Your Title Here. Your Title Here ROCHESTER EYE INSTITUTE 3/23/2016. Infectious Keratitis. Meeting Name January 1, Case Presentation.
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1 Case Presentation ID: 35yo Female Infectious Keratitis CC: irritated, itching, discharge, tearing from the left eye HPI: Several days of increasing irritation of the left eye. No recent injuries, although endorses rubbing for itching. Wears monthly contact lenses and takes them out most nights. Rochester Ophthalmology Conference March 18, 2016 Rachel Wozniak, MD, PhD Case Presentation Exam POcHx: Refractive error - contact lens wearer for 10 years PMHx: none SH: Smokes socially FH: non-contributory OD OS Visual acuity (BCVA) 20/20 20/70 IOP Pupils PERRLA PERRLA EOM Full Full Slit Lamp Exam OD OS Lids/Lashes normal Mild swelling and redness Conjunctiva/Sclera White and quiet 1+ injection Cornea Normal, contact lens in place 2mm x 3.5mm area of opacity with surrounding infiltrate just outside of visual axis inferiorly, underlying stromal edema, overlying 2mm area of epi defect Anterior Chamber Deep and quiet 1+ cell Iris Normal shape, size, Normal shape, size, morphology morphology Lens clear clear Vitreous clear clear 1
2 Diagnosis: Infectious Keratitis (Corneal Ulcer) Epidemiology US based studies in 1950s-1980s: 11.0 per 100,000 people Recent studies: 20.9 to 27.6 per 100,000 person-years Contact lens wearers: per 100,000 person-years 38.5 million contact lens wearers in the US Contact lens wear is the single greatest risk factor for developing keratitis in the United States Erie, J. C., Nevitt, M. P., Hodge, D. O. & Ballard, D. J. Incidence of ulcerative keratitis in a defined population from 1950 through Arch. Ophthalmol. 111, (1993) Jeng, B. H. et al. Epidemiology of ulcerative keratitis in Northern California. Arch. Ophthalmol. 128, (2010). Ibrahim, Boase & Cree. Incidence of Infectious Corneal Ulcers, Portsmouth Study, UK. J Clin Exp Ophthalmol (2012). Doi / S6-001 Dart, J. K., Stapleton, F. & Minassian, D. Contact lenses and other risk factors in microbial keratitis. Lancet 338, (1991) 2
3 Abelson et al Rev of Ophthalmol. 3
4 Rao, G. Oculist.net 2013 Singapore National Eye Centre Singh et al, Fungal Keratitis, Medscape
5 Rao, G. Oculist.net Dr M Srinivasan/Aravind Eye Hospital Infectious keratitis pathway Infectious keratitis pathway Corneal Injury Infection Tissue destruction Corneal Injury Infection Tissue destruction Inflammatory response Inflammatory response Scar Scar Healthy eyes do not develop spontaneous keratitis! Need to have a compromised ocular surface: -Direct injury (trauma, surgery) -Any eye disease that leads to breakdown of the surface Dry eye Recurrent erosions Corneal dystrophies Corneal edema Herpetic infections -Patients who don t heal well Diabetics Immunocompromised Elderly Green et al Cornea 27(1)
6 Why are contact lens wearers at higher risk? What does contact lens wear do to the eye? Dry eye Micro-trauma Allergy Inflammation Brings microorganisms to the surface for prolonged periods of time Courtesy Tasha Sturm/Cabrillo College/asm.org Infectious keratitis pathway Bacterial Fungal Corneal Injury Infection Tissue destruction Nocamels.com Photo by Alena Kubatova Inflammatory response Scar Viral Bacterial Causative Agents Infectious keratitis pathway Often reflect the normal flora of the ocular surface (gram-positive) -coagulase-negative Staphylococci -Staphylococcus aureus -Streptococcus sp. -Corynebacterium If gram-negative organisms are identified: -Pseudomonas aeruginosa -Serratia marcescens -Moraxella sp. Corneal Injury Infection Tissue destruction Inflammatory response Green, M., Apel, A. & Stapleton, F. Risk factors and causative organisms in microbial keratitis. Cornea 27, 22 7 (2008) Ni, N. et al. Seasonal, geographic, and antimicrobial resistance patterns in microbial keratitis: 4-year experience in eastern Pennsylvania. Cornea 34, (2015) Stapleton, F. & Carnt, N. Contact lens-related microbial keratitis: how have epidemiology and genetics helped us with pathogenesis and prophylaxis. Eye (Lond) 26, (2012). Alexandrakis, G., Alfonso, E. C. & Miller, D. Shifting trends in bacterial keratitis in south Florida and emerging resistance to fluoroquinolones. Ophthalmology 107, (2000). Pandita, A. & Murphy, C. Microbial keratitis in Waikato, New Zealand. Clin. Experiment. Ophthalmol. 39, (2011) Scar 6
7 Infectious keratitis pathway Corneal Injury Infection Tissue destruction Johns 2014, I-site Dunbar, 2008, Optom. Manag. Inflammatory response Scar Infectious Keratitis Diagnosis and Treatment Spontaneous keratitis in a healthy eye does not occur! Diagnostics Modify treatment Minimize scar -Contact lens use? -Trauma? (accidental or surgical) -Underlying ocular history -Herpetic disease -ABMD/corneal erosions -dry eye -neurotrophic cornea -Underlying medical history -Diabetes -immune status -recent illness -Tempo of disease -rapidly evolving vs indolent -pain -degree of vision loss 7
8 Infectious Keratitis Diagnosis and Treatment To culture or not to culture Diagnostics Modify Treatment Many cases in the community are treated empirically without culture AAO guidelines: - Large ucler - Centrally located, - Involving mid or deep stroma - Infection that has not been responsive to initial treatment - Atypical features which may indicate fungal, amoebic or mycobacterial keratitis Minimize Scar Hsu, H. Y. et al. Community opinions in the management of corneal ulcers and ophthalmic antibiotics: a survey of 4 states. Eye Contact Lens 36, (2010) American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. Bacterial Keratitis. San Francisco, CA: American Academy of Ophthalmology; Available at: Culture Options -Gram stain (slide) -Aerobic culture Tryptan soy broth Blood agar Chocolate: Neisseria, haemophilus Culture Technique Use Kimura spatula or calcium alginate swab *exception viral = dacron* -Anerobic culture: Thioglycolate broth -Fungal: potato dextrose plate and smear -Mycoplasma (TB): agar in a tube (Middlebrook/Lowenstein) -Acanthomeba: e coli overlay plate on agar -Viral culture: UTM (universal transport media) Yield of cultures 40-60% Delayed cultures does NOT decrease yields may take longer to recover pathogens Ni, N. et al. Seasonal, geographic, and antimicrobial resistance patterns in microbial keratitis: 4-year experience in eastern Pennsylvania. Cornea 34, (2015) Levey, S. B., Katz, H. R., Abrams, D. A., Hirschbein, M. J. & Marsh, M. J. The role of cultures in the management of ulcerative keratitis. Cornea 16, (1997) Indian Journal of Medical Microbiology, Vol. 27, No. 2, April-June, 2009, pp Tissue biopsy Infectious Keratitis Diagnosis and Treatment Advantages: tissue for culture and histopathology Disadvantages: risk of procedure (perforation) Diagnositcs Causal agent was identified in 42% of cases either with culture or histopathologic examination 44% of patients had initial negative cultures from corneal scrapings Complication rate: 3/53 perforation (6%) Modify Treatment Minimize Scar 8
9 Fortified antibiotics Don t wait for culture data/gram stain Empiric treatment: BROAD SPECTRUM Fluoroquinolones: well tolerated, good ocular penetration Currently use: FOURTH GENERATION (Vigamox) Excellent gram-negative, including Pseudomonas Good gram-positive Initial treatment regimen is INTENSE: every 30min-every 1 hour AROUND THE CLOCK Gram negative coverage: -Tobramycin -Gentamycin Gram-positive coverage: -Vancomycin -Cefazolin Advantages: Better coverage Disadvantages: difficult to obtain, limited shelf life, ocular toxicity Infectious Keratitis Diagnosis and Treatment Diagnositcs Resistance 2008 Ocular Tracking Resistance in US Today (TRUST) 2009 Antibiotic Resistance Monitoring in ocular MicRoganisms (ARMOR) Across early fluoroquinolones: Methicillin-sensitive S. aureus (MSSA) susceptibility 80% Methicillin-resistant S. aureus (MRSA) susceptibility 15% Modify Treatment Minimize Scar Asbell, P. A. et al. Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am. J. Ophthalmol. 145, (2008). Haas, W., Pillar, C. M., Torres, M., Morris, T. W. & Sahm, D. F. Monitoring antibiotic resistance in ocular microorganisms: results from the Antibiotic Resistance Monitoring in Ocular microrganisms (ARMOR) 2009 surveillance study. Am. J. Ophthalmol. 152, e3 (2011). Alexandrakis, G., Haimovici, R., Miller, D. & Alfonso, E. C. Corneal biopsy in the management of progressive microbial keratitis. Am. J. Ophthalmol. 129, (2000). Emerging Pseudomonas Resistance Rational treatment strategies: Double coverage? using a multidrug approach similar to HIV or TB Adding better gram+ coverage Vigamox with fortified vancomycin/cefazolin 9
10 Infectious Keratitis Diagnosis and Treatment Steroids in Corneal Ulcers Diagnositcs Modify Treatment Minimize Scar Benefits: suppressing inflammation reduce scarring Disadvantages: increase in infection burden, increase risk of corneal melting, elevated IOP Meta-analysis of existing trials (including SCUT): No benefit nor disadvantage with respect to: -Visual acuity -re-epithelialization -quality of life adverse affects Herretes, S., Wang, X. & Reyes, J. M. Topical corticosteroids as adjunctive therapy for bacterial keratitis. Cochrane Database Syst Rev 10, CD (2014). Sub-analysis of SCUT trial data: 3 month best spectacle-corrected acuity Steroids: 3 days within diagnosis vs 4 or more days Severe ulcers: 3 line improvement if administered within 2-3 days (p=.02) 2 line improvement if administered after 4 days (p=.17) Moderate ulcers: 1 line improvement if administered with 2-3 days (p=.09) 2 lines worse if administered after 4 days (p=.01) Mild ulcers: No significant improvement compare to placebo 2 lines worse if administered after 4 days (p=.01) Severe: CF vision Moderate: 20/40-20/800 Mild: <20/40 Conclusions Corneal ulcers require prompt evaluation and treatment Obtain thorough history remember healthy eyes do not develop keratitis Cultures and smears should be obtained, even if treatment has started Thank You Antibiotic resistance is prevalent fortified antibiotics give the broadest coverage, particularly for gram positive organisms Steroids may provide some benefit with respect to scarring if initiated early 10
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