AMERICAN JOURNAL OF OPHTHALMOLOGY

VOLUME

80

OCTOBER, 1975

NUMBER

ACUTE MACULAR NEURORETINOPATHY

PIERRE J.

M.

BOS,

M.D.

Amsterdam, The Netherlands

AND
AUGUST F.

DEUTMAN,

M.D.

Rotterdam, The Netherlands

Recently we observed four women with a
peculiar acute macular affection, characterized by slight depression of visual acuity and
nararentral scotomas correfip"ti"g w i t n
dark-reddish, wpHgp-sriappfl jrrfrarptinal lesin^g rw^ntinff tr> trip fnvpa.

We performed electroretinography and

electro-oculography in two patients.2 All patients underwent general physical examination and laboratory tests.
CASE REPORTS

Case 1A 29-year-old white woman had noticed

black dots and scotomas in both central visual
fields since April 15, 1971. The onset of the complaints was sudden. She was first seen on April 20,
1971, when corrected visual acuity in both eyes
was 20/20.
Ophthalmologic examination showed no abnormalities outside the macular regions. There were
irregular reflexes and dark, brown-reddish flecks in
the right macula; some had a triangular configuration with the sharp point of the triangle directed
toward the fovea (Fig. 1, left). Some polymorphic
spots were present elsewhere in the macula. In her
left eye (Fig. 1, right), she demonstrated similar
irregular reflexes and some dark red-brownish dots,
like those in her right eye.
Biomicroscopy revealed that these spots were not
located in the pigment epithelium but in the more
superficial retinal structures. Fluorescein angiography was normal (Fig. 2). Kinetic perimetry
showed that the peripheral boundaries of the visual
fields were intact, while static perimetry demonstrated dense scotomas in the 2- to 5-degree area of
both eyes and a slight decrease in central light sensitivity (Fig. 3).
There were no systemic complaints. In her youth
the patient had had a splenectomy because of familial thrombocytopenia, but otherwise she had a noncontributory medical history. She was taking the
oral contraceptive lynestrenol (Lyndiol).
No subjective changes were observed during follow-up and static visual fields were unchanged. The
From the Department of Ophthalmology, Univer- fundus changes were visible, although the lesions
sity of Amsterdam (Dr. Bos), and the Eye Hospital, were less obvious.
Erasmus, University of Rotterdam (Dr. Deutman),
Case 2A 33-year-old white woman noticed a
The Netherlands.
scotoma in her left eye of sudden onset on Sept. 18,
Reprint requests to A. F. Deutman, M.D., De- 1972. Her right eye was completely normal. She
partment of Ophthalmology, University of Nij- had not been ill before the ocular complaints. She
megen, Nijmegen, The Netherlands.
had been using lynestrenol for eight years.
573

The macular pigment epithelium appeared

normal and the retinal vessels did not show
gross abnormalities. The optic disk was unaffected and there were no nerve fiber defects. Visual recovery, when present, progressed slowly over many months.
Since no similar disease process is known
to us, we called this entity acute macular
neuroretinopathy (neuroepitheliopathy)1 because of the acute onset and the localization
of the lesions in the more superficial retinal
layers at the macula.
Two patients were seen in the Amsterdam
Eye Clinic, one patient was seen in the
Rotterdam Eye Hospital, and the fourth was
examined at both hospitals.
Routine ophthalmoscopic examination,
fundus photography, andfluoresceinangiography were done in all patients. The photographic methods have been described.2 Kinetic visual fields were recorded with the
Goldmann perimeter and static perimetry
with the Tubinger perimeter.

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AMERICAN JOURNAL OF OPHTHALMOLOGY

OCTOBER, 1975

Fig. 1 (Bos and Deutman). Case 1. Right macula (left) and left macula (right) showing darkish
wedge-shaped and irregular flecks, localized in the neuroretina.

Fig. 2 (Bos and Deutman). Case 1. Fluorescein

angiography of the right macula showing a normal
fluorescence pattern in the arteriovenous phase.
Two days after the onset of symptoms, she had
normal central vision in both eyes. There was a
dark brown-reddish spot in the macular region of
the left eye close to the fovea (Fig. 4, left). Other-

wise her eyes were normal.

Fluorescein angiography revealed some questionably dilated perimacular capillaries (Fig. 4, right).
There was, however, no leakage of dye recorded in
the late stages of the angiogram, such as seen in
cystoid macular edema.3
Meticulous static perimetry revealed a scotoma in
the 1- to 3-degree area from the center of the left
eye (Fig. S). This scotoma was not as dense as
the scotoma recorded in Case 1.
The patient was last seen in October 1973, when
the symptoms were unaltered. Careful ophthalmoscopy showed a faint discoloration located where
the dark spot was seen originally. Static perimetry
still showed a scotoma that had decreased slightly
in depth (Fig. 6).
Case 3A 24-year-old white woman noticed disturbance of her central vision after visiting a game
reserve where she had had a bout of enteritis. She
claimed she had not been looking at the sun.
On March 2, 1972, she was seen in the Amsterdam University Clinic. Visual acuity in both eyes
was 20/20. Ophthalmologic examination was normal outside the macular regions, which had a
swollen glossy appearance with increased reflexes
and vague, darkish red, wedge-shaped lesions around
the center of the macula. The lesions pointed toward
the fovea with a butterfly-shaped appearance (Fig.
7
>Fluorescein angiography revealed no abnormali-

Fig. 3 (Bos and Deutman). Case 1. Static perimetry (top and bottom) performed with the Tiibinger perimeter showing slightly decreased light sensitivity centrally and paracentrally in the right eye (top) and
dense paracentral scotomas in the left eye (bottom). These scotomas were also seen with kinetic perimetry
(center) in the left eye.

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576

OCTOBER, 1975

Fig. 4 (Bos and Deutman). Case 2, left eye. Macula showing one darkish, wedge-shaped dot superonasally to the fovea. Fluorescein angiography of this macula (right) showed no clear abnormalities.
There is only questionable dilatation of some of the perimacular capillaries.
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2, left eye. September 1972. There
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visible dot. This scotoma was recorded with the Tubinger perimeter
after painstaking care in static
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Fig. 6 (Bos and Deutman). Case

2, left eye. May 1973. Left macula
showing some remnants of the paracentral scotoma shown in Figure 5.

VOL. 80, NO. 4

ACUTE MACULAR NEURORETINOPATHY

577

Fig. 7 (Bos and Deutman). Case 3. March 2, 1972. Right macula (left) and left macula (right) demonstrating wedge-shaped lesions not unlike the shape of a butterfly. However, these lesions are localized
more superficially in the retina than in butterfly-shaped pigment dystrophy and they are not pigmented.
ties (Fig. 8). Static perimetry, however, showed a
paracentral scotoma for maximal luminance above
the center in the right eye (Fig. 9). No scotoma
was seen in the left eye.
On March 29, she was seen at the Rotterdam
Eye Hospital. Visual acuity in both eyes was 20/20.
The Amsler grid test showed three small scotomas,
two temporal to the fixation point in the left eye.
Ophthalmologic examination revealed abnormalities
at the macula that appeared swollen and glossy,
with increased reflexes and vague, darkish red,
wedge-shaped lesions around the center of the
macula. The lesions pointed toward the fovea with
a butterfly-like appearance. The ophthalmoscopically
abnormal areas appeared to correspond almost completely with the scotomas demonstrated on the
Amsler grid.
On April 4, 1973, there was little subjective
change (Fig. 10). Electroretinography and electrooculography were performed and appeared to be
completely normal. The electroretinogram (ERG)
responses were normal. Scotopic and photopic a
and b waves were well above the lower limits of
normal. The electro-oculogram (EOG) showed a
normal light/dark ratio of 2.74 in the right eye and
2.85 in the left eye.
There were no systemic complaints. This patient
was taking the oral contraceptive norgestrel
(Eugynon).
In October 1973, there were no subjective
changes. The same characteristic fimdus changes
were observed, although they were more faint.
Angiography was performed, and was normal. Perimetric details were the same as in March 1972
(Fig. 9).
Case 4A 32-year-old white woman noticed
scotomas in both eyes during a bout of influenza

and high fever in the middle of December 1972.

When seen on Jan. 2, 1973, visual acuity was R.E.:
20/25, and L.E.: 20/66. Visual acuity in the left
eye had always been slightly worse than in her
right eye, probably due to amblyopia.
On Jan. 9, her visual acuity was unchanged. The
Amsler test demonstrated a paracentral scotoma on
the temporal side of the fixation point in the right
eye and a rather large scotoma temporal to the
center in the left eye. Both macular areas appeared

Fig. 8 (Bos and Deutman). Case 3. Fluorescein

angiogram of the right macula revealing no abnormalities in the arteriovenous phase.

578

AMERICAN JOURNAL OF OPHTHALMOLOGY

OCTOBER, 1975

Fig. 9 (Bos and Deutman). Case 3, right eye. Absolute paracentral scotoma in the
45- to 225-degree axis with kinetic perimetry (top) and static perimetry (bottom).
edematous with increased reflexes. There was one
dark-reddish, triangular zone in the right macula,
just nasal to the foveola (Fig. 11, left), and at
least three wedge-shaped darkish-red lesions pointing to the center in the left eye (Fig. 11, right).
The nerve fiber layer was more pronounced nasal
to the center. Otherwise the ocular examination
showed no pathologic findings. Vessels, disk, and
retinal periphery were normal in both eyes and the
media were clear.
Fluorescein angiography demonstrated an intact
retinal pigment epithelium. There were some ques-

tionably dilated perimacular capillaries above the

fovea (Fig. 12, top left), but there were no fluorescein leaks (Fig. 12, top right and bottom left).
With the Goldmann contact lens, the retinal
swelling appeared to be localized to the inner
portion of the sensory retina. The patient was hospitalized on Jan. 16, when vision had not improved.
A general physical and laboratory examination revealed a slightly abnormal glucose tolerance test.
There was no glycosuria. She had hypercholesterolemia (9.9 mM/1; normal, 6.4 mM/1). She had
used contraceptives for many years. The patient

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ACUTE MACULAR NEURORETINOPATHY

579

Fig. 10 (Bos and Deutman). Case 3. April 4, 1973. Right macula (left) and left macula (right) with
the wedge-shaped paracentral dots that are more visible in tht right eye than in the left eye.
received one tablet of xanthinol niacinate (Complamine), twice daily, carbon dioxide inhalation,
clofibrate capsules, and a diet. A neurologic examination, including x-ray films of the sella turcica,
was normal.
On Jan. 18, central visual fields showed a small
paracentral scotoma on the superotemporal side of
the fixation (Fig. 13). On Jan. 29, visual fields were
unchanged, but by May 11, there was a small but
definite decrease in the size and depth of the scotomas (Fig. 14).

Electroretinograms performed on J a a 17, with

diffuse and macular stimulation, were normal. The
visually evoked cortical potentials were also normal.
On May 4, visual acuity was R.E.: 20/25, and
L.E.: 20/50. Subjectively there was not much
change, although the left eye had improved slightly.
On June 27, visual acuity was R.E.: 20/22, and
L.E.: 20/40. She complained of seeing flecks close
to the center in the right eye and paracentral and
temporal flecks in the left eye. The maculae appeared swollen although the swelling had subsided.

Fig. 11 (Bos and Deutman). Case 4. Acute macular neuroretinopathy. Clearly visible darkish wedgeshaped lesions are in the superficial part of the retina. In the left eye (right), these lesions are doverleaf
shaped and the nerve fiber layer demonstrates an increased visibility.

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AMERICAN JOURNAL OF OPHTHALMOLOGY

OCTOBER, 1975

Fig. 12 (Bos and Deutman). Case 4. Fluorescein

angiography of the left macula (top) shows questionably dilated perimacular capillaries on top oi
the macula. However, there is no sign of fluorescein
leakage in the late phases of angiography. Bottorr
left, The right macula also has a normal fluorescence pattern.

On Nov. 19, visual acuity was R.E.: 20/20, and

L.E.: 20/33. The paracentral scotomas were present
and caused considerable disability.
DISCUSSION

This disease appears to be a distinct entity

that, to our knowledge, was described only in
a short communication.1
It is different from the many clinical diseases affecting the central f undus, recognized
in recent years and differentiated from one
another based on the nature of the disease
and the accompanying morphologic changes.
Central serous choroidopathy4 is one such

entity that is well known but poorly understood. It is probably caused by dilation anc
profusely leaking capillaries of the centra
choriocapillaris.
Acute posterior multifocal placoid pig
ment epitheliopathy is another of these enti
ties.5 Although some authors 5 think this dis
ease process is due to pigment epithelia
disease, there are arguments in favor of ;
primary affection of the choriocapillaris.
In both diseases the morphologic change
occurring in the pigment epithelium ar
probably secondary.
The changes in acute retinal pigment epi

VOL. 80, NO. 4

ACUTE MACULAR NEURORETINOPATHY

581

theliitis7*8 appear to be nearly completely

restricted to the pigment epithelium and this
disease has a more favorable course, leading
to complete recovery in six to ten weeks.
There are no cells in the vitreous body or in
the anterior chamber. A viral inflammation
probably causes this self-limiting condition.
Serpiginous (geographic) choroiditis1'9
presents lesions at different stages of evolution. In early lesions there is a definite pale

swelling of the pigment epithelium while

older lesions demonstrate atrophy of the
pigment epithelium and choriocapillaris surrounded by an edematous retinal zone. This
inflammatory disease is characterized by
relentless progression, presents in patients
in their fourth decade and, in our experience,
responds well to corticosteroids.
The so-called presumed histoplasmic choroiditis represents a distinct clinical entity

Fig. 13 (Bos and Deutman). Case 4. January

1973. Central visual fields demonstrating dense
paracentral scotomas on the superonasal side of the
center. Top, right eye; bottom, left eye.

Fig. 14 (Bos and Deutman). Case 4. May 1973.

Central visual fields demonstrating some improvement. The scotomas are slightly smaller and less
dense than in January 1973. Top, right eye; bottom,
left eye.

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AMERICAN JOURNAL OF OPHTHALMOLOGY

Fig. IS (Bos and Deutman). Case 4. Wedgeshaped lesions, shaped not unlike the lesion in acute
macular neuroretinopathy, in a patient with intraretinal hemorrhages due to hypertensive retinopathy.

affecting adults, characterized by subretinal

neovascularization at the fovea. We saw this
ocular syndrome in patients without evidence
of previous infection by Histoplasma capsulatum.1
The disease we present appears to be localized to the more superficial retinal layers,
shown well on binocular slit-lamp examination, while fluorescein angiography displayed
no choroidal or retinal pigment epithelial
abnormalities. The retinal vessels do not
show definite abnormalities and do not leak
fluorescein. The nerve fiber layer is not
obviously affected since no nerve fiber layer
defects were disclosed even after extensive
perimetric examination.
There was no diffuse retinal disturbance
since, in those patients tested, the ERGs and
EOGs were normal. Static perimetry demonstrated a well-localized paracentral retinal
disease with dense scotomas. The lesions
were located predominantly on the nasal
side of the fovea. The wedge-shaped lesions
were shaped not unlike certain intraretinal
hemorrhages (Fig. 15) and, therefore, may
be localized at the same level in the neuroretina.

OCTOBER, 197S

As in all macular diseases without striking

ophthalmoscopic changes, optic neuropathy
has to be differentiated. However, there are
no macular changes in optic neuropathy and
partial or complete optic atrophy occurs in
time. The visual fields and the macular
changes together with the normal appearance
of the optic disk indicated macular pathology
in all four cases. In Case 4, optic nerve
pathology was excluded by normal, visually
evoked cortical potentials and by a normal
neurologic examination.
AddendumRecently
one
of
us
(PJ.M.B.) examined a 30-year-old white
woman who developed acute macular neuroretinopathy a few weeks after an influenzalike disease. Visual acuity was R.E.: 20/20,
and L.E.: 20/100. The maculae showed
wedge-shaped lesions in the superficial retinal
layers (Fig. 16). Paracentral scotomas were
elicited. Color vision was normal. After a
few weeks visual acuity was 20/20 in both
eyes. However, four months after the visual
symptoms started, she still had paracentral
scotomas. No systemic abnormalities were
found. This patient used the oral contraceptive ethinyl estradiol (Neogynon).
Another patient, a 23-year-old white man
who developed visual problems in his right
eye after a bout of influenza, presented with
a mild form of acute macular neuroepitheliopathy. Visual acuity was R.E.: 20/25,
W L.E.: 20/20. Nasally to the right fovea
there was a darkish dot in the superficial
retinal layers (Fig. 17). Fluorescein angiography did not show any abnormality. Color
vision was also normal. Perimetry, however,
demonstrated a small and dense visual field
defect at the site of the ophthalmoscopically
visual lesion. The left eye was completely
normal. The macular picture did not change
during two months of observation.
SUMMARY

An unrecognized acute macular affection

occurred in four women, 24 to 35 years
old, using oral contraceptives who com-

VOL. 80, NO. 4

ACUTE MACULAR NEURORETINOPATHY

plained of a sudden decrease of visual acuity

or paracentral scotomas.
Three patients had bilateral lesions and one
patient had unilateral lesions. These lesions
consisted of darkish brown-red, wedgeshaped dots in the macula pointing to the
fovea. These dots were located mostly on the
nasal side of the macula.
Biomicroscopy showed these lesions were
located in the superficial layers of the retina.

Fig. 17 (Bos and Deutman). A small darkish dot

on the nasal side of the right fovea corresponding
with a deep paracentral scotoma as the only manifestation of acute macular neuroretinopathy.

The retinal vessels, pigment epithelium, and

optic disk showed no distinct pathologic
features. Fluorescein angiography, performed repeatedly, showed some questionably dilated perimacular capillaries without
leakage in two cases.
Static perimetry delineated dense paracentral scotomas. Recovery was slow or
absent, confirmed by perimetric observation.
Ophthalmoscopic, fluorescein angiography,
and perimetric details excluded an affection
of the pigment epithelium, the nerve fiber
layer, and the optic disk. Since the affection
appears to be localized superficially in the
retina, we called this specific entity acute
macular neuroretinopathy.
ACKNOWLEDGMENTS

H. H. A. H6tte, M.D., and R. A. Crone, Ph.D.,

referred Case 3, and H. E. Henkes, Ph.D., referred
Case 4.
REFERENCES

Fig. 16 (Bos and Deutman). Right and left macula (top and bottom, respectively) of a 30-year-old
white woman shows the typical superficial wedgeshaped lesions of acute macular neuroretinopathy.
The wedges point to the center of the fovea.

1. Deutman, A. F.: Fluorescein angiography in

macular diseases. In Henkes, H. E. (ed.) : Photography, Electro-Ophthalmology and EchoOphthalmology in Ophthalmic Practice, vol. 3. The
Hague, W. Junk, 1973, pp. 208-209.
2.
: The Hereditary Dystrophies of the
Posterior Pole of the Eye, thesis. Assen, The
Netherlands, Van Gorcum and Co., 1971.

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AMERICAN JOURNAL OF OPHTHALMOLOGY

3. Gass, J. D. M., and Norton, E. W. D.:

Cystoid macular edema and papilledema following
cataract extraction. Arch. Ophthalmol. 76:646,
1966.
4. Gass, J. D. M.: Pathogenesis of disciform detachment of the neuroepithelium. 1. General concepts and classification. Am. J. Ophthalmol. 63:573,
1967.
5.
: Acute posterior multifocal placoid
pigment epitheliopathy. Arch. Ophthalmol. 80:177,
1968.

OCTOBER, 1975

6. 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.
7. Krill, A. E., and Deutman, A. F.: Acute
retinal pigment epitheliitis. Am. J. Ophthalmol.
74:193, 1972.
8. Deutman, A. F.: Acute retinal pigment
epitheliitis. Am. J. Ophthalmol. 78:571, 1974.
9. Schlaegel, T. F., Jr.: Essentials of Uveitis.
London, Churchill, 1969, pp. 101-103.

OPHTHALMIC MINIATURE

He had only one good eye. The left distinguished only light and shade.
But the good eye was dark-bright, full of observation through the overhanging hair of the brow as in some breeds of dog. For his height he had
a small face. The combination made him conspicuous.
Saul Bellow, Mister Sammler's Planet
New York, Viking Press, 1970