifocal, with variable anterior chamber reactions.  Delay in diagnosis is common due to the protracted clinical course and difficulty of isolating the organism from culture.
    27. 27.  Include corneal scraping to obtain specimens for microbiological stainings and cultures to isolate the causative organismand determine sensitivity to antibiotics.  The majority of community-acquired cases of bacterial keratitis resolve with empirical therapy and are managed without smears or cultures.  Prior to initiating antimicrobial therapy, smears and cultures are indicated in cases where the corneal infiltrate is central, large, deep, is chronic in nature, or has atypical clinical features suggestive of fungal, amoebic, or mycobacterialkeratitis.  In addition, cultures are helpful to guide modification of therapy in patients with a poor clinical response to empirical treatment and to decrease toxicity by eliminating unnecessary drugs.
    28. 28.  Corneal material is obtained by scraping corneal tissues from the advancing borders of the infected area  Obtaining only purulent material usually results in inadequate yield.  Cultures of contact lenses, lens case, and contact lens solution may provide additional information to guide therapy
    29. 29. Media Common isolates Blood Agar Aerobic and facultative, anaerobic bacteria, including P. aeruginosa, S. aureus, S. epidermidis, S. pneumoniae Chocolate Agar Aerobic and facultative, anaerobic bacteria, including H. influenzae, N. gonorrhoeae, and Bartonella species Thyoglicollate broth Aerobic and facultative, anaerobic bacteria Lowenstein-Jensen medium Mycobacterium species Thayer-Martin agar Pathologic Neisseria Sabouraud's dextrose agar Fungi
    30. 30.  Microbial pathogens may be categorized by examining stained smears of corneal scrapings. Stain Organisms visualized Gram stain Best for bacteria; can also visualize fungi, Acanthamoeba Giemsa stain Bacteria, fungi,Chlamydia, Acanthamo eba Acid fast Mycobacterium, Nocardia Calcofluor white Fungi, Acanthamoeba
    31. 31.  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 suggest strongly an infectious process.  It may also be indicated if the infiltrate is located in the mid or deep stroma with overlying uninvolved tissue that yield little material with scraping.[  Using topical anesthesia, a 2–3-mm circular trephine can be used to outline the area to be biopsied.  Femtosecond laser has been recently used to perform lamellar corneal biopsies  The biopsy may also help ulcer healing by debulking or debridement of necrotic tissue.  An option for a deep corneal abscess may be to use a suture that can be passed through the abscess without disturbing the overlying intact corneal epithelium and stroma.
    32. 32.  Topical antibiotic eye drops are capable of achieving high levels of tissue concentration and are the preferred method of treatment in most cases.  Ointments may be useful adjunctive therapy and for use at bedtime in less severe cases, but may impair the penetration of concomitant topical eye drops.  Subconjunctival antibiotics may be helpful where there is imminent scleral spread or perforation or in cases where compliance with the treatment regimen is questionable.  Systemic antibiotics may be considered in severe cases with scleral or intraocular extension of infection.  Systemic therapy is necessary in cases of gonococcalkeratitis due to its fulminant nature and systemic involvement.
    33. 33.  This approach is based on the pre-existing culture and sensitivity data without specifically obtaining corneal specimens from the patients.  Clinicians use broad-spectrum antibiotics to cover potential causative organisms. Fortified antibiotics such as cefazolin or vancomycin for Gram-positive organisms and tobramycin or ceftazidime for Gram-negative organisms are used.  However, prolonged and nonelective use of these fortified antibiotics may cause ocular discomfort and epithelial toxicity.
    34. 34.  The important breakthrough in this empirical approach is the introduction of fluoroquinolone antibiotics, which have been shown by clinical trials to have an efficacy for common ocular pathogens equivalent to that of the fortified antibiotics.  However, there are potential gaps in the antibacterial spectrum of fluoroquinolonemonotherapy.  In the past, monotherapy with fluoroquinolone was generally recommended for contact lens-related Pseudomonas keratitis; however, increasing emergence of ciprofloxacin-resistant P. aeruginosa has been reported, and this treatment strategy should be exercised with caution.
    35. 35.  In this traditional approach, corneal scrapings for staining and microbiological culture are performed in all cases of microbial keratitisbefore treatment is started.  The initial therapy is based on the clinical and epidemiological information and may be modified according to microbiological results.  These patients are more likely to have severe corneal ulcers or infections caused by atypical pathogens.  The major disadvantage of this approach is the inconvenience and cost.  Cultures from routine corneal scrapings are positive in only 60% of patients.  In addition, discrepancy between in vitro antibiotic sensitivity and clinical response is often encountered.
    36. 36.  Topical antibiotics are used initially in the treatment of bacterial keratitis  For central or severe keratitis, a loading dose every 5 to 15 minutes for the first hour, followed by applications every 15 minutes to 1 hour around the clock to achieve a sustained therapeutic level, is recommended.  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 and ciliary spasm in more severe cases.
    37. 37.  Single-drug therapy using a fluoroquinolone (e.g. third or fourth generation) has been shown to be as effective as combination therapy utilizing antibiotics that are fortified. Although the prevalence of resistance to the fluoroquinolones appears to be increasing.  Combination fortified antibiotic therapy is an alternative to consider for severe infection and for eyes unresponsive to treatment.  Frequency of reevaluation 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 is documented.
    38. 38.  The clinical response is best assessed after 48 hours of treatment, as earlier evaluation is usually inconclusive and not helpful in assessing the efficacy of antibiotic treatment.  In general, the initial therapeutic regimen should be modified when the eye shows a lack of improvement or stabilization within 48 hours.  Several clinical features suggestive of a positive response to antibiotic therapy include reduction in pain, reduced amount of discharge, less eyelid edema or conjunctival injection, consolidation and sharper demarcation of the perimeter of the stromal infiltrate, decreased density of the stromal infiltrate, reduced stromal edema and endothelial inflammatory plaque, reduced anterior chamber inflammation, and reepithelialization.
    39. 39.  Despite aggressive therapy, bacterial keratitis can advance causing progressive corneal thinning, descematocele formation and corneal perforation.
    40. 40.  Cyanoacrylate tissue adhesive (N-butyl-2- cyanoacrylate) has been used to treat progressive corneal thinning, descemetocele, and corneal perforation with satisfactory results.  In addition to its tectonic support and bacteriostatic effects, the tissue glue can arrest keratolysis by blocking leukocytic proteases from the corneal wound.  Perforations up to 2–3 mm in diameter can be sealed by the tissue adhesive.  Necrotic tissue and debris should be removed from the ulcer bed prior to application of the glue.  Due to potential corneal toxicity, only the minimum amount of glue required to cover the defect should be used.  The adhesive is usually left in place until it dislodges spontaneously or a keratoplasty is performed.
    41. 41.  Collagen cross linking (CXL) of the cornea has been developed recently as a new treatment for multidrug-resistant infectious keratitis, as documented by several recent case reports.  This technique has showed promising results specially in patients with corneal melting and impending perforation.  Corneal melting has been arrested and complete epithelialization achieved in several cases.  The success rate was higher for bacterial infections than fungal infections  Although randomized controlled trials are needed, the available evidence supports the use of CXL in the treatment of infectious keratitis.
    42. 42.  Conjunctival flap:  Conjunctival flap has been used to treat recalcitrant microbial keratitis.  The flap can bring blood vessels to the infected area, promote healing, and provides a stable surface covering.  A conjunctival flap is particularly useful in cases of nonhealing peripheral corneal ulcer, where the flap can be placed without compromising vision.
    43. 43.  Therapuetickeratoplasty should be considered in cases medically unresponsive, extensive or full-thickness, and/or nearing perforation.  Recently, deep anterior lamellar keratoplasty (DALK) has been suggested as an alternative to therapeutic PK in some cases of infectious keratitis.  A primary advantage of DALK in this setting is the reduction of organism entry into the anterior chamber.  The specimen should be submitted to pathology and microbiology for evaluation.  Topical antibiotic therapy should be continued initially.  Corticosteroids should be used judiciously postoperatively with the primary goal of surgery being eradication of infection.  Careful postoperative evaluation is required as multiple recurrences in the graft have been described.
    44. 44.  Patients with bacterial keratitis should be referred to an ophthalmologist, because the disease has the potential to cause visual loss or blindness.  The majority of patients can be treated on an outpatient basis.  Patients and care providers should be educated about the destructive nature of bacterial keratitis and the need for strict adherence to the therapeutic regimen.  The possibility of permanent visual loss and need for future visual rehabilitation should be discussed.  Remember: “Prevention is better than cure”
    45. 45.  Early detection and appropriate treatment are imperative in order to prevent permanent visual loss from bacterial keratitis.  The risk may be reduced by avoiding or correcting predisposing factors.  For example educating them about the risks of extended-wear lensesand the importance of adherence to techniques that promote contact lens hygienemay reduce the incidence of bacterial keratitis in contact lens users.  Most ocular trauma can be avoided by using protective eyewear for sports and other high-risk activities.  Ocular surface disease such as corneal epithelial defects, severe tear deficiency, or lagophthalmos should be treated.  Patients should be acquainted with the signs and symptoms of infection, and be informed that they should consult an eye specialist promptly if they experience these.