Multimodal Imaging in Acute Macular Neuroretinopathy

A 44-year-old woman noticed bilateral irregular scotomata associated with photopsias of 6-month duration. Ophthalmoscopic examination demonstrated multiple bilateral, pericentral, hypopigmented, petaloid, macular lesions evident on Amsler grid associated with paracentral hyperreflective lesions on optical coherence tomography in the outer plexiform and nuclear layers. Indocyanine green angiography revealed patches of choroidal ischemia consistent with acute macular neuroretinopathy.

Photo and Video Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Multimodal Imaging in Acute Macular Neuroretinopathy Benjamin W. Botsford, MD, Priyanka Kukkar, MD, Gabrielle Bonhomme, MD Abstract: A 44-year-old woman noticed bilateral irregular scotomata associated with photopsias of 6-month duration. Ophthalmoscopic examination demonstrated multiple bilateral, pericentral, hypopigmented, petaloid, macular lesions evident on Amsler grid associated with paracentral hyperreflective lesions on optical coherence tomography in the outer plexiform and nuclear layers. Indocyanine green angiography revealed patches of choroidal ischemia consistent with acute macular neuroretinopathy. Journal of Neuro-Ophthalmology 2021;41:e357–359 doi: 10.1097/WNO.0000000000001128 © 2020 by North American Neuro-Ophthalmology Society A 44-year-old woman with a history of complex migraines with aura and one episode of transient ischemic attack symptoms consistent with central vertigo presented with a 6 -month history of constant bilateral paracentral scotomata in both eyes associated with paracentral photopsias. She initially saw a local optometrist where the examination was reportedly normal. She underwent magnetic resonance imaging and magnetic resonance angiography of the brain which showed evidence of fibromuscular dysplasia of the right carotid artery. Diagnostic bloodwork was performed at that time as part of the initial stroke work-up and revealed an elevated homocysteine level. She denied other ocular or systemic symptoms. Her initial examination demonstrated 20/20 Snellen visual acuity in each eye with normal color vision, intraocular pressure, and no relative afferent pupillary defect. Anterior segment examination was unremarkable. Posterior segment examination demonstrated multiple paracentral hyperpigmented petaloid lesions in the maculae bilaterally (Figs. 1A, C) that are evident on near-infrared Department of Ophthalmology, Eye and Ear Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. The authors report no conflicts of interest. Address correspondence to Gabrielle Bonhomme, MD, Department of Ophthalmology, Eye and Ear Institute, University of Pittsburgh Medical Center, 203 Lothrop Street, 7th Floor, Pittsburgh, PA 15213; E-mail: [e-mail] Botsford et al: J Neuro-Ophthalmol 2021; 41: e357-e359 reflectance (Figs. 1B, D). Screening neurologic examination was normal. Automated 30–2 visual field testing and Amsler grid demonstrated multiple bilateral scotomata (Figs. 2A, B). Macular optic coherence tomography (Cirrus, Zeiss) revealed multiple paracentral hyperreflective band-like lesions in the outer retina of each eye at the level of the outer plexiform layer and/or outer nuclear layer with underlying attenuation of the ellipsoid zone in the right eye (Fig. 2C). Fundus fluorescein angiography was unremarkable (Figs. 1E, G), with indocyanine green angiography (ICGA) demonstrating areas of focal parafoveal hypofluorescence (arrows) which did not correspond directly to the lesions seen on near-infrared reflectance (Figs. 1F, H). These hypofluorescent areas were therefore interpreted as choroidal hypoperfusion, rather than masking artifact. Additional diagnostic laboratory testing including Lyme, syphilis serologies, and QuantiFERONGold were performed to rule out infectious neuroretinitis and were negative. The characteristic findings on infrared imaging, optical coherence tomography (OCT), and fundus examination, as well as the patient’s characteristic description of stereotypical visual symptoms and Amsler grid findings are consistent with the diagnosis of acute macular neuroretinopathy (AMN). Acute macular neuroretinopathy (AMN) is a rare condition that was first described in 1975 by Bos and Duetman as a brownish-red wedge shaped petaloid macular lesion around the fovea with corresponding paracentral scotomas (1). These subjective scotomas generally persist indefinitely, although some resolve partially over months. Most scotomas are perifoveal and therefore spare fixation, thereby not causing significant decreased acuity in affected eyes. Dilated ophthalmoscopic examination is often normal initially, with lesions becoming visible from 3 days to 2 months after symptom onset. Several associations have been identified with the development of AMN including viral infection, oral contraceptives, hypertension/shock, intravenous contrast, caffeine, antiphospholipid antibodies, and pre-eclampsia e357 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay FIG. 1. A. Multicolor images of the right eye demonstrating paracentral hyperpigmented petaloid lesions corresponding to (B) infrared images. C. Multicolor images of the left eye demonstrating paracentral hyperpigmented petaloid lesions corresponding to (D) infrared images. E. Normal fluorescein angiography of the right eye. F. Indocyanine angiography of the right eye demonstrating areas of choroidal hyperperfusion (arrows). G. Normal fluorescein angiography of the left eye. H. Indocyanine angiography of the left eye demonstrating an area of choroidal hyperperfusion (arrows). (2). As many etiologies are also believed to be potentially related to hyperviscosity and endothelial dysfunction, it is possible the hyperhomocysteinemia uncovered in our patient contributed to our patient’s findings. Amsler grid testing, infrared imaging, spectral-domain OCT, fundus autofluorescence, and multifocal electroretinogram are useful in characterizing the precise structural and functional deficits of this condition (3). Although the pathogenesis of AMN is complex, recent research suggests a microvascular ischemic etiology (2). Sarraf et al designed AMN into 2 types: Type 1 is paracentral acute middle maculopathy with inner retinal involvement and hyper-reflectivity on OCT in the outer plexiform and inner nuclear layer, and Type 2 is typical AMN with outer retinal involvement and hyper-reflectivity on OCT in the outer plexiform and outer nuclear layer (4). Our patient demonstrated hyper-reflectivity of the outer plexiform and attenuation of the outer nuclear layer, consistent more with type 2 AMN. Although ICGA is often normal in this condition, choroidal hypoperfusion has been seen on ICGA (2). Our patient demonstrated areas of choroidal hypoperfusion on ICGA as well consistent with the theory that AMN results from simultaneous mild hypoperfusion of the deep capillary plexus and choriocapillaris, causing infarction of both the retina and choroid (5). In conclusion, we present a well-illustrated case of AMN with characteristic imaging findings on OCT and ICGA. Ischemia of both the deep capillary plexus and choriocapillaris may contribute to the characteristic findings in this disease. Factors contributing to hyperviscosity or FIG. 2. A. Amsler grid of the right and left eye demonstrating multiple paracentral scotomata in each eye. B. Automated 30–2 visual fields demonstrating bilateral paracentral scotomata. C. Optical coherence tomography of the right eye and (D) left eye demonstrating bands of paracentral hyperreflectivity at the junction of the outer plexiform and outer nuclear layer OU (arrows) and attenuation of the underlying ellipsoid and interdigitation zones in the right eye (arrowheads). The hyper-reflectivity at the junction of the outer plexiform layer and outer nuclear layer is more pronounced in the tomograph of the left eye. The left eye shows minimal, if any, attenuation of the underlying ellipsoid zone. e358 Botsford et al: J Neuro-Ophthalmol 2021; 41: e357-e359 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay endothelial dysfunction may contribute to the underlying disease process. ocular imaging and our ocular imaging team for their excellent work. REFERENCES STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: B. W. Botsford, P. Kukkar, and G. Bonhomme; b. Acquisition of data: B. W. Botsford, P. Kukkar, and G. Bonhomme; c. Analysis and interpretation of data: B. W. Botsford, P. Kukkar, and G. Bonhomme. Category 2: a. Drafting the manuscript: B. W. Botsford, P. Kukkar, and G. Bonhomme; b. Revising it for intellectual content: B. W. Botsford, P. Kukkar, and G. Bonhomme. Category 3: a. Final approval of the completed manuscript: B. W. Botsford, P. Kukkar, and G. Bonhomme. ACKNOWLEDGMENTS The authors acknowledge Dr. Kunal K Dansingani MBBA, MS, FRCOphth for his assistance with interpretation of Botsford et al: J Neuro-Ophthalmol 2021; 41: e357-e359 1. Bos PJ, Deutman AF. Acute macular neuroretinopathy. Am J Ophthalmol. 1975;80:573–584. 2. Bhavsar KV, Lin S, Rahimy E, Joseph A, Freund KB, Sarraf D, Cunningham ET, Jr. Acute macular neuroretinopathy: a comprehensive review of the literature. Surv Ophthalmol. 2016;61:538–546. 3. Yeh S, Hwang TS, Weleber RG, Watzke RC, Francis PJ. Acute macular outer retinopathy (AMOR): a reappraisal of acute macular neuroretinopathy using multimodality diagnostic testing. Arch Ophthalmol. 2011;129:365–368. 4. Sarraf D, Rahimy E, Fawzi AA, Sohn E, Barbazetto I, Zacks DN, Mittra RA, Klancnik JM, Jr, Mrejen S, Goldberg NR, Beardsley R, Sorenson JA, Freund KB. Paracentral acute middle maculopathy: a new variant of acute macular neuroretinopathy associated with retinal capillary ischemia. JAMA Ophthalmol. 2013;131:1275– 1287. 5. Dansingani KK, Freund KB. Paracentral acute middle maculopathy and acute macular neuroretinopathy: related and distinct entities. Am J Ophthalmol. 2015;160:1–3.e2. e359 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.