Prone positioning is a life-saving measure for many critically unwell patients with COVID-19. However, intensive care staff should be aware of the ocular complications associated with its use, especially as the irreversible vision loss caused by NAION can be devastating for survivors and their families. With awareness of the risk factors which predispose patients to NAION, such as uncontrolled hypertension, sleep apnoea, diabetes mellitus and hypercholesterolaemia, measures can be taken to protect against its development, without interfering with lifesaving treatment[3]. The following discussion first explains how NAION was diagnosed in this case, before highlighting the key aetiological factors contributing to its development. Finally, we recommend measures to protect against NAION in critically unwell patients with COVID-19 where prone positioning may be unavoidable.
Diagnosis of NAION cannot be made without a timely ophthalmic assessment, including VA, IOPs, pupillary responses, confrontational visual fields and fundoscopy[2]. As in this case, bedside fundoscopy can reveal nerve layer haemorrhages and edematous optic discs, which are highly suggestive of anterior NAION in a patient with cardiovascular risk factors[1]. Other features of optic nerve damage, such as reduced VA, colour vision loss and RAPD should also be present[1, 2]. A dilated fundus examination is essential to exclude treatable causes of painless vision loss such as retinal detachment and vitreous haemorrhage[2]. In unilateral NAION examination of the unaffected can also identify patients with “discs at risk”, smaller, crowded optic discs predisposed to ION[2].
An important differential for NAION is central retinal artery occlusion which presents with profound vision loss and a characteristic cherry red spot on fundoscopy[8]. Central retinal artery occlusion has been reported in patients proned perioperatively who experience fluctuations in mean arterial pressure. This occurs as blood supply to the optic nerve is auto-regulated by changes in terminal arteriolar resistance, a mechanism which breaks down at the extremes of mean arterial pressure[13]. In this case, CP’s mean arterial pressure was kept between strict limits of 70-100mmHg, further excluding this diagnosis.
In addition to ophthalmological assessment, brain imaging and a neurological assessment should be conducted in any patient with acute vision loss and cardiovascular risk factors, to exclude a cerebral vascular incident[2]A biochemical blood panel including CRP or ESR is also necessary to exclude giant cell arteritis[2]. Once stable, patients with suspected NAION should undergo urgent ophthalmology referral for slit-lamp examination, OCT imaging, formal visual acuity and fields. These measures help determine the extent of a patient’s vision loss so that they can receive advice regarding driving and qualification for low vision support[2]. More detailed testing can also help elucidate the cause of NAION, allowing targeted risk factor modification to protect any remaining vision.
Prone positioning is an established risk factor for NAION as it can cause alterations in IOP which precipitate nerve hypoperfusion. IOP fluctuations can occur due to external compression of the orbit, via a process resembling orbital compartment syndrome, or indirectly due to increased central venous pressure (CVP[8]. Raised IOP occurring without external pressure to the orbit can occur as no valves are present in the orbital veins, leaving the eye especially vulnerable to positional changes, as raised CVP can translate directly into raised IOP[14].
Knowledge of how prone positioning can lead to NAION may aid its prevention, for example a 10° reverse Trendelenburg position can reduce IOP compared to the neutral or 5° position[3]. Venous return is especially likely to be compromised if the head remains to one side for extended periods, or malpositioning leads to direct pressure on the abdomen obstructing venous return to the heart. Attempts to position patients with the head level or above the heart, aiming to maintain blood pressure within 20 % of baseline, may significantly reduce the risk of ION development[13].
Prone positioning is a key risk factor for the development of NAION in patients with COVID-19 related ARDS. However, multiple other risk factors may have compounded CP’s risk of NAION. For example, life-saving treatments used in conjunction with prone positioning to treat multi-organ failure in critically unwell patients, such as sedation, vasopressors, and anaesthesia, increase the risk of NAION by overwhelming the autoregulatory mechanisms of optic nerve perfusion[3]. These treatments may be unavoidable, but screening for vision loss in patients who have been proned can prevent delayed diagnosis, and late referral for vision support. Blood tests for lipids, Hba1c and blood pressure checks are also important to identify cardiovascular risk factors, which can be controlled to significantly reduce the risk of NAION.
Notably, recent evidence has highlighted the biological plausibility of COVID-19 related hypoxemia and hypercoagulability as independent risk factors for NAION[9,10,11,12]. As NAION is a disease of circulatory insufficiency, it follows that hypoxemia caused by COVID-19 related ARDS may precipitate NAION in prone patients already at risk of hypoperfusion injury[9]. The relationship between COVID-19, hypercoagulability and microvascular disease is still being explored, but is likely to relate to a combination of endothelial injury caused by direct viral invasion and a prothrombotic state triggered by immune-mediated hyperinflammation, viral ACE2 receptor binding and in-situ immunothrombosis[15]. COVID-19 related immunothrombosis may be particularly concerning for the microvascular inflammation and micorembolic disease seen in NAION, and there is reason to believe that careful anticoagulation should play a central role in the management of patients undergoing prone ventilation to treat COVID-19 related ARDS[9,10,11,12].
In conclusion ION is a devastating, but preventable complication of proning, which should be considered in COVID-19 patients treated with prone mechanical ventilation.