You’re sitting in your ophthalmologist’s office, worried about the sudden vision loss you experienced just days after receiving your COVID-19 booster shot. The timing seems too coincidental to ignore, and you’re wondering if the vaccine could have caused your retinal vascular occlusion. You’re not alone in this concern, since the mass rollout of COVID-19 vaccines began in late 2020, isolated reports of retinal vascular events occurring shortly after vaccination have emerged in medical literature. Your doctor explains that while these reports exist, the relationship between vaccination and retinal occlusions is complex and far from definitively established.
What you’re experiencing—retinal vascular occlusion (RVO), encompasses conditions like central or branch retinal vein occlusion (CRVO/BRVO) and retinal artery occlusion (CRAO/BRAO). These are potentially vision-threatening conditions typically associated with cardiovascular risk factors like hypertension and diabetes. The question that has prompted extensive medical investigation is whether COVID-19 vaccines could trigger retinal vascular events, or if such cases are simply coincidental occurrences in an aging, increasingly vaccinated population.
TLDR: Key Takeaways
Bottom Line: Retinal vascular occlusion after COVID-19 vaccination is exceedingly rare, occurring in roughly 3 per 100,000 vaccinated individuals, a rate comparable to background levels and similar to other routine vaccinations.
What We Know:
- Multiple case reports document temporal associations between COVID-19 vaccination and retinal occlusions, but causation remains unproven
- Large epidemiological studies from multiple countries show no significant increase in retinal occlusion risk post-vaccination
- The crude reporting rate is extremely low: approximately 0.36-0.69 cases per million vaccine doses
- Any potential risk appears concentrated in the first 1-2 weeks after vaccination
- Both mRNA and adenoviral vector vaccines have been associated with rare cases
- Critical Context: COVID-19 infection itself is a much more established cause of vascular problems, including retinal occlusions
Key Point: This can potentially be caused by any infection or inflammatory process that affects vascular health, COVID-19 vaccines represent just one of many possible triggers being investigated, and the evidence suggests they are among the least likely culprits.
Medical Consensus: Ophthalmology experts and vaccine safety authorities worldwide have found no evidence that COVID-19 vaccination significantly elevates retinal occlusion risk at the population level. The benefits of vaccination vastly outweigh these extremely rare potential risks.
Technical Deep Dive
Case Reports and Clinical Observations
The medical literature contains numerous case reports documenting temporal associations between COVID-19 vaccination and retinal vascular occlusions. These cases span the spectrum of retinal vascular pathology and have occurred with various vaccine types.
Venous Occlusions: Bialasiewicz et al. reported a case of central retinal vein occlusion (CRVO) occurring immediately after a second dose of an mRNA vaccine[1]. Similarly, Endo et al. described a central retinal vein occlusion soon after mRNA vaccination in an adult patient[2], while Tanaka et al. detailed an exacerbation of branch retinal vein occlusion (BRVO) following Pfizer-BioNTech vaccination[3].
Arterial Occlusions: Cases of retinal artery occlusions have also been documented across vaccine platforms. Abdin et al. reported a central retinal artery occlusion occurring 2 days after ChAdOx1 AstraZeneca vaccination[4], and Thakar et al. described a CRAO after the inactivated Covaxin vaccine[5].
Combined Presentations: In extremely rare instances, patients have developed simultaneous arterial and venous occlusions. Ikegami et al. presented a case of concurrent CRAO and CRVO shortly after an mRNA vaccine[6], while Lee et al. described combined CRAO/CRVO with ischemic optic neuropathy following vaccination[7]. A particularly notable recent case from Japan involved a 45-year-old man who, one day after a Moderna booster, experienced severe vision loss from combined CRVO, incomplete CRAO, and optic disc swelling (papillitis)[8][9]. The authors attributed this to possible post-vaccination inflammation or abnormal immune response, as the patient showed partial improvement with high-dose corticosteroids[10][11].
While these reports establish temporal associations, they cannot prove causality. By late 2021, approximately eight ocular vascular events had been documented in the literature[12], with numbers growing through continued pharmacovigilance. Importantly, most published cases involved older adults or patients with established vascular risk factors—demographics already predisposed to RVO. However, the occurrence of RVO in some younger patients without obvious alternative triggers has motivated researchers to compile and analyze these cases systematically[13][9].
Epidemiological Evidence
Large-scale epidemiological studies provide the most robust evidence regarding the relationship between COVID-19 vaccination and retinal vascular occlusions, and these studies overwhelmingly indicate that such events are exceedingly rare and generally not above background rates.
United States Data: A landmark 2023 JAMA Ophthalmology cohort study by Dorney et al. analyzed over 3.1 million patients who received mRNA vaccines and identified only 104 patients (0.003%) with new RVO diagnoses within 21 days post-vaccination[17]. This acute post-vaccination incidence (~3 per 100,000) was statistically comparable to rates observed after influenza or Tdap vaccinations in pre-pandemic years[18]. After propensity-matching, the risk of RVO following a first COVID vaccination was no different from that after influenza or Tdap vaccination[18]. The authors concluded there was “no evidence suggesting an association between mRNA COVID-19 vaccination and newly diagnosed RVO”[19].
Complementing this analysis, Agarwal et al. (2023) reviewed RVO reports in the U.S. CDC Vaccine Adverse Event Reporting System (VAERS) from December 2020 to July 2022[21][22]. During this period, 1,351 cases of RVO were recorded globally in VAERS. Given the hundreds of millions of doses administered, the crude reporting rates were extremely low: approximately 0.36 per million doses for Pfizer’s BNT162b2, 0.41 per million for Moderna’s mRNA-1273, and 0.69 per million for Johnson & Johnson’s Ad26.COV2.S[23]. The study noted that over 74% of RVO reports followed Pfizer vaccination, reflecting its wider usage rather than increased risk[24]. Approximately 41% of RVO cases and 48% of retinal artery occlusion cases occurred within the first week post-vaccination[16], suggesting temporal clustering worthy of continued monitoring[25].
International Validation: Several population-based studies from different countries have specifically examined retinal occlusion incidence in vaccinated versus unvaccinated populations:
Germany: Feltgen et al. (2022) conducted a retrospective multicenter study of 421 patients presenting with retinal vein/artery occlusions or ischemic optic neuropathy over a 2-month period in mid-2021[26]. While 79% of these patients had received COVID vaccination within 4 weeks prior to onset (reflecting high vaccination rates), comparison with age- and sex-matched controls from the Gutenberg Health Study revealed no association. The adjusted odds ratio was 0.93 (95% CI 0.60–1.45, p = 0.75) for recent vaccination, indicating “no evidence of any association between SARS-CoV-2 vaccination and higher RVO/RAO risk”[27][28][29].
Italy: Pellegrini et al. (2023) performed a multicenter self-controlled case series across five tertiary eye centers, identifying 210 patients with first-ever RVO during 2021 who had received at least one COVID vaccine dose[30]. Using each patient as their own control, the study compared RVO rates in the 28 days after vaccination to other time periods. No increased risk was observed in any post-vaccine interval, with incidence rate ratios of 0.94 (95% CI 0.55–1.58) after Dose 1 and 1.16 (0.70–1.90) after Dose 2 for days 1–28[31][32]. Subgroup analyses by vaccine type, age, or sex similarly found no associations[33][34], leading to the unequivocal conclusion that vaccination did not correlate with higher RVO risk in this Italian cohort[35].
South Korea: Using nationwide healthcare data, Korean researchers conducted both self-controlled and cohort analyses to examine retinal occlusion incidence after vaccination or COVID-19 infection. Within 60 days of COVID vaccination or infection, retinal artery occlusion (RAO) and RVO occurred only rarely, with no significant hazard increase relative to baseline expectations[36][37]. Specifically, incidence rate ratios were approximately 0.95 for RAO and 0.96 for RVO in the 0–28 day risk period after vaccination[38][39]. Park et al. similarly found no increase in 60-day RAO/RVO incidence compared to unexposed controls, reinforcing that any vaccine effect, if present, is too small to detect at the population level[36][40].
Discordant Findings: One notable exception comes from Li et al. (2023) using the TriNetX global health network, which reported a modest increase in retinal occlusion diagnoses among vaccinated individuals over extended follow-up. This analysis propensity-matched ~745,000 vaccinated patients to ~3.87 million unvaccinated patients, tracking outcomes for up to 2 years[41][42]. The investigators found approximately 2.2-fold higher hazard of RVO/RAO in the vaccinated cohort over two years (HR ~2.19, 95% CI 2.00–2.39)[43]. The relative risk increase was particularly noted in the first 12 weeks after vaccination[43][44]. However, absolute incidence remained very low in both groups, the analysis did not exclude individuals who later contracted COVID-19 (potentially confounding results)[45], and differences in methodology may explain why this study observed elevated hazard when others did not[46][47].
Vaccine Platform Comparisons
A clinically relevant question concerns whether specific vaccine platforms carry differential risks for retinal vascular complications. Theoretically, adenoviral vector vaccines have been associated with rare prothrombotic immune reactions (such as vaccine-induced immune thrombotic thrombocytopenia, VITT), potentially predisposing to more thrombotic events including RVO.
VAERS Analysis: The Agarwal et al. VAERS review found slightly higher crude reporting rates for the J&J vaccine (0.69 per million doses) compared to mRNA vaccines (0.36–0.41 per million)[23]. Additionally, RVO cases after the Ad26.COV2.S (Janssen) vaccine had significantly longer mean onset (~54 days) compared to the ~18–23 day average after Pfizer or Moderna[16]. This delayed timing pattern aligns with known VITT profiles and may suggest different underlying mechanisms.
Vaccine-Specific Patterns: Ichhpujani et al. (2022) summarized reported ocular adverse events by vaccine type, finding that retinal hemorrhages and vascular occlusions were most frequently reported with AstraZeneca (ChAdOx1), while mRNA vaccines more commonly had reports of corneal graft rejections, cranial nerve palsies, uveitis, and other inflammatory conditions[48]. Angle-closure glaucoma was also disproportionately noted with AstraZeneca[49]. This suggests adenoviral vectors might be relatively more prone to vascular occlusive events (likely via thrombotic pathways), while mRNA vaccines might trigger inflammatory or immune-mediated ocular events[50].
Controlled Study Findings: However, controlled epidemiological studies have not demonstrated clear vaccine-type differences in RVO risk. The Italian self-controlled study included all four major vaccines (Pfizer, Moderna, AstraZeneca, J&J) and found no association with RVO for any brand[51]. Similarly, the Korean self-controlled analysis found no vaccine brand significantly deviating in RAO/RVO incidence[52][38]. The TriNetX study reported that both Pfizer and Moderna showed small increases in RVO risk after first and second doses (with no significant difference between mRNA brands), while one-dose J&J showed non-significant trends toward increased risk[53][54].
Pathophysiological Mechanisms
Several plausible biological mechanisms could potentially explain rare cases of post-vaccination retinal vascular occlusion, though causality remains unproven:
Vaccine-Induced Immune Thrombosis (VITT): Adenovirus-based vaccines rarely trigger immune responses against platelet factor 4 (PF4), causing VITT syndrome characterized by thrombosis at unusual sites with thrombocytopenia. While retinal veins are not common VITT sites, the same process could theoretically cause ocular thrombosis. Anti-PF4 antibodies induced by adenoviral vaccine components lead to massive platelet activation[60], which could thrombose retinal vessels in susceptible patients. Delayed-onset RVO (1–3 weeks post-vaccine) with systemic symptoms could implicate VITT mechanisms[58][59]. However, reported RVO cases have not explicitly confirmed VITT through PF4 antibody testing, and absence of thrombocytopenia in most cases argues against classic VITT[61][62].
Spike Protein-Mediated Endothelial Dysfunction: Both mRNA and adenoviral vaccines ultimately produce SARS-CoV-2 spike protein antigen. Circulating spike protein or immune complexes might damage vascular endothelial cells or dysregulate the angiotensin-converting enzyme 2 (ACE2) pathway on endothelial surfaces[61][64]. Endothelial injury can expose prothrombotic surfaces and trigger clotting cascades. Since COVID-19 infection causes endotheliitis and hypercoagulability leading to strokes and retinal occlusions[65][66], spike antigen generated by vaccines could theoretically recapitulate similar effects, albeit much more rarely[67].
Immune-Complex–Driven Inflammation: Vaccination induces robust immune responses involving cytokine release and sometimes transient hypercoagulability. Activated immune systems could fulfill elements of Virchow’s triad (endothelial activation, blood flow changes, hypercoagulability) predisposing to thrombosis[68][69]. Intense systemic inflammation or immune complex deposition post-vaccine might precipitate microthrombi in retinal vessels—essentially immune-mediated vasculopathy. Some post-vaccine ocular occlusions have featured concurrent intraocular inflammation or optic disc swelling[10][70], suggesting inflammatory vasculitis components rather than simple fibrin clots. Successful steroid treatment in such cases supports inflammatory mechanisms[8][9].
Additional Mechanisms: Other proposed pathways include molecular mimicry (antibodies cross-reacting with platelet/coagulation factors or retinal antigens) and complement activation promoting prothrombotic states in small vessels[72][62]. These mechanisms could operate in combination in susceptible patients[61].
Importantly, any infection or significant inflammatory process can potentially trigger similar pathways leading to vascular complications. COVID-19 vaccines represent just one of many possible inflammatory stimuli that might rarely precipitate retinal occlusions in predisposed individuals, and current evidence suggests they are among the least likely culprits compared to actual infections.
Expert and Regulatory Assessment
Ophthalmology experts and vaccine safety authorities have closely monitored COVID vaccine ocular effects and generally found minimal risk. The editorial by Jampol and Maguire in JAMA Ophthalmology explicitly stated that current data show no significant safety signal for retinal vascular occlusion with mRNA vaccines, reassuring ophthalmologists about the favorable risk-benefit balance[19][20]. The American Academy of Ophthalmology highlighted large studies emphasizing that retinal occlusions were rare after both COVID infection and vaccination, with no observable risk increase[77][36].
Regulatory Surveillance: Major vaccine safety regulators worldwide (CDC, FDA, EMA, MHRA) have not identified retinal vascular occlusion as a serious safety signal requiring action. The CDC’s VAERS analysis found no alarming reporting rates[25], and their Vaccine Safety Datalink has not flagged RVO in safety updates. European and UK agencies similarly have not issued RVO-specific alerts. One exception occurred in late 2023 when the Saudi Food and Drug Authority announced investigation of a potential RVO safety signal with AstraZeneca vaccine[56], though this remains under evaluation rather than confirmed risk.
Risk-Benefit Assessment: All regulatory bodies and expert organizations uniformly assert that COVID-19 vaccination benefits vastly outweigh rare potential risks. The occurrence of occasional retinal occlusions must be weighed against millions of vaccinations preventing severe COVID-19, which itself causes strokes, blood clots, and retinal occlusions from infection-induced hypercoagulable states. Organizations like WHO and CDC continue endorsing vaccination for eligible individuals with no special RVO-related precautions beyond standard practice[20][74].
Clinical Implications and Ongoing Surveillance
From clinical and public health perspectives, current evidence is reassuring. Patients with retinal occlusion history or vascular risk factors can generally receive COVID vaccines without special concern, though all patients should be counseled to seek prompt eye care for acute vision changes. Ongoing surveillance through VAERS, VigiBase, and other pharmacovigilance systems continues monitoring for safety signals[78][73].
Future Research Directions: Experts recommend that future case reports document inflammatory markers and thrombosis laboratory studies (including PF4 antibodies) to better elucidate underlying pathophysiology if such events occur[73][62]. This would help distinguish true vaccine-related events from coincidental occurrences and clarify mechanisms if causal relationships exist.
Conclusion
Retinal vascular occlusion following COVID-19 vaccination represents an exceedingly rare occurrence that currently lacks evidence for direct causation. While case reports have documented temporal associations across various vaccine platforms, large epidemiological studies from multiple countries consistently show no significant population-level increase in retinal occlusion risk post-vaccination. The crude reporting rates of 0.36-0.69 cases per million doses are extremely low and comparable to background rates seen with other routine vaccinations.
Key Contextual Points:
- Any infection or inflammatory condition can potentially trigger vascular complications, including retinal occlusions
- COVID-19 infection itself is a much more established cause of such vascular problems than vaccination
- The rarity of these events emphasizes they should not deter vaccination in the vast majority of individuals
- Current evidence suggests vaccines are among the least likely triggers compared to natural infections
The medical consensus remains clear: COVID-19 vaccination benefits overwhelmingly outweigh the extremely rare potential risks of retinal vascular events. Continued surveillance and research will further clarify this relationship, but current evidence supports maintaining robust vaccination programs while remaining vigilant for rare adverse events. For patients and healthcare providers, the focus should remain on the well-documented, substantial benefits of vaccination in preventing serious COVID-19 illness and death.
References
[1][2][3][30][31][32][33][34][35][51] Pellegrini et al. (2023). Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series. Eye. https://www.nature.com/articles/s41433-023-02459-2
[4][5][6][7][13][16][21][22][23][24][25][71] Agarwal et al. (2023). Retinal Vascular Occlusion after Severe Acute Respiratory Syndrome Coronavirus Vaccination: A Vaccine Adverse Events Reporting System Database Analysis. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC10281033/
[8][9][10][11][70] Furukawa et al. (2024). Case report: A case of unilateral combined central retinal vein occlusion, incomplete central retinal artery occlusion, and papillitis following a third dose of COVID-19 vaccination. Frontiers in Ophthalmology. https://www.frontiersin.org/journals/ophthalmology/articles/10.3389/fopht.2024.1352962/full
[17][18][19] Dorney et al. (2023). Risk of New Retinal Vascular Occlusion After mRNA COVID-19 Vaccination Within Aggregated Electronic Health Record Data. JAMA Ophthalmology. https://pubmed.ncbi.nlm.nih.gov/37052897/
[20][48][49][50][78] Ichhpujani et al. (2022). COVID-19 Vaccine-Associated Ocular Adverse Effects: An Overview. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC9697513/
[26][27][28][29][75][76] Feltgen et al. (2022). Retinal Vascular Occlusion after COVID-19 Vaccination: More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study. PubMed. https://pubmed.ncbi.nlm.nih.gov/36079030/
[36][37] Park et al. (2023). Retinal Artery and Vein Occlusion Risks after Coronavirus Disease. Science Direct. https://www.sciencedirect.com/science/article/abs/pii/S0161642023006784
[41][42][43][44][53][54][65][66] Li et al. (2023). Risk assessment of retinal vascular occlusion after COVID-19 vaccination. npj Vaccines. https://www.nature.com/articles/s41541-023-00661-7
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