Sex: M
Vaccine: MEN, YF
Symptoms: Activated partial thromboplastin time ratio normal, Angiogram abnormal, Balance disorder, Diarrhoea, Eye pain
Clinical narrative: Initial unsolicited report received from literature on 20-Mar-2018 and additional information received on 22-Mar-2018. Abstract: Purpose: To describe a case of small retinal vessel vasculopathy post-vaccination. Methods: We report the case of a 41-year-old man who presented with a "second blind spot," describing a nasal scotoma in the right eye that started 4 days after vaccinations against Neisseria meningitides and the yellow fever virus, and after a 2-month period of high stress and decreased sleep. Clinical examination, Humphrey visual field testing, and multimodal imaging with fundus photographs, auto fluorescence, fluorescein angiography, and spectral domain optical coherence tomography and angiography were performed. Results: Clinical examination revealed a well-circumscribed, triangular area of retinal graying of about 1-disk diameter in size, located at the border of the temporal macula. This corresponded to a deep scotoma similar in size to the physiologic blind spot on Humphrey visual field 24-2 testing. There was mild hypoautofluoresence of this lesion on auto fluorescence, hypofluorescence on fluorescein angiography, and focal attenuation of a small artery just distal to the bifurcation of an artery supplying the involved area. Spectral domain optical coherence tomography through the lesion conveyed hyper reflectivity most prominent in the inner and outer plexiform layers, with extension of the hyper reflectivity into the ganglion cell and inner nuclear layers. Spectral domain optical coherence tomography angiography demonstrated arteriolar and capillary dropout, more pronounced in the superficial retinal layer compared to the deeper retinal layer. At 1-month follow-up, his scotoma improved with monitoring, with reduction from 32 dB to 7 dB on Humphrey visual field testing. There was clinical resolution of the area of graying and decreased hyper reflectivity on spectral domain optical coherence tomography, with atrophy of the inner retina. Spectral domain optical coherence tomography angiography showed progression of arteriolar and capillary dropout, more so in the superficial than in the deep capillary plexus. Conclusion: We describe a case of small artery occlusion in a previously healthy patient, 4 days after vaccination against N. meningitides and yellow fever. Fluorescein angiography yielded greater diagnostic value than OCTA for evaluating the occlusion, whereas spectral domain optical coherence tomography angiography enabled better visualization of capillary dropout and layer-specific assessment. Further research is required to determine whether vaccination in general, or directed specifically at N. meningitides or yellow fever, is associated with small vessel vasculopathy and the underlying pathogenesis. This case involves 41-year-old male patient who was vaccinated with a dose of MENINGOCOCCAL VACCINE and YELLOW FEVER VACCINE (Batch number, expiration date, dose, route and site of administration was not reported) on an unspecified date. The patient's medical history was remarkable for first-degree atrioventricular block with prolonged QT interval, and surgical history significant only for a ventral hernia repair 15 months before. He had a 5-pack-year history of ongoing cigarette smoking, drinking alcohol occasionally, and he had denied other drug use. Review of systems was notable for diffuse, generalized headaches for the past 2 months as well as occasional, 10- to 15-minute episodes of disequilibrium. Concomitant medications were not reported. On an unspecified date, four days following the vaccination, the patient experienced sudden onset of a scotoma in the nasal portion of his visual field of the right eye, which began 6 days before (presentation to reporter) along with small retinal vessel vasculopathy. On an unspecified date, post vaccination, the patient had non-hemorrhagic diarrhea (patient complaint for the past three days and denied other systemic symptoms.). It was reported that, the scotoma was as similar in size to his physiologic blind spot and he noted that it was constant and had not changed in size or character since onset. On an unspecified date, post vaccination, the patient had mild ocular pain with movement and retro bulbar ache in the right eye. It was also reported that review of systems was notable for diffuse, generalized headaches for the past 2 months as well as occasional, 10 to 15-minute episodes of disequilibrium, but not frank vertigo. Patient also also described 2 months of high stress at work and significantly decreased sleep over that time period. His best-corrected visual acuity was 20/20 in the right and left eyes. Red saturation was equal in the right and left eyes, and Ishihara color plates were 8/8 in the right and left eyes. Dilated fundus examination revealed a well-circumscribed area of graying in the temporal border of the macula in the right eye of about 1-disk diameter in size and mild tortuosity of the retinal vessels in both eyes. There was mild hypoautofluoresence corresponding to the lesion. Fluorescein angiography (Spectralis) revealed normal transit time and choroid filling and conveyed hypo fluorescence corresponding to the lesion starting with choroidal filling phase and most prominent by the time of laminar venous flow. Higher magnification revealed stenosis of a small artery at the bifurcation of the vessels supplying the area of the lesion. Spectral domain optical coherence tomography through the lesion showed hyper reflectivity throughout the inner retina, most prominent in the inner plexiform and outer plexiform layers, although there was extension of the hyper reflectivity into the ganglion cell layer and inner nuclear layer as well. There was vitreomacular adhesion just nasal to the lesion without traction, as well as hypo reflectivity of the outer retina deep to the hyper reflectivity, likely due to shadowing. The hyper reflectivity was confined to the lesion on the en face slabs, beginning in the SRL and most pronounced in the DRL, and with faint hyper reflectivity noted in the avascular retina segment (deep outer nuclear layer to the external limiting membrane) without involvement in the deeper layers. Laboratory workup showed a normal basic metabolic panel, complete blood count, prothrombin time, and partial Thromboplastin time. Magnetic resonance imaging of his brain and orbits with and without contrast, which was ordered to evaluate his persistent headaches and disequilibrium, was normal, specifically with no evidence of retro bulbar optic neuritis. It was also reported that at one-month follow-up, he noted reduction in the degree of his scotoma and resolution of his headaches with an over the counter antihistamine. After that as compared with initial presentation, SD-OCTA showed more pronounced arteriolar and capillary network dropout supplied at the small artery bifurcation into the area of the lesion; this vascular dropout was most prominent in the superficial capillary plexus of the SRL, though also noted in the deep capillary plexus of the DRL. There was marked reduction in the hyper reflectivity on structural en face imaging, again most prominent in the DRL. Patient was recovering from nasal scotoma in the right eye (second blind spot). The patient's other event outcome was not reported. Upon internal review, the company decided to consider the event serious because of important medical event retinal vascular disorder. List of documents held by sender: none.; Sender's Comments: This case concerns a literature article describing an adult patient who was detected with retinal vascular disorder 4 days after vaccination with Meningococcal and Yellow Fever vaccines. The time to onset is compatible with the role of vaccines. However, patient's ophthalmic condition at the time of vaccination was not provided. The history of smoking is a possible confounding factor for this event. Moreover, presence of an ongoing long-term headache points towards a pre-existing vascular or cranial etiology in existence at the time of vaccination. Based upon the reported information, the role of the vaccines cannot be assessed.