Age: 47.0
Sex: F
Vaccine: FLU3
Symptoms: Mycobacterium tuberculosis complex test negative, Ophthalmological examination normal, Optical coherence tomography abnormal, Plasma viscosity normal, Protein S normal
Clinical narrative: This is a serious literature case, initially received on 24-Dec-2018, concerning a 47-year-old, adult, female patient. The patient's current conditions included Raynaud's phenomenon, Barrett's oesophagus and herpes labialis. The patient's concomitant medications included ergocalciferol, omeprazole and valacyclovir for unknown indications. The patient denied use of over-the-counter flu medications or decongestants. On an unspecified date, the patient was administered FLUVIRIN (2016-2017 formula) (dose: 0.5 ml, route of administration; intramuscular, anatomical location, batch number and expiry date: not reported) for an unknown indication. On an unspecified date, nine days after vaccination, the patient developed a greyish central spot in her right eye. On examination, the patient's best-corrected visual acuity (BCVA) was 20/20 Snellen in both eyes. The anterior segment exam was unremarkable in either eyes. Fundus examination of her right eye revealed a few intraretinal blot haemorrhages along with pigment mottling and few drusen in the macula. The left eye was unremarkable except for a few macular drusen. A 24-2 Humphrey visual field (HVF) demonstrated a right supratemporal paracentral scotoma. On unspecified dates, chest X-ray and initial laboratory work-up including complete blood count, comprehensive metabolic panel, lipids and glycated haemoglobin (HbA1c) were normal. Hyperviscosity and hypercoagulability studies including protein electrophoresis, homocysteine, protein C/S, Factor V Leiden, and serum viscosity were also unremarkable. Inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anticardiolipin antibody, antiphospholipid III antibody, C and P anti-neutrophil cytoplasmic antibody (ANCA)] were within normal limits. Testing for syphilis [rapid plasma reagin test (RPR)], Bartonella, tuberculosis and human immunodeficiency virus (HIV) were negative. On an unspecified date, the patient underwent fluorescein angiogram which demonstrated normal transit times and changes consistent with mild vasculitis with late optic nerve staining and peripheral perivascular leakage in the right eye. Indocyanine green angiography and B-scan ultrasonography were normal. On an unspecified date, the patient underwent spectral-domain optical coherence tomography (SD-OCT), 4 days after the onset of symptoms, which showed diffuse hyper-reflectivity of the outer plexiform layer (OPL), Henle's layer and the outer nuclear layer (ONL) at and nasal to the fovea. Near-infrared imaging of the right eye on presentation showed a well demarcated wedge-shaped hypo-reflective macular lesion involving the fovea. SD-OCT through the affected area revealed thinning of the ONL and disruption of the ellipsoid zone (EZ) and interdigitation zone (IZ). The findings of early hyper-reflectivity of the OPL and ONL followed later by thinning of the ONL and disruption of the EZ/IZ are consistent with acute macular neuroretinopathy (AMN). On an unspecified date, the patient underwent projection resolved -optical coherence tomography angiography (PR-OCTA). PR-OCTA B-scans with flow overlay through the AMN lesion demonstrated attenuation of flow signal at the level of the deep capillary plexus (DCP), which is located at the junction between the inner nuclear layer and the OPL. On an unspecified date, at her 3-week follow-up, BCVA remained 20/20 Snellen in both eyes but she continued to complain of a right paracentral scotoma. Fundus examination showed near resolution of the few scattered intraretinal blot haemorrhages and repeat SD-OCT demonstrated similar thinning of the ONL but with some restoration of the EZ/IZ. OCTA B-scans, as well as PR-OCTA, revealed persistent decrease but relatively improved flow signal in the DCP compared to the initial scan suggesting partial reperfusion of the DCP (recovering). At the time of this report, the patient was recovering from the event. The reporter assessed the causality of the event AMN as related to the suspect vaccine (as extensive laboratory testing excluded other infectious, immunologic, or hypercoagulable aetiologies, and the timing of complications 9 days following vaccination, point towards an association between influenza vaccination and the ocular findings in our patient). Reporter's Comments: A 47-year-old female patient with concurrent Herpes labialis infection experienced visual symptoms (greyish central spot in right eye), 9 days after receipt of Fluvirin vaccine which was eventually diagnosed as acute macular neuroretinopathy of right eye. The diagnosis were supported by abnormal fundoscopy, fluorescein angiography, optical coherence tomography, Humphrey visual field tests and PR-OCTA B-scans. Although, the etiology of the event is unknown, inflammatory and immune vascular mechanisms are postulated. Considering the plausible temporal relationship between vaccination and reported event, the causal role of suspect vaccine cannot be ruled out. Hence, company assessed the event acute macular neuroretinopathy as possibly related to suspect vaccine. However, underlying viral infection (Herpes labialis) is considered as risk factor. The company assessed the case as serious (medically significant).