Acute Macular Neuroretinopathy
Assigned status Up to Date by Brad H. Feldman, M.D. on December 24, 2014.
- 1 Disease Entity
- 2 Diagnosis
- 3 Management
- 4 Suggested Reading
Acute Macular Neuroretinopathy
Acute Macular Neuroretinopathy (AMN) is a rare disease first reported in 1975 (by Bos and Deutman). A review article published in 2016 identified 156 eyes of 101 patients with AMN. It is characterized by the sudden-onset of one or more paracentral scotomas, usually affecting only one eye but rarely bilateral, in the absence of any other ocular or visual symptoms. These scotomas persist generally indefinitely, though some resolve partially over months. Such scotomas are perifoveal and therefore spare fixation, and they have not been reported to cause significant impairment of visual function in the affected eye(s).
The etiology is unknown. A vascular etiology is hypothesized.
There are no known risk factors. Dr. Lawrence Yanuzzi MD has lectured that drug abuse involving "poppers" - alkyl nitrites inhaled to produce a chemical "high" - has been occasionally associated in his clinical experience.
The known risk factors include
- Fever (Flu, enteritis, upper respiratory tract infection, pharyngitis, brinchitis, )
- Oral contraceptive pills
- Intravenous contrast
- Intravenous ephedrine
- Pregnancy induced hypertension
- Post-surgery (total hip arthroplasty)
- Road traffic accident/non-ocular trauma
- Hypotension/shock due to several causes
- Sinus infection
The pathology is unknown. The photoreceptor layer is the hypothesized site of pathology based on abnormalities seen via Spectral Domain Optical Coherence Tomography.
Funduscopic examination is often initially normal, and this can last days, weeks or months. During this time, only 2 imaging modalities will show the lesion(s):
- Infrared fundus photography. SD-OCT machines use infrared light to iluminate the macula for the photographer prior to any cross-sectional images being obtained. At this time, lesions are visible as 1 or more dark petalloid perifoveal lesions with the tip pointed toward the fovea. These correspond anatomically to the scotomas if the patient draws them on an Amsler grid, or if they are documented via formal visual field testing.
- SD-OCT through the lesions. The Inner Segment / Outer Segment junction (IS/OS) is the most common site of reported abnormality, and there is focal signal reduction of the IS/OS within the lesion. The External Limiting Membrane may also be similarly affected.
LEFT - Infrared view of left macula. Lesion is dark area at the middle of the green line. RIGHT - Focal signal reduction of the Inner Segment / Outer Segment junction within the lesion.
*** The above lesion was NOT visible on funduscopic examination at the time of this photograph / OCT.
Patient's drawing of her left eye's scotoma, day 6 after symptom onset (same patient on same day as photo above)
A recent report noted apparent loss of photoreceptor outer segments - a finding which reversed in 2 of 4 patients - but outer nuclear layer thinning did not resolve in any of these 4 patients.
- Funduscopic examination. Reports of when the lesions become visible (during funduscopic examination) vary - from 3 days after symptom onset to 2 months after symptom onset. Lesions are 1 or more reddish-brown petalloid perifoveal lesions with the tips of the petals pointed toward the fovea.
*** Different patient from the other photographs above.
Patients are generally healthy women in their teens - 30's. Patients report the sudden onset of 1 or several paracentral scotomas, usually but not always in 1 eye only, without other ocular or visual symptoms. A preceding flu-like ilness is the most common reported association, but many cases do not have this association. Rarer reported associations are hormonal contraceptive use, significant coffee consumption, use of epinephrine and hypotensive episodes.
Important epidemiological facts
- Female in 30s
- >50% bilateral
Initially, the anterior segment and funduscopic examinations are usually normal. Central visual acuity remains unaffected. Within 3 days to 2 months after symptom onset, lesions become visible as 1 or more reddish-brown petalloid perifoveal lesions with the tips of the petals pointed toward the fovea.
The disease has no signs.
Patients present with the sudden onset of 1 or more petal-shaped paracentral scotomas, usually involving only 1 eye, but rarely both eyes are affected. There are no other visual or ocular symptoms. The scotomas are relative (not absolute - they interfere with vision in the affected area but do not completely eliminate vision in that area). Scotomas are generally stable over time without changes. Some patients have gradual but incomplete improvement over months, while others never improve.
A patient's scotomas may not all appear simultaneously - this author followed a patient closely in the first few days after the onset of a single scotoma, which was clearly visible on infrared view of the macula at that time. 8 days later the patient returned reporting a new 2nd scotoma, and this was clearly visible as a new 2nd lesion on infrared imaging.
Important symptoms include
- Visual decline
Clinical diagnosis is based on the patient's history and symptoms as described above, generally with only infrared fundus photography and outer retinal changes on SD-OCT seen as described above. Intraretinal hemorrhage may be associated.
Fluorescein angiography, ICG angiography and fundus autofluorescence are all normal. Stratus OCT has been reported to be incapable of detecting this disease, as it has failed to show any retinal abnormalities when performed at the same visit in which a patient's SD-OCT shows the classic abnormalities.
Rare reports of decreased P1 amplitude on multifocal ERG exist, but this test is not performed in the overwhelming majority of case reports, and the mf ERG on this author's patient showed normal P1 amplitudes when performed 17 days after symptom onset.
See Diagnosis above. If no lesions are visible on funduscopic examination, infrared fundus photography should show the lesions, and SD-OCT through the lesions should show the aforementioned outer retinal changes. If lesions are visible on funduscopic examination, color fundus photography is also useful for documentation.
Most important investigations include the near infrared reflectance image and spectral domain OCT
- Near infrared reflectance (Spectralis)- nearly always picks up the lesion. Lesion shape may be wedge, tear-drop, oval, horse-shoe shaped or petaloid.
- Spectral domain OCT (SDOCT)- OUTER RETINA IS INVOLVED- LIKELY DUE TO THE INVOLVEMENT OF DEEP CAPILLARY PLEXUS. Features include
- A hypereflective plaque at the outer side of the outer plexiform layer,
- Hyperreflectivity of outer nuclear layer,
- Disruption of ellipsoid zone/interdigitation zone
- In late stage thinning of the outer nuclear layer may be seen
- Fundus photo- may not detect early lesions. Visible lesions are reddish-brown or orange or hypopigmented with tear drop shape around the fovea- the sharp point faces towards the fovea.
- Amsler chart- typically shows a corresponding scotoma
- Humphrey/Goldmann visual field may reveal the scotoma
- FFA and ICG angiograms are mostly normal
- Autofluorescence- may not detect the lesion. may be hypo-autofluorescent in slow wave autofluorescence. Hyper-autofluorescence may be noted in near infrared autofluorescence.
If a clinic has SD-OCT and infrared imaging capabilities, then acute macular neuroretinopathy should be easily distinguishable from the other items below. However, the differential technically includes:
- Acute Retinal Pigment Epitheliitis (Krill's disease)
- Multiple Evanescent White Dot Syndrome (MEWDS)
- Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)
- Central Serous Chorioretinopathy (CSCR)
- Optic Neuritis
- Old inner retinal infarcts
None. Even though there are rare associations with hormonal contraceptive use and excessive coffee consumption, there is no recommendation in the literature that patients should discontinue these if they develop this disease.
Medical follow up
Follow-up is at the discretion and comfort level of the physician. If the diagnosis is considered relatively certain based on history and the presence of classic findings, then follow-up may be every few weeks or months simply to document the course of the disease. No intervention can be performed for this disease.
Surgical follow up
Full resolution of scotomas has never been reported. Some scotomas partially resolve, some do not resolve at all. However, there are no reports of this disease causing meaningful vision loss in an eye. Visual prognosis is usually good.
Types of AMN
|Type 1||Type 2|
|Paracentral Acute Middle Maculopathy (PAMM)||Typical Acute Macular Neuroretinopathy/Acute Macular Outer Retinopathy (AMOR)|
|inner retinal involvement||outer retinal involvement|
|hyperreflectivity superficial to the outer plexiform layer (OPL-INL) on SDOCT||hyperreflectivity deep to the outer plexiform layer on SDOCT|
|inner nuclear layer (INL) involved- may lead to thinning of INL||outer nuclear layer (OPL-ONL) involved- may lead to thinning of ONL|
- Turbeville SD, Cowan LD, Gass JD (2003) Acute macular neuroretinopathy: a review of the literature. Surv Ophthalmol 48(1):1–11
- Vance SK, Spaide RF, Freund KB, Wiznia R, Cooney MJ. Outer retinal abnormalities in acute macular neuroretinopathy. Retina. 2011 Mar;31(3):441-5
- Corver HD, Ruys J, Kestelyn-Stevens AM, De Laey J, Leroy BP(2007) Two cases of acute macular neuroretinopathy. Eye 21:1226–1229
- Neuhann IM, Inhoffen W, Koerner S, Bartz-Schmidt KU, Gelisken F. Visualization and follow-up of acute macular neuroretinopathy with the Spectralis HRA+OCT device. Graefes Arch Clin Exp Ophthalmol. 2010 Jul;248(7):1041-4
- Maschi C, Schneider-Lise B, Paoli V, Gastaud P. Acute macular neuroretinopathy: contribution of spectral-domain optical coherence tomography and multifocal ERG. Graefes Arch Clin Exp Ophthalmol. 2010 Nov 20
- Monson BK, Greenberg PB, Greenberg E, Fujimoto JG, Srinivasan VJ, Duker JS (2007) High-speed, ultra-high-resolution optical coherence tomography of acute macular neuroretinopathy. Br J Ophthalmol 91(1):119–120
- Ophthalmology: Expert Consult Premium Edition: Enhanced Online Features and Print (Yanoff, Ophthalmology) by Myron Yanoff MD and Jay S. Duker MD (Dec 11, 2008)
- Bos PJ, Deutman AF. Acute macular neuroretinopathy. Am J Ophthalmol. 1975;80(4): 573-84
- 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(5):538-65.
- 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(10):1275-87.
- 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(3):365-8