Sequential Bilateral Paracentral Acute Middle Maculopathy in a Middle-Aged Woman

Abstract

Purpose: To present a case of sequential paracentral acute middle maculopathy (PAMM) in a middle-aged woman with no cardiovascular risk factors. Methods: A single case was evaluated. Results: A 53-year-old woman with a history of PAMM resulting from perfused central retinal artery occlusion in the left eye presented with PAMM in the right eye 3 years later. The patient had a medical history of treated anemia, stress disorder, and insomnia. Examination of the right eye showed a superior parafoveal crescent of translucent retina without associated edema or hemorrhage. Optical coherence tomography (OCT) showed hyperreflective band-like areas in the superior parafoveal and perifoveal regions. Fluorescein angiography revealed normal arterial filling. OCT angiography showed patchy filling of the middle capillary plexus with normal perfusion of the superficial capillary plexus in the right eye. Conclusions: Although bilateral sequential PAMM is rare, close monitoring in a case of PAMM in 1 eye should be considered.

Introduction

Paracentral acute middle maculopathy (PAMM) is characterized by the presence of parafoveal hyperreflective bands in the inner nuclear layer on spectral-domain optical coherence tomography (SD-OCT) resulting from deep retinal capillary plexus ischemia. ¹ PAMM can present as an isolated entity, even in asymptomatic patients with unknown systemic disease, ² or can be associated with diabetic retinopathy, hypertensive retinopathy, sickle cell retinopathy, retinal artery occlusion (RAO), retinal vein occlusion (RVO), Purtscher retinopathy, and giant cell arteritis (GCA).^3–6

Here, we report a patient with an ocular history of PAMM caused by reperfused central retinal artery occlusion (CRAO) in 1 eye who presented with PAMM in the opposite eye 3 years later. To our knowledge, this is the first report of sequential PAMM in a patient with no history of systemic cardiovascular or ischemic events.

Case Report

A 53-year-old woman presented with acute onset of a paracentral scotoma and vision loss in the left eye. Her medical history was unremarkable except for stress disorder, insomnia, and a remote history of anemia.

On examination, the best-corrected visual acuity (BCVA) was 20/20 OD and counting fingers at 6 ft OS. A relative afferent pupillary defect (rAPD) was detected in the left eye. The intraocular pressure (IOP) was within normal limits in both eyes. The anterior segment in both eyes was unremarkable on slitlamp evaluation.

A fundus examination of the right eye showed a normal optic nerve, normal vasculatures, and a normal retina. In the left eye, the fundus examination showed a normal optic nerve, normal vasculature, and scattered areas of inner retinal whitening in the macula. SD-OCT of the macula showed normal retinal layers in the right eye and hyperreflective bands at the level of the inner nuclear layer and inner plexiform layer in the left eye. Widefield fluorescein angiography (FA) revealed a delay in the arteriovenous transit time in the left eye with some patchy choroidal filling and normal vasculature in the right eye. Figure 1 shows images of the findings.

Figure 1.

Pseudocolor fundus photograph of right eye (A) and SD-OCT imaging of the right macula (B) were unremarkable. (C) Pseudocolor fundus photograph of the left eye was unremarkable. (D) SD-OCT image of the left macula shows the hyperreflective band-like lesions at the inner nuclear and inner plexiform layers of the retina. (E) FA of the left eye at 27 seconds. (F) En face OCT image of the left eye shows a fern-like pattern of hyperreflectivity. (G) FA of the left eye at 34 seconds. (H) FA of the left eye at 42 seconds. All photographs were captured at the initial presentation 3 years earlier.

Abbreviations: FA, fluorescein angiography; OCT, optical coherence tomography; SD-OCT, spectral-domain optical coherence tomography.

The blood workup, including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); echocardiography; carotid ultrasound; hypercoagulability panel; computed tomography (CT) scan of the head; and magnetic resonance imaging (MRI) of the brain were unremarkable. The uncorrected VA recovered to 20/80 after 2 days and then to 20/30⁺² after 3 weeks, with no rAPD in the left eye. The patient was diagnosed with PAMM in the setting of a reperfused CRAO.

Three years later, the patient presented with a 1-day history of acute onset of a paracentral scotoma in the right eye. On examination, the BCVA was 20/30 OD and 20/40⁺² OS, with no improvement on pinhole occlusion and 20/20 pinhole, respectively. Extraocular movements were intact, and the pupils were round and reactive with no rAPD. The IOP by applanation was 14 mm Hg in the right eye and 13 mm Hg in the left eye. A slitlamp examination of the anterior segment showed no abnormality in either eye. A posterior segment examination showed no vitreous cells, a cup-to-disc ratio of 0.45, normal retinal vessels, and a superior parafoveal crescent of translucent retina without associated edema or hemorrhage in the right eye; the fundus examination was normal in the left eye. The retina was flat bilaterally with no breaks noted.

A complete blood cell count, comprehensive metabolic panel, serum lipids, blood sugar, CRP, ESR, HIV, hepatitis C antibody, factor V Leiden, homocysteine, and prothrombin gene mutation were all normal. A CT scan of the head without contrast, MRI of the brain, and carotid artery Doppler as well as SD-OCT, OCT angiography (OCTA), and FA were ordered. Figure 2 shows the findings.

Figure 2.

(A) Pseudocolor fundus photograph of right eye shows areas of petaloid haze in the perifoveal area and superior to macula. (B) SD-OCT image of the right macula shows the hyperreflective band-like lesions at the inner nuclear and inner plexiform layers of the retina. (C) En face OCT image of the right eye shows a fern-like pattern of hyperreflectivity in the inferior macula. (D) OCT angiography of the right eye shows the perifoveal capillary dropout in the inner capillary plexus. (E and F) FA images of the right eye at 43 seconds and 52 seconds show an area of capillary hypoperfusion superior to the fovea. (G) Color fundus photograph of left eye was unremarkable. (H) SD-OCT images of the left macula show focal loss of the inner nuclear and inner plexiform layer. All photographs were captured 3 years after the initial presentation.

Abbreviations: FA, fluorescein angiography; OCT, optical coherence tomography; SD-OCT, spectral-domain optical coherence tomography.

The results of blood workup, CT of the head without contrast, MRI of the brain, and carotid artery Doppler were all within normal limits. Color fundus photography and autofluorescence of the right eye showed areas of petaloid discoloration superior to the macula and parafoveal and perifoveal dark crescent areas, respectively. Fundus photography and autofluorescence of the left eye were all within normal limits. SD-OCT imaging showed hyperreflective band-like areas in the superior parafoveal and perifoveal region without subretinal or intraretinal fluid. FA showed delayed perfusion with hypofluorescence in the superior parafoveal and perifoveal regions without leakage. OCTA showed decreased perfusion of the deep capillary plexus with normal perfusion of the superficial capillary plexus in the right eye.

Given the previous retinal findings in the left eye, blood workup, and imaging modality results, the patient was diagnosed with sequential bilateral PAMM. She was informed of the results of her blood workup, CT of the head without contrast, brain MRI, and carotid artery Doppler as well as fundus photography and retinal imaging findings; her current condition; and her prognosis. Five months after the patient’s initial presentation, the PAMM resolved to inner retinal thinning (likely small branchlet RAO) with a BCVA of 20/20 OU.

Conclusions

PAMM has been reported in cases of venular or arterial insufficiency, systemic venous return impedance, combined vascular insufficiency, ocular surgery sequela, ocular inflammation, ocular or systemic trauma, immune cell-mediated disorders, neurological conditions, and idiopathic conditions. ⁷ It has also been reported after systemic infections and vaccinations as wells as in the presence of medication side effects. ⁷

Bilateral PAMM is rare and has been reported as a consequence of cardiopulmonary surgery, ⁸ methanol intoxication, ⁹ malaria retinopathy associated with severe Plasmodium falciparum infection, ¹⁰ Behçet disease, ¹¹ and COVID infection. ¹² However, sequential PAMM was only reported in patients with systemic vasculopathy and hypertension. ⁵

PAMM lesions usually present as hyperreflective bands detected by OCT at the level of inner nuclear layer during the acute phase. ¹³ In chronic cases, thinning of the inner nuclear layer and reperfusion of the deep capillary plexus after the atrophy of tissue infarction when PAMM lesions resolve can occur. ² It has been shown that the pattern of PAMM is related to the different range of severity and retinal involvement. The fern-like pattern with perivenular involvement presents in early stages with less severity, middle layer ischemia with arteriolar involvement shows in the intermediate stage, and middle and inner layer ischemia presents in the most severe stage of PAMM.^14,15 The presentation of PAMM as isolated resolved lesions in healthy asymptomatic individuals indicates that PAMM is more likely a manifestation of a condition rather than a diagnosis.^16,17

Because PAMM represents an ischemic retinal vascular injury, it should prompt further systemic workup. In a recent study, the incidence of chronic PAMM among hypertensive patients and healthy individuals was 89.9% and 16.7%, respectively. The higher rate of PAMM detected on OCT in patients with mild hypertension indicates that these early alterations in retinal microcirculation might become evident before changes in OCTA parameters.^2,5

Bilateral RAO has been reported in cases of GCA, ¹⁸ antiphospholipid antibody syndrome, ¹⁹ Susac syndrome, ²⁰ Churg-Strauss, ²¹ acute myeloid leukemia, ²² HIV, ²³ and carotid artery occlusions with ocular with cerebral hemodynamic changes. ²⁴ Padrón-Pérez et al ²⁵ reported a case of sequential bilateral RAO caused by an atherogenic embolic event; they suggested that the cause and treatment of any identifiable condition, such as GCA, be promptly investigated.

It is generally believed that PAMM is associated with retinal vascular disorders, mainly RVO, although no definite risk factor has been reported for sequential PAMM. ¹³ Unlike in another case of sequential PAMM, ⁵ our patient did not have a history of systemic vascular or ischemic events and did not contract the COVID infection or receive a vaccination. More studies to elucidate the pathobiology of PAMM to prevent permanent vision loss are necessary.

The vision in our patient recovered after few days in both eyes during both episodes of PAMM. However in another case, Kılıç Müftüoğlu et al ⁵ reported that vision recovered after a few months. The quicker recovery in our patient may be because she had no systemic cardiovascular risk factors and a healthier baseline.

We recommend repeating a thorough workup for patients who present with PAMM (mainly older than 50 years) in the opposite eye because conditions such as GCA can still develop. In such cases, urgent therapy with high-dose steroid therapy to prevent catastrophic vision loss should be initiated. In the presence of other systemic vascular conditions and retinal vascular disorders, modifying the risk factors to apply appropriate secondary prevention measures and treating the underlying disorders to reduce the risk for future vascular events have been suggested.^4,13