Retinal artery occlusion: Novel insights

Central retinal artery occlusion (CRAO) is an ocular emergency, in which retinal ischemia occurs due to sudden blockage of the central retinal artery by an embolus. It leads to extensive cellular damage and visual loss. The formation of collaterals and the duration of retinal ischemia determine the extent of survival of retinal tissue. The incidence of CRAO is reported to be 1 in 10,000 cases at tertiary referral centers, but it could be lower in the general population, reportedly from 1 to 8.5 cases per 100,000.[1-3] CRAO usually develops in older adults, but cases in children and young adults have also been reported.[4] In acute cases, the patient presents with sudden and severe vision loss, which is painless and monocular. Amaurosis fugax or transient blurring of vision may occur in some patients. About 74% to 90% of patients have low vision, which may range from counting fingers to light perception.[5,6] Prolonged retinal ischemia leads to irreversible injury to the retina due to the release of pro-inflammatory mediators.[7] In our earlier report, we highlighted ischemia–reperfusion injury in CRAO. Retinal nerve fiber layer (RNFL) sample 60 was documented. It denotes the thickness of RNFL at the 60th A scan among the 256 A-scans taken along the peripapillary circle of reference. It was observed that on day 3 of injury, there is increased thickness of the retinal nerve fiber layer (RNFL) due to retinal edema, which can also be seen as increased hyper-reflectivity on the spectral domain optical coherence tomography (SD-OCT). Day 7 shows a marked decrease in RNFL thickness, which is suggestive of acute reperfusion injury. By day 30, RNFL thickness returns to almost normal values, which suggest the return of circulation and washout of reperfusion stress mediators. Hyper-reflectivity of inner layers also decreases on SD-OCT. Day 90 shows a marked decrease in the value of average RNFL thickness due to atrophy which can be seen as thinning of retinal layers on SD-OCT.[7] CRAO mainly affects inner retinal layers and outer retinal layers remain intact. Also, the initial 72 hours from the occurrence of CRAO are critical for the initiation of therapy[8,9], after which reperfusion injury occurs. SD-OCT can be instrumental in monitoring inner retinal layers and RNFL thickness. Chaubey et al. reported vasospasm-related retinal artery occlusion after desvenlafaxine (an antidepressant medication) use. It acts by modulating levels of serotonin and noradrenaline, which causes vasospastic effect. Hence, patients on oral desvenlafaxine with transient vision blurring need a thorough systemic and ocular examination.[10] Similarly, cocaine-associated CRAO has also been described. Possible mechanisms of cocaine-related retinal artery occlusion include—inhibition of noradrenaline reuptake by adrenergic nerve endings, direct vasoconstriction of vascular smooth muscle, and increased platelet aggregation.[11,12] Retinal arteriolar occlusion is also associated with migraine. Potent vasoconstrictors such as serotonin (5-hydroxytryptamine) are released immediately before or during migraine attacks, leading to retinal vasospasm.[13] Migraine patients may have other manifestations of vasospasm, as part of a primary vasospastic syndrome.[14] Dynamic focal retinal vasospasm is also implicated in the pathophysiology of migraine-associated retinal artery occlusion.[15] Retinal circulation lacks an autonomic supply. A balance between endothelin-1 (vasoconstrictor) and endothelium-derived nitric oxide (vasodilator) maintains retinal circulation. Levels of endothelin-1 are increased in all vasospastic disorders. Primary vasospastic syndrome involving the ocular circulation can follow a destructive course.[15] Patients with CRAO show vascular endothelial injury, thicker intima-media thickness, and diastolic left ventricular cardiac dysfunction on ultrasonography and transthoracic echocardiography. These measurements are noninvasive and can serve as valuable diagnostic tools for identifying asymptomatic subjects with an increased risk of CRAO development.[16] Kyoto University Substance 121 (KUS121) is an inhibitor of ATPase activities of valosin-containing protein (VCP). VCP is the most abundant soluble ATPase in all mammalian cells including neurons and plays an important role in neurodegeneration.[17,18] VCP is believed to be involved in many cellular functions, which include endoplasmic reticulum-associated and proteasome-mediated protein degradation.[19] KUS121 specifically inhibits the ATPase activity of VCP in pathological conditions, without apparently inhibiting its other cellular functions.[17] Efficacy and safety in preserving the visual function of patients with CRAO are being investigated. Vitrectomy has been attempted in a few cases of central or branch retinal artery occlusion.[19-22] Prompt vitrectomy with PVD induction alone can restore ocular circulation in selected cases. Detaching the hyaloid from the disc may have a role in reperfusion by releasing any abnormal adhesion around the artery. Also, the negative suction forces created during active aspiration may help in displacing the thrombus.[23] A large-scale multicentric study may provide further insight.