Drug-Induced Blindness, Vision Loss: Biological, Ethical, Clinical, and Medicolegal Considerations

Clinicians have responsibility to inform patients of the risks of treatments. Vision-jeopardizing treatments may be best avoided in patients with pre-existing vision deficits or previous inflammation

Aug 19, 2021

A relatively short list of pharmaceutical drugs can cause blindness, vision loss/impairment as a risk or “side effect.” An editor-selected review recommended by the American Academy of Ophthalmology (2013 May) provides four categories of offending drugs: 1) systemic, 2) topical eye drugs, 3) intraocular drugs, and 4) vaccines.

Vaccines reported to be associated with uveitis included Bacille Calmette-Guerin (BCG), influenza, hepatitis B and measles, mumps and rubella (MMR)." American Academy of Ophthalmology. https://www.aao.org/editors-choice/druginduced-uveitis-on-rise 2013 May

Essentially all immunizations are designed to induce nonspecific activation of the innate immune system via inclusion of antigens/immunogens and adjuvants such as aluminum/aluminium; unintended or “off-target” immune activation also occurs via inclusion of allergenic drugs such as antibiotics that are included within these polypharmacy cocktails to prolong shelf life, storage duration. Recently, the newer generation of emergency-authorized unauthorized injections have been noted to pose risk of eye inflammation, visual loss, blindness; these will be listed below as a resource to patients, clinicians, and politicians. This page may be updated with new information as it becomes available; interested persons should revisit this page periodically for any updates.

INTENTIONAL: nonspecific activation of the innate immune system via inclusion of antigens/immunogens and adjuvants such as aluminum/aluminium
UNINTENTIONAL: unintended or “off-target” immune activation also occurs via inclusion of allergenic drugs such as antibiotics that are listed as ingredients in these polypharmacy cocktails to prolong shelf life, storage duration

Cellular/Systemic/Immune Responses (partial listing)

Nonspecific inflammatory responses; activation of pathways such as NFkB, TLRs, and NLRP3: Alum Activates the Bovine NLRP3 Inflammasome. Front Immunol 2017 Nov 9;8:1494. doi: 10.3389/fimmu.2017.01494 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29209310/
Extrusion of cellular DNA in response to aluminum-containing adjuvants: Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells. Proceedings of the National Academy of Sciences (PNAS) March 19, 2013 110 (12) E1122-E1131; https://doi.org/10.1073/pnas.1300392110
Inflammation-driven and drug-driven permeabilization of the blood-brain barrier: "In summary, polysorbate 80 is a promising excipient to increase drug concentration in both plasma and brain via intranasal route." Drug Deliv Transl Res 2019 Feb;9(1):311-318. doi: 10.1007/s13346-018-0580-y. "These results suggested that polysorbate 80 affected the blood-brain barrier and enhanced the brain uptake and analgesic activity of D-kyotorphin." International Journal of Pharmaceutics 1989 Dec https://doi.org/10.1016/0378-5173(89)90266-4
Nonspecific activation of dendritic antigen-presenting cells: "Aluminum adjuvants also activate dendritic cells by binding to membrane lipid rafts. Injection of aluminum-adjuvanted vaccines causes the release of uric acid, DNA, and ATP from damaged cells which in turn activate dendritic cells." Front Immunol 2013 Jan 10;3:406. doi: 10.3389/fimmu.2012.00406
Glial activation; microglial activation; increase in glutaminergic excitotoxicity; neuroinflammation: Because the retina is made of neurons and is largely considered to be an extension of the brain, neuro-inflammatory insults can be seen to directly affect the retina; alternatively, neuronal pathways and the visual cortex of the brain can be directly affected, independent from the eye/retina itself.
Linked-epitope suppression in vaccine-induced immunosuppression resulting in increased infections: "Because of the small number of antigens (3-5 in DTaP vaccines vs >3000 in DTwP vaccines), linked-epitope suppression occurs. Because of linked-epitope suppression, all children who were primed by DTaP vaccines will be more susceptible to pertussis throughout their lifetimes, and there is no easy way to decrease this increased lifetime susceptibility." Journal of the Pediatric Infectious Diseases Society, 2019 Sep, 334–341, https://doi.org/10.1093/jpids/piz005
Vasculitis: Inflammation of the retinal artery (which is the one-and-only source of blood for the retina) can lead to obstruction of blood flow resulting in blindness.

Newer data regarding newer generation of emergency-authorized unauthorized injections noted to pose risk of eye inflammation, visual loss, blindness

"The Pfizer coronavirus vaccine may be linked to a form of eye inflammation called uveitis, according to a multicenter Israeli study led by Prof. Zohar Habot-Wilner from Tel Aviv’s Sourasky Medical Center. The research was conducted at Rambam Health Care Campus, Galilee Medical Center, Shaare Zedek Medical Center, Sheba Medical Center in Tel Hashomer, Kaplan Medical Center and Sourasky. It was accepted for publication by the peer-reviewed ophthalmology journal Retina. Habot-Wilner, head of the Uveitis Service at the hospital, found that 21 people (23 eyes) who had received two shots of the Pfizer vaccine developed uveitis within one to 14 days after receiving their first shot or within one day to one month after the second." https://www.jpost.com/health-science/pfizer-covid-19-vaccine-linked-to-rare-cases-of-eye-inflammation-study-675839
"The patient received the 2nd dose of the Pfizer-BioNTech COVID-19 vaccine on the morning of February 2, 2021. After 3 days, on February 5 late morning, he reported a sudden onset of darkening of the visual field, described as subjective reduction of visual acuity associated with visual distortion. However, the subjective nature of the ophthalmic symptoms was not better investigated since the symptoms disappeared on the same day and the patient preferred not to undergo instrumental evaluation. The morning prior to showing visual symptoms, he reported unilateral, oppressive headache, mainly in his parietal to frontal lobe, without associated symptoms (noise or motion sensitivity, osmophobia, photophobia). The patient, a white adult middle-aged male had no history of ocular problem or migraine, and he had never experienced visual acuity reduction previously. Hours after the onset of the ocular symptoms, he reported light confusion, asthenia, and profound nausea. The severity of symptoms was such to require taking a sick leave from work. He took ibuprofen and eventually after a long rest, the symptoms, including ophthalmologic manifestation, disappeared. He also reported decreased orientation and awareness of his surroundings. Nausea manifested without vomiting, started about 1 h after his lunch. Before the onset of this plethora of symptoms, he only reported low-grade fever and chills the night after the injection. This was followed by 3 days without side effects. All the symptoms, the time of onset, and duration are summarized in Table Table11." Inflamm Res. 2021 Jun 4 : 1–3. doi: 10.1007/s00011-021-01476-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176659/ Very interesting acute transient case; one must wonder what will be his long-term progression as these vaccines are without long-term safety data.

Vaccine-associated uveitis: "All of the widely administered vaccines have been reported to cause uveitis. The ocular inflammation is usually temporary and resolves with topical ocular steroids. During a 26-year period, a total of 289 cases of vaccine-associated uveitis were reported to three adverse reaction reporting databases. Hepatitis B vaccine, either alone or administered with other vaccines, appears to be the leading offender. Clinicians are encouraged to report cases of vaccine- or drug-associated ocular adverse reactions to www.eyedrugregistry.com." Missouri Medicine 2016 Jan-Feb; 113(1): 48–5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139748/
Under-reporting of adverse ocular effects of vaccines: "We believe that adverse ocular effects of vaccines in general are far more prevalent than reported in the literature." Adverse ocular effects following influenza vaccination. Eye 1999;13:381–382 https://www.nature.com/articles/eye1999101.pdf
Bilateral optic neuritis: "A patient is reported in whom bilateral optic neuritis developed following an influenza vaccination. From complete blindness (absence of light perception) in one eye, the patient's vision returned to normal following steroid treatment." Reversible blindness in optic neuritis associated with influenza vaccination. Ann Ophthalmol. 1979 Apr;11(4):545-50 https://www.ncbi.nlm.nih.gov/pubmed/453752
Optic neuritis: "In this child, no infectious, vascular, granulomatous, viral or immune-related cause of optic neuritis was identified. This case provides compelling evidence that supports the nasal flu vaccination as a cause of optic neuritis." Reversible blindness in bilateral optic neruritis associated with nasal flu vaccine. Binocul Vis Strabolog Q Simms Romano. 2012;27(3):171-3 https://www.ncbi.nlm.nih.gov/pubmed/22989339
Ischaemic optic neuropathy: "A 68-year-old man developed bilateral sequential non-arteritic anterior ischaemic optic neuropathy, each episode occurring with a close temporal relationship to influenza vaccination." Bilateral Sequential Non-Arteritic Anterior Ischaemic Optic Neuropathy Following Repeat Influenza Vaccination. Case Rep Ophthalmol 2014;5:267-269 https://doi.org/10.1159/000366472
Bilateral Reversible Optic Neuropathy After Influenza Vaccination: "A previously healthy 6-year-old girl developed bilateral vision loss 1 week after receiving the intramuscular quadrivalent (inactivated influenza vaccine." Journal of Neuro-Ophthalmology 2019;39:496–497 https://journals.lww.com/jneuro-ophthalmology/Citation/2019/12000/Bilateral_Reversible_Optic_Neuropathy_After.9.aspx
Bilateral optic neuritis and loss of vision following influenza vaccination: "We report a 61-year-old woman with bilateral optic neuritis and loss of vision following influenza vaccination. The patient had good recovery of vision following steroid treatment." Bilateral Optic Neuropathy Associated with Influenza Vaccination. Journal of Neuro-Ophthalmology 1996;16:182-184 https://journals.lww.com/jneuro-ophthalmology/Abstract/1996/09000/Bilateral_Optic_Neuropathy_Associated_with.4.aspx#pdf-link
Optic neuritis: "This case provides compelling clinical evidence that implicates influenza vaccination as a cause of optic neuritis." Optic neuritis after influenza vaccination. Am J Ophthalmol. 1997 Nov;124(5):703-4 https://doi.org/10.1016/s0002-9394(14)70918-3
Optic neuritis: "We present evidence for a causal relationship between optic neuritis and the nasally administered live attenuated influenza vaccine." Retrobulbar Optic Neuritis and Live Attenuated Influenza Vaccine. Journal of Pediatric Ophthalmology and Strabismus. 2013;50(1):61 https://doi.org/10.3928/01913913-20121108-01 https://www.healio.com/ophthalmology/journals/jpos/2013-1-50-1/%7B0a16e033-9329-4e6f-a3bb-4a3f0c603e57%7D/retrobulbar-optic-neuritis-and-live-attenuated-influenza-vaccine
Acute macular neuroretinopathy (AMN): "We report a case of acute macular neuroretinopathy (AMN) following routine annual inactivated influenza vaccination." Acute macular neuroretinopathy associated with influenza vaccination with decreased flow at the deep capillary plexus on OCT angiography. American Journal of Ophthalmology Case Reports 2018;10:96-100 https://doi.org/10.1016/j.ajoc.2018.02.008
Bilateral optic neuritis and loss of vision following influenza vaccination: "The authors describe a rare case of bilateral asymmetric optic neuritis with leptomeningeal enhancement on magnetic resonance imaging (MRI) in a previously healthy young woman who received inactivated influenza vaccination 2 weeks before the onset of symptoms." Atypical Optic Neuritis After Inactivated Influenza Vaccination. Neuroophthalmology. 2017 Aug 17;42(2):105-108. doi: 10.1080/01658107.2017.1335333 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858858/
Bilateral optic neuritis: "RESULTS: Our patient developed bilateral optic neuritis on two occasions, 1 year apart. No evidence of neuroretinitis, syphilis, or systemic lupus erythematosus was identified. Influenza vaccination was given 2 weeks before the onset of each episode. CONCLUSION: This case provides compelling clinical evidence that implicates influenza vaccination as a cause of optic neuritis." Optic neuritis after influenza vaccination. Am J Ophthalmol. 1997 Nov;124(5):703-4 https://doi.org/10.1016/s0002-9394(14)70918-3
Optic neuritis: "Two patients, 39 and 23 years of age, were seen with acute optic neuritis 1 month and 2 weeks, respectively, after anthrax booster vaccination and successfully treated with intravenous methylprednisolone. The first patient had a typical presentation and course of unilateral retrobulbar optic neuritis with excellent visual recovery. The second patient had a bilateral anterior optic neuritis and has required chronic immunosuppression to maintain his vision. Retinal and optic nerve autoantibodies were present in the second patient. No cross-reactive epitopes between anthrax vaccine and retina/optic nerve were identified." CONCLUSION: Optic neuritis is a potential adverse reaction of anthrax vaccination. Optic neuritis after anthrax vaccination. Ophthalmology. 2002 Jan;109(1):99-104 https://doi.org/10.1016/S0161-6420(01)00844-2

Ethical, Clinical, and Medicolegal Considerations

Clinicians have a responsibility to inform patients of the risks of treatments. Vision-jeopardizing treatments may be best avoided in patients with pre-existing vision deficits or previous inflammation-driven illnesses. These events are recognized as being systematically under-reported; thus an attempt to describe these reactions as “rare” is baseless.

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