Ocular Immunology and Inflammation

ISSN: 0927-3948 (Print) 1744-5078 (Online) Journal homepage: http://www.tandfonline.com/loi/ioii20

Clinical Manifestations of Ocular Toxoplasmosis

Emmanuelle Delair, Paul Latkany, A. Gwendolyn Noble, Peter Rabiah, Rima

McLeod & Antoine Brézin

To cite this article: Emmanuelle Delair, Paul Latkany, A. Gwendolyn Noble, Peter Rabiah,
Rima McLeod & Antoine Brézin (2011) Clinical Manifestations of Ocular Toxoplasmosis, Ocular
Immunology and Inflammation, 19:2, 91-102, DOI: 10.3109/09273948.2011.564068

To link to this article: http://dx.doi.org/10.3109/09273948.2011.564068

Published online: 23 Mar 2011.

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 Ocular Immunology & Inflammation, 19(2), 91–102, 2011
Copyright © 2011 Informa Healthcare USA, Inc.
ISSN: 0927-3948 print/ 1744-5078 online
DOI: 10.3109/09273948.2011.564068

Original Article

Clinical Manifestations of Ocular Toxoplasmosis

Emmanuelle Delair, MD1, Paul Latkany, MD2, A. Gwendolyn Noble, MD PhD3, Peter
Rabiah, MD4, Rima McLeod, MD5, and Antoine Brézin, MD PhD1
Université Paris Descartes, Service d’Ophtalmologie, Hôpital Cochin, Paris, France, 2New York Eye and Ear Institute,
1

New York University, New York, New York, USA, 3Northwestern University Children’s Memorial Hospital and the
University of Chicago, Chicago, Illinois, USA, 4Northshore University Health System and the University of Chicago,
Chicago, Illinois, USA, and 5The University of Chicago, Chicago, Illinois, USA

Abstract
Downloaded by [Florida Gulf Coast University] at 05:04 06 August 2017

Clinical manifestations of ocular toxoplasmosis are reviewed. Findings of congenital and acute acquired ocular
toxoplasmosis include retinal scars, white-appearing lesions in the active phase often associated with vitritis.
Complications can include fibrous bands, secondary serous or rhegmatogenous retinal detachments, optic
neuritis and neuropathy, cataracts, increased intraocular pressure during active infection, and choroidal neo-
vascular membranes. Recurrences in untreated congenital toxoplasmosis occur in teenage years. Manifestations
at birth are less severe, and recurrences are fewer in those who were treated promptly early in the course
of their disease in utero and in the first year of life. Severe retinal involvement is common at diagnosis of
symptomatic congenital toxoplasmosis in the United States and Brazil. Acute acquired infections also may be
complicated by toxoplasmic retinochoroiditis, with recurrences most common close to the time of acquisition.
Suppressive treatment can reduce recurrent disease.

Keywords  CNVM, congenital toxoplasmosis, rétinal choriditis, Toxoplasma gondii, uveitis

1. Clinical Manifestations of with macular lesion, while peripheral lesions may

Ocular Toxoplasmosis in Typical
Forms
1.1. Symptoms and Consequences of Loss of
Visual Function
Visual symptoms and signs linked to toxoplasmosis
depend on the localization of lesions.1-7 While verbal
children and adults may promptly request an ophthal-
mic examination upon the perception of symptoms,
the diagnosis of ocular toxoplasmosis may be delayed
in preverbal children, and not all older children and
adults recognize the symptoms when they are not
in the posterior pole or associated with a substantial
inflammatory response. Hence, routine follow-up
examinations, not prompted solely by reported
symptoms or signs for persons with congenital and
postnatal ocular toxoplasmosis, are needed to assess
lesions. Major visual impairment may be observed
have no easily detectable effect on vision.2,8-10 Optic
neuritis or optic nerve involvement may result in
visual field defects or loss of color vision.
In active lesions, vitreous inflammation is usually
the first factor leading to symptoms, but a scotoma
or diminished visual acuity may also be the first
symptom leading to the diagnosis. In inactive lesions,
scotomas are directly related to the size and location
of retinochoroidal scars. As vitreous opacities may
persist after active inflammation of the posterior seg-
ment, it may be difficult for patients with poor vision
to distinguish floaters linked to persistent vitreous
opacities from signs of a recurrent active vitritis. For
patients with normal vision, floaters may be easily
distinguishable when they are newly occurring.
Use of an Amsler grid daily by those with retinal
scars can result in early detection of an active retin-
ochoroiditis (Noble et al., unpublished observations,
2010). A vision test can substitute for the Amsler grid

Received 02 February 2011; revised 08 February 2011; accepted 10 February 2011

Correspondence: Rima McLeod, MD, Professor, The University of Chicago, N310, MC 2114, 5841 S. Maryland, Chicago, IL 60637,
USA, E-mail: 7rmcleod@uchicago.edu; or Antoine P. Brézin, MD, PhD, Université Paris Descartes, Centre Cochin Ambulatoire
d’Ophtalmologie, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France, E-mail: antoine.brezin@cch.aphp.fr

91
 92    E. Delair et al.
in younger children. For lesions outside the central 10
degrees, an Amsler grid may not be as useful in detect-
ing new lesions.
1.2. Anterior Uveitis
The severity of anterior uveitis can range from a quiet
anterior chamber to intense anterior uveitis masking
inflammation of the posterior segment and can be either
granulomatous or nongranulomatous inflammation. If
the diagnosis is delayed, prolonged inflammation of the
anterior chamber may lead to irreversible iris synechiae.
In a study of 210 patients with active toxoplasmic retin-
ochoroiditis, intraocular inflammation was more intense
in older patients and increased with the size of areas of
retinochoroiditis and in peripheral lesions.11 Secondary
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ocular hypertension was associated with inflammation
of the anterior segment and occurred in 30% of cases.
Overall, more intense inflammation may be observed
in cases of ocular toxoplasmosis in patients from cer-
tain areas of Central and South America. Also, intense
anterior inflammation may occur secondary to the retin-
ochoroiditis near the ora serrata, which may be missed
on initial examination.
1.3. Cataracts
In children with congenital toxoplasmosis, cataracts
may occur as a complication of retinochoroiditis and
Figure 1  (A) Severe vitritis that is less intense than the classic “headlight in fog” appearance (left). Resolving vitritis caused by under-
lying active lesion (middle). Resolved healed lesion without vitritis (right). (B) Typical form of ocular toxoplasmosis. Active whitish
retinochoroiditis, satellite of a pigmented scar.
may follow severe iridocyclitis. In a study of 173
patients, cataracts occurred in 11.6% of these patients
(27 eyes of 20 patients).12 The cataracts vary in onset,
location, complexity, and progression.12 Cataracts were
most commonly found in children with the most severe
intraocular disease (e.g., retinal detachment) and no
intervention was performed. However, cataracts may
cause severe amblyopia in children and may need to be
removed surgically. It appears to be prudent to admin-
ister antiparasitic medication during surgery to prevent
reactivation of chorioretinitis.12
1.4.Vitritis
Inflammation of the vitreous is usually more intense
near the active retinochoroiditis. However, there may be
no vitritis if the retinal inflammation does not extend to
the inner limiting membrane. In cases of intense vitritis,
epiretinal membranes may develop and vitreoretinal
traction adjacent to the area of retinochoroiditis may
occur. The intensity of the vitritis also appears to reflect
duration of the process prior to diagnosis and treat-
ment, with longer intervals before treatment is initiated
associated with more intense inflammatory response.
“Headlight in the fog” was a phrase for severe vitritis
coined by Richard O’Connor to describe a bright white
reflex seen when one shines the light of the indirect
opthalmoscope into the back of the eye. Figure 1A is an
example of severe vitritis but not as severe as the classic
“headlight in the fog” description. This resolved with
Ocular Immunology & Inflammation
 Clinical manifestations of ocular toxoplasmosis    93

treatment so the underlying active focus then scar are
apparent.
1.5. Fundus Examination
In typical cases active lesions are seen as whitish foci
of retinochoroiditis, without well-limited borders,
frequently adjacent to a pigmented and/or atrophic
scar (Figure 1B). Vasculitis may also be remote from
the lesion. When retinal vessels are close to the lesion,
signs of vasculitis contiguous to the lesion may be seen
(Figure 2). Peri-phlebitis is more frequent than arteritis
and retinal hemorrhages can also be seen. In some cases
with very intense inflammation, vasculitis may be gen-
eralized to retinal areas distant from the primary site of
retinochoroiditis.
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periphery to the center of the lesion, usually leading to
pigmentation (Figure 3A, B). The average time for the
scarring of an active toxoplasmic area of retinochoroidi-
tis often appears to be related to function of the lesion
size and resolution often occurs in approximately 3–4
weeks. With prompt diagnosis and treatment, lesions
may resolve more rapidly and even heal without creat-
ing a scar (Figure 3C left, right).10 Resolution of active
toxoplasmic retinochoroiditis in treated newborn infants
over the first weeks of life and in children also can occur
with rapid initiation of treatment. Figure 3D shows pho-
tographs of the retina of a newborn infant with active
vitritis (left, labeled “near birth”) with clearing of vitritis
and marked but not yet complete resolution of activity
of the lesion 3 weeks later (right, labeled “with ongoing
treatment”).

An active retinochoroidal lesion usually results in an

atrophic retinochoroidal scar, which resolves from the 1.6 Toxoplasma Serology

Confirmation of serologic evidence of T.gondii infec-

tion is an essential part of establishing the diagnosis
of ocular toxoplasmosis. This allows one to suspect the
diagnosis in conjunction with the typical appearance
of the eye lesions. Presence of T.gondii-specific serum
antibody is consistent with and supports the diagnosis
of ocular toxoplasmosis but does not prove it; it just
establishes that the person has the infection.

1.7. Fluorescein Angiography

Photographs of the fundus are useful to document

lesions and to longitudinally assess the evolution of
Figure 2  Scarred and active ocular toxoplasmosis with contigu-
ous vasculitis. lesion, particularly in cases of recurrences. Fluorescein

Figure 3  Follow-up of a toxoplasmic lesion. (A) Active lesion at presentation. (B) Scarred lesion. (C) Active retinal lesion before (left)
and completely resolved normal appearing retina within a month of initiating treatment (right). Adapted from McLeod et al.10 with per-
mission. (D) Retina photographs for newborn infant with active vitritis (left, labeled “near birth”) with clearing of vitritis and marked
but not yet complete resolution of activity of the lesion 3 weeks later (right, labeled “with ongoing treatment”).

© 2011 Informa Healthcare USA, Inc.

 94    E. Delair et al.

angiography can show signs useful to confirm lesion
activity. In some instances small, early active lesions may
be difficult to detect at the edge of an older scar, fluores-
cein angiography may be useful to confirm the diagno-
sis. In typical cases of active disease, a masking lesional
effect at the early phase of the angiography is observed,
followed by hyperfluorescence progressing from the
periphery of the lesion to its center (Figure 4). Vasculitis
contiguous to the lesion is seen as hyperfluorescence of
the vessel walls, which increases in magnitude in the late
phase of the angiography. Scarred quiescent pigmented
lesions have a persistent masking effect, often bordered
by a hyperfluorescent line. Papillitis is frequently seen as
an early staining of the disc, with increasing and lasting
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hyperfluorescence. Cystoid macular edema, even distant
from the active lesion of retinochoroiditis, can be a com-
plication of severe inflammation.
1.8. Optical Coherence Tomography
Scarred areas of retinochoroiditis are characterized
by retinal atrophy at the site of lesions (Figure 5).
Optical coherence tomography is also useful to detect
retinal edema, to quantify subtle serous retinal detach-
ment, which can be triggered by active retinochor-
oiditis (Figure  6), or to detect subretinal new vessel
formation.

Figure 4  Ocular toxoplasmosis with retinal artery occlusion: (A) color fundus photograph, fluorescein angiography; (B) early phase;
(C) late phase.

A C

B D D + )1.00 )2.22 )3,45[mm]

Max Display Dia: 3.45[mm]

246

224

271 254 179 207 231

241

239

150 200 250 300 350 400 450 500 µm

Figure 5  OCT imaging of scarred toxoplasmic lesions and fluorescein angiography. (A) OCT fundus image. (B) Late-phase fluorescein
angiography. (C) OCT imaging showing a retinal thinning at the site of the toxoplasmic scar. (D) OCT thickness map showing areas of
retinal thinning.

Ocular Immunology & Inflammation

 Clinical manifestations of ocular toxoplasmosis    95

2. Rare, Atypical, or Complicated recently treated by intravitreal anti-VEGF therapy with

Forms of Ocular Toxoplasmosis resolution of the choroidal neovascular membrane
(CNVM) and brisk resolution of associated choriore-
2.1. Optic Neuropathy tinitis (Figure 8, bottom) 16,17

The diagnosis of ocular toxoplasmosis is difficult in the

presence of papillitis without other characteristic signs
of retinochoroidal inflammation. Whitish inflammatory
lesions located on the disc with associated vitritis sug-
gest the diagnosis.13 Such lesions located on the disc
border are responsible for visual defects occasionally
referred to as Jensen scotoma (Figure 7).
2.2. Neovascularization
2.3. Retinal Vascular Occlusions
Vein or retinal vascular occlusions may be a compli-
cation of ocular toxoplasmosis (Figure 9). The site of
occluded vessels may directly overlie the area of active
retinochoroiditis or may be contiguous to the lesion.18–20
Fluorescein angiography is useful to confirm the diag-
nosis and to assess the consequences of the retinal vas-
cular occlusion.

Subretinal neovascularization may be a complication

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of toxoplasmic retinochoroiditis (Figure 8, top).14,15 In 2.4. Epiretinal Membranes

addition to fluorescein angiography, indocyanine green
angiography may be useful to visualize the neovascu-
lar membrane. In some instances neovascularization
may regress once inflammation has resolved. In other
instances persistent neovascular membranes histori-
cally may require surgical removal but have been more
Epiretinal membranes can be a complication of a pro-
longed vitritis and are usually attached to or near areas
of retinochoroiditis (Figure 10). Secondary tractions
may be responsible for retinal tears, vitreo-macular
traction with metamorphopsia, and macular edema.

D + )1.00 )2.22 )3,45[mm]

Max Display Dia: 3.45[mm]

306

349

372 440 364 291 304

425

451

150 200 250 300 350 400 450 500 µm

D

Figure 6  OCT,color fundus photograph and fluorescein angiography imaging of ocular toxoplasmosis with serous detachment of the
retina. (A) Color fundus photograph of an active lesion satellite of a toxoplasmic scar. (B) Late phase fluorescein angiography showing
a serous detachment of the retina. (C) OCT imaging of serous retinal detachment. (D) OCT thickness mapping showing of the serous
retinal detachment.

© 2011 Informa Healthcare USA, Inc.

 96    E. Delair et al.

Figure 7  Peripapillary scarred retinochoroiditis. 7A: Fundus photograph. 7B: Goldmann perimetry showing a Jensen’s scotoma.
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Figure 8  (Top) Ocular toxoplasmosis with submacular neovascular membrane: (A).fundus photograph; (B) indocyanin green angiog-
raphy. (Bottom) Choroidal neovascular membrane with hemorrhage presenting with acute loss of vision, which resolved with treatment
with pyrimethamine, sulfadiazine, and intraocular injection of lucentis. Adapted from Benevento et al.16 with permission.

Ocular Immunology & Inflammation


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Figure 9  Ocular toxoplasmosis with retinal vessel occlusion:
(A) arterial occlusion; (B) vein occlusion.
These cases have sometimes been treated with surgi-
cal removal of epiretinal membranes after the active
phase of retinochoroiditis with a favorable visual
outcome.21
2.5. Serous Retinal Detachments
Serous retinal detachments are a complication of retin-
ochoroiditis. Vitritis is usually moderate in these cases.
Serous detachments may extend distally from the area
of retinochoroiditis and be responsible for decreased
visual acuity when they reach the macula. Fluorescein
angiography and optical coherence tomography (OCT)
may be useful to confirm the diagnosis. Angiograms
show an early fluorescence masking and a late-phase
staining. OCT is particularly useful to monitor reattach-
ment of subtle serous exudation.
2.6. Retinal Detachments
Retinal tears may be located near active or scarred
foci of retinochoroiditis. In other instances, including
after intense and prolonged vitritis, vitreoretinal trac-
tion strands or tractional retinal detachments may be
observed (Figure 11).22,23
© 2011 Informa Healthcare USA, Inc.
Clinical manifestations of ocular toxoplasmosis    97
Figure 10  Ocular toxoplasmosis with secondary epiretinal
membrane.
Figure 11  Secondary tractional retinal detachment with a large
area of toxoplasmic retinochoroiditis.
3. The Special Problem of
Congenital Ocular Toxoplasmosis
in the United States and Brazil
When There Is No Prenatal
Diagnosis and Early Treatment
as Contrasted with Ocular
Manifestations in France Where
There Is Prenatal Diagnosis and
Early Treatment of the Fetus by
Treatment of the Mother
Time of detection, treatment, and parasite and host
genetics modify initial presentations. In the United
States, congenital toxoplasmosis is most often diagnosed
by detection of severe signs and symptoms in the new-
born infant in the absence of any systematic prenatal
diagnosis and treatment.2-6,9,24–26 Only Massachusetts and
New Hampshire have a postnatal screening program.27
In a cohort study of children diagnosed at birth, severe
involvement was common at routine ophthalmologic
examinations. Findings are summarized in Table 1.2
Macular lesions were predominant. Although not
widely appreciated by ophthalmoligists, visual acu-
ity may be remarkably good with macular scars.2,9
 98    E. Delair et al.

1,00 1,00

fraction without ocular lesions

fraction without ocular lesions

0,95

0,95
0,90

0,85
0,90

0,80

0,75 0,85
0 6 12 18 24 0 6 12 18 24
age in months age in months

Figure 12  New eye lesions in children who had <8 or ≥8 weeks delay from diagnosis in utero to treatment. (A) Kaplan-Meier plots show-
Downloaded by [Florida Gulf Coast University] at 05:04 06 August 2017

ing the age at diagnosis of a first retinochoroiditis according to the delay between maternal infection and first treatment: <4 weeks (solid
line), 4–8 weeks (dashed line), and >8 weeks (dotted line). (B) Kaplan-Meier estimate of the age at diagnosis of a first retino-choroiditis
during the first 2 years of life among 300 infants. Adapted from Kieffer et al.10 with permission.

Table 1  Ophthalmologic manifestations of congenital toxoplasmosis.

No. of treated patients with No. of historical patients with Total no. of patients with
finding (%) (NO. = 76) finding (%) (NO.= 18) finding (%) (NO. = 94)
Strabismus 26 (34) 5 (28) 31 (33)
Nystagmus 20 (26) 5(28) 25 (27)
Microphthalmia 10(13) 2(11) 12(13)
Phthisis 4(5) 0(0) 4(4)
Microcornea 15 (20) 3(17) 18(19)
Cataract 7 (9) 2(11) 9(10)
Vitritis (active) 3 (4)* 2(11) 5(5)
Retinitis (active) 6(8) 4 (22) 10(11)
Chorioretinal scars 56 (74) 18(100) 74 (79)
Macular 39/72 (54)’ 13/17(76) 52/89 (58)
Juxtapapillary 37/72 (51) 9/17(53) 46/89 (52)
Peripheral 43/72 (58) 14/17(82) 57/89 (64)
Retinal detachment 7(9) 2(11) 9(10)
Optic atrophy 14(18) 5 (28) 19(20)
*Two additional patients, not included in this table, were receiving treatment and retinochoroiditis had resolved, but vitreous cells and
veils persisted at time of examination.
‘Numerator represents number of patients with finding; denominator is the total number, unless otherwise specified. Number in
parentheses is percentage. Patients with bilateral retinal detachment in whom the location of scars was not possible were excluded
from the denominator. Adapted with permission from Mets et al2.

This likely reflects the depth of lesions and degree of
involvement of the fovea, as shown by a study of some
of these patients with OCT9 and in a larger unpub-
lished experience (Latkany, Noble, Rabiah, McLeod
et al, manuscript in preparation, 2011). Occlusion treat-
ment for amblyopia may markedly improve visual
acuity with substantial macular scars (Noble, Menon,
Rabiah, McLeod, et  al., manuscript in preparation).
In the Massachusetts screening program, 19% of the
infants detected had retinal disease.27 Examinations
were at different sites and by different examiners and
not documented with photographs. In Belo Horizointe,
Brazil in a widespread newborn screening program,
50% of the ~200 children had ocular lesions during a
7-month period, reflecting the endemic high incidence
of congenital toxoplasmosis; 50% of the infants had
active retinochoroiditis at birth.28
In contrast to this, in France with systematic prena-
tal treatment, and perhaps also reflecting differences
in parasite and human genetics of those infected or
other influences on well-being during gestation, active
disease and central locations of lesions are rare,29–38 as
are other signs of active disease. This was not always
the case in France. Reviewing the earlier literature,
Couvreur and Desmonts noted 76% of the infants
born had retinal disease before prenatal diagnosis and
treatment were introduced in France.39–45 In a newborn
screening program in Denmark, a similar proportion
infants had retinal disease at birth. A brief period of
treatment (3 months, doses of medicines not specified)

Ocular Immunology & Inflammation


was not sufficient to prevent later disease.46 In the study
in Paris, in the time before initiating treatment of the
fetus, treating the mother significantly modified the rate
of subsequent recurrences in the infants and children up
to the age of 2 years (Figure 12).
4. Clinical Characteristics of
Acquired Ocular Toxoplasmosis
In three large series of ocular toxoplasmosis of acute
acquired origin, the age of patients ranged from 12 to
83 years, with a mean of 56.3 years.47–49 The lack of pig-
mented scar tissue, near or distant to the site of active
retinochoroiditis, is typically associated with postnatally
acquired active toxoplasmic retinochoroiditis. Serologic
testing can confirm the acute acquired infection.
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In postnatally acquired toxoplasmosis, as in congeni-
tal toxoplasmic retinochoroiditis, recurrent lesions also
can be located remote from scarred lesions, although
new lesions are often located as satellites of pigmented
congenital toxoplasmic scars. The average lesion size
may be larger, greater than 3–4 disc diameters, in
acquired infections. Retinochoroidal lesions are more
frequently bilateral in congenital infections.50 Cases
of intermediate uveitis have been reported in rela-
tion with activity of acquired toxoplasmosis. In these
cases, lesions located near the ora serrata can be dif-
ficult to detect and may be missed on initial fundus
examinations.51
In the United States in mothers of congenitally
infected children, 7.7% had retinal lesions consistent
with toxoplasmic retinal scars, although none threat-
ened vision. In this series of 130 mothers of 173 chil-
dren, 7.7% of mothers had retinal lesions consistent with
toxoplasmosis.52
5. Course of Ocular Toxoplasmosis
The natural course of ocular toxoplasmosis as well as
its visual prognosis depends on the frequency for recur-
rences and rapidity with which active disease is treated
so destruction of the retina is minimized.2,9,25,26,38,53,54 In a
study with a 5-year follow-up after an active toxoplas-
mic retinochoroiditis, a recurrence was observed in 79%
of patients.55 The mean time between two recurrences
was 3 years (range 2 months to 25 years). Among 274
active episodes of ocular toxoplasmosis, 78% occurred
in patients aged 15–45 years, with a peak frequency
around the age of 25 years. Recurrences sometimes
occurred in the contralateral eye, e.g., in 15% of cases.
When recurrences occurred in the same eye the active
lesion was usually located near a scarred lesion. In the
U.S. cohorts, peaks of incidence occurred at about 6–7
years and in adolescence (~10–15 years), which was
similar to those in the cohort described by Binquet
et al.38
© 2011 Informa Healthcare USA, Inc.
Clinical manifestations of ocular toxoplasmosis    99
In the prospective study of children in the United
States with congenital toxoplasmosis treated in
infancy, the frequency of new retinochoroiditis lesions
was 31% over a 25-year follow-up. In children with
moderate or severe involvement at birth treated dur-
ing their first year of life it was 34%.25 The incidence
was 10% for those with no evidence of disease at
birth. It was 14% for those with mild involvement at
birth.26 Lesions were central in 14% of children and
peripheral in 25% of cases. New lesions were more
frequently observed from 5 to 7 years and in teenag-
ers (between 15 and 20 years). In untreated patients,
the frequency of new lesions was 72%, with central
lesions in 52% of cases and peripheral lesions in 45%
of cases26 (Figure 13).
In a longitudinal study, the rate of recurrences has
been shown to decrease with time after an episode
of active ocular toxoplasmosis.56 The relative risk for
a recurrence decreased by 72% each decade after an
active toxoplasmic retinochoroiditis. The recurrence
risk was lesser if the first attack occurred later in life,
with a 15% decrease by decade of age at the time of
the first episode. In a study in Brazil, recurrences
were most frequent closer to the time of initial acqui-
sition.56 Recurrences were effectively suppressed with
trimethoprim–sulfamethoxazole (TMP-SMX), but this
treatment had a relatively high rate of hypersensitivity
associated with the SMX.57
7. Susceptibility Genes for Ocular
Toxoplasmosis
Certain genes—e.g., a gene that transports retinylidene
ethanolamine outside rod cells, which is associated with
susceptibility to macular degeneration, and a collagen
gene that is associated with Stickler disease—also have
susceptibility alleles for retinochoroiditis in those with
congenital toxoplasmosis.58 This observation has not
yet been used to predict susceptibility to ocular toxo-
plasmosis but it is possible that it may be useful in this
manner in the future.
8. Conclusions
Typical and atypical findings of congenital and acute
acquired ocular toxoplasmosis include retinal scars,
white-appearing lesions in the active phase often
associated with vitritis when active. Complications
can include fibrous bands, secondary serous or
rhegmatogenous retinal detachments, optic neuri-
tis and neuropathy, cataracts, increased intraocular
pressure during active infection, and choroidal neo-
vascular membranes. Recurrences appear to be the
rule in untreated congenital toxoplasmosis25,26,52–54
and these often occur in the teenage years.25,26,38
Manifestations at birth appear to be much less
 100    E. Delair et al.

0.8 Number of person All Lesions 0.8 Number of person All Lesions
-years at each visit: Central -years at each visit: Central
<3.5 19 Peripheral 1 93 Peripheral
3.5-5 23 3.5 184
5-7.5 35 5 114
7.5-10 36 7.5 103
0.6 10-15 54 0.6 10 218
15-20 15 15 85
20 25
Including Rate

Including Rate
0.4 0.4

0.2 0.2

0 0
<3.5 3.5-5 5-7.5 7.5-10 10-15 15-20 1 3.5 5 7.5 10 15 20
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Visit Visit

Figure 13  Recurrent retinal disease and new lesions in children who are historical patients who missed being treated in the first year
(left) and those who were treated in the first year with pyrimethamine and sulfadiazine (right). Both left and right, incidence rate: number
of patients with new lesions per person-year. Blue shaded area in left and right is confidence interval. Adapted from McLeod et al.10 and
Phan et al.,25, 26 with permission.

severe, and recurrences less frequent in those who Acknowledgment

were treated promptly early in the course of their
disease in utero and in the first year of life.2,25,26,29,30,35,38
Severe retinal involvement is the rule at diagnosis of
symptomatic congenital toxoplasmosis in the United
States; and in Fiocruz, Brazil, active disease is pres-
ent in 50% of newborn infants detected in a newborn
screening program. Recurrences for children not
treated in the first year of life appear to be common
in teenage years. Acute acquired infections also may
be complicated by toxoplasmic retinochoroiditis with
recurrences most common close to the time of acqui-
sition. Suppressive treatment can reduce recurrent
disease. Incidence and manifestations of this disease
vary geographically. For example, in certain areas of
Brazil, 20% of persons have ocular toxoplasmosis,
and 50% of those are over the age of 50 years. When
scars are present at diagnosis and there are no other
manifestations of congenital infection, and serologic
tests reflect a remote rather than an active, recently
acquired infection, the anatomy of the retinal disease
and the signs and symptoms cannot be distinguished
between congenital versus postnatal acquisition of
the infection.
Toxoplasmic retinochoroidal disease is a significant
cause of loss of vision and affects subsequent quality of
life. The natural history of the signs and symptoms of
this infection as described herein are modified by treat-
ment of the parasite when it is actively destroying the
retina, but medicines to eliminate the latent stage, which
is the source of recurrences, are not available at present.
Suppressive treatment with TMP-SMX has been shown
to reduce the incidence of recurrences of infection for
persons in Sao Paulo, Brazil.57
This work was supported by NIH NIAID R01 27530
and gifts from the Taub, Engel, Mann, and Cornwell
families(RM). We thank Daniel Lee and Jane Babiarz for
their assistance with preparation of this manuscript.
Declaration of interest: The authors report no conflicts
of interest. The authors alone are responsible for the
content and writing of the paper.
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