In Vivo Confocal Microscopy Features In Post COVID19 Fungal Endophthalmitis In Type 2 Diabetes

Introduction: Corona virus disease-19 (COVID-19) infection with aggressive treatment has resulted in immunosuppression, and co-existing comorbidities that have made patients vulnerable to secondary infections including fungal infections. Purpose: We describe the clinical presentation, various diagnostic methods including in-vivo confocal microscopy features, management and clinical outcomes in Post COVID-19 fungal endophthalmitis in type II diabetics. Methods: Prospective, interventional study on two patients who recovered from COVID-19 who developed endogenous endophthalmitis presented to a tertiary eye care centre in South India. Results: Fungal infection was diagnosed based on clinical features, confocal microscopy, molecular diagnostic methods and culture methods. Two patients were treated with topical, intravitreal and systemic antifungal therapy. Conclusion: We report for the rst time two cases of post COVID-19 fungal endophthalmitis in two diabetic patients with confocal features. High index of suspicion, early diagnosis, and appropriate management can improve the visual outcome in post COVID-19 fungal endophthalmitis cases.

) He was started on oral antibiotics with weekly tapering dose of oral steroids and oral albendazole. His clinical condition did not improve with above medications and he was referred to us for second opinion.
On examination, Best corrected visual acuity (BCVA) in RE 20/20 and in LE 20/32. Intraocular pressure (IOP) was normal in both eyes. Examination of the right eye was normal. Slit lamp biomicroscopic examination of the LE revealed grade 1 nasal pterygium, spheroidal degeneration on the nasal interpalpebral cornea, diffuse pigmented keratic precipitates on the corneal endothelium ( Figure 1a ( Table 1) with his abnormal CT scan of the chest ndings. ( Table 2) Confocal microscopy was done to scan the cornea using by the HRT II Rostock Cornea Module (Heidelberg Engineering GmbH, Heidelberg, Germany). In vivo confocal microscopy (IVCM) revealed signi cant decrease in the sub basal corneal nerve plexus, activated keratocytes in the stroma with highly re ective ovoid shaped cells were present in the in the corneal endothelium suggestive of candida yeast like structure (Figure 1c). Patient underwent anterior chamber paracentesis in the LE and the aqueous humor was analysed for gram stain, Potassium hydroxide (KOH) mount and PCR for panfungal genome, eubacterial genome and SARS CoV-2. Patient received intravitreal

Case 2
A 37 year Asian Indian male, with a recent history of severe COVID-19 infection two months ago, RT PCR for SARS-COV-2 was positive from the nasopharyngeal swab for which he was admitted for 1 week and he was treated with oral steroids 40mg in tapering doses, T.Favipiravir 1800mg BD rst day followed by 800mg BD for next 13 days and T. Ivermectin12 mg OD for 10 days. Ten days later after being diagnosed with COVID-19, he presented with pain, redness and diminution of vision in the LE for which he consulted multiple hospitals and was diagnosed elsewhere with LE panuveitis with hypopyon and investigations done are shown in Table 3 In addition to corneal endothelial changes, we also noticed the presence of dentritic cells with decreased in subbasal corneal nerve plexus in both the cases and this observation correlated well with decreased corneal sensation in the rst case. We did not test corneal sensation in the second case in view of frank endophthalmitis presentation. Decreased corneal sensation could be explained through corneal nerve involvement. It may be neurotrophic effects of SARS-CoV-2 either directly through viral invasion or indirectly with a mediated immune response 22.23 with superadded fungal infection.
In our cases, onset of endogenous endophthalmitis was possibly a sequelae of post COVID-19 infection. Correct diagnosis and aggressive therapy with topical, intravitreal voriconazole , systemic itraconaole with PPV and allied procedures resulted in resolution of infection in both the cases. In the rst case, clinical presentation was similar to immune mediated uveitis, however confocal microscopy helped us to suspect the infective etiology and inspite of the initial microbiological tests being negative from aqueous humor. Subsequently vitreous biopsy specimen con rmed the presence of Candida tropicalis infection.
In Summary, we report two cases of unilateral endogenous fungal endophthalmitis in post COVID-19 infection in type II diabetic Asian Indian males with confocal ndings of the causative organism. Correct diagnosis with appropriate aggressive therapy helped to salvage the vision in this patients. In this report we demonstrated the confocal patterns using IVCM for diagnosis and treatment in endogenous fungal endophtalmitis in post COVID 19 with type 2 diabetes .However future studies are required to explore the use of IVCM in post covid fungal endophthalmitis for the diagnosis and to monitor the therapeutic response to treatment.

Declarations
Ethics committee approval and consent to participate for this study have been obtained.

Competing interests
The authors declare that they have no competing interests and no funding.