Updates on Covid and the Eyes by Dr. Sandra Lora Cremers VISIONARY EYE DOCTORS

1. Sandra Lora Cremers MD, FACS,1,2
Helen Molteni,1,3
Eyedoc2020@blogspot.com
cell/text: 443-535-2268; drcremers@voeyedr.com
1Department of Research, Visionary Eye Doctors, Rockville, MD.
2Department of Ophthalmology, Johns Hopkins Medicine.
3College of Arts and Sciences, Case Western Reserve University.
COVID-19, the Eye, and the Ocular Surface
November 10, 2020

2. The authors have no financial
interests to disclose.

3. https://www.nbcwashington.com/news/local/face-masks-can-cause-dry-eyes-doctors-say-heres-how-to-get-relief/2461850/

4. Purpose:
● To discuss COVID-19’s chance of entering through the eye
● To discuss eye symptoms and signs of COVID-19
● Discuss Dry Eye Disease as Risk for COVID-19 ocular entry

5. Ophthalmologist Dr. Li died of COVID-19 February 7, 2020.
He contracted virus while treating a glaucoma patient who was asymptomatic.
He tried to warn the medical community about COVID-19.

6. COVID-19 Background:
● COVID-19 is the name of the “novel coronavirus” disease
● SARS-CoV-2 is the name of the virus that causes COVID-19
● Coronaviruses cause mild respiratory illnesses
○ Common cold
○ Severe Acute Respiratory Syndrome (SARS)
○ Middle East Respiratory Syndrome (MERS)
● Emerged from Hubei Province, China in December 2019

7. Can COVID-19 Enter Through Eye:
● Yes
● The conjunctiva has ACE2 on its surface so that the
coronavirus can latch onto it and gain entry into the cells
● Risk: unclear
● Edward E. Manche, MD, a professor of ophthalmology
at Stanford University Medical School: eyes are “the
least common mode of transmission.”

8. Does Daily Wear of Eyeglasses Decrease Risk
of COVID-19? Need more proof.
• Study cohort consisted of 276 patients hospitalized with COVID-19
in Suizhou, China
• Proportion of patients who reported they wore glasses for at least
8 hours/day was 5.8%, a sharp contrast to the 31.5% of glasses
wearers in the local population
• This significant discrepancy suggests that eyeglasses may reduce
susceptibility to COVID-19, perhaps because they act as a physical
barrier to the airborne virus
• Due to the small sample size, further studies are needed to better
establish a correlation between eyewear and the risk of SARS-CoV-
2
Reference: Zeng W, Wang X, Li J, et al. Association of daily wear of eyeglasses and susceptibility to coronavirus disease 2019 infection. JAMA Ophthalmology. 2020.

9. Eye Symptoms and Signs of COVID-19:
Case Report A: 15 COVID-19 patients with Eye Symptoms
● Recent study (Hong, et.al): 56 confirmed COVID-19 patients (24 to 68 years old)
● Fifteen subjects (27%) reported ocular symptoms in the course of COVID-19
○ conjunctivitis
○ sore eyes
○ itching
○ foreign body sensation
○ tearing
○ redness,
○ dry eyes,
○ eye secretions
○ floaters

10. Eye Symptoms and Signs of COVID-19 (continued):
● Among them, 6 (11%) presented with ocular symptoms BEFORE onset of fever or
respiratory symptoms.
○ Of these six subjects, 4 reported the appearance of ocular symptoms 1-7 days
BEFORE the onset of fever or respiratory symptoms, while the remaining two
subjects were uncertain about when their ocular symptoms appeared.
○ 2 subjects developed conjunctivitis AFTER hospitalization
○ 1 of 2 had conjunctival swab samples showed positive virus RNA detection.
● Conclusion: For most coronavirus infections, clinically significant conjunctivitis is
RARELY present. The SARS-CoV-2 was found to infect the mucosa membrane
epithelium and lymphocytes, which are both abundant in ocular surface tissue.
Reference:
1. Hong N, Yu W, Xia J, et al. Evaluation of ocular symptoms and tropism of SARS-CoV-2 in patients confirmed with COVID-19. Acta Ophthalmol. April 26, 2020

11. Case Report B:
Conjunctivitis as a COVID-19 Symptom
• March 1: 29-year-old patient presented the following symptoms after a vacation
to the Philippines: rhinorrhea, cough, nasal congestion, and right eye
conjunctivitis
• Patient was started on oral valacyclovir 500 mg PO TID and moxifloxacin 1
drop QID to the right eye based on a presumed diagnosis of herpetic
keratoconjunctivitis
• Conjunctival irritation, pain, and redness worsened over the next several days,
accompanied by a decline in vision (20/40)]
• Nasal swab test administered on March 8 revealed positive detection of SARS-
CoV-2
• Eye swap from March 6 also indicated presence of SARS-CoV-2
Reference: Cheema, M., Aghazadeh, H., Nazarali, S., et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19). Canadian Journal of Ophthalmology, 2020;45(4), 125-129.

12. Reference: Cheema, M., Aghazadeh, H., Nazarali, S., et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus
disease 2019 (COVID-19). Canadian Journal of Ophthalmology, 2020;45(4), 125-129.
Progression of corneal lesions found from subsequent slit lamp examinations from March 3 to March 6, as
represented in the above visual representations.

13. Reference: Cheema, M., Aghazadeh, H., Nazarali, S., et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus
disease 2019 (COVID-19). Canadian Journal of Ophthalmology, 2020;45(4), 125-129.
Image: Fluorescein
staining, revealing
conjunctivitis of right eye.
Photo was taken 1 day
after the patient returned
from a vacation to the
Philippines.

14. Reference: Cheema, M., Aghazadeh, H., Nazarali, S., et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus
disease 2019 (COVID-19). Canadian Journal of Ophthalmology, 2020;45(4), 125-129.
Image: Conjunctival
injection and aqueous
discharge present in
patient’s right eye.
Photo was taken prior to
the patient’s second
visit to the clinic on
March 5.

15. • 48-year-old COVID-positive female exhibited mild
conjunctival injection of the left eye
• After 4 days, the patient noted minimal
improvement in her left eye, as well as pain and
foreign body sensations that had developed in
the right eye
• Videoconference appointment revealed mild
conjunctival injection and an irregular light reflex
off the palpebral of the inferior of both eyes,
with greater diffuse injection in the right eye
Case Report C:
Conjunctivitis as a COVID-19 Symptom
Reference: Pandit, R. T. The eyes offer conjunctival clue to COVID-19.
Ophthalmology Times, 2020;45(12), 1-16.

16. Is Dry Eye Disease (Ocular Surface Disease) a Risk for COVID-
19 Ocular Entry?
● Likely Yes, but no published proof as of yet with COVID-19
● What we know:
○ In dry eye, a chronic, sometimes subclinical inflammatory reaction is occuring on ocular surface
○ Accumulations of inflammatory molecules at the ocular surface of dry eye patients + stagnant tear film
+decreased level of mucins, can lead to destruction of epithelial tight junctions, and result in sloughing
of the ocular surface epithelia.
○ This results in dye staining of the cornea and conjunctiva.
○ Epithelial anatomy (tight junctions, in particular) is one of several so-called innate immune response
mechanisms that play a crucial role in preventing invasion of microorganisms into the ocular surface.

17. Is Dry Eye Disease a Risk for COVID-19 Ocular Entry?
(continued)
● Innate responses are the first line of defense against infection, responding immediately
○ Mucous membranes (eg, conjunctiva),
○ secreted proteins (eg, lysozyme),
○ mechanical barriers (eg, closure of eyelids) However, if these mechanisms are overwhelmed and/or can
be circumvented, then an organism can take hold, requiring activation and participation of the adaptive
immune system for effective elimination of the pathogen.
● Adaptive immunity: acquired when encounter a specific antigen (eg, microbial/viral/bacterial proteins,
allergens)
○ Demonstrates memory for future encounters as well as specificity to antigens
○ Triggered by innate antigen-presenting cells, such as dendritic cells, and involves activity of various subsets of T lymphocytes and antibody-producing B lymphocytes, which
facilitate pathogen removal and disease resolution.

18. Is Dry Eye Disease a Risk for COVID-19 Ocular
Entry? (continued)
● Autoimmune disease is a risk factor for corneal infection
● Contact Lens is a risk factor for corneal infections
● Intuitively, it makes sense that DED is a risk factor for
viral/bacterial entry.
● Surprisingly, however, there is insufficient
evidence to strongly suggest that a typical
dry eye patient will have an increased risk
for microbial keratitis.
Reference:
Narayanan, et. al., Dry Eye Disease and Microbial Keratitis: Is There a Connection? Ocular Surface 2013, April.

19. 1. McDonald M1, Patel DA2, Keith MS3, Snedecor SJ2. Ocul Surf. 2016 Apr;14(2):144-67. doi: 10.1016/j.jtos.2015.11.002. Epub 2015 Dec 28. Economic and Humanistic Burden of Dry Eye Disease in Europe, North
America, and Asia: A Systematic Literature Review.
2. Yu J, Asche CV, Fairchild CJ. The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea 2011;30:379-87
• The economic cost from a payer’s
perspective is US $3.84 billion.1
• DED costs in terms of loss of productivity: US
$5,362 per patient or about $55.4 billion to
the US Society.2
• >16 million ≥18 years have Diagnosed-DED.
• 2.7% prevalence of Diagnosed-DED among
younger adults aged 18–34 years.
Background: Dry Eye Disease

20. 1. McDonald M1, Patel DA2, Keith MS3, Snedecor SJ2. Ocul Surf. 2016 Apr;14(2):144-67. doi: 10.1016/j.jtos.2015.11.002. Epub 2015 Dec 28. Economic and Humanistic Burden of Dry Eye Disease in Europe, North
America, and Asia: A Systematic Literature Review.
2. Yu J, Asche CV, Fairchild CJ. The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea 2011;30:379-87
• The economic cost from a payer’s
perspective is US $3.84 billion.1
• DED costs in terms of loss of productivity: US
$5,362 per patient or about $55.4 billion to
the US Society.2
• >16 million ≥18 years have Diagnosed-DED.
• 2.7% prevalence of Diagnosed-DED among
younger adults aged 18–34 years.
Background: Dry Eye Disease

21. Background:
Dry Eye Treatment
Options

22. Background:
Dry Eye Treatment
Options

24. Does Mask-Wearing really Increase Dry Eye:
Likely YES
But
Increased Electronic Screen Time Use with COVID-19
Lockdowns are a Greater Risk
Reference: Charters, L. (2020, September 2). COVID-19: Masking the issue of dry eye.

25. Does Mask-Wearing really Increase Dry Eye:
• Wearing a loose-fitting mask causes exhaled air to disperse upward over the
surface of the eye
• Increased air flow can expedite tear film evaporation, leading to dry spots on the
ocular surface
• Contact lens wearers, elderly people, and those in professions that require
extensive screen time are most susceptible to developing dry eye or aggravating
existing dry eye
• Rubbing the eyes to relieve dry eye symptoms increases the risk that the virus will
spread to the eyes and face
• The Centre for Ocular Research and Education (CORE) advises people to properly
address dry eye symptoms by using lubricating eye drops, taking breaks from the
computer, and reducing the time spend in air-conditioned rooms
Reference: Charters, L. (2020, September 2). COVID-19: Masking the issue of dry eye.

26. The Future: Is this The New Normal?
• Should we ask patients to self-
administer vital stains such as a
fluorescein and lissamine green (see
Figure 1) and send us high-definition
pictures to aid diagnosis?
Figure 1: Lissamine green staining test, courtesy of Stefano Barabino, Professor of
Ophthalmology and Head of the Ocular Surface Center at the Sacco Hospital, Milan, Italy.Reference: Santen Pharmaceuticals. (2020, September 16). COVID-19 and Dry Eye
Disease. Retrieved from https://theophthalmologist.com/covid-19-and-dry-eye-disease

27. Call or Text me with any
questions:
cell/text: 443-535-2268;
drcremers@voeyedr.com
Eyedoc2020@blogspot.co
m
THANK YOU for YOUR
ATTENTION!

28. References
1. Mcdonald M, Patel DA, Keith MS, Snedecor SJ. Economic and Humanistic Burden of Dry Eye Disease in Europe, North
America, and Asia: A Systematic Literature Review. The Ocular Surface. 2016;14(2):144-167.
2. Yu J, Asche CV, Fairchild CJ. The Economic Burden of Dry Eye Disease in the United States: A Decision Tree Analysis.
Cornea. 2011;30(4):379-387.
3. Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States
Among Adults Aged 18 Years and Older. American Journal of Ophthalmology. 2017;182:90-98.
4. Avila MY. Restoration of Human Lacrimal Function Following Platelet-Rich Plasma Injection. Cornea. 2014;33(1):18-21.
5. Fernandes G, Yang S. Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering.
Bone Research. 2016;4(1).
6. Zeng W, Wang X, Li J, et al. Association of daily wear of eyeglasses and susceptibility to coronavirus disease 2019
infection. JAMA Ophthalmology. 2020.

29. References
1. Seah IYJ, Anderson DE, Kang AEZ, et al. Assessing viral shedding and infectivity of tears in coronavirus disease 2019 (COVID-19) patients.
Ophthalmology. Published online March 24, 2020. doi:10.1016/j.ophtha.2020.03.026
2. Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J Med
Virol. 2020;92(6):589-594. doi:10.1002/jmv.25725
3. Chen L, Liu M, Zhang Z, et al. Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease. Br J Ophthalmol.
2020;104(6):748-751. doi:10.1136/bjophthalmol-2020-316304
4. Seah I, Agrawal R. Can the coronavirus disease 2019 (COVID-19) affect the eyes? a review of coronaviruses and ocular implications in humans
and animals. Ocul Immunol Inflamm. 2020;28(3):391-395. doi:10.1080/09273948.2020.1738501
5. Li JPO, Lam DSC, Chen Y, Ting DSW. Novel coronavirus disease 2019 (COVID-19): the importance of recognising possible early ocular
manifestation and using protective eyewear. Br J Ophthalmol. 2020;104:297-298. doi: 10.1136/bjophthalmol-2020-315994.
6. Slides: Dr. Amrapali Bobade Veer
REFERENCES:

30. Acknowledgements
● Helen Molteni 1, 2
1Dept of Research, Visionary Eye Doctors, Rockville, MD. 2College of Arts and Sciences, Case Western Reserve University, Cleveland, OH.