Acute Macular Neuroretinopathy
Acute Macular Neuroretinopathy
Acute Macular Neuroretinopathy (AMN) is a rare disease first reported in 1975 (by Bos and Deutman).It is characterized by the sudden-onset of one or more paracentral scotomas. These scotomas generally persist indefinitely, though some resolve partially over months. Most scotomas are perifoveal and therefore spare fixation, and may not cause significant decreased vision in the affected eye(s).
A review article published in 2016 identified the largest series of 156 eyes of 101 patients with AMN. Most cases in this study were reported in young white females in their third decade of life. Usually one eye is affected, although bilateral cases were seen in 45% of cases in this large series.
The etiology is not clear. A microvascular abnormality in deep capillary plexus of the retina is hypothesized.
Many associations have been identified with AMN and include:
- Fever (Flu, enteritis, upper respiratory tract infection, pharyngitis, bronchitis, )
- Oral contraceptive pills
- • Hypotension/shock due to several causes (post-partum, post-surgery, trauma etc)
- • Intravenous contrast
- • Intravenous ephedrine
- • Caffeine
- • Pro-thrombin associated antiphospholipid antibodies
- • Pre-eclampsia
- • Sinus infection
The pathogenesis is not clear; recent evidence points to deep capillary retinal ischemia due to various causes. 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 but the lesions become visible from 3 days to 2 months after symptom onset. Classic retinal lesions involve one or more reddish brown petalloid lesions that surround the fovea. Such lesions can be subtle clinically and may be better seen with red-free light. These correspond closely to amsler grid findings of scotoma. Faint intraretinal hemorrhages can be seen.
The imaging modalities most commonly used to evaluate the lesion(s) are:
1. Infrared fundus photography. SD-Optical Coherence Tomography (OCT) machines use infrared light to illuminate the macula for the photographer prior to any cross-sectional images being obtained. Lesions are visible as dark gray 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.
2. SD-OCT through the lesions. Hyperreflective plaque is seen initially at outer nuclear (ONL) and outer plexiform layers of OCT indicating disruption of photoreceptor cell bodies and their axons. Focal ellipsoid zone (EZ) disruption ensues. With time, EZ reconstitutes but persistent interdigitation zone disruption is noted. The hyper-reflective plaque fades away and is replaced with ONL thinning.
3. OCT-A reveals reduced flow signals in deep retinal capillary plexus, suggesting focal ischemia photoreceptor axons in the outer plexiform layer. Variable recovery of capillary flow signal is noted with time in the deep capillary plexus. However, the entire damaged photoreceptor unit atrophies causing cumulative long-term ONL thinning.
4. Fluoresecein angiography is noted to be normal in most cases. Subtle hypofluorescence of the lesions may be noted early and late phases of the study.
5. Adaptive Optics shows reduced cone photoreceptor density and cone mosaic disruption with incomplete recovery with time.
6. Multifocal ERG reveals diminished amplitudes in most eyes and occasionally , decreased implicit time may also be noted.
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. Bilateral cases have been reported in upto 45% of cases. A preceding flu-like illness 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.
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.
All of the patient's scotomas may not all appear simultaneously but over days. - Other symptoms include
• Scotoma/'shadows'/'spot' • Mild decreased visual acuity ~ 20/30 • Floaters • Metamorphopsia • Photopsia
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 petalloid.
- Spectral domain OCT (SDOCT)-Outer retina is involved due to involvement of deep capillary plexus. Features include
A hypereflective plaque between the outer plexiform and outer nuclear layers. 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 pointing 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 or the lesions may be hypo-autofluorescent. 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
No medication has shown to improve the condition. 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|
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