Quintana v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: February 15, 2022

* * * * * * * * * * * * * * *

HELENE QUINTANA, * No. 15-1273V

*

Petitioner, * Special Master Sanders

*

v. *

* Denial of Entitlement; Influenza

SECRETARY OF HEALTH * (“Flu”) Vaccine; Uveitis; Peripheral

AND HUMAN SERVICES, * Ulcerative Keratitis (“PUK”); Herpes

* Simplex Virus (“HSV”); Herpes Keratitis

Respondent. *

* * * * * * * * * * * * * * *

Ronald Homer, Conway, Homer, P.C., Boston, MA, for Petitioner.

Joseph Lewis, United States Department of Justice, Washington, DC, for Respondent.

DECISION ON ENTITLEMENT 1

On October 28, 2015, Helene Quintana (“Petitioner”) filed a petition for compensation

pursuant to the National Vaccine Injury Compensation Program. 2 Pet. at 1, ECF No. 1; 42 U.S.C.

§§ 300aa-1 to -34 (2012). Petitioner alleges that the influenza (“flu”) vaccine she received on

November 3, 2012, caused her to suffer from peripheral ulcerative keratitis (“PUK”). 3 Pet. at 1.

Petitioner further alleges that her flu vaccine caused her to suffer from “uveitis 4 and subsequently

herpes keratitis 5 and related sequelae.” Pet’r’s Br. at 1, ECF No. 88.

1

This Decision shall be posted on the United States Court of Federal Claims’ website, in accordance with

the E-Government Act of 2002, 44 U.S.C. § 3501 note (2012) (Federal Management and Promotion of

Electronic Government Services). In accordance with Vaccine Rule 18(b), a party has 14 days to identify

and move to delete medical or other information that satisfies the criteria in § 300aa-12(d)(4)(B). Further,

consistent with the rule requirement, a motion for redaction must include a proposed redacted Decision. If,

upon review, I agree that the identified material fits within the requirements of that provision, such material

will be deleted from public access.

2

National Childhood Vaccine Injury Act of 1986, Pub L. No. 99-660, 100 Stat. 3755. Hereinafter, for ease

of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa

(2012).

3

Peripheral ulcerative keratitis (“PUK”) is “a rare type of keratitis with inflammation of the limbal part of

the cornea and nearby sclera, which have cellular infiltration, vascular changes, and ulceration that may

cause blindness; it may be a complication of rheumatoid arthritis or a bacterial infection but sometimes is

idiopathic.” Dorland’s Illustrated Medical Dictionary 1, 979 (32nd ed. 2012) [hereinafter “Dorland’s”].

4

Uveitis is “an inflammation of part or all of the uvea, commonly involving the other tunics of the eye

(sclera, cornea, and retina).” Dorland’s at 2014. The uvea is “vascular layer of eyeball: the middle,

pigmented, vascular coat of the eye, comprising the choroid, the ciliary body, and the iris[.]” Id. at 1990.

5

Herpes keratitis is “a viral infection of the eye caused by the herpes simplex virus (“HSV”). It is a virus

of the genus Simplexvirus that is an etiologic agent of herpes simplex and causes predominantly non[-

After carefully analyzing and weighing all the evidence and testimony presented in this

case in accordance with the applicable legal standards, 6 I find that Petitioner has failed to provide

preponderant evidence that the flu vaccine she received on November 3, 2012, was the cause-in-

fact of her PUK, uveitis, or herpes keratitis. Accordingly, Petitioner is not entitled to compensation.

I. Procedural History

Petitioner filed her petition for compensation on October 28, 2015. Pet. at 1. On November

5, 2015, Petitioner filed her vaccination record and twelve medical records. Pet’r’s Exs. 1–13, ECF

Nos. 8-1–9-4. Petitioner filed one additional medical record and a statement of completion on

December 8, 2015. Pet’r’s Ex. 14, ECF Nos. 10-1, 11. On December 16, 2015, Petitioner submitted

two affidavits. Pet’r’s Exs. 15–16, ECF Nos. 12-1–12-2. Petitioner filed additional medical records

and an amended statement of completion on January 7, 2016. Pet’r’s Exs. 17–18, ECF Nos. 15-1–

15-2, 16.

Respondent filed his Rule 4(c) report on January 26, 2016, recommending that

compensation be denied. Resp’t’s Report, ECF No. 17. A status conference was held on February

23, 2016, to discuss “concern[s] with the timing of onset and a possible alternate cause.” Sched.

Order, ECF No. 18; see also Min. Entry, docketed Feb. 23, 2016. Following the conference, the

presiding special master ordered Petitioner to file medical records “relating to Petitioner’s herpes

diagnosis and treatment[]” and a status report “delineat[ing] next steps and an appropriate

timeline.” Sched. Order at 1. Petitioner filed a status report on March 15, 2016, advising that “no

additional medical records exist regarding herpes treatment or status.” ECF No. 19. Petitioner

indicated that “an appropriate next step is to file a medical expert report.” Id.

On July 12, 2016, after several extensions of time, Petitioner filed an expert report from

Frederick Fraunfelder, M.D., and supporting medical literature. Pet’r’s Exs. 19–20, ECF Nos. 24-

1–24-2. Respondent filed his responsive expert report from Hamid Bassiri, M.D., on September

20, 2016, along with supporting medical literature. Resp’t’s Exs. A–L, ECF Nos. 27-1–27-12.

The parties convened for a status conference on September 29, 2016, at which time the

presiding special master discussed the experts’ reports. Sched. Order, ECF No. 28; see also Min.

Entry, docketed Sept. 29, 2016. The presiding special master noted that the experts failed “to

address Petitioner’s apparent use of Acyclovir . . . [and] that Petitioner’s expert ought to address

the potential alternative causes identified by Respondent’s expert.” Sched. Order at 1. The

presiding special master ordered Petitioner to file medical records reflecting whether she was

]genital infections. Primary infection usually occurs in early childhood and is often asymptomatic, although

gingivostomatitis and pharyngitis may occur. The virus can pass along nerves and remain latent in ganglia,

from which it may be reactivated. Called also herpes simplex virus (“HSV”) . . . .” Dorland’s at 979.

6

While I have reviewed all of the information filed in this case, only those filings and records that are most

relevant to the decision will be discussed. Moriarty v. Sec'y of Health & Hum. Servs., 844 F.3d 1322, 1328

(Fed. Cir. 2016) (“[w]e generally presume that a special master considered the relevant record evidence

even though he does not explicitly reference such evidence in his decision.”) (citation omitted); see also

Paterek v. Sec'y of Health & Hum. Servs., 527 F. App'x 875, 884 (Fed. Cir. 2013) (“[f]inding certain

information not relevant does not lead to—and likely undermines—the conclusion that it was not

considered.”).

2

pursuing a corneal transplant and a status report clarifying her use of Acyclovir. Id. The presiding

special master further ordered Petitioner to file a supplemental expert report. Id.

On October 27, 2016, Petitioner submitted additional medical records and a supplemental

affidavit. Pet’r’s Exs. 21–26, ECF Nos. 29-1–29-5, 30-1, 31. The same day, Petitioner filed a

motion for extension of time to file her remaining outstanding medical records, which was granted.

ECF No. 33. Petitioner filed additional medical records on November 21, 2016. Pet’r’s Exs. 27–

30, ECF Nos. 34-1–34-5. On November 23, 2016, Petitioner filed a motion for extension of time

to file her supplemental expert report, which was granted the same day. ECF No. 35. On December

8, 2016, Petitioner filed an additional medical record. Pet’r’s Ex. 31, ECF No. 36-2. Petitioner

filed her supplemental expert report on January 5, 2017. Pet’r’s Ex. 32, ECF No. 37-1.

This case was reassigned to me on January 9, 2017. ECF Nos. 40–41. After several

extensions of time, Respondent filed his supplemental expert report on April 25, 2017. Resp’t’s

Ex. M, ECF No. 45-1. I held a status conference with the parties on May 9, 2017. See Min. Entry,

docketed May 9, 2017. During the status conference, I discussed my main concerns with

Petitioner’s expert reports, including “a failure to explain the causal mechanism by which an

influenza vaccine causes [T]ype IV hypersensitivity and uveitis; and [] a lack of response to

alternative causes identified by Respondent . . . .” Sched. Order at 1, ECF No. 46. Following the

conference, I ordered Petitioner to file the outstanding medical literature cited in Petitioner’s initial

expert report and an additional supplemental expert report clarifying her medical theory and

addressing the potential alternative causes identified by Respondent’s expert. Id.

Petitioner filed her outstanding medical literature on May 11, 2017. Pet’r’s Exs. 19, Tabs

A, C, ECF Nos. 47-1–47-2. On August 9, 2017, Petitioner submitted a supplemental expert report

and supporting medical literature. Pet’r’s Exs. 33, Tabs A–F, ECF Nos. 49-1–49-7. Respondent

filed a responsive supplemental expert report and supporting medical literature on September 15,

2017. Resp’t’s Exs. N, O, ECF Nos. 52-1–52-2.

On September 29, 2017, the parties communicated via e-mail and agreed to proceed with

an entitlement hearing. Informal Comm., docketed Sept. 29, 2017; Order, ECF No. 53. Petitioner

filed updated medical records on April 9 and April 23, 2018, and December 11 and 17, 2019.

Pet’r’s Exs. 34–40, ECF Nos. 54-1–56-1, 67-1, 70-1. This matter was set for an entitlement hearing

on March 2, 2020. Non-PDF Order, docketed Sept. 3, 2019. Petitioner filed her pre-hearing brief

on December 12, 2019. Pet’r’s Br., ECF No. 69. Respondent filed his pre-hearing response brief

on January 10, 2020. Resp’t’s Resp., ECF No. 72. On January 14, 2020, Petitioner filed additional

updated medical records. Pet’r’s Exs. 41–43, ECF Nos. 74-1–74-3. Petitioner submitted her pre-

hearing reply brief and medical literature on February 14, 2020. Pet’r’s Reply Br., ECF No. 85;

Pet’r’s Exs. 44–45, ECF Nos. 79-1, 81, 82. The entitlement hearing was held as scheduled on

March 2, 2020. See Min. Entry, docketed Mar. 2, 2020.

Following the entitlement hearing, Petitioner filed her opening post-hearing brief on June

10, 2020. Pet’r’s Br., ECF No. 88. On July 27, 2020, Respondent filed his post-hearing response

brief. Resp’t’s Resp., ECF No. 90. Petitioner did not submit a post-hearing reply brief. This matter

is now ripe for consideration.

3

II. Factual Background

A. Medical Records

Petitioner’s pre-vaccination history is rather “unremarkable[,]” and she was “healthy.” Pet.

at 1; Resp’t’s Report at 2; Pet’r’s Exs. 3, 4, ECF Nos. 8-3–8-4. Petitioner received an influenza

vaccine on November 3, 2012. Pet’r’s Ex. 1, ECF No. 8-1. She was fifty-five years old at the time

of vaccination. Pet. at 1. On November 12, 2012, Petitioner reported to Lilia Alvarez, D.O. Pet’r’s

Ex. 2 at 1, ECF No. 8-2. Dr. Alvarez wrote that Petitioner “had [a] stye 7 start after [receiving the]

flu shot. Progressed to turning red and swollen on [November 5, 2012].” Id. Dr. Alvarez also wrote

that Petitioner had a “fever [on November 7, 2012 through November 8, 2012], [which] was gone

by [November 10, 2012].” Id. Dr. Alvarez further wrote that Petitioner “had [another] stye [on

November 10, 2012, which became] worse [on November 11, 2012,]” and that Petitioner was

suffering from “a mild cold.” Id. She noted that Petitioner’s “nasal nerves on cheeks are tender[.]”

Id. Petitioner reported that her vision “fe[lt] blurry from discharge[.]” Id. An examination revealed

yellow mucous and itchiness, along with pain below the eye. Id. Dr. Alvarez’s examination also

revealed a clear cornea. 8 Id. Dr. Alvarez assessed Petitioner with bacterial conjunctivitis 9 of the

right eye greater than the left, and she prescribed Tobradex, 10 an antibiotic eyedrop. Id. at 2.

On November 13, 2012, Petitioner returned to Dr. Alvarez reporting feeling “much better”

after doing hot compresses. Id. Petitioner reported “some mild discomfort, but fe[lt] better and

[was] less swollen[.]” Id. Dr. Alvarez’s examination revealed a “30% improvement” in Petitioner’s

right eye, while her left eye was “better.” Id. Dr. Alvarez directed Petitioner to continue her

antibiotic eye drops for three days and then cut back. Id.

Petitioner returned to Dr. Alvarez for a follow-up on December 10, 2012. Id. at 3. Petitioner

reported “some improvement with [prescription,]” and there was “no discharge[]” but still

itchiness. Id. Dr. Alvarez’s examination revealed dry corneas and yellow discharge and she

diagnosed Petitioner with a bacterial infection. Id. Dr. Alvarez prescribed Petitioner a different

antibiotic eye drop. Id.

On January 7, 2013, Petitioner presented to ophthalmologist Michael W. Foote, M.D., with

complaints of “pain and redness in her right eye[, which she described as a] 7 out of 10 [in]

severity.” Pet’r’s Ex. 5 at 1, ECF No. 8-5. Petitioner reported that this pain began six weeks prior

7

A stye or hordeolum is “a localized, purulent, inflammatory staphylococcal infection of one or more

sebaceous glands . . . of the eyelids[.]” Dorland’s at 869, 1789.

8

A cornea is “the transparent structure forming the anterior part of the fibrous layer of the eyeball. It consists

of five layers: (1) the anterior corneal epithelium, continuous with that of the conjunctiva; (2) the anterior

limiting layer . . .; (3) the substantia propria, or stroma; (4) the posterior limiting layer . . .; and (5) the

endothelium of the anterior chamber.” Dorland’s at 415.

9

Conjunctivitis is “inflammation of the conjunctiva, generally consisting of conjunctival hyperemia

associated with a discharge.” Dorland’s at 405.

10

Tobradex is the “trademark for combination preparations of tobramycin and dexamethasone.” Dorland’s

at 1933. Tobramycin is “effective against a wide range of aerobic gram-negative bacilli and some gram-

positive bacteria, having a range of antibacterial activity similar to that of gentamicin; used topically in the

treatment of external infections of the eye and its adnexa.” Id. Dexamethasone is “an anti-inflammatory and

administered orally in replacement therapy for adrenocortical insufficiency . . . .” Id. at 504.

4

and “is constant.” Id. Petitioner denied any trauma. Id. Dr. Foote’s examination revealed “diffuse

papillary changes” and severe redness of the right eye and “minimal papillary changes, mild

injection” in her left eye. Id. at 2. Dr. Foote’s impression was a “marginal corneal ulcer 11 [in

Petitioner’s] right eye[,]” which Dr. Foote “suspect[ed was of an] infectious etiology.” Id. He noted

that Tobradex and Petitioner’s existing treatment “seem[ed] to make it better[.]” Id. at 1. Dr. Foote

prescribed Vigamox 12 and tobramycin drops 13 and directed Petitioner to follow up the next day.

Id.

Petitioner returned to Dr. Foote on January 8, 2013. Id. at 3. Petitioner complained of

“blurry vision, in and around eye pain, [and] redness. [Her] vision is affected both at near and far.”

Id. In addition to medications described above, Petitioner also reported taking Acyclovir, an

antiviral for herpes infections. 14 Id. Dr. Foote wrote that a “gram stain [of Petitioner’s discharge]

was negative for organism.” Id. Dr. Foote considered the possibility that this was PUK, but

“suspect[ed it was] more likely infectious.” Id.

On January 11, 2013, Petitioner returned to Dr. Foote with worsening symptoms, including

“redness, tearing, and light sensitivity.” Id. at 5. Dr. Foote wrote that Petitioner’s condition was

“presumed to [be] an infectious keratitis but now [he is] suspecting more a peripheral ulcer

keratitis[,] which has progress[ed] dispite [sic] topical antibiotic and negative corneal cultures at

this point.” Id. at 6. He directed Petitioner to continue her current medications, except for

Acyclovir, and prescribed a Medrol Dosepak 15 and Durezol, a steroidal eye drop. Id. at 6, 7.

Petitioner returned to Dr. Foote on January 14, 2013, and reported that her “condition is

improving.” Id. at 9. During this visit, Dr. Foote noted that he “suspect[ed] possible [rheumatoid

arthritis (“RA”)] vs. other autoimmune process, she has a family [history] of autoimmune disorders

. . . .” Id. Dr. Foote also ordered numerous tests, including erythrocyte sedimentation rate (“ESR”),

C-reactive protein, antinuclear antibody (“ANA”), and RA factor. Id. These results returned on

January 28, 2013, and showed a positive ANA and HLA-B27 haplotype. Id. at 15. The same day,

Dr. Foote noted that Petitioner has a sister with possible RA and a son with possible ankylosing

spondylitis. 16 Id. at 21. He also indicated that Petitioner’s corneal ulcer had “slowly” continued to

heal. Id. at 16.

11

A corneal ulcer is also called ulcerative keratitis, which is “keratitis with ulceration of the corneal

epithelium[.]” Dorland’s at 980.

12

Vigamox is the brand name for moxifloxacin. Dorland’s at 1184. Moxifloxacin is an eye drop “effective

against many . . . bacteria.” Id.

13

See supra note 10.

14

Dr. Foote’s notes indicate that Petitioner began taking Acyclovir on January 11, 2013. Pet’r’s Ex. 5 at 1.

However, Dr. Foote noted during Petitioner’s January 8, 2013 appointment that she was on Acyclovir then.

15

A Medrol Dosepak is a prescription of Medrol. Medrol is the “trademark for preparation of

methylprednisolone.” Dorland’s at 1120. Methylprednisolone is “a synthetic glucocorticoid [steroid]

derived from progesterone, used in replacement therapy for adrenocortical insufficiency and as an anti[-

]inflammatory and immunosuppressant in a wide variety of disorders[.]” Id. at 1154.

16

Ankylosing spondylitis is “a chronic multisystem inflammatory disorder associated with presence of the

HLA-B27 antigen, and thus one of the group of seronegative spondyloarthropathies; it usually initially

affects the sacroiliac joints and often later involves other joints of the axial skeleton and peripheral joints,

5

On March 4, 2013, Petitioner returned to Dr. Foote at his “request to re-evaluate blurry

vision in [her] right eye.” Id. at 22. During this visit, Petitioner reported “doing much better from

[her] last visit . . . .” Id. Dr. Foote noted that Petitioner’s ulcer “is finally sealed,” and he decreased

her steroidal and antibiotic eye drops. Id.

On May 10, 2013, Petitioner returned to Dr. Foote to complain of a “reaction to Restasis 17

in both [of her] eyes.” Id. at 28. She described the “severity [as] moderate[,]” and her “vision is

not affected.” Id. Petitioner further described the onset as “sudden” and noted that the symptoms

began “[one] week ago.” Id. Dr. Foote wrote that Petitioner’s PUK had returned. Id. Petitioner

returned to Dr. Foote ten days later, on May 20, 2013. Id. at 33. Petitioner stated that her ulcer was

“improving,” and she “denie[d] redness, pain, light sensitiv[ity], tearing, or itch[iness].” Id. She

also stated that her vision was “better” and that she was taking Durezol, Vigamox, and “art[ificial]

tears.” Id. Dr. Foote reaffirmed the PUK diagnosis and noted that it was “improving.” Id.

Petitioner presented to rheumatologist Karen Smith, M.D., on June 5, 2013. Pet’r’s Ex. 8

at 12, ECF No. 8-8. Dr. Smith noted that Petitioner was “here after severe ulcerative keratitis after

flu shot.” Id. An examination revealed “on eye red injected eye ulcer at right internal lower

quadrant with limbal haze[, but] otherwise” was a normal exam. Id. Dr. Smith diagnosed Petitioner

with “Reiter’s [syndrome] 18 most likely[,]” and she prescribed methotrexate 19 and folic acid. 20 Id.

The same day, Petitioner presented to internist Branch Craige, M.D., to establish care.

Pet’r’s Ex. 9 at 2, ECF No. 8-9. Dr. Craige noted that Petitioner was “here to get acquainted,

frustrated over a second episode of PUK . . .[,] which she attributes to our dry Southwest or

possibly [an] allergy to a vehicle and whatever eyedrops.” Id. However, an addendum entered on

December 1, 2014, states, “[Petitioner] asked us to amend our initial note to reflect the fact that

she attribute[s] her PUK to a reaction to [a flu] vaccine.” Id. He noted that Petitioner had “just

begun therapy with Dr. Karen Smith for Reiter [sic] syndrome[.]” Id. Under past medical history,

Dr. Craige noted that Petitioner’s Reiter’s syndrome with PUK had an “onset [of] 2012[.]” Id. at

3. Upon examination, Dr. Craige wrote that Petitioner’s “right eye seem[ed] somewhat inflamed,”

causing pain and progressive stiffness and restricted range of motion. Extraskeletal manifestations include

ocular, pulmonary, cardiovascular, renal, and neurologic complications.” Dorland’s at 1754.

17

Restasis is the trademark preparation of cyclosporine. Dorland’s at 1629. Cyclosporine is an

immunosuppressant, “produced as a metabolite by the soil fungus Tolypocladium inflatum Gams; it acts by

inhibiting activation of helper T lymphocytes. Administered orally or intravenously to prevent and treat

rejection in organ transplant recipients, to treat severe psoriasis, and as a disease-modifying antirheumatic

drug to treat rheumatoid arthritis; also administered topically to the conjunctiva in the treatment of chronic

dry eye.” Id. at 456.

18

Reiter’s syndrome is “the triad of acute aseptic arthritis, nongonococcal urethritis, and conjunctivitis; . .

. It usually affects young men and runs a self-limited but relapsing course. Some authorities now consider

this symptom complex to be more appropriately classified as reactive arthritis and not distinguished or

named separately.” Dorland’s at 1845.

19

Methotrexate is “a folic acid antagonist that acts by inhibiting synthesis of DNA, RNA, thymidylate and

protein . . . It is also used as an anti[-]psoriatic and antiarthritic in the treatment of severe, recalcitrant,

disabling psoriasis and severe rheumatoid and psoriatic arthritis.” Dorland’s at 1151.

20

Folic acid is “1. a water-soluble vitamin of the B complex . . .; 2. a preparation of folic acid administered

orally or parenterally in the prophylaxis and treatment of folic acid deficiency states, including

megaloblastic anemia.” Dorland’s at 725.

6

but was otherwise normal. Id. His assessment included “Reiter [sic] syndrome, HLA-B27

positive.” Id.

On June 21, 2013, Petitioner returned to Dr. Foote for a follow-up. Pet’r’s Ex. 5 at 45. Dr.

Foote noted that “[t]he erosion over [Petitioner’s] right eye has significantly improved, though the

epithelial is fairly irregular.” Id. at 46. Five days later, on June 26, 2013, Petitioner presented to

Dr. Smith for continued concerns. Pet’r’s Ex. 8 at 11. Dr. Smith wrote that “[Petitioner’s] ulcers

have healed but her eye is redder. . . . She is on her eye drops and has had her contact in place. No

problems with the methotrexate.” Id. Dr. Smith’s examination revealed a “red eye[, but] nothing

else.” Id. Dr. Smith assessed Petitioner with keratitis, prescribed her minocycline, 21 and directed

her to stop methotrexate due to her then-upcoming trip to Norway. Id.

Petitioner returned to Dr. Foote for a follow-up on July 2, 2013. Pet’r’s Ex. 5 at 50. Dr.

Foote wrote that Petitioner exhibited “decreased redness.” Id. Dr. Foote wrote that “[t]he [three]

abrasions noted previously have turned into one large abrasion[,]” and that Petitioner had begun

to take “Pred [F]orte[.] 22” Id.

On July 17, 2013, Petitioner presented to Dr. Smith, who wrote that Petitioner had “severe

right eye pain [with] no fever[,] chills[,] cough or rash.” Pet’r’s Ex. 8 at 10. Upon examination,

Petitioner exhibited “severe uveitis with hypopyon 23” but was “well otherwise.” Id. Dr. Smith’s

assessment was that Petitioner’s condition “needs aggressive control[,]” and she noted that she had

spoken to Dr. Foote Id. She prescribed Cimzia 24 and a higher dose of methotrexate. Id. Dr. Smith

also requested “STAT” Remicade. 25 Id. She wrote that the “severity and suddenness of

[Petitioner’s] flare suggests [B]ehcet’s” syndrome. 26 Id.

Petitioner returned to Dr. Smith on July 26, 2013, for her first dose of Remicade. Id. at 7.

During this visit, Petitioner reported “moderate pain[.]” Id. Dr. Smith’s examination revealed that

Petitioner’s “eye [was] very red [with] no discharge . . . [and] no edema around [her] eye [and]

less corneal edema.” Id. She assessed Petitioner with “hypopyon uveitis” and noted that she would

“defer to optho [sic].” Id. Dr. Smith indicated that Petitioner was scheduled to see two additional

ophthalmologists that day. Id.

21

Minocycline is “a semisynthetic broad-spectrum antibiotic . . . .” Dorland’s at 1168.

22

Pred Forte is the brand name for prednisolone. Prednisolone is “a synthetic glucocorticoid derived from

cortisol, administered orally in replacement therapy for adrenocortical insufficiency and as an anti-

inflammatory and immunosuppressant in a wide variety of conditions.” Dorland’s at 1508.

23

Hypopyon is “an accumulation of pus in the anterior chamber of the eye.” Dorland’s at 905.

24

Cimzia is the trademark preparation of certolizumab pegol. Dorland’s at 361. Certolizumab pegol is “a

tumor necrosis factor blocker used for reduction of signs and symptoms of Crohn disease; administered by

subcutaneous injection.” Id. at 333.

25

Remicade is the trademark preparation of infliximab. Dorland’s at 1623. Infliximab is “a chimeric

human-murine immunoglobulin that acts as a tumor necrosis factor blocker; administered intravenously in

treatment of Crohn disease and rheumatoid arthritis.” Id. at 937.

26

Behcet’s syndrome is “a variant of neutrophilic dermatosis of unknown etiology, involving the small

blood vessels, characterized by recurrent aphthous ulceration of oral and pharyngeal mucous membranes

and genitalia, with skin lesions, severe uveitis, retinal vasculitis, optic atrophy, and often involvement of

the joints, gastrointestinal system, and central nervous system.” Dorland’s at 1822.

7

Petitioner presented to ophthalmologist Mario Di Pascuale, M.D., on July 26, 2013. Pet’r’s

Ex. 10 at 15, ECF No. 9-1. Dr. Di Pascuale wrote that Petitioner “received [the] flu vaccine on

November 2, 2012, then contracted conjunctivitis.” Id. He continued that this “was treated” but

“worsened and [Petitioner] was told [she] had [an] ulcer by Dr. Foote and was treated with

steroids[, which] helped.” Id. During this visit, Petitioner complained of pain, photophobia, and

light sensitivity in her right eye. Id. Dr. Di Pascuale diagnosed Petitioner with PUK and re-

prescribed Acyclovir, while discontinuing Vigamox. Id.

The same day, Petitioner saw a second ophthalmologist, Ruben Ramirez, M.D. Pet’r’s Ex.

6 at 1, ECF No. 8-6. Dr. Ramirez noted that the onset of Petitioner’s condition occurred “after [the]

flu vaccine.” Id. Dr. Ramirez assessed Petitioner with “severe vasculitis with associated

keratitis[,]” although he was “unclear if [it was] infectious[,]” as the culture was negative. Id. at 5.

Dr. Ramirez suggested adding systemic steroids to Petitioner’s medications. Id. On July 30, 2013,

Petitioner was formally prescribed oral steroids by Dr. Di Pascuale. Id. at 4.

Petitioner took a trip to Norway in August of 2013. Pet’r’s Ex. 11 at 1, ECF No. 9-2. On

August 23, 2013, Atle Einar Ostern, M.D., wrote a letter documenting the issues Petitioner

experienced while in Norway. Id. Dr. Ostern wrote that Petitioner “was admitted to the eye

Dep[artment] at Oslo University Hospital [on August 8, 2013].” Id. She noted that Petitioner’s

right eye had “corneal edema . . . with a large corneal epithelial defect[,] which was measured

vertically 4.2 [mms] and horizontally 6.7 [mms, and] corneal sensibility was almost absent.” Id.

Dr. Ostern noted that all specimen cultures were negative. Id. Dr. Ostern wrote that “the condition

may be consistent with an (initial) stromal or endothelial herpes keratitis even if all specimens are

negative[,] ([Petitioner] feels the pain was diminished after starting [sic] taking Acyclovir).” Id.

Dr. Ostern also wrote that the “drastically reduced corneal sensibility . . . has lead [sic] to

neurotrophic keratopathy[,]” for which Dr. Ostern gave Botox injections into the “eyelid to induce

a complete ptosis.” Id. Petitioner was treated with lubricants, prophylactic antibiotics, and

Valacyclovir tablets, 27 which “gradually improved” Petitioner’s condition. Id. Petitioner’s corneal

defect had reduced in size (1.8 mms by 2.5 mms) upon discharge. Id. Petitioner was discharged

with eye gels, ointments, drops, and Valacyclovir, which Dr. Ostern noted “may [need to] be

continued . . . for perhaps months.” Id.

Upon her return to the United States, Petitioner resumed care with Dr. Smith. Pet’r’s Ex. 8

at 6. On August 28, 2013, Dr. Smith wrote that Petitioner received treatment in Norway and had

been diagnosed with “herpetic keratitis/vasculitis.” Id. Dr. Smith noted that a biopsy had “+Abs

[(antibodies)] in the serum.” Id. Dr. Smith diagnosed Petitioner with “Reiter’s keratitis with herpes

as the AG [aggravating] driver.” Id. Her plan was for Petitioner to “stay on the Valtrex [] for a

week then taper off pred[nisone].” Id.

The same day, Petitioner also returned to Dr. Di Pascuale. Pet’r’s Ex. 10 at 11. Petitioner

reported feeling “better” after her treatment in Norway. Id. Dr. Di Pascuale recommended

continuing her treatment. Id. Two days later, on August 30, 2013, Petitioner returned to Dr. Foote.

27

Valacyclovir hydrochloride tablets are “used as an antiviral agent in the treatment of genital herpes and

herpes zoster in immunocompetent adults; administered orally. Following absorption, valacyclovir is

converted by intestinal and hepatic metabolism to the active drug acyclovir.” Dorland’s at 2020. The

trademark preparation is Valtrex. Id. at 2021.

8

Pet’r’s Ex. 5 at 67. Dr. Foote noted that Petitioner was on oral prednisone and Valtrex, but the

remainder of her medications had been discontinued. Id.

On September 9, 2013, Petitioner reported to Dr. Di Pascuale with complaints of “eye

sensitivity and swelling” while she was tapering off prednisone. Pet’r’s Ex. 10 at 9. Upon

examination, Dr. Di Pascuale noted a corneal ulcer that was “significantly improved.” Id. Dr. Di

Pascuale diagnosed Petitioner with keratitis and increased her prednisone dosage. Id.

Petitioner returned to Dr. Smith on October 8, 2013, and reported “some eye pain[,]” so

“she is back on her eye drops.” Pet’r’s Ex. 8 at 5. Dr. Smith noted that Petitioner was on Valtrex

and prednisone. Id. Dr. Smith’s examination revealed a “cloudy right cornea with limbal

injection[.]” Dr. Smith diagnosed Petitioner with “Reiters [sic] [syndrome] with herpes keratitis.”

Id.

On December 2, 2013, Petitioner returned to Dr. Foote, who wrote that “[Petitioner’s] eye

appears fairly quiet today [without] peripheral inflammation.” Pet’r’s Ex. 5 at 70–71. However, he

noted that Petitioner “ha[d] marked corneal vascularization. 28” Id. at 71. Petitioner reported that

she had been in Norway in August and “saw an [sic] uveitis specialist there who [diagnosed] her

with herpetic keratouveitis 29 and stated her HLA-B27 status caused her to have a severe reaction

to [the] herpes virus.” Id.

Petitioner had another follow-up for the ulcer in her right eye with Dr. Foote on April 15,

2014. Id. at 73. Dr. Foote noted that “[t]he severity [of the ulcer] is improving” and “[t]he condition

is resolved.” Id. He wrote that Petitioner’s “[v]ision [wa]s affected both at near and far . . . .” Id.

Dr. Foote indicated that Petitioner “continue[d] to have vascularization . . . [which has] regress[ed]

over time.” Id. He noted that Petitioner “initially presented with peripheral ulcerative keratitis[,]

which was ultimately [diagnosed] as herpetic keratouveitis [that was] exacerbated by her HLA-

B27 status.” Id. Regarding Petitioner’s cataract, Dr. Foote wrote that her “condition is moderate

to severe [and s]he has posterior synechia from previous uveitis episodes.” Id. Dr. Foote

recommended surgical intervention and to continue taking Acyclovir and prednisone. Id.

Petitioner followed up with Dr. Di Pascuale two days later, on April 17, 2014. Pet’r’s Ex.

7 at 22, ECF No. 8-7. Dr. Di Pascuale noted that Petitioner had 20/20 vision in her right eye. Id. at

23. He wrote that Petitioner no longer had a corneal ulcer, but she still had a corneal scar and

neovascularization of the cornea. Id. at 24. Dr. Di Pascuale diagnosed Petitioner with a corneal

28

Corneal vascularization is “any formation of new blood vessels” in the cornea. Dorland’s at 2026.

29

Herpetic keratouveitis is “1. Keratitis caused by infection with herpes simplex virus, often with dendritic

ulceration . . . 2. Keratitis occurring as a complication of herpes zoster ophthalmicus.” Dorland’s at 979.

9

scar, scleritis, 30 and a cataract. 31 Id. He wrote that “cataract surgery will be required at some point.”

Id. at 25.

On May 8, 2014, Petitioner had another follow-up with Dr. Smith, who wrote that

Petitioner was “stable and has not had any new problems other than she was in an accident at work

and fell hard on her right thigh and is still limping.” Pet’r’s Ex. 8 at 2. Dr. Smith’s examination

revealed “some corneal scarring [in Petitioner’s] right eye[,] but no signs of activity [of connective

tissue disease (“CTD”) 32].” Id. Dr. Smith assessed Petitioner with “CTD in remission” and

“traumatic injury right thigh.” Id. Dr. Smith noted that Petitioner’s “CTD [was] in remission [for

six months].” Id.

Petitioner presented to orthopedist Jacob Heydemann, M.D. on May 22, 2014, for right hip

pain that she associated with the work-related injury she experienced on March 15, 2014. Pet’r’s

Ex. 12 at 5–6, ECF No. 9-3. Petitioner explained that while working for ski patrol, she fell on a

patch of ice. Id. Dr. Heydemann wrote that Petitioner “has a viral keratitis from a flu vaccine that

has affected her right eye and [Petitioner] has also been diagnosed with a rheumatoid type pattern,

but its only symptom is that it started after the flu vaccine, unrelated to this trauma [i.e., the hip

injury].” Id. Dr. Heydemann diagnosed Petitioner with joint pain and ordered an MRI, which

showed a “small tear of the anterior lip of the labrum.” Id. at 11. He treated Petitioner’s condition

accordingly. Id. Dr. Heydemann released Petitioner from his care on September 19, 2014, and

noted that Petitioner was still in some hip discomfort. Id. at 1.

Petitioner returned to Dr. Di Pascuale on October 7, 2014. Pet’r’s Ex. 7 at 8. Petitioner

complained of “some headaches and . . . vision fluctuating in the right eye.” Id. at 9. Dr. Di

Pascuale’s examination showed punctate epithelial erosions of both corneas, a right corneal scar

with corneal neovascularization, and bilateral cataracts. Id. at 9–10. Dr. Di Pascuale’s impression

included dry eye syndrome, corneal scar, a flare of scleritis, and cataracts. Id. at 10–11. Dr. Di

Pascuale increased Petitioner’s Acyclovir dosage and steroid eye drops and ordered Petitioner to

follow up in six weeks. Id. at 11.

On November 6, 2014, Petitioner returned to Dr. Smith for a follow-up. Pet’r’s Ex. 8 at 1.

Dr. Smith wrote that Petitioner was “generally stable except she has a permanent eye injury.” Id.

Petitioner reported that her eye injury began after receipt of a flu vaccine. Id. Dr. Smith noted that

“[i]t is immunologically possible that [the flu vaccine] could be the trigger.” Id. Dr. Smith’s

examination revealed that Petitioner had a “red hazy right eye [with a] small amount of clear

discharge[,]” but “otherwise [had a] normal exam.” Id. Dr. Smith assessed Petitioner with

30

Scleritis is “inflammation of the sclera, with dilation of the scleral, episcleral, and bulbar conjunctival

vessels. It may be confined to a sector or diffuse, and presents with severe, boring pain, photophobia,

tearing, and decreased visual acuity. It is often associated with systemic disease, particularly rheumatoid

arthritis.” Dorland’s at 1679.

31

A cataract is “a partial or complete opacity on or in the lens of the eye or its capsule, especially one

impairing vision or causing blindness. Cataracts are classified by their morphology (size, shape, location)

or etiology (cause or time of occurrence).” Dorland’s at 303.

32

Connective tissue disease is “any disease that affects the parts of the body that connect the structures of

the body together . . . [c]onnective tissues are made up of two proteins: collagen and elastin.” Connective

Tissue Diseases, CLEV. CLINIC, https://my.clevelandclinic.org/health/diseases/14803-connective-tissue-

diseases (last visited Feb. 1, 2022).

10

“inflammatory eye disease. 33” Id. Dr. Smith’s plan was for Petitioner to “send [Dr. Smith a]

timeline and lot number for [her] initial incident with [the flu] vaccine and [Dr. Smith would] then

do a letter for [the] vaccine compensation fund[.]” Id.

Petitioner returned to Dr. Di Pascuale on December 4, 2014, complaining of “some

headaches and . . . plunctuating in the right eye.” Pet’r’s Ex. 7 at 6. Dr. Di Pascuale assessed

Petitioner with corneal dry eye syndrome, stable sclerokeratitis, 34 which he noted could be HSV-

related, a corneal scar, and cataracts. Id. at 7, 8. Dr. Di Pascuale increased Petitioner’s Acyclovir

dosage and eye lubricant. Id.

On April 23, 2015, Petitioner returned to Dr. Foote, who wrote that Petitioner’s corneal

ulcer had “essentially resolved.” Pet’r’s Ex. 5 at 78. Dr. Foote also wrote that Petitioner “ha[d]

corneal thinning, which remains stable[, and] she had some calcification as well. In general, there

appears to be some overall reduction in the size of the scar and the vascularity is regressing.” Id.

He indicated that Petitioner was to continue her current treatment regimen, which included

prednisolone, serum tears, and Acyclovir. Id. Dr. Foote noted that “the entire episode began [three]

days subsequent to [a] flu vaccination . . . .” Id.

Petitioner saw Dr. Di Pascuale several months later, on July 2, 2015, complaining of

“blurry vision.” Pet’r’s Ex. 7 at 29. Dr. Di Pascuale diagnosed Petitioner with sclerokeratitis, HSV-

related, which he noted was “stable.” Id. at 31. He also maintained his diagnoses of corneal dry

eye syndrome, a corneal scar, scleritis, and cataracts. Id. Dr. Di Pascuale recommended Petitioner

continue taking Acyclovir and using eye drops. Id.

Petitioner presented to Lookman Lawal, M.D., on April 18, 2016, for complaints of heart

murmurs. Pet’r’s Ex. 35 at 1–2, ECF No. 54-2. Dr. Lawal noted that Petitioner had a “flu shot

reaction [-] eye inflammatory[.]” Id. at 1. He indicated that “[s]he had an autoimmune reaction in

her right eye after a flu shot [two] years ago.” Id. at 2.

On May 6, 2016, Petitioner presented to Dr. Smith for a follow-up and reported vision loss,

sensitivity to light, wind, and dust. Pet’r’s Ex. 30 at 2, ECF No. 34-5. Dr. Smith noted that

Petitioner was on Acyclovir. Id. On November 4, 2016, Petitioner returned to Dr. Smith and stated

that she was doing well throughout the summer but “was given a skin test for [tuberculosis (“TB”)]

and she has had [the Bacille Calmette-Guerin (“BCG”) vaccine for TB] before. She has had an

enormous [reaction] and since then her eyes are flaring.” Id. at 1. Dr. Smith’s examination revealed

that Petitioner was experiencing “erythema and redness [that were] moderate [in Petitioner’s] right

eye [and] mild [in her] left eye.” Id. Dr. Smith wrote a “[n]ote to avoid all things that stimulate

dendritic cells[,] which is vaccines and BCG as it activates her eye disease . . . .” Id. Dr. Smith

continued to monitor Petitioner’s condition and directed her to follow up again in four months. Id.

33

Inflammatory eye disease is an umbrella term for “a range of conditions associated with eye

inflammation” including uveitis, keratitis, conjunctivitis, and thyroid eye disease. Eye Diseases &

Conditions: Eye Inflammation and Inflammatory Eye Disease, PREVENT BLINDNESS,

https://preventblindness.org/eye-inflammation/ (last visited Feb. 1, 2022).

34

Sclerokeratitis is “inflammation of the sclera and of the cornea.” Dorland’s at 1680.

11

Petitioner traveled to Norway in late 2017, and while there, returned to Dr. Ostern. Pet’r’s

Ex. 38 at 1A, ECF No. 56-1. Dr. Ostern summarized Petitioner’s medical history and noted that

“[o]n November 3, 2012, [Petitioner] was given [the flu] vaccine . . . [and three] days later [she

developed a] fever . . . [and] conjunctivitis in both eyes . . . [then d]eveloped assumed peripheral

ulcerative keratitis.” Id. Dr. Ostern continued that “the ulcer redeveloped on [Petitioner’s]

cornea[.]” Id. Dr. Ostern explained that as of the last time Petitioner was in Norway, on August 8,

2013, her diagnosis was “[a]ssumed to be residual [h]erpes [k]eratitis with [u]veitis reaction in

[her] right eye[.]” Id. She noted that Petitioner’s “[s]equelae is seen from assumed residual herpes

keratitis . . . [and h]erpes keratitis can be set off by stress[.]” Id. at 2A. Dr. Ostern wrote that

Petitioner had lost a son in 2015. Id. She continued that “[i]n connection with [a] TB test . . . with

inoculation in October 2016[, Petitioner] got local swelling in arm, but also at the same time strong

swelling around the eyes, mostly around [her] right eye with local irritation without wounds[.]” Id.

Dr. Ostern concluded that Petitioner “seems to react strongly to vaccines, also around the eyes.

This is assumed to secondarily set of [her h]erpes [k]eratitis.” Id. Petitioner has not filed any

additional medical records.

B. Petitioner’s Affidavits

Petitioner submitted three affidavits in support of her petition and did not testify at the

entitlement hearing. See Pet’r’s Exs. 15, 16, 26, ECF Nos. 12-1, 12-2, 30-1. In her first affidavit,

Petitioner averred that no civil actions had previously been filed on her behalf for her vaccine-

related injury. Pet’r’s Ex. 15 at 1.

In her second affidavit, Petitioner explained that prior to receiving her flu shot on

November 3, 2012, she “had never had any major health issues . . . [and she] led an active lifestyle,

playing competitive tennis . . . coach[ing] . . . r[unning] and lift[ing] weights several times per

week.” Pet’r’s Ex. 16 ¶ 1. Petitioner wrote that her occupations as a paramedic and member of a

ski patrol team kept her “physically fit[.]” Id. ¶ 2. She noted that as a paramedic, she was “tasked

with driving the ambulance, triaging medical situations[,] and transporting patients to hospital

destinations.” Id. She elaborated that as a member of the ski patrol, she “extract[ed] injured skiers

from mountainous terrain.” Id.

Petitioner described the timeline of her post-vaccination condition. Petitioner averred that

after receiving the flu shot on November 3, 2012, she “did not notice anything immediately

wrong.” Id. ¶ 3. She wrote that “[s]everal days later, [she] developed a fever and both of [her] eyes

became extremely red, itchy[,] and painful . . . [and] a stye had developed on [her] right eye.” Id.

¶ 4. Petitioner noted that she “thought [it] was just a normal case of conjunctivitis, and [she] waited

to see if it got better . . . [but] it did not.” Id. She explained that “[o]ver the following couple of

days,” her fever went away but her eyes worsened, in that “[t]he redness was getting more intense,”

and her eyes produced a discharge. Id. Petitioner wrote that in response, she sought treatment with

Dr. Alvarez. Id. ¶ 5. Petitioner indicated that “the redness in [he] left eye resolved, but [her] right

eye continued to bother [her,]” which led to her referral to ophthalmologist Dr. Foote. Id.

She wrote that “a few days before Christmas,” prior to presenting to Dr. Foote, her right

eye was getting “progressively worse . . . [and she] noticed a white spot on the cornea of her right

eye.” Id. Petitioner noted her “failing eyesight” around this time. Id. Petitioner described her visit

with Dr. Foote on January 7, 2013, and wrote that “he examined [her] eye and told [her she] had

12

an ulcer on the cornea of [her] right eye.” Id. ¶ 6. She noted that she maintained treatment with Dr.

Foote “[f]or the next several weeks,” and that “the ulcer in [her] right eye started to heal slightly,

but [her] vision was not back to normal.” Id. Petitioner expressed that the tests performed by Dr.

Foote “did not reveal any specific cause for [her] eye problems, but [he] did tell [her] that [she]

was ANA and HLA-B27 positive.” Id. Petitioner noted that Dr. Foote prescribed Acyclovir during

this appointment, but that she “only took the medication for a short time because the virus cultures

were negative, and Dr. Foote told [her] not to take it anymore.” Pet’r’s Ex. 26 ¶ 1. Petitioner

averred that prior to this visit, she had never taken Acyclovir and “had never previously sought

medical care concerning any type of herpes infection[,]” as she had no prior “signs or symptoms

to suggest [she] had a herpes infection.” Id. ¶ 2.

Petitioner continued that in June of 2013, she presented to Dr. Smith, who “performed more

tests and started [her] on methotrexate.” Pet’r’s Ex. 16 ¶ 8. Petitioner noted that she noticed her

eye to be “slightly better[,]” but by July of 2013, “the pain and blurry vision in the right eye

increased dramatically.” Id. Petitioner averred that at that time, she “had recently stopped taking

the steroids that were prescribed to [her], and it appeared [her] eye was worsening.” Id. In response,

Petitioner wrote that she returned to Dr. Foote, “who placed an amniotic membrane graft over [her]

cornea in an attempt to heal the ulcer and get the swelling and redness to go down.” Id.

Petitioner wrote that prior to her travels to Norway in August of 2013, her eye “was very

bad[.]” Id. ¶ 9. She explained that her eye “hurt to even open the refrigerator as any light would

cause [her] great pain . . . [e]ven with the atropine drops[.]” Id. Petitioner corroborated that while

in Norway, she presented to the Eye Clinic at Oslo University Hospital. Id. ¶ 10. She noted that

the doctors told her “that the ulcer had now grown to over [six] millimeters wide.” Id. In response,

“[t]hey injected [her] eye with Botox to get it to close to protect the ulcer and help it to heal[,] . . .

prescribed different medications[,] and stopped the methotrexate.” Id. Petitioner wrote that “[t]his

made [her] eye much more comfortable.” Id. Petitioner noted that her eye “continued to be

stable[]” on oral steroids, antiviral medication, and “large doses of ibuprofen[]” throughout the fall

of 2013. Id. ¶ 11. She wrote that “[o]nce the ulcer had healed . . . [she] maintained it with 3–4

steroid drops a day[,] as well as constant lubrication[.]” Id.

Next, Petitioner described the effect the issues with her right eye have had on her daily life.

Id. ¶¶ 7, 12–14. Petitioner wrote that in the spring of 2013, she “had to forego a job offer from an

ambulance company . . . [, which had] show[n] a lot of interest in hiring [her] because [she] was

licensed in both Texas and New Mexico.” Id. ¶ 7. She averred that she was not able to pursue this

opportunity because of her “worsening eye sight [sic] and the inflammation that continued to affect

[her] eye [and] hindered [her] ability to drive and would have negatively affected [her] work

performance.” Id. Petitioner stated that in January of 2014, she began taking classes to become a

certified EMS instructor, as her “eye issue had taken away [her] ability to actively respond as a

paramedic[.]” Id. ¶ 12. She continued that during teaching, she noticed that her “eyesight posed a

slight problem[]” because her lack of depth perception “made it difficult to show the students how

to intubate properly[] or insert an IV.” Id.

Petitioner continued that her responsibilities as a member of the ski patrol “changed

drastically.” Id. ¶ 7. She noted as a member of the ski patrol, she used to respond to emergencies

by skiing in difficult terrain and transporting injured skiers in a sled. Id. Petitioner cited an

accident, in which she fell in March of 2014 while “bringing an empty toboggan down the

13

mountain[.]” Id. ¶ 13. She wrote that her lack of depth perception “caused [her] to miss some

crucial changes in the terrain and [she] suffered a labral tear in [her] right hip[]” as a result. Id.

Petitioner indicated that “[a]fter [her] eye injury, [she] was relegated to the ski patrol office . . . a

more administrative position.” Id. ¶ 7. She noted that she still continues to work for the ski patrol,

but that she “often find[s her]self tentative on the mountain due to certain light conditions or

questionable terrain[, as she] cannot distinguish well between shadows and actual moguls or

bumps[.]” Id. ¶ 14. Petitioner wrote this “significantly impacts” her safety. Id.

She also described her then-current eye condition. Id. Petitioner explained that her “eye

has been stable[,] and the ulcer has healed, but the whole ordeal has left considerable scarring on

[her] right cornea . . . [and she] continue[s] to have trouble with depth perception.” Id. As an

example, she wrote that she has problems “parking a car . . . because [she] do[es not] fully trust

[her] spatial vision.” Id. Petitioner noted that she no longer plays tennis “at a high level[]” but

instead “just [] for fun, because sometimes [she] cannot even see the tennis ball . . . .” Id. She

expressed that she “strive[s] to live as normal a life as possible in light of the continued problems

with [her] eye.” Id.

III. Experts

A. Expert Review

1. Petitioner’s Expert, Frederick W. Fraunfelder, M.D., M.B.A.

Dr. Fraunfelder received his medical degree from Oregon Health Sciences University

(“OHSU”) in 1994. Pet’r’s Ex. 20 at 3. He completed two post-graduate residencies at Providence

Medical Center in Portland, Oregon, and Alice Springs Hospital in Australia in 1995 and 1997,

respectively. Id. Dr. Fraunfelder completed a residency in ophthalmology at the University of

Washington Medical Center in Seattle, Washington in 2000. Id. He also completed a fellowship in

Cornea/External Disease and Refractive Surgery at the Casey Eye Institute at OHSU in 2002. Id.

The same year, he became board-certified in ophthalmology. Id. at 1. He has served as the

Chairman and Distinguished Professor of the Cornea/External Disease, Ocular Oncology and

Refractive Surgery of the Mason Eye Institute at the University of Missouri since 2014. Id. He

also serves as the Clinic Medical Director in the Department of Ophthalmology at the same

institution. Id. Prior to that, Dr. Fraunfelder was the Director/Chief of the Cornea/External

Disease/Refractive Surgery Division at the Casey Eye Institute from 2008–2014. Id. He became a

Professor of Ophthalmology in the same specialty at OHSU in 2011 until 2014. Id. Dr.

Fraunfelder’s curriculum vitae includes over one-hundred and fifty published articles, book

chapters, and abstracts of which he is a listed author. See id. at 5–17.

During the hearing, Dr. Fraunfelder explained that his clinical practice involves “see[ing]

patients . . . and [he is] a cornea external disease eye specialist[, s]o [he] only see[s] people that

have diseases on the front of the eye and the front half of the eye.” Tr. 12:14–19. Dr. Fraunfelder

stated that he treats patients with uveitis “almost daily[,]” as “[u]veitis is a common condition that

occurs in the front of the eye[.]” Tr. 12:20–24. He estimated that he has seen “hundreds” of patients

with herpes keratitis. Tr. 13:16–23. He made the same estimation in relation to the number of his

patients with uveitis as well. Tr. 13:23–25.

14

Dr. Fraunfelder submitted three expert reports and testified during the hearing. See Pet’r’s

Exs. 19, 32, 33; Tr. 8:20–63:5. Petitioner offered Dr. Fraunfelder as an expert in ophthalmology

without objection, and I recognized him as such. Tr. 14:1–6.

2. Respondent’s Expert, Hamid Bassiri, M.D.

Dr. Bassiri received his medical degree from the University of Pennsylvania in 2004.

Resp’t’s Ex. B at 1. He received his Ph.D. in immunology from the same institution in 2002. Id.

Dr. Bassiri completed a residency in general pediatrics at the Children’s Hospital of Philadelphia

in 2007. Id. He also completed a fellowship in pediatric infectious diseases at the same institution

in 2010. Id. Dr. Bassiri has been an attending physician in the Division of Infectious Disease,

Department of Pediatrics at the Children’s Hospital of Philadelphia since 2011. Id. He has served

as an Assistant Professor of Pediatrics at the Perelman School of Medicine at the University of

Pennsylvania since 2013. Id. He is board-certified in general pediatrics and pediatric infectious

diseases. Id. Dr. Bassiri has received numerous awards and honors, and he holds memberships in

several professional and scientific societies. Id. His curriculum vitae lists over thirty publications,

including articles, book chapters, and editorials of which he is a listed author. See id. at 3–5.

During the hearing, Dr. Bassiri explained that as part of his clinical practice as an attending

in pediatric infectious disease, he “see[s] general infections in presumably immune competent

hosts, [but] what [he] specialize[s] more highly in are hosts who have compromise to their

immunity.” Tr. 64:14–20. He elaborated that he “see[s] many patients with cancer, many patients

who are immune modulators because they have . . . unknown autoimmune diseases and/or have

what we call primary immune deficiencies[.]” Tr. 64:21–25. Dr. Bassiri described his training in

immunology and stated that his “initial training was in T cell development and T cell functions.

And subsequent to that, [he] maintain[s] a lab that examines T cells and non-T cell populations for

use in cancer immunotherapy.” Tr. 65:10–14. He noted that he treats children with dysregulated

immunity as part of his work on a multidisciplinary committee. Tr. 65:17–21. He testified that in

addition to his other responsibilities as the Associate Program Director for the Pediatric Infectious

Disease fellowship, he “see[s] patients roughly about [twenty-five] percent of the time . . . [and]

regularly give[s] lectures . . . regarding different concepts of infectious diseases as well as concepts

in immunology[.]” Tr. 66:5–6, 12–14.

Dr. Bassiri submitted three expert reports and testified at the hearing. See Resp’t’s Exs. A,

M, N; Tr. 64:6–135:5. Respondent offered Dr. Bassiri as an expert in immunology and infectious

disease without objection, and I recognized him as such. Tr. 66:17–21.

B. Expert Reports and Testimony

1. Petitioner’s Expert, Dr. Fraunfelder

Dr. Fraunfelder submitted three expert reports and testified during the hearing. Pet’r’s Exs.

19, 32, 33; Tr. 8–63. Throughout his written and oral testimony, he relied on his specialization in

ophthalmology “to point out that [he is] uniquely qualified to form an opinion in this case.” Pet’r’s

Ex. 32 at 1; Tr. 9–14. In his first expert report, Dr. Fraunfelder wrote that “[t]he event speaks for

itself[,]” and Petitioner’s “flu vaccine administered on November 3, 2012, more likely than not

15

substantially contributed [to] or caused her eye condition[.]” Pet’r’s Ex. 19 at 2. Dr. Fraunfelder

described this as a “domino effect” that began with Petitioner’s flu vaccine. Id. He opined that “it

is reasonable to assume that the flu vaccine led to uveitis. The uveitis led to the [herpes] zoster

(shingles) keratitis. The zoster keratitis led [to] neurotrophic keratitis. The neurotrophic keratitis

led to a permanent corneal scar and the need for a corneal transplant.” Id. Dr. Fraunfelder explained

that this occurred because the flu vaccine caused a Type IV hypersensitivity reaction, which

weakened Petitioner’s immune status, and allowed an opportunistic infection like herpes to occur.

Tr. 43:21–25. He wrote that “but[-]for the November 3, 2012 flu vaccine and subsequent

development of uveitis, [Petitioner] would not have suffered from herpes keratitis.” Pet’r’s Ex. 19

at 2.

First, Dr. Fraunfelder addressed Petitioner’s condition and opined that “shingles occurred

in her eye.” Id. He noted that “[i]t [wa]s most likely unrecognized by her initial doctors treating

her eye condition[]” on November 12, 2012. Id. Dr. Fraunfelder opined that “[i]t was probably

never a peripheral ulcerative keratitis or a bacterial conjunctivitis. It was a uveitis, caused by the

vaccine.” Id. Dr. Fraunfelder stated that he based his opinion on Petitioner’s symptom presentation

recorded in the notes from her November 12, 2012 appointment. Tr. 15:3–25. Petitioner “had a

fever on Tuesday [November 6, 2012] through Wednesday [November 7, 2012,] which was gone

by Friday [November 9, 2012]. She had a stye on Saturday [November 10, 2012,] which was worse

on Friday [November 9, 2012]. And she had a mild cold . . . pain below her eye[,]” blurred vision,

and discharge in the right eye. Tr. 15:13–18 (citing Pet’r’s Ex. 2 at 1). Dr. Fraunfelder opined that

the redness and pain reported during Petitioner’s November 12, 2012 examination were symptoms

of uveitis. Tr. 19:10–17. He later stated that Petitioner “could have been[]” experiencing symptoms

of uveitis during this visit. Tr. 40:11–15. Dr. Fraunfelder indicated that Dr. Alvarez did not perform

tests to confirm the diagnosis of uveitis during Petitioner’s November 12, 2012 visit. Tr. 19:24–

25.

Dr. Fraunfelder stated that “by pure luck,” Dr. Alvarez prescribed treatment, including a

low-potency steroid, that “would undertreat [uveitis] but would treat it.” Tr. 20:15–18. He opined

that “undertreating it with the Tobradex probably would have led to a slight improvement but not

an all-the-way improvement[,] which is exactly what happened in this instance.” Tr. 20:24–25,

21:1–2 (citing Pet’r’s Ex. 2 at 2 indicating a 30% improvement on November 13, 2012). He stated

that Petitioner’s slight improvement following treatment with Tobradex (which undertreats

uveitis) is more consistent with Petitioner having uveitis than herpes keratitis during her November

12, 2012 visit. Tr. 21:9–20. He opined that if Petitioner had the latter, her herpes keratitis would

have gotten worse with steroids. See id.

He then focused on the visit notes from Petitioner’s January 7, 2013 appointment with Dr.

Foote to opine that Petitioner had uveitis and was developing herpes keratitis at that time. Tr. 16:9–

24, 39:5–8; see also Pet’r’s Ex. 19 at 1. As support, Dr. Fraunfelder stated that Dr. Foote “found

some – some things on the exam that were new to what Dr. Alvarez had noted in her exams.” Tr.

16:20–22. Dr. Fraunfelder noted that “[o]f significance[,]” Dr. Foote found “cells [] floating in the

front of the eye [] that hadn’t been noted before.” Tr. 16:22, 17:1–2. Dr. Fraunfelder indicated that

Dr. Foote also noted “keratic precipitates[]” on the back of Petitioner’s cornea, which “are markers

of inflammation in the eye[,]” also not previously noted. Tr. 17:7–9. He wrote that “[k]eratic

precipitates are deposits of inflammatory cells on the back of the cornea and are a sign of uveitis.”

16

Pet’r’s Ex. 19 at 1. Dr. Fraunfelder defined uveitis as “inflammation of any part of the uvea.” Tr.

17:23–24. He opined “[i]t is possible and even probable that [Petitioner] may have had uveitis well

before these findings[]” even though they were not documented in her medical records. Pet’r’s Ex.

19 at 1.

Next, Dr. Fraunfelder explained that the “[f]lu vaccine is not a vaccine with a live virus of

herpes zoster, the virus that causes shingles. However, the flu vaccine can be a trigger to cause an

immunologic reaction[.]” Id. at 2. He continued that “[w]hen a person develops an eye disease . .

. they are susceptible to opportunistic infections from viruses that are dormant within [the body].”

Id. Based on this, Dr. Fraunfelder opined that Petitioner’s “flu vaccine let [sic] to an altered

immune status and shingles occurred in her eye.” Id. He maintained that “the sequence of events

that took place was that the flu vaccine caused uveitis. This resulted in an altered immune status

whereby the zoster virus was able to arise[,] and this led to further damage.” Pet’r’s Ex. 33 at 2.

He wrote that “[z]oster is an opportunistic infection, and it is highly likely it was activated in the

setting of the altered immune state brought about by the uveitis.” Id. By opportunistic, he explained

that herpes zoster “takes the opportunity to cause an infection somewhere when you’re weak.” Tr.

42:21–23. Dr. Fraunfelder stated that Petitioner “had no history of herpes zoster, making it

exceedingly unlikely that the convergence of her flu vaccine, uveitis[,] and zoster was due to

coincidence alone.” Pet’r’s Ex. 33 at 2.

Dr. Fraunfelder commented on Petitioner’s treating physicians’ opinions that her eye

condition was caused or triggered by her flu vaccine. Tr. 41:12–16. He noted that Dr. Ostern did

not feel that Petitioner had PUK, but rather a herpes keratitis. Tr. 48:4–17. He testified that these

opinions are “significant” to him. Tr. 41:15–17. He stated he would have made the same

connection if he were her treater. Tr. 41:16–17. However, Dr. Fraunfelder admitted that throughout

the course of his career, he has not seen a patient whereby a vaccination caused uveitis, which

allowed the herpes keratitis to manifest, as “that’s a rare thing.” Tr. 42:24–25, 43:1–7. Dr.

Fraunfelder then noted that, “if a rare condition occurs to a patient, it is not rare for them.” Pet’r’s

Ex. 32 at 2. He admitted he has, however, seen an infection cause uveitis and then herpes keratitis.

Tr. 43:8–10.

He addressed the connection between the flu vaccine and uveitis. Dr. Fraunfelder stated

that “there’s a general consensus” in the medical community that “vaccine-induced uveitis

occurs[.]” Tr. 31:25–25, 32:1. Dr. Fraunfelder relied on an article by Benage, 35 of which he is also

listed author, to explain that “all vaccines, albeit rarely[,]” can cause an immunologic reaction,

manifesting as uveitis. Pet’r’s Ex. 19 at 2; Pet’r’s Ex. 19, Tab A at 1, ECF No. 81-1 (noting that

“[a]ll of the widely administered vaccines have been reported to cause uveitis.”). The authors noted

that “[d]uring a 26-year period, a total of 289 cases of vaccine-associated uveitis were reported to

three adverse reaction reporting databases. Hepatitis B [(“Hep. B”)] vaccine . . . appears to be the

leading offender.” Pet’r’s Ex. 19, Tab A at 1. Dr. Fraunfelder stated that “the flu vaccine . . . was

the third most common cause for uveitis based on this [] case series.” Tr. 26:19–21. Dr. Fraunfelder

relied on an article by London et al., 36 which used the Naranjo criteria 37 in place of a clinical trial,

35

M. Benage & F.W. Fraunfelder, Vaccine-Associated Uveitis, 113:1 MISSOURI MED. 48–52 (2016).

36

N. London, et al., Drug-induced uveitis, 3 J. OPHTHALMIC INFLAMMATION & INFECTION 43–61 (2013).

37

The Naranjo criteria, or the Adverse Drug Reaction (“ADR”) Probability Scale, was “developed to help

standardize assessment of causality for all adverse drug reactions[.]” It consists of 10 questions that are

17

to show that “the influenza vaccination was ‘probable’ in causation in relation to uveitis.” Tr.

31:13–18 (citing Pet’r’s Ex. 45 at 13, ECF No. 79-2). The authors identified a score of 7 to ascribe

“probable” causation to the flu vaccine and uveitis. Pet’r’s Ex. 45 at 13. Dr. Fraunfelder indicated

that the Naranjo criteria “take[] into account a temporal relationship between taking the drug . . .

positive rechallenge, positive dechallenge . . . take[] into account is there a plausible biological

mechanism, . . . [and] are there other drugs or diseases that could have occurred.” Tr. 30:22–25,

31:1–3.

Dr. Fraunfelder relied on an article by Suhler et al., 38 of which he is also listed author, to

describe the mechanism by which this occurs, a Type IV hypersensitivity reaction. Pet’r’s Ex. 19

at 2; Pet’r’s Ex. 19, Tab D at 4, ECF No. 81-4; see also Tr. 33:20–25, 34:1–3, 35:3–17. He argued

that “vaccines are known to cause [T]ype IV hypersensitivity responses systemically.” Pet’r’s Ex.

19 at 2. Dr. Fraunfelder wrote that “all vaccinations, including [the] influenza vaccination, can

cause a Type IV hypersensitivity reaction.” Pet’r’s Ex. 33 at 1 (citing Pet’r’s Ex. 33, Tab A, ECF

No. 82-1). 39 He explained that a Type IV hypersensitivity reaction alters the immune status of an

individual and makes the patient “immunosuppressed.” Tr. 43:21–25.

However, Dr. Fraunfelder acknowledged that “[t]he mechanisms underlying [T]ype IV

hypersensitivity reactions are complex and not completely understood.” Pet’r’s Ex. 33 at 1. He

relied on an article by Nussenblatt, 40 to explain that “Type IV hypersensitivity mechanisms (i.e.,

T-cell mediated) are of primary importance in the development if [sic] uveitis.” Id.; Pet’r’s Ex. 33,

Tab C, ECF No. 82-3. Dr. Fraunfelder stated that the authors in this study “wanted to know [if] it

is feasible that a systemically applied medicine like a vaccine given in your shoulder . . . could

cause an inflammation inside the eye[.]” Tr. 37:17–20 (citing Pet’r’s Ex. 33, Tab C). The authors

examined “bovine models, rat models[,]” in which “they injected rats [] with retinal S-antigen

systemically not in the eye but in the body.” Tr. 37:21–24. The authors found that “this elicited a

reaction in the eye which led to uveitis and blindness.” Tr. 37:24–25. Nussenblatt explained that

this occurs because “immune cells may ‘home’ to a target organ, [which] is in part due to the

expression of HLA antigens on non-immune tissues in the eye.” Pet’r’s Ex. 33, Tab C at 2. This

observation implicated the importance of T-cell mediation of diseases such as uveitis. Id.

Nussenblatt based his conclusion, in part, on the efficacy of treatment of uveitis with anti-T-cell

answered as either Yes, No, or “unknown.” “Different point values (-1, 0, +1, or +2) are assigned to each

answer.” The questions include “are there previous conclusive reports of this reaction? Did the adverse

event appear after the drug was given? Did the adverse reaction improve when the drug was discontinued,

or a specific antagonist was given? Did the adverse reaction reappear upon readministering the drug? Were

there other possible causes for the reaction? Did the adverse reaction reappear upon administration of

placebo? Was the drug detected in the blood or other fluids in toxic concentrations? Was the reaction

worsened upon increasing the dose? Or, was the reaction lessened upon decreasing the dose? Did the patient

have a similar reaction to the drug or a related agent in the past? Was the adverse event confirmed by any

other objective evidence?” Total scores range from -4 to +13; the reaction is considered definite if the score

is 9 or higher, probable if 5 to 8, possible if 1 to 4, and doubtful if 0 or less. Adverse Drug Reaction

Probability Scale (Naranjo) in Drug Induced Liver Injury, NAT’L CENTER FOR BIOTECHNOLOGY INFO.,

https://www.ncbi.nlm.nih.gov (last visited Dec. 17, 2021).

38

F.W. Fraunfelder, E.B. Suhler, et al., Hepatitis B vaccine and uveitis: an emerging hypothesis suggested

by review of 32 case reports, 29:1 CUTANEOUS & OCULAR TOXICOL. 26–29 (2010).

39

E. Chung, Vaccine Allergies, 3 CLIN. EXP. VACCINE RES. 50–57 (2014).

40

R.B. Nussenblatt, Basic and Clinical Immunology in Uveitis, 31 J. OPHTHALMOL. 368–74 (1987).

18

drugs such as cyclosporine. Id. Dr. Fraunfelder opined that this study supports the fact that a Type

IV hypersensitivity reaction occurs in the development of vaccine-caused uveitis. Tr. 37:14–16.

He argued this “proves the theory in an animal model that a systemically applied immunization

can cause a localized eye inflammation like uveitis.” Tr. 38:1–3.

As further support, Dr. Fraunfelder relied on an article by Meng et al., 41 to discuss the

“critical” role of dendritic cells and T lymphocytes in Type IV hypersensitivity reactions. Pet’r’s

Ex. 33 at 1; Pet’r’s Ex. 33, Tab B, ECF No. 82-2. The authors wrote that “[dendritic cells] take up

and process complex antigens into short peptides which can be represented as peptide – HLA

complexes on the surface of [dendritic cells] for T-cell recognition.” Pet’r’s Ex. 33, Tab B at 5.

They continued that “[t]he interaction of T-cell receptors with peptide – HLA complexes determine

the specificity of the response.” Id. The authors went on to explain that “[d]rug-specific T cells

have been detected in peripheral blood from hypersensitive patients . . . [e]ach T-cell subset can

promote different types of inflammatory responses but also be able to counter-regulate each other.”

Id. Dr. Fraunfelder relied on the principles put forth in the Meng et al. article to argue that there is

“an association between certain drug hypersensitivity reactions and specific HLA alleles, which

could explain why the target organ for [Petitioner] was the eye.” Pet’r’s Ex. 33 at 1.

Dr. Fraunfelder relied on an article by Hassman et al. 42 to show that the flu vaccine can

cause severe inflammation in the central nervous system, which can lead to infection with HSV

and herpes encephalitis. Tr. 45:4–21 (citing Pet’r’s Ex. 44 at 1, ECF No. 79-1). The authors noted

that the flu vaccine triggered the reactivation of a latent HSV infection in 13 out of 38 million

doses over ten years. Pet’r’s Ex. 44 at 5. Dr. Fraunfelder testified that this occurs if the recipient

experiences a “positive rechallenge” to prior flu vaccines. See Pet’r’s Ex. 44 at 5; Tr. 45:4–21. He

explained that “any time there is a rechallenge of a drug, like a vaccine being administered a second

time and then that person gets a reaction again like they did the first time, that’s called a positive

rechallenge.” Tr. 25:15–19. He continued that “if they get a positive rechallenge and they take [the

drug] a second time and another positive rechallenge and they take it a third time, that’s really

strong evidence for a causal relationship with a drug and a side effect.” Tr. 25:23–25, 26:1–2. Dr.

Fraunfelder reiterated that a “positive rechallenge is relevant to an assessment of causation for a

particular vaccine[.]” Tr. 25:12–14. He noted that the authors of the Hassman et al. study found

that the patient developed retinitis each time that he received a vaccine. Tr. 45:16–17 (citing Pet’r’s

Ex. 44 at 1). Dr. Fraunfelder equated this to Petitioner’s case and explained that this occurred

because “the brain is considered a neurologic tissue in the area of the retina because the retina is

contiguous with the nerves of the optic nerve and then the rest of the brain.” Tr. 45:13–16. He

therefore opined that this article provided “really strong evidence for the flu vaccine causing

[central nervous system] side effects including retinitis[,] which is a type of inflammation like

uveitis[,]” in Petitioner’s case. Tr. 45:19–21. As further support, Dr. Fraunfelder noted that the

Suhler et al. 43 study found one patient had “recurrent uveitis after both [the] second and third doses

of [the Hep. B] vaccine.” Tr. 25:10–11 (citing Pet’r’s Ex. 19, Tab D). He also relied on an article

41

X. Meng, et al., Immunological Mechanisms of Drug Hypersensitivity, 22:45 CURR. PHARM. DES. 6734–

47 (2016).

42

L.M. Hassman, et al., Immunologic factors may play a role in herpes simplex virus 1 reactivation in the

brain and retina after influenza vaccination, 6 ID CASES 47–51 (2016).

43

See Fraunfelder & Suhler, et al., supra note 38.

19

by Blanche et al., 44 which discussed a 68-year-old woman who developed uveitis two days after

her first flu vaccine. Tr. 27:23–25, 28:1–10 (citing Pet’r’s Ex. 19, Tab B at 1, ECF No. 81-2).

During his testimony, Dr. Fraunfelder cited an article by Knopf et al., 45 as support for the notion

of rechallenge based on its title, “Recurrent Uveitis After Influenza Vaccination.” Tr. 28:16–17.

He stated that the author “brings up the idea of ‘immune priming’ which is the idea that some event

can make somebody susceptible to eye inflammation such as a trauma or a surgery or a

vaccination.” Tr. 28:19–25, 29:1. Under my questioning, Dr. Fraunfelder admitted that he did not

know if Petitioner had ever received a flu vaccine prior to the one at issue. Tr. 55:17–25.

Regarding timing, Dr. Fraunfelder opined that “Type IV reactions usually occur days after

a reaction.” Tr. 41:4–5. He again relied on the Suhler et al. 46 article, which shows that uveitis

caused by a Type IV hypersensitivity reaction “has occurred at time intervals of up to fifteen days

post vaccination.” Pet’r’s Ex. 33 at 1; Pet’r’s Ex. 33, Tab D. He stated that the authors found that

“the mean number of days until uveitis was reported after a vaccination was three days. And the

range was 1–15 days.” Tr. 24:17–19. Dr. Fraunfelder opined that “[t]his [range] suggests that more

than one mechanism is likely responsible.” Pet’r’s Ex. 33 at 1. He relied on an article by Wildner

et al., 47 to argue that “[s]everal peptides have been shown to induce uveitis via [molecular

mimicry].” Id.; Pet’r’s Ex. 33, Tab F, ECF No. 82-5. However, during his testimony, he abandoned

his theory as it relates to molecular mimicry and instead proceeded on Type IV hypersensitivity

only, “pick[ing one] pony[.]” See Tr. 33:22–25, 34:21.

He then addressed the time of onset in Petitioner’s case. Dr. Fraunfelder opined that “[i]t

is not insignificant that [Petitioner] had no [pre-existing] ocular complaints until nine days after

her flu vaccination.” Pet’r’s Ex. 32 at 1 (citing Pet’r’s Ex. 2 at 1). Dr. Fraunfelder testified that

Petitioner’s “uveitis probably began within a few days of the flu vaccine[]” at the time she

developed a fever. Tr. 53:15–17. He stated that “[p]robably at the time that [Petitioner] presented

with pain and redness and had partially systemic reaction with the fever and the cold [on November

12, 2012], that she probably had uveitis then[.]” Tr. 18:11–14. However, Dr. Fraunfelder opined

that “it was unrecognized by her optometrist[.]” Tr. 18:14–15.

Dr. Fraunfelder explained that Petitioner “had symptoms that fits [sic] within the plausible

biological mechanism of the type for hypersensitivity reaction, that she had symptoms within three

days . . . and then, . . . many weeks later[,] that are consistent with uveitis related to the vaccine.”

Tr. 49:7–14. Dr. Fraunfelder relied on Petitioner’s fever, redness, pain, and blurred vision

beginning three days post vaccination to opine that a Type IV hypersensitivity reaction occurred.

Tr. 38:18–22, 60:3–8. He posited that “in general, if it’s a Type IV reaction, we should expect it

within one day to three days, usually.” Tr. 49:25, 50:1–2. He stated that Petitioner “was having a

[Type IV hypersensitivity] reaction probably at day three[]” when she experienced a fever, which

he opined, was consistent with the filed medical literature. Tr. 41:6 (citing Pet’r’s Ex. 33, Tab D).

44

P. Blanche, et al., Development of Uveitis Following Vaccination for Influenza, 19:5 CLIN. INFECT. DIS.

979 (1994).

45

Petitioner did not file the full article for consideration, it was merely cited in another exhibit. See Tr.

28:11–22; see also Pet’r’s Ex. 19, Tab B.

46

See Fraunfelder & Suhler, et al., supra note 38.

47

G. Wildner, et al., Autoimmune Uveitis Induced by Molecular Mimicry of Peptides from Rotavirus, Bovine

Casein & Retinal S-Antigen, 33 EUR. J. IMMUNOL. 2577–87 (2003).

20

Next, Dr. Fraunfelder responded to Dr. Bassiri’s assertion that alternative causes could

have been responsible for her injuries. He wrote that “Dr. Bassiri postulates on several anecdotes

about what could have happened[,]” but Dr. Fraunfelder noted that he did not agree with Dr.

Bassiri’s proposals. Pet’r’s Ex. 32 at 2. Dr. Fraunfelder agreed that Petitioner is “uniquely

susceptible to herpes keratitis because . . . a person with [the] HLA-B27 haplotype do [sic] express

herpes more than other people after having received an insult such as trauma or surgery, and, in

this case, a vaccine.” Tr. 39:8–13. He therefore opined that Petitioner was “immune primed” to

develop herpes keratitis because of the uveitis and her positive HLA-B27 haplotype. Tr. 39:10–

14. Dr. Fraunfelder wrote, however, that Dr. Bassiri “fail[ed] to consider [] that HLA-B27 status

confers susceptibility and is not a determinant of disease[, a]s . . . many individuals who are HLA-

B27 positive never go on to develop uveitis.” Pet’r’s Ex. 32 at 1. He stated that HLA-B27 is a

“valid reason for uveitis, but in [Petitioner’s] case it’s more likely than not [sic] HLA-B27 as the

primary cause for her uveitis.” Tr. 47:11–13. Dr. Fraunfelder did not focus on whether HSV caused

Petitioner’s uveitis, as he postulated that her flu vaccine caused her uveitis and herpes keratitis.

See, e.g., Pet’r’s Ex. 32 at 1. He did, however, state that a flu vaccine could be a trigger to reactivate

a latent HSV infection. Tr. 44:8–10.

He then proposed a different alternative cause for Petitioner’s uveitis and an explanation

for her cold-like symptoms present on November 12, 2012. Tr. 45:22–25, 46:1–3. He stated “[i]t’s

possible . . . there’s a syndrome that’s well described from [the] flu vaccine called oculorespiratory

syndrome.” Tr. 46:1–3. Dr. Fraunfelder defined this condition as “a constellation of upper

respiratory infectious signs. It’s not infectious though. You might have a cough or a wheeze, stuffy

nose. And then you also get uveitis.” Tr. 46:6–9. He asserted that Petitioner’s fever, cough, and

cold symptoms reported during her November 12, 2012 appointment, could have been symptoms

of oculorespiratory syndrome. Tr. 46:14–17.

On cross-examination, Dr. Fraunfelder conceded that he is not an expert in immunology or

infectious diseases. Tr. 51:15–17, 52:5–7. Dr. Fraunfelder admitted that the Suhler et al. 48 article

talks about the Hepatitis B vaccine, not the flu vaccine. Tr. 53:23–25. He agreed that the article

noted ‘“there is a debate that uveitis occurs because of the [H]epatitis B infection.’” Tr. 54:15–17

(citing Pet’r’s Ex. 19, Tab D). He also conceded that that particular article discussed a Type III

hypersensitivity reaction, not a Type IV as initially postulated, which is the type of reaction that

he maintained occurred in Petitioner’s case. Tr. 54:1–3. When asked about the Benage 49 article,

Dr. Fraunfelder maintained that the authors found an association between vaccines and the

occurrence of uveitis and would not agree that the number of cases identified was small, noting

“[t]hat’s relative.” Tr. 52:12–20. Dr. Fraunfelder agreed that Petitioner developed a herpes

infection, and that they are usually either a primary infection or reactivation. Tr. 55:1–7. However,

Dr. Fraunfelder was “not certain” whether Petitioner suffered a primary infection or reactivation

of the herpes virus. Tr. 55:8–11.

Under my questioning, leaving the type of hypersensitivity reaction aside, I asked Dr.

Fraunfelder to tell me what evidence he relied on to show that Petitioner experienced a

hypersensitivity reaction, in general. Tr. 59–61. He first answered that he relied on her redness,

pain, and loss of vision to indicate a Type IV hypersensitivity reaction occurred, but he later could

48

See Fraunfelder & Suhler, et al., supra note 38.

49

See Benage & Fraunfelder, supra note 35 at 1.

21

not point to specific evidence of a hypersensitivity reaction, generally. See id. In response, he

stated he “just do[esn’t] think that way,” and instead arrived at the conclusion that Petitioner

experienced a Type IV hypersensitivity reaction because of her delayed temporal response and

“the number of days to onset[]” between her vaccination and onset of symptoms. Tr. 61:19–25,

62:1–15.

2. Respondent’s Expert, Dr. Bassiri

Dr. Bassiri submitted three expert reports and testified during the hearing. Resp’t’s Exs. A,

M, N; Tr. 64–135. He relied on his expertise in immunology and specialized knowledge in what

makes patients predisposed to specific types of infections. Tr. 65–66. In his first expert report, Dr.

Bassiri opined that there is no evidence of a causal relationship between the flu vaccine and

Petitioner’s condition. Resp’t’s Ex. A at 2. He wrote that Petitioner’s flu vaccine “is exceedingly

unlikely to have been the cause of the ensuing uveitis.” Id. at 5.

First, Dr. Bassiri questioned Dr. Fraunfelder’s reliance on the Benage 50 article to show a

causal relationship between the flu vaccine and uveitis. Id. at 2. Dr. Bassiri explained that this

article “revealed 28 cases of such an association” between vaccines and uveitis, “over a 30-year

period (1984–2014)[.]” Id.; Resp’t’s Ex. C at 1, ECF No. 27-3. Dr. Bassiri stressed the significance

of this statistical finding and argued that Dr. Fraunfelder has been unable to establish a causal link

between the flu vaccine and uveitis, noting an association only. Resp’t’s Ex. M at 1, 2. Dr. Bassiri

agreed that “there is entirely the possibility that things are associated,” but stated that “if vaccines

caused uveitis, [he] would [] expect to see a lot more cases[.]” Tr. 68:10–11, 22–24. He expressed

that “we would probably see this more commonly than what Dr. Fraunfelder reported to us as 28

cases in 30 years.” Tr. 69:12–14.

In response to the Benage article, Dr. Bassiri cited an article by Grajewski et al., 51 in which

the authors’ findings ‘“argue against a substantial influence of allergies and atopy 52 on the onset

of uveitis.’” Resp’t’s Ex. N at 1 (citing Resp’t’s Ex. O, ECF No. 52-2). The authors of the study

examined patients with uveitis and some who were controls who did not have uveitis, to see if

those with the condition had a significant disproportionately higher level of atopy or allergy to

drugs. Resp’t’s Ex. O at 1. Dr. Bassiri explained that the authors found “there wasn’t a []

statistically significant higher proportionate of atopy or allergy in the patients who [] develop

uveitis.” Tr. 78:12–15. Dr. Bassiri testified that the authors thought “that the presence of atopy or

allergy was probably only minimally contributing to the development of uveitis.” Tr. 78:16–18.

He wrote that “associations are frequently misinterpreted as evidence of causal

connections.” Resp’t’s Ex. A at 2 (emphasis in original). He emphasized that “association is strictly

50

See id.

51

R.S. Grajewski, et al., Analysis of the impact of allergy and atopy on new onset of uveitis, 95:3 ACTA

OPHTHALMOL. 236–41 (2017).

52

Atopy “refers to the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma, and

atopic dermatitis (eczema). Atopy is typically associated with heightened immune responses to common

allergens, especially inhaled allergens and food allergens.” AM. ACAD. OF ALLERGY, ASTHMA &

IMMUNOLOGY, https://www.aaaai.org/Tools-for-the-Public/Allergy,-Asthma-Immunology-

Glossary/Atopy-Defined (last visited Dec. 16, 2021).

22

that [] two events may have some type of temporal connection that lends one to believe that there

may be an association between one event leading to the other.” Tr. 67:9–12. He continued:

[b]ut in reality[,] whenever one pairs a frequent event (in this case influenza

vaccination) with an infrequent one (e.g., uveitis), in the absence of a clear and

proven pathophysiologic and biological causal connection, the chances of the two

events being causally related may be nil, and the existence of a causal relation must

be interpreted with extreme caution. As an analogy, if earthquakes (“rare events”)

were to happen on cloudy days (“frequent events”), then one could claim the

existence of an association between cloudy days and earthquakes. While this

association would be true, the two events would not be causally connected.

Resp’t’s Ex. A at 2 (emphasis in original). He differentiated association from causation and noted

that causation “is one in which there is a mechanistic description that fits one event directly leading

to another and can be repeatedly elicited and more tested experimentally.” Tr. 67:13–16.

On cross-examination, Dr. Bassiri admitted that hypersensitivity reactions, including Type

IV, are “postulated” mechanisms in the literature of how uveitis can occur. Tr. 114:21–25, 115:1–

3. However, Dr. Bassiri opined that Dr. Fraunfelder’s proposed biological mechanism of causation,

a Type IV hypersensitivity reaction, did not occur in Petitioner’s case because neither the timing

of onset nor the symptoms of her condition match what is understood about the mechanism.

Resp’t’s Ex. A at 2–3; see also Tr. 94:19–20. Dr. Bassiri broke down the four types of

hypersensitivity reactions. Tr. 69–70. He explained that the classification of the reaction depends

on the onset time of the reaction, type of cellular involvement, and reactions to drugs or treatment

meant to “block” the reaction. Tr. 70–71, 100:1–20. He noted that Type I hypersensitivity reactions

“can be measured in seconds to minutes” and commonly occur in food allergies, which can be

“deadly in the right setting.” Tr. 70:1–7. Dr. Bassiri compared this to Type IV hypersensitivity

reactions, in which “T cells . . . have seen an antigen, have seen that foreign particle previously

presented to them in the context of another protein on the surface of cells . . . [a]nd then once they

get re[-]exposed, they mount a reaction.” Tr. 70:25, 71:1–6. Dr. Bassiri described a Type IV

reaction as one which produces “a local inflammatory response[]” which “eventually dissipates[.]”

Tr. 71:16, 72:18–19. He explained that the response dissipates because the antigens are eventually

“metabolized, broken down, and they go away.” Tr. 72:19–23. This is the type of reaction Dr.

Bassiri would expect to see from a Type IV hypersensitivity reaction. Tr. 72:14–19. He stated that

this response occurs “within about 24 hours . . . till about 48 hours[.]” Tr. 71:19–20. Dr. Bassiri

testified that “[i]t’s rarer that you have the delay result in occurrence of symptomatology much,

much later like two to three weeks later.” Tr. 73:14–16. To support his assertion, Dr. Bassiri relied

on the article by Chung, 53 to show that “Type IV hypersensitivity reactions typically begin to

manifest within 24–48 hours after antigen encounter (or immunization) and peak at 72–96 hours.”

Resp’t’s Ex. A at 3; Resp’t’s Ex. D at 2, ECF No. 27-4.

Dr. Bassiri noted that Type IV hypersensitivity reactions “are generally considered to be

harmless.” Resp’t’s Ex. N at 1 (citing Resp’t’s Ex. D at 2). He provided two common examples of

53

See Chung, supra note 39.

23

Type IV hypersensitivity reactions, including poison ivy and a PPD test 54 for tuberculosis, which

is read within 48 hours. Tr. 71–72. Dr. Bassiri placed “emphasis on the delayed being in contrast

to the immediate seconds to minutes reaction that we expect with [Type I hypersensitivity]

reactions.” Tr. 72:9–12. Dr. Bassiri stated that there “should not [be] ongoing symptomatology [in

a Type IV reaction] unless there’s an alternative explanation.” Tr. 75:15–17.

Regarding the onset of symptoms, Dr. Bassiri wrote that “Type IV hypersensitivity

[reactions] would not typically present as a ‘stye’” as it did in Petitioner’s case. Resp’t’s Ex. A at

3. He testified that the tenderness noted along Petitioner’s cheeks or nose during her November

12, 2012 appointment with Dr. Alvarez “would be atypical for a delayed-type hypersensitivity

reaction.” Tr. 74:6–10. Dr. Bassiri also noted that Petitioner reported a fever several days post

vaccination. Resp’t’s Ex. A at 3 (citing Pet’r’s Ex. 16 ¶ 4). He continued that “[T]ype IV

hypersensitivity is rarely associated with fever – especially when the inoculum size of the antigen

(e.g., that in influenza vaccines) is small.” Resp’t’s Ex. M at 2; Tr. 73:1–6. He elaborated that

“[v]ery rarely does [a Type IV reaction] involve systemic signs where somebody gets febrile, feels

ill.” Tr. 73:2–3. Dr. Bassiri opined that “[w]hile fever can occur with severe and systemic Type III

hypersensitivity reactions (such as Serum Sickness), it is otherwise not typical in Type III and

Type IV hypersensitivity responses[.]” Resp’t’s Ex. A at 3; see also Tr. 106:16–22. He agreed that

a fever could occur in a Type IV hypersensitivity reaction “if you were to give somebody who has

a prior sensitization a large amount of that antigen, you would have a relatively large or robust

immune response[,] . . . the end result of which could be fever.” Tr. 107:2–8. Dr. Bassiri testified

that he did not see the level of systemic response in Petitioner that he would expect to see to suggest

that a fever was a part of her hypersensitivity reaction. Tr. 130:11–20. He noted that Petitioner was

not “otherwise manifesting signs and symptoms of a severe hypersensitivity reaction.” Resp’t’s

Ex. A at 3. As an example, Dr. Bassiri testified he would have expected to see signs of liver or

kidney dysfunction if Petitioner actually experienced a Type IV or even Type III hypersensitivity

reaction. Tr. 115:18–25. Dr. Bassiri agreed with Dr. Fraunfelder that it is oftentimes difficult to

classify a particular outcome with a particular type of hypersensitivity reaction. Tr. 98:4–6. But he

maintained that “widespread used tests” could have been used in Petitioner’s case to determine the

type of hypersensitivity reaction, but they were not done. Tr. 98:23–25, 99:1–2.

On cross-examination, Dr. Bassiri addressed the Meng et al. 55 article, which stated

‘“delayed type reactions present with much more complex clinical phenotypes ranging from mild

skin reactions to life-threatening reactions.’” Tr. 101:1–4 (citing Pet’r’s Ex. 33, Tab B). Dr. Bassiri

agreed that “that can occur[]” and that Type IV hypersensitivity reactions are more “heterogenous”

than Type I or II reactions. Tr. 101:5–10. He explained this is possible because there are “a variety

of different mechanisms in play . . . that lead to a variety of different . . . side effects[]” depending

on the individual and the formulation of the drug. Tr. 101:11–21, 102:2–3. He agreed that a positive

54

Dr. Bassiri defined a PPD test as one that “test[s] for exposure to tuberculosis in which a small needle is

used to insert under the skin and antigens or foreign materials that are very similar to the components of

the tuberculosis. And what is measured is the actual response.” Tr. 71:9–13. He explained that “if someone

has seen TB before and they have generated T cells that are responsive against TB, what happens in them

is you get an inflammatory response that can actually be measured . . . within about 24 hours.” Tr. 71:13–

19.

55

See Meng, et al., supra note 41 at 1.

24

HLA status can also provoke a different reaction. Tr. 102:20–23. Dr. Bassiri maintained that a

Type IV hypersensitivity reaction did not occur in Petitioner’s case. Tr. 116–117.

Dr. Bassiri disagreed with Dr. Fraunfelder’s statement that “‘all vaccinations, including

[the] influenza vaccination, can cause a Type IV hypersensitivity reaction.’” Resp’t’s Ex. N at 1

(citing Pet’r’s Ex. 33 at 1). Dr. Bassiri relied on the same Chung 56 article to show that “nowhere

in this article is it stated that all vaccines can cause Type IV hypersensitivity.” Resp’t’s Ex. N at 1

(emphasis in original) (citing Resp’t’s Ex. D at 1). He continued that while the article does indicate

that ‘“[a]lmost all the vaccine components can be considered as potential triggers of an allergic

reaction,”’ this “general statement [] does not suggest that all vaccines cause Type IV

hypersensitivities.” See id.

Under my questioning, I asked Dr. Bassiri whether it was possible for a patient to develop

a Type IV hypersensitivity reaction without exposure to the vaccine, but through exposure to the

wild virus itself. Tr. 133:5–8. He explained that “[o]ftentimes when you’ve been exposed to the

wild-type virus, you develop a robust enough T cell response so that if you are exposed again you

never even become symptomatic.” Tr. 134:8–11. He continued that a patient “might never even

know that you were re-exposed because you have antibodies that bind those viruses and clear them

from your system . . . with what are called memory T cells that are formed that can then much

more rapidly take care of any replicating virus.” Tr. 134:12–17.

Dr. Bassiri was asked about Dr. Fraunfelder’s reliance on the Hassman et al. 57 article. Tr.

79–80 (citing Pet’r’s Ex. 44). He stated that this article is “an example” of “the causal relationship,

especially with the positive – [] positive sort of development in a temporal fashion” of HSV and

herpes encephalitis following a flu vaccine. Tr. 79:3–8. However, Dr. Bassiri highlighted some

distinctions between the article and Petitioner’s case. Tr. 79:9. He noted that the article examined

a patient with a pre-existing “immune defect or immune dysregulation.” Tr. 79:14–15. Dr. Bassiri

stated that there is no evidence that Petitioner suffered from an immune defect. Tr. 79:18–20. He

also pointed out that the patient in the article had “repeated reactions” to the vaccines he received.

Tr. 80:7–9. Dr. Bassiri testified that Petitioner “had at least checked a box” indicating that she had

never had a prior reaction to a flu vaccine. Tr. 79:24–25, 80:1–7 (citing Pet’r’s Ex. 1 at 1). Dr.

Bassiri noted that he did not know how many flu vaccines Petitioner had received in the past, but

he knew she had received at least one based on the contents of the same medical record. Tr. 132:1–

15 (citing Pet’r’s Ex. 1 at 1).

He addressed the London et al. 58 article relied upon by Dr. Fraunfelder. Tr. 80:20–25

(citing Pet’r’s Ex. 45). He noted that the article rated associations between the administration of a

drug, such as the flu vaccine, and adverse reactions, such as uveitis, using the Naranjo scale. Tr.

81:1–8. While the authors came up with an association of “probable” (score of 7) between the flu

vaccine and uveitis in a general sense, Dr. Bassiri used the same scale and applied it to the facts of

Petitioner’s case. Tr. 81:9–11. He stated that “if [he] were to go through and score each one of the

criteria for her specific case, actually the value that would be derived and – and generously giving

56

See Chung, supra note 39.

57

See Hassman, et al., supra note 42 at 1.

58

See London, et al., supra note 36 at 1.

25

points to her case would be a value of 3, 59 which would put it in the ‘possible,’ but not the

‘probable’ range.” Tr. 81:12–17. He opined that the main reason for the discrepancy is that the

authors only analyzed “a general guideline” and did not consider the alternative explanations in

the case of Petitioner. Tr. 81:18–22. Dr. Bassiri stated that “quite frankly, those alternative

explanations are much more commonly accepted as a reason for developing uveitis[.]” Tr. 81:23–

25.

Dr. Bassiri questioned Dr. Fraunfelder’s conclusion that Petitioner had uveitis during her

November 12, 2012 appointment with Dr. Alvarez instead of bacterial conjunctivitis, for which

she was treated. Resp’t’s Ex. M at 1. He also criticized Dr. Fraunfelder’s assertion that Petitioner

“had developed uveitis ‘well before the[ January 7, 2013] findings,’” because he failed to provide

“distinct data or proof of this statement.” Resp’t’s Ex. A at 3 (citing Pet’r’s Ex. 19 at 1). Dr. Bassiri

wrote that “it is [] difficult to conclusively know when the uveitis may have started.” Resp’t’s Ex.

A at 3. Dr. Bassiri “emphasized that the signs and symptoms consistent with uveitis were not

documented in [Petitioner] until [January 7, 2013], over two months after her influenza

immunization.” Id. On cross-examination, Dr. Bassiri testified that the symptoms “consistent” with

uveitis “include things like redness of the eye and pain[.]” Tr. 108:6–13. He admitted that

Petitioner’s record from November 12, 2012, shows she was experiencing redness and pain during

that appointment. Tr. 108:14–16 (citing Pet’r’s Ex. 2 at 1). He further admitted that Petitioner’s

affidavit indicates she experienced those same symptoms “contemporaneous with her fever[,]”

three days post-vaccination. Tr. 108:17–21 (citing Pet’r’s Ex. 16 at 1). Dr. Bassiri stated that

Petitioner’s fever, eye pain, and redness occurred approximately three to four days post

vaccination. Tr. 117:11–14.

He stated that a Type IV hypersensitivity reaction occurs “within about 24 hours . . . till

about 48 hours[.]” Tr. 71:19–20. Dr. Bassiri testified that “[i]t’s rarer that you have the delay result

in occurrence of symptomatology much, much later like two to three weeks later.” Tr. 73:14–16.

Based on this, Dr. Bassiri wrote “it is just as reasonable to postulate that other etiologies led to the

development of uveitis in [Petitioner] after the closing of what would be considered a reasonable

window within which to implicate the involvement of the influenza vaccine.” Resp’t’s Ex. A at 3.

Next, Dr. Bassiri indicated that there are “multiple alternative” causes for the development

of uveitis in Petitioner’s case. Resp’t’s Ex. M at 2. He wrote that while Dr. Fraunfelder “postulated

a causal connection for the [] association between influenza vaccination and development of

59

Dr. Bassiri went through each of the Naranjo criteria as it pertained to Petitioner. He awarded a “plus 1”

in response to the first criteria, as there are previous reports of the occurrence of this reaction. Tr. 82:11–

14. He awarded a “plus 2” in response to the second criteria, as the adverse event happened after

administration of the drug (the flu vaccine). Tr. 82:16–18. He awarded a “no” or “not known” (equivalent

to a value of “zero”) in response to the third criteria regarding whether the adverse reaction improved after

the drug was discontinued, as it was only given once. Tr. 82:19–25. The drug was not re-administered, so

he awarded a “zero” for criteria four. Tr. 83:1–4. Criteria five addressed alternative causes, which he

awarded a “minus 1” since he has posited alternative causes for Petitioner’s condition. Tr. 83:5–9. He

awarded scores of “zero” for criteria six through eight, as Petitioner never received a placebo, the flu

vaccine is not known to be “toxic,” and she never received a higher or lower dosage of the vaccine. Tr.

83:10–25. He awarded a zero in response to the ninth criteria based on Petitioner’s history of no adverse

reactions following prior flu vaccines. Tr. 83:24–25, 84:1–4. He awarded a “plus 1” in response to the tenth

criteria, citing the objective evidence of uveitis noted by Dr. Foote on January 7, 2013. Tr. 84:5–10.

26

uveitis, he has not excluded any other possibilities that are known to be causally-related common

causes of uveitis.” Resp’t’s Ex. A at 3. Dr. Bassiri considered two “[o]ther etiologies that much

more commonly result in the development of uveitis[.]” Id. at 3–4 (emphasis in original). First,

Dr. Bassiri discussed the fact that Petitioner “was noted to carry the HLA-B27 allele[.]” Id. at 4

(citing Pet’r’s Ex. 5 at 15). He wrote that “[c]arriers of the HLA-B27 allele have a significantly

elevated frequency of developing recurrent uveitis.” Resp’t’s Ex. A at 4. He stated that this is

relevant in Petitioner’s case because “HLA-B27 is highly associated with the possibility of

development of a number of autoimmune diseases including uveitis[.]” Tr. 86:3–8. He relied on

an article by Wakefield et al., 60 to show that “HLA-B27-mediated uveitis accounts for 18–32% of

all cases of anterior uveitis[.]” Resp’t’s Ex. A at 4; Resp’t’s Ex. K, ECF No. 27-11. On cross-

examination, he admitted that a majority of people that are HLA-B27 positive “never go on to

develop uveitis.” Tr. 112:3–8. However, he noted that the authors of the Wakefield et al. article

still found that 20% of HLA-B27 positive patients do develop uveitis, which is “still quite

significant.” Tr. 112:14–19 (citing Resp’t’s Ex. K). Dr. Bassiri explained that in order for HLA-

B27 uveitis to manifest, “it depends on [an] environmental factor,” which could include infections

or “vaccination . . . in the right setting.” Tr. 112:9–12, 20–24.

Dr. Bassiri addressed the possible mechanism responsible for Petitioner’s HLA-B27

haplotype causing her uveitis. Tr. 84:20–25, 85:1–3. He explained that “immunologists think that

HLA-B27 may be resulting in predisposition to a variety of autoimmune phenomen[a], including

uveitis.” Tr. 85:1–3. He noted this is possible because of molecular mimicry whereby “the HLA-

B27 can present certain parts of antigens or foreign materials in a way that makes it appear to the

T cells that those are similar to self-proteins or self-antigens. And those T cells then inappropriately

would attack those self-tissues[.]” Tr. 85:5–9. Dr. Bassiri also explained that there is evidence that

the HLA-B27 molecule itself can elicit a response in cells when it goes through the process of

“getting folded.” Tr. 85:11–14. He continued that the “folding can actually set off focal

inflammatory signaling by cells. And if you have enough of it going on, that could predispose to

initiation of an inflammatory cascade even in the absence of an actual trigger.” Tr. 85:14–18. He

added one other possibility is that pieces of the HLA-B27, “which eventually get expressed onto

cell surfaces could . . . come together in an inappropriate manner that actually ends up allowing

inflammatory ligons [sic] on other cells to bind them and start an inflammatory cascade, again, in

the absence of a specific trigger.” Tr. 85:19–25, 86:1–2.

Dr. Bassiri also wrote that “reactivation [of HSV] is known to cause uveitis and

neurotrophic keratitis.” Resp’t’s Ex. M at 2; Resp’t’s Ex. A at 4; see also Resp’t’s Ex. F at 1, ECF

No. 27-6. 61 He provided medical literature supporting this conclusion. Resp’t’s Ex. A at 4 (citing

Resp’t’s Ex. J at 1, ECF No. 27-10. 62). The Tsirouki et al. article noted that “[h]erpes and

toxoplasmosis are the leading infectious causes of uveitis.” Resp’t’s Ex. J at 1. Based on this, Dr.

Bassiri posited that he is “not sure why one would invoke an unproven association as being the

cause of [Petitioner’s] uveitis.” Resp’t’s Ex. M at 2. He postulated that “even if [Petitioner’s] HLA-

60

D. Wakefield, et al., What is New HLA-B27 Acute Anterior Uveitis, 19 OCULAR IMMUNOL. &

INFLAMMATION 139–144 (2011).

61

S.B. Engelhard, et al., Infectious Uveitis in Virginia, 9 CLIN. OPHTHALMOL. 1589–94 (2015).

62

T. Tsirouki, et al., A Focus on the Epidemiology of Uveitis, 0:0 OCULAR IMMUNOL. & INFLAMMATION

1–15 (2016).

27

B27, which is also independently a risk factor for uveitis, were not the cause of her uveitis, then

her proven HSV disease very easily could have been.” Id.

Dr. Bassiri opined that Petitioner’s herpesvirus preceded her uveitis and subsequent herpes

keratitis. Tr. 86:11–14. Dr. Bassiri relied on Petitioner’s fever and “mild cold” symptoms noted

several days post vaccination to support his assertion that Petitioner experienced either a primary

or reactivated herpesvirus instead of uveitis at that time. Resp’t’s Ex. A at 4 (citing Pet’r’s Ex 2 at

1). He stated that in both the primary and reactivation of herpesviruses, “one can see systemic

signs of [] an illness, such as fever.” Tr. 75:4–5. Dr. Bassiri also focused on the tenderness noted

in Petitioner’s nose during her November 12, 2012 appointment, and stated that it is relevant

because in the reactivation of herpesvirus, itchiness or irritation can be found. Tr. 74:20–25.

Maintaining that Petitioner’s symptom presentation did not fit that of a Type IV hypersensitivity

reaction, Dr. Bassiri opined that Petitioner’s cold symptoms during her November 12, 2012

appointment with Dr. Alvarez “point towards an alternative hypothesis [] by which this damage

occurred to her, . . . instead of [] the vaccine induc[ing] a delayed-type hypersensitivity, which

resulted in uveitis . . . .” Tr. 76:1–5. He testified that “the possibility exists that she could have had

a herpesvirus infection that then presented as uveitis.” Tr. 76:7–9. He nonetheless agreed that other

than her fever mentioned during her November 12, 2012 appointment, Petitioner did not report

any other cold or flu-like symptoms during November of 2012, or subsequent visits in early 2013.

Tr. 104:11–16, 105–106 (citing Pet’r’s Ex. 2 at 1; Pet’r’s Ex. 16 at 1; Pet’r’s Ex. 38 at 1A).

Dr. Bassiri cited two articles by Darougar & Wishart et al., 63 to explain that “these [cold]

symptoms are common findings accompanying either primary or reactivation [of] herpesvirus

ocular infections.” Resp’t’s Ex. A at 4; Resp’t’s Ex. E at 1, ECF No. 27-5; Resp’t’s Ex. L at 2,

ECF No. 27-12; see also Tr. 75:17–22. The authors found that in primary herpesvirus ocular

infections, upper respiratory tract “cold” symptoms are observed in 35% of patients, with fever in

31% of cases. Resp’t’s Ex. E at 1. They compared that to reactivated herpesvirus ocular infections

and found such upper respiratory tract or cold symptoms increases and occurs in 48% of cases.

Resp’t’s Ex. L at 2.

He focused on Petitioner’s stye diagnosis on November 12, 2012. Resp’t’s Ex. A at 4

(citing Pet’r’s Ex. 2 at 1). Dr. Bassiri opined that this was a manifestation of Petitioner’s

herpesvirus and should not have been diagnosed as a stye by Dr. Alvarez. See id. He posited that

this misdiagnosis occurred “due to the presence of pustules instead of clear-fluid filled vesicles.”

Resp’t’s Ex. M at 2. Dr. Bassiri relied on the same Darougar & Wishart et al. 64 articles, in which

the authors found “15 and 23% of patients with primary or reactivation herpesvirus ocular

infections displayed chronic blepharitis (inflammation of the eyelid margin).” Resp’t’s Ex. A at 4.

Dr. Bassiri concluded that based on “[t]he cadence of what happened to [Petitioner], the presence

of systemic signs and symptoms of disease [fever], and then the focal signs and symptoms of the

disease making you think that there probably are alternative explanations as to what actually

happened to her.” Tr. 74:15–19.

63

S. Darougar & M.S. Wishart, et al., Epidemiological and clinical features of primary herpes simplex

virus ocular infection, 69 BR. J. OPHTHALMOL. 2–6 (1985); M.S. Wishart & S. Darougar, et al., Recurrent

herpes simplex virus ocular infection: epidemiological and clinical features, 9 BR. J. OPHTHALMOL. 669–

72 (1987).

64

See id.

28

Dr. Bassiri addressed the possible mechanism responsible for Petitioner’s herpesvirus

ocular infection causing her uveitis. Resp’t’s Ex. A at 5. He wrote that “viral illnesses, via

molecular mimicry, are frequently postulated to be triggers for development of autoimmune

phenomena such as uveitis.” Id. Dr. Bassiri testified that Petitioner experienced a herpesvirus

which led to uveitis, as herpesviruses can affect “immunocompetent and immunocompromised

hosts[]” and one does not “have to have a defect in [the] immune status to be infected and/or to

actually have reactivation of the disease.” Tr. 86:15–19. Dr. Bassiri stated that while it is true that

people are “more prone” to reactivation of latent viruses, including HSV, if they are

immunocompromised, “you don’t need to have that.” Tr. 94:1–3. He testified that the reactivation

of HSV can occur in “immunocompetent hosts that [] reactivate their herpesvirus family.” Tr.

94:3–5. Dr. Bassiri agreed that “severe stress can induce immune dysfunction which can

predispose to the possibility of reactivation of herpesviruses.” Tr. 109:18–21. He opined that it is

possible, but rare, that a vaccine could also reactivate a latent HSV infection. Tr. 110:18–22. He

posited that if that occurrence was common, however, “we would probably stop giving [the]

influenza vaccination to immunocompromised hosts[.]” Tr. 110:23–25. Dr. Bassiri agreed that it

would be difficult to determine who susceptible people would be before receipt of the vaccine. Tr.

111:4–7.

Dr. Bassiri noted the fact that viral illnesses are triggers for development of an autoimmune

phenomena such as uveitis is significant in Petitioner’s case because she has a family history

consisting of a sister with possible rheumatoid arthritis and a son with possible ankylosing

spondylitis. Resp’t’s Ex. A at 5. He wrote that this suggests “a relatively strong predisposition to

autoimmune diseases.” Id. He also testified that a positive HLA-B27 haplotype may result in a

predisposition to a variety of autoimmune phenomenon, including uveitis. Tr. 85:1–3. Dr. Bassiri

concluded that given Petitioner’s predisposing family history, her positive ANA, and HLA-B27

allele, “it would be reasonable to wonder if she already had a genetic predisposition to

autoimmunity that may have led to development of uveitis triggered by a viral infection.” Resp’t’s

Ex. A at 5; see also Tr. 77:6–20.

Next, Dr. Bassiri highlighted that Dr. Fraunfelder failed to differentiate whether Petitioner

suffered from a primary infection or a reactivation of a latent HSV infection. Resp’t’s Ex. N at 2.

Dr. Bassiri explained that this differentiation is an “important distinction and not merely

semantics[.]” Id. He argued that this omission makes Dr. Fraunfelder’s proposed theory that

Petitioner suffered from an altered immune status that led to her susceptibility of HSV disease and

herpes keratitis, “extremely confusing from an immunological and infectious disease perspective.”

Id. Dr. Bassiri explained that if Petitioner experienced an HSV infection as he posited, Dr.

Fraunfelder’s theory of altered immunity does not make sense because “you don’t need to have

altered immunity in order to develop HSV infections and [] recrudescence [there]of.” Tr. 93:22–

25. He noted that Petitioner did not have an altered immunity. Tr. 87:2–5. He continued that “the

pathogenesis of neither primary nor reactivation [of] HSV disease is consistent with uveitis

resulting in infection[.]” Resp’t’s Ex. N at 2.

Dr. Bassiri admitted that it is “difficult” to know if Petitioner, in fact, had a primary disease.

Tr. 90:9–10. However, he stated it is “entirely more likely because of [] epidemiologically that she

had been exposed to herpesviruses previously.” Tr. 90:10–12. Dr. Bassiri noted that Dr.

Fraunfelder seems to posit that Petitioner “suffered from a primary infection (as suggested by his

29

claim that she had no prior history of herpes zoster)[.]” Resp’t’s Ex. N at 2 (citing Pet’r’s Ex. 33

at 3). Dr. Bassiri argued that if this was true, “there would be no reason to implicate altered

immunity in the pathogenesis of this infection, as primary HSV infections happen very commonly

in healthy[,] non-immunosuppressed individuals[.]” Resp’t’s Ex. N at 2. Dr. Bassiri also argued

that if Dr. Fraunfelder asserted that Petitioner suffered from a reactivation of a latent infection,

“this commonly occurs in immunosuppressed patients. Yet, [Petitioner] was not on any

immunosuppressive medications[.]” Id. He continued that even if Petitioner “were somehow

immunosuppressed, it is unclear why immunosuppression would be associated with T cell

activation (which is a requisite for development of a Type IV hypersensitivity)[.]” Id. He testified

that a Type IV hypersensitivity reaction would not lead to an altered immune system. Tr. 92–93.

He noted that “in fact, hypersensitivity reactions are commonly treated by giving

immunosuppressive medications.” Resp’t’s Ex. N at 2 (emphasis in original). Dr. Bassiri

concluded that “Dr. Fraunfelder’s proposed mechanism for development of uveitis is not consistent

with either type of HSV infection.” Id. Instead, Dr. Bassiri proposed that “what is significantly

more likely is [a] HSV infection resulting in uveitis[.]” Id. Overall, he concluded that “the simplest

explanation here is that [Petitioner’s] HLA-B27 and/or herpesvirus infection, which are well-

known to be associated with uveitis, possibly led to her uveitis . . . .” Tr. 82:2–4.

While Dr. Bassiri maintained that Petitioner did not experience a hypersensitivity reaction

following the flu vaccine, he addressed Dr. Smith’s note from November 4, 2016. Tr. 119:19–22

(citing Pet’r’s Ex. 30 at 1). The note indicated that Petitioner was “given a skin test for TB[,] has

had a BCG shot before [and] ha[d an] enormous reaction and since then her eyes are flaring.” Tr.

119:24, 120:1–2. The note cautioned Petitioner ‘“to avoid all things that stimulate dendritic cells[,]

which is vaccines and BCG as it activates her eye disease.”’ Tr. 120:4–6 (citing Pet’r’s Ex. 30 at

1). He admitted that this warning could have possibly been an indication that Dr. Smith believed

Petitioner had a hypersensitivity reaction to the TB test. Tr. 122:24–25, 123:1, 124:18–24. Dr.

Bassiri, however, noted that Petitioner did not have a reaction to the BCG as a child or the skin

test in 2012, but did have a reaction in 2016. Tr. 120:7–9. He explained that one reason this could

have happened is that “people who receive the BCG in their initial phase will not have a response

to that BCG vaccine. But when [] they have follow-up PPDs, they can have a response to that.”

Tr. 123:11–14. He could not opine as to what caused Petitioner’s flare in 2016, and could therefore

not determine if it was, in fact, a hypersensitivity reaction. Tr. 122:11–22. He acknowledged that

Petitioner’s symptom presentation was described as “waxing and waning[.]” Tr. 123:1–2. But

opined that “all that says is that it gets better and worse potentially depending on what sort of

medication she’s on.” Tr. 123:2–5.

He acknowledged Petitioner’s negative Varicella Zoster virus (“VZV”) antibody test in

January of 2011, prior to the onset of her injury, and compared it to the “+Abs” notation in her

records from Norway in August of 2013. Resp’t’s Ex. A at 4 (citing Pet’r’s Ex. 8 at 7). He noted

that while she was tested for VZV in January of 2011, Petitioner was not tested for HSV. Tr.

90:15–16. He wrote that “Dr. Ostern’s [August 2013] note from Norway reports that specimens

from the cornea and anterior chamber were negative for viruses, bacteria, and fungi[.]” Resp’t’s

Ex. A at 4 (citing Pet’r’s Ex. 11 at 1). As an explanation for the negative test, Dr. Bassiri opined

that “these samples had been obtained well after several rounds of therapy with multiple topical

and systemic antibiotics and antivirals.” Resp’t’s Ex. A at 4; see also Tr. 91:1–13. He relied on an

30

article by Tsatsos et al., 65 to explain that “[i]f herpesviruses such as HSV or VZV were the etiology

for [Petitioner’s] uveitis and keratitis, then it is possible that some of the damage may have been

mitigated by the continued use of appropriate antivirals[.]” Resp’t’s Ex. A at 4; Resp’t’s Ex. I,

ECF No. 27-9.

On cross-examination, Dr. Bassiri reiterated that the mechanism linking vaccines and

uveitis has not been proven. Tr. 96:19–20. When asked what evidence he would require to prove

the mechanism linking vaccines to uveitis, Dr. Bassiri stated that “since obviously one cannot

experiment on humans[,]” he would require animal models. Tr. 96:23–25, 97:1–4. Dr. Bassiri

addressed the Nussenblatt 66 article containing an animal model proffered by Dr. Fraunfelder. Tr.

97:5–6. He testified that he did not place a lot of stock in this animal study. Tr. 131:16–19. Dr.

Bassiri did not agree that the study supports the role of hypersensitivity reactions in the

development of uveitis. Tr. 97:11–18. Instead, he stated the study indicates “what we sort of expect

the immune system to do, which is that if you immunize an animal or human to a particular piece

of the body, that you could break what’s called tolerance . . . and induce a response [] against self-

antigens.” Tr. 97:14–18, 98:1–2, 132:1–3. However, when pressed, he acknowledged that the

Nussenblatt 67 article showed support for a Type IV hypersensitivity reaction causing uveitis in an

animal model. Tr. 115:3–7.

Under my questioning, Dr. Bassiri stated that it does not matter whether Petitioner had a

primary or latent HSV infection. Tr. 125:3–8. He testified that while both forms are associated

with the development of uveitis, a reactivation is “probably much more likely because . . . the

prevalence of people who have HSV as part of them is much larger than the people who acquire it

on a yearly basis[.]” Tr. 125:9–13. He clarified that, independent of a positive HLA-B27 status,

one can experience the reactivation of HSV and develop uveitis. Tr. 125:22–25. He stated that the

converse is also true, “[i]f you have HLA-B27 independent of HSV, you can have uveitis.” Tr.

126:2–3. Dr. Bassiri stressed that in Petitioner’s case, “both of those are playing a role[]” and are

known causes. Tr. 126:4–11. He emphasized that these are not merely known associations of

uveitis but known causes. Tr. 126:7–14. He concluded that Petitioner was “prone for [uveitis] to

happen at any point. And just because it happened after she received her [flu] vaccination is almost

always agnostic to that.” Tr. 126:18–20.

I asked Dr. Bassiri to tell me why, while he did not agree, did Petitioner have more than

one treater opining that she experienced a hypersensitivity reaction to the vaccine and therefore

cautioned her not to get further vaccinations. Tr. 128:14–25, 129:1–5 (citing Pet’r’s Ex. 30 at 1).

He stated that he was “not entirely sure about that.” Tr. 129:18.

IV. Applicable Legal Standards

To receive compensation under the Vaccine Act, a petitioner must demonstrate either that:

(1) the petitioner suffered a “Table injury” by receiving a covered vaccine and subsequently

developing a listed injury within the time frame prescribed by the Vaccine Injury Table set forth

65

M. Tsatsos, et al., Herpes Simplex Virus Keratitis: an update of the pathogenesis and current treatment

with oral and topical antiviral agents, CLIN. EXP. OPHTHALMOL. (2016).

66

See Nussenblatt, supra note 40 at 1.

67

See id.

31

at 42 U.S.C. § 300aa-14, as modified by 42 C.F.R. § 100.3; or (2) that petitioner suffered an “off-

Table injury,” one not listed on the Table, as a result of his receiving a covered vaccine. See 42

U.S.C. §§ 300aa-11(c)(1)(C); Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315, 1321

(Fed. Cir. 2010); Capizzano v. Sec’y of Health & Hum. Servs., 440 F.3d 1317, 1319-20 (Fed. Cir.

2006). Petitioner does not allege a Table injury in this case; thus, she must prove that her injury

was caused-in-fact by a Table vaccine.

To establish causation-in-fact, a petitioner must demonstrate by a preponderance of the

evidence that the vaccine was the cause of the injury. 42 U.S.C. § 300aa-13(a)(1)(A). A petitioner

is required to prove that the vaccine was “not only a but-for cause of the injury but also a substantial

factor in bringing about the injury.” Moberly, 592 F.3d at 1321–22 (quoting Shyface v. Sec’y of

Health & Hum. Servs., 165 F.3d 1344, 1352–53 (Fed. Cir. 1999)).

In the seminal case of Althen v. Sec’y of the Dept. of Health & Hum. Servs, the Federal

Circuit set forth a three-pronged test used to determine whether a petitioner has established a causal

link between a vaccine and the claimed injury. See 418 F.3d 1274, 1278–79 (Fed. Cir. 2005). The

Althen test requires petitioners to set forth: “(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 a proximate temporal relationship between

vaccination and injury.” Id. at 1278. To establish entitlement to compensation under the Program,

a petitioner is required to establish each of the three prongs of Althen by a preponderance of the

evidence. Id. “[C]lose calls regarding causation are resolved in favor of injured claimants.” Id. at

1280. Further, evidence used to satisfy one prong of the test may overlap to satisfy another prong.

Capizzano, 440 F.3d at 1326.

A petitioner who satisfies all three prongs of the Althen test has established a prima facie

showing of causation. Hammitt v. Sec’y of Health & Hum. Servs., 98 Fed. Cl. 719, 726 (2011). A

petitioner who demonstrates by a preponderance of the evidence that he suffered an injury caused

by vaccination is entitled to compensation unless the respondent can demonstrate by a

preponderance of the evidence that the injury was caused by factors unrelated to the vaccination.

See Althen, 418 F.3d at 1278; Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 547 (Fed.

Cir. 1994). In such a case, the government must not merely prove the existence of an alternative

cause, but that such an alternative actually caused the injury. Knudsen, 35 F.3d at 549.

Consequently, when and if Petitioner establishes a prima facie case, the burden then shifts to the

government to prove that an alternative cause, unrelated to the administration of the vaccine, was

the “sole substantial factor” in causing the alleged injury. See de Bazan v. Sec’y of Health & Hum.

Servs., 539 F.3d 1347, 1354 (Fed. Cir. 2008); see also Hammitt, 98 Fed. Cl. at 726 (explaining

that the respondent’s burden is to show that the “factor unrelated” was the “sole substantial factor”

in causing the injury). Additionally, a factor unrelated “may not include ‘any idiopathic,

unexplained, unknown, hypothetical, or undocumentable cause, factor, injury, illness or

condition.’” 42 U.S.C. § 300aa-13(a)(2); see also Doe v. Sec’y of Health & Hum. Servs., 601 F.3d

1349 (Fed. Cir. 2010) (opining that an idiopathic diagnosis cannot be a “factor unrelated,” as it is

idiopathic).

In considering the reliability of a petitioner’s evidence of a prima facie case, the special

master may consider alternative causes for a petitioner’s condition that are reasonably raised in the

32

record, even if the respondent does not pursue a formal alternative cause argument. Doe, 601 F.3d

at 1358. Thus, in weighing a petitioner’s case-in-chief, a special master may consider evidence

that the petitioner’s alleged injury could have been caused by alternative causes. Id. Proof of a

“logical sequence of cause and effect” will eliminate potential likely alternatives. Walther v. Sec’y

of Health & Hum. Servs., 485 F.3d 1146, 1151 (Fed. Cir. 2007).

V. Discussion

A. Petitioner’s Diagnoses

As a factual predicate to proving vaccine-causation, it is Petitioner’s burden to demonstrate

that she actually suffers from the injuries alleged to have been caused by her November 3, 2012

flu vaccination. See Hibbard v. Sec’y of Health & Hum. Servs., 698 F.3d 1358, 1364–65 (Fed. Cir.

2012); Lombardi v. Sec’y of Health & Hum. Servs., 656 F.3d 1343, 1353 (Fed. Cir. 2011);

Broekelschen v. Sec’y of Health & Hum. Servs., 618 F.3d 1339, 1346 (Fed. Cir. 2010) (finding that

in a case where the injury itself is in dispute, it is appropriate for the special master to “first

determine which injury was best supported by the evidence presented in the record before applying

the Althen test so that the special master could subsequently determine causation relative to the

injury.”). The Vaccine Act provides that a treating physician’s diagnosis “shall not be binding on

the special master or court,” but that the special master should consider the “entire record and the

course of the injury” when evaluating how much weight to afford a treating physician’s diagnosis.

42 U.S.C. § 300aa-13(b)(1). In this case, Petitioner alleged that she suffered from PUK, uveitis,

and herpes keratitis. She therefore must show by preponderant evidence that she suffers from each

condition. See Broekelschen, 618 F.3d at 1349; see also Lombardi, 656 F.3d at 1353.

Petitioner has failed to show by preponderant evidence that she suffered from PUK.

Although three of Petitioner’s treaters initially diagnosed her with PUK, they all later ruled it out.

Most notably, two of Petitioner’s treating ophthalmologists altered their diagnoses in light of

Petitioner’s symptomatology and progression. Dr. Foote, who was the first to formally diagnose

Petitioner with PUK, later agreed with Dr. Ostern that Petitioner suffered from herpetic

keratouveitis that was exacerbated by her positive HLA-B27 status. Pet’r’s Ex. 5 at 73–74 (citing

Pet’r’s Ex. 11 at 1). Dr. Di Pascuale, another treating ophthalmologist, concluded that Petitioner

did not have PUK but rather HSV-related sclerokeratitis. Pet’r’s Ex. 7 at 7–8, 29, 31. Dr. Smith, a

rheumatologist, also altered her diagnosis and assessed Petitioner with Reiter’s syndrome with

herpes keratitis, noting specifically “Reiter’s keratitis with herpes as the AG [aggravating] driver.”

Pet’r’s Ex. 8 at 5–6, 11. Dr. Smith also proposed several other conditions to explain Petitioner’s

condition, including inflammatory eye disease, hypopyon uveitis, and Behcet’s syndrome. Id. at

1, 7, 11. Additionally, upon establishing care with ophthalmologist Dr. Ramirez, he noted

Petitioner’s history of PUK but, after his own review, diagnosed her with severe vasculitis with

associated keratitis. Pet’r’s Ex. 6 at 1–4. It is therefore not likely that Petitioner’s treaters believed

she suffered from PUK. 68 In fact, Petitioner’s own expert in ophthalmology opined that she never

68

Petitioner’s primary care physician Branch Craige made a note of Petitioner’s self-reported history of

PUK. Pet’r’s Ex. 9 at 2. He also noted that Petitioner was being treated by Dr. Karen Smith for Reiter’s

syndrome. Id. His separate assessment of Petitioner documented “Reiter [sic] syndrome, HLA-B27

positive.” Id. at 3. Therefore, his reference to Petitioner’s history of PUK does not provide support for such

a diagnosis.

33

suffered from PUK but rather “uveitis caused by the vaccine.” See Pet’r’s Ex. 19 at 2. Dr.

Fraunfelder relied on Petitioner’s symptom presentation and her response to initial treatment on

November 12, 2012, to establish that her condition was consistent with uveitis instead of PUK.

Notably, Petitioner seemed to abandon her claim as it relates to PUK and instead chose to proceed

only with her uveitis and herpes keratitis claims. See, e.g., Pet’r’s Br. at 1, 17. Indeed, Petitioner’s

ensuing claim hinges on her not having PUK. Therefore, Petitioner has failed to show by

preponderant evidence that she suffers from PUK and this condition will not be analyzed in relation

to causation-in-fact.

Petitioner has presented preponderant evidence that she suffered from uveitis. Both

Petitioner’s and Respondent’s experts agree that Petitioner exhibited “well-recognized” symptoms

consistent with uveitis, including inflammation, pain, and redness of the eye. Pet’r’s Ex. 19 at 2;

Resp’t’s Ex. A; Tr. 18, 108. However, the experts disagree about when her uveitis manifested and

the chain of cause and effect resulting in her uveitis. This discrepancy will be discussed with

respect to Althen prongs two and three. However, for the purposes of determining diagnosis,

Petitioner has shown by a preponderant standard that she suffers from uveitis.

Petitioner has also presented preponderant evidence that she suffered from a herpesvirus

infection, which progressed to herpes keratitis. Neither expert disputes the fact that Petitioner

suffered from either a primary or reactivated latent herpesvirus infection. Pet’r’s Ex. 19 at 2;

Resp’t’s Ex. A. Petitioner’s expert opined that Petitioner’s herpesvirus progressed to herpes

keratitis. 69 While Respondent’s expert did not explicitly admit that Petitioner suffered from herpes

keratitis, he implied it in light of her HSV infection, and he did not deny that she has the condition.

Indeed, the fact that several of Petitioner’s treating physicians ultimately diagnosed her with

herpes-related keratitis after ruling out other conditions, as described above, provides preponderant

support for establishing such diagnosis. Additionally, two of Petitioner’s treating

ophthalmologists, Drs. Ostern and Ramirez, diagnosed her with keratitis with an infectious

etiology, such as herpes, despite her cultures being negative. Pet’r’s Ex. 11 at 1; Pet’r’s Ex. 6 at 4.

It is persuasive that, in support for his own theory, Respondent’s expert opined that Petitioner’s

testing from August of 2013 and thereafter did not show signs of viruses, such as the herpesvirus,

because “these samples had been obtained well after several rounds of therapy with multiple

topical and systemic antibiotics and antivirals.” Resp’t’s Ex. A at 4; see also Tr. 91:1–13.

Respondent’s reliance on the Tsatsos et al., 70 article to show that the use of antivirals, such as

Acyclovir, are used to prevent recurrent episodes of HSV is compelling evidence that Petitioner’s

steady treatment course with appropriate antivirals explains her negative cultures at the time of

testing. See Resp’t’s Ex. I at 6. Therefore, Petitioner has shown by a preponderance of the evidence

that she suffers from herpes keratitis.

B. Experts

Although special masters have the discretion to be informed by past rulings and

experiences, case-specific filings and testimony are the most helpful types of evidence, given the

fact-specific nature of each decision. See Doe v. Sec’y of Health & Hum. Servs., 76 Fed. Cl. 328,

338–39 (2007). To that end, experts are an essential piece of a petitioner’s claim and Respondent’s

69

See supra note 5 (defining herpes keratitis as “a viral infection of the eye caused by HSV.”).

70

See Tsatsos, et al., supra note 65 at 1.

34

defense. Where both sides offer expert testimony, a special master’s decision may be “based on

the credibility of the experts and the relative persuasiveness of their competing theories.”

Broekelschen, 618 F.3d at 1347 (citing Lampe v. Sec’y of Health & Hum. Servs., 219 F.3d 1357,

1361 (Fed. Cir. 2000)).

This case ultimately turns not only on Petitioner’s medical history, but also the

persuasiveness of the written reports, supporting documentation, and expert testimony. I therefore

must assess each expert’s expertise in relation to the facts of Petitioner’s case and assign weight

accordingly. This assessment will inform my analysis pursuant to each prong of Althen.

I base this decision on entitlement, in part, on Dr. Bassiri’s credentials and expertise in

immunology and infectious diseases specifically, as compared to Dr. Fraunfelder’s main focus in

ophthalmology. While I in no way discount Dr. Fraunfelder’s understanding and experience

involving immunology, I must afford Dr. Bassiri’s specialized knowledge in immunology and

infectious diseases more weight. Notably, in relevant part, Dr. Bassiri received a Ph.D. in

immunology from the University of Pennsylvania in 2002. Resp’t’s Ex. B at 1. Dr. Bassiri has

been an attending physician in the Division of Infectious Disease, Department of Pediatrics at the

Children’s Hospital of Philadelphia for a decade. Id. He currently sees patients with

immunodeficiencies, and studies T-cell function as part of his research for cancer immunotherapy.

Tr. 65:10–14. He also frequently gives lectures regarding concepts of infectious diseases, such as

herpesviruses and immunology. Tr. 66:5–6, 12–14.

Dr. Fraunfelder is an extremely qualified expert in his field. He has a history of providing

useful testimony and persuasive explanations in cases before me, as well as other special masters

in the Program. In this case however, his ultimate opinion was delivered with ambiguities,

compared to the well-reasoned opinion of Respondent’s expert. See Broekelschen, 618 F.3d at

1347 (citing Lampe, 219 F.3d at 1362) (finding that where both sides offer expert testimony, a

special master’s decision may be “based on the credibility of the experts and the relative

persuasiveness of their competing theories.”). Further, Dr. Bassiri’s background and knowledge in

immunology and infectious diseases is more applicable to this case than Dr. Fraunfelder’s

expertise in ophthalmology when considering the parties’ arguments regarding the immunologic

response involved in Petitioner’s proposed mechanism and the infectious nature and

immunological involvement of herpesviruses, such as HSV.

C. Althen Prong One

Under the first prong of Althen, a petitioner must offer a scientific or medical theory that

answers in the affirmative the question: “can the vaccine[] at issue cause the type of injury

alleged?” See Pafford v. Sec’y of Health & Hum. Servs., No. 01-0165V, 2004 WL 1717359, at *4

(Fed. Cl. Spec. Mstr. July 16, 2004), mot. for rev. denied, 64 Fed. Cl. 19 (2005), aff’d, 451 F.3d

1352 (Fed. Cir. 2006). To satisfy this prong, a petitioner’s theory must be based on a “sound and

reliable medical or scientific explanation.” Knudsen, 35 F.3d at 548. Such a theory must only be

“legally probable, not medically or scientifically certain.” Knudsen, 35 F.3d at 548–49. Petitioners

are not required to identify “specific biological mechanisms” to establish causation, nor are they

required to present “epidemiologic studies, rechallenge[] the presence of pathological markers or

genetic disposition, or general acceptance in the scientific or medical communities.” Capizzano,

35

440 F.3d at 1325 (quoting Althen, 418 F.3d at 1280). Scientific and “objective confirmation” of

the medical theory with additional medical documentation is unnecessary. Althen, 418 F.3d at

1278–81; see also Moberly, 592 F.3d at 1322. However, as the Federal Circuit has made clear,

“simply identifying a ‘plausible’ theory of causation is insufficient for a petitioner to meet her

burden of proof.” LaLonde v. Sec’y of Health & Hum. Servs., 746 F.3d 1334, 1339 (Fed. Cir. 2014)

(citing Moberly, 592 F.3d at 1322). Rather, “[a] petitioner must provide a reputable medical or

scientific explanation that pertains specifically to the petitioner’s case.” Moberly, 592 F.3d at 1322.

In general, “the statutory standard of preponderance of the evidence requires a petitioner to

demonstrate that the vaccine more likely than not caused the condition alleged.” LaLonde, 746

F.3d at 1339.

Furthermore, establishing a sound and reliable medical theory connecting the vaccine to

the injury often requires a petitioner to present expert testimony in support of her claim. Lampe,

219 F.3d at 1361. The Supreme Court’s opinion in Daubert v. Merrell Dow Pharmaceuticals, Inc.,

509 U.S. 579 (1993), requires that courts determine the reliability of an expert opinion before it

may be considered as evidence. “In short, the requirement that an expert’s testimony pertain to

‘scientific knowledge’ establishes a standard of evidentiary reliability.” Id. at 590 (citation

omitted). Thus, for Vaccine Act claims, a “special master is entitled to require some indicia of

reliability to support the assertion of the expert witness.” Moberly, 592 F.3d at 1324. The Daubert

factors are used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec’y

of Health & Hum. Servs., 94 Fed. Cl. 53, 66–67 (2010) (“uniquely in this Circuit, the Daubert

factors have been employed also as an acceptable evidentiary-gauging tool with respect to

persuasiveness of expert testimony already admitted.”). Nothing requires the acceptance of an

expert’s conclusion “connected to existing data only by the ipse dixit of the expert,” especially if

“there is simply too great an analytical gap between the data and the opinion proffered.” Snyder v.

Sec’y of Health & Hum. Servs., 88 Fed. Cl. 706, 743 (2009) (quoting Gen. Elec. Co. v. Joiner, 522

U.S. 136, 146 (1997)).

a. Uveitis

Petitioner has failed to meet her burden under Althen prong one with respect to uveitis.

Petitioner posited a scientific or medical theory explaining the flu vaccine’s role in the

development of uveitis through a Type IV hypersensitivity reaction and the notion of positive

rechallenge. I will discuss each in turn.

i. Type IV Hypersensitivity Reaction

Petitioner relied on the Meng et al. 71 article to describe a Type IV hypersensitivity reaction.

The authors emphasized the role of dendritic cells that “take up and process” antigens which are

then represented on the surface of those cells with specific peptide – HLA complexes for T-cell

recognition. Pet’r’s Ex. 33, Tab B at 5. They explained that from there, the interaction between

dendritic and T cells dictates the specificity of the reaction and location of the inflammatory

response. See id. While Petitioner’s reliance on the Meng et al. article aids my understanding of

the mechanisms underlying a Type IV hypersensitivity response, the article does not advance

Petitioner’s case with respect to the flu vaccine and uveitis under Althen prong one. Petitioner’s

71

See Meng, et al., supra note 41 at 1.

36

main support for her biological mechanism is the Nussenblatt 72 animal model, which she contends

shows that her proposed mechanism connecting the flu vaccine to uveitis has been tested and

documented in the existing medical literature. See Pet’r’s Ex. 33, Tab C. Further, Dr. Fraunfelder

argues that this study proves that a systemically applied immunization can cause a localized

inflammation, such as uveitis, via a Type IV hypersensitivity reaction. Tr. 38:1–3. However,

Petitioner’s reliance on this study is wholly misplaced. While the study discusses the role of Type

IV hypersensitivity reactions in the development of uveitis, it fails to discuss vaccines in general,

or the flu vaccine specifically. Instead, the rats in the study developed localized inflammation after

being injected with a retinal S-antigen. 73 Pet’r’s Ex. 33, Tab C at 2. The article therefore fails to

show how a systemic flu vaccine can produce a localized Type IV hypersensitivity reaction.

Petitioner did not otherwise submit evidence supporting her theory that the flu vaccine can

cause uveitis via a Type IV hypersensitivity reaction. 74 Instead, Petitioner conceded that the

mechanisms underlying Type IV hypersensitivity reactions “are complex and not completely

understood.” Pet’r’s Ex. 33 at 1. While Petitioner is not required to present objective confirmation

or epidemiological studies to support her biological mechanism, she must do more than simply

identify a “plausible” theory of causation. Capizzano, 440 F.3d at 1325 (quoting Althen, 418 F.3d

at 1280); see also LaLonde, 746 F.3d at 1339 (citing Moberly, 592 F.3d at 1322). I therefore find

that Petitioner has failed to show by preponderant evidence that the flu vaccine can cause uveitis

via a Type IV hypersensitivity reaction.

Additionally, while prior decisions of special masters are not binding on my analysis, it is

persuasive that Petitioner’s proposed Type IV hypersensitivity reaction theory has previously been

rejected in the Program. See Yates v. Sec'y of Health & Hum. Servs., No. 14-560V, 2020 WL

72

See Nussenblatt, supra note 40 at 1.

73

A retinal S-antigen (S-ag) is not akin to a vaccine. Rather, it is “found in the photoreceptors of the eye,

[and] is a potent autoantigen that is commonly involved in inflammatory eye disease leading to blindness[.]”

See abstract of Suleyman, et al., Idiotypic Expression of Antibodies to Retinal S-antigen in Experimental

Autoimmune Uveoretinitis, 62(4) IMMUNOL. 537–41 (1987).

74

Petitioner’s reliance on other articles showing a connection between the flu vaccine and uveitis is

informative but inapplicable to Althen prong one, as the articles do not indicate that this phenomenon occurs

because of a Type IV hypersensitivity reaction. For instance, Petitioner relied on the Benage et al. article

to show that an association exists between the flu vaccine and uveitis, as twenty-eight instances were

reported over a thirty-year period. Pet’r’s Ex. 19, Tab A. However, the article does not describe a causal

connection between the flu vaccine and uveitis, nor does it elaborate on the mechanism by which this

occurs. See id. Petitioner relied on the article by London et al., which used the Naranjo criteria in place of

a clinical trial, to determine that the flu vaccine has a “probable” causal association with uveitis. Pet’r’s Ex.

45 at 4, 13. The authors determined this score signified more than a mere possibility of occurrence, but still

less than definite probability. Id. It does not identify a biological mechanism. Id. Similarly, Petitioner also

relied on the article by Suhler et al. to argue that all vaccinations can cause a Type IV hypersensitivity

reaction. Pet’r’s Ex. 19, Tab D at 4. However, Petitioner conceded that the Suhler et al. article is

distinguishable because the article talks about the Hepatitis B vaccine, not the flu vaccine, and the authors

allege a Type III hypersensitivity reaction as the mechanism, not a Type IV. Tr. 53:23–25, 54:1–17 (citing

Pet’r’s Ex. 19, Tab D). The authors also fail to elaborate on the mechanics of a “delayed-type

hypersensitivity reaction[,]” merely stating that it is one possible mechanism for the development of uveitis.

Pet’r’s Ex. 19, Tab D at 4. As Respondent’s expert correctly maintained, the distinctions between the types

of hypersensitivity reaction are not “merely semantics” and instead, implicate different cell responses.

Therefore, I must afford such articles little to no weight.

37

2313691 (Fed. Cl. Spec. Mstr. Apr. 16, 2020), mot. for rev. denied, 150 Fed. Cl. 575 (2020)

(finding that Petitioner failed to explain how a T-cell mediated Type IV hypersensitivity immune

response to a Menactra vaccine can cause lymphocytic myocarditis, as there is a distinction

between lymphocytic myocarditis being viral and eosinophilic myocarditis being a

hypersensitivity reaction.); see also Forrest v. Sec'y of Health & Hum. Servs., No. 10-032V, 2017

WL 4053241 (Fed. Cl. Spec. Mstr. Aug. 10, 2017) (rejecting Petitioner’s argument that four-month

infant vaccinations, including Hep. B, inactivated polio, diphtheria-tetanus-acellular pertussis,

haemophilus influenza, and pneumococcal conjugate vaccines, could cause a Type IV

hypersensitivity reaction resulting in sudden infant death syndrome (“SIDS”). The special master

based this decision, in part, on Petitioner’s failure to provide evidence in favor of a Type IV

response other than the time between vaccination and injury. The special master acknowledged

that the fever the infant experienced post vaccination was not a Type IV response but a humoral

or antibody sensitivity.). While these cases are not completely analogous to Petitioner’s case in

terms of vaccine or injury, the special masters’ reasoning for rejecting the proposed Type IV

hypersensitivity reaction is informative.

ii. Positive Rechallenge

Petitioner has also failed to provide preponderant evidence establishing that the flu vaccine

can cause uveitis via a positive rechallenge. While Dr. Fraunfelder’s testimony explaining the

concept of positive rechallenge is useful, Petitioner did not otherwise present evidence supporting

her claim as it relates to this biological mechanism and uveitis. Dr. Fraunfelder testified that a

positive rechallenge occurs when an individual receives a vaccine more than once and experiences

a negative reaction following each subsequent receipt of the vaccine, as the body has seen that

specific antigen before and reacts the same way. See Tr. 25–26. Even though Petitioner is not

required to provide specifics of the biological mechanism or provide epidemiological studies that

explain her disease pathology, to the extent that she does, they must make sense. Instead,

Petitioner’s submitted medical literature is inconsistent with her claim, and her reliance on the

Suhler et al. 75 article is detrimental to her case. The authors of the article, including Petitioner’s

own expert, studied the Hep. B vaccine and the development of recurrent uveitis. Pet’r’s Ex. 19,

Tab D. The authors found that one patient in the study had recurrent uveitis after the second and

third doses of the Hep. B vaccine. Id. at 1. Another patient in the study developed uveitis after the

first dose of a Hep. B vaccine and again after the second. Id. This article is not completely

analogous to Petitioner’s case because it fails to discuss the flu vaccine. It also fails to support

Petitioner’s proposed biological mechanism of a positive rechallenge, as a patient in the study

developed uveitis after the first exposure to the Hep. B vaccine. See id. As such, this article does

not provide preponderant evidence to support Petitioner’s claim regarding the flu vaccine causing

uveitis via a positive rechallenge.

Petitioner also relies on the Hassman et al. 76 article to argue that a flu vaccine can cause

severe inflammation in the central nervous system and recurrent uveitis through a positive

rechallenge. Pet’r’s Ex. 44 at 1. However, this article is inapplicable to Petitioner’s claim as it

relates to uveitis. The authors of the article found that the flu vaccine can play a role in the

development of severe inflammation of the central nervous system, but only because the flu

75

See Fraunfelder & Suhler, et al., supra note 38 at 1.

76

See Hassman, et al., supra note 42 at 1.

38

vaccine can cause activation of HSV, not uveitis directly. See id. In fact, the article fails to mention

uveitis altogether, and instead discusses retinitis. 77 While such conditions may be medically

comparable because they both involve inflammation of the eye, the article fails to advance

Petitioner’s case pursuant to Althen prong one. Further, Petitioner’s expert testified regarding an

article by Knopf et al. as support for the notion of positive rechallenge based on its title, “Recurrent

Uveitis After Influenza Vaccination.” See Tr. 28:16–17. However, Dr. Fraunfelder did not rely on

this article in any of his written reports. Petitioner did not file the full article, or even an abstract,

for consideration. Instead, it was merely cited in another exhibit and briefly mentioned for the first

time during his testimony. See Tr. 28:11–22; see also Pet’r’s Ex. 19, Tab B. I therefore do not

consider this article as support for Petitioner’s claim. Petitioner has failed to show by preponderant

evidence how the flu vaccine can cause uveitis via a positive rechallenge.

b. Herpesvirus and Herpes Keratitis

Petitioner argues that the flu vaccine causes an altered immune system via a Type IV

hypersensitivity reaction, which creates a susceptibility to HSV, and herpes keratitis can develop.

Petitioner does not, however, present preponderant evidence that a Type IV hypersensitivity

reaction can lead to herpes keratitis. While Petitioner does not explicitly argue that the flu vaccine

triggers HSV reactivation via a positive rechallenge, the record as a whole, including Petitioner’s

submitted medical literature and testimony from both experts, provides evidence that the flu

vaccine can cause HSV reactivation and eventual herpes keratitis via a positive rechallenge. I find

Petitioner has met her burden under Althen prong one with respect to the flu vaccine’s role in the

development of HSV reactivation and subsequent herpes keratitis via the notion of a positive

rechallenge.

i. Type IV Hypersensitivity Reaction

Petitioner alleges that because the flu vaccine can act as an immunological trigger resulting

in an altered immune status and uveitis, said vaccine also creates a susceptibility to HSV and the

development of herpes keratitis. Dr. Fraunfelder argues that this occurs because a Type IV

hypersensitivity reaction alters the immune system and “[w]hen a person develops an eye disease

. . . they are susceptible to opportunistic infections from viruses that are dormant within [the

body,]” such as HSV. Pet’r’s Ex. 19 at 2; Tr. 43:21–25. Respondent’s expert’s testimony regarding

the expected immune response caused by a Type IV hypersensitivity reaction directly contradicts

Dr. Fraunfelder’s argument. Indeed, Dr. Bassiri’s expertise in immunology is evident during his

rebuttal of Dr. Fraunfelder’s argument. Dr. Bassiri explained that a Type IV hypersensitivity

reaction would not lead to an altered immune system, because a Type IV reaction produces a

localized inflammatory response that dissipates, similar to that of a PPD test or poison ivy. Dr.

Bassiri continued that this type of reaction is not systemic and manifests as localized itchiness, not

a fever. Dr. Bassiri then compared the types of hypersensitivity reactions and explained that a

“[T]ype IV hypersensitivity is rarely associated with fever – especially when the inoculum size of

the antigen (e.g., that in influenza vaccines) is small.” Resp’t’s Ex. M at 2; Tr. 73:1–6. He admitted

that a fever could occur in a Type IV hypersensitivity reaction “if you were to give somebody who

77

Retinitis is “inflammation of the retina, marked by impairment of sight, abnormalities of vision, edema,

and exudation into the retina, and occasionally by hemorrhages into the retina. The term is sometimes used

more loosely to denote also noninflammatory disorders of the retina.” Dorland’s at 1633.

39

has a prior sensitization a large amount of that antigen, you would have a relatively large or robust

immune response[,] . . . the end result of which could be fever.” Tr. 107:2–8. It therefore stands to

reason that the typical immunologic response triggered by a Type IV hypersensitivity reaction

would not rise to the level of altering or weakening the immune system when it generally fails to

produce any systemic response.

Turning to the herpesvirus specifically, which is responsible for the development of herpes

keratitis, 78 Dr. Bassiri testified that the manifestation of a primary herpesvirus infection would not

presumably implicate altered immunity “in the pathogenesis of this infection[]” because primary

HSV infections commonly occur without a trigger in immunocompetent individuals. Dr. Bassiri

explained that reactivation of HSV infections can occur if a patient is immunosuppressed because

the patient is more prone to developing latent viruses. He also noted reactivation can occur in

healthy patients, wherein the immune system is not implicated. Based on this, he reasonably

concluded that he did not see an immunological association with T-cell activation and reactivation

of HSV, a requisite for the development of a Type IV hypersensitivity. Overall, Petitioner’s

proposal that a Type IV hypersensitivity reaction weakens the immune system to the point that

“opportunistic” infections like HSV surface, is not sufficiently supported. See Tr. 42:21–23.

Therefore, Petitioner has failed to show how a Type IV hypersensitivity reaction can result in the

manifestation of HSV and the development of herpes keratitis.

ii. Positive Rechallenge

Even though Dr. Bassiri’s testimony refutes Petitioner’s claim with respect to the flu

vaccine causing HSV and herpes keratitis via a Type IV hypersensitivity reaction, the same is not

true regarding the notion of positive rechallenge. Indeed, Dr. Bassiri conceded that it is rare but

“possible” that a vaccine could reactivate a latent HSV infection, which is a “known cause” of

herpes keratitis. 79 See Tr. 110:18–22; Resp’t’s Ex. A at 3–4. This phenomenon is supported by

Petitioner’s reliance on the Hassman et al. 80 article, which noted that the flu vaccine triggered the

reactivation of a latent HSV infection in 13 out of 38 million doses over ten years. Pet’r’s Ex. 44

at 5. While this article did not advance Petitioner’s case with respect to a positive rechallenge and

uveitis, it does provide support for her claim that the flu vaccine can trigger the reactivation of a

HSV infection via a positive rechallenge. Indeed, the authors determined that “disruptions” in the

immune system, such as vaccines, can activate the virus. Id. at 1. To support their conclusion, the

authors noted a study wherein the patient had “three consecutive yearly [HSV] episodes

(encephalitis, seizure, and retinitis), each within days of his influenza vaccination.” Id. The authors

found that, through a positive rechallenge, a flu vaccine can cause severe inflammation in the

central nervous system, which can lead to infection with HSV and herpes encephalitis. Id.; Tr.

45:4–21. However, it is important to note that the authors conceded that “[a] subtle immunological

deficiency in [their] patient may have lowered the threshold for clinically significant HSV

reactivation in the [central nervous system].” Pet’r’s Ex. 44 at 5. Nonetheless, this study supports

Petitioner’s claim related to positive rechallenge, as the patient in the study experienced a re-

occurrence of HSV-related symptoms and ailments upon re-administration of subsequent flu

vaccines.

78

See supra note 5 (defining herpes keratitis as “a viral infection of the eye caused by HSV.”).

79

See id.

80

See Hassman, et al., supra note 42 at 1.

40

While the Hassman et al. study shows that this occurrence is uncommon (13 out of 38

million doses over ten years), I do not find persuasive Respondent’s argument that because we

have not seen this occur often, it could not occur. Simply because HSV does not require a trigger

to manifest does not mean that a flu vaccine could not be the trigger, especially if the individual

has had negative reactions from repeated exposure to the same vaccine. I do not find Dr. Bassiri’s

arguments regarding the rarity of this occurrence to be equivalent to an explanation of the

improbability of this type of occurrence. In fact, Petitioner’s expert also conceded that this

occurrence is rare, and he has not seen it throughout the course of his career in ophthalmology.

However, such concessions do not weaken Petitioner’s argument under Althen prong one. Indeed,

by the nature of the Program, a petitioner’s claims often arise out of the rarest and most unique of

circumstances. As absolute certainty is not the standard in the Program, I find that Petitioner has

presented preponderant evidence establishing that a flu vaccine can trigger HSV through a positive

rechallenge. See Althen, 418 F.3d at 1278–81; see also Moberly, 592 F.3d at 1322 (finding

scientific and “objective confirmation” of the medical theory with additional medical

documentation is unnecessary.). Accordingly, I find Petitioner has satisfied prong one of Althen

with respect to HSV and herpes keratitis.

D. Althen Prong Two

Under the second prong of Althen, a petitioner must prove that the vaccine actually did

cause the alleged injury in a particular case. See Pafford, 2004 WL 1717359, at *4; Althen, 418

F.3d at 1279. 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;

Capizzano, 440 F.3d at 1326; Grant v. Sec’y of Health & Hum. Servs., 956 F.2d 1144, 1148 (Fed.

Cir. 1992). A petitioner does not meet this obligation by showing only a temporal association

between the vaccination and the injury; instead, the petitioner “must explain how and why the

injury occurred.” Pafford, 2004 WL 1717359, at *4 (emphasis in original). The special master in

Pafford noted petitioners “must prove [] both that her vaccinations were a substantial factor in

causing the illness . . . and that the harm would not have occurred in the absence of the

vaccination.” 2004 WL 1717359, at *4 (citing Shyface, 165 F.3d at 1352). A reputable medical or

scientific explanation must support this logical sequence of cause and effect. Hodges v. Sec’y of

Health & Hum. Servs., 9 F.3d 958, 961 (Fed Cir. 1993) (citation omitted). Nevertheless,

“[r]equiring epidemiologic studies . . . or general acceptance in the scientific or medical

communities . . . impermissibly raises a claimant’s burden under the Vaccine Act and hinders the

system created by Congress . . . .” Capizzano, 440 F.3d at 1325–26. “[C]lose calls regarding

causation are resolved in favor of injured claimants.” Althen, 418 F.3d at 1280.

In Program cases, contemporaneous medical records and the opinions of treating

physicians are favored. Capizzano, 440 F.3d at 1326 (citing Althen, 418 F.3d at 1280). Indeed,

when reviewing the record, a special master must consider the opinions of treating physicians.

Capizzano, 440 F.3d at 1326. This is because “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.’” Id. In addition, “[m]edical records, in general, warrant

consideration as trustworthy evidence. The records contain information supplied to or by health

professionals to facilitate diagnosis and treatment of medical conditions. With proper treatment

hanging in the balance, accuracy has an extra premium. These records are also generally

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