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Retinopathy in systemic lupus erythematosusRelationship to disease activity.

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1152
BRIEF REPORT
RETINOPATHY IN SYSTEMIC LUPUS ERYTHEMATOSUS:
RELATIONSHIP TO DISEASE ACTIVITY
ALICE V. KLINKHOFF, CRAIG W. BEATTIE, and ANDREW CHALMERS
Forty-three patients taking chloroquine for systemic lupus erythematosus were followed by one ophthalmologist over a 5-year period. Visual field testing,
color vision testing, and fluorescein angiography were
performed. Retinopathy was detected in 7 patients
(16%1, none of whom had hypertension or diabetes
melitus. Retinal abnormalities included cotton-wool
spots in 4 patients, microaneurysms in 3, and vascular
tortuosity in 4. In 4 patients, these abnormalities were
associated with retinal dysfunction, measured in terms
of abnormal hue discrimination. In 6 of the 7 patients,
the finding of retinopathy coincided with a flare of lupus
activity. In 5 patients, retinopathy improved when the
disease was controlled.
Retinopathy is a well-known complication of
systemic lupus erythematosus (SLE). Before the advent of steroids, retinopathy was reported in 50% of
SLE cases (1,2), However, the incidence of retinopathy in a predominantly outpatient population with
milder disease has been reported to be relatively small
(3). Between 1978 and 1983, 43 SLE patients treated
with chloroquine were referred to one ophthalmologist. This has permitted us to follow the course of SLE
retinopathy in a selected population. It became our
--___
From the Department of Medicine, Division of Rheumatology and the Department of Ophthalmology, University of British
Columbia, Vancouver, BC, Canada.
Alice V. Klinkhoff, MD, FRCP(C): Arthritis Society Fellow
in Rheiiniatology, Division of Rheumatology ; Craig W. Beattie,
MD, FRCS(C): Assistant Professor of Ophthalmology; Andrew
Chalmers, MD, FRCP(C): Associate Professor of Medicine.
Address reprint requests to Alice V. Klinkhoff, MD: Division of Rhoumatology, The Arthritis Centre, 895 West 10 Avenue,
Vancouver, BC, Canada VSZ 1L7.
Submitted for publication January 23, 1985; accepted in
revised form March 7, 1986.
Arthriti.5 and Rheumatism, Vol. 29, No. 9 (September 1986)
impression that retinopathy occurs more frequently
than is commonly believed. When present, retinopathy is seen in association with exacerbation of SLE,
and it resolves when the disease is controlled. We
have reviewed our 5-year experience in studying retinopathy in this SLE population.
Patients add methods. The study population
included all SLE patients referred to one of us (CWB)
between 1978 and 1983 for routine ophthalmologic
evaluation of antimalarial therapy. Forty-three patients satisfied the American Rheumatism Association
revised criteria for SLE (4). The indication for
antimalarial therapy is, generally, moderately active
skin and joint disease that is inadequately controlled
by antiinflammatory drugs and local therapies. The
mean age of the population was 42 years, and the mean
disease duration at the time of initial evaluation was 42
months from the time of diagnosis. In the earlier years
of the practice, most patients were prescribed chloroquine at a dosage of 250 mglday. Gradually, hydroxychloroquine has become the preferred antimalarial
drug and is prescribed almost exclusively by the local
rheumatologists. The common dosage is 200 mgiday .
Some rheumatologists initiate treatment with 400
mg/day and after approximately 2 months, reduce the
dosage to 200 mglday. When symptoms are under
control, it is accepted practice to decrease the drug to
alternate day therapy or to a 3 times weekly dosage
schedule. Average total chloroquine dose for the SLE
patients was 337 gm. The average daily dose of the
drug in the study population was 210 mg.
Ophthalrnologic evaluation was routinely performed prior to starting antimalarial treatment and was
subsequently performed seniiannually. Fluorescein
angiography was performed at the initial evaluation
1153
BRIEF REPORTS
Table 1. Clinical manifestations and ophthalmologic findings in 7 systemic lupus erythematosus (SLE) patients*
Farnsworth
Patient no. (age)
Clinical manifestations
Funduscopy
Glomerulonephritis, vasculitis
Proteinuria 4,800 mg/24 hours
Proteinuria 2,300 mgl24 hours,
vasculitis resolving
RE: cws, ma
Cws and ma resolved
Normal
Vasculitis
Vasculitis resolved
Srd, cws
Srd healing, cws resolved
RE: ma
RE: ma larger, vt
Fluorescein
angiography
100 Huet
Visual
assessment
LE
RE
148
252
116
128
176
168
616 OU
164
112
I67
188
616 OU
153
113
140
200
176
I76
72
84
196
300
1 (30)
August 1982
March 1983
July 1983
2 (38)
January 1978
May 1979
February 1982
January 1983
March 1983
July 1983
3 (26)
January 1983
June 1983
4 (48)
November 1978
January 1979
May 1979
5 (28)
February 1978
July 1978
6 (33)
March 1981
7 (36)
September 1982
* LE
SLE controlled
S L E controlled
Vasculitis flare
Vasculitis resolved
cws
Resolving srd
Ma missed
Ma missed
RE: both ma and vt
regressed
Arthritis, discoid lupus
RE: cws at macula,
bilateral vt
RE: cws resolved,
vt decreased
ou: vt
sLE inactive
Vt resolved
Arthritis
S L E cohtrolled
LE: cws
LE: cws resolved
Normal
24
12
616 OU
Arthritis
Normal
RE: ma, hemorrhage
36
52
616 OU
Migratory thrombophlebitis
ou: vt
Normal
104
112
616 OU
Fever, vasculitis
SLE controlled
Not done
619 R E
618 L E
616 OU
616 RE
619 L E ,
amblyopic
Normal
= left eye; R E = right eye; cws = cotton-wool spot; ma = microaneurysm; OU = both eyes; srd = serous retinal detachment; vt = vascu-
lar tortuosity.
t Normal values: age 20-30, <92; age 30-40, <120; age 40-50, <I44
and was repeated only if a significant change occurred
in funduscopic appearance or in visual function, as
indicated by color vision or visual field testing. The
semiannual ophthalmologic evaluation consisted of
clinical eye examination, quantitative visual field assessment, and measurement of hue discrimination.
Visual fields were assessed by static and kinetic
techniques on a Tubinger perimeter. A minimum of 3
isopters were measured in the kinetic technique; static
thresholds were measured in a vertical meridian
through the central 40" of the retina. Color vision
screening included the Ishihara and Dvorine pseudoisochromatic tests and the Farnsworth Panel D-15.
The Farnsworth 100 Hue test was used to test color
discrimination.
The supervising rheumatologist was advised if a
patient did not attend the scheduled semiannual eye
appointments, and antimalarial drugs were not further
prescribed until the required evaluation was completed. A significant reduction in retinal light sensitivity in those areas of the visual field that are susceptible to chloroquine's toxic effects was considered an
indication of early chloroquine retinal toxicity, and
the antimalarial was promptly discontinued. In this
event, subsequent evaluations were scheduled more
frequently until the visual field defect improved or
resolved.
Results. Retinopathy was detected in 7 of 43
SLE patients. None had diabetes or hypertension.
Ophthalmologic findings and manifestations of clinical
disease activity in those patients who developed
retinopathy are included in Table 1. Retinopathy consisted of cotton-wool spots in 4 patients, microaneurysms in 3 patients, and a serous retinal detachment in
1 patient. The detection of retinopathy coincided with
an exacerbation of SLE in all but 1 patient (patient 2 ) .
BRIEF REPORTS
1 1541
Table 2. Characteristics of systemic lupus erythematosus (SLE) patients with retinopathy
-
SLE
Patient
1
Age/
sex
30/F
Race
Asian
2
38/F
Mediterranean
3
26/F
White
12
4
48/F
Asian
4
5
28/F
White
0.5
6
33/F
White
5
7
36/F
White
16
no.
~
duration
(years)
3
8
Major manifestations*
Vasculitis, proteinuria (3 gm/24 hours),
DNA binding 22%
Malar rash, discoid lupus, vasculitis,
DNA binding 37%
Malar rash, lymphadenopathy, vasculitis, DNA binding 37%
Arthritis, discoid lupus, DNA binding
50%
Rash, arthritis, alopecia, DNA binding
40%
Malar rash, alopecia, arthritis, DNA
binding 10%
Migratory thrombophlebitis, C3 45 units
Medications (daily)
Hydroxychloroquine 200 mg, prednisone
100 mg, azathioprine 150 mg
Chloroquine sulfate 250 mg, prednisone
35 mg
Hydroxychloroquine 200 mg, prednisone
60 mg
Chloroquine sulfate 250 mg
Lupus
activity
criteria
count
2
3
3
3
Chloroquine sulfate 250 mg
3
Chloroquine sulfate 250 mg
2
Hydroxychloroquine 200 mg, prednisone
30 mg
1
* Normal value for DNA binding, 520%; normal range for C3, 70-212 units.
In this patient, retinopathy was first noted when SLE
was clinically well controlled. An increase in aneurysm size and vascular tortuosity was subsequently
observed 6 weeks prior to a flare of SLE. In 5 of 7
patients, retinopathy improved in association with
improved disease control.
The SLE patients who developed retinopathy
are characterized in Table 2 by age, sex, race, and
major disease manifestations. SLE activity was quantified using the Lupus Activity Criteria Count, which
permits 1 unit for each of 6 clinical features, 1 unit for
an abnormal serology result or decreased complement,
and I unit €or the presence of hematuria (5). The
presence of 2 or more criteria constitutes active disease. Only 1 patient had fewer than 2 criteria present
at the time retinopathy was identified. This woman
(patient 7) had a 16-year history of SLE, the major
manifestation of which was recurrent migratory thrombophlebitis. The latter had recently recurred when
ophthalmologic evaluation was performed, and vascular tortuosity was noted on funduscopy. In 3 patients,
retinopathy developed in association with cutaneous
vasculitis. No patient with retinopathy had clinically
evident central nervous system involvement.
Abnormalities in hue discrimination were noted
in 4 of'the 7 SLE patients. In 6 of 8 eyes, abnormalities
in hue discrimination were seen although specific
macular pathologic findings were absent. These findings frequently were detected at the initial evaluation
before antimalarial therapy was started, and improved
or resolved over the followup period while chloroquine was continuously prescribed.
Chloroquine retinopathy, defined as paracentral
visual field depression with or without characteristic
paracentral and central pigmentary macular changes,
was not noted in any patient.
Discussion. Retinopathy in SLE was first reported by Bergmeister in 1929 (6). Initial reports
emphasizing cotton-wool spots suggested a high prevalence of this abnormality, which was seen in 9 of 32
patients described by Shearn and Priofsky (28%) (7).
Subsequently, a variety of lesions have been noted,
including retinal hemorrhages, retinal edema, microaneurysms, arteriolar narrowing, venous engorgement, and tortuosity (8-1 3). Serous retinal detachment
has been rarely described (7,ll J4). Microvascular
abnormalities have been shown with fluorescein angiography, in the absence of lesions visible on funduscopy (15,16). These lesions may occur independently
of hypertension, and their relationship to more severe
SLE has previously been noted (2,7,9,17).
SLE retinopathy is detected not infrequently in
hospitalized patients, and is a common finding in fatal
cases (8-10,13). In the ambulatory SLB population,
retinopathy is considered exceedingly rare (2). In a
New York outpatient series of 61 patients who were
followed over a 10-year period, retinal abnormalities
included singular cotton-wool spots in 2 patients and a
microaneurysm in 1 patient (3). Arteriolar narrowing
was seen predominantly in hypertensive lupus pa-.
tients. In contrast, retinopathy was detected in 15 of 52
normotensive inpatients described in a recent series
(9). We have observed a 16% incidence of retinopathy
in a followup period of 5 years in our population. In
BRIEF REPORTS
general, it is our practice to prescribe chloroquine to
patients who have neither central nervous system nor
renal involvement, but who have moderate symptoms
that are inadequately controlled by nonsteroidal
antiinflammatory drugs and local measures. Thus, our
population is a selected one, which comprises neither
the most mildly nor the most severely affected. Therefore, the apparent differences in reported incidence
primarily reflect differences in patient selection, as
well as intensity of ophthalmologic followup.
Because of structural similarities between retinal and cerebral blood vessels, it has been suggested
that retinal vascular abnormalities may mirror disease
of the cerebral vessels (18,19). Fluorescein angiography has been proposed as a useful method of
assessing suspected cerebral lupus. None of our patients with retinopathy had clinically evident central
nervous system involvement. This finding is in agreement with findings of Lanham et a1 (9), who found no
association between retinopathy and cerebral disease
in a series of 52 hospitalized SLE patients.
In only 1 patient (patient 6) was the fluorescein
angiogram result abnormal when no abnormality was
detected by funduscopy. In 3 patients, abnormalities
detected by funduscopy were not seen on fluorescein
angiography because the limited field of standard
fluorescein photography did not include the regions
where lesions were located.
In 4 SLE patients, hue discrimination was abnormal bilaterally. Hue discrimination defects were
nonspecific in nature and consisted of FM 100 Hue
scores well beyond the ninety-fifth percentile for the
patients’ age group. This was noted in the absence of
specific macular defects in 6 of 8 eyes. In our opinion,
these abnormalities of hue discrimination were not
related to chloroquine therapy. In several patients,
they were detected at initial evaluation prior to starting
chloroquine therapy and they have improved during
followup, while antimalarial drugs were still being
taken. In our experience, when hue discrimination is
impaired in early chloroquine toxicity, typical paracentral visual field defects are always present, and
these abnormalities improve rapidly when the antimalarial drug is discontinued. Such findings were not
noted in any of the SLE patients; however, they
developed in 2 of 35 rheumatoid arthritis (RA) patients
who were followed in our clinic during the same time
period. It is noteworthy, as well, that both the SLE
and RA patients receiving chloroquine have had the
same average daily chloroquine dosage and very sim-
1155
ilar cumulative chloroquine doses (337 gm for SLE
patients, 307 gm for RA patients).
The absence of retinal chloroquine toxicity in
our SL,E patients was similar to findings of Rynes et al
(20), who detected no cases of chloroquine retinopathy
in 31 SLE patients treated with an average of 400 mg
of hydroxychloroquine, daily, for more than a year.
These findings must be interpreted cautiously in view
of the short duration of followup in both of these study
groups. In our SLE patients, duration of followup was
<5 years in all cases. In the Rynes study, only 19 of
the patients had been followed longer than 5 years at
the time of publication (20,21). Previously, a review of
the published literature on chloroquine retinopathy
(22) revealed an excess of reported cases among
patients with discoid and systemic lupus, compared
with the number of cases among RA patients. No
indication of drug dosage, duration of followup, intensity of followup, or number of patients in each disease
category who might be taking these drugs was given,
so this information is difficult to interpret. That report
is, nevertheless, the main reason for the suspicion that
chloroquine retinopathy occurs more frequently in
SLE patients than in RA patients.
Because of the retrospective nature of our
analysis, our observations are limited to the patients
who developed retinopathy during the course of routine ophthalmologic followup. No attempt was made
to collect information on disease activity in the 36 SLE
patients who did not develop retinopathy, or to screen
patients with an exacerbation of SLE for presence of
retinopathy. Our findings in 7 SLE patients with minor
retinal abnormalities confirm previous observations
that the development and resolution of retinopathy
parallel SLE disease activity (13,23-27). Retinopathy
associated with exacerbation of SLE was seen in each
patient, and in 1 patient a retinal deterioration heralded the onset of a severe exacerbation of SLE. For
a significant number of SLE patients, routine ophthalmologic evaluation to detect early chloroquine retinopathy is mandatory. In view of the association of
SLE retinopathy with disease activity, the results of
such testing may provide information useful to the
physician.
Our series illustrates the spectrum of retinopathy seen in a selected ambulatory SLE population.
Tests of retinal function may indicate subclinical
retinopathy. We believe that direct and indirect ophthalmoscopy and FM 100 Hue discrimination tests are
the most sensitive methods of detecting SLE retinopathy. Fluorescein angiography adds little.
BRIEF REPORTS
11516
REFERENCES
1. Baehr G, Klemperer P, Schifrin A: A diffuse disease of
the peripheral circulation (usually associated with lupus
erythematosus and endocarditis). Trans Assoc Am Phys,icians 50:139-155, 1935
2. Dubois EL: The clinical picture of systemic lupus
e:rythematosus, Lupus Erythematosus. Edited by EL
Dubois. Los Angeles, University of Southern California
E’ress, 1974, pp 323-326
3. Gold DH, Morris DA, Henkind P: Ocular findings in
systemic lupus erythematosus. Br J Ophthalmol
56:800-804, 1972
4. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ,
F!othfield NF, Schaller JG, Tala1 N , Winchester RJ: The
1982 revised criteria for the classification of systemic
liipus erythematosus. Arthritis Rheum 25:1271-1277,
1982
5. ZJrowitz MB, Gladman DD, Tozman ECS, Goldsmith
CIH: The lupus activity criteria count. J Rheumatol
11 ~783-787, 1984
6. Blergmeister R: Uber primare and Miliare Tuberkulose
der Retina. Wien Med Schnschr 79: 1 116, 1929
7. Shearn MA, Priofsky B: Disseminated lupus erythematosus. Arch Intern Med 90:790-807, 1952
8., Harvey AM, Shulman LE, Tumulty PA, Conley CL,
Schoenich EH: Systemic lupus erythematosus: review
of the literature and clinical analysis of 138 cases.
Medicine (Baltimore) 33:291437, 1954
9., Lanham IG, Barrie T, Kohner EM, Hughes GRV: SLE
retinopathy: evaluation by fluorescein angiography. Ann
Rheum Dis 41:473-478, 1982
10. Bishko F: Retinopathy in systemic lupus erythematosus:
a case report and review of the literature. Arthritis
Rheum 1557-63, 1972
11. Coppeto J, Lessell S: Retinopathy in systemic lupus
erythematosus. Arch Ophthalmol95:794-797, 1977
12. Plfaffenbach DD, Hollenhorst RW: Microangiopathy of
the retinal arterioles. JAMA 225:480482, 1973
13. Gold D, Feiner L, Henkind P: Retinal arterial occlusive
disease in systemic lupus erythematosus. Arch Ophthalmol 95:1580-1585, 1977
14. Koch FLP, McGuire WP: Intraocular manifestations of
acute lupus erythematosus. Trans Am Ophthalmol SOC
43:343-353, 1945
15. Santos R, Barojas E, Alarcon-Segovia D, Ibanez G:
Retinal microangiography in systemic lupus erythematosus. Am J Ophthalmol 80:249-252, 1975
16. Lachmann S, Hazleman B: Rheumatic diseases and the
eye. Hospital Update (October): 613-633, 1975
17. Clifton F, Greer CH: Ocular changes in acute systemic
lupus erythematosus. Br J Ophthalmol 39: 1-10, 1955
18. Edmonds JP, Bruneau C, Hughes GRV: Assessment of
activity in SLE: a clinical and serological study (abstract). Ann Rheum Dis 34543-544, 1975
19. Grennan DM, Forrester J: Involvement of the eye in
SLE and scleroderma. Ann Rheum Dis 36: 152-156,1977
20. Rynes RI, Krohel G, Falbo A, Reinecke RD, Wolfe B,
Bartholomew LE: Ophthalmologic safety of long-term
hydroxychloroquine treatment. Arthritis Rheum 22:
832-836, 1979
21. Tobin DR, Krohel GB, Rynes RI: Hydroxychloroquine-seven year experience. Arch Ophthalmol 100:
81-83, 1982
22. Voipio H: Incidence of chloroquine retinopathy. Acta
Ophthalmol (Copenh) 44:349-353, 1966
23. Maumenee AE: Retinal lesions in lupus erythematosus.
Am J Ophthalmol 23:971-981, 1940
24. Keil HL: Derrnatomyositis and systemic lupus erythematosus. Arch Intern Med 66:339-383, 1940
25. Klauder JV, Ellis VM: Effective treatment of lupus
erythematosus and exudative retinitis with a gold compound. Arch Ophthalrnol 21:893, 1939
26. Brihaye-Van Geertryden M, Davis P, Toussaint C:
Fundus lesions with disseminated lupus erythernatosus.
Arch Ophthalmol 51:799-801, 1954
27. Aronson AJ, Ordonez NG, Diddie KR, Ernest JT:
Immune-complex deposition in the eye in systemic lupus
erythematosus. Arch Intern Med 139:1312-1313, 1979
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