LAUSR

In Response: We thank Drs Nicholson, Margolin, and Krings for their interest in our article and for raising an important issue regarding the therapeutic potential of endovascular treatments of central retinal artery occlusion (CRAO). That CRAO is a form of acute ischemic stroke and should be treated in an emergent fashion with the same degree of urgency as an acute cerebral ischemic stroke is not at issue. Historically, a major limitation in this field was lack of a uniform definition of visual recovery that did not consistently require functional recovery. In 2015, we introduced a reliable definition of functional visual recovery after CRAO for use in future clinical trials to ensure the term captures clinically relevant improvement and to improve the consistency of evaluating outcomes in clinical research. We defined functional vision precisely and a priori in our analysis as achieving a visual acuity of equal to or greater than 20/100 in the affected eye—3 lines of improvement beyond the threshold of legal blindness in the United States. We evaluated this metric in 7 natural history cohorts over more than 80 years incorporating data for almost 400 patients and found that 17% of patients spontaneously recover. Importantly, there was no heterogeneity in the rate of recovery among the studies. We recommend the adoption of this standard in future clinical studies to ensure comparability between studies. The cilioretinal artery—when it occurs—is a branch of the posterior ciliary circulation and, by definition, conveys an independent blood supply to the macula. In patients with CRAO and a cilioretinal artery, visual deficits are less likely to be disabling from the outset as there is preservation of central vision. By employing a functional threshold of visual acuity loss, patients with CRAO with a cilioretinal artery are likely to be excluded from acute treatment trials. There are numerous, well-documented cases in the ophthalmology literature wherein a person with untreated CRAO and no cilioretinal artery makes a full visual recovery. The meta-analysis that is cited suggesting a recovery rate of 55% in patients treated with intraarterial tPA (tissue-type plasminogen activator) did not apply a consistent definition of recovery and most of the individual studies in that analysis applied a less stringent measure of 3 lines of improvement of visual acuity on the Snellen chart. In the control arm of the EAGLE trial (European Assessment Group for Lysis in the Eye), 60% of untreated patients met this definition of recovery, so in our opinion this meta-analysis does not support another randomized, controlled trial of intraarterial tPA using the same methodology. The authors of the letter correctly point out that whereas endovascular treatment of acute stroke was once controversial, it is now mainstream. However, endovascular treatment that is now the standard of care is mechanical clot retrieval. Intraarterial thrombolysis, by contrast, has largely been abandoned. This does not mean that it will not be shown to be effective for CRAO in the future. Earlier treatment with intraarterial therapy for CRAO and treatment with novel fibrinolytic agents like tenecteplase remain untested and should be explored in future studies. Finally, patients with acute CRAO are at risk for additional cerebrovascular events, so it is essential that there is a collaborative approach to treatment and secondary prevention. The EAGLE trial investigators chose to have regular funduscopic examinations during intraarterial therapy, however, it is not essential that an ophthalmologist be present for the duration of the procedure. The involvement of ophthalmologists, interventional neuroradiologists, neurologists, and other specialties in the acute management of such patients will be determined on availability and on an institution-by-institution basis, however, as a primary ophthalmologic disease there is a central role for ophthalmology in their management and treatment.