An aging population and widespread use of antithrombotic (AT) agents for comorbid conditions presents the dilemma for retinal surgeons of having to perform surgery on patients receiving these agents. Oh et al reported that 14.6%, 28.5%, and 32.3% of patients undergoing vitreoretinal surgery were on antiplatelet (AP) agents in 1993, 2004, and 2008, respectively.¹ Mason et al found warfarin or clopidogrel use in 179 of 289 (62%) consecutive patients undergoing 25-gauge pars plana vitrectomy.²

Retinal surgeon should carefully consider the risks and benefits of either continuing or stopping antithrombotic agents in consultation with patients and their medical providers, because either choice can have serious consequences. For example, an Ophthalmic Mutual Insurance Company (OMIC) closed-claim case study involving a routine vitrectomy for asteroid hyalosis on a patient receiving aspirin and clopidogrel dual antiplatelet therapy (DAPT) that resulted in loss of the eye due to intractable intraoperative bleeding resulted in a $825,000 settlement.³ On the other hand, injudicious and indiscriminate discontinuation of AT agents can result in serious systemic events such as heart attack, stroke, or death.

Because a patient on antithrombotics is at high risk from both ocular and systemic perspectives (Figures 1 and 2), it is important for a retina surgeon to have some working knowledge of the indications, management strategies, and pharmacology of commonly used antithrombotic agents. This review aims to provide retina surgeons knowledge and insight enabling them to effectively communicate these complex issues with patients and their medical providers to strive for the best possible outcomes for each patient.

OVERVIEW OF ANTIPLATELET AGENTS AND ANTICOAGULANTS

Antiplatelet Agents

Antiplatelet agents inhibit platelet activation. Current oral AP agents belong to 3 pharmacologic classes: thromboxane A₂ inhibitor (aspirin), thienopyridines (clopidogrel, prasugrel) and cyclopentyltriazolopyrimidines (ticagrelor [Brilinta; AstraZeneca]) (Table 1).⁴ Aspirin inhibits platelet activation by irreversibly binding the enzyme cyclooxygenase-1, thereby preventing arachidonic acid from metabolizing into thromboxane A₂ (TXA₂), a potent mediator of platelet activation and vasoconstrictor. Aspirin is rapidly absorbed after oral ingestion and is cleared from the plasma within 1 hour. Platelets formed thereafter are not affected. Ten percent to 15% of platelet population is replenished daily. Aspirin is a relatively weak AP agent because it only partially inhibits TXA₂ synthesis; thus, other non-TXA₂ dependent activators, such as adenosine diphosphate (ADP), collagen, and thrombin, can bypass the inhibitory effect of aspirin. Spontaneous recovery of platelet function and in vitro studies have shown that only 30% to 40% of native platelets, corresponding to 3 to 4 days of aspirin interruption, are adequate to produce sufficient TXA₂ to achieve a normal activation and aggregation response.⁵ Therefore, it is unnecessary, and potentially harmful, to interrupt aspirin therapy beyond 3 to 5 days prior to surgery.⁶

Other antiplatelet agents — clopidogrel, ticagrelor, and prasugrel — inhibit ADP-mediated platelet activation by blocking the P2Y12 receptor. These agents work synergistically with aspirin and are commonly used in DAPT in conjunction with aspirin. Ticagrelor is a direct-acting reversible blocker of P2Y12 receptor. It has the fastest onset of action (within 30 minutes) of all antiplatelet agents and achieves more potent inhibition of platelet activation compared to clopidogrel.⁷

Clopidogrel, the most commonly prescribed P2Y12 inhibitor, requires 2-step metabolism in the liver to produce an active metabolite that rapidly and irreversibly binds and inhibits the P2Y12 receptor on the platelet surface for the remainder of their lifespan (7 to 10 days). The onset of action for clopidogrel is 2 to 6 hours, the slowest of all antiplatelet agents. Some patients who are unable to metabolize clopidogrel to its active metabolite may not be responsive to it.

Prasugrel is a thienopyridine, like clopidogrel, which also needs to be converted to an active metabolite by the cytochrome P450–dependent pathway. It has a faster onset of action (30 to 60 minutes) compared to clopidogrel and is the most potent of all P2Y12 inhibitors. It also has the highest risk of major bleeding among all antiplatelet agents, particularly in patients older than 75 years, and those weighing less than 60 kg. It is indicated only for acute coronary syndromes (unstable angina or myocardial infarction) managed with percutaneous coronary intervention (stents), and it carries an FDA black box warning to discontinue at least 7 days prior to any surgery. It is contraindicated in patients with a history of stroke or transient ischemic attack due to an increased risk of intracranial bleed in this subgroup.⁸

The time for platelet function restoration after interruption of P2Y12 blocking agents is 5 days for clopidogrel, 3 days for ticagrelor, and 7 days for prasugrel.⁹ The order of potency of AP agents from greatest to least is prasugrel, ticagrelor, clopidogrel, and aspirin. Both prasugrel and ticagrelor are superior to clopidogrel in cardiovascular outcomes following percutaneous coronary intervention, but they carry an increased risk for bleeding, particularly with prasugrel.¹⁰

Antiplatelet agents are effective in preventing arterial thrombosis and are commonly employed for coronary artery disease, peripheral arterial disease, and secondary prevention following myocardial infarction and ischemic stroke. Dual antiplatelet therapy, consisting of aspirin and a P2Y12 inhibitor, is recommended by the American College of Cardiology for at least 1 year following an acute coronary syndrome (ACS), defined as myocardial infarction or unstable angina regardless of intervention (medical therapy, percutaneous coronary intervention [PCI], or coronary artery bypass surgery), followed by 81 mg/day aspirin indefinitely.^10,11 Current guidelines favor ticagrelor and prasugrel over clopidogrel.¹⁰ Stent thrombosis, the most dreaded complication of DAPT interruption, which can result in acute myocardial infarction and death, is less common with modern second-generation and third-generation drug-eluting stents (DES) compared to bare metal stents (BMS) and first-generation DES. The risk of stent thrombosis is highest in the first month after BMS and first 3 months after DES. It decreases with the passage of time, and American College of Cardiology guidelines permit temporary perioperative interruption of DAPT after 6 months following PCI in selected patients at particularly high risk for bleeding, preferably with intraoperative continuation of aspirin.^10,12 The PARIS registry showed that short-term perioperative interruption of DAPT is not particularly dangerous if it is done after 6 months from PCI and if only 1 agent is interrupted.¹³ Recent data from the TICO and TWILIGHT trials have demonstrated that with newer generation DES, a short DAPT duration (<3 months) or even monotherapy with ticagrelor is safe and reduces major bleeding risk in patients at high risk of bleeding after PCI.^14,15 However, the ischemic and bleeding risk should be balanced in each patient, and this decision should not be made without consulting the patient’s cardiologist, especially in patients with PCI less than 1 year earlier. Dual therapy with aspirin plus clopidogrel or ticagrelor for 21 days followed by aspirin monotherapy is the most recommended AP therapy for secondary prevention following acute ischemic stroke, transient ischemic attack, or retinal artery occlusion.¹⁶

The role of aspirin in primary prevention of atherosclerotic cardiovascular disease (ASCVD) has become controversial in recent years. Approximately 25% of US adults older than 40 years without a history of heart disease or stroke take aspirin. According to a recent review, this may lead to slight cardiovascular benefit (absolute risk reduction 0.41%) but an equally increased risk of major bleeding (absolute risk increase 0.47%).¹⁷ The American College of Cardiology no longer recommends aspirin use for primary prevention of ASCVD in patients 70 years or older but allows it to be considered in selected patients between ages 40 and 70 who have high-risk characteristics.¹⁸ For patients taking aspirin for primary prevention of ASCVD, it is generally safe and reasonable to interrupt aspirin perioperatively.

ANTICOAGULANTS

Anticoagulant agents prevent formation and enlargement of blood clots. Oral anticoagulant agents belong to 1 of 2 classes: vitamin K antagonists (VKAs), such as warfarin, and direct-acting oral anticoagulants (DOACs), also known as novel oral anticoagulants, which include the thrombin (factor IIa) inhibitor dabigatran etexilate (Pradaxa; Boehringer Ingelheim) and factor Xa inhibitors rivaroxaban (Xarelto; Janssen), apixaban, and edoxaban (Savaya; Daiichi Sankyo). Anticoagulants are more effective on the venous side and are commonly used for stroke prophylaxis in atrial fibrillation, deep vein thrombosis, pulmonary embolism, mechanical cardiac valve, cardiomyopathies, and hypercoagulable states such as lupus anticoagulant and factor V deficiency or malignancy.

Warfarin is a VKA that inhibits formation of coagulation factors II, VII, IX and X. It has a variable half-life of 36 hours to 42 hours requiring periodic monitoring of international normalized ratio (INR). For most indications, target INR on warfarin is between 2.0 to 3.0, except for mechanical mitral or combined mitral and aortic valves where target INR should be between 2.5 and 3.5.¹⁹ It may take about 3 days after warfarin interruption for the INR to fall below 2 (subtherapeutic). After resumption of warfarin, it may take about 3 days for INR to reach therapeutic levels.²⁰ If needed, oral or parenteral vitamin K can reverse anticoagulation from warfarin in 12 to 24 hours.¹⁹

Perioperative bridging with low molecular weight heparin in patients with atrial fibrillation during warfarin interruption does not reduce the incidence of systemic thromboembolism and may even be harmful by causing a 4-fold increase in bleeding.²¹ Bridging is therefore not indicated for most patients receiving warfarin, except for those with a mechanical heart valve, recent thromboembolic event, and systemic coagulopathies.^6,21

Direct-acting oral anticoagulants have rapid onset of action (1 to 2 hours), with peak serum concentration in 3 to 4 hours and short half-lives ranging from 7 to 17 hours.²² They have a large therapeutic window that allows correct plasma concentration in patients over a wide weight range (40 kg to 120 kg) with the same standard dose without any need for monitoring. Dabigatran etexilate is converted to active metabolite dabigatran in the liver and inhibits thrombin (factor IIa), preventing it from converting fibrinogen to fibrin during coagulation cascade.

Rivaroxaban, apixaban, and edoxaban are direct inhibitors of factor Xa which converts prothrombin (factor II) to thrombin (factor IIa). Dabigatran and apixaban are administered twice daily, whereas rivaroxaban and edoxaban are dosed once daily. Apixaban has become popular because it has similar efficacy to other direct-acting oral anticoagulants, but less risk of bleeding, particularly gastrointestinal.²³ Novel oral anticoagulants are currently preferred agents over warfarin for stroke prophylaxis in nonvalvular atrial fibrillation and most other indications except mechanical cardiac valve.²⁴ A recent meta-analysis confirmed superiority of direct-acting oral anticoagulants over warfarin for stroke prophylaxis in atrial fibrillation patients and favored apixaban over other direct-acting oral anticoagulants.²⁵ All direct-acting oral anticoagulants are cleared primarily by the kidneys and are contraindicated in patients with severe kidney disease (creatinine clearance below 30 mL/min), in which case warfarin is preferred.

Because DOACs have short half-lives, interruption for 1 to 2 days prior to a surgical procedure is sufficient without the need for bridging with low molecular weight heparin. The American College of Cardiology recommends holding direct-acting oral anticoagulants for 2 half-lives prior to low bleeding risk procedures and 5 half-lives prior to intermediate/high/uncertain bleeding risk procedures.²⁶ Antiplatelet agents and anticoagulants need not be interrupted prior to procedures with no clinically important bleeding risk (eg, intravitreal injections, clear cornea cataract surgery, periocular injections) and should be resumed after adequate hemostasis has been ensured, preferably within 24 to 48 hours after surgery.²⁷

Two reversal agents for DOACs have recently been approved by the FDA: idarucizumab (Praxbind; Boehringer Ingelheim) for dabigatran and andexanet alfa (Adnexxa; Alexion) for apixaban and rivoraxaban.²⁸ However, these reversal agents are expensive and not readily available. Patients on both antiplatelet and anticoagulant agents, for example DAPT following stents in the setting of atrial fibrillation (triple therapy), may be at a particularly high bleeding risk.

SYSTEMIC CONDITIONS THAT INCREASE THE RISK OF BLEEDING

A simple and readily available score, HAS-BLED, originally developed to assess the risk of major bleeding in anticoagulated atrial fibrillation patients, can be used quickly to screen for major systemic conditions that increase the risk of perioperative bleeding (https://www.mdcalc.com/has-bled-score-major-bleeding-risk ).²⁹ The components of the HAS-BLED score are hypertension or systolic blood pressure >160 mmHg (H); abnormal liver/renal function (A); stroke history (S); bleeding history or predisposition (B); labile INR (L); elderly (E); drugs, such as antiplatelets or anticoagulants, and alcohol (D).

Of these, hypertension can and should be managed appropriately prior to proceeding with vitreoretinal surgery. Perioperative hypertension is a risk factor for surgical site bleeding and adverse cardiovascular events. The 2017 guidelines from the American College of Cardiology suggest deferring an elective surgery for systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg.³⁰ Some anesthesia departments have policies to hold diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers on the day of eye surgery performed under local anesthesia; these guidelines unnecessarily put the patients at risk of unsafe perioperative hypertension. A surgeon should develop the habit of measuring the patient’s blood pressure prior to proceeding with the block.

DEFINITION OF MAJOR BLEEDING

An intraocular bleed that compromises vision is considered a major bleed (type 3c, in the same category as intracranial bleed) according to Bleeding Academic Research Consortium (BARC) criteria, and in several other clinical trials.³¹ In the medical literature, surgeries with ≥4% risk of major bleed are considered high bleeding risk procedures.³¹ A major surgery lasting more than 45 minutes is also classified as high bleeding risk procedure.³² Anesthesia literature considers “posterior chamber eye surgery” as high surgical hemorrhagic risk.³³ With those perspectives, most retinal procedures with the exception of simple macular hole, macular pucker, floater removal, or asteroid hyalosis will qualify as high bleeding risk procedures and justify appropriate perioperative adjustment of AP/AC agents.

Certain retinal surgeries, such as diabetic vitrectomy with extensive fibrovascular membranes, sutured IOL, scleral buckle with external drainage of subretinal fluid, chorioretinal biopsy, submacular surgery, surgery for hemorrhagic complications of peripheral exudative hemorrhagic chorioretinopathy, and proliferative vitreoretinopathy surgery involving large retinectomies may be at particularly high risk for perioperative bleeding (Figures 1 and 2). Other ocular factors that increase the risk of perioperative bleeding including suprachoroidal hemorrhage include myopia, glaucoma, inflammation, and hypotony.^34,35

REVIEW OF RETINAL LITERATURE

Anticoagulant and AP agents may increase the risk of submacular hemorrhage in neovascular age-related macular degeneration and of vitreous hemorrhage after acute posterior vitreous detachment.^36-38 Dual antiplatelet therapy and AC may increase the risk of orbital hemorrhage after retrobulbar or peribulbar anesthesia.³⁹ Cases of intractable bleeding during diabetic vitrectomy and complex retinal detachment surgery requiring retinectomy in patients receiving DAPT have been reported.^40,41 Direct-acting oral anticoagulants have been associated with spontaneous vitreous hemorrhage.^42,43

Antiplatelet agents should not be interrupted for intravitreal injections.⁴⁴ Studies on perioperative antithrombotic therapy in vitreoretinal surgery are conflicting and inconclusive due to short sample size and a myriad of unmeasured/uncontrolled confounding variables and are summarized in Table 2. Antithrombotic agents were likely held perioperatively in significant patients in most studies,^45,46 and this crucial information was not available in most (Table 2). Vitreoretinal surgery was performed for a variety of indications in most studies. None performed a thorough analysis of systemic factors that increase bleeding risk. There were very few patients on DAPT, more potent AP agents, or DOACs. Information regarding INR on the day of surgery is not available in most studies. Some studies have shown increased risk of intraoperative hemorrhage in patients on aspirin or warfarin,^47-49 while others have not.

Bemme et al found no association between AC/AP use in retinal detachment surgery.⁴⁵ However, all patients in the vitamin K antagonist group had subtherapeutic INR and the aspirin group (incorrectly) included anyone who took aspirin ≤10 days prior to surgery, making their conclusions invalid.⁵⁰ Brillat et al found that aspirin use, defined as aspirin interruption equal to or less than 5 days prior to surgery, was not associated with an increased risk of bleeding. They found cryotherapy, transscleral drainage of subretinal fluid, and pars plana vitrectomy to be risk factors for perioperative bleeding.⁴⁶ Other authors have also used arbitrary cutoffs to define discontinuation (Table 2). Severe bleeding events have been reported after seemingly low-risk procedures. For example, Lauermann et al reported severe bleeding after removal of silicone oil (3/55 eyes), vitreous floater removal (1/3 eyes), uncomplicated retinal detachment (3/59 eyes), and simple vitreous hemorrhage (1/24 eyes).⁵¹

Grand and Walia found no case of intraocular or periocular hemorrhage during pars plana vitrectomy performed for a variety of indications in 33 eyes on DOAC or prasugrel therapy.⁵² Chandra et al found warfarin and aspirin use to be associated with an increased risk for intraoperative suprachoroidal hemorrhage during pars plana vitrectomy.⁵³ Numerous other risk factors for bleeding identified in these studies include, age, male sex, rhegmatogenous retinal detachment surgery, buckle placement, external drainage of subretinal fluid, cryotherapy, proliferative diabetic retinopathy especially with incomplete preoperative panretinal photocoagulation, and vitrectomy for retained cataract fragments (Table 2). Patients undergoing diabetic vitrectomy appear to have high incidence of intraoperative bleeding and postoperative vitreous hemorrhage. Intravitreal anti-VEGF injection 3 days to 8 days prior to vitrectomy may be considered in these patients.

CONCLUSION

Modern vitrectomy surgery enables more control of intraoperative bleeding compared to many other types of surgeries. Still, given the seriousness and potentially blinding consequences of intraocular bleeding and recognition of intraocular bleed as “severe” bleeding in the medical literature, it is reasonable to attempt to optimize antithrombotic agents and systemic status prior to vitreoretinal surgery, if possible. A clear communication with the patient’s medical providers outlining the bleeding risk of proposed surgery and expected duration of antithrombotic interruption is desirable to optimize the patient’s preoperative status and improve outcomes. The following general suggestions are offered to help accomplish these goals.

1. Categorize the patient’s perioperative bleeding risk into low, intermediate, or high based on the complexity of surgical procedure, systemic factors (HAS-BLED), and the patient’s ocular comorbidities, such as myopia, glaucoma, inflammation, and hypotony.
2. Categorize thrombotic risk into low, intermediate, or high based on type of stent and time since PCI.¹²
3. In general, elective surgery should be avoided if possible in the first 6 months to 12 months after acute coronary syndrome, as recommended by the American College of Cardiology.
4. Consider a detailed discussion with the patient and appropriate communication with other health care providers regarding options in elective cases, including the choice of anesthesia (local in most cases, particularly those with significant systemic comorbid conditions), duration of surgery, and expected duration of interruption of antithrombotic agents. Because these are complex issues, it is advisable to carefully document your discussion, particularly noting the increased bleeding risk due to antithrombotic agents. A special consent form, such as one designed by the Ophthalmic Mutual Insurance Company (https://www.omic.com/hemorrhage-associated-with-ophthalmic-procedures/ ) may be considered to streamline this process.
5. Do not interrupt AC/AP agents any longer than necessary.
6. According to the medical literature, anticoagulants — both VKAs and DOACs — may be held in most cases without bridging (exceptions include mechanical heart valve, recent thromboembolic episode, and some systemic coagulopathies).
7. The generally safe and adequate period of preoperative interruption, approximately equal to 3 elimination half-lives of active compound, is 2 days for DOAC; 3 days for aspirin, ticagrelor, and warfarin; 5 days for clopidogrel; and 7 days for prasugrel (Table 1). If a patient is on DAPT, it is preferable not to stop both agents within the first year. Instead, consider continuing aspirin perioperatively, including on the day of surgery, in consultation with the patient’s cardiologist.
8. Consider making adjustments in surgical technique where AC and AP agents can’t be interrupted, or for surgeries performed as an emergency for macula-on retinal detachment or endophthalmitis (sub-Tenon as opposed to retrobulbar block, minimize cryotherapy, avoid hypotony, avoid external drainage, if possible, electively suture sclerotomies especially in myopic eyes, 400 μg intravitreal dexamethasone in inflamed eyes or those receiving extensive panretinal photocoagulation, ensure hemostasis) (Video 1).

    

9. Consider resumption of antithrombotic agents soon after surgery, generally on the first or second postoperative day, unless the patient has hypotony or choroidal detachments where longer interruption in consultation with medical providers may be considered.
10. Do not hold antihypertensive agents except for diuretics on the day of surgery. Be aware of the patient’s blood pressure, and have the anesthesia provider control it if systolic blood pressure is >160 mmHg. RP

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   37. Kuhli-Hattenbach C, Fischer IB, Schalnus R, Hattenbach L. Subretinal hemorrhages associated with age-related macular degeneration in patients receiving anticoagulation or antiplatelet therapy. Am J Ophthalmol. 2010;149(2):316-321.e1. doi:10.1016/j.ajo.2009.08.033
   38. Witmer MT, Cohen SM. Oral anticoagulation and the risk of vitreous hemorrhage and retinal tears in eyes with acute posterior vitreous detachment. Retina. 2013;33(3):621-626. doi:10.1097/IAE.0b013e3182671006
   39. Huebert I, Heinicke N, Kook D, et al. Dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia. J Cataract Refract Surg. 2015;41(10):2092-2101. doi:10.1016/j.jcrs.2015.10.051
   40. Herbert EN, Mokete B, Williamson TH, Laidlaw DaH. Haemorrhagic vitreoretinal complications associated with combined antiplatelet agents. Br J Ophthalmol. 2006;90(9):1209-1210. doi:10.1136/bjo.2006.095307
   41. Zarei M. Dual antiplatelet therapy may lead to hemorrhagic complications in vitrectomy of proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2019;257(2):425-426. doi:10.1007/s00417-018-4151-1
   42. Shieh W, Sridhar J, Hong BK, et al. Ophthalmic complications associated with direct oral anticoagulant medications. Semin Ophthalmol. 2017;32(5):614-619. doi:10.3109/08820538.2016.1139738
   43. Jun JH, Hwang JC. Association of rivaroxaban anticoagulation and spontaneous vitreous hemorrhage. JAMA Ophthalmol. 2015;133(10):1184-1186. doi:10.1001/jamaophthalmol.2015.2069
   44. Avery RL, Bakri SJ, Blumenkranz MS, et al. Intravitreal injection technique and monitoring: updated guidelines of an expert panel. Retina. 2014;34 Suppl 12:S1-S18. doi:10.1097/IAE.0000000000000399
   45. Bemme S, Lauermann P, Striebe NA, et al. Risk of perioperative bleeding complications in rhegmatogenous retinal detachment surgery: a retrospective single-center study. Graefes Arch Clin Exp Ophthalmol. 2020;258(5):961-969. doi:10.1007/s00417-019-04554-1
   46. Brillat E, Rouberol F, Palombi K, et al. A case-control study to assess aspirin as a risk factor of bleeding in rhegmatogenous retinal detachment surgery. Graefes Arch Clin Exp Ophthalmol. 2015;253(11):1899-1905. doi:10.1007/s00417-014-2900-3
   47. Passemard M, Koehrer P, Juniot A, Bron AM, Creuzot-Garcher C. Maintenance of anticoagulant and antiplatelet agents for patients undergoing peribulbar anesthesia and vitreoretinal surgery. Retina. 2012;32(9):1868-1873. doi:10.1097/IAE.0b013e31825097ae
   48. Fabinyi DCA, O'Neill EC, Connell PP, Clark JB. Vitreous cavity haemorrhage post-vitrectomy for diabetic eye disease: the effect of perioperative anticoagulation and antiplatelet agents. Clin Exp Ophthalmol. 2011;39(9):878-884. doi:10.1111/j.1442-9071.2011.02575.x
   49. Narendran N, Williamson TH. The effects of aspirin and warfarin therapy on haemorrhage in vitreoretinal surgery. Acta Ophthalmol Scand. 2003;81(1):38-40. doi:10.1034/j.1600-0420.2003.00020.x
   50. Kishore K, Mungee S. Comment on “risk of perioperative bleeding complications in rhegmatogenous retinal detachment surgery: a retrospective single-center study”: Bemme S et al. Graefes Arch Clin Exp Ophthalmol. 2020; 258(5). doi:10.1007/s00417-019-04554-1. Graefes Arch Clin Exp Ophthalmol. 2020;258(9):2071-2072. doi:10.1007/s00417-020-04723-7
   51. Lauermann P, Klingelhöfer A, Mielke D, et al. Risk factors for severe bleeding complications in vitreoretinal surgery and the role of antiplatelet or anticoagulant agents. Ophthalmol Retina. 2021;5(8):e23-e29. doi:10.1016/j.oret.2021.04.013
   52. Grand MG, Walia HS. Hemorrhagic risk of vitreoretinal surgery in patients maintained on novel oral anticoagulant therapy. Retina. 2016;36(2):299-304. doi:10.1097/IAE.0000000000000783
   53. Chandra A, Xing W, Kadhim MR, Williamson TH. Suprachoroidal hemorrhage in pars plana vitrectomy: risk factors and outcomes over 10 years. Ophthalmology. 2014;121(1):311-317. doi:10.1016/j.ophtha.2013.06.021
   54. Louison S, Gabrielle P, Soudry A, et al. Perioperative risk of bleeding with antithrombotic agents in macular surgery: a national, prospective, multicentre study. Acta Ophthalmol. 2020;98(8):e991-e997. doi:10.1111/aos.14434
   55. Meillon C, Gabrielle PH, Luu M, Aho-Glele LS, Bron AM, Creuzot-Garcher C. Antiplatelet and anticoagulant agents in vitreoretinal surgery: a prospective multicenter study involving 804 patients. Graefes Arch Clin Exp Ophthalmol. 2018;256(3):461-467. doi:10.1007/s00417-017-3897-1
   56. Ryan A, Saad T, Kirwan C, Keegan DJ, Acheson RW. Maintenance of perioperative antiplatelet and anticoagulant therapy for vitreoretinal surgery. Clin Exp Ophthalmol. 2013;41(4):387-395. doi:10.1111/ceo.12017
   57. Khuthaila MK, Hsu J, Chiang A, et al. Postoperative vitreous hemorrhage after diabetic 23-gauge pars plana vitrectomy. Am J Ophthalmol. 2013;155(4):757-763. doi:10.1016/j.ajo.2012.11.004
   58. Malik AI, Foster RE, Correa ZM, Petersen MR, Miller DM, Riemann CD. Anatomical and visual results of transconjunctival sutureless vitrectomy using subconjunctival anesthesia performed on select patients taking anticoagulant and antiplatelet agents. Retina. 2012;32(5):905-911. doi:10.1097/IAE.0b013e31822f55c4
   59. Chandra A, Jazayeri F, Williamson TH. Warfarin in vitreoretinal surgery: a case controlled series. Br J Ophthalmol. 2011;95(7):976-978. doi:10.1136/bjo.2010.187526
   60. Brown JS, Mahmoud TH. Anticoagulation and clinically significant postoperative vitreous hemorrhage in diabetic vitrectomy. Retina. 2011;31(10):1983-1987. doi:10.1097/IAE.0b013e31821800cd
   61. Fu AD, McDonald HR, Williams DF, et al. Anticoagulation with warfarin in vitreoretinal surgery. Retina. 2007;27(3):290-295. doi:10.1097/01.iae.0000243033.39301.10
   62. Dayani PN, Grand MG. Maintenance of warfarin anticoagulation for patients undergoing vitreoretinal surgery. Trans Am Ophthalmol Soc. 2006;104:149-160.

   Video 1. A simple technique of posterior sub-Tenon anesthetic injection. This technique eliminates potential complications from peribulbar or retrobulbar injections.

2. Consider resumption of antithrombotic agents soon after surgery, generally on the first or second postoperative day, unless the patient has hypotony or choroidal detachments where longer interruption in consultation with medical providers may be considered.
3. Do not hold antihypertensive agents except for diuretics on the day of surgery. Be aware of the patient’s blood pressure, and have the anesthesia provider control it if systolic blood pressure is >160 mmHg. RP

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38. Witmer MT, Cohen SM. Oral anticoagulation and the risk of vitreous hemorrhage and retinal tears in eyes with acute posterior vitreous detachment. Retina. 2013;33(3):621-626. doi:10.1097/IAE.0b013e3182671006
39. Huebert I, Heinicke N, Kook D, et al. Dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia. J Cataract Refract Surg. 2015;41(10):2092-2101. doi:10.1016/j.jcrs.2015.10.051
40. Herbert EN, Mokete B, Williamson TH, Laidlaw DaH. Haemorrhagic vitreoretinal complications associated with combined antiplatelet agents. Br J Ophthalmol. 2006;90(9):1209-1210. doi:10.1136/bjo.2006.095307
41. Zarei M. Dual antiplatelet therapy may lead to hemorrhagic complications in vitrectomy of proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2019;257(2):425-426. doi:10.1007/s00417-018-4151-1
42. Shieh W, Sridhar J, Hong BK, et al. Ophthalmic complications associated with direct oral anticoagulant medications. Semin Ophthalmol. 2017;32(5):614-619. doi:10.3109/08820538.2016.1139738
43. Jun JH, Hwang JC. Association of rivaroxaban anticoagulation and spontaneous vitreous hemorrhage. JAMA Ophthalmol. 2015;133(10):1184-1186. doi:10.1001/jamaophthalmol.2015.2069
44. Avery RL, Bakri SJ, Blumenkranz MS, et al. Intravitreal injection technique and monitoring: updated guidelines of an expert panel. Retina. 2014;34 Suppl 12:S1-S18. doi:10.1097/IAE.0000000000000399
45. Bemme S, Lauermann P, Striebe NA, et al. Risk of perioperative bleeding complications in rhegmatogenous retinal detachment surgery: a retrospective single-center study. Graefes Arch Clin Exp Ophthalmol. 2020;258(5):961-969. doi:10.1007/s00417-019-04554-1
46. Brillat E, Rouberol F, Palombi K, et al. A case-control study to assess aspirin as a risk factor of bleeding in rhegmatogenous retinal detachment surgery. Graefes Arch Clin Exp Ophthalmol. 2015;253(11):1899-1905. doi:10.1007/s00417-014-2900-3
47. Passemard M, Koehrer P, Juniot A, Bron AM, Creuzot-Garcher C. Maintenance of anticoagulant and antiplatelet agents for patients undergoing peribulbar anesthesia and vitreoretinal surgery. Retina. 2012;32(9):1868-1873. doi:10.1097/IAE.0b013e31825097ae
48. Fabinyi DCA, O'Neill EC, Connell PP, Clark JB. Vitreous cavity haemorrhage post-vitrectomy for diabetic eye disease: the effect of perioperative anticoagulation and antiplatelet agents. Clin Exp Ophthalmol. 2011;39(9):878-884. doi:10.1111/j.1442-9071.2011.02575.x
49. Narendran N, Williamson TH. The effects of aspirin and warfarin therapy on haemorrhage in vitreoretinal surgery. Acta Ophthalmol Scand. 2003;81(1):38-40. doi:10.1034/j.1600-0420.2003.00020.x
50. Kishore K, Mungee S. Comment on “risk of perioperative bleeding complications in rhegmatogenous retinal detachment surgery: a retrospective single-center study”: Bemme S et al. Graefes Arch Clin Exp Ophthalmol. 2020; 258(5). doi:10.1007/s00417-019-04554-1. Graefes Arch Clin Exp Ophthalmol. 2020;258(9):2071-2072. doi:10.1007/s00417-020-04723-7
51. Lauermann P, Klingelhöfer A, Mielke D, et al. Risk factors for severe bleeding complications in vitreoretinal surgery and the role of antiplatelet or anticoagulant agents. Ophthalmol Retina. 2021;5(8):e23-e29. doi:10.1016/j.oret.2021.04.013
52. Grand MG, Walia HS. Hemorrhagic risk of vitreoretinal surgery in patients maintained on novel oral anticoagulant therapy. Retina. 2016;36(2):299-304. doi:10.1097/IAE.0000000000000783
53. Chandra A, Xing W, Kadhim MR, Williamson TH. Suprachoroidal hemorrhage in pars plana vitrectomy: risk factors and outcomes over 10 years. Ophthalmology. 2014;121(1):311-317. doi:10.1016/j.ophtha.2013.06.021
54. Louison S, Gabrielle P, Soudry A, et al. Perioperative risk of bleeding with antithrombotic agents in macular surgery: a national, prospective, multicentre study. Acta Ophthalmol. 2020;98(8):e991-e997. doi:10.1111/aos.14434
55. Meillon C, Gabrielle PH, Luu M, Aho-Glele LS, Bron AM, Creuzot-Garcher C. Antiplatelet and anticoagulant agents in vitreoretinal surgery: a prospective multicenter study involving 804 patients. Graefes Arch Clin Exp Ophthalmol. 2018;256(3):461-467. doi:10.1007/s00417-017-3897-1
56. Ryan A, Saad T, Kirwan C, Keegan DJ, Acheson RW. Maintenance of perioperative antiplatelet and anticoagulant therapy for vitreoretinal surgery. Clin Exp Ophthalmol. 2013;41(4):387-395. doi:10.1111/ceo.12017
57. Khuthaila MK, Hsu J, Chiang A, et al. Postoperative vitreous hemorrhage after diabetic 23-gauge pars plana vitrectomy. Am J Ophthalmol. 2013;155(4):757-763. doi:10.1016/j.ajo.2012.11.004
58. Malik AI, Foster RE, Correa ZM, Petersen MR, Miller DM, Riemann CD. Anatomical and visual results of transconjunctival sutureless vitrectomy using subconjunctival anesthesia performed on select patients taking anticoagulant and antiplatelet agents. Retina. 2012;32(5):905-911. doi:10.1097/IAE.0b013e31822f55c4
59. Chandra A, Jazayeri F, Williamson TH. Warfarin in vitreoretinal surgery: a case controlled series. Br J Ophthalmol. 2011;95(7):976-978. doi:10.1136/bjo.2010.187526
60. Brown JS, Mahmoud TH. Anticoagulation and clinically significant postoperative vitreous hemorrhage in diabetic vitrectomy. Retina. 2011;31(10):1983-1987. doi:10.1097/IAE.0b013e31821800cd
61. Fu AD, McDonald HR, Williams DF, et al. Anticoagulation with warfarin in vitreoretinal surgery. Retina. 2007;27(3):290-295. doi:10.1097/01.iae.0000243033.39301.10
62. Dayani PN, Grand MG. Maintenance of warfarin anticoagulation for patients undergoing vitreoretinal surgery. Trans Am Ophthalmol Soc. 2006;104:149-160.