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Multimodal
Imaging in Uveitis

H. Nida Sen
Russell W. Read
Editors

123
Multimodal Imaging in Uveitis
H. Nida Sen • Russell W. Read
Editors

Multimodal Imaging
in Uveitis
Editors
H. Nida Sen Russell W. Read
National Eye Institute Ophthalmology
National Institutes University of Alabama at Birmingham
of Health Birmingham, AL
Bethesda, MD USA
USA

ISBN 978-3-319-23689-6    ISBN 978-3-319-23690-2 (eBook)

https://doi.org/10.1007/978-3-319-23690-2

Library of Congress Control Number: 2017962971

© Springer International Publishing AG 2018

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
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Preface

Ophthalmology is one of the fields in medicine, in which there has been rapid prog-
ress in the availability and widespread acceptance of several new modalities of diag-
nostic imaging. Over the past decade, there have been advances in ophthalmic
imaging, including wider angle, improved resolution, quicker scan times, and
enhanced depth imaging to allow more detailed visualization and better comprehen-
sion of the extent of disease and closer scrutiny of the structural changes which
improved the understanding of pathophysiology of disease.
The gold standard of imaging as an adjunct to clinical care is taking on a new
form, and the ophthalmology community must continually keep abreast of these
advances and be able to appropriately incorporate them into clinical practice. This
is especially true with diseases of the retina and choroid in uveitis, where functional
changes may precede structural changes and having strong knowledge of the
strengths of imaging techniques can help identify disease in initial stages and permit
early institution of treatment.
In view of the considerable progress made, this book aims at providing up-to-
date comprehensive information on the most advanced imaging modalities available
for the assessment of retina and choroid, with a focus on uveitis. For each modality,
a description of the currently known applicability, role, and limitations within dis-
ease entities is reported. Among the newer imaging modalities, detailed attention is
paid to the various OCT technologies such as spectral domain OCT, enhanced depth
imaging OCT, and en face swept-source OCT. Further individual chapters focus on
imaging using adaptive optics, multiview OCT, and OCT angiography.
This book is a modern guide to the ophthalmic imaging techniques that have
revolutionized the diagnosis and management of uveitis during the past decade.

Bethesda, MD, USA H. Nida Sen, MD, MHS

Birmingham, AL, USA  Russell W. Read, MD, PhD

v
Acknowledgements

The editors warmly acknowledge all authors that contributed to make this book a
reality, and to Springer for their support and belief in the project.
Increasing use and better understanding of different modalities described in this
book are sure to improve our knowledge of the disease mechanisms involved in
uveitis and lead to better outcomes.
The challenge with this project is the continual development of newer imaging
modalities; however, the authors focused on the imaging tools that they have learnt
to be the most useful at diagnosis and monitoring of progression in uveitis.
We thank the authors who have assembled their experience and expertise into
this comprehensive and yet very timely book for all ophthalmologists dealing with
diseases of the retina and choroid.
H. Nida Sen and Russell W. Read

vii
Contents

1 Fluorescein Angiography in the Diagnosis and Management

of Uveitis ��������������������������������������������������������������������������������������������������    1
Albert T. Vitale and Nikhil N. Batra
2 Indocyanine Green Angiography in Uveitis������������������������������������������   25
Shilpa Kodati, Samuel P. Burke, and Thomas A. Albini
3 Wide-Field Imaging in Uveitis����������������������������������������������������������������   37
Benjamin P. Nicholson, Karen R. Armbrust, and H. Nida Sen
4 Imaging in Uveitis: Spectral Domain and Enhanced Depth
Imaging Ocular Coherence Tomography����������������������������������������������   51
Wendy M. Smith
5 Fundus Autofluorescence Imaging in Posterior Uveitis������������������������   69
Rubbia Afridi, Aniruddha Agarwal, Mohammad Ali Sadiq,
Muhammad Hassan, Diana V. Do, Quan Dong Nguyen,
and Yasir Jamal Sepah
6 Microperimetry in Uveitis ����������������������������������������������������������������������   87
Himanshu K. Banda, Maggie M. Wei, and Steven Yeh
7 Optical Coherence Tomography Evaluation of the Anterior
Segment in Uveitis Patients ��������������������������������������������������������������������   99
Francesco Pichi and Sunil K. Srivastava
8 Optical Coherence Tomography Angiography in Uveitis�������������������� 107
Francesco Pichi and Sunil K. Srivastava
9 En Face Optical Coherence Tomography���������������������������������������������� 117
Fabio Scarinci, Amani A. Fawzi, and Debra A. Goldstein
10 Multi-view Optical Coherence Tomography ���������������������������������������� 129
William R. Tucker, Robert B. Nussenblatt, and H. Nida Sen

ix
x Contents

11 Adaptive Optics and Its Use in Inflammatory Eye Disease ���������������� 135
Johnny Tam
12 Novel Use of Existing Imaging Modalities to Assess
Intraocular Inflammation ���������������������������������������������������������������������� 151
Alastair K. Denniston and Pearse A. Keane
Index������������������������������������������������������������������������������������������������������������������ 165
Contributors

Rubbia Afridi, MBBS Byers Eye Institute, Stanford University, Palo Alto, CA,
USA
Aniruddha Agarwal, MD Department of Ophthalmology, Advanced Eye Center,
Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh,
India
Thomas A. Albini, MD Bascom Palmer Eye Institute, Miller School of Medicine,
University of Miami, Miami, FL, USA
Karen R. Armbrust Department of Veterans Affairs Medical Center University of
Minnesota, Minneapolis, MN, USA
National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Himanshu K. Banda, MD Emory Eye Center, Atlanta, GA, USA
Nikhil N. Batra, MD Vitreoretinal Division, Section of Ophthalmology, Geisel
School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, Lebanon,
NH, USA
Samuel P. Burke, BA Bascom Palmer Eye Institute, Miller School of Medicine,
University of Miami, Miami, FL, USA
Alastair K. Denniston, PhD, FRCOphth Queen Elizabeth Hospital Birmingham,
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Institute for Inflammation and Ageing, College of Medical and Dental Sciences,
University of Birmingham, Edgbaston, Birmingham, UK
NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital
NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
Diana V. Do, MD Byers Eye Institute, Stanford University, Palo Alto, CA, USA
Amani A. Fawzi, MD Department of Ophthalmology, Northwestern University,
Chicago, IL, USA

xi
xii Contributors

Debra A. Goldstein Department of Ophthalmology, Northwestern University

Feinberg School of Medicine, Chicago, IL, USA
Muhammad Hassan, MBBS Byers Eye Institute, Stanford University, Palo Alto,
CA, USA
Pearse A. Keane, MD, FRCOphth NIHR Biomedical Research Centre for
Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute
of Ophthalmology, London, UK
Shilpa Kodati, MD National Eye Institute, National Institutes of Health, Bethesda,
MD, USA
Quan Dong Nguyen, MD, MSc Byers Eye Institute, Stanford University, Palo
Alto, CA, USA
Benjamin P. Nicholson Great Lakes Eye Care, St. Joseph, MI, USA
Robert B. Nussenblatt Moorfields Eye Hospital, London, UK
Francesco Pichi, MD Cole Eye Institute, Cleveland Clinic Foundation, Cleveland,
OH, USA
Cleveland Clinic Abu Dhabi, Eye Institute, Abu Dhabi, UAE
Mohammad Ali Sadiq, MBBS Byers Eye Institute, Stanford University, Palo
Alto, CA, USA
Fabio Scarinci Department of Ophthalmology, Northwestern University Feinberg
School of Medicine, Chicago, IL, USA
G. B. Bietti Eye Foundation-Istituto di Ricovero e Cura a Carattere Scientifico,
Rome, Italy
H. Nida Sen National Eye Institute, National Institutes of Health, Bethesda, MD,
USA
Moorfields Eye Hospital, London, UK
Yasir Jamal Sepah, MBBS Byers Eye Institute, Stanford University, Palo Alto,
CA, USA
Wendy M. Smith, MD Mayo Clinic, Rochester, MN, USA
Sunil K. Srivastava, MD Cole Eye Institute, Cleveland Clinic Foundation,
Cleveland, OH, USA
Johnny Tam National Eye Institute, National Institutes of Health, Bethesda, MD,
USA
William R. Tucker Moorfields Eye Hospital, London, UK
Contributors xiii

Albert T. Vitale, MD Member of Vitreoretinal Division, Department of

Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of
Utah, Salt Lake City, UT, USA
Maggie M. Wei, BS National Eye Institute, National Institutes of Health, Bethesda,
MD, USA
Steven Yeh, MD Emory Eye Center, Atlanta, GA, USA
Chapter 1
Fluorescein Angiography in the Diagnosis
and Management of Uveitis

Albert T. Vitale and Nikhil N. Batra

Introduction

Fluorescein angiography (FA) is an essential tool in the diagnosis and management of

both infectious and noninfectious intraocular inflammations in patients with interme-
diate, posterior, and panuveitis [1–3]. While, in clinical practice, multimodal imaging
with color fundus photography, optical coherence tomography (OCT), indocyanine
green angiography (ICGA), and fundus autofluorescence (FAF) are frequently
employed in this setting, FA remains a highly sensitive technique for the assessment
of the presence and extent of active retinochoroidal and vascular inflammation, in
monitoring the response to and threshold for anti-inflammatory therapy and the iden-
tification of ocular structural abnormalities associated with visual loss. In some
instances, the type and pattern of vascular and/or retinochoroidal involvement seen on
FA may be particular to specific uveitic entities making it diagnostically very useful.
Fluorescein angiography employs fluorescein sodium (C20H10Na2O5), an orange-­
red crystalline hydrocarbon dye, with a molecular weight of 376 Da that is 80% bound
to protein (primarily albumin). Although the unbound form readily diffuses through
most body fluids including the choriocapillaris, the tight junctions of the retinal vas-
cular endothelial cells and the zona occludens joining adjacent RPE cells normally
prevent the molecule from entering potential spaces within the vitreous cavity, retinal
tissue, and subretinal space. The normal adult dosage is 500 mg [4].

A.T. Vitale, MD (*)

Member of Vitreoretinal Division, Department of Ophthalmology
and Visual Sciences, John A. Moran Eye Center, University of Utah,
Salt Lake City, UT, USA
e-mail: albert.vitale@hsc.utah.edu
N.N. Batra, MD
Vitreoretinal Division, Section of Ophthalmology, Geisel School of Medicine at Dartmouth,
Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
e-mail: nikhil.n.batra@dartmouth.edu

© Springer International Publishing AG 2018 1

H.N. Sen, R.W. Read (eds.), Multimodal Imaging in Uveitis,
https://doi.org/10.1007/978-3-319-23690-2_1
2 A.T. Vitale and N.N. Batra

Table 1.1 Reported complications of fluorescein angiography

Nausea
Vomiting
Allergy
 • Mild: pruritis, sneezing
 • Moderate: urticaria
 • Severe: laryngeal edema, bronchospasm, anaphylaxis
Cough
Dizziness
Vasovagal reaction
 • Syncope
 • Circulatory shock
 • Myocardial infarction
Extravasation and local tissue necrosis
Thrombophlebitis
Nerve palsy
Seizure
Death

Over 50 years of experience with fluorescein angiography has proven it to be a

relatively safe procedure. The most common side effects include nausea, vomiting,
and mild vasovagal reactions, which can occur in approximately 5–10% of patients
[5, 6]. Other side effects are listed in Table 1.1. Although no known teratogenic
effects have been reported, most clinicians avoid fluorescein angiography during
pregnancy, especially in the first trimester [7]. Fluorescein sodium is expressed in
the breast milk of lactating women, a consideration to be kept in mind should angi-
ography be necessary in a breastfeeding patient [8]. Sodium fluorescein is excited
by absorbed light energy in the blue spectrum (465–490 nm) and emits green-­yellow
light (520–530 nm) [9]. Digital-based fluorescein angiography has gained wide
acceptance, replacing film-based systems allowing rapid and easy archival and
retrieval of images for monitoring inflammatory disease progression and response
to treatment [2]. In addition, fluorescein angiography can be performed using a scan-
ning laser ophthalmoscope (SLO) based system which is covered in detail in Chap. 3.

Fluorescein Angiography Interpretation

FA provides both anatomic and functional information primarily with respect to the
retinal circulation and superficial retinal structures and secondarily of the underly-
ing RPE, choriocapillaris, subretinal, and choroidal disease processes (i.e., choroi-
dal neovascular membranes) in a dynamic fashion. The normal FA is divided into
discrete phases following the intravenous injection of dye:
1. Choroidal phase: within 10–15 s of injection, fluorescein first appears in the
choroid (choroidal flush) and the optic nerve.
2. Arterial phase: rapid arterial filling within 2 s following the choroidal phase.
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 3

3. Arteriovenous phase: laminar venous filling followed by full and equally bright
veins and arteries (20–30 s).
4. Recirculation phase: intravascular fluorescence then fades gradually leaving
veins brighter than the arteries. The angiogram is usually complete by 10 min.
Abnormal fluorescence patterns on FA denote pathology and are grouped into
two major categories: hypofluorescence and hyperfluorescence. Table 1.2 lists the
various causes and anatomical basis for these abnormal fluorescein angiography
patterns.

Table 1.2 Abnormal fluorescein angiography patterns

Hypofluorescencea Blockage
 • Blood
 • Pigment
 • Vitreous debris
 • Inflammatory lesions
Vascular filling defect
 • Obstruction
 • Congenital absence
 • Capillary non-perfusion
Hyperfluorescence Increased transmission (window defect)b
 • RPE atrophy
 • Macular hole
Leakage
 • Choroidal neovascularizationc
 • Optic disc edemad
 • Cystoid macular edemae
Staining
 • Inflammatory vasculitis (perivascular staining)f
 • Chorioretinal scar
 • Drusen
Pooling
 • Pigment epithelial detachment (PED)
 • Neurosensory or exudative detachmentg
Abnormal vessel caliber and shapeh
a
The approximate anatomic location of the blocking material can usually be ascertained by the
degree to which the visibility of fluorescence from the retinal or choroidal circulations is obscured.
For example, preretinal hemorrhage would be expected to block both retinal and choroidal fluores-
cence while hemorrhage located in the subretinal space would obstruct visibility of the choroidal
but not the retinal circulation. The distinction between blocked fluorescence and that due to a
hypoperfusion is critically important and usually requires correlation between the findings seen on
FA with those on ophthalmoscopy or fundus photography. Should the area of hypofluorescence
seen on FA match substances or lesions visible on clinical exam, blocked fluorescence is present;
however, if no corresponding blocking material is observed, hypofluorescence is due to a vascular
filling defect
b
Hyperfluorescence due to window defects parallels that of the choroidal fluorescence appearing
bright early and fading late, has distinct borders and is stable in size
c
Early, lacy hyperfluorescence is observed with CNVM, often before filling of the retinal vessels,
with late leakage into the retinal tissues and subretinal space
d
Dilated capillaries associated with inflammatory papillitis hyperfluorescence early and stain the
optic disc late, obscuring the disc margins to a variable degree depending on the degree of leakage,
(continued)
4 A.T. Vitale and N.N. Batra

Table 1.2 (continued)

while frank neovascularization of the disc (NVD) and retinal neovascularization elsewhere (NVE)
characteristically produce early, intense hyperfluorescence with progressive, profuse late leakage
of dye into the vitreous cavity
e
Leakage of dye with late pooling in the outer plexiform layer of the macula render the petaloid
pattern of hyperfluorescence seen with inflammatory macular edema (ME)
f
Retinal vascular occlusion with late staining (or leakage) of the vessel walls on the FA are the
hallmarks of retinal vasculitis
g
Early pinpoint leakage with progressive and expanding leakage at the level of the RPE with late
pooling of fluorescein in the subretinal space typify inflammatory subneurosensory exudative reti-
nal detachment
h
Abnormal retinal vessels are readily apparent as early and hyperfluorescent during vascular filling
phase with variable degrees of leakage in the later stages of the FA

Clinical Utility of FA

Optic Disc Inflammation

Inflammation of the optic nerve is a very common but non-specific sign of active
intraocular inflammation manifested clinically as hyperemia, absence of the cup,
and a variable degree of blurring of the disc margin (Table 1.3). Hyperfluorescence
of dilated disc capillaries is visualized early on FA as late staining of the optic disc
with the extent of disc margin obscuration depending on the degree of dye leakage
(Fig. 1.1a, b). Optic disc inflammation as seen on FA uniformly accompanies uve-
itic macular edema (ME) and, is useful in distinguishing it from noninflammatory
causes of ME and from other forms of optic disc involvement such as neuroretinitis.
Subtle optic nerve hyperfluorescence may denote subclinical inflammation and be
useful as a sign of active disease and in monitoring the response to anti-inflamma-
tory treatment.

Inflammatory Macular Edema

Macular edema is the leading cause of central visual loss among patients with uve-
itis [10, 11]. Inflammatory macular edema is thought to arise from the breakdown
of the inner blood retinal barrier mediated by inflammatory cytokines leading to
increased vascular permeability of the perifoveal capillaries and the accumulation
of fluid within in the outer plexiform layer and sub-neurosensory retina [12].
Angiographically, there is corresponding late leakage and pooling of fluorescein
dye into these spaces with the characteristic pattern of petaloid hyperfluorescence
together with optic disc staining (Table 1.3) (Fig. 1.2). Several studies have demon-
strated that OCT, a noninvasive, quantitative, reproducible modality for the mea-
surement of retinal thickness, can be as effective as FA in demonstrating ME in
patients with uveitis with visual loss correlated with central macular thickness and
the severity of leakage [13–15]. However, it is important to note that FA and OCT
measure different manifestations of an underlying inflammatory disease, the
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis
Table 1.3 Posterior segment abnormalities associated with vison loss: clinical findings and FA
correlates
Structural abnormality Clinical findings
Optic disc inflammation Hyperemia, absence of physiologic
cup, blurring of disc margin,
hemorrhage
Neuroretinitis Features of optic disc inflammation
as above plus:
 • Macular star
 • Exudative macular detachment
Inflammatory macular Loss of foveal depression
edema Macular thickening
Cysts
Retinal NVD: Abnormal vascular net,
Neovascularization hemorrhage, fibrovascular
 – Neovascularization proliferation
of the disc (NVD) NVE: Hemorrhage at border of
 – Neovascularization perfused and non-perfused retina,
elsewhere (NVE) fibrovascular proliferation,
tractional retinal detachment
Retinitis Yellow white retinal necrosis,
Hemorrhage, Associated vasculitis
(arteritis), Vitritis
Retinochoroiditis Focal yellow-white lesion,
Pigmented scar, hemorrhage
Vitritis, associated vasculitis
(phlebitis)
Chorioretinitis Deep creamy lesions (often
multiple discrete or placoid),
associated vasculitis (arteritis or
phlebitis), variable vitritis
Exudative neurosensory Multifocal exudative retinal
retinal detachment detachments, optic disc edema,
choroidal thickening
Choroidal Gray-Green subretinal lesion,
neovascularization Subretinal or intraretinal fluid
Cystoid macular edema, pigmented borders of lesion (PIC,
scar
Outer retinal, RPE, Variable presentation depending on Early hypofluorescence with
choriocapillary disease; see text for descriptions of variable late staining (BSRC,
inflammatory disease specific entities
Retinal vasculitis Perivascular cream colored cuffs,
vessel sheathing, exudation, micro
and macro aneurysms
5
FA findings
Early hyperfluorescence of
dilated disc capillaries, late
staining and leakage
Early hyperfluorescence and late
staining of optic disc, no
leakage from macular capillaries
Late petaloid leakage and
pooling, perifoveal capillary
hyperfluorescence
Profuse late leakage
(intermediate uveitis, BD,
sarcoidosis, SLE, ANCA
associated uveitis)
Blockage from necrosis and
hemorrhage, peri-arteriolar
leakage and staining (ARN,
CMV)
Early blockage, late staining at
lesion borders, periphlebitic
leakage and staining
Early hypofluorescence from
deep choroidal blockage, late
staining at borders of lesions,
perivascular staining
(toxoplasmosis)
Multiple early pinpoint
hyperfluorescent dots within
exudative detachments, late
leakage and pooling into
sub-neurosensory space (VKH,
SO, sarcoidosis, posterior scleritis)
Early lacy hyperfluorescence,
Late leakage which obscures
MFC-PU, serpiginous, VKH,
BSRC, toxoplasmosis)
Serpiginous, APMPPE), early
wreathlike hyperfluorescence
and late staining (MEWDS)
See Tables 1.4, 1.5 and 1.6
6 A.T. Vitale and N.N. Batra

a b

Fig. 1.1 Optic disc inflammation: (a) FA showing early hyperfluorescence of dilated optic nerve
capillaries. (b) Late leakage obscuring the disc borders

Fig. 1.2 Inflammatory

macular edema: FA
showing petaloid
hyperfluorescence with
optic disc staining

pathophysiologic process of vascular leakage, and the anatomic changes in retinal

thickening (or thinning), respectively. Leakage seen on FA may not always be
accompanied by an increase in macular thickness on OCT (Fig. 1.3a, b). Conversely,
macular thickening may occur in the absence of ongoing vascular leakage with
RPE pump dysfunction in the presence of chronic intraretinal or subretinal fluid.
OCT may be the best test for the initial detection and longitudinal monitoring of
inflammatory ME; however, compensated leakage may be present in the absence of
retinal thickening and vice versa.
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 7

a b

Fig. 1.3 Compensated leakage: (a) macular hyperfluorescence on FA; (b) absence of frank
thickening or cysts on OCT

Retinal Vasculitis

Clinically, retinal vasculitis appears as perivascular, creamy-colored cuffs with

varying degrees of exudation and sheathing (Table 1.3). The pattern, type, extent,
and location of retinal vascular staining and leakage may be useful diagnostically
(Tables 1.4, 1.5 and 1.6). In addition, FA is essential for the identification and treat-
ment of vasculitic complications such as retinal nonperfusion, neovascularization,
telangiectasia, arterial-venous (AV) anastomosis, and micro- and macroaneurysms.
As with inflammatory ME, staining and leakage of the vessel walls are sensitive
indicators of inflammatory activity, such as in asymptomatic patients with pars
planitis or BSRC in the absence of clinically apparent signs and in vitrectomized
eyes in which the usual surrogate markers of activity (vitreous cells/haze) may have
been removed. Finally, FA is indicated in the evaluation and management of sys-
temic diseases with retinal vascular involvement such as Behçet’s disease (BD),
ANCA-­associated vasculitides, Susac’s syndrome, and systemic lupus erythemato-
sus (SLE) [16].
Uveitic entities commonly associated with retinal phlebitis and the correspond-
ing FA findings are described in Table 1.4. In sarcoidosis-associated periphlebitis,
the pattern of vascular staining and leakage is characteristically segmental or dis-
continuous and may be associated with yellow perivascular exudates described as
“taches de bougie” (candle wax drippings) (Fig. 1.4). In contrast, a more diffuse
pattern is observed in idiopathic retinal vasculitis and with CMV-associated frosted
branch angiitis [17] (Fig. 1.5). Retinal vascular involvement in pars planitis is
common and may exhibit both segmental and diffuse staining and leakage of the
veins with small vessel hyperfluorescence in a characteristic “fern pattern”
(Fig. 1.6) [18–21]. Wide field imaging may reveal more extensive peripheral vas-
cular staining and leakage than that visualized on conventional FA, particularly
8 A.T. Vitale and N.N. Batra

Table 1.4 Uveitic entities associated with predominantly retinal phlebitis

Staining Primary
Occlusive pattern location
vs. non (segmental (posterior pole
Condition occlusive vs. diffuse) vs. periphery) Other features
Idiopathic retinal Both Diffuse Both Macular Ischemia
vasculitis
Pars planitis Non Both Periphery “Fern pattern” hyperfluorescence
occlusive Peripheral nonperfusion
NVE
Birdshot (BSRC) Non Diffuse Posterior pole Optic disc staining and leakage
occlusive
Sarcoid Both Segmental Both Macroaneurysms
NVE
Tuberculosis Non Segmental Posterior pole Neuroretinitis
occlusive Focal choroiditis
NVE
Eales’ disease Occlusive Segmental Periphery Peripheral nonperfusion
Small vessel BRVO
NVE
Toxoplasmosis Non Both Posterior pole Typical focal retinochoroiditis
occlusive lesion
HIV retinopathy Occlusive Segmental Both Microvasculopathy
CMV retinitis Both Diffuse Both Characteristic necrotic
chorioretinal lesion
Multiple sclerosis Non Both Periphery May be transient
occlusive

Table 1.5 Uveitic entities associated with predominantly retinal arteritis

Staining pattern Primary location
Occlusive vs. (segmental vs. (posterior pole
Condition non occlusive diffuse) vs. periphery) Other features
HSV (ARN) Occlusive Diffuse Both Necrotizing Retinitis
VZV (PORN)
Syphilis Non occlusive Diffuse Both Chorioretinitis
CME
Disc edema
Susac’s Syndrome Occlusive Segmental Both Multiple BRAO with
minimal leakage
IRVAN Occlusive Segmental Both Microaneurysms
Neuroretinitis
Peripheral nonperfusion
SLE Occlusive Both Both BRAO
NVE, NVD
Cotton wool spots
Peripheral nonperfusion
ANCA associated Occlusive Segmental Both Delayed choroidal
(polyarteritis filling
Nodosa, Churg
strauss)
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 9

Table 1.6 Uveitic entities associated with both retinal phlebitis and arteritis
Staining pattern Primary location
Occlusive vs. (segmental vs. (posterior pole Other
Condition non occlusive diffuse) vs. periphery) features
Behçet’s Disease (BD) Both Both Both Macular
ischemia
NVE
CME
Granulomatosis with Occlusive Both Both Rare
polyangiitis (Wegener’s)

a b

Fig. 1.4 Ocular sarcoid: (a) color photograph showing yellow, perivascular exudates (“taches de
bougie”); (b) FA with corresponding segmental periphlebitis and optic nerve leakage (Courtesy of
Ramana Moorthy, MD, FACS)

Fig. 1.5 Color photograph

showing diffuse retinal
periphlebitis (“frosted
branch angiitis”)
associated with CMV
retinitis
10 A.T. Vitale and N.N. Batra

Fig. 1.6 Wide angle FA

showing capillary leakage
in a “fern pattern”

a b

Fig. 1.7 (a) Color fundus photograph with clinically unapparent vasculitis in a birdshot retinocho-
roidopathy patient. (b) Extensive periphlebitis and optic nerve leakage on FA

when posterior pole involvement is absent [22, 23]. In the management of BSRC,
FA reveals critical components of disease activity including the extent of periphle-
bitis and optic nerve leakage which may not be appreciated on clinical exam
(Fig. 1.7a, b).
Posterior and panuveitis primarily associated with retinal arteritis are high-
lighted in Table 1.5. Occlusive arteriolar vasculopathy is invariably present
and is a diagnostic criterion for the acute retinal necrosis syndrome (ARN)
[24] (Fig. 1.8). The FA in Susac’s syndrome discloses characteristic focal, non-
perfused arterioles with multiple areas of segmental staining remote from sites
of bifurcation [25] (Fig. 1.9). The salient diagnostic features of IRVAN syndrome,
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 11

a b

Fig. 1.8 Acute retinal necrosis: (a) color photograph showing confluent retinitis and arteritis.
(b) Corresponding FA reveals occlusive arteriolitis

a b

Fig. 1.9 Susac’s syndrome: (a) color photograph depicting ischemic retinal whitening corre-
sponding to superotemporal branch artery occlusions; (b) FA showing superotemporal branch arte-
riole occlusions with multiple areas of segmental staining remote from sites of bifurcation

retinal arterial vasculitis, multiple macroaneurysms, and neuroretinitis are

highlighted by FA and may help guide treatment with laser photocoagulation
in the presence of significant capillary ­nonperfusion [26] (Fig. 1.10a, b).
Retinal arterial macroaneurysms, while uncommon in uveitis patients in gen-
eral, may be seen with peripheral multifocal chorioretinitis associated with
sarcoidosis [27–29].
The retinopathy associated with SLE and ANCA-associated vasculitides
typically arise from vaso-occlusive events primarily involving the retinal arte-
riolar and choroidal vasculature in the absence intraocular inflammation and
are considered important markers of systemic disease activity [30–32]. The
hallmarks of occlusive retinal vasculitis/vasculopathy on FA include retinal
capillary dropout, nonperfusion, and retinal vascular staining and leakage
which may involve the retinal arterioles, venules, or both. Structural complica-
tions due to consequent retinal ischemia including NVD and NVE, as well as
12 A.T. Vitale and N.N. Batra

a b

Fig. 1.10 Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN). (a) Early FA dem-
onstrating multiple arterial macroaneurysms. (b) Late leakage from optic nerve and aneurysms

Fig. 1.11 Occlusive

retinal vasculitis: FA shows
extensive peripheral
nonperfusion, retinal
vascular staining of both
arterioles and venules, and
arteriovenous anastomoses

those arising from post-occlusive vascular remodeling, such as retinal telangi-

ectasias, microaneurysms, and AV anastomoses may be identified and distin-
guished on the basis of their FA leakage patterns (Fig. 1.11).
The retinal vasculitis associated with Behçet’s disease (BD) and granulomatosis
with polyangiitis (GPA, previously known as Wegener’s Granulomatosis) may
involve both the arterioles and veins and be leaky and/or occlusive (Fig. 1.12).
Fluorescein angiography is essential in the early detection of inflammatory activity
and structural complications in BD. It is also useful to monitor the efficacy of treat-
ment modalities and can be used prognostically as macular ischemia and NVD have
been associated with increased risk of visual loss in patients with BD [33, 34].
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 13

Fig. 1.12 Behçet’s

disease: occlusive retinal
vasculitis with enlargement
of the foveal avascular
zone, temporal macular
nonperfusion, and vascular
remodeling

a b

Fig. 1.13 Retinal neovascularization: (a) FA showing inflammatory disc neovascularization in

pars planitis; (b) FA showing ischemic peripheral neovascularization in Eales’ disease. Also, note
the tortuosity and collaterals proximal to the area of neovascularization

Retinal Neovascularization

Retinal neovascularization (neovascularization of the disc or elsewhere, NVD or

NVE) may complicate the course of a variety uveitic entities and arises as a conse-
quence of retinal ischemia or may be driven by inflammatory mediators alone [35]
(Table 1.3). Peripheral retinal neovascularization typically occurs at the border of
perfused and nonperfused retina and leaks profusely in the late stages of the FA,
whereas AV anastomosis does not. The distinction between inflammatory vs. isch-
emic neovascularization by FA, as well as the identification of post-occlusive vas-
cular abnormalities, is essential as the treatment of each is markedly different
(Fig. 1.13a, b). Disc neovascularization due to persistent intraocular inflammation
14 A.T. Vitale and N.N. Batra

may respond to more aggressive anti-inflammatory therapy alone, whereas NVE

associated with peripheral nonperfusion requires laser photocoagulation, and non-­
leaky shunt vessels may be safely observed [36].

Retinitis, Retinochoroiditis, and Chorioretinitis

Fluorescein angiography is not routinely necessary in the evaluation of most infec-

tious causes of retinitis and retinochoroiditis, but may highlight more extensive
pathology than that seen on ophthalmoscopy, and the pattern seen on FA may be so
stereotypical as to be virtually pathognomonic. For example, acute posterior placoid
chorioretinitis with early hypofluorescence and typical late macular hyperfluores-
cence without exudative detachment is highly suggestive of syphilis [37] (Fig. 1.14a–c).
In West Nile virus (WNV), FA reveals early hypofluorescence with late staining of

a b

Fig. 1.14 Syphilitic posterior placoid chorioretinitis: (a) color photograph showing a pale yellow
subretinal lesion in macula with concomitant papillitis. (b) Early FA with patchy hypofluorescence
along margins of the lesion. (c) Late FA with staining of the placoid lesion with a background of
persistent hypofluorescence and optic disc leakage
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 15

the lesions, while in the subacute phase, there is central hypofluorescence with
peripheral hyperfluorescence creating a targetoid appearance secondary to central
blockage from pigment and peripheral hyperfluorescence due to atrophy (Fig. 1.15).
These angiographic findings, together with a linear clustering of chorioretinal
lesions following the course of the nerve fibers, are highly suggestive of the diagno-
sis of WNV infection [38].
Active and recurrent toxoplasmosis lesions typically block dye early and stain
late from the borders and may be associated with vascular changes primarily
involving the retinal veins but also the arterioles with plaques known as Kyrieleis
arteritis (Table 1.4) (Fig. 1.16). Active choroidal lesions such as those associated

Fig. 1.15 West Nile virus

choroiditis (subacute
phase): FA reveals
characteristic targetoid
central hypofluorescence
with peripheral
hyperfluorescence together
with linear clustering of
chorioretinal lesions

Fig. 1.16 Toxoplasmic

retinochoroiditis: color
photograph of Kyrieleis
perivascular plaques
16 A.T. Vitale and N.N. Batra

with tuberculosis typically exhibit early hypo- or isofluorescence with intense late
hyperfluorescent staining. A segmental retinal periphlebitis involving the post
equatorial veins may also be associated with tuberculosis with active or healed
focal choroidal lesions along the retinal vessels [39–42]. Inactive chorioretinal
lesions and scars typically display early hyperfluorescence with late staining or
window defects.

Exudative Neurosensory Retinal Detachment

Exudative neurosensory retinal detachment develops during the acute uveitic

phase of Vogt-Koyanagi-Harada (VKH) syndrome [43] but may also compli-
cate the course of sympathetic ophthalmia (SO) [44], sarcoidosis-associated
uveitis [45], and posterior scleritis [46] and less commonly in APMPPE [47]
and SLE [48] (Table 1.3). Fluorescein angiography in both VKH and SO dem-
onstrates optic disc leakage and a delay in choroidal perfusion seen as choroi-
dal hypofluorescence during the acute uveitic phase [49]. Multiple, bilateral,
pinpoint hyperfluorescent dots at the level of the RPE are visualized during the
early and mid-phase of the study which increase in intensity, gradually enlarge
and leak with pooling of dye in the sub-neurosensory space in the late phase of
the angiogram (Fig. 1.17a, b). Vascular staining and leakage can also be seen.
In the chronic stage of the disease, RPE atrophy and pigment hyperplasia may
develop with corresponding window and blocking defects seen on FA. These
RPE changes may evolve into a salt and pepper appearance during the conva-
lescent stage with alternating areas of hypofluorescence and hyperfluorescence
[50, 51].

a b

Fig. 1.17 Vogt-Koyanagi-Harada syndrome: (a) early FA with multiple pinpoint hyperfluorescent
dots at the level of the RPE. (b) Late FA with typical leakage and pooling of dye in the sub-neuro-
sensory space
1 Fluorescein Angiography in the Diagnosis and Management of Uveitis 17

Choroidal Neovascularization

Choroidal neovascular membrane (CNVM) may complicate both infectious and

noninfectious posterior and panuveitis, with the potential for severe visual loss.
Inflammatory CNVM develops most often in a Type 2 subretinal neovascular
pattern in which pathologic vessels penetrate through Bruch’s membrane and
proliferate above the RPE within the subretinal space [52]. Angiographically, a
lacy hyperfluorescence corresponding to pathologic vessels is observed, often
before complete filling of the retinal vessels, with late leakage of dye into the
retinal tissues and subretinal space (Table 1.3) (Fig. 1.18a, b). Uveitic entities at
highest risk for the development of CNVM include punctate inner choroidopa-
thy (PIC), multifocal choroiditis and panuveitis (MFC-PU), and VKH and is a
well-described complication of serpiginous choroiditis, BSRC, toxoplasma reti-
nochoroiditis, and other chorioretinal inflammatory entities, albeit less fre-
quently [50, 53, 54].

Outer Retinal, RPE, and Choriocapillary Inflammatory Disease

Multimodal imaging with FA, FAF, OCT, and ICG provides invaluable information
with respect to the nature and location of the pathologic process in a variety of pos-
terior uveitic entities such as those included in the white dot syndromes, posterior
scleritis, and SLE-associated vasculopathy that may affect the inner and/or outer
retina/photoreceptor complex, RPE, choriocapillaris, and choroid [55]. ICGA is the
best tool for the evaluation of the choriocapillaris and the choroid (see Chap. 2).

a b

Fig. 1.18 CNVM complicating punctate inner choroidopathy (PIC). (a) Early lacy hyperfluores-
cence with surrounding blocked fluorescence due to blood and hyperfluorescence of the PIC
lesions. (b) Late leakage of dye from the neovascular complex superior to fovea and staining of the
PIC lesions inferiorly
18 A.T. Vitale and N.N. Batra

a b

Fig. 1.19 Birdshot retinochoroidopathy: (a) late FA highlights periphlebitis, macular capillary,
and optic disc leakage; (b) ICGA reveals hypofluorescent dots more numerous than those seen on
FA or clinical exam

Similarly, ICGA may be a useful adjunct to FA in the detection of occult or recur-

rent CNVM. Likewise, OCT and FAF provide detailed anatomic information with
respect to the integrity of the outer retinal layers and RPE which complement that
obtained from FA studies.
For example, the choroidal lesions of BSRC demonstrate angiographic hetero-
geneity on FA being influenced by the age, degree of inflammatory activity, and
the presence of multiple lesions at different stages of evolution in the same eye. In
contrast, ICGA discloses multiple hypofluorescent spots which are more numer-
ous than those seen on FA and biomicroscopy (Fig. 1.19a, b). Patients with recent
active disease may have fuzzy indistinct choroidal vessels and late diffuse choroi-
dal hyperfluorescence which may respond to therapy to some degree [56, 57].
Similarly, the evaluation of toxoplasmosis retinochoroiditis with both FA and ICG
reveals multiple hypofluorescent satellite dark spots present in the majority of
eyes with active retinochoroiditis, highlighting features not evident on clinical
exam [58, 59].
In serpiginous choroiditis, the FA shows early hypofluorescence at the edge the
acute lesion with late brush fire staining and variable leakage at its margin, while on
FAF imaging, this same area of activity is visualized as hyperautofluorescent [60]
(Fig. 1.20a–c). Similarly, the hypofluorescence visualized throughout all phases of
ICGA matches the hypoautofluorescence seen on FAF, corresponds the area of RPE
and choroidal loss, and is larger than that seen on FA and may be valuable in assess-
ing and monitoring the extent of the disease activity. A localized spot of hyperfluo-
rescence in the mid-phase of the ICGA may be indicative of the presence of a
CNVM.
In the acute stages of APMPPE, both the FA and ICGA show early hypo-
fluorescence of the lesions, more numerous than the placoid lesions seen by
Another random document with
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the Companies disposing, who are to fynde them dyett during that
time, and tenne pounds more to Mr Higgeson towards his present
fitting him and his for the voyage.
Francis Higgison.
Samuel Skelton.
A TRUE RELATION OF THE
LAST VOYAGE TO
NEW ENGLAND
 A trve relacon of ye last voyage to new
England, declaring all circustances wth ye
maner of ye passage wee had by sea, and
what maner of countrey & inhabitants we
found when we came to land: & what is ye
present state & condicon of ye English
people yt are there already.

Faithfully recorded according to ye very truth for ye satisfaction of

very many of my loving friends, who haue earnestly requested
to be truly certifyed in these thinges.
Written from new England July 24, 1629.

It. any Curious Criticke yt lookes for exactnes of phrases or expert

seaman yt regard propriety of sea-termes &c
 A TRVE RELACON of ye last voyage to
new England made ye last Sumer, begun ye 25th
of April being Saturday, Anno doi 1629.

THE copany of New England consisting of many worthy gentlemen in ye

citty of London, Dorcester & other places, ayming at ye glory of God, ye
propagacon of ye gospell of Christ, ye conversio of ye Indians, & ye enlargemt
of ye Kings maties dominions in America, & being authorised by his royall
letters patents for yt end, at their very great costs & chardgs furnished 5
Ships to go to new England, for ye further setling of ye English plantacon yt
yy had already begun there.
The names of ye 5 Shipps were as followeth. The first is called ye Talbot,
a good & strong shipp of 300 tunnes, & 19 pieces of ordinance & served wth
30 mariners. This ship carried about an 100 planters, 6 goates, 5 great
pieces of ordinaunce, wth meale, oatemeale pease, & all maner of munitio
and provisio for ye plantacon for a twelve month. The second ye George,
another strong ship also, about 300 tunnes, 20 pieces of ordinance, served
wth about 30 mariners; her chiefe carriage were cattell, 12 mares, 30 kyne,
& some goates: also ther gad in her 52 planters & other provision. The 3d is
called ye Lyons whelpe, a neate & nimble ship of 120 tunnes, 8 pieces of
ordinaunce, carrying in her many mariners & about 40 planters, specially
fro dorcester & other places thereabouts, wth provision, and 4 goates.
The 4th is called ye 4 sisters, as I heare of about 300 tuns, wch fayre ship
carried many cattell wth passengers & provision.
The 5th is called ye Mayflower, carrying passengers & provision.
Now amongst these 5 ships, ye George hauing the speciall & urgent
cause of hastening her passage sett sayle before ye rest about ye midst of
April. And ye 4 Sisters & ye Mayflower being not throughly furnished,
intended as we heard to sett forth about 3 weeks after vs: But we yt were in
ye Talbot & ye Lions whelpe being ready for or voyage by ye good hand of
Gods providence hoysed or sayle fro Graues end on Saturday ye 25th of
April about 7 a clocke in ye morning. Having but a faynt wynd
[April 25] we could not go farre ytday, but at night wee ancred against
Lie wch is 12 miles fro graues end, & there we rested yt night & kept
[26] Sabbath ye next day.
On monday we sat forward & came to ye flats, a passage soewhat
[27] difficult by reason of ye narrownes of ye channell & shallownes of ye
water: & going ouer this wee were in soe daunger: for or ship being heavy
laden & drawing deepe water was sensibly felt of vs all to strike 3 or 4
tymes on ye ground: but ye wynd blowing soewhat strong we were carried
Swiftly on, & at last by Gods blessing came safe to ancre at Gorin roade.
Tewsday we went a little further, & ancred ouer agt Margret
[28] Towne, staying for a wind for ye downes.
Wednesday we came safely though wth much turning & tacking
[29] thorow ye gullies into ye downes, & stayed yt night.
Thursday, Fryday & Saturday ye wind blew hard fro
[30. May 1. 2.] south west & caused or ship to daunce, & diuers of or
passengers & my wiffe specially were sea sicke. Here ye Kings ship called
ye Assurance pressed 2 of or mariners. Here we saw many Porpuses
playing in ye sea wch yy say is a signe of fowle weather.
Sabbath day a windye day & could: we kept Sabbath staying
[May 3] still at ye downes.
Monday God sent vs a fayre gale of wind north: n: East, whereby
[4] we came merily fro ye downes: & passing Dover we saw 6 or 7 saile
of dunkirkes, wafting after vs: but it seemed yy saw or copany was too
strong for ym, for then wee had wth vs 3 or 4 ships yt went for ye Straits: so
yy returned backe fro pursuing vs any longer. But sayling wth a good wind
wee went speedily, & at night came neere ye Ile of Wight but being darke
wee durst not put into ye channell, but put backe for sea roome 4 houres, &
then other 4 houres sayled backe agayne ye same way.
Tewsday early in ye morning we entred ye channell ye wind being
[5] weake & calme, & passed by Portsmouth very slowly; but in ye
afternoone ye wind quickened, & wee were forced to ancre a little on this
side Cowcastle but ye wind growing more favourable wee weighed & came
to ancre again right against Cowcastle thinking to stay yt night, ye wind
 being very calme. Here I & my wiffe & my daughter Mary & 2
[May] maids & soe others wth vs obtained of ye mr of ye shipp to go a
shoare to refresh vs & to wash or linnens, & so we lay at Cowes yt night.
But ye wind turning when wee were absent, yy hoysed sayle & left vs there,
& ancred 8 miles further ouer agt Yarmouth about 8 of ye clocke at night.
Wednesday betyme in ye morning ye shalope was sent fro ye shipp
[6] to fetch vs to Yarmouth; but ye water prooued rough & or weomen
desired to bee sett on shoare 3 miles short of Yarmouth, & so went on foote
by land & lodged in Yarmouth yt night.
On Thursday & fryday there Mr Beecher allowed by ye copany
[7. 8.] gaue mee 40s to make or provisio of what things we would for the
voyage.
Saturday we went to board agayne: & this day wee had 2 other
[9] men pressed to serve ye Kings Shippe; but we got one agayne by
intreaty.
The Sabbath next day we kept ye shipp where I preached in ye
[10.] morning; & in ye afternoon was intreated to preach at Yarmouth,
where Mr Meare & captayne Borley entertained vs very kyndly, & earnestly
desyred to bee certified of or safe arrivall in new England, & of ye state of ye
countrey
Monday morning blew a fayre wind fro East S: E: And ye lions
[11] whelpe having taken in all her provisio for passengers, about 3 of ye
clocke in ye afternoone wee hoysed sayle for ye Needles, & by Gods
guidance safely passed yt narrow passage a little after 4 a clocke in ye
afternoone. And being entred into ye sea, fro ye top of ye mast we discerned
4 sayle of shipps lying southward fro vs. But night coming on wee tooke in
or long boate & shalope. And ye next day we had a fayre gale of
[12] Easterly wind yt brought vs towards night as farre as ye Lizzard.
Wednesday ye wind still houlding Easterly, wee came as farre as
[13] ye lands end, in ye vtmost part of Cornewall, & so left or deare natiue
soile of England behind vs; & sayling about 10 leagues further we passed
ye Isles of Sillie & launched ye same day a great way into ye maine ocean.
And now my wiffe & other passengers began to feele ye tossing waues of ye
westerne sea, & so were very sea-sicke.
And this is to be noted, yt all this while or passage hath bene vpo ye coast
of England, & so ought truly to be accounted ye first day of or parting wth
ould England.
 Thursday ye same Easterly wind blew all day & night; & ye next
[14] day; so yt soe of ye seamen thought we were coe by this
tyme 100 leagues fro England, but toward night ye wind was
[15] [May] calme.
Saturday we were becalmed all day. This day met vs a little shipp
[16] of Bristoll yt came fro Christopher Ilands.
Sabath being ye first Lords day we held at sea was very calme,
[17.] especially in the morning, but we were disturbed in or morning
Service by ye approach of a Biskaniers shippe, a man of warre, yt made
towards vs, & manned out his boate to viewe vs: But fynding vs too strong
for him he durst not venture to assault vs, but made off.
This day my 2 children Samuel & Mary began to be sicke of ye small-
pockes & purples together, wch was brought into ye ship by one Mr Browne
wch was sicke of ye same at Graues End, who it pleased God to make ye
first occasio of bringing yt contagious sicknes among vs, wherewth many
were after afflicted.
Monday calme still, ye wind being no: w: blowing a little towards
[18.] euening, but contrary to or course.
Tewsday wind so: w: as little helpfull as ye former & blowing uery
[19.] weake. This day ye mr of or ship, my selfe & another went aboard
the Lions whelpe, where Mr Gibs made vs welcoe wth bountifull
entertaynemt. And this day towards night my daughter grew sicker & many
blew Spots were seene vpo her breast, wch affrighted vs. At ye first wee
thought yy had bene ye plague tokens; but we found afterwards yt it was
onely an high measure of ye infectio of ye pockes, wch were strucke agayne
into ye child, & so it was Gods will ye child dyed about 5 of ye clocke at
night, being ye first in or shipp yt was buried in the bowells of ye great
Atlanticke Sea; wch as it was a griefe to vs her parents, & a sorrow to all ye
rest as being ye beginning of a contagious disease & mortality: so in ye
same judgemt it pleased God to remember mercy in ye child, in freeing it fro
a world of misery wherein otherwise shee had liued all her daies. For being
about 4 yeares ould a yeare since, wee know not by what meanes, sweyed
in ye backe, so yt it was broken & grew crooked, & ye joynts of her hipps
were loosed & her knees went crooked pittifull to see. Since wch tyme shee
hath had a most lamentable payne in her belly, & would oft times cry out in
ye day & in her sleep also my belly, wch declared soe extraordinary
distemper. So yt in respect of her wee had cause to take her death as a
blessing fro ye Lord to shorten her miserie.
 Wednesday a wett morning, ye wind was W: S: W: & in ye
[May 20] afternoone N: W: & by W: both being contrary to or course,
wch was to saile W: & by S: Thus it pleased god to lay his hand vpo vs by
sicknes & death & contrary winds; & stirred vp soe of vs to make ye moton
of humbling or selves vnder ye hand of God by keeping a solemne day of
fasting & prayer unto God, to beseech him to remooue ye continuance &
further increase of these evills fro vs. wch was willingly condescended vnto
as a duty very fitting & needfull for or present state and condicon.
Thursday, there being 2 ministers in ye ship, Mr Smith & my selfe,
[21] we endevoured together wth others to consecrate ye day as a
solemne fasting & humiliacon to almighty God, as a furtheraunce of or
present worke. And it pleased God ye ship was becalmed all day, so yt we
were freed fro any encumbraunce: And as soone as we had done prayers,
see & behould ye goodnes of god, about 7 a clocke at night ye wind turned
to n: e: & we had a fayre gale yt night as a manifest evidence of ye Lords
hearing or prayers. I heard soe of ye mariners say, yy thought this was ye
first sea-fast yt euer was kept, & yt yy neuer heard of ye like perfourmed at
sea before.
Fryday ye wind fayre, & east northerly, & for or purpose for new
[22.] England. it did blow strongly & carried vs on amayne wth tossing
waues, wch did affright ym yt were not wonted to such sights.
[May]
Saturday ye same wind blowing but more gently. Now we were
[23.] coforted wth hope of my sonne Samuels recovery of ye pockes.
The 2 Lords day, a fayre day, an orderly wind & prosperous.
[24.]
On Monday a fayre frummegale, ye wind South S: W:
[25] Tewsday about 10 of ye clocke in ye morning, whilest we were at
prayers a strong and sudden blast came fro ye north, yt hoysed vp
[26.] ye waues & tossed vs more then euer before & held vs all yt day till
towards night & then abated by little & little till it was calme. This
day Mr Goffes great dogg fell ouer board & could not be recouered.
Wednesday, ye wind still no: & calme in ye morning, but about
[27.] noone there arose a So: wind, wch encreased more & more, so yt it
seemed to vs yt are land men a sore & terrible storme; for ye wind blew
mightily, ye rayne fell vehemently, ye sea roared & ye waues tossed vs
horribly; besides it was fearfull darke & ye mariners maid was afraid; &
noyse on the other side wth their running here & there, lowd crying one to
another to pull at this & yt rope. The waues powred ymselues
[May 27]
 ouer ye shippe yt ye 2 boates were filled wth water, yt yy were
fayne to strike holes in ye midst of ym to let ye water out. Yea by ye violence
of ye waues ye long boate coard wch held it was broken, & it had like to haue
bene washed ouerboard, had not ye mariners wth much payne & daunger
recouered ye same. But this lasted not many houres; after which it became
a calmish day. All wch while I lay close & warme in my cabine, but farre fro
hauing list to sleepe wth Jonah; my thoughts were otherwise employed as
ye tyme & place required. Then I saw ye truth of ye Scripture Psal. 107, fro
ye 23 to ye 32. And my feare at this tyme was ye lesse, when I rememberd
what a loving friend of myne, a minister accustomed to sea stormes said to
mee yt I might not be dismayed at such stormes, for yy were ordinary at
seas, & it seeldome falls out yt a shipp perisheth at storms if it haue sea-
roome, wch I ye rather wryte yt others as well as my selfe by ye knowledge
hereof may be encouraged & prepared agt these ordinary sea-stormes.
Thursday So: wind: calme at night: On fryday a boistrous
[28 29] wind blowing crosse, but was allayed towards night wth a
showre of rayne. Saturday So: w: wind, but faire & quiett.
[30]
Sabbath day being ye 3 Lords day, fayre & calme; wee saw
[May 31] abundance of grampas fishes, 2 or 3 yards long, & a body as
bigg as an oxe.
Monday ye wind westerly & calme: but besides or being
[June 1] stayed by contrary winds we began to fynd ye temperature of
ye ayre to alter & to become more soletry & subject to vnwholsome foggs.
For coming now to ye height of ye westerne Islands, soe of or men fell sicke
of ye scuruie & others of the small pockes, wch more & more increased: yet
thankes be to God none dyed of it but my owne child mencond. And
therefore, according to or great need we appointed another fast for the next
day.
Tewsday we solemnely celebrate another fast. The Lord yt day
[2.] heard vs before wee prayed & gaue vs aunswere before we called;
for early in ye morning ye wind turned full East, being as fitt a wind as could
blowe. And sitting at my study on ye shipps poope I saw many bonny fishes
& porpuses pursuing one another, and leaping soe of ym a yard aboue ye
water. Also as we were at prayer, vnder ye hatch, soe yt were aboue saw a
whale puffing vp water not farre fro ye shippe. Now my wiffe was prettily
well recouered of her sea sicknesse.
Wednesday a fayre day & fyne gale of full East wind. This day my
[3.] selfe & others saw a large round fish sayling by ye ships side about a
 yard in length & roundnes euery way. The mariners cald it a
[June] sunne fish; it spreadeth out ye finnes like beames on euery side
4, or 5.
Thursday & fryday ye wind full E: we were carried wth
[4, 5.] admiracon on or journey. By this wee were more then halfe way
to new England. This day I saw a fish very straunge to mee, yy call it a
caruell; wch came by ye ship side wafting along ye top of ye water. it
appeared at ye first like a bubble aboue the water as bigg as a mans fist,
but ye fish it selfe is about ye bignes of a mans thum, so yt ye fish it selfe &
ye bubble resembleth a shipp wth sailes, wch therefore is called a caruell.
Saturday wind direct E: still. The 4 Sabb: we kept at sea the wind
[6 7] full full Easterly till noone, & then it came full So: E: a strong gale yt
night & ye next day till night.
[8]
Tewsday ye same wind held till 9 a clock in ye morning: & then a
[9] great showre wch lasted till about 7 at night, & then it was a very
calme. There we sounded wth a dipled lyne aboue 100th fadome &
found no bottome. This day we saw a fish called a turkle, a great & large
shell fish swiming aboue ye water neere ye shippe.
Wednesday wind northerly a fyne gale but calmish in ye
[10] afternoone.
Thursday ye wind at no: an easye gale & fayre morning we
[11 June] saw a mountayne of Ice shyning as white as snow like to a
great rocke or clift on ye shoare. it stood still & therefore we thought it to be
on ground & to reach ye bottome of ye sea. For though there came a mighty
streame fro ye no: yet it mooued not, wch made vs sound, & we found a
banke of 40 fathom deepe whereupo we judged it to rest: & ye height aboue
was as much. Wee also saw 6 or 7 pieces of Ice, floating on ye sea, wch
was broken off fro ye former mountayne, we also saw great store of water
fowle swiming by ye shipp wthin musket shott, of a pyde colour & about ye
bignes of a wild ducke, about 40 in a copany, the mariners call ym hag
birds. Toward night came a fogge, yt ye lions whelp was lost till morning.
And now we saw many bony toes porpuses and grampases every day
more & more.
Fryday foggie & calmish, ye wind northerly in ye morning, but
[12] about noone it came S: E: a dainty loome gale wch carried vs 6
leagues a watch.

[13]
 Saturday ye same wind till night, & we saw great store of
porpuses & grampases.
The 5th Sabbath, ye same wind, towards noone it began to be
[14] foggie, & then it rained till night we went 4 or 5 leagues a watch.
Monday a fayre day but foggie, ye same wind blowing but
[June 15] wth fresh gale carryed vs 7 leagues a watch. In ye afternoone
it blew harder, so ye sea was rough, & we lost ye sight of ye lions whelpe: it
being foggie we drumed for ym & yy shot off a great piece of ordinance but
we feared not one another.
Tewsday wind So: & by E: foggie till about 10 a clocke while we
[16] were at prayers it cleared vp about an houre, & then we saw ye lions
whelpe distant about 2 leagues southward. wee presently tackt about to
meet her & shee did ye same to meete vs, but before we could get together
a thick fogge came, yt we were long in fynding each other. This day we
sounded divers tymes, & found orselves on another banke, at first 40
fathom, after 36. after 33. after 24. wee thought it to haue bene ye banke
ouer agt chap Sable, but we were deceiued, for we knew not certainly
where we were because of ye fogge. After 3 or 4 houres copany we lost ye
lions whelpe agayne: & beate or drume & shot off a great piece of
ordinaunce & yet heard not of ym. But perceiuing ye banke to grow still yt
shallower we found it 27 & 24 fathoms. Therefore being a fogg & fearing
wee were too neere land we tackt about for sea roome for 2 or 3 watches,
& steered Southeast.
Wednesday very foggie still & wind S: and by w: & sounding
[17] found no bottome yt we could reach.
Thursday wind full w: & contrary to vs. This day a notorious
[18] wicked fellow yt was giuen to swearing & boasting of his former
wickednes bragged yt hee had got a wench wth child before hee came this
voyage & mocked at or daies of fast railing & jesting agt puritans, this fellow
fell sicke of ye pockes & dyed. Wee sounded and found 38 fathom, &
stayed for a little to take soe codfish & feasted orselves merily.
Fryday wind west still, a very fayre cleare day. About 4 a clock in
[19] y afternoone soe went vp to ye top of ye mast, & affirmed to or great
e

cofort yy saw land to ye north eastward.

Saturday wind So: w: a fayre gale: we sounded & found 40, 30,
[20] 22, & a little after no ground.
Sabb: being ye 6th Lords day; wind westerly but fayre & calme.
 Monday wind Easterly a fayre gale. This day wee saw a great
[21] deale of froth not farre fro vs: wee feared it might bee soe breach of
agt some new qvote.[2] Therefore ye mr of or shipp hoised out
[22] water
ye shalop & went wth soe of ye men to see what it was; but found it
onely to bee a froath carried by ye streame.
Tewsday ye wind n: E: a fayre gale. This day we examined
[June 23] 5 beastly Sodomiticall boyes, wch confessed their wickednes
not to bee named. The fact was so fowle wee referred ym to bee punished
by ye governor when we came to new England, who afterward sent ym
backe to ye copany to bee punished in ould England as ye crime deserued.
Wednesday wind no: E: a fayre day & cleare: about 9 a clocke in
[24] y morning we espied a shipp about 4 leagues behind vs; wch
e

prooued ye lions whelpe, wch had bene a weeke separated fro vs. we
stayed for [blot (her)] copany. This day a child of goodman Blacke wch had a
cosumpcon before it came to shipp, dyed. This day we had all a cleare &
cofortable sight of America, & of ye Chap Sable yt was ouer agt vs 7 or 8
leagues northward. Here we saw yellow gilliflowers on ye sea.
Thursday wind still no: Ea: a full & fresh gale. In ye after noone
[25] wee had a cleare sight of many Islands & hills by ye sea shoare.
Now we saw abundaunce of makrill, a great store of great whales puffing
vp water as yy goe, soe of ym came neere or shipp: their greatnes did
astonish vs yt saw ym not before: their backs appeared like a little Island. At
5 a clock at[3] night the wind turned S. E. a fayre gale. This day we caught
mackrill.
Fryday a foggie morning, but after cleare and wind calme. We
[26] saw many scools of mackrill, infinite multitudes on every side our
ship. The sea was abundantly stored with rockweed and yellow flowers like
gilly-flowers. By noon we were within 3 leagues of Capan, and as we
sayled along the coasts we saw every hill and dale and every island full of
gay woods and high trees. The nearer we came to the shoare the more
flowers in abundance, sometymes scattered abroad, sometymes joyned in
sheets 9 or 10 yards long, which we supposed to be brought from the low
meadowes by the tyde. Now what with fine woods and greene trees by
land, and these yellow flowers paynting the sea, made us all desirous to
see our new paradise of New England, whence we saw such forerunning
signals of fertilitie afarre off. Coming neare the harbour towards night we
takt about for sea-roome.
 Saturday a foggie morning; but after 8 o’clocke in the morning
[27] very cleare, the wind being somewhat contrary at So. and by West,
we tackt to and againe with getting little; but with much adoe, about 4
o’clock in the afternoone, having with much payne compassed the harbour,
and being ready to enter the same, see how things may suddenly change!
there came a fearfull gust of wind and rayne and thunder and lightning,
whereby we were borne with no little terrour and trouble to our mariners,
having very much adoe to loose downe the sayles when the fury of the
storme held up. But God be praised it lasted but a while and soone abated
agayne. And hereby the Lord shewed us what he could have done with us,
if it had pleased him. But blessed be God, he soone removed this storme
and it was a fayre and sweet evening.
We had a westerly wind which brought us between 5 and 6 o’clock to a
fyne and sweet harbour,[4] 7 miles from the head point of Capan. This
harbour 20 ships may easily ryde therein, where there was an island
whither four of our men with a boate went, and brought backe agayne ripe
strawberries and gooseberries, and sweet single roses. Thus God was
merciful to us in giving us a tast and smell of the sweet fruit as an earnest
of his bountiful goodnes to welcome us at our first arrivall. This harbour was
two leagues and something more from the harbour at Naimkecke, where
our ships were to rest, and the plantation is already begun. But because
the passage is difficult and night drew on, we put into Capan harbour.
The Sabbath, being the first we kept in America, and the 7th
[28] Lord’s day after we parted with England.
Monday we came from Capan, to go to Naimkecke, the wind
[29] northerly. I should have tould you before that the planters spying our
English colours the Governour sent a shalop with 2 men on Saturday to
pilot us. These rested the Sabbath with us at Capan; and this day, by God’s
blessing and their directions, we passed the curious and difficult entrance
into the large spacious harbour of Naimkecke. And as we passed along it
was wonderful to behould so many islands replenished with thicke wood
and high trees, and many fayre greene pastures. And being come into the
harbour we saw the George to our great comfort then being come on
Tuesday which was 7 daies before us. We rested that night with glad and
thankful hearts that God had put an end to our long and tedious journey
through the greatest sea in the world.
The next morning the governour came aboard to our ship, and
[30] bade us kindly welcome, and invited me and my wiffe to come on
shoare, and take our lodging in his house, which we did accordingly.
 Thus you have a faithful report collected from day to day of all the
particulars that were worth noting in our passage.

Now in our passage divers things are remarkeable.

First, through God’s blessing our passage was short and speedy, for
whereas we had 1000 leagues, that is 3000 miles English, to saile from
Ould to New England, we performed the same in 6 weeks and 3 dayes.
Secondly, our passage was comfortable and easie for the most part,
having ordinarily fayre and moderate wind, and being freed for the most
part from stormie and rough seas, saving one night only, which we that
were not used thought to be more terrible than indeed it was, and this was
Wednesday at night May 27th.
Thirdly, our passage was also healthfull to our passengers, being freed
from the great contagion of the scurvie and other maledictions, which in
other passages to other places had taken away the lives of many. And yet
we were in all reason in wonderful danger all the way, our ship being
greatly crowded with passengers; but through God’s great goodness we
had none that died of the pockes but that wicked fellow that scorned at
fasting and prayer. There were indeed 2 little children, one of my owne and
another beside; but I do not impute it meerely to the passage; for they were
both very sickly children, and not likely to have lived long, if they had not
gone to sea. And take this for a rule, if children be healthfull when they
come to sea, the younger they are the better they will endure the sea, and
are not troubled with sea-sicknes as older people are, as we had
experience in many children that went this voyage. My wiffe indeed, in
tossing weather, was something ill by vomiting, but in calme weather she
recovered agayne, and is now much better for the sea sicknes. And for my
owne part, whereas I have for divers yeares past been very sickly and
ready to cast up whatsoever I have eaten, and was very sicke at London
and Gravesend, yet from the tyme I came on shipboard to this day, I have
been straungely healthfull. And now I can digest our ship diett very well,
which I could not when I was at land. And indeed in this regard I have great
cause to give God praise, that he hath made my coming to be a method to
cure me of a wonderful weake stomacke and continual payne of
melancholly wynd from the splene: Also divers children were sicke of the
small pockes, but are safely recovered agayne, and 2 or 3 passengers
towards the latter end of the voyage fell sicke of the scurvie, but coming to
land recovered in a short tyme.
Fourthly, our passage was both pleasurable and profitable. For we
received instruction and delight in behoulding the wonders of the Lord in
the deepe waters, and sometimes seeing the sea round us appearing with
a terrible countenance, and as it were full of high hills and deepe vallyes;
and sometimes it appeared as a most plain and even meadow. And ever
and anon we saw divers kynds of fishes sporting in the great waters, great
grampuses and huge whales going by companies and puffing up water-
streames. Those that love their owne chimney corner, and dare not go farre
beyond their owne townes end shall neever have the honour to see these
wonderfull workes of Almighty God.
Fifthly, we had a pious and christian-like passage; for I suppose
passengers shall seldom find a company of more religious, honest and
kynd seamen than we had. We constantly served God morning and
evening by reading and expounding a chapter, singing, and prayer. And the
Sabbath was solemnely kept by adding to the former, preaching twise and
catechising. And in our great need we kept 2 solemne fasts, and found a
gracious effect. Let all that love and use fasting and praying take notise that
it is as prevaileable by sea as by land, wheresoever it is faithfully
performed. Besides the ship master and his company used every night to
sett their 8 and 12 a clocke watches with singing a psalme and prayer that
was not read out of a booke. This I wryte not for boasting and flattery; but
for the benefit of those that have a mynd to come to New England
hereafter, that if they looke for and desyre to have as prosperous a voyage
as we had, they may use the same meanes to attayne the same. So letting
passe our passage by sea, we will now bring our discourse to land on the
shoare of New England, and I shall by God’s assistance endeavour to
speake nothing but the naked truth, and both acquaint you with the
commodities and discommodities of the country.
NEW-ENGLANDS PLANTATION
&c.
 NEW-ENGLANDS
PLANTATION
OR,
A S H O RT A N D T RV E
DESCRIPTION OF THE
CO MMO DIT IES AND
DISCOMMODITIES
o f t h a t C o u n t r e y.

Written by Mr Higgeson, a reuerend

Diuine now there resident.

Whereunto is added a Letter, sent by

r
M Graues an Enginere, out of New England.
The third Edition, enlarged.

L O ND O N.
Printed by T. and R. Cotes for Michael Sparke,
dwelling at the Signe of the Blue Bible in
Greene-Arbor, 1630.
 To the Reader.
REader, doe not disdaine to reade this Relation: and looke not here
to haue a large Gate and no building within: a full-stuffed Tittle with
no matter in the Booke: But here reade the truth, and that thou shalt
find without any frothy bumbasting words, or any quaint new-deuised
additions, onely as it was written (not intended for the Presse) by a
reuerend Diuine now there liuing, who onely sent it to some Friends
here, which were desirous of his Relations; which is an Epitomy of
their proceedings in the Plantation. And for thy part if thou meanest
to be no Planter nor Venturer doe but lend thy good Prayers for the
furtherance of it. And so I rest a Well-Wisher to all the good designes
both of them which are gone, and of them that are to goe.
M. S.
 NEW-ENGLANDS
PLANTATION.
LEtting passe our Voyage by Sea, we will now begin our discourse
on the shore of New-England. And because the life and wel-fare of
euery Creature heere below, and the commodiousnesse of the
Countrey whereas such Creatures liue, doth by the most wise
ordering of Gods prouidence, depend next vnto himselfe, vpon the
temperature and disposition of the foure Elements, Earth, Water,
Aire, and Fire (For as of the mixture of all these, all sublunary things
are composed; so by the more or lesse injoyment of the wholesome
temper and conuenient vse of these, consisteth the onely well-being
both of Man and Beast in a more or lesse comfortable measure in all
Countreys vnder the Heauens) Therefore I will indeauour to shew
you what New-England is by the consideration of each of these
apart, and truly indeauour by Gods helpe to report nothing but the
naked truth, and that both to tell you of the discommodities as well
as of the commodities, though as the idle Prouerbe is, Trauellers
may lye by autoritie, and so may take too much sinfull libertie that
way. Yet I may say of my selfe as once Nehemiah did in another
case: Shall such a Man as I lye? No verily: It becommeth not a
Preacher of Truth to be a Writer of Falshod in any degree: and
therefore I haue beene carefull to report nothing of new England but
what I haue partly seene with mine owne Eyes, and partly heard and
inquired from the mouths of verie honest and religious persons, who
by liuing in the Countrey a good space of time haue had experience
and knowledge of the state thereof, & whose testimonies I doe
beleeue as my selfe.
 First therefore of the Earth of New-England and all the
appertenances thereof: It is a Land of diuers and sundry sorts all
about Masathulets Bay, and at Charles Riuer is as fat blacke Earth
as can be seene any where: and in other places you haue a clay
soyle, in other grauell, in other sandy, as it is all about our Plantation
at Salem, for so our Towne is now named, Psal. 76. 2.
The forme of the Earth here in the superficies of it is neither too
flat in the plainnesse, nor too high in Hils, but partakes of both in a
mediocritie, and fit for Pasture, or for Plow or meddow ground, as
Men please to employ it: though all the Countrey bee as it were a
thicke Wood for the generall, yet in diuers places there is much
ground cleared by the Indians, and especially about the Plantation:
and I am told that about three miles from vs a Man may stand on a
little hilly place and see diuers thousands of acres of ground as good
as need to be, and not a Tree in the same. It is thought here is good
Clay to make Bricke and Tyles and Earthen-Pot as need to be. At
this instant we are setting a Bricke-Kill on worke to make Brickes and
Tyles for the building of our Houses. For Stone, here is plentie of
Slates at the Ile of Slate in Masathulets Bay, and Lime-stone, Free-
stone, and Smooth-stone, and Iron-stone, and Marble-stone also in
such store, that we haue great Rocks of it, and a Harbour hard by.
Our Plantation is from thence called Marble-harbour.
Of Minerals there hath yet beene but little triall made, yet we are
not without great hope of being furnished in that Soyle.
The fertilitie of the Soyle is to be admired at, as appeareth in the
aboundance of Grasse that groweth euerie where both verie thicke,
verie long, and verie high in diuers places: but it groweth verie wildly
with a great stalke and a broad and ranker blade, because it neuer
had been eaten with Cattle, nor mowed with a Sythe, and seldome
trampled on by foot. It is scarce to be beleeued how our Kine and
Goats, Horses and Hogges doe thriue and prosper here and like well
of this Countrey.
In our Plantation we haue already a quart of Milke for a penny: but
the aboundant encrease of Corne proues this Countrey to bee a
wonderment. Thirtie, fortie, fiftie, sixtie are ordinarie here: yea