**3. Ocular manifestations**

In general, ocular manifestations of COVID-19 are rare. The prevalence of ocular disease is about 11.03% (ranging from 2% to 32%) [4–7].

This data suggest that approximately one out of 10 patients shows at least one ocular symptom.

According to Nasiri et al., the weighted mean between the onset of ocular manifestations and systemic disease was 0.04 days (range, 1–3 days). However, the weighted mean between systemic disease and ocular manifestations was 1.5 days (range, 2–21 days) [5].

The most prevalent ocular manifestation in patients with COVID-19 is follicular conjunctivitis, corresponding to 90% of ocular findings [5, 8]. Most frequent symptoms are dry eye or foreign body sensation (16%), eye redness (13.3%), tearing (12.8%), and itching (12.6%) (see **Table 1**).


## **Table 1.**

*Symptoms and diseases of ocular manifestation in COVID-19 infection included in the reviewed studies (n = 1,021).*

The association between COVID and dry eye is uncertain because this condition might be related to wearing face masks and the stream of air against the ocular surface as well as the overuse of digital devices leading to an evaporative dry eye.

Since conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19. Therefore, attention to ocular manifestations, especially conjunctivitis, could increase the sensitivity of COVID-19 detection among patients during pandemic. As said before, SARS-CoV-2 can be transmitted by tear, so ophthalmologists (mainly given their close contact) and healthcare providers should wear protective devices, such as protective gears and face masks while examining a patient [9].

Other less common conditions are keratitis, episcleritis, keratoconjunctivitis, hordeolum, pingueculitis, and posterior ischemic optic neuropathy. Reports show associations of COVID-19 with uveitic, retinovascular, and neuro-ophthalmic disease due to microvascular injury and inflammation [4, 5, 10–16].

## **3.1 Cornea and conjunctiva**

Unspecific signs of mild viral conjunctivitis: unilateral or bilateral bulbar conjunctiva injection, follicular reaction of the palpebral conjunctiva, watery discharge, and mild eyelid edema [4].

Bilateral chemosis alone may represent third-spacing in a critically ill patient rather than a true ocular manifestation of the virus [4].

Cheema et al. described the first case of keratoconjunctivitis: corneal findings that developed rapidly over 3 days, including transient pseudodendritic lesions and diffuse subepithelial infiltrates with overlying epithelial defects [8].

Navel et al. observed a case of severe hemorrhagic conjunctivitis and pseudomembrane formation [17].

## **3.2 Sclera and episclera**

Cases of episcleritis, anterior scleritis, and necrotizing anterior scleritis have been reported [18–20].

## **3.3 Anterior chamber**

Acute anterior uveitis has also been reported both in isolation and in association with COVID-19-related multi-system inflammatory disease [10, 11].

## **3.4 Retina and choroid**

Vascular, inflammatory, and neuronal changes induced by the virus cause posterior segment manifestations. These are less frequent than anterior segment findings.

There are some case reports showing that the most common retinal involvements are microvascular changes, such as cotton wool spots and microhemorrhages. Usually, these patients had normal visual acuity and pupillary reflexes. Physiopathology is related to a complement-induced prothrombic and inflammatory state causing endothelial damage and microangiopathic injury [6, 21].

Deep retinal capillary plexus ischemia is involved in acute macular neuro-retinopathy (AMN) and paracentral acute middle maculopathy (PAMM), both observed as hyperreflective changes at the level of the outer plexiform and inner nuclear layers [22–25].

## *Ocular Manifestations of COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.106440*

Increased tortuosity of retinal vessels has also been described, but a true relation between such occurrences and COVID-19 has yet to be established [26].

Central vein occlusion is an important complication of COVID-19 and can occur in healthy patients as SARS-CoV-2 infection causes endothelial damage and increases the risk of thrombosis. However, retinal artery occlusion occurred mostly in patients with additional underlying conditions, such as hypertension, obesity, and coronary artery disease [26].

In addition, some studies showed hyper-reflective lesions at the level of ganglion cell and inner plexiform layers more prominently at the papilomacular bundle in patients with COVID-19 [27].

Other studies evaluated changes in retinal microvasculature and retinal layers in patients who recovered from COVID-19 with spectral domain optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA).

OCT-A was performed in patients 6 months post SARS-CoV-2 pneumonia and revealed a significant reduction in vessel density of the superficial capillary plexus and deep capillary plexus as well as retinal nerve fiber layer (RNFL) thinning. These findings are probably related to thrombotic microangiopathy events [28, 29]. There is evidence that retinal layers can be affected, especially in patients with headache and ocular pain symptoms during the COVID-19 period [29].

Other retinal findings were seen in patients with COVID-19: Vitritis; hyperreflective lesions at the level of the inner plexiform and ganglion cell layers in OCT (optical coherence tomography); cotton wool spots, microhemorrhages, dilated veins, and tortuous vessels (due to vascular damage); Purtscher-like retinopathy and acute retinal necrosis (ARN) in immunocompromised patients (probably related to a reactivation of latent herpesvirus and breakdown of blood–retinal barrier allowing an increased inflammatory response) [6, 14–16, 21–23].

Posterior uveitis was observed following COVID-19 infection and vaccine. Cases of serpiginous, ampiginous, and multifocal choroiditis also have been reported. It is believed that autoimmunity is involved in these manifestations [22–25, 30].

## **3.5 Neuro-ophthalmologic manifestations**

Several neuro-ophthalmologic manifestations have been observed: Optic neuritis, papillophlebitis (only one case reported), Adie's tonic pupil, cranial nerve palsy, neurogenic ptosis, Miller Fisher syndrome, and ocular myasthenia gravis [4, 6, 31–37].

It is already known that the SARS-CoV-2 virus has a neurotropism. Some cases of bilateral optic neuritis have been described, but it is possible that this is a consequence of an immune-mediated insult caused by the virus as these patients presented with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies and cerebrospinal fluid (CSF) did not reveal virus presence. There have also been reports of acute optic neuritis following vaccination for COVID-19 [4, 6, 31, 38–41].

A case of multiple sclerosis following COVID-19 infection was reported by Palao et al. These cases suggest that SARS-CoV-2 can either trigger or exacerbate the inflammatory and demyelinating disease [39].

## **3.6 Orbital manifestations**

There have been reports of sinusitis, orbital cellulitis, mucormycosis, orbital myositis, and dacryoadenitis. The most significant of those is mucormycosis as it is an opportunistic pathogen. The hypoxic respiratory environment induced by

SARS-CoV-2 added to an immunocompromised state induced by high-dose steroids and immunosuppressive therapies creates the perfect environment for this fungal infection [42–48].

Singh et al. published a systematic review of 101 reported cases of COVID-19 patients with mucormycosis; these patients were predominantly male (79%), 80% of which had diabetes and 15% with concomitant diabetic ketoacidosis [49].
