November 2013
Volume 54, Issue 12
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Retina  |   November 2013
Efficacy and Safety of Intra-Arterial Thrombolysis in Central Retinal Artery Occlusion
Author Affiliations & Notes
  • Seong Joon Ahn
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Jae Min Kim
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Jeong-Ho Hong
    Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Se Joon Woo
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Jeeyun Ahn
    Department of Ophthalmology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
  • Kyu Hyung Park
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Moon-Ku Han
    Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Cheolkyu Jung
    Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
  • Correspondence: Se Joon Woo, Department of Ophthalmology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, Gyeonggi-do 463-707, Korea; sejoon1@snu.ac.kr
Investigative Ophthalmology & Visual Science November 2013, Vol.54, 7746-7755. doi:10.1167/iovs.13-12952
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      Seong Joon Ahn, Jae Min Kim, Jeong-Ho Hong, Se Joon Woo, Jeeyun Ahn, Kyu Hyung Park, Moon-Ku Han, Cheolkyu Jung; Efficacy and Safety of Intra-Arterial Thrombolysis in Central Retinal Artery Occlusion. Invest. Ophthalmol. Vis. Sci. 2013;54(12):7746-7755. doi: 10.1167/iovs.13-12952.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose.: To investigate the efficacy and safety of intra-arterial thrombolysis (IAT) for acute central retinal artery occlusion (CRAO).

Methods.: Records from 101 CRAO patients treated with either IAT (n = 57) or standard treatment (ST; n = 44) were retrospectively reviewed. ST consisted of ocular massage and intraocular pressure-lowering agents. We used fundoscopic and angiographic findings to categorize CRAO as incomplete (diminished visual acuity [VA] with slight retinal edema, slight cherry-red spot), subtotal (severe VA reduction, cherry-red spot, distinct retinal edema), or total (massive edema, occluded perimacular arterioles, additional choroidal blood flow interruption). One-month and final best-corrected VA (BCVA) of the IAT group were compared with those of the ST group. Early (≤3-day) and final (1-month) reperfusion (improvement of retinal perfusion) rates were compared between groups. Subgroup analyses were performed according to CRAO stage.

Results.: Overall, VA did not significantly differ between groups, but early reperfusion was greater in the IAT group (74.1% vs. 42.9%, P = 0.005). In incomplete CRAO, the IAT group exhibited greater visual improvement after 1 month (1.08 ± 0.21 vs. 0.23 ± 0.26 logarithmic values of the minimum angle of resolution [logMAR], P < 0.001) and at the final visit (1.08 ± 0.53 vs. 0.08 ± 0.57 logMAR, P < 0.001). However, in subtotal and total CRAO, no significant differences in visual outcomes were observed between groups. IAT resulted in clinically insignificant cerebral infarcts, detectable on brain imaging, in 8% of patients. Hemorrhagic transformation was not noted.

Conclusions.: The IAT treatment may provide early restoration of retinal perfusion and offer functional benefits in the management of incomplete CRAO.

Introduction
Central retinal artery occlusion (CRAO) is an ocular vascular occlusive disorder that causes inner retinal ischemia. Visual prognosis in patients with CRAO is poor, as 92% have permanent visual loss, with a final visual acuity (VA) of counting fingers or less, and only up to 8% of patients experience meaningful vision recovery. 17 The stages of CRAO are as follows 8,9 : incomplete CRAO is characterized by diminished VA (but not complete vision loss), slight retinal edema with a slight cherry-red spot on the macula, and delayed (but not completely interrupted) blood flow on fluorescein angiography (FA). Subtotal CRAO results in a severe reduction in VA, distinct edema of the central retina with a cherry-red spot on the macula, and a distinct delay in arterial blood flow. Total CRAO is distinguished from the aforementioned stages by massive retinal edema, without a cherry-red spot, a lack of blood flow in the perimacular arterioles, and an additional blood flow interruption of the choroid. Schmidt and Schumacher 9 reported that of 46 patients with CRAO, 26 (56.5%) patients had subtotal occlusion, 10 (21.7%) had incomplete occlusion, and 10 (21.7%) had total occlusion. In another report, 21.9%, 73.0%, and 5.1% of patients were diagnosed with incomplete, subtotal, and total CRAO, respectively. 8  
Standard treatment modalities for CRAO include ocular massage, anterior chamber paracentesis, intraocular pressure (IOP)-lowering agents (e.g., mannitol, acetazolamide, topical agents), hyperbaric oxygen, anticoagulants, and hemodilution. 57,1024 Thrombolysis has also been used, both intravenously and intra-arterially, for the treatment of CRAO. 1,2534 A placebo-controlled, randomized trial by Chen et al. 25 showed that only 2 of 8 patients treated with an intravenous tissue-type plasminogen activator had an improvement in VA of 3 or more lines. Recently, the European Assessment Group for Lysis in the Eye (EAGLE) trial, a prospective, randomized, multicenter study, 30 compared the effect of intra-arterial thrombolysis (IAT) with that of standard CRAO treatments. This trial showed that the final (1-month) visual outcomes were not different between the IAT and standard treatment (ST) groups, although IAT caused higher rates of treatment-related adverse reactions. 
However, we believe it is unreasonable to disregard IAT as a treatment modality for all cases with CRAO based on the EAGLE trial alone. Although Schmidt and Schumacher 9 reported different IAT efficacies for different CRAO stages, the authors overlooked the heterogeneous nature of CRAO and did not perform a detailed CRAO stage subgroup analysis. Furthermore, the primary outcome was evaluated 1 month after IAT and compared between the two treatment groups. Therefore, a comparison of the long-term procedural results could not be obtained from this randomized, prospective study. In addition, anatomic outcomes, such as central retinal artery reperfusion, were not evaluated, although central retinal artery reperfusion may be a potential benefit of the intervention. 
In the present study, we compared visual and anatomic outcomes between IAT and ST in a relatively large number of patients with CRAO. Additionally, we performed CRAO stage subgroup analyses. Furthermore, we investigated factors associated with IAT treatment outcome and reviewed baseline brain magnetic resonance images (MRI) and those obtained after IAT to evaluate adverse events associated with IAT in depth. 
Methods
Patients
The institutional review board of Seoul National University Bundang Hospital approved this retrospective study, and the study adhered to the tenets of the Declaration of Helsinki. A review of the medical records of consecutive patients diagnosed with acute non-arteritic CRAO from January 2003 through December 2012, at Seoul National University Bundang Hospital, was performed. Patients with an initial significant visual disturbance (≤20/63 Snellen VA) and a follow-up period ≥1 month were included. 
Eligibility Criteria and Treatment
A CRAO was diagnosed with FA and fundoscopy in all patients. Patients meeting the eligibility criteria for thrombolysis (Table 1) at initial presentation were considered for IAT. The eligibility criteria for IAT were symptom duration of <24 hours for subtotal and total CRAO and <7 days for incomplete CRAO. Systemic conditions restricting thrombolysis, including uncontrolled hypertension, coagulation disorders, and antithrombotic treatments, excluded patients from receiving IAT. Cases with combined ocular pathologies that might influence visual outcome or other ocular ischemic disease, such as ocular ischemic syndrome, central retinal vein occlusion, and proliferative diabetic retinopathy, were also excluded. Iatrogenic cases of CRAO were also excluded. 
Table 1
 
Inclusion and Exclusion Criteria of Subjects
Table 1
 
Inclusion and Exclusion Criteria of Subjects
Inclusion criteria
 1) Non-arteritic CRAO
 2) Symptom duration ≤24 h (or ≤7 d in cases of incomplete   CRAO8)
 3) BCVA ≤ 20/63 (Snellen)
 4) Follow-up period ≥ 1 mo
Exclusion criteria
 Ocular factor or disease
  1) Spontaneous improvement of vision or retinal perfusion at   initial presentation (<4 h after symptom onset)
  2) Branch retinal artery occlusion
  3) Combined central retinal vein occlusion
  4) Suspicious ocular ischemic syndrome
  5) Central retinal artery occlusion from iatrogenic cause
  6) Combined ocular pathologies interfering visual outcome (i.e.,   diabetic macular edema)
 Systemic conditions restricting thrombolysis
  1) Uncontrolled hypertension (systolic blood pressure   > 200 mm Hg)
  2) Coagulation disorder
  3) History of heart attack, intracranial hemorrhage, cerebral   infarction, or intracranial surgery within 3 mo
  4) Intracranial hemorrhage in brain MRIs at baseline
  5) Current antithrombotic treatment
  6) A history of allergic reaction to contrast agent
  7) Unable to undergo thrombolysis for carotid and ophthalmic   artery obstruction
The ST group included patients who were eligible for IAT but refused the treatment and those who met the eligibility criteria for IAT but visited the hospital before IAT initiation at our hospital in May 2008. Those patients were treated with ocular massage (repeated manual compression for 10–15 seconds followed by sudden release, using a 3-mirror contact lens for 3–5 minutes) and IOP-lowering agents (topical timolol 0.5%, oral acetazolamide 500 mg). 
After an ophthalmologist provided a detailed procedure description and discussed potential complications, IAT was performed, along with cerebral angiography using a biplane angiographic unit (IntegrisAllura; Philips Medical Systems, Eindhoven, The Netherlands). The microcatheter (Excelsior SL-10; Stryker Neurovascular, Fremont, CA) was placed in the proximal segment of the ophthalmic artery, and up to 500,000 units of urokinase (Green Cross, Yongin, Korea) was slowly injected by hand. During the IAT procedure, an ophthalmologist checked VA and performed fundoscopic examination to evaluate retinal changes following each 100,000-unit injection of urokinase until visual improvement was noticed. If visual improvement was not noted, up to 500,000 units of the thrombolytic was infused, provided the patient had no bleeding risk. 
Examinations
We obtained data pertaining to age, sex, and time from symptom onset to treatment. All measurements of best-corrected VA (BCVA) were obtained using a standardized Snellen chart. Snellen VA measurements were converted into logarithmic minimum angle of resolution (logMAR) equivalent values for statistical analysis. The numerical scores for profound low vision, namely, counting fingers or worse, were substituted for logMAR values, as suggested by Lange et al. 35 The amounts of visual improvement at 1 month and at the final visit were calculated by the change in BCVA from baseline. A clinically significant visual improvement was defined as a visual improvement ≥ 0.3 logMAR. 
To quantify the degree of circulatory disturbance in each case of CRAO, the arm-to-retina time until fluorescein appearance 36 and arteriovenous passage time 37 were evaluated for pre-treatment FA images, obtained at the time of CRAO diagnosis. The central retinal artery was considered reperfused if follow-up FA images showed significantly reduced arm-to-retina time and arteriovenous passage time. Early reperfusion was assessed using FA images obtained within 3 days of treatment, and final reperfusion was evaluated 1 month after treatment. 
In both the IAT and ST groups, adverse reactions were identified by clinical examinations and from patient symptoms. Sixty-five patients, including 35 in the IAT group and 30 in the ST group, underwent brain MRI at baseline. Thirty-one patients in the IAT group underwent brain MRI after IAT. In 25 patients from the IAT group, diffusion-weighted MRI images obtained before and after IAT were compared to detect new ischemic lesions following IAT. Hemorrhagic or ischemic lesions were confirmed by the consensus from one trained neuroradiologist and one trained neurologist. 
Statistical Analyses
We compared final visual and anatomic outcomes (reperfusion status) of the IAT with those of the ST group. After categorizing CRAO as incomplete, subtotal, and total, as suggested by Schmidt et al., 8 we analyzed treatment outcomes between the IAT and ST groups. For comparison, the Mann-Whitney U test or Student's t‐test was used, depending on normality (determined by the Shapiro-Wilk test), to compare means of continuous variables. Dichotomous data were analyzed using the χ2 test or Fisher exact test. 
We also investigated predictive factors for visual outcome. Multiple regression analyses were performed to identify factors associated with 1-month or final BCVA by using clinical parameters. Descriptive statistics were performed with baseline cerebral pathologies and adverse reactions following IAT. Commercial software was used for all statistical analyses (SPSS version 17.0; SPSS, Inc., Chicago, IL; for Windows; Microsoft, Redmond, WA). Statistical significance was assigned at a P value of <0.05. 
Results
Clinical Characteristics of Included Patients
Of 127 consecutive acute nonarteritic CRAO patients evaluated during the study period, 101 (26 [26%] incomplete, 48 [48%] subtotal, 27 [27%] total) CRAO patients met inclusion criteria (Fig. 1). The IAT and ST groups included 57 (13 incomplete, 28 subtotal, 16 total) and 44 (13 incomplete, 20 subtotal, and 11 total) CRAO patients, respectively. The ST group included 33 patients who refused IAT because of safety concerns and 11 patients who visited our hospital before May 2008, the time IAT became available to our acute CRAO patients. All 11 patients were treated with ocular massage and IOP-lowering agents. Representative cases with CRAO are shown in Figure 2. Significant differences in demographic data between IAT (n = 57) and ST (n = 44) groups were not found (Table 2), except for time between symptom onset and treatment in the subtotal (16.4 ± 11.2 hours in the IAT group versus 40.5 ± 30.3 hours in the ST group) and total CRAO subgroups (11.2 ± 6.4 hours in the IAT group versus 33.0 ± 25.5 hours in the ST group). 
Figure 1
 
Flow chart shows our study design and patient inclusion/exclusion criteria.
Figure 1
 
Flow chart shows our study design and patient inclusion/exclusion criteria.
Figure 2
 
Fundus photograph (left column) and fluorescein angiographs obtained before and 1 day after treatment (middle and right columns) for representative cases of subtotal (A) and incomplete (B, C) CRAO. Text (upper right corner) indicates the time at which images were taken; images at lower right corner denote best-corrected VA. The 75-year-old man (A) and 62-year-old man (B) showed anatomic success (early reperfusion) after intra-arterial thrombolysis. Visual acuity in the eye with subtotal CRAO (A) was hand motion at both the first visit and at 1 month after IAT, whereas that with incomplete CRAO (B) improved from counting fingers to 20/100. For the 74-year-old man with incomplete CRAO treated with standard treatment (C), there was no improvement in either VA (stable at 20/1000) or retinal perfusion.
Figure 2
 
Fundus photograph (left column) and fluorescein angiographs obtained before and 1 day after treatment (middle and right columns) for representative cases of subtotal (A) and incomplete (B, C) CRAO. Text (upper right corner) indicates the time at which images were taken; images at lower right corner denote best-corrected VA. The 75-year-old man (A) and 62-year-old man (B) showed anatomic success (early reperfusion) after intra-arterial thrombolysis. Visual acuity in the eye with subtotal CRAO (A) was hand motion at both the first visit and at 1 month after IAT, whereas that with incomplete CRAO (B) improved from counting fingers to 20/100. For the 74-year-old man with incomplete CRAO treated with standard treatment (C), there was no improvement in either VA (stable at 20/1000) or retinal perfusion.
Table 2
 
Comparison Between Demographic and Clinical Characteristics of the IAT and ST Groups
Table 2
 
Comparison Between Demographic and Clinical Characteristics of the IAT and ST Groups
Characteristic IAT Group ST Group P *
No. of patients 57 44 NA
Mean age, y (range) 58.3 ± 14.7 (18–79) 64.5 ± 17.4 (19–90) 0.054
Male:female 36:21 29:15 0.775
Time from symptom onset to treatment, hours (range) 22.7 ± 30.6 (1–172) 35.9 ± 27.6 (2–120) 0.054
 Incomplete CRAO, n = 26 50.5 ± 54.3 (9–172) 29.7 ± 26.8 (4–34) 0.391
 Subtotal CRAO, n = 48 16.4 ± 11.2 (3–42) 40.5 ± 30.3 (2–120) 0.011
 Total CRAO, n = 27 11.2 ± 6.4 (1–23) 33.0 ± 25.5 (5–72) 0.034
Mean follow-up period, mo (range) 9.9 ± 12.4 (1–55) 13.3 ± 19.2 (1–74) 0.308
Mean initial visual acuity, logMAR (range) 2.32 ± 0.47 (0.52–2.9) 2.10 ± 0.66 (0.22–2.9) 0.065
Stage, incomplete:subtotal:total 13:28:16 13:20:11 0.742
Visual Outcome
The mean BCVA values at the initial visit, 1 month after treatment, and final visit are shown in Figure 3. Overall, initial, 1-month, and final BCVAs were not significantly different between the IAT and ST groups (Table 3). Among the patients with subtotal and total CRAO (Table 4), all BCVAs were not significantly different between the two groups. However, subgroup analyses among those with incomplete CRAO revealed significant differences in final BCVA between the groups (1.57 ± 0.73 in the ST group versus 0.83 ± 0.61 in the IAT group, P = 0.020). 
Figure 3
 
Temporal patterns of BCVA in the IAT and ST groups among all patients with CRAO and those with incomplete, subtotal, and total CRAO. Error bars denote upper or lower bound of 95% confidence intervals. *Statistical significance (P < 0.05).
Figure 3
 
Temporal patterns of BCVA in the IAT and ST groups among all patients with CRAO and those with incomplete, subtotal, and total CRAO. Error bars denote upper or lower bound of 95% confidence intervals. *Statistical significance (P < 0.05).
Table 3
 
Comparison Between Overall Anatomic and Visual Outcomes of the IAT and ST Groups
Table 3
 
Comparison Between Overall Anatomic and Visual Outcomes of the IAT and ST Groups
Outcome IAT Group, n = 57 ST Group, n = 44 P
Visual outcome
 Mean amount of visual improvement at 1 mo, logMAR 0.13 ± 0.46 0.05 ± 0.44 0.519
 Mean amount of visual improvement at the final visit, logMAR 0.31 ± 0.63 0.08 ± 0.51 0.062
 No. of eyes with BCVA ≥20/200 at 1 mo, % 6, 10.5 1, 2.3 0.108
 No. of eyes with BCVA ≥20/200 at the final visit, % 11, 19.3 2, 4.5 0.026
 No. of eyes showing clinically significant visual improvement at 1 mo, %* 18, 31.6 12, 27.3 0.639
 No. of eyes showing clinically significant visual improvement* at the final visit, % 24, 42.1 11, 25 0.056
Anatomic outcome
 No. of eyes showing early (≤3 d) reperfusion/no. of FA performed, % 40/54, 74.1 12/28, 42.9 0.005
 No. of eyes showing final (1 mo) reperfusion/no. of FA performed, % 45/51, 88.2 25/31, 80.6 0.346
Table 4
 
Comparison Among Demographic Data, Baseline Clinical Characteristics, and Treatment Outcomes of IAT and ST Groups According to Stage of CRAO
Table 4
 
Comparison Among Demographic Data, Baseline Clinical Characteristics, and Treatment Outcomes of IAT and ST Groups According to Stage of CRAO
Demographic Data Incomplete CRAO, N = 26 P * Subtotal CRAO, N = 48 P Total CRAO, N = 27 P *
IAT Group n = 13 ST Group n = 13 IAT Group n = 28 ST Group n = 20 IAT Group n = 16 ST Group n = 11
Mean age 60.5 ± 10.8 64.3 ± 14.6 0.461 56.4 ± 17.4 67.0 ± 13.4 0.027 59.9 ± 12.7 60.5 ± 25.9 0.945
Male:female 8:5 10:3 0.336 17:11 15:5 0.301 11:5 4:7 0.102
Mean time from symptom onset to treatment, h 50.5 ± 54.3 (9–172) 29.7 ± 26.8 (4–34) 0.391 16.4 ± 11.2 (3–42) 40.5 ± 30.3 (2–120) 0.011 11.2 ± 6.4 (1–23) 33.0 ± 25.5 (5–72) 0.034
Mean initial BCVA, logMAR (range) 1.93 ± 0.58 (20–60-HM) 1.78 ± 0.52 (20–60-HM) 0.532 2.43 ± 0.37 (20–150-NLP) 2.23 ± 0.67 (20–400-NLP) 0.082 2.60 ± 0.29 (HM-NLP) 2.63 ± 0.28 (HM-NLP) 0.810
Visual outcome
 Mean visual  improvement at 1  month, logMAR  (range) 1.08 ± 0.21 (0.40–1.9) 0.23 ± 0.26 (−0.30–1.3) <0.001 0.03 ± 0.40 (−1.4–0.9) −0.03 ± 0.40 (−1.4–1.1) 0.689 0.04 ± 0.11 0.04 ± 0.11 0.926
 Mean visual  improvement at  final visit, logMAR  (range) 1.08 ± 0.53 (0–1.6) 0.08 ± 0.57 (−0.3–1.3) <0.001 0.10 ± 0.53 (−1.4–1.1) 0.07 ± 0.60 (−1.5–1.2) 0.890 0.11 ± 0.36 0.10 ± 0.27 0.961
 No. of eyes with 1-  mo BCVA ≥20/200  (%) 6 (46.2) 1 (7.7) 0.037 0 0 N/A 0 0 N/A
 No. of eyes with  final BCVA ≥20/  200 (%) 9 (69.2) 2 (15.4) 0.008 2 (7.1) 0 0.335 0 0 N/A
 No. of eyes with  clinically  significant visual  improvement at 1  mo (%)‡ 10 (76.9) 6 (46.2) 0.113 4 (14.3) 4 (20) 0.442 0 0 N/A
 No. of eyes with  clinically  significant visual  improvement at  final visit (%)‡ 11 (84.6) 3 (23.1) 0.002 7 (25) 5 (25) 0.628 3 (18.8) 2 (18.2) 0.684
Anatomic outcome
 No. of early (≤3-d)  reperfusion/no. of  FA performed 11/11 (100) 5/9 (55.6) 0.026 21/28 (75) 6/11 (54.5) 0.194 8/15 (53.3) 1/8 (12.5) 0.069
 No. of final (1-mo)  reperfusion/no. of  FA performed 11/11 (100) 5/8 (62.5) 0.058 21/25 (84) 13/15 (86.7) 0.600 13/15 (86.7) 7/8 (87.5) 0.731
Among all patients, the amounts of visual improvement between 1 month (0.13 ± 0.46 [IAT group] vs. 0.05 ± 0.44 logMAR [ST group], P = 0.519) and at the final visit (0.31 ± 0.63 vs. 0.08 ± 0.51, P = 0.062) were not significantly different between the IAT and ST groups. There were no significant differences in visual improvement at 1 month or the final visit between the two groups in subgroup comparisons among patients with subtotal or total CRAO (Table 4). However, statistically significant differences were noted in the comparisons between groups of visual improvement at 1-month and at the final visit among patients with incomplete CRAO (both, P < 0.001). 
The percentages of eyes with a BCVA equal to or better than 20/200 and those with a clinically significant visual improvement (≥0.3 logMAR) in the IAT and ST groups are presented in Figures 4A and 4B, respectively. Among all included patients, percentages were not significantly different between the two groups at 1 month after treatment (P = 0.108 and 0.639, respectively). However, at the final visit, the percentage of eyes with a BCVA equal to or better than 20/200 was significantly greater in the IAT group than in the ST group (19.3% vs. 4.5%, respectively, P = 0.026), whereas the percentages of eyes with clinically significant visual improvement were not significantly different between the two groups (42.1% vs. 25%, respectively, P = 0.056). The percentages of eyes with a BCVA equal to or better than 20/200 and that had a clinically significant visual improvement at the final visit were significantly greater in eyes with incomplete CRAO treated with IAT than in ST eyes (P = 0.008 and 0.002, respectively). In contrast, the same comparisons among the patients with subtotal or total CRAO revealed no significant intergroup differences at 1 month or at the final visit. 
Figure 4
 
(A) Percentages of BCVA ≥ 20/200 and (B) clinically significant visual improvement (≥0.3 logMAR) in the IAT and ST groups among all patients with CRAO and those with incomplete, subtotal, and total CRAO.
Figure 4
 
(A) Percentages of BCVA ≥ 20/200 and (B) clinically significant visual improvement (≥0.3 logMAR) in the IAT and ST groups among all patients with CRAO and those with incomplete, subtotal, and total CRAO.
Anatomic Outcome
The early reperfusion rate, as evaluated by FA, was significantly greater in the IAT group than in the ST group (40 of 54 [74.1%] vs.12 of 28 [42.9%], respectively, P = 0.005), whereas the final reperfusion rate was not significantly different (45 of 51 [88.2%] vs. 25 of 31 [80.6%], respectively, P = 0.346). Subgroup analyses revealed significant differences in early reperfusion rates between the IAT and ST groups with incomplete CRAO (100% vs. 55.6%, P = 0.026), as presented in Table 4
Factors Associated With Visual Outcome
Among the clinical factors examined (e.g., age, sex, CRAO stage, CRAO treatment, initial BCVA, time between symptom and treatment, follow-up period, arm-to-retina time, and arteriovenous passage time), CRAO stage was the only factor significantly associated with 1-month BCVA (P < 0.001, multiple regression analysis). Initial BCVA (P = 0.038) and CRAO stage (P < 0.001) were significantly associated with final BCVA. 
Adverse Reactions
Table 5 shows the neurological and non-neurological adverse reactions associated with IAT, as identified by clinical and laboratory examinations and brain MRI. After IAT, we observed cases of hematoma at the vessel puncture site (n = 2 [3.5%]), increased IOP (n = 2 [3.5%]), hemianopsia (n = 1 [1.8%]), headache (n = 1 [1.8%]), tinnitus (n = 1 [1.8%]), and hyperesthesia (n = 1 [1.8%]) in the IAT group (Table 5). 
Table 5
 
Neurological and Non-Neurological Adverse Reactions after Intra-Arterial Thrombolysis in Patients With Central Retinal Artery Occlusion
Table 5
 
Neurological and Non-Neurological Adverse Reactions after Intra-Arterial Thrombolysis in Patients With Central Retinal Artery Occlusion
Reaction No. of Patients/ No. of MRIs or Examinations Performed, %
Neurological adverse reactions after IAT
 Embolic infarction* 8/31, 25.8
 Symptomatic neurological  deterioration† 1/57, 1.8
 Intracranial hemorrhage 0/31
 Transient ischemic attack 0/31
 Death related to any neurologic  problem 0/57
Non-neurological non-ocular adverse reactions after IAT
 Hematoma at vessel puncture  sites 2/57, 3.5
 Headache 1/57, 1.8
 Tinnitus 1/57, 1.8
 Hyperesthesia 1/57, 1.8
 Treatment-associated infection 0
 Anaphylaxis 0
 Renal dysfunction 0
Ocular adverse reactions after IAT
 Increased intraocular pressure 2/57, 3.5
Brain MRI provided detailed information regarding baseline cerebral pathology and adverse reactions following IAT. Eight of 65 (12.3%) patients with CRAO had concurrent acute or old ischemic lesions, which were detected in baseline MRI images. In the IAT group, post-IAT MRI images showed that 8 of 31 (25.8%) patients had acute infarctions. Diffusion-weighted images identified new ischemic lesions, occurring after IAT in 2 of 25 (8%) patients in the IAT group. Among 8 patients showing acute infarctions on post-IAT brain MRI, 7 cases were asymptomatic and clinically insignificant. Neurologic examinations did not reveal any sign suggestive of cerebral infarct, and the infarcted lesions in MR images were small. However, 1 patient exhibited hemianopsia due to right occipital lobe infarct with posterotemporal branch occlusion of the right middle cerebral artery, followed by immediate mechanical thrombolysis for recanalization, that completely recovered within 7 days. No case presented with intracranial hemorrhage or transient ischemic attack following IAT. 
After a thorough stroke risk factor workup, including assessment of potential cardioembolic stroke sources, we treated the patient with embolic infarction following IAT with an antiplatelet agent and a cholesterol-lowering medication (statin) for the secondary prevention of stroke. Post-IAT headache resolved after oral non-steroidal anti-inflammatory drug therapy within 1 or 2 days, and both tinnitus and hyperesthesia lasted only for a few hours and resolved without treatment. Hematomas occurring at the vessel puncture site were not large in our patients, and hemostasis was obtained with bed rest and by applying manual compression for 10 to 20 minutes. Increased intraocular pressure caused by neovascular glaucoma required topical IOP-lowering medications and, eventually, valve implant surgery for uncontrolled IOP. 
Discussion
This study suggests that IAT may be beneficial for visual recovery in eyes with incomplete CRAO. Although retinal artery reperfusion occurred more frequently in the IAT group among patients with CRAO, patients with subtotal or total CRAO in the IAT group showed visual improvement comparable to those in the ST group. Although the randomized EAGLE trial did not show that IAT was superior to ST, our results suggest that IAT may be beneficial for visual recovery in select cases of CRAO and that it may be a viable treatment option for these cases. However, in 8% of patients, IAT resulted in a new cerebral infarct that was clinically insignificant but was detected by comparing brain MRI images obtained before and after IAT. Therefore, the risk of an associated infarct following IAT should be carefully considered when deciding to perform the treatment. 
Previously, studies by Schmidt et al. 8 and Schmidt and Schumacher 9 suggested dividing the three CRAO stages on the basis of clinical, fundoscopic, and angiographic findings. Their reported subgroup percentages were comparable to ours (26%, 48%, and 27% for incomplete, subtotal, and total CRAO, respectively). Schmidt and Schumacher 9 reported different IAT efficacies according to the stage of CRAO. They suggested that IAT has a beneficial effect in patients with incomplete CRAO. However, their study did not include a control group, which is essential for providing evidence for IAT use in CRAO. By comparing both functional and anatomical outcomes between the IAT and ST groups in patients with CRAO, our study showed that early reperfusion rates were significantly greater in the IAT group than in the ST group, indicating that IAT has a beneficial effect on reperfusion. The anatomic outcomes might be associated with visual outcome, as the temporal changes in BCVA showed different patterns from 1 month after treatment to the final visit between the IAT and ST groups (further improved and deteriorated BCVA, respectively). 
The clinical efficacy of IAT for CRAO has been reported in several retrospective studies and meta-analyses. 2629,31,32,34 However, the treatment outcomes vary greatly from study to study. Our findings, with regard to visual outcomes, differed from those reported in the EAGLE study. More specifically, the BCVA changes at 1 month in the IAT and ST groups in the EAGLE study (0.45 and 0.44 logMAR, respectively) differed from those in our study (0.13 and 0.05 logMAR, respectively). The discrepancies in the types of treatment performed for the ST group (6 modalities in the EAGLE trial versus 3 modalities in our study), the time from onset to treatment (longer in our study), and materials used for thrombolysis may have resulted in the discrepancy between BCVA changes in previous studies and ours. However, the EAGLE study and our study in common showed that overall visual outcomes in the IAT and ST groups were similar. Our study also suggests that IAT may be beneficial when used for treating incomplete CRAO. 
Retinal survival time after CRAO was reported to be as long as 97 to 100 minutes, with irreversible retinal damage occurring beyond 105 minutes in animal experiments. 38 However, the extreme retinal clamping used in those experimental settings does not reflect the actual clinical conditions under which CRAO is treated in humans. For incomplete CRAO, the retinal tolerance time may be prolonged and retinal ischemic injury can be reversible after retinal reperfusion by IAT. For instance, 84.6% of patients with incomplete CRAO in the IAT group showed a clinically significant visual improvement at the final visit, whereas only 14.3% of patients with subtotal CRAO and none with total CRAO had a clinically significant visual improvement after IAT. However, if patients with incomplete CRAO are not treated by IAT and early reperfusion is not obtained, as was the case in the ST group, retinal ischemic injury may lead to permanent vision loss even if reperfusion is spontaneously obtained without invasive procedures in more delayed fashion than in the IAT group. To support this hypothesis, the retinal tolerance time in incomplete CRAO should be investigated in future studies. Regarding the tolerance time, 1 patient with incomplete CRAO showed a clinically significant visual improvement after IAT, which was performed 172 hours after initial symptom onset. On the basis of this finding, our eligibility criterion for IAT was set at an interval of ≤7 days from symptom onset to treatment in cases of incomplete CRAO. 
The major complication related to IAT was cerebral infarct, and minor complications included headache, dizziness, and increased IOP. The EAGLE study reported IAT-related major complications (cerebral and cerebellar hemorrhage) in 2 of 44 patients (4.5%). One of the main reasons for the early termination of the EAGLE trial was the higher rate of complications in the IAT group, including 2 cases with cerebral or cerebellar hemorrhage. The main safety concern after thrombolytic therapy is hemorrhagic transformation of the infarct. 39 Therefore, with regard to evaluating the safety of IAT, baseline brain imaging, which was not obtained in the EAGLE trial or in the study by Chen et al., 25 would be valuable for detecting cerebral infarct before thrombolysis and for assessing the risk of hemorrhage and infarction associated with IAT. 40 In our study, brain MRI data showed that a non-negligible proportion of patients (12.3%) had baseline acute and old ischemic lesions, but no IAT case presented with hemorrhagic transformation. The incidence of embolic infarction after IAT (25.8%) was comparable with that of silent embolic events (23%) following diagnostic angiography and intervention, 41 indicating that IAT for CRAO did not carry an increased risk in comparison to conventional diagnostic and interventional angiography. However, silent infarction can be a precursor of symptomatic stroke and is also associated with progressive brain damage and vascular dementia. 42 Those adverse neurologic reactions should be carefully considered in the context of clinical decision making. 
Our study has several limitations. The retrospective nature of the study introduces inherent possibilities of bias, especially selection bias, because it is difficult to control bias and confounders in retrospective studies. In particular, the time between CRAO onset and treatment could not be controlled in this study. Although not statistically significant, the time from onset to treatment tended to be longer in the ST group, which may have affected our results. However, our main finding of a significant difference in visual outcome between the IAT and ST groups in incomplete CRAO may not have resulted from the longer period between CRAO onset and treatment in the ST group. Among the patients with incomplete CRAO, the period was actually longer in the IAT group than in the ST group. Therefore, although the time from CRAO onset to treatment could not be controlled, our study suggests that IAT may be helpful in visual outcome when used for treating incomplete CRAO. 
Furthermore, the sample size was not sufficient for subgroup comparative analyses among patients with incomplete and total CRAO. The inclusion of patients who refused IAT in the ST group is another weakness in our study design. Direct comparisons of our results with those of previous studies are difficult because our study had a different treatment protocol, inclusion criteria, and visual improvement parameters. Finally, variability in the follow-up period of each patient can be another source of bias when considering the evaluation of final visual outcome. 
In conclusion, IAT may have the advantage of early retinal reperfusion in eyes with acute CRAO and significant efficacy in visual restoration in those with incomplete CRAO. However, the adverse events revealed by clinical examinations and brain MRI indicate that IAT should be performed cautiously and selectively. 
Acknowledgments
Supported by a grant from the National Research Foundation of Korea (Grant 2012R1A2A2A02012821). The authors alone are responsible for the content and writing of the paper. 
Disclosure: S.J. Ahn, None; J.M. Kim, None; J.-H. Hong, None; S.J. Woo, None; J. Ahn, None; K.H. Park, None; M.-K. Han, None; C. Jung, None 
References
Arnold M Koerner U Remonda L Comparison of intra-arterial thrombolysis with conventional treatment in patients with acute central retinal artery occlusion. J Neurol Neurosurg Psychiatry . 2005; 76: 196–199. [CrossRef] [PubMed]
Augsburger JJ Magargal LE. Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol . 1980; 64: 913–917. [CrossRef] [PubMed]
Brown GC Magargal LE. Central retinal artery obstruction and visual acuity. Ophthalmology . 1982; 89: 14–19. [CrossRef] [PubMed]
Arruga J Sanders MD. Ophthalmologic findings in 70 patients with evidence of retinal embolism. Ophthalmology . 1982; 89: 1336–1347. [CrossRef] [PubMed]
Atebara NH Brown GC Cater J. Efficacy of anterior chamber paracentesis and Carbogen in treating acute nonarteritic central retinal artery occlusion. Ophthalmology . 1995; 102: 2029–2034; discussion 2025-2034. [CrossRef] [PubMed]
Mueller AJ Neubauer AS Schaller U Kampik A. Evaluation of minimally invasive therapies and rationale for a prospective randomized trial to evaluate selective intra-arterial lysis for clinically complete central retinal artery occlusion. Arch Ophthalmol . 2003; 121: 1377–1381. [CrossRef] [PubMed]
Rumelt S Brown GC. Update on treatment of retinal arterial occlusions. Curr Opin Ophthalmol . 2003; 14: 139–141. [CrossRef] [PubMed]
Schmidt DP Schulte-Monting J Schumacher M. Prognosis of central retinal artery occlusion: local intraarterial fibrinolysis versus conservative treatment. AJNR Am J Neuroradiol . 2002; 23: 1301–1307. [PubMed]
Schmidt D Schumacher M. Stage-dependent efficacy of intra-arterial fibrinolysis in central retinal artery occlusion (CRAO). Neuroophthalmology . 1998; 20: 125–141. [CrossRef]
Aisenbrey S Krott R Heller R Krauss D Rossler G Heimann K. Hyperbaric oxygen therapy in retinal artery occlusion [in German]. Ophthalmologe . 2000; 97: 461–467. [CrossRef] [PubMed]
Albers GW Amarenco P Easton JD Sacco RL Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest . 2004; 126: 483S–512S. [CrossRef] [PubMed]
Beiran I Goldenberg I Adir Y Tamir A Shupak A Miller B. Early hyperbaric oxygen therapy for retinal artery occlusion. Eur J Ophthalmol . 2001; 11: 345–350. [PubMed]
Ffytche TJ. A rationalization of treatment of central retinal artery occlusion. Trans Ophthalmol Soc U K . 1974; 94: 468–479. [PubMed]
Ffytche TJ Bulpitt CJ Kohner EM Archer D Dollery CT. Effect of changes in intraocular pressure on the retinal microcirculation. Br J Ophthalmol . 1974; 58: 514–522. [CrossRef] [PubMed]
Fraser SG Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev . 2009; CD001989.
Garcia-Arumi J Martinez-Castillo V Boixadera A Fonollosa A Corcostegui B. Surgical embolus removal in retinal artery occlusion. Br J Ophthalmol . 2006; 90: 1252–1255. [CrossRef] [PubMed]
Gombos GM. Anterior chamber paracentesis and carbogen treatment of acute CRAO. Ophthalmology . 1996; 103: 865. [CrossRef] [PubMed]
Hausmann N Richard G. Effect of high dose steroid bolus on occlusion of ocular central artery: angiographic study. BMJ . 1991; 303: 1445–1446. [CrossRef] [PubMed]
Incandela L Cesarone MR Belcaro G Treatment of vascular retinal disease with pentoxifylline: a controlled, randomized trial. Angiology . 2002; 53 (suppl 1); S31–S34. [PubMed]
Magargal LE Goldberg RE. Anterior chamber paracentesis in the management of acute nonarteritic central retinal artery occlusion. Surg Forum . 1977; 28: 518–521. [PubMed]
Rufer F Schroder A Winter R Erb C. Analysis of risk factors and comparison of heparin and hemodilution therapies for retinal artery occlusion [in German]. Ophthalmologe . 2003; 100: 819–824. [CrossRef] [PubMed]
Rumelt S Dorenboim Y Rehany U. Aggressive systematic treatment for central retinal artery occlusion. Am J Ophthalmol . 1999; 128: 733–738. [CrossRef] [PubMed]
Steigerwalt RD Jr Pescosolido N Corsi M Cesarone MR Belcaro GV. Acute branch retinal arterial embolism successfully treated with intravenous prostaglandin E1—case reports. Angiology . 2003; 54: 491–493. [CrossRef] [PubMed]
Weinberger AW Siekmann UP Wolf S Rossaint R Kirchhof B Schrage NF. Treatment of acute central retinal artery occlusion (CRAO) by hyperbaric oxygenation therapy (HBO)—pilot study with 21 patients [in German]. Klin Monbl Augenheilkd . 2002; 219: 728–734. [CrossRef] [PubMed]
Chen CS Lee AW Campbell B Efficacy of intravenous tissue-type plasminogen activator in central retinal artery occlusion: report from a randomized, controlled trial. Stroke . 2011; 42: 2229–2234. [CrossRef] [PubMed]
Biousse V Calvetti O Bruce BB Newman NJ. Thrombolysis for central retinal artery occlusion. J Neuroophthalmol . 2007; 27: 215–230. [CrossRef] [PubMed]
Noble J Weizblit N Baerlocher MO Eng KT. Intra-arterial thrombolysis for central retinal artery occlusion: a systematic review. Br J Ophthalmol . 2008; 92: 588–593. [CrossRef] [PubMed]
Richard G Lerche RC Knospe V Zeumer H. Treatment of retinal arterial occlusion with local fibrinolysis using recombinant tissue plasminogen activator. Ophthalmology . 1999; 106: 768–773. [CrossRef] [PubMed]
Schmidt D Schumacher M Wakhloo AK. Microcatheter urokinase infusion in central retinal artery occlusion. Am J Ophthalmol . 1992; 113: 429–434. [CrossRef] [PubMed]
Schumacher M Schmidt D Jurklies B Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology . 2010; 117: 1367–1375. [CrossRef] [PubMed]
Weber J Remonda L Mattle HP Selective intra-arterial fibrinolysis of acute central retinal artery occlusion. Stroke . 1998; 29: 2076–2079. [CrossRef] [PubMed]
Weill A Cognard C Piotin M Laloum L Castaings L Moret J. Persistent value of intra-arterial fibrinolysis 8 hours or more following central retinal artery occlusion or of its branches [in French]. J Fr Ophtalmol . 1998; 21: 466–470. [PubMed]
Schumacher M Schmidt D Wakhloo AK. Intra-arterial fibrinolytic therapy in central retinal artery occlusion. Neuroradiology . 1993; 35: 600–605. [CrossRef] [PubMed]
Beatty S Au Eong KG. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery: a meta-analysis of the published data. Br J Ophthalmol . 2000; 84: 914–916. [CrossRef] [PubMed]
Lange C Feltgen N Junker B Schulze-Bonsel K Bach M. Resolving the clinical acuity categories “hand motion” and “counting fingers” using the Freiburg Visual Acuity Test (FrACT). Graefes Arch Clin Exp Ophthalmol . 2009; 247: 137–142. [CrossRef] [PubMed]
David NJ Saito Y Heyman A. Arm to retina fluorescein appearance time. A new method of diagnosis of carotid artery occlusion. Arch Neurol . 1961; 5: 165–170. [CrossRef] [PubMed]
Bjarnhall G Maepea O Sperber GO Linden C Monestam E Alm A. Analysis of mean retinal transit time from fluorescein angiography in human eyes: normal values and reproducibility. Acta Ophthalmol Scand . 2002; 80: 652–655. [CrossRef] [PubMed]
Hayreh SS Kolder HE Weingeist TA. Central retinal artery occlusion and retinal tolerance time. Ophthalmology . 1980; 87: 75–78. [CrossRef] [PubMed]
Toni D Fiorelli M Bastianello S Hemorrhagic transformation of brain infarct: predictability in the first 5 hours from stroke onset and influence on clinical outcome. Neurology . 1996; 46: 341–345. [CrossRef] [PubMed]
Arthur A Aaron S. Thrombolysis for artery occlusion. Ophthalmology . 2011; 118: 604; author reply 604–605.
Bendszus M Koltzenburg M Burger R Warmuth-Metz M Hofmann E Solymosi L. Silent embolism in diagnostic cerebral angiography and neurointerventional procedures: a prospective study. Lancet . 1999; 354: 1594–1597. [CrossRef] [PubMed]
Vermeer SE Prins ND den Heijer T Hofman A Koudstaal PJ Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med . 2003; 348: 1215–1222. [CrossRef] [PubMed]
Figure 1
 
Flow chart shows our study design and patient inclusion/exclusion criteria.
Figure 1
 
Flow chart shows our study design and patient inclusion/exclusion criteria.
Figure 2
 
Fundus photograph (left column) and fluorescein angiographs obtained before and 1 day after treatment (middle and right columns) for representative cases of subtotal (A) and incomplete (B, C) CRAO. Text (upper right corner) indicates the time at which images were taken; images at lower right corner denote best-corrected VA. The 75-year-old man (A) and 62-year-old man (B) showed anatomic success (early reperfusion) after intra-arterial thrombolysis. Visual acuity in the eye with subtotal CRAO (A) was hand motion at both the first visit and at 1 month after IAT, whereas that with incomplete CRAO (B) improved from counting fingers to 20/100. For the 74-year-old man with incomplete CRAO treated with standard treatment (C), there was no improvement in either VA (stable at 20/1000) or retinal perfusion.
Figure 2
 
Fundus photograph (left column) and fluorescein angiographs obtained before and 1 day after treatment (middle and right columns) for representative cases of subtotal (A) and incomplete (B, C) CRAO. Text (upper right corner) indicates the time at which images were taken; images at lower right corner denote best-corrected VA. The 75-year-old man (A) and 62-year-old man (B) showed anatomic success (early reperfusion) after intra-arterial thrombolysis. Visual acuity in the eye with subtotal CRAO (A) was hand motion at both the first visit and at 1 month after IAT, whereas that with incomplete CRAO (B) improved from counting fingers to 20/100. For the 74-year-old man with incomplete CRAO treated with standard treatment (C), there was no improvement in either VA (stable at 20/1000) or retinal perfusion.
Figure 3
 
Temporal patterns of BCVA in the IAT and ST groups among all patients with CRAO and those with incomplete, subtotal, and total CRAO. Error bars denote upper or lower bound of 95% confidence intervals. *Statistical significance (P < 0.05).
Figure 3
 
Temporal patterns of BCVA in the IAT and ST groups among all patients with CRAO and those with incomplete, subtotal, and total CRAO. Error bars denote upper or lower bound of 95% confidence intervals. *Statistical significance (P < 0.05).
Figure 4
 
(A) Percentages of BCVA ≥ 20/200 and (B) clinically significant visual improvement (≥0.3 logMAR) in the IAT and ST groups among all patients with CRAO and those with incomplete, subtotal, and total CRAO.
Figure 4
 
(A) Percentages of BCVA ≥ 20/200 and (B) clinically significant visual improvement (≥0.3 logMAR) in the IAT and ST groups among all patients with CRAO and those with incomplete, subtotal, and total CRAO.
Table 1
 
Inclusion and Exclusion Criteria of Subjects
Table 1
 
Inclusion and Exclusion Criteria of Subjects
Inclusion criteria
 1) Non-arteritic CRAO
 2) Symptom duration ≤24 h (or ≤7 d in cases of incomplete   CRAO8)
 3) BCVA ≤ 20/63 (Snellen)
 4) Follow-up period ≥ 1 mo
Exclusion criteria
 Ocular factor or disease
  1) Spontaneous improvement of vision or retinal perfusion at   initial presentation (<4 h after symptom onset)
  2) Branch retinal artery occlusion
  3) Combined central retinal vein occlusion
  4) Suspicious ocular ischemic syndrome
  5) Central retinal artery occlusion from iatrogenic cause
  6) Combined ocular pathologies interfering visual outcome (i.e.,   diabetic macular edema)
 Systemic conditions restricting thrombolysis
  1) Uncontrolled hypertension (systolic blood pressure   > 200 mm Hg)
  2) Coagulation disorder
  3) History of heart attack, intracranial hemorrhage, cerebral   infarction, or intracranial surgery within 3 mo
  4) Intracranial hemorrhage in brain MRIs at baseline
  5) Current antithrombotic treatment
  6) A history of allergic reaction to contrast agent
  7) Unable to undergo thrombolysis for carotid and ophthalmic   artery obstruction
Table 2
 
Comparison Between Demographic and Clinical Characteristics of the IAT and ST Groups
Table 2
 
Comparison Between Demographic and Clinical Characteristics of the IAT and ST Groups
Characteristic IAT Group ST Group P *
No. of patients 57 44 NA
Mean age, y (range) 58.3 ± 14.7 (18–79) 64.5 ± 17.4 (19–90) 0.054
Male:female 36:21 29:15 0.775
Time from symptom onset to treatment, hours (range) 22.7 ± 30.6 (1–172) 35.9 ± 27.6 (2–120) 0.054
 Incomplete CRAO, n = 26 50.5 ± 54.3 (9–172) 29.7 ± 26.8 (4–34) 0.391
 Subtotal CRAO, n = 48 16.4 ± 11.2 (3–42) 40.5 ± 30.3 (2–120) 0.011
 Total CRAO, n = 27 11.2 ± 6.4 (1–23) 33.0 ± 25.5 (5–72) 0.034
Mean follow-up period, mo (range) 9.9 ± 12.4 (1–55) 13.3 ± 19.2 (1–74) 0.308
Mean initial visual acuity, logMAR (range) 2.32 ± 0.47 (0.52–2.9) 2.10 ± 0.66 (0.22–2.9) 0.065
Stage, incomplete:subtotal:total 13:28:16 13:20:11 0.742
Table 3
 
Comparison Between Overall Anatomic and Visual Outcomes of the IAT and ST Groups
Table 3
 
Comparison Between Overall Anatomic and Visual Outcomes of the IAT and ST Groups
Outcome IAT Group, n = 57 ST Group, n = 44 P
Visual outcome
 Mean amount of visual improvement at 1 mo, logMAR 0.13 ± 0.46 0.05 ± 0.44 0.519
 Mean amount of visual improvement at the final visit, logMAR 0.31 ± 0.63 0.08 ± 0.51 0.062
 No. of eyes with BCVA ≥20/200 at 1 mo, % 6, 10.5 1, 2.3 0.108
 No. of eyes with BCVA ≥20/200 at the final visit, % 11, 19.3 2, 4.5 0.026
 No. of eyes showing clinically significant visual improvement at 1 mo, %* 18, 31.6 12, 27.3 0.639
 No. of eyes showing clinically significant visual improvement* at the final visit, % 24, 42.1 11, 25 0.056
Anatomic outcome
 No. of eyes showing early (≤3 d) reperfusion/no. of FA performed, % 40/54, 74.1 12/28, 42.9 0.005
 No. of eyes showing final (1 mo) reperfusion/no. of FA performed, % 45/51, 88.2 25/31, 80.6 0.346
Table 4
 
Comparison Among Demographic Data, Baseline Clinical Characteristics, and Treatment Outcomes of IAT and ST Groups According to Stage of CRAO
Table 4
 
Comparison Among Demographic Data, Baseline Clinical Characteristics, and Treatment Outcomes of IAT and ST Groups According to Stage of CRAO
Demographic Data Incomplete CRAO, N = 26 P * Subtotal CRAO, N = 48 P Total CRAO, N = 27 P *
IAT Group n = 13 ST Group n = 13 IAT Group n = 28 ST Group n = 20 IAT Group n = 16 ST Group n = 11
Mean age 60.5 ± 10.8 64.3 ± 14.6 0.461 56.4 ± 17.4 67.0 ± 13.4 0.027 59.9 ± 12.7 60.5 ± 25.9 0.945
Male:female 8:5 10:3 0.336 17:11 15:5 0.301 11:5 4:7 0.102
Mean time from symptom onset to treatment, h 50.5 ± 54.3 (9–172) 29.7 ± 26.8 (4–34) 0.391 16.4 ± 11.2 (3–42) 40.5 ± 30.3 (2–120) 0.011 11.2 ± 6.4 (1–23) 33.0 ± 25.5 (5–72) 0.034
Mean initial BCVA, logMAR (range) 1.93 ± 0.58 (20–60-HM) 1.78 ± 0.52 (20–60-HM) 0.532 2.43 ± 0.37 (20–150-NLP) 2.23 ± 0.67 (20–400-NLP) 0.082 2.60 ± 0.29 (HM-NLP) 2.63 ± 0.28 (HM-NLP) 0.810
Visual outcome
 Mean visual  improvement at 1  month, logMAR  (range) 1.08 ± 0.21 (0.40–1.9) 0.23 ± 0.26 (−0.30–1.3) <0.001 0.03 ± 0.40 (−1.4–0.9) −0.03 ± 0.40 (−1.4–1.1) 0.689 0.04 ± 0.11 0.04 ± 0.11 0.926
 Mean visual  improvement at  final visit, logMAR  (range) 1.08 ± 0.53 (0–1.6) 0.08 ± 0.57 (−0.3–1.3) <0.001 0.10 ± 0.53 (−1.4–1.1) 0.07 ± 0.60 (−1.5–1.2) 0.890 0.11 ± 0.36 0.10 ± 0.27 0.961
 No. of eyes with 1-  mo BCVA ≥20/200  (%) 6 (46.2) 1 (7.7) 0.037 0 0 N/A 0 0 N/A
 No. of eyes with  final BCVA ≥20/  200 (%) 9 (69.2) 2 (15.4) 0.008 2 (7.1) 0 0.335 0 0 N/A
 No. of eyes with  clinically  significant visual  improvement at 1  mo (%)‡ 10 (76.9) 6 (46.2) 0.113 4 (14.3) 4 (20) 0.442 0 0 N/A
 No. of eyes with  clinically  significant visual  improvement at  final visit (%)‡ 11 (84.6) 3 (23.1) 0.002 7 (25) 5 (25) 0.628 3 (18.8) 2 (18.2) 0.684
Anatomic outcome
 No. of early (≤3-d)  reperfusion/no. of  FA performed 11/11 (100) 5/9 (55.6) 0.026 21/28 (75) 6/11 (54.5) 0.194 8/15 (53.3) 1/8 (12.5) 0.069
 No. of final (1-mo)  reperfusion/no. of  FA performed 11/11 (100) 5/8 (62.5) 0.058 21/25 (84) 13/15 (86.7) 0.600 13/15 (86.7) 7/8 (87.5) 0.731
Table 5
 
Neurological and Non-Neurological Adverse Reactions after Intra-Arterial Thrombolysis in Patients With Central Retinal Artery Occlusion
Table 5
 
Neurological and Non-Neurological Adverse Reactions after Intra-Arterial Thrombolysis in Patients With Central Retinal Artery Occlusion
Reaction No. of Patients/ No. of MRIs or Examinations Performed, %
Neurological adverse reactions after IAT
 Embolic infarction* 8/31, 25.8
 Symptomatic neurological  deterioration† 1/57, 1.8
 Intracranial hemorrhage 0/31
 Transient ischemic attack 0/31
 Death related to any neurologic  problem 0/57
Non-neurological non-ocular adverse reactions after IAT
 Hematoma at vessel puncture  sites 2/57, 3.5
 Headache 1/57, 1.8
 Tinnitus 1/57, 1.8
 Hyperesthesia 1/57, 1.8
 Treatment-associated infection 0
 Anaphylaxis 0
 Renal dysfunction 0
Ocular adverse reactions after IAT
 Increased intraocular pressure 2/57, 3.5
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