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Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019; 163:XX.
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Infectious uveitis in immunodeficient HIV-negative patients:
A retrospective study
Petra Svozilkova, Eva Rihova, Michaela Brichova, Andrea Havlikova, Aneta Klimova, Jarmila Heissigerova
Aims. Cases of infectious uveitis in immunodeficient patients may present with atypical clinical features because the
clinical course of disease is usually affected by the compromised immune system. Therefore, it is sometimes difficult to
determine the correct diagnosis. The aim of this study was to evaluate a prevalence of immunodeficient HIV-negative
individuals among patients with infectious uveitis and to assess diagnostic and therapeutic approaches.
Methods. A retrospective study.
Results. In years 2003-2017, we diagnosed 594 patients with infectious uveitis. In 35 of them, infectious uveitis oc-
curred on the basis of immunodeficiency (malignancy, immunosuppressive therapy etc.). The most common infectious
uveitis was cytomegalovirus retinitis, followed by acute retinal necrosis, herpetic anterior uveitis, endogenous fungal
endophthalmitis, toxoplasmic retinochoroiditis, progressive outer retinal necrosis and syphilis. In indicated cases,
intraocular fluid examination was a valuable diagnostic tool. After initiation of treatment, improvement of BCVA was
observed in 13 eyes, stabilization in 13 eyes and deterioration in 11 eyes. In some patients who experienced adverse
effects of medication, the recommended doses were decreased.
Conclusion. Our experience shows that patients with diagnoses of acute retinal necrosis or progressive outer retinal
necrosis have a poor visual prognosis. The occurrence of cytomegalovirus retinitis signifies a very unfavorable survival
prognosis in patients who underwent hematopoietic stem cell transplantation; the patients in our study died within
1 year from cytomegalovirus retinitis diagnosis.
Key words: herpetic retinal necrosis, cytomegalovirus retinitis, immunodeficiency, fungal endophthalmitis,
toxoplasmic retinochoroiditis
Received: April 14, 2019; Accepted with revision: July 22, 2019; Available online: August 21, 2019
https://doi.org/10.5507/bp.2019.036
Department of Ophthalmology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech
Republic
Corresponding author: Petra Svozilkova, e-mail: petra.svozilkova@lf1.cuni.cz
INTRODUCTION
Infectious uveitis accounts for approximately 17-23%
of all uveitis cases in developed countries. The caus-
ative agents differ throughout the world depending on
geographic and demographic factors. According to ana-
tomical classification, the most common type of uveitis
in Western countries is the anterior form. In contrast,
posterior uveitis is more frequent in Africa, Asia and
South America. Among infectious agents, the most com-
mon are herpes viruses and Toxoplasma gondii1-5. Many
etiological agents are ubiquitous, e.g. seroprevalence of
cytomegalovirus (CMV) rises depending on age of pa-
tients from 60 to 90%. Immunocompetent people have
usually no or minimal symptoms during initial infection.
However, immunodeficient patients (AIDS, malignancy,
immunosuppressive treatment after organ transplantation
or due to autoimmune disease) may develop systemic in-
fectious diseases, carrying a significant risk of morbidity
and mortality6.
Cases of infectious uveitis in immunodeficient patients
may present with atypical clinical features because the
clinical course of disease is usually affected by the com-
promised immune system. Therefore, it is sometimes dif-
ficult to determine the correct diagnosis. Examination
of intraocular fluid can be a valuable tool for confirming
the causative agent. In addition, medications and their
dosages should be adjusted depending on the therapeutic
response and possible toxic adverse effects in immunode-
ficient patients.
The purpose of this retrospective study was to evaluate
a prevalence of immunodeficient HIV-negative individuals
in a group of patients with infectious uveitis and to assess
diagnostic and therapeutic approaches in these patients.
METHODS
A retrospective study was performed in our Centre
for Diagnosis and Treatment of Uveitis, First Faculty of
Medicine, Charles University and General University
Hospital in Prague. Thirty-five patients with immunode-
fiency and infectious uveitis out of 2794 patients with
uveitis were included during the period of 2003-2017. All
of them were HIV-negative. Diagnostic methods and the
effect of treatment including the best-corrected visual acu-
ity (BCVA) were evaluated.
Diagnostic procedures included medical history,
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019; 163:XX.
2
Snellen BCVA, intraocular pressure measurement, slit
lamp biomicroscopy, anterior segment and fundus exami-
nation. In indicated cases also visual field test, ultraso-
nography, optical coherence tomography and intraocular
fluid examination were performed.
Therapeutic approaches included the initiation of anti-
infectious agents in all patients, and pars plana vitrectomy
in 14 patients (3 patients with CMV retinitis, 5 patients
with acute retinal necrosis – ARN, 1 patient with progres-
sive outer retinal necrosis – PORN, and 5 patients with
fungal endophthalmitis).
We evaluated age of patients at time of presentation
of infectious uveitis, unilateral or bilateral involvement,
initial and final BCVA, effect of therapy and possible com-
plications. As improvement or deterioration of BCVA 2 or
more lines of Snellen optotypes were considered.
Treatment of underlying disease was managed by a
specialist (hematooncologist, rheumatologist, nephrolo-
gist etc.).
RESULTS
During the period of 15 years, we monitored and
treated 594 patients with infectious uveitis. In 35 of them
(5.9%), infectious uveitis occurred on basis of immuno-
deficiency (malignancy, immunosuppressive therapy after
organ transplantation or due to autoimmune disease).
The most common infectious uveitis in our study was
CMV retinitis (11 patients); one of these patients had
CMV chronic retinal necrosis. ARN (herpes simplex;
HSV or varicella zoster virus; VZV) was diagnosed in
7 patients, PORN in 1 patient, herpetic anterior uveitis
in 6 patients, endogenous fungal endophthalmitis in 6
patients, toxoplasmic retinochoroiditis in 3 patients and
syphilis in 1 patient (Table 1).
CMV retinitis
Among the patients with CMV retinitis were 8 men
and 3 women. Nine of them had bilateral retinitis; the
remaining 2 patients had unilateral ocular involvement.
The age range was 18-58 years (median 44 years).
Five patients underwent hematopoietic stem cell trans-
plantation (HSCT) due to hematological malignancy. The
main cause was acute myeloid leukemia in 80% of cases.
CMV retinitis occurred in 5-12 months after transplanta-
tion. Two patients had lymphoma (1 patient diffuse large
B-cell lymphoma; DLBCL and 1 patient follicular lym-
phoma). One patient underwent liver transplantation and
was on immunosuppressive medication. Three patients re-
ceived immunosuppressive treatment because of systemic
autoimmune disease (ulcerous colitis, ANCA-associated
vasculitis or psoriatic arthritis). The 58-year-old women
with immunosuppression due to psoriatic arthritis met
the criteria for CMV chronic retinal necrosis.
The main symptom were visual field defects in 5 pa-
tients and decrease of visual acuity in 6 patients. In 10
out of 20 eyes, macula was unaffected; in 10 eyes were
changes in macula (inflammatory infiltration, macular
edema, epiretinal membrane, subretinal hemorrhage, exu-
dative retinal detachment).
BCVA was evaluated in 9 patients; 2 women were
treated by another ophthalmologist after confirmation
of diagnosis at our clinic. The best initial BCVA was 6/6
and the worst was counting fingers with light perception
with correct projection of rays. The best final BCVA was
6/6 and the worst was blindness.
Type and doses of virostatic treatment were consulted
with a specialist (hematooncologist, rheumatologist, ne-
phrologist etc.). Four patients were treated with virostatics
for systemic CMV infection before the development of
CMV retinitis – early after HSCT in 3 patients and after
chemotherapy due to lymphoma in 1 patient.
Three patients with CMV retinitis were treated with in-
travenous ganciclovir; 2 patients received foscarnet. Three
patients were treated with oral ganciclovir. One patient
with systemic lupus erythematosus had indolent form of
CMV retinitis and used no virostatic therapy.
In addition, three patients underwent pars plana vit-
rectomy due to vitreous opacities. Vitreous sample analy-
sis confirmed CMV in two patients; one of them had
CMV chronic retinal necrosis and the second patient had
CMV retinitis and systemic follicular lymphoma. Vitreous
cytological examination revealed some atypical lymphoid
elements in second patient but immunophenotyping did
not detect any B-lymphocytes. Third patient had a nega-
tive PCR result for CMV (Table 2). However, virostatic
therapy was initially effective in this patient. Subsequently,
vitreous opacitities and cystoid macular edema occurred.
In this case, immune recovery uveitis was considered.
After initiation of effective treatment, the improve-
ment of BCVA was observed in 4 eyes of 3 patients; the
stabilization of BCVA was observed in 7 eyes of 7 pa-
tients. There was a decrease of BCVA in 6 eyes of 5 pa-
tients (2 eyes of patient with DLBCL, 4 eyes of 4 patients
with complications – haemophthalmos, macular edema,
exudative retinal detachment); (Table 3). Four patients,
who underwent HSCT, died in 1, 4, 5 and 9 months after
confirmation of CMV retinitis due to complications that
were not related to virostatic treatment.
The follow-up duration was from 1 to 48 months (me-
dian 17 months).
Acute retinal necrosis
Among the patients with ARN were 4 men and 3
women. All of them had unilateral ocular involvement.
The age range was 43-75 years (median 68 years).
Four patients had a history of malignancy (renal carci-
noma, testicular carcinoma, systemic DLBCL, B-cell chro-
nic lymphocytic leukemia); three patients were treated
with immunosuppressive drugs because of autoimmune
disease (ANCA-associated vasculitis, membranous glo-
merulonephritis, rheumatoid arthritis).
All patients were treated with aciclovir or valaciclovir;
the doses were adjusted depending on the overall condi-
tion of the patients. In addition, six patients were treated
with low doses of systemic corticosteroids due to dense
vitreous opacities that are common in cases of ARN. A
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019; 163:XX.
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nephrologist recommended a reduction of doses of aciclo-
vir in three patients with renal disease. The activity of in-
flammatory eye disease was under control in all patients.
Five patients underwent pars plana vitrectomy with
laser barrage of necrotic retinal lesions and silicone oil
instillation; four of them due to persistent vitreous opaci-
ties and one patient due to rhegmatogenous retinal detach-
ment. PCR examination of vitreous samples confirmed
VZV in 2 patients, HSV-1 in 1 patient, HSV-2 in 1 patient
and 1 patient had negative result of PCR (Table 2) but vit-
reous cytologic examination supported the viral etiology
of disease (as evidenced by an almost exclusive lympho-
cytic infiltration with cells in various stages of activation).
The best initial BCVA was 6/12 and the worst was
counting fingers with light perception with correct pro-
jection of rays. In patients, who underwent pars plana
vitrectomy, the best postoperative BCVA was 6/9 and the
worst 1/18 with light perception with correct projection
of rays. The best final BCVA was 6/18 and the worst was
light perception with incorrect projection of rays. The
improvement of BCVA was observed in 3 patients, the
deterioration of BCVA in 4 patients (Table 3). The main
causes for decrease of BCVA were a pale optic disc (4 pa-
tients), dense posterior capsule opacification (3 patients),
macular edema (1 patient) and silicone oil keratopathy
(1 patient).
The follow-up period was from 19 to 115 months (me-
dian 57 months).
Table 1. Etiological types of infectious uveitis in immunocompromised patients.
n (patients) % Male-to-female ratio Median age (years)
Tot a l 35 100 22:13 54
Herpetic uveitis 25 71.4 17: 8 58
Cytomegalovirus retinitis 11 31. 4 8:3 44
Acute retinal necrosis 7 20.0 4:3 68
Progressive outer retinal necrosis 1 2.9 1:0 63
Herpetic anterior uveitis 6 17.1 4:2 54
Fungal endophthalmitis 6 17.1 3:3 73
Toxoplasmic retinochoroiditis 3 8.6 1:2 51
Syphilis 1 2.9 1:0 39
Table 2. Results of vitreous analyses in 14 patients indicated for pars plana vitrectomy.
Diagnosis n
(patients)
PCR
positive/negative
Cultivation
positive/negative
Pathogen
Cytomegalovirus retinitis 3 2/1 - CMV
Acute retinal necrosis 5 4/1 - VZV (2)
HSV-1 (1)
HSV-2 (1)
Progressive outer retinal necrosis 1 1/0 - VZV
Fungal endophthalmitis 5 - 3/2 Candida albicans
PCR, polymerase chain reaction; CMV, cytomegalovirus; HSV-1, herpes simplex virus type 1; HSV-2, herpes simplex virus type 2; VZV, varicella
zoster virus
Table 3. Results of BCVA in immunocompromised patients treated with anti-infectious drugs.
Diagnosis Therapy n
(patients)
Improvement of
BCVA
n (eyes)
Stabilization of
BCVA
n (eyes)
Deterioration of
BCVA
n (eyes)
Cytomegalovirus retinitis ganciclovir
foscarnet
7
2
476
Acute retinal necrosis aciclovir
valaciclovir
6
1
3 - 4
Progressive outer retinal necrosis aciclovir 1 - - 1
Herpetic anterior uveitis aciclovir 6 2 4 -
Fungal endophthalmitis fluconazole 3 3 - -
Toxoplasmic retinochoroiditis azithromycin 2 1 1 -
Syphilis penicillin G 1 - 1 -
BCVA, best-corrected visual acuity. As improvement or deterioration of BCVA 2 or more lines of Snellen optotypes were considered. Patients
who were referred to our clinic for confirmation of diagnosis only were excluded from BCVA evaluation. They were treated and followed up by
another ophthalmologist.
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Progressive outer retinal necrosis
Unilateral PORN was diagnosed in a 63-year-old man.
The patient underwent a heart transplantation three years
ago, and nephrectomy due to Grawitz tumor two years
ago. Since that time, he has been taking immunosuppres-
sive drugs (tacrolimus, mycophenolate mofetil and cor-
ticosteroids). Moreover, the patient has type 2 diabetes
mellitus on insulin medication.
Pars plana vitrectomy with retinectomy, laser barrage
of necrotic retinal lesions, aciclovir lavage (40 µg/mL)
and silicone oil instillation was performed 9 days after in-
travenous aciclovir initiation (1500 mg/per day). PCR ex-
amination of vitreous samples confirmed VZV (Table 2).
The initial BCVA was 6/24 in the affected eye. The
postoperative BCVA was 6/12. Cataract surgery was per-
formed in 11 months after pars plana vitrectomy. The
final BCVA was 1/18 (Table 3). A dense posterior capsule
opacification and a pale optic disc were present. A follow-
up duration was 42 months.
Herpetic anterior uveitis
Herpetic anterior uveitis was diagnosed in 4 men and
2 women. All patients had unilateral ocular involvement.
The age range was 26-74 years (median 54 years).
Three patients had malignancy (B-cell chronic lym-
phocytic leukemia, breast cancer, prostate cancer). Two
of them were treated with chemotherapy. The patient with
prostate cancer underwent radiotherapy. Other three pa-
tients were on immunosuppressive medication. Two of
them underwent renal transplantation and were treated
with tacrolimus, mycophenolate mofetil and corticoste-
roids. One patient had immunosuppression (azathioprine
and corticosteroids) because of idiopathic bowel disease
(ulcerous colitis).
All patients were treated with oral aciclovir; five of
them with a common dose 2 g per day. In one patient,
who underwent renal transplantation, a nephrologist rec-
ommended to initiate the treatment with lower dose of
aciclovir (1.2 g per day) according to renal functions. The
activity of anterior uveitis was under control in all pa-
tients. The 74-year-old woman with B-cell chronic lympho-
cytic leukemia was referred to our clinic only to confirm
the diagnosis and to recommend an appropriate treat-
ment. Aciclovir medication was conducted by another
ophthalmologist.
The best initial BCVA was 6/6 and the worst 6/36.
One patient had amblyopic eye and perceived hand move-
ment and light perception with correct projection of rays.
The best final BCVA was 6/6 and the worst 6/9 (counting
fingers with light perception with correct projection of
rays in amblyopic patient). The improved BCVA occurred
in 2 patients, unchanged remained in 3 patients. No pa-
tient had deterioration of BCVA (Table 3). The follow-up
period was from 29 to 139 months (median 64 months).
Endogenous fungal endophthalmitis
Three men and three women suffered from endoge-
nous fungal endophthalmitis. Four patients had unilateral
ocular involvement and two patients experienced bilateral
endophthalmitis. The age range was 13-86 years (median
73 years).
Three patients had malignancy (colorectal cancer,
prostate cancer and multiple myeloma). Three patients
had type 2 diabetes mellitus (two patients with malignan-
cy and one patient with recent urinary infection treated
with intravenous antibiotics). Two young patients had id-
iopathic bowel disease (ulcerous colitis, Crohn's disease).
Both were treated with combination of corticosteroids
and azathioprine.
Five patients (7 eyes) underwent pars plana vitrectomy
with intravitreal amphotericin B. Candida albicans was
detected in vitreous of three patients; two patients had
negative results (Table 2). All patients were treated with
fluconazole (200-400 mg per day). Two of these patients
were referred to our clinic to confirm the diagnosis and to
recommend effective therapy. Then they were in the care
of a local ophthalmologist. The remaining 3 patients (4
eyes) had the best initial BCVA 6/12 and the worst count-
ing fingers with light perception with correct projection
of rays. The best final BCVA was 6/6 and the worst 6/9.
The improved BCVA occurred in all 3 patients (4 eyes);
(Table 3).
The 73-year-old man with multiple myeloma under-
went enucleation because of painful blind eye. The histo-
logical finding confirmed massive purulent inflammation
with abscess in the vitreous and phlegmonous spread of
inflammation in the retina and choroidea with the affec-
tion of the ciliary body. Fungal hyphae and spores were
detected.
The follow-up period was from 11 to 32 months (me-
dian 19 months).
Toxoplasmic retinochoroiditis
Unilateral toxoplasmic retinochoroiditis was diag-
nosed in 1 man and 2 women. In two patients, it was
a primary infection. A recurrence was identified in one
patient. The age range was 38-61 years (median 51 years).
All three patients suffered from malignancy and un-
derwent chemotherapy (ovarian cancer, colorectal cancer,
chronic myeloid leukemia with HSCT). In addition, one
patient had type 2 diabetes mellitus.
In all three patients, treatment with azithromycin (500
mg on the first day and then 250 mg daily for 6-8 weeks)
was initiated. One woman experienced a progression of
the ocular finding despite of therapy. Furthermore, in
this patient the signs of acute systemic infection were de-
tected in blood samples. We referred this woman to the
Infectious Disease Clinic where treatment with pyrimeth-
amine, sulfadiazine and corticosteroids was started. The
therapy was effective.
In two patients, the initial BCVA was 6/12, resp. 6/9.
The final BCVA was 6/6 in both (Table 3). The 38-year-old
man was referred to our clinic for consultation. Follow-up
was provided by a local ophthalmologist. The follow-up
period in remaining 2 patients was 3, resp. 57 months.
Syphilis
Unilateral mild optic disc edema and macular edema
was observed in a 39-year-old man. The patient has been
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5
treated for 9 months by rheumatologist with azathioprine
and corticosteroids for suspected Behcet’s disease. The
patient suffered from oral and genital aphthous ulcers. We
suspected syphilis, so we indicated blood tests that con-
firmed the diagnosis. Penicillin therapy was initiated in
cooperation with dermatovenerologist. The initial BCVA
was 6/9; the final BCVA was 6/6 (Table 3). A follow-up
duration was 12 months.
DISCUSSION
Larger series of immunodeficient HIV-negative pa-
tients with infectious uveitis of various etiology were rare-
ly mentioned in publications. Hence, we retrospectively
evaluated 35 patients with decreased immune status and
active infectious uveitis.
In the past years, CMV retinitis was the main cause
of decreased visual acuity in patients with AIDS (ref.7-
9). Since the introduction of highly active antiretroviral
therapy (HAART), the proportion of CMV retinitis in this
group of patients has been decreasing. HAART reduced
the incidence of CMV retinitis by 80% (ref.10). Compared
to that the incidence of CMV retinitis in HIV-negative
immunodeficient patients may be increasing. However,
this may be due to increasing numbers of patients with
transplantation. The main risk group are patients after
HSCT (ref.11). In our patients, CMV retinitis developed
within 1 year after HSCT or organ (liver) transplanta-
tion. Similar results published Eid et al. 2008 and Kuo
et al. 2004 (ref.12,13 ). In patients, who are treated with
immunosuppression due to autoimmune disease, is the in-
terval longer. Kuo et al. observed CMV retinitis in 8.5-21
months after initiation of immunosuppressive therapy13.
In our three patients, the interval was 2, 4 and 15 years.
After initiation of virostatic treatment, we observed
the improvement of BCVA in 4 eyes of 3 patients (21%)
and the stabilization of BCVA in 7 eyes of 7 patients
(37%). Eid et al. observed the improvement of BCVA in
4 eyes of 4 patients (28.5%) and the stabilization of BCVA
in 4 eyes of 4 patients (28.5%) (ref.12). The decrease of
BCVA in 6 eyes of 5 our patients (32%) was caused by
complications (optic disc atrophy, macular edema, exuda-
tive retinal detachment, haemophthalmos).
Rhegmatogenous retinal detachment, a frequent com-
plication of CMV retinitis, did not occur in our patients.
However, some studies reported a manifestation of this
complication. Eid et al. have experienced rhegmatogenous
retinal detachment in 1 eye of 1 patient (out of 14 eyes of
9 patients) (ref.12). Kuo et al. observed this complication
in 2 eyes of 2 patients (out of 30 eyes of 18 patients) be-
tween 1st and 7th month since the diagnosis determination.
Two other patients in the same study had rhegmatogenous
retinal detachment during their first visit13.
Four patients with CMV retinitis (36%) died in 1, 4,
5 and 9 months after confirmation of diagnosis. All of
them underwent HSCT. Kuo et al. reported deaths in 10
out of 18 patients (56%) and mean survival time was 11
months after determining the diagnosis of CMV retinitis13.
In elderly patients, with a natural decline of activity
of immune system, CMV retinitis appears to have an in-
creased association with retinal arteriolar occlusions6, 14,15.
Some authors have found that in patients with diabetes
mellitus or on noncytotoxic doses of immunosuppression
due to autoimmune diseases, CMV retinitis can present
with typical, slowly progressive, peripheral granular reti-
nitis, and an atypical panretinal occlusive vasculitis, mim-
icking ARN (ref.6,16). Similar findings were seen in our
58-year-old woman with CMV chronic retinal necrosis,
who used immunosuppression because of psoriatic arthri-
tis. In addition, our patient had some opacities in vitre-
ous, commonly seen in cases of chronic retinal necrosis,
similarly to patients with ARN. Nevertheless, in cases of
HSV or VZV ARN, vitreous haze is usually dense.
It is important to keep in mind that CMV retinitis is
a part of systemic infection with implications for the sec-
ond eye and other organs. This is the reason for initiation
of virostatic therapy by systemic means, with or without
concurrent intravitreal treatment6.
PORN and ARN have been described to represent
two antipoles of the spectrum of herpetic necrotizing
retinopathies. PORN typically affects immunodeficient
patients. Compared to that, ARN predominantly af-
fects immunocompetent people but less frequently can
also develop in slightly immunocompromised patients17.
Diagnosis of ARN is based on clinical findings alone us-
ing the American Uveitis Society's criteria18 . The main
risk of herpetic necrotizing retinopathies is bilateral in-
volvement. In almost one-third of patients the second eye
becomes involved, usually within 1–6 weeks19. In immu-
nodeficient patients, the risk may be higher, especially in
cases with poor tolerance of virostatics. All our patients
had unilateral ocular involvement and the disease was
under control on aciclovir or valaciclovir medication. Five
patients underwent pars plana vitrectomy with transient
improvement of BCVA. In the following period, the dete-
rioration of BCVA was observed in 4 patients mainly due
to optic disc atrophy and/or posterior capsule opacifica-
tion. Optic disc swelling with subsequent atrophy is one
of the main causes of BCVA decrease in patients with
necrotizing herpetic retinopathies20,21.
Another type of infectious uveitis, which may occur
in immunocompromised people, is endogenous fungal
endophthalmitis. The main risk group are patients with
malignancy, diabetes mellitus, on long-term immuno-
suppression or antibiotics, with indwelling intravenous
catheters, or intravenous drug users. Early pars plana
vitrectomy with intravitreal antifungal drugs is indicated
in these patients. This surgical procedure enables to ob-
tain vitreous samples for examination and usually leads
to improvement of BCVA (ref.22). Five of our patients
underwent pars plana vitrectomy with intravitreal admin-
istration of amphotericin B and were treated with oral
fluconazole. The therapy was effective and resulted in
improvement of BCVA. One patient primary underwent
enucleation due to painful blind bulbus. The histological
examination confirmed fungal endophthalmitis.
Furthermore, herpetic anterior uveitis, toxoplasmic
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019; 163:XX.
6
retinochoroiditis and syphilis can affect both – immuno-
deficient or immunocompetent people.
All our patients with herpetic anterior uveitis had
unilateral involvement. Treatment with oral aciclovir was
effective and led to final BCVA between 6/6 to 6/9 (ex-
cept one amblyopic patient). In patients who have only
anterior uveitis without corneal scarring, visual prognosis
is favorable23,24.
Toxoplasmic retinochoroiditis was diagnosed through
clinical grounds alone in our patients. Generally, blood
tests for detection of toxoplasma antibodies of acute phase
(IgA, IgM) have only supporting significance and may be
even negative in cases of isolated eye disease. The serop-
revalence (IgG) for Toxoplasma gondii is high in western
Europe (41-75%) whereas in Vietnam, China and Thailand
it is low1, 25-27. Causes for these regional differences are un-
known; various factors such as diet, hygiene, infection of
the environment by cyst and differences in pathogenicity
of the regional strains might be involved1. Aqueous humor
analysis may be helpful, especially if there are difficulties
in determining the diagnosis. Westeneng et al. detected
Toxoplasma gondii in aqueous humor in 1 out of 21 AIDS
patients and in 10 out of 22 non-AIDS immunocompro-
mised patients. They confirmed ocular toxoplasmosis in
45.5% of non-AIDS immunocompromised patients28. It
was the most common infectious uveitis in this group of
patients. In contrast, toxoplasmic retinochoroiditis was
diagnosed in only 8.6% of cases in our study.
Serological testing is crucial for determination of syph-
ilis. Syphilis is considered as “the great imitator” as it has
many different manifestations and thus mimics many dis-
eases. In addition, syphilis can be presented as any form
of uveitis. Westeneng et al. revealed a strong correlation
between having AIDS and ocular syphilis (6/21 in AIDS
patients vs 0/22 in non-AIDS patients) (ref.28). In our
non-AIDS study, syphilis was confirmed in one patient.
Ocular manifestation was mild optic disc swelling and dis-
crete macular edema. Therapy was initiated immediately
with consequent improvement of BCVA. The delay in
treatment with penicillin can lead to long-standing optic
neuropathy and cystoid macular edema, which is associ-
ated with poor BCVA (ref.29).
In indicated cases, intraocular fluid examination
is a valuable tool for determining the proper diagnosis
through confirming the causative agent. Vitreous sam-
pling allows multiple analyses due to higher volume of
liquid compared to aqueous tapping. On the other hand,
anterior chamber tapping is easy to perform, quick, and
safe method30. PCR methods are widely used for detection
of herpes viruses whereas analyses of intraocular antibody
production play a decisive role in the diagnosis of ocular
toxoplasmosis28. Bacterial or fungal intraocular inflamma-
tion is mainly confirmed by microscopic examination and
cultivation of intraocular fluid samples. In our patients,
pars plana vitrectomy was performed in 16 eyes (14 pa-
tients). Positive results of examination of vitreous samples
were achieved in 11 patients (78.6%).
The important key to the diagnoses of CMV retinitis,
PORN and endogenous infectious endophthalmitis, is the
history of immunodeficiency. Whereas other infectious
uveitides, such herpetic anterior uveitis, ARN, toxoplas-
mic retinochoroiditis or syphilis may affect both – im-
munocompetent and immunocompromised people. The
typical clinical features of uveitis can be altered due to
immunodeficiency. Moreover, the therapy might not be
effective in all cases. In many of our patients, type and
dosages of medication were adjusted according to clinical
response and possible toxic adverse effects. Therefore, in-
terdisciplinary cooperation is crucial to appropriate care
of our patients.
CONCLUSION
Among immunodeficient HIV-negative patients in our
centre, the most common infectious uveitis was cytomega-
lovirus retinitis, followed by acute retinal necrosis, her-
petic anterior uveitis, endogenous fungal endophthalmitis,
toxoplasmic retinochoroiditis, progressive outer retinal
necrosis and syphilis. Our experience shows that patients
with a diagnosis of ARN or PORN have a poor visual
prognosis. The occurrence of CMV retinitis signifies a
very unfavorable survival prognosis in patients who have
undergone HSCT; the patients in our study died within 1
year from CMV retinitisdiagnosis.
ABBREVIATIONS
ARN, Acute retinal necrosis; BCVA, Best-corrected
visual acuity; CMV, Cytomegalovirus; DLBCL, Diffuse
large B-cell lymphoma; HAART, Highly active antiretro-
viral therapy; HSCT, Hematopoietic stem cell transplanta-
tion; HSV, Herpes simplex virus; PCR, Polymerase chain
reaction; PORN, Progressive outer retinal necrosis; VZV,
Varicella zoster virus.
Acknowledgements: This work was supported by the
Research Project of Charles University PROGRES Q25/
LF1/2. The authors thank our Vitreoretinal Department
for performing pars plana vitrectomy in selected patients.
They would also like to thank the Institute of Medical
Biochemistry and Laboratory Diagnostics, First Faculty
of Medicine, Charles University and General University
Hospital in Prague for blood tests and intraocular fluid
examination.
Author contributions: PS, ER: designed the study and data
collection tools; PS: prepared and revised the manuscript;
PS, ER, MB, AH, AK, JH: performed the examination
and contributed to the discussion and content of the re-
port. All authors read and approved the final manuscript.
Conflict of interest statement: The authors state that there
are no conflicts of interest regarding the publication of
this article.
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