BY: ANTIGONE KORDAS

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly challenged the medical community, with diagnosis and therapeusis mainly focusing on the respiratory-related signs and symptoms. While uncommon, ophthalmic complications can occur and affect ~6-12% of COVID-19 patients with ocular symptoms preceding systemic symptoms by 3 hours to 5 days in 13% of patients.

With COVID-19 on the rise throughout the community, it may become commonplace to see patients with viral ocular symptoms or even long-term ocular complications, either as a direct or indirect result of the pandemic. The following article is a guide of what the most common ocular conditions to expect are.

Conjunctivitis

In systemic reviews, the most common ocular manifestation of COVID-19 is conjunctivitis (86%), ocular pain (31–34%), dry eyes (33%), discharge (19%), and redness (11%) .

Since genetic material of the virus (RNA) has been reported to be present within the tears of infected patients, extra care must be taken to not allow the eyes to serve as a transmission route. The first case of reported conjunctivitis and COVID-19 involved a doctor in China who performed a medical inspection at the Wuhan Fever Clinic without wearing any eye protection, therefore highlighting the importance of such procedures, especially within our field. It is also important to note that systemic infection is possible as infected tears can transport the virus through the nasolacrimal duct and towards the nasopharynx.

While the pathogenesis of conjunctivitis caused by COVID-19 is not entirely understood, several theories exist involving transmission via air-borne droplets or hand-eye contact .

Signs: Predominantly bilateral conjunctival hyperemia, chemosis, follicles on palpebral conjunctiva, epiphora, watery discharge, mild eyelid oedema, enlarged pre-auricular or submaxillary lymph nodes. At present, there have been no sight-threatening cases reported and eye involvement was more likely in patients with severe COVID-19. At this stage, conjunctivitis related to COVID-19 is self-limiting and conservative management such as use of lubricating drops and formulations for comfort is recommended.

Kawasaki-Like Disease/Multisystem Inflammatory Syndrome (MIS-C)

Kawasaki Disease (KD) is a type of vasculitis of the medium-sized vasculature with an acute presentation and mostly affecting young children under the age of 5. Towards the beginning of the pandemic in 2020, a strong connection had been observed between KD and COVID-19 within a province of Italy, with a particular study reporting that up to 80% of paediatric patients positive for COVID-19 presented with an increased incidence of more severe KD. More recently however, it has been found that children exposed to COVID-19 develop Kawasaki-like illness, termed Multisystem Inflammatory Syndrome (MIS-C), rather than KD itself. The main difference between MIS-C and typical KD is that MIS-C patients suffer from gastrointestinal issues (diarrhoea, abdominal pain and nausea), shock and coagulopathy more frequently. MIS-C is also more common in older children over the age of 5, with several studies reporting an age range of 7.5-10 years.

Signs of Typical KD: Fever, oropharyngeal and extremity swelling, polymorphous rash (different types of rashes occurring all over the body), mucous membrane changes, strawberry tongue appearance and unilateral cervical lymphadenopathy. More specific ocular manifestations of the condition include iridocyclitis, keratitis, vitreous opacities, papilloedema, subconjunctival haemorrhage and conjunctival injection (specifically bilateral, painless, non-purulent and with limbal sparing).

Image (Courtesy of Robert Sundel, MD): Conjunctivitis in KD with limbal sparing.

RETINAL FINDINGS

Given that COVID-19 targets vascular pericytes expressing ACE-2 and these receptors are found in the ciliary body, retina and RPE, it follows that viral infection can potentially lead to damage of the microvasculature and blood-retina barrier and therefore cause ocular circulation issues. A study examining histological specimens of retinas from deceased COVID-19 patients found particles of the virus in the ganglion cell layer (GCL), inner plexiform, inner nuclear layer (INL), outer plexiform, outer nuclear layer (ONL), retinal pigment epithelium, and choroid..

With the potential for coagulopathy, ischaemia and inflammation with COVID-19, certain conditions may arise during infection include retinopathy. An 8.86-fold increased risk of retinal microvascular pathology has been found in infected patients, including retinal haemorrhages, cotton wool spots, retinal infarcts and thinning of the GCL and INL. A lower vascular density on OCTA has also been found in patients with more severe COVID-19 presentations.

Image: Retinal findings in four patients with COVID-19

A: Shows a cotton wool spot at the superior retinal arcade with subtle microhaemorrhage.

B-D: Shows hyper-reflective lesions of the inner plexiform and ganglion cell layers, a feature observed in all patients. 

Acute macular neuroretinopathy (AMN) and paracentral acute middle maculopathy (PAMM) (involve ischaemia to the deep retinal capillary plexus) have also been found in patients with COVID-19 and are marked by hyperreflective changes of the OPL and INL.

Image: Retinal findings in AMN

A, B: Near-infrared imaging of the right eye (A) and left eye (B) shows multiple hyporeflective lesions in the paracentral macula. The small lesions imaged have a petaloid shape, but most are large and confluent, and almost form a ring around the fovea.

C, D: OCT of the right eye (C) and left eye (D) at the level of the green line in A, B, shows interruption of the ellipsoid zone and the interdigitation zone (black arrows).

Other potential retinal findings include hyperreflective lesions in the inner and outer retina, MEWDS, CRVO and Multifocal Choroiditis with Adie’s pupil.

OCULAR SURFACE DISORDERS

Ocular surface disorders such as exposure keratitis and corneal abrasions have been reported in patients in ICU who are on ventilators and respiratory masks.

NEURO-OPHTHALMOLOGICAL COMPLICATIONS

Neurological complications of COVID-19 include Meningitis, Encephalomyelitis, Polyneuritis, Encephalopathy and Guillain-Barre Syndrome. Patients who have had COVID-19 may potentially present with diplopia secondary to oculomotor nerve palsy due to direct viral infection of the nerve or subsequent inflammation.

A study found that up to 21% of patients with COVID-19 may have systemic neurological problems and ~0.4% have cranial nerve impairment to some extent, including CNIII, CNIV and CNVI. A systemic review also found an increased prevalence of Guillain-Barre Syndrome (a condition where the person’s immune system attacks nerves) in COVID-19 patients compared to the general population (0.15% compared to 0.02%).

Signs: Ophthalmoparesis, abnormal cranial nerve MRI and findings.

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