Corneal Stroma Analysis and Related Ocular Manifestations in Recovered COVID-19 Patients

The purpose of this study was to assess the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on corneal stroma characteristics, ocular manifestations, and post-recovery refractive surgery outcomes after varying recovery durations.

Fresh corneal lenticules from patients with post-coronavirus disease 2019 (COVID-19; recovered within 135 days) and healthy controls (HCs) after small incision lenticule extraction (SMILE) surgery were obtained for experimental validation of SARS-CoV-2 susceptibility, morphological changes, and immune response of the corneal stroma. Corneal optical density (CD) was measured using the Pentacam HR. Corneal epithelium thickness (ET) and endothelium parameters were evaluated by wide-field optical coherence tomography (OCT) and non-contact specular microscopy (SP-1P), respectively. All the patients were assessed after SMILE surgery until 3 month of follow-up.

The cornea was susceptible to SARS-CoV-2 with the presence of SARS-CoV-2 receptors (CD147 and ACE2) and spike protein remnants (4 out of 58) in post-recovery corneal lenticules. Moreover, SARS-CoV-2 infection triggered immune responses in the corneal stroma, with elevated IL-6 levels observed between 45 and 75 days post-recovery, which were then lower at around day 105. Concurrently, corneal mid-stromal nerve length and branching were initially higher in the 60D to 75D group and returned to control levels by day 135. A similar trend was observed in CD within zones 0 to 2 and 2 to 6 and in the hexagonal cells (HEX) ratio in endothelial cells, whereas ET remained consistent. Notably, these changes did not affect the efficacy, safety, or predictability of post-recovery SMILE surgery.

SARS-CoV-2 induces temporal alterations in corneal stromal morphology and function post-recovery. These findings provided a theoretical basis for corneal health and refractive surgery management in the post-COVID-19 milieu.