Discussion
Recurrence of non-arteritic RAO in the same or opposite eye is rare. Susac syndrome is a well-known, although rare, condition in which episodes of retinal vasculitis result in recurrent BRAO. The diagnosis of Susac syndrome involves the visualisation of hyperfluorescence of the arteriolar wall on FA, inner retinal atrophy on optical coherence tomography and lesions in the corpus callosum on brain MRI.16 Herein, however, the recurrence of RAO was related to the recurrence of thromboembolism and/or stenosis, similar to the recurrence of cerebral ischaemia. Surprisingly, all six patients who experienced a recurrence of RAO in the opposite eye had bilateral ICA stenosis with pre-existing heart conditions, including coronary artery disease, atrial fibrillation and cardiac tumour, a significant difference from the same eye recurrence group, which presented with no definite underlying heart diseases. Brain imaging revealed varying degrees of stenosis in both the carotid and large cerebral arteries in most patients who experienced a recurrence of RAO; however, no steno-occlusive lesions were found in the two patients who experienced a recurrence in the same eye. Furthermore, the recurrence of RAO in the same eye predominantly occurred during the immediate period following the initial event, whereas the duration of RAO recurrence in the opposite eye was longer.
The primary causes of CRAO are cardioembolisms and artery-to-artery embolisms of the carotid artery; however, approximately half of all CRAO cases are due to an unknown aetiology, which is much higher than the proportion of stroke cases with unknown causes.17 Differences in cerebrovascular and cardiovascular factors between patients with recurrence in the same eye and those with recurrence in the opposite eye may suggest variations in the thromboembolic risk associated with recurrent RAO.18 19 This implies that although the patients did not have any obvious cerebrovascular abnormalities, and had a low likelihood of systemic vascular disease, there was still a possibility of RAO recurrence. Individuals with a history of diabetes, hypertension, dyslipidaemia and/or cerebrovascular atherosclerosis, however, are more likely to experience a recurrence of RAO, primarily due to retinal emboli composed mainly of cholesterol and platelet-fibrin emboli. These emboli are typically observed in conjunction with mural thrombus formation in the carotid artery or the cardiac valvular structures.20 21
Several studies have examined the occurrence of subsequent strokes following the initial stroke, and most suggest that the risk of recurrent stroke is the highest immediately after the first stroke.22 23 One study found that the 3-year cumulative risk of stroke recurrence was 14%, and that diabetes mellitus and atrial fibrillation were associated with stroke recurrence.24 Other studies have reported 3-year cumulative risks ranging from 6% to 25%.25 26 Although recurrent stroke is common, the recurrence of non-arteritic RAO has rarely been reported. A previous study focusing on emboli and blood flow in the ophthalmic artery analysed using a computational fluid dynamics model proposed that emboli must be of a specific size and location to result in RAO, while other emboli usually flow into the cerebral artery without entering the ophthalmic artery.27 These findings may explain the very low incidence of recurrent RAO compared with stroke recurrence. Given that RAO is associated with a very high risk of cerebrovascular and cardiovascular complications, the recurrence of RAO may be viewed as a subsequent stroke event that increases the likelihood of morbidity and mortality.22–26
Considering the association between RAO and embolic sources from the heart,17 it is crucial to perform cardiac evaluations, such as coronary angiography and transthoracic echocardiography, in addition to brain imaging, especially in high-risk patients. Previous studies have shown that approximately 50% of patients with non-arteritic CRAO have abnormal echocardiographic findings, indicating an embolic source.4 5 Another recent study highlighted that patients with RAO were more likely to have valvular diseases and be readmitted for atrial fibrillation/dysrhythmias than patients with acute ischaemic stroke.25 26
In the present study, all cases of recurrent RAO in the same eye were diagnosed as CRAO. Interestingly, although the initial occurrence was mild in three patients, who presented with incomplete CRAO, the subsequent recurrences were uniformly severe, resulting in complete CRAO and significant vision loss. Conversely, the recurrence of RAO in the contralateral eye presented with both BRAO and CRAO. Although the first occurrence was severe and led to visual deterioration, the second recurrence was relatively mild. In our cohort of six patients with recurrence in the opposite eye, vision was maintained in the opposite eye, ranging from 20/400 to 20/25. Individuals who experience vision loss following the initial RAO incident may struggle with depression and anxiety regarding the potential loss of vision in their remaining eye like patients who lost unilateral vision from age-related macular degeneration (AMD).28 29 Therefore, it is essential to provide psychological and emotional support to these patients.
The present study had several limitations. First, despite our efforts to gather as many cases of recurrent RAO as possible, the incidence of this condition was exceedingly low, resulting in only 11 cases available for presentation. The analysis of such a limited number of patients could potentially impact the results, especially concerning subsequent cerebrovascular and cardiovascular complications. Second, we were unable to analyze data differentiating between CRAO and BRAO, owing to the scarcity of recurrent cases. Third, it may be necessary to extend the follow-up period to >3–5 years for a more comprehensive analysis of the effects of recurrent RAO. Nevertheless, it is a strength of our study that we analysed quite a large number of 850 patients with non-arteritic RAO and thus, we could reveal the approximate incidence of recurrence.
In conclusion, the recurrence of non-arteritic RAO can occur in the same or opposite eye via different mechanisms. Because recurrent RAO can result in severe vision loss, it is crucial to stress the significance of screening for risk factors to patients and to work closely with neurologists and cardiologists.