stuck in a rut: corneal ulcers
TRANSCRIPT
Stuck in a Rut: Corneal Ulcers
Justin Schweitzer OD, FAAOVance Thompson Vision
30,000 cases annually in the US (Bacterial, Fungal, and Acanthamoeba)(Pepose JS et al AJO 1992)
Infective Keratitis rarely occurs in normal eyes because of human cornea’s natural resistance to infection
Infective Keratitis
WHY and HOW?
Corneal Defenses are Breached
Leading to Colonization by Pathogenic Bacteria1. Virulent invading organism2. Normal Ocular Flora
1. Bacteria Colonize the Stroma
2. Antigenic and release enzymes and toxins
3. Antigen‐Anti‐body immune reaction4. Induces an inflammatory reactionPMNs (polymorphonuclear leukocytesmoblize and aggregate at the infection creating an infiltrate
5. PMNs phagocytize and digest the bacteria
6. The stroma is poorly tolerant and undergoesnecrosis and thinning leading to scarring.
Signs and Symptoms
Typically UnilateralPainfulPhotophobicDeeply engorged and inflamedconjunctival and episcleral vessels (diffuse)
Mucopurulent dischargeCorneal EdemaAnterior chamber reactionHypopyonHistory – very importantLocation of defect typically central
Does the type of “bug” matter?
Contact Lens = Pseudomonas aeruginosa (gram neg)(Green M et al. Cornea. 2008;27(1):22‐7, Alexandrakis G et al. Ophthalmology. 2000;107(8): 1497‐502)
Staphylococcus aureus = Most common in North America(gram pos) (Green M et al. Cornea. 2008;27(1):22‐7, Alexandrakis G et al. Ophthalmology. 2000;107(8): 1497‐502)
When to Culture?1.Central lesions that threaten vision2.Risk of perforation3.Scleral tissue involvement4.Injury with vegetative matter5.Institutionalized patients where MRSA is possible6.Lesion is not responding to treatment
Bacterial Keratitis Management and Treatment
Fluoroquinolones2nd Generationofloxacin 0.3%ciprofloxacin 0.3%
3rd Generationlevofloxacin 0.5% and 1.5%
4th Generationgatifloxacin 0.3% and 0.5%moxifloxacin 0.5%
Fortified Antibiotics
tobramycin ‐ cefazolin(gram ‐) (gram +)(pseudomonas)
vancomycin ‐ tobramycin(gram +) (gram ‐)
Fluoroquinolone and fortified antibiotics for treating bacterial corneal ulcers
Gangopadhyay N, Daiell M, Weih L, et al.Br J Ophthalmol
Fluoroquinolone group = shorter duration of therapy= shorter hospital stay
Although serious complications (perforation, evisceration, enucleation) were more common in this group.
Resistance
Early generation fluoroquinolonesEspecially gram +
1. Schaefer F, Bruttin O, et al. Bacterial keratitis: a prospective clinical and microbiological study. Br J Ophthalmol. 20012. Afshari NA, Ma JJ, et al. Trends in resistance to ciprofloxain…..J Ocul Pharmacol Ther. 2008
Ocular Tracking Resistance in the US Today(TRUST) Study
70% of bacteria isolated in hospitals were resistant to at least 1 conventional antibioticAsbell PA, Colby KA, Deng S, et al. Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am J Ophthalmol. 2008 Jun;145(6):951‐58.
moxifloxacin(Vigamox, Moxeza)
gatifloxacin(Zymar, Zymaxid)
besifloxacin(Besivance)
moxifloxacin(Vigamox, Moxeza)
? Equivalent efficacy to fortified therapy
Better tolerability
Gram +/Gram ‐
Sharma N, Goel M, et al. Evaluation of moxifloxacin0.5% in treatment of nonperforated bacterial corneal ulcers: a randomized controlled trial. Ophthalmology. 2013McDonald EM, Ram FS et al. Topical antibiotics for themanagement of bacterial keratitis: an evidence‐basedReview of high quality randomised controlled trials. BrJ Ophthalmol. 2014
Gatifloxacin(Zymar (0.3%), Zymaxid (0.5%))
Gram+ Gram ‐
Afzal Junejo S, Ali Lodhi A, et al. Efficacy of gatifloxacin in acute bacterial corneal ulcer. Pak J Med Sci. 2013
besifloxacin(Besivance)
Only available as an ophthalmic suspension
Gram +Gram –
Most notably ‐MRSA
Haas W. Besifloxacin, a novel fluoroquinolone,has broad‐spectrum in vitro activity against aerobic anaerobic bacteria. Antimicrob Agents Chemother. 2009 Aug;53(8):3552‐60.
Steroids for Corneal Ulcers Trial(SCUT) Study
42 eyes received 0.5% moxifloxacin every hour while awake for 48 hours
Randomized to either topical steroids or placebo
Steroids for Corneal Ulcers Trial(SCUT) Study
Steroid group required more time to re‐epithelialize
4 adverse events in the placebo group and none in the steroid group
No statistically significant difference in VA between the steroid and placebo group at 3 weeks or 3 months
No statistically significant difference in scar size at 3 weeks or 3 months
Amniotic Membrane Grafts (AMG)
Biotissue‐ Prokera, Amniograft, & Amnioguard IOP Ophthalmics‐ Ambiodisk
http://www.iopinc.com/store/ambiodisk/http://www.biotissue.com/products/prokera.aspx
AMG Actions1. Reduces inflammation2. Inhibits scarring3. Inhibits angiogenesis4. Promotes epithelialization5. Possesses anti‐microbial properties6. Restoration of lost corneal thickness*
Indications/Conditions for use
• Acute corneal trauma• Chemical or thermal burn• Non‐healing epithelial defects (herpes, diabetes)
• Neurotrophic corneal ulcers
• Filamentary Keratitis• Severe Dry Eye Syndrome• Recurring epithelial defects
• High risk keratoplastys• Superficial keratectomy• Tube shunt/bleb exposure• Pterygium removal
Kenyon, K. R., & Lam, H. (2013, June 1). Amniotic Membrane: Themes and Variations. Ophthalmology Management, 1‐6.
Corneal Ulcer
Clinical Case
Fungal Keratitis
Geographical Location
Recent Travel to Hot and Humid Areas
Trauma involving Vegetative Material
Contact Lens use or abuse
Immunocompromised individuals
Rosa Jr RH, Miller D, Alfonso EC. The Changing Spectrum of Fungal Keratitis in South Florida. Ophthalmology 1994; 101(6): 1005‐1013. Jurkunas U, Behlau I, Colby K. Fungal Keratitis: Changing Pathogens and Risk Factors. Cornea 2009; 28 (6): 638‐643.
Fungal Keratitis vs Bacterial Keratitis
Fungal go deeper into the layers of the corneaand typically have feathery borders
Bacterial ulcers more painful and have significant inflammation
Culture if you suspect Fungal!
Sabouraud Agar is ideal…it contains an antibacterial agent to promote fungal growth
TreatmentCertain meds are more effective against…
Non‐filamentous
Filamentous
amphotericin 0.15%capsofungin
natamycin?? voriconazole
Amphotericin 0.15%
Compounded Medication
Toxicity is an issueTopical – burning, chemosis, epi cloudingPEE/SPK, cornea turns a greenish hueIntravenous ‐ renal toxicity, chills, fever,anemia
Mycotic Ulcer Treatment Trial(MUTT)
Natamycin outperformed voriconazole
Patients were less likely to suffer perforations or need therapeutic PKP’s on natamycin
Other Options…
Follow daily until signs of improvement
Hourly treatment
Treatment can last months
15% to 36%Treatment fails
1. Anane S, Ben Ayed N, Malek I, et al. Keratomycosis in the area of Tunis: Epidemiological data, diagnostic and therapeutic modalities. Ann Biol Clin 2010;68:4:441‐47. 2. Prajna NV, Mascarenhas J, Krishnan T, et al. Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Arch Ophthalmol 2010;128:6:672‐78.
Clinical Pearls
A corneal infiltrate without overlying epithelial staining, is likely NOT infectious keratitis
Clinical Pearls
A corneal infiltrate without overlying epithelial staining, is likely NOT infectious keratitis
Aggressive use of a strong antibiotic is necessary with infectious keratitis
Clinical Pearls
A corneal infiltrate without overlying epithelial staining, is likely NOT infectious keratitis
Aggressive use of a strong bactericidal antibiotic is necessary with infectious keratitis
Steroids will be most beneficial while the ulcer bed is still open
Clinical Pearls
A corneal infiltrate without overlying epithelial staining, is likely NOT infectious keratitis
Aggressive use of a strong bactericidal antibiotic is necessary with infectious keratitis
Steroids will be most beneficial while the ulcer bed is still open
Steroids will reduce inflammation, speed healing, and reduce the potential of corneal scarring
