Scleritis in Lyme Disease
MEGHAN K. BERKENSTOCK, KAYLA LONG, JOHN B. MILLER, BRYN B. BURKHOLDER, JOHN N. AUCOTT,
AND DOUGLAS A. JABS
• PURPOSE: To estimate the incidence of scleritis in Lyme
disease and report clinical features.
• DESIGN: Incidence rate estimate and case series.
• METHODS: Data were collected from an electronic med-
ical record on patients with scleritis presenting to the
Wilmer Eye Institute between January 1, 2012 and De-
cember 31, 2020. A diagnosis of Lyme disease was made
using the Infectious Diseases Society of America, Ameri-
can Academy of Neurology, and the American College of
Rheumatology 2020 joint criteria plus a response to an-
tibiotic therapy. After identifying all new-onset cases of
scleritis in the database, the proportion of new-onset scle-
ritis with Lyme disease was calculated. The proportion
of Lyme disease cases with scleritis was estimated using
the number of cases with Lyme disease from the Balti-
more metropolitan area reported to the Centers for Dis-
ease Control and Prevention. After querying other major
eye centers in the area for any cases of Lyme disease scle-
ritis, none were identified, and the incidence of Lyme dis-
ease scleritis was estimated using published U.S. Census
data for the greater Baltimore metropolitan area.
• RESULTS: Six cases of Lyme disease scleritis were iden-
tified in the 8-year time frame; 1 additional case was
identified in the following year. Lyme disease scleritis ac-
counted for 0.6% of all cases of scleritis, and 0.052% of
patients with Lyme disease had scleritis. The estimated
incidence of Lyme scleritis was 0.2 per 1,000,000 popu-
lation per year (95% confidence interval 0-0.4), whereas
the estimated incidence of Lyme disease in the area was
3 per 10,000 population per year (95% confidence inter-
val 2.9-3.1). All scleritis cases were anterior, unilateral,
without necrosis, and resolved with antibiotic use with-
out relapse in a median of 39.5 days (range 29-57 days).
Other features of Lyme disease were present in 4 of 7 pa-
tients, including a history of erythema migrans in 2 of 7
patients.
Accepted for publication April 24, 2022.
From the Wilmer Eye Institute (M.K.B., B.B.B., D.A.J.), Department
of Ophthalmology, Johns Hopkins University School of Medicine, Bal-
timore, Maryland; University of North Texas Health Science Center
Texas College of Osteopathic Medicine (K.L.), Fort Worth, Texas; De-
partment of Medicine (J.B.M., J.N.A.), Johns Hopkins University School
of Medicine, Baltimore, Maryland; Johns Hopkins Lyme Disease Clinical
Research Center (J.N.A.), Lutherville, Maryland; Center for Clinical Tri-
als and Evidence Synthesis (D.A.J.), Department of Epidemiology, Johns
Hopkins Bloomberg School of Public Health, Baltimore, Maryland
Inquiries to Meghan Berkenstock, Division of Ocular Immunology,
Wilmer Eye Institute, 600 North Wolfe Street, Baltimore, MD 21287.;
e-mail: mberken2@jhmi.edu
0002-9394/$36.00 © 2022 ELSEVIER INC. ALL RIGHTS RESERVED..
https://doi.org/10.1016/j.ajo.2022.04.017
• CONCLUSIONS: Lyme disease is an uncommon cause
of scleritis in endemic areas. (Am J Ophthalmol
2022;241: 139–144. © 2022 Elsevier Inc. All rights re-
served.)
N
orth American Lyme disease is a multisystem
infectious disease caused by the bacterium Borrelia
burgdorferi.1 Skin disease starts at the site of an in-
fected tick bite, and the Lyme spirochete can disseminate in
the first weeks of infection to the joints, heart, and the ner-
vous system. Ocular involvement in Lyme disease has been
reported at any stage of the disease and involve almost all
ocular and adnexal structures, as well as the cranial nerves
involved in oculomotor function.1
Lyme disease rarely has been reported as a cause of scle-
ritis in several case reports or as isolated cases included as
part of a larger series of scleritis, mostly from endemic areas
of the United States or Europe.1-6 We report a case series
of Lyme disease scleritis collected over a 9-year period in a
Lyme disease endemic region and estimate the incidence of
Lyme scleritis.
PATIENTS AND METHODS
Cases of newly diagnosed scleritis seen at the Wilmer
Eye Institute from January 1, 2012 through December 31,
2020 were identified using the SlicerDicer application in
the EPIC electronic medical record system (EPIC Systems
Corp, Verona, WI). Lyme disease scleritis cases were defined
based on the Infectious Diseases Society of America, Amer-
ican Academy of Neurology, and the American College of
Rheumatology 2020 joint guidelines for the diagnosis of
Lyme disease.7 In brief, the diagnosis of Lyme disease re-
quired either erythema migrans (EM) or a positive serologic
test for Lyme disease. Serologic diagnosis required a positive
enzyme-linked immunosorbent assay test followed by con-
firmatory Western blot test (2 immunoglobulin M [IgM] or
5 immunoglobulin G [IgG] positive bands) concurrent with
or after the diagnosis of scleritis. To determine if there was
active Lyme disease in a patient with a positive IgM test re-
sult alone, a repeat Western blot with 5 positive IgG bands
was required. If EM rash was present, a documented clinical
response to antibiotic therapy was required in patients with-
out a Western blot result. In addition to screening for Lyme
139
disease in all patients with scleritis in our practice, each was
tested for alternative scleritis-associated diseases, including
both treponemal and nontreponemal syphilis serologies, a
chest radiograph, human leukocyte antigen-B27 typing, an-
tineutrophil cytoplasmic antibody testing, and, if nodular
scleritis was present, an interferon gamma release assay test
for tuberculosis.8 , 9 In addition, to decrease the likelihood
that the Lyme serology and the scleritis were merely coin-
cidental, we required that the scleritis responded to appro-
priate antibiotic therapy. The response had to be either to
antibiotic use alone or if the patient had been treated with
antiinflammatory treatment, after the failure of antiinflam-
matory therapy alone to achieve resolution of the scleritis.
Clinical resolution was defined as an absence of injection
of the blood vessels of the episcleral plexus, absence of scle-
ral nodules or necrosis, grade 0 anterior chamber inflamma-
tion, and resolution of corneal infiltrates (if sclerokeratitis
had been present) on examination.10 These investigations
adhered to the Declaration of Helsinki, and approval from
the Johns Hopkins Hospital Institutional Review Board was
obtained for the study.
Data analyzed included demographics, anatomic class of
scleritis, presence of nodules or necrosis, corneal infiltrates,
laterality, systemic Lyme disease manifestations, history of
tick bites, presenting best corrected visual acuity and in-
traocular pressure, Western blot results, antibiotic and an-
tiinflammatory medication use, time until scleritis resolu-
tion with antibiotic therapy alone or with antiinflammatory
agents after the start of antibiotic therapy, recurrences, and
postantibiotic ocular treatments.
The primary outcome was determining the incidence of
both Lyme disease and Lyme scleritis in the greater Balti-
more area. Secondary outcomes included determining the
percent of scleritis cases attributable to Lyme disease, the
percent of Lyme disease patients with scleritis, and identi-
fication of associated clinical and demographic features of
patients with Lyme scleritis. No additional cases of Lyme
scleritis were identified by the other academic medical cen-
ters in the greater Baltimore metropolitan area after query-
ing each of these organizations to identify such cases.
• STATISTICS: The estimated population incidence of scle-
ritis in the Baltimore metropolitan area over the years Jan-
uary 1, 2012 through December 31, 2019 was calculated
as the number of cases of Lyme disease scleritis from the
greater Baltimore metropolitan area divided by the average
Baltimore metropolitan area population during this time
divided by 8 years. The same calculation was repeated for
the estimated population incidence of Lyme disease in the
Baltimore metropolitan area using U.S. Center for Disease
Control and Prevention (CDC) data. We also calculated
95% confidence intervals (CIs). The time interval for the
estimated population incidences included January 1, 2012
through December 31, 2019, as the results of the 2020 CDC
report on Lyme disease and the 2020 Census by the U.S.
Census Bureau were not released at the time of this study.
140 AMERICAN JOURNAL OF OPHTHALMOLOGY
The greater Baltimore metropolitan area is defined by the
U.S. Census Bureau as Baltimore City and the following 5
surrounding counties: Anne Arundel, Carroll, Baltimore,
Harford, and Howard.
RESULTS
Nine hundred eighty cases of scleritis were seen between
January 1, 2012 and December 31, 2020. Six of these cases
were caused by Lyme disease (0.61%). A seventh case of
Lyme scleritis was identified between January 1, 2021 and
September 1, 2021. Table 1 lists the clinical characteris-
tics of the 7 patients with Lyme disease scleritis. The aver-
age age was 43 years (range 24-81 years); 4 of the patients
were male (57%) and 5 were white (72%). Lyme disease–
associated scleritis accounted for 0.6% of all cases of scleri-
tis, and 0.052% of patients with Lyme disease had scleritis.
Other than living in an endemic area, there was no com-
mon demographic information that was consistently seen in
all affected patients. All patients presented with unilateral
anterior scleritis, of which 3 had scleral nodules (Figure 1)
and 3 had diffuse anterior scleritis. One patient had scle-
rokeratitis. There were no cases of scleral necrosis and no
cases of posterior scleritis. The best corrected vision on pre-
sentation was 20/20 or better in all cases. With the excep-
tion of 1 eye with sclerokeratitis and an intraocular pres-
sure (IOP) of 24 mm Hg, all affected eyes had an IOP
within normal range at first evaluation. No patients were
misdiagnosed with noninfectious scleritis; however, 4 pa-
tients were prescribed 1 oral nonsteroidal antiinflammatory
medication for 14 days before having a positive serologic
test for Lyme disease. After diagnosis, all were changed on
antibiotic monotherapy. The nonsteroidal antiinflamma-
tory medications included indomethacin 50 mg twice a day,
ibuprofen 800 mg 3 times a day, or flubriprofen 100 mg 3
times a day (Table 1). All patients were treated with a 28-
day course of doxycycline 100 mg twice a day except for
1 patient who was switched to Cefuroxime 500 mg twice
a day because of gastrointestinal side effects. The median
time until resolution was 39.5 days (range 29-57 days). Af-
ter antibiotic treatment, all cases resolved without relapse.
No patients required additional treatment after resolution.
The eye with elevated IOP at presentation normalized after
antibiotic treatment. The clinical presentations and treat-
ments were noted in Table 1.
In terms of risk factors for Lyme disease, all 7 patients
lived in endemic areas in the Mid-Atlantic States. How-
ever, only 4 of the patients could identify potential outdoor
activities that led to tick exposures, and 3 had removed a
tick from exposed skin. Five had a positive Western Blot
result based on IgG bands (72%). Two patients were diag-
nosed on clinical criteria by presenting with an EM rash and
2 had late symptoms—joint disease or a right bundle branch
block. Both had a documented clinical resolution of these
SEPTEMBER 2022
 TABLE 1. Characteristics of the Study Population of Patients with Lyme Disease Scleritis.

Characteristic Value

Patients, N 7
Demographics
Median age, y (range) 43 (24-81)
Male, n (%) 4 (57)
Race, n (%)
White, non-Hispanic 5 (72)
Black, non-Hispanic 1 (14)
Hispanic 1 (14)
Reside in Baltimore metropolitan area, n (%) 6 (86)
Known tick bite, n (%) 3 (43)
Presence of other ophthalmic manifestations, n (%) 0 (0)
Characteristics of scleritis, n (%)
Unilateral eye disease 7 (100)
Scleritis type
Sectoral anterior scleritis 3 (43)
Nodular anterior scleritis 3 (43)
Necrotizing scleritis 0 (0)
Posterior scleritis 0 (0)
Sclerokeratitis 1 (14)
Characteristics of Lyme disease, n (%)
Erythema migrans 2 (28)
Cardiovascular diseasea 1 (14)
Arthritis 1 (14)
Laboratory data,b n (%)
Positive immunoglobulin M antibody 1 (14)
Positive immunoglobulin G antibody 5 (72)
Antibiotic treatment regimen, n (%)
Intravenous ceftriaxone 0 (0)
Oral doxycycline 7 (100)
Oral cefuroximec 1 (14)
Mean days until resolution (range) 41 (29-57)
Postantibiotic treatment recurrence, n (%) 0 (0)
Antiinflammatory treatment regimen, n (%)
Oral indomethacin 2 (28)
Oral ibuprofen 1 (14)
Oral flurbiprofen 1 (14)
a
Bundle branch block.
b
Two patients were diagnosed based on clinical grounds within 30 days of onset.
c
Cefuroxime prescribed to finish treatment course because of intolerance of doxycycline side effects.

features with antibiotic therapy. One of these patients only

had a positive IgM result and the other was not tested with
a Western blot given the above presentation. DISCUSSION
The estimated incidence of Lyme scleritis was 0.2 per
Although scleritis is most often associated with systemic au-
1,000,000 population per year (95% CI 0-0.4), whereas the
toimmune diseases, infections cause about 10% of the cases
estimated incidence of Lyme disease in the area was 3 per
of scleritis.2 , 11 , 12 The difficulty in diagnosis rests in similar
10,000 population per year (95% CI 2.9-3.1) (Table 2).
presentations requiring a high degree of suspicion by the
Only 3 cases of Lyme scleritis were used to calculate the
clinician to perform a diagnostic evaluation for both as-
estimated incidences as they were diagnosed between Jan-
sociated autoimmune diseases and for infectious causes of
uary 1, 2012 and December 31, 2019. Currently, the number
scleritis.12 , 13 Infectious scleritis may be a manifestation of
of Lyme disease cases released by the CDC is only available
a systemic infection (as with syphilis and Lyme disease) or
through the end of 2019. The remaining cases of Lyme scle-
of a local infection as with herpes simplex virus and vari-
ritis were diagnosed after January 1, 2020.

VOL. 241 LYME DISEASE SCLERITIS 141

FIGURE 1. Nodular scleritis on presentation before antibiotic therapy.

TABLE 2. Estimated Incidence of Scleritis in Baltimore Metropolitan Area.

Outcome Value

Cases of Lyme disease, January 1, 2012 through December 31, 2020a 6

Cases of scleritis, January 1, 2012 through December 31, 2020 980
Scleritis cases caused by Lyme disease, % 0.6
Cases of Lyme disease scleritis in Baltimore metropolitan area, January 1, 2012 through December 31, 2019b 3
Cases of Lyme disease in Baltimore metropolitan area, January 1, 2012 through December 31, 2019 5773
Lyme disease cases with scleritis, % 0.052
Cases of Lyme disease scleritis in Baltimore metropolitan area, January 1, 2012 through December 31, 2019b 3
Baltimore metropolitan area population,a Baltimore metropolitan area, January 1, 2012 through December 31, 2019 2,737,968
Estimated incidence of Lyme disease scleritis, Baltimore metropolitan area, per million population per year (95% CI) 0.2 (0-0.4)
Estimated incidence of Lyme disease, Baltimore metropolitan area, per million population per year (95% CI) 3 (2.9-3.1)

CI = confidence interval.
a
Average population of the 8-year interval.
b
Only 3 cases of Lyme scleritis diagnosed between January 1, 2012 and December 31, 2019 were used to calculate the estimated inci-
dences. Lyme disease data released by the U.S. Centers for Disease Control and Prevention was only available through the end of 2019. The
remaining 4 cases of Lyme scleritis were diagnosed after January 1, 2020.

cella zoster virus scleritis. Specifically, spirochetes are he-
lical, Gram-negative bacteria, and several members of the
phylum—including B. burgdorferi, Treponema pallidum, and
Leptospira—can cause inflammatory eye disease.14-16 Ocular
manifestations of Lyme disease can cause cranial neuropa-
thy, optic neuritis, uveitis, and less frequently scleritis.2
In our small cohort, 83% (5/6 tested) had a positive
Western blot based on reactive IgG criteria. This is simi-
lar to what is seen with acute neurologic and cardiac in-
volvement of disseminated disease, where 85% meet CDC
criteria by enzyme-linked immunosorbent assay and IgG
Western blot, but 100% meet criteria by enzyme-linked im-
munosorbent assay and IgM or IgG Western blot criteria.17
Tick and rash recall were relatively low, and this is similar to
previous studies describing disseminated and late manifes-
tations of untreated Lyme disease. It is estimated that only
5% to 25% of patients with disseminated or late manifesta-
tions of Lyme disease ever recall tick exposure or rash.18 , 19

142 AMERICAN JOURNAL OF OPHTHALMOLOGY SEPTEMBER 2022

 Our study showed that even in an endemic area, scle-
ritis cases caused by Lyme disease are exceedingly uncom-
mon (0.61% in an 8-year period). Furthermore, our study
provides an estimated incidence of scleritis in patients with
Lyme disease, 0.2 cases per 1,000,000 population per year
(95% CI 0-0.4). To further illustrate the rarity of the con-
dition, this is only a fraction of the estimated incidence of
Lyme disease per year in the greater Baltimore metropoli-
tan area, which was 3 cases per 10,000 population per year
(95% CI 2.9-3.1). It is important to note that these statis-
tics may be underestimates as we used only CDC-reported
cases of Lyme disease.
Another important point raised is the increased inci-
dence of Lyme scleritis over time. While the CDC has not
released the number of Lyme disease cases for the year 2020,
the yearly incidence must be higher as 3 cases of Lyme scle-
ritis were diagnosed in 2020 alone compared with 3 cases
in the previous 7 years. While the increasing number of
cases of Lyme scleritis could result from fluctuation alone,
in the years immediately predating our study, the number
of cases of Lyme disease in Maryland increased at an aver-
age of 13% per year.20 This trend was attributed to several
causes, including deforestation leading to changes in tick
habitats and an increased awareness of Lyme disease result-
ing in more diagnoses.20 This yearly rise in cases has con-
tinued through the study period, with increasing numbers
of Lyme disease cases reported by the CDC through the end
of the year 2019 without signs of plateauing.21
There are several limitations to our study. The number of
cases was small, limiting our ability to make inferences from
the descriptive data. Another limitation is that CDC re-
porting of Lyme disease is variable between states and coun-
ties, and there is no standardized nationwide tick surveil-
lance system.22 , 23 Furthermore, the incidence per year is
based on the assumption of constant risk. During the pe-
riod of study, the population in the greater Baltimore area
increased on a yearly basis and there was an increase in
cases over time. The latter could represent an ascertain-
ment bias with increased awareness leading to more diag-
noses vs a true increase in Lyme scleritis cases. All cases of
Lyme scleritis were identified only at the Wilmer Eye In-
stitute and may not represent the total number of scleri-
tis cases in the Mid-Atlantic referral areas. Our results are
based on the assumption that the prevalence of infection
in the mid-Atlantic area is similar to that in the Baltimore
area. However, a survey of other large referral centers in the
greater Baltimore region identified no other cases of scle-
ritis caused by Lyme disease, suggesting that we were un-
likely to have missed many cases of Lyme disease scleritis.
Nevertheless, without assessing the number of cases from
every practice in the area studied, our findings should be
VOL. 241 LYME DISEASE SCLERITIS
considered the best estimate of the population incidence
based on available data. Our data were derived from a Lyme
disease–endemic region and our estimates may not be as
relevant in a non–Lyme disease–endemic region. Without
compelling clinical findings or a patient history, testing for
Lyme serologies outside of an endemic area may lead to a
false positive result. Indeed, in a series from the Nether-
lands, a non–Lyme disease–endemic country, their conclu-
sion was that B. burgdorferi seropositive cases of uveitis typ-
ically were coincident and not caused by Lyme disease.24
Because all of the cases responded to antibiotic therapy, it
is likely that all of the identified cases in our series were
indeed caused by Lyme disease.
In the past, the pathogenesis of Lyme disease scleritis has
been debated as to whether it is caused by direct infection
or by a secondary immune-mediated process. In the initial
case report describing Lyme disease scleritis, the scleritis re-
curred after treatment and was associated with optic neu-
ritis, suggesting the possibility that this was an immune-
mediated process.24 While a tissue biopsy specimen was not
obtained to confirm the presence of B. burgdorferi and a re-
sponse to antibiotics does not by itself confirm a local in-
fection, it is likely that all of the identified cases in our
series were indeed caused by Lyme disease. If the scleritis
was a manifestation of a secondary, parainfectious, immune-
mediated process, clinical resolution would have been ex-
pected with the use of antiinflammatory therapy. However,
all patients in our study were treated with antimicrobial
therapy with complete resolution of symptoms and with-
out recurrence. Other studies have also suggested that Lyme
scleritis tends to develop weeks to months after suspected
exposure.16 , 24 Based on Western blot serologies, response to
oral antimicrobial therapy alone, and concurrent symptoms
at time of diagnosis, our cohort suggests that Lyme scleri-
tis appears to be a manifestation of untreated, disseminated
disease.
Although scleritis is a rare manifestation of Lyme disease,
this is an important condition to consider particularly as the
incidence of Lyme disease continues to increase.20-23 With
only 4 of our patients recollecting a tick bite or the possi-
bility for outdoor exposure, a patient history may offer only
limited diagnostic clues. Despite improved public aware-
ness of early manifestations of Lyme disease, the proportion
of patients presenting with late manifestations of untreated
disease is unchanged decades after its initial description.25
As such, a low threshold of suspicion is needed to con-
sider Lyme disease when evaluating patients with scleritis
because it may be the only manifestation of the disease. Al-
though the incidence is rare, it is important to consider and
test patients in endemic areas given it is a curable type of
scleritis.
143
Acknowledgements All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Funding/Support: This study
received no funding. Financial Disclosures: The authors indicate no financial support or conflicts of interest. All authors attest that they meet the current
ICMJE criteria for authorship. Author Contributions: Conceptualization: M.K.B., J.N.A., D.A.J.; Investigation: M.K.B., K.L., J.B.M., B.B.B., J.N.A.; Data
curation and analysis: M.K.B.; Writing – Original draft: M.K.B., K.L.; Writing – Review and editing: M.K.B., K.L., J.B.M., B.B.B., J.N.A., D.A.J.
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