James H Bates, MD Associate Professor, CWRU School of Medicine University Hospitals Case Medical Center
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Occlusion of the central retinal artery at the lamina cribosa , thus causative material not seen in many cases Platelet-fibrin emboli 15%? (TPA should work) É Cholesterol emboli 57-75%? (? Role for TPA) É Calcific emboli (aortic disease) 10%? (TPA worthless) É
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Retinal survival time 100 minutes experimental complete occlusion in primates É Studies have used 20 hrs- too long É
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Lower IOP/dislodge É Glaucoma
drops É Ocular massage É IV Acetazolamide or mannitol É Anterior chamber paracentesis Ò
Vasodilation É CO2
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inhalation or nitrates
Hemodilution
No controlled randomized trials of CRAO and its therapy Ò Untreated may have 8% chance improvement Ò Conservative therapy may improve it to 15-60% Ò Prior therapy studies were retrospective Ò Testing (FA?), outcomes (Va, visual fields) Ò Diagnosing and excluding properly (cilioretinal artery occlusion or sparing, arteritis) Ò
Therapeutic success may depend on earliest intervention possible Ò What specialist makes the diagnosis of CRAO and by what means? Ò How can the ophthalmologist be involved in timely care? Always on site vs telemedicine? Ò Can ER, Neurology, Interventional Radiology specialists be trained to recognize the entity? Ò
18/31 patients presented with CRAO within 20 hrs of vision loss Ò 15/31 saw ophthalmologist within 20 hrs of vision loss, median 3.3 hours till seen Ò Felt public awareness of entity and its urgency is low Ò Urged direct referral line to ophthalmology Ò
Photos by Nurses using non-mydriatic camera Ò Pts c HA, vision loss, neuro sx, diastolic >120 Ò Compared to findings by ER doctors Ò 200 enrolled pts so far- ER examined 33 Ò By photos, 31 had urgent finding- ER found 1 Ò ER not looking enough, low detection rate Ò ?telemedicine, ER photo training Ò
Review of 7/8 studies trended toward intrarterial therapy Ò Improvements of vision may have been stat significant, but one line improvements are not a sign of success Ò 5% adverse event rate cumulative Ò Criticized studies for comparing heterogeneous samples Ò
German prospective multicenter study intended to enroll 200 patients Ò Stopped at 70 due to interim analysis showing no difference in aggressive conservative treatment and IAF Ò Visual improvement seen in ~60% of both Ò 2 cerebral hemorrhages and overall 37% adverse event with IAF Ò Criticized for questionable design and exclusion, still may be best so far Ò
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German Study 2008 É 50
mg rTPA IV over 1 hour É 28 patients, no adverse events É 32% had significant improvement (3 lines) É 41% achieved better than 20/50 if treated within 6.5 hrs of vision loss (7/17)
Illustrative of issues with therapy and studies Ò 0.9 mg/kg for 1 hour p – CT head and INR<1.6 Ò Enrolled 16 patients 8 treated/8 placebo Ò Intracerebral hemorrhage with 8th treated, severe enough to require rehab, study halted Ò Patients with less than 6 hours of loss showed benefit, none over (small n though) Ò Will reconfigure study, shorter time to treat Ò
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Natural history and Conservative therapy É poor
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studies, widely varying outcomes
Interventional with TPA É Selective
intra-arterial by EAGLE is not supported É IV is not clear, but EAGLE conservative is better
Best to do under research protocol, not cowboying it Ò Time window, complexity of disease, risks may be insurmountable Ò
Exclude patients with vision loss over 6 hours Ò Devise system that can make a diagnosis within that time frame Ò
É Training
of non-ophthalmologists É Telemedicine using fundus images
Better studies with intra-arterial vs low-dose IV Ò If benefit found, patient education to drive treatable patients for therapy Ò
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Rudkin, A. K; Lee, A. W.; Chen, C. S. Central retinal artery occlusion: timing and mode of presentation European Journal of Neurology, Volume 16, Number 6, June 2009, pp. 674-677(4) J Noble, N Weizblit, M O Baerlocher, K T Eng Intra-arterial thrombolysis for central retinal artery occlusion: a systematic review Br J Ophthalmol 2008;92:588-593 Schumacher et al. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology. 2010 Jul;117(7):1367-75. (EAGLE study) Hattenbach LO, Kuhli-Hattenbach C, Scharrer I, Baatz H. Intravenous thrombolysis with low-dose recombinant tissue plasminogen activator in central retinal artery occlusion Am J Ophthalmol. 2008;146:700-706 Digital Ocular Fundus Photography in the Emergency Department: A New Application for Telemedicine? ClinicalTrials.gov identifier: NCT00873613 Australian Flinders IV study, personal communication with Celia Chen, MD (Ophthalmology)