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Paracentral Acute Middle Maculopathy in NonischemicCentral Retinal Vein Occlusion

EHSAN RAHIMY, DAVID SARRAF, MICHAEL L. DOLLIN, JOHN D. PITCHER, AND ALLEN C. HO

PURPOSE: To better characterize a novel spectral-domain optical coherence tomography (OCT) presenta-

tion, termed paracentral acute middle maculopathy, to

describe this finding in patients with nonischemic centralretinal 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 digitalcolor imaging, red-free photography, fluorescein angiog-

raphy, near-infrared reflectance, and spectral-domainOCT images of 484 patients with acute CRVO from 2centers 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 ofage and presented with complaints of paracentral sco-

tomas. All patients demonstrated hyper-reflective plaque-like lesions at the level of the inner nuclear layer by

spectral-domain OCT and showed corresponding dark-

gray 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, thelesions had resolved into areas of inner nuclear layer atro-

phy 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 atthe level of the inner nuclear layer that may develop in

response to ischemia of the intermediate and deep capil-

lary plexuses. This series is the largest to describe thisspectral-domain OCT finding to date, and it is the first

to associate it with nonischemic CRVO. (Am JOphthalmol 2014;158:372–380. 2014 by Elsevier

Inc. All rights reserved.)

RECENTLY, WE IDENTIFIED CHARACTERISTIC BAND-

like hyper-reflective spectral-domain optical coher-

ence tomography (OCT) lesions in patients with

presumed acute macular neuroretinopathy involving themiddle 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 caseseries additionally observed this finding in 4 patients,

including 1 with underlying diabetic retinopathy.3 Retinalcapillary ischemia has been proposed as the causative factor

in the development of these lesions, which localize histo-logically at the level of the intermediate and deep retinalcapillary plexuses flanking the inner and outer boundaries

of the inner nuclear layer, respectively.1,4

This article describes 25 new cases of paracentral acutemiddle maculopathy occurring in association with acute

nonischemic central retinal vein occlusion (CRVO), andwill help to further elucidate the underlying pathogenesis

of these middle retinal lesions.

METHODSINSTITUTIONAL REVIEW BOARD APPROVAL FOR THIS

retrospective 2-center study was obtained through the

Wills Eye Hospital, Philadelphia, Pennsylvania, and theUniversity of California, Los Angeles, Office of the Human

Research Protection Program. Research adhered to the

tenets of the Declaration of Helsinki and was conductedin accordance with regulations set forth by the HealthInsurance Portability and Accountability Act.

Using International Classification of Diseases, 9th Revi-

sion (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 acutemiddle maculopathy lesions and assessed the clinical and

imaging data for each case, focusing primarily on multi-

modal imaging correlations. Baseline and follow-up demo-graphic, clinical and laboratory data were extracted from

patient charts and analyzed. Statistical analysis was

performed by a simple 2-tailed t test using GraphPad Soft-ware (GraphPad, La Jolla, California).

High-resolution digital color imaging, red-free photog-

raphy, and fluorescein angiography at baseline presentation

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 GeneticsDivision, Jules Stein Eye Institute, University of California, LosAngeles, David Geffen School of Medicine, Los Angeles, California(D.S.); and the Greater Los Angeles Veterans Affairs HealthcareCenter, 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: [email protected]

372 0002-9394/$36.00http://dx.doi.org/10.1016/j.ajo.2014.04.024

2014 BY ELSEVIER INC. ALL RIGHTS RESERVED.

mailto:[email protected]

http://dx.doi.org/10.1016/j.ajo.2014.04.024

http://dx.doi.org/10.1016/j.ajo.2014.04.024

mailto:[email protected]



were analyzed, when available, for each patient. Initial

near-infrared reflectance and spectral-domain OCT exami-

nations utilizing the Heidelberg Spectralis (HeidelbergEngineering, Heidelberg, Germany) were evaluated at base-

line in every patient and correlated with subsequent follow-

up scans during the course of a patient’s follow-up whenavailable. We used the registration feature specific to Hei-

delberg Spectralis, which allows each spectral-domainOCT B-scan to be coupled to its exact location on the

near-infrared reflectance image, facilitating point-to-pointcorrelations of the retinal findings between the near-

infrared reflectance and spectral-domain OCT images.

RESULTS

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

demonstrated evidence of concurrent paracentral acute mid-

dle maculopathy at the time of their initial office evaluations.Baseline patient demographics and ocular examination find-

ings in these eyes are outlined in the Table. The mean age atpresentation was 51 years (range, 19–78; standard deviation

(SD), 16.6) in the group with paracentral acute middle

maculopathy, which was significantly younger than the69.6 years (range, 20 to 95; SD, 13.9) in the remainder of

the patients with CRVO (P < .001). There was no genderpredilection for the development of paracentral acute middle

maculopathy (males, 48%; females, 52%).

With respect to pre-existing systemic and ocular comor-bidities, 8 patients had known histories of hypertension, 6

had hypercholesterolemia, 4 had diabetes mellitus, 3 hadsystemic lupus erythematosus, 3 had open-angle glaucoma

with optic disc cupping, and 1 had active pulmonary tuber-culosis who was undergoing treatment. After detailed his-

tories were obtained, 2 patients endorsed current use of

oral contraceptive pills, and 1 individual was a long-distance marathon runner. Hematologic laboratory

workup, when obtained, was negative for any hypercoagu-

lable state in all but 1 case, in which an underlying diag-nosis 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 officeevaluation (range, 1–21 days). Complaints ranged fromgeneralized blurring of the central vision and difficulty

focusing to more specific patterns of paracentral scotomas,

including the following patient descriptions: ‘‘pieces of cen-tral vision missing’’ (Figure 1); ‘‘concentrically arrangedfixed gray spots’’; ‘‘like looking through cracked glass’’;

‘‘numerous small blind spots’’; and ‘‘blank spots in central

vision.’’ On initial examination, Snellen best-correctedvisual 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%)

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 cilioretinalartery 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 nonciliore-tinal artery occlusion patients (P < .001).

The diagnosis of CRVO was established on the basis of

characteristic funduscopic findings: tortuosity and dilata-

tion of the central retinal vein, intraretinal hemorrhagesthroughout all 4 quadrants, and/or optic disc and macularedema. In all eyes, detailed examination of the macula in

the involved eye revealed patchy areas of deep retinal whit-

ening centered within the macula, often in the distributionof the venous tributaries and always correlating with para-

central acute middle maculopathy on spectral-domain

OCT (Figures 1–6). Compared to cotton-wool spots, the

retinal whitening associated with paracentral acute middle

TABLE. Patient Demographics and Ocular Findings in

Paracentral Acute Middle Maculopathy

Age, years

Mean 6 SD 51 6 16.6

Range 19–78

Gender (n ¼ 25)

Male 12 (48%)

Female 13 (52%)

Eye (n ¼ 25)

Right 12 (48%)

Left 13 (52%)

CRVO Type (n ¼ 25)

Nonischemic 25 (100%)

Ischemic 0 (0%)

Systemic/ocular associations

Hypertension 8 (32%)

Hypercholesterolemia 6 (24%)

Diabetes mellitus 4 (16%)

SLE 3 (12%)

Open-angle glaucoma 3 (12%)

OCP use 2 (8%)

Marathon running 1 (4%)

MGUS 1 (4%)

BCVA

Snellen mean 20/120

Snellen range 20/20-HM

logMAR mean 0.767

logMAR range 0–2.28

BCVA ¼ best-corrected visual acuity; CRVO ¼ central retinal

vein occlusion; HM ¼ hand motions; logMAR ¼ logarithm of

the minimum angle of resolution; MGUS ¼ monoclonal gammop-

athy of undetermined significance; OCP ¼ oral contraceptive

pills; SD ¼ standard deviation; SLE ¼ systemic lupus erythema-

tosus.

VOL. 158, NO. 2 373PARACENTRAL ACUTE MIDDLE MACULOPATHY IN VEIN OCCLUSION



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 mid-dle maculopathy were uniquely different in appearance andlocation from associated cilioretinal artery occlusion, when

present (Figure 2), which was more superficial and whiter.

Because of the presence of concurrent retinal hemor-rhages and cotton-wool spots, the extent of paracentral

acute middle maculopathy was not always as readily

apparent on examination; however, with ancillary red-free photography (Figure 4) and near-infrared reflectance

imaging (Figures 1–6), the lesions were more clearlyidentified, appearing dark and more precisely delineated.

Specifically, near-infrared reflectance confirmed the peri-

venular location of paracentral acute middle maculopathyin the majority of cases. Conversely, the fluorescein angio-

gram had no correlation with the lesions (Figure 1 andFigure 4), and no cases displayed angiographic evidence

of an ischemic CRVO (10 or greater disc diameters of capil-

lary nonperfusion).Corresponding spectral-domain OCT imaging registered

through the zones of retinal whitening revealed multifocalhyper-reflective plaquelike lesions at the level of the inner

nuclear layer (Figures 1–6). In 13 cases, the involvement of

paracentral acute middle maculopathy was additionallynoted to extend into the inner plexiform layer. Although

the lesions appeared to cast a shadow over the deeper

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,

1–24; median, 4; SD, 7.6), although 8 of the 25 patients

were lost to follow-up. Average final BCVA at the mostrecent clinic visit was 20/40 (logMAR equivalent, 0.339)

for the entire cohort. More specifically, patients with simul-

taneous cilioretinal artery occlusion experienced partialresolution of vision back to an average BCVA of 20/120

(logMAR equivalent, 0.81), compared to 20/30 (logMARequivalent, 0.20) in the noncilioretinal artery occlusion

patients (P ¼ 0.26). Although 14 (82%) of the 17 patients

tested 20/50 or better at the final visit, the subjective para-central scotomas persisted.

On fundus examination, intraretinal hemorrhages, opticdisc edema and macular edema showed variable degrees of

resolution. On follow-up near-infrared reflectance imaging,

the dark lesions had dissipated, and the most recentspectral-domain OCT examinations revealed zones of

severe inner nuclear layer thinning and a markedly attenu-ated outer plexiform layer band where the hyper-reflective

paracentral acute middle maculopathy lesions had been

located previously (Figure 5 and Figure 6). The shadowinginduced by the overlying lesions seen on spectral-domain

OCT had resolved.

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). Fluo-

rescein 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. Spectral-

domain optical coherence tomography revealed multiple hyper-reflective plaquelike lesions involving the inner nuclear layer (Bottom

right, solid arrows) consistent with paracentral acute middle maculopathy.

374 AUGUST 2014AMERICAN JOURNAL OF OPHTHALMOLOGY



Of the patients, 5 had received serial intravitreal anti-

vascular endothelial growth factor therapy during their

courses (2 with bevacizumab, 3 with ranibizumab) for treat-ment of associated macular edema. Whether a patient

received intravitreal injections did not appear to impactthe timeline to resolution of the paracentral acute middle

maculopathy.

DISCUSSION

PARACENTRAL ACUTE MIDDLE MACULOPATHY REFERS TO

a recently recognized class of characteristic lesions invol-

ving the middle layers of the retina at the level of the inne rnuclear 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 nonische-

mic CRVO. The association of paracentral acute middle

maculopathy with disparate disorders such as acute macular

neuroretinopathy and CRVO may indicate that these

lesions seen on spectral-domain OCT have a wide spectrumof presentation, such that they can occur as isolated events

in typically healthy patients with acute macular neuroretin-opathy and can also occur in various retinal vascular disor-

ders such as CRVO, in which multiple middle retinallesions are identifiable. In either case, the characteristicappearance may be the result of an ischemic insult at the

level of the inner nuclear layer,as thelocationof paracentral

acute middle maculopathy on spectral-domain OCT corre-sponds histologically with the intermediate and deep capil-lary plexuses, and subsequent atrophy of the inner nuclear

layer ensues, often with persistent subjective scotoma.

In 2002, Browning5 published a study concerning 11patients 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

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). Near-

infrared 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 withparacentral acute middle macul-

opathy in contrast to the superficial edema and hyper-reflectivity induced by the cilioretinal artery occlusion (Bottom, broken arrow).




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, themost sensitive tissue for manifesting decreased oxygenation

will be perivenular, especially in the posterior pole, where

oxygen metabolism is highest. In 2003, Paques and associ-ates6 reported on 3 additional patients with CRVO display-

ing 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 withthe 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.7–9 Michaelsonand others have previously emphasized the presence of a

zone surrounding the retinal arteries devoid of any

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 thecapillary 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 fiberlayer with occasional dips into the deeper layers.12 From

the terminal arterioles and venules, precapillary and capil-

lary branches emerge, often at near right angles to the sur-face of the retina. These tributaries then dive into the

deeper retinal layers where they then anastomose laterallyand form an intricate, planar microvascular capillary

network.12 In their seminal work published in 1954,

Michaelson and Campbell10 emphasized a laminar distribu-tion of these capillaries that varied in differing regions of

the retina. Outside the cecocentral area, they proposed

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 thesuperotemporal 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 mul-

tiple hyper-reflective lesions involving the inner nuclear layer (Bottom, solid arrows) consistent with paracentral acute middle macul-

opathy.




that 2 laminas were present: a superficial capillary plexus in

the nerve fiber layer and a deep capillary plexus at the junc-tion 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 plexiformand inner nuclear layers. Terminology notwithstanding,

this 3-dimensional conceptualization of the retinal micro-

vascular network still stands today.4,13,14 In most higher

order mammals, it is recognized that 3 planar capillary

plexuses form during development: (1) the superficialplexus 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.

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 plaque-

like 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 correspond-

ing 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.




The most critical function of the retinal circulation is tosupply oxygen.15 It has been reported that the deep capillary

plexus contributes 10%–15% of the oxygen supply to thephotoreceptor population.16 The photoreceptor axon termi-

nals, 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 deepcapillary plexus for oxygen supply than the photoreceptor

inner and outer segments located closer to the underlyingchoriocapillaris. A steady decline of the diffusion gradientof oxygen from the choriocapillaris to the photoreceptor

axons has been experimentally confirmed by Wangsa-

Wirawan and associates.18 Similarly, studies of cat retinashave demonstrated that oxygen tension in the retina is high-

est near the choroid, bottoms out at the level of the outer

nuclear layer, and then rises again in the superficial retinallayers.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 thechoroidal and retinal circulations.13,21 As such, the outer

plexiform layer and adjacent inner nuclear layer in thiswatershed zone may be especially vulnerable to ischemic

insults to the intermediate and deep capillary plexuses.

In our study, the extent of paracentral acute middlemaculopathy on spectral-domain OCT was noted toinvolve primarily the full thickness of the inner nuclear

layer and, in nearly half of cases, advanced into the over-

lying inner plexiform layer. Subsequently, the lesionsinvariably resolved with thinning of the inner nuclear

layer. That this lesion aligns precisely with the intermedi-

ate and deep capillary plexuses, and given our cohorts’

underlying diagnoses of CRVO coupled with vasculopathicrisk factors, we propose that ischemia of these microvas-

cular 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 tech-niques such as fluorescein angiography cannot assess

adequately the morphology or the integrity of these deeperretinal capillary plexuses, as previously demonstrated byMendis and associates.22

As in previous studies,5,6 we similarly observed that

patients with CRVO and paracentral acute middlemaculopathy (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 widelydebated, the association of paracentral acute

middle maculopathy with cilioretinal artery occlusion

cannot be overlooked. Presumably, cilioretinal arteryocclusion occurs due to the lower arteriolar pressure of thecilioretinal artery compared with that of the central retinal

artery.23–25 Therefore, a sudden occlusion of the central

retinal vein results in a marked rise of the intraluminalpressure that is transmitted throughout the entire retinal

capillary bed.26 Once the intraluminal pressure rises above

that in the already susceptible cilioretinal artery system,

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 clin-

ically. 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 whit-

ening 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 irreg-

ular, attenuated outer plexiform layer (Bottom right, solid arrows).




the result is a relative hemodynamic blockade in the artery,

manifesting as a cilioretinal artery occlusion.26 The possibil-

ity that increased venous intraluminal pressure couldadversely affect other regions of potential vascularinstability,

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 progressionfrom nonischemic CRVO to combined nonischemic

CRVO and cilioretinal artery occlusion formation.Only 20% of the patients in this current study had coex-

isting macular edema at the time of presentation. The pres-

ence of retinal heme or edema may limit the ability todetect paracentral acute middle maculopathy. Further-

more, these lesions are evanescent and may resolve priorto clinical detection. Therefore, the incidence of paracen-

tral acute middle maculopathy in all cases of CRVO may

actually be much higher than the 5.2% we observed. Themultifocal arrangement of paracentral acute middle macul-

opathy we observed in the setting of nonischemic CRVO isunique because our previously reported series describedonly solitary lesions.1 Over time, the hyper-reflective bandsdetected on spectral-domain OCT evolved into atrophy

with attenuation of the inner nuclear and outer plexiform

layers, accounting for persistent scotomas noted onfollow-up examinations as far out as 24 months in certain

patients. Many of these subjective complaints, outlined

in the Results section, may be overlooked, especiallywhen 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 spectral-domain OCT and to counsel patients accordingly, espe-cially 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. Wehave provided clinical and anatomic evidence to support

retinal capillary ischemia as the cause of paracentral acutemiddle maculopathy, but this proposed mechanism has not

yet been proven. Showing causality would require animalmodels of retinal capillary occlusion and subsequent

demonstration of the characteristic findings of paracentral

acute middle maculopathy with multimodal imaging. Moreadvanced imaging systems to identify abnormalities in the

intermediate and deep capillary plexuses will furtherenhance our understanding of paracentral acute middle

maculopathy. More recently, Wang and associates27 have

used ultrahigh-resolution OCT and adaptive optics toimage the retinal capillary system at 3-dimensional resolu-

tion.In summary, paracentral acute middle maculopathy re-

fers to characteristic hyper-reflective spectral-domainOCT 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 entitythat may coexist in various retinal vascular disorders, anal-

ogous 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 identi-fied 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,andthe following were reported.Dr Sarrafis a speaker forHeidelberg andreceivesgrantsupport from Regeneron. Dr Ho is a paid consultant andlecturerforAlcon. 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.); andPreparation, review, or approval of manuscript (E.R., D.S., M.L.D., J.D.P., A.C.H.).

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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.

VOL. 158, NO. 2 380.e1PARACENTRAL ACUTE MIDDLE MACULOPATHY IN VEIN OCCLUSION

am j ophthalmol 2014 rahimy-3

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