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Acute Idiopathic Blind Spot Enlargement Syndrome
A Review of 27 New Cases
Nicholas J. Volpe, MD;
Joseph F. Rizzo III, MD;
Simmons Lessell, MD
Arch Ophthalmol. 2001;119:59-63.
ABSTRACT
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Objective To describe the clinical findings in patients with acute idiopathic
blind spot enlargement (AIBSE).
Methods Medical record review of 27 patients with AIBSE (without sufficient
optic nerve head swelling to cause blind spot enlargement) seen in 2 academic
neuro-ophthalmology units.
Results All patients were women aged between 19 and 53 years. Twenty-three patients
reported positive visual phenomena. Visual acuity was normal in 16 patients.
All patients had enlarged blind spots of variable size and density. Dyschromatopsia
and afferent pupil defects were prevalent. Ophthalmoscopic features included
uveitis, mild optic nerve swelling, granularity of macular pigment, subretinal
white dots, and peripapillary pigment disturbances. Twelve of the 13 patients
who underwent fluorescein angiography had optic disc staining and 5 had retinal
pigment epithelial lesions with late staining. Full-field electroretinogram
results were normal in 8 of 9 patients, although focal electroretinogram results
were abnormal in 8 of 9 patients. Photopsia always decreased but visual fields
did not improve. Six patients experienced recurrence.
Conclusions The clinical features of AIBSE include photopsia, visual field defects,
abnormal findings from fundoscopic and fluorescein angiography, and abnormal
results of focal electroretinography. The disease affects the peripapillary
retina and may cause an afferent pupillary defect. The striking predilection
for the peripapillary retina suggests a local etiologic factor and distinguishes
AIBSE from the multiple evanescent white dot syndrome. Unlike patients with
multiple evanescent white dot syndrome, recovery of visual field did not occur
in patients with AIBSE.
INTRODUCTION
THE CLASSIFICATION of the acute idiopathic blind spot enlargement syndrome
(AIBSE) among various other fundus diseases remains controversial. Our review
of 27 previously unreported cases of this disorder might not only offer insights
into the nosology, but also contribute to the semiology of AIBSE. Our series
suggests a spectrum of peripapillary retinal disease in women with abnormal
parafoveal electroretinography (ERG) results, some evidence of optic neuropathy,
and limited recovery.
SUBJECTS AND METHODS
All 27 patients were examined at the Massachusetts Eye and Ear Infirmary
(Boston) or the Scheie Eye Institute (Philadelphia, Pa) by one of us and diagnosed
with AIBSE from 1989 to 1997. The results are based on a retrospective review
of their records. Each patient had symptomatic, acute onset of a visual disturbance
and demonstrated blind spot enlargement on visual field testing. In none of
these cases was there disc edema sufficient to explain the blind spot enlargement.
The patients had been referred for neuro-ophthalmic evaluation by a comprehensive
ophthalmologist or retinal specialist when a diagnosis could not be established.
All patients had a complete neuro-ophthalmic examination including measurement
of Snellen visual acuity, color vision (Ishihara test plates), pupillary examination,
dilated funduscopy, and either Goldmann or automated (Humphrey) perimetry.
Thirteen patients also had fundus photography with fluorescein angiography.
Full-field and focal ERGs were recorded in 9 patients. The study conformed
to the policies outlined by the institutional review board of studies involving
human subjects at the University of Pennsylvania School of Medicine and the
Harvard Medical School.
RESULTS
All 27 patients were woman aged between 19 and 53 years, 11 (41%) of
whom were taking birth control pills at the time they developed symptoms.
The correct diagnosis was not made by the referring physician in any patient.
Optic neuritis and ophthalmic migraine were common misdiagnoses. Twenty-five
patients complained of decreased vision (Table 1). Twenty-three reported experiencing visual phenomena: in
5 cases the photopsia preceded the onset of visual loss by several weeks.
Pain was reported by only 2 patients and was described as an "ache" not exacerbated
by eye movement.
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Table 1. Initial Symptoms of 27 Patients With Acute Idiopathic Blind
Spot Enlargement
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Results of vision testing are presented in Table 2. Visual acuity was normal in 16 patients (20/25 to 20/50
in 10 and 20/200 in 1). Nine patients had dyschromatopsia and 8 had afferent
pupil defects. All patients had enlarged blind spots. Blindspot enlargement,
present in all patients, was highly variable in terms of size, although all
defects shared the common feature of steep margins (Figure 1).
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Table 2. Measured Visual Dysfunction in 27 Patients With Acute Idiopathic
Blind Spot Enlargement
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Figure 1. Examples of Goldmann (A) and Humphrey
(B) visual fields from 5 different patients with acute idiopathic blind spot
enlargement. Note the highly variable size of the visual field defect as well
as the steep margins of the scotomas.
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Only 8 patients had completely normal anterior segment and ophthalmoscopic
examination results. Ten patients had more than 1 finding on examination (Table 3). The most common abnormalities
were mild disc swelling (not commensurate with the blind spot size) or hyperemia
and peripapillary subretinal pigmentary changes (Figure 2). One patient, who was diagnosed with uveal effusion syndrome
10 years earlier, had a few bone spicules and pigmentary alterations in the
nasal peripheral retina. Late staining of the optic nerve head on fluorescein
angiography was found in 12 patients, 3 of whose discs were ophthalmoscopically
normal. Late-staining retinal pigment epithelial (RPE) lesions with peripapillary
hyperfluorescence were commonly seen (Figure
3). These areas of RPE staining did not correspond to white spots
on ophthalmoscopy. Five patients had multiple white lesions similar to those
described in patients with multiple evanescent white dot syndrome (MEWDS).
Similar fundus findings were not observed in the contralateral, uninvolved
eye.
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Table 3. Opthalmoscopic Findings in 27 Patients With Acute Idiopathic
Blind Spot Enlargement Syndrome*
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Figure 2. The spectrum of ophthalmoscopic
findings in acute idiopathic blind spot enlargement. A and B, Mild optic nerve
head swelling and peripapillary pigmentary changes were the most common findings.
C, Peripapillary atrophy and focal, deep pigment changes in a patient. D,
A peculiar grayish-yellow peripapillary halo (arrow) was seen in 4 patients.
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Figure 3. Late-phase fluorescein angiography
of 2 patients with acute idiopathic blind spot enlargement. A, Disc staining.
Five patients had small isolated, bright deep (late staining) retinal lesions
(arrows). B, The ring of peripapillary deep hyperfluorecence.
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One patient had normal full-field and focal ERG results. Full-field
ERG amplitudes were within normal limits in all patients but 1, whose ERG
showed mildly reduced amplitudes. In 4 patients, intereye differences were
noted, and the full-field ERG amplitudes were slightly less in the affected
eye. However, nasal parafoveal focal ERG results were abnormal in 8 of the
9 patients who had ERGs. The nasal parafoveal response was not recordable
in 1 patient, and a reduction in amplitude or delayed implicit time was found
in the others. One patient demonstrated dysfunction of the nasal parafoveal
retina compared with normal temporal parafoveal retinal responses.
Although all but 1 of the patients with reduced visual acuity improved,
there was no improvement of the enlarged blind spot in the 10 patients who
were followed up. Photopsias always decreased. In 6 patients, either a recurrence
was noted on our follow-up examinations or the current episode was thought
to be a recurrence based on the history. These episodes occurred between 1
and 15 years after the initial visit, and in 2 patients the recurrence occurred
in the opposite eye.
COMMENT
The phrase big blind spot syndrome has been
used to designate several different entities (Figure 4). When associated with significant optic nerve head swelling,
blind spot enlargement results from displacement of the peripapillary retina
and refractive changes. In patients with inflammatory disease of the retina
and choroid, blind spot enlargement corresponds to areas of retina and choroid
that appear abnormal ophthalmoscopically.1
In 1988, Fletcher et al2 described a clinically
distinct syndrome of blind spot enlargement in 7 patients who acutely developed
photopsias and enlargement of the blind spot without optic disc swelling or
choroiditis. In 1984, Jampol et al3 and Takeda
et al4 described a similar condition, common
in women, associated with scotomas and multiple evanescent white lesions at
the level of the RPE (MEWDS). Subsequently it became clear that AIBSE and
MEWDS share clinical features and perhaps represent different forms of the
same disease, with some differences accounted for by the timing of the initial
clinical examination. Interestingly, these clinical syndromes were not recognized
in patients prior to the 1970s.
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Figure 4. Subsets of patients with enlarged
blind spots. Patients with AIBSE (acute idiopathic blind spot enlargement
) had neither sufficient optic disc swelling nor sufficient ophthalmoscopically
visible chorioretinal changes to explain the enlarged blind spot.
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In our series, when all of the clinical findings were taken together
(acute onset of positive visual phenomena, a visual field defect centered
on an enlarged blind spot, and the absence of marked disc swelling), the diagnosis
of AIBSE was relatively easily made. However, we found a high prevalence of
misdiagnoses by the referring physician. The overlap with other common neuro-ophthalmic
entities and the variability of clinical findings make AIBSE an important
entity in neuro-ophthalmic differential diagnoses. Photopsia may be incorrectly
ascribed to migraine. The abrupt onset of a visual field defect in a young
patient might suggest optic neuritis. The presence of an enlarged blind spot
and disc hyperemia might suggest papilledema or a temporal defect from a chiasmal
lesion.
Acute idiopathic blind spot enlargement is a disease of the outer retina
and therefore shares many features with MEWDS. Enlarged blind spots are often
found in MEWDS.3-10
It is possible that the evanescent white dots of MEWDS are present but unrecognized
or ophthalmoscopically obscure in some or all patients with AIBSE. Abnormalities
in the indocyanine green angiography results have been demonstrated in patients
with MEWDS who had no apparent white spots on ophthalmoscopy.11
Callanan and Gass12 suggested that MEWDS, AIBSE,
multifocal choroiditis, acute macular neuroretinopathy (AMN), and acute zonal
occult outer retinopathy (AZOOR) may be a single disease with variable presentation.
Supporting the theory that these signs and symptoms all represent the spectrum
of a single disease are reports of patients with AIBSE and MEWDS who developed
lesions typical of AMN.13-14 Patients
with MEWDS and AIBSE have also been reported to develop multifocal active
or atrophic fundus lesions typical of multifocal choroiditis.15-17
The etiology of AIBSE and all of these other syndromes is unknown, although
they all seem to result from photoreceptor outer segment dysfunction. It is
not surprising that any condition (regardless of etiology) associated with
dysfunction of the outer retina would have a similar presentation. These syndromes
are characterized by acute, focal loss of outer retinal function associated
with photopsias. They occur predominantly in young women, and initially there
are minimal or no fundus changes. Abnormal ERG results are commonly identified.
Our findings suggest that AIBSE is distinct from MEWDS, AZOOR, AMN,
and multifocal choroiditis. Unlike most patients with MEWDS, recovery of visual
field did not occur in our patients with AIBSE. Fundus findings in addition
to intraocular inflammation and disc swelling were common in our patients,
including focal areas of peripapillary deep pigmentary changes that took the
form of atrophic or discolored spots, or a grayish halo around the optic nerve
head (Figure 2). In all of our patients,
the extent of the visual field defects implied retinal dysfunction beyond
any visible abnormalities of the disc or peripapillary retina. Although we
did find a high incidence of funduscopic abnormalities, we agree with Jampol
and Wiredu18 that these abnormalities are different
from those seen in AMN, multifocal choroiditis, and AZOOR. Indeed, at the
time of the initial visit, each of these entities had a highly variable appearance
of the fundus. On the other hand, we did find that some patients with MEWDS
could not be distinguished from patients with AIBSE. Five of our patients
had ophthalmoscopically visible white dots that were consistent with MEWDS.
However, macular pigment granularity, considered pathognomonic of MEWDS, was
recognized in only 2 of our patients. Finally, features common to the series
of patients with AZOOR reported by Gass8 and
Jacobson et al,19 including progression of
visual field loss during weeks or months, progressive ERG worsening, second
eye involvement, chronic photopsia, and late RPE atrophy, were not prominent
in our patients. The clinical courses of our patients were characterized by
resolution of photopsia with stable, persistent visual field defects, suggesting
that photoreceptor dysfunction is permanent but not progressive.
Fluorescein angiographic findings in our patients were similar to those
reported in patients with MEWDS (peripapillary hyperfluorescence from late
RPE staining). However, we found a high incidence (12/13 patients) of disc
staining compared with patients with MEWDS. While disc staining may simply
reflect an altered vascular permeability, it also raises the possibility of
a simultaneous inflammation of the optic nerve. Dodwell et al20
reported optic nerve involvement in MEWDS. While extensive visual field loss
on a retinal basis could cause a relative afferent pupil defect and dyschromatopsia,
simultaneous retinal ganglion cell and photoreceptor dysfunction needs to
be considered.
Focal ERG abnormalities were found in 8 of 9 of our patients studied.
We suggest the use of focal or multifocal ERG to confirm the diagnosis of
AIBSE. The use of focal ERG to diagnose AIBSE was first reported by Fletcher
et al,2 and confirmed by Singh et al.13 Full-field ERG abnormalities in patients with MEWDS
have also been recognized.3, 5-7,21-22
Electroretinogram abnormalities along with photopsia suggest localization
of the disease to the photoreceptors and pigment epithelium. Jacobson et al19 demonstrated full-field ERG abnormalities in AZOOR
and identified a pattern of retinal dysfunction most compatible with outer
segment disease.
Six of our patients had recurrences although none had a progressive
condition. It is unusual for patients to experience recurrences, and therefore,
an autoimmune condition, which typically relapses, would be a less likely
explanation for the retinopathy than an environmentally triggered causative
factor. Although Chung et al23 have reported
elevated levels of serum immunoglobulins in patients with MEWDS, Jacobson
et al19 were unable to demonstrate histochemical
evidence of retinal antibodies in the sera of their patients affected with
AZOOR. Since we did not encounter a single male patient with AIBSE during
an 8-year period, it seems likely that hormonal or genetic factors contribute
to the development of AIBSE. Borruat et al24
found a higher than expected prevalence of HLA-B51 in their patients with
MEWDS. Patients with MEWDS and AZOOR have frequently been noted to have an
antecedent flulike illness, suggesting an environmental trigger, but this
did not seem to be true in our patients.
In addition to peripapillary retinal dysfunction in AIBSE, there may
also be optic neuropathy. Features of peripapillary nasal retina (primarily
involved in AIBSE), such as increased cone density,25-26
blood supply, and proximity to the optic nerve, indicate that it may be uniquely
vulnerable to conditions that do not involve the remainder of the retina.
In our patients with AIBSE, photopsia and abnormal focal ERG and disc staining
results were the most consistent findings. With increasingly accurate diagnosis
rates, more patients will be identified early and a pattern of findings will
lead to an etiology or pathogenetic mechanism for each or all of these conditions.
Assigning a label to a collection of similar signs and symptoms will not further
the cause of determining the disease etiology or etiologies. Therefore, until
a single etiology cause is found for all of these conditions, it is reasonable
to assume they are all distinct entities. Efforts should be made to try and
determine an etiologic factor, and more extensive immunological testing of
both sera and spinal fluid might prove to be helpful to further define the
etiology of this condition. We offer the following definition of AIBSE: absolute
symptomatic enlargement of the blind spot without commensurate swelling of
the optic nerve head occurring in conjunction with presumed disease of the
optic nerve and peripapillary retina.
AUTHOR INFORMATION
Accepted for publication June 2, 2000.
Corresponding author and reprints: Nicholas J. Volpe, MD, Scheie
Eye Institute, 51 N 39th St, Philadelphia, PA 19104 (e-mail: nickvolp{at}mail.med.upenn.edu).
From the Departments of Ophthalmology and Neurology, School of Medicine,
University of Pennsylvania, and the Scheie Eye Institute, Philadelphia (Dr
Volpe); and the Department of Ophthalmology, Harvard Medical School, and the
Massachusetts Eye and Ear Infirmary, Boston (Drs Rizzo and Lessell).
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