<<

30TH Annual OPTOMETRIC PHYSICIAN SYMPOSIUM

January 26th, 2019 Anterior Segment Grand Rounds Blair Lonsberry, O.D., FAAO 1/25/2019

Dendritic Ulcers Case

• 20 year old male presents with a painful – Started that morning when he woke up – reports a watery discharge, no itching, and is not a contact wearer • SLE: – See attached image with NaFl stain

3

Herpes Simplex : Clinical Features

• Characterized by primary outbreak and subsequent reactivation • Primary outbreak is typically mild or subclinical • After primary , the virus becomes latent in the trigeminal ganglion or • Stress, UV radiation, and hormonal changes can reactivate the virus • Lesions are common in the immunocompromised (i.e. recent organ transplant or HIV patients)

1 1/25/2019

Anti‐Viral Medication Pediatric HSV Keratitis Drug Mechanism of Action Bioavailability Dosing Side Effects Acyclovir Acyclovir interferes 10‐30% gets Simplex: Overall very safe • pediatric keratitis has an 80% risk with DNA synthesis absorbed 400 mg Nausea, of recurrence, a 75% risk of stromal disease, and inhibiting viral Short ½ life 5x/day vomiting, a 30% rate of misdiagnosis replication *Metabolized in Zoster: , kidneys 800 mg dizziness, • 80% of children with 5x/day confusion develop scarring, mostly in the central cornea Valacyclovir Acyclovir pro‐drug 95% converted Simplex: Same as acyclovir – results in the development of Equivalent to acyclovir to acyclovir* 500 mg tid but better for Better Zoster: – 25% of children have more than 2 D of astigmatism, management bioavailability 1 g tid most of which is irregular and longer 1/2 • consider pediatric HSV when a patient has life unilateral recurrent disease in the anterior Famciclovir Inhibits DNA chain Superior to Simplex: Same as acyclovir segment (Famvir) elongation acyclovir* 250 mgTID It is metabolized to Zoster: penciclovir where it is 500 mg TID active 10‐20x as long as acyclovir

Herpes Simplex Keratitis Management HSV Stromal Disease

• Topical: – Viroptic () q 2h until epi healed then • HSV Stromal disease is an immune‐mediated disease taper down for 10-14 days. • Increased risk of scarring and high risk of poor visual • Viroptic is toxic to the cornea. prognosis – Zirgan () available, use 5 times a • Requires (HEDS: reduced risk of day until epi healed then 3 times for a week progression by 68%) (US only) – Without epithelial defect: corticosteroids and prophylactic anti‐viral dosage – With epithelial defect: active infection anti‐viral dosage with judicious corticosteroids

2 1/25/2019

How much to dose ? Herpes Simplex Keratitis

• HEDS used QID of prednisolone phosphate • Prophylactic Treatment: – Reduces the rate of recurrence of epithelial and stromal • Current Recommendations: keratitis by ≈ 50% – Mod –severe (especially with neo): 1% • Acyclovir 400 mg BID Prednisolone or Lotemax QID to 6x/day • Valtrex 500 mg QD • Famvir 250 mg QD – Want the lowest dose needed to control the • L‐lysine 1 gram/day: – AAO EBM Treatment Guideline 2014 – Proven to “slow down” and retard the growth of • Topical steroid for 10 weeks (this is based on HEDS results) with oral the herpes virus and inhibit viral replication antiviral • Frequent debilitating recurrences, bilateral involvement, or HSV infection in a monocular patient

Herpes Simplex Epithelial Keratitis Prophylaxis??

• Treatment Regimen: : – Zirgan 5x/day until the ulcer heals, then 3x/day for one week • Pitfalls to Prophylaxis – Oral Valtrex 500 mg 3x/day for 7‐10 days – Reduction of recurrence does not persist once drug – Artificial stopped – Resistance???? – L‐Lysine 2 grams daily? • van Velzen, et. al., (2013) demonstrated that long‐ • Proven to “slow down” and retard the growth of the herpes virus and term ACV prophylaxis predisposes to ACV‐refractory inhibit viral replication – Debride the ulcer? disease due to the emergence of corneal ACVR HSV‐1. • Prior to topical antiviral therapy debridement was treatment of choice • Generally try to avoid use of sharp instruments and use of cotton swab and anesthetic

• RTC 1 day, 4 days, 7 days

3 1/25/2019

Consider Combining APAP with NSAID’s for Mild to Pain Management: Oral Analgesics Moderate Pain Relief

• Conditions potentially requiring us of oral 1:00 pm: Two 325mg Tylenol analgesics: – Corneal ulcers 3:00 pm: Two 200mg Ibuprofen – Herpes simplex/zoster 5:00 pm: Two 325mg Tylenol – Post‐surgical 7:00 pm: Two 200mg Ibuprofen – Trauma – Thermal burns Alternated every 2 hours while awake – Each medication is q 4 hours.

Acetaminophen Ibuprofen

• Adult analgesic dose: 200‐400mg q4hours – Maximum Dosage: 2400 mg/day for pain (approved for 3200 • Mechanism of Action is not well understood. mg/day in arthritis treatment) – Possibly some CNS component – Very weak inhibitor of synthesis • OTC: 200 mg tabs • Rx: 300, 400, 600, 800mg tabs

• One of the most commonly used analgesics for mild • Peak levels 1‐2 hours to moderate pain. – Equal analgesic properties to ASA unless associated with • Most renal toxic of all the NSAID’s inflammation, where it is less effective. • Brand Names: Motrin, Advil, and Nuprin Take home: Good for pain; Good for fever; No effect on inflammation

4 1/25/2019

Indoleacetic Acids: Indomethacin Oral Analgesics: Guidelines

• Adult Dosage: 25‐50 mg TID • Never exceed maximum recommended dosages: • Rx Only: 10mg ‐ 75mg capsules – ASA: 8 grams/day • Mainly used as a short term anti‐inflammatory especially – Acetaminophen: 4 grams/day for conditions that do not respond to less toxic NSAIDS. – Ibuprofen: 1200 mg/day OTC and 2400 mg/day – Indomethacin has a very high level of intolerance compared to other NSAID’s. prescription – Naproxen: 1250 mg/day • Oral NSAID most widely used in Tx of ocular inflammation. – Naproxen Sodium: 1375 mg/day – Codeine: 360 mg/day

Cox‐2 Inhibitors Oral Analgesics: Guidelines

• Selective agents for only COX‐2 designed to protect the GI system from the • Make the proper diagnosis first (ie. Don’t side effects seen with NSAID’s. prescribe without knowing what you are prescribing for!) • Major agent available on the market is Celecoxib (Celebrex). • Treat the underlying cause for the pain – Other agents Valdecoxib (Bextra) and Rofecoxib (Vioxx) were removed from the market due to increased risk of heart attacks and . • Treat the pain at presentation..don’t wait! – It is approved for the treatment of osteoarthritis and rheumatoid arthritis. • Treat pain continuously over a 24 hour schedule – Dosage: 100 mg BID or 200 mg daily • Non‐prescription drugs should be first choice and tend to be low cost • Treat patients with the simplest and safest means to alleve pain

5 1/25/2019

Scheduled Medications –Most Opioids

Opioids Side Effects Schedule Description Optometric Medications

I Not commercially available; no approved indication

• Side Effects are very hard to predict because opioids can Very addictive medications that Oxycodone = OxyContin, OxyFast cause CNS depression or stimulation. are accepted for medicinal use Oxycodone + APAP = Percocet or Tylox Oxycodone + ASA = Percodan Oxycodone + NSAID = Combunox • CNS Side Effects II Hydromorphone (Dilaudid) Codeine Sulfate = Codeine Generic – Dizziness, lightheadedness, sedation, and drowsiness are Meperidine (Demerol) the most common. Hydrocodone + APAP = Lortab or Vicodin – Mood elevation (euphoria) and disorientation can occur in Hydrocodone + Ibuprofen = Vicoprofen some patients. Significant abuse risk, but less Codeine + APAP = Tylenol 3 and Tylenol 4 III potent than I or II. May still – Exacerbated if used in combination with alcohol, contain narcotics. depression medications such as tricyclic antidepressants, Relatively low abuse potential Propoxyphene (Darvon) anticholinergics, antihistamines, anti‐seizure medications, and limited risk Propoxyphene with APAP = Darvocet or muscle relaxants, etc. IV (Removed from Market in November 2010). – Visual symptoms such as blurry vision, , and Pentazocine + APAP (Talacen) can occur. Tramadol Very limited abuse potential. Acetaminophen V May be OTC in some states.

Opioid Side Effects Schedule III Opioids: Codeine

• Usually administered in combination with . – – Respiratory Side Effects: Tylenol 3 = Codeine 30 mg and Acetamenophin 300 mg • Respiratory Depression • Dosage: 1‐2 tablets every 4 hours. – Most serious side effect of the opioids – – Opioids suppress the brainstem respiratory centers Tylenol 4 = Codeine 60 mg and Acetamenophin 300 » Alter tidal volume, respiratory rate, rhythmicity, and mg

responsiveness to CO2 • Dosage: 1 tablet every 4 –6 hours – Does not commonly occur at therapeutic doses in healthy patients, – Also available as generic with 15, 30, or 60 mg of but must use caution in patients with pulmonary disease. Codeine with 300 mg of Acet. or elixer of 12 mg codeine + 120 mg Acet. per 5 mL.

The FDA• hasElixer mandated can be that used all prescription in children medications for pain havemanagement no more than if >3325 mg of Acetaminophenyears. in each capsule/tablet by January 2014.

6 1/25/2019

Schedule II Opioids: Hydrocodone Schedule II Opioids: Oxycodone

• Approximately 6X more potent than codeine. • Approximately 10‐12X more potent than codeine • Milder Side Effects than Codeine: Less – As potent as parenteral morphine when given constipation and sedation. orally.

• Clinically believed to cause more euphoria than • Lower level of side effects in comparison to codeine, but this is not backed by clinical morphine, but high level of euphoria studies. produced, thus higher level of abuse risk.

Schedule II Opioids: Hydrocodone Schedule II Opioids: Oxycodone

• Used in combination with APAP and Ibuprofen. • Available in combination with APAP, ASA, or Ibuprofen. – Lortab: Hydrocodone 5, 7.5, and 10 mg with APAP 325 mg – Percocet Tablets • Dosage: 1‐2 tablet every 4‐6 hours • 2.5, 5, 7.5 or 10 mg Oxycodone with 325 mg Acetaminophen – Lortab Elixer: Hydrocodone 10 mg with APAP 300 / 15 mL • Dosage: 1 tablet every 6 hours • Dosage: 3 tsp every 4‐6 hours – Tylox Capsules – Vicodin: Hydrocodone 5 mg with Acetaminophen 300 mg • 5 mg Oxycodone with 300 mg Acetaminophen – Vicodin HP: Hydrocodone 10 mg with Acetaminophen 300 mg • Dosage: 1 tablet every 6 hours • Dosage: 1 tablet every 4‐6 hours – Percodan Tablets – Vicodin ES: Hydrocodone 7.5 mg with Acetaminophen 300 mg • 4.5 mg Oxycodone HCl • Dosage: 1 tablet every 4 –6 hours • 0.38 mg Oxycodone terephthalate – Vicoprofen: Hydrocodone 7.5 mg with Ibuprofen 200 mg • 325 mg • Dosage: 1 tablet every 6 hours • Dosage: 1 tablet every 4‐6 hours – – Norco: Hydrocodone 5, 7.5, and 10 with 325 mg APAP Combunox • 5 mg Oxycodone with 400 mg Ibuprofen • Dosage: 1 tablet daily to QID

7 1/25/2019

Newly Schedule IV: Tramadol (Ultram) Tramadol + APAP (Ultracet)

• Central acting narcotic • Combination of: – Synethetic analogue of codeine. – 325 mg of APAP – Binds to mu receptors and inhibits norepinephrine and serotonin reuptake. – 37.5 mg of Tramadol – Potential for abuse is very low, but has occurred. • Dosage: 2 tablets • Available as 50 mg tablets. every 4 –6 hours

• Dosage: 50 – 100 mg q4 –6 hours. – Analgesia occurs after 1 hour. • Max: 8 tablets daily – Maximum dose: 400 mg/day

Tramadol Extended Release (Ultram ER) Case

• Available dosages of 100, 200, and 300 mg • 55 yr white female complains of fluctuating extended. vision – Begin taking 100 mg daily X 5 days – Worse at near – Increase by 100 mg if relief not met to 200 mg X 5 days. – Spends 8-10 hours/day on the computer – 300 mg maximum daily. • Medical Hx: • Does not work on all patients –some need heavy – Hypertension for 10 years doses every 4‐6 hours. – Joint pain • Medications: – HCTZ for HTN • More for chronic pain control. – Celebrex for her joint pain

8 1/25/2019

Exam Data Differential Diagnosis of Dry Eye • VA (corrected): OD: 20/25, OS: 20/25 • PERRL • EOM’s: FROM • CVF: FTFC • SLE: – TBUT 5 sec OD, OS – Positive NaFl staining and Lissamine staining of conj and cornea – Decreased tear prism

Additional Testing/Questions DEWS II DED Definition

• Schirmer: < 5 mm of wetting in 5 minutes OD, “Dry eye is a multifactorial disease of the ocular OS surface characterized by a loss of homeostasis of • RF and ANA: normal for patients age the tear film, and accompanied by ocular • SS-A: 2.0 (normal < 1.0), SS-B: 1.9 (normal symptoms, in which tear film instability and <1.0) hyperosmolarity, ocular surface inflammation • Additional symptoms reported: and damage, and neurosensory abnormalities – Patient experiences dry mouth and taking Salagen play etiological roles.”

• Diagnosis: Sjogren’s Syndrome

9 1/25/2019

Signs and Symptoms of Dry Eye

Signs: Symptoms: – Ocular Surface Damage – Grittiness • Corneal Staining ( and/or Rose Bengal) – Burning • Conjunctival Staining (Lissamine Green ) – Irritation – Decreased Tear Quantity – Stringy discharge • Schirmer Score – Blurring of vision • Phenol Red Thread Test – Ocular Surface Disease Index (OSDI) • Tear Meniscus Height – Decreased Tear Quality • Tear Break Up Time (TBUT) • Tear Osmolarity

InflammaDry

• Point of care testing to measure MMP‐9 levels – MMP‐9 is an inflammatory biomarker found to be elevated in patients with dry eye • Marketed by RPS

10 1/25/2019

Treatment Sjogrens

• We initiated: • Chronic AI disease that involves diffuse – Omega-3 supplements (2 grams per day) exocrine gland dysfunction and lymphocytic – Recommended warm compresses and lid washes qhs – Testosterone cream 3% applied to upper lid bid infiltration throughout the body

• Patient had significant improvement in symptoms with the use of the • Decreased lacrimal gland secretion results in K topical testosterone cream. sicca – However, she was still symptomatic at the end of the day and she still had significant staining on her cornea and • Decreased salivary gland secretion results in – Initiated FML tid for 1 month, Restasis bid after 2 weeks • 2 months later patient reported further improvement in her symptoms sicca complex • No conjunctival staining was noted and only slight SPK • Emotional tearing is not affected • Schirmer values improved to OD: 9 mm, OS: 10 mm

SJOGREN’S SYNDROME: Role of Androgens? OLD/NEW CLASSIFICATION • Recent studies have suggested that androgen deficiency • Old: may be the main cause of the – 1o Sjogrens: occurs when sicca complex manifests by dysfunction, tear-film instability and evaporative dry eye itself seen in Sjogren patients • no systemic disease present • Transdermal testosterone 3% promotes increased tear – 2o Sjogrens: occurs in association with collagen production and meibomian gland secretion, thereby vascular disease such as reducing dry eye symptoms (Dr. Charles Connor). • RA and SLE • Progesterone 0.05%/Testosterone 0.05% Ophthalmic • significant ocular/systemic manifestations Solution BID (local compounding pharmacy?) • New: • Topical Testosterone 0.5% drops BID (compounding – The diagnosis of SS should be given to all who fulfill pharmacy) the new criteria while also diagnosing any concurrent organ-specific or multiorgan autoimmune diseases, without distinguishing as primary or secondary.

11 1/25/2019

Sjogren’s Ocular and Systemic Dry Eye Summit

• Recently published article comments: • Held in December 2014 – all patients had dry eye symptoms for – Combination of optometrists, an ophthalmologist and approximately 10.4 years before industry presentation • Goal: – 42% of the patients had systemic – to find a way to encourage optometrists to look for, manifestations resulting from primary SS diagnose and manage dry eye in their patients – SS has been shown to be an independent – Come to a consensus on the minimum: risk factor for the development of non‐ • 3 questions that should be asked to identify dry eye patients Hodgkin’ s lymphoma. • 3 diagnostic tests • 3 initial treatments

REV. as of March 13, 2015 Sjogren’s Ocular and Systemic Consensus on Screening Questions 1. Do your ever feel dry or • Authors recommendation: uncomfortable? – primary SS is associated with vision‐ and life‐ 2. Are you bothered by changes threatening complications in your vision throughout the – presence of SS needs to be explored in patients day? with clinically significant dry eye because dry eye 3. Are you ever bothered by red precedes the occurrence of the systemic eyes? manifestations 4. Do you ever use or feel the need to use drops?

Recommendations from the Dry Eye Summit 2014

12 1/25/2019

Consensus on Baseline Diagnostic Options for Entry Level Dry DREAM Study

1. The lid • In a multicenter, double‐blind clinical trial, we randomly assigned patients with moderate‐to‐ 2. Staining severe dry eye disease to receive a daily oral dose 3. Tear stability of 3000 mg of fish‐derived n−3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). • “The results of the DREAM study do not support REV. as of March 13, 2015 use of omega‐3 supplements for patients with moderate to severe dry eye disease”

Recommendations from the Dry Eye Summit 2014

REV. as of March 13, 2015 Consensus on Baseline Management DREAM Study

1. For all patients: • In DREAM, most dry eye symptoms and signs appear to improve in both arms. A. Ocular lubrication • In each trial group, there was a meaningful B. Lid hygiene statistical change between baseline and 12 C. Nutrition months (with time as a continuous variable) in 2. Topical anti‐inflammatories the conjunctival staining score, the corneal staining score and the tear break‐up time

Recommendations from the Dry Eye Summit 2014

13 1/25/2019

® Introducing TearCare from Sight Sciences, Inc. Preseptal Cellulitis

•TearCare® is the only wearable  therapeutic technology that is Infection and inflammation fully customizable and allows the located anterior to the orbital patient’s eyes to remain open and septum and limited to the blinking during the procedure. superficial periorbital tissues •Soft, flexible powered devices and . conform to the eyelids to deliver a sufficient level of energy to liquefy  Usually follows sinus infection or meibum. internal hordeolum (possibly •Lastly, the specially designed Clearance trauma) Assistant is used to provide a personalized  Eyelid swelling, redness, , gland clearing treatment. pain and low grade fever.

ht Sciences 2018 05967.A p 53/5

Introducing: TearCare® Preseptal Cellulitis

 Infection and inflammation located anterior to the orbital septum and limited to the superficial periorbital tissues and eyelids.  Usually follows sinus infection or internal hordeolum (possibly trauma)  Eyelid swelling, redness, ptosis, pain and low grade fever.  Tx:  Augmentin 500 mg TID or 875 mg BID for 5-7 days  Keflex 500 mg QID 5-7 days  or if moderate to severe IV Fortaz (ceftazidime) 1‐2 g q8h.  If MRSA possible, consider Bactrim/Septra © Sight Sciences 2018 06131.A

14 1/25/2019

Differentiating Orbital vs. Preseptal Penicillins: Augmentin (Clavulin) FINDING ORBITAL PRESEPTAL Decreased Normal • Augmentin is very effective for skin and skin Proptosis Marked Absent structure such as: and Marked Rare/Mild • , Hyperemia • internal hordeola, RAPD Normal • pre-septal cellulitis. Pain and Motility Restricted and Painful Normal – Treatment of: IOP Normal • otitis media, Temperature 102 ‐ 104 Normal/mild elevation • , HA and Assoc. Common Absent • lower respiratory and urinary infections. Symptoms – Given prophylactically to dental surgery patients.

Treatment: Orals for Preseptal, Often IV for Orbital

Penicillins: Augmentin (Clavulin) Penicillins: Augmentin (Clavulin)

• Augmentin is amoxicillin with potassium – It has low: clavulanate (clavulanic acid 125 mg). • GI upset, • Canada: Clavulin • allergic reaction and anaphylaxis. • Clavulanate is a B-Lactamase inhibitor which – Serious complications include: reduces a bacteria’s ability to negate the effect • anemia, of the amoxicillin by inactivating penicillinase • pseudomembranous and (enzyme that inactivates the affect). • Stevens-Johnson syndrome.

15 1/25/2019

Penicillins: Augmentin (Clavulin) Cephalosporins • 1st generation: cefadroxil (Duricef), cefazolin Adults: •(Ancef), cephalexin (Keflex), and cephalothin – 250-500 mg tab q 8hr (tid) • 2nd generations: cefaclor (Ceclor), cefprozil, (also available in chewable cefuroxime (Zinacef), cefotetan, cefoxitin tablets and suspension) • 3rd generation: cefdinir (Omnicef), cefixime, – or 875 mg q 12hr (bid) cefotaxime (Claforan), ceftazidime (Fortaz), – 1000 mg XR: q12 hr and not ceftibuten, ceftizoxime, ceftriaxone (Rocephin for use in children <16 IM/IV). Peds: <3 mos 30mg/kg/day • 4th generation: cefepime divided q12hrs using • Omnicef, Keflex, Ceclor (all orally administered) are suspension effective against most gram positive pathogens and • >3 mos 45-90mg/kg/day divided especially good for skin and soft tissue infections. q12hrs (otitis media 90mg for 10 days)

Cephalosporins Cephalosporins

• Closely related structurally and functionally to the penicillins, • Keflex (cephalexin): – have the same mode of action, – treatment of respiratory, GI, skin and skin – affected by the same resistance mechanisms. structure, and bone infections as well as otitis media – tend to be more resistant to B-lactamases. – Adults: 250-1000 mg every 6 hours • classified as 1st, 2nd, 3rd, and 4th generation based largely on their bacterial susceptibility patterns and resistance to B- • - typical dosing 500 every 6 hours lactamases. – Children: 25-100 mg/kg/day divided 6-8 hours • Should be avoided or used with caution in patients who are allergic to penicillin (apprx 10% x-reaction with penicillin allergy has been reported but thought to be much closer to the 1-2%) – allergic response without allergy to penicillin is 1-2%. • Typically administered IV or IM, poor oral absorption.

16 1/25/2019

Co‐Trimoxazole (Bactrim/Septra) Co-Trimoxazole (Bactrim/Septra)

• Combination of trimethoprim and • Available: sulfamethoxazole – Bactrim/Septra tablets: – shows greater antimicrobial activity – contains 80 mg trimethoprim and 400 mg than equivalent quantities of either sulfamethoxazole drug alone. – dosing 2 tablets every 12 hours • Has broader spectrum of action than the – Bactrim DS/Septra DS (Double Strength) sulfa’s and is effective in treating: • contains 160 mg trimethoprim and 800 mg – UTIs and respiratory tract infections sulfamethoxazole – often considered for treatment of • Dosing 1 tablet every 12 hours MRSA skin infections

Epithelial (Anterior) Basement Membrane Co‐Trimoxazole (Bactrim/Septra) Dystrophy (EBMD or ABMD)

• Resistance is more difficult because has to • Abnormal basement membrane production develop resistance to both drugs. • Not all patients are symptomatic (range 10‐69%) • Adverse effects include: • Most common symptom is mild FB sensation – severe potential for dermatologic reactions, which is worse in dry weather, wind and air – GI upset, conditioning – blood disorders, and • from irregular astigmatism or rapid – drug potentiation. TBUT • Pain is usually secondary to a RCE (recurrent corneal erosion) in apprx 10%

17 1/25/2019

Epithelial (Anterior) Basement Membrane Epithelial (Anterior) Basement Membrane Dystrophy (EBMD or ABMD) Dystrophy (EBMD or ABMD) • Easy to overlook: • Often referred to as: – maps, – typically bilateral though often asymmetric, – dots or – females>males, – fingerprints – often first diagnosed b/w ages of 40‐70

71

Epithelial (Anterior) Basement Membrane Epithelial (Anterior) Basement Membrane Dystrophy (EBMD or ABMD) Dystrophy (EBMD or ABMD): Treatment • Most common findings are: • Typically directed towards preventing RCE – chalky patches, – intraepithelial • If RCE’s develop: microcysts, and – awake with painful – fine lines (or any eye that improves as combination) in the day wears on central 2/3rd of cornea – chalky patches/dots in lower 2/3rd of cornea

70

18 1/25/2019

RCE: Treatment Diamond Burr Polishing

• Initial treatment • Removes abnormal basement membrane includes: • May also promote scarring – use of hyperosmotic ointment at bedtime, – bandage and – lubrication.

73

Recurrent Corneal Erosion: Treatment Herpes Zoster

• If severe enough to cause vision loss or repeated 1. Primary infection –Chicken pox (Varicella) episodes: • Usually in children • oral doxycycline with/without topical corticosteroid • Highly contagious*** – Doxy 50 mg bid and FML tid for 4‐8 weeks – both meds inhibit key metalloproteinases important in disease • Very itchy maculopapular rash with vesicles that crust pathogenesis over after ≈ 5 days – Azasite (topical azithromycin) • 96% of people develop by 20 years of age • debridement, • stromal puncture, or • Vaccine now available • PTK • Latest development: amniotic membrane transplant e.g. Prokera

19 1/25/2019

Herpes Zoster Herpes Zoster • Other Eye Complications (Acute): 2. Reactivation – (Herpes Zoster) – Anterior (most common ocular manifestation) • More often in the elderly and immunosuppressed – Acute epithelial keratitis (pseudodendrites) (AIDS) – – Systemic work‐up if Zoster in someone < 40 – Stromal (interstitial) interstitial keratitis • Can get shingles anywhere on the body – Endotheliitis (disciform keratitis) – • Herpes Zoster Ophthalmicus (HZO) – Shingles involving the dermatome supplied by the ophthalmic division of the CNV (trigeminal) » 15% of zoster cases

Herpes Zoster Herpes Zoster

• Symptoms: • Associated factors include increasing age, immune deficiency and stress. – Generalized malaise, tiredness, fever • Only people who had natural infection with wild‐ – , tenderness, paresthesias (tingling), and type VZV or had varicella vaccination can develop pain on one side of the scalp herpes zoster. • Will often precede rash • Children who get the varicella vaccine appear to – Rash on one side of the forehead have a lower risk of herpes zoster compared with – people who were infected with wild‐type VZV. – Eye pain & sensitivity

20 1/25/2019

Herpes Zoster NEW!! Shingrix HZ Vaccine

• A person's risk for herpes zoster increases sharply • Approved in US/Canada as of October 2017 • non‐live antigen, to trigger a targeted immune response, after 50 years of age. with a specifically designed adjuvant to enhance this • Almost 1 out of 3 people in the United States will response and help address the natural age‐related decline develop herpes zoster during their lifetime. of the immune system • Shingrix is 97% effective against shingles for people • A person’s risk of developing post‐herpetic neuralgia between the ages of 50 and 69 and 91% effective for also increases sharply with age. people 70 or older. • It is 91% effective against postherpetic neuralgia for people 50 and older. • These rates are based on evidence presented to the committee from clinical trials with over 38,000 total participants.

Herpes Zoster NEW!! Shingrix HZ Vaccine

• Management includes: • recommended for healthy adults aged 50 – oral antivirals: years and older to prevent shingles and • 800mg acyclovir 5x/day related complications • valacyclovir (Valtrex) 1g TID, • famciclovir (Famvir) 500 mg TID • recommended for adults who previously – effectiveness of therapy is best started within 72 hours received the current shingles vaccine – oral (clinical trials show variable results but often (Zostavax®) to prevent shingles and related prescribed with antiviral to reduce pain) complications – management of pain (capsaicin, tricyclic antidepressants, gabapentin). • the preferred vaccine for preventing shingles – If ocular complications, consider topical steroids (Pred and related complications Forte QID).

21 1/25/2019

Case Viral Conjunctivitis

• 27 year old pharmacy student presents to the • Most common infectious clinic on emergent basis keratitis presenting on – complains about red/painful eyes for the past 2 days emergent basis – started OD then transferred to OS • 62% caused by adenovirus – reports a watery discharge, no itching, and is not a contact lens wearer • Two major types: – reports that others in his class have had a similar red – Pharyngoconjunctival eye fever (PCF) – no seasonal, food or drug allergies – Epidemic – has taken Visine 4‐5 times/day since eyes became red (EKC) but hasn’t helped much

Conjunctivitis Viral Conjunctivitis

• PCF: history of recent/current upper respiratory infection – classic triad of fever, pharyngitis, and acute follicular conjunctivitis. Bacterial Conjunctivitis – occurs more commonly in children, is caused by serotypes 3 and 7, and is spread by respiratory secretions. – tearing and foreign body sensation that is initially unilateral.

Viral Conjunctivitis Blepharo-conjunctivitis

22 1/25/2019

Viral Conjunctivitis AdenoPlus

• PCF: • Have you heard about this? • corneal involvement is not a key feature, there is occasionally a punctate keratitis; • SEIs are rare. • self-limiting condition that varies in severity and may last from 4 days to 2 weeks • Treatment if symptomatic though topical steroids are rarely needed.

Viral Conjunctivitis Viral Conjunctivitis:

• EKC: highly contagious with a history of • Gritty sensation coming in contact with someone having a red • Watery discharge  Pseudomembranes in eye. • Sticky in mornings severe cases – Adenovirus 8 common variant leading to “rule of 8’s” • Follicular response  Subconjunctival hemes • First 8 days red eye with fine SPK • Chemosis • Next 8 days deeper focal epithelial lesions • Following 8 potential development of infiltrates • • Resolution • SPK • AdenoPlus available to use for adenoviral • Infiltrates possible confirmation • Positive lymph nodes – AdenoPlus is currently being marketed and distributed by RPS (as of August 2014)

23 1/25/2019

Management Available in Canada!

• Consider the use of anti-inflammatory treatment to relieve patient symptoms and improve comfort – Alrex QID OU – Lotemax QID OU • New: Lotemax gel (indicated for post-op but has longer contact time than standard lotemax) • EKC patients are typically very uncomfortable and would benefit from anti-inflammatory treatment – especially if infiltrates or pseudomembrane present

Management Management

• Betadine (Melton-Thomas Protocol): • Antivirals used in HSV keratitis are – Proparacaine ineffective in treatment of viral – 4-5 drops of Betadine 5% • Get patient to close eye and gently roll them around conjunctivitis – After one minute, lavage the eye – New Update: in conversation with several – Lotemax 4 times a day for 4 days colleagues, Zirgan 4-5 times/day has shown • Alternative: Betadine swabsticks. significant improvement in patients over a 7- – 5% Betadine solution only comes in 30 ml bottles cost 10 time period. $14.00. • Important to stress limited contact with – Case of 200 Betadine swabsticks apprx. 45 dollars. others, frequent hand washing, not sharing of towels, etc.

24 1/25/2019

Efficacy of Hospital Germicides against Adenovirus 8, a Common Cause of Epidemic Keratoconjunctivitis in Health Care Facilities. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 2006, p. 1419–1424

An important finding from our study was that of the four disinfectants recommended by the CDC and Association for Professionals in Infection Control and Epidemiology for elimination of adenovirus type 8 from ophthalmic instruments, two (70% isopropyl alcohol and 3% hydrogen peroxide) were found to be ineffective. Based on these data, 3% hydrogen peroxide and 70% isopropyl alcohol are not effective against adenovirus that is capable of causing epidemic keratoconjunctivitis and similar viruses and should no longer be used for disinfecting applanation tonometers.

EKC Disinfection

• Commercial grade disinfectants that include compounds such as: – peracetic acid, – aldehydes [glutaraldehyde and ortho‐phthalaldehyde], – chlorine‐based products [1,900 to 6,000 ppm available free chlorine], – ethanol mixed with quaternary ammonium compounds) • E.g. Cidex, DisCide

25 1/25/2019

Corneal Ulcers When to culture?

• Infective bacterial and fungal corneal lesions cause • 1,2,3 Rule: severe pain and loss of vision • Signs and Symptoms: • 1 mm from visual axis – Pain, , tearing • 2 infiltrates (or more) – Mucopurulent discharge with generalized conjunctival injection • 3mm or greater in size – Decreased VA (esp if on visual axis) – Possible AC reaction and • Nosocomial infections – Dense infiltrate • Immuno-compromised patient – Satellite lesions around main lesion may indicate fungal infection • Post-surgical

Associated Factors Sterile vs Infectious Infiltrates

• Contact lens wear, especially soft and extended wear lens • Recent history of corneal trauma • Topical steroid use • History of exposure to vegetative matter (fungal etiology)

26 1/25/2019

Peripheral (Sterile) Corneal Ulcers • The Steroids for Corneal Ulcers Trial (SCUT) • Conclusions: – no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers – researchers did find significant vision improvement for one specific subgroup of the study by using steroid therapy on patients with severe ulcers • Application to Clinical Practice: – Adjunctive topical corticosteroid use does not improve 3- month vision in patients with bacterial corneal ulcers unless in the severe category

Infectious Corneal Ulcer Management • Infective ulcers need to be cultured! • If contact lens wearer, consider culture of contact lens • Intensive topical antibiotic regimen, consider fortified preparations, subconjunctival injections. – loading dose of Gati/Moxi/Besivance 2gtts q 15 min x 1 hour, – 1gt q 30 min x 6 hours, – 1 gt q 1 hr until f/u in 24 hours.

27 1/25/2019

Pseudomonas case report

“Doxycycline as an adjunctive therapy…may help to stabilize corneal breakdown and prevent subsequent perforation.”

AM. McElvanney

750

28 Ocular Urgencies and Emergencies Blair Lonsberry, O.D., FAAO 1/25/2019

What Classifies an Emergency? • Any condition in which the patient has the potential for: Diagnosing and Managing Ocular – vision loss, – currently experiencing vision loss, Emergencies and Urgencies – permanent structural damage, Blair Lonsberry, MS, OD, MEd., FAAO – pain or discomfort, Professor of – or is an “emergency” for the patient. Pacific University College of Optometry [email protected] • It is important to be able to triage a walk-in patient and, more importantly, a call-in patient.

Eye Care and the Emergency Department What questions to ask? Eye Care and the Emergency Department Onset suddenly noticed or sudden onset? • Non‐ related ocular ER visits comprised 51% of ocular‐related visits7 Visual Loss any loss of vision? • Only 3% of ocular‐related ER visits required hospitalization7 loss vs. blurry vision • 75% of the time, there was a clinically significant change in the diagnosis when care was first delivered at the ED or PCP and then followed up by a visit to an one eye or both eye care specialist part of or all transient vs. permanent Pain is there pain? constant? scale (1-10) Redness is there any redness? location? 7. Erin A.Nash and Curtis E. Margo, “Patterns of Emergency Department Visits for Disorders of the Eye and Ocular Adnexa,” Archives of , volume 116, September 1998, pp. 1222 – 1226. Associated Factors contact lens wear? trauma? discharge? 8. Hau S, Ioannidis A, Masaoutis P, Verma S. Patterns of ophthalmological complaints presenting to a dedicated ophthalmic Accident & Emergency department: inappropriate use and patients' perspective. Emerg Med J. 2008 Nov;25(11):740-4. photophobia? medical history (eg. DM)

1 1/25/2019

Visual Loss Monocular vs. Binocular • Visual loss varies greatly in meaning from patient to • Ocular or pathology causes monocular vision loss patient • lesion at or posterior to chiasm causes loss – ranging from blur to complete blindness and may affect one – VF defects become more congruous the further back in the or both eyes visual pathway • Components include: – Homonymous VF defects noted posterior to chiasm – acuity, • Difference between mono vs. bino usually straightforward, – visual field, keeping the following in mind: – color and brightness may be affected jointly or separately – Patients occasionally mistake homonymous (similar loss of visual field in both eyes) for a monocular loss • Detailed history and extent of vision loss crucial

Profound Loss of Vision Visual Defects • Referring to a complete or greatly diminished vision affecting the whole field • Common causes of severe vision loss: Vascular central retinal vein occlusion, occlusion, vitreous heme Inflammatory

Infiltrative

Mechanical

2 1/25/2019

Monocular General Appearance • Differentiate between eyes that have lost all • Posture and Motor control useful vision and those that have blurred vision – What posture does patient assume while sitting in • Blurring of vision is not localized and may be the exam chair caused by pathology anywhere from cornea to – Are there any signs of involuntary motor activity optic nerve such as tremors • Need to get anatomical diagnosis first before • E.g. damage to the cerebellum may produce a tremor that considering the cause usually worsens with movement of the affected limb

General Appearance Neurological Screening: Cerebrum • Level of consciousness – When introducing yourself be aware • Frontal lobe of the patient’s gross level of consciousness? – Emotions, drive, affect, • Is the patient awake, alert and self-awareness, and responsive? responses related to • Personal Hygiene and Dress emotional states – Is it appropriate for the environment, temperature, age and – Motor cortex associated social status of the patient? with voluntary skeletal – Is the patient malodorous or movement and speech disheveled? formation (Broca)

3 1/25/2019

Right vs Left Brain Injury TBI • So what happens if one side of the brain is injured? Neuro‐Optometric Rehabilitation Association – People who have an injury to the right side of (NORA) the brain "don't put things together" and fail to www.nora.cc process important information. • As a result, they often develop a "denial syndrome" and say "there's nothing wrong with me.“

Right vs Left Brain Injury Case History • The left side of the brain deals more with language and helps • 38 black male, complaining that the vision in to analyze information given to the brain. his right eye is blurry. – If you injure the left side of the brain, you're aware that things aren't working (the right hemisphere is doing its job) – Got the current Rx 3 weeks previously, and but are unable to solve complex problems or do a complex started out good but in last couple of days activity. OD vision has become blurry – People with left hemisphere tend to be more depressed, have more organizational problems, and have • Medical Hx: no current health concerns and problems using language. no medications

4 1/25/2019

Entrance Skills

• Va’s: OD: 20/25, OS: 20/20 • Pupils: PERRL • CVF: full to finger count • EOM’s: FROM • Amsler: central metamorphopsia OD • HVF: 10-2 (see VF)

Central Serous • an exudative chorioretinopathy characterized by an exudative neurosensory retinal detachment with or without an associated detachment of the retinal pigment epithelium (RPE) • Patients experience blurry vision, metamorphopsia and • individuals between 20 and 50 years of age

5 1/25/2019

Central Serous Retinopathy Central Serous Retinopathy • incidence in men vs women is approximately 6 to • 80% to 90% of cases resolve spontaneously within 3 1 months • • Treatment options: associated with stress and stress hormones (ie, – include laser photocoagulation, corticosteroids and epinephrine); – "safety‐enhanced" PDT, • individuals with a "type A personality" who are – Acetazolamide reduced the time for subjective and objective under stress CSR resolution, but it had no effect on final VA or recurrence rate. Most patients in the experimental group in that study had • recurrence in the ipsilateral eye is approximately side effects from the acetazolamide, including paresthesias, 30% and CSR in the fellow eye was 32% nervousness, and gastric upset

Central Serous Retinopathy Central Serous Retinopathy • Treatment options: – Topical NSAIDs: • Conflicting reports • Michael Singer, MD, from Medical Center Ophthalmology in San Antonio reported an increase in resolution time by 50% • PRADEEP VENKATESH, MD reports that NSAIDS treatment could possibly slow down or cause a rebound CSR

6 1/25/2019

Latest Treatment Under Investigation Entrance Skills • Eplerenone is a mineralocorticoid antagonist receptor currently used in the treatment of hypertension and congestive heart failure. • Literature has demonstrated improved resolution of CSR with no serious adverse effects. • Several randomized clinical trials are currently underway.

13 YR Female Fundus Photos

7 1/25/2019

OCT From the Experts

• Vogt‐Koyanagi‐Harada (VKH) disease is a multisystemic disorder characterized by granulomatous panuveitis with exudative retinal detachments that is often associated with neurologic and cutaneous manifestations. • VKH disease occurs more commonly in patients with a genetic predisposition to the disease, including those from Asian, Middle Eastern, Hispanic, and Native American populations.

Retina Consult From the Experts • Referred patient to and they confirmed • VKH: the diagnosis of VKH. – Patients have no prior history of ocular trauma or • She was begun on oral prednisone 60 mg per surgery day and she was re‐evaluated in 1 week. – Patients have no evidence of another ocular disease based on clinical or laboratory evidence • At the follow up, there was reduction in her – Patients have bilateral ocular involvement. serous retinopathy and vision was improved.

8 1/25/2019

From the Experts 30 YR WM • VKH: • Patient calls from his PCP office asking if we can see him – The neurologic and auditory signs include the following: today because he has had red/painful eyes for over a week • Malaise, fever, headache, nausea, abdominal pain, stiffness of the and has not resolved neck and back, or a combination of these factors; headache alone is not sufficient to meet the definition of meningitis • Medical history: • Tinnitus – Past week has been experiencing painful urination and • Cerebrospinal fluid pleocytosis discharge – Integumentary signs include the following: – New sexual partner apprx 10 days ago, who also had developed • Alopecia: loss of body hair a red eye • Poliosis: loss of pigment in hair – Chlamydia and gonorrhea testing were negative • Vitiligo: loss of skin pigmentation in blotchy pattern – Has tested positive for HSV2 but no current flare up

35

VKH Treatment 30 YO WM • For most patients with bilateral serous detachments and • Medications: severe visual loss, begin therapy with systemic prednisone – In the past week patient: (1‐2 mg/kg/day). • 2 courses of azythromycin (1 gram each) • Injection of rocephin • The length of treatment and subsequent taper must be • Injection of penicillin G individualized for each patient. • Currently taking doxycycline 100 mg bid – Most patients require therapy for 6 months and occasionally up • Valtrex 1 gram 3 times per day for 7 days (d/c 1 day ago) to 1 year before successful tapering of systemic corticosteroids. • Was on Vigamox qid for 7 days (d/c 1 day ago) – Systemic therapy should not be discontinued during the 3 • VA: 6/7.5 (20/25) OD, OS months following the onset of the disease because of the risk • Entrance skills unremarkable though some pain on eye movement for recurrence.

36

9 1/25/2019

30 YO WM 30 YO WM • SLE: • Started patient on the miracle drop – 2+ injection conjunctival – Tobradex 4 times per day and scheduled patient to come back the next both eyes day – 1‐2+ lid • 1 day f/u – Mixed papillary and – Patient was feeling better follicular response – Less redness and much reduced photophobia and discomfort – No improvement on painful urination or discharge and is now seeing – 1‐2+ diffuse SPK (no blood in his urine staining noted above infiltrates) – Continue tobradex 4 times per day and RTC in 4 days for f/u with dilation and told to contact PCP to update on the blood in the urine – No cells or flare noted

37 39

30 YO WM 30 YO WM • AdenoPlus: • 4 day f/u: – Patient says his eyes are doing great and that all of his – Performed on the right eye (patient felt that was urogenital problems abruptly stopped on Saturday the worst eye) – Discussion with PCP: Kidney stone – Negative – What was going on with the eye? • Viral conjunctivitis likely EKC

What did we learn from this?

38 40

10 1/25/2019

Lid Nevi Congenital Nevus • Lid nevi: – congenital or acquired – occur in the anterior lamella of the • Most nevi of the skin are not considered to be eyelid and can be visualized at the eyelid margin. at increased risk of malignancy. • The congenital eyelid nevus is a special category with implications for – However, the large congenital melanocytic malignant transformation. • With time, slow increased nevus appears to have an increased risk of pigmentation and slight enlargement malignant transformation of 4.6% during a can occur. • An acquired nevus generally 30 year period becomes apparent between the ages of 5 and 10 years as a small, flat, lightly pigmented lesion

Congenital Nevus Acquired Lid Nevi • The nevus is generally well circumscribed and not • Acquired nevi are classified associated with ulceration. as: – junctional (involving the • The congenital nevus of the basal /dermis junction), typically flat in eyelids may present as a appearance "kissing nevus" in which the – intradermal (involving only melanocytes are present the dermis), tend to be dome symmetrically on the upper and shaped or pedunculated – compound (involving both lower eyelids. dermis and epidermis) tend – Presumably this nevus was to be dome shaped present prior to eyelid separation

11 1/25/2019

Pre‐Malignant Eyelid Lesions: Keratoacanthoma Pre‐Malignant Eyelid Lesions: Actinic Keratosis • Appears as a solitary, rapidly • Also known as solar or growing nodule on sun senile keratosis exposed areas of middle-aged and older individuals • Most common pre- • Nodule is usually umbilicated malignant skin lesion with a distinctive crater filled • Develops on sun-exposed with keratin areas and commonly • Lesion develops over weeks and undergoes spontaneous affect the face, hands and involution within 6 mo to scalp (less commonly the leave an atrophic eyelids) – Predominately white males

Pre‐Malignant Eyelid Lesions: Keratoacanthoma Pre‐Malignant Eyelid Lesions: Actinic Keratosis

• Lesion on the eyelids may • Appear as multiple, flat- produce mechanical problems topped papules with an such as or ptosis. adherent white scale. • Differential SCC, BCC, verruca • Development of SCC in vulgaris and molluscum untreated lesions as high • Many pathologists consider it a as 20% type of low grade SCC • Management is surgical • Complete excision is excision or cryotherapy recommended as there are (following ) invasive variants

12 1/25/2019

Malignant Eyelid Lesions: Basal Cell (BCC) Malignant Eyelid Lesions: Basal Cell Carcinoma

• Most common malignant • Diagnosis is initially made from its clinical appearance, especially with lesion of the lids (85-90% the noduloulcerative type with its of all malignant epi eyelid raised pearly borders and central tumors) ulcerated crater – categorized into two basic types: • 50-60% of BCC affect the noduloulcerative and morpheaform lower lid followed by – The morpheaform variant is typically diffuse, relatively flat with indistinct medial canthus 25-30% borders. This variant is more and upper lid 15% aggressive and can be invasive despite showing less obvious features.

Malignant Eyelid Lesions: Basal Cell Carcinoma (BCC) Malignant Eyelid Lesions: Basal Cell Carcinoma

• Etiology is linked to • Definitive diagnosis made on excessive UV exposure histopathological examination of in fair-skinned, ionizing biopsy specimens radiation, arsenic – loss of adjacent cilia is strongly exposure and suggestive of malignancy and occurs • Metastases is rare but commonly with basal cell carcinoma local invasion is of the eyelid common and can be • Surgery is generally accepted as very destructive treatment of choice – Mohs’ surgery technique

13 1/25/2019

Malignant Eyelid Lesions: Squamous Cell Carcinoma (SCC) Malignant Eyelid Lesions: Squamous Cell Carcinoma (SCC)

• Much less common than • Presents as a BCC on the eyelid but erythematous, indurated, hyperkeratotic plaque or has much higher nodule with irregular potential for metastatic margins spread • Lesions have a high • Typically affects elderly, tendency towards ulceration and tend to fair-skinned and usually affect lid margin and found on the lower lid medial canthus

Malignant Eyelid Lesions: Squamous Cell Carcinoma (SCC) Malignant Eyelid Lesions: Squamous Cell Carcinoma (SCC)

• Environmental and • Diagnosis requires intrinsic factors biopsy initiate cell growth • Surgical excision is – Many SCC arise recommended from actinic lesions – Mohs’ technique

14 1/25/2019

Malignant Eyelid Lesions: Carcinoma Malignant Eyelid Lesions: Sebaceous Gland Carcinoma • Highly malignant neoplasm that arises from the meibomian glands, • Upper lid origin in about Zeis and the sebaceous glands of 2/3 of all cases the caruncle and eyebrow • Typically affects older • Aggressive tumor with a high individuals, women more so recurrence rate, significant than men metastatic potential and notable • has also been reported in mortality rate younger individuals who are • rates of misdiagnosis have immunosuppressed or who been reported as high as have received radiation 50% treatment.

Malignant Eyelid Lesions: Sebaceous Gland Carcinoma Malignant Eyelid Lesions: Sebaceous Gland Carcinoma

• Relatively rare, 1/3 most common • Presents as a firm, yellow eyelid malignancy nodule that resembles a • Uncommon in the Caucasian . population and represents only 3% • May mimic: of eyelid malignancies, – chronic blepharoconjunctivitis, – most common eyelid – meibomianitis or malignancy in Asian Indian – chalazion that does not population, where it represents respond to standard approximately 40% or more of therapies eyelid malignancies

15 1/25/2019

Malignant Eyelid Lesions: Malignant Malignant Eyelid Lesions: Sebaceous Gland Carcinoma Melanoma • Risk factors include congenital • Diagnosis is by biopsy and dysplastic nevi, changing • cutaneous moles, excessive Treatment is surgical sun exposure and sun excision with sensitivity, family history, age microscopic monitoring greater than 20 and white. • History of severe sunburns of the margins rather than cumulative actinic exposure thought to be a major risk factor

Malignant Eyelid Lesions: Malignant Malignant Eyelid Lesions: Malignant Melanoma Melanoma • MM of the eyelid • Flat lesion with irregular accounts for about 1% of all eyelid malignancies borders and variable • Incidence been increasing pigmentation typically and it causes about 2/3 of occurring in sun all tumor related deaths exposed areas from cutaneous • Incidence increases with • Confirmed diagnosis by age biopsy

16 1/25/2019

Malignant Eyelid Lesions: Malignant Case Melanoma • Prognosis and metastatic • 65 year old Caucasian patient presents with potential are linked to the sudden onset loss/blurring of vision in the right depth of invasion and eye thickness of the tumor • PMHx: HTN for 15 years, takes “water pill” • Treatment is wide surgical • VA’s: 20/60 OD, 20/25 OS excision confirmed with • Pupils: PERRL –APD histological monitoring • CVF: Inferior defect right eye, no defects noted in the left eye

Malignant Eyelid Lesions: Malignant Vision Loss Without Pain: Melanoma / • Microvascular complications resulting in capillary closure & abnormal permeability • S&S include; – blurring of vision ( and shifts), – sudden drop in vision (vitreous heme), – dot and blot hemes, – exudate, – cotton wool spots, – neovascularization (, retina and disc)

17 1/25/2019

Branch Retinal Vein Occlusion: VEGF and DME Signs/Symptoms • BRVO: sudden, painless, visual field defect. – patients may have normal vision. – quadrantic VF defect, – dilated tortuous retinal veins with superficial hemes and CWS – typically occurs at A/V crossing (sup/temp)

Vision Loss Without Pain: BRVO Vein Occlusion • Associated with: • BRVO more common than CRVO and has more – hypertension, favorable prognosis – Overall 50-60% of BRVO patients will maintain VA of 20/40 or – coronary artery disease, better – DM and • Visual loss results from: – peripheral vascular disease. – • – Foveal hemorrhage Usually seen in elderly patients (60-70), slight male – Vitreous heme and hyperopic predilection. – • Second most common vascular disease after – RD diabetic retinopathy. – Macular ischemia – Neovascularization complications

18 1/25/2019

Study Design (n=397) BRVO Central Retinal Vein Occlusion: BRAnch retinal Vein Occlusion study safety/efficacy Macular Edema Secondary to BRVO Signs/Symptoms • CRVO: thrombus occurring at lamina 1:1:1 Randomization is classical theory but new evidence indicates that the occlusion is typically Ranibizumab Ranibizumab Sham 0.3 mg 0.5 mg in the optic nerve posterior to the (n=132) (n=134) (n=131) lamina cribrosa Monthly Injections (last at 5M) – decreased VA ranging from near Rescue Laser (if eligible beginning at Month 3) Month 6 12M Primary normal to hand motion with PRN ranibizumab for all patients Endpoint majority 20/200 range Rescue Laser (if eligible beginning at Month 9) RibiRanibizumab b Ranibizumab Ranibizumab – dilated tortuous vessels, with 0.5 mgg 0.3 mg 0.5 mg numerous retinal hemes and CWS

Mean Change from Baseline BCVA BRVO Central Retinal Vein Occlusion Sham/0.5 mg (n=132) 0.3 mg Ranibizumab (n=134) 0.5 mg Ranibizumab (n=131) • Visual morbidity and blindness are primarily from: 20 +18.3* 18 +18.3 16 +16.4 – persistent macular edema, +16.6* 14 +11.6 12 +12.1 – macular ischemia and 10 8 +10.2 6 +7.3 – neovascular +3.1

Baseline BCVA BCVA Baseline 4 (ETDRS Letters) (ETDRS 2 Mean Change from 0 0246810127 Day 0–Month 5 Months 6–11 Month Monthly Treatment PRN Treatment The gain of additional 3 lines occurred at a rate of 61% of 0.5 AVT grp, 55% for 0.3 AVT & 29% placebo

19 1/25/2019

Study Design CRUISE (n=392) Central Retinal Vein Occlusion Central Retinal vein occlCRVOUsIon Study: Efficacy & safety • CRVO’s can be ischemic or non. Macular Edema Secondary to CRVO

– Classical definition of ischemic is 10-disc area of 1:1:1 Randomization non-perfusion found on angiography Ranibizumab Ranibizumab Sham 0.3 mg 0.5 mg – RAPD and ERG maybe better predictor (n=130) (n=132) (n= 130) Monthly Injections (last at 5M): 6M tx period Month 6 – VA’s typically worse in ischemic 12M trial Primary – Increased number of cotton wool spots with PRN Lucentis available for for all patients: 6M tx period Endpoint decreased VA maybe predictive Ranibizumab Ranibizumab 0.5 mgg 0.3 mg 0.5 mg

Mean Change from Baseline BCVA Central Retinal Vein Occlusion CRVO Sham/0.5 mg (n=130) 0.3 mg Ranibizumab (n=132) 0.5 mg Ranibizumab (n=130) 18 • Ischemic CRVO may lead to iris neovascularization and 16 +14.9* neovascular glaucoma 14 +13.9 +13.9 from

(ETDRS 12 +12.7* – Estimated apprx 20% of CRVO’s are ischemic with 10 8 45% of those developing neo BCVA

+7.3 Change

Letters) 6 • Regular examinations (1-2 wks) to monitor for ischemia or 4 +0.8 neo development Mean 2 Baseline 0 – should include gonio as angle neo can precede iris ‐2 07 24681012 rubeosis Day 0–Month 5 Months 6–11 Monthly Treatment Month PRN Treatment Pts with >/= 3 line improvement was noted in 48% of .5 AVT, 26 of .3 AVT & 17% of sham

20 1/25/2019

Vision Loss Without Pain: CRAO Artery Occlusion • Primarily embolic in nature from cholesterol, calcifications, plaques. • CRAO has profound vision loss • Usually occurs in elderly associated with: with history of . – hypertension (67%), – Vision is usually CF (count – carotid occlusive disease (25%), fingers) to LP (light – DM (33%) and perception) with positive APD. – cardiac valvular disease. – Diffuse retinal whitening with • Sudden loss of unilateral, painless vision arteriole constriction, cherry – defect dependent upon location of occlusion red macula.

Vision Loss Without Pain: Ophthalmic Emergency Artery Occlusion • Treatment is controversial due to poor prognosis • BRAO typically located and questionable benefit. in temporal retinal • Treat immediately before workup, if patient bifurcations. presents within 24 hours of visual loss: – Digital ocular massage, – systemic acetozolamide (500 mg IV or po), – topical ocular hypertensive drops (Iopidine, B‐blocker), – anterior chamber paracentesis, – consider admission to hospital for carbogen Tx (high carbon dioxide)

21 1/25/2019

Retinal Tear Flashes and • Patients often present complaining of “spots” or “cobwebs” in front of their eyes • Causes of floaters include: posterior vitreous detachment (PVD), retinal tear, vitreous heme, uveitis. • Since PVD and retinal tears present the same way, a RT has to be eliminated • Ask the patient whether spots move with eye and continue to move after the eye has stopped • Large spots could be blood clots

Posterior Vitreous Detachment (PVD) Flashes and Floaters • Sudden onset typically means a PVD, retinal tear or heme • If the spots appear after flashing light, then retinal tear must be eliminated • Myopes tend to have floaters and will notice them for a long time • Key is to rule out potentially sight threatening condition for the floaters, ie retinal tear. • Patients with retinal condition such as lattice degeneration and myopes need to be educated about S&S of RD (flashes and floaters) – 8-11% population has lattice – Risk of RD with lattice is <1% – 30-50% of patients with a RD have lattice

22 1/25/2019

Flashes and Floaters: Management • A patient who presents with a sudden onset PVD without retinal breaks or hemorrhage requires repeat peripheral examination in six weeks, as the risk of retinal complications is highest within the six weeks following vitreous detachment. • If no retinal breaks are seen at that point, routine yearly examination is all that is needed

23 Judicious Prescribing Curtis DuBois, O.D. 1/25/2019

• I have no relevant financial relationship with any product, medication, or drug company mentioned in this presentation. Judicious Prescribing for the Oklahoma Optometrist

Curtis A. DuBois, OD Financial Disclosures

• I have no relevant passion for the material presented here today. • You don’t either. • It’s still important.

Presentation Disclosures Introduction

1 1/25/2019

• 1) Review optometry’s role in prescribing controlled medication. • 2) Review the Drug Schedule for narcotic prescriptions. • 3) Pain management options. • 4) Senate Bill 1446 updates. • 5) Review basics and procedures for writing narcotic prescriptions. • 6) Review the Oklahoma mandatory Prescription Monitoring Program (PMP).

Course Objectives Optometry’s Role

*A drug or other substance affecting mood or behavior. In moderation, can dull the senses, relieve pain, and induce profound sleep but in excessive doses causes stupor, coma, or convulsions Dangerous or Controlled? Narcotic?

2 1/25/2019

Schedule Description Example I drugs with no currently accepted medical use and a high potential for heroin, lysergic acid diethylamide (LSD), marijuana abuse. (cannabis), 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote • Drugs, substances, and certain chemicals used to make drugs are classified into five distinct categories or schedules depending upon the drug’s acceptable medical use and the drug’s II drugs with a high potential for abuse, with use potentially leading to Combination products with less than 15 milligrams of abuse or dependency potential. severe psychological or physical dependence. These drugs are also hydrocodone per dosage unit (Vicodin), cocaine, • Schedule I drugs have a high potential for abuse and the potential to create severe considered dangerous. methamphetamine, methadone, hydromorphone (Dilaudid), meperidine (Demerol), oxycodone psychological and/or physical dependence. As the drug schedule changes-- Schedule II, (OxyContin), fentanyl, Dexedrine, Adderall, and Ritalin. Schedule III, etc., so does the abuse potential-- Schedule V drugs represents the least potential DEA moved hydrocodone products for abuse. (hydrocodone/acetaminophen) from Schedule III to -https://www.dea.gov/drug-scheduling Schedule II, effective October 6, 2014.

III drugs with a moderate to low potential for physical and psychological Products containing less than 90 milligrams of codeine dependence. Schedule III drugs abuse potential is less than Schedule I per dosage unit (Tylenol with codeine), ketamine, and Schedule II drugs but more than Schedule IV. anabolic steroids, testosterone

IV drugs with a low potential for abuse and low risk of dependence. Xanax, Soma, Darvon, Darvocet, Valium, Ativan, Talwin, Drug Schedules/ Controlled Now in a Table Ambien, Tramadol V drugs with lower potential for abuse than Schedule IV and consist of preparations with less than 200 milligrams of preparations containing limited quantities of certain narcotics. Schedule codeine or per 100 milliliters (Robitussin AC), Lomotil, V drugs are generally used for antidiarrheal, antitussive, and analgesic Motofen, Lyrica

Epithelial • Oklahoma oral medication and controlled substance legislation passed in 1994. • You have a responsibility to each patient and to the profession. defects • You have a professional responsibility to prescribe controlled substances appropriately, guarding against abuse while ensuring that your patients have medication available when they need it. • You have a personal responsibility to protect your practice from becoming an easy target for Post drug diversion. You must become aware of the potential situations where drug diversion can Trauma occur and safe- guards that can be enacted to prevent this diversion surgical

What are these typically used Professional Conduct for in Optometry?

3 1/25/2019

• Etiology- Biggest question. “Is this Before Initiating Follow- pain ocular in origin?” • Nature of pain- frequency, onset, treatment Treatment up location, duration, association, relief (Good idea to measure pain here) • Etiology • Topicals • License • What is already working?- What • Nature of Pain historically does not work? Some •Orals limitations patients more responsive to oral • What works? • Nothing? • Appropriate NSAIDs • Patient History follow-up • History- Allergies? H/O abuse, Liver timeline function, Heart function, polypharmacy, • Discontinuing Check PMP! medication Decision Making Before you treat

• Summary for House Bill 1948: Effective date November 1, 2015 • Mandatory PMP check for new patients or after 180 days elapsed since last PMP check for patient prior to physician prescribing one of the following: opiates, • State licensing boards are responsible for enforcing this provision and synthetic opiates, semi-synthetic opiates, benzodiazepine, or carisoprodol (exclusions setting policy. for Hospice or end-of-life, or patients residing in nursing facility) • Nine professional licensing boards now have access to the PMP (including the • Physicians may designate a staff member to run the patient PMP on the physician’s Board of Examiners in Optometry). behalf. • The bill requires that OBN provide a list of the top twenty prescribers to each of • Physicians may include a copy of the patient’s PMP in the patient’s medical record. the licensing boards. A web application has been provided to the boards for • Access to the OBN PMP is now granted to medical practitioners and their staff compliance checks and identification of the top prescribers. employed by federal agencies treating patients in the state of Oklahoma.

Mandatory PMP Checks: Mandatory PMP Checks:

4 1/25/2019

• The Oklahoma Prescription Monitoring Program (PMP) was enacted into law by the Oklahoma Anti-Drug Diversion Act (63 O.S. Section: 2-309). The statute requires all dispensers of Schedule II, III, IV, and V controlled substances to submit prescription dispensing information to OBNDDC using the ASAP Version 4, Release 2 (4.2) standard within five (5) minutes of dispensing a scheduled narcotic.

Rules of Pharmacies to report

5 1/25/2019

You can also search yourself as the provider on the website to verify that you wrote the prescriptions for all the patients listed.

Topicals- NSAIDs, Cycloplegics, Steroids Oral Analgesics: > OTC NSAIDS- Aspirin, Acetaminophen, Ibuprofen* Non-Narcotic Prescription (NSAIDs): Oral Controlled • > Look for kidney Analgesics/Narcotic: disease, upper GI disease, liver disease. • > Codeine, Hydrocodone, Tramadol, Darvocet Initiating the Treatment

6 1/25/2019

• Prescriber Information: doctor’s name, address, phone number, license • Sarau, Alexandra, et al. “Efficacy of Topical Analgesics in Pain or* DEA number Control for Corneal Abrasions: A Systematic Review.” Cureus, 27 • Do NOT preprint DEA number on any prescription pad due to risk of theft Mar. 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5415171/. • Patient Information: name, age/DOB, address (required for schedule II), weight for children if known • Date Prescribed: The date is either the date the prescription was signed or • Topical therapies that actually showed pain reduction were a date that the doctor has indicated the prescription shouldn’t be dispensed NSAIDs. Topical aesthetics and cycloplegics “did not demonstrate before. A prescription for a controlled substance can be filled for up to 28 significant improvements in either healing rates or pain control.” days after the date it was written and most other prescriptions can be filled up to 6 months later. • Downfalls to orals? Prescription Writing Basics Which is Best? Necessary parts included on a prescription:

• Signatura (Sig): Latin or English abbreviations that tell the patient how to use the • Superscription: This is the Rx symbol that designates the document as a medication. The Pharmacist translates the instructions for patient use. You may prescription. It is an abbreviation from a Latin phrase that means “take thou” or also want to include the reason for the medication. “to take”. • Instill (1) ggt OU x 7 days for eye infection • Refill data: Provide the number of refills the patient should need to complete the • Inscription: Drug name, concentration, and type of preparation (sol, susp, ung) cycle of drug treatment. No refills allowed for any controlled substance without • Subscription (Disp): Instructions to the pharmacist on how to compound fortified examination. if needed. More often used to specify the quantity desired (number of • “..prescribing...schedule for a period not exceeding five (5) days of supply, and capsules or tablets) for a regular medication or the bottle size (mL bottle size). the issuance of refills for such prescriptions following sufficient physical Especially on controlled substances, write out the number of pills in words so that examination of the patient for the purpose of diagnosis and treatment of ocular it is more difficult to alter. abnormalities.”

Prescription Writing Basics Prescription Writing Basics Necessary parts included on a prescription: Necessary parts included on a prescription:

7 1/25/2019

• Substitution permitted: Specify if the pharmacist can substitute for a generic form, or if it must be dispensed as written. Generic drug names are not capitalized, but name brand drugs are capitalized. (prednisolone acetate 1% vs Pred Forte 1%) • Signature: The doctor’s signature and degree finalize the legal document. A signature stamp can be used for noncontrolled substances. Prescriptions for controlled drugs require a handwritten signature and DEA number.

Prescription Writing Basics Necessary parts included on a prescription:

← No refills on controlled substances without examination. ← Count?

8 1/25/2019

• Arguably one of the most important aspects of writing controlled substances Rx. All done! Hand it over and say your prayers, right? • Go back to the etiology/ causation • Let’s just be safe and say daily…. • Refill? Follow-up

• Mostly directed at D.O.’s and M.D.’s • Effective November 1, 2018. • Limits opioid/Schedule II Rx’s to initial (7) days then mandatory reassessment. (Can be conducted by supervised practitioner, i.e. P.A.) • Second Rx can, again, be only for (7) days without “consultation” from provider. • Optometry is already stricter than this law, so no changes in our practice, but useful information. Thank you! Curtis A. DuBois O.D. [email protected] Senate Bill 1446

9 Retina Update Stephanie Cooper, O.D. and Kyle Piwonka, D.O. 1/25/2019

clinicaltrials.gov

Approximately 1,000 retinal studies going on all the time. Retina Update KYLE PIWONKA, DO STEPHANIE COOPER, OD, FAAO, DIPLOMATE ABO

FINANCIAL DISCLOSURES TOPICS Dr. Piwonka – None ARMD Dr. Cooper – Alimera Sciences Diabetes Technology Inherited Retinal Dystrophy

1 1/25/2019

Beckman Simple Classification of AMD

ARMD –What’s new Important messages: •Early AMD begins with the presence of medium drusen with dry and wet AMD •Intermediate AMD has large drusen and/or pigment alterations

Ferris FL, et al. Ophthalmology. 2013; 120(4):844‐851

Pathogenesis of AMD New Concepts in AMD Pathophysiology •Difficult to unravel •Multifactorial • Genetics • At least 19 risk loci now identified* • Loci show enrichment for genes involved in: • Regulation of complement activity • Lipid metabolism •Disease concept: ’dry’ vs ‘wet’ • Extracellular matrix remodeling • Angiogenesis •Mechanisms for atrophy and CNV • Environmental •Role of the •Age associated • How/when does AMD begin? •Probably not one disease • Common final pathway

Fritsche LG, et al. Nat Genet. 2013;56(8):552‐560 Gelfand BD, et al. Trends Mol Med. 2016;22(8):656‐670

2 1/25/2019

Points for Consideration •Is the atrophy that is developing in these eyes the same as in non‐ neovascular AMD? •Is the atrophy seen in the 2 eyes of this patient the same? •Why is the atrophy developing? • Natural history of non‐neovascular AMD • Destructive effects of the exudative process • Class effect of anti‐VEGF therapy? • Combination? •If there could be a relationship between atrophy and anti‐VEGF therapy, should I change my approach to these patients? • Less aggressive or discontinuous therapy? • Consequences of undertreatment?

IR and OCT Long Term Studies After Anti‐VEGF Therapy

3 1/25/2019

Atrophy was not uncommon even at 2 Long Term Studies After Anti‐VEGF Therapy years in randomized trials

Baseline risk factors for atrophy: ‐Atrophy in the fellow eye ‐Intra‐retinal fluid at the foveal center

Lower rates of atrophy at M24 in patients with highest Long Term Studies After Anti‐VEGF Therapy injection number in the PRN treatment arms (HARBOR trial) •On average, the vision at the Seven‐Up visit was worse than the baseline vision at entry into the MARINA and ANCHOR •43% of study eyes had a stable or improved letter score compared to ANCHOR/MARINA baseline measurements, whereas 43% declined by 15 letters or more •Why were they losing vision? • “Macular atrophy” was present in 98% of study eyes (71% w GA alone vs 7.3% at baseline) • Progression of macular atrophy was associated significantly with visual decline over this 5yr period • Areas of definite decreased FAF was 35% larger than the original CNVM lesion

4 1/25/2019

So How Do We Make Sense of This? Mechanisms for Atrophy and CNV •A small amount of SRF is the sign of a CNV membrane that has not been ‘eliminated’, but •An intact blood‐retinal barrier confers a relative immune privilege to the retina perhaps has been controlled •The resident inflammatory cells of the retina are the microglia and they play a key role in • Does not mean you should leave fluid untreated (may lead to loss of control and irreversible damage) maintaining the status quo (‘homeostasis’) • Eyes needing more treatment in the PRN group presumably had these membranes with persistent/residual activity •Oxidative stress and inflammation (immune dysregulation) are thought to be the key processes • • Complement deposition, aluRNA accumulation, amyloid deposition  leading to inflammasome Could CNV be the eye’s response to prevent atrophy? activation •Could a persistent type 1 membrane (CNV under the RPE) without exudation be the optimal • Multiple mechanisms converge leading to RPE damage and ultimately atrophy and/or CNV outcome? •Any number of factors can disrupt this delicate balance, overwhelm the protective system, and initiate the disease process

Ambati J, et al. Nat Rev Immunol. 2013;13(6):438‐451.

Summary Point Mechanisms for Atrophy and CNV •With cellular injury, the blood‐retina barrier is disrupted and additional mechanisms of injury/wound healing may be initiated •‘Wet’ and ‘Dry’ AMD are not mutually exclusive and should not be considered separate disease • Ex, recruitment of peripheral immune immune cells (macrophages) processes •This can lead to a proliferative angiogenic response (CNV) and/or additional cellular injury (atrophy) •Concept is supported by the fact that genetic polymorphisms that are associated with AMD •Early intervention will need to target these factors (including CHF and HTRA1) confer similar statistical risk of developing both dry and wet AMD •Targeting the immune dysregulation or preventing the death of injured retinal/RPE cells would appear to be reasonable approaches to therapy once the disease process has been initiated

Ambati J, et al. Nat Rev Immunol. 2013;13(6):438‐451.

5 1/25/2019

Predicting GA development

•Various features of drusen and retinal/choroidal layers evaluated as potential risk factors for local GA development •575 individual drusenoid lesions followed over What can we learn about this pathophysiologic time on tracked Spectralis scans process from our clinical diagnostics? •Research question: can we use these observations regarding drusen on OCT to predict which drusenoid lesions go on to develop atrophy?

Precursors to Atrophy Methods: •Drusen height •Choroidal thickness below the drusen AREDS color photo analysis: •Presence of hyper‐reflective foci above the • When considering areas of incident GA, review drusen of color photographs prior to development of • Innermost extent of the HRF atrophy frequently revealed the presence of large drusen/drusenoid PEDs •Internal reflectivity of the drusen (homogeneous vs heterogeneous)

Cukras C, et al. Ophthalmology. 2010;117(3):489‐499.

6 1/25/2019

Methods:

•Integrity/disruption of the ellipsoid zone •External limiting membrane integrity •RPE integrity •Presence of atrophy (defined as loss of the RPE band and thinning of the outer retina with increased choroidal reflectivity)

Results Significant baseline predictors of development of new atrophy (at month 6 and final follow‐up) •Loss of RPE band integrity •Pigment migration/IRHF •Heterogenous internal reflectivity •Local choroidal thickness <135 microns

*listed in order of importance

7 1/25/2019

Proposed Sequence of Drusen to Atrophy Other OCT Observations in Intermediate AMD

•Reticular Pseudodrusen or Subretinal Drusenoid Deposits on OCT • Presence brings a higher risk for both GA and CNV •Predisposition to accumulate and then coalesce; they then frequently begin to disappear •When they disappear, the photoreceptors often times disappear along with them • This can lead to a situation where you get outer retinal atrophy without RPE atrophy • This is another way of losing vision in the setting of AMD

Spaide RF. Retina. 2013;33(9):1800‐1808.

Proposed Sequence of Drusen to Atrophy Other OCT Observations in Intermediate AMD

•Pigment migration •Hyporeflective Drusen

• Remember: BOTH are precursors of atrophy • And BOTH are also, precursors of CNV activity!!

8 1/25/2019

Precursor Events to Neovascular AMD Precursor Events to Neovascular AMD

•Hyporeflective pigment epithelial detachments/drusen •What’s going on? • Early fibrovascular infiltration •How do we know? • OCT angiography confirmation •Important to note: no evidence thus far to suggest such asymptomatic lesions should be treated (Rosenfeld – intermediate/asyptomatic early neovascular AMD)

Precursor Events to Neovascular AMD Role of the Choroid •Rick Spaide, MD and others have demonstrated the choroid is much thinner in eyes with AMD and in patients with age‐ related choroidal atrophy (ARCA) • Hypothesis: Thin choroid (insufficiency) leads to atrophy • Could CNV be a compensatory response? •ARCA: • Common problem. Typical features of AMD (large drusen absent) • Older patient with non‐specific complaints: trouble reading, trouble with adaptation to lighting changes *6 months later cystoid changes have occurred *typer 3 CNV lesion (RAP lesion)

9 1/25/2019

Role of the Choroid •OCT angiography in Geographic Atrophy • Whereas the choriocapillaris was apparently absent in the region of atrophy in eyes with Stargardt’s • …..it was reduced, but NOT absent in eyes with GA from AMD Current Management of the Dry AMD Patient • Pellegrini M, et al. Ophthalmology. 2016;123(9):1879‐1886 • Nadia Waheed, MD has demonstrated impairment of choriocapillaris flow at the margins of GA lesions through VISTA analysis

Summary Current management of the dry AMD patient includes: •There has been considerable progress in our understanding of the pathophysiology of both dry • Assessment of risk for progression and wet AMD • Cannot modify many of the risk factors •There is an increased recognition that dry and wet AMD are not dichotomous processes, but that CNV is an interval event in some patients, and atrophy is the ultimate end‐stage of the • Age, race, gender, genetics (yet!) disease • Fundus risk factors: large drusen, pigment alterations, reticular •Oxidative stress and immune dysregulation are key pathogenic mechanisms and will likely be pseudodrusen…. important targets of future therapeutics • Useful to provide prognosis to patients • May be useful to adjust follow‐up interval • Higher risk patients  q4 months • Lower risk patients  q6 months (or longer)

10 1/25/2019

Assessment of risk for progression: Current management of the dry AMD patient includes: • Micronutrient supplementation (AREDS2 formulation) in high‐risk patients

RULE: 50% ‐ 25% ‐ 12% ‐ 3% Risk for development of Advanced AMD

Ferris FL et al. AREDS report No. 18.

Current management of the dry AMD patient includes: AREDS1 • Lifestyle modification as appropriate to reduce risk • Focus our management on what we can modify • Healthy lifestyle recommendations based on the best available data • Strongest: • Do not smoke • Healthy diet ‐ green leafy vegetables, fish, reduced fat intake • Exercise • Less strong, but may be reasonable: • Wear sunglasses when outdoors in sun • Blood pressure control (safe level as determined by internist)

• Periodic monitoring for progression to advanced (esp wet) AMD

Age Related Eye Disease Study Research Group. Arch Ophthalmol. 2001;119(10):1417‐36

11 1/25/2019

Big Controversy: Are AREDS vitamins AREDS2 harmful for some patients? •Subgroup analysis with subgroups chose based on outcome •Could not be replicated with residual cohort •Final conclusion at this time: Individual genotype did not influence the response to treatment with AREDS supplements •Genetic testing prior to treatment with AREDS supplements is NOT recommended Age Related Eye Disease Study 2 (AREDS2): Lutein/Zeazanthin and Omega‐3 Supplementation Trial.

Big Controversy: Are AREDS vitamins harmful for some patients? Future Treatments: Geographic Atrophy •Complement inhibitors •Visual cycle modulation and protection •Neuroprotection •Trophic factors •Stem cell therapy

Awh CC, et al. Ophthalmology. 2013: 120(11);2317‐2323. Chew EY, et al. Ophthalmology. 2014: 121(11)2173‐2180

12 1/25/2019

Lampalizumab Complement inhibitors (Anti‐factor D Monoclonal Fab)

Conclusions and Relevance: • Lampalizumab did not reduce GA enlargement vs sham during 48 weeks of treatment • Prespecified subgroup, complement factor I profile, also without benefit • Results highlight the substantial and consistent enlargement of GA, at a mean of approximately 2mm2 per year **multiple inhibitors are being looked at in clinical trials currently

Ambati J, et al. Nat Rev Immunol. 2013;13(6)438‐451 Holz FG, et al. JAMA Ophtal. 2018;136(6):666‐677

Lampalizumab (Anti‐factor D Monoclonal Fab) Visual cycle modulation and protection •Emixustat hydrochloride • Mechanism of action: slows visual cycle activity to reduce the accumulation of toxic vitamin A byproducts • Oral tablet with systemic absorption •Seattle Study, Phase 2b/3 • No significant difference in lesion growth rate • No significant difference in mean change of BCVA from baseline to m24

**First evidence of a possible treatment effect with a complement inhibitor in GA (MAHALO Phase II Study)

Regillo CD, et al. Presented at AAO‐SSD. 2013. Clinicaltrials.gov – Seattle Study

13 1/25/2019

Neuroprotection Trophic factors

•Brimonidine CNTO Study: • Highly selective alpha 2 adrenergic receptor • Umbilical cells are not stem cells and do not agonist transform into tissue in the body. Umbilical cells • In vitro, cyto‐protective effects have been instead provide support to the existing tissue demonstrated in RPE and Mueller cells through the release or trophic factors • In vivo, thought to be neuroprotective on retinal • Umbilical cells injected subretinally through a structure and visual function suprachoroidal surgical approach •Phase 2a (dose ranging, safety, and efficacy) • Phase 2b, randomized, masked, controlled efficacy phase • Primary outcome = change in size of GA at • Single subretinal administration month 12 • 6 month primary outcome • Brimonidine implant (400ug vs 200ug) at day 1 • 60 month follow‐up and month 6

Clinicaltrials.gov. Brimonidine. 2016. Clinicaltrials.gov ‐ CNTO Study. 2012.

BEACON ‐ Phase 2b Stem Cell Therapy A phase‐2, safety and efficacy study of brimonidine intravitreal •Schwartz et al conducted a study using hESCs on 2 eyes implant in geographic atrophy secondary to AMD • • Primary outcome measure = change from baseline in atrophic lesion area in the study eye • Dry AMD • Secondary outcome measure = change from baseline BCVA and low‐luminance BCVA •Increase in pigmentation in eye with Stargardt’s macular dystrophy • 400ug brimonidine implant vs sham at day 1 and q3 months through month 21 • 2 year study •Proof of concept • Status: ongoing. Anticipate completion February 2019 •No short‐term safety issues: hyperproliferation, tumorigenicity, ectopic tissue formation, tissue rejection) •No long‐term safety issues (9 eyes with Stargardt’s and 9 with AMD)

Schwartz SD, et al. Lancet. 2012;379:713‐720 Schwartz SD, et al. Lancet. 2015;385:509‐516

14 1/25/2019

Summary PANORAMA Study •Currently, there is no known safe and effective therapy for GA • N=402 • •Many new approaches being evaluated to target numerous Sham vs Aflibercept injections every 8 weeks and every 16 weeks mechanisms of action • Mild to severe NPDR per Diabetic Retinopathy Severity Scale • 58.4% of Aflibercept groups had ≥ 2‐step improvement from baseline vs 6% sham •GA may finally have a treatment available to prevent progression • 4.5% of Aflibercept groups progressed to PDR or CI‐DME vs 25.6% sham •Ultimate goal for GA will be to replenish damaged retina • Changing paradigm of treatment from only PDR and/or DME to severe NPDR even without DME

CI vs. Non‐CI DME • Use of “CSME” becoming obsolete secondary to use of OCT • Center‐involving or ”CI” DME is considered a foveal thickness >250‐300µm (“normal” is 200‐215µm) Diabetes

reviewofoptometry.com

15 1/25/2019

A1c Recommendation New Methods of Glucose Monitoring • The ACP is now recommending an A1c goal of 7.0‐8.0% for Type 2 diabetes • CGM = Continuous Glucose Monitoring • DexCom • Abbott Freestyle Libre • Omnipod • Medtronic

randeye.com

TIR = Time in Range Iluvien® • Amount of time per day that BS is within range (70‐180) • 0.19mg Flucinolone acetonide • More predictive of BS control than A1c • Intravitreal injected, slow‐release steroid implant • FDA approved for treatment of DME • Shown to last up to 36 months

diatribe.com

16 1/25/2019

Other Injectables Argus II Retinal Prosthesis Device • Available injectables are VEGF‐A inhibitors • At least 7 have been implanted in the US • Brolucizumab – smallest active unit of anti‐VEGF‐A allows for higher concentration and dosing • FDA approved for treatment of late‐stage RP o DME trials to begin shortly (HAWK and HARRIER clinical trials for ARMD completed) • Epiretinal prosthetic device surgically implanted on and in the eye with an external headset • Abicipar pegol – DARPin (genetically engineered protein) with every 8‐12 week injection (camera and transmitter) worn by the user. o Phase 2 PALM showed similar efficacy to monthly ranibizumab injections • Provides electrical stimulation to the retina to induce visual/color perception • Faricimab – anti‐VEGF A and anti‐Ang2 which are key drivers in angiogenesis causing increased vessel permeability, inflammation and neovascularization. Combining the two is thought to improve treatment outcomes and reduce treatment burden. o Phase 2 BOULEVARD showed significant increase in VA gains over ranibizumab o Now in Phase 3 YOSEMITE and RHINE studies comparing to aflibercept • Conbercept – inhibits VEGF‐A, VEGF‐B and placental growth factor o FRONTIER and SAILING studies showed improved VA and DME decrease, additional trials beginning soon

Artificial Intelligence • AI system made the correct referral decision for more than 50 eye diseases with 94% accuracy • AI ability to make referral recommendations based on 3D OCTs “reaches or exceeds” the ability of expert clinicians • Trial of 900 diabetic patients on FDA approved Idx‐DR found 46% no DR, 29% mod NPDR, 22% sev NPDR, 2% PDR, 3.5% CSME, 2.3% center involved DME, 5.1% CSME and/or CI DME Technology •Takes a few minutes to run test, approx 30 sec to obtain dx, pt may require dilation • Systems may see ILM reflections as exudates in younger patients; therefore, more reliable in patients over 65

17 1/25/2019

Artificial Retina Augmented Reality • Created using graphene, molybdenum disulphide and thin layers of gold, alumina and silicon • Ocutrx headset with uses complex algorithms to reposition video pixels from blurred vision nitrate areas to adjacent areas of viable vision. o Useful in cases of central vision loss –ARMD, Stargardt’s • It it more flexible and thinner than other retinal implants and better replicates the shape, size and function of the retina, without causing mechanical disruption. • Absorbs light, passes it to external circuit board and impulses are transferred to visual cortex •Researchers are hoping to use this technology to form “electronic tattoos” to be placed on the skin, heart, etc. to collect health data in real time.

news‐medical.net oculenz.com

Ellex Laser • Yag vitreolysis of floaters o Possibly need multiple sessions o SE: posterior capsule tears, retinal burns, foveal burns, choroidal rupture, choroidal rupture Inherited Retinal • 2RT “retinal rejuvenation” for slowing AMD progression o LEAD study, 36 months, 292 patients, subthreshold nanosecond laser vs sham laser q6mo o Progression to late AMD was not significantly slowed o Post‐hoc analysis showed slowed progression in patients without coexistent reticular pseudodrusen at Dystrophy baseline but increased progression was observed in patients with pseudodrusen at baseline o Further trials recommended

retinalphysician.com

18 1/25/2019

Voretigene neparvovec‐rzyl • Replacement gene therapy for mutated RPE65 gene • RPE65 mutations account for 10% of AR Leber congenital amaurosis and early‐onset retinal dystrophy • FDA approval January 2018 • Subretinal injection 2mm distal to fovea • $425,000 per eye

Gene therapies in progress

Choroideremia X‐linked juvenile Stargardt disease Enrolling patients in phase 3 trial of emixustat HCl CNGB3 and CNGA3 Fast track status by FDA Gyrate atrophy pigmentosa RPGR, RLBP1, PDE6A, Effective in canine model and PDE6B Leber hereditary optic neuropathy Usher syndrome MYO7A and USH2A retinatoday.com

19 Complex Case Management A Panel Discussion Ryan Conley, D.O., Ben Stephens, M.D., Brett Enyart, O.D., Liz Batchelor, O.D., and Dawn Pewitt, O.D., FAAO 1/25/2019

Financial Disclosure Complex Case Management We have no relevant financial relationship with any product, medication, or drug in company mentioned in this presentation.

Ryan Conley, DO, Benjamin Stephens, MD, Brett Enyart, OD, and Liz Batchelor, OD

Case 1 Screening Exam

• 25 YOM referred for refractive surgery evaluation, custom-view iLasik • H/o soft CL wear x 14 years, does not sleep in CL • Manifest OD -6.00 -0.75 x 070 20/20 • Patient wore CL to exam today • Manifest OS -5.25 -0.50 x 090 20/20 • Stable x 1 year OD & OS

1 1/25/2019

What am I What am I looking at? looking at?

Exam, Case 1

What am I • Entrance: Dcc 20/40 OD, 20/20 OS • Pachymetry: 435 OD, 451 OS looking at? • Manifest: • SLE: OD slight apical bow • OD -5.75 -2.00 x074 20/40 • Dx: , unstable OD>OS • OS -5.00 -0.50 x094 20/20 • RGP Overrefraction: • OD -5.75 Sph, 46.00 BC, 20/20-2

2 1/25/2019

Considerations

What am I • Current treatment options: looking at? • Corneal Crosslinking alone • Intacs alone • Combination of both CXL and Intacs • Managing patient expectations • Future Options • Specialty contact ? • Any refractive surgery options?

Plan: Corneal Crosslinking Case 2: Hyperopic Refractive Surgery

• Patient age • 53 YOM • Central Corneal thickness • He is interested in surgery to improve near vision, but he has noticed that his distance vision is not as sharp as it used to be. • Treatment response • Dsc OD 20/30 OS 20/25 • Manifest refraction OD +1.50-0.75x110 • Based upon treatment outcome, may consider ICL in the future. • Manifest refraction OS +1.00-0.75x051 • Currently only wearing OTC +2.50 reading

3 1/25/2019

Case 2: Hyperopic Refractive Surgery Case 2: Hyperopic Refractive Surgery

• RX: OD +1.50-0.75x110 OS +1.00-0.75x051 • Patient elects for RLE: TECNIS Symfony® with LenSx® • Pachs OD 558μm OS 562μm • 1 month Post-op Visit: • OD K’s 43.10@91/43.89@1 (-0.79@91) • Dsc OD 20/20-1 RX: Plano • Dsc OS 20/20-1 RX: Plano • OS K’s 43.81@74/44.05@164 (-0.24@74) • Nsc OU 20/30 • Surgical Options: • Lasik OU to improve DVA • What if…1 week Post-op Visit: • Monovision Lasik • Dsc OD 20/30 RX: +0.50-0.75x090 laser arcuate 35@ axis 0 • Dsc OS 20/25 RX: +0.25-0.50x085 laser arcuate 20@ axis 180 • Lasik OU with slight monovision in one eye followed by KAMRA® Inlay • Consider opening the arcuate incisions in office with a Sinskey hook • Refractive Lens Exchange (RLE)

Case 2: Hyperopic Refractive Surgery Case 2: Hyperopic Refractive Surgery

• What about younger hyperopic patients? • 3 month Post-op: RLE TECNIS Symfony® with LenSx® OU • 24 YOF • OD Dsc 20/25 Nsc 20/40 RX: Plano • RX OD: +7.50-0.50x160 20/20 • OS Dsc 20/30 Nsc 20/20 RX: -0.75sph • RX OS: +8.00-0.75x170 20/20 • Patient is happy with vision and occasionally wears glasses for night driving. • Surgical Options: • Similar Case: 44YOM • Lasik/PRK • RX OD +4.75-2.25x148, OS +5.00-1.50x158 • Implantable Collamer Lens (ICL) • Post Toric RLE with LenSx OU • Dsc OD 20/20, OS 20/20 • Refractive Lens Exchange (RLE) • Wearing OTC reading glasses

4 1/25/2019

Case 3 Oculoplastic Consultation

• 83 yom interested in to improve vision OS • Dermatochalasis • K. sicca on Restasis BID, PF AT, Retaine MGD, GenTeal PM, Pataday • No • h/o filaments • Ectropion with horizontal laxity • OS>OD • Floppy Eyelid Syndrome • BCVA OD 20/20, OS 20/40 • ERM OS

Foreign body sensation OS>OD at multiple visits; symptoms wax and wane

Oculoplastic Consultation Oculoplastic Consultation

FES contributing to GPC and ocular discomfort. Involutional Ectropion Bilateral LL. Lower eyelid laxity with tendency towards ectropion. Ocular Recommend lubrication & metal shield at bedtime. irritation due to secondary to laxity. Suggest lateral canthal resuspension to Reviewed relationship to sleep apnea & patient tighten the eyelids and possible cheek elevation via myocutaneous flap to support the lower eyelids. currently using a CPAP. Recommend surgery with lateral canthal suspension vs wedge resection of the upper eyelid.

5 1/25/2019

Oculoplastics Future considerations

• 2w post-op bilateral ectropion repair. Mild post-op bruising. • Patient ocular pain and FB symptoms resolved post ectropion repair • For Floppy Eyelid Syndrome, consider 2nd stage surgical intervention with wedge resection of the left or right upper eyelid if symptoms worsen.

Case 4 Exam

HPI: 75 yo F with POAG x 20 years. Presented to her primary eye doctor with • VA: • L/C/S: erythematous upper and lower lids • OU, Follicles OU decreased vision and noted to have elevated IOP OS with anterior chamber • OD: 20/40 PH 20/25 • OS: 20/60 PH NI • K: KP on endo OU, peripheral sub-epithelial reaction OU infiltrates OU • IOP: • PMH: Unremarkable. No hx of prior ocular infections or inflammation • AC: 1+ cell OD, 2+ cell OS • OD: 16 • Iris: WNL OU, no TIDs • PSHx: CE IOL OU in 2006 • OS: 38 • Lens: PCIOL OU • PUPILS: ERRL, no APD • FH: unremarkable • Vit: Syneresis OU, no cell • EOM: FULL • Meds: Combigan BID OU (started 6 months prior) • Nerve: 0.4 c/d OD, 0.25 c/d OS, no edema • Gonio: Open to CB OU, few PAS OU OU • Allergies: NKDA • Macula: Flat OU, no CME • Periphery: WNL OU

6 1/25/2019

Exam Considerations

• Elevated IOP + anterior uveitis  consider Herpetic etiology • Bilateral involvement  less likely Herpetic • Brimonidine component (Combigan)  consider allergy • Peripheral K infiltrates  consider staph marginal keratitis

Becker, Heidi I. “Anterior Uveitis and Concurrent Allergic Conjunctivitis Associated With Long-Term Use of Topical 0.2% Brimonidine Tartrate.” Archives of Ophthalmology, vol. 122, no. 7, Jan. 2004, p. 1063

PLAN OUTCOME

• Stop Combigan • Unremarkable uveitis lab work up (HSV, VZV, HLA-B27, FTA-ABS, RPR, ANA) • Add Diamox 250 mg QID and Rhopressa QHS • Rapid improvement in inflammation and IOP down to mid teens within 2 weeks • Cover with Valtrex 1000 mg BID • IOP controlled long term with Rhopressa QHS • Start Pred Forte Q2H OU • No recurrence of inflammation since stopping Combigan • Extensive uveitis blood work sent

7 1/25/2019

OUTCOME Case 5

• “A Controlled Trial of Oral Acyclovir for Iridocyclitis Caused by Herpes Simplex • 74 yom referred for cataract evaluation Virus.” Archives of Ophthalmology, vol. 114, no. 9, Jan. 1996, p. 1065. • Manifest OD +1.25 -2.25 x075 20/20-2 BAT-M 20/60 • Becker, Heidi I. “Anterior Uveitis and Concurrent Allergic Conjunctivitis • Manifest OS Plano DS 20/40-2 BAT-M 20/200 AssociatedWith Long-Term Use of Topical 0.2% Brimonidine Tartrate.” Archives of Ophthalmology, vol. 122, no. 7, Jan. 2004, p. 1063 • ABMD OU • Watts, P, and N Hawksworth. “Delayed Hypersensitivity to Brimonidine Tartrate • Combined OU 0.2% Associated with High Intraocular Pressure.” Eye, vol. 16, no. 2, 2002, pp. • Trace ERM OU 132–135.

Case 5

What am I • Patient expectations looking at? • Traditional vs LenSx • Standard IOL vs Toric IOL • Corneal vs refractive astigmatism • Magnitude and pattern of corneal astigmatism (regular vs irregular) • Does presence of ABMD affect surgery plan?

8 1/25/2019

What am I What am I looking at? looking at?

Cataract Surgery Plan Case 6

• LenSx, standard IOL, OS recommended first • 75 yom referred for cataract evaluation • 1w p/o ceiol OS: Dsc 20/20-1 Manifest Rx: Plano OS • Manifest OD +1.00 -1.00 x135 20/30+2 BAT-M 20/60 • Recommend 2nd • Manifest OS +2.25 -1.75 x070 20/30+2 BAT-M 20/100 • Dry eye OU • Combined cataracts OU

9 1/25/2019

Case 6

What am I • Patient expectations – patient only wants correcting IOL • Corneal vs refractive astigmatism looking at? • Magnitude and pattern of corneal astigmatism (regular vs irregular) • Does presence of dry eye affect surgery plan?

Cataract Surgery Plan

What am I • LenSx, standard IOL, OS recommended first looking at? • Patient not ideal candidate for Presbyopia Correcting IOL • 1w p/o ceiol OS: Dsc 20/25-1 Manifest Rx: +0.50 -1.00 x090 20/25+2 OS • Recommend 2nd eye surgery • 1d p/o ceiol OD: Dsc 20/25

• Patient very happy with outcome.

10 1/25/2019

Case 7 Case 7, Exam

• 62 yof presents with eye pain OD x 1 month • OD Dsc 20/60 PHNI, eccentric fixation • Ochx: • OS Dsc 20/150-1 PH 20/100-1 Dcc 20/40-1 RGP lens OS • Cataract extraction OD (~50 years ago, congenital? Pt unsure) • OD cornea: PK, graft in place, loose suture, 2+SPK, diffuse edema, no folds • ACIOL (likely placed at later date, Pt unsure) • OD A/C: 1+ cell • PK OD 1998, repeat PK OD 1999 • OD Lens: AC IOL, residual cortex remaining around margin • DSEK OD 2013 • IOP: OD 21, OS 21 • PCIOL OS • Pachymetry: OD 837, OS 610 • Current gtts: cipro QID OD, combigan BID OD, pred acetate Qday OD

Case 7, Considerations Case 7

• What is causing what in this eye? • Corneal Transplant Failure OD. • Uveitis? • Discussed possible repeat DSEK in future. • Graft Failure? • Continue Pred. • AC IOL ? • Continue Combigan as directed by referring provider • Retained Lens Cortex?

• Treatment: remove exposed suture

11 1/25/2019

Case 8 Case 8, Exam

• 60 yom referred for cataract evaluation • CC: decreased VA x 6 months, glare • Ochx: none except • Manifest OD +1.25 -1.25 x092 20/20 BAT-M 20/100 • Lasik OU, 1992 • Manifest OS +1.50 -1.00 x062 20/20 BAT-M 20/200 • Laser retinopexy OD, 04/2017 • Combined cataracts OU • RD OS, 03/2016 • Other exam findings as expected given patient history • Strab sx Dr. Cole, 07/2018 • Scleral buckle removed 06/17/16

Case 8

What am I • Patient expectations looking at? • Traditional vs LenSx • Standard IOL vs Toric IOL • Corneal vs refractive astigmatism • Magnitude and pattern of corneal astigmatism (regular vs irregular) • Does prior refractive affect surgery plan?

Prior refractive surgery has increased risk of Refractive Surprise and possible IOL exchange

12 1/25/2019

Cataract Surgery Plan

What am I • Traditional surgery, OS first looking at? • 1w p/o ceiol OS: Dsc 20/20 Manifest Rx: Plano OS • Recommend 2nd eye surgery

Thank you!

Ryan Conley, DO Benjamin Stephens, MD Brett Enyart, OD Liz Batchelor, OD

13