The novel severe acute respiratory syndrome coronavirus 2, which causes a syndrome known as coronavirus 2019 (COVID-19), has been designated a global pandemic by the World Health Organization.1 The vast majority of patients with COVID-19 are advised to isolate and recuperate at home. The stay-at-home restrictions and limited access to ambulatory ophthalmology care inadvertently may delay the recognition of ocular signs and symptoms associated with COVID-19.
Currently, we have minimal data on the incidence and severity of ocular manifestations of nonhospitalized COVID-19–positive patients. Characterizing ocular manifestations in this cohort will help ophthalmologists learn how, if at all, this virus affects the eye in an ambulatory population. To answer these questions, an electronic Research Electronic Data Capture (REDCap)2 , 3 survey was developed (Appendix 1, available at www.aaojournal.org), and distributed to participants of the COVID Volunteer Research database, which was created by the Vanderbilt Institute for Clinical and Translational Research. Every adult who underwent testing for COVID-19 at one of Vanderbilt University Medical Center’s walk-in locations was provided the opportunity to volunteer to participate in future research studies. Patients were tested either because of COVID-19–like symptoms or because they were at risk for occupational reasons or after exposure to an affected person. The database is maintained at a central secure location, and the survey was approved exempt by the institutional review board/ethics committee of Vanderbilt University Medical Center. The study was performed in accordance with the tenets of the Declaration of Helsinki. Study data were collected and managed using REDCap2 , 3 tools hosted at Vanderbilt University Medical Center. The survey questionnaire was sent to participants independent of their COVID-19 test results. Basic demographic questions as well as underlying medical and ocular history were investigated. Allergy questions were added to tease out seasonal ocular and systemic symptoms that are common in the middle Tennessee region and may be mistaken for COVID-19 during the pandemic. Descriptive statistics were performed for this analysis.
The survey was distributed to approximately 1100 eligible persons who had provided written informed consent. Participants responded to the survey 1 to 4 weeks after receiving the results of their COVID-19 testing. A total of 458 surveys were completed during the study period. Eight surveys were removed from the analysis because of incomplete or missing data. Of the remaining 450 surveys, 144 (32.0%) were completed by persons showing positive results for COVID-19, and 306 (68.0%) were completed by persons showing negative results for COVID-19 (Table S1, available at www.aaojournal.org).
Among COVID-19–positive patients, the most common nonocular symptoms experienced were muscle aches or weakness (77.1%), cough (74.3%), headache (73.6%), loss of smell or taste (69.4%), and fever (68.1%). Other than the loss of smell or taste, these symptoms were experienced at a similar rate in respondents showing negative results for COVID-19, which is not surprising because they underwent testing as a result of the presence of flu-like symptoms (Table S2, available at www.aaojournal.org).
Approximately 47% (68/144) of COVID-19–positive patients reported at least 1 overlapping eye-related symptom. The most commonly reported ocular symptoms in survey respondents showing positive results for COVID-19 were eye pain (19.4%), photophobia (13.9%), flashes or floaters (11.8%), blurry vision (11.1%), and red eyes (10.4%). Only 20.6% (14/68) noted ocular symptoms before systemic symptoms, with 26.5% (18/68) of respondents still experiencing persistent eye symptoms despite recovery from systemic illness. Notably, 54% (164/306) of COVID-19–negative patients reported at least 1 ocular symptom. No statistically significant differences were found favoring these symptoms in COVID-19–positive patients compared with COVID-19–negative patients in our cohort. Red eye (21.9%) and excessive tearing (17.6%) were found at a significantly higher rate in COVID-19–negative survey respondents (Table 1 ). Similarly, 15.2% (25/164) noted ocular symptoms before systemic symptoms, with 23.2% of respondents (38/164) still experiencing persistent eye symptoms despite recovery from systemic illness, which was not statistically different from the COVID-19–positive cohort. Although more than 50% of the entire surveyed cohort reported some history of environmental allergy, no statistically significant difference was found between COVID-19–positive patients (53.5%) and COVID-19–negative patients (54.9%; Table S3, available at www.aaojournal.org).
Table 1.
Ocular Symptoms Experienced by Patients Showing Positive and Negative Results for Coronavirus 2019
| Symptom | Positive Results, No. (%) | Negative Results, No. (%) | Odds Ratio | P Value |
|---|---|---|---|---|
| Red eyes | 15 (10.4) | 67 (21.9) | 0.41 | 0.0024 |
| Eye pain | 28 (19.4) | 56 (18.3) | 1.08 | 0.8186 |
| Epiphora | 10 (6.9) | 54 (17.6) | 0.35 | 0.0016 |
| Photophobia | 20 (13.9) | 60 (19.6) | 0.66 | 0.147 |
| Blurry vision | 16 (11.1) | 39 (12.7) | 0.86 | 0.7287 |
| Diplopia | 2 (1.4) | 5 (1.6) | 0.85 | 0.8264 |
| Flashes or floaters | 17 (11.8) | 33 (10.8) | 1.11 | 0.7017 |
| Scotoma | 2 (1.4) | 7 (2.3) | 0.60 | 0.5189 |
| Tunnel vision | 5 (3.5) | 7 (2.3) | 1.54 | 0.4765 |
| Flickering lights | 3 (2.1) | 5 (1.6) | 1.28 | 0.7505 |
| Other | 8 (5.6) | 29 (9.5) | 0.56 | 0.1524 |
To date, the reports on ocular findings have been limited. Conjunctivitis4 has been reported; however, recent reports show a low prevalence of conjunctivitis and chemosis in COVID-19–hospitalized patients.5 , 6 OCT and retinal findings of 12 adult patients from São Paulo, Brazil, described cotton-wool spots and microhemorrhages, suggesting ischemic changes in the papillomacular bundle with no signs of intraocular inflammation.7 As clinics start to reopen, we must anticipate the ocular conditions that could represent either direct end-organ damage resulting from COVID-19 infection or sequelae after cytokine release, thromboembolic phenomena, or secondary ischemic events.
In our cohort, the most common symptoms experienced were red eye, photophobia, epiphora, and eye pain. Interestingly, some of these symptoms were more likely to be noted among COVID-19–negative patients rather than COVID-19–positive patients. Although it is important to take all necessary precautions, we hope these data will reassure patients and physicians that every red eye is not necessarily a sign of COVID-19. To elucidate further why several patients may have red eyes and seemingly allergic ocular symptoms, we explored the history of drug and environmental allergies among cohorts. The COVID-19–negative patients showed higher rates of self-reported drug allergies; this is of unclear clinical significance.
This analysis has several limitations. The analysis is based on patient reports, and therefore is subject to recall bias and selection bias. We received responses from 458 of more than 1000 participants, which may suggest patients with ocular symptoms were more likely to respond to a study about ocular associations with COVID-19. The study was conducted in an urban setting where the prevalence of COVID-19 was higher than in surrounding counties, and our respondents were predominantly white. The strengths of the study are the large number of responses from patients who were not hospitalized, which is more than 80% of affected COVID-19 patients.
In conclusion, this retrospective patient survey found no association between ocular symptoms and COVID-19 positivity in an outpatient population.
Footnotes
Financial Disclosure(s): The author(s) have made the following disclosure(s): S.N.P.: Financial support – Alcon
Supported by the National Center for Advancing Translational Sciences, the National Institutes of Health, Bethesda, Maryland (grant no.: UL1 TR000445); Research to Prevent Blindness, Inc., New York, New York (unrestricted grant to the Vanderbilt Eye Institute); and a Research to Prevent Blindness and American Academy of Ophthalmology (San Francisco, California) Intelligent Research in Sight Registry grant (S.S.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The sponsor or funding organization had no role in the design or conduct of this research.
HUMAN SUBJECTS: Human subjects were included in this study. The human ethics committees at Vanderbilt University Medical Center approved the study. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.
No animal subjects were included in this study.
Author Contributions:
Conception and design: Gangaputra, Patel
Analysis and interpretation: Gangaputra, Patel
Data collection: Gangaputra, Patel
Obtained funding: National Center for Advancing Translational Sciences, the National Institutes of Health; Research to Prevent Blindness, Inc.; American Academy of Ophthalmology
Overall responsibility: Gangaputra, Patel
Supplementary Data
References
- 1.Cucinotta D., Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed. 2020;91:157–160. doi: 10.23750/abm.v91i1.9397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Harris P.A., Taylor R., Thielke R. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381. doi: 10.1016/j.jbi.2008.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019; Jul;95:103208. https://doi.org/10.1016/j.jbi.2019.103208. Epub 2019 May 9. [DOI] [PMC free article] [PubMed]
- 4.Cheema M, Aghazadeh H, Nazarali S, et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19). Can J Ophthalmol. 2020; Apr 2;S0008-4182(20)30305-7. https://doi.org/10.1016/j.jcjo.2020.03.003. Online ahead of print. [DOI] [PMC free article] [PubMed]
- 5.Guan W.J., Ni Z.Y., Hu Y. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Zhou Y., Duan C., Zeng Y. Ocular findings and proportion with conjunctival SARS-COV-2 in COVID-19 patients. Ophthalmology. 2020;127(7):982–983. doi: 10.1016/j.ophtha.2020.04.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Marinho P.M., Marcos A.A.A., Romano A.C. Retinal findings in patients with COVID-19. Lancet. 2020;395(10237):1610. doi: 10.1016/S0140-6736(20)31014-X. 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.