Disclosures

. Dr. Harthan has no direct financial or proprietary interest in any In-Office Care of the Emergency Patient: companies, products or services mentioned in this presentation. Corneal Urgencies and Emergencies . Dr. Harthan speaks, consults and/or does research for: COPE ID: 50189-AS  Allergan  B+L Jennifer S. Harthan, OD, FAAO, FSLS Chief, Center for Clinical Excellence  Contamac Associate Professor Illinois College of Optometry  Metro October 27, 2017  Shire

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Overview Format for Today’s Discussion

. Corneal Abrasions . Presentation of Case . Corneal Erosions . Chemical Injuries . Corneal Lacerations . Review Etiology of Condition . Corneal Foreign Bodies . Corneal Ulcers . Corneal Hydrops . Discuss Management Options . Epidemic . Herpes Simplex Virus Dendritic . Herpes Zoster Ophthalmicus

Triage Symptoms can point you in the right direction…

. Emergent Situation . Redness  Requires immediate action . Discharge  Patient is seen same day . Foreign body sensation . Itching . Urgent Situation . Burning  Requires patient be seen within 24-36 hours . Lid edema . . Pain . Routine Situation . Changes in vision  Requires patient to be seen within a few days to a week

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Corneal Abrasion Management Potential Complications

. Antibiotic bid to q2hr . Corneal scarring . Ointment qid . Copious Lubrication . Infectious keratitis . NSAID . Cycloplegic . . Bandage CL Decreased vision . Pressure Patch . Amniotic Membranes . Recurrent erosions . Follow up every 24 hours

90 y/o AAF

2 Recurrent Corneal Erosion (RCE) Etiology and Pathophysiology RCE Acute Management

Repeated episodes of . Previous traumatic corneal abrasion spontaneous superficial . Similar to treatment for erosions abrasions  Fingernail, tree branch, paper  Antibiotics . Corneal dystrophies  Copious Lubrication  Anterior basement membrane, Lattice, Granular  Cycloplegics . Disturbance to Bowman’s layer  NSAIDs (topical vs oral)  Bandage CL  Follow up every 24 hours to . Age: 24-73 (highest prevalence between 3rd and 4th decade) several days . M=F (slightly higher female)  May need to debride . Interval between initial abrasion and first recurrence: 2 days to 16 years  If not healing in 24-48 . 10% cases bilateral hours

http://www.reviewofoptometry.com/content/d/cornea/c/53899/

RCE Prophylactic/Long-term Management

. Hypertonic therapy . Amniotic membranes  Muro 128 drops or ung qid . Autologous Serum . Doxycycline (50-100 mg bid) . Topical corticosteroids . Vitamin C  Lotemax . Surgical . Azasite  Anterior stromal puncture . Restasis and punctal plugs  Phototherapeutic keratectomy . Bandage and/or scleral lenses (PTK)  Superficial keratectomy

**Most require combination therapy***

61 y/o AAF

3 24 y/o AAF Chemical Injuries

. Potentially vision threatening! . No matter how busy… Chemical burns are seen FIRST! . By-pass VA, quickly check pH, then begin immediate irrigation IRRIGATE, IRRIGATE, IRRIGATE!! . Time and action are critical

. Severity is related to: Mild = (good  Properties of the chemical prognosis)  Area of affected surface Severe = white eye (poor  Duration of exposure prognosis)

Etiology Chemical Injuries

. Eye injuries account for 4-7% of workplace injuries . Acidic Burns . Alkali Burns  84% are chemical burns  Sulfuric (battery acid),  Lime, ammonia, . Incidence hydrofluoric, sodium hydroxide  30 per 10,000 hydrochloric  82-91% men (16-45 y/o)  Very damaging- can  90% accidental  Usually a self-limiting easily penetrate all  Alkali 2x more common burn ocular layers  2/3 occur at work  Low pH: 6.9 or lower  High pH: 7.1 or greater  10% Intentional  Assault

Grading of Severity

. Grade I . Grade II  Involves corneal  Partial loss of limbal epithelium only stem cells  Limbal stem cells  Focal limbal ischemia spared  <1/3 of limbus  No limbal ischemia  Hazy cornea  Cornea remains clear  Anterior segment  Prognosis: Excellent structures are visible  Prognosis: Good

4 Grading of Severity Chemical Injuries Management

. Grade III . Grade IV . Depends upon severity of burn  Total loss of corneal  Complete loss of corneal  Severe burns (aka significant ischemia, open , epithelium epithelium and limbal stem cells periocular open wounds) = immediate external  Loss of most limbal stem referral cells  Opaque cornea   Mild to moderate = treat the problem  Stromal haze No view of or  “Porcelainization”  Extensive limbal ischemia  > ½ Limbal ischemia  Copious irrigation with normal saline for at least 30  Prognosis: Extremely  min and repeat every 30 minutes until neutral pH is 1/3 to ½ of limbus poor  Prognosis: Guarded reached

Medical Management Goals of Treatment: Reduce Surgical Management Goal: Promote inflammation, promote epithelial revascularization of the regeneration, and prevent corneal limbus, restore limbal stem ulceration cells, re-establish fornices . Double eversion of the upper . Limbal stem cell . Steroids transplantation . Debridement of necrotic . BCL . Amniotic membrane grafting epithelium . Sclerals . Division of conjunctival bands . Artificial tears . Correction of eyelid . Ascorbic acid (Vitamin C) deformities . Antibiotic ointment . Citric acid . Tarsorrhaphy . Cycloplegic agents . Doxycycline . Penetrating Keratoplasty . Keratoprosthesis Follow up every 24 hours! . Punctal plugs

54 y/o CM

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Potential Complications

. Corneal . Punctal stenosis or occlusion Opacification/Scarring . Limbal stem cell deficiency . Symblepharon . Pannus formation . Dry Eye . . Ocular Ischemia . . Corneal Neovascularization . Loss of limbal stem cells – irregular corneal surface

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17 y/o AAF

6 Corneal Lacerations Corneal Lacerations

. Etiology: . Immediate Referral . Small, partial- thickness lacerations may generally be treated as  Industrial accidents abrasions with patching therapy . Larger wounds often require immediate surgery  Traffic accidents . No ointment should be applied to the eye . Seidel Test  Home accidents  Positive = full thickness  Negative = partial thickness  Assault . Fox shield over eye for protection  Need to keep anterior chamber intact  Traumatic would rupture

29 y/o CM Corneal Foreign Body Removal

. ***Accurate assessment of depth of penetration before removal***  Pupil irregularities, iris tears, transillumination defects, opacities, , shallow A/C, low IOP . Irrigation . Sterile cotton swab or sponge . Spud . Jeweler’s forceps . Needles . Alger brush . May need to remove deeper rust rings at a later date after they have migrated to the surface

7 Corneal Foreign Body Treatment

. After removal of foreign body  Measure size of resultant epithelial defect  Treat as for corneal abrasion Look for signs of intraocular FB: . Cycloplegic • Corneal . Antibiotic laceration, iris tear, lens opacity, . Bandage contact lens collapsed anterior . Corticosteroids chamber, low IOP  After re-epithelialization to reduce scarring . Follow up  24 hours

23 y/o AAF

Corneal Ulcer Etiology

. Bacterial . INFECTION of the cornea by microbes  S. aureus  S. pneumoniae . Characterized by excavation of the corneal epithelium, Bowman’s, and stroma  M. lacunata  P. aeruginosa . Infiltration . Necrosis of tissue . Fungal . Ideally all cases should be cultured  Fusarium . Realistically…  Aspergillus  >2mm in size  Candida  <3mm from visual axis  >1/4 corneal depth . Acanthamoeba

8 Corneal Ulcer Risk Factors Corneal Ulcer Signs/Symptoms

. Clinical manifestations . Eyelid disorders . Contact lenses  Foreign body sensation . Chronic corneal disease  Poor personal hygiene  Followed by increasing pain and photophobia . Refractive surgery  Contaminated solutions  Decreased VA .  Lens surface deposits  Marked conjunctival hyperemia and inflammation . Chronic lacrimal drainage  Non-compliance with  Ciliary flush obstruction disinfection  Pupillary constriction . Immunosuppression  Lens manipulation  Mucopurulent discharge . Trauma  Corneal hypoxia with  Anterior chamber reaction, with or without hypopyon extended wear  Ragged, irregular epithelial ulceration with underlying necrotic stromal infiltration and surrounding epithelial edema

Signs in Chronological Order Ulcer Vs. Infiltrate

Enlargement of Progressive • Infiltrate Infiltrate • Enlarging Ulceration • Circum-corneal • Stromal edema hypopyon • Corneal injection • Small perforation hypopyon • Endophthalmitis Epithelial Severe Defect Infiltration

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Corneal Ulcer Treatment

. Discontinue CL wear . Fortified subconjunctival or IV antibiotics . Culture  Cefazolin, vancomycin, . Broad spectrum topical gentamycin, tobramycin antibiotic therapy . Cycloplegic  Consider loading dose of . Topical corticosteroids antibiotic  SCUT study  One drop q 5 min for 15-30 . Amniotic Membrane min . PKP  One drop q 30-60 min for . CXL? 24 hrs

9 Treatment Treatment

. Filamentous fungi: Natamycin 5% (Natacyn) q1hr . Topical treatment often includes a combination of agents: (including during sleep)  Loading dose (first 1-3 days)  Chlorhexidine 0.02% and/or PHMB (polyhexamethylene . Yeast: Amphotericin B 0.15% q5min x 1 hour, then q1hr biguanide) 0.02%  Flucytosine orally 150mg/kg/day or topically 1% 1gt  AND q30mins to inhibit fungal growth  Propamidine isethionate 0.1% (BroleneTM) . No Steroids  POSSIBLY INCLUDE  Neomycin solution or fluoroquinolone . Consider hospitalization **Natamycin is the only commercially available . All meds q1hr (also during sleep) . Voriconazole antifungal for ophthalmic . Each drug given at the same interval separated by 5 minutes use in the US

Corneal Ulcer

. Follow up every 24 hours . Pain level, inflammation, and size of defect should decrease continually . Taper medications as needed . Refer non-compliant patients and worsening ulcers

25 y/o AAF presented to ER

. CC: “bubble on pupil” OD, x 1 . (-) meds day . PMH: (+)HTN, seasonal . (+) tearing, blurred vision, allergies, developmental eye rubbing disability . (-) pain, photophobia . Decreased VA, longstanding . (-) CL wear

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10 . VAsc:  OD 20/400 @ 2 ft  OS 20/70-2 . PERRL(-)APD . EOMS: FROM . CVF:  Restricted OD  FULL OS

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Pachymetry After 3 months of treatment

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Pachymetry after 3 months Corneal Hydrops- Signs & Symptoms

. Decreased vision . Conjunctival Injection . Pain . Corneal Edema . Redness . Break in Descemet’s . Photophobia . Bullae . . CL Intolerance . **Underlying Corneal Ectasia

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11 Standard Treatment Regimen and Inflammation?

Topical Antibiotic Prevent infection from ruptured . Keratoconus may be a “quasi-inflammatory” disorder bullae . Tears from keratoconic eyes showed elevated levels of Topical Hypertonic Solution Decrease corneal edema  Pro-inflammatory marker IL-6  Pro-inflammatory marker TNFα  Tissue degrading MMP-9’s Cycloplegic Pain management . Keratoconus may be due to an imbalance between pro- inflammatory and anti-inflammatory cytokines

Copious Artificial Tears Reduce surface irritation

Why Doxycycline? Why Vitamin C?

. Inhibitor of MMP-9’s . Excellent anti-oxidant . Indirect anti-inflammatory properties properties . Decrease apoptosis of . Beneficial in treatment of corneal tissue recurrent corneal erosions . Decreased scarring when . Promotes corneal healing used both orally and intravenously in cases of infectious keratitis

[email protected] Epidemic Keratoconjunctivitis (EKC) Epidemic Keratoconjunctivitis (EKC) Pathogenesis Clinical Manifestations- Acute Phase

 Bilateral in majority of cases  Pre-auricular lymphadenopathy . Occurs in two phases  Preceded by URI  Potential pseudomembrane  One week to 10 days after formation  Acute inoculation:  Corneal involvement  Sudden onset of profuse serous  Begins unilaterally, then less severe in fellow  discharge SPK eye  Periorbital pain  May appear as early as first or second week  Severe follicular  Follows 7-16 day course  Virus-infected cells  Chemosis  May form focal keratitis  Sequelae  Petechial hemes on palpebrum  Moderate to severe eyelid  More severe corneal involvement edema

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12 [email protected] Epidemic Keratoconjunctivitis (EKC) Clinical Manifestations- Sequelae phase

 Variable course

 Subepithelial infiltrates  Within 7-14 days after onset of ocular symptoms  Early in third week

 Variable number, location and density

 Variable affect on VA

 Delayed hypersensitivity reaction to viral antigen in overlying epithelium.

 Immunopathologic response to viral infection of keratocytes in the superficial corneal stroma.

Photo courtesy of Dr. Stephanie Klemencic

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[email protected] [email protected]

**Photophobia and reduced VA from adenoviral subepethelial infiltrates may persist for months to years.**

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[email protected] [email protected] Epidemic Keratoconjunctivitis (EKC) Management

 Patient is contagious!  Topical NSAID  Patient education  Cidofovir? (prophylaxis?)  Hygiene!!!!  Zirgan  Discard contact lenses  Betadine 5% Sterile  Supportive therapy Ophthalmic Prep  Peeling of Solution pseudomembrane  Cyclosporine A 0.5-  Topical corticosteroids 2.0%

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13 [email protected] [email protected] 5% Betadine Ophthalmic Prep Solution

. Used for pre-surgical prep

. Off-label use for moderate to severe EKC

 60 second treatment followed by lavage

 Pre- and post- treatment with topical NSAID

 Topical steroid qid x 4-6 days

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[email protected] Patient Concerns:

. Am I contagious?

. How long am I contagious for?

. Do I need to stay home from work/school?

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Herpetic : Review Herpes Simplex

. HSV eye disease is a wide spectrum of clinical problems. . HSV I . HSV II  Oral herpes  Genital herpes   . Ranges from dermatitis of eyelid, blepharitis of the lid Upper body Lower body margin, conjunctivitis, epithelial keratitis, stromal  Affects eye, mouth, skin  Less commonly affects the above the waist and eye, but tends to be more keratitis and iritis. respiratory tract severe  Less commonly affects  Sexual and neonatal genitals transmission  Transmission by direct contact

14 Herpes Simplex Herpes Simplex: Dendritic Keratitis

. Can affect anterior to posterior segment! . Symptoms: . Signs: . Corneal aesthesiometry  Foreign body sensation  Conjunctival hyperemia  Side that has herpetic infection will show reduced sensitivity!  Increased lacrimation  Early SPK that then takes  Measurement:  Photophobia on dendrite pattern  Cochet-Bonnet aethesiometer  Pain  Branching (dendritic) epithelial lesion  Cotton wisp   Dental floss Knob-like end bulbs that stain with fluorescein and lissamine green

Herpes Simplex: Dendritic Keratitis Herpetic Eye Disease

. Treatment:  Topical antivirals . NEVER PUT A STEROID ON AN ACTIVE DENDRITE  Viroptic (Trifluridine) - 9x/day until re-epithelialization; then  But put one on just about every other ocular herpetic 5x/day x 7 days sequela  Zirgan (Ganciclovir) – 5x/day until re-epithelialization; then tid  Disciform keratitis x 7 days  Stromal keratitis   Oral antiviral as alternative or in conjunction Herpetic iritis  Acyclovir 400mg 5x/day  Pseudodendrites?  Valacyclovir 500mg tid  Famciclovir 250mg tid

[email protected] [email protected] Mechanisms of Ocular Involvement

1. Direct viral invasion  epithelial keratitis or conjunctivitis

2. Secondary inflammation  , , keratitis,  Inflammation and/or degeneration of peripheral nerves, central ganglia or altered CNS signal processing may attribute to PHN

3. Reactivation  necrosis and inflammation in ganglia  neurotrophic keratitis

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15 [email protected] [email protected] Recurrent Infection: HZO varicella-zoster virus Clinical Manifestation (VZV) Headache, malaise, fever, chills

Neuralgic pain and chicken pox shingles hyperesthesia/edema of (varicella) (herpes zoster) dermatome(s)

Clear vesicle eruption; followed by yellowing and possible scarring

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[email protected]

HZV Dendrites vs. HSV Dendrites True Dendrite Pseudodendrite Herpes Simplex Herpes Zoster . HZV Dendrites: . HSV Dendrites:  Grayish-white  Branching lesion  Raised  Flat  “Painted on” appearance  Terminal end bulbs  Coarse and fragmented  Stain well centrally with  No end bulbs NaFl  Stain poorly with NaFl  Peripheral cells/ end bulbs  Stain well with RB stain with RB/LG  “Nummular Keratitis”

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[email protected] Herpes Simplex vs Herpes Zoster Varicella Zoster: Herpes Zoster Ophthalmicus Herpes SIMPLEX Herpes ZOSTER Dermatomal distribution Limited More complete . Management: Dendrite appearance Larger, more branching, Smaller, less branching,  Topical antivirals: not effective discrete, delicate pattern, coarse, blunted pattern,  more central usually peripheral Oral antivirals: dosage is double that for simplex  Best if initiated within 48-72 hours Epithelium Ulcerated Blunted dendrite with slightly  Most debilitating sequelae: post-herpectic neuralgia raised edges  Each case is individual:  i.e. if uveitis, treat uveitis appropriately Ok to use a steroid with End bulbs Present Absent  Topical artificial tears pseudodendrites! Scarring of skin Rare Common  Topical erythromycin ointment Postherpetic neuralgia Rare Common  Can spread over lesions as they crust over

Iris atrophy Rare Common

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16 [email protected] [email protected] Hutchinson’s Sign ***Herpes Antiviral Treatment***

Herpes Simplex Herpes Zoster Acyclovir 400 mg 5x/day PO 800 mg 5x/day PO (Zovirax) Valacyclovir 500 mg TID PO 1000 mg TID PO (Valtrex) Famcyclovir 250 mg TID PO 500 mg TID PO (Famvir)

•Goal: Tx within 72 hours of Sn/Sx to ↓ risk of PHN and risk of ocular complications

•Ideally Tx with prodromal Sn/Sx (tingling, numbness along CN V1 dermatome) to achieve maximum benefit of Tx

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Oral Antivirals Oral Antivirals

. Contraindications: . Effectively treats all expressions of acute herpes simplex disease  Caution with renal insufficiency – consult PCP  i.e. orals expressed in tears, can treat epithelial HSK . Side effects:  Gastric distress . High efficacy and high safety profile  Mild nausea  Very well tolerated . Notes:  Few side effects and little resistance  Drink more water while taking antivirals  Start within 72 hours for best effect . All clinically perform identically  Can also be used to prevent recurrence of stromal disease by approximately  Aim to Rx least dosage, usually valacyclovir 50%  However, acyclovir is least expensive  Acyclovir: 400mg bid x 1 year+  Valacyclovir: 500mg qd x 1 year+ . Note that acyclovir comes as a liquid suspension  Kids or adults with difficulty swallowing pills

Herpetic Eye Disease Study: HEDS Herpetic Prophylactic Treatment

. Older HEDS: focused on treatment of active disease  No benefit to adding oral acyclovir in stromal keratitis if the patient is Acyclovir 400mg bid already taking topical steroids and antivirals Valacyclovir 500mg qd  Topical prednisone is helpful in treating stromal keratitis Famciclovir 250mg qd

. Newer HEDS: focused on prevention of recurrence  Oral acyclovir 400mg bid reduced rate of recurrence of ANY form of . All reduce: ocular herpes in the following year by 41%  Frequent debilitating recurrences  Gives 50% reduction in the recurrence of severe forms of ocular herpes  Bilateral involvement  If patient already taking trifluridine gives no added benefit in  HSV infection in a monocular patient preventing epithelial disease from developing into stromal disease or iritis

17 [email protected] Important Patient Education Varicella Zoster …Questions that may arise Am I contagious? . Primary Infection = Chicken Pox Recommend . Yes Zostavax vaccine to  Varivax vaccine . Lesions contain high concentrations of VZV all patients >50 y/o . Spread via contact and airborne route . Can cause primary varicella (chicken pox) in susceptible persons . Secondary Infection = Zoster/Shingles For how long?  Zostavax vaccine . Once rash appears until lesions crust . Approximately 14 days

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[email protected] [email protected] Ocular Complications of HZO

. Conjunctivitis . Pupil anomalies (Horner Syndrome, tonic pupil) . Lid scarring . Lipid-filled granulomata . Keratitis  nummular, stromal, disciform, mucous plaque, neurotrophic . Episcleritis . Scleritis . Uveitis . Iris atrophy . Cataracts . Glaucoma, secondary to trabeculitis . CN palsies (CNIII most common) . Make sure to dilate! . . Acute retinal necrosis . Progressive outer retinal necrosis Ocular manifestations can occur 4 to 6 days after skin 105 vesicles erupt 106Facial lesions healing/starting to crust

[email protected] [email protected]

Day 7

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• Large corneal abrasion • Corneal edema w/ corneal folds • Sub-conjunctival hemorrhage nasally

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Clinical Pearls

. Thorough history . Symptoms can point you in the right direction Thank You! . Careful examination [email protected] . Treat each case individually  Consider newer approaches . Follow up appropriately . Refer as necessary

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