Incidence Rate of Herpes Zoster

Ophthalmicus
A Retrospective Cohort Study from 1994 through 2018
Christina L. Kong, BS,1 Ryan R. Thompson, MSPH,1 Travis C. Porco, PhD, MPH,1,2,3 Eric Kim, MA,1
Nisha R. Acharya, MD, MS1,2,3,4

Purpose: To analyze the incidence rate (IR) of herpes zoster ophthalmicus (HZO) and differences by age,
gender, race, and region from 1994 through 2018.
Design: Retrospective, observational cohort study.
Participants: Patients with a new International Classification of Diseases, Ninth or Tenth Edition, codes for
herpes zoster (HZ) and HZO from January 1, 1994, through December 31, 2018, in the OptumLabs Data
Warehouse (OptumLabs, Cambridge, MA).
Methods: OptumLabs Data Warehouse, a longitudinal, real-world data asset with de-identified administrative
claims and electronic health record data, was used to identify enrollees with continuous enrollment in the
database for 365 days or more. Patients with no history of HZ or HZO and a new code for HZ and HZO were
counted as incident cases. The IR of HZO was calculated by year, 10-year age groups, gender, race, and region.
Main Outcome Measures: Differences in IR from 1994 through 2018 by 10-year age groups and gender.
Results: From 1994 through 2018, 633 474 cases of HZ were reported, with 49 745 (7.9%) having HZO. The
incidence of HZO increased from 1994 through 2018 by an estimated 1.1 cases per 100 000 person-years
annually (95% confidence interval [CI], 1.0e1.3; P < 0.001). The estimated relative increase was 3.6% annually
(95% CI, 3.0%e4.1%). HZO IR increased in all ages over 10 years until 2007, then began declining in individuals
younger than 21 and older than 60, stabilizing in individuals 21 to 30 years old, and increasing more slowly among
individuals 31 to 60 years old. Men showed an HZO incidence rate ratio (IRR) of 0.74 compared with women.
Compared with white patients, the IRRs were 0.70, 0.75, and 0.64 for Asians, black patients, and Hispanics,
respectively.
Conclusions: The incidence of HZO has increased 3.6% per year from 1994 to 2018 in the United States.
Since 2008, HZO incidence declined in individuals younger than 21 years and older than 60 years while increasing
at a lower rate in middle-aged adults. Given the continued increase, greater efforts should be made to vaccinate
eligible adults 50 years of age and older. More research on earlier vaccination is warranted. Ophthalmology 2019;-
:1e7 ª 2019 by the American Academy of Ophthalmology

Herpes zoster (HZ), also known as shingles, occurs in 1 in 3 (CDC) revealed that HZ rates have continued to rise in
individuals during their lifetime in the United States and adults through 2016.8e10 However, these studies did not
typically manifests as a painful dermatomal rash.1 Herpes report on HZO incidence. There is no consensus on why HZ
zoster ophthalmicus (HZO), a form of HZ that occurs has been increasing, although several theories do exist. One
when varicella zoster virus reactivates along the theory is that that the introduction of the varicella vaccine in
ophthalmic branch of the trigeminal nerve, will develop in 1996 lowered exposure to wild-type varicella infection in
approximately 10%e20% of cases of HZ.2 Of those the population, decreasing immune boosting. Others have
individuals with HZO, 50% to 71% show ocular speculated that the rising HZ incidence may be the result of
involvement with complications such as keratitis, uveitis, an increase in immunocompromised conditions or changes
retinal necrosis, and loss of vision, leading to significant in health-seeking behavior, leading to increased diagnosis of
pain, morbidity, and decreased quality of life.3e6 It is also HZ.11e13 Another major factor that may be affecting HZ
now recognized that approximately 20% of patients with epidemiology is the introduction of vaccines for HZ: Zos-
HZO may have a chronic course requiring ongoing tavax (zoster vaccine live [ZVL]; Merck & Co, Inc,
treatment.7 Whitehouse Station, NJ) and Shingrix (recombinant zoster
The few studies on HZ incidence suggest that rates have vaccine [RZV]; GlaxoSmithKline, Philadelphia, PA). Since
been increasing in the 2 decades up to 2012, and a 2018 the introduction of ZVL in 2006 and RZV in 2017, few
report from the Center for Disease Control and Prevention reports on the influence of these vaccines on HZ rates have

ª 2019 by the American Academy of Ophthalmology https://doi.org/10.1016/j.ophtha.2019.10.001 1

Published by Elsevier Inc. ISSN 0161-6420/19
 Ophthalmology Volume -, Number -, Month 2019

been published, and even fewer have looked at vaccine ef- Food and Drug Administration approved ZVL) as the cut point
fect on HZO.8,9 was conducted. When comparing gender, race or ethnicity, and
Aside from a small population study that showed region, we calculated the IR ratio using bootstrap resampling of
increasing HZO from 1980 through 2007, the available in- years to compute approximate 95% confidence intervals (CIs; a
highly conservative procedure that avoids relying on the very
formation on HZO epidemiology has been limited.4 A
large number of person-years as a basis for inference).
retrospective study of a single-site tertiary care center sug- Between 1994 and 2018, the IR of HZO was calculated by year,
gests an increase in new HZO cases and an age shift toward 10-year age groups, 10-year birth cohorts, gender, race, and
younger individuals from 2007 through 2013; however, the geographic region. Data were stratified into 10-year age groups
referral bias inherent to this type of study makes it difficult starting at younger than 1 year of age. Age groups also were
to estimate if there has been a change in HZO over time.14 aggregated into 10-year age groups to tabulate changes in the slope
Overall, knowledge on HZO incidence rates (IRs) and of HZO incidence overall and by gender from the periods 1994
whether they are shifting is lacking. through 2007 and 2008 through 2018. As a sensitivity analysis, we
Given the significant morbidity associated with HZO, also standardized the IRs by age, gender, and race or ethnicity
studies on HZO epidemiologic features are crucial for using the average of the years 2014 through 2018 in the OLDW
database. Standardized IRs were analyzed in the same way using
informing public health policy and directing clinician ef-
broken-stick Huber robust regression with adjustments for age.
forts. In particular, the introduction of the vaccines for HZ Statistical significance testing was conducted at a level of P < 0.01.
emphasizes the need to understand who is at greatest risk All statistical analyses were conducted in R software version
of HZO and how these trends are changing over time. The 3.5 (The R Project for Statistical Computing, Vienna, Austria).
objective of this study was to examine the IR of HZO in Only de-identified data were available for analysis, and thus,
the American population from 1994 through 2018 and to informed consent was not required for this study. The University of
assess by age, race, gender, and geographic region. California, San Francisco, Institutional Review Board approved the
study, and the described research adhered to the tenets of the
Declaration of Helsinki.
Methods
A retrospective, observational cohort study was conducted of more Results
than 200 million records in the de-identified healthcare claims
database OptumLabs Data Warehouse (OLDW; OptumLabs, From January 1, 1994, through December 31, 2018, 633 474
Cambridge, MA).15 OptumLabs Data Warehouse is a data asset cases of HZ were reported, of which 49 745 (7.9%) included a
that contains administrative claims and electronic health record code specific for HZO. The IR of HZO increased from 1994
data for United States patients enrolled in commercial insurance, through 2018 by an estimated 1.1 cases per 100 000 person-years
Medicare Advantage, or Medicare Part D plans. Comparisons annually (95% CI, 1.0e1.3; P < 0.001). The estimated relative
between the OLDW and United States Census Bureau show that increase in the HZO IR was 3.6% per year (95% CI, 3.0%e
the age, gender, race, and geographic distributions of OLDW 4.1%). For individuals younger than 50 years with known race
enrollees are similar to those of the United States population for (representing 88% of the available person-years), the standard-
both the commercially insured and the Medicare Advantage ized IR increased an average of 0.31 cases per 100 000 person-
groups.16 Less representation in the West exists for Medicare years (95% CI, 0.20e0.41) from 1994 through 2018. For in-
Advantage enrollees in OLDW compared with United States dividuals older than 70 years, the standardized IR changed an
Census estimates, with fairly comparable representation in all average of e0.86 cases per 100 000 person-years (95% CI, e1.36
other regions.15 to e0.37) from 2010 through 2018.
To be included in the study, enrollees must have been enrolled Figure 1 demonstrates the IR of HZO by 10-year age groups
continuously for 365 days or more and not have a history of HZ from 1994 through 2018. The age-specific IRs changed from 1994
and HZO. Between January 1, 1994, and December 31, 2018, more through 2007 compared with 2008 and beyond, which is explained
than 63 million unique people were represented in the OLDW. further in Table 1. Using broken-stick regression, the slope of the
Cases of HZ and HZO were identified by using International HZO IR shifted from e0.24 (95% CI, e0.36 to e0.11) to e0.37
Classification of Diseases (ICD), Ninth and Tenth Editions, codes. (95% CI, e0.52 to e0.22) per 100 000 person-years per year in
Patients with 1 new code for HZ (ICD-9 053.XX, ICD-10 individuals in the 0 to 10 years age group, 0.74 (95% CI,
B02.XX) and HZO (ICD-9 0532.X, ICD-10 B023.X) were coun- 0.47e1.00) to 0.14 (95% CI, e0.17 to 0.46) in the 41 to 50 years
ted as an incident case. Information was extracted on the patients’ age group, and 6.23 (95% CI, 5.05e7.40) to e2.26 (95% CI,
year of birth, gender, race (Asian, black, Hispanic, white, other), e2.96 to e1.57) in individuals 61 to 70 years of age (Table 1). The
and geographic region (Midwest, Northeast, South, West, and changes in the slopes of HZO incidences among all age groups
other). The exact date of birth is not available through OLDW. from 1994 through 2007 compared with 2008 through 2018 were
Therefore, age was approximated by year of birth (i.e., a patient statistically significant except for in children between 0 and 10
categorized as 1 year of age in 1994 experienced his or her 1-year years of age (P ¼ 0.56). Using 2006 as the cut point did not
birthday in 1994). Data were not available for individuals born change the overall trends in HZO IR. Results were similar based
before 1930. on the standardized IRs, except that there was no statistically
The time trend in the overall incidence was assessed through significant evidence of a change in slope for the age group 31 to
Huber robust regression of the estimated annual IR on calendar 40 years of age (P ¼ 0.24).
year, using 10-year age-time intervals and broken-stick models of Table 2 shows that HZO IR increased by 10-year age group,
the time ranges from 1994 through 2007 and 2008 through 2018, starting with an average of 4.8 cases per 100 000 person-years in
adjusting for age.17 The specific time ranges were established to children ages 1 to 10 and rising to 131.6 in ages 81 to 90 from 1994
examine HZO IRs before and after the Advisory Committee on to 2018. Incidence rates also increased by decade of birth, with the
Immunization Practices’ (ACIP) recommendation for the ZVL oldest cohort, born in 1930 through 1939, having the highest
vaccine in 2008.18 A sensitivity analysis using 2006 (the year the average IR of 115.7 cases per 100 000 person-years and individuals

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 Kong et al 
Incidence of Herpes Zoster Ophthalmicus

Figure 1. Graph showing the incidence rate of herpes zoster ophthalmicus by 10-year age groups from 1994 through 2018.

born in 2010 through 2019 having an IR of 2.1 cases per 100 000 real-world data set. Before the ACIP recommendation for
person-years from 1994 through 2018. ZVL in 2008, HZO IRs were decreasing in children between
Compared to females, males had a lower overall HZO IR ratio 0 to 10 years of age and increasing in all older age groups.
(IRR) of 0.74 (95% CI, 0.72e0.76). For patients of both genders However, from 2008 and beyond, HZO IRs began to decline
older than 10 years, the HZO IR slopes increased from 1994
significantly among individuals younger than 21 years and
through 2007 and shifted among different age groups from 2008
through 2018 (Table 3). Compared with white patients, Asians older than 60 years. Herpes zoster ophthalmicus IRs began
showed an IRR of 0.70 (95% CI, 0.67e0.73), black patients stabilizing in those 21 to 30 years of age and continued to
showed an IRR of 0.75 (95% CI, 0.72e0.79), and Hispanics increase, but at a less significant rate, among individuals
showed an IRR of 0.64 (95% CI, 0.60e0.67). Compared with between 31 and 60 years of age.
the Northeast, the Midwest showed an IRR of 0.80 (95% CI, In children younger than 10 years, the incidence of HZO
0.75e0.85), the West showed an IRR of 0.71 (95% CI, cases decreased from 1994 through 2007 but dropped more
0.66e0.76), and the South showed an IRR of 0.77 (95% CI, precipitously from 2008 through 2018. The decreasing IRs
0.71e0.81). may be secondary to the introduction of the varicella vac-
cine in 1996, and the continued rapid decline in the past
Discussion decade may be associated with the implementation of the 2-
dose varicella vaccination program in 2006. Varicella
From 1994 through 2018, the HZO IR increased 3.6% per vaccination is widespread, with more than 80% of children
year in this study using a large United States administrative older than 7 years having 2-dose coverage in 2012.9 This

Table 1. Slopes of Herpes Zoster Ophthalmicus Incidence Rates per Year from 1994 through 2018 by 10-Year Age Groups

Year Range
1994e2007 2008e2018
Slope of Herpes Zoster 95% Confidence Slope of Herpes Zoster 95% Confidence
Age (yrs) Ophthalmicus Incidence Ratey Interval Ophthalmicus Incidence Rate Interval P Value*
0-10 e0.24 e0.36 e0.11 e0.37 e0.52 e0.22 0.56
11-20 0.49 0.35 0.63 e0.74 e0.91 e0.57 <0.001
21-30 0.43 0.23 0.63 e0.04 e0.29 0.20 0.002
31-40 0.59 0.39 0.80 0.18 e0.07 0.43 0.001
41-50 0.74 0.47 1.00 0.14 e0.17 0.46 <0.001
51-60 1.18 0.81 1.55 0.31 e0.14 0.76 <0.001
61-70z 6.23 5.05 7.40 e2.26 e2.96 e1.57 <0.001
71þx d d d e3.76 e4.95 e2.56 d

d ¼ not available.
*P value corresponds to comparison of slopes between the 2 time intervals.
y
Change in HZO incidence rate per 100 000 person-years per year.
z
The slope was computed from 2000 through 2007 given that the available data do not include individuals born before 1930 and the full age range could not
be captured until 2000.
x
The slope was not available for ages 71 or older for the first period from 1994 through 2007 because the available data do not include individuals born
before 1930.

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 Ophthalmology Volume -, Number -, Month 2019

Table 2. Incidence Rates of Herpes Zoster Ophthalmicus by Age Herpes zoster ophthalmicus incidence in the 31- to
Group, Decade of Birth, Gender, Race, and Region from 1994 60-year-old groups has continued to increase since 2008,
through 2018 although at a slower rate than before that time. The
decreasing HZO IRs among the younger and older pop-
No. of Cases Person-Years Incidence Rate*
ulation suggests that a larger proportion of new HZO
Age group (yrs) cases may be occurring in individuals between 31 and 60
0e10 638 13 301 196 4.8 years of age because the overall rate continues to in-
11e20 1305 16 767 397 7.8 crease. Although changes in incidence are difficult to
21e30 1768 13 357 953 13.2
31e40 4243 18 900 676 22.4
determine from retrospective studies from single centers,
41e50 6999 21 701 978 32.3 1 study reported that HZO cases were increasing among
51e60 10 732 19 660 935 54.6 individuals younger than 50 years, with the percentage of
61e70 10 449 12 796 084 81.7 all HZO cases going from 16.2% between 1996 and 2004
71e80 10 030 8 834 445 113.5 to 29.6% between 2005 and 2012 in this age group.12
81e90 3581 2 721 988 131.6 Another study from a tertiary care center found that the
Unknown 0 2195 0.0
average age of HZO onset went from 61 years in 2007
Decade of birth
1930e1939 12 021 10 390 005 115.7 to 56 years in 2013.14 The increase in HZO incidence
1940e1949 11 652 14 780 355 78.8 among the middle-age groups parallels the recent CDC
1950e1959 10 653 20 624 339 51.7 report that found a continued increase in HZ rates among
1960e1969 7485 21 497 818 34.8 those between 35 and 55 years of age.8
1970e1979 3903 17 258 873 22.6 It is not possible to attribute the changing HZ and HZO
1980e1989 2178 15 020 071 14.5 epidemiology to a particular cause with an observational
1990e1999 1420 16 063 776 8.8
2000e2009 391 10 447 890 3.7
study, but there are several potential explanations. One
2010e2019 42 1 959 525 2.1 theory is that intermittent exposure to wild-type varicella
Unknown 0 2195 0.0 helped boost natural immunity and that universal varicella
Gender vaccination has decreased such exposure, leading to waning
Female 28 937 65 077 059 44.5 immunity and reactivation of the varicella virus at a younger
Male 20 653 62 390 951 33.1 age.2,11,21,22 Yet, studies in Canada and the United Kingdom
Othery 155 576 837 26.9
Race
from a time when there was no comprehensive varicella
Asian 1404 4 674 280 30.0 vaccination program in those countries demonstrated an
Black 3456 10 739 351 32.2 increase in overall HZ incidence, suggesting that there
Hispanic 2958 10 748 465 27.5 may be additional factors in effect.23 Other investigators
White 35 089 81 371 550 43.1 have theorized that the live virus within the varicella
Otherz 1660 5 899 176 28.1 vaccine has led to increasing cases of HZ, but this has
Unknown 5178 14 612 025 35.4
been proven unlikely because the IRs for HZ were similar
Region
Midwest 15 034 37 808 500 39.8 before and after the introduction of the vaccine.13
Northeast 6284 12 683 745 49.5 The continued rise in HZO in the 31- to 60-year-old
South 19 898 52 400 469 38.0 groups raises questions about the age recommendations for
West 6015 17 151 919 35.1 HZ vaccination. In 2017, RZV was approved by the Food
Otherx 2514 8 000 214 31.4 and Drug Administration for adults without contraindica-
tions who are 50 years of age or older. Soon after, the ACIP
*Incidence rate is the number of cases per 100 000 person-years. adopted this more efficacious vaccine as the preferred one
y
z
Individuals who had both male and female or neither gender listed. for this age group.24 The American Academy of
Individuals who were of a race that was not 1 of the 4 listed races. Ophthalmology also recommends RZV in accordance with
x
Individuals who had 2 or more regions or neither region listed.
the Food and Drug Administration approval.25 Zoster
vaccine live coverage historically has been low, with only
0.9% to 31.8% coverage by state in 2014 and
decline in HZO in young children is similar to the HZ trends 31% nationwide in 2015.20,26 Coverage data for RZV is
published in a 2018 study by the CDC that found declining not yet known because of its recent approval. Given the
rates of HZ among children younger than 18 years from changing epidemiologic trends and risks associated with
1998 through 2016.9 In a multi-database study from 2003 HZO, it is crucial to continue advocating for HZ
through 2014 looking at varicella vaccination, researchers vaccination in eligible adults.27 In addition, further study
found that HZ incidence declined by 72% among 0- to 17- into whether HZ vaccination is indicated in individuals
year-olds.19 The decline in HZO incidence since 2008 in younger than 50 years is needed.
individuals older than 60 years raises the question of This study demonstrated that females and white patients
whether the zoster vaccine is having an impact in this age are at higher risk of developing HZO. Through 2007, HZO
group. The CDC report noted a deceleration in HZ cases IRs increased for both males and females older than 10
among a similar older age group.8 Zoster vaccine years. Since 2008, the IRs have been declining in the
coverage is thought to be low, with an upper estimate of youngest and oldest age groups for both males and females.
31% in 2015, but at this level, it may be having an impact A previous study from Hawaii failed to find evidence of a
on incidence in the age group that is vaccine eligible.20 difference in HZO incidence by gender but did not stratify

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 Kong et al 
Incidence of Herpes Zoster Ophthalmicus

Table 3. Slopes of Herpes Zoster Ophthalmicus Incidence Rates per Year from 1994 through 2018 by 10-Year Age Groups and Gender

Year Range
1994e2007 2008e2018
Slope of Herpes Zoster Slope of Herpes Zoster
Gender Age (yrs) Ophthalmicus Incidence Rate* 95% Confidence Interval Ophthalmicus Incidence Rate 95% Confidence Interval
Male 0e10 e0.01 e0.18 to 0.15 e0.47 e0.67 to e0.27
11e20 0.60 0.41e0.78 e0.80 e1.03 to e0.58
21e30 0.57 0.30e0.83 0.04 e0.28 to 0.35
31e40 0.42 0.15e0.70 0.15 e0.18 to 0.48
41e50 0.79 0.45e1.13 0.03 e0.39 to 0.44
51e60 1.42 1.01e1.83 0.05 e0.44 to 0.55
61e70y 4.69 3.31e6.06 e1.87 e2.69 to e1.05
71þz d d e4.35 e6.00 to e2.69
Female 0e10 e0.06 e0.20 to 0.09 e0.29 e0.47 to e0.12
11e20 0.63 0.45e0.81 e0.72 e0.93 to e0.50
21e30 0.78 0.51e1.04 e0.24 e0.56 to 0.08
31e40 0.91 0.61e1.21 0.19 e0.17 to 0.55
41e50 0.78 0.38e1.17 0.21 e0.26 to 0.69
51e60 1.14 0.56e1.72 0.59 e0.11 to 1.29
61e70y 7.69 5.91e9.46 e2.69 e3.75 to e1.63
71þz d d e3.26 e5.02 to e1.50

d ¼ not available.
*Change in herpes zoster ophthalmicus incidence rate per 100 000 person-years annually.
y
The slope was computed from 2000 through 2007 given that the available data do not include individuals born before 1930 and the full age range could not
be captured until 2000.
z
The slope was not available for ages 71þ for the first period from 1994 through 2007 for both men and women because the available data do not include
individuals born before 1930.

by age. The same study also showed that HZO was more of the small numbers of cases. Owing to the focus on pa-
common among non-Pacific Islanders but did not differen- tients in commercial healthcare programs, Medicare Part D
tiate further by race and ethnicity.28 The risk of HZO by and Medicare Advantage, the presented data may underes-
gender and race aligns with studies on HZ that found that timate the true incidence of HZO if some patients left the
women and white patients are at higher risk.13,29,30 healthcare plan at 65 years of age. However, this would
Herpes zoster ophthalmicus rates were found to be have been the case throughout the study period and would
highest in the Northeastern United States and lowest in the not affect the ability to detect a change in incidence. The
West, which may have some relation to ZVL coverage. A database also does not account for individuals who are either
2014 analysis demonstrated that vaccination rates were the uninsured or have other forms of insurance. However,
second lowest in the Northeast at 30.3% and highest in the OLDW is relatively generalizable to the United States
West at 37.4%.26 Little information is available on the role population given the demographic similarities to the United
of geographic location and risk of HZ or HZO, although States Census. Coding for HZO diagnosis has been found to
some reports have indicated a possible association be highly accurate, but undercoding for HZO or changes in
between ultraviolet exposure and HZ risk.31 The health-seeking behavior could affect results.32 This study
correlation between HZO and geographic region seen in counted a single code for HZO as an incident diagnosis if
this study is hypothesis generating and requires further a patient met the enrollment eligibility criteria. This
study. criterion was used to include patients who may not have
This study has certain limitations. The observational returned for a subsequent evaluation after their initial
nature of this analysis complicates any measures of causa- diagnosis of HZO, which may occur particularly when
tion from being made in relation to the trends seen in HZO there is no intraocular involvement. Overall, such
incidence, given potential unmeasured confounders. We are limitations would be unlikely to account fully for the
not able to compare HZO incidence between the periods magnitude of change seen in the HZO IR.
before and after the introduction of the varicella vaccine in In conclusion, after the ACIP recommended ZVL in
1996, which would have provided additional clarification on 2008, HZO rates have declined in the youngest and oldest
changing HZO patterns. Analyses were conducted at the age groups while continuing to increase among individuals
level of aggregate data and cannot be used to infer between 31 to 60 years of age. Given the potential shift in
individual-level changes in risk. Different choices of cut HZO burden toward middle-aged individuals, it is crucial
point for the broken-stick regression or the use of more for clinicians to support vaccination efforts for individuals
general polynomial trend models would result in modest 50 years of age and older. These results also raise the
differences in estimated HZO IR slopes. Statistical estimates question of whether HZ vaccine recommendations should
of trends in the youngest age groups are less reliable because be re-evaluated for individuals in younger age groups.

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Acknowledgments 16. Optum Labs. Optum Research Data Assets. Cambridge, MA:
Optum Labs; 2014. https://www.optum.com/content/dam/
The authors thank Nina Veeravalli, OptumLabs, for extensive help optum/resources/productSheets/5302_Data_Assets_Chart_
with review of the data. Sheet_ISPOR.pdf. Accessed 20.09.19.
17. Sen A, Srivastava M. Regression Analysis: Theory, Methods
and Applications. Berlin, Heidelberg: Springer; 1990.
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Footnotes and Financial Disclosures

1
Originally received: September 5, 2019. F. I. Proctor Foundation, University of California, San Francisco, San
Final revision: September 25, 2019. Francisco, California.
Accepted: October 1, 2019. 2
Department of Ophthalmology, University of California, San Francisco,
Available online: ---. Manuscript no. 19-00288.
San Francisco, California.

6
 Kong et al 
Incidence of Herpes Zoster Ophthalmicus
3
Department of Epidemiology and Biostatistics, University of California, of California, San Francisco approved the study. All research adhered to the
San Francisco, San Francisco, California. tenets of the Declaration of Helsinki.
4
OptumLabs, Visiting Fellow, Cambridge, Massachusetts. No animal subjects were included in this study.
Presented at: Ocular Microbiology and Immunology Group Meeting, Author Contributions:
October 2019, San Francisco, California. Conception and design: Kong, Thompson, Porco, Kim, Acharya
Financial Disclosure(s): Analysis and interpretation: Kong, Thompson, Porco, Kim, Acharya
The author(s) have made the following disclosure(s): C.L.K.: Nonfinancial Data collection: Porco, Kim, Acharya
support e OptumLabs (Cambridge, MA).
Obtained funding: Acharya
R.R.T.: Nonfinancial support e OptumLabs (Cambridge, MA).
Overall responsibility: Kong, Thompson, Porco, Acharya
T.C.P.: Nonfinancial support e OptumLabs (Cambridge, MA).
E.K.: Nonfinancial support e OptumLabs (Cambridge, MA). Abbreviations and Acronyms:
ACIP ¼ Advisory Committee on Immunization Practices; CDC ¼ Centers
N.R.A.: Advisory board e AbbVie, Santen; Nonfinancial support e for Disease Control and Prevention; CI ¼ confidence interval; HZ ¼ herpes
OptumLabs (Cambridge, MA). zoster; HZO ¼ herpes zoster ophthalmicus; ICD ¼ International Classifi-
Supported by the National Institutes of Health, Bethesda, Maryland (grant cation of Diseases; IR ¼ incidence rate; IRR ¼ incidence rate ratio;
nos.: 1R01 EY028739-01 and 5R01 EY028739-02). The National Institutes OLDW ¼ OptumLabs Data Warehouse; RZV ¼ recombinant zoster vac-
of Health had no role in the design or conduct of this research. OptumLabs cine; ZVL ¼ zoster vaccine live.
Warehouse research credit through OptumLabs, Cambridge, Massachusetts,
Correspondence:
and an OptumLabs Visiting Fellow. OptumLabs participated in the review of
the manuscript. Nisha R. Acharya, MD, MS, F. I. Proctor Foundation, University of Cali-
fornia, San Francisco, 513 Parnassus Avenue, S309, San Francisco, CA
HUMAN SUBJECTS: No human subjects were included in this study. 94143. E-mail: [email protected].
Given that the study was performed using de-identified data, informed
consent was not required. The Institutional Review Board at the University