Paracentral Acute Middle Maculopathy in Nonischemic

Central Retinal Vein Occlusion

EHSAN RAHIMY, DAVID SARRAF, MICHAEL L. DOLLIN, JOHN D. PITCHER, AND ALLEN C. HO
To better characterize a novel spectraldomain optical coherence tomography (OCT) presentation, termed paracentral acute middle maculopathy, to
describe this finding in patients with nonischemic central
retinal vein occlusion (CRVO), and to support a proposed
pathogenesis of intermediate and deep retinal capillary
ischemia.
! DESIGN: Retrospective observational case series.
! METHODS: Clinical histories, high-resolution digital
color imaging, red-free photography, fluorescein angiography, near-infrared reflectance, and spectral-domain
OCT images of 484 patients with acute CRVO from 2
centers were evaluated for the presence of coexisting
paracentral acute middle maculopathy.
! RESULTS: Of 484 patients diagnosed with CRVO, 25
(5.2%) demonstrated evidence of concurrent paracentral
acute middle maculopathy. Patients averaged 51 years of
age and presented with complaints of paracentral scotomas. All patients demonstrated hyper-reflective plaquelike lesions at the level of the inner nuclear layer by
spectral-domain OCT and showed corresponding darkgray lesions on near-infrared reflectance and perivenular
deep retinal whitening on color fundus photography.
There was no fluorescein angiographic correlate to these
lesions. On follow-up spectral-domain OCT imaging, the
lesions had resolved into areas of inner nuclear layer atrophy with persistence of scotomas.
! CONCLUSIONS: Paracentral acute middle maculopathy
refers to characteristic hyper-reflective spectral-domain
OCT lesions involving the middle layers of the retina at
the level of the inner nuclear layer that may develop in
response to ischemia of the intermediate and deep capillary plexuses. This series is the largest to describe this
spectral-domain OCT finding to date, and it is the first
to associate it with nonischemic CRVO. (Am J
Ophthalmol 2014;158:372380. ! 2014 by Elsevier
Inc. All rights reserved.)
! PURPOSE:

Accepted for publication Apr 23, 2014.

From Mid Atlantic Retina, The Retina Service of Wills Eye Hospital,
Thomas Jefferson University, Philadelphia, Pennsylvania (E.R., M.L.D.,
J.D.P., A.C.H.); the Retinal Disorders and Ophthalmic Genetics
Division, Jules Stein Eye Institute, University of California, Los
Angeles, David Geffen School of Medicine, Los Angeles, California
(D.S.); and the Greater Los Angeles Veterans Affairs Healthcare
Center, Los Angeles, California (D.S.).
Inquiries to Allen C. Ho, Mid Atlantic Retina, The Retina Service of
Wills Eye Hospital, Thomas Jefferson University, Philadelphia,
Pennsylvania; e-mail: acho@att.net

372

2014 BY

ECENTLY, WE IDENTIFIED CHARACTERISTIC BAND-

like hyper-reflective spectral-domain optical coherence tomography (OCT) lesions in patients with
presumed acute macular neuroretinopathy involving the
middle layers of the retina at the level of the inner nuclear
layer, a novel finding we termed paracentral acute middle
maculopathy.1,2 Since these initial reports, a smaller case
series additionally observed this finding in 4 patients,
including 1 with underlying diabetic retinopathy.3 Retinal
capillary ischemia has been proposed as the causative factor
in the development of these lesions, which localize histologically at the level of the intermediate and deep retinal
capillary plexuses flanking the inner and outer boundaries
of the inner nuclear layer, respectively.1,4
This article describes 25 new cases of paracentral acute
middle maculopathy occurring in association with acute
nonischemic central retinal vein occlusion (CRVO), and
will help to further elucidate the underlying pathogenesis
of these middle retinal lesions.

METHODS
INSTITUTIONAL REVIEW BOARD APPROVAL FOR THIS

retrospective 2-center study was obtained through the

Wills Eye Hospital, Philadelphia, Pennsylvania, and the
University of California, Los Angeles, Office of the Human
Research Protection Program. Research adhered to the
tenets of the Declaration of Helsinki and was conducted
in accordance with regulations set forth by the Health
Insurance Portability and Accountability Act.
Using International Classification of Diseases, 9th Revision (ICD-9), billing codes for CRVO, 2 of our authors
(ER, DS) reviewed the spectral-domain OCT imaging
database at each of their retinal care centers and studied
the findings of 484 cases of CRVO diagnosed between
January 2010 and September 2013. We identified 25 cases
of acute CRVO with simultaneous acute paracentral acute
middle maculopathy lesions and assessed the clinical and
imaging data for each case, focusing primarily on multimodal imaging correlations. Baseline and follow-up demographic, clinical and laboratory data were extracted from
patient charts and analyzed. Statistical analysis was
performed by a simple 2-tailed t test using GraphPad Software (GraphPad, La Jolla, California).
High-resolution digital color imaging, red-free photography, and fluorescein angiography at baseline presentation

ELSEVIER INC. ALL

RIGHTS RESERVED.

0002-9394/$36.00
http://dx.doi.org/10.1016/j.ajo.2014.04.024

were analyzed, when available, for each patient. Initial

near-infrared reflectance and spectral-domain OCT examinations utilizing the Heidelberg Spectralis (Heidelberg
Engineering, Heidelberg, Germany) were evaluated at baseline in every patient and correlated with subsequent followup scans during the course of a patients follow-up when
available. We used the registration feature specific to Heidelberg Spectralis, which allows each spectral-domain
OCT B-scan to be coupled to its exact location on the
near-infrared reflectance image, facilitating point-to-point
correlations of the retinal findings between the nearinfrared reflectance and spectral-domain OCT images.

RESULTS
OF THE 484 PATIENTS DIAGNOSED WITH CRVO, 25 (5.2%)

demonstrated evidence of concurrent paracentral acute middle maculopathy at the time of their initial office evaluations.
Baseline patient demographics and ocular examination findings in these eyes are outlined in the Table. The mean age at
presentation was 51 years (range, 1978; standard deviation
(SD), 16.6) in the group with paracentral acute middle
maculopathy, which was significantly younger than the
69.6 years (range, 20 to 95; SD, 13.9) in the remainder of
the patients with CRVO (P < .001). There was no gender
predilection for the development of paracentral acute middle
maculopathy (males, 48%; females, 52%).
With respect to pre-existing systemic and ocular comorbidities, 8 patients had known histories of hypertension, 6
had hypercholesterolemia, 4 had diabetes mellitus, 3 had
systemic lupus erythematosus, 3 had open-angle glaucoma
with optic disc cupping, and 1 had active pulmonary tuberculosis who was undergoing treatment. After detailed histories were obtained, 2 patients endorsed current use of
oral contraceptive pills, and 1 individual was a longdistance marathon runner. Hematologic laboratory
workup, when obtained, was negative for any hypercoagulable state in all but 1 case, in which an underlying diagnosis of monoclonal gammopathy of undetermined
significance was uncovered.
Patients typically presented with subjective central
visual deficits that began, on average, 8.3 days prior to office
evaluation (range, 121 days). Complaints ranged from
generalized blurring of the central vision and difficulty
focusing to more specific patterns of paracentral scotomas,
including the following patient descriptions: pieces of central vision missing (Figure 1); concentrically arranged
fixed gray spots; like looking through cracked glass;
numerous small blind spots; and blank spots in central
vision. On initial examination, Snellen best-corrected
visual acuity (BCVA) ranged from 20/20 to hand motions,
with an average of 20/120 (logarithm of minimal angle of
resolution [logMAR] equivalent, 0.76). The vast majority
of eyes demonstrated good initial acuity, with 14 (56%)
VOL. 158, NO. 2

TABLE. Patient Demographics and Ocular Findings in

Paracentral Acute Middle Maculopathy
Age, years
Mean 6 SD
Range
Gender (n 25)
Male
Female
Eye (n 25)
Right
Left
CRVO Type (n 25)
Nonischemic
Ischemic
Systemic/ocular associations
Hypertension
Hypercholesterolemia
Diabetes mellitus
SLE
Open-angle glaucoma
OCP use
Marathon running
MGUS
BCVA
Snellen mean
Snellen range
logMAR mean
logMAR range

51 6 16.6
1978
12 (48%)
13 (52%)
12 (48%)
13 (52%)
25 (100%)
0 (0%)
8 (32%)
6 (24%)
4 (16%)
3 (12%)
3 (12%)
2 (8%)
1 (4%)
1 (4%)
20/120
20/20-HM
0.767
02.28

BCVA best-corrected visual acuity; CRVO central retinal

vein occlusion; HM hand motions; logMAR logarithm of
the minimum angle of resolution; MGUS monoclonal gammopathy of undetermined significance; OCP oral contraceptive
pills; SD standard deviation; SLE systemic lupus erythematosus.

of 25 patients presenting with BCVA of 20/50 or better;

however, 8 (32%) of 25 had vision of 20/200 or worse, all
of which were noted to have concurrent cilioretinal artery
occlusion (Figure 2). Altogether, simultaneous cilioretinal
artery occlusion was a common occurrence in our cohort
(10 (40%) of 25 patients), and their mean BCVA of 20/
800 (logMAR equivalent, 1.60) was significantly lower
than the 20/40 (logMAR equivalent: 0.26) for noncilioretinal artery occlusion patients (P < .001).
The diagnosis of CRVO was established on the basis of
characteristic funduscopic findings: tortuosity and dilatation of the central retinal vein, intraretinal hemorrhages
throughout all 4 quadrants, and/or optic disc and macular
edema. In all eyes, detailed examination of the macula in
the involved eye revealed patchy areas of deep retinal whitening centered within the macula, often in the distribution
of the venous tributaries and always correlating with paracentral acute middle maculopathy on spectral-domain
OCT (Figures 16). Compared to cotton-wool spots, the
retinal whitening associated with paracentral acute middle

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN VEIN OCCLUSION

373

FIGURE 1. Patient 1, with paracentral acute middle maculopathy. A 37-year-old female receiving therapy for active pulmonary
tuberculosis presented with acute vision loss in the right eye and noted that pieces of central vision were missing, as illustrated
by Amsler grid testing (Top left). Visual acuity was 20/25 at presentation, and retinal examination of the right eye (Top middle)
was consistent with acute central retinal vein occlusion and perivenular retinal whitening in the temporal macula (solid arrow). Fluorescein angiography (Top right) was unremarkable. Near-infrared reflectance imaging (Bottom left) demonstrated multifocal dark
gray lesions at the terminal tips of the venous branches corresponding to the retinal whitening observed clinically. Spectraldomain optical coherence tomography revealed multiple hyper-reflective plaquelike lesions involving the inner nuclear layer (Bottom
right, solid arrows) consistent with paracentral acute middle maculopathy.

maculopathy was noticeably distinct, appearing as a duller

gray-white in color, less opaque, deeper in the retina, and
not following the distribution of the nerve fiber layer
(Figure 3). Similarly, the lesions of paracentral acute middle maculopathy were uniquely different in appearance and
location from associated cilioretinal artery occlusion, when
present (Figure 2), which was more superficial and whiter.
Because of the presence of concurrent retinal hemorrhages and cotton-wool spots, the extent of paracentral
acute middle maculopathy was not always as readily
apparent on examination; however, with ancillary redfree photography (Figure 4) and near-infrared reflectance
imaging (Figures 16), the lesions were more clearly
identified, appearing dark and more precisely delineated.
Specifically, near-infrared reflectance confirmed the perivenular location of paracentral acute middle maculopathy
in the majority of cases. Conversely, the fluorescein angiogram had no correlation with the lesions (Figure 1 and
Figure 4), and no cases displayed angiographic evidence
of an ischemic CRVO (10 or greater disc diameters of capillary nonperfusion).
Corresponding spectral-domain OCT imaging registered
through the zones of retinal whitening revealed multifocal
hyper-reflective plaquelike lesions at the level of the inner
nuclear layer (Figures 16). In 13 cases, the involvement of
paracentral acute middle maculopathy was additionally
noted to extend into the inner plexiform layer. Although
the lesions appeared to cast a shadow over the deeper
374

retinal layers, they spared the ellipsoid and interdigitation

bands, which were always intact by spectral-domain OCT.
Associated macular edema was an uncommon finding,
noted in the spectral-domain OCT scans of only 5 (20%)
of 25 patients.
Mean duration of follow-up was 7.2 months (range,
124; median, 4; SD, 7.6), although 8 of the 25 patients
were lost to follow-up. Average final BCVA at the most
recent clinic visit was 20/40 (logMAR equivalent, 0.339)
for the entire cohort. More specifically, patients with simultaneous cilioretinal artery occlusion experienced partial
resolution of vision back to an average BCVA of 20/120
(logMAR equivalent, 0.81), compared to 20/30 (logMAR
equivalent, 0.20) in the noncilioretinal artery occlusion
patients (P 0.26). Although 14 (82%) of the 17 patients
tested 20/50 or better at the final visit, the subjective paracentral scotomas persisted.
On fundus examination, intraretinal hemorrhages, optic
disc edema and macular edema showed variable degrees of
resolution. On follow-up near-infrared reflectance imaging,
the dark lesions had dissipated, and the most recent
spectral-domain OCT examinations revealed zones of
severe inner nuclear layer thinning and a markedly attenuated outer plexiform layer band where the hyper-reflective
paracentral acute middle maculopathy lesions had been
located previously (Figure 5 and Figure 6). The shadowing
induced by the overlying lesions seen on spectral-domain
OCT had resolved.

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FIGURE 2. Patient 2, with paracentral acute middle maculopathy. A 68-year-old male with diabetes mellitus and hypertension
presented with acute vision loss in the left eye. Visual acuity was counting fingers, at presentation, and funduscopy of the left eye
(Top left) was consistent with acute central retinal vein occlusion and associated cilioretinal artery occlusion (broken arrow). In
the temporal macula, a subtle pattern of retinal whitening was noted around the venous branches (Top left, solid arrow). Nearinfrared reflectance imaging (Top right) demonstrated dark-gray lesions in the distribution of the cilioretinal artery (broken arrow)
and temporal perivenular branches (solid arrow). Spectral-domain optical coherence tomography displayed hyper-reflective plaquelike
lesions involving the inner nuclear layer (Bottom, solid arrow) in the temporal macula, consistent with paracentral acute middle maculopathy in contrast to the superficial edema and hyper-reflectivity induced by the cilioretinal artery occlusion (Bottom, broken arrow).

Of the patients, 5 had received serial intravitreal antivascular endothelial growth factor therapy during their
courses (2 with bevacizumab, 3 with ranibizumab) for treatment of associated macular edema. Whether a patient
received intravitreal injections did not appear to impact
the timeline to resolution of the paracentral acute middle
maculopathy.

DISCUSSION
PARACENTRAL ACUTE MIDDLE MACULOPATHY REFERS TO

a recently recognized class of characteristic lesions involving the middle layers of the retina at the level of the inner
nuclear layer as detected by spectral-domain OCT imaging.1
The present study is the largest to date characterizing this
entity and is the first to show its association with nonischemic CRVO. The association of paracentral acute middle
VOL. 158, NO. 2

maculopathy with disparate disorders such as acute macular

neuroretinopathy and CRVO may indicate that these
lesions seen on spectral-domain OCT have a wide spectrum
of presentation, such that they can occur as isolated events
in typically healthy patients with acute macular neuroretinopathy and can also occur in various retinal vascular disorders such as CRVO, in which multiple middle retinal
lesions are identifiable. In either case, the characteristic
appearance may be the result of an ischemic insult at the
level of the inner nuclear layer, as the location of paracentral
acute middle maculopathy on spectral-domain OCT corresponds histologically with the intermediate and deep capillary plexuses, and subsequent atrophy of the inner nuclear
layer ensues, often with persistent subjective scotoma.
In 2002, Browning5 published a study concerning 11
patients with nonischemic CRVO in whom he noted a
transient pattern of patchy ischemic retinal whitening
located preferentially in a perivenular distribution around
the macula. He proposed that because the oxygen

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN VEIN OCCLUSION

375

FIGURE 3. Patient 3, with paracentral acute middle maculopathy. A 19-year-old healthy female taking oral contraceptive pills
presented with acute onset of a fixed blue spot in the center of her left visual field. Visual acuity was 20/30, and ophthalmoscopy
of the left eye (Top left) revealed an acute central retinal vein occlusion with perivenular retinal whitening along the tributaries of the
superotemporal arcade (solid arrow). Near-infrared reflectance imaging (Top right) demonstrated perivenular dark-gray lesions (solid
arrow) in the distribution of the retinal whitening observed clinically. Spectral-domain optical coherence tomography showed multiple hyper-reflective lesions involving the inner nuclear layer (Bottom, solid arrows) consistent with paracentral acute middle maculopathy.

saturation of blood diminishes during transit to the venous

system, the tissue adjacent to veins becomes exposed to the
lowest oxygen levels. Thus, in the setting of CRVO, the
most sensitive tissue for manifesting decreased oxygenation
will be perivenular, especially in the posterior pole, where
oxygen metabolism is highest. In 2003, Paques and associates6 reported on 3 additional patients with CRVO displaying this pattern of macular perivenular whitening in a
fern-like distribution. Neither of these reports, however,
had the benefit of ancillary spectral-domain OCT imaging.
It is clear that these described syndromes correlate with
the characteristic paracentral acute middle maculopathy
lesions seen by spectral-domain OCT in our 25 cases of
CRVO described in this article, because 3 additional case
reports corroborating these multimodal imaging findings
have since been reported in the literature.79 Michaelson
and others have previously emphasized the presence of a
zone surrounding the retinal arteries devoid of any
376

capillaries.10,11 The veins, on the other hand, do not

have a capillary-free zone. Rather, the capillaries are
thought to be densest about the venular portions of the
capillary meshwork.10 Such a distribution may help to
explain the likelihood of the paracentral acute middle
maculopathy we detected to be perivenular in distribution.
The main branches of the central retinal artery and vein
course horizontally throughout the superficial nerve fiber
layer with occasional dips into the deeper layers.12 From
the terminal arterioles and venules, precapillary and capillary branches emerge, often at near right angles to the surface of the retina. These tributaries then dive into the
deeper retinal layers where they then anastomose laterally
and form an intricate, planar microvascular capillary
network.12 In their seminal work published in 1954,
Michaelson and Campbell10 emphasized a laminar distribution of these capillaries that varied in differing regions of
the retina. Outside the cecocentral area, they proposed

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FIGURE 4. Patient 4, with paracentral acute middle maculopathy. A 68-year-old female with hypertension presented with fixed
spots in the central vision of the left eye. Visual acuity was 20/200 at presentation, and retinal examination (Top left) demonstrated
an acute central retinal vein occlusion. In the temporal macula, subtle perivenular retinal whitening was observed (Top left, solid
arrow), which was enhanced by red-free imaging (Top middle, solid arrow). Fluorescein angiography was unremarkable (Top right);
however, near-infrared reflectance imaging (Bottom left) uncovered fern-like perivenular dark grey lesions corresponding to the
retinal whitening observed clinically. Spectral-domain optical coherence tomography demonstrated multiple hyper-reflective plaquelike lesions involving the inner nuclear layer (Bottom right, solid arrows) consistent with paracentral acute middle maculopathy.

FIGURE 5. Patient 5, with paracentral acute middle maculopathy. A 19-year-old healthy male presented with acute vision loss in the
left eye. Visual acuity was 20/50 at presentation, and retinal examination (Left) demonstrated an acute central retinal vein occlusion.
Retinal whitening in the distribution of the cilioretinal artery (Left, broken arrow) and around the venous branches in the temporal
macula (Left, solid arrow) was visualized. Near-infrared reflectance imaging (Top middle) demonstrated dark gray lesions corresponding to these patches of retinal whitening. Spectral-domain optical coherence tomography (OCT) displayed multiple hyper-reflective
plaquelike lesions involving the inner nuclear layer (Top right, solid arrows) consistent with paracentral acute middle maculopathy.
At 4-week follow-up, the near-infrared lesions (Bottom middle) were resolving, while corresponding spectral-domain OCT scans
showed partial resolution of the hyper-reflective lesions as well as multiple zones of inner nuclear layer thinning and an irregular,
attenuated outer plexiform layer (Bottom right, solid arrows) without any visible funduscopic correlate.

that 2 laminas were present: a superficial capillary plexus in

the nerve fiber layer and a deep capillary plexus at the junction of the inner nuclear and outer plexiform layers. In the
macular region, the deep plexus was then believed to split,
forming an additional plexus between the inner plexiform
and inner nuclear layers. Terminology notwithstanding,
this 3-dimensional conceptualization of the retinal microvascular network still stands today.4,13,14 In most higher
VOL. 158, NO. 2

order mammals, it is recognized that 3 planar capillary

plexuses form during development: (1) the superficial
plexus forms within the ganglion cell layer; (2) the
intermediate and (3) the deep vascular plexuses form at
the inner and outer edges of the inner nuclear layer,
respectively.4 In postmortem studies of human donor
eyes, Tan and associates14 identified each of these 3 layers
in addition to a layer at the nerve fiber layer level.

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN VEIN OCCLUSION

377

FIGURE 6. Patient 6, with paracentral acute middle maculopathy. A 56-year-old previously healthy female presented with acute
onset difficulty focusing with the right eye. Visual acuity was 20/60 at presentation, and funduscopy (Top left) revealed an acute
central retinal vein occlusion and extensive perivenular retinal whitening in the macula (solid arrow). Near-infrared reflectance
imaging (Top middle) demonstrated fern-like perivenular dark grey lesions corresponding to the retinal whitening observed clinically. Spectral-domain optical coherence tomography (OCT) revealed multiple hyper-reflective bands involving the inner nuclear
layer (Top right, solid arrows) consistent with paracentral acute middle maculopathy. A subsequent hematologic work-up uncovered
an underlying diagnosis of monoclonal gammopathy of undetermined significance. At 3-week follow-up, the perivenular retinal whitening was clinically resolving (Bottom left), as were the near-infrared lesions (Bottom middle). The corresponding spectral-domain
OCT scans showed partial resolution of the hyper-reflective lesions and multiple zones of inner nuclear layer thinning plus an irregular, attenuated outer plexiform layer (Bottom right, solid arrows).

The most critical function of the retinal circulation is to

supply oxygen.15 It has been reported that the deep capillary
plexus contributes 10%15% of the oxygen supply to the
photoreceptor population.16 The photoreceptor axon terminals, located in the outer plexiform layer, are replete with
oxygen-dependent mitochondria, as demonstrated by Stone
and associates,17 and may rely more heavily on the deep
capillary plexus for oxygen supply than the photoreceptor
inner and outer segments located closer to the underlying
choriocapillaris. A steady decline of the diffusion gradient
of oxygen from the choriocapillaris to the photoreceptor
axons has been experimentally confirmed by WangsaWirawan and associates.18 Similarly, studies of cat retinas
have demonstrated that oxygen tension in the retina is highest near the choroid, bottoms out at the level of the outer
nuclear layer, and then rises again in the superficial retinal
layers.19,20 The location of the minimum oxygen tension is
assumed to be located in a watershed region, where
oxygen contribution may be provided by both the
choroidal and retinal circulations.13,21 As such, the outer
plexiform layer and adjacent inner nuclear layer in this
watershed zone may be especially vulnerable to ischemic
insults to the intermediate and deep capillary plexuses.
In our study, the extent of paracentral acute middle
maculopathy on spectral-domain OCT was noted to
involve primarily the full thickness of the inner nuclear
layer and, in nearly half of cases, advanced into the overlying inner plexiform layer. Subsequently, the lesions
invariably resolved with thinning of the inner nuclear
layer. That this lesion aligns precisely with the intermediate and deep capillary plexuses, and given our cohorts
378

underlying diagnoses of CRVO coupled with vasculopathic

risk factors, we propose that ischemia of these microvascular networks is the likely cause of the observed lesions.
The extent of inner plexiform layer involvement, when
noted, may be representative of a more severe ischemic
insult to the adjacent intermediate capillary plexus. It is
important to emphasize that traditional imaging techniques such as fluorescein angiography cannot assess
adequately the morphology or the integrity of these deeper
retinal capillary plexuses, as previously demonstrated by
Mendis and associates.22
As in previous studies,5,6 we similarly observed that
patients with CRVO and paracentral acute middle
maculopathy (1) tend to be younger, (2) do not appear to
demonstrate any consistent systemic disease association,
(3) often have a negative laboratory workup in search of
coagulation abnormalities or inflammatory disorders, (4)
present with nonischemic CRVO, and (5) have a higher
association of cilioretinal artery occlusion (40%).
Although the proposed pathophysiologic mechanism of
combined CRVO and cilioretinal artery occlusion is widely
debated, the association of paracentral acute
middle maculopathy with cilioretinal artery occlusion
cannot be overlooked. Presumably, cilioretinal artery
occlusion occurs due to the lower arteriolar pressure of the
cilioretinal artery compared with that of the central retinal
artery.2325 Therefore, a sudden occlusion of the central
retinal vein results in a marked rise of the intraluminal
pressure that is transmitted throughout the entire retinal
capillary bed.26 Once the intraluminal pressure rises above
that in the already susceptible cilioretinal artery system,

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the result is a relative hemodynamic blockade in the artery,

manifesting as a cilioretinal artery occlusion.26 The possibility that increased venous intraluminal pressure could
adversely affect other regions of potential vascular instability,
such as that in the watershed zone subserved by the deep and/
or intermediate capillary plexuses, is an intriguing one. If so,
CRVO with paracentral acute middle maculopathy may
serve as an intermediate disease state in the progression
from nonischemic CRVO to combined nonischemic
CRVO and cilioretinal artery occlusion formation.
Only 20% of the patients in this current study had coexisting macular edema at the time of presentation. The presence of retinal heme or edema may limit the ability to
detect paracentral acute middle maculopathy. Furthermore, these lesions are evanescent and may resolve prior
to clinical detection. Therefore, the incidence of paracentral acute middle maculopathy in all cases of CRVO may
actually be much higher than the 5.2% we observed. The
multifocal arrangement of paracentral acute middle maculopathy we observed in the setting of nonischemic CRVO is
unique because our previously reported series described
only solitary lesions.1 Over time, the hyper-reflective bands
detected on spectral-domain OCT evolved into atrophy
with attenuation of the inner nuclear and outer plexiform
layers, accounting for persistent scotomas noted on
follow-up examinations as far out as 24 months in certain
patients. Many of these subjective complaints, outlined
in the Results section, may be overlooked, especially
when the BCVA is preserved and there is no evidence of
macular edema or underlying angiographic abnormalities.
It is important, therefore, for ophthalmologists to identify
paracentral acute middle maculopathy on spectraldomain OCT and to counsel patients accordingly, especially if there are corresponding visual sequelae.

Limitations of our study include its retrospective nature,

the relatively small number of eyes (25) studied, and the
high number of patients (8) without clinical follow-up.
Nevertheless, this is the largest case series to date
describing this unique finding of paracentral acute middle
maculopathy in the setting of nonischemic CRVO. We
have provided clinical and anatomic evidence to support
retinal capillary ischemia as the cause of paracentral acute
middle maculopathy, but this proposed mechanism has not
yet been proven. Showing causality would require animal
models of retinal capillary occlusion and subsequent
demonstration of the characteristic findings of paracentral
acute middle maculopathy with multimodal imaging. More
advanced imaging systems to identify abnormalities in the
intermediate and deep capillary plexuses will further
enhance our understanding of paracentral acute middle
maculopathy. More recently, Wang and associates27 have
used ultrahigh-resolution OCT and adaptive optics to
image the retinal capillary system at 3-dimensional resolution.
In summary, paracentral acute middle maculopathy refers to characteristic hyper-reflective spectral-domain
OCT lesions involving the middle layers of the retina at
the level of the inner nuclear layer that develop in response
to ischemia of the intermediate and deep capillary plexuses.
This series describes in particular paracentral acute middle
maculopathy in the setting of coexisting nonischemic
CRVO; however, it appears that this is a unique entity
that may coexist in various retinal vascular disorders, analogous to a deeper cotton-wool spot in the middle retina.
This finding is probably much more common than has
been reported to date, and additional cases may be identified as the ophthalmic community becomes more aware of
its presentation and diagnosis.

ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST,
and the following were reported. Dr Sarraf is a speaker for Heidelberg and receives grant support from Regeneron. Dr Ho is a paid consultant and lecturer for
Alcon. Contributions of Authors: Concept and design (E.R., D.S., A.C.H.); Analysis and interpretation of data (E.R., D.S., M.L.D., J.D.P., A.C.H.); and
Preparation, review, or approval of manuscript (E.R., D.S., M.L.D., J.D.P., A.C.H.).

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AMERICAN JOURNAL OF OPHTHALMOLOGY

AUGUST 2014

Biosketch
Ehsan Rahimy, MD is currently a first-year vitreoretinal fellow at Wills Eye Hospital. He received his undergraduate degree
in Cellular & Molecular Biology from the University of Michigan, followed by medical school training at Baylor College of
Medicine. He most recently completed his residency in ophthalmology at the Jules Stein Eye Institute, UCLA.

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