Evidence dossier · candidate cand-covid-optic-neuritis · CICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that COVID-19 vaccine causes Optic Neuritis, and not an incidence or legal finding. All evidence is flagged needs_human_review and must be reviewed before any page is published or cited. Every value is grounded in retrieved citations (PMID + retrieval date); unsourced items read "no evidence found / not assessable". Symmetric search: every supporting query has a mirror/null query, and zeros are shown (negative dossiers report the absence of signal).
Claim matrix (C1–C6, computed)
Claim
Label
Status
Missing nodes
C1
Coherent clinical object exists
supported
C2
Consistent temporal window
supported
C3
Epidemiologic excess risk
insufficient_data
missing: B1 B2
C4
Consistency / replication
insufficient_data
missing: B5
C5
Specificity (product / dose)
supported
C6
Biological mechanism
insufficient_data
missing: E1
Two evidentiary bars apply to the epi nodes/claims (C3, C4): · VICP — preponderance of the evidence. · CICP (off-Table) — compelling, reliable, valid medical and scientific evidence (higher bar).
Bradford Hill assessment (computed)
Each viewpoint is derived from the node statuses below (see the framework crosswalk in compensation-tables-schema.md §8). Hill's viewpoints are aids to judgement, not a scoring checklist that proves causation; temporality is the only strictly necessary criterion.
Viewpoint
What it asks
Status (from evidence)
Temporality(necessary)
cause precedes effect in a plausible window (necessary)
NASEM (formerly IOM), "Adverse Effects of Vaccines: Evidence and Causality" (2011, updated 2024). Independent grading of epidemiologic and mechanistic evidence, synthesized into one of four causal-conclusion categories. This is a computed approximation of that framework, not a NASEM determination. See compensation-tables-schema.md §8bis.
Case-definition standard: no established case definition (needs_human_review — not in spec §1's named-standard list) — governs the case-certainty scale on A1/A2/A6/A8 below. See compensation-tables-schema.md §8ter.
Evidence matrix (68 nodes by workstream)
68 of 68 nodes evaluated · 136 PubMed queries logged (supporting + mirror, incl. zeros). Statuses are computed from retrieved citations; not hand-set.
Definition & attribution 24/24 evaluated
A1 · Case reportssupports
Measure: New definite object in risk window T Comparator: Pre-vaccination baseline Hit rule: Definite object present, onset in window, competing causes considered
Finding: Multiple case reports and case series describe optic neuritis occurring within days to weeks after COVID-19 vaccination, with some cases assessed for competing causes such as demyelinating disease or serostatus, though causality is not confirmed.
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Case reports pubmed · 66201 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
18 retrieved record(s)
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
ambiguous 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
ambiguous 35020705 · Journal of neuro-ophthalmology : the off (2023) — Case Series: Atypical Optic Neuritis After COVID-19 Vaccination.
supports_node 36366396 · Vaccines (2022) — Bilateral Optic Neuritis after COVID-19 Vaccination: A Case Report.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
A2 · Series with objective confirmationsupports
Measure: Definite object plus objective test Comparator: Reference range / diagnostic criteria Hit rule: Objective confirmation in >=1 case per the working definition
Finding: The retrieved evidence includes multiple case reports and case series describing optic neuritis following COVID-19 vaccination, with some cases having objective clinical findings such as visual acuity reduction, relative afferent pupillary defect, and MRI findings, but the evidence consists entirely of uncontrolled case reports/series without systematic objective confirmation in all cases.
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Series with objective confirmation pubmed · 5687 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
16 retrieved record(s)
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
does_not_resolve 41306776 · Frontiers in pharmacology (2025) — HPV vaccine-related thyroid adverse events: temporal patterns and reporting trends.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A3 · Onset histogramsupports
Measure: Distribution of onset times after dose Comparator: Pre-specified risk window Hit rule: Onset clusters inside the pre-specified window (not uniform/flat)
Finding: The retrieved evidence consists solely of case reports and small case series (total ~54 pooled cases, with onset times ranging from hours to ~12 days post-vaccination), showing a non-uniform clustering of optic neuritis onset within days to two weeks after COVID-19 vaccination, consistent with a pre-specified risk window.
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Onset histogram pubmed · 48 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
21 retrieved record(s)
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
supports_node 36366396 · Vaccines (2022) — Bilateral Optic Neuritis after COVID-19 Vaccination: A Case Report.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
ambiguous 35020705 · Journal of neuro-ophthalmology : the off (2023) — Case Series: Atypical Optic Neuritis After COVID-19 Vaccination.
ambiguous 36855075 · BMC ophthalmology (2023) — Hyperacute optic neuritis in a patient with COVID-19 infection and vaccination: a case report.
A4 · Temporal plausibilitysupports
Measure: Onset latency vs object pathophysiology Comparator: Object's known natural latency Hit rule: Onset latency consistent with the object's pathophysiology
Finding: Multiple case reports and case series describe optic neuritis occurring within days to a few weeks after COVID-19 vaccination, with onset latencies as short as 2 hours to 2 weeks, which is consistent with the hypothesized immune-mediated pathophysiology of post-vaccine optic neuritis.
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Temporal plausibility pubmed · 77 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
21 retrieved record(s)
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
supports_node 36366396 · Vaccines (2022) — Bilateral Optic Neuritis after COVID-19 Vaccination: A Case Report.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
ambiguous 35020705 · Journal of neuro-ophthalmology : the off (2023) — Case Series: Atypical Optic Neuritis After COVID-19 Vaccination.
supports_node 36855075 · BMC ophthalmology (2023) — Hyperacute optic neuritis in a patient with COVID-19 infection and vaccination: a case report.
A5 · Onset-interval documentationsupports
Measure: Onset interval documented in source Comparator: Dose date Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: Multiple case reports and case series document that optic neuritis onset intervals after COVID-19 vaccination are explicitly recorded (e.g., 1 week, 5–12 days, 8 days, 2 days, within 2 hours), with temporal intervals clearly stated in the primary sources.
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Onset-interval documentation pubmed · 46 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
22 retrieved record(s)
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
ambiguous 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
supports_node 36366396 · Vaccines (2022) — Bilateral Optic Neuritis after COVID-19 Vaccination: A Case Report.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
ambiguous 35020705 · Journal of neuro-ophthalmology : the off (2023) — Case Series: Atypical Optic Neuritis After COVID-19 Vaccination.
ambiguous 36855075 · BMC ophthalmology (2023) — Hyperacute optic neuritis in a patient with COVID-19 infection and vaccination: a case report.
A6 · Differential diagnosis excludedmixed
Measure: Competing causes assessed and excluded Comparator: Likely alternative diagnoses Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: Retrieved case series and reviews report optic neuritis occurring after COVID-19 vaccination, with some cases assessed for competing causes (e.g., MOG or aquaporin-4 serostatus), but none explicitly document systematic exclusion of all pre-specified competing causes as required by the working definition.
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Differential diagnosis excluded pubmed · 473 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
13 retrieved record(s)
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
does_not_resolve 41306776 · Frontiers in pharmacology (2025) — HPV vaccine-related thyroid adverse events: temporal patterns and reporting trends.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 40902666 · Journal of the American Academy of Derma (2026) — Drug and vaccine-associated pemphigoid in patients aged 50 years and older: A pharmacovigilance study.
A7 · Rechallenge / re-exposuresupports
Measure: Object recurs on a further dose Comparator: First-dose response Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: Multiple case reports describe optic neuritis occurring after a subsequent COVID-19 vaccine dose, including a case following the second dose of Moderna mRNA-1273 and a case after a booster vaccination, meeting the rechallenge criterion of recurrence after re-exposure.
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Rechallenge / re-exposure pubmed · 48 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
21 retrieved record(s)
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
supports_node 35957600 · European journal of ophthalmology (2023) — Optic neuritis following COVID-19 vaccination: Do autoimmune diseases play a role?
ambiguous 36855075 · BMC ophthalmology (2023) — Hyperacute optic neuritis in a patient with COVID-19 infection and vaccination: a case report.
ambiguous 35020705 · Journal of neuro-ophthalmology : the off (2023) — Case Series: Atypical Optic Neuritis After COVID-19 Vaccination.
A8 · Adjudicated by criteria (no established case definition)no_data
Measure: Object adjudicated by published criteria Comparator: Published clinical / Brighton criteria Hit rule: Cases adjudicated to 'definite' by a published criterion set
Finding: All retrieved evidence consists of uncontrolled case reports and case series describing optic neuritis after COVID-19 vaccination, but none of the reports adjudicate cases as 'definite' by a published criterion set or use the specified adjudication methodology required for this node.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Adjudicated by criteria pubmed · 85 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
20 retrieved record(s)
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
ambiguous 35957600 · European journal of ophthalmology (2023) — Optic neuritis following COVID-19 vaccination: Do autoimmune diseases play a role?
supports_node 36855075 · BMC ophthalmology (2023) — Hyperacute optic neuritis in a patient with COVID-19 infection and vaccination: a case report.
ambiguous 35020705 · Journal of neuro-ophthalmology : the off (2023) — Case Series: Atypical Optic Neuritis After COVID-19 Vaccination.
A9 · Natural-history consistencysupports
Measure: Course matches the object's natural history Comparator: Known natural history of the object Hit rule: Clinical course (onset, peak, recovery) matches the object's natural history
Finding: The retrieved case series and literature reviews consistently report optic neuritis onset days to weeks after COVID-19 vaccination, with most cases showing improvement after steroid treatment, which is consistent with the typical clinical course of optic neuritis (acute onset, peak within days, recovery often partial or complete).
supporting: COVID-19 vaccine Optic Neuritis case report OR case series Natural-history consistency pubmed · 149 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
15 retrieved record(s)
ambiguous 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
A10 · No confounding objectno_data
Measure: Not attributable to a co-occurring condition Comparator: Co-occurring illness that could produce the object Hit rule: Object not better explained by a co-occurring condition (infection, etc.)
Finding: The retrieved evidence consists exclusively of case reports and case series describing temporal associations between COVID-19 vaccination and subsequent optic neuritis. None of the studies systematically assess or exclude co-occurring conditions such as infections or autoimmune diagnoses as alternative explanations for the optic neuritis, and many cases were found to have underlying seropositivity for MOG or AQP4 or to meet criteria for multiple sclerosis.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis case report OR case series No confounding object pubmed · 65 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
20 retrieved record(s)
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 35086265 · Indian journal of ophthalmology (2022) — Optic neuritis following COVID-19 vaccination: Coincidence or side-effect? - A case series.
supports_node 37901633 · Case reports in ophthalmology (2023) — Optic Neuritis following Second Administration of COVID-19 Vaccine: A Case Report.
ambiguous 35957600 · European journal of ophthalmology (2023) — Optic neuritis following COVID-19 vaccination: Do autoimmune diseases play a role?
supports_node 36366396 · Vaccines (2022) — Bilateral Optic Neuritis after COVID-19 Vaccination: A Case Report.
supports_node 36855075 · BMC ophthalmology (2023) — Hyperacute optic neuritis in a patient with COVID-19 infection and vaccination: a case report.
D1 · Predicted site of injuryno_data
Measure: Object at the site the mechanism predicts Comparator: Predicted anatomic site from the mechanism Hit rule: Object localizes to the anatomic site the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis anatomic localization Predicted site of injury mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Predicted site of injury not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D2 · Spared structuresno_data
Measure: Structures the mechanism should spare are spared Comparator: Structures predicted unaffected Hit rule: Structures predicted spared by the mechanism are indeed spared
mirror: COVID-19 vaccine Optic Neuritis Spared structures not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D3 · Local vs systemic distributionno_data
Measure: Distribution matches mechanism scope Comparator: Local (injection site) vs systemic expectation Hit rule: Observed distribution (local vs systemic) matches the mechanism's predicted scope
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis anatomic localization Local vs systemic distribution mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Local vs systemic distribution not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D4 · Kinetics classno_data
Measure: Onset/offset kinetics match the mechanism Comparator: Expected kinetic class (acute vs chronic) Hit rule: Onset and offset kinetics are in the class the mechanism predicts
mirror: COVID-19 vaccine Optic Neuritis Kinetics class not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D5 · Platform-mechanism matchno_data
Measure: Mechanism is consistent with the platform Comparator: Mechanistic expectation for the platform Hit rule: The proposed mechanism is biologically consistent with the vaccine platform
mirror: COVID-19 vaccine Optic Neuritis Platform-mechanism match not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H3 · Targeted treatment reversesno_data
Measure: A targeted treatment reverses the object in patients Comparator: Treatment-naive / placebo Hit rule: A mechanism-directed treatment reverses the object (vs control treatment)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Targeted treatment reverses intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
Measure: No node's finding contradicts another Comparator: Internal consistency across nodes Hit rule: No evaluated node directly contradicts another (coherence)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis No internal contradiction coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis No internal contradiction inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
I2 · Analogy to a known objectno_data
Measure: Object analogous to a well-established analog Comparator: Established analog's profile Hit rule: The object's profile matches a well-established analog on key features
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Analogy to a known object coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Analogy to a known object inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
I5 · Latency coherenceno_data
Measure: Observed latency matches the mechanism's latency Comparator: Mechanism-predicted latency Hit rule: Observed onset latency is coherent with the mechanism's predicted latency
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Latency coherence coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Latency coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
J1 · Pre-specificationno_data
Measure: Window/hit-rule pre-specified before data Comparator: Pre-specified vs post-hoc Hit rule: The risk window, object, and hit rule were pre-specified before data were seen
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Pre-specification pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Pre-specification post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 42569385 · Frontiers in medicine (2026) — Antibiotic-associated adverse events in bone and joint infections: a FAERS pharmacovigilance study.
does_not_resolve 38983297 · Radiology case reports (2024) — Identification of perineural invasion at imaging staging as a novel potential risk factor in rectal cancer: A case report.
J2 · Contrary-evidence logno_data
Measure: Contrary evidence is logged, not omitted Comparator: Support-only dossier Hit rule: Contrary / null / refuting findings are logged and shown alongside support
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Contrary-evidence log pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Contrary-evidence log post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 42474879 · Biological trace element research (2026) — Cadmium Exposure and Osteoporosis: A Spatially Contextualized Adverse Outcome Pathway Integrating Epidemiology, Toxicogenomics and Transcriptomics.
Measure: Claim not based on temporality alone Comparator: Sequence-only evidence Hit rule: The claim is not supported by temporal sequence alone (independent evidence exists)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis No temporality-only claim pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis No temporality-only claim post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 42474879 · Biological trace element research (2026) — Cadmium Exposure and Osteoporosis: A Spatially Contextualized Adverse Outcome Pathway Integrating Epidemiology, Toxicogenomics and Transcriptomics.
Measure: Passive-surveillance findings bounded correctly Comparator: Active-surveillance confirmation Hit rule: Passive-surveillance signals are framed as hypothesis-generating, not confirmatory
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Passive-surveillance role pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Passive-surveillance role post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
4 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 42474879 · Biological trace element research (2026) — Cadmium Exposure and Osteoporosis: A Spatially Contextualized Adverse Outcome Pathway Integrating Epidemiology, Toxicogenomics and Transcriptomics.
does_not_resolve 42569385 · Frontiers in medicine (2026) — Antibiotic-associated adverse events in bone and joint infections: a FAERS pharmacovigilance study.
Measure: Dose/lot exposure mapped to the object Comparator: Unmapped exposure Hit rule: Dose / lot exposure is mapped to the object where the mechanism predicts it
Finding: No evidence found. The retrieved PMIDs do not address COVID-19 vaccine, optic neuritis, dose mapping, or the specified risk window; one is about immune-related adverse events from immune checkpoint inhibitors and the other about antibiotic-associated adverse events in bone and joint infections.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Dose mapping pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Dose mapping post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 42569385 · Frontiers in medicine (2026) — Antibiotic-associated adverse events in bone and joint infections: a FAERS pharmacovigilance study.
Epidemiologic chassis 13/13 evaluated
B1 · Excess vs baselineno_data
Measure: RR/IRR vs unexposed or prior window Comparator: Unvaccinated person-time or pre-vaccination window Hit rule: RR/IRR > 1 with CI excluding 1 after pre-specified confounders
Finding: No retrieved evidence directly addresses the association between COVID-19 vaccination and optic neuritis. The retrieved studies focus on drug overdose, abnormal uterine bleeding, arrhythmias after COVID-19, rotavirus vaccine safety, myasthenia gravis exacerbation, Guillain-Barré syndrome, non-alcoholic fatty liver disease, and cardiovascular outcomes, none of which involve optic neuritis or relevant confounders.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Excess vs baseline incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Excess vs baseline pubmed · 88528 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 34489307 · Gut (2022) — Non-alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort.
does_not_resolve 40794640 · European heart journal (2026) — Cardiovascular benefit of continuous positive airway pressure according to high-risk obstructive sleep apnoea: a multi-trial analysis.
B2 · SCCSno_data
Measure: Self-controlled case series risk ratio Comparator: Individuals' own risk intervals (no-event) Hit rule: SCCS risk ratio > 1 in the post-vaccination window, CI excluding 1
Finding: No retrieved study provides an SCCS risk ratio for optic neuritis after COVID-19 vaccination. Evidence consists only of case reports and systematic reviews of case reports (PMID 36590026, PMID 36298623, PMID 36040199), which are unsuitable for the SCCS node definition requiring a risk ratio with CI excluding 1.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis SCCS incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk SCCS pubmed · 88636 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 36226469 · Epilepsia (2022) — Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 39795956 · International journal of molecular scien (2024) — The Potential Metalloestrogenic Effect of Aluminum on Breast Cancer Risk for Antiperspirant Users.
does_not_resolve 33274462 · Journal of the European Academy of Derma (2021) — Clinical utility of skin cancer and melanoma risk scores for population screening: TRoPICS study.
B3 · Cohort / risk-intervalno_data
Measure: Incidence rate ratio in defined window Comparator: Pre-specified risk vs comparison interval Hit rule: IRR > 1 in the pre-specified window, CI excluding 1, stratified by age/sex
Finding: No retrieved evidence provides a cohort or self-controlled risk interval study estimating an incidence rate ratio for optic neuritis following COVID-19 vaccination with a pre-specified risk window, stratified by age and sex. The available evidence consists of case series and systematic reviews of case reports (e.g., PMID 36298623, PMID 39111095) and studies on other outcomes or vaccines (e.g., PMID 40440921 on Guillain-Barré syndrome) that do not meet the specified hit rule for Node B3.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Cohort / risk-interval incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Cohort / risk-interval pubmed · 88137 hits · run 2026-09-07
10 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
ambiguous 36298623 · Vaccines (2022) — COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients.
ambiguous 36040199 · QJM : monthly journal of the Association (2022) — COVID-19 vaccine-associated optic neuritis.
B4 · Meta-analysis / poolingno_data
Measure: Pooled effect across studies Comparator: Pooled estimate with heterogeneity Hit rule: Pooled estimate > 1 (or < 1) with quantified heterogeneity (I2)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Meta-analysis / pooling incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Meta-analysis / pooling pubmed · 111968 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 29402646 · Journal of the American Medical Director (2018) — Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others.
ambiguous 36040199 · QJM : monthly journal of the Association (2022) — COVID-19 vaccine-associated optic neuritis.
B5 · Negative-control outcomesno_data
Measure: No excess for outcomes the vaccine should not cause Comparator: Negative-control outcomes (unaffected by mechanism) Hit rule: Null for negative-control outcomes while target outcome is positive (specificity)
Finding: No retrieved evidence directly addresses optic neuritis as a negative-control outcome after COVID-19 vaccination; the studies focus on mortality, arrhythmias, Guillain-Barré syndrome, seizure, and other adverse events, but not optic neuritis.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Negative-control outcomes incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Negative-control outcomes pubmed · 88339 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 36226469 · Epilepsia (2022) — Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 42371637 · JAMA internal medicine (2026) — Prenatal Acetaminophen (Paracetamol) Use and the Risk of Autism and/or Attention-Deficit/Hyperactivity Disorder Among Sibling-Matched Cohorts.
does_not_resolve 38833248 · JAMA network open (2024) — Valproate Use During Spermatogenesis and Risk to Offspring.
B6 · Other-antigen comparisonno_data
Measure: Risk vs a different-antigen comparator Comparator: Comparator product with a different antigen Hit rule: Risk specific to the target antigen, not shared with the comparator antigen
Finding: No retrieved evidence directly compares risk of optic neuritis after COVID-19 vaccination versus a different-antigen comparator; the available studies on optic neuritis are case reports or case series without a comparator antigen, and the self-controlled case series studies in the retrieved set address other outcomes (mortality, overdose, arrhythmias, Guillain-Barré syndrome, seizure, myasthenia gravis, abnormal uterine bleeding) or COVID-19 infection itself, not optic neuritis.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Other-antigen comparison incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Other-antigen comparison pubmed · 88101 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 36226469 · Epilepsia (2022) — Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study.
Measure: Per-100k risk in window Comparator: Absolute incidence per 100k Hit rule: Absolute risk reported and stable across the window (not an artifact of rarity)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Absolute risk incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Absolute risk pubmed · 111368 hits · run 2026-09-07
14 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 36226469 · Epilepsia (2022) — Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
B8 · Platform splitno_data
Measure: Risk by vaccine platform / product Comparator: Platform (mRNA vs viral vector, etc.) Hit rule: Risk attributable to a specific platform, not to 'a vaccine' generally
Finding: The retrieved evidence includes case reports and systematic reviews of optic neuritis following COVID-19 vaccination [PMID 36590026, PMID 36298623, PMID 36040199], but no platform-specific risk estimates (e.g., comparing mRNA vs. viral vector vs. protein subunit) or controlled epidemiological studies that attribute risk to a specific platform. All identified studies are case-series or reviews without a denominator or comparator, and none address the node's requirement for a platform-attributable risk measure.
supporting: COVID-19 vaccine Optic Neuritis Platform split incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Platform split pubmed · 88166 hits · run 2026-09-07
10 retrieved record(s)
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 41345827 · BMC cardiovascular disorders (2025) — Machine learning-based prediction of atherosclerotic cardiovascular disease risk in adults with diabetes or prediabetes.
Measure: Risk by age / sex / host structure Comparator: Unstratified estimate Hit rule: Risk concentrated in a defined host subgroup (e.g. young males), stable across sources
Finding: The retrieved evidence includes case reports and a VAERS analysis of optic neuritis following COVID-19 vaccination, but no source provides a defined host subgroup (e.g., by age or sex) with stable risk across studies; the only epidemiological study (PMID 37314860) reports relative reporting rates from VAERS without subgroup-specific risk stratification.
supporting: COVID-19 vaccine Optic Neuritis Host-structure stratification incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Host-structure stratification pubmed · 88099 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
ambiguous 36298623 · Vaccines (2022) — COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients.
B10 · Formulation / component changeno_data
Measure: Risk tracks a formulation change Comparator: Pre- vs post-change formulation Hit rule: Risk change tracks a documented formulation / component change over time
Finding: No retrieved evidence directly assesses risk tracking of optic neuritis after COVID-19 vaccination in relation to a formulation/component change over time. The closest evidence is a systematic review of case reports and case series (PMID 36298623) and a brief report (PMID 36590026) documenting optic neuritis cases after COVID-19 vaccination, but these studies do not examine formulation changes or temporal risk trends.
supporting: COVID-19 vaccine Optic Neuritis Formulation / component change incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no association OR null OR no increased risk Formulation / component change pubmed · 88261 hits · run 2026-09-07
9 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 41092926 · Lancet (London, England) (2025) — Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 su
Measure: Risk shifts with a formulation change in the field Comparator: Pre- vs post-change formulation Hit rule: Observed risk tracks a real-world formulation change (natural experiment)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Formulation natural experiment intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
Measure: Risk signal appears/disappears across a pause or policy change Comparator: Pre- vs post-pause period Hit rule: The signal appears or disappears coherently with a rollout / pause (H4)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Policy / pause signal intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Policy / pause signal no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
I3 · Infection coherenceno_data
Measure: Pattern is coherent with or distinct from infection Comparator: Infection-matched comparison Hit rule: The post-vaccine pattern is coherent with (or clearly distinct from) the infection pattern
Finding: The retrieved evidence describes a prospective, multi-center follow-up study of post-vaccination optic neuritis (ON) following SARS-CoV-2 vaccination, but does not compare the clinical pattern of post-vaccine ON with the pattern of infection-associated ON, nor does it state whether the two patterns are coherent or distinct.
supporting: COVID-19 vaccine Optic Neuritis Infection coherence coherence OR latency OR susceptibility pubmed · 870024 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Infection coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
supports_node 41318886 · Graefe's archive for clinical and experi (2026) — Treatment of post-vaccination optic neuritis: implications from the global SARS-CoV-2 vaccination effort.
Mediator & biological gradient 24/24 evaluated
C1n · Dose strength gradientno_data
Measure: Risk vs dose strength (dose size) Comparator: Lower dose strength Hit rule: Monotonic dose-response in dose strength (larger dose -> higher risk)
Finding: No retrieved evidence directly assesses a dose-strength gradient for optic neuritis risk after COVID-19 vaccination. The only case reports and case series available (e.g., PMID 34900001, 39111095, 38829714) describe occurrences after single doses of various vaccines but do not compare risk by dose size or strength.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Dose strength gradient dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no dose effect OR no dose-response Dose strength gradient pubmed · 143 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
does_not_resolve 34776011 · Infectious diseases of poverty (2021) — Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: a systematic review and meta-analysis.
does_not_resolve 38382130 · Clinical neurology and neurosurgery (2024) — COVID-19 vaccine response in Neuromyelitis Optica Spectrum Disorder.
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
C2n · Dose number gradientno_data
Measure: Risk vs dose number (1st vs 2nd vs 3rd) Comparator: First dose Hit rule: Risk increases (or shows a defined pattern) with dose number
Finding: Two case series (PMID 39111095, PMID 38829714) and a single case report (PMID 34900001) describe optic neuritis after COVID-19 vaccination, but none report risk stratified by dose number (1st vs 2nd vs 3rd) or a dose-dependent gradient. No retrieved evidence addresses dose number as a risk factor.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Dose number gradient dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no dose effect OR no dose-response Dose number gradient pubmed · 587 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 38382130 · Clinical neurology and neurosurgery (2024) — COVID-19 vaccine response in Neuromyelitis Optica Spectrum Disorder.
ambiguous 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
ambiguous 36586226 · Journal of clinical neuroscience : offic (2023) — Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.
supports_node 41318886 · Graefe's archive for clinical and experi (2026) — Treatment of post-vaccination optic neuritis: implications from the global SARS-CoV-2 vaccination effort.
C3n · Measured-exposure tertilesno_data
Measure: Risk vs measured exposure tertile Comparator: Lowest-exposure tertile Hit rule: Risk ordered by measured-exposure tertile (high > mid > low)
Finding: The retrieved evidence includes case reports and case series of optic neuritis following COVID-19 vaccination (e.g., PMID 34900001, 39111095, 38829714, 36586226, 36256905) but provides no quantitative data on risk stratified by measured-exposure tertiles of vaccine exposure.
supporting: COVID-19 vaccine Optic Neuritis Measured-exposure tertiles dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no dose effect OR no dose-response Measured-exposure tertiles pubmed · 32 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
does_not_resolve 38382130 · Clinical neurology and neurosurgery (2024) — COVID-19 vaccine response in Neuromyelitis Optica Spectrum Disorder.
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
ambiguous 36586226 · Journal of clinical neuroscience : offic (2023) — Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.
supports_node 41318886 · Graefe's archive for clinical and experi (2026) — Treatment of post-vaccination optic neuritis: implications from the global SARS-CoV-2 vaccination effort.
C4n · Organoid concentration curveno_data
Measure: Effect vs antigen concentration in organoid Comparator: Vehicle / zero antigen Hit rule: Dose-dependent effect across a graded concentration curve
Finding: The retrieved evidence includes multiple case reports and case series describing optic neuritis following COVID-19 vaccination, but no in vitro organoid concentration-curve experiments were identified that test a dose-dependent effect of the vaccine or its antigens on optic neuritis in an organoid model.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Organoid concentration curve dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no dose effect OR no dose-response Organoid concentration curve pubmed · 43 hits · run 2026-09-07
9 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 38382130 · Clinical neurology and neurosurgery (2024) — COVID-19 vaccine response in Neuromyelitis Optica Spectrum Disorder.
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
supports_node 41318886 · Graefe's archive for clinical and experi (2026) — Treatment of post-vaccination optic neuritis: implications from the global SARS-CoV-2 vaccination effort.
supports_node 36256905 · Ocular immunology and inflammation (2023) — Bilateral Atypical Optic Neuritis following ChAdOx1_nCoV-19 Vaccination: A Putative Plausibility.
supports_node 36586226 · Journal of clinical neuroscience : offic (2023) — Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.
C5n · EC50 vs Cmax coherencemixed
Measure: Measured exposure reaches effect threshold Comparator: Pharmacokinetic Cmax vs EC50 Hit rule: Achieved exposure (Cmax/tissue) plausibly reaches the in-vitro EC50
Finding: Multiple case reports and case series describe optic neuritis occurring within days to weeks after COVID-19 vaccination, with temporality and exclusion of other causes suggesting a possible association, but no controlled epidemiological study directly demonstrates that measured exposure (Cmax/tissue) plausibly reaches the in-vitro EC50 for this adverse event.
supporting: COVID-19 vaccine Optic Neuritis EC50 vs Cmax coherence dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis no dose effect OR no dose-response EC50 vs Cmax coherence pubmed · 32 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
does_not_resolve 34776011 · Infectious diseases of poverty (2021) — Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: a systematic review and meta-analysis.
does_not_resolve 38382130 · Clinical neurology and neurosurgery (2024) — COVID-19 vaccine response in Neuromyelitis Optica Spectrum Disorder.
supports_node 39111095 · Journal francais d'ophtalmologie (2024) — Optic neuritis following COVID-19 vaccination: Case series and review of the literature.
supports_node 38829714 · Journal of neuro-ophthalmology : the off (2024) — Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.
does_not_resolve 36586226 · Journal of clinical neuroscience : offic (2023) — Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.
E1 · Mediator identified in casesno_data
Measure: Mediator present in affected tissue/cells Comparator: Unaffected tissue / control Hit rule: The hypothesized mediator is detected in the affected compartment and not (or less) in control
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Mediator identified in cases in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Mediator identified in cases not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E2 · Mediator in healthy vaccineesno_data
Measure: Mediator detectable after vaccination Comparator: Pre-vaccination baseline Hit rule: Mediator appears after vaccination and tracks the exposure window
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Mediator in healthy vaccinees in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Mediator in healthy vaccinees not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E3 · Infection contrastno_data
Measure: Mediator absent/low after natural infection Comparator: Recovered natural infection Hit rule: Mediator signal is specific to vaccination vs a comparable natural-infection control
Finding: The retrieved evidence includes two case reports and a cohort study on optic neuritis after COVID-19 vaccination, but none compare mediator levels or signal specificity to natural infection controls, nor do they assess mediator absence after natural infection.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Infection contrast in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Infection contrast not associated mechanism pubmed · 5 hits · run 2026-09-07
4 retrieved record(s)
supports_node 37431875 · Journal of investigative medicine high i (2023) — Bilateral Optic Neuritis and Hypophysitis With Diabetes Insipidus 1 Month After COVID-19 mRNA Vaccine: Case Report and Literature Review.
supports_node 41318886 · Graefe's archive for clinical and experi (2026) — Treatment of post-vaccination optic neuritis: implications from the global SARS-CoV-2 vaccination effort.
ambiguous 38010696 · Investigative ophthalmology & visual sci (2023) — Neuro-Ophthalmic Adverse Events of COVID-19 Infection and Vaccines: A Nationwide Cohort Study.
ambiguous 37634758 · Ophthalmology (2024) — Optic Neuritis and Cranial Neuropathies Diagnosis Rates before Coronavirus Disease 2019, in the Initial Pandemic Phase, and Post-Vaccine Introduction.
E4 · Transfer to recipientno_data
Measure: Phenotype/mediator transferred to a recipient system Comparator: Control transfer Hit rule: The effect / mediator transfers to a naive recipient system
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Transfer to recipient in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Transfer to recipient not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E5 · Transfer specificityno_data
Measure: Transfer requires the specific mediator Comparator: Transfer with mediator present Hit rule: Transfer effect is lost when the specific mediator is removed
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Transfer specificity in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Transfer specificity not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E6 · Depletion / knockdownno_data
Measure: Removing the mediator reduces the effect Comparator: Non-targeted knockdown Hit rule: Knockdown / depletion of the mediator reduces the phenotype
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Depletion / knockdown in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
Measure: Adding the mediator restores the effect Comparator: Add-back of a control protein Hit rule: Adding back the mediator (not a control) restores the phenotype
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Add-back rescue in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
Measure: Neutralizing the mediator blocks the effect Comparator: Isotype control Hit rule: Neutralization of the mediator (not an isotype control) blocks the phenotype
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Neutralization in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Neutralization not associated mechanism pubmed · 1 hits · run 2026-09-07
E9 · Isotype controlno_data
Measure: Isotype control does not reproduce the effect Comparator: Active antibody Hit rule: An isotype control fails to reproduce the block/activation
Finding: No retrieved evidence directly addresses whether an isotype control fails to reproduce the block/activation in the context of COVID-19 vaccine-associated optic neuritis. The studies instead report clinical cases and relapse risks in NMOSD patients after vaccination.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Isotype control in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Isotype control not associated mechanism pubmed · 6 hits · run 2026-09-07
3 retrieved record(s)
supports_node 36289118 · Neurological sciences : official journal (2023) — First manifestation of AQP4-IgG-positive neuromyelitis optica spectrum disorder following the COVID-19 mRNA vaccine BNT162b2.
does_not_resolve 35421782 · Multiple sclerosis and related disorders (2022) — Humoral response to SARS-CoV-2 infection and vaccines against COVID-19 in patients with neuromyelitis optica spectrum disorders: Impact of immunosuppressive tre
does_not_resolve 35216793 · Multiple sclerosis and related disorders (2022) — Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD.
F1 · Full product reproducesno_data
Measure: Full vaccine product reproduces the effect Comparator: No-product control Hit rule: The full product (not a subcomponent) reproduces the effect
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Full product reproduces component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Full product reproduces no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
6 retrieved record(s)
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F2 · Empty vector / particleno_data
Measure: Vector/particle without antigen reproduces (or not) Comparator: Full product Hit rule: Effect attributed to (or excluded from) the vector/particle backbone alone
Finding: The retrieved evidence discusses virus-vectored and bacterial-vectored vaccines for influenza, measles, and cancer, but none of the abstracts mention optic neuritis, COVID-19 vaccines, or adverse events related to vaccine vectors. No evidence was found connecting empty vector/particle backbones to optic neuritis.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Empty vector / particle component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F4 · Irrelevant cargono_data
Measure: Irrelevant cargo does not reproduce the effect Comparator: Vector with the target antigen Hit rule: Irrelevant cargo fails to reproduce the effect (specificity)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Irrelevant cargo component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F5 · Infection preparationno_data
Measure: Infection preparation vs product comparison Comparator: Product-derived preparation Hit rule: Effect compares correctly between infection and product preparations
Finding: The retrieved evidence discusses various live viral and bacterial vaccine vectors (influenza, measles, adenovirus, Newcastle disease virus) used for heterologous antigen delivery, but contains no mention of optic neuritis or any adverse event related to COVID-19 vaccination.
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Infection preparation component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F6 · Cytokine / adjuvant mixno_data
Measure: Cytokine/adjuvant mix alone reproduces (or not) Comparator: Individual components Hit rule: The effect is (or is not) reproducible by the cytokine/adjuvant mix alone
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Cytokine / adjuvant mix component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F7 · Component combinationno_data
Measure: Defined component combination reproduces the effect Comparator: Single components Hit rule: A defined combination reproduces the effect that single components do not
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Component combination component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
G1 · 2D human cellsno_data
Measure: Effect reproduced in 2D human cell culture Comparator: Untreated / control cells Hit rule: Effect reproduced in 2D primary human cells
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis 2D human cells animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis 2D human cells not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G2 · Organoid / chipno_data
Measure: Effect reproduced in organoid / organ-on-chip Comparator: Unexposed organoid Hit rule: Effect reproduced in a 3D organoid / organ-on-chip system
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Organoid / chip animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Organoid / chip not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H1 · Block in vitro / in vivono_data
Measure: Blocking the mediator/mechanism prevents the effect Comparator: Control intervention Hit rule: Blocking the mechanism prevents or reverses the effect (not with a control intervention)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Block in vitro / in vivo intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Block in vitro / in vivo no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
Clinical / animal / host 7/7 evaluated
E10 · Host-line dependenceno_data
Measure: Effect depends on host line/cell type Comparator: Susceptible host line Hit rule: Effect is restricted to a defined host line / genotype, not universal
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis mechanism Host-line dependence in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
Measure: Effect in animal via the clinical route of administration Comparator: Vehicle, same route Hit rule: Effect reproduced in an animal using the clinical route of administration
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Animal, clinical route animal OR organoid OR cell model pubmed · 1818475 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Animal, clinical route not reproduced model pubmed · 1 hits · run 2026-09-07
G4 · Susceptible animalno_data
Measure: Effect in a susceptible animal model Comparator: Non-susceptible model Hit rule: Effect in a defined susceptible animal model
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Susceptible animal animal OR organoid OR cell model pubmed · 1818475 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Susceptible animal not reproduced model pubmed · 1 hits · run 2026-09-07
G5 · Replication across labsno_data
Measure: Effect replicated in an independent lab Comparator: Original result Hit rule: The key effect is replicated in an independent laboratory
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Replication across labs animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Replication across labs not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G6 · Blinded scoringno_data
Measure: Outcomes scored blinded Comparator: Unblinded reference Hit rule: Primary outcomes scored by a blinded assessor
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Blinded scoring animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Blinded scoring not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G7 · Experimental time courseno_data
Measure: Effect follows a defined experimental time course Comparator: No-exposure time course Hit rule: The effect's onset/offset follows a defined experimental time course
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Experimental time course animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Experimental time course not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
I4 · Susceptibility traitno_data
Measure: A host trait / marker defines susceptibility Comparator: Trait-negative hosts Hit rule: A defined host trait / marker enriches for susceptibility
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Optic Neuritis Susceptibility trait coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Optic Neuritis Susceptibility trait inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
How this was built
Per node: a supporting and a mirror PubMed query built from the node's measure / population / comparator / hit_rule; top hits fetched (title + abstract); each record classified (supports / refutes / ambiguous) by xAI with a heuristic fallback; a per-node synthesis is generated strictly from the retrieved PMIDs; the node status is then rolled up to C1–C6. Full query provenance is shown per node above. Reproduce the build: python -m evidence_run. Data: data/evidence_run/state.json.