Professional Disclosures. Corneal Workshop: Keratitis Management. Keratitis. Keratitis 5/3/2013

Transcription

1 Corneal Workshop: Keratitis Management Elizabeth Yeu, MD Cornea, Cataract, Anterior Segment, Refractive Surgery Virginia Eye Consultants May 1, 2013 Professional Disclosures Allergan: Advisory Board, Speakers Bureau Bausch + Lomb: Advisory Board Rhein Medical: Advisory Board Bacterial Herpetic Blepharokeratitis Keratitis Keratitis Infectious: Microbial keratitis-- MK Bacterial Viral Parasitic: acanthamoeba Fungal Non-infectious Inflammatory: blepharokeratitis, PUK Interstitial Others 1

2 Bacterial Keratitis Gram-positive cocci: Staph spp., Strep pneumoniae Aerobic gram-negative bacilli: Pseudomonas aerugenosa, Haemophilus influenzae, Moraxella catarrhalis Enteric gram-negative bacilli or colonization of normal skin flora: S. aureus, S. epidermides, Serratia spp., Strep viridans General guidelines Ulcer: Epithelial defect + WBC recruitment within stroma Infectious or sterile Infiltrate: grey/white opacities from coalescence of WBCs Localized or diffuse Usually infectious Peripheral (PUK, Mooren s, marginal keratitis) more commonly inflammatory and not infectious General Guidelines Appearance of infiltrate Sharply dilineated, ovoid: gm + Irregular, indistinct borders: gm Feathery borders: fungal, strep pneumo Crystalline: strep pneumoniae Ring infiltrate: Pseudomonas, HSV, acanthamoeba, Neisseria, Corynebacterium, Nocardia, anesthetic abuse 2

3 General Guidelines Appearance of infiltrate Aggressive suppuration ( soupy ): gm ( ) Infiltrate with intact epithelium: sterile, fungus, H. aegyptius, Neisseria gonorrhoeae, Listeria monocytogenes Satellite lesions: fungal, atypical mycobacteria, nocardia Raised, clumpy borders of gray-white epithelium: neurotrophic or toxic General guidelines Usual suspects Duration Indolent: acanthamoeba, gm +, fungal Fulminant: gm ( ) Amount of tissue destruction and thinning Gm ( ) spp., particularly pseudomonas aeruginosa, cause great necrosis very quickly CL wear p. aeruginosa Spontaneous MK enteric/ skin flora Scleral buckle, canalicular tubes atypical mycobacterium Vegetation, trauma fungus Water-related acanthamoeba 3

4 Usual suspects When to refer? PKP: gm + organism Often strep pneumoniae (steroids) Tx: start broad spectrum fluoro S. pneumo Vancomycin 2.5% Culture, inc. sutures! Culture - Rules of Within 1 mm of visual axis Ulcers with 2 or more infiltrates 3 mm or more in diameter Indications for Referral Indications for Referral Anything central, necrosing or thinning Poor response to single treatment Poorly healing epithlium Extended duration Post-surgical Trauma-related: vegetation, FB Inflammatory melt If considering immediate referral, prior to starting meds, consider not starting any treatment in order to obtain highest yield on culture Culturing the cornea Procedure Chemistry lab set up, alcohol lamp Sterile Kimura spatulas Slides Culture plates and tubes Anesthetize the cornea Preservative-free tetracaine Scrape ulcer base / leading edge of infiltrate Place specimen on slide, then culture media Smears fixing organisms to be stained / observed Culture microbial growth Sterilize spatula over flame between slides / cultures 4

5 Culturing the cornea Treatment Diagnostic Commonly, can be THERAPEAUTIC! D/C CL wear Primary goal eliminate the pathogens Secondary goal prevent host destruction Treated as bacterial initially Small infiltrates empirically (<1.0mm) Cycloplegics bid-qid Cyclopentolate 1%, homatropine 5%, scopolamine 0.25%, atropine 1% Treatment Fluoroquinolones common standard Besifloxacin: 3 rd generation fluoro, excellent broad spectrum, inc MRSA and pseudomonas Moxifloxacin: 4 th generation,? Fungal coverage Vision threatening Fortified antibiotics Tobramycin/gentamycin (15mg/mL) aggressively ATC Cefazolin (50mg/mL), ceftazadime (50mg/ml) or vancomycin (25mg/mL) Natamycin 5% Suspension Sticky Poor penetration common Voriconazole 1% Mold, yeast Amphotericin 0.15% Yeast Treatment: Fungal Keratitis Treatment: Acanthamoeba keratitis Triple or quad Rx 1. Chlorhexadine 0.02% or PHMB 0.02% 2. Propamadine 0.1% or hexamadine 0.1% 3. Itraconazole or voriconazole p.o. 4. Neomycin 5. +/- steroids Steroids? Yes or no? Always an interesting topic of discussion Yes No Maybe so? 5

6 Steroids for Corneal Ulcer Trial Objective: To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers Results: No significant difference was observed 3-month BSCVA (P =.82) Infiltrate/scar size (P =.40) Time to reepithelialization (P =.44) Corneal perforation (P >.99) Steroids? Steroids Aggressive suppuration to necrosis Healing bacterial MK PKP patients, not fungal Steroid stress test Exacerbates fungal MK Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, Ray KJ, Hong KC, Oldenburg CE, Lee SM, Zegans ME, McLeod SD, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. Potential Treatment Option Collagen cross-linking Riboflavin phototherapy In vitro studies: Ribloflavin phototherapy can eradicate S. aureus, MRSA, P.aeruginosa (Martins SA, et al. IOCS. 2008; 49: ) Help heal refractory bacterial MK and halt thinning (Panda A, et al. Cornea Oct; 31(10):1210-3) Patient Presentation Patient Presentation 62 yo WM h/o hyperopic LASIK + cataracts uneventful cataract surgery Loose epithelium near edge of prior LASIK flap BCL POD 1, looks great POW 1: BCL fell out yesterday when I was poolside, so my wife picked it up, rinsed it off with her solution and put it back in 6

7 Patient Presentation Patient: Clinical course Minimal injection, superotemporal 1x2 mm ant stromal infiltrate, no thinning Plan: D/C BCL Start moxifloxacin q2 hours ATC Over the next 2 days, infiltrate shrinking in size, but epithelium not quite healing over Add FML qid, decrease moxi to qid Patient Presentation Continued therapy for 2 more days On return, infiltrate returning slightly larger?? Wrong diagnosis or superinfection Confocal microscopy performed 7

8 Patient Presentation Gm stain and CW hyphael elements Voriconazole 1% q1 h ATC, Voriconazole 200 mg bid Culture: Paecilomyces spp. Clinical scenario 36 yo male, 2 nd opinion of persistent geographic ulcer Red eye OD began ~5w ago 3 rd episode in 5 y Trifluridine x4w, at qid Zymar qid Update: Herpes Keratitis Persistent HSV geographic ulcer OD Herpetic keratitis Regarding herpetic keratitis. Not too much has changed in the treatment of HSV keratitis over the years 8

9 HSV: Background HSV 1: oral, nasal, ocular, throat sores HSV 2: genital sores Neurotrophic and neuroinvasive viruses HSV-1 and -2 persist in the body Become latent and hide from the immune system in the cell bodies of neurons After primary infection, reactivation can occur anytime Ocular HSV infections generally reactivation HSV blepharitis can be primary infection: more commonly seen in kids HSV: Epidemiology Worldwide: HSV 65% - 90% U.S. HSV 1: ~ 50% - 80% HSV 2: ~ 20% HSV Keratitis HSV Keratitis Epithelial Stromal Endotheliitis Metaherpetic and Neurotrophic Epithelial Stromal Endotheliitis Metaherpetic and Neurotrophic Corneal HSV Disease: Epithelial HSV Dendritic Keratitis Dendritic Geographic Marginal ulcer Infection of epi cells Base stains with fluorescein, infected balloon cells stain with rose bengal 9

10 HSV Epithelial Keratitis Question Disease course < 2 weeks 95% spontaneously heal in 14 days Treatment speeds up resolution Topical Oral What is your treatment of choice for management of HSV epithelial keratitis? 1. Debriding the epithelium 2. Topical trifluridine 1% gtt 3. Topical ganciclovir 0.15% gel 4. Oral anti-viral therapy 5. Debriding the epithelium + medicine HSV Epithelial Keratitis HSV Epi keratitis: Treatment Treatment trends: General ophthalmologist: topical Cornea: oral Greater trend towards topical treatment with topical GCV 0.15 % gel Trifluridine 1% (TFT): 8x/day (q2h) until epithelium heals, usually 5-10 days Taper off within 2 weeks Trifluridine 1% Very toxic to epithelium: Delayed healing Conjunctival scarring Punctal stenosis Do not use > 2 weeks HSV Epithelial Keratitis: Treatment Ganciclovir gel 0.15% (GCV) 5x/day while awake x 7 days, then TID for 7 days Side effect profile: Much less epitheliopathy Eye irritation (20%), punctate keratitis (5%), conj hyperemia (5%) 10

11 HSV Epithelial Keratitis: Treatment Ganciclovir gel 0.15% (GCV): Since 1995, the GCV 0.15% available in 30 countries within Europe, Asia, Africa and South America ACV 3% ung and GCV 0.15% gel standard of care in Europe Approved by FDA in 2009 HSV Epithelial Keratitis: GCV 0.15% studies All phase II/IIII GCV 0.15% studies have been abroad GCV 0.15% gel vs. ACV 0.3% ung GCV as effective as ACV Less blurring than ACV Average healing time 7-8 days 82% - 88% healing rate HSV Epithelial Keratitis: GCV 0.15% studies HSV Epithelial Keratitis May be useful as prophylaxis* 6 patients: 3 s/p PKP, no recurrences *Tabbara Kf, Treatment of herpetic keratitis, Ophthalmology, 2005;112:1640. Oral treatment: Acyclovir 400mg 5x/day (2g/day) Valacyclovir (Valtrex ) 500mg-1gm TID Famcyclovir mg BID In kids: Acyclovir 200mg/5cc qid HSV Keratitis Immune-mediated stromal keratitis Epithelial Stromal (15%): immune, necrotizing Endotheliitis Metaherpetic and Neurotrophic Not active infection Occurs up to years after original epithelial keratitis Often chronic, recurrent inflammation 11

12 Stromal keratitis: Clinical appearance Herpetic Stromal Keratitis Epithelium intact Stromal infiltration Edema Stromal vascularization lipid AC reaction Corneal HSV Disease: Stromal Necrotizing Necrosis, dense infiltrate Epi defect (+) infected stromal cells & immune reaction Treatment: HSV Stromal Keratitis Non-necrotizing stromal keratitis Topical prednisolone 1% 4-8x/day Topical difludprednate NOTE: When steroids > bid, must use anti-viral prophylaxis (topical or oral) Necrotizing Aggressive topical steroids Anti-viral for ACTIVE HSV disease Epithelial Stromal HSV Keratitis Endotheliitis: Disciform, diffuse, linear Metaherpetic and Neurotrophic Corneal HSV Disease: Endotheliitis Immune reaction involving endothelial cells (? live virus) Clinical appearance KP Stromal and epithelial edema Iritis Minimal to no stromal infiltration 3 forms: disciform, diffuse, linear 12

13 Disciform endotheliitis Most common Occurs some time after infectious epithelial keratitis Disc-shaped area of edema over KP Diffuse and linear HSV endotheliitis Diffuse: dense retrocorneal plaque HSV endotheliitis: Treatment HSV Keratitis: Recurrence Disciform Topical steroids Anti-viral prophylaxis Diffuse and linear Aggressive topical steroids Anti-viral to for active infection Rate of recurrence: 1 year: 9.6% 2 years: 22.9% 10 years: 49.5% Can cause severe vision loss, esp epithelial and stromal keratitis Management: Immune diseases (Non-necrotizing) stromal, disciform endotheliitis Prednisolone 1% qid to q2h Anti-viral prophylaxis Once controlled, very slow taper of steroid May always require topical steroid, even TIW When prophylaxis? Prevent recurrences HEDS, ACV x1y all forms by ~41% (19% vs. 32%) and stromal keratitis recurrence by 50% (14% vs. 28%) Prevent reactivation during steroid use 13

14 Oral prophylaxis Topical prophylaxis Acyclovir 400mg bid Famciclovir mg qd-bid Valacyclovir 500mg qd-bid Trifluridine: variable TID drop for drop until steroid down to QD GCV gel:?? No solid recommendations YET I use BID - TID HSV Keratitis When metaherpetic or neurotrophic disease? Epithelial Stromal Endotheliitis Metaherpetic and Neurotrophic Epi defect on topical anti-viral >2 w Geographic versus metaherpetic/neurotrophic ulcer HSV-infected balloon cells stain Shape of lesion Geographic Sterile Metaherpetic/ neurotrophic ulcer Poor sensation Oval, rolled edges, smooth borders Within IPF Courtesy of MB Hamill, MD 14

15 Management: HSV ulcer> 2 weeks Stop topical anti-viral Change to oral anti-viral prn No preservatives Non-preserved ung q2h BCL Amniotic membrane Omega-3 FA, Doxycycline (+) stromal inflammation: cautious steroids Neurotrophic Ulcers Amniotic membrane transplant Prokera: Self-retaining, cryopreserved AMT on 16 mm PMMA ring Self-retaining AMT Management: HSV Ulcer > 2 weeks Fairly easy insertion: exam lane Can stain cornea with NaFL without removal Topical meds penetrate through AMT AMT soaks up meds Surgical options Amniotic membrane, esp if thin Conjunctival flap Lateral tarsorrhaphy Keratoplasty 15

16 Back to the patient 36 yo male, 2 nd opinion of persistent geographic ulcer Red eye OD began ~5w ago 3 rd episode in 5 y Trifluridine x4w, at qid Zymar qid Back to the patient. Poor k sensation OD Dx: Neurotrophic ulcer Photos courtesy of S. Pflugfelder, MD Herpes. Attacks the weak- worse in atopes, humbles the physicianfools the best of us, mocks your treatment- hides only to return, and returns more than the taxman -Ivan R. Schwab, MD Blepharokeratitis Blepharokeratoconjunctivitis Blepharokeratitis BKC is disease entity of adolescents- a syndrome usually associated with anterior or posterior lid margin blepharitis, accompanied by episodes of conjunctivitis, and a keratopathy including punctate erosions, punctate keratitis, phlyctenules, marginal keratitis, and ulceration Ocular Rosacea Phlyctenulosis Marginal keratitis 16

17 Ocular Rosacea Ocular Rosacea Ocular Rosacea Ocular Rosacea c/o Parag Majmudar, MD Most common in middle-aged female Flushed cheeks and nose telangiectasis Vasomotor lability aggravated by coffee, tea, alcohol, spicy foods, anxiety, hormonal changes Rhinophyma (bulbous nose) sebaceous gland hypertrophy Ocular Rosacea Etiology: unknown Colonization of lid margins with flora (S. epidermides, P. acnes) produce lipases which may alter MG secretions inflammation S. epidermides found only in pustules, not in unaffected skin; may be transported by Demodex mites Ocular Rosacea Ocular findings ~50% Blepharitis, MGD, lid thickening, telangiectasis Chronic, diffuse conjunctival injection, esp within IPF Corneal involvement ~5-30% (Jarmuda S, et al. J Med Microbiol August 2012) 17

18 Ocular Rosacea: Corneal Findings Phlyctenulosis Punctate epithelial erosions Marginal infiltrates Corneal pannus Stromal thinning, perforation Corneal scars Phlyctenulosis Phlyctenulosis Inflammatory raised gelatinous nodules in cornea or conjunctiva Hypersensitivity reaction c/o Parag Majmudar, MD Phlyctenulosis: etiology Most commonly associated with staphylococcal blepharitis Others TB P. acnes N. gonorrheae, Chlamydia HSV C. albicans Endemic parasites Phlyctenulosis More common in children and adolescents W > M, 2:1 Up to half of patients w/ bilateral presentation 18

19 Phlyctenulosis Marginal Keratitis Phlyctenule can migrate towards center of cornea + Feeder vessels May ulcerate w/ stromal WBC infiltrate Heal with scarring May lead to significant visual impairment c/o EyeRounds.org Marginal Keratitis Marginal Keratitis AKA catarrhal infiltrate Hypersensitivity reaction to Staphylococcus? May be related to Demodex blepharitis, esp with recurrent disease Marginal Keratitis Marginal Keratitis Creamy white infiltrate(s) in peripheral cornea Infiltrate smooth, distinct borders Single or multiple Overlying epi defect smaller than infiltrate 1-2 mm clear zone from limbus Infiltrate then epi ulceration KNV Most commonly occur where cornea crosses lid margin 19

20 Blepharokeratitis: Treatment Treat inflammation and blepharitis Combo steroid/ antibiotic work well (Tobramycin/dexamethasone) FML or Pred acetate 1% Antibiotic ointment to lids Blepharokeratitis: Treatment Oral antibiotic Doxycycline 20 mg to 200 mg qd/bid (I prefer Doxy 50 mg bid, then taper to qd) Minocycline 20 to 40 mg qd Azithromycin 250 to 500 mg qd x 3 days, for 3-5 weeks Azithromycin works wonders in children and adolescents! Blepharokeratitis Device in action Nutritional supplements: O3FA/O6FA Lid hygiene If recurrent, may consider Demodex tx In-office MG expression Probing IPL Lipiflow c/o Preeya Gupta, MD Device in action Suture Removal Wow.. 20

21 Suture Removal Conclusion: MK Broad spectrum fluoroquinolone Besifloxacin or moxifloxacin Withhold steroids until clinical improvement observed Rule for MK referrals Do not initiate tx if planning to refer same day better yield Conclusion: HSV Blepharokeratitis HSV epithelial keratitis: active infection No steroid with epithelial defect Topical tx option less toxic Reconsider tx or diagnosis if >10-14 days Stromal or disciform keratitis aggressive steroid initially, very slow taper Always use oral or topical anti-viral prophylaxis with steroid use Geographic ulcer? Be aware of possible neurotrophic/ metaherpetic keratopathy! Triple therapy : Topical steroid Topical antibiotic ointment or gtt Oral antibiotic O3FA/O6FA Blepharokeratitis THANK YOU Lid hygiene Think Demodex for recurrent disease or chronic blepharitis In-office MG expression treatment 21