Am J Ophthalmol 2015 Sridhar

7/21/2019 Am J Ophthalmol 2015 Sridhar

http://slidepdf.com/reader/full/am-j-ophthalmol-2015-sridhar 1/12

Optical Coherence Tomography Angiographyand En Face Optical Coherence Tomography

Features of Paracentral Acute MiddleMaculopathy

JAYANTH SRIDHAR, ABTIN SHAHLAEE, EHSAN RAHIMY, BRYAN K. HONG, M. ALI KHAN,JOSEPH I. MAGUIRE, JAMES P. DUNN, SONIA MEHTA, AND ALLEN C. HO

PURPOSE: To characterize the optical coherence to-

mography (OCT) angiography, en face OCT, and micro-perimetry features of paracentral acute middle

maculopathy in both the acute phase and after resolution,

and to propose a classification of distinct subtypes of thisentity. DESIGN: Retrospective observational case series. METHODS: Clinical histories, high-resolution digital

color imaging, spectral-domain OCT images, fluorescein

angiography, OCT angiography images, and en faceOCT images of 16 patients with paracentral acute middle

maculopathy were evaluated. Microperimetry was avail-

able in 6 patients. RESULTS: The most common referring diagnoses wereisolated branch retinal arterial occlusion (5/16), com-

bined central retinal vein and cilioretinal artery occlusion

(4/16), and isolated central retinal vein occlusion (4/16).All patients demonstrated hyperreflective plaque-like

lesions at the level of the inner nuclear layer on

spectral-domain OCT, with no fluorescein angiographiccorrelate. OCT angiography demonstrated variable areas

of capillary dropout within the superficial and deep retinalcapillary plexi in these areas. En face OCT highlighted

confluent areas of middle retina hyperreflectivity corre-

sponding to these lesions. Three distinct en face OCT pat-terns were observed: arteriolar, fern-like, and globular.

Microperimetry demonstrated relative scotomas mapping

to the area of middle retinal hyperreflectivity seen on enface OCT. CONCLUSIONS: Paracentral acute middle maculopathy

may be best evaluated with the use of en face OCT imag-ing, which corresponds to subjective and objective visualfield defects. En face OCT appearance may be used to

classify paracentral acute maculopathy into distinct

subtypes. (Am J Ophthalmol 2015;-:-–-.

2015 by Elsevier Inc. All rights reserved.)

PARACENTRAL ACUTE MIDDLE MACULOPATHY IS A

recently characterized presentation of deep retinalcapillary ischemia, manifesting as hyperreflective

bands within the middle retina on spectral-domain

optical coherence tomography (OCT) imaging.1,2 Whilethe initial description detailed lesions occurring in

isolation, subsequent reports have observed this findingin conjunction with other retinovascular conditions,

including branch (BRAO) and central (CRAO) retinal

arterial occlusion, central retinal vein occlusion(CRVO), diabetic retinopathy, sickle cell retinopathy,

and Purtscher retinopathy.3–5 Most recently,

Christenbury and associates described the first case of paracentral acute middle maculopathy imaged withOCT angiography, demonstrating attenuation of the

deep capillary plexus in the area of involvement.6 Taken

together, these observations further support a vaso-occlusive origin for these lesions.

The purpose of the current study was to describe the

natural evolution of paracentral acute middle maculop-athy in 16 additional cases evaluated with OCT angi-

ography, and to better elucidate the involvement of the adjacent retinal capillary plexuses, which to date

have been unable to be adequately assessed with tradi-

tional fluorescein angiography. Furthermore, these find-ings were correlated to en face OCT imaging, which

has not been previously reported for this condition,

and microperimetry, when available. A new classifica-tion of distinct subtypes of paracentral acute middlemaculopathy is then proposed based on en face OCT

appearances.

METHODS

INSTITUTIONAL REVIEW BOARD APPROVAL WAS OBTAINED

through the Wills Eye Hospital, Philadelphia, Pennsylva-

nia, for a retrospective observational case series. Research

adhered to the tenets of the Declaration of Helsinki andwas conducted in accordance with regulations set forthby the Health Insurance Portability and Accountability

Act (HIPAA).

Accepted for publication Sep 10, 2015.From Mid Atlantic Retina, The Retina Service of Wills Eye Hospital,

Thomas Jefferson University, Philadelphia, Pennsylvania.Inquiries to Allen C. Ho, Mid Atlantic Retina, The Retina Service of

Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA19107; e-mail: [email protected]

0002-9394/$36.00http://dx.doi.org/10.1016/j.ajo.2015.09.016

1 2015 BY ELSEVIER INC. ALL RIGHTS RESERVED.

mailto:[email protected]

http://dx.doi.org/10.1016/j.ajo.2015.09.016

http://dx.doi.org/10.1016/j.ajo.2015.09.016

mailto:[email protected]



Clinical records and imaging were reviewed to iden-

tify all cases with spectral-domain OCT imagingshowing paracentral acute middle maculopathy lesions

at a single academic private-practice office location

from January 1, 2015 to July 30, 2015. Available enface OCT and OCT angiogaphy imaging cases were

identified. OCT angiography and en face OCT wasperformed using the Avanti RTVue XR (Optovue,

Fremont, California, USA), which obtains volumetricdata from horizontal and vertical acquisitions that canbe automatically segmented to specific depths. Using

these data, side-by-side OCT angiography and en face

OCT images can be generated at the levels of the super-ficial capillary plexus, the deep capillary plexus, thenormally avascular outer retina, and the choriocapilla-

ris.7,8 Baseline and follow-up demographic, clinical,

laboratory, and imaging data were extracted frompatient charts. High-resolution digital color photog-

raphy, fluorescein angiography, and red-free photog-

raphy were included in review, when available, for

each patient. Microperimetric examination using the

Macular Integrity Assessment (MAIA; CenterVue,

Padova, Italy) was available and reviewed for 6 patients.

RESULTS

THE PATIENT DEMOGRAPHIC, OCULAR EXAMINATION, IM-

aging, and microperimetry findings (when available) aresummarized in Table 1. The mean age at presentationwas 53 years, and 9 of the 16 patients (56%) were male.

Ten individuals (63%) presented with acute-onset nonspe-

cific visual loss, 3 (19%) reported a paracentral scotoma,and 3 (19%) described an altitudinal field cut. Of the 10 pa-tients with sudden vision loss, 2 (20%) experienced a par-

tial resolution of symptoms within 30 minutes of onset.

The most common referring diagnoses were isolatedBRAO (5/16, 31%), combined CRVO with cilioretinal ar-

tery occlusion (4/16, 25%), and isolated CRVO (4/16,

25%). Seven patients had known histories of hypertension;

1 of these patients also had diabetes mellitus, 1 patient

FIGURE 1. Optical coherence tomography angiography and en face optical coherence tomography features of paracentral acute mid-

dle maculopathy. Patient 10 was a 76-year-old man who presented with an inferior field cut in the setting of central retinal vein oc-

clusion. Spectral-domain optical coherence tomography (OCT) demonstrated superior graying on near-infrared reflectance (Top left)

with middle retinal hyperreflectivity in the corresponding area (Top right). Fluorescein angiography (Bottom left) showed areas of

blockage reflecting preretinal and intraretinal heme and intact perfusion to superior macula. En face OCT (Bottom right, top row)

at the level of the superficial (left), middle (middle), and outer (right) retina demonstrated band-like hyperreflectivity at the level

of the middle retina. OCT angiography at the same levels (Bottom right, bottom row) is notable for absence of deep capillary plexus

dropout at the level of the middle retina.

VOL. -, NO. - 3OCT ANGIOGRAPHY OF PARACENTRAL ACUTE MIDDLE MACULOPATHY



presented after cardiac catheterization, and another lostvision 1 hour after a chiropractic procedure. Associatedconditions in the remaining 9 patients included recent

cosmetic facial filler injection, post-viral illness, amyloid-

osis, beta thalassemia, presumed herpes simplex uveitis,prepapillary vascular loop with trauma, sickle cell anemiawith dehydration on a cruise ship, mechanical heart valve

on anticoagulation, and transcontinental flight with dehy-

dration.Snellen best-corrected visual acuity (BCVA) on presen-

tation ranged from 20/20 to hand motions. Two individuals

(13%) had bilateral vision loss; vision in these cases was

finger count OU and 20/25 OD and 20/200 OS, respec-tively. The patient with hand motions visual acuity hadconcurrent ischemic optic neuropathy.

All patients demonstrated hyperreflective plaque-like

lesions at the level of the inner nuclear layer onspectral-domain OCT, consistent with paracentral acutemiddle maculopathy (Figure 1 top). Fluorescein angiog-

raphy did not consistently reveal any correlate to these le-

sions (Figure 1 bottom left). En face OCT highlightedconfluent areas of middle retina hyperreflectivity corre-

sponding to the lesions (Figure 1 bottom right). OCT angi-

ography demonstrated variable areas of capillary dropout


dle maculopathy, arteriolar pattern. Patient 9 was a 60-year-old woman who presented with a paracentral scotoma in the setting of a

branch retinal arterial occlusion proven on fluorescein angiography (Top row). Spectral-domain optical coherence tomography

(OCT; Second row, left) demonstrated nasal middle retinal hyperreflectivity approaching the fovea. Montage OCT angiography at

the level of the superficial plexus (Second row, right) disclosed multiple areas of capillary dropout. Review of en face OCT (Third

row) and OCT angiography (Bottom row) demonstrated a large area of middle retinal hyperreflectivity in an arteriolar distribution

with more extensive capillary dropout at the level of the deep plexus. Microperimetry (Bottom right) confirmed a superior altitudinal

defect in the same distribution.

4 --- 2015AMERICAN JOURNAL OF OPHTHALMOLOGY



within the superficial and deep retinal capillary plexi in thearea corresponding to the paracentral acute middle macul-

opathy lesions (Figure 1, bottom right, bottom row). Micro-

perimetry disclosed relative scotomas mapping to the areaof middle retinal hyperreflectivity as seen on en face

OCT (Figure 2).

Three distinct patterns of these areas on en face OCTwere observed: arteriolar, globular, and fern-like

(Table 2). The arteriolar pattern was seen in 11 patients

(63%) and showed a characteristic band-like middle retinahyperreflectivity mirroring the distribution of a large

retinal arteriole (Figure 2). The globular pattern was notedin 4 patients (25%) with either a focal ovoid patch or

multifocal ovoid patches of middle retina hyperreflectivity

(Figure 3). The fern-like pattern was observed in 2 patients(13%) in the setting of CRVO with multilobulated parafo-

veal middle retina hyperreflectivity (Figure 4). Of note, 1patient with a combined CRVO and cilioretinal artery oc-

clusion had both the arteriolar and fern-like pattern.

On follow-up en face OCT, areas of middle retina hyper-reflectivity showed resolution, with variable areas of hypo-

reflectivity representing middle retinal atrophy (Figure 5).OCT angiography of the deep capillary plexus showed

capillary dropout in the same areas.

DISCUSSION

ONLY RECENTLY RECOGNIZED, PARACENTRAL ACUTE

middle maculopathy, or PAMM for short, was initially

described as a presumed variant of acute macular neuroretin-opathy.1,9 It has since been established that these lesions can

be associated with a multitude of retinal vascular diseaseprocesses, including CRVO, CRAO, BRAO, and diabeticretinopathy, among others.3,4,10 Chen and associates

recently described paracentral acute middle maculopathy

occurring in the setting of disparate vascular conditions,such as sickle cell crisis, Purtscher retinopathy, hypertensiveretinopathy, and post–upper respiratory infection.5

Owing to the OCT localization of these lesions at the

level of the inner nuclear layer, they have been postulatedto represent an ischemic insult of the adjacent intermediate

and deep capillary plexuses.3 It is well established that the

retina has a multilayered capillary network consisting of

the superficial plexus at the level of the ganglion cell layer

and the intermediate and deep plexuses at the superficialand deep edges of the inner nuclear layer, respectively.11–13

The middle retina including the inner nuclear layer and

outer plexiform layer is felt to be a watershed zone thatmay be most vulnerable to ischemia of the deeper

capillary plexuses.14

OCT angiography represents a relatively new technol-ogy with the ability to not only noninvasively image the su-

perficial capillary plexus traditionally seen on fluorescein

angiography butalso to capture the flow of the deeper capil-lary plexuses.7,8,15 There have been significant publications

describing OCT angiography findings in healthy subjects,juxtafoveal telangiectasia, and choroidal neovascular

membranes in exudative age-related macular degeneration,

central serous chorioretinopathy, and other diseases.16–20

De Carlo and associates recently demonstrated the ability

to capture wide-field OCT angiography montage imagesextending anterior to the major arcades.21

OCT angiography has only previously been described for

1 case of paracentral acute middle maculopathy in thesetting of CRAO.6 That case showed severe hypoperfusion

of the deep capillary plexus; however, the images were ob-tained weeks after the onset of symptoms. While some of the cases in the current series demonstrated capillarydropout acutely, the majority demonstrated apparently

normal flow in the deeper capillary plexuses, despite the

supposition that the lesions represent ischemia at thatlevel. The authors suggest that in these cases with normal

flow initially there was likely a transient hypoperfusion of

the deeper plexuses that resulted in the functional abnor-mality in the absence of acute structural change on OCT

angiography. In the absence of a true occlusive event(ie, CRAO or BRAO), the retina may also have the ability

to autoregulate flow to the deeper plexi so that OCT angi-ography initially reflects normal flow.

Over time, there was pruning and dropout of the deeper

plexuses on OCT angiography matching the middle retinal

atrophy, typical of paracentral acute middle maculopathylesions in other series.1,3,5 Given the initial normal flowseen in conjunction with the spectral-domain OCT le-

sions, there is the strong possibility that reperfusion injury

plays a role in the subsequent development of atrophy. It iswell known in cases of cerebral, myocardial, and spinal cord

ischemia, for example, that reperfusion after an ischemic

event actually may accelerate damage owing to increased

levels of oxygen-derived free radicals and inflammatory

TABLE 2. Patterns of Middle Retina En Face Optical Coherence Tomography Hyperreflectivity in Paracentral Acute Middle

Maculopathy

Pattern Appearance Presumed Mechanism

Arteriolar Band-like areas in distribution of major arteriole Transient or true arterial o cclusion

Fern-like Multilobulated central area tracking along veins Perivenular capillary ischemia

Globular Ovoid focal or multifocal areas Distal precapillary or capillary ischemia




cytokines.22–25 In the case of myocardial ischemia, forexample, an ongoing challenge is that percutaneous

coronary intervention may paradoxically further damagemyocytes in the first minutes after reperfusion.26 Giventhe similarities between retinal tissue and myocardial and

neural tissue, an identical process at the level of the middle

retina could result in cellular apoptosis and capillarydropout over time. Rat models of retinal ischemia andreperfusion injury have previously demonstrated the role

of both free radical damage and apoptosis with caspase acti-

vation in inner retinal loss.27,28 Schmid and associatesdemonstrated that induced ischemia in a rat model

affected inner retinal cells more than outer retinal cells,

with an increase in apoptotic cells in both the ganglion

cell and inner nuclear layers.29 As a result, they hypothe-

sized that owing to reperfusion there may be a delayeddegeneration mediated by apoptosis occurring more than

2 weeks after the original ischemic insult. While furtherstudy at the cellular level would be necessary to provethat this is the exact mechanism in paracentral acute mid-

dle maculopathy, it suggests the potential of therapy to

reduce reperfusion injury, such as pharmacologic optionsor induced hypothermia, to alter the inner retinal remodel-ing process. Rey-Funes and associates described that expo-

sure of a rat retinal model to asphyxia in normothermic

conditions resulted in high levels of expression of angio-genic and gliotic factors when compared to asphyxic expo-

sure in hypothermic conditions.30

In contrast to OCT angiography, en face OCT has

existed for nearly a decade since its original description.31


dle maculopathy, fern-like pattern. Patient 12 was a 52-year-old man who presented with a central retinal vein occlusion and foveal

blunting in the right eye (Top row, left). Microperimetry showed paracentral scotomas (Top row, middle). En face optical coherence

tomography (OCT) at the level of the middle retina (Top row, right) showed a fern-like pattern of perivenular hyperreflectivity. Re-

view of en face OCT (Middle row) and OCT angiography (Bottom row) demonstrated sparing of other retinal levels with normal su-

perficial and deep capillary plexus flow.




However, technological advances allow current en faceOCT images to be captured at specific retinal layers, allow-

ing for several potential clinical applications. Sakimoto

and associates and Imai and associates used en face OCTto show retinal nonperfusion and inner retinal thinning,respectively, in branch retinal vein occlusion.32,33Alasil

recently reported the use of en face imaging of the

choroid in polypoidal choroidal vasculopathy.34

Rahimy and associates previously described the en face

appearance of paracentral acute middle maculopathy le-

sions on near-infrared reflectance as dark-gray areas.3

While those images showed more subtle changes, the en

face OCT middle retina cuts in the current series showobvious well-demarcated areas of hyperreflectivity. This al-

lows for the separation of paracentral acute middle macul-

opathy lesions into the 3 different subtypes based onmorphologic appearance, which may have implicationson the underlying disease mechanism. The band-like arte-

riolar pattern simulates the distribution of a BRAO. Even

in the absence of a true BRAO, we presume that transientocclusion of a large retinal arteriole with rapid restoration

of normal flow could induce ischemia in the watershed zone

of the middle retina while sparing the nerve fiber and gan-

glion cell layers. In contrast, the smaller, oval patches of


dle maculopathy, evolution on follow-up. Serial en face optical coherence tomography (OCT; Top panels) and OCT angiography

(Middle panels) at the level of the middle retina (Bottom panels) show the evolution of paracentral middle maculopathy for Patient

10. Initial imaging (left column) demonstrated band-like superior hyperreflectivity on en face OCT with normal capillary flow. By

3 weeks (middle column) hyperreflectivity had disappeared on en face OCT with early patchy capillary dropout. By 8 weeks (right

column) there was hyporeflectivity at the level of the middle retina due to atrophy and there was more pronounced deep capillary

plexus pruning.




hyperreflectivity seen in the focal and multifocal globular

patterns likely represent distal ischemic events in smaller

terminal retinal arterioles, precapillaries, and capillaries.Thus, the patients with the globular pattern had suspected

microembolic events, whether due to sickling of red blood

cells (Patient 13), iatrogenic emboli (Patient 14),suspected emboli from mechanical heart valve (Patient

15), or Purtscher-like retinopathy with presumed comple-ment activation (Patient 16). Finally, the fern-like pattern

seen in 2 patients with CRVO had been previouslyobserved both as perivenular whitening on examination

and as perivenular graying on near-infrared reflec-

tance.3,35–37 This is presumably due to the high density of capillaries, including deep plexus ones, in the perivenular

distribution.38 Of note, 4 patients in this series hadCRVO with concomitant cilioretinal artery occlusion. In

prior series of paracentral middle maculopathy in the

setting of CRVO, 40% of patients had cilioretinal arteryocclusion.3 The presumed mechanism is the elevated intra-

luminal pressure of the central retinal vein transmittingacross the cilioretinal artery system and causing transientocclusion.39

Microperimetry using macular integrity assessment of-

fers eye-tracking technology allowing for measurement

of visual function with structural correlation and hasbecome rapidly popular as a detector of macular dysfunc-

tion.40 Only 1 case of microperimetry in the setting of

deep capillary ischemia had been previously reported.41

In the 6 patients with microperimetry available, the sco-

tomas measured correlated directly with the areas of theretina with the paracentral acute middle maculopathy

lesions on en face OCT. As such, microperimetry may

be a useful adjunct to spectral-domain OCT, OCT

angiography, and en face OCT in the detection of subtleparacentral scotomas in patients with paracentral acute

middle maculopathy. Recently, however, the test-retest

repeatability of microperimetry in the detection of deepscotoma borders has come into question.42 Future investi-

gation is warranted to continue to evaluate the applica-tions of this technology in the setting of deep capillary

ischemia.Limitations of this study include its retrospective nature

and the relatively small number of patients included. Much

like prior series, this series relies on a theorized and un-proven mechanism of deep retinal capillary ischemia as

the cause of paracentral acute middle maculopathy. Inaddition, a study with long-term follow-up of the chronic

appearance of paracentral acute middle maculopathy le-

sions on OCT angiography and en face OCT would be use-ful.

In conclusion, paracentral acute middle maculopathymay be best evaluated with the use of OCT angiographyand en face OCT imaging, with microperimetry as anadjunct test to map out correlative paracentral scotomas.

En face OCT may not only help the ophthalmologist to

recognize this unique presentation more easily than stan-dard OCT, but it may also allow for its subclassification

into clinically distinct subtypes. As more cases of paracen-

tral acute middle maculopathy are reported, our under-standing of the role of the intermediate and deep

capillary plexus in this entity will be improved by a multi-modal imaging approach.

FUNDING/SUPPORT: THE AUTHORS HAVE NO FUNDING OR SUPPORT TO DISCLOSE FOR THIS PUBLICATION. A.C.H. HASreceived research grant funding in the past from Alcon, Allergan, Avalanche, Genentech, Iconic, Janssen/Johnson & Johnson, NEI/NIH, Ophthotech,PanOptica, Regeneron, Second Sight, and Thrombogenics. Financial Disclosures: J.M. is a speaker for Regeneron and Genentech and on the advisoryboard for Genentech. A.C.H. is a scientific advisor for Aerpio, Alcon, Allergan, DigiSight, Beaver EndoOptiks, Janssen, Genentech, ONL, Ophthotech,Optovue, PanOptica, PRN, Regeneron, Second Sight, and Thrombogenics. The other authors have no disclosures, nor do they have any proprietary orfinancial interest in any of the work discussed in this manuscript. All authors attest that they meet the current ICMJE requirements to qualify as authors.

REFERENCES

1. 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.

2. 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.

3. Rahimy E, Sarraf D, Dollin ML, Pitcher JD, Ho AC. Paracen-

tral middle maculopathy in nonischemic central retinal vein

occlusion. Am J Ophthalmol 2014;158(2):372–380.

4. 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.

5. Chen X, Rahimy E, Sergott RC, et al. Spectrum of retinal

vascular diseases associated with paracentral acute middle

maculopathy. Am J Ophthalmol 2015;160(1):26–34.

6. Christenbury JG, Klufas MA, Sauer TC, Sarraf D. OCT angi-ography of paracentral acute middle maculopathy associated

with central retinal artery occlusion and deep capillary

ischemia. Ophthalmic Surg Lasers Imaging Retina 2015;46(5):

579–581.

7. Savastano MC, Lumbroso B, Rispoli M. In vivo characteriza-

tion of retinal vascularization morphology using optical

coherence tomography angiography. Retina 2015; http://dx.

doi.org/10.1097/IAE.0000000000000635.

8. Spaide RF, Klancnik JM, Cooney MJ. Retinal vascular

layers imaged by fluorescein angiography and optical coher-

ence tomography angiography. JAMA Ophthalmol 2015;

133:45–50.


http://refhub.elsevier.com/S0002-9394(15)00568-1/sref1


































http://dx.doi.org/10.1097/IAE.0000000000000635






































9. Tsui I, Sarraf D. Paracentral acute middle maculopathy and

acute macular neuroretinopathy. Ophthalmic Surg Lasers Imag-

ing Retina 2013;44(6 Suppl):S33–S35.

10. Dansingani KK, Freund KB. Paracentral acute middle macul-

opathy and acute macular neuroretinopathy: related and

distinct entities. Am J Ophthalmol 2015;160(1):1–3.

11. Dorrell MI, Friedlander M, Smith LEH. Retinal vascular

development. In: Joussen AM, Gardner TW, Kirchhof B,

Ryan SJ, eds. Pathogenesis of Retinal Vascular Disease.

Berlin, Germany: Springer Berlin Heidelberg; 2007:24–37.

12. Snodderly DM, Weinhaus RS, Choi JC. Neural-vascular rela-

tionships in central retina of macaque monkeys (Macaca

fascicularis). J Neurosci 1992;12(4):1169–1193.

13. Tan PE, 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.

14. Alder VA, Cringle SJ. Vitreal and retinal oxygenation.

Graefes Arch Clin Exp Ophthalmol 1990;228(2):151–157.

15. Puliafito CA. OCT angiography: the next era of OCT tech-

nology emerges. Ophthalmic Surg Lasers Imaging Retina 2014;

45(5):360.

16. Matsunaga D, Yi J, Puliafito CA, Kashan AH. OCT angiog-

raphy in healthy human subjects. Ophthalmic Surg Lasers Im-

aging Retina 2014;45(6):510–515.

17. Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular

layers in macular telangiectasia type 2 imaged by optical

coherence tomographic angiography. JAMA Ophthalmol

2015;133(1):66–73.

18. Kuehlewein L, Bansal M, Lenis TL, et al. Optical coherence

tomography angiography of type 1 neovascularization in age-

related macular degeneration. Am J Ophthalmol 2015;160(4):

739–748.e2.

19. De Carlo TE, Bonini Filho MA, Chin AT, et al. Spectral-

domain optical coherence tomography angiographyof choroidal

neovascularization. Ophthalmology 2015;122(6):1228–1238.20. Bonini Filho MA, de Carlo TE, Ferrara D, et al. Association

of choroidal neovascularization and central serous choriore-

tinopathy with optical coherence tomography angiography.

JAMA Ophthalmol 2015;133(8):899–906.

21. De Carlo TE, Salz DA,Waheed NK, et al. Visualization of the

retinal vasculature using wide-field montage optical coher-

ence tomography angiography. Ophthalmic Surg Lasers Imaging

Retina 2015;46(6):611–616.

22. Fox KA, Bergmann SR, Sobel BE. Patophysiology of myocar-

dial reperfusion. Annu Rev Med 1985;36:125–144.

23. McCord JM. Oxygen-derived free radicals in postischemic

tissue injury. N Engl J Med 1985;312(3):159–163.

24. Kogure K, Yamasaki Y, Matsuo Y, Kato H, Onodera H.Inflammation of the brain after ischemia. Acta Neurochir

Suppl 1996;66:40–43.

25. Chan PH. Mitochondria and neuronal death/survival

signaling pathways in cerebral ischemia. Neurochem Res

2004;29(11):1943–1949.

26. Lonborg JT. Targeting reperfusion injury in the era of primary

percutaneous coronary intervention: hope or hype? Heart

2015;101(20):1612–1618.

27. Szabo ME, Droy-Lefaix MT, Doly M, Carre C, Braquet P.

Ischemia and reperfusion-induced histologic changes in

the rat retina. Demonstration of a free-radical medicated

mechanism. Invest Ophthalmol Vis Sci 1991;32(5):

1471–1478.

28. Lam TT, Abler AS, Tso MO. Apoptosis and caspases after

ischemia-reperfusion injury in rat retina. Invest Ophthalmol

Vis Sci 1999;40(5):967–975.

29. Schmid H, Renner M, Dick HM, Joachim SC. Loss of inner

retinal neurons after retinal ischemia in rats. Invest Ophthal-

mol Vis Sci 2014;55(4):2777–2787.

30. Rey-Funes M, Dorfman VB, Ibarra ME, et al. Hypothermia

prevents gliosis and angiogenesis development in an experi-

mental model of ischemic proliferative retinopathy. Invest

Ophthalmol Vis Sci 2013;54(4):2836–2846.

31. van Velthoven ME, Verbraak FD, Yannuzzi LA, et al. Imag-

ing the retina by en face optical coherence tomography.

Retina 2006;26(2):129–136.

32. Sakimoto S, Gomi F, Sakaguchi H, et al. Analysis of retinal

nonperfusion using depth-integrated optical coherence to-

mography images in eyes with branch retinal vein occlusion.

Invest Ophthamol Vis Sci 2015;56(1):640–646.

33. Imai A, Toriyama Y, Iesato Y, Hirano T, Murata T. En face

swept-source optical coherence tomography detecting thin-

ning of inner retinal layers as an indicator of capillary nonper-

fusion. Eur J Ophthalmol 2015;25(2):153–158.

34. Alasil T, Ferrara D, Adhi M, et al. En face imaging of the

choroid in polypoidal choroidal vasculopathy using swept-

source optical coherence tomography. Am J Ophthalmol

2015;159(4):634–643.

35. Browning DJ. Patchy ischemic retinal whitening in acute

central retinal vein occlusion. Ophthalmology 2002;109(11):

2154–2159.

36. Paques M, Gaudric A. Perivenular macular whitening during

acute central retinal vein occlusion. Arch Ophthalmol 2003;121(10):1488–1491.

37. Pichi F, Morara M, Veronese C, et al. Perivenular whitening

in central retinal vein occlusion described by fundus auto-

fluoresence and spectral-domain optical coherence tomogra-

phy. Retina 2012;32(7):1438–1439.

38. Michaelson IC, Campbell AC. The anatomy of the finer

retinal vessels. Trans Ophthalmol Soc U K 1940;60:71–76.

39. Hayreh SS, Fraterrigo L, Jonas J. Central retinal vein occlu-

sion associated with cilioretinal artery occlusion. Retina

2008;28(4):581–594.

40. Hanout M, Horan N, Do DV. Introduction to microperimetry

and its use in analysis of geographic atrophy in age-related

macular degeneration. Curr Opin Ophthalmol 2015;26(3):149–156.

41. 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.

42. Wu Z, Jung CJ, Ayton LN, Luu CD, Guymer RH. Test-

retest repeatability of microperimetry at the border of

deep scotomas. Invest Ophthalmol Vis Sci 2015;56(4):

2606–2611.




























































































































































































































































































Biosketch

Dr Jayanth Sridhar received his undergraduate and medical degrees from the University of Miami, FL. He completed his

residency training at the Bascom Palmer Eye Institute and is currently a senior vitreoretinal surgical fellow and clinical

instructor at Wills Eye Hospital and Thomas Jefferson University in Philadelphia, PA. His research interests include

applications of novel imaging techniques to retinal disease and utilizing new technology to improve the quality of

medical student and resident education.

VOL. -, NO. - 10.e1OCT ANGIOGRAPHY OF PARACENTRAL ACUTE MIDDLE MACULOPATHY



Biosketch

Abtin Shahlaee, MD, is a post-doctoral research fellow at Wills Eye Hospital. He received his medical degree from Tehran

University of Medical Sciences and was was a former research assistant at the Department of Ophthalmology at the Medical

University of Vienna. His current research projects focus on retinal imaging and diseases of the retina. His career goals

include training in ophthalmology in an academic setting with a long-term plan of becoming a successful clinician scientist.

10.e2 --- 2015AMERICAN JOURNAL OF OPHTHALMOLOGY

Am J Ophthalmol 2015 Sridhar

Documents

Transcript of Am J Ophthalmol 2015 Sridhar