Small fiber neuropathy in the cornea of Covid-19 patients associated with the generation of ocular surface disease

Abstract

Purpose: To describe the association between Sars-CoV-2 infection and small fiber neuropathy in the cornea identified by in vivo corneal confocal microscopy.

Methods: Twenty-three patients who had overcome COVID-19 were recruited to this observational retrospective study. Forty-six uninfected volunteers were also recruited and studied as a control group. All subjects were examined under in vivo confocal microscopy to obtain images of corneal subbasal nerve fibers in order to study the presence of neuroma-like structures, axonal beadings and dendritic cells. The Ocular Surface Disease Index (OSDI) questionnaire and Schirmer tear test were used as indicators of Dry Eye Disease (DED) and ocular surface pathology.

Results: Twenty-one patients (91.31%) presented alterations of the corneal subbasal plexus and corneal tissue consistent with small fiber neuropathy. Images from healthy subjects did not indicate significant nerve fiber or corneal tissue damage. Eight patients reported increased sensations of ocular dryness after COVID-19 infection and had positive DED indicators. Beaded axons were found in 82.60% of cases, mainly in patients reporting ocular irritation symptoms. Neuroma-like images were found in 65.22% patients, more frequently in those with OSDI scores >13. Dendritic cells were found in 69.56% of patients and were more frequent in younger asymptomatic patients. The presence of morphological alterations in patients up to 10 months after recovering from Sars-CoV-2 infection points to the chronic nature of the neuropathy.

Conclusions: Sars-CoV-2 infection may be inducing small fiber neuropathy in the ocular surface, sharing symptomatology and morphological landmarks with DED and diabetic neuropathy.

Keywords: COVID-19; Corneal neuropathy; Dry eye disease; In vivo confocal microscopy.

Fig. 1

Results of the ACCMetrics automatic quantification of subbasal plexus of patients that have overcome COVID-19 infection compared with healthy corneas. Significant differences are represented with asterisks (* = p < 0.05; ** = p < 0.01).

Fig. 2

IVCM captures from healthy subjects and patients that have overcome COVID19 infection, showing typical morphological signs of small fiber neuropathy.

Fig. 3

Results of the quantification of morphological signs of small fiber neuropathy (neuroma, beaded axons and dendritic cells) found in patients that have overcome COVID-19 infection and in healthy controls. In A we show the percentage of signs of lesions at the basal level of the corneal epithelium in groups of age. In B, C, and D, we show the comparison between the amount of neuroma, beaded axons or DC in post-COVID-19 patients and in healthy subjects. Significant differences are represented with asterisks (* = p < 0.05; ** = p < 0.01).

Fig. 4

Summary of results of ocular surface IVCM biomarkers and DED symptoms developed after COVID-19 infection. In A, OSDI Scores before and after COVID19 infection (Pt = patient). In B, we show the distribution of IVCM biomarkers (neuroma, beaded axons or DC) attending to DED symptoms severity (OSDI scores). In C, we show the proportion of post-COVID-19 patients as a function of DED severity.

Fig. 5

Proportion of IVCM morphological biomarkers related with the time elapsed from RT-PCR COVID-19 positive diagnosis and ophthalmological examination.