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Clinical Trial
. 2018 May 29;13(5):e0198114.
doi: 10.1371/journal.pone.0198114. eCollection 2018.

Intravenous thrombolysis in acute central retinal artery occlusion - A prospective interventional case series

Maximilian Schultheiss  1   2 , Florian Härtig  3 , Martin S Spitzer  1   2 , Nicolas Feltgen  4 , Bernhard Spitzer  5 , Johannes Hüsing  6 , André Rupp  7 , Ulf Ziemann  3 , Karl U Bartz-Schmidt  2 , Sven Poli  3
Affiliations
Clinical Trial

Intravenous thrombolysis in acute central retinal artery occlusion - A prospective interventional case series

Maximilian Schultheiss et al. PLoS One. .

Abstract

Background: No evidence-based therapy exists for non-arteritic central retinal artery occlusion (NA-CRAO). Retinal ischemic tolerance is low; irreversible damage occurs within four hours of experimental NA-CRAO. In previous randomized trials evaluating intra-arterial or intravenous thrombolysis (IVT) in NA-CRAO, only one patient was treated this early. In December 2013, the Departments of Neurology & Stroke and Ophthalmology at University Hospital Tuebingen, Germany, decided to treat patients using IVT within 4.5 hours of NA-CRAO, the therapeutic window established for ischemic stroke.

Materials and methods: Consecutive NA-CRAO patients with severe visual loss received IVT after exclusion of intracranial hemorrhage. Follow-up was conducted at day 5 (d5) and day 30 (d30). Visual outcomes were compared to the conservative standard treatment (CST) arm of the EAGLE-trial.

Results: Until August 2016, 20 patients received IVT within 4.5 hours after NA-CRAO with a median onset-to-treatment time of 210 minutes (IQR 120-240). Visual acuity improved from baseline mean logarithm of the minimum angle of resolution 2.46±0.33 (SD) (light perception) to 1.52±1.09 (Snellen equivalent: 6/200) at d5 (p = 0.002) and 1.60±1.08 (Snellen equivalent: 6/240) at d30. Compared to the EAGLE CST-arm, functional recovery to reading ability occurred more frequently after IVT: 6/20 (30%) versus 1/39 (3%) at d5 (p = 0.005) and at d30 5/20 (25%) versus 2/37 (5%) (p = 0.045). Two patients experienced serious adverse events (one angioedema and one bleeding from an abdominal aortic aneurysm) but recovered without sequelae.

Conclusions: IVT within 4.5 hours after symptom onset may represent an effective treatment of NA-CRAO. Randomized trials are warranted to evaluate efficacy and safety of early IVT in acute NA-CRAO.

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Conflict of interest statement

Sven Poli received speaker’s honoraria and reimbursement for congress travels from Boehringer-Ingelheim. All other authors have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Patient flow.
BCVA = best corrected visual acuity, CRAO = central retinal artery occlusion, IVT = intravenous thrombolysis, INR = international normalized ratio, LogMAR = logarithm of the minimum angle of resolution.
Fig 2
Fig 2
Evolution of best corrected visual acuity over time (BCVA): (A) mean BCVA of our intravenous thrombolysis (IVT) cohort (N = 20) and of the conservative standard treatment (CST) group of the EAGLE-trial [7]. (B) individual BCVA of our IVT-cohort and (C) of the EAGLE CST-arm. Functional blindness (LogMAR >1.3) and functional recovery (LogMAR ≤0.5) are indicated by a gray and blue background, respectively. LogMAR = logarithm of the minimum angle of resolution.
Fig 3
Fig 3. Categorical presentation of best corrected visual acuity.
Categorical presentation of best corrected visual acuity (according to the current version of the WHO International Classification of Diseases [14]) at baseline and at day 30 of our intravenous thrombolysis cohort and of the conservative standard treatment group of the EAGLE-trial [7]. We defined favorable outcome as mild or no visual impairment (LogMAR ≤0.5, indicated in blue). Unfavorable outcome includes moderate or severe visual impairment (LogMAR >0.5 to ≤1.3) and functional blindness (LogMAR >1.3). LogMAR = logarithm of the minimum angle of resolution.
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