Paracentral Acute Middle Maculopathy as a Manifestation of Giant Cell Arteritis

Abstract

Giant cell arteritis (GCA) may produce large areas of retinal infarction due to cilioretinal or central/branch retinal artery occlusions. However, focal retinal ischemia in the form of cotton-wool spots (CWS) from nonperfusion of smaller, more distal vessels may also occur in GCA, sometimes as an isolated finding (1). Here, we describe another form of focal retinal ischemia—paracentral acute middle maculopathy (PAMM)—as a manifestation of biopsy-proven GCA. CASE 1 A 75-year-old white woman with a history of hypertrophic cardiomyopathy and carotid stenosis developed acute blurring of her vision in the left eye. An outside ophthalmologist observed extensive CWS in her left posterior pole. Carotid Doppler ultrasonography demonstrated less than 50% stenosis of the right and 50%–69% stenosis of the left internal carotid artery. Consequently, left carotid endarterectomy was performed for presumed ocular ischemic syndrome. However, 3 weeks postoperatively, she complained of acute blurred vision of the right eye and was noted to have developed multifocal CWS in this eye. Upon referral to our institution, visual acuity by pinhole was 20/80 in the right eye and 20/40 in the left eye. The slit-lamp exam revealed 2+ nuclear sclerotic and cortical cataracts bilaterally. Dilated fundus exam of the right eye showed extensive CWS of the posterior pole, with peripapillary retinal swelling but no optic disc edema, whereas the left eye showed small residual CWS and pigmentary mottling (Fig. 1A, B). No intra-arterial plaques were noted in either eye. Optical coherence tomography (OCT) of the right macula showed multifocal retinal nerve fiber layer (RNFL) thickening corresponding to CWS and patchy hyper-reflectivity of the inner nuclear layer (INL) consistent with PAMM (Fig. 1C). Fluorescein angiography (FA) of the right eye revealed patchy choroidal filling, delayed arterial filling, and blockage from CWS (Fig. 1D). The patient denied recent headaches, jaw claudication, or scalp tenderness. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normal (10 mm/h and 0.26 mg/dL, respectively). Nevertheless, clinical suspicion for GCA remained high, and oral prednisone 60 mg/d was started. Right superficial temporal artery biopsy revealed mural inflammation, scattered giant cells, and intimal thickening, consistent with GCA. Repeat OCT 1 month later demonstrated the resolution of PAMM with interval focal INL thinning (Fig. 1E).FIG. 1.: Concurrent cotton-wool spots and paracentral acute middle maculopathy in giant cell arteritis. A and B. Fundus photographs of the right (A) and left (B) eyes upon referral to our institution. The right eye exhibits numerous acute cotton-wool spots along the vascular arcades and nasal to the optic disc, whereas the left eye shows faint resolving cotton-wool spots near the superotemporal arcade and inferior to the optic disc. C. Optical coherence tomography (OCT) of the right eye, showing multifocal inner nuclear layer hyper-reflectivity consistent with paracentral acute middle maculopathy (PAMM; green arrowheads) and focal retinal nerve fiber layer thickening consistent with a small cotton-wool spot (purple arrowhead). D. Fluorescein angiography of the right eye demonstrating patchy choroidal filling as well as darker patches of blockage from cotton-wool spots. E. Macular OCT 1 month later showing resolution of the PAMM lesions, replaced by focal thinning of the inner nuclear layer (green arrowheads).CASE 2 A 58-year-old white man with a history of focal segmental glomerulosclerosis, hypertension, hyperlipidemia, and coronary artery disease presented for evaluation of progressive, painless vision loss of the left eye. He had developed acute loss of vision in his inferior visual field, progressing over 2 weeks to involve his central vision and superior hemifield. He denied painful eye movements, jaw claudication, scalp tenderness, or frequent headaches. On exam, visual acuity was 20/20 by pinhole in the right eye and hand-motions in the left eye. The left pupil was sluggishly reactive and manifested a relative afferent pupillary defect. The fundus examination revealed a normal-appearing right optic disc with a cup-to-disc ratio of 0.1 and a left optic disc with 360-degree edema and a large flame-shaped hemorrhage inferiorly (Fig. 2A, B). No overt evidence of retinal arterial nonperfusion was observed. FA showed normal choroidal filling, leakage at the optic disc and low-grade leakage vs. staining at 2 foci inferonasal to the fovea in the left eye (Fig. 2C). OCT revealed the peripapillary RNFL to be normal in the right eye and grossly swollen in the left eye (Fig. 2D). A focal patch of INL hyper-reflectivity consistent with PAMM was observed in the nasal macula of the left eye (Fig. 2E).FIG. 2.: Concurrent anterior ischemic optic neuropathy and paracentral acute middle maculopathy in giant cell arteritis. A and B. Fundus photographs of the right (A) and left (B) eyes on initial presentation. The left eye exhibits optic disc edema with peripapillary hemorrhages. C. Fluorescein angiography of the left eye demonstrating leakage at the optic disc and at 2 small vessels inferonasal to the fovea. D. Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) of the left eye on initial presentation, demonstrating abnormal thickening in all quadrants. E. Macular OCT of the left eye on initial presentation, demonstrating inner nuclear layer hyper-reflectivity in the nasal macula, consistent with paracentral acute middle maculopathy (PAMM; green arrowhead). F. Repeat OCT of the RNFL 6 weeks later, demonstrating resolution of RNFL thickening and interval development of severe atrophy. G. Repeat macular OCT at 6 weeks, revealing resolution of the PAMM lesion, replaced by inner nuclear layer thinning and underlying expansion of the outer nuclear layer (green arrowhead).The apparent simultaneous optic nerve and retinal ischemia and the retinal vascular leakage in this patient raised concern for vasculitis. Magnetic resonance angiography showed no evidence of central nervous system vasculitis. ESR was elevated to 50 mm/h, whereas CRP was normal (0.14 mg/dL). Prednisone 60 mg/d was started and left temporal artery biopsy performed 1 week later. It revealed multifocal macrophage infiltration into the intima and tunica media with fragmentation of the elastic lamina, consistent with focal GCA responding to corticosteroid therapy. The patient was referred to rheumatology and his prednisone slowly tapered. Repeat OCT 5 weeks postoperatively revealed interval RNFL thinning and resolution of the previously observed area of PAMM, replaced by focal INL thinning (Fig. 2F, G). PAMM represents focal ischemia of the INL secondary to nonperfusion of the intermediate and deep capillary plexuses of the retinal circulation (2,3). It manifests on OCT as a small focus or broader band of INL hyper-reflectivity. Not a diagnosis in and of itself, PAMM has been associated with a number of conditions resulting in retinal microvascular hypoperfusion, such as nonproliferative diabetic retinopathy, sickle cell retinopathy, retinal vasculitis, inflammatory chorioretinopathies, Purtscher retinopathy, central retinal vein occlusion, and retinal artery occlusion (4). As a microvascular ischemic process, PAMM is analogous to the more frequently observed CWS, an infarction of the RNFL from nonperfusion of the superficial capillary plexus. Compared with CWS, the deeper PAMM lesions are duller-gray in color and less opaque, giving them a subtle appearance easily missed on funduscopy (3). As retinal infarcts, PAMM lesions are evanescent and may resolve with permanent focal thinning of the INL from loss of retinal neurons (2), as demonstrated by both our patients. Although reported once previously in a patient with a nondiagnostic temporal artery biopsy (5), our series is the first in which PAMM has been described in biopsy-proven GCA. Possible mechanistic explanations for PAMM (or CWS) in GCA include arteritic involvement of precapillary arterioles, microemboli from inflamed proximal retinal arteries, or capillary plexus endothelial injury. Long considered devoid of elastin, distal retinal arteries/arterioles were recently reported to immunolabel for elastin (6), raising the possibility of GCA-related immuno-reactivity against elastin within these vessels. In neither of our patients was PAMM an isolated finding, because both presented with well-described ocular manifestations of GCA—Patient 1 with numerous CWS and Patient 2 with anterior ischemic optic neuropathy. However, pursuing a diagnosis of GCA was nontrivial in these patients. Both of them denied classic GCA symptoms, such as temporal headache, jaw claudication, and scalp tenderness, and they also lacked significant elevations in serum inflammatory markers (entirely normal in Patient 1). Particularly in the case of Patient 2, the observation of concurrent acute PAMM decreased the likelihood that his optic disc edema simply represented the more common clinical entity of nonarteritic anterior ischemic optic neuropathy. Therefore, these cases highlight the importance of obtaining and carefully scrutinizing OCT imaging of patients with ocular ischemia. Identification of a subtle ischemic lesion such as PAMM affecting a separate vascular bed than a patient's predominant ocular pathology may strongly hint at the presence of an underlying systemic disease such as GCA. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S. M. Gospe and M. A. El-Dairi; b. Acquisition of data: S. M. Gospe and M. Hadziahmetovic; c. Analysis and interpretation of data: A. S. Ahuja, M. A. El-Dairi, M. Hadziahmetovic, and S. M. Gospe. Category 2: a. Drafting the manuscript: A. S. Ahuja and S. M. Gospe; b. Revising it for intellectual content: M. A. El-Dairi and M. Hadziahmetovic. Category 3: a. Final approval of the completed manuscript: A. S. Ahuja, M. A. El-Dairi, M. Hadziahmetovic, and S. M. Gospe.

Topics & Concepts