5/9/17

Eyelid abscess vs. Preseptal Cellulitis vs. Orbital Cellulitis Grand rounds: A string of anterior segment • Preseptal Cellulitis • Orbital Cellulitis – Usually upper eyelid – All the same signs of pearls swelling preseptal with – Pain, tenderness, – Proptosis redness – EOM restrictions/pain Nathan Lighthizer, O.D., F.A.A.O. with eye movements – Usually caused by – Pupillary involvement Blair Lonsberry, O.D., F.A.A.O. adjacent infection (hordeolum, – Usually an extension dacryocystitis) from an ethmoid sinusitis

Preventing Resistance Oral Antibiotic • Just one organism, methicillin-resistant Staphylococcus aureus (MRSA), kills Paradigm more Americans every year (∼19,000) than emphysema, HIV/AIDS, Parkinson's disease, and homicide combined – most serious MRSA infections, an estimated 85%, are associated with a healthcare exposure, but nearly 14% of the infections are community- associated. • Almost 2 million Americans per year develop hospital-acquired infections (HAIs), resulting in 99,000 deaths the vast majority of which are due to antibiotic- Penicillins Cephalosporins Fluoro- Macrolides Sulfa resistant pathogens quinolones • CDC: Get Smart: Know When Antibiotics Work – teaches both the provider and the patient when antibiotics should be used. • The IDSA suggests five to seven days is long enough to treat a bacterial Augmentin infection without encouraging resistance in adults, though children should still Keflex Zithromax Bactrim DS 875mg BID or Levaquin or get the longer course 500 mg TID 500mg TID “Z-pak” Cipro 800/160 BID – this is different than previous guidelines of treating infections from 10-14 days.

5/9/17

Ocular TRUST 3: Ongoing Longitudinal Surveillance Ocular Trust 3 of Antimicrobial Susceptibility in Ocular Isolates

• Background: • Antimicrobials tested represent six classes of drugs: • Ocular TRUST is an ongoing annual survey of nationwide – fluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin, antimicrobial susceptibility patterns of common ocular pathogens. moxifloxacin); • To date, more than 1,000 isolates from ocular infections have been – dihydrofolate reductase inhibitors (trimethoprim); submitted to an independent, central laboratory for in vitro – macrolides (azithromycin); testing. – aminoglycosides (tobramycin); • Ocular TRUST, now in its third year, remains the only – polypeptides (polymyxin B); and longitudinal nationwide susceptibility surveillance program – β-lactams (penicillin). specific to ocular isolates. • Staphylococci were classified as methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) based on susceptibility to oxacillin.

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Ocular Trust 3: Results Oral Antibiotic • most antimicrobials, except penicillin and polymyxin B, continue Paradigm to be highly active against MSSA (azithromycin shows only moderate activity) • with the exception of trimethoprim and tobramycin, less than one-third of MRSA strains are susceptible to ophthalmic antimicrobials Penicillins Cephalosporins Fluoro- Macrolides Sulfa quinolones • susceptibility profiles remain virtually identical for the fluoroquinolones, regardless of methicillin phenotype

• S. aureus is more susceptible to the fluoroquinolones than to Augmentin Keflex Zithromax Bactrim DS macrolides, as represented by azithromycin 875mg BID or Levaquin or 500 mg TID 500mg TID “Z-pak” Cipro 800/160 BID

Herpes Zoster Herpes Zoster

• Nearly 1 million Americans develop ***Varicella-Zoster Virus*** shingles each year • Herpes DNA virus that causes 2 distinct • Ocular involvement accounts for up to syndromes 25% of presenting cases 1. Primary infection – Chicken pox (Varicella) • Usually in children • Over 50% incur long term ocular damage • Highly contagious*** • Very itchy maculopapular rash with vesicles that crust over after ≈ 5 days • 96% of people develop by 20 years of age • Vaccine now available

Herpes Zoster Herpes Zoster

***Varicella-Zoster Virus*** • Herpes DNA virus that causes 2 distinct • Herpes DNA virus that causes 2 distinct syndromes syndromes 2. Reactivation – Shingles (Herpes Zoster) 1. Primary infection – Chicken pox (Varicella) • More often in the elderly and immunosuppressed (AIDS) • Usually in children – Systemic work-up if Zoster in someone < 40 • Highly contagious*** • Can get shingles anywhere on the body • Very itchy maculopapular rash with vesicles that • Herpes Zoster Ophthalmicus (HZO) crust over after ≈ 5 days – Shingles involving the dermatome supplied by the • 96% of people develop by 20 years of age ophthalmic division of the CNV (trigeminal) • Vaccine now available » 15% of zoster cases

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Herpes Zoster Herpes Zoster

• Symptoms: • Signs: – – Generalized malaise, tiredness, fever Maculopapular rash -> vesicles -> pustules -> – Headache, tenderness, paresthesias (tingling), crusting on the forehead and pain on one side of the scalp*** – Respects the midline*** • Will often precede rash – – Rash on one side of the forehead Hutchinson sign • rash on the tip or side of the – Red eye nose*** – Eye pain & light sensitivity – Classically does not involve the lower lid – Numerous other ocular signs

Herpes Zoster Herpes Zoster

• Other Eye Disease (Acute): • Other Eye Disease (Acute): – Episcleritis – Acute epithelial keratitis (pseudodendrites) – Scleritis – Conjunctivitis – Anterior uveitis – – IOP elevation Stromal (interstitial) interstitial keratitis – Retinitis – Endotheliitis (disciform keratitis) – Choroiditis – Neurotrophic keratitis – Neurological complications (nerve palsies) – Vascular occlusion

– Treat the complications just like as if they were primary conditions

Herpes Zoster Herpes Zoster

• Other Eye Disease (Chronic): • Treatment: – Neurotrophic keratitis – 50% – Treat the complications just like as if they were primary conditions – Scleritis – Oral antivirals – must be started within 72 hours – Mucous plaque keratitis – 5% of symptoms** – Eyelid scarring • Acyclovir 800mg 5x/day x 7-10 days • Valtrex 1000mg 3x/day X 7-10 days • Famciclovir 500mg 3x/day X 7-10 days – Topical ointment to skin lesions to help prevent scarring • Bacitracin, erythromycin

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Herpes Zoster Herpes Zoster • Post-herpetic Neuralgia • Prevention: – Constant or intermittent pain that persists for – Zostivax vaccine more than one month after the rash has healed – Older patients with early severe pain and larger • Live attenuated herpes virus area are at greater risk • Only given to people who know they had chicken – Can be so severe that it leads to depression & pox as a child*** suicide • Only studied in patients > 60 yo – Improves with time – 51% reduction in incidence of HZ • Only 2% of pts affected 5 years out – 60% reduction in symptom severity in those who got HZ – Tx: – 66.5% reduction in post-herpetic neuralgia • Cool compresses • Topical capsaicin ointment or lidocaine cream • Analgesics (Tylenol 3, Vicoden) • Amitriptyline 25mg PO TID • Neurotin (Gabapentin)

Viral conjunctivitis Viral conjunctivitis

• Signs: • Signs: – Red eye (conj hyperemia) – Red eye (conj hyperemia) – Watery discharge – Watery discharge – Follicles in the inferior fornix – Follicles in the inferior fornix & conj & conj – (+) PA node*** – (+) PA node***

– Red/swollen eyelids – Red/swollen eyelids – Petechial sub-conj hemes – Petechial sub-conj hemes – SPK – SPK – SEI’s (sub-epithelial infiltrates) – SEI’s (sub-epithelial infiltrates) – Pseudomembranes/membranes – Pseudomembranes/membranes often seen in EKC often seen in EKC

EKC conjunctivitis EKC conjunctivitis

• Diagnosis • Diagnosis – Based on clinical symptoms – Based on clinical symptoms • Treatment: • Treatment: – Cool compresses – Cool compresses – Artificial tears – Artificial tears – “get the red out drops” – “get the red out drops” • Vasoconstrictors such as Visine • Vasoconstrictors such as Visine – Hygiene*** – Hygiene*** – Quarantine/Isolation – Quarantine/Isolation

– Betadine 5% solution??? – Betadine 5% solution??? – Zirgan??? – Zirgan??? – Lotemax/Pred Forte QID??? – not until late – Lotemax/Pred Forte QID??? – not until late

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Herpes Simplex Herpes Simplex

• Most common virus found in humans • Recurrent infection: – 60-99% are infected by 20 years old – After primary infection the virus is carried to the sensory ganglion for that dermatome (trigeminal • Double stranded DNA virus ganglion) where a latent infection is established. – HSV type 1 (HSV-1) – Latent virus is incorporated in host DNA and cannot – HSV type 2 (HSV-2) be eradicated – Stressors (trauma, UV light, fever, hormonal changes, finals week, etc) cause reactivation of the virus and it • Primary infection is transported in the sensory axons to the periphery - – Occurs in childhood via droplet exposure > clinical signs/symptoms – Subclinical infection in most – Ocular recurrence -> 10% at one year, 50% at ten • Secondary infection (recurrence) years

Herpes Simplex Keratitis Herpes Simplex Keratitis

• Epithelial Keratitis: • Epithelial Keratitis: – Symptoms: – Signs (con’t): • Ocular irritation, redness, photophobia, watering, • Mild associated subepithelial haze blurred vision • Elevated IOP*** • Persistant SPK and irregular epithelium as the – Signs: ulcer is healing • Swollen opaque epithelial cells arranged in a course punctate or stellate pattern – Differential diagnosis: • Central desquamation results in a dendrite*** • Herpes zoster 1. Central ulceration • Healing corneal abrasion 2. Terminal end bulbs • Acanthamoeba keratitis • ***Corneal sensation is reduced*** • Medicamentosa

Herpes Simplex Keratitis Herpes Simplex Keratitis

• Epithelial Keratitis: • Epithelial Keratitis: – Treatment: – Treatment (con’t): • Zirgan (ganciclovir gel 0.15%) • Debridement of the dendritic ulcer??? – 5x/day until the dendrite disappears – 3x/day for another week • Oral antivirals??? • IOP control • Viroptic (trifluridine solution 1%) – Avoid prostaglandins??? – 9x/day until the dendrite disappears • Steroids??? – 5x/day for another week

• Oral antivirals (if topical not well tolerated): – Follow-up – Acyclovir 400 mg 5x/day X 7-10 days • Day 1, 4, 7 – Valtrex 500 mg 3x/day X 7-10 days – Famvir 250 mg 3x/day X 7-10 days

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Herpes Simplex Keratitis Herpes Simplex Keratitis

• Marginal keratitis: • Immune Stromal Keratitis (ISK): – Very rare – 2% of initial ocular HSV presentations – 20-61% of recurrent disease – Looks like a marginal infiltrate....but – 88% non-necrotizing – In HSV marginal keratitis: – 1. Much more pain 7% necrotizing 2. Deep neovascularization 3. No clear zone between – ***Can be visually devastating*** infiltrate and limbus

Herpes Simplex Keratitis Herpes Simplex Keratitis

• Immune Stromal Keratitis: • Immune Stromal Keratitis: – Symptoms: – Signs (non-necrotizing): • Stromal haze (inflammation & edema) • Gradual blurred vision • Neovascularization (deep) • Halos • Immune ring • Discomfort/Pain • Scarring and/or thinning • Redness • Intact epithelium*** – Signs (necrotizing): • All of the above • More dense infiltration • Often w/ overlying epithelial defect • Necrosis and/or ulceration • ***high perforation risk***

Herpes Simplex Keratitis Herpes Simplex Keratitis

• Immune Stromal Keratitis: • Endotheliitis: AKA Disciform Keratitis – Treatment: – Not considered a primary form of stromal keratitis • Topical steroids • Stromal edema is present secondary to endothelial – Pred Forte QID-q2H inflammation – Durezol BID-QID – Lotemax QID – Symptoms: • Topical anti-viral cover • Blurred vision – Viroptic (trifluridine 1%) QID • Halos – Zirgan (ganciclovir 0.15%) QID • Discomfort/Pain • Redness • Topical cyclosporin (Restasis), AT’s, ung’s to facilitate epithelial healing if ulceration is present

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Herpes Simplex Keratitis Herpes Simplex Keratitis

• Endotheliitis: AKA Disciform Keratitis • Endotheliitis: AKA Disciform Keratitis – Signs: – Treatment: • Central zone of stromal edema often with • Topical steroids overlying epithelial edema – Pred Forte QID-q2H • KP’s underlying the edema – Durezol BID-QID • AC reaction – Lotemax QID • • IOP may be elevated Topical anti-viral cover – Viroptic (trifluridine 1%) QID • Reduced corneal sensation – Zirgan (ganciclovir 0.15%) TID • Healed lesions often have a faint ring of stromal or subepithelial opacification and thinning • Topical cyclosporin (Restasis), AT’s, ung’s to facilitate epithelial healing if ulceration is present

Herpes Simplex Keratitis Neurotrophic Keratopathy

• Neurotrophic Keratitis: • Signs: – Keratopathy occurs from loss of trigeminal – Decreased corneal sensation*** innervation to the cornea resulting in complete or – Interpalpebral SPK partial anaesthesia – Persistent epithelial defects in which the – The cornea is numb so the pt doesn’t blink epithelium at the edge of the lesion appears rolled and thickened, and is poorly attached – Sx’s: • Irritation/burning/FB sensation – Advanced cases may have sterile ulceration, • Redness keratitis, and/or corneal melt • Tearing • Pt may be surprisingly asymptomatic** • Decreased vision

Neurotrophic Keratopathy Neurotrophic Keratopathy

• Tx: • Tx: – Find out the cause – Healing an ulcer that won’t heal – D/C any meds that may be responsible 1. Autologous serum – Lubricate, lubricate, lubricate*** 2. Prokera • Preservative free AT’s, gels, and ung’s q1h-QID – Amniotic membrane in a CL skirt – Topical Ab drops and/or ung (Polytrim QID, etc) – Taping the eyelids at night to ensure adequate 1. Also could use a scleral lens closure – In severe cases: • Patching, tarsorrhaphy, Botox to induce ptosis

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Autologous Serum Autologous Serum

1. Draw 40cc of blood through venipuncture 2. Centrifuge for 5 minutes @ 1500 rpm • Severe dry eye patients 3. Centrifuging will divide the blood into its • Graft vs. Host Disease separate components • Filamentary Keratitis 4. Place 1cc of serum in each bottle • Neurotrophic keratitis 5. Add 4cc of saline to make a concentration of 20% • Chronic Stainers serum eye drops 6. 20% serum eye drop concentration

Herpes Simplex Epithelial Herpes Simplex Keratitis Keratitis • My Regimen: • Prophylactic Treatment: – Zirgan 5x/day until the ulcer heals, then 3x/day – Reduces the rate of recurrence of epithelial and for one week stromal keratitis by ≈ 50% – Oral Valtrex 500 mg 3x/day for 7-10 days • Acyclovir 400 mg BID – Artificial tears • Valtrex 500 mg QD • Famvir 250 mg QD

– L-Lysine 2 grams daily? • L-lysine 1 gram/day – Debride the ulcer? • Frequent debilitating recurrences, bilateral involvement, or HSV infection in an only eye • RTC 1 day, 4 days, 7 days

Recurrent Corneal Erosions Herpes Simplex (RCE’s)

• Visual Prognosis: • Tendency for minor trauma to cause – 90% 20/40 or better after 12 years significant corneal epithelial disturbances • Pathophysiology – 3% 20/100 or worse after 12 years – Abnormally weak attachment between the basal cells of the corneal epithelium and their basement membrane • Most common causes of the weak attachment – Mechanical trauma** – Corneal dystrophy** – Corneal surgery

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Recurrent Corneal Erosions Recurrent Corneal Erosions

• Sx’s: • Signs: – Acute, severe pain** – Epithelial defect may be present, – Photophobia ** usually in the inferior – Redness interpalpebral area – Blepharospasm – Tearing

***Usually sx’s present first thing in the morning upon opening the eyes.*** And often this is recurrent

Recurrent Corneal Erosions Recurrent Corneal Erosions

• Signs: • Tx: – If no defect is present, look for loose, irregular – Acutely: epithelium • Lubrication** (pooling of NaFl, rapid TBUT) • Topical Ab (Polytrim QID, erythro or bacitracin ung) – Signs of corneal dystrophies (will be bilateral) • Pain control: – Cycloplegic (Homatropine BID) • Muro 128 drops or ung

• Bandage lens??? – Alleviates pain, does not improve healing

Recurrent Corneal Erosions Recurrent Corneal Erosions

• Tx: • Surgical Tx: – After the epithelium heals (recalcitrant RCE’s): – Anterior stromal micropuncture • Fresh Kote TID (15ml bottle $25) – Debridement of epithelium with polishing of • Muro 128 ung qhs (3.5g tube $10) Bowman’s membrane with a diamond burr or • Lotemax QID X 2 weeks, BID X 6 weeks excimer laser (PTK) • Doxycycline 20-50mg BID – Azasite BID (2.5ml bottle $78)

**Avoid chronic long-term AT ung**

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Acanthamoeba keratitis Acanthamoeba Keratitis

• History of CL wear w/ poor lens hygiene • Sx’s: • Often a history of hot tub/swimming – Severe pain** pool/swimming in the river – Redness • Symptoms: – Tearing – Severe pain out of proportion to clinical picture – Decreased vision – Redness & photophobia – Photophobia – All over the course of several weeks – Minimal discharge • Signs: – Early -> Pseudodendrites These sx’s tend to develop over a period of weeks.** – Late -> Ring-shaped stromal infiltrate H/O CL hygiene problems and swimming in lenses**

Acanthamoeba Keratitis Acanthamoeba Keratitis

• Signs: • Signs: – Epithelial or subepithelial infiltrates – Radial keratoneuritis** appearing as pseudodendrites early on • Perineural infiltrates seen during the first 1-4 weeks – Patchy anterior stromal infiltrates can – Gradual enlargement and coalescence of the also appear early infiltrates to form a ring infiltrate** • Inflammation in the cornea doesn’t look that bad** – Corneal thinning, melting, perforation, scleritis, hypopyon

Acanthamoeba Keratitis Fungal keratitis

• Tx: • Often a history of vegetative trauma, CL – Topicals: wear • PHMB 0.02% drops q1h • H/O poor response to topical Ab’s • Chlorhexidine 0.02% q1h – Fine line agents can be given separately or together • Symptoms: • Propamidine 1% (Brolene) q1h – Pain, photophobia, tearning, FB sensation – Orals: • Pain often less than what the clinical picture would • Voriconazole 200 mg BID indicate • Itraconazole 200-400 mg QD • Signs: – Cycloplegics (homatropine BID) – Stromal infiltrate w/ a feathery border – Topical steroids?? – Satellite lesions surrounding the primary – Pain control infiltrate – Surgery

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Fungal Keratitis Fungal Keratitis

• Sx’s: • Signs: – Gradual onset of pain – Gray-white stromal infiltrate with indistinct – Irritation/grittiness “fluffy” or “feathery” borders/margins – Photophobia – Often surrounded by fingerlike satellite – Blurred vision lesions in the adjacent stroma – Watery or mucopurulent discharge

H/O cornea infection diagnosed as bacterial** H/O vegetative trauma, CL abuse, chronic steroid use

Fungal Keratitis Fungal Keratitis

• Signs: • Tx: – Epithelial defect overlying the ulcer – Pts may require hospitalization – Topical meds: • However can be quite small and sometimes is not • present Natamycin 5% (for filamentous fungi)* • Amphotericin B 0.15% (for Candida)* – Infiltrates may progressively enlarge and extend • Both q1h around the clock initially and then tapered into deeper tissue over 6-12 weeks • Necrosis, thinning and perforation can occur – Orals meds: • Voriconazole 200 mg BID • Itraconazole • Fluconazole – Cycloplegics (homatropine BID) – Surgical (PKP or DALK)

Which topical antibiotic is your “go-to” choice for a suspected MRSA infectious Bacterial Keratitis bacterial ulcer? A. Zymaxid/Zymar • Tx: B. Polytrim – Hospitalization??? – No CL’s*** C. Besivance – Pain relief D. Moxeza/Vigamo – Topical Ab’s: (amount & strength depends on the ulcer) x • Besivance, Moxeza, or Zymaxid q1h around the clock for E. Ciloxan 24-48 hours & tapering according to clinical progress • Besivance (or Moxeza or Zymaxid) & Tobramycin (or F. Tobramycin Gentamicin) q1h alternating around the clock

G. Vancomycin • Fortified Ab’s??? (large ulcers, visual axis, hypopyon) – Fortified Vancomycin, cephalosporins and/or gentamicin

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Ocular Trust 3: Results Bacterial Keratitis

• most antimicrobials, except penicillin and polymyxin B, continue • Tx: to be highly active against MSSA (azithromycin shows only moderate activity) – Steroids??? • with the exception of trimethoprim and tobramycin, • Reduce inflammation, improve comfort, and minimize less than one-third of MRSA strains are susceptible corneal scarring…but evidence that they improve final to ophthalmic antimicrobials visual outcome is limited • Will make herpes, fungal, acanth much worse • Epithelialization may be slowed by steroids • susceptibility profiles remain virtually identical for the fluoroquinolones, regardless of methicillin phenotype • Can cause corneal thinning (but not usually) • • S. aureus is more susceptible to the fluoroquinolones than to DO NOT USE until clinical improvement is seen with macrolides, as represented by azithromycin Ab’s alone • Pred Forte QID – Doxycycline or Azasite??? • Inhibit MMP-9

Thank you for your attention!

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