REVIEW

CURRENT
OPINION Ocular toxoplasmosis: background and evidence for
an antibiotic prophylaxis
Michael Reich a,b and Friederike Mackensen a,b

Purpose of review
The purpose of this review was to provide an overview of current data on antibiotic prophylaxis in ocular
toxoplasmosis.
Recent findings
Studies showing the prophylactic effect of long-term antibiotics are discussed. Prophylaxis seems to be
justified in patients with a high risk of recurrence because of antibiotics potential side-effects. Therefore,
predisposing factors leading to a higher risk of recurrence and the time period during which an antibiotic
prophylaxis is most appropriate are reviewed. Finally, a patient-individualized treatment recommendation is
summarized.
Summary
In the current literature, two prospective, randomized case-control studies exist, which show the protective
effect of an antibiotic prophylaxis. Hematologic, gastrointestinal and dermatologic complications are
potential side-effects. Especially during the first year after suffering a recurrence, an antibiotic prophylaxis
seems to be justified. The risk of a recurrence is inter alia influenced by the duration of the disease, the
immune status of the host and the patients age. Therefore, an antibiotic prophylaxis should be considered
for patients who have recently been infected with ocular toxoplasmosis, for middle-aged and elderly
patients and patients with a compromised immune system. This should be discussed with each patient
individually, especially if the lesion is close to the macula.
Keywords
chorioretinitis, ocular toxoplasmosis, prophylaxis, therapy, uveitis

INTRODUCTION and preserve vision and quality of life [5,13 ,14,

&&

&&

Ocular toxoplasmosis is the leading cause of 15,16 ,17].

posterior uveitis in the world [13]. It is character-
ized by a necrotizing retinochorioiditis with a sig-
nificant risk for scar formation and subsequent
reduction for vision. Unfortunately, no curative
treatment approach exists and even the effect of
current treatment approaches to active ocular tox-
This review aims to provide an overview of the
existing data on antibiotic prophylaxis of ocular
toxoplasmosis recurrences. Also, we present current
data identifying patients who are at the greatest risk
of recurrence, in order to prevent unnecessary
exposure of patients to the toxic effects of the anti-
&&

oplasmosis is discussed controversially [48]. Only a
few controlled studies with methodological weak-
nesses have been looking at the effect of antibiotics
in active ocular toxoplasmosis [5] and no consensus
exists on which antibiotic regime to choose [7].
Ocular toxoplasmosis is often associated with recur-
rences that can cause progressive loss of vision and
quality of life [9]. Treatment of an acute ocular
toxoplasmosis does not seem to have a protective
effect on subsequent ocular toxoplasmosis recur-
rences [1012]. Therefore, antibiotic prophylaxis
has been discussed as an alternative therapeutic
strategy aiming to reduce the risk of recurrence
microbial drugs [9,16 ]. The best time period in
a
Department of Ophthalmology and bInterdisciplinary Uveitis Center,
University of Heidelberg, Heidelberg, Germany
Correspondence to Friederike Mackensen, Interdisciplinary Uveitis
Center, Im Neuenheimer Feld, 400, D-69120 Heidelberg, Germany.
Tel: +49 6221 56-38558;
e-mail: Friederike.Mackensen@med.uni-heidelberg.de
Michael Reich, Interdisciplinary Uveitis Center, Im Neuenheimer Feld
400, D-69120 Heidelberg, Germany.
E-mail: m.reich.heidelberg@web.de
Curr Opin Ophthalmol 2015, 26:498505
DOI:10.1097/ICU.0000000000000205

www.co-ophthalmology.com Volume 26
Number 6
November 2015

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS

An antibiotic prophylaxis seems to be an alternative
therapeutic strategy in ocular toxoplasmosis reducing
the risk of recurrence and preserving vision and quality
of life.

There is level 1 evidence that intermittent use of
trimethoprim 160 mg/sulfamethoxazole 800 mg (every
23 days) following an active lesion of ocular
toxoplasmosis significantly reduces the risk of
recurrence for at least 1 year.

Hematologic, gastrointestinal and dermatological side-
effects can be an issue of an antibiotic prophylaxis.

At least the first year, possibly the first 2 years after
suffering a recurrence seem to be a suitable time
period during which an antibiotic prophylaxis is
most appropriate.

Recently acquired active lesions, short disease-duration,
a compromised host immune system and being middle-
aged or elderly at the time of an active lesion
(especially during the first active lesion) predispose for
a higher risk of recurrence. Therefore, patients
displaying one or more risk factors should be educated
on the option and possibilities of an
antibiotic prophylaxis.
which an antibiotic prophylaxis should be admin-
istered, as well as factors predisposing for a higher
risk of recurrence, will be discussed. Finally, a
patient-individualized treatment recommendation
will be summarized.
ANTIBIOTIC PROPHYLAXIS IN OCULAR
TOXOPLASMOSIS
Evidence on the effect of an antibiotic prophylaxis in
patients with ocular toxoplasmosis is listed in Table 1
&&
[13 ,14,1821]. Because of criteria of evidence-based
medicine, study design and group sizes (power), the
results of two prospective, randomized casecontrol
studies from Latin America are of special interest
&&
(level 1 of evidence-based medicine) [13 ,14]. Sil-
veria et al. [14] included 124 patients who were
treated every third day either with placebo or with
cotrimoxazol (trimethoprim 160 mg/sulfamethoxa-
&&
zole 800 mg). Felix et al. [13 ] included 95 patients
who were treated every second day either with a
placebo or with cotrimoxazol. Both studies showed
the protective effect of an antibiotic prophylaxis
significantly reducing recurrences (Silveria et al.:
recurrence rate of 23.8% in the control group vs.
6.6% in the study group; Felix et al.: 12.8% in the
control group vs. 0% in the study group). For detailed
information regarding both studies, see Table 1.
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Ocular toxoplasmosis Reich and Mackensen
Side-effects associated with an antibiotic prophy-
laxis are an important issue. Four patients (6.6%) in
the treatment group of Silveria et al. [14] withdrew
from the study because of mild allergic reactions.
Additionally, two patients in the study group
(3.3%) and four patients in the control group
(6.3%) were lost to follow-up. No side-effects
&&
occurred in the study of Felix et al. [13 ] (one patient
in each group was lost to follow-up). Therefore,
there are only limited data in the current literature
describing possible side-effects while undergoing an
antibiotic prophylaxis of ocular toxoplasmosis.
Described side-effects in patients receiving conven-
tional antibiotic therapy, usually prescribed over
68 weeks after an active lesion of ocular toxoplas-
mosis, allow drawing conclusions regarding possible
side-effects under an antibiotic prophylaxis. Hema-
tologic, gastrointestinal and dermatological compli-
cations may occur [22]. In the study of Rothova et al.
[22] the frequency of serious side-effects was 26% for
pyrimethamine (thrombocytopenia and leucope-
nia), 17% for clindamycin (diarrhea and mild hep-
atotoxicity) and 4% for cotrimoxazole. Sulfadiazine-
induced side-effects included allergic reactions, such
as rashes and fever. Because of the few side-effects, the
low cost and the wide availability [23], the use of
cotrimoxazole seems to be a suitable and reasonable
&&
choice for an antibiotic prophylaxis [13 ,14].
The low frequency of side-effects seen with cotri-
moxazole makes the fact that the authors Silveria
et al. and Felix et al. observed only a few or no side-
effects during their study credible. With a higher
case number one would surely observe more side-
effects. The most common side-effects being
described in the literature are mild gastrointestinal
symptoms including nausea, vomiting, occasionally
diarrhea, anorexia, cramps, glossitis, stomatitis or
jaundice in less than 3% of patients [2426]. Skin
eruptions of any type are seen less often, but eryth-
ema multiforme, StevensJohnson syndrome, toxic
epidermal necrolysis (Lyells syndrome) and exfo-
liative dermatitis, although rare, may be serious or
even fatal possible complications [2426].
In summary, there is level 1 evidence that inter-
mittent use of cotrimoxazole (every 23 days) fol-
lowing an active lesion of ocular toxoplasmosis
significantly reduces the risk of recurrence for at
least 1 year [5]. Because of possible side-effects,
long-term antibiotic treatment should only be used
in patients with a high risk of recurrence.
PATIENT SELECTION AND THE BEST TIME
PERIOD
Patients with ocular toxoplasmosis are assumed to
be at a lifetime risk of recurrence because of tissue
www.co-ophthalmology.com 499
 500
Table 1. Evidence for an antibiotic prophylaxis in ocular toxoplasmosis

Level of Patients Recurrence

evidence- included rate (%)
based Study Control Time period Study Control
Study design medicine group group Used prophylaxis (months) group group P-value

&&
Felix et al. [13 ] Prospective, randomized, 1 47 48 Every second day: 12 0.0 (n 0) 6.6 (n 4) 0.026
double-blinded case trimethoprim 160 mg/sulfamethoxazole 800 mg
control study
Silveria et al. [14] Prospective, randomized 1 61 63 Every third day: 20 12.8 23.8 0.01
casecontrol study trimethoprim 160 mg/sulfamethoxazole 800mg (n 6) (n 15)
Small children, every third day, 0.375 ml/kg:
liquid suspension of trimethoprim 40 mg/5 ml

www.co-ophthalmology.com
and sulfamethoxazole 200 mg/5 ml
Cochereau-Massin Retrospective observational 4 38a Every day: Up to 40 24-month
Ocular manifestations of systemic disease

et al. [18] case series (45 HIV- (i) Pyrimethamine 25 mg (sulfadiazine 23 g or (median 8) recurrence rate:
infected patients) less and  clindamycin 1.2 g, according to the (i) 0.18
patients tolerance) (ii) 0.20
(ii) Pyrimethamine 50 mg (sulfadiazine 23 g
or less and  clindamycin 1.2 g, according to
the patients tolerance)
Kopec et al. [19] Case report 5 2 Twice a day: 18 0.0 (n 0)
trimethoprim 160 mg/sulfamethoxazole 800 mg
Gagliuso et al. [20] Case report (16 AIDS- 5 11a Cases 1, 7, 10: pyrimethamine (unknown dosage) unknown 0.0 (n 0)
patients) Cases 2, 3: pyrimethamine/sulfadiazine/
clindamycin (unknown dosage)
Cases 4, 6, 8: pyrimethamine/clindamycin
(unknown dosage)
Case 11: pyrimethamine/leucovorin (unknown
dosage)
Cases 13, 15: pyrimethamine/sulfadiazine
(unknown dosage)
Holland et al. [21] Case report (8 AIDS- 5 5a Case 4: pyrimethamine (25 mg twice a day)/ Up to 12 Infection became
patients) tetracycline (250 mg four times daily)/folinic clinically inactive with
acid (5 mg daily) drug therapy in all
Case 5: spiramycin (1 g four times daily), after 4 patients; reactivation
months: occurred when therapy
pyrimethamine (100 mg daily)/clindamycin was stopped in 2 of
(300 mg three times daily) 3 patients

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

Case 6: pyrimethamine (50 mg daily)/sulfadiazine
(2.5 g daily)
Case 7: tetracycline (250 mg four time daily)
Case 8: pyrimethamine (25 mg daily)/sulfadiazine
(2 g four times daily)

a
Patients receiving an antibiotic prophylaxis. Patients with no reconstructable maintenance therapy were not included in the table.

Volume 26
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November 2015


cysts remaining in the retina after the initial infec-
tion with Toxoplasma gondii [27]. The cause of the
tissue cysts reactivation and thus the triggers of a
recurrence of ocular toxoplasmosis remain unclear.
In the current literature, the following aspects have
been discussed in association with a higher risk of
recurrence of ocular toxoplasmosis: increased risk of
recurrence after suffering an active lesion of ocular
toxoplasmosis; influence of the duration of the
disease; influence of the hosts immune status; influ-
ence of pregnancy; influence of patient-age; influ-
ence of intraocular surgery; influence of serotype of
T. gondii; influence of other possible risk factors such
as sex or ethnic background of the host.
INCREASED RISK OF RECURRENCE AFTER
SUFFERING AN ACTIVE LESION OF
OCULAR TOXOPLASMOSIS
The published studies agree that the risk of recur-
rence is highest in the first year following the most
recent episode, implying a decrease of the risk of
recurrence over the recurrence-free survival time
[2831]. Clustering of recurrences remains a con-
&&
troversial issue [28,29 ,31]. A decrease of the risk of
recurrence with an increasing recurrence-free sur-
vival time may be explained by the decreased via-
bility of tissue cysts over time, reducing the pool of
organisms and therefore the risk of reactivation
&
[9,28,32 ]. Changes in tissue cysts with a reduced
release of parasites, endocrine fluctuations and tran-
sient humoral/cellular immunoreactivity might
present other possible explanations of the decrease
in the risk of recurrences with regard to the duration
of the disease [33,34]. None of these supposed fac-
tors has, however, been proven in highly evidence-
based studies.
As the risk of recurrence is at its highest in the
first year after the most recent episode
&&
[28,29 ,30,31], the first year after suffering a recur-
rence could be defined as a time period during
which an antibiotic prophylaxis could be justified.
INFLUENCE OF THE DURATION OF
DISEASE
It seems that the longer the time interval elapsed
since the first episode of the disease, the smaller the
risk of recurrence. Holland et al. [28] described a 72%
risk-reduction for each decade after the first episode.
&&
According to the results of Reich et al. [29 ], a 43%
risk-reduction for each decade can be calculated.
The difference of the risk-reduction between those
two studies can be attributed to the fact that the
study of Reich et al. solely used data of patients with
primary ocular toxoplasmosis for analysis.
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Ocular toxoplasmosis Reich and Mackensen
The results of both studies suggest that the risk
of recurrence is at its highest at the time of the first
active lesion (primary ocular toxoplasmosis). The
presence of an active lesion without a preexisting
scar in the same eye is a strong argument for a
primary/acquired infection with T. gondii [35]. The
presence of IgM and/or IgA in the serum of the
patient can be used as diagnostic criteria to support
initial ocular infection with T. gondii [36].
In conclusion, an antibiotic prophylaxis may be
justified for patients with primary ocular toxoplas-
mosis or patients having recently been infected.
INFLUENCE OF THE IMMUNE STATUS OF
THE HOST
A compromised host immune system seems to be
among the risk factors predisposing for a higher risk
of recurrence of ocular toxoplasmosis. Severe pro-
gression of T. gondii-infection as well as an increased
risk of recurrence was observed in AIDS patients
[1921,37,38] and in patients receiving immunosup-
pressant therapy [39,40]. Regarding ocular toxoplas-
mosis, a severe course of the disease in elderly patients
has also been attributed to alterations in host immun-
ity [4144]. In addition, de-la Torre et al. and Jasper
et al. (Cochrane database of systematic reviews)
described a worse outcome and higher risk of recur-
rence in patients receiving corticosteroid monother-
apy [30,45]. Therefore, patients with a compromised
immune system, either because of systemic disease or
long-term medical treatment, seem to be at higher
risk of recurrence. Antibiotic prophylaxis should be
recommended to those patients.
INFLUENCE OF PREGNANCY
During pregnancy, a partial suppression of cell-
mediated immunity develops in order to facilitate
survival of the semi-allogeneic fetus. Therefore,
some latent ocular diseases, such as uveitis, may
benefit from the partial suppression of the cell-
mediated immunity, whereas others, such as infec-
tions, may worsen during pregnancy [4648].
Especially, infections with cytomegalovirus or the
human herpes virus 6 seem to reactivate more fre-
quently [49,50]. Concerning the risk of recurrence of
ocular toxoplasmosis, a more frequent reactivation
has also been suspected [33,5153]. Two recent
studies by Braakenburg et al. and Reich et al., how-
ever, showed no increase in the risk of recurrence of
preexisting ocular toxoplasmosis during pregnancy
& &
[54 ,55 ]. Therefore, antibiotic prophylaxis and
additional ophthalmological examinations during
pregnancy on women with preexisting ocular tox-
oplasmosis seem unnecessary.
www.co-ophthalmology.com 501
Ocular manifestations of systemic disease
INFLUENCE OF PATIENT-AGE
The influence of patient age is controversially dis-
cussed in the literature. Although Garweg et al. and
Bustillo et al. assigned a higher risk of recurrence to
patients of younger age [31,56], Holland et al. and
Reich et al. described a higher risk of recurrence in
&&
patients of older age [28,29 ]. For more detailed
information regarding all four studies, see Table 2.
The absolute number of active lesions is highest
&&
in younger patients [28,29 ,31,51,5658]. There-
fore, the assumption might be made that younger
patients possess a higher risk of recurrence [31,56].
Nevertheless, it should be kept in mind that the
sero-prevalence of T. gondii infection increases with
age, demonstrating the highest rates of infection in
adolescents and young adults [5965]. An even
greater number of patients acquire an infection with
T. gondii at a younger age, leading to the conclusion
that the absolute number of new infections contin-
ues to decrease with increasing age. Nonetheless,
recurrences occur especially at the beginning of
an infection (see Influence of the Duration of
Disease). Therefore, the age-related distribution of
active lesions can be explained by the fact that
more patients acquire an infection at a younger
age. Consequently, the presence of a higher absolute
number of active lesions at a younger age cannot
lead to the conclusion that individuals at a younger
age possess a higher risk of recurrence [66].
The comparison of the risk of recurrence
between relatively arbitrarily chosen age groups
has methodological weaknesses. Therefore, we
think that our study (Reich et al.) provides meth-
odologically stronger results regarding the contro-
versially discussed influence of patient age on the
&&
risk of recurrence [29 ]. The study showed that the
risk of recurrence is influenced by the patient age at
the time of any active lesion. Using solely data of
patients with primary ocular toxoplasmosis, we
were able to show that the risk of recurrence in
the first few years of disease is positively correlated
with patient age at the time of the first active lesion.
With this approach, unfortunately, group sizes were
low (15 patients). Therefore, a study with a con-
siderably larger number of patients would be desir-
able to confirm these results.
Concerning the influence of patient age on the
risk of recurrence, one can summarize that older age
at the time of the first active lesion and at the time of
any active lesion seems to predispose for a higher
risk of recurrence. Therefore, middle-aged or elderly
patients could be treated with an antibiotic prophy-
laxis after suffering an active lesion of ocular toxo-
plasmosis. A special indication exists for patients
suffering their first active lesion of ocular toxoplas-
mosis (primary ocular toxoplasmosis) at middle-age
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Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
or older. Antibiotic prophylaxis should be recom-
mended to those patients.
INFLUENCE OF INTRAOCULAR SURGERY
The influence of intraocular surgery on the risk of
recurrence of ocular toxoplasmosis is controver-
&
sially discussed in the literature [67 ,6870].
Bosch-Driessen et al. [68] showed a higher risk of
recurrence in 14 patients who had undergone a
cataract extraction compared with 45 controls. In
&
contrast, Heringer et al. [67 ] showed no significant
reactivation rate in a retrospective analysis of 69
ocular toxoplasmosis patients who underwent intra-
ocular surgery. Despite the disadvantage of not hav-
ing a control group, Heringer et al. also showed
noteworthy results because of a higher sample size.
In conclusion, it remains unclear whether intra-
ocular surgery influences the risk of recurrence of
ocular toxoplasmosis and thus necessitates the use
of an antibiotic prophylaxis for patients who
undergo intraocular surgery. Antibiotic prophylaxis
should be considered on the basis of other risk
factors as listed above.
INFLUENCE OF TOXOPLASMA GONDII
SEROTYPE
Assumptions have been made that there is a corre-
lation between the risk of recurrence and T. gondii
&
serotype [9,32 ,71,72]. Serotype I, which is the pre-
dominate serotype in Latin America, is discussed to
cause more severe disease [9,72]. Serotype II is less
aggressive and predominates in Europe/North
America [73]. Furthermore, Shobab et al. [71]
showed that a novel detected serotype being referred
to as nonreactive seems to be associated with a
higher risk of recurrence in German patients, under-
scoring the value of T. gondii serotype-screening for
management of ocular toxoplasmosis. As the two
trials on antibiotic prophylaxis have been con-
ducted in Brazil, the results may not necessarily
apply to the European serotype.
INFLUENCE OF OTHER POSSIBLE RISK
FACTORS
An influence of other host-specific factors, such as
sex and ethnical background as well as pre or post-
natal infection with T. gondii, could not be shown in
&&
up to level 2 evidence-based studies [28,29 ,58].
CONCLUSION
An antibiotic prophylaxis seems to be an alternative
therapeutic strategy in ocular toxoplasmosis. Used
in patients with a high risk of recurrence, such a
Volume 26
Number 6
November 2015
 Table 2. Recent studies regarding the influence of patient age on the risk of recurrence of ocular toxoplasmosis

Level of
evidence- Patients included Mean
based Study Subgroup with primary follow-
Study design medicine group ocular toxoplasmosis up (y) Methods Effect variable Result P-value

Bustillo et al. Cross-sectional 2 158 Development of active 1) Incidence rate of Highest and lowest
[56] cohort study disease in different active ocular results (n > 5):
age groups was toxoplasmosis 1) 2544 y: 42.1
analyzed (95% CI) (32.1 to 54.
2) 12-month 4564 y: 15.6
prevalence ratio (9.4 to 24.
of active ocular 2) 2544 y: 58.5
toxoplasmosis (46.6 to 72.7)
(95% CI) 4564 y: 23.0
(15.3 to 33.2)
Holland et al. Longitudinal cohort 2 143 33 7.2 (range 0.3 to 41) Two groups were 1) RR of recurrence 1) 0.62 (0.40 to
[28] study created: (95% CI) 0.94)
group 1 >40 y at the 2) RR of recurrence 2) 1.74 (1.06 to
time of episode adjusted for 2.86)
group 2 40 y duration of
disease (95% CI)
Reich et al. Retrospective 4 84 33 11.36  9.50 Patients with primary Mean number of 1A) T. gondii- 1) <0.037
&&
[29 ] observational ocular toxoplasmosis recurrences per specific antibiotic 2) 0.002
case series with were subdivided y  standard treatment:

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follow-up regarding received deviation 0.17  0.19
examination drug therapy 1B) Corticosteroid
subsequent to the first monotherapy:
active lesion 0.47  0.17
Patient age at the time 1C) No therapy:
of any active lesion 0.18  0.11
was plotted against 2) 0.29  0.24
the time interval to
the subsequent
recurrence
Garweg Retrospective 4 63 6.5  7.6 Patients were allocated Percentage of group 1: 66% <0.05
et al. [31] observational according to median patients who suffered
case series age at the time of the suffered recurrences
first ocular recurrences group 2: 39%
manifestation: suffered
group 1 <20.9 y recurrences

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

group 2 20.9 y

www.co-ophthalmology.com
95% CI, 95% confidence interval; RR, relative risk; y, years.
Ocular toxoplasmosis Reich and Mackensen

503
Ocular manifestations of systemic disease
Option of an antibiotic prophylaxis
following the conventional treatment of an active lesion of
Ocular Toxoplasmosis (OT)
All patients with an active lesion
A one-year antibiotic prophylaxis can be
discussed
Frequent recurrences (> every 3 years)
First active lesion (primary OT) < 10 years ago
Middle-aged or elderly patients
A one-year antibiotic prophylaxis can be
offered
Very frequent recurrences (> every 2 years)
First active lesion (primary OT)
Middle-aged or elderly patients suffering primary OT in mid/older
age
Vision threatening localization of the active lesion
Compromised immune system
A one- or two- year antibiotic prophylaxis can be
recommended
At least one point has to be fulfilled.
FIGURE 1. Individual recommendation for a patient suffering
from a recurrence or the first active lesion of ocular
toxoplasmosis. An antibiotic prophylaxis following the
conventional treatment of an active lesion of ocular
toxoplasmosis may be justified for patients who are at a
higher risk of recurrence because of the presence of one or
more of the listed risk factors.
disease management strategy could reduce the risk
of recurrence and therefore may be able to preserve
vision and quality of life. To avoid unnecessary
antibiotics side-effects, it is necessary to identify
the patients with the greatest risk of recurrences
in order to prevent subjects who would not benefit
from treatment from being subjected to the toxic
effect of long-term antimicrobial drugs. On the basis
of the results of this review, Fig. 1 summarizes a
patient-individualized treatment recommendation
regarding the option of an antibiotic prophylaxis for
patients suffering an active lesion of ocular toxo-
plasmosis. The flowchart, according to the existing
risk factors, illustrates the degree of importance with
which an antibiotic prophylaxis should be recom-
mended to the individual patient. Furthermore, the
suitable time-period during which an antibiotic
prophylaxis may be justified is mentioned. With
future findings and data the proposed strategy of
treatment should be adapted.
Acknowledgements
M.R. is a recipient of scholarships from the Studienstif-
tung des deutschen Volkes and the Dr Gabriele Lederle
Stiftung. He thanks these organizations for their sup-
port. The funding organizations had no role in the design
or conduct of the research.
504 www.co-ophthalmology.com
Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
Financial support and sponsorship
None.
Conflicts of interest
M.R. has no conflicts of interests; F.M. has been primary
investigator in several industry sponsored trials in the
last 2 years: Abbvie, Allergan, Novartis, Servier; has
served on an advisory board for Allergan, Abbvie and
Merck Serono and received lecture honoraria by Heidel-
berg Engineering and MSD. These organizations had no
role in the design or conduct of the research presented.
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An excellent review discussing in detail inter alia the current clinical understanding
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