Optical Coherence Tomographic Angiography in Acute Macular Neuroretinopathy | Macular Diseases | JAMA Ophthalmology | JAMA Network
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Figure 1.  Multimodal Imaging Testing of Patient 1’s Right Eye With Bilateral Acute Macular Neuroretinopathy
Multimodal Imaging Testing of Patient 1’s Right Eye With Bilateral Acute Macular Neuroretinopathy

Color fundus photograph (A) and corresponding near-infrared reflectance image (B) demonstrating typical tear-drop–shaped brownish, hyporeflective parafoveal lesions. Spectral-domain optical coherence tomography (OCT) through the lesion illustrates disruption of the inner segment ellipsoid zone and thinning of the outer nuclear layer (C). Early- (D) and late- (E) phase fluorescein angiogram of both eyes. Optical coherence tomographic angiograms of the superficial (F), deep retinal capillary plexus (G), choriocapillaris (CC) (H), and outer choroid (I). There are flow voids at the level of the choriocapillaris corresponding to the classic tear-drop brownish lesions (H). The zones of CC flow deficit with OCT angiography were color coded (J and M) and overlaid on the en face structural OCT that was obtained with segmentation at the level of the ellipsoid (K) or outer nuclear level (N). The color-coded CC flow voids colocalize precisely with the en face ellipsoid loss and hyperreflective lesions but are slightly larger (L and O).

Figure 2.  Multimodal Imaging Testing of Patient 1’s Left Eye With Bilateral Acute Macular Neuroretinopathy
Multimodal Imaging Testing of Patient 1’s Left Eye With Bilateral Acute Macular Neuroretinopathy

Color fundus photograph (A) and corresponding near-infrared reflectance image (B) demonstrating typical tear-drop–shaped brownish, hyporeflective parafoveal lesions. Spectral-domain optical coherence tomography (OCT) through the lesion illustrates disruption of the inner segment ellipsoid zone and thinning of the outer nuclear layer (C). Early- (D) and late- (E) phase fluorescein angiogram of both eyes. Optical coherence tomographic angiograms of the superficial (F), deep retinal capillary plexus (G), choriocapillaris (CC) (H), and outer choroid (I). There are flow voids at the level of the choriocapillaris corresponding to the classic tear-drop brownish lesions (H). The zones of CC flow deficit with OCT angiography were color coded (J and M) and overlaid on the en face structural OCT that was obtained with segmentation at the level of the ellipsoid (K) or outer nuclear level (N). The color-coded CC flow voids colocalize precisely with the en face ellipsoid loss and hyperreflective lesions but are slightly larger (L and O).

Figure 3.  Multimodal Imaging Testing of Patient 2
Multimodal Imaging Testing of Patient 2

Color fundus photograph (A) and corresponding near-infrared reflectance image delineating multiple parafoveal hyporeflective lesions (B, arrowheads). C, Spectral-domain optical coherence tomography (OCT) through the lesion depicts hyperreflectivity at the level of the outer plexiform and outer nuclear layers and associated disruption of the inner segment ellipsoid. Early- (D) and late- (E) phase fluorescein angiogram of the left eye. Optical coherence tomographic angiograms of the superficial retinal capillary plexus (F), deep retinal capillary plexus (G), choriocapillaris (CC) (H), and choroid (I) demonstrate flow void areas in the CC only (H, arrowheads). Color coding of the flow void zones of the CC (J and M) colocalize precisely with the areas of ellipsoid zone loss seen on structural en face OCT (K). The areas of outer nuclear later hyperreflectivity (N) are significantly smaller compared with the areas of CC flow deficit (O), indicating CC ischemia as a driving etiology in the disorder.

1.
Bos  PJ, Deutman  AF.  Acute macular neuroretinopathy.  Am J Ophthalmol. 1975;80(4):573-584.PubMedGoogle ScholarCrossref
2.
Bhavsar  KV, Lin  S, Rahimy  E,  et al.  Acute macular neuroretinopathy: a comprehensive review of the literature [published online March 10, 2016].  Surv Ophthalmol. doi:10.1016/j.survophthal.2016.03.003PubMedGoogle Scholar
3.
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.e1, 2.PubMedGoogle ScholarCrossref
4.
Monson  BK, Greenberg  PB, Greenberg  E, Fujimoto  JG, Srinivasan  VJ, Duker  JS.  High-speed, ultra-high-resolution optical coherence tomography of acute macular neuroretinopathy.  Br J Ophthalmol. 2007;91(1):119-120.PubMedGoogle ScholarCrossref
5.
Mrejen  S, Pang  CE, Sarraf  D,  et al.  Adaptive optics imaging of cone mosaic abnormalities in acute macular neuroretinopathy.  Ophthalmic Surg Lasers Imaging Retina. 2014;45(6):562-569.PubMedGoogle ScholarCrossref
6.
Browning  AC, Gupta  R, Barber  C, Lim  CS, Amoaku  WM.  The multifocal electroretinogram in acute macular neuroretinopathy.  Arch Ophthalmol. 2003;121(10):1506-1507.PubMedGoogle ScholarCrossref
7.
Audo  I, Gocho  K, Rossant  F,  et al.  Functional and high-resolution retinal imaging monitoring photoreceptor damage in acute macular neuroretinopathy.  Graefes Arch Clin Exp Ophthalmol. 2016;254(5):855-864.PubMedGoogle ScholarCrossref
8.
Hayreh  SS.  The choriocapillaris.  Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1974;192(3):165-179.PubMedGoogle ScholarCrossref
9.
Sarraf  D, Rahimy  E, Fawzi  AA,  et al.  Paracentral acute middle maculopathy: a new variant of acute macular neuroretinopathy associated with retinal capillary ischemia.  JAMA Ophthalmol. 2013;131(10):1275-1287.PubMedGoogle ScholarCrossref
10.
Dansingani  KK, Freund  KB.  Paracentral acute middle maculopathy and acute macular neuroretinopathy: related and distinct entities.  Am J Ophthalmol. 2015;160(1):1-3.e2.PubMedGoogle ScholarCrossref
11.
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.e1.PubMedGoogle ScholarCrossref
12.
Dansingani  KK, Inoue  M, Engelbert  M, Freund  KB.  Optical coherence tomographic angiography shows reduced deep capillary flow in paracentral acute middle maculopathy.  Eye. 2015;29:1620-1624.Google ScholarCrossref
13.
Deutman  AF, Oosterhuis  JA, Boen-Tan  TN, Aan de Kerk  AL.  Acute posterior multifocal placoid pigment epitheliopathy: pigment epitheliopathy of choriocapillaritis?  Br J Ophthalmol. 1972;56(12):863-874.PubMedGoogle ScholarCrossref
14.
Maier  M, Wehrmann  K, Lohmann  CP, Feucht  N.  OCT angiography findings in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) [in German] [published online May 9, 2016].  Ophthalmologe. doi:10.1007/s00347-016-0256-2PubMedGoogle Scholar
15.
Mrejen  S, Sarraf  D, Chexal  S, Wald  K, Freund  KB.  Choroidal involvement in acute posterior multifocal placoid pigment epitheliopathy.  Ophthalmic Surg Lasers Imaging Retina. 2016;47(1):20-26.PubMedGoogle ScholarCrossref
Brief Report
November 2016

Optical Coherence Tomographic Angiography in Acute Macular Neuroretinopathy

Author Affiliations
  • 1Associated Retinal Consultants, William Beaumont School of Medicine, Oakland University, Royal Oak, Michigan
JAMA Ophthalmol. 2016;134(11):1310-1314. doi:10.1001/jamaophthalmol.2016.3513
Abstract

Importance  Acute macular neuroretinopathy (AMN) is a rare, yet increasingly recognized, entity identified predominantly in young healthy females with acute onset of paracentral scotomas. The exact pathophysiology is unknown but an underlying vascular process is suspected. This study used optical coherence tomographic angiography (OCTA) to assess for any evidence of vascular flow abnormality in the retina or choroid in this elusive disease.

Observations  Three eyes from 2 young female patients with classic features of AMN are presented. Multimodal imaging testing, including near-infrared reflectance, spectral-domain OCT, and OCTA (Carl Zeiss Meditec), were performed. Near-infrared reflectance identified typical hyporeflective tear-drop parafoveal lesions, which corresponded to OCTA flow deficits at the level of the choriocapillaris.

Conclusions and Relevance  Recognizing that these findings are based only on 3 eyes from 2 patients, lesions in AMN may result from a vascular insult in the choriocapillaris. The evaluation of OCTA was with the knowledge of the AMN diagnosis, which may have biased the interpretation.

Introduction

The original description of acute macular neuroretinopathy (AMN) by Bos and Deutman1 was based solely on clinical observation and conventional dye-based fluorescein angiography. The advent of multimodal imaging enabled a more detailed characterization of the lesions occurring in AMN and a greater understanding of the underlying pathophysiology. While deep retinal capillary plexus (DCP) ischemia has been proposed as the etiology of AMN,2 it fails to fully explain the characteristic outer retinal spectral-domain (SD) optical coherence tomographic (OCT) imaging findings observed in these patients. Even in the most severe forms of inner retinal ischemia, as occurs in a central retinal artery occlusion, disruptions in the outer retina are not observed, unless the choroidal circulation is affected.3 We describe 2 female patients with AMN who underwent multimodal imaging including OCT angiography (OCTA) that identified flow deficits at the level of the choriocapillaris (CC).

Report of Cases

This study was approved by the institutional review board/ethics committee of Associated Retinal Consultants/William Beaumont Hospital, Royal Oak, Michigan. Informed consent was obtained from both patients before the initiation of the study.

Case 1

A healthy woman in her twenties presented with a 1-month history of vision distortion in both eyes. Medications included an oral contraceptive (a combination pill of norethindrone and ethinyl estradiol). The patient reported a viral prodrome 2 to 3 weeks prior to the initiation of her visual symptoms. Best-corrected visual acuity measured 20/15 OD and 20/20 OS, and Amsler grid testing results were remarkable for bilateral paracentral scotomas. Anterior segment examination was within normal limits. Retinal examination identified classic tear-drop–shaped brownish lesions with the apices oriented toward the fovea in the right and left eyes (Figure 1A and Figure 2A). These lesions were more prominent with near-infrared reflectance (NIR) imaging (Figure 1B and Figure 2B). Spectral-domain OCT illustrated attenuation of the ellipsoid zone (EZ) with overlying areas of outer nuclear layer (ONL) thinning (Figure 1C and Figure 2C). Fluorescein angiography was unremarkable in both eyes (Figure 1D and E and Figure 2D and E). Optical coherence tomographic angiography identified flow deficits at the level of the CC that colocalized with the NIR and SD-OCT lesions (Figure 1H and Figure 2H). The superficial retinal capillary plexus (SCP) (Figure 1F and Figure 2F), the deep retinal capillary plexus (DCP) (Figure 1G and Figure 2G), and the outer choroid were entirely unremarkable with OCTA (Figure 1I and Figure 2I). The zones of CC flow deficit identified with OCTA were color coded (Figure 1J and Figure 2J) and overlaid on the en face structural OCT with segmentation at the level of the EZ (hyporeflective lesions) (Figure 1K and L and Figure 2K and L) and ONL (hyperreflective lesions) (Figure 1N and O and Figure 2N and O). The zones of CC flow deficit colocalized precisely with the hyperreflective and hyporeflective outer retinal lesions but were slightly larger in area.

Case 2

A healthy woman in her thirties presented with acute decreased vision in her left eye. Medications included an oral contraceptive (a combination pill of norethindrone and ethinyl estradiol) and vitamin D3 supplementation. The patient reported an upper respiratory tract infection 2 weeks before presentation. Best-corrected visual acuity measured 20/20 OD and 20/200 OS. Anterior and posterior segment examination was unremarkable in both eyes (Figure 3A). Near-infrared reflectance imaging revealed hyporeflective wedge-shaped paracentral lesions nasal, inferior, and superotemporal to fixation in the left eye (Figure 3B, arrowheads). Spectral-domain OCT through the lesions showed associated disruption of the EZ and ONL hyperreflectivity (Figure 3C). Fluorescein angiography was unremarkable (Figure 3D and E). Optical coherence tomographic angiography of the SCP and DCP were unremarkable (Figure 3F and G). Corresponding flow deficits at the level of the CC were identified and colocalized with the lesions noted on NIR and SD-OCT imaging (Figure 3H). The outer choroid was unremarkable with OCTA (Figure 3I). The zones of CC flow reduction were color coded (Figure 3J and M) and overlaid on the en face structural OCT segmented at the level of the EZ (hyporeflective lesions) (Figure 3K) and ONL (hyperreflective lesions) (Figure 3N) and precise colocalization was illustrated (Figure 3L and O). The patient’s visual acuity improved to 20/50 OS at the 1-month follow-up visit, with partial OCT restoration of the EZ abnormalities.

Discussion

In this report, evidence of OCTA flow reduction at the level of the CC is provided in 2 patients with AMN. Of note, OCTA findings of the SCP and DCP were unremarkable in both cases. The zones of CC flow deficit colocalized precisely with the areas of ONL and EZ abnormality identified with en face OCT but were larger, indicating that the CC flow deficits were not the result of signal attenuation but rather a driving etiology of the disorder. A compromise in the perfusion of the CC can explain the ONL and EZ abnormalities that are so characteristic of AMN. Photoreceptor loss in AMN has been established using several advanced imaging modalities, including ultra–high-resolution SD-OCT,4 adaptive optics,5 and multifocal electroretinography.6,7 Furthermore, we postulate that the oval, tear-drop–shaped lesions seen in AMN are associated with the morphology of the parafoveal CC and the lesions may represent ischemia of a single or several CC lobules.8

Paracentral acute middle maculopathy (PAMM) was initially characterized as a variant of AMN.9 However, recent evidence suggests that PAMM is a distinct clinical finding that is associated with a broad spectrum of retinal vascular diseases and that develops due to ischemia of the DCP.10,11 Paracentral acute middle maculopathy abnormalities are identified as bandlike hyperreflective inner nuclear layer lesions with SD-OCT and are never associated with signs of photoreceptor dysfunction. Optical coherence tomographic angiography has confirmed DCP ischemia as the inciting etiology of PAMM.12 The cases illustrated herein more conclusively show that AMN may be the result of CC ischemia, thus distinguishing it entirely from PAMM.

Acute macular neuroretinopathy may represent the milder side of a spectrum of disorders caused by CC ischemia.13,14 Acute posterior multifocal placoid pigment epitheliopathy exhibits demographic and multimodal imaging findings that are strikingly similar to AMN. Both disorders are self-limiting and are often preceded by a viral prodrome affecting predominantly young individuals. Acute SD-OCT findings, including ONL hyperreflectivity and EZ disruption, are very characteristic in each condition.15 However, the abnormalities identified with fluorescein and indocyanine angiography, which are so typical of placoid disorders, are not seen with AMN. Choriocapillaris flow deficits in AMN may be sufficiently mild to be detected with OCTA but not conventional dye-based angiography.

Conclusions

In summary, our findings provide another example in which OCTA may further expand our understanding of retinal and choroidal pathophysiology. While the observations in these 3 eyes from 2 patients should not be interpreted as proving cause and effect, the results do suggest that CC flow abnormalities may be associated with the cause of AMN. Further studies would be needed to validate this observation.

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Article Information

Corresponding Author: Sandeep Randhawa, MD, Associated Retinal Consultants, William Beaumont School of Medicine, Oakland University, 3535 W 13 Mile Rd, Ste 344, Royal Oak, MI 48073 (srandhawa@arcpc.net).

Accepted for Publication: August 7, 2016.

Published Online: September 29, 2016. doi:10.1001/jamaophthalmol.2016.3513

Author Contributions: Drs Thanos and Randhawa had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Thanos, Faia, Yonekawa, Randhawa.

Acquisition, analysis, or interpretation of data: All Authors.

Drafting of the manuscript: Thanos, Yonekawa, Randhawa.

Critical revision of the manuscript for important intellectual content: Faia, Yonekawa, Randhawa.

Administrative, technical, or material support: Faia, Yonekawa, Randhawa.

Study supervision: Thanos, Yonekawa, Randhawa.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

References
1.
Bos  PJ, Deutman  AF.  Acute macular neuroretinopathy.  Am J Ophthalmol. 1975;80(4):573-584.PubMedGoogle ScholarCrossref
2.
Bhavsar  KV, Lin  S, Rahimy  E,  et al.  Acute macular neuroretinopathy: a comprehensive review of the literature [published online March 10, 2016].  Surv Ophthalmol. doi:10.1016/j.survophthal.2016.03.003PubMedGoogle Scholar
3.
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.e1, 2.PubMedGoogle ScholarCrossref
4.
Monson  BK, Greenberg  PB, Greenberg  E, Fujimoto  JG, Srinivasan  VJ, Duker  JS.  High-speed, ultra-high-resolution optical coherence tomography of acute macular neuroretinopathy.  Br J Ophthalmol. 2007;91(1):119-120.PubMedGoogle ScholarCrossref
5.
Mrejen  S, Pang  CE, Sarraf  D,  et al.  Adaptive optics imaging of cone mosaic abnormalities in acute macular neuroretinopathy.  Ophthalmic Surg Lasers Imaging Retina. 2014;45(6):562-569.PubMedGoogle ScholarCrossref
6.
Browning  AC, Gupta  R, Barber  C, Lim  CS, Amoaku  WM.  The multifocal electroretinogram in acute macular neuroretinopathy.  Arch Ophthalmol. 2003;121(10):1506-1507.PubMedGoogle ScholarCrossref
7.
Audo  I, Gocho  K, Rossant  F,  et al.  Functional and high-resolution retinal imaging monitoring photoreceptor damage in acute macular neuroretinopathy.  Graefes Arch Clin Exp Ophthalmol. 2016;254(5):855-864.PubMedGoogle ScholarCrossref
8.
Hayreh  SS.  The choriocapillaris.  Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1974;192(3):165-179.PubMedGoogle ScholarCrossref
9.
Sarraf  D, Rahimy  E, Fawzi  AA,  et al.  Paracentral acute middle maculopathy: a new variant of acute macular neuroretinopathy associated with retinal capillary ischemia.  JAMA Ophthalmol. 2013;131(10):1275-1287.PubMedGoogle ScholarCrossref
10.
Dansingani  KK, Freund  KB.  Paracentral acute middle maculopathy and acute macular neuroretinopathy: related and distinct entities.  Am J Ophthalmol. 2015;160(1):1-3.e2.PubMedGoogle ScholarCrossref
11.
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.e1.PubMedGoogle ScholarCrossref
12.
Dansingani  KK, Inoue  M, Engelbert  M, Freund  KB.  Optical coherence tomographic angiography shows reduced deep capillary flow in paracentral acute middle maculopathy.  Eye. 2015;29:1620-1624.Google ScholarCrossref
13.
Deutman  AF, Oosterhuis  JA, Boen-Tan  TN, Aan de Kerk  AL.  Acute posterior multifocal placoid pigment epitheliopathy: pigment epitheliopathy of choriocapillaritis?  Br J Ophthalmol. 1972;56(12):863-874.PubMedGoogle ScholarCrossref
14.
Maier  M, Wehrmann  K, Lohmann  CP, Feucht  N.  OCT angiography findings in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) [in German] [published online May 9, 2016].  Ophthalmologe. doi:10.1007/s00347-016-0256-2PubMedGoogle Scholar
15.
Mrejen  S, Sarraf  D, Chexal  S, Wald  K, Freund  KB.  Choroidal involvement in acute posterior multifocal placoid pigment epitheliopathy.  Ophthalmic Surg Lasers Imaging Retina. 2016;47(1):20-26.PubMedGoogle ScholarCrossref
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