Association between subconjunctival hemorrhage and hemorrhagic disorders: a nationwide population-based study.

Subconjunctival hemorrhage (SCH) is a benign eye condition that is often noticeable and leads to medical attention. Despite previous studies investigating the relationship between SCH and cardiovascular diseases, the relationship between SCH and bleeding disorders remains controversial. In order to gain further insight into this association, a nationwide cohort study was conducted using data from the National Health Insurance Service-National Sample Cohort version 2.0 from 2006 to 2015. The study defined SCH using a diagnostic code and compared the incidence and risk factors of intracerebral hemorrhage (ICH) and gastrointestinal (GI) bleeding in 36,772 SCH individuals and 147,088 propensity score (PS)-matched controls without SCH. The results showed that SCH was associated with a lower risk of ICH (HR = 0.76, 95% CI = 0.622-0.894, p = 0.002) and GI bleeding (HR = 0.816, 95% CI = 0.690-0.965, p = 0.018) when compared to the PS-matched control group. This reduced risk was more pronounced in females and in the older age group (≥ 50 years), but not observed in males or younger age groups. In conclusion, SCH dose not increase the risk of ICH and major GI bleeding and is associated with a decreased incidence in females and individuals aged ≥ 50 years.

Prevalence and Causes of Subconjunctival Hemorrhage in Children.

OBJECTIVE: Subconjunctival hemorrhage (SCH) is a reported sign of occult abusive injury, but there are limited published data about SCH during childhood. We sought to determine the prevalence and causes of SCH in children. METHODS: This is a retrospective cross-sectional study of children seen by pediatric ophthalmologists in an outpatient setting over 4 years. Primary outcomes were prevalence and causes of SCH, based on history, physical ocular and nonocular findings, and laboratory and imaging studies. Subconjunctival hemorrhage prevalence was determined including and excluding eye surgery to reduce bias in the prevalence estimate. RESULTS: We studied 33,990 children, who underwent 86,277 examinations (median age, 5 years; range, 2 days to 18 years; 9282 younger than 2 years, 13,447 age 2-7 years, 11,261 age 8-18 years). There were 949 cases of SCH (1.1%; 95% confidence interval, 1.0-1.2). When surgery was excluded, there were 313 cases (prevalence, 0.4%; 95% confidence interval, 0.3-0.4), of which 261 (83%) were due to trauma; 40 (13%) ocular surface inflammation, including infectious conjunctivitis; 7 (2%) orbital or conjunctival lesion; 3 (1%) vessel rupture from choking or cough; and 2 (1%) coagulopathy related. Across all ages, including less than 2 years, trauma and inflammation together accounted for 94% to 97% of all cases of SCH. CONCLUSIONS: Subconjunctival hemorrhage is uncommon in children. The great majority of cases are due to trauma. All children with SCH, including infants and young children, should be closely examined to identify other ocular or nonocular signs of trauma.

Risk Factors for Severe Bleeding Complications in Vitreoretinal Surgery and the Role of Antiplatelet or Anticoagulant Agents.

PURPOSE: To evaluate the influences and risk factors for severe bleeding complications during vitreoretinal surgery and to investigate the role of antiplatelet and anticoagulant agents. DESIGN: Prospective trial. PARTICIPANTS: Patients undergoing vitreoretinal surgery. METHODS: The procedures included were pars plana vitrectomy and scleral buckling. We developed a uniform classification to grade the bleeding severity. Bleeding was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and 1 day later, the incidence and the severity of bleeding events was documented on a standardized form. A grade of 3 or more was defined as severe bleeding. Furthermore, the influence of known systemic disorders before surgery, the type of anesthesia, type of surgical procedure, intraoperative blood pressure, and the use or change of antiplatelet or anticoagulant agents on intraoperative bleeding was analyzed. MAIN OUTCOME MEASURES: Incidence and risk factors for severe intraoperative bleeding events. RESULTS: Data from 374 eyes undergoing vitreoretinal procedures were included in our study (mean age, 67.6 ± 12.9 years). A severe intraoperative bleeding event was observed in 15 eyes (4%). We found that concomitant diseases such as diabetes mellitus and carotid artery stenosis, the presence of diabetic retinopathy, younger age, and scleral buckling combined with a transscleral puncture were associated significantly with severe bleeding events. By contrast, use of antiplatelet or anticoagulant agents, or both, had no significant influence on severe intraoperative bleeding events. CONCLUSIONS: Although external manipulations during buckling surgery (e.g., drainage of subretinal fluid) and concomitant diseases such as diabetes mellitus and carotid artery stenosis influences the risk of severe intraoperative bleeding events, we did not detect an increased risk related to coexisting antiplatelet or anticoagulant medication use, or both.

The Results of Preoperative Use of Topical Brimonidine in Strabismus Surgery.

Purpose: In this study, we wanted to retrospectively evaluate the effect of the use of topical brimonidine on intraoperative bleeding and surgical hemostasis before strabismus surgery. Methods: Brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops were applied 6 and 3 min before surgery to 44 eyes of 22 patients in group 1 for vasoconstriction. Drops were not applied to 46 eyes of 23 patients in group 2. Preoperative and postoperative photographs and video images were taken. Black-and-white images were used to define the surface areas of the blood vessels. The surface area was calculated by counting the black pixels with ImageJ software. Results: In group 1, redness of eye was observed, on average, at preoperative 339.25 ± 11.52 pixels and intraoperative 247.93 ± 10.63 pixels (P < 0.001). But there was no change in group 2 (preoperative 338.87 ± 8.45 pixels to intraoperative 339.71 ± 9.52 pixels, P > 0.05). The incidence of intraoperative bleeding evaluated by the number of eyes on which cautery was used shows that it was significantly less in group 1 than in group 2 (P < 0.001). Conclusions: The use of topical brimonidine before strabismus surgery facilitates clear monitoring of anatomical structures during surgery by effectively controlling hemorrhage. In the postoperative period, it significantly reduces subconjunctival hemorrhage.

Value of Coronary Artery Calcium Scanning in Association With the Net Benefit of Aspirin in Primary Prevention of Atherosclerotic Cardiovascular Disease.

Importance: Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit from aspirin therapy is unclear. Objective: To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds. Design, Setting, and Participants: Prospective population-based cohort study of Dallas Heart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020. Exposures: Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher. Main Outcomes and Measures: Major bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis-derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds. Results: A total of 2191 participants (mean [SD], age 44 [9.1] years, 1247 women [57%], and 1039 black individuals [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and ≥100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P < .001; HR, 5.3; 95% CI, 3.6-7.9; P < .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk. Conclusions and Relevance: Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.

Efficacy and safety of non-vitamin K-antagonist oral anticoagulants for retinal vascular diseases in patients with atrial fibrillation: Korean cohort study.

We investigated the prevalence of retinal vascular occlusion and intraocular bleeding and compare their risks in patients undergoing anticoagulant therapy, either with non-vitamin K-antagonist oral anticoagulants (NOAC) or warfarin. We performed a cohort study (January 2015 to April 2018) in 281,970 patients with nonvalvular atrial fibrillation (AF) using health claims in the nationwide database of the Health Insurance Review and Assessment service of Korea. A Cox-proportional hazard regression was used to calculate the hazard ratio (HR) for retinal vascular occlusion or intraocular bleeding. The HR of retinal vascular occlusion was estimated to 1.59 (95% confidence interval [CI], 1.35-1.86) for NOAC users compared to that with warfarin users. Among the various types of NOACs, all NOACs showed higher risk of retinal vascular occlusion than did warfarin. For intraocular bleeding, the HR was estimated to be 0.86 (95% CI, 0.75-0.98) for NOAC users compared with that with warfarin users. The risk of retinal vascular occlusion was higher in NOAC users than in warfarin users, while the risk of intraocular bleeding was lower with NOAC therapy. NOACs were not found to be as effective as warfarin for retinal vascular occlusion, but safe in terms of intraocular bleeding.

Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor.

Intraocular bleeding is a devastating clinical event due to its potentially blinding nature. It is not known if determine if dual antiplatelet therapy using aspirin and potent P2Y12 inhibitors increases this risk. We searched MEDLINE and ClinicalTrials.gov for randomized controlled trials that were phase III, randomly assigned patients to dual antiplatelet therapy with either aspirin and a potent P2Y12 inhibitor or aspirin and clopidogrel, had follow-up of 6 months, and at least 200 patients. Corresponding authors were contacted for intraocular bleeding data. Inverse-variance, weighted, fixed-effects meta-analysis was undertaken, with random-effects meta-analysis performed as a sensitivity analysis. Four trials enrolling 42,850 patients were included. The median follow-up ranged from 12 to 14 months. There was overall low risk of bias. Pooled analysis demonstrated no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (risk ratio 0.89, 95% confidence interval 0.58 to 1.36). There was no significant heterogeneity observed across trials (I2 statistic 0%, p = 0.98). The use of random-effects meta-analysis did not change the effect estimate or confidence intervals, and the results appeared similar when stratified by potent P2Y12 inhibitor (p = 0.97). In conclusion, this collaborative meta-analysis of dual antiplatelet trials does not suggest that the risk of intraocular bleeding is increased with the use of potent P2Y12 inhibitors compared with clopidogrel. Our results suggest that these potent P2Y12 inhibitors may continue to be used cautiously where indicated as part of dual antiplatelet therapy, even in those at high risk of spontaneous intraocular bleeding.

Safety of cataract surgery in patients treated with the new oral anticoagulants (NOACs).

PURPOSE: To evaluate the safety of phacoemulsification of cataract in patients taking new oral anticoagulants (NOACs). METHODS: In a prospective case series, consecutive patients on NOACs (dabigatran, rivaroxaban, or apixaban) who were referred for uncomplicated cataract surgery to the eye institute underwent a thorough ophthalmological and hematological evaluation. Rivaroxaban and apixaban anti-factor Xa tests, and diluted thrombin time for dabigatran, were used for monitoring anticoagulation levels in blood. Blood was drawn for these tests just prior to surgery and at a peak level of the drug at about 4 h post-surgery (2 h after the drug was given). All surgeries were videotaped and patients were examined at 1 and 7 days after the operation. The main outcome measures included assessment of intra-operative, postoperative ocular bleeding, and other related complications. RESULTS: Thirty-five eyes of 25 unrelated patients ranging in age from 63 to 92 years (mean 77.6 years) underwent phacoemulsification. Intra-operative bleeding was observed in 5 eyes from the conjunctiva or limbus at the main incision site. No intraocular bleeding occurred. No hemorrhagic complications were observed during the 1-week follow-up. According to anti-factor Xa levels prior to surgery and following surgery, 85% of the patients were on therapeutic levels of NOACs. CONCLUSIONS: Clear corneal incision phacoemulsification performed under topical anesthesia can be safely performed in simple cases of cataract without discontinuing NOAC treatment.

Ocular and systemic risk factors associated with recurrent disc hemorrhage in primary open-angle glaucoma.

PURPOSE: To evaluate the risk factors associated with recurrent disc hemorrhage (DH), defined for the present study as at least 3 occurrences of DH in primary open-angle glaucoma (POAG). METHODS: A total of 178 POAG patients (89 eyes showing at least 3 occurrences of DH and 89 age-matched control eyes with a minimum of 10 years' follow-up without DH) were included in a retrospective, case-control study. Ocular factors were evaluated by a retrospective chart review, and systemic factors were evaluated by a telephone survey. Associations between factors and recurrent DH were investigated by logistic regression analysis. The Kaplan-Meier survival analysis and Cox proportional-hazards regression models were used to evaluate glaucoma progression and to identify the factors predictive of glaucoma progression. RESULTS: Univariate regression analysis revealed the association of recurrent DH with low baseline intraocular pressure (IOP) [odds ratio (OR), 0.88; 95% confidential interval (CI), 0.80-0.98; P = 0.014], lower percentage reduction of IOP (OR, 0.96; 95% CI, 0.93-0.99; P = 0.020), cold extremities (OR, 2.80; 95% CI, 1.03-7.60; P = 0.043), prone or lateral decubitus sleeping position (OR, 2.14; 95% CI, 1.13-4.03; P = 0.019), and sleeping disorders (OR, 2.33; 95% CI, 1.05-5.15; P = 0.037). Multivariate regression analysis revealed that a lower percentage reduction in IOP (OR, 0.96; 95% CI, 0.93-1.00; P = 0.046) increased the risk of recurrent DH. The control group exhibited a greater cumulative probability of non-progression than the recurrent DH group (P = 0.01, by log-rank test). The Cox proportional-hazards regression model showed that recurrent DH was associated with glaucoma progression [hazard ratio (HR), 1.88; 95% CI; 1.66-3.05; P = 0.01. CONCLUSIONS: Among the ocular and systemic factors, only lower-percentage reduction of IOP in POAG was associated with recurrent DH. DH recurrence is associated with glaucoma progression and may be dependent on IOP.

Dermatologic Vasculature Diseases as a Risk Factor of Subconjunctival Hemorrhage.

To evaluate the relationship between subconjunctival hemorrhage (SCH) and dermatologic vasculature diseases (DVDs) via the national health insurance research database (NHIRD) of Taiwan. This retrospective cohort study used data from the NHIRD for the 2009 to 2013 period. Patients diagnosed with DVDs were enrolled in the study group, and a propensity score-matching population was selected as the control group after exclusion. The main outcome was set as the development of SCH in both groups. Multivariable Cox regression analysis and survival analysis were performed to estimate the adjusted hazard ratio (aHR) and cumulative probability of SCH. A total number of 3426 patients were enrolled and split equally into the study and the control groups. There was no prominent difference between the age, gender, urbanization, income level, systemic co-morbidities, and ocular diseases between the two groups after matching. During the whole study period, 131 patients in the study group and 98 patients in the control group developed SCH with a significant higher aHR of 2.69 in the study group (p < 0.05). In the survival analysis, the study group also demonstrated a higher cumulative probability of developing SCH than the control group throughout the study period (p = 0.02). In conclusion, the presence of DVDs may be a risk factor for the development of SCH.

Oxymetazoline: reduction of subconjunctival hemorrhage incidence after intravitreal injections.

OBJECTIVE: Subconjunctival hemorrhage (SCH) is an important minor side effect that might affect patient compliance to antivascular endothelial growth factor (anti-VEGF) intravitreal injection treatment (IVI). We sought to compare SCH incidence and pain score responses after topical oxymetazoline in naïve patients undergoing a single IVI of ranibizumab for diabetic macular edema. METHODS: Prospective, randomized, double-blinded, single centre study. One hundred two patients naïve to anti-VEGF were assigned to receive either topical oxymetazoline or placebo 30 minutes before IVI. SCH incidence and area were measured by slit lamp 24 hours after, and pain was evaluated 5 minutes and 24 hours after. RESULTS: SCH incidence was reported on 72% in control group versus 51% in oxymetazoline group (p = 0.037). Mean size of SCH was 16.82 mm2 in control group versus 12.55 mm2 in oxymetazoline group (p = 0.394). Prevalence of local pain in the overall study population was 60%. No significant statistical difference was achieved between groups 5 minutes or 24 hours after IVI in either pain scale evaluation. CONCLUSION: Administration of topical oxymetazoline 30 minutes before IVI is a single, harmless, cost-effective intervention that decreases the incidence of subconjunctival hemorrhage. This may considerably improve patient treatment satisfaction and promote compliance to IVI therapy.

Intracapsular hemorrhage rates in non-fixated nylon sheet orbital implants for orbital fracture management.

PURPOSE: To examine the incidence of intracapsular hemorrhage in orbital fracture repair with non-fixated nylon sheet implants. METHODS: A retrospective chart review of 227 patients presenting from January 2013 to December 2016 for orbital fracture repair with nylon sheet implants. RESULTS: Of the 331 orbital fractures repaired over 4 years, a total of 227 met inclusion criteria. The average implant thickness was 0.38 mm and no implants were fixated. Four total implants (1.8%) were removed due to complications; one each secondary to exploration for ongoing postoperative diplopia, immediate post-operative orbital hemorrhage, a cystic mass anterior to the implant, and pain. There were no cases of intracapsular hemorrhage nor infection for any of the 227 patients over 4 years. CONCLUSIONS: To the authors knowledge, this represents the largest case series to date to assess the rate of intracapsular hemorrhage in non-fixated nylon sheet orbital implants. In the 227 cases reviewed over a 4-year period, there were no cases of intracapsular hemorrhage. This suggests a much lower complication rate than previously reported. PRéCIS: A case series of 227 patients who underwent orbital fracture repair with non-fixated nylon sheet implants.

Anticoagulation: a practical guide for strabismus surgeons.

An increasing number of surgical strabismus patients are taking oral anticoagulant and antiplatelet agents, with more diverse mechanisms of action than those used in the past. The decision as to whether to continue these drugs throughout the perioperative period is difficult and must be based on the balance between hemorrhagic and thrombotic risk. To help guide strabismus surgeons with clinical management in these cases, we review potential hemorrhagic complications of strabismus surgery and examine the use of anticoagulant and antiplatelet drugs during the perioperative period. Surgical strategies that might help minimize intraoperative hemorrhage in patients on anticoagulant therapy are also discussed.

The Prevalence of Adverse Ocular Hemorrhagic Events in Patients Utilizing Oral Anticoagulant and Antiplatelet Therapy in Routine Clinical Practice.

BACKGROUND AND OBJECTIVE: Previous literature assessing ocular hemorrhagic complications of anticoagulant/antiplatelet medications in routine clinical practice is limited. This study evaluates the prevalence of spontaneous ocular hemorrhagic events associated with anticoagulation/antiplatelet therapy. PATIENTS AND METHODS: A retrospective study was performed to identify patients taking anticoagulants (rivaroxaban [Xarelto; Janssen Pharmaceuticals, Beerse, Belgium], bivalirudin [Angiomax; The Medicines Company, Parsippany, NJ], lepirudin [Refludan; Bayer HealthCare Pharmaceuticals, Berlin, Germany], dabigatran [Pradaxa; Boehringer Ingelheim, Ingelheim am Rhein, Germany], and argatroban) and antiplatelet agents (clopidogrel [Plavix; Bristol-Myers Squibb, New York City, NY], prasugrel [Effient; Lilly Medical, Indianapolis, IN], and ticagrelor [Brilinta; AstraZeneca, Cambridge, UK]) who presented for an eye examination. Location of hemorrhage, relevant systemic and ocular comorbidities, baseline demographics, and concomitant aspirin use were noted. RESULTS: A total of 44 patients with spontaneous ocular hemorrhage were identified. Thirty patients had a single episode, whereas 14 patients had multiple episodes (two or more hemorrhagic events). Prevalence of spontaneous ocular hemorrhage on prasugrel (7.2%) and rivaroxaban (3.1%) was higher compared to dabigatran (1.9%), clopidogrel (2.0%), and ticagrelor (2.7%). CONCLUSION: Prevalence of spontaneous ocular hemorrhage with use of anticoagulant/antiplatelet agents is higher in routine clinical practice as compared to previously reported literature. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:27-34.].

Ocular Manifestations in Leukemias and Their Correlation with Hematologic Parameters at a Tertiary Care Setting in South India.

PURPOSE: To determine the prevalence of ocular manifestations and the association of these manifestations with hematologic parameters among patients with leukemia attending a hemato-oncology unit at a tertiary care government hospital in South India. DESIGN: This was a cross-sectional observational study. PARTICIPANTS: All patients attending a hemato-oncology unit at a tertiary care government hospital in South India who were diagnosed with acute or chronic leukemia that was confirmed by a bone marrow biopsy. METHODS: Consecutive patients with leukemia presenting at the hematology clinic underwent standardized leukemia blood workup and comprehensive ophthalmic evaluation. Patient demographics, the type of leukemia, ophthalmic features, and hematological parameters such as hemoglobin level, white blood cell count, and platelet counts were recorded. The association between ophthalmic manifestations and blood counts was analyzed using multivariable regression analysis. MAIN OUTCOME MEASURES: The study measured the prevalence of various ocular manifestations in different types of leukemias and their association with hematologic parameters. RESULTS: In total, 133 eyes of 133 patients were examined during the study period. The prevalence of leukemic ophthalmopathy was found to be 68% in cases of acute myeloid leukemia, 42% in cases of acute lymphoid leukemia, 33% in cases of chronic lymphoid leukemia, and 13% in cases of chronic myeloid leukemia. Vision-threatening complications such as subhyaloid hemorrhage involving the posterior pole (20%) and vitreous hemorrhage (10%) were seen exclusively in patients with acute leukemias. Multivariable logistic regression after adjusting for the type of leukemia, patient age, and white blood cell and platelet counts showed that the hemoglobin level was the only factor predictive of developing subhyaloid hemorrhage (every 1-g/L increment increase in hemoglobin level led to a 30% reduction in the likelihood of developing subhyaloid hemorrhage; 95% confidence interval 0.5-0.9; P = 0.02). The probability of developing subhyaloid hemorrhage was reduced by >50% when hemoglobin level improved from 5 to 7 g/L and when platelet count improved from 10 000 to 50 000 cells/mm3 for both types of acute leukemia. There was no association between white blood cell counts and ophthalmic manifestations. CONCLUSION: Leukemic ophthalmopathy is more common in acute and myeloid cases and less common in chronic and lymphoid subtypes. It is predominantly due to secondary rheological changes. Blood transfusion should be considered when hemoglobin level and platelet count decrease below 7 g/L and 50 000 cells/mm3, respectively, to prevent vision-threatening complications. Patients with acute leukemias should undergo ophthalmic screening at baseline and then periodically to prevent visual morbidity.

Association of Novel Oral Antithrombotics With the Risk of Intraocular Bleeding.

Importance: Novel oral anticoagulation and antiplatelet therapies have become a mainstay of treatment for thromboembolic disease. However, the safety profile of these medications has not been completely characterized. Objective: To determine the risk of developing intraocular hemorrhages with novel oral antithrombotic therapy compared with that of traditional antithrombotic agents. Design, Setting, and Participants: In this retrospective cohort study, a large national insurance claims database was used to generate 2 parallel analyses. All patients with incident use of dabigatran etexilate or rivaroxaban between January 1, 2010, and September 30, 2015, were compared with patients with incident use of warfarin sodium. Similarly, patients with new use of prasugrel hydrochloride were compared with those with new use of clopidogrel bisulfate. Both analyses required the patient to be in the insurance plan for at least 24 months prior to initiation of therapy and excluded patients with any previous diagnosis of intraocular hemorrhages or any prescription for the comparator medications. Furthermore, the antiplatelet analysis required a diagnosis of acute coronary syndrome or a myocardial infarction within 60 days of initiation of pharmacologic therapy. The anticoagulant analysis excluded patients with end-stage renal disease, renal transplants, and those with heart valve disease. Main Outcomes and Measures: Incident intraocular hemorrhages at 90 and 365 days. Multivariate Cox proportional hazards regression models were used to compare the hazard ratio (HR) of developing an intraocular hemorrhage in individuals taking novel agents compared with those taking traditional medications. Results: A total of 146 137 patients taking warfarin (76 714 women and 69 423 men; mean [SD] age, 69.8 [11.8] years) were compared with 64 291 patients taking dabigatran or rivaroxaban (31 576 women and 32 715 men; mean [SD] age, 67.6 [11.7] years). Cox proportional hazards regression revealed a decreased hazard for developing an intraocular hemorrhage with dabigatran or rivaroxaban at 365 days (HR, 0.75; 95% CI, 0.58-0.97; P = .03), but not at 90 days (HR, 0.73; 95% CI, 0.22-2.63; P = .13). A total of 103 796 patients taking clopidogrel (37 578 women and 66 218 men; mean [SD] age, 68.0 [11.3] years) were compared with 8386 patients taking prasugrel (1988 women and 6380 men; mean [SD] age, 61.0 [9.6] years) and no increased hazard for developing an intraocular hemorrhage with prasugrel was seen at 90 days (HR, 0.75; 95% CI, 0.29-1.92; P = .55) or 365 days (HR, 1.19; 95% CI, 0.69-2.04; P = .53). Conclusions and Relevance: These results suggest a decreased risk of intraocular hemorrhage associated with novel direct thrombin inhibitors and direct factor Xa inhibitors, but no difference for P2Y12 inhibitors compared with traditional vitamin K anticoagulation and antiplatelet therapy, respectively.

Risk of Intraocular Bleeding With Novel Oral Anticoagulants Compared With Warfarin: A Systematic Review and Meta-analysis.

Importance: It is unclear if the risk of intraocular bleeding with novel oral anticoagulants differs compared with warfarin. Objective: To characterize the risk of intraocular bleeding with novel oral anticoagulants compared with warfarin. Data Sources: A systematic review and meta-analysis was undertaken in an academic medical setting. MEDLINE and ClinicalTrials.gov were searched for randomized clinical trials published up until August 2016. This search was supplemented by manual bibliography searches of identified trials and other review articles. Study Selection: Studies were eligible for inclusion if they were phase 3 randomized clinical trials, enrolled patients with atrial fibrillation or venous thromboembolism, compared a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) with warfarin, and recorded event data on intraocular bleeding. Data on intraocular bleeding were pooled using inverse-variance, weighted, fixed-effects meta-analysis. Data Extraction and Synthesis: The PRISMA guidelines were used for abstracting data and assessing quality. Independent extraction was performed by 2 investigators. Main Outcomes and Measures: Intraocular bleeding events and associated risk ratio for novel oral anticoagulants compared with warfarin. Results: Twelve trials investigating 102 627 patients were included. Randomization to novel oral anticoagulants was associated with a 22% relative reduction in intraocular bleeding compared with warfarin (risk ratio, 0.78; 95% CI, 0.61-0.99). There was no significant heterogeneity observed (I2 = 4.8%, P = .40). Comparably lower risks of intraocular bleeding with novel oral anticoagulants were seen in subgroup analyses, with no significant difference according to the indication for anticoagulation (P for heterogeneity = .49) or the novel oral anticoagulant type (P for heterogeneity = .15). Summary estimates did not differ materially when random-effects meta-analytic techniques were used. Conclusions and Relevance: These results suggest that novel oral anticoagulants reduce the risk of intraocular bleeding by approximately one-fifth compared with warfarin. Similar benefits were seen in both patients with atrial fibrillation and venous thromboembolism. Our data have particular relevance for patients at higher risk of spontaneous retinal and subretinal bleeding. These findings may also have important implications in the perioperative period, in which the use of novel oral anticoagulants may be superior. Future studies are required to better characterize the optimal management of patients with both ophthalmic disease and cardiovascular comorbidities requiring anticoagulation.

Incidence and management of haemorrhagic Descemet membrane detachment in canaloplasty and phacocanaloplasty.

PURPOSE: To report the incidence and management of haemorrhagic Descemet membrane detachment (HDMD) in canaloplasty and phacocanaloplasty. METHODS: This study included 105 eyes of 92 patients with uncontrolled open angle glaucoma who underwent canaloplasty and phacocanaloplasty between 2010 and 2014. Eyes that developed either HDMD or non-HDMD were identified. The main outcome measures were the development of HDMD and non-HDMD, best corrected visual acuity, recovery time after Descemet membrane detachment (DMD), intra-ocular pressure (IOP) and number of antiglaucoma medications. Each eye was managed according to the time of development, type and extent of DMD. RESULTS: Ten eyes (9.5%) developed DMD- four eyes underwent canaloplasty (3.8%) and six eyes underwent phacocanaloplasty (5.7%). Three of 10 eyes developed non-HDMD while seven of 10 developed HDMD, the majority of HDMD cases occurred in combination with phacocanaloplasty (five of seven). The non-HDMD eyes resolved completely within 2 weeks without intervention. One eye with HDMD was observed for 2 weeks, before a 15% sulphur hexafluoride (SF6) intracameral injection was given. The patient developed a dense corneal stain that was resolving slowly over 30 months. One eye with HDMD underwent YAG laser membranotomy 2 weeks after being identified, which regained corneal transparency 1 month after treatment, while the remaining five eyes underwent immediate surgical drainage and regained corneal transparency 1 day post-procedure. CONCLUSION: HDMD occurred in up to 6.7% in canaloplasty and phacocanaloplasty procedures, mostly during catheter withdrawal and the viscodilation step. Early recognition and management prevented further manipulation.

Prevalence of hemostatic alterations in patients with recurrent spontaneous subconjunctival hemorrhage.

BACKGROUND: Subconjunctival hemorrage (SCH) is a frequent, mild bleeding manifestation and a common cause of consultation. Hemostatic alterations are possible causes of SCH but their role and prevalence is unknown. We assessed the prevalence of hemostatic abnormalities in patients with spontaneous, recurrent SCH to clarify the role of the hemostasis laboratory in this clinical setting. METHODS: A total of 105 SCH patients (21-78 years, 65 females) with no identifiable cause (hypertension-trauma-conjunctivitis) or concomitant treatments (NSAIDs- aspirin-oral anticoagulants-antiplatelet agents) and 53 age and sex-matched healthy controls (HCs) (22-72 years, 29 females) were evaluated for skin bleeding time, PFA-100®, blood clotting screening, platelet count, light transmission aggregomery, VWF:Ag, VWF:RCo, RIPA, FVIII activity, FXIII antigen and activity and ISTH Bleeding Severity Score (BSS). RESULTS: Prevalence of hemostatic abnormalities was not higher in the SCH population than in HCs BSS was 0.83 (95% CI 0.62-1.06) in SCH and 0.66 (0.37-0.95) in HC (p=NS). Type I Von Willebrand disease was diagnosed in one SCH and none HC patients, a prevalence not significantly different (p=NS by χ2). CONCLUSIONS: The prevalence of hemostatic alterations in patients with recurrent, spontaneous SCH is not different from the general population; hemostatic screening or second level tests are of no use in patients with recurrent SCH and no other bleedings.