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Retrobulbar hemorrhage and prasugrel

  • Kanwal S. Matharu
    Affiliations
    McGovern Medical School at UTHealth
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  • Stacy V. Smith
    Affiliations
    Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas
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  • Andrew G. Lee
    Correspondence
    Correspondence to: Andrew G. Lee, MD, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, Scurlock 450, Houston, Texas, 77030.
    Affiliations
    Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas

    Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medicine, Houston, Texas, Department of Ophthalmology, UTMB (Galveston), Baylor College of Medicine, University of Iowa Hospitals and Clinics, and the University of Texas M.D. Anderson Cancer Center Houston, Texas
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Published:August 26, 2016DOI:https://doi.org/10.1016/j.jcjo.2016.07.003
      Retrobulbar hemorrhage (RBH) is the accumulation of blood in the orbit behind the globe. Although some hemorrhages are minor and do not result in significant mass effect, an RBH is an ophthalmologic emergency requiring immediate surgical intervention. An RBH manifests as acute ipsilateral orbital pain and proptosis and can be variably associated with loss of vision, ophthalmoplegia, subconjunctival hemorrhage, and increased intraocular and intraorbital pressure.
      • Cionni R.J.
      • Osher R.H.
      Retrobulbar hemorrhage.
      Most cases of RBH are traumatic or postsurgical, but some occur spontaneously in patients with bleeding diatheses. Another etiology for RBH is retrobulbar anesthesia injection.
      • Cionni R.J.
      • Osher R.H.
      Retrobulbar hemorrhage.
      The use of antiplatelet therapy has not been considered to be a significant risk factor for RBH
      • Cionni R.J.
      • Osher R.H.
      Retrobulbar hemorrhage.
      • Kallio H.
      • Paloheimo M.
      • Maunuksela E.L.
      Haemorrhage and risk factors associated with retrobulbar/peribulbar block: a prospective study in 1383 patients.
      ; yet newer, more potent antiplatelet agents may carry significantly more risk for RBH. We report a case of RBH causing blindness in a patient taking aspirin and prasugrel. To our knowledge, this is the first such case reported in the English-language ophthalmic literature.

      Case Report

      A 62-year-old female with proliferative diabetic retinopathy presented for panretinal photocoagulation (PRP) of her right eye after failing intravitreal bevacizumab therapy. At this time, her visual acuity was 20/40-1 OD and 20/80+1 OS. Intraocular pressures (IOPs) were 11 and 9 mm Hg in her right and left eyes, respectively. Proliferative diabetic retinopathy and diabetic macular edema of the left eye had been managed previously with both focal laser therapy and intravitreal triamcinolone OS.
      Her medical history was significant for coronary artery disease, hypertension, hyperlipidemia, diabetes mellitus, and hypothyroidism. Her past surgical history included placement of a coronary artery everolimus-eluting platinum chromium stent 4 months previously and cataract extraction with intraocular lens placement OS. Her medications included prasugrel, aspirin 81 mg, metformin, insulin, pregabalin, pravastatin, carvedilol, losartan, hydrochlorothiazide, potassium chloride, acetaminophen with codeine, prednisone, levothyroxine, and lubricating drops. She has allergies to penicillin and latex.
      Before the PRP procedure OD, the patient received a retrobulbar injection of 4 mL of 4% lidocaine OD with an unspecified needle gauge. She immediately reported acute pain and no light perception (NLP) vision OD. Obvious proptosis and lid ecchymosis OD were present. IOP was 53 mm Hg OD. Indirect ophthalmoscopy revealed a perfused central retinal artery OD. The patient underwent emergent lateral canthotomy and cantholysis OD. Medical management included oral acetazolamide and topical brimonidine/timolol, brinzolamide, and travaprost. Serial IOP measurements over several hours ranged between 35 and 40 mm Hg OD, but the optic nerve and retina appeared well perfused. The patient was discharged with oral acetazolamide and topical glaucoma medications and returned 5 hours later for re-examination. The IOP was stable at 35 mm Hg, and the optic nerve appeared well perfused. Vision, however, remained NLP, and she continued to report considerable pain. She underwent an urgent orbitotomy via a transconjunctival approach and a 360-degree conjunctival peritomy with drainage of the RBH.
      On postoperative day 1, the patient remained in significant pain. She was NLP OD and was mildly proptotic with lid edema OD. An orbital magnetic resonance imaging study revealed high intraconal T1 signal consistent with residual RBH OD. An endoscopic endonasal orbital decompression of the medial wall and floor was performed OD. Pain, IOP elevation, and proptosis improved, but she remained NLP OD. On hospital day 4, she underwent another orbital floor decompression because orbit computed tomography scan showed residual RBH. The patient also received intravenous methylprednisolone followed by oral taper.
      On neuro-ophthalmologic evaluation before discharge, vision remained NLP OD and was 20/30 OS. IOP measured 15 mm Hg OD and 18 mm Hg OS. There was a relative afferent pupillary defect OD. External exam revealed ecchymosis of upper and lower lids OD. There was no residual proptosis, but there was moderate chemosis and residual subconjunctival hemorrhage OD. Ductions OD showed –2 underaction of abduction and –1 underaction on elevation and adduction. Fundoscopy revealed scattered hemorrhages present consistent with nonproliferative diabetic retinopathy OU with diabetic macular edema OS. At 1 month follow-up, the optic nerve was atrophic OD and vision remained NLP OD.

      Discussion

      RBH is a potentially visually devastating complication of retrobulbar anesthesia. Although older literature suggests that antiplatelet agents are safe in retrobulbar anesthesia,
      • Kallio H.
      • Paloheimo M.
      • Maunuksela E.L.
      Haemorrhage and risk factors associated with retrobulbar/peribulbar block: a prospective study in 1383 patients.
      newer antiplatelet agents have higher potency and increased risk for bleeding. One study examined outcomes of 36 eyes of 33 patients who underwent vitreoretinal surgical operations while being treated systemically with newer medications including prasugrel.
      • Grand M.G.
      • Walia H.
      Hemorrhagic risk of vitreoretinal surgery in patients maintained on novel oral anticoagulant therapy.
      Although no eyes suffered perioperative bleeding complications, the sample size was likely too small to identify an increased incidence of a relatively rare complication.
      • Grand M.G.
      • Walia H.
      Hemorrhagic risk of vitreoretinal surgery in patients maintained on novel oral anticoagulant therapy.
      Additionally, single agents may not increase the risk as much as dual antiplatelet therapy.
      • Kallio H.
      • Paloheimo M.
      • Maunuksela E.L.
      Haemorrhage and risk factors associated with retrobulbar/peribulbar block: a prospective study in 1383 patients.
      • Kiire C.A.
      • Mukherjee R.
      • Ruparelia N.
      • Keeling D.
      • Prendergast B.
      • Norris J.H.
      Managing antiplatelet and anticoagulant drugs in patients undergoing elective ophthalmic surgery.
      RBH has been documented in 3 other patients receiving dual antiplatelet therapies.
      • Huebert I.
      • Heinicke N.
      • Kook D.
      • et al.
      Dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia.
      Increased medication potency compounded by the use of multiple agents may raise the risk for bleeding significantly, despite earlier studies suggesting otherwise that examined patients on single-agent therapy with less potent therapies.
      Drug-eluting stents, like the one our patient had placed 4 months before her RBH, have rapidly gained traction in cardiology due to their lower risk for coronary restenosis (10%) compared with balloon angioplasty (40%) and bare-metal stents (30%).
      • Dehmer G.J.
      • Smith K.J.
      Drug-eluting coronary artery stents.
      Restenosis due to stent thrombosis has a mortality rate approaching 45%.
      • Pfisterer M.E.
      Editorial: late stent thrombosis after drug-eluting stent implantation for acute myocardial infarction a new red flag is raised.
      Therefore, many cardiologists recommend dual antiplatelet therapy for at least 1 year after stenting to prevent thrombosis.
      • Bavry A.A.
      • Bhatt D.L.
      Drug-eluting stents: dual antiplatelet therapy for every survivor?.
      Prasugrel, a thienopyridine, selectively and irreversibly inhibits the P2Y12 receptor. This receptor is coupled to an inhibitory G protein involved in the platelet activation and aggregation cascades. By blocking this receptor, prasugrel modulates “platelet procoagulant activity, thrombin generation, P-selectin expression, soluble CD40L, and inflammation marker release.”
      • Alexopoulos D.
      P2Y12 Receptor inhibitors in acute coronary syndromes: from the research laboratory to the clinic and vice versa.
      Additionally, prasugrel shows increased potency, faster onset, and more consistent action across patients compared with clopidogrel.
      • Alexopoulos D.
      P2Y12 Receptor inhibitors in acute coronary syndromes: from the research laboratory to the clinic and vice versa.
      The TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel — Thrombolysis In Myocardial Infarction-38) compared the efficacy and safety of prasugrel and clopidogrel in combination with aspirin. In TRITON-TIMI 38, prasugrel significantly reduced the frequency of ischemic events but also significantly increased the frequency and severity of major bleeding events.
      • Mariani M.
      • Mariani G.
      • De Servi S.
      Efficacy and safety of prasugrel compared with clopidogrel in patients with acute coronary syndromes: results of TRITON-TIMI 38 trials.
      We report a case of RBH after retrobulbar block before PRP in a patient on dual-antiplatelet therapy with aspirin and prasugrel. Large trials involving prasugrel have shown increased efficacy for preventing coronary stent thrombosis. Unfortunately, these same trials showed an increased risk for hemorrhage. Ophthalmologists should consider the risks and benefits of retrobulbar injections in patients requiring ophthalmic procedures and might consider the following countermeasures to reduce risk: delay the procedure until after the need for dual antiplatelet therapy; hold prasugrel in the perioperative period; use alternate local anesthetic routes (e.g., topical, sub-Tenon, or peribulbar); use hyaluronidase as an adjunct to local anesthesia; use ultrasound guidance
      • Palte H.
      Ophthalmic regional blocks: management, challenges, and solutions.
      ; and ultimately obtain specific informed consent before retrobulbar anesthesia in higher risk patients taking these newer agents.

      Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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