Acute Macular Neuroretinopathy Secondary to Rickettsia typhi Infection

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Acute Macular Neuroretinopathy Secondary to Rickettsia typhi Infection Humsini Viswanath, MPH, MS, Subahari Raviskanthan, MBBS, Peter W. Mortensen, MD, Helen K. Li, MD, Andrew G. Lee, MD A cute macular neuroretinopathy (AMN) is an uncommon but increasingly recognized condition characterized by an acute, painless, paracentral scotoma with a corresponding wedge-shaped retinal lesion pointing toward the fovea. Common associations include flu-like illness, oral contraceptives, sympathomimetics such as epinephrine and ephedrine, hypotension or shock, and pre-eclampsia (1–3). Optical coherence tomography (OCT) of the macula has dramatically improved clinicians’ ability to localize and identify the lesion and make a diagnosis. We report a case of AMN secondary to Rickettsia typhi infection. To the best of our knowledge, this is the first such case described in the English language ophthalmic literature. CASE REPORT A 30-year-old Caucasian woman presented and was seen by a neuro-ophthalmology team with a 2-week history of fever of 102°, nausea, vomiting, headache, neck pain, and dry cough. She had tested negative for COVID-19 on 4 occasions. Laboratory investigations were significant for a transaminitis, with ALT 909 U/L (normal 5–50 U/L) and AST 618 U/L (normal 10–35 U/L). The patient was treated with a course of oral azithromycin. After initial symptomatic improvement, fevers recurred, and she developed a perception of a “leaf-like image” in her left eye. She had no significant medical history, medications, or family history of disease. The patient was not on oral contraceptive, and she had no recent exposure to Texas A and M College of Medicine (HV, AGL), Bryan, Texas; Department of Ophthalmology (SR, PWM, HKL, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Community Retina Group (HKL), Houston, Texas; Departments of Ophthalmology (AGL), Neurology, and Neurosurgery, Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Department of Ophthalmology (AGL), the University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology—Blanton Eye Institute, Houston Methodist Hospital 6560 Fannin St. Ste 450 Houston, TX 77030; Email: aglee@ houstonmethodist.org Viswanath et al: J Neuro-Ophthalmol 2023; 43: e67-e69 over-the-counter medication. She was a former smoker and had alcohol consumption equivalent to 6 standard drinks a week. The patient had an outdoor cat and a dog, who had recently killed and brought an opossum into her house. She reported a recent flea infestation in her house. Visual acuity was 20/20 in both eyes. Pupils were isocoric without a relative afferent pupillary defect. The remainder of her eye examination was normal. No clinical abnormality was detected on funduscopy. Amsler grid testing revealed a wedgeshaped scotoma (Fig. 1A) corresponding with a discrete hyporeflective area seen on near-infrared imagery (Fig. 1B). Automated 24-2 automated perimetry did not show abnormalities. OCT revealed an attenuated outer nuclear layer and decreased prominence of the ellipsoid zone and interdigitation zone of the papillomacular bundle in the left eye (Fig. 1C) corresponding with the same area as the “leaf”-shaped scotoma in the left eye. Computerized tomography (CT) of the brain was performed to exclude a mass lesion or hydrocephalus as a cause of the symptoms. CT of the chest, abdomen, and pelvis was also performed in the emergency department as part of the sepsis workup given her multiple recurrent fevers without clear cause and abnormal liver function tests. MRI of the brain was also normal. Serum C-reactive protein was 0.54 mg/dL (normal 0– 0.50 mg/dL). Antinuclear antibody (ANA) was 1:80 in a speckled pattern, but the remainder of routine laboratory testing was negative. Rickettsia typhi titers were significantly elevated (IgG = 1:512 and IgM .1:1,024, normal ,1:64). The patient was treated with doxycycline for 14 days. At six-month follow-up, automated 10-2 field revealed scotoma at the temporal periphery (Fig. 2), which matched her persisted Amsler grid finding. No other abnormal findings were detected with examination and retinal angiogram. DISCUSSION AMN is an uncommon condition. It was first described by Bos and Deutman in 4 women (1). AMN is typically characterized by a wedge-shaped retinal lesion pointing toward the fovea, with paracentral scotomas, normal retinal vessels, optic disc, and nerve fiber (1,2). Infection, inflammation, and ischemia have all been implicated as cause of the vasculopathy (2). Deep capillary plexus of retina and inner choroid were suggested as the level of vasculopathy, but whether one or both levels are involved is unclear (3). e67 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. A. Patient’s depiction of her scotoma on an Amsler grid, showing a leaf-shaped paracentral scotoma. B. Near-infrared image showing dark gray leaf-shaped lesion with well-demarcated margins. C. Optical coherence tomography of the left eye showing an attenuated outer nuclear layer and decreased prominence of the ellipsoid zone and interdigitation zone of the papillomacular bundle in the left eye. In a review of 101 AMN cases, 47.5% of AMN cases were associated with a fever or flu-like illness (2). AMN with serology confirmed infection include dengue fever (4), influenza virus (5), and SARS-CoV-2 (6). No reported cases were associated with R. typhi or other rickettsial illnesses. Hudson et al reported 2 patients with R. typhi reporting blurriness and a “black spot” in their vision (7). On examination, intraretinal hemorrhages and retinal whitening were seen, suggestive of retinitis and neuroretinits, and one patient had optic nerve edema. In both patients, the symptoms and hemorrhages and retinal whitening resolved after treatment (7). In another case report, a series of 9 patients with R. typhi, 8 had bilateral ocular involvement with 3 having only ocular symptoms (8). Findings included vitreous inflammation, white retinal lesions, retinal vascular leakage, and optic disc swelling. Fundus changes completely disappeared within 8 weeks of initial examination (8). Rickettsial typhus retinitis is usually self-limiting with good visual outcomes. Retinal infiltrates may result from intraretinal multiplication or immune-mediated response (9). AMN was the only ocular finding in our patient. It is possible that AMN was the only ocular manifestation of her systemic infection or that other eye findings had already resolved. To the best of our knowledge, this is the first reported case of AMN in a patient with R. typhi infection. Clinicians should remain aware of AMN causing visual symptoms that can mimic retrobulbar optic neuropathy. In patients with fever and constitutional symptoms suggestive of infection, the possibility of rickettsial disease should be considered, including R. typhi. Serologic confirmation with IgM and IgG titers would confirm the diagnosis. Macular OCT and near-infrared imaging co-localize the retinal finding to make the diagnosis of AMN. STATEMENT OF AUTHORSHIP Conception and design: H. Viswanath, S. Raviskanthan, P. W. Mortensen, H. K. Li, A. G. Lee; Acquisition of data: H. Viswanath, S. Raviskanthan, P. W. Mortensen, H. K. Li, A. G. Lee; Analysis and interpretation of data: H. Viswanath, S. Raviskanthan, P. W. Mortensen, H. K. Li, A. G. Lee. Drafting the manuscript: H. Viswanath, S. Raviskanthan, P. W. Mortensen, H. K. Li, A. G. Lee; Revising it for intellectual content: H. Viswanath, S. Raviskanthan, P. W. Mortensen, H. K. Li, A. G. Lee. Final approval of the completed manuscript: H. 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