ACUTE MACULAR NEURORETINOPATHY

J A M E S A. R U S H , M . D .

Charlottesville,

Virginia
acuity was 6/6 (20/20) in each eye. Both anterior
segments were normal. Direct and indirect ophthalmoscopy demonstrated pertinent findings restricted
to the macula of the left eye. In the fovea, there were
three discrete, although faint, reddish-brown lesions
that had an arrowhead or a wedge shape, pointing
toward a normal foveolar light reflex (Fig. 1). Biomicroscopy through a Goldmann contact lens showed
three superficial, vague areas of dusty, dusky deposits that merged imperceptibly with normal retina.
There were no deep areas of altered pigmentation or
exudative deposits in the retina. No commonly identifiable changes in retinal structure were noted.
Fluorescein angiograms were normal (Fig. 2),
confirming the integrity of the retinal pigment epithelium and retinal vasculature, and substantiating the
gossamer-like quality of the observed lesions. The
patient was able to reproduce scotomas on an
Amsler grid (Fig. 3). Goldmann perimetry revealed
no abnormality other than that on the Amsler grid,
although the varying illuminance and size of the test
objects corresponded well with both the densities of
the ophthalmoscopically observed lesions and the
subjective appreciation described by the patient.
No change in the visual acuity, and no change in
the subjective scotomas, occurred in six months of
follow-up observation. The lesions neither coalesced nor regressed. The patient still finds the
scotomas most bothersome, but has refused to consider cessation of the oral contraceptive hormone.

Recently, B o s and D e u t m a n examined

four patients with an unusual macular
affliction characterized by minimal depression of vision and scotomas that corresponded to peculiar foveal lesions situated in the superficial retina. T h e y termed
this illness acute macular neuroretinopathy.
1

Their four patients were women, aged

2 4 to 3 3 years, and all were taking oral
contraceptives. T w o of the four patients
had experienced a mild, apparently infectious illness: one had an acute "enteritis,"
and the other, " a bout of influenza."
T h r e e of the four patients had bilateral
involvement, although one of these did
not manifest simultaneous bilateral involvement. F u n d i and visual fields were
abnormal, but fluorescein angiograms in
all four, and electroretinograms with
electro-oculograms ( E O G ) in both patients tested, were normal.
Recently, I observed a woman with a
remarkably
similar malady. T o my
knowledge, this is the first case reported
in the United States.
CASE REPORT

A 24-year-old white woman complained of "seeing spots in her left eye." She had been healthy until
late in December 1975, when she contracted "a
cold." Six weeks later, she developed an acute
pharyngitis, that, although culture-negative, was
treated with erythromycin. When her symptoms
resolved two weeks later, she noted three tearshaped spots in front of her left eye. They were
constant, and always appeared where she "focused."
At an ocular examination two days later, without
cessation of symptoms, she admitted to having had
"migraine" in high school. She had been taking oral
contraceptives for many years. Her general history
was otherwise unremarkable.
At that visit on March 10, 1976, her best corrected

From the University of Virginia Medical Center,

Eye Clinic, Charlottesville, Virginia.
Reprint requests to James A. Rush, M.D., 1404
Hazel St., Charlottesville, VA 22901.
490

Fig. 1 (Rush). Fovea of the left eye. Normal light

reflex is surrounded by one temporal and two nasal
wedges or teardrops, pointing to the foveola (arrows).

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491

pigment epitheliopathy were female, but

only three of them were known to be
taking oral contraceptives. All patients
recovered and only one patient had a
recurrence. Despite speculation concerning the causea viral infection or its
sequelae etiology and pathogenesis
are unknown. Whether it is primarily a
disease of choriocapillaris or retinal pigment epithelium is still being debated.
Clinically distinct, acute retinal pigment epitheliitis was described in 1 9 7 2 .
Only four cases have been reported
since.
T h e lesions were ophthalmoscopically distinct, and restricted to the
macula. They were multiple, and resembled gray to black pigment spots, surrounded by halo zones. T h e y were usually monocular, asymptomatic, and caused
a moderate visual lossmost cases better
than 6/22 (20/70) and only one had 6/30
(20/100)although recovery was the rule.
Fluorescein angiography showed hypofluorescence in the central dark areas and
9

10

11

1 2 , 1 3

14

1 5 , 1 6

Fig. 2 (Rush). Left eye. Late phase fluorescein

angiogram showing absence of window defects,
blocked transmission, or capillary leakage.

DISCUSSION

Several idiopathic acute posterior pole

lesions have been described recently. In
1968, G a s s first described three young
women with moderately severe loss of
central vision bilaterally, in whose posterior pole areas were seen multiple
cream-colored lesions, apparently located
at the pigment epithelial level. He termed
this entity acute posterior multifocal placoid pigment epitheliopathy, and noted
that these lesions did not extend beyond
the equator and generally were less than 1
disk diameter in size. Despite a superficial resemblance to choroiditis, no inciting agent was ascertained, and his patients recovered normal, or nearly normal,
acuity in several months.
Later reports documented that this condition was not benign, being associated
with papillitis and retinovasculitis. It
has been associated with bilateral serous
detachments in two patients, and erythema nodosum in two o t h e r s .
Several
patients developed this after an acute
viral i l l n e s s .
Twenty-seven of the 51 p a t i e n t s
with acute posterior multifocal placoid
2

->
r \

5,6

7,8

2 - 1 3

Fig. 3 (Rush). Amsler grid demonstrates the teardrop or wedge shapes of parafoveal scotomas pointing toward fixation. Large horizontal scotoma was
most prominent, followed by inferonasal scotoma
whose corresponding lesion was closest to the foveola.

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AMERICAN JOURNAL O F OPHTHALMOLOGY

hyperfluorescence in the halo zones.

Leakage was not demonstrated. Thes e lesions did not look like those of acute
posterior multifocal placoid pigment epitheliopathy, being considerably smaller,
and healing without scar formation.
However, the retinal pigment epithelium
is implicated because the E O G s , when
they have been recorded, have been baseline or subnormal. Like acute posterior
multifocal placoid pigment epitheliopathy, the illness is idiopathic, and recovery
is common. Only one of the ten reported
cases occurred after an acute viral illness.
Acute macular neuroretinopathy was
first described in 1 9 7 5 , when four detailed and two supplemental cases from
Europe were reported. Typically, acute
macular neuroretinopathy manifests three
to five reddish-brown foveal lesions, occurs predominantly in women and often
after mild viral illnesses. T h e s e lesions
assume a peculiar wedge-shaped or teardrop configuration, pointing to the umbo,
and characteristically do not cause a decline in visual acuity (Snellen). Yet, they
are bothersome, as they infringe upon
the foveola and produce small central
scotomas. T h e lesions are subtle, and
are best seen with the direct ophthalmoscope by using red-free light and motion
parallax.
1

Our case is typical of acute macular

neuroretinopathy: a young woman recovering from a viral upper respiratory infection noted the onset of three central scotomas corresponding to parafoveal deposits
of the unusual shape and coloration previously described. Visual acuity, peripheral fields, and fluorescein angiograms
were normal. Central fields, as depicted
on Amsler grid, showed scotomas corresponding to the fundus lesions.
O f seven patients, six women including
my patient with acute macular neuroretinopathy were taking oral contraceptives.
None of the other women had a remission, but no knowledge of discontin-

APRIL, 1977

uation of the hormone is available. My

patient was bothered by disruptive scotomas, but declined to consider longterm cessation of the pill. Therefore,
whether the association is causal or casual
is speculative.
There is some overlapping in these
three different conditions (Table). T h e y
are more common in women, but are
increasingly being diagnosed in m e n .
They may occur after viral illnesses. T h e y
may be related to oral hormones. T h e y
occur primarily, yet not exclusively, in
younger people. T h e y affect the posterior
pole.
These lesions, although superficially
similar, differ in appearance, and differ on
fluorescein
angiography. Furthermore,
acute macular neuroretinopathy is a disease of the more superficial sensory layers
of the retina, whereas the other two entities have involved the retinal pigment
epithelium.
Although acute macular neuroretinopathy is associated with the least decline in
visual acuity, it is the one disease that
undergoes the least amount of amelioration of symptoms. Whereas acute posterior multifocal placoid pigment epitheliopathy is associated with an initial dramatic decline in acuity, and the acute retinal
epitheliitis is manifested by a moderate to
severe loss of vision, recovery, although
slow, ultimately occurs. On the other
hand, in acute macular neuroretinopathy,
the paracentral scotomas have never been
documented to regress.
Finally, all three illnesses are idiopathic. As the number of cases of acute posterior multifocal placoid pigment epitheliopathy mounts, the association with viral
illness is becoming a potential source of
research. Although most cases of acute
macular neuroretinopathy occurred after
a viral illness, a relationship to viral infection has not yet been proven. Furthermore, although all six women with acute
macular neuroretinopathy had been re1

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493

TABLE
D I F F E R E N T I A L DIAGNOSIS O F M A C U L A R L E S I O N S *

APMPPE "
2

Sex
Appearance

13

24 M , 2 7 F
Cream-colored plaques

Location

Posterior pole
to equator
Systemic infection Common
Associated ocular Common
inflammation
Laterality
Usually bilateral
Diminished acuity Marked
Fluorescein study Abnormal
Recovery
Months to years
Cause
Possibly
infection-related
Pathology
Choriocapillaris
and RPE

Pigment
Epitheliitis "
14

16

Acute Macular
Neuroretinopathy

4 M, 6 F
Gray-black spots
with halo
Macula

1 M, 5 F
Red-brown wedge

Rare
None

4 of 6
None

Usually monocular
Moderate
Abnormal
Weeks to months
Unknown

Either
Mild
Normal
None
Possibly infection
or hormone
Sensory retina

RPE

Fovea

*M indicates male; F , female; RPE, retinal pigment epithelium; and APMPPE, acute posterior multifocal
placoid pigment epitheliopathy.

ceiving oral contraceptives, this avenue of

research may be restricted because one
other patient was a man.
Further awareness of the existence of,
and the differentiation among, these three
illnesses, and the accumulation of more
clinical experience, will necessarily lead
to a further delineation of pathophysiology.
1

scopic findings. Fluorescein angiograms

were normal. She had been taking oral
contraceptives for many years. Although
viral illness and oral contraceptives have
been associated with acute macular neuroretinopathy, no etiology was proven, and
no treatment is known. T h e patient remains symptomatic after a six-month
follow-up.

SUMMARY

A 24-year-old white woman convalescing from a viral upper respiratory infection suddenly developed three positive
scotomas around the fixation point in her
left eye. T h e fundus had three corresponding lesions that appeared to be
characteristic of acute macular neuroretinopathy. Situated in the fovea, subtle,
reddish-brown, wedge- or tear-shaped lesions were best seen with the direct ophthalmoscope using red-free light. Visual
acuity was 6/6 (20/20), and peripheral
fields were normal. T h e patient's reproduction of the scotomas on an Amsler grid
sheet mirrored the observed ophthalmo-

REFERENCES

1. Bos, P. J. M., and Deutman, A. F.; Acute

macular neuroretinopathy. Am. J . Ophthalmol. 80:
573, 1975.
2. Gass, J. D. M.: Acute posterior multifocal placoid pigment epitheliopathy. Arch. Ophthalmol. 80:
177, 1968.
3. Kirkham, T. H., Ffytche, T. J., and Sanders,
M. D.: Placoid pigment epitheliopathy with retinal
vasculitis and papillitis. Br. J. Ophthalmol. 56:875,
1972.
4. Bird, A. C , and Hamilton, A. M.: Placoid
pigment epitheliopathy. Br. J. Ophthalmol. 56:881,
1972.
5. Deutman, A. F., Oosterhuis, J. A., Boen-tan, T.
N., and Aan de Kerk, A. L.: Acute posterior multifocal placoid pigment epitheliopathy. Br. J. Ophthalmol. 56:863, 1972.
6. Van Buskirk, E . M., Lessei, S., and Friedman,

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AMERICAN JOURNAL O F OPHTHALMOLOGY

E.: Pigmentary epitheliopathy and erythema nodosum. Arch. Ophthalmol. 85:369, 1971.
7. Ryan, S. J., and Maumenee, A. E.: Acute posterior multifocal placoid pigment epitheliopathy.
Am. J. Ophthalmol. 74:1066, 1972.
8. Annesley, W. H., Tomer, T. L., and Shields, J.
A.: Multifocal placoid pigment epitheliopathy. Am.
J. Ophthalmol. 76:511, 1973.
9. Lewis, R. A.: Acute posterior multifocal placoid pigment epitheliopathy. Arch. Ophthalmol. 93:
235, 1975.
10. Azar, P. Jr., Gohd, R. S., Waltman, D., and
Gitter, K. A.: Acute multifocal placoid pigment
epitheliopathy associated with an adenovirus type 5
infection. Am. J. Ophthalmol. 80:1003, 1975.
11. Holt, W. S., Regan, C. D. S., and Trempe, C :

APRIL, 1977

Acute posterior multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 81:403, 1976.
12. Savino, P. J., Weinberg, R. J., Yassin, J. G.,
and Pilkerton, A. R.: Diverse manifestations of acute
posterior multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 77:659, 1974.
13. Fishman, G. A., Rabb, M. F., and Kaplan, J.:
Acute posterior multifocal placoid pigment epitheliopathy. Arch. Ophthalmol. 92:173, 1974.
14. Krill, A. E., and Deutman, A. F.: Acute retinal
epitheliitis. Am. J. Ophthalmol. 74:193, 1972.
15. Deutman, A. F.: Acute retinal epitheliitis. Am.
J. Ophthalmol. 78:571, 1974.
16. Friedman, M. W.: Bilateral recurrent acute
retinal pigment epitheliitis. Am. J. Ophthalmol. 79:
567, 1975.

OPHTHALMIC MINIATURE

But suddenly the Mirror went altogether dark, as dark as i f a hole

had opened in the world o f sight, and F r o d o looked into emptiness.
In the black abyss there appeared a single E y e that slowly grew,
until it filled nearly all the Mirror. S o terrible was it that F r o d o stood
rooted, unable to cry out or to withdraw his gaze. T h e E y e was
rimmed with fire, but was itself glazed, yellow as a cat's, watchful
and intent, and the black slit o f its pupil opened on a pit, a window
into nothing.
J . R. R. T o l k i e n , The Lord of the Rings,
Part 1. The Fellowship
of the Ring
New York, Ballantin e Books