Coronavirus invaded multiple Ocular cell types and caused a variety of pathologic changes but, surprisingly, no inflammation, a small autopsy study showed.

Ocular tissue from patients who had COVID-19 at autopsy showed that the SARS-CoV-2 spike RNA localized in neuronal cells of the retina, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the Optic Nerve. Common pathologic changes associated with coronavirus infection included cytoid bodies, vascular changes, and retinal edema.

The study was the first to demonstrate presence of the virus in multiple ocular cell types by means of in-situ hybridization (ISH), which validated previous studies that relied exclusively on polymerase chain reaction (PCR)-based methods, reported Daniel S. Chertow, MD, MPH, of the National Institute of Allergy and Infectious Diseases, and co-authors in the American Journal of Pathology.

“What was surprising was the absence of inflammation, contrasting with what we have seen in other viral infections of the Eye such as herpesvirus, where infection is typically associated with significant inflammation and tissue damage,” Chertow said in a statement from the journal. “This study shows important new insights into SARS-CoV-2 ocular pathogenesis. Specifically, this is the first report to definitively localize SARS-CoV-2 to the retinal inner and outer nuclear cells, retinal ganglion cells, and ocular surface by ISH.”

The research highlights the eye as a potential target of coronavirus infection and supports further study to evaluate short- or longer-term ocular effects of COVID-19, he added.

“This research is interesting in that it shows that the majority of people who passed away from COVID-19 had some evidence of the virus in their eyes – either the presence of virus itself in a minority – or the presence of viral RNA,” said Sonal Tuli, MD, of the University of Florida in Gainesville and spokesperson for the American Academy of Ophthalmology. “They address the lack of inflammation, as most of the changes they saw were related to the indirect effects of the virus, such as blood clots and leakage from the blood vessels, rather than inflammation due to the tissues getting infected by the virus. That is another interesting finding. In addition, I would suspect that most were on steroids at the time they passed away so any inflammation, if present, would be suppressed.”

Studies have shown that SARS-CoV-2 infects tissues throughout the body, including ocular tissues and fluids. In a previous study, investigators found viral nucleocapsid (n) RNA in ocular fluids or tissue in autopsy cases of 23 of 38 patients who had COVID-19. By means of PCR techniques, viral RNA was detected in the cornea, choroid/sclera, lens, retina, optic nerve, vitreous humor, and aqueous humor in 14-59% of cases.

Despite prior studies, information about cellular localization of SARS-CoV-2 remained limited, Chertow and co-authors noted. Viral particle localization in specific ocular cells can provide information about the ocular effects of viral infection. Toward that end, the authors re-examined a subgroup of eyes from the prior autopsy study. The objectives were to evaluate macroscopic and microscopic histopathology and cellular localization by ISH analysis of SARS-CoV-2 spike gene RNA.

The study involved eyes from 25 patients. Ocular tissue from four patients was evaluated by ISH to characterize cellular location of the spike gene RNA. Eyes from the remaining 21 patients were examined by histopathology.

Investigators identified potential COVID-19-associated macroscopic lesions in the retina in six of 21 eyes. Microscopic examination revealed small neovascularization, retinal sclerotic vessels, retinal vascular occlusion with fibrin/thrombi in retinal vessels, and vitreous hemorrhages. Eleven eyes contained cytoid bodies in the nerve fiber layer of the neuroretina and/or optic nerve head. Seven eyes had focal loss of photoreceptor cells, and 14 eyes exhibited retinal/choroidal vascular dilation, congestion, and tortuosity.

Six eyes had serous retinal edema in the inner and outer nuclear layers, and five eyes had optic nerve head edema. Two eyes had fluid accumulation in the outer plexiform layer. Evidence of inflammation was limited to one eye with mild lymphocyte infiltration on the optic nerve and one eye with minimal choroidal monocytic inflammation.