am j ophthalmol 2015 chen
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Spectrum of Retinal Vascular DiseasesAssociated With Paracentral Acute Middle
Maculopathy
XUEJING CHEN, EHSAN RAHIMY, ROBERT C. SERGOTT, RENATA P. NUNES, EDUARDO C. SOUZA,NETAN CHOUDHRY, NATHAN E. CUTLER, SAMUEL K.S. HOUSTON, MARION R. MUNK,
AMANI A. FAWZI, SONIA MEHTA, JEAN-PIERRE HUBSCHMAN, ALLEN C. HO, AND DAVID SARRAF
PURPOSE: To evaluate the spectrum of retinal diseases
that can demonstrate paracentral acute middle maculop-
athy and isolated ischemia of the intermediate and deepcapillary plexus. DESIGN: Retrospective, multicenter, observationalcase series. METHODS: This is a retrospective case series review of 9
patients (10 eyes) from 5 centers with paracentral acutemiddle maculopathy lesions and previously unreported
retinal vascular etiologies. Case presentations and multi-
modal imaging, including color photographs, near-infraredreflectance, fluorescein angiography, spectral-domain opti-
cal coherence tomography (SD OCT), and orbital colorDoppler imaging, are described. Baseline and follow-up
findings are correlated with clinical presentation, demo-graphics, and systemic associations. RESULTS: Five men and 4 women, aged 27–66 years,
were included. Isolated band-like hyperreflective lesionsin the middle retinal layers, otherwise known as paracentral
acute middle maculopathy, were observed in all patients atbaseline presentation. Follow-up SD OCT analysis of these
paracentral acute middle maculopathy lesions demon-
strated subsequent thinning of the inner nuclear layer.Novel retinal vascular associations leading to retinal
vasculopathy and paracentral acute middle maculopathy
include eye compression injury causing global ocularischemia, sickle cell crisis, Purtscher’s retinopathy, inflam-
matory occlusive retinal vasculitis, post-H1N1 vaccine,hypertensive retinopathy, migraine disorder, and post–
upper respiratory infection.
CONCLUSION: Paracentral acute middle maculopathy
lesions may develop in a wide spectrum of retinal vascular
diseases. They are best identified with SD OCT analysisand may represent ischemia of the intermediate and
deep capillary plexus. These lesions typically result inpermanent thinning of the inner nuclear layer and are
critical to identify in order to determine the cause of
unexplained vision loss. (Am J Ophthalmol2015;160(1):26–34. 2015 by Elsevier Inc. All rights
reserved.)
THE RETINAL CAPILLARY SYSTEM IN THE CENTRAL
macula is a layered vascular structure composedof the superficial and deep capillary plexus.1,2
The latter consists of an intermediate and deepplexus along the inner and outer aspect of the inner
nuclear layer, respectively.1,2 The superficial capillaryplexus is visible with fluorescein angiography and
ischemia of this structure may manifest as a cotton-
wool spot. However, fluorescein angiography fails toadequately visualize the intermediate and deep plex-
uses.3 Before the advent of spectral-domain opticalcoherence tomography (SD OCT), abnormalities in
these deeper plexuses, located in the middle retina,
were not readily appreciated.Recently the term ‘‘paracentral acute middle maculop-
athy’’ has been added to our vernacular and refers to the
presence of a hyperreflective parafoveal band at the levelof the inner nuclear layer on SD OCT that co-localizes pre-
cisely with the intermediate and deep capillary plexuses.4
The subsequent development of inner nuclear layer thin-
ning corresponding to the original paracentral acute mid-
dle maculopathy lesion indicates that the primaryetiology may be ischemia of the intermediate and deep
capillary systems.
Paracentral acute middle maculopathy has recentlybeen associated with various retinal vascular diseases,including nonproliferative diabetic retinopathy, central
retinal vein occlusion, and retinal artery occlusion,
further supporting the possible underlying ischemic na-ture of this SD OCT finding.5–7 This series will present
an additional 9 cases of paracentral acute middle
maculopathy associated with various disorders not listed
See Accompanying Editorial on page 1.Accepted for publication Apr 2, 2015.
From the Stein Eye Institute, Department of Ophthalmology,University of California Los Angeles (X.C., J.-P.H., D.S.); and GreaterLos Angeles Veterans Affairs Healthcare Center (X.C., D.S.), LosAngeles, California; Wills Eye Hospital (E.R., R.C.S., N.E.C., S.K.S.H.,S.M., A.C.H.), Philadelphia, Pennsylvania; Department of Ophthalmology, Universidade Federal of Sao Paulo (R.P.N., E.C.S.),Sao Paulo, Brazil; Herzig Eye Institute (N.C.), Toronto, Canada; andDepartment of Ophthalmology, Feinberg School of Medicine,
Northwestern University (M.R.M., A.A.F.), Evanston, Illinois.Inquiries to David Sarraf, Retina Disorders and Ophthalmic Genetics
Division, Stein Eye Institute, 100 Stein Plaza, Los Angeles, CA 90095;e-mail: [email protected]
26 0002-9394/$36.00http://dx.doi.org/10.1016/j.ajo.2015.04.004
2015 BY ELSEVIER INC. ALL RIGHTS RESERVED.
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above, including ocular compression causing global
ischemia, sickle cell retinopathy, retinal vasculitis,Purtscher’s retinopathy, and other etiologies.
METHODS
INSTITUTIONAL REVIEW BOARD APPROVALS FOR RETRO-
spective chart reviews were obtained commensurate withthe respective institutional requirements prior to the begin-
ning of the study. The research adhered to the tenets of theDeclaration of Helsinki and was conducted in accord with
regulations set forth by the Health Insurance Portabilityand Accountability Act. This was a multicenter, retrospec-tive, observational case series review of the clinical and
multimodal imaging findings for 10 eyes (9 patients) with
paracentral acute middle maculopathy. The diagnosticcriteria for paracentral acute middle maculopathy includedband-like hyperreflectivity on SD OCT in the middle mac-
ula centered on the inner nuclear layer that evolved into
thinning of that retinal layer. Multimodal imaging includedcolor fundus photographs (Carl Zeiss Meditec, Dublin,
California, USA; Topcon Medical Systems, Oakland,
New Jersey, USA), near-infrared reflectance (SPECTRA-
LIS; Heidelberg Engineering, Heidelberg, Germany),
fluorescein angiography (Carl Zeiss Meditec; Topcon Med-
ical Systems), SD OCT (SPECTRALIS; Heidelberg Engi-neering), and orbital color Doppler imaging (Logiq 700;General Electric Medical Systems, Milwaukee, Wisconsin,
USA). Detailed clinical evaluation was performed andassociated systemic etiologies were identified. Baseline
and follow-up SD OCT findings were correlated with the
clinical presentation, demographics, systemic associations,and baseline and final visual acuities, as well as adjunctive
imaging findings.
RESULTS
TEN EYES WITH PARACENTRAL ACUTE MIDDLE MACULOP-
athy in 9 patients (5 men and 4 women) were identified
and collected for this study. Patient ages ranged from 27to 66 years (mean 39 years). Hyperreflectivity on SDOCT in the middle retinal layers was observed for all pa-
tients in the acute presentation, followed by thinning of
the inner nuclear layer with follow-up SD OCT analysis.All patients presented with a form of retinal vascular dis-
ease. Four cases are described in detail below, and 5 other
cases are summarized in the Table and Figure 1, with the
baseline and follow-up SD OCT images included.
TABLE.Cases 5–9 of This Case Series Describing Retinal Vascular Diseases Associated With Paracentral Acute Middle Maculopathy
CaseNo.
Age/
Sex Presentation Systemic Disease Eye Disease Eye
Baseline
BCVA Baseline Fundus
Follow-up
BCVA
5 2 7/F 2–3 mo nths o f visio n los s OS
and ‘‘changing vision’’ OD.
In-clinic BP was 180/80
Migraines, OCP,
Adderall use,
HTN
Hypertensive
retinopathy
OD 20/20 Nasal parafoveal, wedge-
shaped, yellowish white
lesion
20/20
OS CF Superonasal, parafoveal,
wedge-shaped, yellowish
white lesion
CF
6 50/M Acute-onset blurry vision
OD. Recent BP ranged
from 112/71 to 195/88
depending on medication
compliance
HTN, CHF,
pulmonary
hypertension,
alcohol abuse
Hypertensive
retinopathy,
pseudophakia
OD 20/30 Nasal parafoveal wedge-
shaped yellowish lesion
(localizes to PAMM) with
an adjacent, more
superficial-appearing
white lesion (localizes
to a CWS)
20/40
7 28/M Acute-onset paracentral
scotoma OD
Migraine with
visual aura
_ OD 20/20 Normal dilated exam 20/20
8 53/F Acute onset of paracentralscotomas OD 2–3 days
after H1N1 vaccine
Hypothyroidism,HTN, anxiety
Pseudophakia OD 20/50 Scattered parafovealwhitening (localizes with
PAMM), peripapillary
CWSs
20/50
9 3 7/M Acu te o nset of scot oma O D
2 weeks after a URI
Recent URI _ OD 20/25 Temporal parafoveal wedge-
shaped light-yellow lesion
20/20
BCVA ¼ best-corrected visual acuity; BP ¼ blood pressure; CF ¼ count fingers; CHF ¼ congestive heart failure; CWS ¼ cotton-wool spot;
HTN ¼ hypertension; OCP ¼ oral contraceptive pills; PAMM ¼ paracentral acute middle maculopathy; URI ¼ upper respiratory infection.
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CASE 1: A 61-year-old African-American man with a
history of hypertension, hyperlipidemia, diabetes mellitus,and obstructive sleep apnea presented with an acute onset
of multiple paracentral scotomas in the right eye after fall-
ing asleep overnight with his head on top of his hands. Re-view of systems was otherwise negative. Visual acuity was
20/25 in the right eye and 20/20 in the left. Anterior
segment and dilated examinations were unremarkable.Orbital color Doppler imaging showed an absence of flowin the right central retinal artery, right nasal and temporal
short posterior ciliary artery, and left nasal short posterior
ciliary artery. Flow in the right ophthalmic artery wasnormal. Erythrocyte sedimentation rate, C-reactive pro-
tein, and platelets were all within normal limits. He was
started immediately on high-dose steroids because of theconcern for giant cell arteritis. A subsequent stroke evalu-
ation showed <50% bilateral carotid stenosis and an inci-dental 2.2 mm right internal carotid artery aneurysm.
Subsequent bilateral temporal artery biopsies returned
negative for giant cell arteritis and steroid tapering wasinitiated. Repeat orbital color Doppler imaging 2 days after
the initial presentation showed improved flow rates and ve-
locities in the right central retinal artery and right temporalshort posterior ciliary artery. An absence of flow persistedin the short nasal posterior ciliary artery bilaterally. At
the 2-week follow-up interval, the paracentral scotomas
persisted, with vision remaining 20/25 bilaterally. Fluores-cein angiography showed bilateral global delayed perfu-
sion. Bilateral near-infrared reflectance imaging showed
multiple parafoveal dark-gray lesions, and SD OCTthrough these lesions revealed multiple paracentral acute
middle maculopathy lesions (Figure 2).
CASE 2: A 28-year-old African-American woman with
sickle cell disease presented with bilateral paracentral sco-tomas in the absence of other signs of occlusive crisis (eg,
bone pain, chest pain, abdominal pain). Visual acuity at pre-
sentation was 20/50 in her right eye and 20/200 in her lefteye. Macular examination showed a wedge of deep retinal
whitening nasal to each fovea without any other stigmataof sickle cell retinopathy,such as retinal hemorrhages, irides-
cent spots, pigment clumps, or peripheral neovasculariza-tion. Fluorescein angiography showed bilateral capillary
pruning and temporal retinal vascular nonperfusion. SDOCT showed hyperreflective bands at the level of the innernuclear layer corresponding to the white macular lesions,
consistent with paracentral acute middle maculopathy,
and inner retinal atrophy of the temporal macula typicalof old branch retinal artery occlusions (Figure 3).
CASE 3: A 36-year-old Brazilian woman presented with a
central scotoma of her right eye and floaters in the left eye
for 1 week. She had a prior history of flu-like illness withgastrointestinal symptoms and right-sided retro-orbital pain.
Medical history was remarkable for a pregnancy-induced
deep vein thrombosis. Visual acuity was 20/150 in the right
eye and 20/25 in the left eye. Anterior examination wasnormal. Dilated retinal examination showed papillitis, occlu-
sive vasculitis, and multifocal retinal infiltrates in each eye
and inferotemporal retinal ischemia in the right eye, all of which was confirmed with fluorescein angiography. SD
OCT through the zone of inferotemporal ischemia showedparacentral acute middle maculopathy temporal to the fovea
and both superficial and deep capillary ischemia nasal to thefovea. The patient was started on prednisone 60 mg daily.Vision later improved to 20/25 in the right eye (Figure 4).
CASE 4: A 29-year-old Hispanic man sustained a motorvehicle accident with loss of consciousness and presentedwith vision loss of the left eye. Visual acuity was count fin-
gers in the left eye with a relative afferent pupillary defect.
Anterior segment examination was notable for left-sidedperiorbital ecchymosis and subconjunctival hemorrhage.
Fundus examination showed multiple superficial, polyg-
onal, white lesions in the posterior pole radiating from
the optic nerve and parafoveal white-yellow lesions sparing
FIGURE 1. Spectral-domain optical coherence tomography (SD
OCT) images of paracentral acute middle maculopathy associated
with additional examples of retinal vascular disease in Cases 5–9.
Cases 7 and 9 show en face images of paracentral acute middlemaculopathy lesions with baseline SD OCT. CWS: cotton-wool
spot; PAMM: paracentral acute middle maculopathy.
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the retinal vessels. Fluorescein angiography showed hypo-
perfusion corresponding to these lesions and vascular
leakage. The patient was diagnosed with Purtscher’s reti-nopathy. SD OCT through the white lesions showed
edema extending from the nerve fiber layer to the innerplexiform layer, indicating ischemia of the superficial, in-
termediate, and deep capillary plexuses. SD OCT through
the parafoveal white-yellow lesions demonstrated paracen-tral acute middle maculopathy consistent with ischemia of
the intermediate and deep capillary plexuses and previously
referred to as Purtscher Flecken (Figure 5).
CASES 5–9: The Table and Figure 1 provide a summary of
the clinical data for Cases 5–9.
DISCUSSION
IN 2013, SARRAF AND ASSOCIATES DESCRIBED PARACEN-
tral acute middle maculopathy lesions in 5 patients aged
54–65 years who presented with paracentral scotomas.1,2,8
Two of these patients had no significant history, while the
FIGURE 2. Case 1. Prolonged globe compression leading to severe compromise in the flow of the central retinal artery and short
posterior ciliary artery, as measured by orbital color Doppler imaging and leading to paracentral acute middle maculopathy seen on
spectral-domain optical coherence tomography (SD OCT) analysis. (Left, first and second from top) Normal-appearing fundus pho-
tographs 2 days after presentation. (Right, first and second from top) Near-infrared reflectance shows parafoveal light-gray lesions in
the right eye, and SD OCT shows that the light-gray lesions correspond with paracentral acute middle maculopathy (dotted arrows).
(Right, third from top) Near-infrared reflectance and SD OCT are unremarkable for the left eye. (Bottom) Table shows systolic blood
flow velocities as measured by Doppler for Case 1. At baseline presentation, the flow rates within the central retinal artery, nasal pos-
terior ciliary artery, and temporal posterior ciliary artery are absent or severely reduced. On follow-up there is an increase in flow rate
for each (except for nasal posterior ciliary artery of the right eye) corresponding to slow reperfusion after relief of extended intraor-
bital pressure. OD: right eye; OS: left eye; CRA: central retinal artery; NPCA: nasal posterior ciliary artery; TPCA: temporal pos-
terior ciliary artery; OA: ophthalmic artery. The top portion of the figure has 2 columns of sub-images (not 3) – the left column has
square images, the right column has rectangular images.
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remaining 3 presented after severe hypovolemia, flu-likeillness, and excessive coffee use suggestive of vasoconstric-tion. Since the original description, a number of other
retinal vascular disorders including diabetic retinopathy,
central retinal vein occlusion, and retinal artery occlusionhave been associated with paracentral acute middle macul-opathy lesions. Based on the characteristic SD OCT
appearance and the patient demographics associated with
this clinical finding, paracentral acute middle maculopathyis currently thought to be a result of ischemia of the inter-
mediate and deep capillary plexuses,3,4,9 and may
theoretically be seen in any patient with retinal vascular
disease or systemic vasculopathic risk factors.4–7,9
Paracentral acute middle maculopathy lesions inevitablytransition from their characteristic band-like hyperreflec-tivity on SD OCT to isolated atrophy of the inner nuclear
layer on extended follow-up. This paper discusses several
novel entities associated with paracentral acute middlemaculopathy lesions, further supporting an underlyingischemic pathogenesis.
Case 1 illustrates an at-risk vasculopathic patient who
placed prolonged pressure on his globe, increasing the intra-orbital pressure above the intraluminal pressure in the retro-
orbital arteries, resulting in global ischemia of the central
retinal and ciliary vascular systems. This presumably led to
ischemia of the intermediate and deep capillary plexuses
FIGURE 3. Case 2. A patient with sickle cell crisis presenting with vision loss and bilateral paracentral acute middle maculopathy
lesions. (Top, first and second left) Color fundus photography shows nasal parafoveal whitening. (Middle, first and second left) Fluo-
rescein angiography shows old temporal branch retinal artery occlusions (solid arrows) but normal nasal parafoveal regions bilaterally.
(Bottom, first and second left) Near-infrared reflectance shows nasal parafoveal light-gray lesions in both eyes. (Right, top 4 images)
Spectral-domain optical coherence tomography (SD OCT) showing nasal paracentral acute middle maculopathy lesions (dotted arrows)
corresponding to the light-gray lesions in near-infrared reflectance and temporal inner and middle retinal atrophy corresponding to the
old branch retinal artery occlusions. (Right, bottom 2 images) Follow-up SD OCT shows stable temporal inner and middle retinal at-
rophy, as well as inner nuclear layer atrophy (dotted arrows) corresponding to prior paracentral acute middle maculopathy lesions.
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and the development of paracentral acute middle maculop-
athy lesions with SD OCT analysis. Orbital color Dopplerimaging, an established means to measure retro-orbital
hemodynamics,5–7,10 demonstrated hypoperfusion, further
supporting the correlation between paracentral acutemiddle maculopathy and global ocular ischemia. Re-
establishment of perfusion was achieved with relief of external compression.11
Sickle cell disease can cause occlusion of the retinalvasculature owing to sickled erythrocytes that impedeintravascular transit, leading to ischemia and neovasculari-
zation. Retinal arterial occlusion often occurs along the
horizontal meridian temporal to the fovea involving termi-nal arteriolar branches.12,13 We identified paracentralacute middle maculopathy lesions nasally, suggesting that
an additional level of ischemic insult can occur in these
patients. SD OCT imaging may be especially importantin sickle patients to identify these middle-level infarcts
and explain the development of paracentral scotomas
and/or vision loss not explained by clinical examination
or fluorescein angiography.
Acute occlusive retinal vasculitis can be complicated by
macular edema, intraretinal hemorrhage, and infarc-tion.14,15 Cotton-wool spots and capillary drop-out seen
on fluorescein angiography are frequently described find-
ings associated with retinal vasculitis and related ischemia.In addition, retinal vasculitis can cause ischemia at the
middle macular level involving the intermediate anddeep capillary plexuses, as suggested by paracentral acute
middle maculopathy with SD OCT analysis in Case 3.5Purtscher’s retinopathy occurs from head trauma, and
Purtscher’s-like retinopathy has been described to occur
in acute pancreatitis, fat embolic syndrome and long
bone injury, chronic renal failure, childbirth, connectivetissue disorders, amniotic fluid embolization, prostate sur-gery, and pancreatic cancer.16,17 Multiple theories on the
pathogenesis of Purtscher’s have been proposed, but
occlusion of the precapillary arterioles with intermediate-sized emboli is considered the most likely.16 Purtscher
Flecken refer to the typical vessel-sparing, polygonal, white
retinal lesions that develop parafoveally.18 SD OCT imag-
ing in Case 4 demonstrates that Purtscher Flecken are, in
FIGURE 4. Case 3. The case of occlusive retinitis with paracentral acute middle maculopathy lesions within a bed of inferotemporal
ischemia in theright eye. (Top row) Color fundus photograph andfluorescein angiography of the right eye showing papillitis, scattered
inflammatory infiltrates, and a large area of inferior retinal ischemia. The left eye shows papillitis and scattered inflammatory infil-
trates. (Middle row and Bottom row) Spectral-domain optical coherence tomography through the area of inferotemporal ischemia
shows paracentral acute middle maculopathy (dotted arrow) with ischemia of the intermediate and deep capillary plexuses, andischemia of the superficial, intermediate, and deep capillary plexuses nasally (solid arrow).
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fact, paracentral acute middle maculopathy lesions. Coady
and associates9 described a case of Purtscher’s-like retinop-
athy in a woman with metastatic pancreatic cancer alsowith paracentral acute middle maculopathy lesions corre-
sponding to Purtscher Flecken.
As is the case with a cotton-wool spot, our study indi-
cates that the list of diseases associated with the SD
OCT clinical finding of paracentral acute middle maculop-
athy is long and diverse and includes common conditions
such as hypertension and migraine disorder, as well asrare autoimmune etiologies (eg, post-H1N1 vaccination).
Any of these disorders, along with the more common
retinal vasculopathies such as diabetic retinopathy and
retinal vascular occlusion, can cause ischemia at either
FIGURE 5. Case 4. Post-traumatic Purtscher retinopathy in the left eye. (Top, first and second from left) Color fundus photography
showing superficial, white cotton-wool spots radiating from the optic nerve in the left eye. Vessel-sparing, wedge-shaped yellowish
white lesions are seen parafoveally. (Top, right) Red-free image of the left eye. (Second row) Spectral-domain optical coherence to-mography (SD OCT) showing that cotton-wool spot (solid arrow) spans the full thickness of the inner retina, illustrating ischemia of
the superficial and intermediate capillary plexuses. (Third row and Fourth row) SD OCT through the parafoveal yellow-white lesions
showing paracentral acute middle maculopathy lesions (dotted arrows) correlating to ischemia of the intermediate and deep capillary
plexuses. The paracentral acute middle maculopathy lesions correspond precisely with previously described Purtscher Flecken.
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the superficial or deep capillary level, particularly within
the posterior pole.
The oxygen demand of the macula, especially at the levelof the inner nuclear layer, outer plexiform layer, and photore-
ceptor inner segments, is higher than any other region in the
retina.19,20 While the choroidal vasculature is denser in themacula to help meet this greater metabolic demand, oxygen
diffusion from the choroid to the retina is inherentlylimited by retinal thickness,21 which is greatest parafoveally.
Furthermore, high visual resolution requires optimal opticalpenetrance, thereby limiting the density of the parafoveal
capillary system.20 Together these limitations suggest that
the parafoveal macula, particularly the middle retinal layers,where a watershed-like region exists (as previously discussed
by Yu and associates7), has a high perfusion demand whosesupply is limited by structure, placing it at greatest risk for
an ischemic insult. The fact that paracentral acute middle
maculopathy lesions are in the middle macula and predomi-nantly parafoveal aligns with an ischemic etiology.
Studies in post mortem eyes show that the parafovealcapillary plexuses are supplied and drained by a 1 arte-riole–1 venule unit.22 An average of 8.9 such wedge-shaped units surround the foveal avascular zone in a
radial formation.22 Additionally, each parafoveal arte-
riole is surrounded by a 50-mm capillary-free zone.16 Para-central acute middle maculopathy lesions and Purtscher
Flecken are characteristically paracentral, wedge-
shaped, with a clear region between the retinal whitening
and adjacent arteriole, corresponding precisely to
ischemia of 1 capillary unit from embolization of its
precapillary arteriole.Fluorescein angiography is currently the gold standard
for imaging ischemia, but its resolution is insufficient to
identify isolated loss of the deep capillary plexus and is,in fact, typically normal with paracentral acute middle
maculopathy lesions. Ex vivo human studies of paracentralacute middle maculopathy are unlikely to be helpful as the
lesions are transient. In fact, the true pathogenesis of para-central acute middle maculopathy lesions can only be
proven with in vivo imaging that has sufficient resolution
to study fine retinal blood flow or animal models of pre-arteriolar and capillary occlusion. OCT angiography or
adaptive-optics OCT may be the answer, and studies usingthese modalities are already ongoing.23,24 The increasing
number of associated retinal vascular diseases, as
illustrated in this article, continues to support anunderlying ischemic origin of paracentral acute middle
maculopathy. Its affinity to localize to the parafovealmacula, its typical wedge-shaped appearance, peri-arteriolar sparing in ischemia owing to pre-capillary arteri-olar occlusion upstream, peri-venular pattern of ischemia
owing to increased venous pressure downstream in central
retinal vein occlusion, and its presence within the bed of arterial occlusions all support the theory that paracentral
acute middle maculopathy lesions are attributable to inter-
mediate and deep capillary plexus ischemia.
ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST.Financial Disclosures: R.C.S. is a consultant for Biogen Idec (Cambridge, MA), Merck (Kenilworth, NJ), Sanofi-Genzyme (Cambridge, MA), Teva
(Israel), Novartis (New York, NY), Heidelberg Engineering (Germany), Janssen (Horsham, PA), Lundbeck (Deerfield, IL), ThromboGenics (Belgium),Merck Serono (Rockland, MA), Mallinckrodt (Ireland), United States Department of Defense (Washington, DC), and United States Food and DrugAdministration (Silver Spring, MD). N.C. is a consultant for Bayer (Pittsburgh, PA), Novartis (New York, NY), Alcon (Johns Creek, GA), Optos(Scotland, United Kingdom), Bausch and Lomb (Bridgewater, NJ), and Allergan (Irvine, CA). A.A.F. is a consultant for Carl Zeiss Meditec (Dublin,CA). A.C.H. is a consultant for Alcon (Johns Creek, GA), Genentech (San Francisco, CA), Janssen (Horsham, PA), Regeneron (Tarrytown, NY),and ThromboGenics (Belgium). Funding/Support: D.S. has a research grant from Regeneron (Tarrytown, NY) and Genentech (San Francisco, CA),as well as an optical coherence tomography machine for research use from Optovue (Fremont, CA). All authors attest that they meet the current ICMJErequirements to qualify as authors.
The authors would like to acknowledge Wonchon Lin, MD and Mitra Nejad, MD (Stein Eye Institute, University of California Los Angeles, LosAngeles, California) for their assistance in providing information for Cases 4 and 6.
REFERENCES
1. Tan PEZ, Yu PK, Balaratnasingam C, et al. Quantitative
confocal imaging of the retinal microvasculature in the hu-
man retina. Invest Ophthalmol Vis Sci 2012;53(9):5728–5736.
2. Chan G, Balaratnasingam C, Yu PK, et al. Quantitative
morphometry of perifoveal capillary networks in the human
retina. Invest Ophthalmol Vis Sci 2012;53(9):5502–5514.
3. Spaide RF, Klancnik JM, Cooney MJ. Retinal vascular layers
imaged by fluorescein angiography and optical coherence to-
mography angiography. JAMA Ophthalmol 2015;133(1):45–50.
4. Rahimy E, Sarraf D. Paracentral acute middle maculopathy
spectral-domain optical coherence tomography feature of
deep capillary ischemia. Curr Opin Ophthalmol 2014;25(3):
207–212.
5. Yu S, Wang F, Pang CE, Yannuzzi LA, Freund KB. Multi-
modal imaging findings in retinal deep capillary ischemia.
Retina 2014;34(4):636–646.6. Rahimy E, Sarraf D, Dollin ML, Pitcher JD, Ho AC. Paracen-
tral acute middle maculopathy in nonischemic central retinal
vein occlusion. Am J Ophthalmol 2014;158(2):372–380.
7. Yu S, Pang CE, Gong Y, et al. The spectrum of superficial and
deep capillary ischemia in retinal artery occlusion. Am J
Ophthalmol 2015;159(1):53–63.
8. SarrafD, Rahimy E, Fawzi AA, et al. Paracentral acute middle
maculopathy: a new variant of acute macular neuroretinop-
athy associated with retinal capillary ischemia. JAMA
Ophthalmol 2013;131(10):1275–1287.
9. Coady PA, Cunningham ET, Vora RA, et al. Spectral domain
optical coherence tomography findings in eyes with acute
VOL. 160, NO. 1 33RETINAL DISEASES WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY
7/23/2019 Am J Ophthalmol 2015 Chen
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ischaemic retinal whitening. Br J Ophthalmol 2014; http://dx.
doi.org/10.1136/bjophthalmol-2014-304900.
10. Aburn NS, Sergott RC. Orbital colour Doppler imaging. Eye
1993;7(5):639–647.
11. Dimitrova G. Colour Doppler imaging of ocular and orbital
blood vessels in retinal diseases. European Ophthalmic Review
2011;5(1):16–19.
12. Brasileiro F, Martins TT, Campos SB, et al. Macular and peri-
papillary spectral domain optical coherence tomography
changes in sickle cell retinopathy. Retina 2015;35(2):257–263.
13. Murthy RK, Grover S, Chalam KV. Temporal macular thinning
on spectral-domainopticalcoherence tomography in proliferative
sickle cell retinopathy. Arch Ophthalmol 2011;129(2):247–249.
14. Abu El-Asrar AM, Herbort CP, Tabbara KF. Retinal vascu-
litis. Ocul Immunol Inflamm 2005;13(6):415–433.
15. Talat L, Lightman S, Tomkins-Netzer O. Ischemic retinal vascu-
litis and its management. J Ophthalmol 2014;2014:197675.
16. Agrawal A, McKibbin MA. Purtscher’s and Purtscher-like ret-
inopathies: a review. Surv Ophthalmol 2006;51(2):129–136.
17. Takakura A, Stewart PJ, Johnson RN, Cunningham ET.
Purtscher-like retinopathy after prostate surgery. Retin Cases
Brief Rep 2014;8(4):245–246.
18. Behrens-Baumann W, Scheurer G, Schroer H. Pathogenesis
of Purtscher’s retinopathy. Graefes Arch Clin Exp Ophthalmol
1992;230(3):286–291.
19. Yu D-Y, Cringle SJ, Su E-N. Intraretinal oxygen distribution
in the monkey retina and the response to systemic hyperoxia.
Invest Ophthalmol Vis Sci 2005;46(12):4728–4733.
20. Yu D-Y, Yu PK, Cringle SJ, Kang MH, Su E-N. Functional
and morphological characteristics of the retinal and choroidal
vasculature. Prog Retin Eye Res 2014;40:53–93.
21. Provis J. Development of the primate retinal vasculature. Prog
Retin Eye Res 2001;20(6):799–821.
22. Yu PK, Balaratnasingam C, Cringle SJ, McAllister IL, Provis J,
Yu D-Y. Microstructure and network organization of the
microvasculature in the human macula. Invest Ophthalmol Vis
Sci 2010;51(12):6735–6743.
23. Wang Q, Kocaoglu OP, Cense B, et al. Imaging retinal capil-
laries using ultrahigh-resolution optical coherence tomogra-
phy and adaptive optics. Invest Ophthalmol Vis Sci 2011;
52(9):6292–6299.
24. Jia Y, Tan O, Tokayer J, et al. Split-spectrum amplitude-
decorrelation angiography with optical coherence tomogra-
phy. Opt Express 2012;20(4):4710–4725.
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Biosketch
Xuejing Chen is a second year ophthalmology resident at the Stein Eye Institute, University of California Los Angeles. She
received her undergraduate degree in electrical and computer engineering from the California Institute of Technology and
her master’s degree in computer science from Carnegie Mellon University. She worked as a program officer at ORBIS
International prior to completing medical school at Yale and internship at Memorial Sloan Kettering Cancer Center.
VOL. 160, NO. 1 34.e1RETINAL DISEASES WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY