A Case of Post-COVID-19-Associated Paracentral Acute Middle Maculopathy and Giant Cell Arteritis-Like Vasculitis

A 47-year-old man with a history of COVID-19 infection 2 months before presentation, presented with a scotoma of the paracentral visual field of the right eye. After thorough testing and evaluation, a diagnosis of paracentral acute middle maculopathy (PAMM) was established. Two months later, the patient developed temporal headache and jaw claudication. High-dose steroids were initiated, and workup for giant cell arteritis (GCA) was undertaken. The patient experienced resolution of the symptoms within 24 hours of steroid initiation. ESR, CRP, and temporal artery biopsy results were normal, although all were obtained more than 2 weeks after steroid initiation. To the best of our knowledge, our patient represents the first individual to date to potentially implicate COVID-19 in both small and large vessel vasculitis in the ophthalmic setting.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD A Case of Post-COVID-19–Associated Paracentral Acute Middle Maculopathy and Giant Cell Arteritis-Like Vasculitis Go L. Jonathan, DO, Fair M. Scott, DO, Kay D. Matthew, MD Abstract: A 47-year-old man with a history of COVID-19 infection 2 months before presentation, presented with a scotoma of the paracentral visual field of the right eye. After thorough testing and evaluation, a diagnosis of paracentral acute middle maculopathy (PAMM) was established. Two months later, the patient developed temporal headache and jaw claudication. High-dose steroids were initiated, and workup for giant cell arteritis (GCA) was undertaken. The patient experienced resolution of the symptoms within 24 hours of steroid initiation. ESR, CRP, and temporal artery biopsy results were normal, although all were obtained more than 2 weeks after steroid initiation. To the best of our knowledge, our patient represents the first individual to date to potentially implicate COVID-19 in both small and large vessel vasculitis in the ophthalmic setting. Journal of Neuro-Ophthalmology 2021;41:351–355 doi: 10.1097/WNO.0000000000001348 © 2021 by North American Neuro-Ophthalmology Society whitening corresponding to the location of the scotoma was found on posterior examination of the right eye. Optical coherence tomography (OCT), fluorescein angiography, and fundus autofluorescence studies were obtained. OCT macula of the right eye demonstrated a focal area of inner retinal hyperreflectivity from the level of the inner plexiform layer (IPL) to the outer plexiform layer (OPL), consistent with a diagnosis of paracentral acute middle maculopathy (PAMM). Fundus autofluorescence demonstrated an area of hypoautofluorescence and fluorescein angiogram demonstrated an area of relative hypofluorescence, both findings corresponding to the lesion on posterior segment examination. A diagnosis of PAMM was made at this time. Two months later, the patient developed a temporal headache and jaw claudication. High-dose steroids were OBJECTIVES T o describe a case of COVID-19-associated paracentral acute middle maculopathy and giant cell arteritis (GCA)-like vasculitis. OBSERVATIONS A 47-year-old man with a history of COVID-19 infection 2 months before presentation, presented with a scotoma of the paracentral visual field of the right eye. An area of retinal Department of Ophthalmology, Larkin Community Hospital, South Miami, Florida. The authors report no conflicts of interest. Address correspondence to Matthew D. Kay, MD, Larkin Community Hospital, 7031 SW 62nd Avenue, South Miami, FL 33143; E-mail: [e-mail] Jonathan et al: J Neuro-Ophthalmol 2021; 41: 351-355 FIG. 1. Fundus photograph of the right eye with the white arrow demonstrating a focal area of superotemporal parafoveal retinal whitening. 351 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. Optical coherence tomography macula of the right eye with the black arrow demonstrating a focal area of inner retinal hyperreflectivity from the level of the inner plexiform layer extending to the outer plexiform layer, consistent with a diagnosis of paracentral acute middle maculopathy. initiated because there was a significant concern for GCA. The patient experienced resolution of the symptoms within 24 hours of steroid initiation. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests were obtained and were both within normal limits. Nonetheless, a temporal artery biopsy (TAB) was still pursued given the overwhelmingly characteristic presentation consistent with GCA. The TAB also returned negative; however, it is important to note that at the time of obtaining all diagnostic studies, the patient had been on high-dose steroids for at least 2 weeks. Tocilizumab therapy has been initiated, and rheumatology is continuing to manage the steroid taper. RESULTS AND CONCLUSIONS To the best of our knowledge, our patient represents the first individual to date to potentially implicate COVID-19 in both small and large vessel vasculitis in the ophthalmic setting. COVID-19 has demonstrated associations with 352 both large and small vessel vasculitic pathology throughout the body. It is thus possible that the inflammation of the medium-sized to large-sized arteries implicated in GCA and the small capillaries of the deep capillary plexus implicated in PAMM, may both be caused by underlying vasculitic sequelae of infection with the COVID-19 virus. A 47-year-old man presented to a community eye clinic complaining of a 2-day history of a new blind spot described as a “firefly” located in the visual field of his right eye, at approximately the 7-o’clock position of the paracentral visual field. The patient had a medical history of COVID-19 infection 2 months before presentation, with a persistent positive polymerase chain reaction test and with a ocular history of laser-assisted in situ keratomileusis (LASIK) procedure in both eyes. Otherwise, the patient was healthy and denied any history of diabetes, hypertension, rheumatologic disease, steroid use, or any other drugs or medications. Jonathan et al: J Neuro-Ophthalmol 2021; 41: 351-355 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 3. Fundus autofluorescence of the right eye with the black arrow demonstrating an area of hypoautofluorescence corresponding to the lesion on examination. FIG. 4. Fluorescein angiogram of the right eye with the black arrow demonstrating an area of hypofluorescence corresponding to the lesion on examination. Visual acuity at this time was 20/20 in both eyes. There was no afferent pupillary defect. Confrontational visual fields were normal at this time. Kinetic tonometry demonstrated pressures of 14 mm of mercury (mm Hg) in the right eye and 13 mm Hg in the left eye. Anterior segment examination was unremarkable with the exception of LASIK flaps in both eyes. Posterior segment examination was significant for a superotemporal parafoveal area of retinal whitening in the right eye (Fig. 1). The differential diagnosis at this juncture included PAMM, acute macular neuroretinopathy (AMN), cotton wool spot, exudation, solar retinopathy, and artifactual finding. An OCT study, fluorescein angiogram, and a fundus autofluorescence study were obtained (Figs. 2–4). OCT macula of the right eye demonstrated a focal area of inner retinal hyperreflectivity from the level of the IPL to the OPL, consistent with a diagnosis of PAMM. Fundus autofluorescence demonstrated an area of hypoautofluorescence and fluorescein angiogram demonstrated an area of relative hypofluorescence, both findings corresponding to the lesion on posterior segment examination. At this time, a diagnosis of PAMM was made. Out of an abundance of caution and considering the lack of any previous cardiovascular history in this patient, the patient was sent to his primary care doctor for further cardiovascular evaluation with the intention of ruling out any source of emboli. All workup including carotid ultrasound and echocardiogram were negative. Our patient continued follow-up over the next 2 months with slight improvement of OCT findings but no subjective improvement of the scotoma in the right eye. Two months after initial presentation (now 4 months after initial COVID-19 infection), our patient began experiencing right-sided temporal scalp pain and tenderness. The patient also complained of a dull ache around his jaw in the region of the muscles of mastication. He did not experience any episodes of amaurosis fugax, myalgias, fever, or weight loss. The patient sought medical attention at an urgent care, where he was given a 6-day course of methylprednisolone, with his temporal pain immediately subsiding within hours of his initial steroid dose. After completion of the course of methylprednisolone, his headache and scalp tenderness returned within 24 hours. The patient spoke to his family physician who gave him a 1-week course of prednisone 60 mg daily, which resolved his symptoms. Examination on presentation to our care was normal with the exception of tenderness to palpation of the right temporal region. The patient was promptly referred for neuro-ophthalmic consultation. Neuro-ophthalmic examination was normal with normal color vision, no afferent pupillary defect normal 242 Humphrey visual field, normal ocular motility, and normal posterior examination. There was exquisite focal right temporal tenderness without cord formation and preservation of temporal artery pulse bilaterally. OCT continued to demonstrate inner retinal hyperreflectivity corresponding to the lesion that was no longer visible on posterior segment examination. Although the young age of 47 years is inconsistent with the typical age of presentation of GCA, the symptomatology was so overwhelmingly suggestive of the disease that workup was initiated. An ESR, CRP and a complete blood cell count with platelets were obtained and were all within normal limits. Nonetheless, a TAB was still pursued given the overwhelmingly characteristic presentation consistent with GCA. The TAB Jonathan et al: J Neuro-Ophthalmol 2021; 41: 351-355 353 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution also returned negative; however, it is important to note that at the time of obtaining all diagnostic studies, the patient had been on high-dose steroids for at least 2 weeks. Our patient has since established care with rheumatology, who initiated tocilizumab therapy. Although steroid taper has been attempted twice, the patient complains of flaring of temporal pain and tenderness whenever taper to 40 mg/day has been attempted. Our patient’s scotomas are still without subjective change and OCT findings still persist, although are slightly less hyperreflective. DISCUSSION We present in this article a case of PAMM and GCA-like vasculitis in association with COVID-19 infection. To the best of our knowledge, this is the first COVID-19-related case with potentially both PAMM and GCA-like symptomatology presenting in the same individual. We conducted a MEDLINE search using the PubMed database (National Library of Medicine) through January 4, 2021. Various combinations of keywords were used, including COVID-19 and vasculitis, temporal arteritis, GCA, neuroretinitis, maculopathy, macula, macular neuroretinitis, AMN, and PAMM. Our systematic review of the literature revealed 4 articles of unique pertinence to our case. The first was a series of 2 case reports from Virgo et al. (1) In one case, a patient developed PAMM roughly 35 days after initial COVID19 infection, and in another case, a patient developed AMN roughly 16 days after initial COVID-19 infection. Authors report characteristic hyperreflective inner and outer plexiform layers consistent with PAMM and hyperreflective change of the OPL consistent with AMN (1). Gascon et al also reported on a case of PAMM/AMN in a 53-year-old presenting with scotoma and dyschromatopsia 8 days after initial COVID-19 infection (2). Quintana-Castenedo et al reported on a case of retinal vasculitis in an 11-year-old patient who presented with chilblains and COVID-19 positivity, although was otherwise asymptomatic (3). Finally, Riera-Marti et al reported on a patient who had GCA-like symptomatology with a positive halo sign of the temporal artery on ultrasound and slightly increased FDG-PET uptake of the abdominal aorta, but negative ESR, CRP, and with resolution of temporal pain spontaneously without any corticosteroid therapy (4). COVID-19 has been shown to play a role in thrombosis and endothelial pathology involving arteries, veins, arterioles, venules, and capillaries throughout the body (5). There are many proposed mechanisms in the rapidly evolving literature, but Becker et al provide a nice summary of some proposed mechanisms. Numerous metabolic and chemical products of inflammation may go on to target and damage endothelial cells. Extracellular histones are cytotoxic to the microcirculatory endothelium and can be increased in proinflammatory states. Furthermore, neutrophilic activa354 tion can damage the endothelial glycocalyx (6). Finally, COVID-19 has demonstrated its vasculopathic mechanisms of action in diseases such as Kawasaki-like disease and multisystemic inflammatory disease in children (6). The associations between COVID-19 infection and a wide variety of vasculitic pathologies outside of Kawasakilike disease and multisystemic inflammatory disease are mounting. There have been numerous articles linking ANCA-associated vasculitis with new COVID-19 infections (7,8). AlGhoozi et al reported on a case of HenochSchonlein purpura secondary to COVID-19 infection (9). Bressler et al reported on a case of new onset granulomatosis with polyangiitis associated with COVID-19 infection (10). Vasculitic etiology for neurologic sequelae of COVID-19 infection has also been documented (11,12). Small vessel vasculitis has also been implicated in dermatological manifestations of COVID-19 (13,14). COVID-19 has demonstrated associations with both large and small vessel vasculitic pathology throughout the body (5–14). It is thus possible that the inflammation of the medium-sized to large-sized arteries implicated in GCA and the small capillaries of the deep capillary plexus implicated in PAMM may both be caused by underlying vasculitic sequelae of infection with the COVID-19 virus. To the best of our knowledge, our patient represents the first individual to date to potentially implicate COVID-19 in both small and large vessel vasculitis in the ophthalmic setting. 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