1. Herpes Zoster and the Zoster Eye Disease Study (ZEDS)
Elisabeth J Cohen, MD
Professor of Ophthalmology
New York University SoM
NYU Langone Health

2. Financial Disclosures
I have no financial disclosures or conflicts of interest.

3. Presentations of Varicella Zoster Virus (VZV) Infection
Herpes Zoster (HZ) caused by reactivation of latent VZV in persons who had chicken pox
Typical painful, unilateral, vesicular, dermatomal rash
Pain pre rash in 74%: unilateral, first time ever, mod/severe
Lee Clin Neurol Neurosurg 2017;152:90
Herpes Zoster Sine Herpete: radicular pain without rash
Lewis BMJ 1958
Severe uveitis
Schwab Ophthalmology 97;104:1421
Stroke due to HZ: 63% hx rash
Nagel Neurology 2008; 70:853-60
HZ without rash dx missed!

4. What’s New in Herpes Zoster
Increasing incidence of zoster
Decreasing age of onset of zoster
Risk factors before and after zoster
Varicella Zoster Virus (VZV) trigger for temporal/giant cell arteritis
Zoster Eye Disease Study (ZEDS) NEI funded with CC at NYU is a randomized controlled clinical trial to evaluate prolonged suppressive antiviral treatment to reduce complications of Herpes Zoster Ophthalmicus: Please refer your HZO patients for evaluation!
Efficacy and safety of vaccines against zoster: need to increase use!
Zoster Vaccine Live (ZVL, Zostavax)
CDC recommended immunocompetent age 60+ since 2008
FDA approved immunocompetent age 50+ since 2011
Recombinant Zoster Vaccine (RZV, Shingrix)
FDA approved Oct, 2017 for age 50+
CDC recommended Jan, 2018 immunocompetent age 50+

5. Herpes Zoster (HZ) / Shingles
Common disease
1,200,000 new cases/yr in US
Suaya Open Forum Infect Dis 2014
10-20% involve Vth nerve
>95% age 40+ in USA have had varicella, are at risk for HZ
1 in 3 in US will have zoster
1 in 2 age 85
More common (~2x), severe in immunocompromised persons
> 90% of people with HZ are not immunocompromised
Misconception #1
Healthy people are not at risk for zoster and its potentially disabling sequelae- we are!

6. Incidence of Zoster
Increasing incidence of HZ over 60 yrs in population-based study
v in MN
Incidence up >4-fold in all ages
Increased pre and post varicella vaccination
Kawai Clin Infect Dis. 2016; 15:63:221
Incidence HZ age MarketScan insurance claims
No acceleration of increase after varicella vaccine
Age 65+ plateau after 2007, not due to HZ vaccination
Continued increase age 35-64
Harpaz JID 2018:218 (Suppl 2) S57

7. Age at Onset of Zoster
Rate goes up with age, but number of cases highest in 50’s
Yawn Neurology 2013; 81:928 (Figure 1)
Insinga J Gen Intern Med 2005;20: (2)
Ghaznawi Ophthalmology 2011;118:2242 (3)
Misconception #2
Herpes Zoster is only a disease of the elderly- it affects large number of people in their prime too!

8. Decreasing Age at Onset of HZO
Age of onset of HZO (Chen Cornea 2015; 34:535)
400 pts (58% women) HZO v
Mean age yrs yrs P<0.05
Less than age 60 yrs % % P<0.05
Less than age % % P<0.05
Age at presentation HZO (Davies Br J Ophthalmol 2016; 100:312)
>900 acute HZO patient
Decrease in mean age yrs to yrs P<0.05
Conclusions include: Recommend zoster vaccination adults age 50 years and older

9. Role of Varicella Vaccination in Zoster Increase
Postponement of HZ by encounters with varicella “boosts” immunity (Hope-Simpson Proc R soc Med. 1965;58: 9-20)
Many think varicella/chicken pox vaccination cause of increase in zoster However rise in zoster began before varicella vaccination
Yawn. Mayo Clin Proc 2007; 82:1341, Kawai Clin Infect Dis 2016; 63:221-6
Harpaz JID 2018:218 (Suppl 2) S57-61.
Routine varicella vaccination not widespread in Europe (ex France, UK!)
Rates of HZ similar in these countries without varicella vaccination
Cause of increasing incidence of zoster is unknown!

10. Risk Factors for Development of Herpes Zoster
Well known: increasing age , immunocompromise, female sex
Recent additions to risk factors
Family history 3x, depression 4x, stress 3x, history of zoster 80%
Marin Open Forum Infect Dis Jun 13;3; Kawai, Yawn Mayo Clin Proc 2017;92:1806
Heart failure 2x
Wu BMC Infect Dis 2015; 15:17
Traumatic brain injury 3x
Tung PLoSOne 2015 Jun 11;10
Diabetes 45%, asthma 50%, acute kidney, autoimmune disease 70%
Suaya Open Forum Infectious Diseases 2014 Sep; Peng J Asthma 2016 Jul 13 [epub]
Yang Sci Rep 2015 Sep3;5:13747; Kawai, Yawn Mayo Clin Proc 2017 Dec;92:1806
Statin use
13% inc risk: case control study in UK, high dose 27% inc risk
Matthews Br J Dermatol 2016; 175:
25% inc risk: population based prospective study in S Korea.
Age % inc risk (Kim MC PLoS One Jun 14)
Review 5 studies: in 2 inc risk HZ < 49 yrs old, vaccinate younger pts on statins? (Zuin Eur J Clin Microbiol Infect Dis 2018 epub)
Implications regarding importance of vaccination against zoster in patients with wide variety of medical conditions (EJC: Just do it!)

11. Smoking and Zoster
Association of cigarette smoking with a past history and incidence of HZ
Ban J Epidemiol Infect Jan 16:1-6 [epub ahead of print]
Community-based prospective cohort study over 3 years in Japan
Baseline survey: > 12,000 with information on smoking and history HZ
3 years active surveillance for incidence HZ
Past history HZ: current vs never smokers: 0.67 odds ratio
Incidence of HZ: current vs never smokers: 0.52 hazards ratio
Conclusions
Smoking inversely related to prevalence and incidence of HZ
Not to encourage smoking!
Personal comment: Study change in rates of smoking vs. HZ

12. Complications of HZ: Postherpetic Neuralgia (PHN)
Most common complication of zoster
Defined as pain/itch beyond 3 months after onset of zoster
Occurs in ~30% of HZO with eye involvement, mostly age 65+
Borkar Ophthalmology 2103; 120:451-6
Systematic reviews of risk factors for PHN
Age, severity prodomal and acute pain, rash, HZO
Forbes Pain July 25 [epub], Kawai Int J Infect Dis. 2015; 34:
Zoster risk factor for development major depression
Chen, M. H. Psychosom Med, 2014; 76:
Zoster is most common cause of suicide due to pain in people age 70 years and older
Hess, TM. Minn Med. 1990; 73:37-40

13. Anecdote
My mother worked full time to age 67…She then got very ill with Shingles. Her optic nerve was involved and she was in severe pain. You could not even touch her hair or face. She suffered for many weeks…She was never the same….The chronic pain caused her to sleep for most of the day, she resigned as a deacon of the church as she could no longer attend services or meetings due to the pain. The pain never really went totally away… I received the vaccine about 2 years ago, and pray I never get the disease. Neither the polio (age 12), meningitis (age 41), or RA (age 67 treated with methotrexate) stopped my very active mother, but the shingles destroyed her life.
KC 2017

14. Zoster long known risk factor for stroke
55%-2x inc stroke within 1-3 months, decreasing over 6-12 mos
Yawn Mayo Clin Proc 2016; 91:33
especially younger pts < 40 yrs old
2-4x risk stroke after HZO vs HZ
Zoster reported as risk for heart disease
HZ risk for MI < age 40 yrs
Inc risk arrhythmia, CAD mean age 46
Severe HZ (hosp) risk for afib
Breuer. Neurology 2014;82:1
Wu. J Med Virol 2014; 86:772-7
HZ risk for peripheral artery disease
13% inc overall, 27% inc < 50 yrs old
Lin Medicine 2016;95:e4480
Zoster Risk for Stroke, Heart, Vascular Disease Nagel JID 2018: 218 (Suppl2) S107; Warren-Gash S102

15. VZV as Trigger for Giant Cell (Temporal) Arteritis (GCA) Gilden, White, Khmeleva. Neurology.2015; 84:
50 sections per temporal artery (TA) biopsy (vs normal 3)
Immunohistology for VZV antigen, PCR for VZV DNA
VZV antigen in 74% (61/82) GCA+ temporal arteries
In sections adjacent to VZV, giant cell pathology in 89%
GCA is VZV vasculopathy of TA
Antiviral treatment may benefit steroid treated GCA/TA patients
Should study in RCT
BUT: Only 3/25 GCA+ TAs + VZV antigen, 1 case GCA after HZO
Buckingham Am J Ophthalmol 2018;187:51
Gilden >5000 slides vs.<1000/bx
Nagel JID 2018:218(suppl2)S107
Courtesy of Don Gilden

16. Corneal Disease Classification of HZO
Recommend use same as HSV
White.2014, Jul
Epithelial keratitis
Infectious dendriform
Stromal keratitis
Without ulceration
With ulceration (not microbial infection)
Endothelial keratitis
Uveitis
Neurotrophic keratopathy
With or without melting/perforation
With or without microbial superinfection
Presentation Title Goes Here

17. Complications of HZO Zoster can involve any tissue of eye and orbit!
Epidemiology HZO (N=67)
Recurrent disease (after quiet off meds 3 mos):
8% at 1 yr % at 3yrs % at 5 yrs % 6 yrs
Chronic (persistent active disease >90 days) in 23%
Uveitis, increased IOP, chronic disease are risk factors for recurrent and/or chronic disease
Tran Ophthalmology 2016;123:
Outcomes cataract surgery in chronic HZO (N=24)
Early improvement in VA, decreased by last fu due to retina
He J Cataract Refract Surg. 2015; 41:771-7
Well treated HZO may be associated with posterior segment problems more often than expected
Increased risk wet AMD post HZO
Retrospective cohort study >1000 HZO, >5000 controls with 3 yr fu
HR >4.5 for HZO to develop wet AMD, due to inflammation or vasculopathy? (Ho Acta Ophthalmologica 2018)

18. Treatment of Herpes Zoster (HZ)
Oral antivirals within 72 hours of rash are approved and recommended
Valacyclovir 1000 mg three times daily for 7 days
Famciclovir 500 mg three times daily for 7 days
Acyclovir 800 mg five times daily for 7 days (not as effective)
Reduces chronic eye disease from 50% to 30%, does not reduce PHN
Herpes Zoster Vignette (Cohen JI N Eng J Med 2013;369:255-63)
“Antiviral treatment most beneficial for persons who have complications of HZ or who are at increased risk for complications, such as older persons and immunocompromised persons…
My opinion: Antiviral treatment should be given to all people with HZ as soon as possible, since complications typically develop more than 72 hours after onset when treatment should be given, and can occur in relatively young and healthy people!!!

19. Case
A healthy person in her 50’s, developed unilateral radicular thoracic pain and a rash a wk later. Treatment for HZ was begun, next day had leg numbness and weakness with transverse myelitis due to HZ. At 1 year, still had PHN with constant 5/10 pain
Lessons
Recommend vaccine at age 50+
Can’t predict who will have serious complications of HZ!

20. Possible New Treatment for HZO
The Zoster Eye Disease Study (ZEDS) funded by NEI in to conduct a multicenter, Randomized, placebo controlled Clinical Trial (RCT) to determine whether prolonged, suppressive valacyclovir treatment reduces complications of Herpes Zoster Ophthalmicus (HZO), including eye disease and/or postherpetic neuralgia
Presentation Title Goes Here

21. ZEDS Study Structure
60 Participating Clinical Centers (>200 investigators in 29 states)
Coordinating Center (CC) at NYU Langone Health
Study Chair: Elisabeth Cohen, Co-Chair Bennie Jeng, U MD
Multiple PIs: Judith Hochman, CC NYUSoM, NYULH
Executive Committee: Stephen McLeod, Todd Margolis, Christopher Rapuano, James Chodosh, Anat Galor, Alice Matoba, Shahzad Mian
NYULH PCC: Ilyse Haberman PI
Medical monitors: Laura Balcer, Michael Perskin
CC staff leader: Jacqueline Arciniega
Clinical Event Review Committee: Kathryn Colby Chair
Presentation Title Goes Here

22. Background and Rationale of ZEDS
Acute high dose oral antiviral treatment is recommended for Herpes Zoster Ophthalmicus (HZO), but there is no standard approach to antiviral treatment for ocular complications of HZO.
Rationale of the Zoster Eye Disease Study (ZEDS)
First:
Relatively recent knowledge of infectious pathogenesis of complications of Herpes Zoster and HZO
Second:
Significant benefit of suppressive antiviral treatment in reducing recurrent Herpes Simplex Virus (HSV) eye disease
HZO and HSV keratitis, caused by different herpes viruses, are analogous in many ways

23. Rationale for Zoster Eye Disease Study (ZEDS)
Evidence that Herpes Zoster is associated with chronic active infection with the varicella zoster virus (VZV)
Active infection contributes to chronic eye disease
Dendriform epithelial keratitis PCR+ for VZV and responds to topical ganciclovir
Iritis: AC is PCR+ for VZV
Pavan Langston D. Arch Ophthalmol 1995; 111:1381
Hu AY, Am J Ophthalmol 2010; 149:214
Aggarwal S. Cornea. 2014; 33(2):109
Takase Jpn J Opthalmol 2014; 58:473

24. Rationale of Zoster Eye Disease Study
Herpetic Eye Disease Study (HEDS) Acyclovir Prevention Trial (APT)
HEDS Study Group. N Eng J Med 1998; 339:
HEDS Study Group. Arch Ophthalmol 2000;118:
Long-term suppressive treatment with oral acyclovir resulted in 45% reduction in recurrent Herpes Simplex Virus disease at 1 yr
Antiviral treatment was most beneficial in reducing stromal keratitis
Suppressive antiviral treatment is now standard of care for HSV keratitis, and has improved outcomes
ZEDS trial analogous to the HEDS APT study for ocular disease caused by varicella zoster virus (VZV)
Valacyclovir, prodrug of acyclovir, has higher plasma concentration than acyclovir required for VZV
Similar trial design: RCT of 1 yr of suppressive valacyclovir vs. placebo with follow-up every 3 months for 18 months

25. Overview of Study Design
Immunocompetent HZO patients, 18 years and older
History of typical unilateral vesicular rash in V1 distribution
Episode in medical record within the year prior to enrollment of
Dendriform epithelial keratitis
Stromal keratitis
Endothelial keratitis
Iritis
Can be called by wide variety of names: pseudodendrites, keratouveitis, disciform keratitis, uveitis…
Randomized 1:1 ratio to double masked valacyclovir 1000 mg or placebo daily for 1 yr
Randomized in 4 strata
Age of onset HZO: < 60 years vs years or more
Time since onset HZO < 6 months vs months or more
Enroll 1050 study participants over 3 years, complete in 5 years
As of 10/31/2018 : 144 study participants, 100 randomized
WE NEED TO ENROLL MORE STUDY PARTICIPANTS!!!

26. Primary Objective and Endpoint
To evaluate whether or not suppressive valacyclovir treatment compared with placebo will delay time to first occurrence by 12 months of new or worsening
Dendriform epithelial keratitis (DEK)
Stromal keratitis without ulceration(SK)
Endothelial keratitis (EK) (disciform keratitis)
Iritis (IR)
Stromal keratitis with ulceration (SKU)
With pre-specified treatment requirements to be a primary endpoint

27. Exclusion Criteria
Immunocompromise by CDC criteria for impaired cellular immunity due to disease or treatment (making ineligible for zoster vaccine)
History of lymphoma, hematopoietic stem cell transplant
AIDS or HIV with CD4 count less than or equal to 200
Immunosuppressive therapy including prednisone 20+mg daily. chemotherapy for cancer, mmune modulators, especially anti-tumor necrosis agents
Refractive surgery, other than at cataract surgery, within 5 yrs, corneal transplant
Renal insufficiency with eGFR) < 45
Requires val, acv, or famvir, for genital, ocular HSV
Pregnant, nursing, or do not agree to use contraception for one year
Vaccination against zoster within 1 month
Incarceration, unable to give informed consent, comply with protocol, or complete 18 months of follow-up

28. Definitions Endpoints of Stromal Keratitis With or Without Ulceration, Endothelial Keratitis, Iritis and Dendriform Epithelial Keratitis
Stromal Keratitis without ulceration: Localized or diffuse stromal infiltrates with or without keratic precipitates, corneal edema, or corneal neovascularization, and is without an epithelial defect by fluorescein staining.
Endothelial Keratitis: Disciform (localized) or diffuse corneal stromal, and usually epithelial edema, with keratic precipitates out of proportion to anterior chamber reaction (none or trace: 5 cells or less per field).
Iritis: Anterior chamber reaction graded ≥1+ (6 or more cells/field using 1x1mm slit beam) in the absence of suspected or proven microbial keratitis.
Stromal Keratitis with ulceration: Stromal infiltrates with an overlying epithelial defect by fluorescein staining due to active stromal keratitis and not neurotrophic keratopathy or suspected or proven microbial superinfection. Microbial superinfection should be ruled out by negative corneal smears and cultures and/or lack of response to intensive antibiotic treatment every hour.
Dendriform Epithelial Keratitis: Linear or elongated, often branching lesion(s) on the corneal surface that stain at least minimally with fluorescein. They are usually elevated, non-ulcerated, and without terminal bulbs.

32. Secondary Study Objectives and Endpoints
To evaluate whether or not the effect of treatment on primary endpoint persists for 6 months after treatment by comparing rates of new or worsening DEK, SK, EK, IR by 18 months follow-up in participants randomized to valacyclovir or placebo
To test hypothesis that suppressive valacyclovir treatment reduces the incidence, severity, duration of postherpetic neuralgia (PHN) compared to placebo at 12 and 18 months
PHN measured by worst pain in last 24 hours on scale of 1-10
Severity of PHN by potency and dosage of medications used

33. Other Secondary Endpoints
Development of specific disease manifestations of HZO
Primary endpoints: DEK, SK, EK, I
Neurotrophic keratopathy with and without melting, perforation, presumed or proven microbial superinfection
Episcleritis, Scleritis
Effect of past history of specific manifestations on their recurrence
Glaucoma: by IOP (22 mm Hg+ and 6 mmHg+ rise) and medical/surgical treatment required
Impact of vaccination against zoster on HZO endpoints by treatment group (valacyclovir vs. placebo)

34. Study Visits and Treatment
Prescreening review of medical records and discussion with potential study participant by investigator, coordinator and CC re eligibility
Screening visit
Consent obtained, then eGFR and pregnancy tests ordered
Enrollment/randomization visit within 30 days of tests
Study medication consisting of 3 mos supply of masked valacyclovir and placebo pills dispensed, to be taken 2 pills once daily
Valacyclovir 500 mg used because 1000 mg too big for encapsulation (and option for bid and daily dosing if side effects)
Follow up visits every 3 months for 18 months
12 month study visit: study medication discontinued
Presentation Title Goes Here

35. Schedule of Case Report Forms

36. Please support ZEDS to try to improve outcomes in HZO by referring your patients to a study investigator nearby: Ilyse Haberman

37. Vaccination to Prevent Zoster
Randomized clinical trial of Zoster Vaccine Live (ZVL) pts age 60+
61% reduced burden of illness (incidence, severity, duration)
66% decrease in postherpetic neuralgia (secondary endpoint)
51% decrease incidence zoster
Efficacy against incidence zoster 64% age v. 38% in 70+
Effect on severity disease greater among persons age 70+
Oxman NEJM 2005; 352:2271
In 2006 ZVL, Zostavax (Merck) approved by FDA, recommended by CDC for adults age 60+ without immunocompromise
MMWR June 6, 2008 / 57(05); 1-30
1n 2011 FDA approved vaccine for age 50+ after shown to decrease incidence of HZ 70% in persons age 50-59
Schmader Clinical Infectious Diseases 2012;54(7):

38. Contraindications www.cdc.gov/vaccines
Immunocompromise
Diseases affecting cell mediated immunity
Leukemia, lymphoma, ca of bone marrow, lymphatics
AIDS or clinical signs of HIV including CD4+ < or = 200
Hx of stem cell transplant
Unspecified cellular immundeficiency
Immunosuppressive treatment
Prednisone 20 mg daily for 2+wks, wait 1month after stop
Chemotherapy (more than low dose for inflammatory diseases), wait 3mos
Recombinant immune mediators and immune modulation, especially antitumor necrosis factor meds, wait 1 m after off these meds
Anaphylactic allergy to gelatin, neomycin
Pregnancy (“unlikely in target age group”)

39. ZVL Safety Data Mild local reactions in younger > older pts
Age 50-59: 69% : 58% 70+: 41%
Oxman MN et al. N Eng J Med 2005;352: ,
Tyring SK et al. Vaccine 2007;25:
Localized inflammation (N=190,000)
Age 50s 10x; 60s 2.5x; 70s 1.5x; vs. age 80+
Tseng J Intern Med 2012; 271:
Using FDA grading scale: 1 mild, 2 mod, 3 severe
Grade 3: Age 50s: 1.2%, 60s: 0.3%, %
Popmihajlov Hum Vaccin Immunotherl 2018 July 19
10 year review of AEs reported to Merck
34 millions doses
14 SAEs caused by OKA strain of attenuated VZV in vaccine
5 immunosuppressed, 1 fatal HZ (and 2 reported elsewhere)
Willis ED Vaccine 2017 Dec 19;35:7231,
Alexander KE Vaccine 2018 jun 22 epub
Cunningham JID 2108; 218 (Suppl2) S127.

40. Case Reports of Complications in Ophthalmic Literature
Episodes of zoster keratitis, uveitis 2-5 wks after zoster vaccination
Recommend monitor HZO patients 4-6 wks after zoster vaccine
Vaccinate with caution in HZO
Khalifa, Jacoby, Margolis Arch Ophthalmol 2010; 128:1079
Sham Arch Opthalmol 2012; 130:793
Hwang Cornea 2013;32:508-9
Jastrzebski A Cornea 2017; 36:740
My opinion: despite some risk of recurrent inflammation, recommend vaccine 1-3 yrs post HZO, when stable, and monitor patients
6% risk second episode in 6-8 yrs
Yawn Mayo Clin Proc. 2011; 86:88, Shiraki 2017; PMID:
Acute retinal necrosis after HZ vaccine in 1 renal transplant and 1 CLL pt (contraindicated) and 1 end-stage renal disease pt
Charkoudian Arch Ophthalmol 2011;129:1495
Menghini Retin Cases Brief rep 2018 july 25
Betjes Immune cell dysfunction …in end-stage renal disease. Nat Rev Nephrol 2013; 9:255
Zoster Vaccine Live contraindicated if impaired cellular immunity!!
Presentation Title Goes Here

41. New Recombinant Zoster Vaccine (RZV) Lal H et al
New Recombinant Zoster Vaccine (RZV) Lal H et al. N Engl J Med 2015; 372: Cunningham N Engl J Med 2016; 375: Cunningham. J Infect Dis 2018; 218 (suppl2) S127
Adjuvanted herpes zoster subunit (HZ/su) vaccine (GlaxoSmithKline)
Recombinant VZV glycoprotein E antigen, novel AS01B adjuvant
ZOE-50 RCT in immunocompetent adults age 50 years and older
2 IM injections 2 months apart of vaccine or saline placebo
Results: ~97% efficacy for all age groups
Grade 3 severe acute symptoms interfering with activities in 17%
Vaccine efficacy pooled in 2 ZOE-70 , ZOE-50 trials in
Results: efficacy : ~90% in vaccine recipients age 70s and 80s
Efficacy against HZ over time persisted: 85% yr 4
Editorial: Local or systemic reactions preventing normal activity in 12% vaccine raises concern about adherence to necessary 2 dose schedule.
Neuzil N Engl J Med 2016;
FDA approved Recombinant Zoster Vaccine (RZV) Oct, 2017 age 50+
CDC recommended Jan 26, 2018 MMWR for immunocompetent 50+
Presentation Title Goes Here

42. FDA Label for Shingrix
Recombinant Zoster Vaccine (RZV) indicated for prevention HZ in adults age 50 years and older
Not just immunocompetent adults!
Immunosuppressive treatment may reduce effectiveness
Administer 2 doses IM at 0 and 2 to 6 months
No evidence interference immune response if given with a flu vaccine
VZV glycoprotein E antigen vial reconstituted with AS01B adjuvant
Before and after reconstituted: refrigerate, discard if frozen (vs ZVL)
Contraindications: anaphylaxis to component of vaccine or after a dose
Adverse reactions/events:
Local: pain 78%: General: myalgia 45%, fatigue 44%
Local and general reactions less age 70+ than age 50-69
Age 50-59: pain 88%, myalgia 57%, fatigue 57%: grade 3: 8-10%

43. Advisory Committee on Immunization Practices (ACIP) Recommended HZ Su Vaccine (RZV, Shingrix) October, 2017
Herpes Zoster subunit (HZ/su) vaccine (Shingrix) recommended for immunocompetent adults age 50 years and older
Recommended for immunocompetent adults previously received ZVL (Zostavax)
Shingrix is preferred over Zostavax (vote 8 to 7)
CDC accepted all ACIP recommendations in MMWR Jan 2018
Dooling, Guo, Pater, Lee, Moore, Belongia, Harpaz. MMWR Jan 26, 2018; 67:

44. Reactivation of HZO after RZV
89 yo with HZO stable 1 yr on low dose topical steroids
3 wks after first dose RZV developed recurrent stromal keratitis
Responsive to full strength topical steroid treatment
Lehmann, Matoba Ophthalmology 2018; 125:1682
My opinion re timing RZV in HZO
When stable
Monitor pre and post 2 shots
Not urgent: HZ stimulates CMI 1yr+

45. Under-Usage of Zoster Vaccine in USA
Usage of Zoster Vaccine Live among immunocompetent age 60 years+
2010 : 14% 2011: 16% 2012: 20% : 24% 2014: 28%
2015: 31% (MMWR Surveill Summ May 5;66: 1-32)
National and State-Specific Shingles Vaccination
Overall among age 60+: 32%, variable: NY- 26%
Age 50-59: 6% maybe due to lack of recommendation by CDC
Lu PJ Am J Prev Med 2017; 52:362-72
Barriers
High cost
Complex/partial insurance coverage
Lack of strong recommendation by doctors

46. Increasing Vaccination Against Zoster at NYULH
Interventions in 2011:
Education of physicians and patients
Available at Pharmacy
Epic EMR reminders and alerts
Studies supported by Merck Investigator Initiated Program
Survey Division of General Internal Medicine MDs knowledge, attitudes, practices pre and 1 yr post interventions
Elkin. Cornea. 2013; 32:976, Elkin. Eye & Contact Lens. 2014; 40:225-31
Obtained written consent to screen patients in Ophthalmology Clinic at Bellevue for contraindications, have nurse give vaccine there to 100 eligible, willing patients at no cost to them
Jung J. Am J Ophthalmol 2013; 155:787-95

47. Bellevue Ophthalmology Clinic Results
Do you have a regular doctor? Yes 94%
If yes, how many visits last year? : 77%
Would you consider getting the shingles vaccine if a doctor recommended it? Yes 89%
Most common reason patients who would follow a MD’s recommendation declined vaccine (N=49) was they wanted to speak with their primary care doctor
Recommendations of primary care doctors regarding vaccination are most important, but ophthalmologists and other doctors should recommend vaccination against zoster too, and will be more effective if have a strong relationship with patients!
Kollipara Cutis 2015; 95:251.
Presentation Title Goes Here

48. Changes from Baseline to One Year Follow-up Surveys 2011-2012 of Primary Care Doctors
Baseline Follow Up
30% 70% p<0.05
66% 69%
94-97% 94%
There are approx. 1,000,000 cases of shingles per yr in US
2. Importance of vaccines
Herpes zoster vaccine
Pneumonia and flu vaccines
Yellow: doses
Red: prescribers

49. 2017 Follow-up Survey of Primary Care MDs at NYULH Tsui, Gillespie, Perskin, Zabar, Wu, Cohen. Cornea 2018 accepted pending revisions
Similar internet survey re knowledge, attitudes and practices re zoster vaccine 5 yrs after interventions to increase usage, prior to RZV
Results: 26% (138/530) response rate
Rates (estimated) of Zoster Vaccination of immunocompetent
Age 60+ : %
Age 50-59: %
Rates of pneumococcal vaccination age 65+: 72%
Rates of annual flu vaccination: average 67%
Attitudes re important clinical priority of vaccinations (p<0.001)
Zoster: 76% agreed 35% strongly agreed
Pneumococcal: 94% 68%
Influenza 93% 74%
99% agree ACIP/CDC recommendations important determinants
Stronger recommendation by primary care doctors still necessary!!!

50. When Zoster Hits Close to Home
Anecdote 2017: 58 year old friend
Last year I was told by a doctor friend to get a shingles shot. My thought was that’s for old people- boy was I wrong!! Six months later I had a pain in my neck that kept me up at night and 2 days later I had a rash from the top of my back around my neck to my chest. I knew it was SHINGLES. I was so mad at myself for not getting the vaccine. It’s been 4 months and it is still painful and it feels like it is going to stay with me forever. I tell everyone I meet, please go to your doctor and get the vaccine as soon as you can. I have reached out to friends around the world, and will keep telling everyone this is nothing to fool with!
Evidence
Impact of personal zoster awareness on zoster vaccine uptake in the US
Harpaz R Vaccine 2017;35:
Vaccine uptake marked increased immediately after zoster in a spouse
Relative incidence vaccination 7x during month post vs 6 months pre
Relative incidence 14x when spouse severe zoster requiring opiates
No increase in pneumonia vaccination during month post HZ

51. We Can Do Better to Protect Our Patients Against Zoster!
How do we encourage MDs to strongly recommend vaccination against zoster???
Increase vaccination rate of doctors as evidence of importance
Bonanni Vaccine
AAO Policy Statement updated 2018: ophthalmologists should recommend zoster vaccine age 50 years and older
Ophthalmology 2018;125:1813
Importance of a moral obligation to do the right thing to change behavior (Arthur Caplan PhD)
Presentation Title Goes Here

52. Thank you for referring your HZO patients for possible enrollment into the Zoster Eye Disease Study (ZEDS)!