Thrombolysis in acute retinal ischemia treated with tenecteplase

Summary

Central retinal artery occlusion (CRAO), a type of acute retinal arterial ischemia, analogous to an ocular stroke, is a medical emergency that warrants immediate diagnosis and treatment. CRAO usually presents with sudden, painless, monocular vision loss. Ipsilateral carotid artery disease is an important associated finding in these patients. The primary limitation to effective treatment of CRAO is that patients are rarely seen in the acute stage. Moreover, there are no guidelines for effective treatment. We report a patient with right CRAO whose treatment with intravenous thrombolysis with tenecteplase and anterior chamber paracentesis with ocular massage resulted in a good clinical outcome.

Introduction

Acute central retinal artery occlusion (CRAO) is an ocular emergency. Without timely intervention, the visual prognosis is poor. The American Heart Association (AHA) defines central nervous system infarction as brain, spinal cord, or retinal cell death attributable to ischemia, based on pathological, imaging, and/or clinical evidence. Despite being recognized as equivalent to brain infarction, which warrants the adoption of thrombolysis as the standard of care, the net benefit regarding acute reperfusion therapies in CRAO remains controversial.1–3 We report a patient with right CRAO who was treated with intravenous thrombolysis with tenecteplase.

Case Report

A 62-year-old man from South India with a history of long-standing, well controlled hypertension (olmesartan, 20 mg daily) and no other known comorbidities presented emergently to Neurology Outpatient Services at Manipal Hospital, Bangalore, with sudden, painless loss of vision in the right eye that started 4 hours prior to presentation. There was no history of headache, diplopia, ptosis, altered sensorium, limb weakness, or incoordination. His general physical examination was normal, and his blood pressure was 140/80 mm Hg. Visual acuity was hand movements close to the face. Visual acuity in the left eye was 6/6. On ophthalmological examination, a relative afferent pupillary defect was noted in the right eye; the left eye pupil reacted briskly to light. Both eyes had a Van Herick grade 4 peripheral anterior chamber depth, grade 1 nuclear sclerosis, and an intraocular pressure (IOP) of 14 mm Hg by Goldmann applanation tonometry. Fundus examination of the right eye revealed retinal whitening, with a small area of perfused retina temporal to the disc due to a patent cilioretinal artery. Arteriolar narrowing was noted (Figure 1).

Figure 1.

A, Optical coherence tomography (OCT) images on presentation showing thickening and hyper-reflectivity of the inner retinal layers of the right eye (left) and distortion of the retinal layer architecture compared with the left eye (right). B, OCT at 6 weeks’ follow-up showing the right and left macula with resolution of retinal edema and foveal thinning in the right eye due to loss of retinal cells. C, OCT of the right eye showing comparison between first visit and 6-week review; resolution of thickening of inner retinal layers with foveal thinning was noted. D, Fundus photograph of the right eye showing retinal whitening with an area of sparing temporal to the disc due to a patent cilioretinal artery; arteriolar narrowing was also noted. E, Follow-up photograph showing resolution of retinal whitening 24 hours following thrombolysis. F, Fundus photograph of the right eye showing dull foveal reflex with resolution of retinal whitening/edema; minimal arteriolar narrowing was noted.

Left eye examination was normal, with minimal arteriolar narrowing. The rest of the neurological examination was normal. The patient had undergone magnetic resonance imaging of the brain prior to arriving at our hospital that showed normal brain parenchyma with absent flow voids in the right internal carotid artery on T2 sequences. He was diagnosed with CRAO in the right eye, with cilioretinal sparing, and was immediately transferred to the emergency department.

He was empirically administered dorzolamide eye drops 2% one drop thrice daily for 2 weeks to help improve retinal perfusion. Ophthalmologic interventions included digital ocular massage and anterior chamber paracentesis. After discussion with the patient and family and after obtaining informed consent, tenecteplase 0.25 mg/kg was administered intravenously as a single-dose bolus at 4 hours 15 minutes after symptom onset: 18 mg of tenecteplase was administered, according to the patient’s body mass. Our therapy of choice, alteplase was not available at that time. There were no contraindications for thrombolysis.

After thrombolysis, the patient was transferred to the intensive care unit for monitoring (primarily for changes in sensorium, blood pressure, and heart rate) every 15 minutes for 4 hours, then every 30 minutes for 4 hours, and thereafter hourly. No investigations were warranted, because no symptomatic changes or neurological deficits were noted. The patient underwent a computed tomography (CT) scan of the brain 24 hours after thrombolysis, which was normal. CT angiogram of the head and neck showed complete occlusion of the right internal carotid artery, with maintained anterior circulation flow across anterior and posterior communicating arteries. The other major vessels appeared normal (Figure 2).

Figure 2.

Computed tomography angiogram showing total occlusion of the right internal carotid artery (RICA) in its course in the neck (A–B) and in the petrous temporal bone (C). The left internal carotid artery (LICA) appears normal (D–E).

He remained hemodynamically stable and started treatment with aspirin 75 mg daily, clopidogrel 75 mg daily and atorvastatin 20 mg daily. Complete blood count liver function test, vitamin B12 level, and lipid profile were unremarkable except for mild elevation of serum homocysteine. Cardiac evaluation was normal, and the patient was scheduled for follow-up visits with a cardiologist and a neurologist. He continued treatment with topical medications for lowering IOP and improving retinal perfusion until follow-up with the ophthalmologist.

Significant improvement in vision was noted 4 hours after thrombolysis; the patient could count fingers at 1 meter. Slit-lamp examination showed minimal conjunctival congestion. The corneal needle track sealed well, with no evidence of leak with Van Herick’s grade 2 of anterior chamber depth (slightly shallow compared with before the procedure), mild anterior chamber flare, and no cells noted. IOP was 12 mm Hg. The patient’s vision further improved to counting fingers at 3 meters 24 hours after thrombolysis, and he was discharged 72 hours later with a visual acuity of 6/60.

Subsequent follow-up 2 weeks later showed a clearing of retinal whitening, with improvement in the field of vision by confrontation testing. Follow-up at 6 weeks showed near complete resolution of retinal thickening and whitening. Best-corrected visual acuity was 6/9.

Discussion

In the present case, intravenous thrombolysis was initiated within 4.5 hours of vision loss due to CRAO. The patient’s clinical signs resolved, and visual acuity in the affected eye improved quickly, steadily, and without adverse events. We attribute the outcome in this case to rapid diagnosis and treatment, including thrombolytic tenecteplase. Digital massage, anterior chamber paracentesis, and the patent macular cilioretinal artery may also have contributed to recovery.

Several retrospective and prospective studies3 have shown that administration of intravenous thrombolytic agents within 4–6 hours of presentation of vision loss results in significant improvement of visual acuity. Compared to alteplase, tenecteplase has several practical advantages, including its longer half-life, preparation and administration as a single intravenous bolus, higher recanalization rates, and reduced risk of intracerebral hemorrhages— all of which make it a useful, noninferior agent in the treatment of CRAO.4 A previously reported case5 also noted a successful reperfusion outcome in CRAO after administration of tenecteplase; to our knowledge, our case is the only other to document use of this agent in CRAO. While the patient in the earlier report developed CRAO after undergoing a coiling procedure for a para-ophthalmic left artery aneurysm, our patient presented to us directly with CRAO in the right eye, with subsequent CT angiography showing a fully occluded right carotid artery.5

This case report highlights the need for studies that can establish a set of guidelines to facilitate thrombolysis as a timely therapeutic intervention in CRAO patients. In this regard, three randomized trials are currently in progress in Europe to evaluate treatment of acute CRAO with intravenous thrombolytics versus placebo: (1) THEIA, a phase III randomized, blinded, double dummy, multicenter study assessing the efficacy and safety of intravenous thrombolysis (alteplase) in patients with acute CRAO; (2) REVISION, an early reperfusion therapy with intravenous alteplase for recovery of vision in acute CRAO; and (3) TenCRAOS, a prospective, randomized-controlled, double-dummy, double-blind phase 3 multicenter trial of tenecteplase 0.25 mg/kg and placebo versus acetylsalicylic acid and placebo (two arms with 1:1 block randomization).6 The TenCRAOS trial does not include patients with CRAO having cilioretinal artery sparing (as in our case). We believe that our report reinforces the positive outcomes of treatment with intravenous thrombolysis in CRAO that are being evaluated in the aforementioned clinical trials. Table 1 summarizes various studies conducted to date using tissue plasminogen activators as thrombolytic agents, demonstrating their efficacy in improving visual outcomes of patients presenting with CRAO.7–12

Table 1.

Previous studies using intravenous thrombolysis as a treatment modality in patients presenting with acute central retinal artery occlusion

In contrast to intravenous thrombolysis, the European Assessment Group for Lysis in the Eye (EAGLE) study of 2002, a randomized, controlled, prospective multicenter clinical superiority trial compared local intraarterial fibrinolysis with conservative standard treatment. The study demonstrated similar efficacies in both treatment modalities, with a higher rate of adverse reactions in patients treated with thrombolytic agents. However, several smaller nonrandomized studies, including case reports, case series, and cohort studies, have demonstrated clinical effectiveness of intraarterial thrombolysis over conservative management. Unfortunately, the studies varied in designs, inclusion criteria, therapeutic procedures, natural history of the disease, and visual improvement definitions, making it impossible to compare success rates.13 Future studies should also evaluate atherosclerotic risk factors, including family history of cerebrovascular and cardiovascular disease, diabetes, hypertension, hyperlipidemia, past history of atherosclerotic cardiac or cerebrovascular disease, valvular heart disease, or transient ischemic events, such as transient monocular blindness, transient ischemic attacks, and anginal symptoms.1,2,6

The outcome in our case cannot, without due caution, be attributed to tenecteplase. Two-thirds of patients presenting with CRAO with cilioretinal artery sparing with an initial visual acuity of counting fingers or worse have reported spontaneous improvement in visual outcomes within the first 7 days of onset.14 Also, we did not have OCT angiography (OCT-A) or fluorescein angiography (FFA) images after therapy, which could have demonstrated the reperfusion more accurately. These objective methods to assess reperfusion could not be performed because of the emergent nature of our case, where assessing clinical improvement was our primary concern. We recommend that future studies consider more objective measures to assess reperfusion outcomes following thrombolysis, such as OCT-A, FFA, and Doppler imaging of the central retinal artery. A single case report is insufficient to base a recommendation of tenecteplase as a thrombolytic agent in patients presenting with CRAO; nevertheless, the clinical results in our case indicate that further, systematic investigation of this particular agent is warranted.