Ocular Symptoms among Nonhospitalized Patients Who Underwent COVID-19 Testing
Authors: Sapna S. Gangaputra, Shriji N. Patel
Journal: Ophthalmology (2020)

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.1Cucinotta D. Vanelli M. WHO declares COVID-19 a pandemic.Acta Biomed. 2020; 91: 157-160PubMed Google Scholar 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)2Harris P.A. Taylor R. Thielke R. et al.Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.J Biomed Inform. 2009; 42: 377-381Crossref PubMed Scopus (30677) Google Scholar,3Harris 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.Google Scholar 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 REDCap2Harris P.A. Taylor R. Thielke R. et al.Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.J Biomed Inform. 2009; 42: 377-381Crossref PubMed Scopus (30677) Google Scholar,3Harris 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.Google Scholar 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 1Ocular Symptoms Experienced by Patients Showing Positive and Negative Results for Coronavirus 2019SymptomPositive Results, No. (%)Negative Results, No. (%)Odds RatioP ValueRed eyes15 (10.4)67 (21.9)0.410.0024Eye pain28 (19.4)56 (18.3)1.080.8186Epiphora10 (6.9)54 (17.6)0.350.0016Photophobia20 (13.9)60 (19.6)0.660.147Blurry vision16 (11.1)39 (12.7)0.860.7287Diplopia2 (1.4)5 (1.6)0.850.8264Flashes or floaters17 (11.8)33 (10.8)1.110.7017Scotoma2 (1.4)7 (2.3)0.600.5189Tunnel vision5 (3.5)7 (2.3)1.540.4765Flickering lights3 (2.1)5 (1.6)1.280.7505Other8 (5.6)29 (9.5)0.560.1524 Open table in a new tab To date, the reports on ocular findings have been limited. Conjunctivitis4Cheema 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.Google Scholar has been reported; however, recent reports show a low prevalence of conjunctivitis and chemosis in COVID-19–hospitalized patients.5Guan W.J. Ni Z.Y. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (20525) Google Scholar,6Zhou Y. Duan C. Zeng Y. et al.Ocular findings and proportion with conjunctival SARS-COV-2 in COVID-19 patients.Ophthalmology. 2020; 127: 982-983Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar 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.7Marinho P.M. Marcos A.A.A. Romano A.C. et al.Retinal findings in patients with COVID-19.Lancet. 2020; 395 (2020): 1610Abstract Full Text Full Text PDF PubMed Scopus (378) Google Scholar 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. Download .pdf (.11 MB) Help with pdf files Table S1 Download .pdf (.09 MB) Help with pdf files Table S2 Download .pdf (.1 MB) Help with pdf files Table S3 Download .pdf (.04 MB) Help with pdf files Appendix 1