Robertson v. Secretary of Health and Human Services

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 18-554V
Filed: November 10, 2022
PUBLISHED
Special Master Horner
SCOTT ROBERTSON,
Petitioner, Optic neuritis (“ON”);
v. nonarteritic anterior ischemic
optic neuropathy (“NAION”);
SECRETARY OF HEALTH AND Influenza (“flu”) vaccine
HUMAN SERVICES,
Respondent.
Ronald Homer, Conway, Homer, P.C., Boston, MA, for petitioner.
Voris Johnson, U.S. Department of Justice, Washington, DC, for respondent.
DECISION 1
On April 17, 2018, petitioner filed a petition under the National Childhood Vaccine
Injury Act, 42 U.S.C. § 300aa-10-34 (2012), 2 alleging that the influenza (“flu”) vaccine
he received on October 28, 2016, caused him to suffer relapsing optic neuropathy
and/or neuritis. (ECF No. 1, p. 1.) Subsequently, the parties’ experts agreed that the
best diagnosis for petitioner’s condition is nonarteritic anterior ischemic optic neuropathy
(“NAION”). (Ex. 30, p. 1; Ex. B, p. 5.) On August 13, 2021, petitioner filed his motion
for a ruling on the record alleging that the flu vaccine caused-in-fact his NAION. (ECF
No. 65, pp. 1 n.2, 27-29.) For the reasons set forth below, I conclude that that petitioner
is not entitled to compensation.
1 Because this decision contains a reasoned explanation for the special master’s action in this case, it will
be posted on the United States Court of Federal Claims’ website in accordance with the E-Government
Act of 2002. See 44 U.S.C. § 3501 note (2012) (Federal Management and Promotion of Electronic
Government Services). This means the decision will be available to anyone with access to the
Internet. In accordance with Vaccine Rule 18(b), petitioner has 14 days to identify and move to redact
medical or other information the disclosure of which would constitute an unwarranted invasion of privacy.
If the special master, upon review, agrees that the identified material fits within this definition, it will be
redacted from public access.
2Within this decision, all citations to § 300aa will be the relevant sections of the Vaccine Act at 42 U.S.C.
§ 300aa-10-34.
1
I. Applicable Statutory Scheme
Under the National Vaccine Injury Compensation Program, compensation
awards are made to individuals who have suffered injuries after receiving vaccines. In
general, to gain an award, a petitioner must make a number of factual demonstrations,
including showing that an individual received a vaccination covered by the statute;
received it in the United States; suffered a serious, long-standing injury; and has
received no previous award or settlement on account of the injury. Finally – and the key
question in most cases under the Program – the petitioner must also establish a causal
link between the vaccination and the injury. In some cases, the petitioner may simply
demonstrate the occurrence of what has been called a “Table Injury.” That is, it may be
shown that the vaccine recipient suffered an injury of the type enumerated in the
“Vaccine Injury Table,” corresponding to the vaccination in question, within an
applicable time period following the vaccination also specified in the Table. If so, the
Table Injury is presumed to have been caused by the vaccination, and the petitioner is
automatically entitled to compensation, unless it is affirmatively shown that the injury
was caused by some factor other than the vaccination. § 300aa-13(a)(1)(A); § 300 aa-
11(c)(1)(C)(i); § 300aa-14(a); § 300aa-13(a)(1)(B).
In many cases, however, the vaccine recipient may have suffered an injury not of
the type covered in the Vaccine Injury Table. In such instances, an alternative means
exists to demonstrate entitlement to a Program award. That is, the petitioner may gain
an award by showing that the recipient’s injury was “caused-in-fact” by the vaccination
in question. § 300aa-13(a)(1)(B); § 300aa-11(c)(1)(C)(ii). In such a situation, of course,
the presumptions available under the Vaccine Injury Table are inoperative. The burden
is on the petitioner to introduce evidence demonstrating that the vaccination actually
caused the injury in question. Althen v. Sec’y of Health & Human Servs., 418 F.3d
1274, 1278 (Fed. Cir. 2005); Hines v. Sec’y of Health & Human Servs., 940 F.2d 1518,
1525 (Fed. Cir. 1991).
The showing of “causation-in-fact” must satisfy the “preponderance of the
evidence” standard, the same standard ordinarily used in tort litigation. § 300aa-
13(a)(1)(A); see also Althen, 418 F.3d at 1279; Hines, 940 F.2d at 1525. Under that
standard, the petitioner must show that it is “more probable than not” that the
vaccination was the cause of the injury. Althen, 418 F.3d at 1279. The petitioner need
not show that the vaccination was the sole cause but must demonstrate that the
vaccination was at least a “substantial factor” in causing the condition, and was a “but
for” cause. Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352 (Fed. Cir.
1999). Thus, the petitioner must supply “proof of a logical sequence of cause and effect
showing that the vaccination was the reason for the injury[,]” with the logical sequence
being supported by “reputable medical or scientific explanation, i.e., evidence in the
form of scientific studies or expert medical testimony.” Althen, 418 F.3d at 1278; Grant
v. Sec’y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). A petitioner
may not receive a Vaccine Program award based solely on his or her assertions; rather,
the petition must be supported by either medical records or by the opinion of a
competent physician. § 300aa-13(a)(1).
2
In what has become the predominant framing of this burden of proof, the Althen
court described the “causation-in-fact” standard, as follows:
Concisely stated, Althen’s burden is to show by preponderant evidence that
the vaccination brought about her injury by providing: (1) a medical theory
causally connecting the vaccination and the injury; (2) a logical sequence
of cause and effect showing that the vaccination was the reason for the
injury; and (3) a showing of proximate temporal relationship between
vaccination and injury. If Althen satisfies this burden, she is “entitled to
recover unless the [government] shows, also by a preponderance of the
evidence, that the injury was in fact caused by factors unrelated to the
vaccine.”
Althen, 418 F.3d at 1278 (citations omitted). The Althen court noted that a petitioner
need not necessarily supply evidence from medical literature supporting petitioner’s
causation contention, so long as the petitioner supplies the medical opinion of an
expert. Id. at 1279-80. The court also indicated that, in finding causation, a Program
factfinder may rely upon “circumstantial evidence,” which the court found to be
consistent with the “system created by Congress, in which close calls regarding
causation are resolved in favor of injured claimants.” Id. at 1280.
In this case, petitioner has alleged that the flu vaccine caused him to suffer
nonarteritic anterior ischemic optic neuropathy (“NAION”). (ECF No. 65, pp. 1 n.2, 27-
29.) Since NAION is not listed on the Vaccine Injury Table relative to the flu vaccine,
petitioner must satisfy the above-described Althen test for establishing causation-in-fact.
II. Procedural History
On April 17, 2018, petitioner filed a petition alleging that he received a flu vaccine
on October 28, 2016, that caused relapsing optic neuropathy and/or neuritis. (ECF No.
1, p. 1.) This case was originally assigned to Special Master Sanders. (ECF No. 4.)
On April 20, 2018, petitioner filed his affidavit and medical records. (ECF Nos. 8-10.)
From May 21, 2018, through April 22, 2019, petitioner subsequently filed additional
medical records. (ECF Nos. 13, 19, 21, 25.) On May 16, 2019, respondent filed his
Rule 4(c) report, arguing that the evidence presented did not meet petitioner’s burden
and recommending against compensation. (ECF No. 28.) Respondent further argued
that petitioner’s diagnosis appeared to be CRION, a “separate clinical entity from
monophasic ON and its key clinical features include relapsing inflammatory ON and
steroid dependency.” (Id. at 7.)
This case was reassigned to my docket on August 28, 2019. (ECF No. 34.) On
October 9, 2019, petitioner filed additional medical records. (ECF No. 37.) On
November 18, 2019, petitioner filed an expert report from Thomas Hedges III, M.D.
(neuro-ophthalmologist). (ECF No. 40.) On March 31, 2020, respondent filed an expert
report from Michael Wilson, M.D., MAS (neuroimmunologist). (ECF No. 44.)
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Subsequently both parties filed supplemental expert reports on April 29 and June 30,
2020. (ECF No. 45 (Dr. Hedges); ECF No. 48 (Dr. Wilson).).
A Rule 5 conference was held on September 18, 2020. (ECF No. 50.) In the
subsequent Rule 5 Order, I noted that diagnosis was an unresolved issued in this case.
(Id.) In his petition, petitioner alleged that he suffered either optic neuritis or
neuropathy; and respondent disputed optic neuritis as a diagnosis but suggested a type
of neuropathy. (Id.) Petitioner’s expert Dr. Hedges opined that petitioner’s diagnosis is
nonarteritic ischemic optic neuropathy. (Id.) Respondent’s expert Dr. Wilson agreed
with the assessment of NAION though he did not dismiss the possible diagnosis of optic
neuritis. (Id.) With regard to causation, I observed that Dr. Hedges cited four case
reports showing that NAION can occur post-influenza vaccination (Ex. 24, p. 2), though
I cautioned that standing alone these case reports are not highly persuasive. (ECF No.
50.)
On January 19, 2021, petitioner filed an expert report from Omid Akbari, Ph.D.
(allergy and immunology). (ECF Nos. 53-57.) Respondent filed a responsive expert
report from Dr. Wilson on March 23, 2021. (ECF No. 60.) On June 14, 2021, the
parties filed a joint status report proposing a ruling on the written record. (ECF No. 64.)
On August 13, 2021, petitioner filed his motion for a ruling on the record. (ECF No. 65.)
On October 13, 2021, respondent filed his responsive brief. (ECF No. 66.) On
November 10, 2021, petitioner filed his reply. (ECF No. 68.)
I have determined that the parties have had a full and fair opportunity to present
their cases and that it is appropriate to resolve this issue without a hearing. See
Vaccine Rule 8(d); Vaccine Rule 3(b)(2); Kreizenbeck v. Sec’y of Health & Human
Servs., 945 F.3d 1362, 1366 (Fed. Cir. 2020) (noting that “special masters must
determine that the record is comprehensive and fully developed before ruling on the
record.”). Accordingly, this matter is now ripe for resolution.
III. Factual History
a. As reflected in the medical records
Prior to vaccination, petitioner’s history was significant for a motor vehicle
accident in March 2014 with cervical and lumbar pain. (Exs. 5, 12, 15.) He also had a
history of tobacco use, hypertension, and hyperlipidemia. (See, e.g., Ex. 5, pp. 1-2
(4/18/2017 record listing hypertension and hyperlipidemia as active problems, and
noting “[c]urrent everyday [sic] smoker”); id. at 13 (7/16/2014 record noting “tobacco
use” under the social history section); Ex. 7, p. 2 (12/22/2016 record noting that
petitioner “[c]hews tobacco”).) Petitioner also suffers from obstructive sleep apnea.
(Ex. 2, p. 5.)
Petitioner received a Fluvirin vaccine on October 28, 2016. (Ex. 1, p. 1.) On
December 5, 2016, petitioner presented to Jennifer Roman, O.D., complaining of blurry
vision in his left eye. (Ex. 13, p. 11.) He reported a sudden onset on Tuesday
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(November 29), which had slowly worsened over the last couple of days. (Id.)
Petitioner indicated that he recently had a cold. (Id. at 11; see also Ex. 3, pp. 4-8
(petitioner reporting that he had a cold over Thanksgiving).) On examination, the
optometrist observed left optic disc swelling. (Ex. 13, pp. 11-16; Ex. 3, p. 3.) Dr.
Roman referred petitioner to the emergency room for suspected NAION. (Ex. 13, p.
16.)
That same day, December 5, 2016, petitioner presented to the Emergency
Department (“ED”) at UF Health Shands. (Ex. 3, p. 3.) He reported noticing floaters /
spots in his left field of vision approximately three-to-four days earlier, which had
enveloped his whole eye. (Id.) Petitioner also reported eye pressure but denied eye
pain. (Id. at 4-6.) A review of systems was positive for nasal congestion and discharge.
(Id. at 4.) His differential diagnoses included papilledema, optic neuropathy, anterior
ischemic optic neuropathy, and papillophlebitis. (Id. at 5.) An ophthalmologist was
consulted and ordered a brain MRI, which confirmed the presence of left-sided palpable
edema without associated enhancement and changes of chronic ischemic white matter
demyelination in the brain as seen in the setting of chronic small vessel disease. (Id. at
6, 52-53.) There was no evidence of an intracranial mass lesion, infectious /
inflammatory process, or MR findings of intracranial hypertension. (Id. at 6.) The
ophthalmologist diagnosed petitioner with optic nerve swelling and optic atrophy of the
left eye of unknown etiology, and recommended Brimonidine eye drops. (Id.) Petitioner
was discharged the following day to follow up with an ophthalmologist. (Id. at 6, 14.)
On December 9, 2016, petitioner was evaluated by ophthalmologist Stephen
Potter, M.D., at the University of Florida (“UF”) Eye Center for painless vision loss and
optic disc edema in the left eye. (Ex. 8, p. 1.) He also developed atrophy in his left eye.
(Id. at 10.) The ophthalmologist indicated that petitioner’s differential diagnosis was
“most likely post-vaccination optic neuritis given flu-shot 1 month prior to presentation vs
post-infectious optic neuritis (less likely given negative labs; baronella [sic] pending) vs
autoimmune optic neuritis (MS-spectrum).” (Id. at 2; Ex. 4, p. 43.) He recommended
admission to the hospital for treatment with intravenous (“IV”) steroids. (Ex. 8, p. 2.)
Petitioner was subsequently admitted to the hospital for three days of treatment with IV
steroids and then discharged with an oral steroid taper. (Ex. 4, pp. 39-44; Ex. 19, pp. 4-
5.)
On January 5, 2017, petitioner presented to neuro-ophthalmologist Hazem
Samy, M.D., at the UF Eye Center. (Ex. 8, pp. 4-5.) Dr. Samy diagnosed petitioner with
left eye papillitis “[p]ost-vaccination vs post-infectious vs autoimmune optic neuritis (MS-
spectrum . . . Received flu vaccine 1 month prior to presentation.” (Id.) Petitioner
reported improved visual acuity and visual field as well as resolved edema. (Id.) Dr.
Samy ordered petitioner to continue taking Brimonidine and “[a]void flu vaccination in
future.” (Id.)
On January 27, 2017, petitioner returned to Dr. Samy with new onset of mild
swelling / edema of the optic nerve with flame hemorrhage in his right eye. (Ex. 8, pp.
9-15.) Dr. Samy started petitioner on treatment with oral prednisone. (Id. at 11.)
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Petitioner returned to Dr. Samy emergently almost a week later, on February 2, 2017,
complaining of worsening blurry vision in his right eye. (Id. at 15.) Dr. Samy suspected
possible sequential NAION of the right eye. (Id. at 15-16.) Petitioner had mild inferior
optic nerve edema, which was stable since his previous visit. (Id.) Dr. Samy
recommended continuing treatment with prednisone. (Id. at 16.) In follow-up two
weeks later, petitioner’s vision was stable. (Id. at 17.)
Petitioner returned to Dr. Samy’s office on March 12, 2017, complaining of
worsening visual disturbances in his right eye with decreasing prednisone dosage. (Ex.
8, p. 22.) The doctor recommended that petitioner go to the hospital to receive another
round of IV steroids. (Id. at 25; Ex. 3, pp. 82-83.) The ER sent petitioner to the infusion
center for treatment to avoid having to be admitted to the hospital. (Id. at 87.)
Petitioner subsequently received two days of IV steroids for right ischemic optic
neuropathy. (Ex. 10, pp. 1-50.)
Petitioner followed up with Dr. Samy on March 16, 2017, complaining that his
right eye seemed worse. (Ex. 8, p. 26.) Dr. Samy’s impression based on petitioner’s
presentation and clinical course was that he had chronic relapsing AION. 3 (Id. at 30.)
Petitioner continued to follow up with Dr. Samy for CRON in April, May, and July 2017.
(Ex. 5, pp. 1-6; Ex. 8, pp. 32-37; Ex. 19, pp. 1-5.) A skin punch biopsy collected on April
14, 2017, showed no evidence of vasculitis or vasculopathy. (Ex. 8, p. 44.) At a May
19, 2017 visit, Dr. Samy noted that petitioner had slight improvement in his visual field
defects and stable visual acuity. (Id. at 38.)
On April 4, 2017, petitioner established care with a new primary care physician,
Brian Pecoraro, D.O., at Ocala Family Wellness Center. (Ex. 5, p. 7.) Dr. Pecoraro
noted in petitioner’s active problems optic neuritis—for which he was being monitored
by ophthalmology and treated with steroids. (See, e.g., Ex. 5, pp. 1-5.)
On July 7, 2017, petitioner complained to Dr. Samy that his vision had been off
for the past four days after tapering his prednisone. (Ex. 19, pp. 4-5.) Dr. Samy
recommended starting CellCept, an immune-modulating agent. (Id.) However,
because it would take about three months for CellCept to be effective, Dr. Samy
recommended another round of IV steroids followed by increasing petitioner’s
prednisone in the interim. (Id. at 5.) Consequently, petitioner received three days of IV
steroids at the infusion center from July 12 through 14, 2017. (Id. at 6; Ex. 10, pp. 50-
110.)
In follow-up on July 21, 2017, petitioner indicated that his vision was off in the
previous visit. (Ex. 19, pp. 11-12.) Petitioner underwent subsequent C-spine MRI to
rule out neuromyelitis optica. (Ex. 22, pp. 1-2.) The impression was “[n]o evidence of
abnormal T2 signal changes or abnormal contrast enhancement of the cervical or
thoracic spinal cord which could suggest inflammation/demyelination.” (Id. at 2.) There
3Dr. Samy maintained the diagnosis of CRON (chronic relapsing optic neuropathy) throughout
subsequent visits, noting sequential NAION as a previous impression. (See, e.g., Ex. 5, pp. 1-6; Ex. 8,
pp. 32-37; Ex. 19, pp. 1-35; Ex. 21, pp. 1-3.)
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was no significant disc disease or canal narrowing in the cervical or thoracic spine. (Id.)
Thereafter, petitioner followed up with Dr. Samy on August 11, September 22, and
December 14, 2017; and on February 23, May 25, and November 12, 2018, for CRON.
(Ex. 19, pp. 13-39; Ex. 21, pp. 1-3.) During that time, petitioner experienced some
improvement in his visual acuity and visual fields on prednisone and CellCept, and there
was no recurrence of inflammation in the optic nerves. (Id.) Petitioner discontinued
prednisone in February 2018 without a subsequent change in his vision. (Ex. 19, pp.
34-35.) In his November 12, 2018, visit Dr. Samy remarked that petitioner developed
“optic neuropathy [in] early 2017 which was post vaccination but in a pattern suggestive
of possible ischemia in disc without cup followed by a few months later with the other
eye.” (Ex. 21, p. 3.) “The clinical course of the optic neuropathy showed recurrences
after tapering of the oral steroid which made the diagnosis CRION (chronic relapsing
inflammatory optic neuropathy).” (Id.) Dr. Samy explained to petitioner he would need
to taper off the CellCept and continue regular blood testing. (Id. at 4.)
b. Petitioner’s affidavit
On October 28, 2016, petitioner received a flu vaccine at his local Walgreens.
(Ex. 16, p. 1.) Several weeks later, shortly after Thanksgiving, petitioner describes
losing vision in his left eye, “[i]t started as a hazy halo around the outside of my left eye,
which progressively closed in and led to a complete loss of vision in my left eye when I
woke up on December 5, 2016.” (Id. at 1-2.) That day petitioner presented to an
optometrist who sent him to the emergency room at Shands Hospital in Gainesville,
Florida. (Id. at 2.) He was discharged on December 6, 2016, and told to follow up with
an ophthalmologist. (Id.)
Petitioner returned to work soon after discharge. (Ex. 16, p. 2.) Petitioner avers
that he was concerned that his employer would feel that he was unable to work due to
his vision loss. (Id.) While on the job petitioner suffered a right thumb injury while
operating a spring-loaded jack. (Id.) In January 2017, petitioner avers that he
established care with ophthalmologist Dr. Hazem Samy. (Id. at 3.) Despite treatment
petitioner asserts that he still had significant deficits in his vision in his left eye. (Id.)
Subsequently petitioner began to experience vision issues in his right eye in
March 2017. (Ex. 16, p. 3.) He avers that he was “more aware of what was occurring
with [his] right eye,” so he immediately went to Dr. Samy’s office, where he saw Dr.
Andres Gonzalez, who sent him directly to Shands Hospital to receive three days of IV
steroid treatments. (Id.) Petitioner avers that following his onset of optic neuritis, his
vision loss has been permanent. (Id.) He continued taking steroids to prevent further
episodes, which caused additional health issues. (Id.) Petitioner describes taking
Metformin, arnica (due to bruising that developed after taking steroids), vitamin B12 and
CoQ10 supplements, and using an APAP machine. (Id.)
Petitioner avers that his condition caused him to miss three to four weeks of
work, and that he can no longer perform mechanic or welding work because of his
difficulties with depth perception. (Ex. 16, pp. 3-4.) As a result, petitioner avers that he
7
“need[s] to be much more cautious at work and [his] end product is not as good as it
was prior to [his] vision loss.” (Id.) He asserts that he is unable to do his job to the best
of his ability and is concerned about future employment. (Id.)
Petitioner describes difficulty watching his daughter’s softball games and award
ceremonies. (Ex. 16, p. 4.) His condition also impacts his ability to drive, especially at
night. (Id. at 5.) He avers that he faces financial instability due to the medical bills he
incurred during treatment. (Id.) Petitioner continues follow-up treatment with Dr. Samy
every sixty to ninety days. (Id.) He avers that his vision has stabilized but has not
improved. (Id. at 6.) Petitioner describes a small area of tunnel vision in the bottom
right-hand corner of his left eye, a hazy halo around the outside of the eye, and a blind
spot in the lower right-hand corner of his right eye. (Id.)
IV. Summary of Expert Opinions
a. Petitioner’s Experts
i. Thomas R. Hedges, III, M.D.
Dr. Hedges received his medical degree from Tufts University. (Ex. 25.) He
completed his residency in ophthalmology at Massachusetts Eye and Ear Infirmary at
Harvard Medical School. (Id.) Dr. Hedges completed an ophthalmic pathology
fellowship at that the Massachusetts Eye and Ear Infirmary at Harvard Medical School.
(Id.) He subsequently completed a fellowship in neuro-ophthalmology at the University
of California, San Francisco. (Id.) Dr. Hedges is board certified in ophthalmology. (Id.)
He has served as an ophthalmologist at Tufts Medical Center since 1991. (Id.) He
currently serves as a professor of ophthalmology and neurology at Tufts University.
(Id.) His research interests include qualitative and quantitative evaluation of the retinal
nerve fiber layer using photographic methods, computerized image enhancement, and
Optical Coherence Tomography; Color Doppler imaging of orbital and extracranial blood
vessels in vascular diseases affecting the eye; multifocal electroretinography and visual
evoked potential recording. (Id.) He has co-authored several works on optic and
peripheral neuropathy. (Id.)
Dr. Hedges opines that petitioner’s correct diagnosis is NAION. (Ex. 24, p. 1.)
According to Dr. Hedges, anterior ischemic optic neuropathy is relatively common, but
the exact pathogenesis is unknown. (Id. at 2.) It appears to be multifactorial, with
various associations, but no one direct cause has been identified. (Id.) Dr. Hedges
observes that petitioner has some of the associated risk factors, including hypertension
and sleep apnea, but he stresses that “these are associations, not direct causative
factors.” (Id.) Dr. Hedges opines that these risk factors combined with a physiologic
response to vaccination “pushed beyond normal function and past regulatory
mechanisms, more likely than not, resulted in injury to [petitioner’s] optic nerves.” (Id.)
He asserts that the most plausible mechanism is that of immune complex mediated
vasculopathy/vasculitis, leading to inflammation and resultant ocular nerve injury. (Id.)
This is a form of type Ill hypersensitivity whereby proteins contained in the vaccine
8
stimulate an antibody reaction causing formation of antigen-antibody complexes, which
can block small blood vessels or attach to the walls of small blood vessels stimulating
inflammation and then blockage of the vessels leading to damage, in this case, to the
optic nerve. (Id.)
In support of his theory, Dr. Hedges observes that post-vaccination optic neuritis
is well-documented in the medical literature and is believed to be similar to other
instances of damage to other cranial nerves following vaccination, especially with
regard to the seventh nerve (Bell’s) palsy following vaccination. (Ex. 24, p. 2 (citing
Janaki Patel et al., Development of Optic Neuritis After Vaccination, a CDC/FDA
Vaccine Adverse Event Reporting System (VAERS) Study, 1990-2017, 90 NEUROLOGY
1 (2018) (Ex. 26)).) Dr. Hedges cites four case reports of anterior ischemic neuropathy
following vaccination. (Id.) In 1998, Kawasaki et al. reported two cases of anterior
ischemic optic neuropathy following influenza vaccination. (Id. (citing Aki Kawasaki et
al., Bilateral Anterior Ischemic Optic Neuropathy Following Influenza Vaccination, 18 J.
NEURO-OPHTHALMOLOGY 56 (1998) (Ex. 27)).) The authors postulated that an immune
complex-mediated vasculopathy caused the optic nerve damage. (Id.) Next, Dr.
Hedges cites Ray and Dreizin, who reported a case of a 61-year-old man with bilateral
optic neuropathy “similar to [petitioner] who had some response to steroid treatment.”
(Id. (citing Cheryl Ray & Ivy Dreizin, Bilateral Optic Neuropathy Associated with
Influenza Vaccination, 16 J. NEURO-OPHTHALMOLOGY 182 (1996) (Ex. 28)).) Most
recently, Manasseh et al. reported another case of bilateral sequential NAION following
repeat influenza vaccination. (Id. (citing Gemma Manasseh et al., Bilateral Sequential
Non-Arteritic Anterior Ischaemic Optic Neuropathy Following Repeat Influenza
Vaccination, 5 CASE REP. OPHTHALMOLOGY 267 (2014) (Ex. 29)).) Like Kawasaki et al.,
the authors opined that immune complex vasculitis was a more likely mechanism than
demyelination damaging the optic nerve.
Regarding timing, Dr. Hedges opines that petitioner experienced onset of
symptoms approximately 4.5 weeks post vaccination. (Ex. 24, p. 2.) He opines that this
is an appropriate timeframe for symptom development because immune-mediated
disorders typically develop within 6 to 8 weeks following a triggering event. (Id.)
Moreover, Dr. Hedges represents that this is consistent with the timing of symptom
onset in the case reports. (Id.) On average those patients experienced onset of NAION
within one to four weeks post-flu vaccination. (Id.)
In his supplemental report, Dr. Hedges opines that skin biopsies in patients with
immune hypersensitivity reactions are “frequently normal, especially when performed
months later.” (Ex. 30, p. 1.) Petitioner’s skin biopsy was performed in April 2017, over
six months post-vaccination. (Id.) Respondent’s expert Dr. Wilson argues that a
temporally proximate viral illness may have equally served as an infectious trigger for
petitioner’s injury. (Ex. B.) In response, Dr. Hedges opines that any potential illness is
ill-defined, and no viral or bacterial infection was ever identified. (Ex. 30, p. 1.)
Furthermore, he stresses that upper respiratory infections are common, frequently
coincidental and generally not considered to be associated with or causal of ON or
NAION. (Id. at 1-2.)
9
ii. Omid Akbari, Ph.D.
Dr. Akbari received his Master of Science degree from the University College of
London. (Ex. 32.) He received his Ph.D. in cellular and molecular immunology from the
National Institute for Medical Research in London. (Id.) Dr. Akbari completed his
postdoctoral fellowship at Stanford University. (Id.) He currently serves as a professor
of Allergy and Immunology and professor of Medicine at Keck School of Medicine,
University of Southern California. (Ex. 31.) Prior to that Dr. Akbari was an assistant
professor at Harvard Medical School and held an appointment as senior scientist at
Stanford University. (Id.) Dr. Akbari’s research is focused on the role of immune
tolerance and how immune cells induce autoimmune and allergic diseases. (Id.) He
has served on several NIH study sections, including special emphasis panel related to
research in vaccine, infectious diseases, and immunology. (Id.)
Regarding petitioner’s diagnosis, Dr. Akbari observed that “[t]he possibility of
[optic neuritis] was not ruled out as some patients with ON are steroid refractory and do
not exhibit demyelination in regular MRI scan.” (Ex. 31, p. 3.) He acknowledges that
Dr. Hedges and Dr. Wilson have opined that petitioner may have atypical optic neuritis,
though it is more likely that he suffers from NAION. (Id.) Still, in his expert report Dr.
Akbari discusses how the flu vaccine can cause optic neuritis and/or vasculitis, leading
to ischemic complications and optic nerve injury. (Id.)
First Dr. Akbari proposes a theory of molecular mimicry, “which support[s] the
notion and describe[s] how [the] influenza vaccine can induce immune responses,
which are often associated with inflammation, vasculitis[,] and optic nerve injury.” (Ex.
31, p. 6-8.) He cites two studies involving multiple sclerosis, neuromyelitis and
demyelinating disease. (Id. at 6.) Markovic-Plese et al. proposed cross-reactivity of a
CD4+ T-cell clone specific for the immunodominant influenza virus hemagglutinin
peptide (sequence YVKQSTLKL) derived from a patient with neuromyelitis and
demyelinating disease, including MS. (Silva Markovic-Plese et al., High Level of Cross-
Reactivity in Influenza Virus Hemagglutinin-Specific CD4+ T Cell Response:
Implications for the Initiation of Autoimmune Response in Multiple Sclerosis, 169 J.
NEUROIMMUNOLOGY 31 (2005) (Ex. 50)).) In another study by Harvard group
Wucherpfennig et al., a panel of 129 peptides that matched the molecular mimicry motif
was tested on seven specific T cell clones from patients with neuromyelitis and
demyelinating disease. (Kai Wucherpfennig et al., Recognition of the Immunodominant
Myelin Basic Protein Peptide by Autoantibodies and HLA-DR2-Restricted T Cell Clones
from Multiple Sclerosis Patients, 100 J. CLIN. INVEST. 1114 (1997) (Ex. 54)).) Seven viral
and one bacterial peptide efficiently activated three of these clones. (Id.) From these
studies Dr. Akbari proposes that the influenza vaccine petitioner received “contains a
protein that cross-reacts with myelin based antigens in humans who had demyelinating
disease.” (Ex. 31, p. 6.) Dr. Akbari draws support for this theory from studies showing
that self-reactive T cells were also shown to cause optic neuritis in both rat models and
non-human primates. (Id. (citing F.X. Weilbach et al., T-Cell Receptor V Beta-Element
Expression in Peripheral Nerves of Lewis Rats Suffering from Experimental
Autoimmune Neuritis, 79 J. NEUROIMMUNOL. 69 (1997) (Ex. 52); Jeffrey Bajramovic et
10
al., Oligodendrocyte-Specific Protein Is Encephalitogenic in Rhesus Macaques and
Induces Specific Demyelination of the Optic Nerve, 38 EUR. J. IMMUNOL. 1452 (2008)
(Ex. 53)).) Alternatively, Dr. Akbari proposes another peptide to the major protein in the
myelin sheath known as myelin basic protein in the influenza A vaccines. (Ex. 31, p. 7.)
The amino acid sequence, FYKNLI, has high homology to myelin basic protein FFKNIV.
(Id.) He explains that the only variations are one aromatic amino acid “f” for “y” and two
aliphatic amino acids, leucine and isoleucine. (Id.) This, according to Dr. Akbari, is an
undeniable example of molecular mimicry with influenza A strains that appear in the
vaccine petitioner received.
Dr. Akbari explains that NAION is the most common form of ischemic optic
neuropathy and the second most common form of optic neuropathy. (Ex. 31, p. 7.) He
writes, “[i]t is presumed to be due to a transient disruption in the circulation of the optic
nerve head leading to hypoperfusion and ischemia.” (Id.) Several hypotheses have
been proposed including generalized hypoperfusion, nocturnal hypotension, local
autoregulation failure, vasospasm, venous inflammation, vasculitis and thrombosis. (Id.
(citing Shauna Berry et al., Nonarteritic Anterior Ischemic Optic Neuropathy: Cause,
Effect, and Management, 9 EYE & BRAIN 23 (2017) (Ex. 56)).) Although rare, Dr. Akbari
opines that vasculitis has been reported as an adverse event following influenza
vaccination. (Id.) Among 45 published reports, Watanabe identified 65 patients who
developed vasculitis after influenza vaccination. (Id. (citing Toru Watanabe, Vasculitis
Following Influenza Vaccination: A Review of Literature, 13 CURR. RHEUMATOL. REV. 188
(2017) (Ex. 57)).) Hadden et al. also reported several case reports with vasculitic
neuropathy after influenza vaccination. (Id. (citing Robert Hadden et al., Vasculitic
Peripheral Neuropathy: Case Definition and Guidelines for Collection, Analysis, and
Presentation of Immunization Safety Data, 35 VACCINE 1567 (2017) (Ex. 58)).) Still
other investigators also reported cases associating flu vaccination with optic
neuropathy. (Id. (citing Emily Li & Adeniyi Fisayo, Bilateral Reversible Optic Neuropathy
After Influenza Vaccination, 39 J. NEURO-OPHTHALMOL. 496 (2019) (Ex. 59); Kawasaki et
al., supra, at Ex. 27 (also filed as Ex. 60)).)
Dr. Akbari further opines that cytokines may also play a role in inducing
vasculitis. (Ex. 31, p. 8.) He observes that Song et al. published a meta-analysis to
investigate possible associations between IL-1ɑ, IL-1β, and IL-1 receptor antagonist
(IL1RN) polymorphisms and vasculitis. (Id. (citing Song et al., Associations Between
Interleukin-1 Polymorphisms and Susceptibility to Vasculitis: A Meta-Analysis, 75 Z.
RHEUMATOL. 406 (2016) (Ex. 67)).) According to Dr. Akbari, the results strongly suggest
that IL-1 polymorphism is associated with susceptibility to vasculitis. (Id.) Besides the
IL-1 cytokine family, Dr. Akbari identifies other pro-inflammatory cytokines such as IL-6
which were associated with a strong ability to polarize immune cells to produce IL-17
and induce vasculitis and optic neuropathy. (Id. (citing Hajime Yoshifjui,
Pathophysiology of Large Vessel Vasculitis and Utility of Interleukin-6 Inhibition
Therapy, 29 MODERN RHEUMATOL. 287 (2019) (Ex. 68)).) Since these cytokines are
“potent stimulators of adaptive responses,” Dr. Akbari concludes that the inflammasome
is likely a primary target causing vascular inflammation. (Id. (citing G.A. Ramirez et al.,
11
Intravascular Immunity as a Key to Systemic Vasculitis: A Work in Progress, Gaining
Momentum, 175 CLIN. EXP. IMMUNOL. 150 (2014) (Ex. 69)).)
Still further, Dr. Akbari proposes a mechanism involving T cell dysfunction. (Ex.
31, pp. 8-9.) He opines that the influenza vaccine has been shown to stimulate
regulatory T cells and T effector cells in normal individuals post-vaccination. (Id. at 9.)
A balance in the levels of regulatory T cells and T effector cells maintains the
homeostatic and disease-free state. (Id.) A shift in the balance towards T regulatory
cells causes a decrease in anti-cancer immunity, resulting in cancer. (Id.) In contrast, a
shift in the balance towards T effector cells causes a decrease in T regulatory cell levels
and T effector cells hyperactivation—leading to autoimmune disorders, such as optic
neuropathy. (Id.) In petitioner’s case, Dr. Akbari proposes pathogenic T effector cells
caused injury directly to the nerve or, alternatively, caused inflammation in the vascular
system that resulted in optic nerve injury—simply due to T regulatory cells. (Id. (citing
Huabin Zheng et al., Increased Th17 Cells and IL-17 in Rats with Traumatic Optic
Neuropathy, 10 MOL. MED. REP. 1954 (2014) (Ex. 48); Shin-Min Wang et al., The
Regulatory T Cells in Antiinfluenza Antibody Response Post Influenza Vaccination, 8
HUM. VACCIN. IMMUNOTHER. 1243 (2012) (Ex. 71); Thi Hong Khanh Vu et al., CD4(+) T-
Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic
Retinopathy, 190 AM. J. PATHOL. 1723 (2020) (Ex. 72)).) Moreover, Dr. Akbari cites a
cohort study of elderly patients who received the flu vaccine who demonstrated only a
limited responsiveness to the vaccine, but a higher inflammatory status. (Ex. 31, p. 9
(citing I. Herrero-Fernandez et al., Effect of Homeostatic T-Cell Proliferation in the
Vaccine Responsiveness Against Influenza in Elderly People, 16 IMMUNITY & AGEING 1
(2019) (Ex. 73)).) Dr. Akbari concludes that T regulatory cells post-flu vaccination “may
trigger autoimmune diseases such as optic associated inflammation result[ing] in
neuropathies in some individuals.”
Lastly, Dr. Akbari opines that host susceptibility to the development of optic
neuropathy is one of the most important factors in the development of the disease—and
independent of the initiating pathologic cause. (Ex. 31, p. 9.) Specifically, he points to
animal models, one using rodents and one using primates, of NAION that demonstrate
the role of immune cells in creating inflammation leading to ocular damage. (Id. at 10-
11 (citing Steven Bernstein et al., Functional and Cellular Responses in a Novel Rodent
Model of Anterior Ischemic Optic Neuropathy, 44 INVEST. OPTHALMOL. VIS. SCI. 4153
(2003) (Ex. 78); Celia Chen et al., A Primate Model of Nonarteritic Anterior Ischemic
Optic Neuropathy, 49 INVEST. OPHTHALMOL. VIS. SCI. 2985 (2008) (Ex. 79)).) Dr. Akbari
acknowledges that these animal models have been criticized as not reflecting the true
NAION because the experimental ischemic lesions are induced primarily in the
intraretinal region of the central retinal artery circulation, rather than in the deeper
posterior ciliary artery circulation. (See id.) While a model of the optic nerve injury that
includes ON and NAION with conformity to the features of the human disease has yet to
be created, Dr. Akbari stresses that “the cooperation between immune cells causing
inflammation suggests it is likely that [the] genetic background of the host is a critical
component to the pathogenesis of optic neuritis and NAION.” (Id. at 11.)
12
b. Respondent’s Expert, Michael Wilson, M.D., MAS
Dr. Wilson received his medical degree from the University of California, San
Francisco School of Medicine. (Ex. C.) He completed his residency in neurology at the
Harvard Neurology Residency Program at Massachusetts General Hospital and
Brigham and Women's Hospital. (Id.) Dr. Wilson completed his clinical fellowship in
neuro-infectious diseases at Massachusetts General Hospital. (Id.) Subsequently, he
completed postdoctoral fellowships in neurovirology and metagenomics. (Id.) Dr.
Wilson received his Master of Applied Science degree from the University of California,
San Francisco. (Id.) He is a board-certified neurologist with subspecialty training in
neuro-infectious diseases and neuroimmunology. (Ex. B, p. 1.) He serves as an
associate professor of Neurology at UCSF in the Division of Neuroimmunology and Glial
Biology and is a Principal Investigator of a lab “that has pioneered the development of
metagenomic next-generation sequencing to diagnose neurologic infections in patients
with meningitis, encephalitis and other neuroinflammatory conditions.” (Id.) He has co-
authored three New England Journal of Medicine publications and multiple publications
in other top peer-reviewed journals. (Id.) In addition, his lab has developed
comprehensive autoantibody and viral antibody discovery assays to search for antigenic
targets and triggers of neuroinflammatory diseases, including multiple sclerosis and
autoimmune encephalitis. (Id.) Dr. Wilson’s research is funded by the National
Institutes of Health, the National Multiple Sclerosis Society as well as several private
foundations. (Id.)
Dr. Wilson agrees that “it is not clear that [petitioner’s] clinical presentation was
consistent with optic neuritis.” (Ex. B, p. 4.) Dr. Wilson opines that “sequential NAION
is a more likely diagnosis.” (Id. at 5.) He summarizes, “[t]he petitioner’s expert and I
are in agreement that although optic neuritis cannot be completely excluded, the weight
of the evidence favors the alternate diagnosis entertained by [petitioner’s] treating
physicians,” NAION. (Ex. D, p. 1.)
Although Dr. Hedges opines that an immune complex vasculitis triggered by the
influenza vaccine led to ischemic complications, Dr. Wilson stresses that petitioner’s
skin biopsy showed no clear evidence of vasculitis. (Ex. B, p. 4.) Moreover, Dr. Wilson
observes that there is no record of a fluorescein angiogram to look for evidence of
vasculitis in the retina, and systemic markers commonly associated with immune
complex deposition, such as complement levels, are not available. (Id.)
Dr. Wilson also distinguishes petitioner’s case from the case reports cited by Dr.
Hedges. (Ex. B, p. 4.) Dr. Wilson stresses that the case reports of bilateral NAION
cited by Dr. Hedges occurred sequentially after two separate influenza vaccinations
whereas petitioner’s bilateral optic nerve injury occurred after a single vaccination. (Id.
(citing Manasseh et al., supra, at Ex. 29).) Both patients reported in Kawasaki et al. had
eye pain which Dr. Wilson opines is more consistent with an optic neuritis than NAION.
(Id. (citing Kawasaki et al., supra, at Ex. 27).) Moreover, the second case report by
Kawasaki et al., had a coincident febrile systemic illness suggesting that in addition to
the vaccination the patient also had an acute infection. (Id.) Lastly, the two cases
13
described in Kawasaki and the case reported by Ray and Dreizin had bilateral vision
loss either occur simultaneously or within days of each other whereas petitioner’s vision
loss was truly sequential with his right eye becoming symptomatic only 2 months after
the symptoms appeared in the left eye. (Ex. B, pp. 4-5.) According to Dr. Wilson “[i]t is
this aspect of [petitioner’s] case – the progressive and evolving illness over multiple
months – that is importantly inconsistent with the short-lived, monophasic inflammatory
reactions like optic neuritis and Guillain-Barré syndrome that are typically associated
with vaccine complications.” (Ex. D, p. 1.)
Dr. Wilson agrees that symptom onset 4 weeks post-vaccination is within the
time window for post-vaccination syndromes. (Ex. B, p. 5.) However, Dr. Wilson
contends that petitioner had a viral upper respiratory tract infection (“URI”) even more
proximate temporally to the onset of his vision symptoms. (Id.) He opines that there is
no evidence suggesting that an influenza vaccination would be any more likely to trigger
this process than a viral URI. (Id.) Moreover, he stresses that petitioner had a number
of non-inflammatory risk factors for NAION. (Ex. D, p. 2.)
In response to Dr. Akbari, Dr. Wilson acknowledges that scientific literature might
support the theory that rare immune responses to vaccination(s) can cause vascular
inflammation. (Ex. E, p. 1.) However, he again stresses that petitioner’s skin biopsy
showed no clear evidence of vasculitis, nor are there any other results demonstrating an
immune complex deposition. (Id.) Dr. Wilson suggests that petitioner’s poor clinical
response to a variety of immunosuppressive agents argues against his condition as
having a significant inflammatory component as well. (Id. at 2.)
Dr. Akbari relies on literature demonstrating the association between non-
vasculitic, demyelinating complications (e.g., optic neuritis) and influenza vaccination.
In response, Dr. Wilson stresses that although petitioner’s doctors reasonably
speculated at various stages of his illness that optic neuritis was a diagnostic possibility,
he continues to agree with petitioner’s treating physicians that the evidence favors the
alternate diagnosis of NAION. (Ex. E, p. 2.)
V. Discussion
a. Diagnosis
“The function of a special master is not to ‘diagnose’ vaccine-related injuries, but
instead to determine ‘based on the record as a whole and the totality of the case,
whether it has been shown by a preponderance of the evidence that a vaccine caused
the [petitioner]’s injury.’” Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367,
1382 (Fed. Cir. 2009) (quoting Knudsen v. Sec’y of Health & Human Servs., 35 F.3d
543, 549 (Fed. Cir. 1994)). “Although the Vaccine Act does not require absolute
precision, it does require the petitioner to establish an injury – the Act specifically
creates a claim for compensation for ‘vaccine-related injury or death.’” Stillwell v. Sec’y
of Health & Human Servs., 118 Fed. Cl. 47, 56 (2014) (quoting 42.U.S.C. § 300aa-
11(c)). Accordingly, the Federal Circuit has concluded that it is “appropriate for the
14
special master to first determine what injury, if any, [is] supported by the evidence
presented in the record before applying the Althen test to determine causation.”
Lombardi v. Sec’y of Health & Human Servs., 656 F.3d 1343, 1351-53 (Fed. Cir. 2011).
As noted during my prior Rule 5 conference, there was some uncertainty among
petitioner’s treating physicians as to petitioner’s correct diagnosis – in particular optic
neuritis versus NAION. (ECF No. 50.) In that regard, petitioner’s motion for a ruling on
the record includes some argumentation in his opening brief addressing optic neuritis.
(ECF No. 65, pp. 29-30 n.16 (medical literature demonstrating a connection between
vaccination and optic neuritis).) Additionally, petitioner suggests “should the Court find
an expanded Althen analysis applied to the development of optic neuritis helpful to its
consideration of petitioner’s claim, petitioner can comply with such a request in his reply
brief.” (Id. at 29 n.15.) Such an expanded analysis is not warranted, however, because
there is preponderant evidence on this record that petitioner suffered NAION. In fact,
both parties have sections addressing diagnosis in their respective briefs in which they
both explicitly confirm there is no dispute as to diagnosis – that diagnosis being NAION.
(Id. at 27-29; ECF No. 66, p. 7.)
While petitioner’s treating physicians were not definitive in their diagnosis, among
the expert opinions offered in this case, both parties’ experts agree that petitioner’s
correct diagnosis is NAION. (Ex. 30, p. 1; Ex. 31, p. 3; Ex. D, p. 1.) According to Dr.
Hedges, NAION and optic neuritis have “overlapping clinical profiles.” (Ex. 30, p. 1.)
However, Dr. Hedges concludes on petitioner’s behalf that petitioner suffers from an
atypical presentation of NAION. (Ex. 24, p. 2.) Additionally, Dr. Wilson opines for
respondent “petitioner’s expert and I are in agreement that although optic neuritis
cannot be completely excluded, the weight of the evidence favors the alternate
diagnosis entered by [petitioner’s] treating physicians,” NAION. (Ex. D, p. 1.) Dr. Akbari
noted that the possibility of optic neuritis was not ruled out, but likewise accepted the
NAION diagnosis. (Ex. 31, pp. 1, 3.)
Importantly, the literature makes clear that optic neuritis and NAION are not the
same condition and do not have the same etiology—NAION is ischemic / vascular
rather than demyelinating. (Chen et al., supra, at Ex. 79, p. 1 (NAION “is an optic nerve
(ON) stroke and a leading cause of sudden ON-related vision loss”).) NAION is
presumed to be due a transient disruption in the circulation of the optic nerve head
leading to hypoperfusion and ischemia. (Berry et al., supra, at Ex. 56, p. 24.) The
transient disruption is thought to be caused by generalized hypoperfusion, nocturnal
hypotension, local autoregulation failure, vasospasm, venous occlusion, or thrombosis,
though the exact cause remains unclear. (Id.) Still other patients are thought to be
predisposed to NAION because of their small cup-to-disc ratio, or “crowded optic disk
head.” (Id.) When localized swelling occurs in a fixed space anterior to the rigid lamina
cribosa, Barry et al. explain that the capillaries could become more easily compressed
and secondary ischemia may result. (Id.) Systemic diseases, such as hypertension,
diabetes, and hypercholesterolemia can cause decreased perfusion to the optic nerve
head, secondary to microvascular compromise that puts individuals with these diseases
at risk of NAION. (Id.) Dr. Wilson also draws this distinction between optic neuritis and
15
NAION in his report. (Ex. E, p. 2 (optic neuritis is “a non-vasculitic, demyelinating
complication[]” unlike NAION).)
Prior cases in the Vaccine Program where petitioners have alleged vaccine-
caused optic neuritis have addressed causation in terms of autoimmune demyelination.
Reinhardt v. Sec’y of Health & Human Servs., No. 17-1257V, 2021 WL 1851491, at *16
(Fed. Cl. Spec. Mstr. Apr. 2, 2021); Althen v. Sec’y of Health & Human Servs., 58 Fed.
Cl. 270, 285 (2003) (recognizing that optic neuritis represents a central demyelinating
disease of the optic nerve and is not a “vasculitis” illness), aff’d, 418 F.3d 1274 (Fed.
Cir. 2005). However, even setting aside a specific diagnosis, petitioner in this case
exhibited no evidence of demyelination on MRI. (Ex. 3, pp. 52-55.) Moreover, given the
record as a whole, the evidence favors the diagnosis of NAION entertained by
petitioner’s treating physicians and favored by both parties’ experts, including most
notably petitioner’s own expert in neuro-ophthalmology. This points to a different
underlying disease process. Thus, the fact that petitioner’s NAION is preponderantly
established does affect the resulting Althen analysis. 4
b. Althen prong one
Under Althen prong one, petitioners must provide a “reputable medical theory,”
demonstrating that the vaccine received can cause the type of injury alleged. Pafford,
451 F.3d at 1355-56 (citations omitted). To satisfy this prong, petitioner’s theory must
be based on a “sound and reliable medical or scientific explanation.” Knudsen v. Sec’y
of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). Such a theory must only
be “legally probable, not medically or scientifically certain.” Id. at 549. However,
petitioners may satisfy the first Althen prong without resort to medical literature,
epidemiological studies, demonstration of a specific mechanism, or a generally
accepted medical theory. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367,
1378-79 (Fed. Cir. 2009) (citing Capizzano v. Sec’y of Health & Human Servs., 440
F.3d 1317, 1325-26 (Fed. Cir. 2006)).
Scientific evidence offered to establish Althen prong one is viewed “not through
the lens of the laboratorian, but instead from the vantage point of the Vaccine Act’s
4 For example: In Katz v. Secretary of Health & Human Services, petitioner alleged that he suffered optic
neuritis caused in fact by his hepatitis B vaccination. No. 04-714V, 2005 WL 6117659 (Fed. Cl. Spec.
Mstr. Nov. 30, 2005). Petitioner’s first expert proposed a diagnosis of optic neuritis, which was disputed
by respondent’s expert, who advocated an alternate diagnosis of ischemic optic neuropathy. Id. at *6.
The special master found that petitioner more likely than not suffered from a non-demyelinating
inflammatory optic neuritis. Id. at *18. Petitioner’s expert was charged with explaining how petitioner's
hepatitis B vaccination can cause and did cause her optic neuritis. Id. He offered the molecular mimicry
theory to explain how the vaccine might have caused the production of antibodies, which then attacked
healthy tissue. Id. However, the molecular mimicry theory proposed by Dr. Waisbren relied upon a
similarity between a substance in the hep B vaccine and the myelin of the human nervous system. Id.The fatal flaw with this proposed mechanism was that petitioner exhibited no evidence of demyelination.
Id. Without any evidence of demyelination, the special master found that “Dr. Waisbren's molecular
mimicry proposal is of no use to explain how the hepatitis B vaccine may have caused petitioner’s optic
neuritis. Dr. Stivelman's diagnosis and Dr. Waisbren's theory of causation are mismatched.” Id.16
preponderant evidence standard.” Id. at 1380. Accordingly, special masters must take
care not to increase the burden placed on petitioners in offering a scientific theory
linking vaccine to injury. Contreras v. Sec’y of Health & Human Servs., 121 Fed. Cl.
230, 245 (2015) (“Plausibility . . . in many cases may be enough to satisfy Althen prong
one.”). But this does not negate or reduce a petitioner’s ultimate burden to establish his
entitlement to damages by preponderant evidence. W.C. v. Sec’y of Health & Human
Servs., 704 F.3d 1352, 1356 (Fed. Cir. 2013) (citations omitted). Nonetheless, although
petitioners cannot be required to show “epidemiologic studies, rechallenge, the
presence of pathological markers or genetic disposition, or general acceptance in the
scientific or medical communities to establish a logical sequence of cause and effect”
(Capizzano, 440 F.3d at 1325), the special master may consider and evaluate such
evidence when filed. Andreu, 569 F.3d at 1379 (special masters may consider medical
literature and epidemiological evidence, when it is submitted, in “reaching an informed
judgment as to whether a particular vaccine likely caused a particular injury”).
Petitioner’s theory derives primarily from Dr. Akbari while Dr. Hedges principally
relied on case reports. (Ex. 31, pp. 6-10; Ex. 24, p. 2.) Dr. Akbari proposes several
theories ranging from molecular mimicry to vaccine-induced vasculitis to T-cell
dysfunction. (Ex. 31, pp. 6-10.) However, as explained above, given that petitioner’s
NAION is preponderantly established, Dr. Akbari’s extended discussion of
demyelinating optic neuritis is irrelevant. On the whole, the literature filed in this case
supports that NAION is likely due to a stroke-like mechanism affecting blood supply to
the retina. (Chen et al., supra, at Ex. 79; Berry et al., supra, at Ex. 56; A.H. Ropper et
al., eds. Chapter 12: Disturbances of Vision, in VICTOR’S PRINCIPLES OF NEUROLOGY
(11th ed. 2019) (Ex. B, Tab 2); D. Vaughan et al., eds. Chapter 14: Neuro-
Ophthalmology, in VAUGHAN & ASHBURY’S GENERAL OPHTHALMOLOGY (19th ed. 2004)
(Ex. B, Tab 3); Nathan Kerr et al., Non-Arteritic Anterior Ischaemic Optic Neuropathy: A
Review and Update: 16 J. CLIN. NEUROSCIENCE 994 (2009) (Ex. B, Tab 4).)
Both of petitioner’s experts acknowledge that the pathophysiology of NAION is
unknown. (Ex. 24, p. 3; Ex. 31, p. 8.) However, as the name suggests, both
acknowledge that it results from ischemia. (Ex. 30, p. 1; Ex. 31, p. 8.) Dr. Akbari
supports ischemia as underlying cause of NAION based on a number of publications,
including experimental animal models. (Ex. 31 (citing Berry et al., supra, at Ex. 56;
Khanh et al., supra, at Ex. 72; Chen et al., supra, at Ex. 79).) Notably, however, the
animal models do not themselves include any studies examining vaccine-causation.
(Khanh et al., supra, at Ex. 72; Bernstein et al., supra, at Ex. 78; Chen et al., supra, at
Ex. 79; Hayreh, supra, at Ex. 80.) Moreover, gaps in petitioner’s theory are further
drawn out in Dr. Akbari’s own concession that the animal models of NAION that he
relies on “have been criticized as not reflecting true NAION.” (Ex. 31, pp. 7, 10-11; see
also Chen et al., supra, at Ex. 79; Hayreh, supra, at Ex. 80.) Additionally, in both Khanh
et al. and Chen et al., the authors discuss how the retinal injury itself recruits
inflammation to the eye in NAION. (Khanh, supra, at Ex. 72, p. 1732; Chen et al.,
supra, at Ex. 79, p. 7 (“the inflammation can cause increased tissue destruction, edema,
and compression of adjacent vessels and axons, resulting in further loss of visual
sensory function and decreasing the likelihood of significant visual recovery”).) This
17
complicates any discussion of inflammation associated with NAION as being part of the
etiology of the condition as opposed to a consequence of the condition.
Dr. Akbari’s resulting theory otherwise turns largely on his broader discussion of
post-vaccination vasculitis. (Ex. 31, pp. 7-8.) Importantly, however, not all vasculitides
are the same. The vasculitides are a heterogenous group of disorders associated with
organ dysfunction caused by inflammatory disease of blood vessels. (Hadden et al.,
supra, at Ex. 58, p. 1567.) The various clinical manifestations of different vasculitides
depend on local immunologic environments, tissue vulnerabilities, and blood flow
distributions. (Id.) Systemic vasculitis involves multiple organs and tissues, whereas in
some patients, vasculitis is restricted to a single organ or tissue. (Id.) Thus, while Dr.
Wilson conceded on respondent’s behalf that “the scientific literature might support this
general assertion about rare maladaptive immune responses to vaccinations causing
vascular inflammation” (Ex. E, p. 1 (emphasis removed)), he was clear in opining that
the fact that the flu vaccine might be capable of causing vasculitis in some contexts is
not in itself evidence that it causes NAION. 5 (Id.) Rather, Dr. Wilson stresses that
NAION is of unknown pathogenesis. (Id. at 1-2.) Examining the vasculitide literature
relied upon by Dr. Akbari, he is not persuasive in linking vaccines to NAION.
Watanabe et al. (2017), sought reports of vasculitides following influenza
vaccination. (Watanabe et al., supra, at Ex. 57.) Among 45 published reports the
authors identified 65 patients. (Id. at 189.) As the study makes clear, not all forms of
vasculitis have the same consequences. The authors divided the vasculitides of total
cases into six major categories according to the predominant size of the vessel involved
(large vessel, medium vessel, and small vessel vasculitis), single organ-involved
vasculitis compared to systemic disease (rheumatoid vasculitis), and finally vasculitis
associated with a probable etiology (HBV-associated vasculitis). (Id.) The small vessel
vasculitides were further subdivided to ANCA-associated vasculitis, immune complex
vasculitis, and unclassified. (Id.) The most frequently reported symptom was skin rash
(37/57), followed by arthralgia or arthritis (31/57), fever (20/57) and malaise (15/57).
(Id.) Unsurprisingly, the highest reported involved organ was skin (37/57), followed by
joints (31/57), kidney (24/57), muscle (16/57), gastrointestinal tract (13/57), lung (10/57),
peripheral nervous system (7/57), eye (8/57), central nervous system (7/57), and nose
or mouth (3/57). (Id.) Dr. Akbari relies on this paper for the proposition that there were
eight reports of ocular involvement. (Ex. 31, p. 7.) However, the eight cases he cites
5 Special masters have likewise distinguished between different vasculitides in prior cases. See Kelly v.
Sec’y of Health & Human Servs., No. 17-1475V, slip op. (Fed. Cl. Spec. Mstr. Oct. 12, 2022)
(distinguishing polymyalgia rheumatica and giant cell arteritis); Suliman v. Sec’y of Health & Human
Servs., No. 13-993V, 2018 WL 6803697 (Fed. Cl. Spec. Mstr. Nov. 27, 2018) (same); see also Temes v.
Sec’y of Health & Human Servs., No.16-1465V, 2020 WL 4198036 at *19-20 (Fed. Cl. Spec. Mstr. May
12, 2020) (distinguishing cryoglobulinemia and leukocytoclastic vasculitis); Schultz v. Sec’y of Health &
Human Servs., No. 16-539V, 2020 WL 1039161, at *7 (Fed. Cl. Spec. Mstr. Jan. 24, 2020) (criticizing Dr.
Shoenfeld’s opinion, in part, for conflating petitioner’s stroke with vasculitis); Guzman v. Sec’y of Health &
Human Servs., No. 15-736V, 2019 WL 2723392, at *20 (Fed. Cl. Spec. Mstr. May 14, 2019)
(distinguishing cutaneous vasculitis and chronic urticaria).
18
occurred in the context of ANCA-associated vasculitis, a broader systemic vasculitis. 6
(Watanabe et al., supra, at Ex. 57, p. 191.) That is not analogous to NAION. Only five
cases overall involved single organ vasculitis and of those only one involved retinal
arteritis. (Id.) None involved ischemic optic neuropathy, either arteritic or nonarteritic.
(See id.) There was no indication that any particular vasculitis demonstrated a higher
probability of vaccine-causation, though the most common type of vasculitis was small
vessel vasculitis—somehow leading the authors to conclude that caution should be
required for patients with small vessel vasculitis (in particular those with ANCA-
associated or reactivated-IgAV vasculitis). (Id. at 193-94.) Among all the reported post-
influenza vaccination vasculitides, Watanabe et al. concluded that the majority of
studies did not find a causal association between vaccination and subsequent
development of vasculitis. (Id. at 193.)
Hadden et al. (2017), reviewed twelve case reports proposing a possible
association of vasculitis with previous immunization. (Hadden et al., supra, at Ex. 58, p.
1568.) Dr. Akbari cites this article presumably for the six cases reported post influenza
vaccination. (Id.) However, this paper addresses the case definition and analysis for
vasculitic peripheral neuropathy. (Id.) NAION is specifically identified as a CNS
condition. 7 (Chen et al., supra, at Ex. 79, p. 2.) Vasculitic peripheral neuropathy
typically manifests as an asymmetric neuropathy resulting from ischemic axonal injury.
(Hadden et al., supra, at Ex. 58, p. 1567.) Unlike NAION, vasculitic neuropathies
typically manifest with subacute stepwise progression or progressive worsening,
although some patients exhibit more insidious chronic progression over many years.
(Id. at 1568.) Even setting aside this distinction, Hadden et al. concluded that no causal
relationship existed between immunization and systemic or nonsystemic (single-organ)
vasculitic neuropathy has been established. (Id.)
Given the above, Dr. Akbari ultimately concludes only that “the scientific research
supports the assertion that stimulation of the immune system following vaccinations is a
plausible medical theory causally linking the influenza vaccination with the development
of vasculitis and inflammation that resulted in symptoms in [petitioner] including optic
neuropathy and vision loss.” (Ex. 31, p. 10 (emphasis added).) Given that Dr. Akbari
has only opined that petitioner’s medical theory is “plausible,” his opinion less helpful to
petitioner in meeting his legal burden. See, e.g., Boatmon v. Sec’y of Health & Human
Servs., 941 F.3d 1351, 1360 (Fed. Cir. 2019) (citing Moberly v. Sec’y of Health &
Human Servs., 592 F.3d 1315, 1322 (Fed. Cir. 2010)) (reaffirming that a “plausible” or
“possible” causal theory does not satisfy a petitioner’s burden).
6ANCA-associated vasculitides are a subgroup of small vessel vasculitis in which there are circulating
antineutrophil cytoplasmic autoantibodies (ANCA). ANCA-associated vasculitis, DORLAND’S MEDICAL
DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=116898 (last accessed Nov. 9,
2022).
7NAION is an isolated infarct of the anterior optic nerve—the optic nerve “is a central nervous system
(CNS) tract composed of retinal ganglion cell (RGC) axons that synapse in the lateral geniculate nuclei.”
(Chen et al., supra, at Ex. 79, p. 2.)
19
The remaining supporting evidence consists of case reports. Ray and Dreizin
(1996) reported a 61-year-old woman who developed progressive visual loss in both
eyes within three weeks following influenza vaccination. (Ray & Dreizin, supra, at Ex.
28.) Among the possible causes, the authors note the strong possibility of temporal
arteritis, given the patient’s age. (Id. at 183.) Temporal arteritis was ruled out, however,
given the patient had no jaw claudication, headaches, fevers, or myalgias, or
arthralgias. (Id.) Two separate sedimentation rates were normal and both temporal
artery biopsies were negative. (Id.) Other ischemic causes such as small vessel
disease associated with hypertensive disease were reportedly considered, however, the
authors indicated that “these rarely occur in both eyes simultaneously, and the patient
[here] was healthy.” (Id. at 183-84.) A compressive mass or infiltrative tumor was
excluded on MRI and by the normal histopathology of the optic nerve sheath. (Id. at
184.) Laboratory tests also ruled out meningeal carcinomatosis, sarcoid, Lyme disease,
Leber’s optic neuropathy, and systemic lupus. (Id.) A heavy metal screening revealed
elevated mercury—and while mercury has been reportedly associated with peripheral
neuropathies and cerebellar symptoms, the authors stress that it has not been causally
associated with optic neuropathies. (Id.) The authors stress that optic neuropathy is a
diagnosis of exclusion. (Id.) While Ray and Dreizin suggest it is possible their patient’s
abrupt onset of bilateral vision loss was caused by the influenza vaccine, the authors
acknowledge several caveats. (Id.) First, optic neuropathy does not follow influenza
vaccination as often as acute inflammatory demyelinating polyneuropathy (GBS). (Id.)
While the patient’s visual recovery coincided with restarting steroids—the authors
question: “Was her recovery due just to time or was it from the combined use of
prednisone, or from the prednisone alone?” (Id.) Lastly, the authors note that their
patient underwent a left optic nerve sheath fenestration (“ONSF”) at the time she
restarted prednisone—“which too may have played a role in her recovery.” (Id.)
Kawasaki et al. (1998), reported two cases of anterior ischemic optic neuropathy
following influenza vaccination. (Kawasaki et al., supra, at Ex. 27.) The first case was a
47-year-old woman who complained of decreased vision in her right eye one week after
her influenza vaccination—associated with transient eye pain. (Id. at 56.) Five days
later she developed blurriness in the left eye. (Id.) The patient demonstrated
moderately edematous optic discs with splinter hemorrhages and cotton-wool spots.
(Id.) Her laboratory tests were largely normal. (Id.) She was treated with prednisone
and subsequently developed segmental disc atrophy—the results of her examination
remained unchanged at one year. (Id.) The second case involved a 51-year-old
woman who became febrile with chills and myalgias one-day post vaccination. (Id.)
These symptoms resolved over three weeks. (Id.) Four weeks later, she complained of
ear pain, headache, and blurry vision—first in her right eye then in her left eye. (Id.)
Both optic discs were edematous. (Id.) Despite IV methylprednisolone, her vision
progressively worsened over several weeks. (Id.) Lab tests were all normal except for
disc edema. (Id.) Her visual function was unchanged at two months, and bilateral optic
disc atrophy had developed. (Id. at 57.) The authors proposed two possible
mechanisms for the lack of visual recovery, either (1) an allergic cross-reaction to viral
antigens stimulating optic nerve inflammation and demyelination severe enough to
cause direct axonal injury or (2) immune-mediated vasculitis causing ischemic optic
20
neuropathy. (Id. at 58.) However, the authors expressly note that “[n]o pathologic
examination of vaccination-associated optic neuritis currently exists to help differentiate
these two mechanisms.” (Id. at 58-59.)
Manasseh et al. (2014), reported a case of a 68-year-old man who developed
bilateral NAION, with each episode occurring in close temporal proximity to influenza
vaccination. (Manasseh et al., supra, at Ex. 29.) The patient reported a two-day history
of reduced visual acuity ten days after receiving an influenza vaccine. (Id. at 267.) The
patient was subsequently diagnosed with AION, which was later refined to NAION. (Id.
at 268.) Over the next three months the patient’s visual acuity in the left eye recovered
with a persistent field defect. However, the following year, six days after receiving the
influenza vaccine, he returned with a new-onset visual field defect in his right eye. (Id.)
Ocular findings were again normal apart from swelling in the superior disc margin in the
right eye, and laboratory studies excluded giant cell arteritis. (Id.) The patient was
treated with a prednisone taper. (Id.) The authors observed that the patient was over
65, had a history of diabetes mellitus and was hypermetropic with small optic discs and
taking tadalafil—“all of which are known or potential risk factors for NA-AION.” (Id.)
Moreover, the authors point out that the cumulative incidence of second-eye
involvement in NA-AION is 18% at one year and 25% at three years. (Id.) Taken
together, Manasseh et al. report “our case probably represents a chance occurrence,
especially as there is some evidence that within-season influenza vaccination leads to a
reduced incidence of stroke and other cardiovascular events.” (Id.)
Li & Fisayo (2019) reported a case of bilateral optic neuritis occurring one week
after influenza vaccination in a previously healthy six-year-old child. (Li & Fisayo, supra,
at Ex. 59, p. 496.) Examination revealed severe optic disc swelling with vessel
obscuration bilaterally and peripapillary hemorrhages on the left. (Id.) MRI of the brain,
orbits, and spinal cord showed increased T2/FLAIR signal and abnormal enhancement
in the retrobulbar optic nerves bilaterally, but no white matter lesions in the brain or
spinal cord. (Id.) Six days after the last dose of IV steroids, the patient experienced
decreased vision in the left eye. (Id.) The patient started oral prednisone, and two
weeks later visual acuities returned to 20/20 with normal color vision in each eye. (Id.)
There is no indication that this patient had NAION.
Generally, case reports offer circumstantial evidence of vaccine causation and
therefore should not be summarily rejected. Case reports “‘do not[, however,] purport to
establish causation definitively, and this deficiency does indeed reduce their evidentiary
value’. . . [but] ‘the fact that case reports can by their nature only present indicia of
causation does not deprive them of all evidentiary weight.’” Paluck v. Sec’y of Health &
Human Servs., 104 Fed. Cl. 457, 475 (2012) (quoting Campbell v. Sec’y of Health &
Human Servs., 97 Fed. Cl. 650, 668 (2011), aff’d, 786 F.3d 1373 (Fed. Cir. 2015)).
Case reports often present a detailed report of symptoms, signs, diagnosis, treatment,
and follow-up care. Oftentimes petitioners in the Program will highlight the usefulness
of case reports in cases of novel, unusual or rare diseases. See Patton v. Sec’y of
Health & Human Servs., 157 Fed. Cl. 159, 166-67 (2021). But see Crutchfield v. Sec’y
of Health & Human Servs., No. 09-39V, 2014 WL 1665227, at *19 (Fed. Cl. Spec. Mstr.
21
Apr. 7, 2014) (“single case reports of Disease X occurring after Factor Y . . . do not
offer strong evidence that the temporal relationship is a causal one—the temporal
relationship could be pure random chance”), aff’d, 125 Fed. Cl. 251 (2014).
Here, I am not persuaded by respondent’s contention that eye pain suggestive of
optic neuritis is dispositive where Kawasaki et al. are clear in concluding that the
diagnosis is NAION. Both patients suffered eye pain which Dr. Wilson opines is more
consistent with an optic neuritis than NAION. (Ex. B, p. 4 (citing Kawasaki et al., supra,
at Ex. 27).) Indeed, some researchers consider eye pain to be an atypical feature for
NAION. (Berry et al., supra, at Ex. 56, p. 24.) Moreover, Kawasaki et al. acknowledge
that optic neuritis can present with bilateral vision loss and optic disc edema may or
may not present acutely. (Kawasaki et al., supra, at Ex. 27, p. 56.) The presentation of
both patients in Kawasaki’s case report would have been seemingly atypical for both
AION and optic neuritis. (See id.) Yet, Kawasaki et al. concluded that in their two
patients, the pattern of visual field loss, segmental disc changes, and failure of visual
recovery is more consistent with AION than with a demyelinating optic neuritis. (Id. at
59.) However, I am persuaded by the fact that the case reports filed in this case
describe acute onset—whereas petitioner had sequential onset approximately two
months after the symptoms appeared in the left eye. (Kawasaki et al., supra, at Ex. 27;
Ray & Dreizin, supra, at Ex. 28.) In his second report, Dr. Wilson notes this is in
contrast to acute monophasic conditions that are typically associated with vaccines.
(Ex. D, p. 1.) The issue here is that a fluctuating condition in one eye might be
explained by the resulting nerve damage from the initial inflammatory event. But to
have a new onset occurring in a separate eye at a separate time speaks to some kind of
chronicity in the underlying cause that is not necessarily consistent with vaccine
causation. 8
At first blush, the case report from Manasseh suggests the possibility for a
challenge-rechallenge event. 9 Respondent argues this is immaterial because there is
no evidence petitioner experienced a recurrence of NAION after a second dose of flu
vaccine. (ECF No. 66, p. 11 n.4.) However, I find that this is a factor that increases the
evidentiary value of that case report. The Institute of Medicine (IOM) “has stated that
rechallenge is proof of causation . . . The IOM has also stated that where causation is
8Relatedly, Dr. Akbari observes that petitioner experienced optic disc swelling in his right eye
approximately one month after the steroid taper. (Ex. 31, p. 4 (citing Ex. 8, pp. 6-10).) Though, on the
other hand, Dr. Wilson stresses that petitioner only ever had an incomplete response to steroid treatment.
(Ex. B, p. 4.) When patients respond well to steroids, it is support of an inflammatory etiology (e.g., optic
neuritis). (Id.)
9 Within the context of the Vaccine Program, the Federal Circuit has described:
A rechallenge event occurs when a patient who had an adverse reaction to a vaccine
suffers worsened symptoms after an additional injection of the vaccine. The chief special
master stated that this evidence of rechallenge constituted ‘such strong proof of causality
that it is unnecessary to determine the mechanism of cause—it is understood to be
occurring.’
Capizzano, 440 F.3d at 1322 (internal citation omitted).
22
proven, biologic plausibility is a given.” Capizzano v. Sec’y of Health & Human Servs.,
2004 WL 1399178, *2 (Fed. Cl. Spec. Mstr. 2004) (citing Christopher P. Howson et al.,
Institute of Medicine, Adverse Effects of Pertussis and Rubella Vaccines, 48, 53 (1991);
Kathleen R. Stratton et al., Institute of Medicine, Adverse Events Associated with
Childhood Vaccines: Evidence Bearing on Causality, 21 (1994)). It was not disputed
that the petitioner in Capizzano did not suffer a challenge-rechallenge event.
Capizzano v. Sec’y of Health & Human Servs., 2006 WL 3419789, at *12 (Fed. Cl.
Spec. Mstr. 2006). However, what I find most critical in this case report is the authors’
overall conclusion that the patient’s development of sequential bilateral NAION was a
chance occurrence—noting the patient’s risk factors for developing NAION independent
of the vaccine administered. (Manasseh et al., supra, at Ex. 29, p. 268.)
On balance, the case reports provide some support for petitioner’s claim, but not
enough without more given that the causes of NAION are unknown. See, e.g., W.C. v.
Sec’y of Health & Human Servs., No. 07-456V, 2011 WL 4537887, at *13 (Fed. Cl.
Spec. Mstr. Feb. 22, 2011) (“case reports are generally weak evidence of causation
because case reports cannot distinguish a temporal relationship from a causal
relationship”), mot. for review den’d, 100 Fed. Cl. 440 (2011), aff’d, 704 F.3d 1352 (Fed.
Cir. 2013); Caves v. Sec’y of Health & Human Servs., No. 07-443V, 2010 WL 5557542,
at *14 (Fed. Cl. Spec. Mstr. Nov. 29, 2010) (“case reports do[] not help [petitioners]
meet [their] burden of demonstrating a persuasive and reliable theory causally
connecting” vaccine to injury), mot. for review den’d, 100 Fed. Cl. 119 (2011), aff’d, 463
Fed. App’x 932 (Fed. Cir. 2012); Ryman v. Sec’y of Health & Human Servs., 65 Fed. Cl.
35, 39 (2005) (“case reports are the least reliable type of evidence for establishing
vaccine injury causation”); Pearson v. Sec’y of Health & Human Servs., No. 17-489V,
2019 WL 1150044, at *11 (Fed. Cl. Spec. Mstr. Feb. 7, 2019) (noting that “probative
weight given to [case reports] in Program cases is limited”); Knorr v. Sec’y of Health &
Human Servs., No. 15-1169V, 2018 WL 6991548, at *30 (Fed. Cl. Spec. Mstr. Dec. 7,
2018) (“substantial authority also notes that case reports are not robust evidence
favoring causation (even under the Program’s comparatively lenient preponderance
evidentiary standard)”).
Taking all of this together, petitioner’s claim that the flu vaccine can cause
NAION is not preponderantly supported. Dr. Akbari offered molecular mimicry to
explain how the vaccine might have caused the production of antibodies, which
subsequently attacked healthy tissue. However, the molecular mimicry theory proposed
by Dr. Akbari relies upon a similarity between a substance in the flu vaccine and the
myelin of the human nervous system. The fatal flaw with this proposed mechanism is
that NAION is ischemic / vascular rather than demyelinating. Without any evidence of
demyelination, Dr. Akbari’s molecular mimicry proposal is of no use to explain how the
flu vaccine may have caused petitioner’s NAION. Dr. Akbari’s further reliance on a
broader discussion of vasculitis is likewise unpersuasive. Nor do the case reports cited
by Drs. Akbari and Hedges provide preponderant support. Thus, for all these reasons,
petitioner has not met his burden under Althen prong one.
23
c. Althen prong two
The second Althen prong requires proof of a logical sequence of cause and
effect, usually supported by facts derived from a petitioner's medical records. Althen,
418 F.3d at 1278; Andreu, 569 F.3d at 1375-77; Capizzano, 440 F.3d at 1326; Grant v.
Sec’y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). In establishing
that a vaccine “did cause” the injury, the opinions and views of the injured party’s
treating physicians are entitled to some weight. Andreu, 569 F.3d at 1367; Capizzano,
440 F.3d at 1326 (“medical records and medical opinion testimony are favored in
vaccine cases, as treating physicians are likely to be in the best position to determine
whether a ‘logical sequence of cause and effect show[s] that the vaccination was the
reason for the injury’”) (quoting Althen, 418 F.3d at 1280). Medical records are
generally viewed as particularly trustworthy evidence, since they are created
contemporaneously with the treatment of the patient. Cucuras v. Sec’y of Health &
Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).
However, medical records and/or statements of a treating physician’s opinion do
not per se bind the special master to adopt the conclusions of such an individual, even if
they must be considered and carefully evaluated. See § 13(b)(1) (providing that “[a]ny
such diagnosis, conclusion, judgment, test result, report, or summary shall not be
binding on the special master or court”); Snyder v. Sec’y of Health & Human Servs., 88
Fed. Cl. 706, 746 n.67 (2009) (“there is nothing ... that mandates that the testimony of a
treating physician is sacrosanct—that it must be accepted in its entirety and cannot be
rebutted”). As with expert testimony offered to establish a theory of causation, the
opinions or diagnoses of treating physicians are only as trustworthy as the
reasonableness of their suppositions or bases. The views of treating physicians should
also be weighed against other, contrary evidence also present in the record—including
conflicting opinions among such individuals. Hibbard v. Sec’y of Health & Human
Servs., 100 Fed. Cl. 742, 749 (2011) (not arbitrary or capricious for special master to
weigh competing treating physicians’ conclusions against each other), aff’d, 698 F.3d
1355 (Fed. Cir. 2012); Caves v. Sec'y of Health & Human Servs., 100 Fed. Cl. 119, 136
(2011), aff’d, 463 Fed. App’x 932 (Fed. Cir. 2012); Veryzer v. Sec’y of Health & Human
Servs., No. 06-522V, 2011 WL 1935813, at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011),
mot. for review den’d, 100 Fed. Cl. 344, 356 (2011), aff’d without opinion, 475 Fed.
App’x 765 (Fed. Cir. 2012).
Petitioner stresses that his treating physicians documented the onset of his vision
loss “in the context of his recent flu vaccination repeatedly.” (ECF No. 65, p. 37 (citing
Ex. 8, p. 2 (Dr. Potter 12/9/2016); Ex. 4, p. 43 (Dr. Sharma 12/9/2016); Ex. 8, p. 5 (Dr.
Samy 1/5/2017); Ex. 8, p. 10 (Dr. Samy 1/27/2017); Ex. 8, p. 15 (Dr. Samy 2/2/2017);
Ex. 8, p. 21 (Dr. Samy 2/17/2017); Ex. 8, p. 38 (Dr. Samy 5/19/2017); Ex. 21, p. 3 (Dr.
Samy 11/12/2018)).) However, the context of those records reveals that his treaters
considered vaccine-causation within the context of a differential diagnosis that
concurrently considered the possibility of infectious and autoimmune etiologies. In each
of Dr. Samy’s reports he additionally notes “suspected post-vaccination vs post-
infectious vs autoimmune optic neuritis (MS-spectrum).” (Ex. 8, pp. 2, 5, 10, 15, 21,
24
38.) The notation from Dr. Sharma in the emergency department similarly reflects “[a]s
per ophthalmology he has most likely post-vaccination optic neuritis . . . vs post-
infectious optic neuritis . . . vs autoimmune optic neuritis.” (Ex. 4, p. 43.) In petitioner’s
final visit with Dr. Samy on November 11, 2018, he noted that petitioner “developed
optic neuropathy [in] early 2017 which was post vaccination but in a pattern suggestive
of possible ischemia in disc without cup followed by a few months later with the other
eye.” (Ex. 21, p. 3 (emphasis added).) Considering Dr. Samy’s records as a whole, his
statements of mere suspicion fall short of an opinion supporting a vaccine-causation of
petitioner’s condition. See Cedillo v. Sec’y of Health & Human Servs., 617 F.3d 1328,
1348 (Fed. Cir. 2010) (special master did not err in affording little weight to the opinions
of petitioner’s treating physicians where “none of the treating physicians concluded that
the MMR vaccine caused [petitioner’s] autism”); Moberly, 592 F.3d at 1324-25 (finding
no treating physician evidence to support the claim of causation where the “medical
records regarding the temporal proximity of the [vaccination] to the seizures were all
speculative”); Stapleford v. Sec’y of Health & Human Servs., No. 03-234V, 2009 WL
1456441, at *17 n.24 (Fed. Cl. Spec. Mstr. May 1, 2009) (referencing medical record “is
quite different from an indication that such physician has reached a conclusion
concerning a causal relationship”) (emphasis in original), aff’d, 89 Fed. Cl. 456 (Fed. Cl.
2009). Moreover, “[a] treating physician’s recognition of a temporal relationship does
not advance the analysis of causation.” Isaac v. Sec’y of Health & Human Servs., No.
08-601V, 2012 WL 3609993, at *26 (Fed. Cl. Spec. Mstr. July 30, 2012); see also
Devonshire v. Sec’y of Health & Human Servs., No. 99-031V, 2006 WL 2970418, at *19
(Fed. Cl. Spec. Mstr. Sept. 28, 2006) (medical expert’s “post hoc ergo prompter hoc
reasoning . . . has been consistently rejected by the Court and is ‘regarded as neither
good logic nor good law’”) (quoting Fricano v. U.S., 22 Cl. Ct. 796, 800 (1991)
(emphasis in original)).
However, I am also not persuaded that respondent has presented petitioner’s
prior infection as a significant consideration. Respondent stresses that petitioner had
an upper respiratory infection roughly two weeks prior to the onset of his symptoms,
“which under his experts’ causation theory would be just as likely to have caused
petitioner’s NAION.” (ECF No. 66, p. 1.) In his second report, however, Dr. Wilson
agrees the relationship between infection and NAION is unclear. (Ex. D, p. 1.) Nor
does the medical literature filed in this case bear out any suspected infectious etiology.
Indeed, upon initial presentation, petitioner’s treating physicians felt a post-infectious
injury was less likely given his negative labs. (Ex. 8, p. 2.)
However, Dr. Wilson also discussed other factors relevant to Althen prong two.
First, and most notably, petitioner had other non-inflammatory risk factors for NAION
including hypertension, smoking, age, and sleep apnea. (Ex. 5, pp. 1-2, 13; Ex. 7, p. 2;
Ex. 2, p. 5.) As Berry et al. explained:
Systemic diseases that may cause decreased perfusion to the optic nerve
head secondary to microvascular compromise might increase the patient’s
risk of NAION. These include hypertension, diabetes, and
hypercholesterolemia. Other risk factors noted in the literature are
25
nocturnal hypotension, smoking, obstructive sleep apnea, anemia,
hypercoagulable states, disc drusen, ocular and nonocular surgery, and
migraines.
(Berry et al., supra, at Ex. 56, p. 2; see also Kerr et al., supra, at Ex. B, Tab 4, pp. 2-3;
Vaughan et al., supra, at Ex. B, Tab 3, pp. 25-26.) Dr. Hedges acknowledges that
petitioner had risk factors for NAION but attempts to minimize this fact by suggesting
“these are associations, not direct causative factors.” (Ex. 24, p. 2.) However, this is
not persuasive given that Dr. Hedges nonetheless further opines that the risk factors
were contributory in petitioner’s own case. Specifically, he opined that “[t]hese risk
factors combined with a physiologic response to vaccination” ultimately caused
petitioner’s optic nerve injury. (Id.) Dr. Wilson also stresses that petitioner’s skin biopsy
showed no clear evidence of vasculitis. (Ex. B, p. 4.) Moreover, Dr. Wilson observes
that there is no record of a fluorescein angiogram to look for evidence of vasculitis in the
retina, and systemic markers commonly associated with immune complex deposition,
such as complement levels, are not available. (Id.)
Overall, petitioner has not preponderantly proven that his flu vaccination did
cause his NAION. Though some of his treating physicians considered and reported a
temporal association, none concluded that his vision loss was caused by his flu
vaccination. Moreover, petitioner has not preponderantly demonstrated a logical
sequence of cause and effect implicating his vaccination as a cause of his injury. Thus,
petitioner has not met his burden under Althen prong two.
d. Althen prong three
The third Althen prong requires establishing a “proximate temporal relationship”
between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term
has been equated to the phrase “medically-acceptable temporal relationship.” Id. A
petitioner must offer “preponderant proof that the onset of symptoms occurred within a
timeframe which, given the medical understanding of the disorder's etiology, it is
medically acceptable to infer causation.” Bazan v. Sec’y of Health & Human Servs.,
539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for what is a medically
acceptable timeframe must also coincide with the theory of how the relevant vaccine
can cause an injury (Althen prong one’s requirement). Id. at 1352; Shapiro v. Sec’y of
Health & Human Servs., 101 Fed. Cl. 532, 542 (2011), recons. den’d after remand, 105
Fed. Cl. 353 (2012), aff’d mem., 503 Fed. App’x 952 (Fed. Cir. 2013); Koehn v. Sec’y of
Health & Human Servs., No. 11-355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30,
2013), mot. for review den’d, (Fed. Cl. Dec. 3, 2013), aff’d, 773 F.3d 1239 (Fed. Cir.
2014).
Here, because petitioner has failed to meet his preponderant burden pursuant to
Althen prongs one and two, he cannot prevail. In the interest of completeness,
however, I note briefly that respondent’s expert, Dr. Wilson, agrees with the contention
that “symptom onset approximately 4 weeks after vaccination is within the time window
for post-vaccination syndromes.” (Ex. B, p. 5.) He specifically stated that the timing of
petitioner’s symptoms “could be consistent with a vaccine-triggered complication.” (Id.)
26
Accordingly, had petitioner proven his case with respect to the first two Althen prongs, it
is likely he would have also prevailed with regard to Althen prong three.
VI. Conclusion
Petitioner has my sympathy for the injury he endured. Considering the record as
a whole under the standards applicable in this Program, however, petitioner has not
preponderantly established either that his October 28, 2016, flu vaccination caused his
condition. Accordingly, petitioner is not entitled to compensation. Therefore, this case
is dismissed. 10
IT IS SO ORDERED.
s/Daniel T. Horner
Daniel T. Horner
Special Master
10In the absence of a timely-filed motion for review of this Decision, the Clerk of the Court shall enter
judgment accordingly.
27