Paracentral Acute Middle Maculopathy Associated With Anterior Ischemic Optic Neuropathy and Cilioretinal Artery Occlusion in Giant Cell Arteritis

Paracentral acute middle maculopathy (PAMM) is a relatively new optical coherence tomography finding, defined by hyperreflectivity in the inner nuclear layer. In this article, we present a case of a 73-year-old woman who presented with transient vision loss followed by the sudden onset of complete vision loss to counting fingers at 1 foot for one day in the left eye. Dilated examination showed a right cotton wool spot, left pallid optic disc edema, and retinal edema in the distribution of the cilioretinal artery. OCT demonstrated hyperreflective band at the level of the inner nuclear layer, compatible with PAMM. Clinical and laboratory findings were consistent with GCA, for which she was prescribed high-dose oral prednisone, with confirmation of GCA on a subsequent temporal artery biopsy. PAMM may be seen in the context of GCA, and OCT of the macula serves as an important adjunct to define the retinal manifestations of this condition.

Photo and Video Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Paracentral Acute Middle Maculopathy Associated With Anterior Ischemic Optic Neuropathy and Cilioretinal Artery Occlusion in Giant Cell Arteritis Michelle Kasimov, BSc(C), Marko M. Popovic, MD MPH(C), Jonathan A. Micieli, MD, CM, FRCSC FIG. 1. A. Fundus photography demonstrating a single peripapillary cotton wool spot at the level of the superior arcade (right eye) and chalky white optic disc edema and whitening around the distribution of the cilioretinal artery (left eye). B. Intravenous fluorescein angiography of early, mid, and late phases demonstrating delayed choroidal filling, markedly delayed filling in the left cilioretinal artery, and leakage from the optic disc in the left eye. Abstract: Paracentral acute middle maculopathy (PAMM) is a relatively new optical coherence tomography finding, defined by hyperreflectivity in the inner nuclear layer. In this article, we present a case of a 73-year-old woman who presented with transient vision loss followed by the sudden onset of complete vision loss to counting fingers at 1 foot for one day in the left eye. Dilated examination showed a right cotton wool spot, left pallid optic disc edema, and retinal edema in the distribution of the cilioretinal artery. Faculty of Health (MK), York University, Toronto, Ontario, Canada; Department of Ophthalmology and Vision Sciences (MMP, JAM), University of Toronto, Toronto, Ontario, Canada; Kensington Vision and Research Centre (JAM), Toronto, Ontario, Canada; and Department of Ophthalmology (JAM), St. Michael’s Hospital/Unity Health Toronto, Toronto, Ontario, Canada. M. M. Popovic: PSI Foundation—financial support (to institution). The authors report no conflicts of interest. Address correspondence to Jonathan A. Micieli, MD, CM, FRCSC, Kensington Vision and Research Centre 340 College Street, Suite 501 Toronto, ON, Canada M5T 3A9; E-mail: jmicieli@kensingtonhealth. org Kasimov et al: J Neuro-Ophthalmol 2022; 42: e437-e439 OCT demonstrated hyperreflective band at the level of the inner nuclear layer, compatible with PAMM. Clinical and laboratory findings were consistent with GCA, for which she was prescribed high-dose oral prednisone, with confirmation of GCA on a subsequent temporal artery biopsy. PAMM may be seen in the context of GCA, and OCT of the macula serves as an important adjunct to define the retinal manifestations of this condition. Journal of Neuro-Ophthalmology 2022;42:e437–e439 doi: 10.1097/WNO.0000000000001306 © 2021 by North American Neuro-Ophthalmology Society A 73-year-old woman presented to the emergency department with severe vision loss in the left eye. This was preceded by 10 days of transient vision loss in the left eye that occurred multiple times per day lasting a few minutes. She also reported jaw claudication and decreased appetite during those 10 days. The patient was otherwise healthy and did not take regular medications. e437 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay Examination revealed a visual acuity of 20/20 in the right eye and counting fingers at 1 foot in the left eye with a left relative afferent pupillary defect. Dilated fundus examination revealed a cotton wool spot superiorly in the right eye and pallid optic disc edema and retinal edema in the distribution of the cilioretinal artery in the left eye (Fig. 1A). Intravenous fluorescein angiography showed delayed choroidal filling, markedly delayed filling in the left cilioretinal artery, and leakage from the optic disc in the left eye (Fig. 1B). Optical coherence tomography showed hyperreflectivity in the inner retina in the distribution of the cilioretinal artery (Fig. 2A). More peripheral to this area in the paracentral retina, there was a hyperreflective band at the level of the inner nuclear layer, compatible with PAMM (Fig. 2B). Because of a concern for giant cell arteritis, inflammatory blood markers were obtained. At presentation, she had a hemoglobin count of 105 g/L, platelets of 422 · 109/L, ESR of 97 mm/hr, and CRP of 116.1 mg/L (normal less than 5). She was prescribed high-dose corticosteroids, and a temporal artery biopsy was obtained, which showed an inflammatory cell infiltrate involving all 3 layers of the artery consisting of lymphocytes, macrophages, and multinucleated giant cells. She was continued on oral prednisone after the confirmation of the diagnosis of GCA. Her symptoms resolved, and her inflammatory blood markers returned to normal over the next several weeks. Follow-up 1 month later revealed a significantly improved central vision in the left eye (20/30), but a persistent paracentral and nasal visual field defect. PAMM is characterized on OCT as a hyperreflective band at the level of the inner nuclear layer (INL), representing an INL infarction due to impaired perfusion of the deep retinal capillary plexus (1). PAMM is not visible with IVFA because it does not provide sufficient depth resolution and does not adequately illustrate the deep vascular plexus (1). The most commonly described associations with PAMM include primary retinal vascular diseases, such as central retinal vein occlusion, hypercoagulable states, iatrogenic complications from procedures, or medication side effects (2). We were able to retrieve one previous report of PAMM in the context of GCA associated with an immune checkpoint inhibitor. This was in an 86-year-old man with a history of treated choroidal melanoma and metastatic uveal melanoma for which he was receiving pembrolizumab, presented with acute vision loss to the uninvolved eye. Although he denied other symptoms of GCA, a temporal artery biopsy confirmed the diagnosis. In the eye affected by GCA, there was also hyperreflectivity in the middle retinal layers characteristic of PAMM (3). Anterior ischemic optic neuropathy associated with a cilioretinal artery occlusion (CilRAO) is highly characteristic of a vasculitis such as GCA (4). The blood supply to the optic nerve head is from the posterior ciliary arteries and peripapillary choroid, whereas the cilioretinal artery is an anatomic variant that arises from this system. PAMM has been associated with CilRAO (4). A study by Pichi et al (5) examined 53 cases of CilRAO and found PAMM in 28 patients with isolated CilRAO and in 23 other patients with CilRAO associated with central retinal vein occlusion (CRVO). Interestingly, the last 2 patients presented with CilRAO secondary to GCA but did not have PAMM. The authors hypothesized that PAMM caused by CilRAO may represent the first stage of an ischemic cascade in the retinal capillary plexus that leads to a regional infarction of the inner nuclear layer. Besides GCA, other types of vasculitis have been associated with PAMM. For instance, a 10-year-old boy from the United States presented with a 1-week duration of vision loss after having been diagnosed with influenza A (6). He was later found to have PAMM in the context of influenza-induced leukocytoclastic vasculitis. A 27-year-old man from India was diagnosed with PAMM 2 years after being initially diagnosed with idiopathic cutaneous leukocytoclastic vasculitis that was controlled with colchicine (7). Although he did not have any visual symptoms, a recurrent rash and abdominal pain led to a systemic workup that included a dilated fundus examination which revealed signs of a CRVO, with an OCT scan confirming PAMM. A 36year-old Brazilian woman presented with a central scotoma FIG. 2. A. Swept-source optical coherence tomography image of the left eye, demonstrating a hyperreflectivity in the retinal nerve fiber layer and a band at the level of the inner nuclear layer, compatible with paracentral acute middle maculopathy. B. Just superior (top panel) and inferior (bottom panel) to the cilioretinal artery occlusion there was isolated hyperreflectivity of the inner nuclear layer due to paracentral acute middle maculopathy. e438 Kasimov et al: J Neuro-Ophthalmol 2022; 42: e437-e439 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay of her right eye and floaters in the left eye that lasted approximately one week. An OCT scan confirmed PAMM associated with acute occlusive retinal vasculitis (8). Finally, a 35-year-old Australian woman presented with sudden vision loss in the right eye and multiple cotton wool spots around the right macula and optic disc. She was diagnosed with PAMM secondary to retinal arteriole vasculitis in the context of Susac syndrome (i.e., retinocochleocerebral vasculopathy) (9). 3. 4. 5. CONCLUSION This is a rare case of a patient with GCA and PAMM patient with GCA and PAMM in the same eye. In a patient with GCA, this is the first case that demonstrates PAMM secondary to cilioretinal artery occlusion. Further work should be conducted exploring the pathophysiology and significance of PAMM in patients with GCA. REFERENCES 1. Scharf J, Freund KB, Sadda S, Sarraf D. Paracentral acute middle maculopathy and the organization of the retinal capillary plexuses. Prog Retin Eye Res. 2020:100884. doi:10.1016/ j.preteyeres.2020.100884. Epub ahead of print. PMID: 32783959. 2. Moura-Coelho N, Gaspar T, Ferreira JT, Dutra-Medeiros M, Cunha JP. Paracentral acute middle maculopathy – review of the Kasimov et al: J Neuro-Ophthalmol 2022; 42: e437-e439 6. 7. 8. 9. literature. Graefes Arch Clinc Exp Ophthalmol.. 2020. doi:10.1007/s00417-020-04826-1. Narala R, Reddy SA, Mruthyunjaya P. Giant cell arteritis manifesting as retinal arterial occlusion and paracentral acute middle maculopathy in a patient on pembrolizumab for metastatic uveal melanoma. Am J Ophthalmol Case Rep. 2020;20:100891. Hayreh SS. Acute retinal arterial occlusive disorders. Prog Retin Eye Res. 2011;30:359–394. Pichi F, Fragiotta S, Freund KB, Au A, Lembo A, Nucci P, Sebastiani S, Gutierrez Hernandez JC, Interlandi E, Pellegrini F, Dolz-Marco R, Gallego-Pinazo R, OrellanaRios J, Adatia FA, Munro M, Abboud EB, Ghazi N, Cunha Souza E, Amer R, Neri P, Sarraf D. Cilioretinal artery hypoperfusion and its association with paracentral acute middle maculopathy. Br J Ophthalmol. 2019;103:1137–1145. Shield RA, Oska SR, Farley ND, Randhawa S. Influenza-induced acute macular neuroretinopathy with cerebral involvement in a ten-year-old boy. Opthalmic Surg Lasers Imaging Retina. 2020;51:293–297. Akhavanrezayat A, Hien DL, Pham BH, Nguyen HV, Tuong Ngoc TT, Al-Moujahed A, Uludag G, Karkhur S, Doan HL, Nguyen QD. Impending central retinal vein occlusion in patient with idiopathic cutaneous leukocytoclastic vasculitis. Am J Ophthalmol Case Rep. 2020;20:100934. Chen X, Rahimy E, Sergott RC, Nunes RP, Souza EC, Choudhry N, Cutler NE, Houston SK, Munk MR, Fawzi AA, Mehta S, Hubschman JP, Ho AC, Sarraf D. Spectrum of retinal vascular diseases associated with paracentral acute middle maculopathy. Am J Ophthalmol. 2015;160:26–34.e1. Haider AS, Viswanathan D, Williams D, Davies P. Paracentral acute middle maculopathy in susac syndrome. Retin Cases Brief Rep. 2020;14:150–156. e439 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.