A literature search found that viruses might be identified on the ocular surface through the analysis of conjunctival swabs or Schirmer strips, but studies mainly focused on AdV, HSV and SARS-CoV-2, while other viruses were still not deeply investigated.
Studies that focused on the detection of AdV and HSV were linearly developed over the last 20 years and randomly conducted all over the world. In contrast, in 2020, scientists exponentially published studies on SARS-CoV-2 because the virus was first seen in the last days of 2019; in a few months, the WHO declared its disease as a pandemic, and the world’s research efforts were completely directed to overcoming this pandemic. The evolution of published articles on AdV, HSV and SARS-CoV-2 is represented in Fig. 2.
In contrast to SARS-CoV (54), SARS-CoV-2 RNA was found by RT-PCR in conjunctival swabs (40-48), although samples were collected from a few patients, and only a low and varying percentage of them presented positive results and/or ocular symptoms (46). Most of these studies were developed in China (40, 41, 43, 47), mainly because the country was the first epicenter of the disease. In some cases, ocular manifestations are one of the first symptoms, and because of that, academic societ believes the eye may contribute to the understanding of COVID-19 pathophysiology (6, 7). Recently, new studies proved the presence of in the conjunctiva, limbus, and cornea, with prominent staining in the superficial epithelium surface, key factors for the infection of SARS-CoV-2 in human cells (55). Those results collaborate for the necessity of ocular protection in preventing the spread of viruses.
Research on viral screening was, most of the time, correlated with external ocular symptoms with the purpose of solving clinical doubts between pathogenic agents and of looking after methods for a fast accurate viral diagnosis. Studies on VZV, CMV and EBV were mostly combined with HSV to determine coinfection and differential diagnosis (32-34).
Only one study correlated viral detection on the ocular surface with intraocular symptoms. This study was published in 2000 and aimed to verify the efficacy of intravenous ganciclovir treatment in immunocompromised AIDS patients with CMV retinitis. The results showed a high clinical relevance for confirming and differentiating the diagnoses of CMV retinitis when ophthalmoscopic findings were associated with PCR methods on conjunctival swab samples (49). No other studies on the topic were found in this review, probably because the incidence of CMV retinitis in the Acquired Immunodeficiency Syndrome (AIDS) population significantly decreased with the introduction of effective antiretroviral therapy and early accurate diagnosis (56-59).
The most commonly used method for sample collection was conjunctival swabs. This method also collects conjunctival cells, while Schirmer strips allow only the collection of tears, since fluids pass to the filter paper because of gravity, viscosity, and capillary flow dynamics – the same physical processes that explain how liquids impregnate porous materials differently (60, 61). Consequently, the samples collected represent two different materials: tears, cells and fluids dispersed in the conjunctival sac and tears and substances dissolved in it.
Samples were mainly analyzed by PCR or RT-PCR, depending on the viral genetic material, DNA or RNA, respectively. PCR variations are widely used because they allow the replication and detection of low loads of viral DNA/RNA (62). The point-of-care test was also compared with PCR effectiveness, sensitivity and specificity where high, but this field was only explored in AdV (30), probably because of epidemiological factors related to uncontrolled and fast spread of AdV conjunctivitis (63).
This review included a large number of articles, 36, from many different countries and time periods, fact that collaborated for a broad comprehension of how the detection of viruses on the ocular surface was worldwide studied in the last decades. The results of this article may contribute for future research by clarifying key concepts that might assist the design of future researches on ocular viruses.
In conclusion, viruses can be detected through the analysis of samples collected by Schirmer strips and conjunctival swabs, and studies were generally conducted to understand viral infection, to develop accurate diagnostic methods and to follow patients’ response to treatment. However, this study has some limitations: only three databases were consulted, and new articles on the theme are constantly being published, which might exclude relevant outcomes. Moreover, among the analyzed studies, most were developed on a small number of patients and lacked clear definitions of collection time and viral persistence since the onset of the diseases. Additional studies with larger populations and time permanence are necessary to develop more assertive conclusions on this topic.