Case of the Month

Edited by Robert N. Johnson, MD

Case History

A 39-year-old morbidly obese woman presented with acute onset painless bilateral vision loss for 2 weeks. In particular, she noted a discrete right superior visual field defect. Her left eye was amblyopic.

On examination, visual acuity was 20/250 in the right eye and light perception in the left eye.  Pupils were equal round and reactive with no afferent pupillary defect.  The intraocular pressures and anterior segment were unremarkable. Fundus examination demonstrated bilateral disc edema with a subtle retinal whitening in the right inferior macula (Figure 2A). Fluorescein angiography revealed normal perfusion, a patent cilioretinal artery in the right eye, and late leakage of the optic nerve (Figure 2B). Ocular coherence tomography (OCT) showed elevation of the optic nerve as well as a hyperreflective band in the inner nuclear layer (Figure 2) which corresponded to an area of decreased perfusion on OCT angiography within the deep capillary plexus (Figure 3).

Figure 3: SD-OCT scan through the right macula and nerve. Note the hyperreflective band in the middle retinal layers.

Figure 4: En-face OCT of the right macula showing the extent of the hyperreflective changes in the inner nuclear layers of the right macula. The OCT-Angiogram of the right macula shows reduced retinal perfusion in the deep retinal capillary plexus.

Differential Diagnosis

Acute macular neuroretinopathy, Retinal vascular occlusion, Idiopathic intracranial hypertension, Vasoconstriction (Migraine, Medication induced)

Additional History and Diagnosis

The patient had a history of morbid obesity and was taking amitriptyline for chronic headaches. She underwent magnetic resonance imaging, lumbar puncture, as well as an extensive laboratory workup with a neurologist which only revealed an elevated opening pressure.  She was diagnosed with paracentral acute middle maculopathy (PAMM) in the setting of idiopathic intracranial hypertension (IIH) and started on acetazolamide in addition to a weight loss regimen. Three months later the disc edema was seen to resolve with improvement in the vision to 20/32 and 20/400 in the right and left eyes respectively. Focal atrophy of the inner nuclear layer in the region of previous ischemia was observed (Figure 5).

Figure 5: SD-OCT of the right macula 3 months after her initial evaluation. The disc edema has resolved, but note the area of atrophy of the inner nuclear layer in the area of prior retinal ischemia.

Discussion

Paracentral acute middle maculopathy is a clinical entity first described by David Sarraf as a variant of acute macular neuroretinopathy (AMN).¹ We now understand that they represent distinct entities. Acutely, PAMM lesions are characterized by hyperreflective bands at the level of the inner nuclear layer on spectral domain OCT which spares the outer retina. Typically these lesions then progress to atrophy of the affected inner retina leaving persistent visual deficits as in our patient. In AMN, the hyperreflective band-like lesions occur at the junction of the outer plexiform and outer nuclear layers.²

Understanding the microvascular anatomy of the central retinal artery and vein aids in explaining the mechanism of PAMM. The central macula contains capillary plexus networks which sprout into a superficial, intermediate, and deep systems.  The superficial system lies within the ganglion cell and nerve fiber layers. The intermediate plexus is supplies the inner portion of the inner nuclear layer (INL) while the deep plexus supplies the outer part of the INL.^3,4 Parafoveally, limited capillary density and oxygen diffusion in these layers form a watershed zone.⁵ Ischemia of these susceptible regions results in PAMM when the intermediate and deep capillary systems are specifically affected. In contrast AMN is thought to be due to ischemia specifically of the deep capillary plexus, though some studies now also suggest a possible contributing role from the choriocapillaris.^6,7

PAMM may be idiopathic or due to secondary causes. Potential etiologies may be separated into local retinal vascular etiologies (ie. retinal vascular occlusions, diabetic retinopathy, hypertensive retinopathy, vasculitis) and extrinsic vascular causes (ie. migraines, medications, hypovolemia, orbital compression).^1,8 Our case is the first to be reported in the setting of IIH. We postulate that swelling of the optic nerve resulted in mechanical compression of the retinal vessels which reduces ocular perfusion pressure.

There is no treatment for PAMM, and primary management involves identifying and addressing causative factors. In summary PAMM is a clinical finding of retinal ischemia within the deeper capillary plexuses, and has emerged as a result of improvements in spectral domain-OCT imaging.

Adapted from Denny MR, Ananda K, Chen JJ, Johnson RN. Paracentral acute middle maculopathy associated with idiopathic intracranial hypertension. Retinal cases and brief reports. January 3, 2019.

References

1. 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; 131:1275-1287.
2. Rahimy E, Kuehlewein L, Sadda SR, Sarraf D. Paracentral Acute Middle Maculopathy: What We Knew Then and What We Know Now. Retina 2015; 35:1921-1930.
3. Snodderly DM, Weinhaus RS, Choi JC. Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis). J Neurosci 1992;12:116-1193.
4. Tan PEZ, Yu PK, Balaratnasingam C, et al. Quantitative con- focal imaging of the retinal microvasculature in the human retina. Invest Ophthalmol Vis Sci 2012;53:5728–5736.
5. Yu S, Wang F, Pang CE, et al. Multimodal imaging findings in retinal deep capillary ischemia. Retina 2014;34:636–646.
6. Bhavasar KV, Lin S, Rahimy E, et al. Acute macular neuroretinopathy: A comprehensive review of the literature. Surv Ophthalmol 2016 Sep-Oct; 61(5):538-65.
7. Lee SY, Cheng JL, Gehrs KM, et al. Choroidal features of aucte macular neuroretinopathy via optical coherence tomography angiography and correlation with serial multimodal imaging. JAMA Ophthalmol 2017 Nov; 135(11):1177-1183.
8. Chen X, Rahimy E, Sergott RC, et al. Spectrum of retinal vascular diseases associated with paracentral acute middle maculopathy. Am J Ophthalmol 2015;160:26–34.

Additional Images added April, 2019

Figure 6: Color photos of the nerve and macula of the right and left eye 3 months after presentation. Note resolution of the disc edema and significant sheathing and narrowing of the arterioles in both eyes (more prominently in the right eye.