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Birdshot Chorioretinopathy
Long-term Manifestations and Visual Prognosis
Aniki Rothova, MD, PhD,1 Tos T. J. M. Berendschot, PhD,1 Kiki Probst, MD,1 Bram van Kooij, MD,1
G. Seerp Baarsma, MD2
Purpose: To ascertain the clinical features and long-term visual prognosis of birdshot chorioretinopathy
(BCR), and to identify patients at risk of visual loss.
Design: Retrospective noncomparative case series.
Participants: Fifty-five consecutive patients with HLA-A29 –positive BCR who were identified in ophthalmology departments of the University Medical Center of Utrecht and The Eye Hospital Rotterdam, of whom 37
were observed for at least 5 years.
Intervention: A review of the medical and photographic and/or angiographic records of 55 patients with
HLA-A29 –positive BCR.
Main Outcome Measures: Numerous variables were compared, including age and gender distribution,
onset and course of BCR, ocular manifestations, therapeutic strategies and their outcomes, complications,
systemic diseases, visual acuity (VA), and features associated with poor visual outcome.
Results: Loss of VA was gradual; the number of affected eyes with VA less than 20/200 increased from 9 of
108 (8%) at onset to 22 of 73 (30%) at 5 years and 19 of 49 (39%) at 10 years of follow-up. The cause of
compromised VA was predominantly macular edema and macular atrophy (42 of 55 [76% of cases]). We found
strong associations between the VA at onset and visual outcome after 5 and 10 years (P ⫽ 0.005 and P ⫽ 0.006,
respectively). Mean VA at the 5-year follow-up was significantly lower if macular leakage was observed on
angiography (P⬍0.001). No differences in annual loss of VA were observed between patients treated by standard
therapeutic modalities and untreated patients.
Conclusion: The visual prognosis of BCR in a spectrum of uveitis is poor, and the recommended therapeutic
regimens have had no effect on long-term visual prognosis. New treatment strategies are needed for this blinding
disorder. Ophthalmology 2004;111:954 –959 © 2004 by the American Academy of Ophthalmology.
Birdshot chorioretinopathy (BCR) is a chronic intraocular
inflammatory disease of unknown origin that is responsible
for 1% to 2% of all uveitis cases.1– 4 The typical ocular
features include bilateral vitreitis and multiple hypopigmented choroidal spots in the absence of severe anterior
segment inflammation.5 Birdshot chorioretinopathy is
strongly associated with HLA-A29 (98% in BCR, vs. 7% in
the general population).5,6 Birdshot chorioretinopathy is
predominantly considered to be an ocular disorder without
systemic manifestations.5,7 Occasionally, systemic hypertension has been noted, and a small number of patients
complained of hearing loss, vitiligo, and mood disorders.5,8 –10
The course of BCR is, in the majority of patients, chronic
Originally received: April 28, 2003.
Accepted: September 8, 2003.
Manuscript no. 230274.
1
Uveitis Center, F. C. Donders Institute of Ophthalmology, University
Medical Center of Utrecht, Utrecht, The Netherlands.
2
The Eye Hospital Rotterdam, Rotterdam, The Netherlands.
Supported in part by the Dr. F. P. Fischer Foundation, Utrecht, The
Netherlands.
Correspondence to Aniki Rothova, MD, PhD, F. C. Donders Institute of
Ophthalmology, University Medical Center, P.O. Box 85 500, 3508 GA
Utrecht, The Netherlands. E-mail: [email protected].
954
© 2004 by the American Academy of Ophthalmology
Published by Elsevier Inc.
and progressive. The recommended treatment consists of
symptomatic administration of anti-inflammatory drugs and
prevention and/or treatment of complications.5,9,10 In the
past, several studies with variable follow-up periods have
attempted to assess the prognosis of BCR; however, the
results were contradictory. We report on the long-term
visual prognosis of BCR and on clinical manifestations
associated with this disorder in a cohort of 55 patients.
Patients and Methods
We conducted a retrospective analysis of the medical records of 72
consecutive patients with clinical features of BCR who consulted
the ophthalmologic department of the University Medical Center
of Utrecht and The Eye Hospital Rotterdam between 1990 and
2001. All patients underwent a complete clinical examination and
the standard screening protocol for uveitis, which included determination of the erythrocyte sedimentation rate, red and white
blood cell counts, glucose levels, and serum angiotensin-converting enzyme levels; serologic tests for syphilis; and chest radiography. Of 72 patients with a clinical diagnosis of BCR, 7 were
HLA-A29 negative, considered as a separate group, and not included in this series. Ten patients were observed for less than 1
year or were seen only once for a second opinion. In the present
study we included 55 HLA-A29 –positive BCR patients observed
ISSN 0161-6420/04/$–see front matter
doi:10.1016/j.ophtha.2003.09.031
Rothova et al 䡠 Birdshot Chorioretinopathy
Table 1. Visual Acuity Data over Time in Birdshot Chorioretinopathy (Affected Eyes)
Follow-up
Baseline
(N ⫽ 108)
1 Year
(N ⫽ 98)
2 Years
(N ⫽ 77)
5 Years
(N ⫽ 73)
10 Years
(N ⫽ 49)
Visual
Acuity
N
%
N
%
N
%
N
%
N
%
ⱕ20/200
20/200–20/60
Totalⱕ20/60
9
12
21
8
11
19
14
10
24
14
10
24
18
8
26
23
10
33
22
10
32
30
14
44
19
9
28
39
18
57
for at least 1 year, of whom 48 were observed for 2 years, 37 for
at least 5 years, and 25 for 10 years.
The clinical diagnosis of BCR was based on criteria formulated
by Vitale—in short, bilateral disease characterized by multiple
deep choroidal creamy-white lesions combined with vitreitis without snowbanking in eyes with the absence of severe anterior
segment inflammation.5,7–12 All patients were HLA-A29 positive.
Visual acuity (VA) was measured using the Snellen chart
projection unit. The testing distance was 6 m. Legal blindness was
defined as a best-corrected VA of the affected eye of ⱕ20/200.13
Visual outcome was defined as the optimal VA at the 5- and
10-year follow-ups (not the worst VA at any visit or at a nonstandardized follow-up point).
We compared numerous variables, including gender and age
distributions, clinical systemic and ocular features, laboratory data,
therapeutic strategies and their outcomes, complications, and VA,
as well as possible risk factors for visual loss. Cardiovascular
disease was considered present in patients with myocardial infarction, treated angina pectoris, deep systemic thrombosis, and cerebrovascular accident. For purposes of this study, patients with
systemic hypertension were also included. Three patients with a
temporary rise in blood pressure due to systemic medications were
excluded.
The SPSS statistical software package (10.0.7; SPSS Inc.,
Chicago, IL) was used for data analysis. Because left and right
eyes cannot be assumed to be independent, we performed statistical analyses for left eyes only, for right eyes only, for the mean
of the left and right eyes, and for the better seeing eye. All choices
led to the same conclusions. Here we present the analysis performed on the mean of the left and right eyes. These are also the
values shown in the figures. Before analysis, VA was always
transformed to logarithm of the minimum angle of resolution
acuity. Logarithm of the minimum angle of resolution is defined as
the 10-base logarithm of the VA.
We used Student’s t test to evaluate the differences in visual
outcome between categorical variables like gender and treatments
used. Analysis of variance was used to study differences in VA
between variables such as age at onset and time to diagnosis. A
general linear model with repeated measurements was used to
study the progression of VA. We used the Pearson correlation
coefficient for calculation of the correlation between VA values at
onset and those at follow-up points. Chi-square tests were used to
study possible associations between categorical variables. P values
of ⬍0.05 were considered statistically significant. The approval of
the local ethical committee was not needed for this retrospective
study.
Results
In total, 26 females and 29 males were included in this study. All
patients were Caucasian. Bilateral involvement was present in 54
of the patients; the remaining patient had undergone enucleation of
one eye 10 years before the onset of BCR (due to uveal melanoma). One amblyopic eye with an optimal VA of 20/100 was not
included in the analysis of visual outcome, which resulted in 108
affected eyes.
Mean age at first presentation to the ophthalmologist with
complaints of BCR was 53 years (median, 53; range, 23–75).
Birdshot chorioretinopathy became manifest in patients above the
age of 40 years in 46 of 55 (84%) patients. The average interval
from presentation to the ophthalmologist to the diagnosis of BCR
was 3 years (median, 2; range, 0 –20). At the onset of the disease,
9 of 108 (8%) affected eyes had a VA of less than 20/200; 12 of
108 (11%) had a VA of less than 20/60 but better than 20/200
(Table 1). None had a bilateral VA of less than 20/200, and 4
patients (7%) had a bilateral acuity of less than 20/60 (Table 2).
Chorioretinal lesions adjacent to the optic disc (Fig 1) were noted
in 19 of 47 (40%) patients.
Visual acuity data over time are presented in Figures 2 and 3
and Tables 1 and 2. The decline of VA was gradual during the
follow-up, and no changes between the initial and late periods
were noted. Strong association between the VA at onset and visual
outcome after 5 and 10 years was observed (P ⫽ 0.005 and P ⫽
0.006, respectively; Fig 2). No difference in the progression of
visual loss was identified between the eyes with good and poor
outcomes (Fig 3). Also, no difference in visual outcome was found
for gender, age at onset, time to diagnosis, and/or treatments used.
At 5 years of follow-up, 22 of 73 (30%) affected eyes had a VA of
ⱕ20/200, and 10 of 73 (14%) had one between 20/200 and 20/60
(Tables 1, 2). A bilateral VA of ⱕ20/200 was noted for 5 of 37
(14%) patients, and one between 20/200 and 20/60 was noted for
Table 2. Visual Acuity Data over Time in Birdshot Chorioretinopathy (Patients with Bilateral Visual Loss)
Follow-up
Baseline
(N ⫽ 55)
1 Year
(N ⫽ 54)
2 Years
(N ⫽ 39)
5 Years
(N ⫽ 37)
10 Years
(N ⫽ 25)
Visual Acuity of
Best Eye
N
%
N
%
N
%
N
%
N
%
ⱕ20/200
20/200–20/60
Totalⱕ20/60
0
4
4
0
7
7
2
5
7
4
9
13
5
2
7
13
5
18
5
6
11
14
16
30
5
4
9
20
16
36
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Ophthalmology Volume 111, Number 5, May 2004
Figure 1. Chorioretinal lesions adjacent to the optic disc in a patient with
birdshot chorioretinopathy.
6 of 37 (16%). The cause of compromised VA was predominantly
cystoid macular edema (CME) and/or retinochoroidal atrophy
(specifically in 42 of 55 [76%] cases); the remaining cases were
caused by glaucoma, retinal pucker, optic atrophy, and subretinal
neovascularization. The mean VA at the 5-year follow-up was
significantly lower if macular leakage on angiography was observed (P⬍0.001).
Systemic immunosuppressive and immunomodulatory drugs
were used in 36 of 55 cases (corticosteroids in 36; methotrexate in
6; cyclosporin A in 16; and miscellaneous in 7, including colchicine, plaquenil, azathioprine, nonsteroidal anti-inflammatory
drugs, and infliximab). A combination of immunosuppressive
drugs and corticosteroids was used in 25 cases, and corticosteroids
alone in 11. Acetazolamide was given in 24 cases (in combination
with anti-inflammatory drugs in 20 cases and as a monotherapy in
4). Fifteen patients had no systemic treatment. The annual loss of
VA did not differ between the treated and untreated patients (Fig
4), and differences between specific types of treatments used or for
the use of acetazolamide were not observed.
The complications occurring at the 5-year follow-up are summarized in Table 3. Complications included CME in 31 of 37
patients (84%), cataract in 22 of 37 (60%), and glaucoma in 7 of
37 (19%). Visual fields (VFs) exhibited profound defects in all of
27 patients tested, and furthermore, 44% (12 of 27) showed unexpected central and/or peripheral VF remnants only. In the majority of patients, retinal vascular abnormalities were observed
(attenuated retinal vessels in 83%, irregular veins in 72%, and
arteriovenous filling time on fluorescein angiography longer than
10 seconds in 46% of patients). Lesions adjacent to the optic disc
developed over the years in 25 of 35 (71%). Patients with this
anomaly had lower VA at the 2- and 5-year follow-ups than those
without (P ⫽ 0.02 and P ⫽ 0.03, respectively). (Sub)retinal
neovascularization developed in 5 of 37 (14%) patients observed
for at least 5 years.
Of the 37 HLA-A29 –positive patients with BCR assessed at
the 5-year follow-up, 1 had biopsy-proven sarcoidosis, 7 (19%)
reported previous skin malignancy (1 had melanoma, and 6 had
basal cell carcinoma), 1 had had a uveal melanoma in the past, and
6 had malignancies of various origins (mamma, lung, prostate, and
bladder). Cardiovascular disease was present in 21 of 37 (58%)
patients (including systemic hypertension in 17 of 37 [46%]). Of
37 patients with completed 5-year follow-up, 18 (49%) had cardiovascular disease present during the 5-year follow-up period. Of
those, 8 developed bilateral VA loss, in contrast to 3 of 19 in those
without cardiovascular disease during follow-up (P ⫽ 0.06). A
bilateral VA of ⱕ20/200 was present in 4 of 6 patients with
pre-existent cardiovascular disease, in contrast to 1 of 14 without
cardiovascular disease (P ⫽ 0.04).
Discussion
This study reports on the visual prognosis of patients suffering from BCR and describes progressive loss of central
VA over the years, caused predominantly by CME and/or
Figure 2. Visual acuity (VA) data over time in birdshot chorioretinopathy, mean for all and divided according to baseline VA. Log Mar ⫽ logarithm of
the minimum angle of resolution.
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Rothova et al 䡠 Birdshot Chorioretinopathy
Figure 3. Visual acuity (VA) data over time in birdshot chorioretinopathy, divided according to visual outcome at 10 years of follow-up. LogMar ⫽
logarithm of the minimum angle of resolution.
macular atrophy. This process was not reversed by the
anti-inflammatory treatments used. In addition, a high prevalence of vascular disease and skin malignancy was noted in
BCR, a disease so far considered a purely ocular disorder.
Long-term visual prognosis of BCR was repeatedly reported to be poor: 16% of BCR patients in Europe and 22%
of BCR patients in the United States developed a VA of
ⱕ20/200.7,10,12 Our series disclosed legal blindness (a bilateral VA of ⱕ20/200) in 14% and 20% of patients (after
5- and 10-year follow-ups, respectively), which is in concordance with previous literature. In contrast, legal blindness was reported to occur in 4% of all patients with
uveitis.3 Of all the eyes in our study affected with BCR,
57% developed visual impairment (an acuity of ⱕ20/60), in
contrast to 35% in a general uveitis population.3 The major
cause of visual loss in uveitis was thought to be CME, and
the frequent occurrence of CME in BCR (84%, vs. 30% in
all with uveitis) might explain this excessive loss of vision.3
The prevalence of CME in BCR was previously reported in
about half of patients, less than the 84% noted in our
patients.5,7,12 The higher frequency found in this series
might be explained by a uniform follow-up of 5 years in all
of our patients.
General characteristics of BCR noted in the previous
reports included Caucasian race, middle age at onset, and
bilateral ocular involvement, which is in concordance with
our series.5,7,10,12 The slight female predominance (60%)
described in previous studies was not noted by us (no
gender preference found in this report). A prevalence of
(sub)retinal neovascularization was previously reported in
approximately 6% to 13%; in our series it was
14%.10,12,14 –17 Various studies have shown that BCR usu-
Figure 4. Visual acuity data over time in birdshot chorioretinopathy and the use of systemic immunomodulatory and immunosuppressive treatment
(corticosteroids, cyclosporin A, and methotrexate). LogMar ⫽ logarithm of the minimum angle of resolution.
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Ophthalmology Volume 111, Number 5, May 2004
Table 3. Ocular Complications of Birdshot Chorioretinopathy
(at 5 Years of Follow-up)
Cystoid macular edema
Cataract
Glaucoma*
(Sub)retinal neovascularization†
Extensive visual defect (n ⫽ 28)‡
N ⴝ 37
%
31
22
7
(4)⫹1
11
84
60
19
14
39
*An additional 2 patients had ocular hypertension.
†
Four with subretinal and 1 with retinal neovascularization.
‡
Central and/or peripheral rest.
ally remains active for approximately 10 to 12 years, and
after that the active inflammation slowly declines, resulting
in atrophic changes of the retina and optic disc.5,10,11,18 One
study reported a self-limiting course in 20%.10 Although
some authors argued that BCR is most severe during the
first 2 to 4 years of activity and, in consequence, requires
most aggressive treatment in this initial period of the disease, others report on a prolonged course with frequent
remissions.19 Our findings favor the observation of chronic
activity with a gradual visual loss over years.20
To date, no strong evidence exists with which to answer
questions about the effectiveness of immunosuppressive
medications in treating visual loss from BCR.5,7,9,10,12 The
recommended treatment includes systemic and local steroids, cytotoxic and immunomodulatory agents, and their
diverse combinations, and exact indications for treatment
are not well defined.5,7,9,10,12,20 –22 Loss of VA (⬍20/40)
and/or severe inflammation seen on fluorescein angiography
were the usual indications for systemic anti-inflammatory
treatment. It was recommended not to treat patients with a
VA of higher than 20/40.9,10 Our results indicate that a more
aggressive approach might be justified in view of the poor
prognosis, especially in those with macular edema. Undoubtedly it is important to treat BCR (as all intraocular
inflammations) during active inflammation, because the
treatment of quiescent old scars is pointless.7 Intermittent
treatment of exacerbations did not prevent visual loss.20
Whether the treatment of BCR during an early disease
period is crucial for visual outcome is, however, not known.
Visual complaints of BCR patients might seem out of
proportion to the measured VA.5,10 Birdshot chorioretinopathy patients complain frequently of not having useful vision
outside, abnormal color vision, and reading difficulties.
Therefore, central VA alone is not the only parameter for
treatment efficacy; VF examinations and electroretinogram
might be extremely helpful parameters when assessing the
degree of visual impairment and development of the disease. Visual fields and electroretinograms were pathologic
even in BCR patients with full central acuity.10,20,23–25
In general, BCR occurs in healthy individuals, but cardiovascular disease (specifically, systemic hypertension)
was previously noted in 20% to 23%.10,12,14 In our series,
the prevalence of hypertension was 46% at the 5-year follow-up, compared with an estimated lifetime prevalence of
44%.26 In the Dutch population older than 55 years, 31% to
39% suffer from hypertension.27,28 We suggest that the
958
presence of cardiovascular disease—specifically, hypertension—might negatively influence visual prognosis in BCR
patients. But the questions of whether the presence of cardiovascular disease really affects the long-term visual outcome of patients with BCR and whether its control can
reduce retinal complications cannot be answered with our
retrospective data.
In our patients, 7 of 35 (20%) reported skin malignancies
(6 with basal cell carcinoma and 1 with skin melanoma).
One additional BCR patient had uveal melanoma. He had
developed BCR in his only eye 10 years after his other eye
was enucleated because of malignant melanoma of the
choroid. Basal cell carcinoma is the most common malignancy in Caucasians, with a lifetime risk of 30%.29 The
prevalence of basal cell carcinoma in the general population
is approximately 38/100 000 to 300/100 000 person-years,
but the data on prevalence of basal cell carcinoma in our age
population are missing, so that the prevalence of skin malignancy in the general population cannot be compared with
our BCR sample.29 Malignant melanoma of the skin reaches
4/100 000 per year to 12/100 000 per year.29,30 The combination of the 2 rare diseases (melanoma and BCR) might be
coincidental, but also might be related due to a yet unknown
factor. In both diseases, autoimmune reactions against human ocular tissues were reported.31–37 The clinical association between melanoma and uveitis was noticed in melanomatous swine and occasional patients.31,32,38,39 The exact
role of HLA-A29 in the pathogenesis of BCR has not yet
been identified; the etiologic hypotheses favor the inducement of autoimmune reactions against human ocular antigens after the contact of foreign microorganisms or other
substances with HLA-A29.35 Interestingly, the MAGE
genes (a group of genes that encode for antigenic, tumorspecific peptides, which are recognized by a clone of cytotoxic T-lymphocytes derived from the patient bearing the
tumor) are presented by HLA-A29 molecules on human
melanoma.40
At present, no randomized controlled trials have been
conducted to study the efficacy of early treatment in BCR.
However, no strong evidence to date exists with which to
answer the question of whether late immunosuppressive
treatment is effective in treating visual loss from BCR.
Despite the limitations of the retrospective nature of this
study, we have provided an up-to-date description of the
clinical manifestations, course, and prognosis of BCR.
These data might be of value when advising and treating
patients with this ocular disorder of poor visual prognosis.
References
1. Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J
Ophthalmol 1980;89:31– 45.
2. Smit RL, Baarsma GS, de Vries J. Classification of 750
consecutive uveitis patients in the Rotterdam Eye Hospital. Int
Ophthalmol 1993;17:71– 6.
3. Rothova A, Suttorp-van Schulten MS, Treffers WF, Kijlstra
A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 1996;80:332– 6.
4. Rodriguez A, Calonge M, Pedroza-Seres M, et al. Referral
Rothova et al 䡠 Birdshot Chorioretinopathy
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
patterns of uveitis in a tertiary eye care center. Arch Ophthalmol 1996;114:593–9.
Vitale AT. Birdshot chorioretinopathy. In: Foster CS, Vitale
AT, eds. Diagnosis and Treatment of Uveitis. Philadelphia:
WB Saunders Co.; 2002:731– 41.
Baarsma GS, Priem HA, Kijlstra A. Association of birdshot
retinochoroidopathy and HLA-A29 antigen. Curr Eye Res
1990;9:63– 8.
Levinson RD, Gonzales CR. Birdshot retinochoroidopathy:
immunopathogenesis, evaluation, and treatment. Ophthalmol
Clin North Am 2002;15:343–50.
Priem HA, Kijlstra A, Noens L, et al. HLA typing in birdshot
chorioretinopathy. Am J Ophthalmol 1988;105:182–5.
Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis: Fundamentals and Clinical Practice. St. Louis: Mosby-Year Book
Inc.; 1996:325–33.
Gasch AT, Smith JA, Whitcup SM. Birdshot retinochoroidopathy. Br J Ophthalmol 1999;83:241–9.
Opremcak EM. Birdshot retinochoroiditis. In: Albert DM,
Jakobiec FA, eds. Principles and Practice of Ophthalmology:
Basic Sciences. Philadelphia: WB Saunders Co.; 1994:475–
80.
Priem HA, Oosterhuis JA. Birdshot chorioretinopathy: clinical
characteristics and evolution. Br J Ophthalmol 1988;72:646 –
59.
Kraut JA, McCabe CP. The problem of low vision. Definitions
and common problems. In: Albert DM, Jacobiec FA, eds.
Principles and Practice of Ophthalmology: Basic Sciences.
Philadelphia: WB Saunders Co.; 1994:3664 – 6.
Priem H. Vascular manifestations in birdshot chorioretinopathy [in French]. Bull Soc Belge Ophtalmol 1989;230:41– 8.
Soubrane G, Coscas G, Binaghi M, et al. Birdshot retinochoroidopathy and subretinal new vessels. Br J Ophthalmol 1983;
67:461–7.
Brucker AJ, Deglin EA, Bene C, Hoffman ME. Subretinal
choroidal neovascularization in birdshot retinochoroidopathy.
Am J Ophthalmol 1985;99:40 – 4.
Barondes MJ, Fastenberg DM, Schwartz PL, Rosen DA. Peripheral retinal neovascularization in birdshot retinochoroidopathy. Ann Ophthalmol 1989;21:306 – 8.
Rothova A, Van Schooneveld MJ. The end stage of birdshot
retinochoroidopathy [letter]. Br J Ophthalmol 1995;79:
1058 –9.
Fuerst DJ, Tessler HH, Fishman GA, et al. Birdshot retinochoroidopathy. Arch Ophthalmol 1984;102:214 –9.
Oh KT, Christmas NJ, Folk JC. Birdshot retinochoroiditis:
long term follow-up of a chronically progressive disease. Am
J Ophthalmol 2002;133:622–9.
LeHoang P, Cassoux N, George F, et al. Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy. Ocul Immunol Inflamm 2000;8:49 –57.
Vitale AT, Rodriguez A, Foster CS. Low-dose cyclosporine
therapy in the treatment of birdshot retinochoroidopathy. Ophthalmology 1994;101:822–31.
Hirose T, Katsumi O, Pruett RC, et al. Retinal function in
birdshot retinochoroidopathy. Acta Ophthalmol (Copenh)
1991;69:327–37.
24. Priem HA, De Rouck A, De Laey JJ, Bird AC. Electrophysiologic studies in birdshot chorioretinopathy. Am J Ophthalmol
1988;106:430 – 6.
25. de Courten C, Herbort CP. Potential role of computerized
visual field testing for the appraisal and follow-up of birdshot
chorioretinopathy. Arch Ophthalmol 1998;116:1389 –91.
26. Wolf-Maier K, Cooper RS, Banegas JR, et al. Hypertension
prevalence and blood pressure levels in 6 European countries,
Canada, and the United States. JAMA 2003;289:2363–9.
27. van Rossum CT, van de Mheen H, Witteman JC, et al.
Prevalence, treatment, and control of hypertension by sociodemographic factors among the Dutch elderly. Hypertension
2000;35:814 –21.
28. Klungel OH, de Boer A, Paes AH, et al. Cardiovascular
diseases and risk factors in a population-based study in The
Netherlands: agreement between questionnaire information
and medical records. Neth J Med 1999;55:177– 83.
29. Diepgen TL, Mahler V. The epidemiology of skin cancer. Br
J Dermatol 2002;146(suppl 61):1– 6.
30. Coebergh JW, Neumann HA, Vrints LW, et al. Trends in the
incidence of non-melanoma skin cancer in the SE Netherlands
1975-1988: a registry-based study. Br J Dermatol 1991;125:
353–9.
31. Albert DM, Sober AJ, Fitzpatrick TB. Iritis in patients with
cutaneous melanoma and vitiligo. Arch Ophthalmol 1978;96:
2081– 4.
32. Sober AJ, Haynes HA. Uveitis, poliosis, hypomelanosis, and
alopecia in a patient with malignant melanoma. Arch Dermatol 1978;114:439 – 41.
33. Cui J, Bystryn JC. Melanoma and vitiligo are associated with
antibody responses to similar antigens on pigment cells. Arch
Dermatol 1995;131:314 – 8.
34. Heaton JM, Mills RP. Sensorineural hearing loss associated
with birdshot retinochoroidopathy. Arch Otolaryngol Head
Neck Surg 1993;119:680 –1.
35. Nussenblatt RB, Mittal KK, Ryan S, et al. Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune
responsiveness to retinal S-antigen. Am J Ophthalmol 1982;
94:147–58.
36. de Smet MD, Yamamoto JH, Mochizuki M, et al. Cellular
immune responses of patients with uveitis to retinal antigens
and their fragments. Am J Ophthalmol 1990;110:135– 42.
37. Jobin D, Thillaye B, de Kozak Y, et al. Severe retinochoroidopathy: variations of humoral and cellular immunity to Santigen in a longitudinal study. Curr Eye Res 1990;9(suppl):
91– 6.
38. Feeney-Burns L, Alspaugh M, Burns RP, Gao CL. Uveitis in
melanomatous swine: lack of evidence for humoral immune
melanocyte destruction. Invest Ophthalmol Vis Sci 1985;26:
551– 60.
39. Chang MA, Fournier G, Koh HK, et al. Ocular abnormalities
associated with cutaneous melanoma and vitiligo-like leukoderma. Graefes Arch Clin Exp Ophthalmol 1986;224:529 –35.
40. Luescher IF, Romero P, Kuznetsov D, et al. HLA photoaffinity labeling reveals overlapping binding of homologous melanoma-associated gene peptides by HLA-A1, HLA-A29, and
HLA-B44. J Biol Chem 1996;271:12463–71.
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