We read with great interest the study by Hsia et al.¹ regarding the risk assessment of uveitis after COVID-diagnosis. We appreciate the authors' attention to detail by eliminating possible confounding variables that may contribute to uveitis development. Furthermore, we were impressed by the robust study design incorporating propensity score matching, long follow-ups, and immense study size of more than 4 million patients using the TriNetX analytics platform.

Nevertheless, to enhance this study, we recommend the following considerations.

First, this study utilized the US research network, covering about 92 million patients to form a COVID-19 cohort and a non-COVID-19 control group, each with 2 million patients, of which 62.5% and 62.4% were white, respectively. However, this underrepresents the white population by 13% compared to the 75.5% white representation in the 2022 US census and thereby overrepresents racial minorities. This important limitation should be heeded as there are disparities in vision health access among different ethnic groups in the United States.² The study by Elam et al.² found that unemployed individuals have been associated with higher incidences of visual impairment, disproportionately burdening racially minoritized populations. Therefore, with the underrepresentation of the white population and overrepresentation of racial minorities in this study, uveitis cases in the United States could be skewed. Future studies should align the racial composition of study groups more closely with national demographics.

Second, the authors identified COVID-19 cases based on positive PCR tests or antibody immunoassays. Yet, Binny et al.'s study in New Zealand illustrates how PCR test sensitivity fluctuates across the COVID-19 infection timeline, influenced by viral load and patient age.³ The sensitivity of PCR tests peaks at 92.7% between 4 and 5 days postinfection, then drops to 88% from 5 to 14 days, while specificity remains near 100%.³ This indicates a higher likelihood of false negatives and very low false positives in PCR testing. Highlighting this significant limitation in the discussion section would be beneficial.

Third, this study excluded those diagnosed with uveitis within 6 months before COVID-19 infection, potentially overlooking undiagnosed, self-limiting cases that may resurface postinfection. Studies reported that 10% of cases of intermediate uveitis resolve spontaneously, and although anterior uveitis tends to be self-limiting, it can give rise to severe complications.^{4, 5} Additionally, uveitis relapses, as documented in Grunwald et al.'s research, might occur independently of COVID-19.⁶ This can lead to incorrect attribution of such cases to COVID-19. However, differentiating between uveitis cases with a COVID-19-related cause and those without has proven to be a challenging task. Currently, there is a shortage of medical literature that comprehensively explains the pathophysiology of uveitis in patients with COVID-19. An intriguing perspective on this matter is presented in a 2020 article by Hung et al.⁷ Instead of suggesting that COVID-19 increases the risk of uveitis development, Hung et al.⁷ proposed that uveitis may predispose patients to COVID-19. This is because individuals with uveitis often receive systemic immunosuppressants to manage their ocular symptoms, potentially leading to a weakened immune response and an elevated susceptibility to contracting COVID-19. Moreover, their frequent visits to outpatient facilities could increase contact with COVID. Further research into the pathophysiology of uveitis in COVID-19 patients could prove beneficial in distinguishing uveitis cases with an underlying COVID-19 cause from those without, potentially enhancing the quality of future studies on this topic.

In conclusion, the study by Hsia et al.¹ is a major milestone toward incorporating uveitis assessment among COVID-19 patients in healthcare guidelines. This study has tremendous potential to save numerous patients from glaucoma, cataracts, and permanent vision loss. To improve this study, we recommend authors to adjust study groups so that white patients are adequately represented, discuss the possibility of false negatives from PCR testing, and consider cases of self-limiting uveitis and relapses independent of COVID-19.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.