Indian J Ophthalmol. May 2014; 62(5): 642–644.
Nonarteritic anterior ischemic optic neuropathy as the presenting
manifestation of primary antiphospholipid syndrome
Betul Tugcu, Nur Acar,1 Cigdem Tanrıverdi Coskun, Selda Celik,2 and Fadime Ulviye Yigit
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Nonarteritic anterior ischemic optic neuropathy (NAION) has been reported in association
with a number of systemic conditions. However, it has rarely been reported with
antiphospholipid syndrome (APS). APS is an autoimmune disorder characterized by
vascular (arterial, venous, or small vessel) thrombosis or pregnancy morbidity. Diagnosis
of APS is based on having at least one clinical (vascular occlusion and/or pregnancy
complications) finding and one laboratory criterion (repeated positivity for lupus
anticoagulants and/or antibodies targeted against cardiolipin or β (2)-glycoprotein in 3
months) at the same time. Ocular involvement in APS includes a broad spectrum of
manifestations from the anterior and posterior segment, or the presence of
neuroophthalmologic features. Neuroophthalmologic features are transient visual loss,
ischemic optic neuropathy (ON), and progressive optic nerve atrophy.
NAION has rarely been reported as the prevailing sign of APS. We here described a case
presenting with NAION in whom a primary APS was subsequently diagnosed.
A 36 year old Caucasian woman was admitted because of headache and sudden unilateral
visual loss in her left eye (LE). She was not a smoker or alcohol consumer. The patient
did not have hypertension, hyperlipidemia, and diabetes mellitus. She had a history of
abortion in the second trimester. Physical examination was normal.
Ophthalmological examination showed a left relative afferent pupillary defect (RAPD)
and swelling of the left optic disc (OD) with accompanying pallor. Visual acuities (VA)
were 20/20 and 6/20 in the right and LE, respectively. Color vision was impaired in the
LE with Ishihara color plates. Visual field testing with automated perimetry (Humphrey
Field Analyser Model 750i, HFA II, Carl Zeiss Meditec Inc. Dublin, CA, USA; 1994-
2000 central 30-2 threshold test) showed a dense inferior arcuate defect [Fig. 1].
Examination of the right eye was normal. Initially, a diagnosis of ON was made and
intravenous methylprednisolone was started and given 1 g/day for 3 consecutive days.
Oral prednisolone 1 mg/ kg/ day was started on day 4 and continued for 1 week and
stopped in 1 month by tapering the dose each week. VA increased to 0.7 on day 1, to 0.9
on day 2, and to 1.0 at week 1.
Visual field test demonstrates an inferior arcuate defect in the LE
At follow-up examination at the end of the first month, the visual acuity in the LE was
20/20 and pupillary light reflexes were normal. Cup/disc (c/d) ratio was analyzed with
Optical Coherens Tomography (Optovue Fourier domain OCT, Optovue Inc, Freemont,
CA, USA). Horizontal c/d ratio was 0.54 in RE and 0.40 in LE. Vertical c/d ratio was 0.32
in RE, and 0.41 in LE. OD edema in LE resolved leaving partial atrophy in the superior
part of the optic disc and the visual field test revealed partial improvement of the inferior
arcuate defect. Corticosteroid therapy was stopped. Two months later, she presented again
with blurred vision in her LE. The VAs were 20/20 in both eyes, with no RAPD. The OD
had a slight pallor superiorly [Fig. 2]. Fluorescein angiography showed a patchy
background choroidal flourescence and a relative delay in arterio-venous filling in the
superior temporal retinal vessels compared with the inferior temporal ones [Fig. 3]. No
leakage from the disc or vessels was observed.
Fundus photograph of the LE. Note the optic disk pallor in the superior half
Fundus fluorescein angiography of the LE. Fluorescein angiography showed a patchy
background choroidal flourescence and a relative delay in arterio-venous filling in the
superior temporal retinal vessels compared with the inferior temporal ones in the ...
Extensive investigations for hypertension, hyperlipidemia, diabetes mellitus,
atherosclerosis, cardiac diseases connective tissue, and autoimmune disorders were
performed. As there was no clinical signs or findings of infectious disease, no extensive
work-up was performed. Renal and liver tests, glucose, and lipid profile were all normal.
Factor V Leiden and prothrombin gene mutations were absent. SLE and other connective
tissue disorders were excluded with intensive investigations. APS was detected in the
immunological examination [lupus anticoagulant 62.9 s (normal 31-44); anticardiolipin
antibodies IgG, 18.86 (normal 0-10), IgM 30.90 (normal 0-7)]. Primary APS was
diagnosed based on the above clinical and laboratory findings and treatment with oral
anticoagulant (coumadin 5 mg/day), antiagregan (coraspin 100 mg/day), and
antiinflammatory drug (hydroxychloroquine 200 mg/day) was started immediately. We
tested lupus anticoagulant and anticardiolipin antibodies IgG and IgM 3 months later, and
they were still at high levels, which confirmed the diagnosis.
The patient remained asymptomatic under treatment. One year later, the patient had 20/20
vision in both eyes and did not have any new thrombotic events. She is still under the
above-mentioned treatment with excellent treatment efficacy regarding the INR values
and without side effects.
The systemic features of the APS syndrome are characterized by large variability
depending on the affected organs. However, studies on the frequency and clinical
presentation of the ocular manifestation as the presenting sign of APS in patients suffering
from unexplained ocular disease are missing. Herein, we present a case of NAION as
the first manifestation of APS, which is very rarely described.
Ocular involvement associated with APS include vaso-occlusive retinopathy and ON.
Prevalence of ocular vaso-occlusive disease has been estimated in 29% of patients with
primary APS, but ON is a very rare manifestation of primary APS and only a few isolated
cases have been reported in the literature. Tsironi et al. reported a case series with
ocular disorders as the prevailing manifestations of APS. The first patient had bilateral
retinal occlusive disease and the second and third patient had unilateral NAION with
macular edema. Our case was also unilateral, which responsed to CS therapy with
recurrence of blurred vision after its cessation. Reino et al. reviewed cases of ON in
APS from the recent literature. ON was associated with systemic thrombotic
manifestations, most commonly with neurological disorders followed by cardiac disease,
arterial and venous thrombosis, miscarriage, and livedo reticularis. However, in our
case there was no systemic thrombotic events. The only important finding was her history
of abortion. The most probable pathogenesis of ON is an abnormal microcirculation
secondary to thrombosis of the small arterial vessels that arise from the choroidal
circulation and supply the anterior portion of optic nerve caused by antiphospholipid
antibodies, similar to other clinical manifestations of the primary APS. Giorgi and
Gabrieli suggested that a monolateral ON in patients with significant levels of aPL
could be considered as a focal lesion due to microthrombotic events involving the ciliary
Treatment of ON in primary APS is controversial and should be individually tailored.
Anticoagulation therapy can prevent future events not only in eyes but also episodes in
other vital organs.[5,8] As thrombosis with no evidence of vasculitis seems to be probably
the most important mechanism of this ON, treatment with aspirin or anticoagulants must
be tried, although in several occasions prednisolone has also been used. Corticosteroids
have no established role in the treatment of APS but are used for rheumatic symptoms in
patients with accompanying systemic autoimmune illness. However, high doses of
corticosteroids are usually given empirically to patients with severe thrombocytopenia,
hemolytic anemia, and catastrophic APS.
Our patient received systemic steroids because of the initial diagnosis of ON. As APS was
diagnosed during rheumatologic work-up 2 months after the completion of the steroid
therapy, anticoagulant therapy with antiinflammatory drug hydroxychloroquine was
started. The protective effect of hydroxychloroquine on thrombosis in systemic lupus
erythematosus patients has been shown in the literature. Furthermore, use of this drug has
been considered as a new approach on prevention of the thrombosis in the APS.[9,10]
In conclusion, albeit rarely ON may be observed as a presenting manifestation in primary
APS, it is advisable that patients with ON in whom the etiology is uncertain may be tested
for the presence of antiphospholipid antibodies. Due to the important diagnostic and
therapeutic implications of APS, the possibility of ocular features as the first clinical
manifestation of APS, particularly in patients with no evident risk factors for ocular
disease, should be kept in mind of ophthalmologists.