Downloaded 319 times
Uploaded byLibby Daugherty
Keratitis
This document provides an overview of infectious keratitis. Keratitis is an infection of the cornea that is usually caused by contact lens use or trauma. Bacterial keratitis is the most common type and can progress rapidly, threatening vision. Diagnosis involves fluorescein staining and corneal scrapings for analysis. Treatment involves topical antibiotics like fluoroquinolones every hour along with cycloplegics for pain. Other types include fungal, viral like herpes simplex, and rare parasitic infections like acanthamoeba. Early diagnosis and aggressive treatment are important to prevent vision loss and perforation of the cornea.
More Related Content
Keratitis
- 1. SEEING REDA NO V E R V I E W O F I N F E C T I O U S K E R A T I T I S L I B B Y D A U G H E R T Y , P H A R M D C A N D I D A T E M A T T H E W P O S T , P H A R M D , B C P P S C H I L D R E N ’ S H E A L T H C A R E O F A T L A N T A A T S C O T T I S H R I T E U N I V E R S I T Y O F G E O R G I A – A P P E 4 – E M E R G E N C Y M E D I C I N E
- 2. KERATITIS • Infection ofone or many layers of the cornea • Mostly due to contact lens use, especially with improper use or hygiene • Distinguishing the causative agent is important and difficult • Vision-threatening – Early consultation with ophthalmology is important – Aggressive treatment is warranted
- 3. CORNEA ANATOMY • Layerof clear columnar cells that covers the front part of the eye. • Consistent with the sclera • Covers the anterior chamber which includes the iris/pupil. • Corneal epithelium is only 1-2 cells thick • Stroma is made of keratin
- 4. PATHOLOGY Damage to the cornealepithelium introduces microflora to the stroma Microflora infect the keratin of the stroma Corneal inflammation attracts neutrophils to the cornea Enzymes released by neutrophils exacerbate inflammatory necrosis Progressive inflammation quickly leads to corneal perforation Wound healing often leaves scarring
- 5. PRESENTATION Early/Common • Redness • Rapidonset of mild-moderate pain • Decreased/blurry vision • Photophobia • Tearing Late/Severe • Visible infiltrate(s) • Eyelid edema • Conjunctival inflammation • Hypopyon • Discharge
- 6. DIAGNOSIS • Fluorescein Stain –Binds to keratin – Cannot penetrate corneal epithelium – Only binds to the part of the cornea that has lost its epithelium – Illuminates under fluorescent light • Corneal Scraping – Provide anesthesia first – Bacterial and fungal cultures Fluorescein stain applied to eye and washed out with saline. Viewed under cobalt lamp to visualize defects in the corneal epithelium.
- 7. INFECTIOUS ETIOLOGIES Bacterial • Singularinfiltrate • Solid border Fungal • Large hypopyon • Feathered/fuzzy border • Satellite infiltrates Herpetic • Dendritic lesion Acanthamoebi c • Variety of infiltrates
- 8.
- 9. BACTERIAL KERATITIS • Mostcommon form of Keratitis (90-95% of all cases) • Rapidly progressive (2-3 days) • Sight-threatening • Pathogens – Streptococcal spp. – Pseudomonas – Staphylococcus spp. – Atypical bacteria – Anaerobes
- 10. RISK FACTORS • LASIKsurgery • Contact lens use – Extended wear – Improper hygiene – Sleeping with contacts – Swimming with contacts • Ophthalmic corticosteroids • Corneal injury • Enropion • Chronic dry eye
- 11. PRESENTATION SYMPTOMS • Redness • Changesin vision • Pain • Photophobia • Cornea may be clear or hazy • Hypopyon may be present COMPLICATIONS • Corneal thinning – Increases risk for further infection – Increases risk for perforation • Perforation – Infection of the inner eye – Often results in permanent loss of sight – May result in loss of eye entirely
- 12. MANAGEMENT • Ophthalmology consult •Corneal scrapings sent for culture, staining and analysis • Topical bactericidal antibiotics – Broad Spectrum • 4th Generation Fluoroquinolone • Fortified Cephalosporin + Aminoglycoside – Frequent Administration • Every hour for at least 24 hours • May reduce to every 2 hours while awake after signs of improvement • Tapered per clinical improvement (per ophthomologist) • Cycloplegia as needed for pain – Atropine 1% 1-2 drops 4 times daily – Cylopentolate (Cyclogyl) 0.5-2% 1- 2 drops every 5-10 minutes – Cyclopentolate/Phenylephrine (Cyclomydril) 0.2% 1 drop every 5- 10 minutes
- 13. FLUOROQUINOLONES • 2nd Generation –Ciprofloxacin 0.3% (Ciloxan) – Ofloxacin 0.3% (Ocuflox) • 3rd Generation – Levofloxacin 0.5% • 4th Generatoin – Moxifloxacin 0.5% (Moxeza, Vigamox) – Gatifloxacin 0.5% (Zymaxid) Pros Cons
- 14. FORTIFIED ANTIBIOTICS • Aminoglycosides –Gentamicin 14mg/ml (1.4%) – Tobramycin 14mg/ml (1.4%) – Amikacin 2.5% • Cephalosporins – Cefazolin 50mg/ml (5%) – Ceftazidime 50mg/ml (5%) Pros Cons Multiple agents Poor stability Requires compounding Good tolerability Low resistance Broad coverage
- 15. FORTIFIED ANTIBACTERIAL EYEDROPS AMINOGLYCOSIDES • Tombramycinand Gentamicin 1.4% – Add 2ml (80mg) of the parenteral solution to the commercially available eyedrops – Stable for 7 days in the fridge (4°C) – Stable for 4 days at room temperature • Amikacin 2.5% – Add 2ml (250mg) of the parenteral solution to 8ml of artificial tears – Stable for 7 days in the fridge (4°C) CEPHALOSPORINS • Cefazolin 3.3% (33mg/ml) – Reconstitute 500mg with 2ml 0.9% NaCl and add to 13ml of artificial tears – Stable for 4 days at room temperature • Ceftazidime 5% (50mg/ml) – Reconstitute 1g with 10ml sterile water – Mix 7.5ml of solution with 7.5ml sterile water – Stable for 7 days in the fridge
- 16. FORTIFIED ANTIBACTERIAL EYEDROPS • Vancomycin31mg/ml (3.1%) – Reconstitute 500mg with 5ml sterile water – Stable for 28 days in the fridge (4°C) • Colistin 0.19% – Add 10ml sterile water to 75mg Colistimethate sodium (Xylistin) powder to make 7.5mg/ml solution – Add 1 ml of the 7.5mg/ml solution to 3ml distilled water to make topical 0.19% drops • Linezolid 2ml/ml (0.2%) – Use the 200mg/100ml parenteral solution directly • Imipenem-Cilastin 1% – Add 10ml sterile water to 500/500mg parenteral solution to make a 50mg/ml solution. – Add 1ml of the 50mg/ml solution to 4ml sterile water to make topical 1% drops – Stable in an amber bottle for 3 days in the fridge (4°C)
- 17. ADJUNCTIVE THERAPY STEROIDS • Controversial •Decreases inflammation – Minimizes scarring – Reduces stromal necrosis – Delays wound healing/epithelium regrowth – May increase risk of perforation • Regimens – Dexamethasone 0.15 Q2H – Prednisolone 1% QID • If used, should not be started until after signs of clinical improvement on antibacterial therapy (24-48 hours) ORAL ANTIBIOTICS • Indications – Juxtalimbal ulcer – Perforation – Atypical infections • Regimens – Fluoroquinolones – Cephalosporin/Aminoglycoside – Macrolides
- 18.
- 19. FUNGAL KERATITIS • Difficultto distinguish from bacterial based on visual exam alone – May be more fuzzy/feathered – May be extra satellite lesions • Often results in more severe disease – Fungal growth is slower, but uninhibited by epithelial membranes – Delays in diagnosis • Pathogens – Candida – Aspergillus – Fusarium
- 20. FUNGAL KERATITIS RISK FACTORS •Vegetation – Ocular trauma – Particles • Tropical climate • Immunodeficiency MANAGEMENT • Topical antifungals – Amphotericin B 0.15% – Voriconazole 1% – Natamycin 5% (Natacyn) • Oral antifungals – Fluconazole – Ketoconazole • Cycloplegia • Topical antibiotics
- 21. FORTIFIED ANTIFUNGALS EYEDROPS • AmphoteracinB 0.15% – Add 10ml sterile water to 50mg powder for injection. – Add 3ml of solution to 7ml artificial tears – Stable for 7 days in fridge – Stable for 4 days at room temperature • Voriconazole 1% – Mix 2ml Ringer’s Lactate with 200mg lyophilized powder – Stable for 30 days in fridge (4°C) INTRASTROMAL INJECTION • Amphoteracin B 5-10μg/0.1ml • Voriconazole 50μg/0.1ml • For severe disease only – Intensely painful – High risk of systemic absorption/toxicity
- 22. VIRAL KERATITISA K A“ H E R P E T I C K E R A T I T I S ”
- 23. VIRAL KERATITIS Herpetic Adenoviral •Herpetic Keratitis – Caused by Herpes simplex virus (HSV- 1) – Easily identifiable “dendritic” appearance • Adenoviral Keratitis – Caused by Adenovirus – Occurs most often following adenoviral conjunctivitis – Ocular reaction to adenovirus particles – Small sub-epithelial infiltrates – Self-limiting
- 24. HERPETIC KERATITIS BACKGROUND • Mostcommon cause of infectious blindness worldwide • Presentation is exactly the same as bacterial keratitis, except: • Characteristic lesions initially present in a dendritic pattern • Good prognosis if treated MANAGEMENT • Topical antivirals – Ganciclovir (Zirgan) – Trifluridine (Viroptic) • Systemic antivirals – Acyclovir (Zovirax) – Valacyclovir (Valtrex) • Cycloplegia – Atropine – Cyclopentolate (+/- Phenylephrine) • NO STEROIDS!
- 25. PARASITIC KERATITISA K A“ A C A N T H A M O E B I C K E R A T I T I S ”
- 26. ACANTHAMOEBIC KERATITIS • ExtremelyRare • Generally associated with contact lens use while swimming • Has been associated with contaminated contact lens solution • Poor prognosis – Delay in diagnosis – Limited/ineffective therapies – Resilient infection (cysts)
- 27. ACANTHAMOEBIC KERATITIS • Systemicantifungals – Voriconazole – Ketoconazole • Topical Biguanides – Chlorhexadine 0.02% – Polyhexamethylene biguanide (PHMB) 0.02% • +/- Topical antiprotozoals (diamidines) – Pentamidine isethionate (Pentam) 0.1% – Propamidine isethionate (Brolene) 0.1% – Hexamidine (Desmodine) 0.1% • Topical antifungals – Natamycin (Natacyn, Pimaricin) – Neomycin (Neo-Polycin) • Cycloplegia • Steroids • Check the CDC website!
- 28. REFERENCES • "Acanthamoeba -Granulomatous Amebic Encephalitis (GAE); Keratitis." Centers for Disease Control and Prevention, 22 Oct. 2013. Web. 04 Oct. 2016. • DeLoss, Karen S. "Complications of Contact Lenses." Ed. Jonathan Trobe and Janet L. Wilterdink. UpToDate. Wolters Kluwer, 17 Sept. 2016. Web. 4 Oct. 2016. • Forooghian, Farzin. "Oral Fluoroquinolones and the Risk of Retinal Detachment." Journal of the American Medical Association 307.13 (2012): 1414. Web. • Gangopadhyay, N. "Fluoroquinolone and Fortified Antibiotics for Treating Bacterial Corneal Ulcers." British Journal of Ophthalmology 84.4 (2000): 378-84. Web. 4 Oct. 2016. • Goldstein, Michael H., Regis P. Kowalski, and Y.jerold Gordon. "Emerging Fluoroquinolone Resistance in Bacterial Keratitis." Ophthalmology 106.7 (1999): 1213-318. Web. 4 Oct. 2016.
- 29. REFERENCES • Hillenkamp, Jost,Rainer Sundmacher, and Thomas Reinhard. "Treatment of Adenoviral Keratoconjunctivitis." Essentials in Ophthalmology Cornea and External Eye Disease (n.d.): 163-72. Web. • Jacobs, Deborah S., Jonathan Trobe, and Janet L. Wilterdink. "Evaluation of the Red Eye." UpToDate. Wolters Kluwer, 24 Feb. 2016. Web. 4 Oct. 2016. • Keratitis. Perf. Paul Bolin. Keratitis. CRASH! Medical Review Series, 21 Nov. 2015. Web. 4 Oct. 2016. • Shah, Sushmita G., and Dikhil S. Gokhale. "Instruction Manual for Preparation of Fortified Antimicrobial Eye Drops." Bombay Ophthalmologists' Association, n.d. Web. 4 Oct. 2016. • Sugar, Alan. "Herpes Simplex Keratitis." Ed. Jonathan Trobe and Jennifer Mitty. UpToDate. Wolters Kluwer, 17 Aug. 2016. Web. 4 Oct. 2016. • Thompson, Andrew M. "Ocular Toxicity of Fluoroquinolones." Clinical & Experimental Ophthalmology Clin Exp Ophthalmol 35.6 (2007): 566-77. Web.
- 30. QUESTIONS?T H AN K Y O U F O R Y O U R T I M E A N D A T T E N T I O N !
Editor's Notes
- #3 Layers… Infections generally start on the outer layers Quickly will cause ulcers and penetrate down into deeper layers AKA “Ulcerative Keratitis” or “Corneal Ulceration” Corneal Ulcer vs Corneal Abrasion Abrasions Non-infectious Heal spontaneously within 24-48 hours as the epithelium grows back Will never have an infiltrate Associated with recent mechanical trauma (fingernail to eye)
- #4 Columnar cells similar to collagen, mainly made of keratin.
- #5 Immune system is somewhat of an enemy here Killing the infection erodes cell layers Allows for deeper penetration into the eye Corneal perforation = blindness, systemic infection
- #6 Keratitis pain is not severe, usually just irritating (3-4/10). Foreign body sensation. Red Eye has large differential Conjunctivitis = infection of mucous membranes inside eyelids/around eyes; no change in vision Uveitis = miosis Glaucoma = severe pain (10/10), ↓IOP
- #7 Damage to the cornea is hard to see because the cornea is clear
- #8 Very difficult to tell just from visual examination Conjunctivitis = generalized eye redness Keratitis = circumferential pattern, especially right around sclera cornea transition (circumcorneal redness) Hypopyon = collection of pus in the anterior chamber Large hypopyon in fungal infections due to slow-growing infection with early penetration into the anterior chamber (fungi grow slow, but they grow deep)
- #10 Atypicla bacteria = Neisseria, Listeria, Mycobacterium, Nocardia, etc. Neisseria, Corynebacterium, H. flu and Shigella can all cross Bowman’s Layer and infect an intact cornea (no abrasion required) Anaerobes/Oral flora from people using saliva to clean their contact lenses
- #11 LASIK = remolding of the cornea = trauma Risk of blindness warned about before surgery, keratitis is a major concern Corticosteroids inhibit the immune system Using them increases the risk of bacterial colonization Enropion = genetic condition in which a portion of the eyelid is inverted or folded inward
- #13 Bactericidal is important Quick killing Take burden away from immune system Pseudomonal coverage is very important These directions differ from the recommendations on Lexicomp which are more appropriate for Conjunctivitis Unlike conjunctivitis, bacterial keratitis is a rapidly progressing, sight-threatening infection and requires extremely aggressive treatment. You can use ointments instead of drops to allow patients time to sleep, but ointments have very poor corneal penetration. Not recommended in severe infections. Source of pain is ciliary body spasms. Cycloplegia relaxes/paralyzes the ciliary body. Cyclopentolate with phenylephrine (Cyclomydril) is preferred in infants due to lower cyclopentolate concentration and lower risk of systemic absorption. Apply finger pressure to lacrimal sac for 1-2 minutes after administration to decrease risk of systemic absorption.
- #14 Monotherapy 4th generation FQs have better penetration into the cornea than previous generations Also better GP coverage Local toxicities (dose dependent) Corneal precipitates/crystallization delay healing and result in corneal perforation in up to10% of cases Retinal detachment FQs have destructive effect on connective tissue (e.g. tendonopathy) Increased incidence of retinal detachment is a consequence of degeneration of ocular connective tissue and collagen FQ monotherapy is associated with shorter duration of (intensive) care and shorter hospital stays However, serious complications from antibiotic use occur much more often with FQs
- #15 Fortified antibiotics are created by adding the intravenous formulation of an antibiotic to The commercially prepared ophthalmic solution Higher concentration Better penetration into the cornea Artificial tears To create an ophthalmic solution that is otherwise not commercially available Cephalosporins Cefazolin is most commonly used for GP coverage in Keratitis Ceftazidime used with pseudomonas keratitis Topical product not available commercially because they are unstable in solution and must be re-prepared every 4-5 days Aminoglycosides Pseudomonas coverage (double coverage when used with ceftazidime) The main toxicity of these preparations is the retardation effect of the epithelial-healing rate (aminoglycosides, vancomycin) and the corneal and conjunctival toxic effects (aminoglycosides). However, fortified antibiotic drops remain the standard therapy for severe bacterial keratitis, given their corneal penetration and the possibility of the synergic and combined effect of an antibiotic association.
- #16 Fortified antibiotics are created by adding the intravenous formulation of an antibiotic to The commercially prepared ophthalmic solution Higher concentration Better penetration into the cornea Artificial tears To create an ophthalmic solution that is otherwise not commercially available Cephalosporins aren’t available commercially as ophthalmic solutions because Insoluble Poor stability (3-4 days) Alternative preparations: Cefazolin and Ceftazidime 5% Reconstitute 500mg parenteral solution with 2ml sterile water and add to 8ml of artificial tears Stable for 7 days in the fridge Stable for 3 days at room temperature
- #17 For MRSA Linezolid and Vancomyin are bacteriostatic (Argument over whether Vanc is static or cidal per mechanism, but functionally it is static) Colistin and Cabapenems are bactericidal Alternative preparation: Vancomycin 50mg/ml (5%) Reconstitute 500mg with 2ml sterile water and add to 8ml of artificial tears Stable for 28 days in the fridge (4°C)
- #18 If used, corticosteroids should not be started until after signs of clinical improvement on antibacterial therapy (24-48 hours) Macrolides for atypical infections Erythromycin is least toxic and most tolerable but has worst penetration into cornea Juxalimbal = near border with sclera
- #20 Candida = Yeast Fusarium/Aspergillus = Fillamentous Fusarium linked to recent contamination of contact lens solution Associated with vision loss in 26-63% of cases due to delay in diagnosis
- #21 Coinfection with bacteria occurs in ~20% of cases Prophylactic topical antibiotics are often used Oral antifungals for deep eye infections Both Fluconazole and Ketoconazole have good levels in the anterior chamber Amphoteracin B is DOC for yeast infections (Candida) Voriconazole is DOC for filamentous fungi (Aspergillus) Natamycin is the only commercially available ophthalmic antifungal – great for filamentous fungi, esp Fusarium
- #22 Amphoteracin B 5-10μg/0.1ml Voriconazole 50μg/0.1ml
- #24 HSV-1 is the “non STD” herpes Can also be caused by HSV-2 though Adenovirus is by far the most common cause of viral conjunctivitis
- #25 Ganciclovir: Apply 1 drop in affected eye 5 times daily (approximately every 3 hours while awake) until corneal ulcer heals, then apply 1 drop 3 times daily for 7 days Viroptic: Instill 1 drop into affected eye(s) every 2 hours while awake, to a maximum of 9 drops/day, until re-epithelialization of corneal ulcer occurs; then use 1 drop every 4 hours while awake for another 7 days Acyclovir also available as an ointment that can be used while patient sleeps Other topical antivirals (no dosing information) Vidarabine Idoxuridine Steroids have no benefit in viral infection and are likely to cause harm Steroids prolong viral replication Worsen infection High chance of perforation High likelihood of blindness
- #27 Good outcomes when treated early before deep penetration can occur (rarely happens) Acanthamoeba spp. implicated as human pathogens: A. culbertsoni A. polyphagia A. castellanii A. astronyxis A. hatchetti A. rhysodes A. divionensis A. lugdunensis A. lenticulata
- #28 Treatment for 6-12 months Antimicrobial treatment is controversial and poorly-studied Investigational “new” drug for FLA (Free Living Amoeba) infections: Miltefosine. Naegleria, Balamuthia, Acanthamoeba Call the CDC Emergency Operations Center at 770-488-7100 None of these drugs (except systemic antifungals) is commercially available or approved for use in the US, but they can be obtained from compounding pharmacies. Leiter’s Park Avenue Pharmacy, San Jose, CA (800-292-6773; www.leiterrx.com) is a compounding pharmacy that specializes in ophthalmic drugs. Propamidine is available over the counter in the UK and Australia. Hexamidine is available in France. The combination of chlorhexidine, natamycin (pimaricin) and debridement also has been successful. Debridement is most useful during the stage of corneal epithelial infection. Most cysts are resistant to neomycin; its use is no longer recommended. Azole antifungal drugs (ketoconazole, itraconazole) have been used as oral or topical adjuncts. Use of corticosteroids is controversial